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Ketogenic Diet and Cancer: A Case Report and Feasibility Study at VA Central California Healthcare System
Background
Ketogenic diet (KD) is a high-fat and low carbohydrate diet that has been reported as a treatment option for patients with cancer. KD creates a metabolic state in which blood glucose levels are reduced and ketone bodies are elevated. Cancer cells are unable to use ketone bodies for energy and metabolism due to mitochondrial dysfunction. We published the efficacy of KD in patients with cancer after failure of chemotherapy. 1 This case report is presented to evaluate the feasibility of KD concurrent with chemoimmunotherapy.
Case Report
Patient is a 69-year-old male who presented with iron deficiency anemia in 2018. Colonoscopy and biopsy showed colon adenocarcinoma. He underwent resection which confirmed stage IIIC disease. He received adjuvant treatment with FOLFOX but quickly developed pancreatic and omental metastasis. He was started on FOLFIRI + bevacizumab followed by pancreatic mass resection in 2019. Molecular testing revealed wild type KRAS, positive BRAF V600E, and high MSI. He received encorafenib + cetuximab until disease progression. Treatment was changed to pembrolizumab until PET scan showed progression. His CEA increased to 1031 in January 2021. He was subsequently started on KD concurrent with trifluridine + tipiracil + bevacizumab. He progressed after 10 months. Therapy was changed to ipilimumab + nivolumab with continuation of KD. He was strictly adherent to KD with low Glucose Ketone Index of 8.2 (confirming ketosis) but in 2022 his GKI level started to rise. His CEA, however, significantly decreased to 20 in March 2022 and PET scan showed stable disease. He presently is on maintenance nivolumab + KD while maintaining an excellent quality of life by EORTC QLQ scores.
Conclusions
The use of KD concurrently with chemotherapy and immunotherapy is still under investigation. Our case report shows that KD is tolerable with treatment and can possibly contribute to controlling progression of metastatic cancer. We are starting an investigator initiative KD trial that received a grant from R&D at VACCHCS. We will present the study protocol in poster presentation.
1. Tan-Shalaby JL, Carrick J, Edinger K, et al. Modified Atkins diet in advanced malignancies - final results of a safety and feasibility trial within the Veterans Affairs Pittsburgh Healthcare System]. Nutr Metab (Lond). 2016;13:52. Published 2016 Aug 12. doi:10.1186/s12986-016-0113-y
Background
Ketogenic diet (KD) is a high-fat and low carbohydrate diet that has been reported as a treatment option for patients with cancer. KD creates a metabolic state in which blood glucose levels are reduced and ketone bodies are elevated. Cancer cells are unable to use ketone bodies for energy and metabolism due to mitochondrial dysfunction. We published the efficacy of KD in patients with cancer after failure of chemotherapy. 1 This case report is presented to evaluate the feasibility of KD concurrent with chemoimmunotherapy.
Case Report
Patient is a 69-year-old male who presented with iron deficiency anemia in 2018. Colonoscopy and biopsy showed colon adenocarcinoma. He underwent resection which confirmed stage IIIC disease. He received adjuvant treatment with FOLFOX but quickly developed pancreatic and omental metastasis. He was started on FOLFIRI + bevacizumab followed by pancreatic mass resection in 2019. Molecular testing revealed wild type KRAS, positive BRAF V600E, and high MSI. He received encorafenib + cetuximab until disease progression. Treatment was changed to pembrolizumab until PET scan showed progression. His CEA increased to 1031 in January 2021. He was subsequently started on KD concurrent with trifluridine + tipiracil + bevacizumab. He progressed after 10 months. Therapy was changed to ipilimumab + nivolumab with continuation of KD. He was strictly adherent to KD with low Glucose Ketone Index of 8.2 (confirming ketosis) but in 2022 his GKI level started to rise. His CEA, however, significantly decreased to 20 in March 2022 and PET scan showed stable disease. He presently is on maintenance nivolumab + KD while maintaining an excellent quality of life by EORTC QLQ scores.
Conclusions
The use of KD concurrently with chemotherapy and immunotherapy is still under investigation. Our case report shows that KD is tolerable with treatment and can possibly contribute to controlling progression of metastatic cancer. We are starting an investigator initiative KD trial that received a grant from R&D at VACCHCS. We will present the study protocol in poster presentation.
Background
Ketogenic diet (KD) is a high-fat and low carbohydrate diet that has been reported as a treatment option for patients with cancer. KD creates a metabolic state in which blood glucose levels are reduced and ketone bodies are elevated. Cancer cells are unable to use ketone bodies for energy and metabolism due to mitochondrial dysfunction. We published the efficacy of KD in patients with cancer after failure of chemotherapy. 1 This case report is presented to evaluate the feasibility of KD concurrent with chemoimmunotherapy.
Case Report
Patient is a 69-year-old male who presented with iron deficiency anemia in 2018. Colonoscopy and biopsy showed colon adenocarcinoma. He underwent resection which confirmed stage IIIC disease. He received adjuvant treatment with FOLFOX but quickly developed pancreatic and omental metastasis. He was started on FOLFIRI + bevacizumab followed by pancreatic mass resection in 2019. Molecular testing revealed wild type KRAS, positive BRAF V600E, and high MSI. He received encorafenib + cetuximab until disease progression. Treatment was changed to pembrolizumab until PET scan showed progression. His CEA increased to 1031 in January 2021. He was subsequently started on KD concurrent with trifluridine + tipiracil + bevacizumab. He progressed after 10 months. Therapy was changed to ipilimumab + nivolumab with continuation of KD. He was strictly adherent to KD with low Glucose Ketone Index of 8.2 (confirming ketosis) but in 2022 his GKI level started to rise. His CEA, however, significantly decreased to 20 in March 2022 and PET scan showed stable disease. He presently is on maintenance nivolumab + KD while maintaining an excellent quality of life by EORTC QLQ scores.
Conclusions
The use of KD concurrently with chemotherapy and immunotherapy is still under investigation. Our case report shows that KD is tolerable with treatment and can possibly contribute to controlling progression of metastatic cancer. We are starting an investigator initiative KD trial that received a grant from R&D at VACCHCS. We will present the study protocol in poster presentation.
1. Tan-Shalaby JL, Carrick J, Edinger K, et al. Modified Atkins diet in advanced malignancies - final results of a safety and feasibility trial within the Veterans Affairs Pittsburgh Healthcare System]. Nutr Metab (Lond). 2016;13:52. Published 2016 Aug 12. doi:10.1186/s12986-016-0113-y
1. Tan-Shalaby JL, Carrick J, Edinger K, et al. Modified Atkins diet in advanced malignancies - final results of a safety and feasibility trial within the Veterans Affairs Pittsburgh Healthcare System]. Nutr Metab (Lond). 2016;13:52. Published 2016 Aug 12. doi:10.1186/s12986-016-0113-y
Capturing Pathology Workload Required for a Precision Oncology Molecular Test (POMT)
Background
Precision oncology has made nextgeneration sequencing a part of daily practice. With indications for comprehensive genomic profiling expanding, there will be further attendant increases in pathology workload. The pathology workforce shortage is one of the greatest barriers to precision oncology and an understanding of pathology workload associated with POMTs is necessary to address this barrier and plan for the future.
Methods
In this presentation we aim to provide, or at least contribute to, such an understanding through a review of the process at our site and measurement of associated time for each step. We began by conceptualizing the process in order to develop a process map. We then measured the average time for each step. We reviewed our anatomic pathology records for 2021 to determine the number of POMTs then calculated cumulative time investment on POMTs. A theoretical number of relative value units (RVUs) for POMTs was calculated using the new pathology clinical consultation CPT codes (80503-80506), and this was compared to the total anatomic pathology RVUs actually generated in 2021.
