Bruce Wilson

PHILADELPHIA — A new Web-based tool may accurately predict the 10-year risk of local breast cancer recurrence in women who have had breast-conserving surgery, Dr. Mona Sanghani said at the annual meeting of the American Society for Therapeutic Radiology and Oncology.

The tool, named IBTR! for “Ipsilateral Breast Tumor Recurrence” calculates an evidence-based estimate of the 10-year ipsilateral breast tumor recurrence risk with and without the addition of whole breast radiation therapy. Online users at http://tufts-nemc.org/ibtr

The model assumes that all pathologic specimens have been microscopically assessed with hematoxylin and eosin staining of serial sections, and it is presumed that patients who are node positive (with the exception of micrometastatic lymph node disease) will receive chemotherapy. The tool indicates that the program is not intended for use in the postmastectomy setting, and is not meant to address patients with multicentric disease or with in situ-only disease.

The program is intended for use by health professionals to guide medical decision making regarding the use of radiation therapy in patients who have undergone breast-conserving surgery and appropriate axillary evaluation.

According to Dr. Sanghani, lead author of the report and an oncology resident at Tufts-New England Medical Center in Boston, a large database was not available to calculate local recurrence estimates across all the prognostic factors, so the model was constructed using published studies of breast-conserving surgery, both with and without radiation therapy.

The first step was to establish the baseline local recurrence (LR) rates in the overall breast-conserving therapy population. This was done by reviewing 11 randomized trials and constructing a random effects model, which yielded an LR rate of 7% in patients receiving breast-conserving surgery plus radiotherapy, and an LR of 24% for patients receiving breast-conserving surgery alone. “This was with an average data follow-up of 9–10 years,” Dr. Sanghani said.

The second step was to identify the important prognostic factors for local recurrence. Although the researchers had preferred to adhere to data from randomized clinical trials comparing breast-conserving therapy (BCT) alone versus BCT plus radiotherapy, they did not sufficiently address multiple risk factors (for example, margin status and lymphovascular invasion). So they included published single-institution data when necessary to compensate for gaps in the data. After this, they computed the approximate best estimate relative risk (RR) ratio for each prognostic factor. “After all these estimates were made, in an iterative fashion, we tested these RR ratios in the model against variations in all the other risk factors to ensure that the output for the model was clinically sound,” Dr. Sanghani said. “The model is constructed so that the RR for each prognostic factor independently modulates the baseline LR rate of 7% and 24%.”

Risk factors included in the model are patient age, margin status, lymphovascular invasion, use of tamoxifen, use of chemotherapy, tumor size, and tumor grade. Factors which were excluded because they did not have a sufficiently strong effect on local recurrence rates in the trials were lymph node status, estrogen- and progesterone-receptor status, presence of an extensive intraductal component, and histology.

“Our tool provides physicians with information regarding the risk of breast cancer returning in the same breast for any individual patient, which can then help them evaluate the potential benefit of additional treatments needed to cure the cancer, including radiation therapy,” said Dr. Sanghani. She cautioned that the tool needs to be validated by independent clinical data before it is widely used.

PHILADELPHIA — A new Web-based tool may accurately predict the 10-year risk of local breast cancer recurrence in women who have had breast-conserving surgery, Dr. Mona Sanghani said at the annual meeting of the American Society for Therapeutic Radiology and Oncology.

The tool, named IBTR! for “Ipsilateral Breast Tumor Recurrence” calculates an evidence-based estimate of the 10-year ipsilateral breast tumor recurrence risk with and without the addition of whole breast radiation therapy. Online users at http://tufts-nemc.org/ibtr

The model assumes that all pathologic specimens have been microscopically assessed with hematoxylin and eosin staining of serial sections, and it is presumed that patients who are node positive (with the exception of micrometastatic lymph node disease) will receive chemotherapy. The tool indicates that the program is not intended for use in the postmastectomy setting, and is not meant to address patients with multicentric disease or with in situ-only disease.

The program is intended for use by health professionals to guide medical decision making regarding the use of radiation therapy in patients who have undergone breast-conserving surgery and appropriate axillary evaluation.

