2011 ASCO Annual Meeting

Efforts to build on the effectiveness of trastuzumab with a dual blockade of the HER2 pathway continue to suggest such a strategy has the potential to enhance outcomes for HER2-positive breast cancer patients.

Genentech announced this summer that the combination of trastuzumab (Herceptin) and docetaxel (Taxotere) with the investigational agent pertuzumab (Omnitarg) met the primary end point of improved progression-free survival in the randomized, double-blind, placebo-controlled phase III CLEOPATRA trial.

A monoclonal antibody, pertuzumab prevents the HER2 receptor from pairing with other HER receptors, including HER1/EGFR, HER3, and HER4, according to Genentech. The Roche-owned company released no data, but said it expects to submit the trial results for "global regulatory approval" this year. A spokesperson said the results will be submitted at "an upcoming medical meeting,"

Trastuzumab emtansine (formerly known as trastuzumab-DM1) is also in ongoing trials, assessing it in various combinations involving trastuzumab, pertuzumab, and lapatinib (Tykerb), the last of which is a dual inhibitor of HER2 and the epidermal growth factor receptor (EGFR). Genentech is developing this experimental antibody-drug conjugate, with Immunogen. It sought accelerated approval based on a positive phase II study last summer but was rebuffed by the Food and Drug Administration on grounds that patients in the trial had not exhausted other therapies.

Since then, the combination of trastuzumab and lapatinib – both approved for HER2-positive breast cancer – was shown to boost complete response rates to 74% when combined with preoperative chemotherapy in a phase II trial reported in June at the annual meeting of the American Society of Clinical Oncology (ASCO).

The study was one of a trio of neoadjuvant trials that evaluated whether complete responses rates could be bettered by adding lapatinib to chemotherapy plus trastuzumab or by combining lapatinib and trastuzumab without chemotherapy, but with the option of endocrine therapy.

Trastuzumab, Lapatinib, and Chemotherapy

Investigators in the phase II CHER-LOB study defined pathological complete response (pCR) as the complete disappearance of invasive residual disease in the breast and axillary nodes. Among 115 evaluable women, the pCR rate increased from 25.7% with chemotherapy plus trastuzumab (arm A) and 27.8% with chemotherapy plus lapatinib (arm B) to 43.1% with the addition of lapatinib to chemotherapy plus trastuzumab (arm C).

The cardiac safety data were reassuring, with no reports of heart failure or significant loss of left ventricular function. Diarrhea, however, was a significant toxicity that caused dose reductions and treatment interruptions in the majority of patients receiving chemotherapy plus lapatinib, acknowledged Dr. Valentina Guarneri of the Modena (Italy) University Hospital. Grade 3 or higher diarrhea was reported in 36% of 39 patients in arm B and 33% of 46 patients in arm C. Permanent lapatinib discontinuation occurred in 25.6% and 13%, respectively.

Because of the high incidence of diarrhea, the protocol was amended to reduce continuous daily dosing of lapatinib from 1,500 mg to 1,250 mg in arm B and from 1,000 mg to 750 mg in arm C. After the amendment, dose reductions fell from 80% to 54% in arm B and from 55% to 34% in arm C, she said.

Chemotherapy consisted of weekly paclitaxel 80 mg/m² for 12 weeks followed by four cycles of fluorouracil 600 mg/m² plus epirubicin 75 mg/m² plus cyclophosphamide 600 mg/m² every 3 weeks (FE₇₅C). Trastuzumab 4 mg/m² was given as a loading dose, followed by 2 mg/m² every week.

A Similar Protocol but With Modifications

The second trial extended the 24-week preoperative FE₇₅C chemotherapy sequence to 26 weeks after a 2-week run-in period of anti-HER2 therapy and used weekly paclitaxel after, rather than before, FE₇₅C. Also, the daily lapatinib dose was set at 1,250 mg in arm B and increased from 750 mg-1,000 mg in arm C. Trastuzumab dosing was the same as above.

Using this protocol, pCR rates among 78 evaluable women reached 54% with chemotherapy plus trastuzumab (arm A), 45% with chemotherapy plus lapatinib (arm B), and 74% with double HER2 blockade plus chemotherapy (arm C), reported Dr. Frankie Ann Holmes with Texas Oncology in Houston.

Patients had stage II-III biopsy proven invasive HER2-positive breast cancer, whereas CHER-LOB limited enrollment to stage II-IIIA disease.

Headed in the Right Direction

Invited discussant Dr. Gunther von Minckwitz, with the German Breast Group, said that despite the small patient numbers, the pCR rates were quite impressive, especially for the study presented by Dr. Holmes, and are in range with previous trials using longer chemotherapy regimens.

The difference in pCR rates between the two studies could be explained by the small sample sizes and differences in patient characteristics. "Still the tendency is going in the same direction," he observed.

Dr. von Minckwitz urged caution in using pCR as an end point, however, particularly among patients with HER2-positive and estrogen receptor (ER)-positive disease. His own meta-analysis presented at ASCO of seven German neoadjuvant breast trials using anthracycline/taxane regimens with or without trastuzumab, showed that pCR strongly correlates with disease-free survival in higher risk groups such as ductal, HER2-positive, and ER-negative disease, but not in luminal A-like and ER-positive/HER2-positive tumors (Abstract 1028).

Lapatinib vs. Trastuzumab Sans Chemo

The third study used neoadjuvant lapatinib 1,000 mg daily plus trastuzumab at a loading dose of 4 mg/kg followed by 2 mg/kg weekly, without chemotherapy, in women with large HER2-positive tumors (median 6 cm; range 1.5-30 cm). In an effort to overcome estrogen receptor crosstalk, ER-positive patients also received letrozole (Femara), plus goserelin, if premenopausal.

A pCR, defined as no invasive cancer in the breast only, was achieved by 28% of the 64 evaluable patients – 21% of ER-positive and 40% of ER-negative patients, Dr. Jenny C. Chang reported on behalf of the Translational Breast Cancer Research Consortium (TBCRC) 006 investigators. No patient progressed during the 12 weeks of targeted therapy alone.

The secondary end point of residual disease of less than 1 cm (near pCR) was seen in 56% of ER-positive and 48% of ER-negative patients, suggesting that these patients may benefit from longer therapy, she said. In all, 62% of patients were ER positive, 62% had a tumor size greater than 5 cm, and 54% were premenopausal.

The regimen in the phase II TBCRC 006 study was very well tolerated, with only five patients discontinuing therapy and 3 reports of grade 3/4 abnormal liver function tests that completely resolved.

Further study is needed before suggesting that select patients with HER2-positive tumors may not need neoadjuvant chemotherapy, said Dr. Chang, director of the Methodist Cancer Center in Houston.

The data compare favorably with those reported at the 2010 San Antonio Breast Cancer Symposium from the phase II NEOSPHERE trial, in which 17% of patients overall, 6% of ER-positive and 29% of ER-negative patients experienced a pCR after 12 weeks of neoadjuvant trastuzumab plus the monoclonal antibody, pertuzumab, Dr. von Minckwitz observed.

New insights are expected from three upcoming neoadjuvant chemotherapy trials in HER2-positive breast cancer: Cancer and Leukemia Group B 40601, European Organization for Research and Treatment of Cancer 10054 and a National Surgical Adjuvant Breast and Bowel Project B-41.

Molecular Profiles Begin to Emerge

Dr. Holmes and her colleagues conducted a variety of molecular analyses in tumor samples from 49 patients before and after anti-HER2 therapy. She reported that their findings indicate the following:

• Baseline phosphorylated EGFR tyrosine1068 is a marker of nonresponse to lapatinib.

• Baseline activation of autophagy correlates with no pCR to all therapies.

• Baseline ratios of phosphorylated Forkhead box O to PTEN and PI3K correlate with response.

• Phosphorylated STAT5 after trastuzumab correlates with pCR.

The molecular profiles suggest that pCR tumors rely on a truncated, rudimentary social network, while resistant tumors use a far more extensive network of autophagy and stem cell–regulated pathways to evade therapy and are thus harder to kill, Dr. Holmes said.

"Despite the limitations, this exploratory analysis shows that the pathway to accelerating the cure of breast cancer is available in every oncologist’s office if she or he can network to tissue-based research trials," she said.

The CHER-LOB investigators tested tumor samples for p95HER2, which is expressed in approximately 30% of HER2-positive breast cancer patients and thought to confer resistance to trastuzumab. No significant differences were observed in all treatment arms in pCR rates based on p95HER2 expression, Dr. Guarneri said.

The p95HER2 results contradict earlier research, observed Dr. von Minckwitz. "We really have to design these biomarker studies very cautiously and the first [issue] we have to address is that we have to have sufficient numbers to study," he added.

CHER-LOB was supported by GlaxoSmithKline. Dr. Guarneri reports no conflicts. Dr. Holmes reports a consultant-advisory role with Phillips Home Monitoring and honoraria from Genentech and Novartis. Dr. Chang reports no relevant conflicts. Dr. Von Minckwitz reports honoraria from Amgen, Roche, and Sanofi-Aventis and research funding from Abraxis BioScience, Amgen, Bayer, GSK, Novartis, Pfizer, Roche, Sanofi-Aventis, and bioMérieux.

Efforts to build on the effectiveness of trastuzumab with a dual blockade of the HER2 pathway continue to suggest such a strategy has the potential to enhance outcomes for HER2-positive breast cancer patients.

Genentech announced this summer that the combination of trastuzumab (Herceptin) and docetaxel (Taxotere) with the investigational agent pertuzumab (Omnitarg) met the primary end point of improved progression-free survival in the randomized, double-blind, placebo-controlled phase III CLEOPATRA trial.

A monoclonal antibody, pertuzumab prevents the HER2 receptor from pairing with other HER receptors, including HER1/EGFR, HER3, and HER4, according to Genentech. The Roche-owned company released no data, but said it expects to submit the trial results for "global regulatory approval" this year. A spokesperson said the results will be submitted at "an upcoming medical meeting,"

Trastuzumab emtansine (formerly known as trastuzumab-DM1) is also in ongoing trials, assessing it in various combinations involving trastuzumab, pertuzumab, and lapatinib (Tykerb), the last of which is a dual inhibitor of HER2 and the epidermal growth factor receptor (EGFR). Genentech is developing this experimental antibody-drug conjugate, with Immunogen. It sought accelerated approval based on a positive phase II study last summer but was rebuffed by the Food and Drug Administration on grounds that patients in the trial had not exhausted other therapies.

Since then, the combination of trastuzumab and lapatinib – both approved for HER2-positive breast cancer – was shown to boost complete response rates to 74% when combined with preoperative chemotherapy in a phase II trial reported in June at the annual meeting of the American Society of Clinical Oncology (ASCO).

The study was one of a trio of neoadjuvant trials that evaluated whether complete responses rates could be bettered by adding lapatinib to chemotherapy plus trastuzumab or by combining lapatinib and trastuzumab without chemotherapy, but with the option of endocrine therapy.

Trastuzumab, Lapatinib, and Chemotherapy

Investigators in the phase II CHER-LOB study defined pathological complete response (pCR) as the complete disappearance of invasive residual disease in the breast and axillary nodes. Among 115 evaluable women, the pCR rate increased from 25.7% with chemotherapy plus trastuzumab (arm A) and 27.8% with chemotherapy plus lapatinib (arm B) to 43.1% with the addition of lapatinib to chemotherapy plus trastuzumab (arm C).

The cardiac safety data were reassuring, with no reports of heart failure or significant loss of left ventricular function. Diarrhea, however, was a significant toxicity that caused dose reductions and treatment interruptions in the majority of patients receiving chemotherapy plus lapatinib, acknowledged Dr. Valentina Guarneri of the Modena (Italy) University Hospital. Grade 3 or higher diarrhea was reported in 36% of 39 patients in arm B and 33% of 46 patients in arm C. Permanent lapatinib discontinuation occurred in 25.6% and 13%, respectively.

Because of the high incidence of diarrhea, the protocol was amended to reduce continuous daily dosing of lapatinib from 1,500 mg to 1,250 mg in arm B and from 1,000 mg to 750 mg in arm C. After the amendment, dose reductions fell from 80% to 54% in arm B and from 55% to 34% in arm C, she said.

Chemotherapy consisted of weekly paclitaxel 80 mg/m² for 12 weeks followed by four cycles of fluorouracil 600 mg/m² plus epirubicin 75 mg/m² plus cyclophosphamide 600 mg/m² every 3 weeks (FE₇₅C). Trastuzumab 4 mg/m² was given as a loading dose, followed by 2 mg/m² every week.

A Similar Protocol but With Modifications

The second trial extended the 24-week preoperative FE₇₅C chemotherapy sequence to 26 weeks after a 2-week run-in period of anti-HER2 therapy and used weekly paclitaxel after, rather than before, FE₇₅C. Also, the daily lapatinib dose was set at 1,250 mg in arm B and increased from 750 mg-1,000 mg in arm C. Trastuzumab dosing was the same as above.

Using this protocol, pCR rates among 78 evaluable women reached 54% with chemotherapy plus trastuzumab (arm A), 45% with chemotherapy plus lapatinib (arm B), and 74% with double HER2 blockade plus chemotherapy (arm C), reported Dr. Frankie Ann Holmes with Texas Oncology in Houston.

Patients had stage II-III biopsy proven invasive HER2-positive breast cancer, whereas CHER-LOB limited enrollment to stage II-IIIA disease.

Headed in the Right Direction

Invited discussant Dr. Gunther von Minckwitz, with the German Breast Group, said that despite the small patient numbers, the pCR rates were quite impressive, especially for the study presented by Dr. Holmes, and are in range with previous trials using longer chemotherapy regimens.

The difference in pCR rates between the two studies could be explained by the small sample sizes and differences in patient characteristics. "Still the tendency is going in the same direction," he observed.

Dr. von Minckwitz urged caution in using pCR as an end point, however, particularly among patients with HER2-positive and estrogen receptor (ER)-positive disease. His own meta-analysis presented at ASCO of seven German neoadjuvant breast trials using anthracycline/taxane regimens with or without trastuzumab, showed that pCR strongly correlates with disease-free survival in higher risk groups such as ductal, HER2-positive, and ER-negative disease, but not in luminal A-like and ER-positive/HER2-positive tumors (Abstract 1028).

Lapatinib vs. Trastuzumab Sans Chemo

The third study used neoadjuvant lapatinib 1,000 mg daily plus trastuzumab at a loading dose of 4 mg/kg followed by 2 mg/kg weekly, without chemotherapy, in women with large HER2-positive tumors (median 6 cm; range 1.5-30 cm). In an effort to overcome estrogen receptor crosstalk, ER-positive patients also received letrozole (Femara), plus goserelin, if premenopausal.

A pCR, defined as no invasive cancer in the breast only, was achieved by 28% of the 64 evaluable patients – 21% of ER-positive and 40% of ER-negative patients, Dr. Jenny C. Chang reported on behalf of the Translational Breast Cancer Research Consortium (TBCRC) 006 investigators. No patient progressed during the 12 weeks of targeted therapy alone.

The secondary end point of residual disease of less than 1 cm (near pCR) was seen in 56% of ER-positive and 48% of ER-negative patients, suggesting that these patients may benefit from longer therapy, she said. In all, 62% of patients were ER positive, 62% had a tumor size greater than 5 cm, and 54% were premenopausal.

The regimen in the phase II TBCRC 006 study was very well tolerated, with only five patients discontinuing therapy and 3 reports of grade 3/4 abnormal liver function tests that completely resolved.

Further study is needed before suggesting that select patients with HER2-positive tumors may not need neoadjuvant chemotherapy, said Dr. Chang, director of the Methodist Cancer Center in Houston.

The data compare favorably with those reported at the 2010 San Antonio Breast Cancer Symposium from the phase II NEOSPHERE trial, in which 17% of patients overall, 6% of ER-positive and 29% of ER-negative patients experienced a pCR after 12 weeks of neoadjuvant trastuzumab plus the monoclonal antibody, pertuzumab, Dr. von Minckwitz observed.

New insights are expected from three upcoming neoadjuvant chemotherapy trials in HER2-positive breast cancer: Cancer and Leukemia Group B 40601, European Organization for Research and Treatment of Cancer 10054 and a National Surgical Adjuvant Breast and Bowel Project B-41.

Molecular Profiles Begin to Emerge

Dr. Holmes and her colleagues conducted a variety of molecular analyses in tumor samples from 49 patients before and after anti-HER2 therapy. She reported that their findings indicate the following:

• Baseline phosphorylated EGFR tyrosine1068 is a marker of nonresponse to lapatinib.

• Baseline activation of autophagy correlates with no pCR to all therapies.

• Baseline ratios of phosphorylated Forkhead box O to PTEN and PI3K correlate with response.

• Phosphorylated STAT5 after trastuzumab correlates with pCR.

The molecular profiles suggest that pCR tumors rely on a truncated, rudimentary social network, while resistant tumors use a far more extensive network of autophagy and stem cell–regulated pathways to evade therapy and are thus harder to kill, Dr. Holmes said.

"Despite the limitations, this exploratory analysis shows that the pathway to accelerating the cure of breast cancer is available in every oncologist’s office if she or he can network to tissue-based research trials," she said.

The CHER-LOB investigators tested tumor samples for p95HER2, which is expressed in approximately 30% of HER2-positive breast cancer patients and thought to confer resistance to trastuzumab. No significant differences were observed in all treatment arms in pCR rates based on p95HER2 expression, Dr. Guarneri said.

The p95HER2 results contradict earlier research, observed Dr. von Minckwitz. "We really have to design these biomarker studies very cautiously and the first [issue] we have to address is that we have to have sufficient numbers to study," he added.

CHER-LOB was supported by GlaxoSmithKline. Dr. Guarneri reports no conflicts. Dr. Holmes reports a consultant-advisory role with Phillips Home Monitoring and honoraria from Genentech and Novartis. Dr. Chang reports no relevant conflicts. Dr. Von Minckwitz reports honoraria from Amgen, Roche, and Sanofi-Aventis and research funding from Abraxis BioScience, Amgen, Bayer, GSK, Novartis, Pfizer, Roche, Sanofi-Aventis, and bioMérieux.

Efforts to build on the effectiveness of trastuzumab with a dual blockade of the HER2 pathway continue to suggest such a strategy has the potential to enhance outcomes for HER2-positive breast cancer patients.

Genentech announced this summer that the combination of trastuzumab (Herceptin) and docetaxel (Taxotere) with the investigational agent pertuzumab (Omnitarg) met the primary end point of improved progression-free survival in the randomized, double-blind, placebo-controlled phase III CLEOPATRA trial.

A monoclonal antibody, pertuzumab prevents the HER2 receptor from pairing with other HER receptors, including HER1/EGFR, HER3, and HER4, according to Genentech. The Roche-owned company released no data, but said it expects to submit the trial results for "global regulatory approval" this year. A spokesperson said the results will be submitted at "an upcoming medical meeting,"

Trastuzumab emtansine (formerly known as trastuzumab-DM1) is also in ongoing trials, assessing it in various combinations involving trastuzumab, pertuzumab, and lapatinib (Tykerb), the last of which is a dual inhibitor of HER2 and the epidermal growth factor receptor (EGFR). Genentech is developing this experimental antibody-drug conjugate, with Immunogen. It sought accelerated approval based on a positive phase II study last summer but was rebuffed by the Food and Drug Administration on grounds that patients in the trial had not exhausted other therapies.