Results
Of the 7007 anatomic pathology cases, there were 706 cancers and 446 that required POMTs. At our institution, it was determined that on average 1.5 hours – about 50 minutes of pathologist time and 40 minutes of technician time – was needed to complete the tasks necessary to fulfillment of requests for POMTs. For all of 2021, 669 hours of pathology staff time were dedicated to POMTs. With the ability to bill for this time, we would have generated 13.2% (1142/8640) more anatomic pathology RVUs.
Conculsions
In light of this, we have implemented measures to bill for these formerly uncaptured activities such that our documented productivity more accurately reflects our workload. This will hopefully result in more appropriate resource allocation such that the barrier created by pathology understaffing is recast as a buttress in support of precision oncology practice.
Background
Precision oncology has made nextgeneration sequencing a part of daily practice. With indications for comprehensive genomic profiling expanding, there will be further attendant increases in pathology workload. The pathology workforce shortage is one of the greatest barriers to precision oncology and an understanding of pathology workload associated with POMTs is necessary to address this barrier and plan for the future.
Methods
In this presentation we aim to provide, or at least contribute to, such an understanding through a review of the process at our site and measurement of associated time for each step. We began by conceptualizing the process in order to develop a process map. We then measured the average time for each step. We reviewed our anatomic pathology records for 2021 to determine the number of POMTs then calculated cumulative time investment on POMTs. A theoretical number of relative value units (RVUs) for POMTs was calculated using the new pathology clinical consultation CPT codes (80503-80506), and this was compared to the total anatomic pathology RVUs actually generated in 2021.
Results
Of the 7007 anatomic pathology cases, there were 706 cancers and 446 that required POMTs. At our institution, it was determined that on average 1.5 hours – about 50 minutes of pathologist time and 40 minutes of technician time – was needed to complete the tasks necessary to fulfillment of requests for POMTs. For all of 2021, 669 hours of pathology staff time were dedicated to POMTs. With the ability to bill for this time, we would have generated 13.2% (1142/8640) more anatomic pathology RVUs.
Conculsions
In light of this, we have implemented measures to bill for these formerly uncaptured activities such that our documented productivity more accurately reflects our workload. This will hopefully result in more appropriate resource allocation such that the barrier created by pathology understaffing is recast as a buttress in support of precision oncology practice.
Background
Precision oncology has made nextgeneration sequencing a part of daily practice. With indications for comprehensive genomic profiling expanding, there will be further attendant increases in pathology workload. The pathology workforce shortage is one of the greatest barriers to precision oncology and an understanding of pathology workload associated with POMTs is necessary to address this barrier and plan for the future.
Methods
In this presentation we aim to provide, or at least contribute to, such an understanding through a review of the process at our site and measurement of associated time for each step. We began by conceptualizing the process in order to develop a process map. We then measured the average time for each step. We reviewed our anatomic pathology records for 2021 to determine the number of POMTs then calculated cumulative time investment on POMTs. A theoretical number of relative value units (RVUs) for POMTs was calculated using the new pathology clinical consultation CPT codes (80503-80506), and this was compared to the total anatomic pathology RVUs actually generated in 2021.
Results
Of the 7007 anatomic pathology cases, there were 706 cancers and 446 that required POMTs. At our institution, it was determined that on average 1.5 hours – about 50 minutes of pathologist time and 40 minutes of technician time – was needed to complete the tasks necessary to fulfillment of requests for POMTs. For all of 2021, 669 hours of pathology staff time were dedicated to POMTs. With the ability to bill for this time, we would have generated 13.2% (1142/8640) more anatomic pathology RVUs.
Conculsions
In light of this, we have implemented measures to bill for these formerly uncaptured activities such that our documented productivity more accurately reflects our workload. This will hopefully result in more appropriate resource allocation such that the barrier created by pathology understaffing is recast as a buttress in support of precision oncology practice.
Castration-Resistant Prostate Cancer—Not Only Challenging to Treat, but Difficult to Define
Purpose
Examine the impact of different definitions of castration resistance used to identify patients with castration-resistant prostate cancer (CRPC) using electronic health records (EHR).
Background
CRPC is a form of prostate cancer that is resistant to treatment with androgen deprivation therapy (ADT) and is associated with higher morbidity and mortality. Widely used guidelines like the Prostate Cancer Working Group 3 (PCWG 3), the American Urological Association (AUA), and many others differ in their definitions of castration-resistance. Until now, the feasibility of identifying CRPC using different definitions from EHR data has not been studied.
Methods/Data Analyisis
EHR data from the Veterans Health Administration (01/2006-12/2020) were used to identify veterans with CRPC according to the following criteria: 1) PCWG 3—a PSA increase ?25% from the nadir with a minimum rise of 2 ng/mL, while castrate (testosterone < 50 ng/mL); 2) AUA—2 consecutive PSA rises of ?0.2 ng/mL; 3) CRPC screening—a PSA rise of > 0.0 ng/mL within a window of 7–90 days.
Results
36,101 unique patients were identified using 1 of (or a combination of) the 3 CRPC criteria. Approximately 12,775 (35%) patients met all 3 criteria, while 8,589 (24%) were identified by AUA, 4,785 (13%) by CRPC screening, and 145 (0.4%) by PCWG3. A total of 8,377 (23%) patients met both the AUA and CRPC screening criteria, 1,219 (3%) patients met the AUA and PCWG3 criteria, and 211 (1%) met the PCWG3 and CRPC screening criteria.
Conculsions/Implications
Although several definitions can be used to identify CRPC patients, a combination of these definitions results in the greatest yield of CRPC patients identified using EHR data. Even though the PCWG3 criterion is frequently used in both clinical trials research and retrospective observational research, PCWG3 may miss many patients meeting other criteria and should not be used by itself when studying patients with CRPC identified from EHR data.
Purpose
Examine the impact of different definitions of castration resistance used to identify patients with castration-resistant prostate cancer (CRPC) using electronic health records (EHR).
Background
CRPC is a form of prostate cancer that is resistant to treatment with androgen deprivation therapy (ADT) and is associated with higher morbidity and mortality. Widely used guidelines like the Prostate Cancer Working Group 3 (PCWG 3), the American Urological Association (AUA), and many others differ in their definitions of castration-resistance. Until now, the feasibility of identifying CRPC using different definitions from EHR data has not been studied.
Methods/Data Analyisis
EHR data from the Veterans Health Administration (01/2006-12/2020) were used to identify veterans with CRPC according to the following criteria: 1) PCWG 3—a PSA increase ?25% from the nadir with a minimum rise of 2 ng/mL, while castrate (testosterone < 50 ng/mL); 2) AUA—2 consecutive PSA rises of ?0.2 ng/mL; 3) CRPC screening—a PSA rise of > 0.0 ng/mL within a window of 7–90 days.
Results
36,101 unique patients were identified using 1 of (or a combination of) the 3 CRPC criteria. Approximately 12,775 (35%) patients met all 3 criteria, while 8,589 (24%) were identified by AUA, 4,785 (13%) by CRPC screening, and 145 (0.4%) by PCWG3. A total of 8,377 (23%) patients met both the AUA and CRPC screening criteria, 1,219 (3%) patients met the AUA and PCWG3 criteria, and 211 (1%) met the PCWG3 and CRPC screening criteria.
Conculsions/Implications
Although several definitions can be used to identify CRPC patients, a combination of these definitions results in the greatest yield of CRPC patients identified using EHR data. Even though the PCWG3 criterion is frequently used in both clinical trials research and retrospective observational research, PCWG3 may miss many patients meeting other criteria and should not be used by itself when studying patients with CRPC identified from EHR data.
Purpose
Examine the impact of different definitions of castration resistance used to identify patients with castration-resistant prostate cancer (CRPC) using electronic health records (EHR).
Background
CRPC is a form of prostate cancer that is resistant to treatment with androgen deprivation therapy (ADT) and is associated with higher morbidity and mortality. Widely used guidelines like the Prostate Cancer Working Group 3 (PCWG 3), the American Urological Association (AUA), and many others differ in their definitions of castration-resistance. Until now, the feasibility of identifying CRPC using different definitions from EHR data has not been studied.
