Federal Practitioner

INTRODUCTION

Medulloblastoma (MB) is rarely seen in adulthood. Treatment guidelines are derived from studies of the pediatric population, results favoring the Packer regimen (cisplatin plus cyclophosphamide or lomustine plus vincristine). MB rarely has extraneural metastases, especially the bone marrow.

CASE PRESENTATION

A 32-year-old female with a past medical history of cerebellar MB confirmed on surgical pathology status post resection, weekly radiation and vincristine treatment presented to us in clinic to re-establish care. She was lost to follow-up 9 months after initial diagnosis and wished to continue treatment. She was started on Lomustine, Cisplatin and Vincristine after discussion with our colleagues at MSKCC, where she had received her initial treatment. After cycle three, she developed intractable bone pain and pancytopenia. Bone marrow biopsy revealed metastasis of Sonic Hedgehog Desmoplastic/nodular variant MB. PET and CT imaging confirmed metastatic disease in the bone marrow and repeat MRI brain showed abnormal nodular enhancement. CSF analysis to assess for spinal metastasis was negative. The patient was started on Temozolomide, Irinotecan and Bevacizumab with significant improvement in bone pain and radiological improvement noted on PET and CT scans. After cycle six, the patient had increased bone pain and repeat FDG-PET showed increased uptake, however, she continued to receive treatment and her pain has improved off narcotics.

DISCUSSION

We highlight a case of adult MB in the bone marrow responsive to temozolomide, irinotecan and bevacizumab. We conducted a literature search using PubMed, Medline and Web of Science between 1990 to 2022. In 2021, COG Phase 2 screening trial showed bevacizumab, temozolamide/irinotecan therapy significantly reduced the risk of death with recurrent MBs, two studies included patients up to 21 and 23 years of age. Other modalities showing some response include Vincristine plus cyclophosphamide as well as high dose carboplatin, thiotepa and etoposide alongside autologous SCT. Vismodegib has also shown varied response of 15 months in two adults with extraneural MB metastasis. Given the unique entity of adult MB and extraneural metastasis, limitations include small sample and lack of generalizability.

CONCLUSIONS

Extraneural metastasis of MB yields a poor prognosis. Future considerations include randomized trials to establish efficacy of Temozolomide, Irinotecan plus Bevacizumab in this population.

INTRODUCTION

Medulloblastoma (MB) is rarely seen in adulthood. Treatment guidelines are derived from studies of the pediatric population, results favoring the Packer regimen (cisplatin plus cyclophosphamide or lomustine plus vincristine). MB rarely has extraneural metastases, especially the bone marrow.

CASE PRESENTATION

A 32-year-old female with a past medical history of cerebellar MB confirmed on surgical pathology status post resection, weekly radiation and vincristine treatment presented to us in clinic to re-establish care. She was lost to follow-up 9 months after initial diagnosis and wished to continue treatment. She was started on Lomustine, Cisplatin and Vincristine after discussion with our colleagues at MSKCC, where she had received her initial treatment. After cycle three, she developed intractable bone pain and pancytopenia. Bone marrow biopsy revealed metastasis of Sonic Hedgehog Desmoplastic/nodular variant MB. PET and CT imaging confirmed metastatic disease in the bone marrow and repeat MRI brain showed abnormal nodular enhancement. CSF analysis to assess for spinal metastasis was negative. The patient was started on Temozolomide, Irinotecan and Bevacizumab with significant improvement in bone pain and radiological improvement noted on PET and CT scans. After cycle six, the patient had increased bone pain and repeat FDG-PET showed increased uptake, however, she continued to receive treatment and her pain has improved off narcotics.

DISCUSSION

We highlight a case of adult MB in the bone marrow responsive to temozolomide, irinotecan and bevacizumab. We conducted a literature search using PubMed, Medline and Web of Science between 1990 to 2022. In 2021, COG Phase 2 screening trial showed bevacizumab, temozolamide/irinotecan therapy significantly reduced the risk of death with recurrent MBs, two studies included patients up to 21 and 23 years of age. Other modalities showing some response include Vincristine plus cyclophosphamide as well as high dose carboplatin, thiotepa and etoposide alongside autologous SCT. Vismodegib has also shown varied response of 15 months in two adults with extraneural MB metastasis. Given the unique entity of adult MB and extraneural metastasis, limitations include small sample and lack of generalizability.

CONCLUSIONS

Extraneural metastasis of MB yields a poor prognosis. Future considerations include randomized trials to establish efficacy of Temozolomide, Irinotecan plus Bevacizumab in this population.

INTRODUCTION

Medulloblastoma (MB) is rarely seen in adulthood. Treatment guidelines are derived from studies of the pediatric population, results favoring the Packer regimen (cisplatin plus cyclophosphamide or lomustine plus vincristine). MB rarely has extraneural metastases, especially the bone marrow.

CASE PRESENTATION

A 32-year-old female with a past medical history of cerebellar MB confirmed on surgical pathology status post resection, weekly radiation and vincristine treatment presented to us in clinic to re-establish care. She was lost to follow-up 9 months after initial diagnosis and wished to continue treatment. She was started on Lomustine, Cisplatin and Vincristine after discussion with our colleagues at MSKCC, where she had received her initial treatment. After cycle three, she developed intractable bone pain and pancytopenia. Bone marrow biopsy revealed metastasis of Sonic Hedgehog Desmoplastic/nodular variant MB. PET and CT imaging confirmed metastatic disease in the bone marrow and repeat MRI brain showed abnormal nodular enhancement. CSF analysis to assess for spinal metastasis was negative. The patient was started on Temozolomide, Irinotecan and Bevacizumab with significant improvement in bone pain and radiological improvement noted on PET and CT scans. After cycle six, the patient had increased bone pain and repeat FDG-PET showed increased uptake, however, she continued to receive treatment and her pain has improved off narcotics.

DISCUSSION

We highlight a case of adult MB in the bone marrow responsive to temozolomide, irinotecan and bevacizumab. We conducted a literature search using PubMed, Medline and Web of Science between 1990 to 2022. In 2021, COG Phase 2 screening trial showed bevacizumab, temozolamide/irinotecan therapy significantly reduced the risk of death with recurrent MBs, two studies included patients up to 21 and 23 years of age. Other modalities showing some response include Vincristine plus cyclophosphamide as well as high dose carboplatin, thiotepa and etoposide alongside autologous SCT. Vismodegib has also shown varied response of 15 months in two adults with extraneural MB metastasis. Given the unique entity of adult MB and extraneural metastasis, limitations include small sample and lack of generalizability.

CONCLUSIONS

Extraneural metastasis of MB yields a poor prognosis. Future considerations include randomized trials to establish efficacy of Temozolomide, Irinotecan plus Bevacizumab in this population.

BACKGROUND/PURPOSE

Tumor lysis syndrome (TLS) occurs when malignant cells rapidly break down. This may lead to hyperuricemia, hyperkalemia, hyperphosphatemia, and/or hypocalcemia. Rasburicase reduces uric acid in cancer patients undergoing anti-cancer therapy. However, caution is required as rasburicase is contraindicated for patients with glucose- 6-phosphate dehydrogenase (G6PD) deficiency due to the increased risk of hemolysis. G6PD deficiency is more prevalent among African Americans (AA), affecting approximately 12% of this population. The FDA recommends testing for G6PD deficiency in higher risk groups before administering rasburicase.

METHODS

A retrospective analysis was conducted at the Louis Stokes Cleveland VAMC from February 1, 2018, to January 31, 2023 addressing appropriate use of rasburicase and incidence of G6PD deficiency and hemolysis. Appropriate use was defined by: TLS (2 or more: uric acid ≥ 8 or 25% increase; K+ ≥ 6.0 or 25% increase; Phos > 4.5mg/dL, or 25% increase; or calcium < 7, or 25% decrease, from baseline) or at high risk for TLS (CLL: venetoclax use w/lymph node > 10cm or WBC > 25k and elevated uric acid; AML: WBC > 100k; ALL: WBC > 100k and LDH 2x ULN; Burkitt lymphoma: LDH 2x ULN).