According to Dr. Sanghani, lead author of the report and an oncology resident at Tufts-New England Medical Center in Boston, a large database was not available to calculate local recurrence estimates across all the prognostic factors, so the model was constructed using published studies of breast-conserving surgery, both with and without radiation therapy.

The first step was to establish the baseline local recurrence (LR) rates in the overall breast-conserving therapy population. This was done by reviewing 11 randomized trials and constructing a random effects model, which yielded an LR rate of 7% in patients receiving breast-conserving surgery plus radiotherapy, and an LR of 24% for patients receiving breast-conserving surgery alone. “This was with an average data follow-up of 9–10 years,” Dr. Sanghani said.

The second step was to identify the important prognostic factors for local recurrence. Although the researchers had preferred to adhere to data from randomized clinical trials comparing breast-conserving therapy (BCT) alone versus BCT plus radiotherapy, they did not sufficiently address multiple risk factors (for example, margin status and lymphovascular invasion). So they included published single-institution data when necessary to compensate for gaps in the data. After this, they computed the approximate best estimate relative risk (RR) ratio for each prognostic factor. “After all these estimates were made, in an iterative fashion, we tested these RR ratios in the model against variations in all the other risk factors to ensure that the output for the model was clinically sound,” Dr. Sanghani said. “The model is constructed so that the RR for each prognostic factor independently modulates the baseline LR rate of 7% and 24%.”

Risk factors included in the model are patient age, margin status, lymphovascular invasion, use of tamoxifen, use of chemotherapy, tumor size, and tumor grade. Factors which were excluded because they did not have a sufficiently strong effect on local recurrence rates in the trials were lymph node status, estrogen- and progesterone-receptor status, presence of an extensive intraductal component, and histology.

“Our tool provides physicians with information regarding the risk of breast cancer returning in the same breast for any individual patient, which can then help them evaluate the potential benefit of additional treatments needed to cure the cancer, including radiation therapy,” said Dr. Sanghani. She cautioned that the tool needs to be validated by independent clinical data before it is widely used.

PHILADELPHIA — A new Web-based tool may accurately predict the 10-year risk of local breast cancer recurrence in women who have had breast-conserving surgery, Dr. Mona Sanghani said at the annual meeting of the American Society for Therapeutic Radiology and Oncology.

The tool, named IBTR! for “Ipsilateral Breast Tumor Recurrence” calculates an evidence-based estimate of the 10-year ipsilateral breast tumor recurrence risk with and without the addition of whole breast radiation therapy. Online users at http://tufts-nemc.org/ibtr

The model assumes that all pathologic specimens have been microscopically assessed with hematoxylin and eosin staining of serial sections, and it is presumed that patients who are node positive (with the exception of micrometastatic lymph node disease) will receive chemotherapy. The tool indicates that the program is not intended for use in the postmastectomy setting, and is not meant to address patients with multicentric disease or with in situ-only disease.

The program is intended for use by health professionals to guide medical decision making regarding the use of radiation therapy in patients who have undergone breast-conserving surgery and appropriate axillary evaluation.

According to Dr. Sanghani, lead author of the report and an oncology resident at Tufts-New England Medical Center in Boston, a large database was not available to calculate local recurrence estimates across all the prognostic factors, so the model was constructed using published studies of breast-conserving surgery, both with and without radiation therapy.

The first step was to establish the baseline local recurrence (LR) rates in the overall breast-conserving therapy population. This was done by reviewing 11 randomized trials and constructing a random effects model, which yielded an LR rate of 7% in patients receiving breast-conserving surgery plus radiotherapy, and an LR of 24% for patients receiving breast-conserving surgery alone. “This was with an average data follow-up of 9–10 years,” Dr. Sanghani said.

The second step was to identify the important prognostic factors for local recurrence. Although the researchers had preferred to adhere to data from randomized clinical trials comparing breast-conserving therapy (BCT) alone versus BCT plus radiotherapy, they did not sufficiently address multiple risk factors (for example, margin status and lymphovascular invasion). So they included published single-institution data when necessary to compensate for gaps in the data. After this, they computed the approximate best estimate relative risk (RR) ratio for each prognostic factor. “After all these estimates were made, in an iterative fashion, we tested these RR ratios in the model against variations in all the other risk factors to ensure that the output for the model was clinically sound,” Dr. Sanghani said. “The model is constructed so that the RR for each prognostic factor independently modulates the baseline LR rate of 7% and 24%.”