Since then, the combination of trastuzumab and lapatinib – both approved for HER2-positive breast cancer – was shown to boost complete response rates to 74% when combined with preoperative chemotherapy in a phase II trial reported in June at the annual meeting of the American Society of Clinical Oncology (ASCO).

The study was one of a trio of neoadjuvant trials that evaluated whether complete responses rates could be bettered by adding lapatinib to chemotherapy plus trastuzumab or by combining lapatinib and trastuzumab without chemotherapy, but with the option of endocrine therapy.

Trastuzumab, Lapatinib, and Chemotherapy

Investigators in the phase II CHER-LOB study defined pathological complete response (pCR) as the complete disappearance of invasive residual disease in the breast and axillary nodes. Among 115 evaluable women, the pCR rate increased from 25.7% with chemotherapy plus trastuzumab (arm A) and 27.8% with chemotherapy plus lapatinib (arm B) to 43.1% with the addition of lapatinib to chemotherapy plus trastuzumab (arm C).

The cardiac safety data were reassuring, with no reports of heart failure or significant loss of left ventricular function. Diarrhea, however, was a significant toxicity that caused dose reductions and treatment interruptions in the majority of patients receiving chemotherapy plus lapatinib, acknowledged Dr. Valentina Guarneri of the Modena (Italy) University Hospital. Grade 3 or higher diarrhea was reported in 36% of 39 patients in arm B and 33% of 46 patients in arm C. Permanent lapatinib discontinuation occurred in 25.6% and 13%, respectively.

Because of the high incidence of diarrhea, the protocol was amended to reduce continuous daily dosing of lapatinib from 1,500 mg to 1,250 mg in arm B and from 1,000 mg to 750 mg in arm C. After the amendment, dose reductions fell from 80% to 54% in arm B and from 55% to 34% in arm C, she said.

Chemotherapy consisted of weekly paclitaxel 80 mg/m² for 12 weeks followed by four cycles of fluorouracil 600 mg/m² plus epirubicin 75 mg/m² plus cyclophosphamide 600 mg/m² every 3 weeks (FE₇₅C). Trastuzumab 4 mg/m² was given as a loading dose, followed by 2 mg/m² every week.

A Similar Protocol but With Modifications

The second trial extended the 24-week preoperative FE₇₅C chemotherapy sequence to 26 weeks after a 2-week run-in period of anti-HER2 therapy and used weekly paclitaxel after, rather than before, FE₇₅C. Also, the daily lapatinib dose was set at 1,250 mg in arm B and increased from 750 mg-1,000 mg in arm C. Trastuzumab dosing was the same as above.

Using this protocol, pCR rates among 78 evaluable women reached 54% with chemotherapy plus trastuzumab (arm A), 45% with chemotherapy plus lapatinib (arm B), and 74% with double HER2 blockade plus chemotherapy (arm C), reported Dr. Frankie Ann Holmes with Texas Oncology in Houston.

Patients had stage II-III biopsy proven invasive HER2-positive breast cancer, whereas CHER-LOB limited enrollment to stage II-IIIA disease.

Headed in the Right Direction

Invited discussant Dr. Gunther von Minckwitz, with the German Breast Group, said that despite the small patient numbers, the pCR rates were quite impressive, especially for the study presented by Dr. Holmes, and are in range with previous trials using longer chemotherapy regimens.

The difference in pCR rates between the two studies could be explained by the small sample sizes and differences in patient characteristics. "Still the tendency is going in the same direction," he observed.

Dr. von Minckwitz urged caution in using pCR as an end point, however, particularly among patients with HER2-positive and estrogen receptor (ER)-positive disease. His own meta-analysis presented at ASCO of seven German neoadjuvant breast trials using anthracycline/taxane regimens with or without trastuzumab, showed that pCR strongly correlates with disease-free survival in higher risk groups such as ductal, HER2-positive, and ER-negative disease, but not in luminal A-like and ER-positive/HER2-positive tumors (Abstract 1028).

Lapatinib vs. Trastuzumab Sans Chemo

The third study used neoadjuvant lapatinib 1,000 mg daily plus trastuzumab at a loading dose of 4 mg/kg followed by 2 mg/kg weekly, without chemotherapy, in women with large HER2-positive tumors (median 6 cm; range 1.5-30 cm). In an effort to overcome estrogen receptor crosstalk, ER-positive patients also received letrozole (Femara), plus goserelin, if premenopausal.

A pCR, defined as no invasive cancer in the breast only, was achieved by 28% of the 64 evaluable patients – 21% of ER-positive and 40% of ER-negative patients, Dr. Jenny C. Chang reported on behalf of the Translational Breast Cancer Research Consortium (TBCRC) 006 investigators. No patient progressed during the 12 weeks of targeted therapy alone.

The secondary end point of residual disease of less than 1 cm (near pCR) was seen in 56% of ER-positive and 48% of ER-negative patients, suggesting that these patients may benefit from longer therapy, she said. In all, 62% of patients were ER positive, 62% had a tumor size greater than 5 cm, and 54% were premenopausal.

The regimen in the phase II TBCRC 006 study was very well tolerated, with only five patients discontinuing therapy and 3 reports of grade 3/4 abnormal liver function tests that completely resolved.

Further study is needed before suggesting that select patients with HER2-positive tumors may not need neoadjuvant chemotherapy, said Dr. Chang, director of the Methodist Cancer Center in Houston.

The data compare favorably with those reported at the 2010 San Antonio Breast Cancer Symposium from the phase II NEOSPHERE trial, in which 17% of patients overall, 6% of ER-positive and 29% of ER-negative patients experienced a pCR after 12 weeks of neoadjuvant trastuzumab plus the monoclonal antibody, pertuzumab, Dr. von Minckwitz observed.

New insights are expected from three upcoming neoadjuvant chemotherapy trials in HER2-positive breast cancer: Cancer and Leukemia Group B 40601, European Organization for Research and Treatment of Cancer 10054 and a National Surgical Adjuvant Breast and Bowel Project B-41.

Molecular Profiles Begin to Emerge

Dr. Holmes and her colleagues conducted a variety of molecular analyses in tumor samples from 49 patients before and after anti-HER2 therapy. She reported that their findings indicate the following:

• Baseline phosphorylated EGFR tyrosine1068 is a marker of nonresponse to lapatinib.

• Baseline activation of autophagy correlates with no pCR to all therapies.

• Baseline ratios of phosphorylated Forkhead box O to PTEN and PI3K correlate with response.

• Phosphorylated STAT5 after trastuzumab correlates with pCR.

The molecular profiles suggest that pCR tumors rely on a truncated, rudimentary social network, while resistant tumors use a far more extensive network of autophagy and stem cell–regulated pathways to evade therapy and are thus harder to kill, Dr. Holmes said.

"Despite the limitations, this exploratory analysis shows that the pathway to accelerating the cure of breast cancer is available in every oncologist’s office if she or he can network to tissue-based research trials," she said.

The CHER-LOB investigators tested tumor samples for p95HER2, which is expressed in approximately 30% of HER2-positive breast cancer patients and thought to confer resistance to trastuzumab. No significant differences were observed in all treatment arms in pCR rates based on p95HER2 expression, Dr. Guarneri said.

The p95HER2 results contradict earlier research, observed Dr. von Minckwitz. "We really have to design these biomarker studies very cautiously and the first [issue] we have to address is that we have to have sufficient numbers to study," he added.

CHER-LOB was supported by GlaxoSmithKline. Dr. Guarneri reports no conflicts. Dr. Holmes reports a consultant-advisory role with Phillips Home Monitoring and honoraria from Genentech and Novartis. Dr. Chang reports no relevant conflicts. Dr. Von Minckwitz reports honoraria from Amgen, Roche, and Sanofi-Aventis and research funding from Abraxis BioScience, Amgen, Bayer, GSK, Novartis, Pfizer, Roche, Sanofi-Aventis, and bioMérieux.

CHICAGO – Dose-dense temozolomide was no more effective than standard adjuvant temozolomide for patients with newly diagnosed glioblastoma in the randomized, phase III Radiation Treatment Oncology Group 0525 study.

Among 833 patients, the primary end point of median overall survival was 16.6 months with standard temozolomide (Temodar) vs. 14.9 months with dose-dense temozolomide (P = .63; hazard ratio 0.87).

Median progression-free survival was also similar at 5.5 months vs. 6.7 months (P = .06; HR, 0.87), Dr. Mark R. Gilbert reported at the meeting

RTOG 0525 was designed as a successor to the landmark EORTC (European Organisation for Research and Treatment of Cancer) trial that helped establish radiation plus concomitant and adjuvant temozolomide as the international standard of care for newly diagnosed glioblastoma (N. Engl. J. Med. 2005;352:987-96). It also helped to identify patients with MGMT (O⁶-methylguanine-DNA methyltransferase)–methylated tumors as a subpopulation that appeared to derive greater benefit from temozolomide (N. Engl. J. Med. 2005;352:997-1003).

It was hoped that dose-dense therapy would further enhance the efficacy of temozolomide in MGMT-methylated tumors and would deplete the endogenous reservoir of MGMT in nonmethylated MGMT tumors, as well as induce sensitivity to temozolomide, an oral alkylating agent. The MGMT gene encodes a DNA repair enzyme that can cancel the effects of alkylating chemotherapy.

Although the therapeutic end point was not reached, the study confirmed the prognostic value of MGMT promoter methylation status, said Dr. Gilbert, a professor of neuro-oncology at the University of Texas M.D. AndersonCancer Center in Houston.

MGMT-methylated tumors, compared with unmethylated tumors, were associated with significant improvements in median overall survival (21.2 months vs. 14 months; P less than .0001; HR, 1.74) and progression-free survival (8.7 months vs. 5.7 months; P less than .0001; HR, 1.63).

However, MGMT methylation status did not predict response to the dose-dense schedule, he said. No significant differences in overall or progression-free survival were observed between unmethylated and methylated tumors, regardless of treatment with standard or dose-dense temozolomide.

A Cox proportional hazard model showed that MGMT status and recursive partitioning analysis (RPA) class IV vs. III were significant predictors of overall and progression-free survival, whereas the treatment arm and type of radiation therapy (EORTC vs. RTOG) were not, Dr. Gilbert said.

He observed that RTOG 0525 had a slightly different population than did the EORTC trial in that it required a surgical procedure, enrolled patients older than 70 years, and required all patients to make it through chemoradiation to be randomized.

Invited discussant Dr. Jeffrey S. Abrams of the National Cancer Institute said "We’re all disappointed that it wasn’t positive, but there’s reason to take heart."

He observed that in 2.5 years of accrual, the group conducted what is likely the largest glioblastoma study to date, had a 98% tumor tissue collection rate, and ran a very well-conducted trial in an international collaboration. RTOG 0525 was conducted at 185 North American and 24 European centers by the RTOG, EORTC, and North Central Cancer Treatment Group.

"I think this bodes well for this sort of collaborative process that will speed the development of better treatments for glioblastoma," Dr. Abrams said.

He suggested that the trial may have failed because adjuvant temozolomide is not the active part of the regimen. He pointed out that a randomized, phase II Greek trial increased adjuvant temozolomide to 150 mg/m² every 2 weeks, but saw no improvement in outcome (J. Clin. Oncol. 2005;23:2372-7) and that a small, single-institution study reported comparable survival outcomes with standard temozolomide when temozolomide was administered during the radiation phase at a lower dose of 50 mg/m² without maintenance (Strahlenther Onkol. 2005;181:372-7).

In RTOG 0525, 833 patients received concurrent radiation at 200 cGy in 30 fractions plus temozolomide 75 mg/m² daily, followed by 1:1 randomization to 6-12 cycles of standard temozolomide, starting at 150 mg/m² and escalating to 200 mg/m² if tolerated on days 1-5 of a 28-day cycle, or dose-dense temozolomide starting at 75 mg/m² and escalating to 100 mg/m² if tolerated on days 1-21 of a 28-day cycle.

Roughly one-fourth of patients were younger than 50 years old, more than half underwent total resection, and 45% had minor symptoms.

Grade 3-5 adverse events were significantly more common in the dose-dense arm, compared with the conventional arm (194 vs. 120; P less than .001), but they were mostly lymphopenia (107 vs. 51) and fatigue (33 vs. 12). No opportunistic infections occurred, Dr. Gilbert said.

The study was supported by Schering-Plough/Merck, the maker of temozolomide. Dr. Gilbert reported a consultant/advisory role with Genentech, and honoraria and research funding from Genentech and Merck. Several of his coauthors reported financial relationships with firms including Merck. Dr. Abrams reported that RTOG 0525 also receives funding from the National Cancer Institute, where he is employed.

CHICAGO – Dose-dense temozolomide was no more effective than standard adjuvant temozolomide for patients with newly diagnosed glioblastoma in the randomized, phase III Radiation Treatment Oncology Group 0525 study.

Among 833 patients, the primary end point of median overall survival was 16.6 months with standard temozolomide (Temodar) vs. 14.9 months with dose-dense temozolomide (P = .63; hazard ratio 0.87).

Median progression-free survival was also similar at 5.5 months vs. 6.7 months (P = .06; HR, 0.87), Dr. Mark R. Gilbert reported at the meeting

RTOG 0525 was designed as a successor to the landmark EORTC (European Organisation for Research and Treatment of Cancer) trial that helped establish radiation plus concomitant and adjuvant temozolomide as the international standard of care for newly diagnosed glioblastoma (N. Engl. J. Med. 2005;352:987-96). It also helped to identify patients with MGMT (O⁶-methylguanine-DNA methyltransferase)–methylated tumors as a subpopulation that appeared to derive greater benefit from temozolomide (N. Engl. J. Med. 2005;352:997-1003).

It was hoped that dose-dense therapy would further enhance the efficacy of temozolomide in MGMT-methylated tumors and would deplete the endogenous reservoir of MGMT in nonmethylated MGMT tumors, as well as induce sensitivity to temozolomide, an oral alkylating agent. The MGMT gene encodes a DNA repair enzyme that can cancel the effects of alkylating chemotherapy.

Although the therapeutic end point was not reached, the study confirmed the prognostic value of MGMT promoter methylation status, said Dr. Gilbert, a professor of neuro-oncology at the University of Texas M.D. AndersonCancer Center in Houston.

MGMT-methylated tumors, compared with unmethylated tumors, were associated with significant improvements in median overall survival (21.2 months vs. 14 months; P less than .0001; HR, 1.74) and progression-free survival (8.7 months vs. 5.7 months; P less than .0001; HR, 1.63).

However, MGMT methylation status did not predict response to the dose-dense schedule, he said. No significant differences in overall or progression-free survival were observed between unmethylated and methylated tumors, regardless of treatment with standard or dose-dense temozolomide.

A Cox proportional hazard model showed that MGMT status and recursive partitioning analysis (RPA) class IV vs. III were significant predictors of overall and progression-free survival, whereas the treatment arm and type of radiation therapy (EORTC vs. RTOG) were not, Dr. Gilbert said.

He observed that RTOG 0525 had a slightly different population than did the EORTC trial in that it required a surgical procedure, enrolled patients older than 70 years, and required all patients to make it through chemoradiation to be randomized.

Invited discussant Dr. Jeffrey S. Abrams of the National Cancer Institute said "We’re all disappointed that it wasn’t positive, but there’s reason to take heart."

He observed that in 2.5 years of accrual, the group conducted what is likely the largest glioblastoma study to date, had a 98% tumor tissue collection rate, and ran a very well-conducted trial in an international collaboration. RTOG 0525 was conducted at 185 North American and 24 European centers by the RTOG, EORTC, and North Central Cancer Treatment Group.

"I think this bodes well for this sort of collaborative process that will speed the development of better treatments for glioblastoma," Dr. Abrams said.

He suggested that the trial may have failed because adjuvant temozolomide is not the active part of the regimen. He pointed out that a randomized, phase II Greek trial increased adjuvant temozolomide to 150 mg/m² every 2 weeks, but saw no improvement in outcome (J. Clin. Oncol. 2005;23:2372-7) and that a small, single-institution study reported comparable survival outcomes with standard temozolomide when temozolomide was administered during the radiation phase at a lower dose of 50 mg/m² without maintenance (Strahlenther Onkol. 2005;181:372-7).

In RTOG 0525, 833 patients received concurrent radiation at 200 cGy in 30 fractions plus temozolomide 75 mg/m² daily, followed by 1:1 randomization to 6-12 cycles of standard temozolomide, starting at 150 mg/m² and escalating to 200 mg/m² if tolerated on days 1-5 of a 28-day cycle, or dose-dense temozolomide starting at 75 mg/m² and escalating to 100 mg/m² if tolerated on days 1-21 of a 28-day cycle.

Roughly one-fourth of patients were younger than 50 years old, more than half underwent total resection, and 45% had minor symptoms.

Grade 3-5 adverse events were significantly more common in the dose-dense arm, compared with the conventional arm (194 vs. 120; P less than .001), but they were mostly lymphopenia (107 vs. 51) and fatigue (33 vs. 12). No opportunistic infections occurred, Dr. Gilbert said.

The study was supported by Schering-Plough/Merck, the maker of temozolomide. Dr. Gilbert reported a consultant/advisory role with Genentech, and honoraria and research funding from Genentech and Merck. Several of his coauthors reported financial relationships with firms including Merck. Dr. Abrams reported that RTOG 0525 also receives funding from the National Cancer Institute, where he is employed.

CHICAGO – Dose-dense temozolomide was no more effective than standard adjuvant temozolomide for patients with newly diagnosed glioblastoma in the randomized, phase III Radiation Treatment Oncology Group 0525 study.

Among 833 patients, the primary end point of median overall survival was 16.6 months with standard temozolomide (Temodar) vs. 14.9 months with dose-dense temozolomide (P = .63; hazard ratio 0.87).

Median progression-free survival was also similar at 5.5 months vs. 6.7 months (P = .06; HR, 0.87), Dr. Mark R. Gilbert reported at the meeting

RTOG 0525 was designed as a successor to the landmark EORTC (European Organisation for Research and Treatment of Cancer) trial that helped establish radiation plus concomitant and adjuvant temozolomide as the international standard of care for newly diagnosed glioblastoma (N. Engl. J. Med. 2005;352:987-96). It also helped to identify patients with MGMT (O⁶-methylguanine-DNA methyltransferase)–methylated tumors as a subpopulation that appeared to derive greater benefit from temozolomide (N. Engl. J. Med. 2005;352:997-1003).

It was hoped that dose-dense therapy would further enhance the efficacy of temozolomide in MGMT-methylated tumors and would deplete the endogenous reservoir of MGMT in nonmethylated MGMT tumors, as well as induce sensitivity to temozolomide, an oral alkylating agent. The MGMT gene encodes a DNA repair enzyme that can cancel the effects of alkylating chemotherapy.

Although the therapeutic end point was not reached, the study confirmed the prognostic value of MGMT promoter methylation status, said Dr. Gilbert, a professor of neuro-oncology at the University of Texas M.D. AndersonCancer Center in Houston.

MGMT-methylated tumors, compared with unmethylated tumors, were associated with significant improvements in median overall survival (21.2 months vs. 14 months; P less than .0001; HR, 1.74) and progression-free survival (8.7 months vs. 5.7 months; P less than .0001; HR, 1.63).

However, MGMT methylation status did not predict response to the dose-dense schedule, he said. No significant differences in overall or progression-free survival were observed between unmethylated and methylated tumors, regardless of treatment with standard or dose-dense temozolomide.

