Advertisement

Annals of Surgical Oncology

, Volume 26, Issue 11, pp 3701–3708 | Cite as

Better Defining the Role of Total Neoadjuvant Radiation: Changing Paradigms in Locally Advanced Pancreatic Cancer

  • Roberto J. Vidri
  • Anne O. Vogt
  • Dougald C. Macgillivray
  • Ian J. Bristol
  • Timothy L. FitzgeraldEmail author
Pancreatic Tumors

Abstract

Background

This study was designed to better define the role of radiation (Neo-Rad) in addition to neoadjuvant multiagent chemotherapy (NAT) for the treatment of locally advanced pancreatic cancer.

Methods

Retrospective cohort study using the NCDB. Individuals with AJCC clinical T3/T4 pancreatic carcinoma who underwent resection and multiagent chemotherapy were included. Kaplan–Meier, logistic-regression, and Cox proportional-hazard models were used for analysis.

Results

A total of 2703 patients were included; 2039 had T3 and 664 had T4 tumors, and 1092 (40.4%) received Neo-Rad. Median follow-up was 22.5 months. During the study period, there was increased use of NAT and a decline in the use of Neo-Rad. Addition of Neo-Rad did not affect 30-day (2.51% vs. 3.24%, p = 0.272) or 90-day mortality (5.23% vs. 6.38%, p = 0.216). Neo-Rad was not associated with improved overall survival on univariable (25.95 vs. 24.7 months, p = 0.202), or multivariable analyses (hazard ratio [HR] 0.94; 95% confidence interval [CI] 0.85–1.05). Time from diagnosis to definitive surgery was increased by Neo-Rad (204 vs. 115 days, p < 0.001). Neo-Rad was associated with increased pathologic downstaging in T3 (32.8% vs. 14.4%) (odds ratio [OR] 2.90; 95% CI 2.30–3.66) and T4 tumors (88.9% vs. 77.8%) (OR 2.29; 95% CI 1.44–3.67); complete pathologic response (5.3% vs. 1.6%) (OR 2.89; 95% CI 1.73–4.83), and increased R0 resection rates (85.7% vs. 76.8%) (OR 1.79; 95% CI 1.44–2.23).

Conclusions

The use of neoadjuvant therapy is increasing for the treatment of locally advanced pancreatic cancer. The addition of radiation to neoadjuvant chemotherapy is associated with improved antineoplastic effectiveness (downstaging, complete pathologic response), surgical resection (R0 rates), but has no effect on overall survival.