Risk factors included in the model are patient age, margin status, lymphovascular invasion, use of tamoxifen, use of chemotherapy, tumor size, and tumor grade. Factors which were excluded because they did not have a sufficiently strong effect on local recurrence rates in the trials were lymph node status, estrogen- and progesterone-receptor status, presence of an extensive intraductal component, and histology.

“Our tool provides physicians with information regarding the risk of breast cancer returning in the same breast for any individual patient, which can then help them evaluate the potential benefit of additional treatments needed to cure the cancer, including radiation therapy,” said Dr. Sanghani. She cautioned that the tool needs to be validated by independent clinical data before it is widely used.

PHILADELPHIA — Adjuvant external beam radiation therapy with or without vaginal brachytherapy can lead to improved overall survival for some women with high-risk endometrial carcinoma, according to a study reported at the annual meeting of the American Society for Therapeutic Radiology and Oncology.

“Endometrial adenocarcinoma remains the most commonly diagnosed [gynecologic] malignancy in the United States, but optimal treatment for stage I and II disease remains controversial,” said Dr. Christopher M. Lee of the department of radiation oncology, Huntsman Cancer Hospital, Salt Lake City. He noted that selected high-risk subgroups have increased local-regional recurrence rates and decreased survival, but which of those patients might benefit from adjuvant radiation is still controversial.

In this retrospective analysis, Dr. Lee and colleagues utilized the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry database to identify women with stage IC/grade 3 and stage II endometrial carcinoma without N1 or M1 disease. Specifically, they extracted data from the SEER 11 registries and Alaska data set containing data on patients diagnosed between 1988 and 2001. They identified 4,010 patients—all of whom had undergone hysterectomy with bilateral salpingo-oophorectomy—and analyzed prognostic factors such as age, race, cancer stage, tumor grade, extent of surgery, and whether or not they had received postoperative external beam radiation therapy (EBRT) with or without brachytherapy. Of the patients, 31.3% had received EBRT and 26.2% had received EBRT plus brachytherapy. “It was interesting to us that 42.5% of this population had received no further adjuvant treatment,” Dr. Lee said.

A Kaplan-Meier analysis revealed that patients with stage II/grade 1 disease received no additional survival benefit from either EBRT or brachytherapy, alone or combined. However, patients with stage IC/grade 3–4, stage II/grade 2, and stage II/grade 3–4 disease all received additional benefit with EBRT plus or minus brachytherapy. “Of interest, there were significant improvements in overall survival between external beam radiation versus EBRT versus EBRT plus [brachytherapy] in both the stage IC high-grade and the stage II high-grade cohorts,” Dr. Lee said.

Further analysis revealed that older age, late diagnosis, black race, and no nodal exam at the time of hysterectomy all had a detrimental effect on survival. After controlling for these factors, the authors found that there was a significant overall survival advantage with EBRT plus or minus brachytherapy for patients with stage IC/grade 3–4, stage II/grade 2, and stage II/grade 3–4 disease, but not with stage II/grade 1 disease. Contrary to the prior results, there was no improvement in overall survival with the addition of brachytherapy to EBRT. These data show that “the improvement in overall survival is really due to the EBRT component” and not to the additional brachytherapy component,” Dr. Lee said.

Because of the retrospective nature of the trial, he cautioned against making too many conclusions about the data. “In the future, we would like to continue to look into and delineate the clinical and biological factors that would help us guide treatment and help us to account for the disparities we see between different patient cohorts, and to continue to develop a standardized and a risk-adaptive or stratified approach for adjuvant treatment for these patients,” Dr. Lee said.

PHILADELPHIA — Adjuvant external beam radiation therapy with or without vaginal brachytherapy can lead to improved overall survival for some women with high-risk endometrial carcinoma, according to a study reported at the annual meeting of the American Society for Therapeutic Radiology and Oncology.