RESULTS

50 patients were identified who received rasburicase. 21/50 (42%) did not meet criteria for appropriate use. 44/50 (88%) underwent G6PD testing. The average time from G6PD testing order to obtaining the results was 3.4 days; 18/50 patients (36%) had G6PD resulted prior to rasburicase administration, and 26 patients (52%) received rasburicase prior to G6PD results. Overall, 13/50 (26%) were AA. Of the AA pts, 12/13 (92%) were tested for G6PD. Of these 12, 1/12 was found to be G6PD deficient and this patient experienced G6PD deficiency-induced hemolysis after rasburicase. None of the non-AA pts (0/31) tested were found to be G6PD deficient.

IMPLICATIONS

There was a high (42%) level of inappropriate use of rasburicase. G6PD deficiency was uncommon and only found in the AA population. To reduce inappropriate use, rasburicase orders will be restricted to medical oncology. G6PD testing will be limited to AA pts, with pathology to develop a rapid turnaround time for results prior to rasburicase administration to prevent hemolysis.

BACKGROUND/PURPOSE

Tumor lysis syndrome (TLS) occurs when malignant cells rapidly break down. This may lead to hyperuricemia, hyperkalemia, hyperphosphatemia, and/or hypocalcemia. Rasburicase reduces uric acid in cancer patients undergoing anti-cancer therapy. However, caution is required as rasburicase is contraindicated for patients with glucose- 6-phosphate dehydrogenase (G6PD) deficiency due to the increased risk of hemolysis. G6PD deficiency is more prevalent among African Americans (AA), affecting approximately 12% of this population. The FDA recommends testing for G6PD deficiency in higher risk groups before administering rasburicase.

METHODS

A retrospective analysis was conducted at the Louis Stokes Cleveland VAMC from February 1, 2018, to January 31, 2023 addressing appropriate use of rasburicase and incidence of G6PD deficiency and hemolysis. Appropriate use was defined by: TLS (2 or more: uric acid ≥ 8 or 25% increase; K+ ≥ 6.0 or 25% increase; Phos > 4.5mg/dL, or 25% increase; or calcium < 7, or 25% decrease, from baseline) or at high risk for TLS (CLL: venetoclax use w/lymph node > 10cm or WBC > 25k and elevated uric acid; AML: WBC > 100k; ALL: WBC > 100k and LDH 2x ULN; Burkitt lymphoma: LDH 2x ULN).

RESULTS

50 patients were identified who received rasburicase. 21/50 (42%) did not meet criteria for appropriate use. 44/50 (88%) underwent G6PD testing. The average time from G6PD testing order to obtaining the results was 3.4 days; 18/50 patients (36%) had G6PD resulted prior to rasburicase administration, and 26 patients (52%) received rasburicase prior to G6PD results. Overall, 13/50 (26%) were AA. Of the AA pts, 12/13 (92%) were tested for G6PD. Of these 12, 1/12 was found to be G6PD deficient and this patient experienced G6PD deficiency-induced hemolysis after rasburicase. None of the non-AA pts (0/31) tested were found to be G6PD deficient.

IMPLICATIONS

There was a high (42%) level of inappropriate use of rasburicase. G6PD deficiency was uncommon and only found in the AA population. To reduce inappropriate use, rasburicase orders will be restricted to medical oncology. G6PD testing will be limited to AA pts, with pathology to develop a rapid turnaround time for results prior to rasburicase administration to prevent hemolysis.

BACKGROUND/PURPOSE

Tumor lysis syndrome (TLS) occurs when malignant cells rapidly break down. This may lead to hyperuricemia, hyperkalemia, hyperphosphatemia, and/or hypocalcemia. Rasburicase reduces uric acid in cancer patients undergoing anti-cancer therapy. However, caution is required as rasburicase is contraindicated for patients with glucose- 6-phosphate dehydrogenase (G6PD) deficiency due to the increased risk of hemolysis. G6PD deficiency is more prevalent among African Americans (AA), affecting approximately 12% of this population. The FDA recommends testing for G6PD deficiency in higher risk groups before administering rasburicase.

METHODS

A retrospective analysis was conducted at the Louis Stokes Cleveland VAMC from February 1, 2018, to January 31, 2023 addressing appropriate use of rasburicase and incidence of G6PD deficiency and hemolysis. Appropriate use was defined by: TLS (2 or more: uric acid ≥ 8 or 25% increase; K+ ≥ 6.0 or 25% increase; Phos > 4.5mg/dL, or 25% increase; or calcium < 7, or 25% decrease, from baseline) or at high risk for TLS (CLL: venetoclax use w/lymph node > 10cm or WBC > 25k and elevated uric acid; AML: WBC > 100k; ALL: WBC > 100k and LDH 2x ULN; Burkitt lymphoma: LDH 2x ULN).

RESULTS

50 patients were identified who received rasburicase. 21/50 (42%) did not meet criteria for appropriate use. 44/50 (88%) underwent G6PD testing. The average time from G6PD testing order to obtaining the results was 3.4 days; 18/50 patients (36%) had G6PD resulted prior to rasburicase administration, and 26 patients (52%) received rasburicase prior to G6PD results. Overall, 13/50 (26%) were AA. Of the AA pts, 12/13 (92%) were tested for G6PD. Of these 12, 1/12 was found to be G6PD deficient and this patient experienced G6PD deficiency-induced hemolysis after rasburicase. None of the non-AA pts (0/31) tested were found to be G6PD deficient.

IMPLICATIONS

There was a high (42%) level of inappropriate use of rasburicase. G6PD deficiency was uncommon and only found in the AA population. To reduce inappropriate use, rasburicase orders will be restricted to medical oncology. G6PD testing will be limited to AA pts, with pathology to develop a rapid turnaround time for results prior to rasburicase administration to prevent hemolysis.

BACKGROUND

Minimal residual disease (MRD) testing in myeloma has been shown to be a strong prognostic marker for progression-free and overall survival. Limited data suggest MRD results may also be useful for therapy discontinuation decisions. The clonoSEQ Assay utilizes next generation sequencing involving a bone marrow sample, obtained at the time of diagnosis, to identify patient-specific sequence(s).

DISCUSSION

The same methodology is then applied later to assess for MRD. Although widely adopted at most US academic centers, there has been limited use of MRD across VA centers. In 2022 the Cleveland Louis Stokes VAMC partnered with Adaptive Biotechnologies to develop a process for MRD/clonoSEQ testing in myeloma pts. Hematology, Pathology, Medicine, Administration and Adaptive Biotechnologies representatives met to develop a streamlined process for ordering, sample procurement, billing and result documentation. In 5/2022 the 1st specimen was sent. EQUATE is a national cooperative group trial requiring baseline clono- SEQ testing with a positive sequence ID. Daratumumab hyaluronidase (part of standard treatment) is provided to the institution at no cost on the trial but otherwise would cost the VA $5,797.38/dose. clonoSEQ costs VA $1950/test. There have been 14 specimens sent involving 12 pts: 12 baseline marrow and 2 for MRD (posttransplant). All of the baseline specimens were found to have an identifiable sequence. Both of the MRD tracking specimens were positive. The average turnaround time for clonoSEQ results was 13.2 days (range 7 to 18 days). 4 of the 12 pts with a positive initial clonoSEQ ID qualified for the EQUATE trial but would not have been deemed eligible without the baseline clonoSEQ results. 2 of these pts have enrolled on the trial and started treatment. Costs for 14 clonoSEQ tests: $27,300. Estimated cost savings for the 2 pts enrolled onto EQUATE: $127, 542.36/pt/year= $255,084.72/year. Overall cost savings: $227,784.72.

CONCLUSIONS

An efficient process for baseline and post-treatment (MRD) clonoSEQ testing in myeloma pts was developed. Although expensive, use of this test resulted in significant overall cost savings by allowing enrollment onto a clinical trial. In addition, if studies determine that negative MRD results can guide therapeutic decisions, use of clonoSEQ testing may result in further benefits.

BACKGROUND

Minimal residual disease (MRD) testing in myeloma has been shown to be a strong prognostic marker for progression-free and overall survival. Limited data suggest MRD results may also be useful for therapy discontinuation decisions. The clonoSEQ Assay utilizes next generation sequencing involving a bone marrow sample, obtained at the time of diagnosis, to identify patient-specific sequence(s).

