Neoadjuvant Radiotherapy After (m)FOLFIRINOX for Borderline Resectable Pancreatic Adenocarcinoma: A TAPS Consortium Study

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  • 1 Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York;
  • | 2 Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands;
  • | 3 Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas;
  • | 4 Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands;
  • | 5 Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York;
  • | 6 Department of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania;
  • | 7 Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; and
  • | 8 Department of Surgery, Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Background: The value of neoadjuvant radiotherapy (RT) after 5-fluorouracil with leucovorin, oxaliplatin, and irinotecan, with or without dose modifications [(m)FOLFIRINOX], for patients with borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) is uncertain. Methods: We conducted an international retrospective cohort study including consecutive patients with BR PDAC who received (m)FOLFIRINOX as initial treatment (2012–2019) from the Trans-Atlantic Pancreatic Surgery Consortium. Because the decision to administer RT is made after chemotherapy, patients with metastases or deterioration after (m)FOLFIRINOX or a performance score ≥2 were excluded. Patients who received RT after (m)FOLFIRINOX were matched 1:1 by nearest neighbor propensity scores with patients who did not receive RT. Propensity scores were calculated using sex, age (≤70 vs >70 years), WHO performance score (0 vs 1), tumor size (0–20 vs 21–40 vs >40 mm), tumor location (head/uncinate vs body/tail), number of cycles (1–4 vs 5–8 vs >8), and baseline CA 19-9 level (≤500 vs >500 U/mL). Primary outcome was overall survival (OS) from diagnosis. Results: Of 531 patients who received neoadjuvant (m)FOLFIRINOX for BR PDAC, 424 met inclusion criteria and 300 (70.8%) were propensity score–matched. After matching, median OS was 26.2 months (95% CI, 24.0–38.4) with RT versus 32.8 months (95% CI, 25.3–42.0) without RT (P=.71). RT was associated with a lower resection rate (55.3% vs 72.7%; P=.002). In patients who underwent a resection, RT was associated with a comparable margin-negative resection rate (>1 mm) (70.6% vs 64.8%; P=.51), more node-negative disease (57.3% vs 37.6%; P=.01), and more major pathologic response with <5% tumor viability (24.7% vs 8.3%; P=.006). The OS associated with conventional and stereotactic body RT approaches was similar (median OS, 25.7 vs 26.0 months; P=.92). Conclusions: In patients with BR PDAC, neoadjuvant RT following (m)FOLFIRINOX was associated with more node-negative disease and better pathologic response in patients who underwent resection, yet no difference in OS was found. Routine use of RT cannot be recommended based on these data.

Submitted October 9, 2021; final revision received January 17, 2022; accepted for publication January 28, 2022.

Author contributions: Conceptualization: Janssen, Crane, van Eijck, Ellsworth, Jarnagin, O’Reilly, Paniccia, Reyngold, Besselink, Katz, Tzeng, Zureikat, Koerkamp, Wei. Data curation: Janssen, van Dam, Prakash, Doppenberg. Formal analysis: Janssen, van Dam, Koerkamp, Wei. Funding acquisition: Janssen, Koerkamp. Investigation: Janssen, Prakash, Doppenberg. Methodology: Janssen, van Dam, Reyngold, Koerkamp, Wei. Project administration: Janssen, Prakash. Supervision: van Eijck, Besselink, Katz, Tzeng, Zureikat, Koerkamp, Wei. Validation: Janssen, van Dam, Doppenberg, Crane, van Eijck, Ellsworth, Jarnagin, O’Reilly, Paniccia, Reyngold, Besselink, Katz, Tzeng, Zureikat, Koerkamp, Wei. Visualization: Janssen. Writing – original draft: Janssen. Writing – review and editing: All authors.

Disclosures: Dr. O’Reilly has disclosed receiving institution grant/research support from Genentech/Roche, Celgene/Bristol-Myers Squibb, BioNTech, AstraZeneca, Arcus, and Elicio; serving as a scientific advisor for Cytomx Therapeutics and Rafael Therapeutics; receiving consultant fees from and serving as a scientific advisor for Seagen, Boehringer Ingelheim, BioNTech, Ipsen, Merck, IDEAYA, Silenseed, Novartis, AstraZeneca, Noxxon, BioSapien, Cend Therapeutics, Thetis, Autem, ZielBio, and Tempus; and having a spouse who is receiving consultant fees from and serving as a scientific advisor for Agios, Genentech/Roche, and Eisai. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: Research reported in this article was supported by KWF Kankerbestrijding (10955), ZonMW (843004108), Living with Hope Foundation, Vereniging Trustfonds Erasmus Universiteit Rotterdam, and NIH/NCI Cancer Center Support Grant P30 CA008748 (Dr. O’Reilly).

Correspondence: Alice C. Wei, MD, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-886A, New York, NY 10065. Email: weia@mskcc.org

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