The sequential radiographic effects of preoperative chemotherapy and (chemo)radiation on tumor anatomy in patients with localized pancreatic cancer

Perri, Giampaolo; Prakash, Laura R.; Malleo, Giuseppe; Caravati, Andrea; Varadhachary, Gauri R.; Fogelman, David R.; Shubham, P.; Koay, Eugene J.; Joseph, Haritha Therese; Maggino, Laura; Milella, Michèle; Kim, M.; Ikoma, Naruhiko; Tzeng, Ching Wei D.; Salvia, Roberto; Lee, J.; Bassi, Claudio; Katz, Matthew H.

doi:10.1016/j.pan.2020.07.395

Cited by 3 publications

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“…FOLFIRINOX treatment often leads to a stabilization of the disease, or partial response occurs in a minority of the PDAC patients, while others do not respond by showing disease progression during treatment 6 . However, even among the responders, most patients develop rapid therapy resistance, resulting in disease progression after treatment.…”

Section: Introductionmentioning

confidence: 99%

Organoids Derived from Neoadjuvant FOLFIRINOX Patients Recapitulate Therapy Resistance in Pancreatic Ductal Adenocarcinoma

Farshadi

Chang

Sampadi

et al. 2021

Clinical Cancer Research

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Purpose: We investigated whether organoids can be generated from resected tumors of patients who received eight cycles of neoadjuvant FOLFIRINOX chemotherapy before surgery, and evaluated the sensitivity/resistance of these surviving cancer cells to cancer therapy. Experimental Design:We generated a library of 10 PDAC organoid lines: five each from treatment-naive and FOLFIRINOX-treated patients. We, first, assessed the histological, genetic, and transcriptional characteristics of the organoids and their matched primary PDAC tissue. Next, the organoids' response to treatment with single agents -5-FU, irinotecan, and oxaliplatinof the FOLFIRINOX regimen as well as combined regimen was evaluated.Finally, global mRNA-seq analyses were performed to identify FOLFIRINOX resistance pathways.Results: All 10 patient-derived PDAC organoids recapitulate histological, genetic, and transcriptional characteristics of their primary tumor tissue. Neoadjuvant FOLFIRINOXtreated organoids display resistance to FOLFIRINOX (5/5), irinotecan (5/5) and oxaliplatin (4/5) when compared to treatment-naive organoids (FOLFIRINOX: 1/5, irinotecan: 2/5, oxaliplatin: 0/5). 5-FU treatment responses between naive and treated organoids were similar.Comparative global transcriptome analysis of treatment-naive and FOLFIRINOX samplesin both organoids and corresponding matched tumor tissuesuncovered modulated pathways mainly involved in genomic instability, energy metabolism, and innate immune system. Conclusion:Resistance development in neoadjuvant FOLFIRINOX organoids, recapitulating their primary tumor resistance, suggests continuation of FOLFIRINOX therapy as an adjuvant treatment may not be advantageous for these patients. Gene expression profiles of PDAC organoids identify targetable pathways involved in chemoresistance development upon neoadjuvant FOLFIRINOX treatment, thus opening up combination therapy possibilities.Research.

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Section: Introductionmentioning

confidence: 99%

Organoids Derived from Neoadjuvant FOLFIRINOX Patients Recapitulate Therapy Resistance in Pancreatic Ductal Adenocarcinoma

Farshadi

Chang

Sampadi

et al. 2021

Clinical Cancer Research

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“…Sixty-eight per cent of patients eventually underwent pancreatectomy with R0 resection in 93% of cases and a median overall survival of 21.7 months (29). The role for radiation in the preoperative setting remains as well controversial (30). Two different trials aimed to assess the efficacy of perioperative radiotherapy, one from Korea (NCT01458717) and one from the Netherlands (PREOPANC-1).…”

Section: Preoperative Therapy: Evidence From Clinical Trialsmentioning

confidence: 99%

Neoadjuvant therapy in resectable pancreatic cancer—is this the way forward?—a narrative review

