Safety and Efficacy of Neoadjuvant Chemoradiotherapy with Moderately Hypofractionated Intensity-modulated Radiotherapy for Resectable Pancreatic Cancer: A Prospective, Open-label, Phase II Study

Overview

Journal Cancer Med

Specialty Oncology

Date 2023 Aug 31

PMID 37649318

Authors

Toshihiko Masui

Kazuyuki Nagai

Takayuki Anazawa

Yosuke Kasai

Akitada Yogo

Michio Yoshimura

Takashi Mizowaki

Norimitsu Uza

Akihisa Fukuda

Shigemi Matsumoto

Masashi Kanai

Hiroyoshi Isoda

Yoshiya Kawaguchi

Shinji Uemoto

Etsuro Hatano

Affiliations

Soon will be listed here.

Abstract

Background: Resectable pancreatic cancer (RPC) is potentially resectable on admission, and the impact of neoadjuvant therapy on these tumors is controversial. Moreover, the safety and efficacy of neoadjuvant chemoradiotherapy with moderately hypofractionated intensity-modulated radiation therapy (NACIMRT) for RPC have not been studied. Here, we conducted a phase II study to evaluate the safety and efficacy of hypofractionated NACIMRT for RPC.

Methods: A total of 54 RPC patients were enrolled and treated according to the study protocol. We used moderately hypofractionated (45 Gy in 15 fractions) IMRT with gemcitabine to shorten the duration of radiotherapy and reduce gastrointestinal toxicity. The primary endpoint was overall survival (OS), and we subsequently analyzed the microscopically margin-negative resection (R0) rate, disease-free survival (DFS), and histologic effects and safety of NACIMRT.

Results: Median OS for the cohort was 40.0 months. Forty-two patients (77.8%) underwent pancreatectomy after NACIMRT. Median DFS was 20.3 months. The R0 resection rate was 95.2% (40/42) per protocol and 85.2% (46/54) for the cohort. There were no intervention-related deaths during the study period. Local treatment response, as assessed by the CAP classification, showed no residual tumor in 4.8% of patients. Overall, 23.9% of patients experienced CTCAE grade 3 or 4 during NACIMRT. Adjuvant therapy was initiated in 88% of patients undergoing resection. Postoperative complications grade ≥3b on the Clavien-Dindo scale occurred in 4.8% of patients. CA19-9 level at enrollment was an independent prognostic factor for OS and DFS.

Conclusions: This is the first prospective study of hypofractionated IMRT as neoadjuvant therapy for RPC. Hypofractionated NACIMRT for RPC could be safely introduced with a high induction rate of adjuvant chemotherapy, with an overall survival of 40.0 months.

Citing Articles

Neoadjuvant Chemoradiotherapy Using Moderately Hypofractionated Intensity-Modulated Radiotherapy Versus Upfront Surgery for Resectable Pancreatic Cancer: A Retrospective Cohort Study.

Yamane K, Anazawa T, Nagai K, Kasai Y, Masui T, Izuwa A Ann Surg Oncol. 2025; .

PMID: 39893341 DOI: 10.1245/s10434-025-16956-z.

Safety and efficacy of neoadjuvant chemoradiotherapy with moderately hypofractionated intensity-modulated radiotherapy for resectable pancreatic cancer: A prospective, open-label, phase II study.

Masui T, Nagai K, Anazawa T, Kasai Y, Yogo A, Yoshimura M Cancer Med. 2023; 12(18):18611-18621.

PMID: 37649318 PMC: 10557863. DOI: 10.1002/cam4.6470.

References

Masui T, Nagai K, Anazawa T, Kasai Y, Yogo A, Yoshimura M . Safety and efficacy of neoadjuvant chemoradiotherapy with moderately hypofractionated intensity-modulated radiotherapy for resectable pancreatic cancer: A prospective, open-label, phase II study. Cancer Med. 2023; 12(18):18611-18621. PMC: 10557863. DOI: 10.1002/cam4.6470. View

Eguchi H, Takeda Y, Takahashi H, Nakahira S, Kashiwazaki M, Shimizu J . A Prospective, Open-Label, Multicenter Phase 2 Trial of Neoadjuvant Therapy Using Full-Dose Gemcitabine and S-1 Concurrent with Radiation for Resectable Pancreatic Ductal Adenocarcinoma. Ann Surg Oncol. 2019; 26(13):4498-4505. DOI: 10.1245/s10434-019-07735-8. View