DISCUSSION

The same methodology is then applied later to assess for MRD. Although widely adopted at most US academic centers, there has been limited use of MRD across VA centers. In 2022 the Cleveland Louis Stokes VAMC partnered with Adaptive Biotechnologies to develop a process for MRD/clonoSEQ testing in myeloma pts. Hematology, Pathology, Medicine, Administration and Adaptive Biotechnologies representatives met to develop a streamlined process for ordering, sample procurement, billing and result documentation. In 5/2022 the 1st specimen was sent. EQUATE is a national cooperative group trial requiring baseline clono- SEQ testing with a positive sequence ID. Daratumumab hyaluronidase (part of standard treatment) is provided to the institution at no cost on the trial but otherwise would cost the VA $5,797.38/dose. clonoSEQ costs VA $1950/test. There have been 14 specimens sent involving 12 pts: 12 baseline marrow and 2 for MRD (posttransplant). All of the baseline specimens were found to have an identifiable sequence. Both of the MRD tracking specimens were positive. The average turnaround time for clonoSEQ results was 13.2 days (range 7 to 18 days). 4 of the 12 pts with a positive initial clonoSEQ ID qualified for the EQUATE trial but would not have been deemed eligible without the baseline clonoSEQ results. 2 of these pts have enrolled on the trial and started treatment. Costs for 14 clonoSEQ tests: $27,300. Estimated cost savings for the 2 pts enrolled onto EQUATE: $127, 542.36/pt/year= $255,084.72/year. Overall cost savings: $227,784.72.

CONCLUSIONS

An efficient process for baseline and post-treatment (MRD) clonoSEQ testing in myeloma pts was developed. Although expensive, use of this test resulted in significant overall cost savings by allowing enrollment onto a clinical trial. In addition, if studies determine that negative MRD results can guide therapeutic decisions, use of clonoSEQ testing may result in further benefits.

BACKGROUND

Minimal residual disease (MRD) testing in myeloma has been shown to be a strong prognostic marker for progression-free and overall survival. Limited data suggest MRD results may also be useful for therapy discontinuation decisions. The clonoSEQ Assay utilizes next generation sequencing involving a bone marrow sample, obtained at the time of diagnosis, to identify patient-specific sequence(s).

DISCUSSION

The same methodology is then applied later to assess for MRD. Although widely adopted at most US academic centers, there has been limited use of MRD across VA centers. In 2022 the Cleveland Louis Stokes VAMC partnered with Adaptive Biotechnologies to develop a process for MRD/clonoSEQ testing in myeloma pts. Hematology, Pathology, Medicine, Administration and Adaptive Biotechnologies representatives met to develop a streamlined process for ordering, sample procurement, billing and result documentation. In 5/2022 the 1st specimen was sent. EQUATE is a national cooperative group trial requiring baseline clono- SEQ testing with a positive sequence ID. Daratumumab hyaluronidase (part of standard treatment) is provided to the institution at no cost on the trial but otherwise would cost the VA $5,797.38/dose. clonoSEQ costs VA $1950/test. There have been 14 specimens sent involving 12 pts: 12 baseline marrow and 2 for MRD (posttransplant). All of the baseline specimens were found to have an identifiable sequence. Both of the MRD tracking specimens were positive. The average turnaround time for clonoSEQ results was 13.2 days (range 7 to 18 days). 4 of the 12 pts with a positive initial clonoSEQ ID qualified for the EQUATE trial but would not have been deemed eligible without the baseline clonoSEQ results. 2 of these pts have enrolled on the trial and started treatment. Costs for 14 clonoSEQ tests: $27,300. Estimated cost savings for the 2 pts enrolled onto EQUATE: $127, 542.36/pt/year= $255,084.72/year. Overall cost savings: $227,784.72.

CONCLUSIONS

An efficient process for baseline and post-treatment (MRD) clonoSEQ testing in myeloma pts was developed. Although expensive, use of this test resulted in significant overall cost savings by allowing enrollment onto a clinical trial. In addition, if studies determine that negative MRD results can guide therapeutic decisions, use of clonoSEQ testing may result in further benefits.

PURPOSE

To analyze associations between colorectal cancer progression and diet scores calculated using published scoring approaches for three dietary patterns: Healthy Eating Index (HEI), Mediterranean Diet (Mediterranean), and Dietary Approaches to Stop Hypertension Diet (DASH).

BACKGROUND

Little is known about whether longterm risk for progression to colorectal cancer is associated with recommended healthy dietary patterns among US veterans. Previous studies of veterans have shown higher intake of fiber and vitamin D reduced risk, and red meat increased risk for finding colorectal cancer precursors during colonoscopy. However, studying dietary patterns in aggregate may be more clinically relevant for longitudinal studies of colorectal cancer prevention.

METHODS

3,121 asymptomatic US veterans aged 50-75 received colonoscopy between 1994-97 and were followed through 2009. Most significant colonoscopy findings (MSCF) across the study period were: (i) no neoplasia (NN), (ii) non-advanced adenomas (NAAs) or (iii) advanced neoplasia (AN). Baseline dietary questionnaire data were used to calculate three dietary pattern (HEI, Mediterranean, and DASH) scores.

DATA ANALYSIS

Multinomial logistic regression models were used in a cross-sectional analysis to test for associations represented by adjusted odds ratios (aOR) between MSCF and dietary pattern scores, controlling for demographics and clinical risk factors.

RESULTS

Among 3,023 participants with complete data, 97% were male, and 83.8% were White. Increasing scores, representing healthier diets, for each dietary pattern had similar or lower odds for NAAs and AN, respectively, versus NN. They were HEI: aOR: 1.00, 95% CI: 0.99-1.01 and aOR 0.97, 95% CI: 0.99-1.01; Mediterranean: aOR: 0.98, 95% CI: 0.95-1.02 and aOR 0.95, 95% CI: 0.90-0.999; DASH: aOR: 0.99, 95% CI: 0.99- 1.00 and aOR 0.99, 95% CI: 0.98-0.999. Across each dietary pattern, higher whole grain and fiber category scores generally had lower odds for NAAs and AN.

CONCLUSIONS

Study results revealed that overall higher dietary quality and specific dietary components of whole grain or fiber intake, based on three different dietary patterns suggest lower odds for CRC precursors. Findings indicate potential differences in dietary intake patterns and more research is needed to determine the benefit of developing tailored CRC screening and surveillance clinical guidelines.

PURPOSE

To analyze associations between colorectal cancer progression and diet scores calculated using published scoring approaches for three dietary patterns: Healthy Eating Index (HEI), Mediterranean Diet (Mediterranean), and Dietary Approaches to Stop Hypertension Diet (DASH).

BACKGROUND

Little is known about whether longterm risk for progression to colorectal cancer is associated with recommended healthy dietary patterns among US veterans. Previous studies of veterans have shown higher intake of fiber and vitamin D reduced risk, and red meat increased risk for finding colorectal cancer precursors during colonoscopy. However, studying dietary patterns in aggregate may be more clinically relevant for longitudinal studies of colorectal cancer prevention.

METHODS

3,121 asymptomatic US veterans aged 50-75 received colonoscopy between 1994-97 and were followed through 2009. Most significant colonoscopy findings (MSCF) across the study period were: (i) no neoplasia (NN), (ii) non-advanced adenomas (NAAs) or (iii) advanced neoplasia (AN). Baseline dietary questionnaire data were used to calculate three dietary pattern (HEI, Mediterranean, and DASH) scores.

DATA ANALYSIS

Multinomial logistic regression models were used in a cross-sectional analysis to test for associations represented by adjusted odds ratios (aOR) between MSCF and dietary pattern scores, controlling for demographics and clinical risk factors.