Methods/Data Analyisis
EHR data from the Veterans Health Administration (01/2006-12/2020) were used to identify veterans with CRPC according to the following criteria: 1) PCWG 3—a PSA increase ?25% from the nadir with a minimum rise of 2 ng/mL, while castrate (testosterone < 50 ng/mL); 2) AUA—2 consecutive PSA rises of ?0.2 ng/mL; 3) CRPC screening—a PSA rise of > 0.0 ng/mL within a window of 7–90 days.
Results
36,101 unique patients were identified using 1 of (or a combination of) the 3 CRPC criteria. Approximately 12,775 (35%) patients met all 3 criteria, while 8,589 (24%) were identified by AUA, 4,785 (13%) by CRPC screening, and 145 (0.4%) by PCWG3. A total of 8,377 (23%) patients met both the AUA and CRPC screening criteria, 1,219 (3%) patients met the AUA and PCWG3 criteria, and 211 (1%) met the PCWG3 and CRPC screening criteria.
Conculsions/Implications
Although several definitions can be used to identify CRPC patients, a combination of these definitions results in the greatest yield of CRPC patients identified using EHR data. Even though the PCWG3 criterion is frequently used in both clinical trials research and retrospective observational research, PCWG3 may miss many patients meeting other criteria and should not be used by itself when studying patients with CRPC identified from EHR data.
A Rare Case of HHV8+ Multicentric Castleman Disease Presenting as Dermatitis
Introduction
Castleman disease (CD) is a rare non-neoplastic disorder presenting as lymphadenopathy. Skin involvement and progression to lymphomas are uncommon, and such presentation can pose a diagnostic challenge. We describe an interesting case of multicentric CD presenting as a rash.
Case Description
A 79-year-old male presented with a 1-year history of blanchable maculopapular rash and new onset dyspnea in the absence of fever, fatigue or weight loss. Examination revealed axillary, cervical and inguinal lymphadenopathy, and firm splenomegaly. Initial labs were notable for leukocytosis, occasional lymphoplasmacytic cells, anemia, thrombocytopenia, negative HIV screen, and elevated ESR and LDH. Further testing identified polyclonal hypergammaglobulinemia. CT scans revealed generalized lymphadenopathy, splenomegaly with infarcts and unilateral pleural effusion. An inguinal lymph node needle biopsy, skin biopsy and pleural fluid cytology were concerning for lymphoplasmacytic, so he was started on rituximab and bendamustine. However, B cell clonality could not be demonstrated, making these findings concerning for Castleman disease.
Results
Human herpesvirus 8 (HHV-8) testing performed on the inguinal lymph node sample came out positive, and he was diagnosed with HHV-8 positive multicentric Castleman disease and continued on weekly rituximab. He demonstrated an excellent response with complete resolution of rash, palpable lymphadenopathy and anemia after 4 cycles of treatment.
Discussion
Castleman disease (CD) is a rare disorder of polyclonal B cell proliferation classically presenting as lymphadenopathy with constitutional symptoms. Cutaneous presentations include eruptive angiomas or petechial rash but can be variable. Intrinsic or viral IL-6 play a key role in the pathogenesis of the disease. CD can be localised or multicentric (related to HHV-8 +/- HIV or idiopathic), and these subtypes differ in prognosis and management, with HIV and HHV-8 co-positivity indicating worse outcomes. While human IL-6 in unicentric and idiopathic multicentric disease respond well to IL-6 receptor antagonists, viral IL-6 in HHV-8 associated cases has a limited response. This is the rationale for preferring anti-CD20 therapy with rituximab in these patients.
Conculsions
Correct biopsy specimen, keen analysis of distinct pathologic features, and HHV-8 testing on tissue sample guide the diagnosis as HHV-8 serology can be falsely negative.
Introduction
Castleman disease (CD) is a rare non-neoplastic disorder presenting as lymphadenopathy. Skin involvement and progression to lymphomas are uncommon, and such presentation can pose a diagnostic challenge. We describe an interesting case of multicentric CD presenting as a rash.
Case Description
A 79-year-old male presented with a 1-year history of blanchable maculopapular rash and new onset dyspnea in the absence of fever, fatigue or weight loss. Examination revealed axillary, cervical and inguinal lymphadenopathy, and firm splenomegaly. Initial labs were notable for leukocytosis, occasional lymphoplasmacytic cells, anemia, thrombocytopenia, negative HIV screen, and elevated ESR and LDH. Further testing identified polyclonal hypergammaglobulinemia. CT scans revealed generalized lymphadenopathy, splenomegaly with infarcts and unilateral pleural effusion. An inguinal lymph node needle biopsy, skin biopsy and pleural fluid cytology were concerning for lymphoplasmacytic, so he was started on rituximab and bendamustine. However, B cell clonality could not be demonstrated, making these findings concerning for Castleman disease.
Results
Human herpesvirus 8 (HHV-8) testing performed on the inguinal lymph node sample came out positive, and he was diagnosed with HHV-8 positive multicentric Castleman disease and continued on weekly rituximab. He demonstrated an excellent response with complete resolution of rash, palpable lymphadenopathy and anemia after 4 cycles of treatment.
Discussion
Castleman disease (CD) is a rare disorder of polyclonal B cell proliferation classically presenting as lymphadenopathy with constitutional symptoms. Cutaneous presentations include eruptive angiomas or petechial rash but can be variable. Intrinsic or viral IL-6 play a key role in the pathogenesis of the disease. CD can be localised or multicentric (related to HHV-8 +/- HIV or idiopathic), and these subtypes differ in prognosis and management, with HIV and HHV-8 co-positivity indicating worse outcomes. While human IL-6 in unicentric and idiopathic multicentric disease respond well to IL-6 receptor antagonists, viral IL-6 in HHV-8 associated cases has a limited response. This is the rationale for preferring anti-CD20 therapy with rituximab in these patients.
Conculsions
Correct biopsy specimen, keen analysis of distinct pathologic features, and HHV-8 testing on tissue sample guide the diagnosis as HHV-8 serology can be falsely negative.
Introduction
Castleman disease (CD) is a rare non-neoplastic disorder presenting as lymphadenopathy. Skin involvement and progression to lymphomas are uncommon, and such presentation can pose a diagnostic challenge. We describe an interesting case of multicentric CD presenting as a rash.
Case Description
A 79-year-old male presented with a 1-year history of blanchable maculopapular rash and new onset dyspnea in the absence of fever, fatigue or weight loss. Examination revealed axillary, cervical and inguinal lymphadenopathy, and firm splenomegaly. Initial labs were notable for leukocytosis, occasional lymphoplasmacytic cells, anemia, thrombocytopenia, negative HIV screen, and elevated ESR and LDH. Further testing identified polyclonal hypergammaglobulinemia. CT scans revealed generalized lymphadenopathy, splenomegaly with infarcts and unilateral pleural effusion. An inguinal lymph node needle biopsy, skin biopsy and pleural fluid cytology were concerning for lymphoplasmacytic, so he was started on rituximab and bendamustine. However, B cell clonality could not be demonstrated, making these findings concerning for Castleman disease.
Results
Human herpesvirus 8 (HHV-8) testing performed on the inguinal lymph node sample came out positive, and he was diagnosed with HHV-8 positive multicentric Castleman disease and continued on weekly rituximab. He demonstrated an excellent response with complete resolution of rash, palpable lymphadenopathy and anemia after 4 cycles of treatment.
Discussion
Castleman disease (CD) is a rare disorder of polyclonal B cell proliferation classically presenting as lymphadenopathy with constitutional symptoms. Cutaneous presentations include eruptive angiomas or petechial rash but can be variable. Intrinsic or viral IL-6 play a key role in the pathogenesis of the disease. CD can be localised or multicentric (related to HHV-8 +/- HIV or idiopathic), and these subtypes differ in prognosis and management, with HIV and HHV-8 co-positivity indicating worse outcomes. While human IL-6 in unicentric and idiopathic multicentric disease respond well to IL-6 receptor antagonists, viral IL-6 in HHV-8 associated cases has a limited response. This is the rationale for preferring anti-CD20 therapy with rituximab in these patients.
