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Clinical Studies

The road to tailored adjuvant chemotherapy for all four non-pancreatic periampullary cancers: An international multimethod cohort study

British Journal of Cancer volume 131, pages 117–125 (2024)Cite this article

Subjects

Abstract

Background

Despite differences in tumour behaviour and characteristics between duodenal adenocarcinoma (DAC), the intestinal (AmpIT) and pancreatobiliary (AmpPB) subtype of ampullary adenocarcinoma and distal cholangiocarcinoma (dCCA), the effect of adjuvant chemotherapy (ACT) on these cancers, as well as the optimal ACT regimen, has not been comprehensively assessed. This study aims to assess the influence of tailored ACT on DAC, dCCA, AmpIT, and AmpPB.

Patients and methods

Patients after pancreatoduodenectomy for non-pancreatic periampullary adenocarcinoma were identified and collected from 36 tertiary centres between 2010 - 2021. Per non-pancreatic periampullary tumour type, the effect of adjuvant chemotherapy and the main relevant regimens of adjuvant chemotherapy were compared. The primary outcome was overall survival (OS).

Results

The study included a total of 2866 patients with DAC (n = 330), AmpIT (n = 765), AmpPB (n = 819), and dCCA (n = 952). Among them, 1329 received ACT, and 1537 did not. ACT was associated with significant improvement in OS for AmpPB (P = 0.004) and dCCA (P < 0.001). Moreover, for patients with dCCA, capecitabine mono ACT provided the greatest OS benefit compared to gemcitabine (P = 0.004) and gemcitabine – cisplatin (P = 0.001). For patients with AmpPB, no superior ACT regime was found (P > 0.226). ACT was not associated with improved OS for DAC and AmpIT (P = 0.113 and P = 0.445, respectively).

Discussion

Patients with resected AmpPB and dCCA appear to benefit from ACT. While the optimal ACT for AmpPB remains undetermined, it appears that dCCA shows the most favourable response to capecitabine monotherapy. Tailored adjuvant treatments are essential for enhancing prognosis across all four non-pancreatic periampullary adenocarcinomas.

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Fig. 1: Methodology with summary of inclusions and comparisons.
Fig. 2: Duodenal adenocarcinoma.
Fig. 3: Ampullary adenocarcinoma intestinal subtype.
Fig. 4: Ampullary adenocarcinoma pancreatobiliary.
Fig. 5: Distal cholangiocarcinoma.

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Data availability

Due to the sensitive nature of the research and the privacy of participants involved, the data supporting the findings of this study are not publicly available. Data can be made available upon reasonable request to the corresponding author, subject to compliance with applicable privacy laws and ethical guidelines.

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Funding

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Author information

Authors and Affiliations

  1. Department of Surgery, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy

    Bas A. Uijterwijk, Daniël H. Lemmers, Clarissa Ferarri & Mohammed Abu Hilal

  2. Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands

    Bas A. Uijterwijk, Daniël H. Lemmers & Marc G. Besselink

  3. Cancer Center Amsterdam, Amsterdam, the Netherlands

    Bas A. Uijterwijk, Daniël H. Lemmers, Johanna W. Wilmink, Geert Kazemier & Marc G. Besselink

  4. Oncology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Michele Ghidini

  5. Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands

    Johanna W. Wilmink

  6. Department of Medical Oncology, Fondazione Poliambulanza, Brescia, Italy

    Alberto Zaniboni

  7. Department of Surgery, Royal Free London NHS Foundation Trust, London, UK

    Giuseppe Kito Fusai

  8. Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy

    Alessandro Zerbi

  9. Department of Pancreatic Surgery, IRCCS Humanitas Research Hospital, Rozzano, Italy

    Alessandro Zerbi

  10. Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands

    Bas Groot Koerkamp

  11. Catharina Hospital Eindhoven, Department of Surgery, Eindhoven, Netherlands

    Misha Luyer

  12. Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden

    Poya Ghorbani

  13. Department of Surgery, University Hospital of Verona, Verona, Italy

    Roberto Salvia

  14. Department of Surgery, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK

    Steven White

  15. Department of Surgery, Hospital del Mar, Barcelona, Spain

    Benedetto Ielpo

  16. Singapore General Hospital, Department of Hepatopancreatobiliary and Transplant Surgery, Duke-National University of Singapore, Singapore, Singapore