Notes

References

  1. 1.
    Mirkin KA, Hollenbeak CS, Gusani NJ, Wong J. Trends in utilization of neoadjuvant therapy and short-term outcomes in resected pancreatic cancer. Am J Surg. 2017;214(1):80–8.CrossRefGoogle Scholar
  2. 2.
    Parmar AD, Vargas GM, Tamirisa NP, Sheffield KM, Riall TS. Trajectory of care and use of multimodality therapy in older patients with pancreatic adenocarcinoma. Surgery. 2014;156(2):280–9.CrossRefGoogle Scholar
  3. 3.
    Shubert CR, Bergquist JR, Groeschl RT, et al. Overall survival is increased among stage III pancreatic adenocarcinoma patients receiving neoadjuvant chemotherapy compared to surgery first and adjuvant chemotherapy: an intention-to-treat analysis of the National Cancer Database. Surgery. 2016;160(4):1080–96.CrossRefGoogle Scholar
  4. 4.
    Mirkin KA, Hollenbeak CS, Wong J. Survival impact of neoadjuvant therapy in resected pancreatic cancer: a prospective cohort study involving 18,332 patients from the National Cancer Data Base. Int J Surg. 2016;34:96–102.CrossRefGoogle Scholar
  5. 5.
    Mokdad AA, Minter RM, Zhu H, et al. Neoadjuvant therapy followed by resection versus upfront resection for resectable pancreatic cancer: a propensity score matched analysis. J Clin Oncol. 2017;35(5):515–22.CrossRefGoogle Scholar
  6. 6.
    Marsh RDW, Baker M, Catenacci DV, et al. Peri-operative modified FOLFIRINOX (mFOLFIRINOX) in resectable pancreatic cancer (PDAC): a pilot study. Alexandria: American Society of Clinical Oncology; 2016.CrossRefGoogle Scholar
  7. 7.
    Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–25.CrossRefGoogle Scholar
  8. 8.
    Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691–703.CrossRefGoogle Scholar
  9. 9.
    NCCN (NCCN). Pancreatic adenocarcinoma. 2017; Version 3.2017. https://www.nccn.org/professionals/physician_gls/default.aspx. Accessed 15 July 2018.
  10. 10.
    Balaban EP, Mangu PB, Khorana AA, et al. Locally advanced, unresectable pancreatic cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2016;34(22):2654–68.CrossRefGoogle Scholar
  11. 11.
    Neoptolemos JP, Stocken DD, Friess H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004;350(12):1200–10.CrossRefGoogle Scholar
  12. 12.
    Moghanaki D. Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Gastrointestinal Tumor Study Group. Cancer. 1987;59:2006–10.CrossRefGoogle Scholar
  13. 13.
    Stessin AM, Meyer JE, Sherr DL. Neoadjuvant radiation is associated with improved survival in patients with resectable pancreatic cancer: an analysis of data from the surveillance, epidemiology, and end results (SEER) registry. Int J Radiat Oncol Biol Phys. 2008;72(4):1128–33.CrossRefGoogle Scholar
  14. 14.
    Talamonti MS, Small W, Mulcahy MF, et al. A multi-institutional phase II trial of preoperative full-dose gemcitabine and concurrent radiation for patients with potentially resectable pancreatic carcinoma. Ann Surg Oncol. 2006;13(2):150–8.CrossRefGoogle Scholar
  15. 15.
    Turrini O, Ychou M, Moureau-Zabotto L, et al. Neoadjuvant docetaxel-based chemoradiation for resectable adenocarcinoma of the pancreas: new neoadjuvant regimen was safe and provided an interesting pathologic response. Eur J Surg Oncol. 2010;36(10):987–92.CrossRefGoogle Scholar
  16. 16.
    Colbert LE, Hall WA, Nickleach D, et al. Chemoradiation therapy sequencing for resected pancreatic adenocarcinoma in the National Cancer Data Base. Cancer. 2014;120(4):499–506.CrossRefGoogle Scholar
  17. 17.
    Kim EJ, Ben‐Josef E, Herman JM, et al. A multi‐institutional phase 2 study of neoadjuvant gemcitabine and oxaliplatin with radiation therapy in patients with pancreatic cancer. Cancer. 2013;119(15):2692–700.CrossRefGoogle Scholar
  18. 18.
    Katz MH, Ou F-S, Herman JM, et al. Alliance for clinical trials in oncology (ALLIANCE) trial A021501: preoperative extended chemotherapy vs. chemotherapy plus hypofractionated radiation therapy for borderline resectable adenocarcinoma of the head of the pancreas. BMC Cancer. 2017;17(1):505.CrossRefGoogle Scholar
  19. 19.
    Bilimoria KY, Bentrem DJ, Stewart AK, Winchester DP, Ko CY. Comparison of commission on cancer-approved and -nonapproved hospitals in the United States: implications for studies that use the National Cancer Data Base. J Clin Oncol. 2009;27(25):4177–4181.CrossRefGoogle Scholar
  20. 20.
    O’Reilly EM, Perelshteyn A, Jarnagin WR, et al. A single-arm, nonrandomized phase II trial of neoadjuvant gemcitabine and oxaliplatin in patients with resectable pancreas adenocarcinoma. Ann Surg. 2014;260(1):142–8.CrossRefGoogle Scholar
  21. 21.
    Rose JB, Rocha FG, Alseidi A, et al. Extended neoadjuvant chemotherapy for borderline resectable pancreatic cancer demonstrates promising postoperative outcomes and survival. Ann Surg Oncol. 2014;21(5):1530–7.CrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2019

Authors and Affiliations

  • Roberto J. Vidri
    • 1
    • 2
  • Anne O. Vogt
    • 1
  • Dougald C. Macgillivray
    • 1
  • Ian J. Bristol
    • 1
  • Timothy L. Fitzgerald
    • 1
    • 3
    Email author
  1. 1.Division of Surgical OncologyTufts University School of Medicine-Maine Medical CenterPortlandUSA
  2. 2.Division of SurgerySt. Mary’s Regional Medical CenterLewistonUSA
  3. 3.Maine Medical Center Cancer InstituteScarboroughUSA

Personalised recommendations