RESULTS

Among 3,023 participants with complete data, 97% were male, and 83.8% were White. Increasing scores, representing healthier diets, for each dietary pattern had similar or lower odds for NAAs and AN, respectively, versus NN. They were HEI: aOR: 1.00, 95% CI: 0.99-1.01 and aOR 0.97, 95% CI: 0.99-1.01; Mediterranean: aOR: 0.98, 95% CI: 0.95-1.02 and aOR 0.95, 95% CI: 0.90-0.999; DASH: aOR: 0.99, 95% CI: 0.99- 1.00 and aOR 0.99, 95% CI: 0.98-0.999. Across each dietary pattern, higher whole grain and fiber category scores generally had lower odds for NAAs and AN.

CONCLUSIONS

Study results revealed that overall higher dietary quality and specific dietary components of whole grain or fiber intake, based on three different dietary patterns suggest lower odds for CRC precursors. Findings indicate potential differences in dietary intake patterns and more research is needed to determine the benefit of developing tailored CRC screening and surveillance clinical guidelines.

PURPOSE

To analyze associations between colorectal cancer progression and diet scores calculated using published scoring approaches for three dietary patterns: Healthy Eating Index (HEI), Mediterranean Diet (Mediterranean), and Dietary Approaches to Stop Hypertension Diet (DASH).

BACKGROUND

Little is known about whether longterm risk for progression to colorectal cancer is associated with recommended healthy dietary patterns among US veterans. Previous studies of veterans have shown higher intake of fiber and vitamin D reduced risk, and red meat increased risk for finding colorectal cancer precursors during colonoscopy. However, studying dietary patterns in aggregate may be more clinically relevant for longitudinal studies of colorectal cancer prevention.

METHODS

3,121 asymptomatic US veterans aged 50-75 received colonoscopy between 1994-97 and were followed through 2009. Most significant colonoscopy findings (MSCF) across the study period were: (i) no neoplasia (NN), (ii) non-advanced adenomas (NAAs) or (iii) advanced neoplasia (AN). Baseline dietary questionnaire data were used to calculate three dietary pattern (HEI, Mediterranean, and DASH) scores.

DATA ANALYSIS

Multinomial logistic regression models were used in a cross-sectional analysis to test for associations represented by adjusted odds ratios (aOR) between MSCF and dietary pattern scores, controlling for demographics and clinical risk factors.

RESULTS

Among 3,023 participants with complete data, 97% were male, and 83.8% were White. Increasing scores, representing healthier diets, for each dietary pattern had similar or lower odds for NAAs and AN, respectively, versus NN. They were HEI: aOR: 1.00, 95% CI: 0.99-1.01 and aOR 0.97, 95% CI: 0.99-1.01; Mediterranean: aOR: 0.98, 95% CI: 0.95-1.02 and aOR 0.95, 95% CI: 0.90-0.999; DASH: aOR: 0.99, 95% CI: 0.99- 1.00 and aOR 0.99, 95% CI: 0.98-0.999. Across each dietary pattern, higher whole grain and fiber category scores generally had lower odds for NAAs and AN.

CONCLUSIONS

Study results revealed that overall higher dietary quality and specific dietary components of whole grain or fiber intake, based on three different dietary patterns suggest lower odds for CRC precursors. Findings indicate potential differences in dietary intake patterns and more research is needed to determine the benefit of developing tailored CRC screening and surveillance clinical guidelines.

PURPOSE

Assess the clinical impact (CI) of UV-related DNA damage signatures (UVsig) in Veterans with cancer of unknown primary (CUP) and cancer of extracutaneous origin (CEO).

BACKGROUND

UVsig have been reported in CUP and CEO (i.e. head and neck cancer and lung cancer). The presence of UVsig suggests a cutaneous origin and potential misclassification of CEO using conventional histopathologic evaluation. Literature on the association of UVsig in pan-cancer genomics is limited.

METHODS

This is a retrospective study of Veterans who underwent comprehensive genomic profiling with FoundationOne CDx during 2/1/2019 to 9/30/2022 through the VA National Precision Oncology Program. The outcome was the CI of UVsig (high, medium, and low) determined by blinded chart reviews: (1) high: UVsig leading to change in diagnoses (CID) and a different first-line therapy (FLT) would have been offered; (2) medium: UVsig leading to CID, but appropriate FLT offered; (3) low: diagnoses modified by clinicians and treated as cutaneous cancers. NCCN Guidelines were referenced for FLT.

DATA ANALYSIS

Descriptive statistics and chi-square tests were utilized to evaluate the UVsig CI.

RESULTS

Among 5,565 cases with 10 or more assessable alterations for UVsig analysis, 650 (11.7%) were positive for UVsig. CUP and CEO cohorts each had 41 cases analyzed. In the CUP cases, 20 (48.8%), 9 (21.9%), and 12 (29.3%) were categorized as having high, medium, and low CI, respectively; and in the CEO cases, it was 22 (53.7%), 15 (36.6%), and 4 (9.8%). There was no difference statistically between the CUP and CEO groups on the percentage distribution of CI (p=0.06). Among the 42 out of 82 cases having high CI, 37 (88.1%) received cytotoxic chemotherapy without any indication, and 5 (11.9%) were not offered immunotherapy (IO) as FLT. More than half of the 82 cases had high CI; more than 90% of the CEO cases had high and medium CI.

IMPLICATIONS

UVsig serves as a useful biomarker for cancers with cutaneous origin. About 1% of the 5,565 cases analyzed had high UVsig CI. Knowledge of UVsig could lead to omission of chemotherapy (hence avoiding toxicities) or addition of IO (for potential benefits).

PURPOSE

Assess the clinical impact (CI) of UV-related DNA damage signatures (UVsig) in Veterans with cancer of unknown primary (CUP) and cancer of extracutaneous origin (CEO).

BACKGROUND

UVsig have been reported in CUP and CEO (i.e. head and neck cancer and lung cancer). The presence of UVsig suggests a cutaneous origin and potential misclassification of CEO using conventional histopathologic evaluation. Literature on the association of UVsig in pan-cancer genomics is limited.

METHODS

This is a retrospective study of Veterans who underwent comprehensive genomic profiling with FoundationOne CDx during 2/1/2019 to 9/30/2022 through the VA National Precision Oncology Program. The outcome was the CI of UVsig (high, medium, and low) determined by blinded chart reviews: (1) high: UVsig leading to change in diagnoses (CID) and a different first-line therapy (FLT) would have been offered; (2) medium: UVsig leading to CID, but appropriate FLT offered; (3) low: diagnoses modified by clinicians and treated as cutaneous cancers. NCCN Guidelines were referenced for FLT.

DATA ANALYSIS

Descriptive statistics and chi-square tests were utilized to evaluate the UVsig CI.

RESULTS

Among 5,565 cases with 10 or more assessable alterations for UVsig analysis, 650 (11.7%) were positive for UVsig. CUP and CEO cohorts each had 41 cases analyzed. In the CUP cases, 20 (48.8%), 9 (21.9%), and 12 (29.3%) were categorized as having high, medium, and low CI, respectively; and in the CEO cases, it was 22 (53.7%), 15 (36.6%), and 4 (9.8%). There was no difference statistically between the CUP and CEO groups on the percentage distribution of CI (p=0.06). Among the 42 out of 82 cases having high CI, 37 (88.1%) received cytotoxic chemotherapy without any indication, and 5 (11.9%) were not offered immunotherapy (IO) as FLT. More than half of the 82 cases had high CI; more than 90% of the CEO cases had high and medium CI.

IMPLICATIONS

UVsig serves as a useful biomarker for cancers with cutaneous origin. About 1% of the 5,565 cases analyzed had high UVsig CI. Knowledge of UVsig could lead to omission of chemotherapy (hence avoiding toxicities) or addition of IO (for potential benefits).

PURPOSE

Assess the clinical impact (CI) of UV-related DNA damage signatures (UVsig) in Veterans with cancer of unknown primary (CUP) and cancer of extracutaneous origin (CEO).

BACKGROUND

UVsig have been reported in CUP and CEO (i.e. head and neck cancer and lung cancer). The presence of UVsig suggests a cutaneous origin and potential misclassification of CEO using conventional histopathologic evaluation. Literature on the association of UVsig in pan-cancer genomics is limited.