    Brian K. P. Goh

  17. Department of Surgery, Pisa University Hospital, Pisa, Italy

    Ugo Boggi

  18. Amsterdam UMC, location VUmc, Amsterdam, the Netherlands

    Geert Kazemier

  19. Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA

    Michael G. House

  20. Department of Academic Surgery, The Royal Marsden Hospital, London, UK

    Vasileios K. Mavroeidis

  21. Department of Hepatobiliary and Pancreatic Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK

    Vasileios K. Mavroeidis & Zahir Soonawalla

  22. Department of Surgery in Linköping and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden

    Bergthor Björnsson

  23. Division of Oncologic and Mini-invasive General Surgery, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy

    Michele Mazzola

  24. Department of Surgery, Miguel Servet University Hospital, Zargosa, Spain

    Mario Serradilla

  25. Department of Surgery, Hellenic Anticancer Hospital ‘Saint Savvas’, Athens, Greece

    Dimitris Korkolis

  26. Department of Surgery, Virginia Mason, Seattle, WA, USA

    Adnan Alseidi

  27. Faculty of medicine, University of Birmingham, Birmingham, UK

    Keith J. Roberts

  28. Hepatobiliary and Pancreatic Surgical Unit, Nouvel Hôpital Civil (NHC), Strasbourg, France

    Patrick Pessaux

  29. Department of Surgery, Baylor College of Medicine, Houston, USA

    William E. Fisher

  30. Fiona Stanley Hospital, Department of Surgery, Perth, WA, Australia

    Sharnice Koek

  31. Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Tara S. Kent

  32. Department of General Surgery, Paracelsus Medical University Nürnberg, 90419, Nürnberg, Germany

    Miljana Vladimirov

  33. Department of Surgery, University Medical Center Schleswig-Holstein, campus Lübeck, Lübeck, Germany

    Louisa Bolm

  34. West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK

    Nigel Jamieson

  35. University Hospital of Parma, Department of Surgery, Parma, Italy

    Raffaele Dalla Valle

  36. Department of Surgery, Martin-Luther University Halle-Wittenberg, Halle (Saale), Germany

    Jorg Kleeff

  37. Department of Digestive, Oncologic and Metabolic Surgery, Institut Mutualiste Montsouris, Paris, France

    Alessandro Mazzotta

  38. Department of Surgery, University Hospital Virgen de la Victoria, Malaga, Spain

    Miguel Angel Suarez Muñoz

  39. Hospital de Sant Pau, Department of Surgery, Barcelona, Spain

    Santiago Sánchez Cabús

  40. Department of Surgery, University of Calgary, Calgary, AB, Canada

    Chad G. Ball

  41. Department of Surgery, Jefferson Medical College, Philadelphia, USA

    Adam C. Berger

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  1. Bas A. Uijterwijk
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  2. Daniël H. Lemmers
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Consortia

International Study Group on non-pancreatic periampullary Cancer (ISGACA)

  • Bas A. Uijterwijk
  • , Daniël H. Lemmers
  • , Michele Ghidini
  • , Johanna W. Wilmink
  • , Alberto Zaniboni
  • , Giuseppe Kito Fusai
  • , Alessandro Zerbi
  • , Bas Groot Koerkamp
  • , Misha Luyer
  • , Poya Ghorbani
  • , Roberto Salvia
  • , Steven White
  • , Benedetto Ielpo
  • , Brian K. P. Goh
  • , Ugo Boggi
  • , Geert Kazemier
  • , Michael G. House
  • , Vasileios K. Mavroeidis
  • , Bergthor Björnsson
  • , Michele Mazzola
  • , Mario Serradilla
  • , Dimitris Korkolis
  • , Adnan Alseidi
  • , Keith J. Roberts
  • , Zahir Soonawalla
  • , Patrick Pessaux
  • , William E. Fisher
  • , Sharnice Koek
  • , Tara S. Kent
  • , Miljana Vladimirov
  • , Louisa Bolm
  • , Nigel Jamieson
  • , Raffaele Dalla Valle
  • , Jorg Kleeff
  • , Alessandro Mazzotta
  • , Miguel Angel Suarez Muñoz
  • , Santiago Sánchez Cabús
  • , Chad G. Ball
  • , Adam C. Berger
  • , Clarissa Ferarri
  • , Marc G. Besselink
  •  & Mohammed Abu Hilal

Contributions

Study conception and design: BU, DL, MG, HW, AZ, CF, MB, MA. Acquisition of data: GF, AZ, BK, ML, PG, RS, SW, BI, WG, UB, GK, MH, VM, BB, MM, MS, DK, AA, KR, ZS, PP, WF, SK, TK, MV, LB, NJ, RD, JK, AM, MM, SC, CB, AB, Analysis and interpretation of data: BU, DL, MG, HW, AZ, CF, MB, MA. Drafting of manuscript: BU, DL, MG, HW, AZ, CF, MB, MA. Critical revision: BU, DL, MG, HW, AZ, GF, AZ, BK, ML, PG, RS, SW, BI, WG, UB, GK, MH, VM, BB, MM, MS, DK, AA, KR, ZS, PP, WF, SK, TK, MV, LB, NJ, RD, JK, AM, MM, SC, CB, AB, CF, MB, MA.

Corresponding authors

Correspondence to Bas A. Uijterwijk or Mohammed Abu Hilal.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

The study was approved by the Ethical Committee of Brescia, Italy (number NP 5269 - STUDIO NPPC 15.03.2022). The need for written informed consent was waived due to the retrospective nature of the research.

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Uijterwijk, B.A., Lemmers, D.H., Ghidini, M. et al. The road to tailored adjuvant chemotherapy for all four non-pancreatic periampullary cancers: An international multimethod cohort study. Br J Cancer 131, 117–125 (2024). https://doi.org/10.1038/s41416-024-02692-w

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  • DOI: https://doi.org/10.1038/s41416-024-02692-w

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