A Cox proportional hazard model showed that MGMT status and recursive partitioning analysis (RPA) class IV vs. III were significant predictors of overall and progression-free survival, whereas the treatment arm and type of radiation therapy (EORTC vs. RTOG) were not, Dr. Gilbert said.

He observed that RTOG 0525 had a slightly different population than did the EORTC trial in that it required a surgical procedure, enrolled patients older than 70 years, and required all patients to make it through chemoradiation to be randomized.

Invited discussant Dr. Jeffrey S. Abrams of the National Cancer Institute said "We’re all disappointed that it wasn’t positive, but there’s reason to take heart."

He observed that in 2.5 years of accrual, the group conducted what is likely the largest glioblastoma study to date, had a 98% tumor tissue collection rate, and ran a very well-conducted trial in an international collaboration. RTOG 0525 was conducted at 185 North American and 24 European centers by the RTOG, EORTC, and North Central Cancer Treatment Group.

"I think this bodes well for this sort of collaborative process that will speed the development of better treatments for glioblastoma," Dr. Abrams said.

He suggested that the trial may have failed because adjuvant temozolomide is not the active part of the regimen. He pointed out that a randomized, phase II Greek trial increased adjuvant temozolomide to 150 mg/m² every 2 weeks, but saw no improvement in outcome (J. Clin. Oncol. 2005;23:2372-7) and that a small, single-institution study reported comparable survival outcomes with standard temozolomide when temozolomide was administered during the radiation phase at a lower dose of 50 mg/m² without maintenance (Strahlenther Onkol. 2005;181:372-7).

In RTOG 0525, 833 patients received concurrent radiation at 200 cGy in 30 fractions plus temozolomide 75 mg/m² daily, followed by 1:1 randomization to 6-12 cycles of standard temozolomide, starting at 150 mg/m² and escalating to 200 mg/m² if tolerated on days 1-5 of a 28-day cycle, or dose-dense temozolomide starting at 75 mg/m² and escalating to 100 mg/m² if tolerated on days 1-21 of a 28-day cycle.

Roughly one-fourth of patients were younger than 50 years old, more than half underwent total resection, and 45% had minor symptoms.

Grade 3-5 adverse events were significantly more common in the dose-dense arm, compared with the conventional arm (194 vs. 120; P less than .001), but they were mostly lymphopenia (107 vs. 51) and fatigue (33 vs. 12). No opportunistic infections occurred, Dr. Gilbert said.

The study was supported by Schering-Plough/Merck, the maker of temozolomide. Dr. Gilbert reported a consultant/advisory role with Genentech, and honoraria and research funding from Genentech and Merck. Several of his coauthors reported financial relationships with firms including Merck. Dr. Abrams reported that RTOG 0525 also receives funding from the National Cancer Institute, where he is employed.

CHICAGO – Dose-dense temozolomide was no more effective than standard adjuvant temozolomide for patients with newly diagnosed glioblastoma in the randomized, phase III Radiation Treatment Oncology Group 0525 study.

Among 833 patients, the primary end point of median overall survival was 16.6 months with standard temozolomide (Temodar) vs. 14.9 months with dose-dense temozolomide (P = .63; hazard ratio 0.87).

Median progression-free survival was also similar at 5.5 months vs. 6.7 months (P = .06; HR, 0.87), Dr. Mark R. Gilbert reported at the meeting

RTOG 0525 was designed as a successor to the landmark EORTC (European Organisation for Research and Treatment of Cancer) trial that helped establish radiation plus concomitant and adjuvant temozolomide as the international standard of care for newly diagnosed glioblastoma (N. Engl. J. Med. 2005;352:987-96). It also helped to identify patients with MGMT (O⁶-methylguanine-DNA methyltransferase)–methylated tumors as a subpopulation that appeared to derive greater benefit from temozolomide (N. Engl. J. Med. 2005;352:997-1003).

It was hoped that dose-dense therapy would further enhance the efficacy of temozolomide in MGMT-methylated tumors and would deplete the endogenous reservoir of MGMT in nonmethylated MGMT tumors, as well as induce sensitivity to temozolomide, an oral alkylating agent. The MGMT gene encodes a DNA repair enzyme that can cancel the effects of alkylating chemotherapy.

Although the therapeutic end point was not reached, the study confirmed the prognostic value of MGMT promoter methylation status, said Dr. Gilbert, a professor of neuro-oncology at the University of Texas M.D. AndersonCancer Center in Houston.

MGMT-methylated tumors, compared with unmethylated tumors, were associated with significant improvements in median overall survival (21.2 months vs. 14 months; P less than .0001; HR, 1.74) and progression-free survival (8.7 months vs. 5.7 months; P less than .0001; HR, 1.63).

However, MGMT methylation status did not predict response to the dose-dense schedule, he said. No significant differences in overall or progression-free survival were observed between unmethylated and methylated tumors, regardless of treatment with standard or dose-dense temozolomide.

A Cox proportional hazard model showed that MGMT status and recursive partitioning analysis (RPA) class IV vs. III were significant predictors of overall and progression-free survival, whereas the treatment arm and type of radiation therapy (EORTC vs. RTOG) were not, Dr. Gilbert said.

He observed that RTOG 0525 had a slightly different population than did the EORTC trial in that it required a surgical procedure, enrolled patients older than 70 years, and required all patients to make it through chemoradiation to be randomized.

Invited discussant Dr. Jeffrey S. Abrams of the National Cancer Institute said "We’re all disappointed that it wasn’t positive, but there’s reason to take heart."

He observed that in 2.5 years of accrual, the group conducted what is likely the largest glioblastoma study to date, had a 98% tumor tissue collection rate, and ran a very well-conducted trial in an international collaboration. RTOG 0525 was conducted at 185 North American and 24 European centers by the RTOG, EORTC, and North Central Cancer Treatment Group.

"I think this bodes well for this sort of collaborative process that will speed the development of better treatments for glioblastoma," Dr. Abrams said.

He suggested that the trial may have failed because adjuvant temozolomide is not the active part of the regimen. He pointed out that a randomized, phase II Greek trial increased adjuvant temozolomide to 150 mg/m² every 2 weeks, but saw no improvement in outcome (J. Clin. Oncol. 2005;23:2372-7) and that a small, single-institution study reported comparable survival outcomes with standard temozolomide when temozolomide was administered during the radiation phase at a lower dose of 50 mg/m² without maintenance (Strahlenther Onkol. 2005;181:372-7).

In RTOG 0525, 833 patients received concurrent radiation at 200 cGy in 30 fractions plus temozolomide 75 mg/m² daily, followed by 1:1 randomization to 6-12 cycles of standard temozolomide, starting at 150 mg/m² and escalating to 200 mg/m² if tolerated on days 1-5 of a 28-day cycle, or dose-dense temozolomide starting at 75 mg/m² and escalating to 100 mg/m² if tolerated on days 1-21 of a 28-day cycle.

Roughly one-fourth of patients were younger than 50 years old, more than half underwent total resection, and 45% had minor symptoms.

Grade 3-5 adverse events were significantly more common in the dose-dense arm, compared with the conventional arm (194 vs. 120; P less than .001), but they were mostly lymphopenia (107 vs. 51) and fatigue (33 vs. 12). No opportunistic infections occurred, Dr. Gilbert said.

The study was supported by Schering-Plough/Merck, the maker of temozolomide. Dr. Gilbert reported a consultant/advisory role with Genentech, and honoraria and research funding from Genentech and Merck. Several of his coauthors reported financial relationships with firms including Merck. Dr. Abrams reported that RTOG 0525 also receives funding from the National Cancer Institute, where he is employed. ☐

CHICAGO – Dose-dense temozolomide was no more effective than standard adjuvant temozolomide for patients with newly diagnosed glioblastoma in the randomized, phase III Radiation Treatment Oncology Group 0525 study.

Among 833 patients, the primary end point of median overall survival was 16.6 months with standard temozolomide (Temodar) vs. 14.9 months with dose-dense temozolomide (P = .63; hazard ratio 0.87).

Median progression-free survival was also similar at 5.5 months vs. 6.7 months (P = .06; HR, 0.87), Dr. Mark R. Gilbert reported at the meeting

RTOG 0525 was designed as a successor to the landmark EORTC (European Organisation for Research and Treatment of Cancer) trial that helped establish radiation plus concomitant and adjuvant temozolomide as the international standard of care for newly diagnosed glioblastoma (N. Engl. J. Med. 2005;352:987-96). It also helped to identify patients with MGMT (O⁶-methylguanine-DNA methyltransferase)–methylated tumors as a subpopulation that appeared to derive greater benefit from temozolomide (N. Engl. J. Med. 2005;352:997-1003).

It was hoped that dose-dense therapy would further enhance the efficacy of temozolomide in MGMT-methylated tumors and would deplete the endogenous reservoir of MGMT in nonmethylated MGMT tumors, as well as induce sensitivity to temozolomide, an oral alkylating agent. The MGMT gene encodes a DNA repair enzyme that can cancel the effects of alkylating chemotherapy.

Although the therapeutic end point was not reached, the study confirmed the prognostic value of MGMT promoter methylation status, said Dr. Gilbert, a professor of neuro-oncology at the University of Texas M.D. AndersonCancer Center in Houston.

MGMT-methylated tumors, compared with unmethylated tumors, were associated with significant improvements in median overall survival (21.2 months vs. 14 months; P less than .0001; HR, 1.74) and progression-free survival (8.7 months vs. 5.7 months; P less than .0001; HR, 1.63).

However, MGMT methylation status did not predict response to the dose-dense schedule, he said. No significant differences in overall or progression-free survival were observed between unmethylated and methylated tumors, regardless of treatment with standard or dose-dense temozolomide.

A Cox proportional hazard model showed that MGMT status and recursive partitioning analysis (RPA) class IV vs. III were significant predictors of overall and progression-free survival, whereas the treatment arm and type of radiation therapy (EORTC vs. RTOG) were not, Dr. Gilbert said.

He observed that RTOG 0525 had a slightly different population than did the EORTC trial in that it required a surgical procedure, enrolled patients older than 70 years, and required all patients to make it through chemoradiation to be randomized.

Invited discussant Dr. Jeffrey S. Abrams of the National Cancer Institute said "We’re all disappointed that it wasn’t positive, but there’s reason to take heart."

He observed that in 2.5 years of accrual, the group conducted what is likely the largest glioblastoma study to date, had a 98% tumor tissue collection rate, and ran a very well-conducted trial in an international collaboration. RTOG 0525 was conducted at 185 North American and 24 European centers by the RTOG, EORTC, and North Central Cancer Treatment Group.

"I think this bodes well for this sort of collaborative process that will speed the development of better treatments for glioblastoma," Dr. Abrams said.

He suggested that the trial may have failed because adjuvant temozolomide is not the active part of the regimen. He pointed out that a randomized, phase II Greek trial increased adjuvant temozolomide to 150 mg/m² every 2 weeks, but saw no improvement in outcome (J. Clin. Oncol. 2005;23:2372-7) and that a small, single-institution study reported comparable survival outcomes with standard temozolomide when temozolomide was administered during the radiation phase at a lower dose of 50 mg/m² without maintenance (Strahlenther Onkol. 2005;181:372-7).

In RTOG 0525, 833 patients received concurrent radiation at 200 cGy in 30 fractions plus temozolomide 75 mg/m² daily, followed by 1:1 randomization to 6-12 cycles of standard temozolomide, starting at 150 mg/m² and escalating to 200 mg/m² if tolerated on days 1-5 of a 28-day cycle, or dose-dense temozolomide starting at 75 mg/m² and escalating to 100 mg/m² if tolerated on days 1-21 of a 28-day cycle.

Roughly one-fourth of patients were younger than 50 years old, more than half underwent total resection, and 45% had minor symptoms.

Grade 3-5 adverse events were significantly more common in the dose-dense arm, compared with the conventional arm (194 vs. 120; P less than .001), but they were mostly lymphopenia (107 vs. 51) and fatigue (33 vs. 12). No opportunistic infections occurred, Dr. Gilbert said.

The study was supported by Schering-Plough/Merck, the maker of temozolomide. Dr. Gilbert reported a consultant/advisory role with Genentech, and honoraria and research funding from Genentech and Merck. Several of his coauthors reported financial relationships with firms including Merck. Dr. Abrams reported that RTOG 0525 also receives funding from the National Cancer Institute, where he is employed. ☐

CHICAGO – Dose-dense temozolomide was no more effective than standard adjuvant temozolomide for patients with newly diagnosed glioblastoma in the randomized, phase III Radiation Treatment Oncology Group 0525 study.

Among 833 patients, the primary end point of median overall survival was 16.6 months with standard temozolomide (Temodar) vs. 14.9 months with dose-dense temozolomide (P = .63; hazard ratio 0.87).

Median progression-free survival was also similar at 5.5 months vs. 6.7 months (P = .06; HR, 0.87), Dr. Mark R. Gilbert reported at the meeting

RTOG 0525 was designed as a successor to the landmark EORTC (European Organisation for Research and Treatment of Cancer) trial that helped establish radiation plus concomitant and adjuvant temozolomide as the international standard of care for newly diagnosed glioblastoma (N. Engl. J. Med. 2005;352:987-96). It also helped to identify patients with MGMT (O⁶-methylguanine-DNA methyltransferase)–methylated tumors as a subpopulation that appeared to derive greater benefit from temozolomide (N. Engl. J. Med. 2005;352:997-1003).

It was hoped that dose-dense therapy would further enhance the efficacy of temozolomide in MGMT-methylated tumors and would deplete the endogenous reservoir of MGMT in nonmethylated MGMT tumors, as well as induce sensitivity to temozolomide, an oral alkylating agent. The MGMT gene encodes a DNA repair enzyme that can cancel the effects of alkylating chemotherapy.

Although the therapeutic end point was not reached, the study confirmed the prognostic value of MGMT promoter methylation status, said Dr. Gilbert, a professor of neuro-oncology at the University of Texas M.D. AndersonCancer Center in Houston.

MGMT-methylated tumors, compared with unmethylated tumors, were associated with significant improvements in median overall survival (21.2 months vs. 14 months; P less than .0001; HR, 1.74) and progression-free survival (8.7 months vs. 5.7 months; P less than .0001; HR, 1.63).

However, MGMT methylation status did not predict response to the dose-dense schedule, he said. No significant differences in overall or progression-free survival were observed between unmethylated and methylated tumors, regardless of treatment with standard or dose-dense temozolomide.

A Cox proportional hazard model showed that MGMT status and recursive partitioning analysis (RPA) class IV vs. III were significant predictors of overall and progression-free survival, whereas the treatment arm and type of radiation therapy (EORTC vs. RTOG) were not, Dr. Gilbert said.

He observed that RTOG 0525 had a slightly different population than did the EORTC trial in that it required a surgical procedure, enrolled patients older than 70 years, and required all patients to make it through chemoradiation to be randomized.

Invited discussant Dr. Jeffrey S. Abrams of the National Cancer Institute said "We’re all disappointed that it wasn’t positive, but there’s reason to take heart."

He observed that in 2.5 years of accrual, the group conducted what is likely the largest glioblastoma study to date, had a 98% tumor tissue collection rate, and ran a very well-conducted trial in an international collaboration. RTOG 0525 was conducted at 185 North American and 24 European centers by the RTOG, EORTC, and North Central Cancer Treatment Group.

"I think this bodes well for this sort of collaborative process that will speed the development of better treatments for glioblastoma," Dr. Abrams said.

He suggested that the trial may have failed because adjuvant temozolomide is not the active part of the regimen. He pointed out that a randomized, phase II Greek trial increased adjuvant temozolomide to 150 mg/m² every 2 weeks, but saw no improvement in outcome (J. Clin. Oncol. 2005;23:2372-7) and that a small, single-institution study reported comparable survival outcomes with standard temozolomide when temozolomide was administered during the radiation phase at a lower dose of 50 mg/m² without maintenance (Strahlenther Onkol. 2005;181:372-7).

In RTOG 0525, 833 patients received concurrent radiation at 200 cGy in 30 fractions plus temozolomide 75 mg/m² daily, followed by 1:1 randomization to 6-12 cycles of standard temozolomide, starting at 150 mg/m² and escalating to 200 mg/m² if tolerated on days 1-5 of a 28-day cycle, or dose-dense temozolomide starting at 75 mg/m² and escalating to 100 mg/m² if tolerated on days 1-21 of a 28-day cycle.

Roughly one-fourth of patients were younger than 50 years old, more than half underwent total resection, and 45% had minor symptoms.

Grade 3-5 adverse events were significantly more common in the dose-dense arm, compared with the conventional arm (194 vs. 120; P less than .001), but they were mostly lymphopenia (107 vs. 51) and fatigue (33 vs. 12). No opportunistic infections occurred, Dr. Gilbert said.

The study was supported by Schering-Plough/Merck, the maker of temozolomide. Dr. Gilbert reported a consultant/advisory role with Genentech, and honoraria and research funding from Genentech and Merck. Several of his coauthors reported financial relationships with firms including Merck. Dr. Abrams reported that RTOG 0525 also receives funding from the National Cancer Institute, where he is employed. ☐

CHICAGO – The newly minted Lung Cancer Mutation Consortium detected a driver mutation in 54% of lung adenocarcinoma tumors, allowing clinicians to use the information in real time to select erlotinib as initial therapy or to direct patients to trials targeting their specific mutation.

The collaborative effort points to the revolutionary changes taking place in the management of lung adenocarcinoma and the potential for personalized treatment in routine practice.

"While an individual mutation may be quite rare, having a mutation of some kind that is actionable is very common in adenocarcinoma," said Dr. Mark G. Kris, who presented the findings at the annual meeting of the American Society of Clinical Oncology (ASCO).

Earlier this year, the National Comprehensive Cancer Network and ASCO recommended epidermal growth factor receptor (EGFR) mutation testing to identify patients with advanced non-small cell lung cancer (NSCLC) who may benefit from EGFR tyrosine kinase inhibitors such as erlotinib (Tarceva) and gefitinib (Iressa). Adenocarcinoma is the most common form of NSCLC, accounting for up to 50% of cases in the United States.

Dr. Kris said new mutations can be quickly added to the testing process and that they plan to maintain and expand the scope of the consortium when federal funding ends for the National Cancer Institute–sponsored initiative made up of 14 cancer centers across the country.

"I think this can serve as a model for other institutions developing similar programs in lung cancer and for other cancers," said Dr. Kris, chief of thoracic oncology at Memorial Sloan-Kettering Cancer Center in New York.

A total of 1,234 patients with stage IV lung adenocarcinoma agreed to undergo testing for 10 known mutations using standard multiplexed assays and fluorescence in situ hybridization. Inadequate tissue in 170 patients (14%) resulted in a study group of 1,064 patients. Mutations were identified in 280 (54%) of 516 tumor specimens tested to date (95% confidence interval 50%-59%).

As suspected, the most common mutations were KRAS (22%), EGFR (17%), and EML4-ALK rearrangement (7%), Dr. Kris said. Other mutations were: BRAF (2%) and PIK3CA, HER2, MET amplification, MEK1, NRAS, and AKT1.

The vast majority (97%) of mutations were mutually exclusive. Of the 14 double-mutant tumors, the two molecular lesions most commonly seen together were MET amplification and PIK3CA, he said.

Four sites had testing available prior to the study, with seven additional sites now able to provide multiplex mutation testing. Preliminary data from 121 patients enrolled at a single site show that driver mutations were found in 60 (59%) of 102 patients in whom testing was completed. That information was used to direct therapy in 30% of patients – 19 to receive erlotinib up front and 16 to go on a trial of an agent targeting their specific mutation.

