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Clinical Impact of UV Mutational Signatures in Veterans With Cancer
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).
Development of a National Precision Oncology Program (NPOP) Dashboard Suite and Data Mart For Monitoring Somatic Molecular Testing Use
BACKGROUND
As of May 2023, the Veterans Affairs (VA) National Precision Oncology Program (NPOP) has provided somatic molecular testing for nearly 36,000 Veterans with cancer. Automated tools to monitor test use (locally and nationally) have only been available for NGS testing in advanced stage lung and prostate cancer. To better track utilization of NPOP supported testing across all cancer indications, and to support strategies to promote wider adoption, we developed an automated data architecture to monitor program operations. Here, we describe the development of the NPOP data mart and summarize the core components of the NPOP Somatic Molecular Testing dashboards.
METHODS
SQL Server Integration Services was used to build the backend data mart, which required the ingestion of vendor-specific XML data and subsequent harmonization with data found in the VA’s Corporate Data Warehouse (CDW). The NPOP somatic testing dashboards, developed using Power BI, are securely hosted in the cloud, and accessible through SharePoint.
DATA ANALYSIS
The NPOP dashboard suite displays key measures using descriptive statistics, including counts, proportions, means, medians, and standard deviations. To support the visualization of comparisons we leveraged stacked and clustered bar charts, and violin plots.
RESULTS
The NPOP data mart refreshes nightly providing users with near real-time data. The NPOP somatic testing dashboards include an all vendor combined report and sub-reports organized by vendors: Foundation Medicine, Personalis, and Personal Genome Diagnostics and Tempus. All reports contain four views with the ability to toggle between tests ordered or completed. For current NPOP vendors, patient level data and turnaround time views were developed. Data are stratified by test category (i.e., NGS Solid, NGS Liquid, Heme, IHC) and can be viewed longitudinally (i.e., across time) and filtered by test date, VA facility, patient demographics, and cancer characteristics (diagnosis, stage). To date, over 50,000 tests have been ordered (90% through Foundation Medicine).
IMPLICATIONS
The NPOP data mart and operational dashboards synthesizes vast amounts of data into a visually consumable format that supports monitoring the uptake and variation of somatic molecular testing services being offered across the VA.
BACKGROUND
As of May 2023, the Veterans Affairs (VA) National Precision Oncology Program (NPOP) has provided somatic molecular testing for nearly 36,000 Veterans with cancer. Automated tools to monitor test use (locally and nationally) have only been available for NGS testing in advanced stage lung and prostate cancer. To better track utilization of NPOP supported testing across all cancer indications, and to support strategies to promote wider adoption, we developed an automated data architecture to monitor program operations. Here, we describe the development of the NPOP data mart and summarize the core components of the NPOP Somatic Molecular Testing dashboards.
METHODS
SQL Server Integration Services was used to build the backend data mart, which required the ingestion of vendor-specific XML data and subsequent harmonization with data found in the VA’s Corporate Data Warehouse (CDW). The NPOP somatic testing dashboards, developed using Power BI, are securely hosted in the cloud, and accessible through SharePoint.
DATA ANALYSIS
The NPOP dashboard suite displays key measures using descriptive statistics, including counts, proportions, means, medians, and standard deviations. To support the visualization of comparisons we leveraged stacked and clustered bar charts, and violin plots.
RESULTS
The NPOP data mart refreshes nightly providing users with near real-time data. The NPOP somatic testing dashboards include an all vendor combined report and sub-reports organized by vendors: Foundation Medicine, Personalis, and Personal Genome Diagnostics and Tempus. All reports contain four views with the ability to toggle between tests ordered or completed. For current NPOP vendors, patient level data and turnaround time views were developed. Data are stratified by test category (i.e., NGS Solid, NGS Liquid, Heme, IHC) and can be viewed longitudinally (i.e., across time) and filtered by test date, VA facility, patient demographics, and cancer characteristics (diagnosis, stage). To date, over 50,000 tests have been ordered (90% through Foundation Medicine).
IMPLICATIONS
The NPOP data mart and operational dashboards synthesizes vast amounts of data into a visually consumable format that supports monitoring the uptake and variation of somatic molecular testing services being offered across the VA.
BACKGROUND
As of May 2023, the Veterans Affairs (VA) National Precision Oncology Program (NPOP) has provided somatic molecular testing for nearly 36,000 Veterans with cancer. Automated tools to monitor test use (locally and nationally) have only been available for NGS testing in advanced stage lung and prostate cancer. To better track utilization of NPOP supported testing across all cancer indications, and to support strategies to promote wider adoption, we developed an automated data architecture to monitor program operations. Here, we describe the development of the NPOP data mart and summarize the core components of the NPOP Somatic Molecular Testing dashboards.
METHODS
SQL Server Integration Services was used to build the backend data mart, which required the ingestion of vendor-specific XML data and subsequent harmonization with data found in the VA’s Corporate Data Warehouse (CDW). The NPOP somatic testing dashboards, developed using Power BI, are securely hosted in the cloud, and accessible through SharePoint.
DATA ANALYSIS
The NPOP dashboard suite displays key measures using descriptive statistics, including counts, proportions, means, medians, and standard deviations. To support the visualization of comparisons we leveraged stacked and clustered bar charts, and violin plots.
RESULTS
The NPOP data mart refreshes nightly providing users with near real-time data. The NPOP somatic testing dashboards include an all vendor combined report and sub-reports organized by vendors: Foundation Medicine, Personalis, and Personal Genome Diagnostics and Tempus. All reports contain four views with the ability to toggle between tests ordered or completed. For current NPOP vendors, patient level data and turnaround time views were developed. Data are stratified by test category (i.e., NGS Solid, NGS Liquid, Heme, IHC) and can be viewed longitudinally (i.e., across time) and filtered by test date, VA facility, patient demographics, and cancer characteristics (diagnosis, stage). To date, over 50,000 tests have been ordered (90% through Foundation Medicine).
IMPLICATIONS
The NPOP data mart and operational dashboards synthesizes vast amounts of data into a visually consumable format that supports monitoring the uptake and variation of somatic molecular testing services being offered across the VA.
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