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Time to Initiation of Adjuvant Chemotherapy in Pancreas Cancer: A Multi-Institutional Experience

  • Pancreatic Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Despite randomized trials addressing adjuvant therapy (AT) for pancreas cancer, the ideal time to initiate therapy remains undefined. Retrospective analyses of the ESPAC-3 trial demonstrated that time to initiation of AT did not impact overall survival (OS). Given the absence of confirmatory data outside of a clinical trial, we sought to determine if AT timing in routine clinical practice is associated with OS differences.

Methods

Perioperative data of pancreatectomies for ductal adenocarcinoma from five institutions (2005–2015) were assessed. Delay in AT was defined as initiation >12 weeks after surgery. Multivariate analysis was performed to identify predictors of mortality.

Results

Of 867 patients, 172 (19.8%) experienced omission of AT. Improved OS was observed in patients who received AT compared with patients who did not (24.8 vs. 19.1 months, p < 0.01). Information on time to initiation of AT was available in 488 patients, of whom 407 (83.4%) and 81 (16.6%) received chemotherapy ≤12 and >12 weeks after surgery, respectively. There were no differences in recurrence-free survival or OS (all p > 0.05) between the timely and delayed AT groups. After controlling for perioperative characteristics and tumor pathology, patients who initiated AT ≤ 12 or > 12 weeks after surgery had a 50% lower odds of mortality than patients who only underwent resection (p < 0.01).

Conclusions

In a multi-institutional experience of resected pancreas cancer, delayed initiation of AT was not associated with poorer survival. Patients who do not receive AT within 12 weeks after surgery are still appropriate candidates for multimodal therapy and its associated survival benefit.

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References

  1. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30.

    Article  PubMed  Google Scholar 

  2. Sohn TA, Yeo CJ, Cameron JL, et al. Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg. 2000;4(6):567–79.

    Article  CAS  PubMed  Google Scholar 

  3. Cameron JL, He J. Two thousand consecutive pancreaticoduodenectomies. J Am Coll Surg. 2015;220(4):530–6.

    Article  PubMed  Google Scholar 

  4. Xia BT, Ahmad SA. Clinical Considerations for Pancreatic Cancer. Semin Roentgenol. 2016;51(2):74–81.

    Article  PubMed  Google Scholar 

  5. 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.

    Article  CAS  PubMed  Google Scholar 

  6. Oettle H, Post S, Neuhaus P, et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007;297(3):267–77.

    Article  CAS  PubMed  Google Scholar 

  7. Neoptolemos JP, Stocken DD, Bassi C, et al. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA. 2010;304(10):1073–81.

    Article  CAS  PubMed  Google Scholar 

  8. Valle JW, Palmer D, Jackson R, et al. Optimal duration and timing of adjuvant chemotherapy after definitive surgery for ductal adenocarcinoma of the pancreas: ongoing lessons from the ESPAC-3 study. J Clin Oncol. 2014;32(6):504–12.

    Article  PubMed  Google Scholar 

  9. Saeed H, Hnoosh D, Huang B, et al. Defining the optimal timing of adjuvant therapy for resected pancreatic adenocarcinoma: a statewide cancer registry analysis. J Surg Oncol. 2016;114(4):451–55.

    Article  CAS  PubMed  Google Scholar 

  10. Mirkin KA, Greenleaf EK, Hollenbeak CS, Wong J. Time to the initiation of adjuvant chemotherapy does not impact survival in patients with resected pancreatic cancer. Cancer. 2016;122(19):2979–87.

    Article  CAS  PubMed  Google Scholar 

  11. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.

    Article  CAS  PubMed  Google Scholar 

  12. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649–55.

    Article  CAS  PubMed  Google Scholar 

  13. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471–4.

    Article  PubMed  Google Scholar 

  14. Clavien PA, Barkun J, de Oliveira ML, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250(2):187–96.

    Article  PubMed  Google Scholar 

  15. Merkow RP, Bilimoria KY, Tomlinson JS, et al. Postoperative complications reduce adjuvant chemotherapy use in resectable pancreatic cancer. Ann Surg. 2014;260(2):372–77.