"In truth, we used it for every patient because when we did not find an EGFR mutation, we did not give them erlotinib," Dr. Kris said.

The turnaround time for mutational testing varied by site, but generally took only a few days. The great majority of time is in specimen acquisition, preparation, and submission to the molecular lab.

"Those are formidable obstacles that we all have to face," Dr. Kris said. "But I think with programs like this, we’ll get over those."

Invited discussant Dr. Ramaswamy Govindan, a professor of medicine at Washington University in St. Louis, said EGFR mutation testing is ready for routine clinical use and that EML4 ALK fusion testing will soon be ready. He pointed out that there are more than 15,000 NSCLC mutations alone in the Catalog of Somatic Mutations in Cancer database and that many questions remain, including the cost-effectiveness of mutational testing.

"It’s important to remember that not all mutations are created equal," he said.

Dr. Govindan described the most important aspect of the presentation as the linking of the consortium to targeted clinical trials. Last year he was coauthor of a review that found only 8% of nearly 500 ongoing clinical trials in NSCLC used biomarkers for patient selection (J Thorac. Oncol. 2010 Aug;5:1116-9). He contrasted that study with the observation that no fewer than 112 drugs were discussed at this year’s Targeted Therapies in Lung Cancer meeting.

Some of the agents being evaluated in trials linked to the consortium include: crizotinib for EML4-ALK rearrangements, tivantinib plus erlotinib for KRAS mutations, erlotinib plus the investigational agents OSI 906 or MM 121 for EFGR mutations and an afatinib trial targeting HER2 led by Dr. Kris.

The Lung Cancer Mutation Consortium was funded by an American Recovery and Relief grant. Dr. Kris reports consulting for ArQule, BI, Chugai Pharma and Pfizer. Dr. Govindan reports consulting for Taiho and honoraria from AstraZeneca, GlaxoSmithKline, and BI.

CHICAGO – The newly minted Lung Cancer Mutation Consortium detected a driver mutation in 54% of lung adenocarcinoma tumors, allowing clinicians to use the information in real time to select erlotinib as initial therapy or to direct patients to trials targeting their specific mutation.

The collaborative effort points to the revolutionary changes taking place in the management of lung adenocarcinoma and the potential for personalized treatment in routine practice.

"While an individual mutation may be quite rare, having a mutation of some kind that is actionable is very common in adenocarcinoma," said Dr. Mark G. Kris, who presented the findings at the annual meeting of the American Society of Clinical Oncology (ASCO).

Earlier this year, the National Comprehensive Cancer Network and ASCO recommended epidermal growth factor receptor (EGFR) mutation testing to identify patients with advanced non-small cell lung cancer (NSCLC) who may benefit from EGFR tyrosine kinase inhibitors such as erlotinib (Tarceva) and gefitinib (Iressa). Adenocarcinoma is the most common form of NSCLC, accounting for up to 50% of cases in the United States.

Dr. Kris said new mutations can be quickly added to the testing process and that they plan to maintain and expand the scope of the consortium when federal funding ends for the National Cancer Institute–sponsored initiative made up of 14 cancer centers across the country.

"I think this can serve as a model for other institutions developing similar programs in lung cancer and for other cancers," said Dr. Kris, chief of thoracic oncology at Memorial Sloan-Kettering Cancer Center in New York.

A total of 1,234 patients with stage IV lung adenocarcinoma agreed to undergo testing for 10 known mutations using standard multiplexed assays and fluorescence in situ hybridization. Inadequate tissue in 170 patients (14%) resulted in a study group of 1,064 patients. Mutations were identified in 280 (54%) of 516 tumor specimens tested to date (95% confidence interval 50%-59%).

As suspected, the most common mutations were KRAS (22%), EGFR (17%), and EML4-ALK rearrangement (7%), Dr. Kris said. Other mutations were: BRAF (2%) and PIK3CA, HER2, MET amplification, MEK1, NRAS, and AKT1.

The vast majority (97%) of mutations were mutually exclusive. Of the 14 double-mutant tumors, the two molecular lesions most commonly seen together were MET amplification and PIK3CA, he said.

Four sites had testing available prior to the study, with seven additional sites now able to provide multiplex mutation testing. Preliminary data from 121 patients enrolled at a single site show that driver mutations were found in 60 (59%) of 102 patients in whom testing was completed. That information was used to direct therapy in 30% of patients – 19 to receive erlotinib up front and 16 to go on a trial of an agent targeting their specific mutation.

"In truth, we used it for every patient because when we did not find an EGFR mutation, we did not give them erlotinib," Dr. Kris said.

The turnaround time for mutational testing varied by site, but generally took only a few days. The great majority of time is in specimen acquisition, preparation, and submission to the molecular lab.

"Those are formidable obstacles that we all have to face," Dr. Kris said. "But I think with programs like this, we’ll get over those."

Invited discussant Dr. Ramaswamy Govindan, a professor of medicine at Washington University in St. Louis, said EGFR mutation testing is ready for routine clinical use and that EML4 ALK fusion testing will soon be ready. He pointed out that there are more than 15,000 NSCLC mutations alone in the Catalog of Somatic Mutations in Cancer database and that many questions remain, including the cost-effectiveness of mutational testing.

"It’s important to remember that not all mutations are created equal," he said.

Dr. Govindan described the most important aspect of the presentation as the linking of the consortium to targeted clinical trials. Last year he was coauthor of a review that found only 8% of nearly 500 ongoing clinical trials in NSCLC used biomarkers for patient selection (J Thorac. Oncol. 2010 Aug;5:1116-9). He contrasted that study with the observation that no fewer than 112 drugs were discussed at this year’s Targeted Therapies in Lung Cancer meeting.

Some of the agents being evaluated in trials linked to the consortium include: crizotinib for EML4-ALK rearrangements, tivantinib plus erlotinib for KRAS mutations, erlotinib plus the investigational agents OSI 906 or MM 121 for EFGR mutations and an afatinib trial targeting HER2 led by Dr. Kris.

The Lung Cancer Mutation Consortium was funded by an American Recovery and Relief grant. Dr. Kris reports consulting for ArQule, BI, Chugai Pharma and Pfizer. Dr. Govindan reports consulting for Taiho and honoraria from AstraZeneca, GlaxoSmithKline, and BI.

CHICAGO – The newly minted Lung Cancer Mutation Consortium detected a driver mutation in 54% of lung adenocarcinoma tumors, allowing clinicians to use the information in real time to select erlotinib as initial therapy or to direct patients to trials targeting their specific mutation.

The collaborative effort points to the revolutionary changes taking place in the management of lung adenocarcinoma and the potential for personalized treatment in routine practice.

"While an individual mutation may be quite rare, having a mutation of some kind that is actionable is very common in adenocarcinoma," said Dr. Mark G. Kris, who presented the findings at the annual meeting of the American Society of Clinical Oncology (ASCO).

Earlier this year, the National Comprehensive Cancer Network and ASCO recommended epidermal growth factor receptor (EGFR) mutation testing to identify patients with advanced non-small cell lung cancer (NSCLC) who may benefit from EGFR tyrosine kinase inhibitors such as erlotinib (Tarceva) and gefitinib (Iressa). Adenocarcinoma is the most common form of NSCLC, accounting for up to 50% of cases in the United States.

Dr. Kris said new mutations can be quickly added to the testing process and that they plan to maintain and expand the scope of the consortium when federal funding ends for the National Cancer Institute–sponsored initiative made up of 14 cancer centers across the country.

"I think this can serve as a model for other institutions developing similar programs in lung cancer and for other cancers," said Dr. Kris, chief of thoracic oncology at Memorial Sloan-Kettering Cancer Center in New York.

A total of 1,234 patients with stage IV lung adenocarcinoma agreed to undergo testing for 10 known mutations using standard multiplexed assays and fluorescence in situ hybridization. Inadequate tissue in 170 patients (14%) resulted in a study group of 1,064 patients. Mutations were identified in 280 (54%) of 516 tumor specimens tested to date (95% confidence interval 50%-59%).

As suspected, the most common mutations were KRAS (22%), EGFR (17%), and EML4-ALK rearrangement (7%), Dr. Kris said. Other mutations were: BRAF (2%) and PIK3CA, HER2, MET amplification, MEK1, NRAS, and AKT1.

The vast majority (97%) of mutations were mutually exclusive. Of the 14 double-mutant tumors, the two molecular lesions most commonly seen together were MET amplification and PIK3CA, he said.

Four sites had testing available prior to the study, with seven additional sites now able to provide multiplex mutation testing. Preliminary data from 121 patients enrolled at a single site show that driver mutations were found in 60 (59%) of 102 patients in whom testing was completed. That information was used to direct therapy in 30% of patients – 19 to receive erlotinib up front and 16 to go on a trial of an agent targeting their specific mutation.

"In truth, we used it for every patient because when we did not find an EGFR mutation, we did not give them erlotinib," Dr. Kris said.

The turnaround time for mutational testing varied by site, but generally took only a few days. The great majority of time is in specimen acquisition, preparation, and submission to the molecular lab.

"Those are formidable obstacles that we all have to face," Dr. Kris said. "But I think with programs like this, we’ll get over those."

Invited discussant Dr. Ramaswamy Govindan, a professor of medicine at Washington University in St. Louis, said EGFR mutation testing is ready for routine clinical use and that EML4 ALK fusion testing will soon be ready. He pointed out that there are more than 15,000 NSCLC mutations alone in the Catalog of Somatic Mutations in Cancer database and that many questions remain, including the cost-effectiveness of mutational testing.

"It’s important to remember that not all mutations are created equal," he said.

Dr. Govindan described the most important aspect of the presentation as the linking of the consortium to targeted clinical trials. Last year he was coauthor of a review that found only 8% of nearly 500 ongoing clinical trials in NSCLC used biomarkers for patient selection (J Thorac. Oncol. 2010 Aug;5:1116-9). He contrasted that study with the observation that no fewer than 112 drugs were discussed at this year’s Targeted Therapies in Lung Cancer meeting.

Some of the agents being evaluated in trials linked to the consortium include: crizotinib for EML4-ALK rearrangements, tivantinib plus erlotinib for KRAS mutations, erlotinib plus the investigational agents OSI 906 or MM 121 for EFGR mutations and an afatinib trial targeting HER2 led by Dr. Kris.

The Lung Cancer Mutation Consortium was funded by an American Recovery and Relief grant. Dr. Kris reports consulting for ArQule, BI, Chugai Pharma and Pfizer. Dr. Govindan reports consulting for Taiho and honoraria from AstraZeneca, GlaxoSmithKline, and BI.

CHICAGO – Circulating tumor necrosis factor appears to play a role in the cognitive dysfunction called "chemo brain" that some women experience after receiving chemotherapy as part of their primary treatment for newly diagnosed breast cancer.

Preliminary data on 93 women in a prospective observational cohort study show that women who underwent chemotherapy had higher levels of circulating tumor necrosis factor (TNF) than did similar women who had not received chemotherapy as part of their primary treatment.

The chemotherapy group also started the study with worse quality of life and poorer cognitive function, compared with patients who did not have chemotherapy before enrolling in the study. None of the women had started endocrine therapy at that point.

"These effects are specific to TNF and were not associated with other biomarkers of inflammation studied," Dr. Patricia A. Ganz reported at the annual meeting of the American Society of Clinical Oncology.

TNF may, therefore, represent a biologic target for pharmacologic therapy, as well as a biomarker that could help identify patients at increased risk for so-called "chemo brain," cognitive complaints during adjuvant chemotherapy that can persist for years afterward in up to 25% of breast cancer survivors, according to Dr. Ganz, director of prevention and control research at the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles.

The study is thought to be among the first to comprehensively examine the relationship between inflammatory markers and cognitive changes in breast cancer patients, she said. It was suggested in part by a study of doxorubicin exposure in an animal model, which found systemic increases in the proinflammatory cytokine TNF-alpha. This cytokine is able to cross the blood-brain barrier and accumulate in the central nervous system (Neurobiol. Dis. July 2006;23:127-39).

The current study enrolled 191 women within 3 months of completion of primary therapy (surgery, radiation, and/or chemotherapy), and prior to initiating endocrine therapy for recently diagnosed breast cancer. All women underwent comprehensive assessments at baseline, 6 months, and 12 months after enrollment. A subset of 16 women also participated in a PET scan substudy and had brain scans at baseline and 12 months later.

The longitudinal data reported by Dr. Ganz was based on the first 93 women with complete cytokine assessments: 49 women who received chemotherapy and 44 women who did not have chemotherapy as part of their primary treatment. Similar proportions of both groups had undergone mastectomy (28% overall) and radiotherapy (76% overall) during primary treatment; 72% of the total population went on to receive endocrine therapy. The women had a mean age of 51 years and were enrolled an average of 7 months after diagnosis of breast cancer.

At baseline, the postchemotherapy group reported significantly poorer quality of life and functioning on several standardized measures, including the SF36 physical and mental component summary scales, sleep, fatigue, and depression.

Self-reported measures of cognitive complaints, including the multidimensional Patients Assessment of Own Functioning Inventory, also suggested that they had greater memory impairments. A significant correlation was found between the memory subscale score in the chemotherapy group (correlation with log r = 0.33, P = .05).

Fasting blood specimens were tested for four inflammatory markers: interleukin-1 receptor antagonist, interleukin-6, C-reactive protein, and soluble TNF receptor type II (sTNFRII), which provides a stable assessment of TNF-alpha activity.

Only sTNFRII was significantly increased in the chemotherapy-treated group (2,492.5 pg/mL vs. 2,115.6 pg/mL in the other patients, P = .007). Over the course of the year, it decreased to the point where the difference between groups was no longer significant.

In the 16 patients with complete PET scan data, soluble TNF receptor level at baseline was negatively correlated with metabolic activity in the inferior frontal gyrus in chemotherapy-treated patients (P = .04). Patients with higher levels of TNF receptor had lower levels of metabolic activity. This also improved over 12 months.

Finally, genetic analysis suggests that the GG allele of the TNF-alpha 308 single nucleotide polymorphism was associated with more cognitive complaints. It may enhance the patient’s vulnerability to cognitive complaints and cognitive dysfunction.

Discussant Karen Mustian, Ph.D., of the University of Rochester (N.Y.) said, "The strengths of this study include its prospective longitudinal design as well as the examination of potential biological mechanisms, including inflammation, genetic polymorphisms, and cerebral function."

She described examination of biomarkers and mechanisms as important in supportive care research, and expressed optimism that this type of research has only just begun.

The study was funded by the National Cancer Institute and the Breast Cancer Research Foundation. Dr. Ganz and Dr. Mustian said they had no relevant relationships.

CHICAGO – Circulating tumor necrosis factor appears to play a role in the cognitive dysfunction called "chemo brain" that some women experience after receiving chemotherapy as part of their primary treatment for newly diagnosed breast cancer.

Preliminary data on 93 women in a prospective observational cohort study show that women who underwent chemotherapy had higher levels of circulating tumor necrosis factor (TNF) than did similar women who had not received chemotherapy as part of their primary treatment.

The chemotherapy group also started the study with worse quality of life and poorer cognitive function, compared with patients who did not have chemotherapy before enrolling in the study. None of the women had started endocrine therapy at that point.

"These effects are specific to TNF and were not associated with other biomarkers of inflammation studied," Dr. Patricia A. Ganz reported at the annual meeting of the American Society of Clinical Oncology.

TNF may, therefore, represent a biologic target for pharmacologic therapy, as well as a biomarker that could help identify patients at increased risk for so-called "chemo brain," cognitive complaints during adjuvant chemotherapy that can persist for years afterward in up to 25% of breast cancer survivors, according to Dr. Ganz, director of prevention and control research at the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles.

The study is thought to be among the first to comprehensively examine the relationship between inflammatory markers and cognitive changes in breast cancer patients, she said. It was suggested in part by a study of doxorubicin exposure in an animal model, which found systemic increases in the proinflammatory cytokine TNF-alpha. This cytokine is able to cross the blood-brain barrier and accumulate in the central nervous system (Neurobiol. Dis. July 2006;23:127-39).

The current study enrolled 191 women within 3 months of completion of primary therapy (surgery, radiation, and/or chemotherapy), and prior to initiating endocrine therapy for recently diagnosed breast cancer. All women underwent comprehensive assessments at baseline, 6 months, and 12 months after enrollment. A subset of 16 women also participated in a PET scan substudy and had brain scans at baseline and 12 months later.

The longitudinal data reported by Dr. Ganz was based on the first 93 women with complete cytokine assessments: 49 women who received chemotherapy and 44 women who did not have chemotherapy as part of their primary treatment. Similar proportions of both groups had undergone mastectomy (28% overall) and radiotherapy (76% overall) during primary treatment; 72% of the total population went on to receive endocrine therapy. The women had a mean age of 51 years and were enrolled an average of 7 months after diagnosis of breast cancer.

At baseline, the postchemotherapy group reported significantly poorer quality of life and functioning on several standardized measures, including the SF36 physical and mental component summary scales, sleep, fatigue, and depression.

Self-reported measures of cognitive complaints, including the multidimensional Patients Assessment of Own Functioning Inventory, also suggested that they had greater memory impairments. A significant correlation was found between the memory subscale score in the chemotherapy group (correlation with log r = 0.33, P = .05).

Fasting blood specimens were tested for four inflammatory markers: interleukin-1 receptor antagonist, interleukin-6, C-reactive protein, and soluble TNF receptor type II (sTNFRII), which provides a stable assessment of TNF-alpha activity.

Only sTNFRII was significantly increased in the chemotherapy-treated group (2,492.5 pg/mL vs. 2,115.6 pg/mL in the other patients, P = .007). Over the course of the year, it decreased to the point where the difference between groups was no longer significant.

In the 16 patients with complete PET scan data, soluble TNF receptor level at baseline was negatively correlated with metabolic activity in the inferior frontal gyrus in chemotherapy-treated patients (P = .04). Patients with higher levels of TNF receptor had lower levels of metabolic activity. This also improved over 12 months.

Finally, genetic analysis suggests that the GG allele of the TNF-alpha 308 single nucleotide polymorphism was associated with more cognitive complaints. It may enhance the patient’s vulnerability to cognitive complaints and cognitive dysfunction.

Discussant Karen Mustian, Ph.D., of the University of Rochester (N.Y.) said, "The strengths of this study include its prospective longitudinal design as well as the examination of potential biological mechanisms, including inflammation, genetic polymorphisms, and cerebral function."

She described examination of biomarkers and mechanisms as important in supportive care research, and expressed optimism that this type of research has only just begun.

The study was funded by the National Cancer Institute and the Breast Cancer Research Foundation. Dr. Ganz and Dr. Mustian said they had no relevant relationships.

CHICAGO – Circulating tumor necrosis factor appears to play a role in the cognitive dysfunction called "chemo brain" that some women experience after receiving chemotherapy as part of their primary treatment for newly diagnosed breast cancer.

Preliminary data on 93 women in a prospective observational cohort study show that women who underwent chemotherapy had higher levels of circulating tumor necrosis factor (TNF) than did similar women who had not received chemotherapy as part of their primary treatment.

The chemotherapy group also started the study with worse quality of life and poorer cognitive function, compared with patients who did not have chemotherapy before enrolling in the study. None of the women had started endocrine therapy at that point.

"These effects are specific to TNF and were not associated with other biomarkers of inflammation studied," Dr. Patricia A. Ganz reported at the annual meeting of the American Society of Clinical Oncology.

