Building towards Precision Oncology for Pancreatic Cancer: Real-World Challenges and Opportunities

Wang, Yifan; Lakoma, Anna; Zogopoulos, George

doi:10.3390/genes11091098

Cited by 11 publications

(15 citation statements)

References 118 publications

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“…However, implementing this testing for all patients with PDAC remains an ongoing challenge. 4,5 Hereditary predisposition accounts for up to 10% of PDAC cases. 6 Identification of deleterious germline mutations through multigene genetic testing can inform treatments for the proband and screening for family members.…”

Section: Introductionmentioning

confidence: 99%

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Implementation of an Embedded In-Clinic Genetic Testing Station to Optimize Germline Testing for Patients with Pancreatic Adenocarcinoma

et al. 2021

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Background. Germline genetic testing is universally recommended for patients with pancreatic cancer, but testing remains infrequent. In 5/2018, we implemented a systematic patient intake workflow featuring an in-clinic Genetic Testing Station (GTS) at the University of California San Francisco (UCSF) to expedite genetic counseling and facilitate sample collection. We sought to determine the impact of this innovation on rates of genetic counseling and testing. Methods. Medical records, patient intake records, and genetic test reports were retrospectively reviewed for new patients with pancreatic cancer eligible for germline testing at UCSF during 5/2018-5/2019. Primary outcomes included the rate of offered genetic counseling and confirmed germline testing. Data were compared for periods before and after GTS implementation. Associations between demographic characteristics and testing rates were assessed.Results. Genetic counseling/testing was offered to 209 (94%) of 223 eligible patients, and 158 (71%) completed testing (135 at UCSF, 23 elsewhere). Compared to a traditional referral-based genetic counseling model, confirmed testing increased from 19% to 71%, patient attrition between referral and genetics appointment decreased from 36% to 3%, and rate of pathogenic variant detection increased from 20% to 33%. Patients who were younger, identified as non-Hispanic White, and spoke English as a primary language were more likely to complete testing. Conclusions. Implementation of a systematic patient intake workflow and in-clinic GTS resulted in the highest reported real-world rate of germline testing for patients with pancreatic cancer. Healthcare disparities were identified and will guide future innovation. This report provides a model for other centers to create a similar testing infrastructure. The Oncologist ;9999:• • Implications for Practice: This study demonstrates that a systematic patient intake workflow and associated in-clinic genetic testing station improve delivery of genetic counseling and completion of germline testing for patients with pancreatic cancer. To our knowledge, we report the highest real-world rate of confirmed genetic testing in this patient population. We detail our innovation to guide replication at other medical centers and facilitate guideline-concordant care for patients with pancreatic cancer. This infrastructure can also be applied to other cancers for which germline testing is recommended.

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Section: Introductionmentioning

confidence: 99%

“…The development of screening programs and biomarker-driven therapies has established the importance of universal germline genetic testing to improve PDAC outcomes. However, implementing this testing for all patients with PDAC remains an ongoing challenge [4,5].…”

Section: Introductionmentioning

confidence: 99%

Implementation of an Embedded In-Clinic Genetic Testing Station to Optimize Germline Testing for Patients with Pancreatic Adenocarcinoma

et al. 2021

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“…These findings have inspired an effort to profile the genetic signatures of PDAC patient tumours and use this information to inform individual patient clinical care. However, rather than understanding the subtype that characterises a particular patient’s tumour, the focus has shifted to identify patients that harbour clinically actionable targets [ 14 , 15 , 16 , 17 , 18 , 19 ]. Using tissue obtained from biopsy of patients with locally advanced or metastatic PDAC, Aguirre and colleagues [ 20 ] identified specific gene expression signatures that might be therapeutically relevant.…”

Section: Current Trends In Pdac Precision Medicinementioning

confidence: 99%

Does the Microenvironment Hold the Hidden Key for Functional Precision Medicine in Pancreatic Cancer?