    Article  PubMed  Google Scholar 

  16. Biagi JJ, Raphael MJ, Mackillop WJ, Kong W, King WD, Booth CM. Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer: a systematic review and meta-analysis. JAMA. 2011;305(22):2335–42.

    Article  CAS  PubMed  Google Scholar 

  17. Porschen R, Bermann A, Loffler T, et al. Fluorouracil plus leucovorin as effective adjuvant chemotherapy in curatively resected stage III colon cancer: results of the trial adjCCA-01. J Clin Oncol. 2001;19(6):1787–94.

    Article  CAS  PubMed  Google Scholar 

  18. Twelves C, Wong A, Nowacki MP, et al. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med. 2005;352(26):2696–704.

    Article  CAS  PubMed  Google Scholar 

  19. Arkenau HT, Bermann A, Rettig K, Strohmeyer G, Porschen R, Arbeitsgemeinschaft Gastrointestinale O. 5-Fluorouracil plus leucovorin is an effective adjuvant chemotherapy in curatively resected stage III colon cancer: long-term follow-up results of the adjCCA-01 trial. Ann Oncol. 2003;14(3):395–9.

    Article  CAS  PubMed  Google Scholar 

  20. Neoptolemos JP, Palmer DH, Ghaneh P, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017;389(10073):1011–24.

    Article  CAS  PubMed  Google Scholar 

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Funding

No sources of funding were used to assist in the preparation of this study.

Conflict of interest

Brent T. Xia, Syed A. Ahmad, Ali H. Al Humaidi, Dennis J. Hanseman, Cecilia G. Ethun, Shishir K. Maithel, David A. Kooby, Ahmed Salem, Clifford S. Cho, Sharon M. Weber, Susan J. Stocker, Mark S. Talamonti, David J. Bentrem, and Daniel E. Abbott have no conflicts of interest to declare.

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Authors and Affiliations

  1. Division of Surgical Oncology, Department of Surgery, University of Cincinnati, Cincinnati, OH, USA

    Brent T. Xia MD, Syed A. Ahmad MD, Ali H. Al Humaidi MD & Dennis J. Hanseman PhD

  2. Division of Surgical Oncology, Department of Surgery, Emory University, Atlanta, GA, USA

    Cecilia G. Ethun MD, Shishir K. Maithel MD & David A. Kooby MD

  3. Division of Surgical Oncology, Department of Surgery, University of Wisconsin, Madison, WI, USA

    Ahmed Salem MD, Clifford S. Cho MD, Sharon M. Weber MD & Daniel E. Abbott MD

  4. Division of Surgical Oncology, Department of Surgery, University of Michigan, Ann Arbor, MI, USA

    Clifford S. Cho MD

  5. Department of Surgery, Northwestern University, Chicago, IL, USA

    Susan J. Stocker LPN & David J. Bentrem MD

  6. Department of Surgery, NorthShore University HealthSystem, Evanston, IL, USA

    Susan J. Stocker LPN & Mark S. Talamonti MD

Authors
  1. Brent T. Xia MD
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  2. Syed A. Ahmad MD
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  3. Ali H. Al Humaidi MD
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  4. Dennis J. Hanseman PhD
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  5. Cecilia G. Ethun MD
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  6. Shishir K. Maithel MD
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  7. David A. Kooby MD
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  8. Ahmed Salem MD
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  9. Clifford S. Cho MD
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  10. Sharon M. Weber MD
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  11. Susan J. Stocker LPN
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  12. Mark S. Talamonti MD
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  13. David J. Bentrem MD
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  14. Daniel E. Abbott MD
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Corresponding author

Correspondence to Daniel E. Abbott MD.

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Xia, B.T., Ahmad, S.A., Al Humaidi, A.H. et al. Time to Initiation of Adjuvant Chemotherapy in Pancreas Cancer: A Multi-Institutional Experience. Ann Surg Oncol 24, 2770–2776 (2017). https://doi.org/10.1245/s10434-017-5918-z

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  • DOI: https://doi.org/10.1245/s10434-017-5918-z

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