“Endometrial adenocarcinoma remains the most commonly diagnosed [gynecologic] malignancy in the United States, but optimal treatment for stage I and II disease remains controversial,” said Dr. Christopher M. Lee of the department of radiation oncology, Huntsman Cancer Hospital, Salt Lake City. He noted that selected high-risk subgroups have increased local-regional recurrence rates and decreased survival, but which of those patients might benefit from adjuvant radiation is still controversial.

In this retrospective analysis, Dr. Lee and colleagues utilized the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry database to identify women with stage IC/grade 3 and stage II endometrial carcinoma without N1 or M1 disease. Specifically, they extracted data from the SEER 11 registries and Alaska data set containing data on patients diagnosed between 1988 and 2001. They identified 4,010 patients—all of whom had undergone hysterectomy with bilateral salpingo-oophorectomy—and analyzed prognostic factors such as age, race, cancer stage, tumor grade, extent of surgery, and whether or not they had received postoperative external beam radiation therapy (EBRT) with or without brachytherapy. Of the patients, 31.3% had received EBRT and 26.2% had received EBRT plus brachytherapy. “It was interesting to us that 42.5% of this population had received no further adjuvant treatment,” Dr. Lee said.

A Kaplan-Meier analysis revealed that patients with stage II/grade 1 disease received no additional survival benefit from either EBRT or brachytherapy, alone or combined. However, patients with stage IC/grade 3–4, stage II/grade 2, and stage II/grade 3–4 disease all received additional benefit with EBRT plus or minus brachytherapy. “Of interest, there were significant improvements in overall survival between external beam radiation versus EBRT versus EBRT plus [brachytherapy] in both the stage IC high-grade and the stage II high-grade cohorts,” Dr. Lee said.

Further analysis revealed that older age, late diagnosis, black race, and no nodal exam at the time of hysterectomy all had a detrimental effect on survival. After controlling for these factors, the authors found that there was a significant overall survival advantage with EBRT plus or minus brachytherapy for patients with stage IC/grade 3–4, stage II/grade 2, and stage II/grade 3–4 disease, but not with stage II/grade 1 disease. Contrary to the prior results, there was no improvement in overall survival with the addition of brachytherapy to EBRT. These data show that “the improvement in overall survival is really due to the EBRT component” and not to the additional brachytherapy component,” Dr. Lee said.

Because of the retrospective nature of the trial, he cautioned against making too many conclusions about the data. “In the future, we would like to continue to look into and delineate the clinical and biological factors that would help us guide treatment and help us to account for the disparities we see between different patient cohorts, and to continue to develop a standardized and a risk-adaptive or stratified approach for adjuvant treatment for these patients,” Dr. Lee said.

PHILADELPHIA — Adjuvant external beam radiation therapy with or without vaginal brachytherapy can lead to improved overall survival for some women with high-risk endometrial carcinoma, according to a study reported at the annual meeting of the American Society for Therapeutic Radiology and Oncology.

“Endometrial adenocarcinoma remains the most commonly diagnosed [gynecologic] malignancy in the United States, but optimal treatment for stage I and II disease remains controversial,” said Dr. Christopher M. Lee of the department of radiation oncology, Huntsman Cancer Hospital, Salt Lake City. He noted that selected high-risk subgroups have increased local-regional recurrence rates and decreased survival, but which of those patients might benefit from adjuvant radiation is still controversial.

In this retrospective analysis, Dr. Lee and colleagues utilized the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry database to identify women with stage IC/grade 3 and stage II endometrial carcinoma without N1 or M1 disease. Specifically, they extracted data from the SEER 11 registries and Alaska data set containing data on patients diagnosed between 1988 and 2001. They identified 4,010 patients—all of whom had undergone hysterectomy with bilateral salpingo-oophorectomy—and analyzed prognostic factors such as age, race, cancer stage, tumor grade, extent of surgery, and whether or not they had received postoperative external beam radiation therapy (EBRT) with or without brachytherapy. Of the patients, 31.3% had received EBRT and 26.2% had received EBRT plus brachytherapy. “It was interesting to us that 42.5% of this population had received no further adjuvant treatment,” Dr. Lee said.

