Short-Course or Total Neoadjuvant Chemotherapy in Resectable and Borderline Resectable Pancreatic Cancer - Current Status and Future Perspectives

Knut Jørgen Labori1,2
1Department of Hepato-pancreato-biliary Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway
2Institute of Clinical Medicine, University of Oslo, Oslo, Norway

Tóm tắt

Neoadjuvant therapy improves overall survival compared with a surgery-first approach in patients with borderline resectable pancreatic cancer (BRPC). Evidence of higher quality is required to determine whether neoadjuvant therapy has potential benefits and improves survival for patients with resectable pancreatic cancer (RPC). Most randomized controlled trials (RCTs) have explored short-course neoadjuvant chemotherapy (SNT), but total neoadjuvant chemotherapy (TNT) is now the experimental arm of ongoing RCTs. This article reviews the current status of SNT and TNT in RPC and BRPC, and provides perspectives of future challenges and research directions in this field.

Từ khóa


Tài liệu tham khảo

Huang, 2019, Resection of pancreatic cancer in Europe and USA: an international large-scale study highlighting large variations, Gut., 68, 130, 10.1136/gutjnl-2017-314828

2021, NCCN Practice Guidelines in Oncology

Mavros, 2021, Clinical trials of systemic chemotherapy for resectable pancreatic cancer: a review, JAMA Surg., 156, 663, 10.1001/jamasurg.2021.0149

Conroy, 2018, FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer, N Engl J Med., 379, 2395, 10.1056/NEJMoa1809775

Bockhorn, 2014, Borderline resectable pancreatic cancer: a consensus statement by the International Study Group of Pancreatic Surgery (ISGPS), Surgery., 155, 977, 10.1016/j.surg.2014.02.001

Neoptolemos, 2004, A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer, N Engl J Med., 350, 1200, 10.1056/NEJMoa032295

Neoptolemos, 2010, Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial, JAMA., 304, 1073, 10.1001/jama.2010.1275

Oettle, 2013, Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial, JAMA., 310, 1473, 10.1001/jama.2013.279201

Neoptolemos, 2017, Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial, Lancet., 389, 1011, 10.1016/S0140-6736(16)32409-6

van Dam, 2022, Neoadjuvant therapy or upfront surgery for resectable and borderline resectable pancreatic cancer: a meta-analysis of randomised controlled trials, Eur J Cancer., 160, 140, 10.1016/j.ejca.2021.10.023

Lambert, 2019, An update on treatment options for pancreatic adenocarcinoma, Ther Adv Med Oncol., 11, 1758835919875568, 10.1177/1758835919875568

ClinicalTrials.gov identifier

ClinicalTrials.gov identifier

Labori, 2017, Neoadjuvant chemotherapy versus surgery first for resectable pancreatic cancer (Norwegian Pancreatic Cancer Trial - 1 (NorPACT-1)) - study protocol for a national multicentre randomized controlled trial, BMC Surg., 17, 94, 10.1186/s12893-017-0291-1

Schwarz, 2018, Resectable pancreatic adenocarcinoma neo-adjuvant FOLF(IRIN)OX-based chemotherapy - a multicenter, non-comparative, randomized, phase II trial (PANACHE01-PRODIGE48 study), BMC Cancer., 18, 762, 10.1186/s12885-018-4663-4

Sohal, 2021, Efficacy of perioperative chemotherapy for resectable pancreatic adenocarcinoma: a phase 2 randomized clinical trial, JAMA Oncol., 7, 421, 10.1001/jamaoncol.2020.7328

Ghaneh, 2020, ESPAC-5F: Four-arm, prospective, multicenter, international randomized phase II trial of immediate surgery compared with neoadjuvant gemcitabine plus capecitabine (GEMCAP) or FOLFIRINOX or chemoradiotherapy (CRT) in patients with borderline resectable pancreatic cancer, J Clin Oncol., 38, 4505, 10.1200/JCO.2020.38.15_suppl.4505

Janssen, 2021, Total neoadjuvant FOLFIRINOX vs. neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine for resectable and borderline resectable pancreatic cancer (PREOPANC-2 trial): study protocol for a nationwide multicenter randomized controlled trial, BMC Cancer., 21, 300, 10.1186/s12885-021-08031-z