Conculsions
Correct biopsy specimen, keen analysis of distinct pathologic features, and HHV-8 testing on tissue sample guide the diagnosis as HHV-8 serology can be falsely negative.
Identification of Clinically Actionable Genomic Alterations in Colorectal Cancer Patients From the VA National Precision Oncology Program (NPOP)
Purpose
Colorectal cancer (CRC) is the fourth most common cancer at VA and the third leading cause of cancer-related death in the USA. The VA National Precision Oncology Program (NPOP) was established in 2016 with the goal of implementing standardized, streamlined methods for molecular testing of veterans with cancer and has enabled comprehensive genomic profiling (CGP) and precision medicine as part of routine cancer care. Obtaining CGP of predictive biomarkers in cancer tissue, including mutations in genes (e.g., KRAS, NRAS and BRAF), tumor mutation burden (TMB) and microsatellite instability status (MSI) can be used to support treatment decisions with targeted and immunotherapies.
Methods
In this study we describe the frequencies of these clinical biomarkers in colon adenocarcinoma (COAD), rectal adenocarcinoma (READ), and other colon or rectum histologies (CROT); and compare these frequencies to a published cohort of metastatic CRC using Chi-square test (Yaeger et al., 2018).
Results
A total of 1802 patients with CRC were included in this study. COAD was the most frequent disease site (76.9%) followed by READ (19.1%). Approximately 52.9% of COAD patients harbored at least one highly actionable biomarker (defined as having an FDA-approved indication) including NRAS/ KRAS/BRAF wildtype (38.0%), TMB-H (12.9%), BRAF V600E (9.7%), MSI-H (8.9%), and NTRK fusion or rearrangement (0.3%). About 52.0% of patients with READ had these biomarkers, while this rate was (16.4%) in CROT. Among patients with COAD and READ, those with BRAF V600E mutations were more likely to be older, White, not Hispanic or Latino, and lived in urban areas compared to those without BRAF V600E. Relative to those with NRAS/KRAS/BRAF mutations, patients with NRAS/KRAS/BRAF wildtype were frequently younger. Relative to the frequency of biomarkers from a cBioPortal cohort of metastatic CRC, the frequency of NRAS wildtype was significantly lower in patients with COAD and READ tested through NPOP.
Consulsions
In this cohort, ~53 % of patients with COAD and 52% of patients with READ have highly actionable biomarkers and are potentially eligible for FDAapproved targeted therapies. Future studies examining cancer outcomes with regard to the use of targeted therapies in the setting of actionable gene alterations, TMB, and MSI are warranted.
Purpose
Colorectal cancer (CRC) is the fourth most common cancer at VA and the third leading cause of cancer-related death in the USA. The VA National Precision Oncology Program (NPOP) was established in 2016 with the goal of implementing standardized, streamlined methods for molecular testing of veterans with cancer and has enabled comprehensive genomic profiling (CGP) and precision medicine as part of routine cancer care. Obtaining CGP of predictive biomarkers in cancer tissue, including mutations in genes (e.g., KRAS, NRAS and BRAF), tumor mutation burden (TMB) and microsatellite instability status (MSI) can be used to support treatment decisions with targeted and immunotherapies.
Methods
In this study we describe the frequencies of these clinical biomarkers in colon adenocarcinoma (COAD), rectal adenocarcinoma (READ), and other colon or rectum histologies (CROT); and compare these frequencies to a published cohort of metastatic CRC using Chi-square test (Yaeger et al., 2018).
Results
A total of 1802 patients with CRC were included in this study. COAD was the most frequent disease site (76.9%) followed by READ (19.1%). Approximately 52.9% of COAD patients harbored at least one highly actionable biomarker (defined as having an FDA-approved indication) including NRAS/ KRAS/BRAF wildtype (38.0%), TMB-H (12.9%), BRAF V600E (9.7%), MSI-H (8.9%), and NTRK fusion or rearrangement (0.3%). About 52.0% of patients with READ had these biomarkers, while this rate was (16.4%) in CROT. Among patients with COAD and READ, those with BRAF V600E mutations were more likely to be older, White, not Hispanic or Latino, and lived in urban areas compared to those without BRAF V600E. Relative to those with NRAS/KRAS/BRAF mutations, patients with NRAS/KRAS/BRAF wildtype were frequently younger. Relative to the frequency of biomarkers from a cBioPortal cohort of metastatic CRC, the frequency of NRAS wildtype was significantly lower in patients with COAD and READ tested through NPOP.
Consulsions
In this cohort, ~53 % of patients with COAD and 52% of patients with READ have highly actionable biomarkers and are potentially eligible for FDAapproved targeted therapies. Future studies examining cancer outcomes with regard to the use of targeted therapies in the setting of actionable gene alterations, TMB, and MSI are warranted.
Purpose
Colorectal cancer (CRC) is the fourth most common cancer at VA and the third leading cause of cancer-related death in the USA. The VA National Precision Oncology Program (NPOP) was established in 2016 with the goal of implementing standardized, streamlined methods for molecular testing of veterans with cancer and has enabled comprehensive genomic profiling (CGP) and precision medicine as part of routine cancer care. Obtaining CGP of predictive biomarkers in cancer tissue, including mutations in genes (e.g., KRAS, NRAS and BRAF), tumor mutation burden (TMB) and microsatellite instability status (MSI) can be used to support treatment decisions with targeted and immunotherapies.
Methods
In this study we describe the frequencies of these clinical biomarkers in colon adenocarcinoma (COAD), rectal adenocarcinoma (READ), and other colon or rectum histologies (CROT); and compare these frequencies to a published cohort of metastatic CRC using Chi-square test (Yaeger et al., 2018).
Results
A total of 1802 patients with CRC were included in this study. COAD was the most frequent disease site (76.9%) followed by READ (19.1%). Approximately 52.9% of COAD patients harbored at least one highly actionable biomarker (defined as having an FDA-approved indication) including NRAS/ KRAS/BRAF wildtype (38.0%), TMB-H (12.9%), BRAF V600E (9.7%), MSI-H (8.9%), and NTRK fusion or rearrangement (0.3%). About 52.0% of patients with READ had these biomarkers, while this rate was (16.4%) in CROT. Among patients with COAD and READ, those with BRAF V600E mutations were more likely to be older, White, not Hispanic or Latino, and lived in urban areas compared to those without BRAF V600E. Relative to those with NRAS/KRAS/BRAF mutations, patients with NRAS/KRAS/BRAF wildtype were frequently younger. Relative to the frequency of biomarkers from a cBioPortal cohort of metastatic CRC, the frequency of NRAS wildtype was significantly lower in patients with COAD and READ tested through NPOP.
Consulsions
In this cohort, ~53 % of patients with COAD and 52% of patients with READ have highly actionable biomarkers and are potentially eligible for FDAapproved targeted therapies. Future studies examining cancer outcomes with regard to the use of targeted therapies in the setting of actionable gene alterations, TMB, and MSI are warranted.
Evaluation of the Prostate Cancer Molecular Testing Pathway (PCMTP) Within the Veterans Health Administration (VHA)
Purpose
The PCMTP was developed to provide standardized decision support for molecular testing for veterans with prostate cancer.
Background
Prior to the precision medicine era, molecular tumor testing in prostate cancer was not standard of care. Field practitioners were unfamiliar with the role of molecular testing in clinical care. The PCMTP provides direction for germline and tumor testing in appropriate patients with prostate cancer. The expectation is that at least 80% of veterans will be pathway adherent. The PCMTP is an Oncology Clinical Pathway (OCP) that supports evidence-based practice providing highquality, safe, and cost-effective care for veterans reducing variability of care in the VHA.