TNF may, therefore, represent a biologic target for pharmacologic therapy, as well as a biomarker that could help identify patients at increased risk for so-called "chemo brain," cognitive complaints during adjuvant chemotherapy that can persist for years afterward in up to 25% of breast cancer survivors, according to Dr. Ganz, director of prevention and control research at the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles.

The study is thought to be among the first to comprehensively examine the relationship between inflammatory markers and cognitive changes in breast cancer patients, she said. It was suggested in part by a study of doxorubicin exposure in an animal model, which found systemic increases in the proinflammatory cytokine TNF-alpha. This cytokine is able to cross the blood-brain barrier and accumulate in the central nervous system (Neurobiol. Dis. July 2006;23:127-39).

The current study enrolled 191 women within 3 months of completion of primary therapy (surgery, radiation, and/or chemotherapy), and prior to initiating endocrine therapy for recently diagnosed breast cancer. All women underwent comprehensive assessments at baseline, 6 months, and 12 months after enrollment. A subset of 16 women also participated in a PET scan substudy and had brain scans at baseline and 12 months later.

The longitudinal data reported by Dr. Ganz was based on the first 93 women with complete cytokine assessments: 49 women who received chemotherapy and 44 women who did not have chemotherapy as part of their primary treatment. Similar proportions of both groups had undergone mastectomy (28% overall) and radiotherapy (76% overall) during primary treatment; 72% of the total population went on to receive endocrine therapy. The women had a mean age of 51 years and were enrolled an average of 7 months after diagnosis of breast cancer.

At baseline, the postchemotherapy group reported significantly poorer quality of life and functioning on several standardized measures, including the SF36 physical and mental component summary scales, sleep, fatigue, and depression.

Self-reported measures of cognitive complaints, including the multidimensional Patients Assessment of Own Functioning Inventory, also suggested that they had greater memory impairments. A significant correlation was found between the memory subscale score in the chemotherapy group (correlation with log r = 0.33, P = .05).

Fasting blood specimens were tested for four inflammatory markers: interleukin-1 receptor antagonist, interleukin-6, C-reactive protein, and soluble TNF receptor type II (sTNFRII), which provides a stable assessment of TNF-alpha activity.

Only sTNFRII was significantly increased in the chemotherapy-treated group (2,492.5 pg/mL vs. 2,115.6 pg/mL in the other patients, P = .007). Over the course of the year, it decreased to the point where the difference between groups was no longer significant.

In the 16 patients with complete PET scan data, soluble TNF receptor level at baseline was negatively correlated with metabolic activity in the inferior frontal gyrus in chemotherapy-treated patients (P = .04). Patients with higher levels of TNF receptor had lower levels of metabolic activity. This also improved over 12 months.

Finally, genetic analysis suggests that the GG allele of the TNF-alpha 308 single nucleotide polymorphism was associated with more cognitive complaints. It may enhance the patient’s vulnerability to cognitive complaints and cognitive dysfunction.

Discussant Karen Mustian, Ph.D., of the University of Rochester (N.Y.) said, "The strengths of this study include its prospective longitudinal design as well as the examination of potential biological mechanisms, including inflammation, genetic polymorphisms, and cerebral function."

She described examination of biomarkers and mechanisms as important in supportive care research, and expressed optimism that this type of research has only just begun.

The study was funded by the National Cancer Institute and the Breast Cancer Research Foundation. Dr. Ganz and Dr. Mustian said they had no relevant relationships.

CHICAGO – Circulating tumor necrosis factor appears to play a role in the cognitive dysfunction called "chemo brain" that some women experience after receiving chemotherapy as part of their primary treatment for newly diagnosed breast cancer.

Preliminary data on 93 women in a prospective observational cohort study show that women who underwent chemotherapy had higher levels of circulating tumor necrosis factor (TNF) than did similar women who had not received chemotherapy as part of their primary treatment.

The chemotherapy group also started the study with worse quality of life and poorer cognitive function, compared with patients who did not have chemotherapy before enrolling in the study. None of the women had started endocrine therapy at that point.

"These effects are specific to TNF and were not associated with other biomarkers of inflammation studied," Dr. Patricia A. Ganz reported at the annual meeting of the American Society of Clinical Oncology.

TNF may, therefore, represent a biologic target for pharmacologic therapy, as well as a biomarker that could help identify patients at increased risk for so-called "chemo brain," cognitive complaints during adjuvant chemotherapy that can persist for years afterward in up to 25% of breast cancer survivors, according to Dr. Ganz, director of prevention and control research at the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles.

The study is thought to be among the first to comprehensively examine the relationship between inflammatory markers and cognitive changes in breast cancer patients, she said. It was suggested in part by a study of doxorubicin exposure in an animal model, which found systemic increases in the proinflammatory cytokine TNF-alpha. This cytokine is able to cross the blood-brain barrier and accumulate in the central nervous system (Neurobiol. Dis. July 2006;23:127-39).

The current study enrolled 191 women within 3 months of completion of primary therapy (surgery, radiation, and/or chemotherapy), and prior to initiating endocrine therapy for recently diagnosed breast cancer. All women underwent comprehensive assessments at baseline, 6 months, and 12 months after enrollment. A subset of 16 women also participated in a PET scan substudy and had brain scans at baseline and 12 months later.

The longitudinal data reported by Dr. Ganz was based on the first 93 women with complete cytokine assessments: 49 women who received chemotherapy and 44 women who did not have chemotherapy as part of their primary treatment. Similar proportions of both groups had undergone mastectomy (28% overall) and radiotherapy (76% overall) during primary treatment; 72% of the total population went on to receive endocrine therapy. The women had a mean age of 51 years and were enrolled an average of 7 months after diagnosis of breast cancer.

At baseline, the postchemotherapy group reported significantly poorer quality of life and functioning on several standardized measures, including the SF36 physical and mental component summary scales, sleep, fatigue, and depression.

Self-reported measures of cognitive complaints, including the multidimensional Patients Assessment of Own Functioning Inventory, also suggested that they had greater memory impairments. A significant correlation was found between the memory subscale score in the chemotherapy group (correlation with log r = 0.33, P = .05).

Fasting blood specimens were tested for four inflammatory markers: interleukin-1 receptor antagonist, interleukin-6, C-reactive protein, and soluble TNF receptor type II (sTNFRII), which provides a stable assessment of TNF-alpha activity.

Only sTNFRII was significantly increased in the chemotherapy-treated group (2,492.5 pg/mL vs. 2,115.6 pg/mL in the other patients, P = .007). Over the course of the year, it decreased to the point where the difference between groups was no longer significant.

In the 16 patients with complete PET scan data, soluble TNF receptor level at baseline was negatively correlated with metabolic activity in the inferior frontal gyrus in chemotherapy-treated patients (P = .04). Patients with higher levels of TNF receptor had lower levels of metabolic activity. This also improved over 12 months.

Finally, genetic analysis suggests that the GG allele of the TNF-alpha 308 single nucleotide polymorphism was associated with more cognitive complaints. It may enhance the patient’s vulnerability to cognitive complaints and cognitive dysfunction.

Discussant Karen Mustian, Ph.D., of the University of Rochester (N.Y.) said, "The strengths of this study include its prospective longitudinal design as well as the examination of potential biological mechanisms, including inflammation, genetic polymorphisms, and cerebral function."

She described examination of biomarkers and mechanisms as important in supportive care research, and expressed optimism that this type of research has only just begun.

The study was funded by the National Cancer Institute and the Breast Cancer Research Foundation. Dr. Ganz and Dr. Mustian said they had no relevant relationships.

CHICAGO – Circulating tumor necrosis factor appears to play a role in the cognitive dysfunction called "chemo brain" that some women experience after receiving chemotherapy as part of their primary treatment for newly diagnosed breast cancer.

Preliminary data on 93 women in a prospective observational cohort study show that women who underwent chemotherapy had higher levels of circulating tumor necrosis factor (TNF) than did similar women who had not received chemotherapy as part of their primary treatment.

The chemotherapy group also started the study with worse quality of life and poorer cognitive function, compared with patients who did not have chemotherapy before enrolling in the study. None of the women had started endocrine therapy at that point.

"These effects are specific to TNF and were not associated with other biomarkers of inflammation studied," Dr. Patricia A. Ganz reported at the annual meeting of the American Society of Clinical Oncology.

TNF may, therefore, represent a biologic target for pharmacologic therapy, as well as a biomarker that could help identify patients at increased risk for so-called "chemo brain," cognitive complaints during adjuvant chemotherapy that can persist for years afterward in up to 25% of breast cancer survivors, according to Dr. Ganz, director of prevention and control research at the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles.

The study is thought to be among the first to comprehensively examine the relationship between inflammatory markers and cognitive changes in breast cancer patients, she said. It was suggested in part by a study of doxorubicin exposure in an animal model, which found systemic increases in the proinflammatory cytokine TNF-alpha. This cytokine is able to cross the blood-brain barrier and accumulate in the central nervous system (Neurobiol. Dis. July 2006;23:127-39).

The current study enrolled 191 women within 3 months of completion of primary therapy (surgery, radiation, and/or chemotherapy), and prior to initiating endocrine therapy for recently diagnosed breast cancer. All women underwent comprehensive assessments at baseline, 6 months, and 12 months after enrollment. A subset of 16 women also participated in a PET scan substudy and had brain scans at baseline and 12 months later.

The longitudinal data reported by Dr. Ganz was based on the first 93 women with complete cytokine assessments: 49 women who received chemotherapy and 44 women who did not have chemotherapy as part of their primary treatment. Similar proportions of both groups had undergone mastectomy (28% overall) and radiotherapy (76% overall) during primary treatment; 72% of the total population went on to receive endocrine therapy. The women had a mean age of 51 years and were enrolled an average of 7 months after diagnosis of breast cancer.

At baseline, the postchemotherapy group reported significantly poorer quality of life and functioning on several standardized measures, including the SF36 physical and mental component summary scales, sleep, fatigue, and depression.

Self-reported measures of cognitive complaints, including the multidimensional Patients Assessment of Own Functioning Inventory, also suggested that they had greater memory impairments. A significant correlation was found between the memory subscale score in the chemotherapy group (correlation with log r = 0.33, P = .05).

Fasting blood specimens were tested for four inflammatory markers: interleukin-1 receptor antagonist, interleukin-6, C-reactive protein, and soluble TNF receptor type II (sTNFRII), which provides a stable assessment of TNF-alpha activity.

Only sTNFRII was significantly increased in the chemotherapy-treated group (2,492.5 pg/mL vs. 2,115.6 pg/mL in the other patients, P = .007). Over the course of the year, it decreased to the point where the difference between groups was no longer significant.

In the 16 patients with complete PET scan data, soluble TNF receptor level at baseline was negatively correlated with metabolic activity in the inferior frontal gyrus in chemotherapy-treated patients (P = .04). Patients with higher levels of TNF receptor had lower levels of metabolic activity. This also improved over 12 months.

Finally, genetic analysis suggests that the GG allele of the TNF-alpha 308 single nucleotide polymorphism was associated with more cognitive complaints. It may enhance the patient’s vulnerability to cognitive complaints and cognitive dysfunction.

Discussant Karen Mustian, Ph.D., of the University of Rochester (N.Y.) said, "The strengths of this study include its prospective longitudinal design as well as the examination of potential biological mechanisms, including inflammation, genetic polymorphisms, and cerebral function."

She described examination of biomarkers and mechanisms as important in supportive care research, and expressed optimism that this type of research has only just begun.

The study was funded by the National Cancer Institute and the Breast Cancer Research Foundation. Dr. Ganz and Dr. Mustian said they had no relevant relationships.

CHICAGO – Circulating tumor necrosis factor appears to play a role in the cognitive dysfunction called "chemo brain" that some women experience after receiving chemotherapy as part of their primary treatment for newly diagnosed breast cancer.

Preliminary data on 93 women in a prospective observational cohort study show that women who underwent chemotherapy had higher levels of circulating tumor necrosis factor (TNF) than did similar women who had not received chemotherapy as part of their primary treatment.

The chemotherapy group also started the study with worse quality of life and poorer cognitive function, compared with patients who did not have chemotherapy before enrolling in the study. None of the women had started endocrine therapy at that point.

"These effects are specific to TNF and were not associated with other biomarkers of inflammation studied," Dr. Patricia A. Ganz reported at the annual meeting of the American Society of Clinical Oncology.

TNF may, therefore, represent a biologic target for pharmacologic therapy, as well as a biomarker that could help identify patients at increased risk for so-called "chemo brain," cognitive complaints during adjuvant chemotherapy that can persist for years afterward in up to 25% of breast cancer survivors, according to Dr. Ganz, director of prevention and control research at the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles.

The study is thought to be among the first to comprehensively examine the relationship between inflammatory markers and cognitive changes in breast cancer patients, she said. It was suggested in part by a study of doxorubicin exposure in an animal model, which found systemic increases in the proinflammatory cytokine TNF-alpha. This cytokine is able to cross the blood-brain barrier and accumulate in the central nervous system (Neurobiol. Dis. July 2006;23:127-39).

The current study enrolled 191 women within 3 months of completion of primary therapy (surgery, radiation, and/or chemotherapy), and prior to initiating endocrine therapy for recently diagnosed breast cancer. All women underwent comprehensive assessments at baseline, 6 months, and 12 months after enrollment. A subset of 16 women also participated in a PET scan substudy and had brain scans at baseline and 12 months later.

The longitudinal data reported by Dr. Ganz was based on the first 93 women with complete cytokine assessments: 49 women who received chemotherapy and 44 women who did not have chemotherapy as part of their primary treatment. Similar proportions of both groups had undergone mastectomy (28% overall) and radiotherapy (76% overall) during primary treatment; 72% of the total population went on to receive endocrine therapy. The women had a mean age of 51 years and were enrolled an average of 7 months after diagnosis of breast cancer.

At baseline, the postchemotherapy group reported significantly poorer quality of life and functioning on several standardized measures, including the SF36 physical and mental component summary scales, sleep, fatigue, and depression.

Self-reported measures of cognitive complaints, including the multidimensional Patients Assessment of Own Functioning Inventory, also suggested that they had greater memory impairments. A significant correlation was found between the memory subscale score in the chemotherapy group (correlation with log r = 0.33, P = .05).

Fasting blood specimens were tested for four inflammatory markers: interleukin-1 receptor antagonist, interleukin-6, C-reactive protein, and soluble TNF receptor type II (sTNFRII), which provides a stable assessment of TNF-alpha activity.

Only sTNFRII was significantly increased in the chemotherapy-treated group (2,492.5 pg/mL vs. 2,115.6 pg/mL in the other patients, P = .007). Over the course of the year, it decreased to the point where the difference between groups was no longer significant.

In the 16 patients with complete PET scan data, soluble TNF receptor level at baseline was negatively correlated with metabolic activity in the inferior frontal gyrus in chemotherapy-treated patients (P = .04). Patients with higher levels of TNF receptor had lower levels of metabolic activity. This also improved over 12 months.

Finally, genetic analysis suggests that the GG allele of the TNF-alpha 308 single nucleotide polymorphism was associated with more cognitive complaints. It may enhance the patient’s vulnerability to cognitive complaints and cognitive dysfunction.

Discussant Karen Mustian, Ph.D., of the University of Rochester (N.Y.) said, "The strengths of this study include its prospective longitudinal design as well as the examination of potential biological mechanisms, including inflammation, genetic polymorphisms, and cerebral function."

She described examination of biomarkers and mechanisms as important in supportive care research, and expressed optimism that this type of research has only just begun.

The study was funded by the National Cancer Institute and the Breast Cancer Research Foundation. Dr. Ganz and Dr. Mustian said they had no relevant relationships.

CHICAGO – The quality of care that older cancer survivors receive for comorbid conditions such as diabetes and heart failure varies by tumor type, according to a retrospective, cross-sectional analysis of database records for more than 25,000 people.

Colorectal cancer survivors fared the worst of three tumor cohorts studied. Compared with a control group of cancer-free patients, they were more likely to receive acute and chronic care that was subpar on a variety of measures, Claire Snyder, Ph.D., reported at the annual meeting of the American Society of Clinical Oncology.

Breast cancer survivors fared best, receiving equivalent acute and better chronic care than did cancer-free controls. Prostate cancer survivors came out somewhere in the middle, receiving worse acute care but better chronic care.

The study "does not explain why care was or was not provided," Dr. Snyder said, listing its limitations. She hopes to explore why survivor care varies by tumor type as well as possible relationships with cost, she added.

"The issue of comorbid-condition care in cancer survivors has been understudied. As our treatments improve and survivors live longer with a history of a cancer diagnosis, quality care for comorbid conditions takes on greater importance," said Dr. Snyder of Johns Hopkins University in Baltimore.

Cancer survivors’ health care needs include surveillance for recurrence and monitoring for the physical and psychosocial long-term and late effects of the disease and its treatment, she said. Their needs also include general primary and preventive care, and often care for comorbid conditions.

This study used data from the SEER (Surveillance, Epidemiology and End Results)–Medicare database, a cancer registry linked with Medicare claims data. The nation’s 17 SEER registries cover a representative sample of more than one-quarter of the U.S. population. Medicare claims data on noncancer controls who live in SEER regions were used for comparison.

The study population was diagnosed with locoregional breast, prostate, or colorectal cancer in 2004. They were at least 66 years old and were enrolled in fee-for-service Medicare during the study period. They had survived at least 3 years from diagnosis, and had no evidence of ongoing cancer treatment.

The 8,661 cancer survivors in the study were "frequency matched" with 17,322 cancer-free controls. Slightly more than half of the cancer group (4,559) had survived prostate cancer; 2,231 had survived colorectal cancer; and 1,871 survived breast cancer. The study period covered years 2 and 3 from day of diagnosis.

The final sample had a mean age of approximately 75 years; nearly two-thirds were men, and 85% were white. More than 88% in both case and control groups lived in an urban area.

There were 9 quality indicators for care of chronic conditions, and 19 for care of acute conditions. To calculate the percentage of survivors receiving appropriate care, investigators divided the number of cases and controls who received appropriate care by the number eligible for each indicator.

A summary analysis showed that among colorectal cancer survivors, there were four indicators of worse chronic care (chronic obstructive pulmonary disease visits, lipid monitoring after angina, diabetes eye exams, and diabetes monitoring), and three indicators of worse acute care (visits after acute MI and heart failure hospitalizations, and cholecystectomy), compared with controls.

Prostate cancer survivors had three indicators of worse acute care (ECG after heart failure, chest film after heart failure, and cholecystectomy), but two indicators of better chronic care (COPD and diabetes visits).

The breast cancer survivors did better on COPD and diabetes visits.

Quality indicators for the care of chronic conditions included the following:

• Visit frequency of 6 months for chronic stable angina, heart failure, COPD, and diabetes.

• Visit frequency of 12 months for transient ischemic attack (TIA).

• Cholesterol test every 6 months for patients with hypercholesterolemia who were hospitalized with acute MI.

• Lipid profile up to 1 year after initial diagnosis of angina.

• Yearly eye exam for diabetes patients.

• Glycosylated hemoglobin and fructosamine every 6 months for diabetes patients.

Quality indicators for the care of acute conditions included the following:

• Visits up to 4 weeks after discharge after hospitalization for acute MI, unstable angina, heart failure, cerebrovascular accident, TIA, diabetes, malignant or otherwise severe hypertension, or gastrointestinal bleed.

• Visits up to 2 weeks after discharge for patients hospitalized with depression.

• Visits up to 1 week after diagnosis of unstable angina (visit or hospitalization).