Versteijne, 2020, Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer: results of the dutch randomized phase III PREOPANC trial, J Clin Oncol., 38, 1763, 10.1200/JCO.19.02274

Unno, 2019, Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 vs. upfront surgery for resectable pancreatic cancer (Prep-02/JSAP-05), J Clin Oncol., 37, 189, 10.1200/JCO.2019.37.4_suppl.189

Motoi, 2019, Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP05), Jpn J Clin Oncol., 49, 190, 10.1093/jjco/hyy190

Ettrich, 2018, Neoadjuvant plus adjuvant or only adjuvant nab-paclitaxel plus gemcitabine for resectable pancreatic cancer - the NEONAX trial (AIO-PAK-0313), a prospective, randomized, controlled, phase II study of the AIO pancreatic cancer group, BMC Cancer., 18, 1298, 10.1186/s12885-018-5183-y

Reni, 2018, Safety and efficacy of preoperative or postoperative chemotherapy for resectable pancreatic adenocarcinoma (PACT-15): a randomised, open-label, phase 2-3 trial, Lancet Gastroenterol Hepatol., 3, 413, 10.1016/S2468-1253(18)30081-5

Kim, 2021, Total neoadjuvant therapy for operable pancreatic cancer, Ann Surg Oncol., 28, 2246, 10.1245/s10434-020-09149-3

Versteijne, 2022, Neoadjuvant chemoradiotherapy versus upfront surgery for resectable and borderline resectable pancreatic cancer: long-term results of the dutch randomized PREOPANC trial, J Clin Oncol., 10.1200/JCO.21.02233.

Janssen, 2021, Added value of radiotherapy following neoadjuvant FOLFIRINOX for resectable and borderline resectable pancreatic cancer: a systematic review and meta-analysis, Ann Surg Oncol., 28, 8297, 10.1245/s10434-021-10276-8

Nasjonalt handlingsprogram med retningslinjer for diagnostikk, behandling og oppfølging av pancreaskreft

Janssen, 2019, Neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer: a systematic review and patient-level meta-analysis, J Natl Cancer Inst., 111, 782, 10.1093/jnci/djz073

van Roessel, 2020, Evaluation of adjuvant chemotherapy in patients with resected pancreatic cancer after neoadjuvant FOLFIRINOX treatment, JAMA Oncol., 6, 1733, 10.1001/jamaoncol.2020.3537

Murphy, 2018, Total neoadjuvant therapy with FOLFIRINOX followed by individualized chemoradiotherapy for borderline resectable pancreatic adenocarcinoma: a phase 2 clinical trial, JAMA Oncol., 4, 963, 10.1001/jamaoncol.2018.0329

Datta, 2021, Association of total neoadjuvant therapy with major pathologic response and survival in localized pancreatic cancer: a multi-institutional analysis of 504 patients, J Clin Oncol., 39, 4145, 10.1200/JCO.2021.39.15_suppl.4145

Truty, 2021, Factors predicting response, perioperative outcomes, and survival following total neoadjuvant therapy for borderline/locally advanced pancreatic cancer, Ann Surg., 273, 341, 10.1097/SLA.0000000000003284

Tzeng, 2012, Defined clinical classifications are associated with outcome of patients with anatomically resectable pancreatic adenocarcinoma treated with neoadjuvant therapy, Ann Surg Oncol., 19, 2045, 10.1245/s10434-011-2211-4

Labori, 2016, Impact of early disease progression and surgical complications on adjuvant chemotherapy completion rates and survival in patients undergoing the surgery first approach for resectable pancreatic ductal adenocarcinoma - A population-based cohort study, Acta Oncol., 55, 265, 10.3109/0284186X.2015.1068445

Groot, 2018, Patterns, timing, and predictors of recurrence following pancreatectomy for pancreatic ductal adenocarcinoma, Ann Surg., 267, 936, 10.1097/SLA.0000000000002234

Alva-Ruiz, 2022, Neoadjuvant chemotherapy switch in borderline resectable/locally advanced pancreatic cancer, Ann Surg Oncol., 29, 1579, 10.1245/s10434-021-10991-2

van Roessel, 2021, Scoring of tumour response after neoadjuvant therapy in resected pancreatic cancer: systematic review, Br J Surg., 108, 119, 10.1093/bjs/znaa031