METHODS

This is a retrospective study of Veterans who underwent comprehensive genomic profiling with FoundationOne CDx during 2/1/2019 to 9/30/2022 through the VA National Precision Oncology Program. The outcome was the CI of UVsig (high, medium, and low) determined by blinded chart reviews: (1) high: UVsig leading to change in diagnoses (CID) and a different first-line therapy (FLT) would have been offered; (2) medium: UVsig leading to CID, but appropriate FLT offered; (3) low: diagnoses modified by clinicians and treated as cutaneous cancers. NCCN Guidelines were referenced for FLT.

DATA ANALYSIS

Descriptive statistics and chi-square tests were utilized to evaluate the UVsig CI.

RESULTS

Among 5,565 cases with 10 or more assessable alterations for UVsig analysis, 650 (11.7%) were positive for UVsig. CUP and CEO cohorts each had 41 cases analyzed. In the CUP cases, 20 (48.8%), 9 (21.9%), and 12 (29.3%) were categorized as having high, medium, and low CI, respectively; and in the CEO cases, it was 22 (53.7%), 15 (36.6%), and 4 (9.8%). There was no difference statistically between the CUP and CEO groups on the percentage distribution of CI (p=0.06). Among the 42 out of 82 cases having high CI, 37 (88.1%) received cytotoxic chemotherapy without any indication, and 5 (11.9%) were not offered immunotherapy (IO) as FLT. More than half of the 82 cases had high CI; more than 90% of the CEO cases had high and medium CI.

IMPLICATIONS

UVsig serves as a useful biomarker for cancers with cutaneous origin. About 1% of the 5,565 cases analyzed had high UVsig CI. Knowledge of UVsig could lead to omission of chemotherapy (hence avoiding toxicities) or addition of IO (for potential benefits).

BACKGROUND/PURPOSE

Febrile neutropenia (FN) is considered a life-threatening oncologic emergency that requires prompt recognition of the condition and expeditious administration of antibiotics. In 2021, a neutropenic workgroup in the VA Northeast Ohio Healthcare System (VANEOHS) began working on updating the neutropenic policy to match current neutropenic guidelines. In 2022, the policy was approved, and the following changes were implemented (1) timing of antibiotic administration changed from two hours to one hour of fever presentation (2) absolute neutrophil count (ANC) criteria changed from an ANC of ≤ 1.0 K/cmm to an ANC of ≤ 0.5 K/cmm or an ANC that is expected to decrease to ≤ 0.5 K/cmm during the next 48 hours.

SYNTHESIS OF LITERATURE

Each hour that antibiotics are delayed is associated with a decrease in survival and an increase in mortality of 7.6% (Koenig et al, 2019).

INTERVENTIONS

The existing neutropenic policy, order sets, and antibiogram were updated. The physicians, pharmacists, and nurses from the neutropenic workgroup conducted educational in-services with their respective groups. Badge backers were created for inpatient nursing staff to wear as a quick reference. Posters were hung in the medicine team workrooms. A protected health information (PHI) Outlook email was set up to automatically generate, notifying workgroup members when initial antibiotics are administered to a patient with neutropenic fever. This email allows “real time” tracking of initial antibiotic administration. A certificate of recognition was created to email to nurses who administer antibiotics within the 1-hour timeframe.

RESULTS

Monthly chart audits of timing from fever presentation to antibiotic administration are conducted. Data is reported monthly at the neutropenic workgroup meetings. The following data was gathered after implementation and shows gram negative antibiotic administration within one hour of fever presentation: September 2022, 100% (n = 1), October 2022, 100% (n = 1), November 2022, N/A (n = 0), December 2022, N/A (n = 0), January 2023, N/A (n = 0), February 2023, 100% (n = 1), March 2023, 100% (n = 1), and April 2023, N/A (n = 0).

IMPLICATIONS

Continue to monitor data to ensure targets are met and reevaluate process as needed.

BACKGROUND/PURPOSE

Febrile neutropenia (FN) is considered a life-threatening oncologic emergency that requires prompt recognition of the condition and expeditious administration of antibiotics. In 2021, a neutropenic workgroup in the VA Northeast Ohio Healthcare System (VANEOHS) began working on updating the neutropenic policy to match current neutropenic guidelines. In 2022, the policy was approved, and the following changes were implemented (1) timing of antibiotic administration changed from two hours to one hour of fever presentation (2) absolute neutrophil count (ANC) criteria changed from an ANC of ≤ 1.0 K/cmm to an ANC of ≤ 0.5 K/cmm or an ANC that is expected to decrease to ≤ 0.5 K/cmm during the next 48 hours.

SYNTHESIS OF LITERATURE

Each hour that antibiotics are delayed is associated with a decrease in survival and an increase in mortality of 7.6% (Koenig et al, 2019).

INTERVENTIONS

The existing neutropenic policy, order sets, and antibiogram were updated. The physicians, pharmacists, and nurses from the neutropenic workgroup conducted educational in-services with their respective groups. Badge backers were created for inpatient nursing staff to wear as a quick reference. Posters were hung in the medicine team workrooms. A protected health information (PHI) Outlook email was set up to automatically generate, notifying workgroup members when initial antibiotics are administered to a patient with neutropenic fever. This email allows “real time” tracking of initial antibiotic administration. A certificate of recognition was created to email to nurses who administer antibiotics within the 1-hour timeframe.

RESULTS

Monthly chart audits of timing from fever presentation to antibiotic administration are conducted. Data is reported monthly at the neutropenic workgroup meetings. The following data was gathered after implementation and shows gram negative antibiotic administration within one hour of fever presentation: September 2022, 100% (n = 1), October 2022, 100% (n = 1), November 2022, N/A (n = 0), December 2022, N/A (n = 0), January 2023, N/A (n = 0), February 2023, 100% (n = 1), March 2023, 100% (n = 1), and April 2023, N/A (n = 0).

IMPLICATIONS

Continue to monitor data to ensure targets are met and reevaluate process as needed.

BACKGROUND/PURPOSE

Febrile neutropenia (FN) is considered a life-threatening oncologic emergency that requires prompt recognition of the condition and expeditious administration of antibiotics. In 2021, a neutropenic workgroup in the VA Northeast Ohio Healthcare System (VANEOHS) began working on updating the neutropenic policy to match current neutropenic guidelines. In 2022, the policy was approved, and the following changes were implemented (1) timing of antibiotic administration changed from two hours to one hour of fever presentation (2) absolute neutrophil count (ANC) criteria changed from an ANC of ≤ 1.0 K/cmm to an ANC of ≤ 0.5 K/cmm or an ANC that is expected to decrease to ≤ 0.5 K/cmm during the next 48 hours.

SYNTHESIS OF LITERATURE

Each hour that antibiotics are delayed is associated with a decrease in survival and an increase in mortality of 7.6% (Koenig et al, 2019).

INTERVENTIONS

The existing neutropenic policy, order sets, and antibiogram were updated. The physicians, pharmacists, and nurses from the neutropenic workgroup conducted educational in-services with their respective groups. Badge backers were created for inpatient nursing staff to wear as a quick reference. Posters were hung in the medicine team workrooms. A protected health information (PHI) Outlook email was set up to automatically generate, notifying workgroup members when initial antibiotics are administered to a patient with neutropenic fever. This email allows “real time” tracking of initial antibiotic administration. A certificate of recognition was created to email to nurses who administer antibiotics within the 1-hour timeframe.

RESULTS

Monthly chart audits of timing from fever presentation to antibiotic administration are conducted. Data is reported monthly at the neutropenic workgroup meetings. The following data was gathered after implementation and shows gram negative antibiotic administration within one hour of fever presentation: September 2022, 100% (n = 1), October 2022, 100% (n = 1), November 2022, N/A (n = 0), December 2022, N/A (n = 0), January 2023, N/A (n = 0), February 2023, 100% (n = 1), March 2023, 100% (n = 1), and April 2023, N/A (n = 0).

IMPLICATIONS

Continue to monitor data to ensure targets are met and reevaluate process as needed.

PURPOSE

Study clinical characteristics of Rectal Mucinous Adenocarcinoma (RMA).

BACKGROUND

RMA is a rare histological subtype with an impaired response to chemoradiotherapy and an overall poor prognosis. High-grade tumors are associated with older age. Previous studies have shown conflicting results on prognosis.

