Observational Study

. 2024 Jun 3;7(6):e2417625.

doi: 10.1001/jamanetworkopen.2024.17625.

Pathological Complete Response in Patients With Resected Pancreatic Adenocarcinoma After Preoperative Chemotherapy

Thomas F Stoop^{1

2

3}, Atsushi Oba^{1

4

5}, Y H Andrew Wu^{1

6

7}, Laurel E Beaty⁸, Kathryn L Colborn^{9

10}, Boris V Janssen^{2

3

11}, Mohammed H Al-Musawi¹², Salvador Rodriguez Franco¹, Toshitaka Sugawara^{1

5}, Oskar Franklin^{1

13}, Ajay Jain¹⁴, Akio Saiura¹⁵, Alain Sauvanet¹⁶, Alessandro Coppola¹⁷, Ammar A Javed^{2

3

6

7

18}, Bas Groot Koerkamp¹⁹, Braden N Miller¹⁴, Claudia E Mack²⁰, Daisuke Hashimoto²¹, Damiano Caputo^{22

23}, Dyre Kleive²⁴, Elisabetta Sereni^{6

7

25}, Giulio Belfiori²⁶, Hirofumi Ichida¹⁵, Jacob L van Dam¹⁹, Jeanne Dembinski¹⁶, Keiichi Akahoshi⁵, Keith J Roberts²⁷, Kimitaka Tanaka²⁸, Knut J Labori²⁴, Massimo Falconi²⁶, Michael G House²⁹, Motokazu Sugimoto³⁰, Minoru Tanabe⁵, Naoto Gotohda³⁰, Paul S Krohn³¹, Richard A Burkhart^{6

7}, Rohan G Thakkar³², Rupaly Pande²⁷, Safi Dokmak¹⁶, Satoshi Hirano²⁸, Stefan K Burgdorf³¹, Stefano Crippa²⁶, Stijn van Roessel^{2

3}, Sohei Satoi^{1

21}, Steven A White³², Thilo Hackert³³, Trang K Nguyen²⁹, Tomohisa Yamamoto²¹, Toru Nakamura²⁸, Vismaya Bachu^{6

7}, William R Burns^{6

7}, Yosuke Inoue⁴, Yu Takahashi⁴, Yuta Ushida⁴, Zohra V Aslami^{6

7}, Caroline S Verbeke³⁴, Arantza Fariña^{3

11}, Jin He^{6

7}, Johanna W Wilmink^{3

35}, Wells Messersmith³⁶, Joanne Verheij^{3

11}, Jeffrey Kaplan³⁷, Richard D Schulick¹, Marc G Besselink^{2

3}, Marco Del Chiaro¹

Affiliations

¹ Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora.
² Amsterdam UMC, University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands.
³ Cancer Center Amsterdam, Amsterdam, the Netherlands.
⁴ Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan.
⁵ Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
⁶ Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
⁷ The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland.
⁸ Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora.
⁹ Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora.
¹⁰ Adult and Child Center for Outcomes Research and Delivery Science, University of Colorado Anschutz Medical Campus, Aurora.
¹¹ Amsterdam UMC, University of Amsterdam, Department of Pathology, Amsterdam, the Netherlands.
¹² Clinical Trials of Office, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora.
¹³ Department of Diagnostics and Intervention, Surgery, Umeå University, Umeå, Sweden.
¹⁴ Division of Surgical Oncology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City.
¹⁵ Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan.
¹⁶ Department of Surgery, Hôpital Beaujon, Clichy, France.
¹⁷ Dipartimento di Chirurgia Sapienza Università di Roma, Rome, Italy.
¹⁸ Division of Surgical Oncology, Department of Surgery, New York University Medical Center, New York, New York.
¹⁹ Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
²⁰ Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany.
²¹ Department of Surgery, Kansai Medical University, Osaka, Japan.
²² Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy.
²³ Research Unit of General Surgery, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy.
²⁴ Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
²⁵ Unit of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Truty, Verona, Italy.
²⁶ Pancreatic and Transplant Surgery Unit, San Raffaele Hospital IRCCS, Vita-Salute University, Milano, Italy.
²⁷ Hepato-Pancreato-Biliary Unit, Department of Surgery, University Hospitals of Birmingham, Birmingham, UK.
²⁸ Department of Gastroenterological Surgery II, Hokkaido University, Faculty of Medicine, Hokkaido, Japan.
²⁹ Department of Surgery, Indiana University School of Medicine, Indianapolis.
³⁰ Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa, Japan.
³¹ Department of Surgery and Transplantation, Copenhagen University Hospital, Copenhagen, Denmark.
³² Department of Hepato-Pancreatico-Biliary and Transplant Surgery, Freeman Hospital, Newcastle University, Newcastle upon Tyne, UK.
³³ Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
³⁴ Department of Pathology, Oslo University Hospital, University of Oslo, Oslo, Norway.
³⁵ Amsterdam UMC, University of Amsterdam, Department of Medical Oncology, Amsterdam, the Netherlands.
³⁶ Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora.
³⁷ Department of Pathology, University of Colorado School of Medicine, Aurora.

PMID: 38888920
PMCID: PMC11185983
DOI: 10.1001/jamanetworkopen.2024.17625

Observational Study

Pathological Complete Response in Patients With Resected Pancreatic Adenocarcinoma After Preoperative Chemotherapy

Thomas F Stoop et al. JAMA Netw Open. 2024.