• ECG during emergency department visit for unstable angina.

• ECG up to 3 months after initial diagnosis of heart failure.

• ECG up 2 days of initial diagnosis of TIA.

• Chest radiograph up to 3 months after initial diagnosis of heart failure.

• Carotid imaging up to 2 weeks after initial diagnosis for patients hospitalized with carotid artery stroke.

• Carotid endarterectomy up to 2 months after carotid imaging for cerebrovascular accident patients with eventual carotid endarterectomy.

• Carotid endarterectomy up to 2 months after carotid imaging for TIA patients with eventual carotid endarterectomy.

• Cholecystectomy for patients with cholelithiasis plus cholecystitis, cholangitis, or gallstone pancreatitis.

• Arthroplasty or internal fixation of hip during hospital stay for hip fracture.

Among the study’s strengths, Dr. Snyder said that it examined the initial transition from acute cancer treatment to survivorship, an important time to ensure that survivors do not get lost in transition.

Discussant Lynne I. Wagner, Ph.D., of Northwestern University in Chicago said that this represented a novel contribution to the evidence base in survivorship care. "The comorbidity issues are extremely important. This is probably the tip of the iceberg in terms of what’s going on," she said.

The study was funded by the National Cancer Institute. Neither Dr. Snyder nor Dr. Wagner disclosed relevant relationships.

CHICAGO – The quality of care that older cancer survivors receive for comorbid conditions such as diabetes and heart failure varies by tumor type, according to a retrospective, cross-sectional analysis of database records for more than 25,000 people.

Colorectal cancer survivors fared the worst of three tumor cohorts studied. Compared with a control group of cancer-free patients, they were more likely to receive acute and chronic care that was subpar on a variety of measures, Claire Snyder, Ph.D., reported at the annual meeting of the American Society of Clinical Oncology.

Breast cancer survivors fared best, receiving equivalent acute and better chronic care than did cancer-free controls. Prostate cancer survivors came out somewhere in the middle, receiving worse acute care but better chronic care.

The study "does not explain why care was or was not provided," Dr. Snyder said, listing its limitations. She hopes to explore why survivor care varies by tumor type as well as possible relationships with cost, she added.

"The issue of comorbid-condition care in cancer survivors has been understudied. As our treatments improve and survivors live longer with a history of a cancer diagnosis, quality care for comorbid conditions takes on greater importance," said Dr. Snyder of Johns Hopkins University in Baltimore.

Cancer survivors’ health care needs include surveillance for recurrence and monitoring for the physical and psychosocial long-term and late effects of the disease and its treatment, she said. Their needs also include general primary and preventive care, and often care for comorbid conditions.

This study used data from the SEER (Surveillance, Epidemiology and End Results)–Medicare database, a cancer registry linked with Medicare claims data. The nation’s 17 SEER registries cover a representative sample of more than one-quarter of the U.S. population. Medicare claims data on noncancer controls who live in SEER regions were used for comparison.

The study population was diagnosed with locoregional breast, prostate, or colorectal cancer in 2004. They were at least 66 years old and were enrolled in fee-for-service Medicare during the study period. They had survived at least 3 years from diagnosis, and had no evidence of ongoing cancer treatment.

The 8,661 cancer survivors in the study were "frequency matched" with 17,322 cancer-free controls. Slightly more than half of the cancer group (4,559) had survived prostate cancer; 2,231 had survived colorectal cancer; and 1,871 survived breast cancer. The study period covered years 2 and 3 from day of diagnosis.

The final sample had a mean age of approximately 75 years; nearly two-thirds were men, and 85% were white. More than 88% in both case and control groups lived in an urban area.

There were 9 quality indicators for care of chronic conditions, and 19 for care of acute conditions. To calculate the percentage of survivors receiving appropriate care, investigators divided the number of cases and controls who received appropriate care by the number eligible for each indicator.

A summary analysis showed that among colorectal cancer survivors, there were four indicators of worse chronic care (chronic obstructive pulmonary disease visits, lipid monitoring after angina, diabetes eye exams, and diabetes monitoring), and three indicators of worse acute care (visits after acute MI and heart failure hospitalizations, and cholecystectomy), compared with controls.

Prostate cancer survivors had three indicators of worse acute care (ECG after heart failure, chest film after heart failure, and cholecystectomy), but two indicators of better chronic care (COPD and diabetes visits).

The breast cancer survivors did better on COPD and diabetes visits.

Quality indicators for the care of chronic conditions included the following:

• Visit frequency of 6 months for chronic stable angina, heart failure, COPD, and diabetes.

• Visit frequency of 12 months for transient ischemic attack (TIA).

• Cholesterol test every 6 months for patients with hypercholesterolemia who were hospitalized with acute MI.

• Lipid profile up to 1 year after initial diagnosis of angina.

• Yearly eye exam for diabetes patients.

• Glycosylated hemoglobin and fructosamine every 6 months for diabetes patients.

Quality indicators for the care of acute conditions included the following:

• Visits up to 4 weeks after discharge after hospitalization for acute MI, unstable angina, heart failure, cerebrovascular accident, TIA, diabetes, malignant or otherwise severe hypertension, or gastrointestinal bleed.

• Visits up to 2 weeks after discharge for patients hospitalized with depression.

• Visits up to 1 week after diagnosis of unstable angina (visit or hospitalization).

• ECG during emergency department visit for unstable angina.

• ECG up to 3 months after initial diagnosis of heart failure.

• ECG up 2 days of initial diagnosis of TIA.

• Chest radiograph up to 3 months after initial diagnosis of heart failure.

• Carotid imaging up to 2 weeks after initial diagnosis for patients hospitalized with carotid artery stroke.

• Carotid endarterectomy up to 2 months after carotid imaging for cerebrovascular accident patients with eventual carotid endarterectomy.

• Carotid endarterectomy up to 2 months after carotid imaging for TIA patients with eventual carotid endarterectomy.

• Cholecystectomy for patients with cholelithiasis plus cholecystitis, cholangitis, or gallstone pancreatitis.

• Arthroplasty or internal fixation of hip during hospital stay for hip fracture.

Among the study’s strengths, Dr. Snyder said that it examined the initial transition from acute cancer treatment to survivorship, an important time to ensure that survivors do not get lost in transition.

Discussant Lynne I. Wagner, Ph.D., of Northwestern University in Chicago said that this represented a novel contribution to the evidence base in survivorship care. "The comorbidity issues are extremely important. This is probably the tip of the iceberg in terms of what’s going on," she said.

The study was funded by the National Cancer Institute. Neither Dr. Snyder nor Dr. Wagner disclosed relevant relationships.

CHICAGO – The quality of care that older cancer survivors receive for comorbid conditions such as diabetes and heart failure varies by tumor type, according to a retrospective, cross-sectional analysis of database records for more than 25,000 people.

Colorectal cancer survivors fared the worst of three tumor cohorts studied. Compared with a control group of cancer-free patients, they were more likely to receive acute and chronic care that was subpar on a variety of measures, Claire Snyder, Ph.D., reported at the annual meeting of the American Society of Clinical Oncology.

Breast cancer survivors fared best, receiving equivalent acute and better chronic care than did cancer-free controls. Prostate cancer survivors came out somewhere in the middle, receiving worse acute care but better chronic care.

The study "does not explain why care was or was not provided," Dr. Snyder said, listing its limitations. She hopes to explore why survivor care varies by tumor type as well as possible relationships with cost, she added.

"The issue of comorbid-condition care in cancer survivors has been understudied. As our treatments improve and survivors live longer with a history of a cancer diagnosis, quality care for comorbid conditions takes on greater importance," said Dr. Snyder of Johns Hopkins University in Baltimore.

Cancer survivors’ health care needs include surveillance for recurrence and monitoring for the physical and psychosocial long-term and late effects of the disease and its treatment, she said. Their needs also include general primary and preventive care, and often care for comorbid conditions.

This study used data from the SEER (Surveillance, Epidemiology and End Results)–Medicare database, a cancer registry linked with Medicare claims data. The nation’s 17 SEER registries cover a representative sample of more than one-quarter of the U.S. population. Medicare claims data on noncancer controls who live in SEER regions were used for comparison.

The study population was diagnosed with locoregional breast, prostate, or colorectal cancer in 2004. They were at least 66 years old and were enrolled in fee-for-service Medicare during the study period. They had survived at least 3 years from diagnosis, and had no evidence of ongoing cancer treatment.

The 8,661 cancer survivors in the study were "frequency matched" with 17,322 cancer-free controls. Slightly more than half of the cancer group (4,559) had survived prostate cancer; 2,231 had survived colorectal cancer; and 1,871 survived breast cancer. The study period covered years 2 and 3 from day of diagnosis.

The final sample had a mean age of approximately 75 years; nearly two-thirds were men, and 85% were white. More than 88% in both case and control groups lived in an urban area.

There were 9 quality indicators for care of chronic conditions, and 19 for care of acute conditions. To calculate the percentage of survivors receiving appropriate care, investigators divided the number of cases and controls who received appropriate care by the number eligible for each indicator.

A summary analysis showed that among colorectal cancer survivors, there were four indicators of worse chronic care (chronic obstructive pulmonary disease visits, lipid monitoring after angina, diabetes eye exams, and diabetes monitoring), and three indicators of worse acute care (visits after acute MI and heart failure hospitalizations, and cholecystectomy), compared with controls.

Prostate cancer survivors had three indicators of worse acute care (ECG after heart failure, chest film after heart failure, and cholecystectomy), but two indicators of better chronic care (COPD and diabetes visits).

The breast cancer survivors did better on COPD and diabetes visits.

Quality indicators for the care of chronic conditions included the following:

• Visit frequency of 6 months for chronic stable angina, heart failure, COPD, and diabetes.

• Visit frequency of 12 months for transient ischemic attack (TIA).

• Cholesterol test every 6 months for patients with hypercholesterolemia who were hospitalized with acute MI.

• Lipid profile up to 1 year after initial diagnosis of angina.

• Yearly eye exam for diabetes patients.

• Glycosylated hemoglobin and fructosamine every 6 months for diabetes patients.

Quality indicators for the care of acute conditions included the following:

• Visits up to 4 weeks after discharge after hospitalization for acute MI, unstable angina, heart failure, cerebrovascular accident, TIA, diabetes, malignant or otherwise severe hypertension, or gastrointestinal bleed.

• Visits up to 2 weeks after discharge for patients hospitalized with depression.

• Visits up to 1 week after diagnosis of unstable angina (visit or hospitalization).

• ECG during emergency department visit for unstable angina.

• ECG up to 3 months after initial diagnosis of heart failure.

• ECG up 2 days of initial diagnosis of TIA.

• Chest radiograph up to 3 months after initial diagnosis of heart failure.

• Carotid imaging up to 2 weeks after initial diagnosis for patients hospitalized with carotid artery stroke.

• Carotid endarterectomy up to 2 months after carotid imaging for cerebrovascular accident patients with eventual carotid endarterectomy.

• Carotid endarterectomy up to 2 months after carotid imaging for TIA patients with eventual carotid endarterectomy.

• Cholecystectomy for patients with cholelithiasis plus cholecystitis, cholangitis, or gallstone pancreatitis.

• Arthroplasty or internal fixation of hip during hospital stay for hip fracture.

Among the study’s strengths, Dr. Snyder said that it examined the initial transition from acute cancer treatment to survivorship, an important time to ensure that survivors do not get lost in transition.

Discussant Lynne I. Wagner, Ph.D., of Northwestern University in Chicago said that this represented a novel contribution to the evidence base in survivorship care. "The comorbidity issues are extremely important. This is probably the tip of the iceberg in terms of what’s going on," she said.

The study was funded by the National Cancer Institute. Neither Dr. Snyder nor Dr. Wagner disclosed relevant relationships.

CHICAGO – The quality of care that older cancer survivors receive for comorbid conditions such as diabetes and heart failure varies by tumor type, according to a retrospective, cross-sectional analysis of database records for more than 25,000 people.

Colorectal cancer survivors fared the worst of three tumor cohorts studied. Compared with a control group of cancer-free patients, they were more likely to receive acute and chronic care that was subpar on a variety of measures, Claire Snyder, Ph.D., reported at the annual meeting of the American Society of Clinical Oncology.

Breast cancer survivors fared best, receiving equivalent acute and better chronic care than did cancer-free controls. Prostate cancer survivors came out somewhere in the middle, receiving worse acute care but better chronic care.

The study "does not explain why care was or was not provided," Dr. Snyder said, listing its limitations. She hopes to explore why survivor care varies by tumor type as well as possible relationships with cost, she added.

"The issue of comorbid-condition care in cancer survivors has been understudied. As our treatments improve and survivors live longer with a history of a cancer diagnosis, quality care for comorbid conditions takes on greater importance," said Dr. Snyder of Johns Hopkins University in Baltimore.

Cancer survivors’ health care needs include surveillance for recurrence and monitoring for the physical and psychosocial long-term and late effects of the disease and its treatment, she said. Their needs also include general primary and preventive care, and often care for comorbid conditions.

This study used data from the SEER (Surveillance, Epidemiology and End Results)–Medicare database, a cancer registry linked with Medicare claims data. The nation’s 17 SEER registries cover a representative sample of more than one-quarter of the U.S. population. Medicare claims data on noncancer controls who live in SEER regions were used for comparison.

The study population was diagnosed with locoregional breast, prostate, or colorectal cancer in 2004. They were at least 66 years old and were enrolled in fee-for-service Medicare during the study period. They had survived at least 3 years from diagnosis, and had no evidence of ongoing cancer treatment.

The 8,661 cancer survivors in the study were "frequency matched" with 17,322 cancer-free controls. Slightly more than half of the cancer group (4,559) had survived prostate cancer; 2,231 had survived colorectal cancer; and 1,871 survived breast cancer. The study period covered years 2 and 3 from day of diagnosis.

The final sample had a mean age of approximately 75 years; nearly two-thirds were men, and 85% were white. More than 88% in both case and control groups lived in an urban area.

There were 9 quality indicators for care of chronic conditions, and 19 for care of acute conditions. To calculate the percentage of survivors receiving appropriate care, investigators divided the number of cases and controls who received appropriate care by the number eligible for each indicator.

A summary analysis showed that among colorectal cancer survivors, there were four indicators of worse chronic care (chronic obstructive pulmonary disease visits, lipid monitoring after angina, diabetes eye exams, and diabetes monitoring), and three indicators of worse acute care (visits after acute MI and heart failure hospitalizations, and cholecystectomy), compared with controls.

Prostate cancer survivors had three indicators of worse acute care (ECG after heart failure, chest film after heart failure, and cholecystectomy), but two indicators of better chronic care (COPD and diabetes visits).

The breast cancer survivors did better on COPD and diabetes visits.

Quality indicators for the care of chronic conditions included the following:

• Visit frequency of 6 months for chronic stable angina, heart failure, COPD, and diabetes.

• Visit frequency of 12 months for transient ischemic attack (TIA).

• Cholesterol test every 6 months for patients with hypercholesterolemia who were hospitalized with acute MI.

• Lipid profile up to 1 year after initial diagnosis of angina.

• Yearly eye exam for diabetes patients.

• Glycosylated hemoglobin and fructosamine every 6 months for diabetes patients.

Quality indicators for the care of acute conditions included the following:

• Visits up to 4 weeks after discharge after hospitalization for acute MI, unstable angina, heart failure, cerebrovascular accident, TIA, diabetes, malignant or otherwise severe hypertension, or gastrointestinal bleed.

• Visits up to 2 weeks after discharge for patients hospitalized with depression.

• Visits up to 1 week after diagnosis of unstable angina (visit or hospitalization).

• ECG during emergency department visit for unstable angina.

• ECG up to 3 months after initial diagnosis of heart failure.

• ECG up 2 days of initial diagnosis of TIA.

• Chest radiograph up to 3 months after initial diagnosis of heart failure.

• Carotid imaging up to 2 weeks after initial diagnosis for patients hospitalized with carotid artery stroke.

• Carotid endarterectomy up to 2 months after carotid imaging for cerebrovascular accident patients with eventual carotid endarterectomy.

• Carotid endarterectomy up to 2 months after carotid imaging for TIA patients with eventual carotid endarterectomy.

• Cholecystectomy for patients with cholelithiasis plus cholecystitis, cholangitis, or gallstone pancreatitis.

• Arthroplasty or internal fixation of hip during hospital stay for hip fracture.

Among the study’s strengths, Dr. Snyder said that it examined the initial transition from acute cancer treatment to survivorship, an important time to ensure that survivors do not get lost in transition.

Discussant Lynne I. Wagner, Ph.D., of Northwestern University in Chicago said that this represented a novel contribution to the evidence base in survivorship care. "The comorbidity issues are extremely important. This is probably the tip of the iceberg in terms of what’s going on," she said.

The study was funded by the National Cancer Institute. Neither Dr. Snyder nor Dr. Wagner disclosed relevant relationships.

CHICAGO – The quality of care that older cancer survivors receive for comorbid conditions such as diabetes and heart failure varies by tumor type, according to a retrospective, cross-sectional analysis of database records for more than 25,000 people.

Colorectal cancer survivors fared the worst of three tumor cohorts studied. Compared with a control group of cancer-free patients, they were more likely to receive acute and chronic care that was subpar on a variety of measures, Claire Snyder, Ph.D., reported at the annual meeting of the American Society of Clinical Oncology.

Breast cancer survivors fared best, receiving equivalent acute and better chronic care than did cancer-free controls. Prostate cancer survivors came out somewhere in the middle, receiving worse acute care but better chronic care.

The study "does not explain why care was or was not provided," Dr. Snyder said, listing its limitations. She hopes to explore why survivor care varies by tumor type as well as possible relationships with cost, she added.

"The issue of comorbid-condition care in cancer survivors has been understudied. As our treatments improve and survivors live longer with a history of a cancer diagnosis, quality care for comorbid conditions takes on greater importance," said Dr. Snyder of Johns Hopkins University in Baltimore.

Cancer survivors’ health care needs include surveillance for recurrence and monitoring for the physical and psychosocial long-term and late effects of the disease and its treatment, she said. Their needs also include general primary and preventive care, and often care for comorbid conditions.

This study used data from the SEER (Surveillance, Epidemiology and End Results)–Medicare database, a cancer registry linked with Medicare claims data. The nation’s 17 SEER registries cover a representative sample of more than one-quarter of the U.S. population. Medicare claims data on noncancer controls who live in SEER regions were used for comparison.

The study population was diagnosed with locoregional breast, prostate, or colorectal cancer in 2004. They were at least 66 years old and were enrolled in fee-for-service Medicare during the study period. They had survived at least 3 years from diagnosis, and had no evidence of ongoing cancer treatment.

The 8,661 cancer survivors in the study were "frequency matched" with 17,322 cancer-free controls. Slightly more than half of the cancer group (4,559) had survived prostate cancer; 2,231 had survived colorectal cancer; and 1,871 survived breast cancer. The study period covered years 2 and 3 from day of diagnosis.

The final sample had a mean age of approximately 75 years; nearly two-thirds were men, and 85% were white. More than 88% in both case and control groups lived in an urban area.

There were 9 quality indicators for care of chronic conditions, and 19 for care of acute conditions. To calculate the percentage of survivors receiving appropriate care, investigators divided the number of cases and controls who received appropriate care by the number eligible for each indicator.