Methods
The National Oncology Program Office assembled a Prostate Cancer Team (PCT) to develop OCPs. The pathways were incorporated into note templates that record clinical decisions using text and metadata (Health Factors [HF]), and record pathway adherence for the 4 key nodes of the PCMTP. The templates were pilot-tested and improved using an iterative process over a 3-month period. Further evaluation was conducted by the Office of Human Factors Engineering and the National Clinical Template Workgroup, utilizing a heuristic evaluation to ensure standardization, interoperability, and reduce duplication. HF data were retrieved from the Corporate Data Warehouse using a custom-built dashboard. Descriptive statistics of PCMTP use are presented.
Results
Between 4/1/2021 and 6/22/2022, 6276 health factors were generated from 1707 unique veterans in whom this clinical pathway was accessed. 328 distinct providers participated at 61 sites. Average veteran age was 73 years. (range 45-100) including 42% Black and 56% White. Of 1243 veterans considered for germline testing, 96.6% had germline testing ordered and for 1102 veterans considered for tumor testing, 93.3% had tumor testing ordered.
Conclusions
Pathway adherence exceeded the 80% benchmark. Race representation was diverse and reflective of the VA prostate cancer population. About 46% of VA oncology practices have used the PCMTP for ~11% of the estimated 15,000 veterans with metastatic prostate cancer in VHA. Increased use of this pathway is expected to improve outcomes for veterans with prostate cancer
Purpose
The PCMTP was developed to provide standardized decision support for molecular testing for veterans with prostate cancer.
Background
Prior to the precision medicine era, molecular tumor testing in prostate cancer was not standard of care. Field practitioners were unfamiliar with the role of molecular testing in clinical care. The PCMTP provides direction for germline and tumor testing in appropriate patients with prostate cancer. The expectation is that at least 80% of veterans will be pathway adherent. The PCMTP is an Oncology Clinical Pathway (OCP) that supports evidence-based practice providing highquality, safe, and cost-effective care for veterans reducing variability of care in the VHA.
Methods
The National Oncology Program Office assembled a Prostate Cancer Team (PCT) to develop OCPs. The pathways were incorporated into note templates that record clinical decisions using text and metadata (Health Factors [HF]), and record pathway adherence for the 4 key nodes of the PCMTP. The templates were pilot-tested and improved using an iterative process over a 3-month period. Further evaluation was conducted by the Office of Human Factors Engineering and the National Clinical Template Workgroup, utilizing a heuristic evaluation to ensure standardization, interoperability, and reduce duplication. HF data were retrieved from the Corporate Data Warehouse using a custom-built dashboard. Descriptive statistics of PCMTP use are presented.
Results
Between 4/1/2021 and 6/22/2022, 6276 health factors were generated from 1707 unique veterans in whom this clinical pathway was accessed. 328 distinct providers participated at 61 sites. Average veteran age was 73 years. (range 45-100) including 42% Black and 56% White. Of 1243 veterans considered for germline testing, 96.6% had germline testing ordered and for 1102 veterans considered for tumor testing, 93.3% had tumor testing ordered.
Conclusions
Pathway adherence exceeded the 80% benchmark. Race representation was diverse and reflective of the VA prostate cancer population. About 46% of VA oncology practices have used the PCMTP for ~11% of the estimated 15,000 veterans with metastatic prostate cancer in VHA. Increased use of this pathway is expected to improve outcomes for veterans with prostate cancer
Purpose
The PCMTP was developed to provide standardized decision support for molecular testing for veterans with prostate cancer.
Background
Prior to the precision medicine era, molecular tumor testing in prostate cancer was not standard of care. Field practitioners were unfamiliar with the role of molecular testing in clinical care. The PCMTP provides direction for germline and tumor testing in appropriate patients with prostate cancer. The expectation is that at least 80% of veterans will be pathway adherent. The PCMTP is an Oncology Clinical Pathway (OCP) that supports evidence-based practice providing highquality, safe, and cost-effective care for veterans reducing variability of care in the VHA.
Methods
The National Oncology Program Office assembled a Prostate Cancer Team (PCT) to develop OCPs. The pathways were incorporated into note templates that record clinical decisions using text and metadata (Health Factors [HF]), and record pathway adherence for the 4 key nodes of the PCMTP. The templates were pilot-tested and improved using an iterative process over a 3-month period. Further evaluation was conducted by the Office of Human Factors Engineering and the National Clinical Template Workgroup, utilizing a heuristic evaluation to ensure standardization, interoperability, and reduce duplication. HF data were retrieved from the Corporate Data Warehouse using a custom-built dashboard. Descriptive statistics of PCMTP use are presented.
Results
Between 4/1/2021 and 6/22/2022, 6276 health factors were generated from 1707 unique veterans in whom this clinical pathway was accessed. 328 distinct providers participated at 61 sites. Average veteran age was 73 years. (range 45-100) including 42% Black and 56% White. Of 1243 veterans considered for germline testing, 96.6% had germline testing ordered and for 1102 veterans considered for tumor testing, 93.3% had tumor testing ordered.
Conclusions
Pathway adherence exceeded the 80% benchmark. Race representation was diverse and reflective of the VA prostate cancer population. About 46% of VA oncology practices have used the PCMTP for ~11% of the estimated 15,000 veterans with metastatic prostate cancer in VHA. Increased use of this pathway is expected to improve outcomes for veterans with prostate cancer
New Delivery Models Improve Access to Germline Testing for Patients With Advanced Prostate Cancer
Objectives
The VA Oncology Clinical Pathway for Prostate Cancer is the first to include both tumor and germline testing to inform treatment and clinical trial eligibility for advanced disease. Anticipating increased germline testing demand, new germline testing delivery models were created to augment the existing traditional model of referring patients to genetics providers (VA or non-VA) for germline testing. The new models include: a non-traditional model where oncology clinicians perform all pre- and post-test activities and consult genetics when needed, and a hybrid model where oncology clinicians obtain informed consent and place e-consults for germline test ordering, results disclosure, and genetics follow-up, as needed. We sought to assess germline testing by delivery model.
Methods
Data sources included the National Precision Oncology Program (NPOP) dashboard and NPOP-contracted germline testing laboratories. Patient inclusion criteria: living as of 5/2/2021 with VA oncology or urology visits after 5/2/2021. We used multivariate regression to assess associations between patient characteristics and germline testing between 5/3/2021 (pathway launch) and 5/2/2022, accounting for clustering of patients within ordering clinicians.
Results
We identified 16,041 patients from 129 VA facilities with average age 75 years (SD, 8.2; range, 36- 102), 28.7% Black and 60.0% White. Only 5.6% had germline testing ordered by 60 clinicians at 67 facilities with 52.2% of orders by the hybrid model, 32.1% the non-traditional model, and 15.4% the traditional model. Patient characteristics positively associated with germline testing included care at hybrid model (OR, 6.03; 95% CI, 4.62-7.88) or non-traditional model facilities (OR, 5.66; 95% CI, 4.24-7.56) compared to the traditional model, completing tumor molecular testing (OR, 5.80; 95%CI, 4.98-6.75), and Black compared with White race (OR, 1.24; 95%CI, 1.06-1.45). Compared to patients aged < 66 years, patients aged 66-75 years and 76-85 years were less likely to have germline testing (OR, 0.74; 95%CI, 0.60-0.90; and OR, 0.67; 95%CI, 0.53-0.84, respectively).
Conclusions/Implications
Though only a small percentage of patients with advanced prostate cancer had NPOP-supported germline testing since the pathway launch, the new delivery models were instrumental to improving access to germline testing. Ongoing evaluation will help to understand observed demographic differences in germline testing. Implementation and evaluation of strategies that promote adoption of the new germline testing delivery models is needed. 0922FED AVAHO_Abstracts.indd 15 8
Objectives
The VA Oncology Clinical Pathway for Prostate Cancer is the first to include both tumor and germline testing to inform treatment and clinical trial eligibility for advanced disease. Anticipating increased germline testing demand, new germline testing delivery models were created to augment the existing traditional model of referring patients to genetics providers (VA or non-VA) for germline testing. The new models include: a non-traditional model where oncology clinicians perform all pre- and post-test activities and consult genetics when needed, and a hybrid model where oncology clinicians obtain informed consent and place e-consults for germline test ordering, results disclosure, and genetics follow-up, as needed. We sought to assess germline testing by delivery model.