METHODS

Retrospective analysis of National Cancer Database was conducted from 2004-2020 for subjects with histology code 8480 in primary sites C19 and C20 (rectosigmoid-junction and rectum, n = 14,044), using multivariate analysis with Cox regression.

RESULTS

Median age of diagnosis was 65 years with 69.5% were in the 45-75 years age range. 59.2% were male while 40.8% were female. 84.7% were White, 9.7% were Black, 0.4% were American Indian and 3.4% were Asian. 6.9% were Hispanic. 33.9% were in the upper-income quartile. 40.6% were seen at community cancer programs while 33% went to academic programs. 36.5% had stage III RMA. Out of the 14,044 patients with RMA, 10,546 received surgery, 5,179 received chemotherapy, 233 received immunotherapy and 55 received hormone therapy. Patients >75 years had significantly lower overall survival (OS) compared to those <45 years (HR 0.67). Female patients had significantly higher OS than male (HR - 0.07). Black patients had significantly lower OS than White (HR 0.08). Hispanic patients had significantly higher OS than non- Hispanic (HR - 0.14). Patients with private and government insurance had significantly higher OS than noninsured patients (HR - 0.35 and - 0.26 respectively). Patients with median higher-income quartiles had significantly higher OS than lower quartiles (HR - 0.13). Academic facilities had significantly higher OS than community programs (HR - 0.13). Patients who received surgery had significantly higher OS than those that did not (HR - 0.67); median survival for patients who received surgery was 71 months vs 28 months for non-surgical candidates.

CONCLUSIONS

Surgery is the most important treatment modality in RMA. Uninsured, older Black male patients from lower-income quartiles had significantly lower OS. Access to academic centers also contributed to differences in OS outcomes which throws light on healthcare disparities.

IMPLICATIONS

Additional studies need to be conducted for viable solutions to assist with social determinants of healthcare in RMA.

PURPOSE

Study clinical characteristics of Rectal Mucinous Adenocarcinoma (RMA).

BACKGROUND

RMA is a rare histological subtype with an impaired response to chemoradiotherapy and an overall poor prognosis. High-grade tumors are associated with older age. Previous studies have shown conflicting results on prognosis.

METHODS

Retrospective analysis of National Cancer Database was conducted from 2004-2020 for subjects with histology code 8480 in primary sites C19 and C20 (rectosigmoid-junction and rectum, n = 14,044), using multivariate analysis with Cox regression.

RESULTS

Median age of diagnosis was 65 years with 69.5% were in the 45-75 years age range. 59.2% were male while 40.8% were female. 84.7% were White, 9.7% were Black, 0.4% were American Indian and 3.4% were Asian. 6.9% were Hispanic. 33.9% were in the upper-income quartile. 40.6% were seen at community cancer programs while 33% went to academic programs. 36.5% had stage III RMA. Out of the 14,044 patients with RMA, 10,546 received surgery, 5,179 received chemotherapy, 233 received immunotherapy and 55 received hormone therapy. Patients >75 years had significantly lower overall survival (OS) compared to those <45 years (HR 0.67). Female patients had significantly higher OS than male (HR - 0.07). Black patients had significantly lower OS than White (HR 0.08). Hispanic patients had significantly higher OS than non- Hispanic (HR - 0.14). Patients with private and government insurance had significantly higher OS than noninsured patients (HR - 0.35 and - 0.26 respectively). Patients with median higher-income quartiles had significantly higher OS than lower quartiles (HR - 0.13). Academic facilities had significantly higher OS than community programs (HR - 0.13). Patients who received surgery had significantly higher OS than those that did not (HR - 0.67); median survival for patients who received surgery was 71 months vs 28 months for non-surgical candidates.

CONCLUSIONS

Surgery is the most important treatment modality in RMA. Uninsured, older Black male patients from lower-income quartiles had significantly lower OS. Access to academic centers also contributed to differences in OS outcomes which throws light on healthcare disparities.

IMPLICATIONS

Additional studies need to be conducted for viable solutions to assist with social determinants of healthcare in RMA.

PURPOSE

Study clinical characteristics of Rectal Mucinous Adenocarcinoma (RMA).

BACKGROUND

RMA is a rare histological subtype with an impaired response to chemoradiotherapy and an overall poor prognosis. High-grade tumors are associated with older age. Previous studies have shown conflicting results on prognosis.

METHODS

Retrospective analysis of National Cancer Database was conducted from 2004-2020 for subjects with histology code 8480 in primary sites C19 and C20 (rectosigmoid-junction and rectum, n = 14,044), using multivariate analysis with Cox regression.

RESULTS

Median age of diagnosis was 65 years with 69.5% were in the 45-75 years age range. 59.2% were male while 40.8% were female. 84.7% were White, 9.7% were Black, 0.4% were American Indian and 3.4% were Asian. 6.9% were Hispanic. 33.9% were in the upper-income quartile. 40.6% were seen at community cancer programs while 33% went to academic programs. 36.5% had stage III RMA. Out of the 14,044 patients with RMA, 10,546 received surgery, 5,179 received chemotherapy, 233 received immunotherapy and 55 received hormone therapy. Patients >75 years had significantly lower overall survival (OS) compared to those <45 years (HR 0.67). Female patients had significantly higher OS than male (HR - 0.07). Black patients had significantly lower OS than White (HR 0.08). Hispanic patients had significantly higher OS than non- Hispanic (HR - 0.14). Patients with private and government insurance had significantly higher OS than noninsured patients (HR - 0.35 and - 0.26 respectively). Patients with median higher-income quartiles had significantly higher OS than lower quartiles (HR - 0.13). Academic facilities had significantly higher OS than community programs (HR - 0.13). Patients who received surgery had significantly higher OS than those that did not (HR - 0.67); median survival for patients who received surgery was 71 months vs 28 months for non-surgical candidates.

CONCLUSIONS

Surgery is the most important treatment modality in RMA. Uninsured, older Black male patients from lower-income quartiles had significantly lower OS. Access to academic centers also contributed to differences in OS outcomes which throws light on healthcare disparities.

IMPLICATIONS

Additional studies need to be conducted for viable solutions to assist with social determinants of healthcare in RMA.

BACKGROUND

The National Precision Oncology Program (NPOP) provides comprehensive genomic profiling (CGP) through external vendors to patients within the Veterans Affairs Healthcare System who meet testing guidelines. We sought to assess the concordance of cancer therapy recommendations between Foundation Medicine (FM), one of the NPOP vendors, and OncoKB, an FDA-recognized public precision oncology knowledge database, which annotates human genetic variants associated with therapies guidance at varying levels of evidence.

METHODS

We selected FM CGP test reports with at least one therapy recommendation regardless of FDA approval or level of evidence were selected to compare FM and OncoKB therapy annotations of different mutation types, including short variants (SVs), rearrangements, and copy number alterations (CNAs) between 02/01/2019-03/13/2023. Therapy recommendations of annotations for unique combinations of gene, variant, and cancer type from FM and OncoKB were compared. Comparisons were scored as an Exact Match (EM) if FM and OncoKB therapy annotation was the same or a Partial Match (PM) if the FM therapy annotation was a subset of OncoKB’s or vice versa.

RESULTS

For annotations involving FDA-approved therapies, a total of 10,435 cases were compared for SVs, 546 for rearrangements, and 732 for CNAs. Among SVs annotations, 7,029 (67.4%) were EM and 787 (7.5%) were PM. Of rearrangement annotations, 328 (60.1%) were EM and 95 (17.4%) were PM. Of CNA annotations, 469 (64.1%) were EM and 28 (3.8%) were PM. For off-label therapies, agreement between annotation sources was much lower in all above scenarios. Examples included 3022 (29%) cases were identified as EM plus PM for SVs, 324 (59.3%) for rearrangements, and 42 (5.7%) for CNAs.

CONCLUSIONS

Therapy recommendations were inconsistent between FM and OncoKB annotation services, with a substantial disagreement among both FDA-approved and off-label therapy annotations. The limitation of time difference of annotations performed between FM and OncoKB therapy annotations accounted for some disagreement. Establishing accuracy and improving concordance between different annotation services is needed to better match treatments to patients and improve provider trust and reliability of annotation service.