A summary analysis showed that among colorectal cancer survivors, there were four indicators of worse chronic care (chronic obstructive pulmonary disease visits, lipid monitoring after angina, diabetes eye exams, and diabetes monitoring), and three indicators of worse acute care (visits after acute MI and heart failure hospitalizations, and cholecystectomy), compared with controls.

Prostate cancer survivors had three indicators of worse acute care (ECG after heart failure, chest film after heart failure, and cholecystectomy), but two indicators of better chronic care (COPD and diabetes visits).

The breast cancer survivors did better on COPD and diabetes visits.

Quality indicators for the care of chronic conditions included the following:

• Visit frequency of 6 months for chronic stable angina, heart failure, COPD, and diabetes.

• Visit frequency of 12 months for transient ischemic attack (TIA).

• Cholesterol test every 6 months for patients with hypercholesterolemia who were hospitalized with acute MI.

• Lipid profile up to 1 year after initial diagnosis of angina.

• Yearly eye exam for diabetes patients.

• Glycosylated hemoglobin and fructosamine every 6 months for diabetes patients.

Quality indicators for the care of acute conditions included the following:

• Visits up to 4 weeks after discharge after hospitalization for acute MI, unstable angina, heart failure, cerebrovascular accident, TIA, diabetes, malignant or otherwise severe hypertension, or gastrointestinal bleed.

• Visits up to 2 weeks after discharge for patients hospitalized with depression.

• Visits up to 1 week after diagnosis of unstable angina (visit or hospitalization).

• ECG during emergency department visit for unstable angina.

• ECG up to 3 months after initial diagnosis of heart failure.

• ECG up 2 days of initial diagnosis of TIA.

• Chest radiograph up to 3 months after initial diagnosis of heart failure.

• Carotid imaging up to 2 weeks after initial diagnosis for patients hospitalized with carotid artery stroke.

• Carotid endarterectomy up to 2 months after carotid imaging for cerebrovascular accident patients with eventual carotid endarterectomy.

• Carotid endarterectomy up to 2 months after carotid imaging for TIA patients with eventual carotid endarterectomy.

• Cholecystectomy for patients with cholelithiasis plus cholecystitis, cholangitis, or gallstone pancreatitis.

• Arthroplasty or internal fixation of hip during hospital stay for hip fracture.

Among the study’s strengths, Dr. Snyder said that it examined the initial transition from acute cancer treatment to survivorship, an important time to ensure that survivors do not get lost in transition.

Discussant Lynne I. Wagner, Ph.D., of Northwestern University in Chicago said that this represented a novel contribution to the evidence base in survivorship care. "The comorbidity issues are extremely important. This is probably the tip of the iceberg in terms of what’s going on," she said.

The study was funded by the National Cancer Institute. Neither Dr. Snyder nor Dr. Wagner disclosed relevant relationships.

CHICAGO – The quality of care that older cancer survivors receive for comorbid conditions such as diabetes and heart failure varies by tumor type, according to a retrospective, cross-sectional analysis of database records for more than 25,000 people.

Colorectal cancer survivors fared the worst of three tumor cohorts studied. Compared with a control group of cancer-free patients, they were more likely to receive acute and chronic care that was subpar on a variety of measures, Claire Snyder, Ph.D., reported at the annual meeting of the American Society of Clinical Oncology.

Breast cancer survivors fared best, receiving equivalent acute and better chronic care than did cancer-free controls. Prostate cancer survivors came out somewhere in the middle, receiving worse acute care but better chronic care.

The study "does not explain why care was or was not provided," Dr. Snyder said, listing its limitations. She hopes to explore why survivor care varies by tumor type as well as possible relationships with cost, she added.

"The issue of comorbid-condition care in cancer survivors has been understudied. As our treatments improve and survivors live longer with a history of a cancer diagnosis, quality care for comorbid conditions takes on greater importance," said Dr. Snyder of Johns Hopkins University in Baltimore.

Cancer survivors’ health care needs include surveillance for recurrence and monitoring for the physical and psychosocial long-term and late effects of the disease and its treatment, she said. Their needs also include general primary and preventive care, and often care for comorbid conditions.

This study used data from the SEER (Surveillance, Epidemiology and End Results)–Medicare database, a cancer registry linked with Medicare claims data. The nation’s 17 SEER registries cover a representative sample of more than one-quarter of the U.S. population. Medicare claims data on noncancer controls who live in SEER regions were used for comparison.

The study population was diagnosed with locoregional breast, prostate, or colorectal cancer in 2004. They were at least 66 years old and were enrolled in fee-for-service Medicare during the study period. They had survived at least 3 years from diagnosis, and had no evidence of ongoing cancer treatment.

The 8,661 cancer survivors in the study were "frequency matched" with 17,322 cancer-free controls. Slightly more than half of the cancer group (4,559) had survived prostate cancer; 2,231 had survived colorectal cancer; and 1,871 survived breast cancer. The study period covered years 2 and 3 from day of diagnosis.

The final sample had a mean age of approximately 75 years; nearly two-thirds were men, and 85% were white. More than 88% in both case and control groups lived in an urban area.

There were 9 quality indicators for care of chronic conditions, and 19 for care of acute conditions. To calculate the percentage of survivors receiving appropriate care, investigators divided the number of cases and controls who received appropriate care by the number eligible for each indicator.

A summary analysis showed that among colorectal cancer survivors, there were four indicators of worse chronic care (chronic obstructive pulmonary disease visits, lipid monitoring after angina, diabetes eye exams, and diabetes monitoring), and three indicators of worse acute care (visits after acute MI and heart failure hospitalizations, and cholecystectomy), compared with controls.

Prostate cancer survivors had three indicators of worse acute care (ECG after heart failure, chest film after heart failure, and cholecystectomy), but two indicators of better chronic care (COPD and diabetes visits).

The breast cancer survivors did better on COPD and diabetes visits.

Quality indicators for the care of chronic conditions included the following:

• Visit frequency of 6 months for chronic stable angina, heart failure, COPD, and diabetes.

• Visit frequency of 12 months for transient ischemic attack (TIA).

• Cholesterol test every 6 months for patients with hypercholesterolemia who were hospitalized with acute MI.

• Lipid profile up to 1 year after initial diagnosis of angina.

• Yearly eye exam for diabetes patients.

• Glycosylated hemoglobin and fructosamine every 6 months for diabetes patients.

Quality indicators for the care of acute conditions included the following:

• Visits up to 4 weeks after discharge after hospitalization for acute MI, unstable angina, heart failure, cerebrovascular accident, TIA, diabetes, malignant or otherwise severe hypertension, or gastrointestinal bleed.

• Visits up to 2 weeks after discharge for patients hospitalized with depression.

• Visits up to 1 week after diagnosis of unstable angina (visit or hospitalization).

• ECG during emergency department visit for unstable angina.

• ECG up to 3 months after initial diagnosis of heart failure.

• ECG up 2 days of initial diagnosis of TIA.

• Chest radiograph up to 3 months after initial diagnosis of heart failure.

• Carotid imaging up to 2 weeks after initial diagnosis for patients hospitalized with carotid artery stroke.

• Carotid endarterectomy up to 2 months after carotid imaging for cerebrovascular accident patients with eventual carotid endarterectomy.

• Carotid endarterectomy up to 2 months after carotid imaging for TIA patients with eventual carotid endarterectomy.

• Cholecystectomy for patients with cholelithiasis plus cholecystitis, cholangitis, or gallstone pancreatitis.

• Arthroplasty or internal fixation of hip during hospital stay for hip fracture.

Among the study’s strengths, Dr. Snyder said that it examined the initial transition from acute cancer treatment to survivorship, an important time to ensure that survivors do not get lost in transition.

Discussant Lynne I. Wagner, Ph.D., of Northwestern University in Chicago said that this represented a novel contribution to the evidence base in survivorship care. "The comorbidity issues are extremely important. This is probably the tip of the iceberg in terms of what’s going on," she said.

The study was funded by the National Cancer Institute. Neither Dr. Snyder nor Dr. Wagner disclosed relevant relationships.

CHICAGO – The quality of care that older cancer survivors receive for comorbid conditions such as diabetes and heart failure varies by tumor type, according to a retrospective, cross-sectional analysis of database records for more than 25,000 people.

Colorectal cancer survivors fared the worst of three tumor cohorts studied. Compared with a control group of cancer-free patients, they were more likely to receive acute and chronic care that was subpar on a variety of measures, Claire Snyder, Ph.D., reported at the annual meeting of the American Society of Clinical Oncology.

Breast cancer survivors fared best, receiving equivalent acute and better chronic care than did cancer-free controls. Prostate cancer survivors came out somewhere in the middle, receiving worse acute care but better chronic care.

The study "does not explain why care was or was not provided," Dr. Snyder said, listing its limitations. She hopes to explore why survivor care varies by tumor type as well as possible relationships with cost, she added.

"The issue of comorbid-condition care in cancer survivors has been understudied. As our treatments improve and survivors live longer with a history of a cancer diagnosis, quality care for comorbid conditions takes on greater importance," said Dr. Snyder of Johns Hopkins University in Baltimore.

Cancer survivors’ health care needs include surveillance for recurrence and monitoring for the physical and psychosocial long-term and late effects of the disease and its treatment, she said. Their needs also include general primary and preventive care, and often care for comorbid conditions.

This study used data from the SEER (Surveillance, Epidemiology and End Results)–Medicare database, a cancer registry linked with Medicare claims data. The nation’s 17 SEER registries cover a representative sample of more than one-quarter of the U.S. population. Medicare claims data on noncancer controls who live in SEER regions were used for comparison.

The study population was diagnosed with locoregional breast, prostate, or colorectal cancer in 2004. They were at least 66 years old and were enrolled in fee-for-service Medicare during the study period. They had survived at least 3 years from diagnosis, and had no evidence of ongoing cancer treatment.

The 8,661 cancer survivors in the study were "frequency matched" with 17,322 cancer-free controls. Slightly more than half of the cancer group (4,559) had survived prostate cancer; 2,231 had survived colorectal cancer; and 1,871 survived breast cancer. The study period covered years 2 and 3 from day of diagnosis.

The final sample had a mean age of approximately 75 years; nearly two-thirds were men, and 85% were white. More than 88% in both case and control groups lived in an urban area.

There were 9 quality indicators for care of chronic conditions, and 19 for care of acute conditions. To calculate the percentage of survivors receiving appropriate care, investigators divided the number of cases and controls who received appropriate care by the number eligible for each indicator.

A summary analysis showed that among colorectal cancer survivors, there were four indicators of worse chronic care (chronic obstructive pulmonary disease visits, lipid monitoring after angina, diabetes eye exams, and diabetes monitoring), and three indicators of worse acute care (visits after acute MI and heart failure hospitalizations, and cholecystectomy), compared with controls.

Prostate cancer survivors had three indicators of worse acute care (ECG after heart failure, chest film after heart failure, and cholecystectomy), but two indicators of better chronic care (COPD and diabetes visits).

The breast cancer survivors did better on COPD and diabetes visits.

Quality indicators for the care of chronic conditions included the following:

• Visit frequency of 6 months for chronic stable angina, heart failure, COPD, and diabetes.

• Visit frequency of 12 months for transient ischemic attack (TIA).

• Cholesterol test every 6 months for patients with hypercholesterolemia who were hospitalized with acute MI.

• Lipid profile up to 1 year after initial diagnosis of angina.

• Yearly eye exam for diabetes patients.

• Glycosylated hemoglobin and fructosamine every 6 months for diabetes patients.

Quality indicators for the care of acute conditions included the following:

• Visits up to 4 weeks after discharge after hospitalization for acute MI, unstable angina, heart failure, cerebrovascular accident, TIA, diabetes, malignant or otherwise severe hypertension, or gastrointestinal bleed.

• Visits up to 2 weeks after discharge for patients hospitalized with depression.

• Visits up to 1 week after diagnosis of unstable angina (visit or hospitalization).

• ECG during emergency department visit for unstable angina.

• ECG up to 3 months after initial diagnosis of heart failure.

• ECG up 2 days of initial diagnosis of TIA.

• Chest radiograph up to 3 months after initial diagnosis of heart failure.

• Carotid imaging up to 2 weeks after initial diagnosis for patients hospitalized with carotid artery stroke.

• Carotid endarterectomy up to 2 months after carotid imaging for cerebrovascular accident patients with eventual carotid endarterectomy.

• Carotid endarterectomy up to 2 months after carotid imaging for TIA patients with eventual carotid endarterectomy.

• Cholecystectomy for patients with cholelithiasis plus cholecystitis, cholangitis, or gallstone pancreatitis.

• Arthroplasty or internal fixation of hip during hospital stay for hip fracture.

Among the study’s strengths, Dr. Snyder said that it examined the initial transition from acute cancer treatment to survivorship, an important time to ensure that survivors do not get lost in transition.

Discussant Lynne I. Wagner, Ph.D., of Northwestern University in Chicago said that this represented a novel contribution to the evidence base in survivorship care. "The comorbidity issues are extremely important. This is probably the tip of the iceberg in terms of what’s going on," she said.

The study was funded by the National Cancer Institute. Neither Dr. Snyder nor Dr. Wagner disclosed relevant relationships.

CHICAGO – The quality of care that older cancer survivors receive for comorbid conditions such as diabetes and heart failure varies by tumor type, according to a retrospective, cross-sectional analysis of database records for more than 25,000 people.

Colorectal cancer survivors fared the worst of three tumor cohorts studied. Compared with a control group of cancer-free patients, they were more likely to receive acute and chronic care that was subpar on a variety of measures, Claire Snyder, Ph.D., reported at the annual meeting of the American Society of Clinical Oncology.

Breast cancer survivors fared best, receiving equivalent acute and better chronic care than did cancer-free controls. Prostate cancer survivors came out somewhere in the middle, receiving worse acute care but better chronic care.

The study "does not explain why care was or was not provided," Dr. Snyder said, listing its limitations. She hopes to explore why survivor care varies by tumor type as well as possible relationships with cost, she added.

"The issue of comorbid-condition care in cancer survivors has been understudied. As our treatments improve and survivors live longer with a history of a cancer diagnosis, quality care for comorbid conditions takes on greater importance," said Dr. Snyder of Johns Hopkins University in Baltimore.

Cancer survivors’ health care needs include surveillance for recurrence and monitoring for the physical and psychosocial long-term and late effects of the disease and its treatment, she said. Their needs also include general primary and preventive care, and often care for comorbid conditions.

This study used data from the SEER (Surveillance, Epidemiology and End Results)–Medicare database, a cancer registry linked with Medicare claims data. The nation’s 17 SEER registries cover a representative sample of more than one-quarter of the U.S. population. Medicare claims data on noncancer controls who live in SEER regions were used for comparison.

The study population was diagnosed with locoregional breast, prostate, or colorectal cancer in 2004. They were at least 66 years old and were enrolled in fee-for-service Medicare during the study period. They had survived at least 3 years from diagnosis, and had no evidence of ongoing cancer treatment.

The 8,661 cancer survivors in the study were "frequency matched" with 17,322 cancer-free controls. Slightly more than half of the cancer group (4,559) had survived prostate cancer; 2,231 had survived colorectal cancer; and 1,871 survived breast cancer. The study period covered years 2 and 3 from day of diagnosis.

The final sample had a mean age of approximately 75 years; nearly two-thirds were men, and 85% were white. More than 88% in both case and control groups lived in an urban area.

There were 9 quality indicators for care of chronic conditions, and 19 for care of acute conditions. To calculate the percentage of survivors receiving appropriate care, investigators divided the number of cases and controls who received appropriate care by the number eligible for each indicator.

A summary analysis showed that among colorectal cancer survivors, there were four indicators of worse chronic care (chronic obstructive pulmonary disease visits, lipid monitoring after angina, diabetes eye exams, and diabetes monitoring), and three indicators of worse acute care (visits after acute MI and heart failure hospitalizations, and cholecystectomy), compared with controls.

Prostate cancer survivors had three indicators of worse acute care (ECG after heart failure, chest film after heart failure, and cholecystectomy), but two indicators of better chronic care (COPD and diabetes visits).

The breast cancer survivors did better on COPD and diabetes visits.

Quality indicators for the care of chronic conditions included the following:

• Visit frequency of 6 months for chronic stable angina, heart failure, COPD, and diabetes.

• Visit frequency of 12 months for transient ischemic attack (TIA).

• Cholesterol test every 6 months for patients with hypercholesterolemia who were hospitalized with acute MI.

• Lipid profile up to 1 year after initial diagnosis of angina.

• Yearly eye exam for diabetes patients.

• Glycosylated hemoglobin and fructosamine every 6 months for diabetes patients.

Quality indicators for the care of acute conditions included the following:

• Visits up to 4 weeks after discharge after hospitalization for acute MI, unstable angina, heart failure, cerebrovascular accident, TIA, diabetes, malignant or otherwise severe hypertension, or gastrointestinal bleed.

• Visits up to 2 weeks after discharge for patients hospitalized with depression.

• Visits up to 1 week after diagnosis of unstable angina (visit or hospitalization).

• ECG during emergency department visit for unstable angina.

• ECG up to 3 months after initial diagnosis of heart failure.

• ECG up 2 days of initial diagnosis of TIA.

• Chest radiograph up to 3 months after initial diagnosis of heart failure.

• Carotid imaging up to 2 weeks after initial diagnosis for patients hospitalized with carotid artery stroke.

• Carotid endarterectomy up to 2 months after carotid imaging for cerebrovascular accident patients with eventual carotid endarterectomy.

• Carotid endarterectomy up to 2 months after carotid imaging for TIA patients with eventual carotid endarterectomy.

• Cholecystectomy for patients with cholelithiasis plus cholecystitis, cholangitis, or gallstone pancreatitis.

• Arthroplasty or internal fixation of hip during hospital stay for hip fracture.

Among the study’s strengths, Dr. Snyder said that it examined the initial transition from acute cancer treatment to survivorship, an important time to ensure that survivors do not get lost in transition.

Discussant Lynne I. Wagner, Ph.D., of Northwestern University in Chicago said that this represented a novel contribution to the evidence base in survivorship care. "The comorbidity issues are extremely important. This is probably the tip of the iceberg in terms of what’s going on," she said.

The study was funded by the National Cancer Institute. Neither Dr. Snyder nor Dr. Wagner disclosed relevant relationships.

CHICAGO – The quality of care that older cancer survivors receive for comorbid conditions such as diabetes and heart failure varies by tumor type, according to a retrospective, cross-sectional analysis of database records for more than 25,000 people.

Colorectal cancer survivors fared the worst of three tumor cohorts studied. Compared with a control group of cancer-free patients, they were more likely to receive acute and chronic care that was subpar on a variety of measures, Claire Snyder, Ph.D., reported at the annual meeting of the American Society of Clinical Oncology.

Breast cancer survivors fared best, receiving equivalent acute and better chronic care than did cancer-free controls. Prostate cancer survivors came out somewhere in the middle, receiving worse acute care but better chronic care.

The study "does not explain why care was or was not provided," Dr. Snyder said, listing its limitations. She hopes to explore why survivor care varies by tumor type as well as possible relationships with cost, she added.

"The issue of comorbid-condition care in cancer survivors has been understudied. As our treatments improve and survivors live longer with a history of a cancer diagnosis, quality care for comorbid conditions takes on greater importance," said Dr. Snyder of Johns Hopkins University in Baltimore.

Cancer survivors’ health care needs include surveillance for recurrence and monitoring for the physical and psychosocial long-term and late effects of the disease and its treatment, she said. Their needs also include general primary and preventive care, and often care for comorbid conditions.