Methods
Data sources included the National Precision Oncology Program (NPOP) dashboard and NPOP-contracted germline testing laboratories. Patient inclusion criteria: living as of 5/2/2021 with VA oncology or urology visits after 5/2/2021. We used multivariate regression to assess associations between patient characteristics and germline testing between 5/3/2021 (pathway launch) and 5/2/2022, accounting for clustering of patients within ordering clinicians.
Results
We identified 16,041 patients from 129 VA facilities with average age 75 years (SD, 8.2; range, 36- 102), 28.7% Black and 60.0% White. Only 5.6% had germline testing ordered by 60 clinicians at 67 facilities with 52.2% of orders by the hybrid model, 32.1% the non-traditional model, and 15.4% the traditional model. Patient characteristics positively associated with germline testing included care at hybrid model (OR, 6.03; 95% CI, 4.62-7.88) or non-traditional model facilities (OR, 5.66; 95% CI, 4.24-7.56) compared to the traditional model, completing tumor molecular testing (OR, 5.80; 95%CI, 4.98-6.75), and Black compared with White race (OR, 1.24; 95%CI, 1.06-1.45). Compared to patients aged < 66 years, patients aged 66-75 years and 76-85 years were less likely to have germline testing (OR, 0.74; 95%CI, 0.60-0.90; and OR, 0.67; 95%CI, 0.53-0.84, respectively).
Conclusions/Implications
Though only a small percentage of patients with advanced prostate cancer had NPOP-supported germline testing since the pathway launch, the new delivery models were instrumental to improving access to germline testing. Ongoing evaluation will help to understand observed demographic differences in germline testing. Implementation and evaluation of strategies that promote adoption of the new germline testing delivery models is needed. 0922FED AVAHO_Abstracts.indd 15 8
Objectives
The VA Oncology Clinical Pathway for Prostate Cancer is the first to include both tumor and germline testing to inform treatment and clinical trial eligibility for advanced disease. Anticipating increased germline testing demand, new germline testing delivery models were created to augment the existing traditional model of referring patients to genetics providers (VA or non-VA) for germline testing. The new models include: a non-traditional model where oncology clinicians perform all pre- and post-test activities and consult genetics when needed, and a hybrid model where oncology clinicians obtain informed consent and place e-consults for germline test ordering, results disclosure, and genetics follow-up, as needed. We sought to assess germline testing by delivery model.
Methods
Data sources included the National Precision Oncology Program (NPOP) dashboard and NPOP-contracted germline testing laboratories. Patient inclusion criteria: living as of 5/2/2021 with VA oncology or urology visits after 5/2/2021. We used multivariate regression to assess associations between patient characteristics and germline testing between 5/3/2021 (pathway launch) and 5/2/2022, accounting for clustering of patients within ordering clinicians.
Results
We identified 16,041 patients from 129 VA facilities with average age 75 years (SD, 8.2; range, 36- 102), 28.7% Black and 60.0% White. Only 5.6% had germline testing ordered by 60 clinicians at 67 facilities with 52.2% of orders by the hybrid model, 32.1% the non-traditional model, and 15.4% the traditional model. Patient characteristics positively associated with germline testing included care at hybrid model (OR, 6.03; 95% CI, 4.62-7.88) or non-traditional model facilities (OR, 5.66; 95% CI, 4.24-7.56) compared to the traditional model, completing tumor molecular testing (OR, 5.80; 95%CI, 4.98-6.75), and Black compared with White race (OR, 1.24; 95%CI, 1.06-1.45). Compared to patients aged < 66 years, patients aged 66-75 years and 76-85 years were less likely to have germline testing (OR, 0.74; 95%CI, 0.60-0.90; and OR, 0.67; 95%CI, 0.53-0.84, respectively).
Conclusions/Implications
Though only a small percentage of patients with advanced prostate cancer had NPOP-supported germline testing since the pathway launch, the new delivery models were instrumental to improving access to germline testing. Ongoing evaluation will help to understand observed demographic differences in germline testing. Implementation and evaluation of strategies that promote adoption of the new germline testing delivery models is needed. 0922FED AVAHO_Abstracts.indd 15 8
MYO1E DNA Methylation in U.S. Military Veterans With Adenocarcinoma of the Lung Is Associated With Increased Mortality Risk
Project Purpose
The aim is to assess the role of MYO1E in survival among veterans with lung adenocarcinoma (LUAD).
Background
Veterans have a higher smoking exposure than civilians; a higher incidence of lung cancer; and a younger age at diagnosis of lung cancer. We recently showed that MYO1E DNA methylation and RNA expression in LUAD are associated with survival among civilians.
Methods
This is a retrospective cohort study involving LUAD among civilians and veterans with biopsy or pathologically proven LUAD from surgical specimens. DNA extraction and isolation from FFPE cancer tissues was performed using methylation-onbeads as previously published, followed by qMSP with bisulfite treatment to quantify DNA methylation. RNA extraction and quantification from lung tissues was obtained as described in previous publications.
Data Analysis
Differences were assessed with Wilcoxon rank sum test for continuous variables and Fisher’s exact test for categorical. Two-tailed log-rank test was used to estimate overall survival differences and Cox hazard models, to quantify risk of mortality using hazard ratios (HRs) with 95% confidence intervals (CIs).
Results
There were 91 LUAD patients, 27 veterans and 64 civilians. Veterans were older than civilians, aged 70 years vs aged 66 years (P = .003); with higher proportions of males, 93% vs 69% (P = .03); higher proportion of African Americans, 67% vs 39% (P = .03); smoking more, 50 pack-year vs 40 (0.005), and having a higher proportion of grade I, 78% vs 55% (P = .036). Survival was statistically longer for MYO1E high DNA methylation group 48 months vs 33 for low methylation (P = .049). MYO1E RNA expression did not show statistically significant differences (P = .32). Multivariate Cox regression analysis adjusted by age, veteran/civil status, gender, race, packyear, and stage showed that DNA methylation was significantly associated with mortality risk (HR 5.14; 95% CI, 1.12-23.60) (P = .035).
Conclusions/Implications
This study suggests the utility of MYO1E DNA methylation as a prognostic biomarker for veterans with LUAD. Further studies are necessary to understand the role of MYO1E in chemotherapy resistance and microenvironment immune modulation. Given the low expression of MYO1E in blood cells, MYO1E DNA methylation has the potential to be used as circulating tumor marker in liquid biopsies.
Project Purpose
The aim is to assess the role of MYO1E in survival among veterans with lung adenocarcinoma (LUAD).
Background
Veterans have a higher smoking exposure than civilians; a higher incidence of lung cancer; and a younger age at diagnosis of lung cancer. We recently showed that MYO1E DNA methylation and RNA expression in LUAD are associated with survival among civilians.
Methods
This is a retrospective cohort study involving LUAD among civilians and veterans with biopsy or pathologically proven LUAD from surgical specimens. DNA extraction and isolation from FFPE cancer tissues was performed using methylation-onbeads as previously published, followed by qMSP with bisulfite treatment to quantify DNA methylation. RNA extraction and quantification from lung tissues was obtained as described in previous publications.
Data Analysis
Differences were assessed with Wilcoxon rank sum test for continuous variables and Fisher’s exact test for categorical. Two-tailed log-rank test was used to estimate overall survival differences and Cox hazard models, to quantify risk of mortality using hazard ratios (HRs) with 95% confidence intervals (CIs).