A Kaplan-Meier analysis revealed that patients with stage II/grade 1 disease received no additional survival benefit from either EBRT or brachytherapy, alone or combined. However, patients with stage IC/grade 3–4, stage II/grade 2, and stage II/grade 3–4 disease all received additional benefit with EBRT plus or minus brachytherapy. “Of interest, there were significant improvements in overall survival between external beam radiation versus EBRT versus EBRT plus [brachytherapy] in both the stage IC high-grade and the stage II high-grade cohorts,” Dr. Lee said.

Further analysis revealed that older age, late diagnosis, black race, and no nodal exam at the time of hysterectomy all had a detrimental effect on survival. After controlling for these factors, the authors found that there was a significant overall survival advantage with EBRT plus or minus brachytherapy for patients with stage IC/grade 3–4, stage II/grade 2, and stage II/grade 3–4 disease, but not with stage II/grade 1 disease. Contrary to the prior results, there was no improvement in overall survival with the addition of brachytherapy to EBRT. These data show that “the improvement in overall survival is really due to the EBRT component” and not to the additional brachytherapy component,” Dr. Lee said.

Because of the retrospective nature of the trial, he cautioned against making too many conclusions about the data. “In the future, we would like to continue to look into and delineate the clinical and biological factors that would help us guide treatment and help us to account for the disparities we see between different patient cohorts, and to continue to develop a standardized and a risk-adaptive or stratified approach for adjuvant treatment for these patients,” Dr. Lee said.

PHILADELPHIA — Radiotherapy after mastectomy decreases breast cancer-specific and overall mortality, but only for patients who are at substantial risk of local-regional failure, such as those with node-positive disease, Paul McGale, Ph.D., reported at the annual meeting of the American Society for Therapeutic Radiology and Oncology.

Moreover, if local-regional failure is not a substantial risk, postmastectomy radiotherapy can increase overall mortality, said Dr. McGale, an investigator with the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) and a statistician with the Clinical Trial Service Unit, Oxford, England.

In an EBCTCG meta-analysis of 26 trials with 11,000 women who had undergone axillary clearance, radiotherapy did not reduce 15-year breast cancer-related mortality in women with no nodal involvement (pN0) and overall mortality was poorer with radiotherapy than without it. But on average, 15-year survival was improved for women with pN1–3 or pN4+ disease.

These results provide updated information to guide clinicians in their decisions about which breast cancer patients should receive radiotherapy. The 2000 National Institutes of Health consensus conference recommendations state that women with a high risk of locoregional tumor recurrence after mastectomy (those with pN4+ disease or an advanced primary tumor) would benefit from postoperative radiotherapy (www.consensus.nih.gov/2000/2000AdjuvantTherapyBreastCancer114 html.htm

These recommendations are now supported by the EBCTCG meta-analysis. But at that time, the role of postmastectomy radiotherapy for women with one to three positive lymph nodes was uncertain, and the EBCTCG findings reveal that they too can benefit from radiotherapy.

The EBCTCG was inaugurated in 1984–1985 with the aim of reviewing, every 5 years, the worldwide evidence on the treatment of early breast cancer through direct collaboration among the trialists. According to Dr. McGale, “systematic overviews can help limit selective biases from undue emphasis on particular studies and also help limit random errors in assessing long-term outcome.” Two reports from the fourth 5-year cycle were published last year (Lancet 2005;365:1687–717; Lancet 2005;366:2087–106). The current cycle of data collection involves more than 150 trial centers with more than 300,000 women with breast cancer randomized to approximately 400 trials over the past few decades.

During the first 9 years of the meta-analysis, 5,000 women died, and from year 10 onward, 2,000 women died, Dr. McGale said. In all trials, radiotherapy was directed at the axilla or supraclavicular fossa, and in most trials, it involved the chest wall and internal mammary chain. A total of 34% of 1,847 node-negative patients and 67% of 9,106 node-positive patients received systemic therapy.

The meta-analysis showed that at 15 years, radiotherapy had no significant effect on breast cancer mortality in women with pN0 disease; however, women with pN1–3 or pN4+ disease who received radiotherapy had lower mortality rates than those who did not. With regard to all-cause mortality, radiotherapy had a clear detrimental effect on patients with pN0 disease but significantly benefited patients with nodal involvement. (See box.)