2021

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Background: Pancreatic cancer represents a systemic disease, and its treatment ideally includes the administration of systemic therapy regardless of its anatomical stage.Methods: In this brief narrative review, the most recent literature will be highlighted, together with updates, new perspectives on the topic, and the authors own personal view.Results: While preoperative therapy has recently become the new standard for borderline resectable stages, adjuvant therapy after surgery remains the current standard of care for resectable disease. However, to deliver systemic therapy in the postoperative setting implies that a significant subset of patients, not fully recovering after a pancreatectomy, will never receive appropriate treatment. Administration of chemotherapy before pancreatectomy may represent the only way to assure optimal treatment, simultaneously selecting patients for surgery according to tumor biology. For these reasons, many high-volume centers for pancreatic surgical oncology are increasingly considering this strategy also for patients with resectable disease.Conclusions: Nonetheless, available data to support this paradigm shift are still germinal, and the optimal modalities and timing of preoperative therapy are eagerly debated as well.

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“…4,5 By contrast, CT evaluation of tumor response after NAT is believed to underestimate the pathological response. [6][7][8] In a recent meta-analysis, CT showed 45% summary sensitivity and 85% summary specificity for predicting R0 resection of PDAC following NAT. 9 Given this drawback, evidence from observational studies recommends considering resection of PDAC unless metastasis is apparent.…”

Section: Introductionmentioning

confidence: 99%

“…Multidetector CT showed 73%‐97% accuracy for predicting R0 resection in patients treated with first‐line surgery 4,5 . By contrast, CT evaluation of tumor response after NAT is believed to underestimate the pathological response 6–8 . In a recent meta‐analysis, CT showed 45% summary sensitivity and 85% summary specificity for predicting R0 resection of PDAC following NAT 9 .…”

Section: Introductionmentioning

confidence: 99%

Prediction of margin‐negative resection of pancreatic ductal adenocarcinoma following neoadjuvant therapy: Diagnostic performance of NCCN criteria for resection vs CT‐determined resectability

Jang

Choi

Byun

et al. 2022

J Hepato Biliary Pancreat

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Background: Accurate assessment of pancreatic ductal adenocarcinoma (PDAC) resectability after neoadjuvant therapy (NAT) is crucial. Recently, the NCCN introduced criteria for resection of PDAC following NAT. Methods:We analyzed 127 patients who underwent NAT and pancreatectomy for PDAC between January 2010 and March 2020. CT-determined resectability according to the NCCN guideline and CA 19-9 level was evaluated before and after NAT. Diagnostic performance of the NCCN criteria for margin-negative (R0) resection was investigated and compared with CT alone.Results: R0 resection was achieved in 104 (81.9%) patients. After NAT, there were 30 (23.6%) resectable, 90 (70.9%) borderline resectable, and seven (5.5%) locally advanced tumors. Significantly decreased or stable CA 19-9 levels were noted in 114 (89.8%) patients. The sensitivity and specificity of the NCCN criteria were 87.5% (91/104) and 21.7% (5/23), respectively, which were significantly different from CT including only resectable PDAC (26.9% [28/104] and 91.3% [21/23]; P < .001), but less prominently different from CT including resectable and borderline resectable PDAC (95.2% [99/104]; P = .022 and 8.7% [2/23]; P = .375). Conclusions:The NCCN criteria for resection following NAT showed high sensitivity and low specificity for predicting R0 resection. It had supplementary benefit over CT alone, mainly in preventing underestimation of R0 resection. K E Y W O R D SCA-19-9 antigen, carcinoma, pancreatic ductal, computed tomography, margin of excision, neoadjuvant therapy This retrospective study was approved by our Institutional Review Board (IRB No. 2020-0251), which waived the need for informed patient consent.

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The sequential radiographic effects of preoperative chemotherapy and (chemo)radiation on tumor anatomy in patients with localized pancreatic cancer

Cited by 3 publications

References 0 publications

Organoids Derived from Neoadjuvant FOLFIRINOX Patients Recapitulate Therapy Resistance in Pancreatic Ductal Adenocarcinoma

Organoids Derived from Neoadjuvant FOLFIRINOX Patients Recapitulate Therapy Resistance in Pancreatic Ductal Adenocarcinoma

Neoadjuvant therapy in resectable pancreatic cancer—is this the way forward?—a narrative review

Prediction of margin‐negative resection of pancreatic ductal adenocarcinoma following neoadjuvant therapy: Diagnostic performance of NCCN criteria for resection vs CT‐determined resectability

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