Results
There were 91 LUAD patients, 27 veterans and 64 civilians. Veterans were older than civilians, aged 70 years vs aged 66 years (P = .003); with higher proportions of males, 93% vs 69% (P = .03); higher proportion of African Americans, 67% vs 39% (P = .03); smoking more, 50 pack-year vs 40 (0.005), and having a higher proportion of grade I, 78% vs 55% (P = .036). Survival was statistically longer for MYO1E high DNA methylation group 48 months vs 33 for low methylation (P = .049). MYO1E RNA expression did not show statistically significant differences (P = .32). Multivariate Cox regression analysis adjusted by age, veteran/civil status, gender, race, packyear, and stage showed that DNA methylation was significantly associated with mortality risk (HR 5.14; 95% CI, 1.12-23.60) (P = .035).
Conclusions/Implications
This study suggests the utility of MYO1E DNA methylation as a prognostic biomarker for veterans with LUAD. Further studies are necessary to understand the role of MYO1E in chemotherapy resistance and microenvironment immune modulation. Given the low expression of MYO1E in blood cells, MYO1E DNA methylation has the potential to be used as circulating tumor marker in liquid biopsies.
Project Purpose
The aim is to assess the role of MYO1E in survival among veterans with lung adenocarcinoma (LUAD).
Background
Veterans have a higher smoking exposure than civilians; a higher incidence of lung cancer; and a younger age at diagnosis of lung cancer. We recently showed that MYO1E DNA methylation and RNA expression in LUAD are associated with survival among civilians.
Methods
This is a retrospective cohort study involving LUAD among civilians and veterans with biopsy or pathologically proven LUAD from surgical specimens. DNA extraction and isolation from FFPE cancer tissues was performed using methylation-onbeads as previously published, followed by qMSP with bisulfite treatment to quantify DNA methylation. RNA extraction and quantification from lung tissues was obtained as described in previous publications.
Data Analysis
Differences were assessed with Wilcoxon rank sum test for continuous variables and Fisher’s exact test for categorical. Two-tailed log-rank test was used to estimate overall survival differences and Cox hazard models, to quantify risk of mortality using hazard ratios (HRs) with 95% confidence intervals (CIs).
Results
There were 91 LUAD patients, 27 veterans and 64 civilians. Veterans were older than civilians, aged 70 years vs aged 66 years (P = .003); with higher proportions of males, 93% vs 69% (P = .03); higher proportion of African Americans, 67% vs 39% (P = .03); smoking more, 50 pack-year vs 40 (0.005), and having a higher proportion of grade I, 78% vs 55% (P = .036). Survival was statistically longer for MYO1E high DNA methylation group 48 months vs 33 for low methylation (P = .049). MYO1E RNA expression did not show statistically significant differences (P = .32). Multivariate Cox regression analysis adjusted by age, veteran/civil status, gender, race, packyear, and stage showed that DNA methylation was significantly associated with mortality risk (HR 5.14; 95% CI, 1.12-23.60) (P = .035).
Conclusions/Implications
This study suggests the utility of MYO1E DNA methylation as a prognostic biomarker for veterans with LUAD. Further studies are necessary to understand the role of MYO1E in chemotherapy resistance and microenvironment immune modulation. Given the low expression of MYO1E in blood cells, MYO1E DNA methylation has the potential to be used as circulating tumor marker in liquid biopsies.
Molecular Profiling of Lung Malignancies in Veterans: What We Have Learned About the Impact of Agent Orange Exposure
Background
There are no studies in oncologic literature that report biomarker alterations in Vietnam War veterans with lung cancers. Our study elucidates genetic mutations in veterans with lung cancer exposed to Agent Orange (AO) and compares them to non-Agent Orange exposed (NAO) veterans.
Methods
We collected data of veterans with lung cancers from VA Central California Health Care System who had NGS testing via Foundation One CDx from January 2007 to January 2022. We collected data of AO versus NAO veterans including age, race, gender, smoking and exposure history, histologic subtypes, treatment modalities, PDL-1, and molecular mutations. Median PFS and OS were calculated between AO and NAO in all veterans and adenocarcinoma group after first-line therapy in months by Kaplan-Meier R log-rank test.
Results
There were total of 58 lung cancer veterans, 27 AO and 31 NAO. 33 (56.9%) veterans had adenocarcinoma (20 AO vs 13 NAO). Veterans were White (81%), male (93%) and all had tobacco exposure. The median age at diagnosis was 72 years in both groups. 65.5% had stage III-IV disease. Veterans with AO adenocarcinoma had more early stage I-II disease (50%) as compared to NAO (16%). The AO group had more PDL1 expression (TPS > 1%). 15/31 (48.4%) NAO received immunotherapy vs 7/27 (25.9%) AO. 104 molecular mutations were identified. Veterans with AO had more ROS1, MET, and NRAS while NAO had more EGFR, KRAS, and NF1 mutations. In adenocarcinoma group, AO had more MET and less KRAS while NAO has more KRAS, TP53, and EGFR. The median PFS and OS for all veterans with AO vs NAO were 8 mo vs 6 mo and 12 mo vs 10 mo, respectively (non-significant [NS]). In adenocarcinoma group the median PFS and OS for AO vs NAO veterans were 8 mo vs 4 mo and 11.75 mo vs 6 mo, respectively (NS).
Conclusions
Our study is the first to report molecular biomarkers in AO and NAO veterans with lung cancers. We found different markers between the groups. The median PFS and OS of AO and adenocarcinoma AO veterans were longer due to early stage diagnoses while NAO vetera
Background
There are no studies in oncologic literature that report biomarker alterations in Vietnam War veterans with lung cancers. Our study elucidates genetic mutations in veterans with lung cancer exposed to Agent Orange (AO) and compares them to non-Agent Orange exposed (NAO) veterans.
Methods
We collected data of veterans with lung cancers from VA Central California Health Care System who had NGS testing via Foundation One CDx from January 2007 to January 2022. We collected data of AO versus NAO veterans including age, race, gender, smoking and exposure history, histologic subtypes, treatment modalities, PDL-1, and molecular mutations. Median PFS and OS were calculated between AO and NAO in all veterans and adenocarcinoma group after first-line therapy in months by Kaplan-Meier R log-rank test.
Results
There were total of 58 lung cancer veterans, 27 AO and 31 NAO. 33 (56.9%) veterans had adenocarcinoma (20 AO vs 13 NAO). Veterans were White (81%), male (93%) and all had tobacco exposure. The median age at diagnosis was 72 years in both groups. 65.5% had stage III-IV disease. Veterans with AO adenocarcinoma had more early stage I-II disease (50%) as compared to NAO (16%). The AO group had more PDL1 expression (TPS > 1%). 15/31 (48.4%) NAO received immunotherapy vs 7/27 (25.9%) AO. 104 molecular mutations were identified. Veterans with AO had more ROS1, MET, and NRAS while NAO had more EGFR, KRAS, and NF1 mutations. In adenocarcinoma group, AO had more MET and less KRAS while NAO has more KRAS, TP53, and EGFR. The median PFS and OS for all veterans with AO vs NAO were 8 mo vs 6 mo and 12 mo vs 10 mo, respectively (non-significant [NS]). In adenocarcinoma group the median PFS and OS for AO vs NAO veterans were 8 mo vs 4 mo and 11.75 mo vs 6 mo, respectively (NS).
Conclusions
Our study is the first to report molecular biomarkers in AO and NAO veterans with lung cancers. We found different markers between the groups. The median PFS and OS of AO and adenocarcinoma AO veterans were longer due to early stage diagnoses while NAO vetera
Background
There are no studies in oncologic literature that report biomarker alterations in Vietnam War veterans with lung cancers. Our study elucidates genetic mutations in veterans with lung cancer exposed to Agent Orange (AO) and compares them to non-Agent Orange exposed (NAO) veterans.