Dr. McGale noted that overall mortality after radiotherapy is a balance of benefits and hazards. “With better radiotherapy regimens, reductions in breast cancer mortality may be more, and hazards of radiotherapy may be less. If absolute recurrence risks are lower nowadays, absolute gains from radiotherapy may be correspondingly lower,” he said.

In a discussion, Dr. Abram Recht of the department of radiation oncology at Harvard Medical School, Boston, noted that although the EBCTCG meta-analysis has the typical advantages of meta-analyses (large patient numbers, reduction of publication bias), it has limited or no data on important prognostic factors, such as histopathology and hormone receptor status. Also, the efficacy and toxicity of treatments used in different trials may vary markedly, but these factors tend to be overlooked. And finally, the results do not give information about the long-term toxicity of more modern postmastectomy radiotherapy regimens, especially in combination with cardiotoxic systemic therapy, he said.

ELSEVIER GLOBAL MEDICAL NEWS

PHILADELPHIA — Radiotherapy after mastectomy decreases breast cancer-specific and overall mortality, but only for patients who are at substantial risk of local-regional failure, such as those with node-positive disease, Paul McGale, Ph.D., reported at the annual meeting of the American Society for Therapeutic Radiology and Oncology.

Moreover, if local-regional failure is not a substantial risk, postmastectomy radiotherapy can increase overall mortality, said Dr. McGale, an investigator with the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) and a statistician with the Clinical Trial Service Unit, Oxford, England.

In an EBCTCG meta-analysis of 26 trials with 11,000 women who had undergone axillary clearance, radiotherapy did not reduce 15-year breast cancer-related mortality in women with no nodal involvement (pN0) and overall mortality was poorer with radiotherapy than without it. But on average, 15-year survival was improved for women with pN1–3 or pN4+ disease.

These results provide updated information to guide clinicians in their decisions about which breast cancer patients should receive radiotherapy. The 2000 National Institutes of Health consensus conference recommendations state that women with a high risk of locoregional tumor recurrence after mastectomy (those with pN4+ disease or an advanced primary tumor) would benefit from postoperative radiotherapy (www.consensus.nih.gov/2000/2000AdjuvantTherapyBreastCancer114 html.htm

These recommendations are now supported by the EBCTCG meta-analysis. But at that time, the role of postmastectomy radiotherapy for women with one to three positive lymph nodes was uncertain, and the EBCTCG findings reveal that they too can benefit from radiotherapy.

The EBCTCG was inaugurated in 1984–1985 with the aim of reviewing, every 5 years, the worldwide evidence on the treatment of early breast cancer through direct collaboration among the trialists. According to Dr. McGale, “systematic overviews can help limit selective biases from undue emphasis on particular studies and also help limit random errors in assessing long-term outcome.” Two reports from the fourth 5-year cycle were published last year (Lancet 2005;365:1687–717; Lancet 2005;366:2087–106). The current cycle of data collection involves more than 150 trial centers with more than 300,000 women with breast cancer randomized to approximately 400 trials over the past few decades.

During the first 9 years of the meta-analysis, 5,000 women died, and from year 10 onward, 2,000 women died, Dr. McGale said. In all trials, radiotherapy was directed at the axilla or supraclavicular fossa, and in most trials, it involved the chest wall and internal mammary chain. A total of 34% of 1,847 node-negative patients and 67% of 9,106 node-positive patients received systemic therapy.

The meta-analysis showed that at 15 years, radiotherapy had no significant effect on breast cancer mortality in women with pN0 disease; however, women with pN1–3 or pN4+ disease who received radiotherapy had lower mortality rates than those who did not. With regard to all-cause mortality, radiotherapy had a clear detrimental effect on patients with pN0 disease but significantly benefited patients with nodal involvement. (See box.)

Dr. McGale noted that overall mortality after radiotherapy is a balance of benefits and hazards. “With better radiotherapy regimens, reductions in breast cancer mortality may be more, and hazards of radiotherapy may be less. If absolute recurrence risks are lower nowadays, absolute gains from radiotherapy may be correspondingly lower,” he said.