This study used data from the SEER (Surveillance, Epidemiology and End Results)–Medicare database, a cancer registry linked with Medicare claims data. The nation’s 17 SEER registries cover a representative sample of more than one-quarter of the U.S. population. Medicare claims data on noncancer controls who live in SEER regions were used for comparison.

The study population was diagnosed with locoregional breast, prostate, or colorectal cancer in 2004. They were at least 66 years old and were enrolled in fee-for-service Medicare during the study period. They had survived at least 3 years from diagnosis, and had no evidence of ongoing cancer treatment.

The 8,661 cancer survivors in the study were "frequency matched" with 17,322 cancer-free controls. Slightly more than half of the cancer group (4,559) had survived prostate cancer; 2,231 had survived colorectal cancer; and 1,871 survived breast cancer. The study period covered years 2 and 3 from day of diagnosis.

The final sample had a mean age of approximately 75 years; nearly two-thirds were men, and 85% were white. More than 88% in both case and control groups lived in an urban area.

There were 9 quality indicators for care of chronic conditions, and 19 for care of acute conditions. To calculate the percentage of survivors receiving appropriate care, investigators divided the number of cases and controls who received appropriate care by the number eligible for each indicator.

A summary analysis showed that among colorectal cancer survivors, there were four indicators of worse chronic care (chronic obstructive pulmonary disease visits, lipid monitoring after angina, diabetes eye exams, and diabetes monitoring), and three indicators of worse acute care (visits after acute MI and heart failure hospitalizations, and cholecystectomy), compared with controls.

Prostate cancer survivors had three indicators of worse acute care (ECG after heart failure, chest film after heart failure, and cholecystectomy), but two indicators of better chronic care (COPD and diabetes visits).

The breast cancer survivors did better on COPD and diabetes visits.

Quality indicators for the care of chronic conditions included the following:

• Visit frequency of 6 months for chronic stable angina, heart failure, COPD, and diabetes.

• Visit frequency of 12 months for transient ischemic attack (TIA).

• Cholesterol test every 6 months for patients with hypercholesterolemia who were hospitalized with acute MI.

• Lipid profile up to 1 year after initial diagnosis of angina.

• Yearly eye exam for diabetes patients.

• Glycosylated hemoglobin and fructosamine every 6 months for diabetes patients.

Quality indicators for the care of acute conditions included the following:

• Visits up to 4 weeks after discharge after hospitalization for acute MI, unstable angina, heart failure, cerebrovascular accident, TIA, diabetes, malignant or otherwise severe hypertension, or gastrointestinal bleed.

• Visits up to 2 weeks after discharge for patients hospitalized with depression.

• Visits up to 1 week after diagnosis of unstable angina (visit or hospitalization).

• ECG during emergency department visit for unstable angina.

• ECG up to 3 months after initial diagnosis of heart failure.

• ECG up 2 days of initial diagnosis of TIA.

• Chest radiograph up to 3 months after initial diagnosis of heart failure.

• Carotid imaging up to 2 weeks after initial diagnosis for patients hospitalized with carotid artery stroke.

• Carotid endarterectomy up to 2 months after carotid imaging for cerebrovascular accident patients with eventual carotid endarterectomy.

• Carotid endarterectomy up to 2 months after carotid imaging for TIA patients with eventual carotid endarterectomy.

• Cholecystectomy for patients with cholelithiasis plus cholecystitis, cholangitis, or gallstone pancreatitis.

• Arthroplasty or internal fixation of hip during hospital stay for hip fracture.

Among the study’s strengths, Dr. Snyder said that it examined the initial transition from acute cancer treatment to survivorship, an important time to ensure that survivors do not get lost in transition.

Discussant Lynne I. Wagner, Ph.D., of Northwestern University in Chicago said that this represented a novel contribution to the evidence base in survivorship care. "The comorbidity issues are extremely important. This is probably the tip of the iceberg in terms of what’s going on," she said.

The study was funded by the National Cancer Institute. Neither Dr. Snyder nor Dr. Wagner disclosed relevant relationships.

CHICAGO – The quality of care that older cancer survivors receive for comorbid conditions such as diabetes and heart failure varies by tumor type, according to a retrospective, cross-sectional analysis of database records for more than 25,000 people.

Colorectal cancer survivors fared the worst of three tumor cohorts studied. Compared with a control group of cancer-free patients, they were more likely to receive acute and chronic care that was subpar on a variety of measures, Claire Snyder, Ph.D., reported at the annual meeting of the American Society of Clinical Oncology.

Breast cancer survivors fared best, receiving equivalent acute and better chronic care than did cancer-free controls. Prostate cancer survivors came out somewhere in the middle, receiving worse acute care but better chronic care.

The study "does not explain why care was or was not provided," Dr. Snyder said, listing its limitations. She hopes to explore why survivor care varies by tumor type as well as possible relationships with cost, she added.

"The issue of comorbid-condition care in cancer survivors has been understudied. As our treatments improve and survivors live longer with a history of a cancer diagnosis, quality care for comorbid conditions takes on greater importance," said Dr. Snyder of Johns Hopkins University in Baltimore.

Cancer survivors’ health care needs include surveillance for recurrence and monitoring for the physical and psychosocial long-term and late effects of the disease and its treatment, she said. Their needs also include general primary and preventive care, and often care for comorbid conditions.

This study used data from the SEER (Surveillance, Epidemiology and End Results)–Medicare database, a cancer registry linked with Medicare claims data. The nation’s 17 SEER registries cover a representative sample of more than one-quarter of the U.S. population. Medicare claims data on noncancer controls who live in SEER regions were used for comparison.

The study population was diagnosed with locoregional breast, prostate, or colorectal cancer in 2004. They were at least 66 years old and were enrolled in fee-for-service Medicare during the study period. They had survived at least 3 years from diagnosis, and had no evidence of ongoing cancer treatment.

The 8,661 cancer survivors in the study were "frequency matched" with 17,322 cancer-free controls. Slightly more than half of the cancer group (4,559) had survived prostate cancer; 2,231 had survived colorectal cancer; and 1,871 survived breast cancer. The study period covered years 2 and 3 from day of diagnosis.

The final sample had a mean age of approximately 75 years; nearly two-thirds were men, and 85% were white. More than 88% in both case and control groups lived in an urban area.

There were 9 quality indicators for care of chronic conditions, and 19 for care of acute conditions. To calculate the percentage of survivors receiving appropriate care, investigators divided the number of cases and controls who received appropriate care by the number eligible for each indicator.

A summary analysis showed that among colorectal cancer survivors, there were four indicators of worse chronic care (chronic obstructive pulmonary disease visits, lipid monitoring after angina, diabetes eye exams, and diabetes monitoring), and three indicators of worse acute care (visits after acute MI and heart failure hospitalizations, and cholecystectomy), compared with controls.

Prostate cancer survivors had three indicators of worse acute care (ECG after heart failure, chest film after heart failure, and cholecystectomy), but two indicators of better chronic care (COPD and diabetes visits).

The breast cancer survivors did better on COPD and diabetes visits.

Quality indicators for the care of chronic conditions included the following:

• Visit frequency of 6 months for chronic stable angina, heart failure, COPD, and diabetes.

• Visit frequency of 12 months for transient ischemic attack (TIA).

• Cholesterol test every 6 months for patients with hypercholesterolemia who were hospitalized with acute MI.

• Lipid profile up to 1 year after initial diagnosis of angina.

• Yearly eye exam for diabetes patients.

• Glycosylated hemoglobin and fructosamine every 6 months for diabetes patients.

Quality indicators for the care of acute conditions included the following:

• Visits up to 4 weeks after discharge after hospitalization for acute MI, unstable angina, heart failure, cerebrovascular accident, TIA, diabetes, malignant or otherwise severe hypertension, or gastrointestinal bleed.

• Visits up to 2 weeks after discharge for patients hospitalized with depression.

• Visits up to 1 week after diagnosis of unstable angina (visit or hospitalization).

• ECG during emergency department visit for unstable angina.

• ECG up to 3 months after initial diagnosis of heart failure.

• ECG up 2 days of initial diagnosis of TIA.

• Chest radiograph up to 3 months after initial diagnosis of heart failure.

• Carotid imaging up to 2 weeks after initial diagnosis for patients hospitalized with carotid artery stroke.

• Carotid endarterectomy up to 2 months after carotid imaging for cerebrovascular accident patients with eventual carotid endarterectomy.

• Carotid endarterectomy up to 2 months after carotid imaging for TIA patients with eventual carotid endarterectomy.

• Cholecystectomy for patients with cholelithiasis plus cholecystitis, cholangitis, or gallstone pancreatitis.

• Arthroplasty or internal fixation of hip during hospital stay for hip fracture.

Among the study’s strengths, Dr. Snyder said that it examined the initial transition from acute cancer treatment to survivorship, an important time to ensure that survivors do not get lost in transition.

Discussant Lynne I. Wagner, Ph.D., of Northwestern University in Chicago said that this represented a novel contribution to the evidence base in survivorship care. "The comorbidity issues are extremely important. This is probably the tip of the iceberg in terms of what’s going on," she said.

The study was funded by the National Cancer Institute. Neither Dr. Snyder nor Dr. Wagner disclosed relevant relationships.

CHICAGO – The quality of care that older cancer survivors receive for comorbid conditions such as diabetes and heart failure varies by tumor type, according to a retrospective, cross-sectional analysis of database records for more than 25,000 people.

Colorectal cancer survivors fared the worst of three tumor cohorts studied. Compared with a control group of cancer-free patients, they were more likely to receive acute and chronic care that was subpar on a variety of measures, Claire Snyder, Ph.D., reported at the annual meeting of the American Society of Clinical Oncology.

Breast cancer survivors fared best, receiving equivalent acute and better chronic care than did cancer-free controls. Prostate cancer survivors came out somewhere in the middle, receiving worse acute care but better chronic care.

The study "does not explain why care was or was not provided," Dr. Snyder said, listing its limitations. She hopes to explore why survivor care varies by tumor type as well as possible relationships with cost, she added.

"The issue of comorbid-condition care in cancer survivors has been understudied. As our treatments improve and survivors live longer with a history of a cancer diagnosis, quality care for comorbid conditions takes on greater importance," said Dr. Snyder of Johns Hopkins University in Baltimore.

Cancer survivors’ health care needs include surveillance for recurrence and monitoring for the physical and psychosocial long-term and late effects of the disease and its treatment, she said. Their needs also include general primary and preventive care, and often care for comorbid conditions.

This study used data from the SEER (Surveillance, Epidemiology and End Results)–Medicare database, a cancer registry linked with Medicare claims data. The nation’s 17 SEER registries cover a representative sample of more than one-quarter of the U.S. population. Medicare claims data on noncancer controls who live in SEER regions were used for comparison.

The study population was diagnosed with locoregional breast, prostate, or colorectal cancer in 2004. They were at least 66 years old and were enrolled in fee-for-service Medicare during the study period. They had survived at least 3 years from diagnosis, and had no evidence of ongoing cancer treatment.

The 8,661 cancer survivors in the study were "frequency matched" with 17,322 cancer-free controls. Slightly more than half of the cancer group (4,559) had survived prostate cancer; 2,231 had survived colorectal cancer; and 1,871 survived breast cancer. The study period covered years 2 and 3 from day of diagnosis.

The final sample had a mean age of approximately 75 years; nearly two-thirds were men, and 85% were white. More than 88% in both case and control groups lived in an urban area.

There were 9 quality indicators for care of chronic conditions, and 19 for care of acute conditions. To calculate the percentage of survivors receiving appropriate care, investigators divided the number of cases and controls who received appropriate care by the number eligible for each indicator.

A summary analysis showed that among colorectal cancer survivors, there were four indicators of worse chronic care (chronic obstructive pulmonary disease visits, lipid monitoring after angina, diabetes eye exams, and diabetes monitoring), and three indicators of worse acute care (visits after acute MI and heart failure hospitalizations, and cholecystectomy), compared with controls.

Prostate cancer survivors had three indicators of worse acute care (ECG after heart failure, chest film after heart failure, and cholecystectomy), but two indicators of better chronic care (COPD and diabetes visits).

The breast cancer survivors did better on COPD and diabetes visits.

Quality indicators for the care of chronic conditions included the following:

• Visit frequency of 6 months for chronic stable angina, heart failure, COPD, and diabetes.

• Visit frequency of 12 months for transient ischemic attack (TIA).

• Cholesterol test every 6 months for patients with hypercholesterolemia who were hospitalized with acute MI.

• Lipid profile up to 1 year after initial diagnosis of angina.

• Yearly eye exam for diabetes patients.

• Glycosylated hemoglobin and fructosamine every 6 months for diabetes patients.

Quality indicators for the care of acute conditions included the following:

• Visits up to 4 weeks after discharge after hospitalization for acute MI, unstable angina, heart failure, cerebrovascular accident, TIA, diabetes, malignant or otherwise severe hypertension, or gastrointestinal bleed.

• Visits up to 2 weeks after discharge for patients hospitalized with depression.

• Visits up to 1 week after diagnosis of unstable angina (visit or hospitalization).

• ECG during emergency department visit for unstable angina.

• ECG up to 3 months after initial diagnosis of heart failure.

• ECG up 2 days of initial diagnosis of TIA.

• Chest radiograph up to 3 months after initial diagnosis of heart failure.

• Carotid imaging up to 2 weeks after initial diagnosis for patients hospitalized with carotid artery stroke.

• Carotid endarterectomy up to 2 months after carotid imaging for cerebrovascular accident patients with eventual carotid endarterectomy.

• Carotid endarterectomy up to 2 months after carotid imaging for TIA patients with eventual carotid endarterectomy.

• Cholecystectomy for patients with cholelithiasis plus cholecystitis, cholangitis, or gallstone pancreatitis.

• Arthroplasty or internal fixation of hip during hospital stay for hip fracture.

Among the study’s strengths, Dr. Snyder said that it examined the initial transition from acute cancer treatment to survivorship, an important time to ensure that survivors do not get lost in transition.

Discussant Lynne I. Wagner, Ph.D., of Northwestern University in Chicago said that this represented a novel contribution to the evidence base in survivorship care. "The comorbidity issues are extremely important. This is probably the tip of the iceberg in terms of what’s going on," she said.

The study was funded by the National Cancer Institute. Neither Dr. Snyder nor Dr. Wagner disclosed relevant relationships.

CHICAGO – The quality of care that older cancer survivors receive for comorbid conditions such as diabetes and heart failure varies by tumor type, according to a retrospective, cross-sectional analysis of database records for more than 25,000 people.

Colorectal cancer survivors fared the worst of three tumor cohorts studied. Compared with a control group of cancer-free patients, they were more likely to receive acute and chronic care that was subpar on a variety of measures, Claire Snyder, Ph.D., reported at the annual meeting of the American Society of Clinical Oncology.

Breast cancer survivors fared best, receiving equivalent acute and better chronic care than did cancer-free controls. Prostate cancer survivors came out somewhere in the middle, receiving worse acute care but better chronic care.

The study "does not explain why care was or was not provided," Dr. Snyder said, listing its limitations. She hopes to explore why survivor care varies by tumor type as well as possible relationships with cost, she added.

"The issue of comorbid-condition care in cancer survivors has been understudied. As our treatments improve and survivors live longer with a history of a cancer diagnosis, quality care for comorbid conditions takes on greater importance," said Dr. Snyder of Johns Hopkins University in Baltimore.

Cancer survivors’ health care needs include surveillance for recurrence and monitoring for the physical and psychosocial long-term and late effects of the disease and its treatment, she said. Their needs also include general primary and preventive care, and often care for comorbid conditions.

This study used data from the SEER (Surveillance, Epidemiology and End Results)–Medicare database, a cancer registry linked with Medicare claims data. The nation’s 17 SEER registries cover a representative sample of more than one-quarter of the U.S. population. Medicare claims data on noncancer controls who live in SEER regions were used for comparison.

The study population was diagnosed with locoregional breast, prostate, or colorectal cancer in 2004. They were at least 66 years old and were enrolled in fee-for-service Medicare during the study period. They had survived at least 3 years from diagnosis, and had no evidence of ongoing cancer treatment.

The 8,661 cancer survivors in the study were "frequency matched" with 17,322 cancer-free controls. Slightly more than half of the cancer group (4,559) had survived prostate cancer; 2,231 had survived colorectal cancer; and 1,871 survived breast cancer. The study period covered years 2 and 3 from day of diagnosis.

The final sample had a mean age of approximately 75 years; nearly two-thirds were men, and 85% were white. More than 88% in both case and control groups lived in an urban area.

There were 9 quality indicators for care of chronic conditions, and 19 for care of acute conditions. To calculate the percentage of survivors receiving appropriate care, investigators divided the number of cases and controls who received appropriate care by the number eligible for each indicator.

A summary analysis showed that among colorectal cancer survivors, there were four indicators of worse chronic care (chronic obstructive pulmonary disease visits, lipid monitoring after angina, diabetes eye exams, and diabetes monitoring), and three indicators of worse acute care (visits after acute MI and heart failure hospitalizations, and cholecystectomy), compared with controls.

Prostate cancer survivors had three indicators of worse acute care (ECG after heart failure, chest film after heart failure, and cholecystectomy), but two indicators of better chronic care (COPD and diabetes visits).

The breast cancer survivors did better on COPD and diabetes visits.

Quality indicators for the care of chronic conditions included the following:

• Visit frequency of 6 months for chronic stable angina, heart failure, COPD, and diabetes.

• Visit frequency of 12 months for transient ischemic attack (TIA).

• Cholesterol test every 6 months for patients with hypercholesterolemia who were hospitalized with acute MI.

• Lipid profile up to 1 year after initial diagnosis of angina.

• Yearly eye exam for diabetes patients.

• Glycosylated hemoglobin and fructosamine every 6 months for diabetes patients.

Quality indicators for the care of acute conditions included the following:

• Visits up to 4 weeks after discharge after hospitalization for acute MI, unstable angina, heart failure, cerebrovascular accident, TIA, diabetes, malignant or otherwise severe hypertension, or gastrointestinal bleed.

• Visits up to 2 weeks after discharge for patients hospitalized with depression.

• Visits up to 1 week after diagnosis of unstable angina (visit or hospitalization).

• ECG during emergency department visit for unstable angina.

• ECG up to 3 months after initial diagnosis of heart failure.

• ECG up 2 days of initial diagnosis of TIA.

• Chest radiograph up to 3 months after initial diagnosis of heart failure.

• Carotid imaging up to 2 weeks after initial diagnosis for patients hospitalized with carotid artery stroke.

• Carotid endarterectomy up to 2 months after carotid imaging for cerebrovascular accident patients with eventual carotid endarterectomy.

• Carotid endarterectomy up to 2 months after carotid imaging for TIA patients with eventual carotid endarterectomy.

• Cholecystectomy for patients with cholelithiasis plus cholecystitis, cholangitis, or gallstone pancreatitis.

• Arthroplasty or internal fixation of hip during hospital stay for hip fracture.

Among the study’s strengths, Dr. Snyder said that it examined the initial transition from acute cancer treatment to survivorship, an important time to ensure that survivors do not get lost in transition.

Discussant Lynne I. Wagner, Ph.D., of Northwestern University in Chicago said that this represented a novel contribution to the evidence base in survivorship care. "The comorbidity issues are extremely important. This is probably the tip of the iceberg in terms of what’s going on," she said.

The study was funded by the National Cancer Institute. Neither Dr. Snyder nor Dr. Wagner disclosed relevant relationships.