Methods
We collected data of veterans with lung cancers from VA Central California Health Care System who had NGS testing via Foundation One CDx from January 2007 to January 2022. We collected data of AO versus NAO veterans including age, race, gender, smoking and exposure history, histologic subtypes, treatment modalities, PDL-1, and molecular mutations. Median PFS and OS were calculated between AO and NAO in all veterans and adenocarcinoma group after first-line therapy in months by Kaplan-Meier R log-rank test.
Results
There were total of 58 lung cancer veterans, 27 AO and 31 NAO. 33 (56.9%) veterans had adenocarcinoma (20 AO vs 13 NAO). Veterans were White (81%), male (93%) and all had tobacco exposure. The median age at diagnosis was 72 years in both groups. 65.5% had stage III-IV disease. Veterans with AO adenocarcinoma had more early stage I-II disease (50%) as compared to NAO (16%). The AO group had more PDL1 expression (TPS > 1%). 15/31 (48.4%) NAO received immunotherapy vs 7/27 (25.9%) AO. 104 molecular mutations were identified. Veterans with AO had more ROS1, MET, and NRAS while NAO had more EGFR, KRAS, and NF1 mutations. In adenocarcinoma group, AO had more MET and less KRAS while NAO has more KRAS, TP53, and EGFR. The median PFS and OS for all veterans with AO vs NAO were 8 mo vs 6 mo and 12 mo vs 10 mo, respectively (non-significant [NS]). In adenocarcinoma group the median PFS and OS for AO vs NAO veterans were 8 mo vs 4 mo and 11.75 mo vs 6 mo, respectively (NS).
Conclusions
Our study is the first to report molecular biomarkers in AO and NAO veterans with lung cancers. We found different markers between the groups. The median PFS and OS of AO and adenocarcinoma AO veterans were longer due to early stage diagnoses while NAO vetera
Utilization of Next Generation Sequencing in Metastatic Colorectal Cancer
Introduction
Metastatic colorectal cancer (mCRC) is one of the most common and lethal cancers. Nextgeneration sequencing (NGS) has been recommended as a tool to help guide treatment by identifying actionable genetic mutations. However, data regarding realworld usage of NGS in a Veterans Affairs (VA) health care system is lacking. We conducted a retrospective observational study of the patterns of NGS usage in patients with mCRC at the South Texas Veterans Affairs Healthcare System (STVAHCS).
Methods
We identified patients with a diagnosis of mCRC evaluated and treated at STVAHCS between January 1, 2018 and June 1, 2022. We assessed the prevalence of utilizing NGS on solid tumor samples performed by Foundation One and identified the presence of different molecular aberrations detected by NGS.
Results
65 patients were identified. Median age was 68 years. 63 (96.9%) were males and 2 (3.1%) were females. 29 (44.6%) were Hispanic, 25 (38.5%) were White, 10 (15.4%) were African American and 1 (1.5%) was Pacific Islander. NGS was performed in 34 (52.3%) patients. The most common reasons for not performing NGS were unknown/not documented (54.8%), early mortality (29%), lack of adequate tissue (12.9%) and patient refusal of treatment (3.2%). The most common molecular aberrations identified in patients who had NGS were TP53 (73.5%), APC (64.7%), KRAS (47.1%), ATM (20.6%), SMAD4 (14.7%) and BRAF (14.7%). All patients who had NGS were found to have at least one identifiable mutation.
Conclusions
Approximately 50% of patients with mCRC did not have NGS performed on their tissue sample. This rate is similar to other real-world studies in non-VA settings. Documented reasons for lack of NGS testing included inadequate tissue and early patient mortality. Other potential reasons could be lack of efficient VA clinical testing protocols, use of simple molecular testing rather than comprehensive NGS testing and limited knowledge of availability of NGS among providers. Measures that can be taken to increase utilization of NGS include incorporating NGS testing early in the disease course, incorporating testing into VA clinical pathways, improving physician education, increasing the size of solid tissue samples and ordering liquid biopsies where solid tissue is deficient.
Introduction
Metastatic colorectal cancer (mCRC) is one of the most common and lethal cancers. Nextgeneration sequencing (NGS) has been recommended as a tool to help guide treatment by identifying actionable genetic mutations. However, data regarding realworld usage of NGS in a Veterans Affairs (VA) health care system is lacking. We conducted a retrospective observational study of the patterns of NGS usage in patients with mCRC at the South Texas Veterans Affairs Healthcare System (STVAHCS).
Methods
We identified patients with a diagnosis of mCRC evaluated and treated at STVAHCS between January 1, 2018 and June 1, 2022. We assessed the prevalence of utilizing NGS on solid tumor samples performed by Foundation One and identified the presence of different molecular aberrations detected by NGS.
Results
65 patients were identified. Median age was 68 years. 63 (96.9%) were males and 2 (3.1%) were females. 29 (44.6%) were Hispanic, 25 (38.5%) were White, 10 (15.4%) were African American and 1 (1.5%) was Pacific Islander. NGS was performed in 34 (52.3%) patients. The most common reasons for not performing NGS were unknown/not documented (54.8%), early mortality (29%), lack of adequate tissue (12.9%) and patient refusal of treatment (3.2%). The most common molecular aberrations identified in patients who had NGS were TP53 (73.5%), APC (64.7%), KRAS (47.1%), ATM (20.6%), SMAD4 (14.7%) and BRAF (14.7%). All patients who had NGS were found to have at least one identifiable mutation.
Conclusions
Approximately 50% of patients with mCRC did not have NGS performed on their tissue sample. This rate is similar to other real-world studies in non-VA settings. Documented reasons for lack of NGS testing included inadequate tissue and early patient mortality. Other potential reasons could be lack of efficient VA clinical testing protocols, use of simple molecular testing rather than comprehensive NGS testing and limited knowledge of availability of NGS among providers. Measures that can be taken to increase utilization of NGS include incorporating NGS testing early in the disease course, incorporating testing into VA clinical pathways, improving physician education, increasing the size of solid tissue samples and ordering liquid biopsies where solid tissue is deficient.
Introduction
Metastatic colorectal cancer (mCRC) is one of the most common and lethal cancers. Nextgeneration sequencing (NGS) has been recommended as a tool to help guide treatment by identifying actionable genetic mutations. However, data regarding realworld usage of NGS in a Veterans Affairs (VA) health care system is lacking. We conducted a retrospective observational study of the patterns of NGS usage in patients with mCRC at the South Texas Veterans Affairs Healthcare System (STVAHCS).
Methods
We identified patients with a diagnosis of mCRC evaluated and treated at STVAHCS between January 1, 2018 and June 1, 2022. We assessed the prevalence of utilizing NGS on solid tumor samples performed by Foundation One and identified the presence of different molecular aberrations detected by NGS.
Results
65 patients were identified. Median age was 68 years. 63 (96.9%) were males and 2 (3.1%) were females. 29 (44.6%) were Hispanic, 25 (38.5%) were White, 10 (15.4%) were African American and 1 (1.5%) was Pacific Islander. NGS was performed in 34 (52.3%) patients. The most common reasons for not performing NGS were unknown/not documented (54.8%), early mortality (29%), lack of adequate tissue (12.9%) and patient refusal of treatment (3.2%). The most common molecular aberrations identified in patients who had NGS were TP53 (73.5%), APC (64.7%), KRAS (47.1%), ATM (20.6%), SMAD4 (14.7%) and BRAF (14.7%). All patients who had NGS were found to have at least one identifiable mutation.
Conclusions
Approximately 50% of patients with mCRC did not have NGS performed on their tissue sample. This rate is similar to other real-world studies in non-VA settings. Documented reasons for lack of NGS testing included inadequate tissue and early patient mortality. Other potential reasons could be lack of efficient VA clinical testing protocols, use of simple molecular testing rather than comprehensive NGS testing and limited knowledge of availability of NGS among providers. Measures that can be taken to increase utilization of NGS include incorporating NGS testing early in the disease course, incorporating testing into VA clinical pathways, improving physician education, increasing the size of solid tissue samples and ordering liquid biopsies where solid tissue is deficient.