In a discussion, Dr. Abram Recht of the department of radiation oncology at Harvard Medical School, Boston, noted that although the EBCTCG meta-analysis has the typical advantages of meta-analyses (large patient numbers, reduction of publication bias), it has limited or no data on important prognostic factors, such as histopathology and hormone receptor status. Also, the efficacy and toxicity of treatments used in different trials may vary markedly, but these factors tend to be overlooked. And finally, the results do not give information about the long-term toxicity of more modern postmastectomy radiotherapy regimens, especially in combination with cardiotoxic systemic therapy, he said.

ELSEVIER GLOBAL MEDICAL NEWS

PHILADELPHIA — Radiotherapy after mastectomy decreases breast cancer-specific and overall mortality, but only for patients who are at substantial risk of local-regional failure, such as those with node-positive disease, Paul McGale, Ph.D., reported at the annual meeting of the American Society for Therapeutic Radiology and Oncology.

Moreover, if local-regional failure is not a substantial risk, postmastectomy radiotherapy can increase overall mortality, said Dr. McGale, an investigator with the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) and a statistician with the Clinical Trial Service Unit, Oxford, England.

In an EBCTCG meta-analysis of 26 trials with 11,000 women who had undergone axillary clearance, radiotherapy did not reduce 15-year breast cancer-related mortality in women with no nodal involvement (pN0) and overall mortality was poorer with radiotherapy than without it. But on average, 15-year survival was improved for women with pN1–3 or pN4+ disease.

These results provide updated information to guide clinicians in their decisions about which breast cancer patients should receive radiotherapy. The 2000 National Institutes of Health consensus conference recommendations state that women with a high risk of locoregional tumor recurrence after mastectomy (those with pN4+ disease or an advanced primary tumor) would benefit from postoperative radiotherapy (www.consensus.nih.gov/2000/2000AdjuvantTherapyBreastCancer114 html.htm

These recommendations are now supported by the EBCTCG meta-analysis. But at that time, the role of postmastectomy radiotherapy for women with one to three positive lymph nodes was uncertain, and the EBCTCG findings reveal that they too can benefit from radiotherapy.

The EBCTCG was inaugurated in 1984–1985 with the aim of reviewing, every 5 years, the worldwide evidence on the treatment of early breast cancer through direct collaboration among the trialists. According to Dr. McGale, “systematic overviews can help limit selective biases from undue emphasis on particular studies and also help limit random errors in assessing long-term outcome.” Two reports from the fourth 5-year cycle were published last year (Lancet 2005;365:1687–717; Lancet 2005;366:2087–106). The current cycle of data collection involves more than 150 trial centers with more than 300,000 women with breast cancer randomized to approximately 400 trials over the past few decades.

During the first 9 years of the meta-analysis, 5,000 women died, and from year 10 onward, 2,000 women died, Dr. McGale said. In all trials, radiotherapy was directed at the axilla or supraclavicular fossa, and in most trials, it involved the chest wall and internal mammary chain. A total of 34% of 1,847 node-negative patients and 67% of 9,106 node-positive patients received systemic therapy.

The meta-analysis showed that at 15 years, radiotherapy had no significant effect on breast cancer mortality in women with pN0 disease; however, women with pN1–3 or pN4+ disease who received radiotherapy had lower mortality rates than those who did not. With regard to all-cause mortality, radiotherapy had a clear detrimental effect on patients with pN0 disease but significantly benefited patients with nodal involvement. (See box.)

Dr. McGale noted that overall mortality after radiotherapy is a balance of benefits and hazards. “With better radiotherapy regimens, reductions in breast cancer mortality may be more, and hazards of radiotherapy may be less. If absolute recurrence risks are lower nowadays, absolute gains from radiotherapy may be correspondingly lower,” he said.

In a discussion, Dr. Abram Recht of the department of radiation oncology at Harvard Medical School, Boston, noted that although the EBCTCG meta-analysis has the typical advantages of meta-analyses (large patient numbers, reduction of publication bias), it has limited or no data on important prognostic factors, such as histopathology and hormone receptor status. Also, the efficacy and toxicity of treatments used in different trials may vary markedly, but these factors tend to be overlooked. And finally, the results do not give information about the long-term toxicity of more modern postmastectomy radiotherapy regimens, especially in combination with cardiotoxic systemic therapy, he said.

ELSEVIER GLOBAL MEDICAL NEWS