BACKGROUND

The National Precision Oncology Program (NPOP) provides comprehensive genomic profiling (CGP) through external vendors to patients within the Veterans Affairs Healthcare System who meet testing guidelines. We sought to assess the concordance of cancer therapy recommendations between Foundation Medicine (FM), one of the NPOP vendors, and OncoKB, an FDA-recognized public precision oncology knowledge database, which annotates human genetic variants associated with therapies guidance at varying levels of evidence.

METHODS

We selected FM CGP test reports with at least one therapy recommendation regardless of FDA approval or level of evidence were selected to compare FM and OncoKB therapy annotations of different mutation types, including short variants (SVs), rearrangements, and copy number alterations (CNAs) between 02/01/2019-03/13/2023. Therapy recommendations of annotations for unique combinations of gene, variant, and cancer type from FM and OncoKB were compared. Comparisons were scored as an Exact Match (EM) if FM and OncoKB therapy annotation was the same or a Partial Match (PM) if the FM therapy annotation was a subset of OncoKB’s or vice versa.

RESULTS

For annotations involving FDA-approved therapies, a total of 10,435 cases were compared for SVs, 546 for rearrangements, and 732 for CNAs. Among SVs annotations, 7,029 (67.4%) were EM and 787 (7.5%) were PM. Of rearrangement annotations, 328 (60.1%) were EM and 95 (17.4%) were PM. Of CNA annotations, 469 (64.1%) were EM and 28 (3.8%) were PM. For off-label therapies, agreement between annotation sources was much lower in all above scenarios. Examples included 3022 (29%) cases were identified as EM plus PM for SVs, 324 (59.3%) for rearrangements, and 42 (5.7%) for CNAs.

CONCLUSIONS

Therapy recommendations were inconsistent between FM and OncoKB annotation services, with a substantial disagreement among both FDA-approved and off-label therapy annotations. The limitation of time difference of annotations performed between FM and OncoKB therapy annotations accounted for some disagreement. Establishing accuracy and improving concordance between different annotation services is needed to better match treatments to patients and improve provider trust and reliability of annotation service.

BACKGROUND

The National Precision Oncology Program (NPOP) provides comprehensive genomic profiling (CGP) through external vendors to patients within the Veterans Affairs Healthcare System who meet testing guidelines. We sought to assess the concordance of cancer therapy recommendations between Foundation Medicine (FM), one of the NPOP vendors, and OncoKB, an FDA-recognized public precision oncology knowledge database, which annotates human genetic variants associated with therapies guidance at varying levels of evidence.

METHODS

We selected FM CGP test reports with at least one therapy recommendation regardless of FDA approval or level of evidence were selected to compare FM and OncoKB therapy annotations of different mutation types, including short variants (SVs), rearrangements, and copy number alterations (CNAs) between 02/01/2019-03/13/2023. Therapy recommendations of annotations for unique combinations of gene, variant, and cancer type from FM and OncoKB were compared. Comparisons were scored as an Exact Match (EM) if FM and OncoKB therapy annotation was the same or a Partial Match (PM) if the FM therapy annotation was a subset of OncoKB’s or vice versa.

RESULTS

For annotations involving FDA-approved therapies, a total of 10,435 cases were compared for SVs, 546 for rearrangements, and 732 for CNAs. Among SVs annotations, 7,029 (67.4%) were EM and 787 (7.5%) were PM. Of rearrangement annotations, 328 (60.1%) were EM and 95 (17.4%) were PM. Of CNA annotations, 469 (64.1%) were EM and 28 (3.8%) were PM. For off-label therapies, agreement between annotation sources was much lower in all above scenarios. Examples included 3022 (29%) cases were identified as EM plus PM for SVs, 324 (59.3%) for rearrangements, and 42 (5.7%) for CNAs.

CONCLUSIONS

Therapy recommendations were inconsistent between FM and OncoKB annotation services, with a substantial disagreement among both FDA-approved and off-label therapy annotations. The limitation of time difference of annotations performed between FM and OncoKB therapy annotations accounted for some disagreement. Establishing accuracy and improving concordance between different annotation services is needed to better match treatments to patients and improve provider trust and reliability of annotation service.

PURPOSE

To improve the time to release of blood products for patients with severe or life-threatening bleeding.

BACKGROUND

Exsanguination, and the resultant coagulopathy, is the number one cause of trauma-related death. Massive transfusion protocols (MTP) improve mortality by shortening the time to transfusion and correcting coagulopathy. Many patients do not meet criteria for massive transfusion (> 10 units RBCs in 24 hours), yet present with clinical instability and require rapid release (RR) of uncrossmatched blood. A quality improvement initiative was performed to identify barriers to the MTP/RR protocol at a single institution.

METHODS/DATA

A multidisciplinary subcommittee was formed to evaluate the safety and efficacy of the current MTP/RR process. Timed mock-MTP/RR trials were conducted to identify areas of delay with a goal to achieve a blood to bedside (B2B) time of under 10 minutes.

RESULTS

Timed mock-MTP/RR trials were conducted, which revealed a baseline B2B time of approximately 30 minutes. We identified problems and categorized them in terms of ordering (phase 1) and processing (phase 2). We found significant delays in phase 1. Reasons for delay were varied and included difficulty logging into the computer, staff unavailable to place orders (involved in resuscitation efforts), orders entered incorrectly, etc. Once orders were received, the blood bank could process them quickly in phase 2. Using root cause analysis, we discovered a critical step was to remove the barrier of electronic ordering. For this, a new process was developed in which the blood bank could accept verbal orders to release uncrossmatched blood during a medical emergency. Over the course of one year, a new policy for MTP/RR was drafted, an education training video was recorded, informational flyers were printed, and training drills were conducted. A repeat mock-MTP/RR scenario was performed after the change showing the B2B time was reduced by 90% from pre-intervention values to under 3 minutes. Since implementation, no new safety signals have been received, and the staff have reported improved satisfaction with the MTP/RR process.

IMPLICATIONS

A critical piece of any MTP/RR is the immediate availability of blood. Allowing verbal orders for blood products reduced time to transfusion by 90%. Through multidisciplinary effort, safe and efficient release of uncrossmatched blood products for nontraumatic massive transfusion can be achieved.

PURPOSE

To improve the time to release of blood products for patients with severe or life-threatening bleeding.

BACKGROUND

Exsanguination, and the resultant coagulopathy, is the number one cause of trauma-related death. Massive transfusion protocols (MTP) improve mortality by shortening the time to transfusion and correcting coagulopathy. Many patients do not meet criteria for massive transfusion (> 10 units RBCs in 24 hours), yet present with clinical instability and require rapid release (RR) of uncrossmatched blood. A quality improvement initiative was performed to identify barriers to the MTP/RR protocol at a single institution.

METHODS/DATA

A multidisciplinary subcommittee was formed to evaluate the safety and efficacy of the current MTP/RR process. Timed mock-MTP/RR trials were conducted to identify areas of delay with a goal to achieve a blood to bedside (B2B) time of under 10 minutes.

RESULTS

Timed mock-MTP/RR trials were conducted, which revealed a baseline B2B time of approximately 30 minutes. We identified problems and categorized them in terms of ordering (phase 1) and processing (phase 2). We found significant delays in phase 1. Reasons for delay were varied and included difficulty logging into the computer, staff unavailable to place orders (involved in resuscitation efforts), orders entered incorrectly, etc. Once orders were received, the blood bank could process them quickly in phase 2. Using root cause analysis, we discovered a critical step was to remove the barrier of electronic ordering. For this, a new process was developed in which the blood bank could accept verbal orders to release uncrossmatched blood during a medical emergency. Over the course of one year, a new policy for MTP/RR was drafted, an education training video was recorded, informational flyers were printed, and training drills were conducted. A repeat mock-MTP/RR scenario was performed after the change showing the B2B time was reduced by 90% from pre-intervention values to under 3 minutes. Since implementation, no new safety signals have been received, and the staff have reported improved satisfaction with the MTP/RR process.