Motoi F, Kosuge T, Ueno H, Yamaue H, Satoi S, Sho M . 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. 2019; 49(2):190-194. DOI: 10.1093/jjco/hyy190. View

Siegel R, Miller K, Jemal A . Cancer statistics, 2019. CA Cancer J Clin. 2019; 69(1):7-34. DOI: 10.3322/caac.21551. View

Versteijne E, Vogel J, Besselink M, Busch O, Wilmink J, Daams J . Meta-analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer. Br J Surg. 2018; 105(8):946-958. PMC: 6033157. DOI: 10.1002/bjs.10870. View

Uesaka K, Boku N, Fukutomi A, Okamura Y, Konishi M, Matsumoto I . Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet. 2016; 388(10041):248-57. DOI: 10.1016/S0140-6736(16)30583-9. View

Bergquist J, Puig C, Shubert C, Groeschl R, Habermann E, Kendrick M . Carbohydrate Antigen 19-9 Elevation in Anatomically Resectable, Early Stage Pancreatic Cancer Is Independently Associated with Decreased Overall Survival and an Indication for Neoadjuvant Therapy: A National Cancer Database Study. J Am Coll Surg. 2016; 223(1):52-65. DOI: 10.1016/j.jamcollsurg.2016.02.009. View

Goto Y, Nakamura A, Ashida R, Sakanaka K, Itasaka S, Shibuya K . Clinical evaluation of intensity-modulated radiotherapy for locally advanced pancreatic cancer. Radiat Oncol. 2018; 13(1):118. PMC: 6019294. DOI: 10.1186/s13014-018-1063-5. View

Smith B, R Bellon J, Blitzblau R, Freedman G, Haffty B, Hahn C . Radiation therapy for the whole breast: Executive summary of an American Society for Radiation Oncology (ASTRO) evidence-based guideline. Pract Radiat Oncol. 2018; 8(3):145-152. DOI: 10.1016/j.prro.2018.01.012. View

10.

Tsai S, George B, Wittmann D, Ritch P, Krepline A, Aldakkak M . Importance of Normalization of CA19-9 Levels Following Neoadjuvant Therapy in Patients With Localized Pancreatic Cancer. Ann Surg. 2018; 271(4):740-747. DOI: 10.1097/SLA.0000000000003049. View

11.

Nakamura T, Hayashi T, Kimura Y, Kawakami H, Takahashi K, Ishiwatari H . HOPS-R01 phase II trial evaluating neoadjuvant S-1 therapy for resectable pancreatic adenocarcinoma. Sci Rep. 2022; 12(1):9966. PMC: 9200853. DOI: 10.1038/s41598-022-14094-0. View

12.

Masui T, Nagai K, Anazawa T, Sato A, Uchida Y, Nakano K . Impact of neoadjuvant intensity-modulated radiation therapy on borderline resectable pancreatic cancer with arterial abutment; a prospective, open-label, phase II study in a single institution. BMC Cancer. 2022; 22(1):119. PMC: 8800301. DOI: 10.1186/s12885-022-09244-6. View

13.

Versteijne E, van Dam J, Suker M, Janssen Q, Groothuis K, Akkermans-Vogelaar J . Neoadjuvant Chemoradiotherapy Versus Upfront Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Long-Term Results of the Dutch Randomized PREOPANC Trial. J Clin Oncol. 2022; 40(11):1220-1230. DOI: 10.1200/JCO.21.02233. View

14.

Koontz B, Bossi A, Cozzarini C, Wiegel T, DAmico A . A systematic review of hypofractionation for primary management of prostate cancer. Eur Urol. 2014; 68(4):683-91. DOI: 10.1016/j.eururo.2014.08.009. View

15.

Breslin T, Hess K, Harbison D, Jean M, Cleary K, Dackiw A . Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: treatment variables and survival duration. Ann Surg Oncol. 2001; 8(2):123-32. DOI: 10.1007/s10434-001-0123-4. View

16.

Huguet F, Cerbai C, Ta M, Sarrade T, Evin C, Aziez S . Neoadjuvant treatment of pancreatic adenocarcinoma: Chemoradiation or stereotactic body radiation therapy?. Cancer Radiother. 2022; 26(6-7):858-864. DOI: 10.1016/j.canrad.2022.06.020. View

17.

Tamburrino D, Partelli S, Crippa S, Manzoni A, Maurizi A, Falconi M . Selection criteria in resectable pancreatic cancer: a biological and morphological approach. World J Gastroenterol. 2014; 20(32):11210-5. PMC: 4145759. DOI: 10.3748/wjg.v20.i32.11210. View