Perri, 2020, Response to preoperative therapy in localized pancreatic cancer, Front Oncol., 10, 516, 10.3389/fonc.2020.00516

Evans, 2015, Non-metastatic pancreatic cancer: resectable, borderline resectable, and locally advanced-definitions of increasing importance for the optimal delivery of multimodality therapy, Ann Surg Oncol., 22, 3409, 10.1245/s10434-015-4649-2

Perri, 2021, Radiographic and serologic predictors of pathologic major response to preoperative therapy for pancreatic cancer, Ann Surg., 273, 806, 10.1097/SLA.0000000000003442

Tsai, 2020, Importance of normalization of CA19-9 levels following neoadjuvant therapy in patients with localized pancreatic cancer, Ann Surg., 271, 740, 10.1097/SLA.0000000000003049

Ye, 2020, The prognostic value of CA19-9 response after neoadjuvant therapy in patients with pancreatic cancer: a systematic review and pooled analysis, Cancer Chemother Pharmacol., 86, 731, 10.1007/s00280-020-04165-2

Katz, 2012, Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators, Cancer., 118, 5749, 10.1002/cncr.27636

Perri, 2020, Response and survival associated with first-line FOLFIRINOX vs gemcitabine and nab-paclitaxel chemotherapy for localized pancreatic ductal adenocarcinoma, JAMA Surg., 155, 832, 10.1001/jamasurg.2020.2286

Panda, 2021, Borderline resectable and locally advanced pancreatic cancer: FDG PET/MRI and CT tumor metrics for assessment of pathologic response to neoadjuvant therapy and prediction of survival, Am J Roentgenol., 217, 730, 10.2214/AJR.20.24567

Lee, 2021, Metabolic activity by FDG-PET/CT after neoadjuvant chemotherapy in borderline resectable and locally advanced pancreatic cancer and association with survival, Br J Surg., 109, 61, 10.1093/bjs/znab229

Evangelista, 2021, The role of FDG PET/CT or PET/MRI in assessing response to neoadjuvant therapy for patients with borderline or resectable pancreatic cancer: a systematic literature review, Ann Nucl Med., 35, 767, 10.1007/s12149-021-01629-0

Kamarajah, 2021, Adjuvant chemotherapy associated with survival benefit following neoadjuvant chemotherapy and pancreatectomy for pancreatic ductal adenocarcinoma: a population-based cohort study, Ann Surg Oncol., 28, 6790, 10.1245/s10434-021-09823-0

Chantrill, 2015, Precision medicine for advanced pancreas cancer: the individualized molecular pancreatic cancer therapy (IMPaCT) trial, Clin Cancer Res., 21, 2029, 10.1158/1078-0432.CCR-15-0426

Tiriac, 2018, Organoid profiling identifies common responders to chemotherapy in pancreatic cancer, Cancer Discov., 8, 1112, 10.1158/2159-8290.CD-18-0349

Heredia-Soto, 2021, Liquid biopsy in pancreatic cancer: are we ready to apply it in the clinical practice?, Cancers., 13, 1986, 10.3390/cancers13081986

Gemenetzis, 2018, Circulating tumor cells dynamics in pancreatic adenocarcinoma correlate with disease status: results of the prospective CLUSTER study, Ann Surg., 268, 408, 10.1097/SLA.0000000000002925

Bernard, 2019, Circulating nucleic acids are associated with outcomes of patients with pancreatic cancer, Gastroenterology., 156, 108, 10.1053/j.gastro.2018.09.022

Yin, 2021, Improved assessment of response status in patients with pancreatic cancer treated with neoadjuvant therapy using somatic mutations and liquid biopsy analysis, Clin Cancer Res., 27, 740, 10.1158/1078-0432.CCR-20-1746

Miyabayashi, 2021, Molecular and phenotypic profiling for precision medicine in pancreatic cancer: current advances and future perspectives, Front Oncol., 11, 682872, 10.3389/fonc.2021.682872

Pishvaian, 2020, Overall survival in patients with pancreatic cancer receiving matched therapies following molecular profiling: a retrospective analysis of the Know Your Tumor registry trial, Lancet Oncol., 21, 508, 10.1016/S1470-2045(20)30074-7

Mosele, 2020, Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group, Ann Oncol., 31, 1491, 10.1016/j.annonc.2020.07.014