Reshaping preoperative treatment of pancreatic cancer in the era of precision medicine

Casolino, Raffaella; Braconi, Chiara; Malleo, Giuseppe; Paiella, Salvatore; Bassi, Claudio; Milella, Michèle; Dreyer, Stephan; Froeling, Fieke E. M.; Chang, David K.; Biankin, Andrew V.; Golan, Talia

doi:10.1016/j.annonc.2020.11.013

Cited by 49 publications

(53 citation statements)

References 112 publications

(210 reference statements)

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“…Patients with locally advanced PC and an HRR gene mutation may have an increased rate of conversion to resectability following induction FFX 32. In our series, all three patients with an HRR gene mutation who were resected following neoadjuvant FFX had a marked pathological response (<10% residual cancer), consistent with previous reports 32–34…”

Section: Discussionsupporting

confidence: 89%

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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Section: Discussionsupporting

confidence: 89%

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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“…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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“…A genomic-driven approach could pave the way to the entrance of personalized medicine, even in the preoperative treatment of PDAC [89]. Indeed, the implementation of biomarkers at an earlier stage could help in identifying the best candidates to an upfront resection, and in helping clinicians in the decision making of the best neoadjuvant therapy.…”

Section: Novel Molecular Targets and Possible Implications For Treatment Of Early-stage Pancreatic Cancermentioning

confidence: 99%

“…Neoadjuvant therapy reduces the accuracy of tumor restaging, but this effect seems not to affect the determination of resectability [89]. Nowadays, surgical resectability of PDAC after chemoradiotherapy is usually based on NCCN guidelines [6].…”

Section: Imaging Assessment Of Response To Therapy: Where Are We Headed?mentioning

confidence: 99%

Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma: Role of the Radiologist and Oncologist in the Era of Precision Medicine

Vernuccio

Messina²,

Merz

et al. 2021

Diagnostics

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The incidence and mortality of pancreatic ductal adenocarcinoma are growing over time. The management of patients with pancreatic ductal adenocarcinoma involves a multidisciplinary team, ideally involving experts from surgery, diagnostic imaging, interventional endoscopy, medical oncology, radiation oncology, pathology, geriatric medicine, and palliative care. An adequate staging of pancreatic ductal adenocarcinoma and re-assessment of the tumor after neoadjuvant therapy allows the multidisciplinary team to choose the most appropriate treatment for the patient. This review article discusses advancement in the molecular basis of pancreatic ductal adenocarcinoma, diagnostic tools available for staging and tumor response assessment, and management of resectable or borderline resectable pancreatic cancer.

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Reshaping preoperative treatment of pancreatic cancer in the era of precision medicine

Cited by 49 publications

References 112 publications

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

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

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

Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma: Role of the Radiologist and Oncologist in the Era of Precision Medicine

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