. 2024 Jun 3;7(6):e2417625.

doi: 10.1001/jamanetworkopen.2024.17625.

Authors

Affiliations

¹ Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora.
² Amsterdam UMC, University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands.
³ Cancer Center Amsterdam, Amsterdam, the Netherlands.
⁴ Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan.
⁵ Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
⁶ Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
⁷ The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland.
⁸ Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora.
⁹ Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora.
¹⁰ Adult and Child Center for Outcomes Research and Delivery Science, University of Colorado Anschutz Medical Campus, Aurora.
¹¹ Amsterdam UMC, University of Amsterdam, Department of Pathology, Amsterdam, the Netherlands.
¹² Clinical Trials of Office, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora.
¹³ Department of Diagnostics and Intervention, Surgery, Umeå University, Umeå, Sweden.
¹⁴ Division of Surgical Oncology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City.
¹⁵ Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan.
¹⁶ Department of Surgery, Hôpital Beaujon, Clichy, France.
¹⁷ Dipartimento di Chirurgia Sapienza Università di Roma, Rome, Italy.
¹⁸ Division of Surgical Oncology, Department of Surgery, New York University Medical Center, New York, New York.
¹⁹ Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
²⁰ Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany.
²¹ Department of Surgery, Kansai Medical University, Osaka, Japan.
²² Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy.
²³ Research Unit of General Surgery, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy.
²⁴ Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
²⁵ Unit of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Truty, Verona, Italy.
²⁶ Pancreatic and Transplant Surgery Unit, San Raffaele Hospital IRCCS, Vita-Salute University, Milano, Italy.
²⁷ Hepato-Pancreato-Biliary Unit, Department of Surgery, University Hospitals of Birmingham, Birmingham, UK.
²⁸ Department of Gastroenterological Surgery II, Hokkaido University, Faculty of Medicine, Hokkaido, Japan.
²⁹ Department of Surgery, Indiana University School of Medicine, Indianapolis.
³⁰ Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa, Japan.
³¹ Department of Surgery and Transplantation, Copenhagen University Hospital, Copenhagen, Denmark.
³² Department of Hepato-Pancreatico-Biliary and Transplant Surgery, Freeman Hospital, Newcastle University, Newcastle upon Tyne, UK.
³³ Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
³⁴ Department of Pathology, Oslo University Hospital, University of Oslo, Oslo, Norway.
³⁵ Amsterdam UMC, University of Amsterdam, Department of Medical Oncology, Amsterdam, the Netherlands.
³⁶ Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora.
³⁷ Department of Pathology, University of Colorado School of Medicine, Aurora.

PMID: 38888920
PMCID: PMC11185983
DOI: 10.1001/jamanetworkopen.2024.17625

Abstract

Importance: Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking.

Objective: To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy.

Design, setting, and participants: This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months.

Exposures: Preoperative chemotherapy (with or without radiotherapy) followed by resection.

Main outcomes and measures: The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively.

Results: Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89).

Conclusions and relevance: This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Stoop reported receiving grants from the Dutch Cancer Society, Deltaplan Alvleesklierkanker, Cultuurfonds (Jan de Ruijsscher/Pia Huisman Fonds) for a research fellowship at the University of Colorado Anschutz Medical Campus, and Cancer Center Amsterdam Travel Grant for a research fellowship at the University of Colorado Anschutz Medical Campus outside the submitted work. Dr Satoi reported receiving grants from Nihon Servier, Amino-Up Co, and Boston Scientific outside the submitted work. Dr Wilmink reported receiving grants from MSD and Servier, medication from Nordic, and personal fees from Astra Zeneca outside the submitted work. Dr Del Chiaro reported receiving grants from Boston Scientific and Haemonetics Inc outside the submitted work. No other disclosures were reported.

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References

1. Springfeld C, Ferrone CR, Katz MHG, et al. . Neoadjuvant therapy for pancreatic cancer. Nat Rev Clin Oncol. 2023;20(5):318-337. doi:10.1038/s41571-023-00746-1 - DOI - PubMed
1. Bratlie SO, Wennerblom J, Vilhav C, Persson J, Rangelova E. Resectable, borderline, and locally advanced pancreatic cancer: “the good, the bad, and the ugly” candidates for surgery? J Gastrointest Oncol. 2021;12(5):2450-2460. doi:10.21037/jgo-2020-slapc-04 - DOI - PMC - PubMed
1. Brown ZJ, Heh V, Labiner HE, et al. . Surgical resection rates after neoadjuvant therapy for localized pancreatic ductal adenocarcinoma: meta-analysis. Br J Surg. 2022;110(1):34-42. doi:10.1093/bjs/znac354 - DOI - PubMed
1. Isaji S, Mizuno S, Windsor JA, et al. . International consensus on definition and criteria of borderline resectable pancreatic ductal adenocarcinoma 2017. Pancreatology. 2018;18(1):2-11. doi:10.1016/j.pan.2017.11.011 - DOI - PubMed
1. Oba A, Del Chiaro M, Satoi S, et al. . New criteria of resectability for pancreatic cancer: a position paper by the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS). J Hepatobiliary Pancreat Sci. 2022;29(7):725-731. doi:10.1002/jhbp.1049 - DOI - PubMed

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Pathological Complete Response in Patients With Resected Pancreatic Adenocarcinoma After Preoperative Chemotherapy

Affiliations

Pathological Complete Response in Patients With Resected Pancreatic Adenocarcinoma After Preoperative Chemotherapy

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