Kokkinos

Jensen

Sharbeen

et al. 2021

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and no significant improvement in patient survival has been seen in the past three decades. Treatment options are limited and selection of chemotherapy in the clinic is usually based on the performance status of a patient rather than the biology of their disease. In recent years, research has attempted to unlock a personalised treatment strategy by identifying actionable molecular targets in tumour cells or using preclinical models to predict the effectiveness of chemotherapy. However, these approaches rely on the biology of PDAC tumour cells only and ignore the importance of the microenvironment and fibrotic stroma. In this review, we highlight the importance of the microenvironment in driving the chemoresistant nature of PDAC and the need for preclinical models to mimic the complex multi-cellular microenvironment of PDAC in the precision medicine pipeline. We discuss the potential for ex vivo whole-tissue culture models to inform precision medicine and their role in developing novel therapeutic strategies that hit both tumour and stromal compartments in PDAC. Thus, we highlight the critical role of the tumour microenvironment that needs to be addressed before a precision medicine program for PDAC can be implemented.

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“…Most patients are diagnosed at an advanced stage when empiric chemotherapy is the mainstay treatment option. Despite new chemotherapy regimens, the 5-year survival remains under 10% 2. These clinical failures, together with the advent of next-generation sequencing, have driven the development of biomarker-based treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

“…Approximately 10% of index PC cases are associated with a hereditary component 3 4. Genetic susceptibility to PC is associated with pathogenic germline alterations (PGA) in several genes, including the homologous recombination repair (HRR) genes ( BRCA1 , BRCA2 , PALB2 ), mismatch repair (MMR) genes ( MLH1 , MSH2 , MSH6 , PMS2 ), ATM , CDKN2A , STK11 and TP53 2. Identifying PGAs in real time carries important treatment implications for patients with PC.…”

Section: Introductionmentioning

confidence: 99%

Oncology clinic-based germline genetic testing for exocrine pancreatic cancer enables timely return of results and unveils low uptake of cascade testing

et al. 2021

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BackgroundTraditional medical genetics models are unable to meet the growing demand for germline genetic testing (GT) in patients with exocrine pancreatic cancer (PC). This study investigates the impact of an ambulatory oncology clinic-based GT model.MethodsFrom 2012 to 2021, patients with PC were prospectively enrolled and considered for GT. Two chronological cohorts were compared: (1) the preuniversal genetic testing (pre-UGT) cohort, which received GT based on clinical criteria or family history; and (2) the post-UGT cohort, where an 86-gene panel was offered to all patients with PC.ResultsOf 847 eligible patients, 735 (86.8%) were enrolled (pre-UGT, n=579; post-UGT, n=156). A higher proportion of the post-UGT cohort received prospective GT (97.4% vs 58.5%, p<0.001). The rate of pathogenic germline alterations (PGA) across both cohorts was 9.9%, with 8.0% of PGAs in PC susceptibility genes. The post-UGT cohort had a higher prevalence of overall PGAs (17.2% vs 6.6%, p<0.001) and PGAs in PC susceptibility genes (11.9% vs 6.3%, p<0.001). The median turnaround time from enrolment to GT report was shorter in the post-UGT cohort (13 days vs 42 days, p<0.001). Probands with a PGA disclosed their GT results to 84% of their first-degree relatives (FDRs). However, only 31% of informed FDRs underwent GT, and the number of new cases per index case was 0.52.ConclusionA point-of-care GT model is feasible and expedites access to GT for patients with PC. Strategies to increase the uptake of cascade testing are needed to maximise the clinical impact of an oncology clinic-based GT model.

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Building towards Precision Oncology for Pancreatic Cancer: Real-World Challenges and Opportunities

Cited by 11 publications

References 118 publications

Implementation of an Embedded In-Clinic Genetic Testing Station to Optimize Germline Testing for Patients with Pancreatic Adenocarcinoma

Implementation of an Embedded In-Clinic Genetic Testing Station to Optimize Germline Testing for Patients with Pancreatic Adenocarcinoma

Does the Microenvironment Hold the Hidden Key for Functional Precision Medicine in Pancreatic Cancer?

Oncology clinic-based germline genetic testing for exocrine pancreatic cancer enables timely return of results and unveils low uptake of cascade testing

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