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    1 Comment for this article
    Early vs late adjuvant chemo for resected pancreas
    Philip Champion |
    The authors admit that the reason for delaying start of chemo was not assessed, and there is a high chance that patients who started late were less fit, therefore likely to do worse with or without chemo.
    Pushing patients who are less fit into starting a toxic adjuvant chemo because of this publication might lead to a higher moribidity and mortality from the chemotherapy.
    Original Investigation
    August 14, 2019

    Association of Timing of Adjuvant Therapy With Survival in Patients With Resected Stage I to II Pancreatic Cancer

    Author Affiliations
    • 1Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York
    • 2Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
    • 3Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut
    • 4Jacobs School of Medicine and Biomedical Sciences, University at Buffalo-State University of New York (SUNY), Buffalo
    JAMA Netw Open. 2019;2(8):e199126. doi:10.1001/jamanetworkopen.2019.9126
    Key Points español 中文 (chinese)

    Question  Is the timing of adjuvant therapy in resected pancreatic cancer associated with better survival?

    Findings  This cohort study of 7548 patients with stage I to II pancreatic cancer in the National Cancer Database suggested improved survival when adjuvant therapy was initiated 28 to 59 days after surgery. Patients who recovered slowly from surgery still benefited from delayed adjuvant therapy initiated more than 12 weeks after the procedure compared with patients who received surgery alone.

    Meaning  Shared decision-making between clinicians and patients is needed to individualize when to initiate adjuvant therapy based on patients’ postoperative recovery.


    Importance  Surgery followed by adjuvant chemotherapy or chemoradiation is widely used to treat resectable pancreatic cancer. Although studies suggest initiation of adjuvant therapy within 12 weeks of surgery, there is no clear time interval associated with better survival.

    Objective  To evaluate the ideal timing of adjuvant therapy for patients with stage I to II resected pancreatic cancer.

    Design, Setting, and Participants  This cohort study included 7548 patients with stage I to II resected pancreatic cancer (5453 with adjuvant therapy; 2095 without adjuvant therapy) from the National Cancer Database from 2004 to 2015. Data were collected from January 2014 to December 2015 and analyzed from December 2018 to May 2019.

    Exposures  Adjuvant chemotherapy or chemoradiation at various time intervals.

    Main Outcomes and Measures  Overall survival (OS).

    Results  A total of 7548 patients (3770 male [49.9%]; median [interquartile range] age, 67 [59-74] years) were identified from the National Cancer Database. Among 5453 patients with adjuvant therapy, a Cox model with restricted cubic splines identified the lowest mortality risk when adjuvant therapy was started 28 to 59 days after surgery. Patients were divided into early (n = 269, adjuvant therapy initiated within <28 days), reference (n = 3048, adjuvant therapy initiated within 28-59 days), and late (n = 2136, adjuvant therapy initiated after >59 days) interval cohorts. Median (interquartile range) overall follow-up was 38.6 (24.6-62.0) months. Compared with the reference interval cohort on multivariable analysis, both the early cohort (hazard ratio, 1.17; 95% CI, 1.02-1.35; P = .03) and the late cohort (hazard ratio, 1.09; 95% CI, 1.02-1.17; P = .008) were associated with worse mortality. Similarly, the reference interval cohort had improved OS compared with the early cohort in 268 propensity-matched pairs (2-year OS, 52.5% [95% CI, 46.7%-59.0%] vs 45.1% [95% CI, 39.5%-51.6%]; P = .02) and compared with the late cohort in 2042 propensity-matched pairs (2-year OS, 51.3% [95% CI, 49.1%-53.6%] vs 45.4% [95% CI, 43.3%-47.7%]; P = .01). Patients who received adjuvant therapy more than 12 weeks after surgery (n = 683) had improved OS compared with surgery alone in both multivariable analysis (hazard ratio, 0.75; 95% CI, 0.66-0.85; P < .001) and 655 propensity-matched pairs (2-year OS, 47.2% [95% CI, 43.5%-51.3%] vs 38.0% [95% CI, 34.4%-42.0%]; P < .001).

    Conclusions and Relevance  Patients with stage I to II pancreatic cancer who commenced adjuvant therapy within 28 to 59 days after primary surgical resection had improved survival outcomes compared with those with adjuvant therapy before 28 days or after 59 days. Patients who recovered slowly from surgery still benefited from delayed adjuvant therapy initiated more than 12 weeks after surgery compared with patients who underwent surgery only.