IMPLICATIONS

A critical piece of any MTP/RR is the immediate availability of blood. Allowing verbal orders for blood products reduced time to transfusion by 90%. Through multidisciplinary effort, safe and efficient release of uncrossmatched blood products for nontraumatic massive transfusion can be achieved.

PURPOSE

To improve the time to release of blood products for patients with severe or life-threatening bleeding.

BACKGROUND

Exsanguination, and the resultant coagulopathy, is the number one cause of trauma-related death. Massive transfusion protocols (MTP) improve mortality by shortening the time to transfusion and correcting coagulopathy. Many patients do not meet criteria for massive transfusion (> 10 units RBCs in 24 hours), yet present with clinical instability and require rapid release (RR) of uncrossmatched blood. A quality improvement initiative was performed to identify barriers to the MTP/RR protocol at a single institution.

METHODS/DATA

A multidisciplinary subcommittee was formed to evaluate the safety and efficacy of the current MTP/RR process. Timed mock-MTP/RR trials were conducted to identify areas of delay with a goal to achieve a blood to bedside (B2B) time of under 10 minutes.

RESULTS

Timed mock-MTP/RR trials were conducted, which revealed a baseline B2B time of approximately 30 minutes. We identified problems and categorized them in terms of ordering (phase 1) and processing (phase 2). We found significant delays in phase 1. Reasons for delay were varied and included difficulty logging into the computer, staff unavailable to place orders (involved in resuscitation efforts), orders entered incorrectly, etc. Once orders were received, the blood bank could process them quickly in phase 2. Using root cause analysis, we discovered a critical step was to remove the barrier of electronic ordering. For this, a new process was developed in which the blood bank could accept verbal orders to release uncrossmatched blood during a medical emergency. Over the course of one year, a new policy for MTP/RR was drafted, an education training video was recorded, informational flyers were printed, and training drills were conducted. A repeat mock-MTP/RR scenario was performed after the change showing the B2B time was reduced by 90% from pre-intervention values to under 3 minutes. Since implementation, no new safety signals have been received, and the staff have reported improved satisfaction with the MTP/RR process.

IMPLICATIONS

A critical piece of any MTP/RR is the immediate availability of blood. Allowing verbal orders for blood products reduced time to transfusion by 90%. Through multidisciplinary effort, safe and efficient release of uncrossmatched blood products for nontraumatic massive transfusion can be achieved.

BACKGROUND

Cancer risk assessment and genetic counseling are the processes to identify and counsel people at risk for familial or hereditary cancer syndromes. They serve to inform, educate and empower patients and family members to make informed decisions about testing, cancer screening, and prevention. Additionally, genetic testing can also provide therapeutic options and opportunities for research.

METHODS

Prior to this program initiative, there were no cancer genetics services available at the VA Pittsburgh Medical Center (VAPHS) and 100% of genetics consults were referred to the community. Each year over $100,000 was spent outside of VAPHS on genetic testing and counseling. Community care referral resulted in fragmented care, prolonged wait times of 3 to 5 months, communication issues, and added financial cost to the institution. Corporal Michael J. Crescenz VA Medical Center (CMCVAMC) had previously created a genetics consultation service staffed with an advanced practice nurse that increased access to genetics services and testing rates at the facility-level. VAPHS recently established an interfacility telegenetics clinic with CMCVAMC to provide virtual genetic counseling services to Veterans at VAPHS. Under this program, VAPHS providers place an interfacility consult for Veterans who need cancer genetics services. The consult is received and reviewed by the CMCVAMC team. VAPHS patients are then seen by CMCVAMC providers via VVC or CVT and provide recommendations regarding additional genetic testing and follow-up.

RESULTS

The telegenetics clinic opened in October 2022. The clinic initially focused on patients with metastatic prostate cancer but has since expanded to provide care for all patients for whom genetics testing and/ or counseling is recommended by NCCN guidelines. Since initiation, 29 consults have been placed and 26 have been completed or are in process (89.6%). In the year prior to creation of the clinic, only 31 of 67 (46%) of referred patients completed genetics evaluation.

CONCLUSIONS

Due to the success of the clinic, plans to expand services to the VISN-level and within VAPHS to include high risk breast cancer assessment are underway. Efforts to provide genetic counseling services via virtual care modalities have the potential to increase access to care and to improve outcomes for veterans with cancer.

BACKGROUND

Cancer risk assessment and genetic counseling are the processes to identify and counsel people at risk for familial or hereditary cancer syndromes. They serve to inform, educate and empower patients and family members to make informed decisions about testing, cancer screening, and prevention. Additionally, genetic testing can also provide therapeutic options and opportunities for research.

METHODS

Prior to this program initiative, there were no cancer genetics services available at the VA Pittsburgh Medical Center (VAPHS) and 100% of genetics consults were referred to the community. Each year over $100,000 was spent outside of VAPHS on genetic testing and counseling. Community care referral resulted in fragmented care, prolonged wait times of 3 to 5 months, communication issues, and added financial cost to the institution. Corporal Michael J. Crescenz VA Medical Center (CMCVAMC) had previously created a genetics consultation service staffed with an advanced practice nurse that increased access to genetics services and testing rates at the facility-level. VAPHS recently established an interfacility telegenetics clinic with CMCVAMC to provide virtual genetic counseling services to Veterans at VAPHS. Under this program, VAPHS providers place an interfacility consult for Veterans who need cancer genetics services. The consult is received and reviewed by the CMCVAMC team. VAPHS patients are then seen by CMCVAMC providers via VVC or CVT and provide recommendations regarding additional genetic testing and follow-up.

RESULTS

The telegenetics clinic opened in October 2022. The clinic initially focused on patients with metastatic prostate cancer but has since expanded to provide care for all patients for whom genetics testing and/ or counseling is recommended by NCCN guidelines. Since initiation, 29 consults have been placed and 26 have been completed or are in process (89.6%). In the year prior to creation of the clinic, only 31 of 67 (46%) of referred patients completed genetics evaluation.

CONCLUSIONS

Due to the success of the clinic, plans to expand services to the VISN-level and within VAPHS to include high risk breast cancer assessment are underway. Efforts to provide genetic counseling services via virtual care modalities have the potential to increase access to care and to improve outcomes for veterans with cancer.

BACKGROUND

Cancer risk assessment and genetic counseling are the processes to identify and counsel people at risk for familial or hereditary cancer syndromes. They serve to inform, educate and empower patients and family members to make informed decisions about testing, cancer screening, and prevention. Additionally, genetic testing can also provide therapeutic options and opportunities for research.

METHODS

Prior to this program initiative, there were no cancer genetics services available at the VA Pittsburgh Medical Center (VAPHS) and 100% of genetics consults were referred to the community. Each year over $100,000 was spent outside of VAPHS on genetic testing and counseling. Community care referral resulted in fragmented care, prolonged wait times of 3 to 5 months, communication issues, and added financial cost to the institution. Corporal Michael J. Crescenz VA Medical Center (CMCVAMC) had previously created a genetics consultation service staffed with an advanced practice nurse that increased access to genetics services and testing rates at the facility-level. VAPHS recently established an interfacility telegenetics clinic with CMCVAMC to provide virtual genetic counseling services to Veterans at VAPHS. Under this program, VAPHS providers place an interfacility consult for Veterans who need cancer genetics services. The consult is received and reviewed by the CMCVAMC team. VAPHS patients are then seen by CMCVAMC providers via VVC or CVT and provide recommendations regarding additional genetic testing and follow-up.

RESULTS

The telegenetics clinic opened in October 2022. The clinic initially focused on patients with metastatic prostate cancer but has since expanded to provide care for all patients for whom genetics testing and/ or counseling is recommended by NCCN guidelines. Since initiation, 29 consults have been placed and 26 have been completed or are in process (89.6%). In the year prior to creation of the clinic, only 31 of 67 (46%) of referred patients completed genetics evaluation.

CONCLUSIONS

Due to the success of the clinic, plans to expand services to the VISN-level and within VAPHS to include high risk breast cancer assessment are underway. Efforts to provide genetic counseling services via virtual care modalities have the potential to increase access to care and to improve outcomes for veterans with cancer.