Skip to main content

Advertisement

SpringerLink
Log in

Trends in Receipt and Timing of Multimodality Therapy in Early-Stage Pancreatic Cancer

  • 2015 SSAT Plenary Presentation
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Introduction

Pancreatic cancer is considered a systemic disease at presentation. Therefore, multimodality therapy with surgical resection and chemotherapy is the standard of care for locoregional disease. We described treatment patterns and time trends with regard to age and treatment center in the receipt of multimodality therapy.

Methods

We used the National Cancer Data Base to identify patients ≥18 years old with stage I and II pancreatic adenocarcinoma. Treatment was defined as no treatment, resection only, chemotherapy only, or multimodality therapy, which consisted of both chemotherapy (neoadjuvant or adjuvant) and resection. Trends in the receipt and type of treatment were compared.

Results

Of 39,441 patients, 22.8 % of patients received no treatment, 18.5 % received chemotherapy only, 23.0 % underwent surgical resection alone, and 35.8 % of patients received multimodality therapy. Receipt of multimodality therapy increased from 31.3 % in 2004 to 37.9 % in 2011 (p < 0.0001). Patients >55 years were less likely to receive multimodality therapy (56–64 years: OR 0.83, 95 % CI 0.78–0.89; 65–75: OR 0.60, 95 % CI 0.55–0.65; ≥76: OR 0.17, 95 % CI 0.16–0.19 compared to patients 18–55). Compared to community hospitals, patients treated at an NCI-designated center were more likely to receive multimodality therapy (OR 1.62, 95 % CI 1.46–1.81) and, if they received multimodality therapy, delivery of chemotherapy in the neoadjuvant compared to adjuvant setting (OR 2.82, 95 % CI 2.00–3.98).

Conclusion

Despite increased use of multimodality therapy, it remains underutilized in all patients and especially in older patients. Receipt of multimodality therapy and neoadjuvant therapy is highly dependent on treatment at NCI-designated cancer centers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Siegel, R., D. Naishadham, and A. Jemal, Cancer statistics, 2013. CA Cancer J Clin, 2013. 63(1): p. 11-30.

    Article  PubMed  Google Scholar 

  2. Sugiura, T., K. Uesaka, K. Mihara, et al., Margin status, recurrence pattern, and prognosis after resection of pancreatic cancer. Surgery, 2013. 154(5): p. 1078-86.

    Article  PubMed  Google Scholar 

  3. Raut, C.P., J.F. Tseng, C.C. Sun, et al., Impact of resection status on pattern of failure and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma. Ann Surg, 2007. 246(1): p. 52-60.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Hernandez, J., J. Mullinax, W. Clark, et al., Survival after pancreaticoduodenectomy is not improved by extending resections to achieve negative margins. Ann Surg, 2009. 250(1): p. 76-80.

    Article  PubMed  Google Scholar 

  5. Smaglo, B.G. and M.J. Pishvaian, Postresection chemotherapy for pancreatic cancer. Cancer J, 2012. 18(6): p. 614-23.

    Article  PubMed  CAS  Google Scholar 

  6. Kooby, D.A., T.W. Gillespie, Y. Liu, et al., Impact of adjuvant radiotherapy on survival after pancreatic cancer resection: an appraisal of data from the national cancer data base. Ann Surg Oncol, 2013. 20(11): p. 3634-42.

    Article  PubMed  Google Scholar 

  7. Mayo, S.C., D.F. Austin, B.C. Sheppard, et al., Adjuvant therapy and survival after resection of pancreatic adenocarcinoma: a population-based analysis. Cancer, 2010. 116(12): p. 2932-40.

    Article  PubMed  Google Scholar 

  8. Kosuge, T., T. Kiuchi, K. Mukai, et al., A multicenter randomized controlled trial to evaluate the effect of adjuvant cisplatin and 5-fluorouracil therapy after curative resection in cases of pancreatic cancer. Jpn J Clin Oncol, 2006. 36(3): p. 159-65.

    Article  PubMed  Google Scholar 

  9. Cooper, A.B., H.M. Holmes, J.K. des Bordes, et al., Role of neoadjuvant therapy in the multimodality treatment of older patients with pancreatic cancer. J Am Coll Surg, 2014. 219(1): p. 111-20.

    Article  PubMed  Google Scholar 

  10. Tzeng, C.W., H.S. Tran Cao, J.E. Lee, et al., Treatment sequencing for resectable pancreatic cancer: influence of early metastases and surgical complications on multimodality therapy completion and survival. J Gastrointest Surg, 2014. 18(1): p. 16-24; discussion 24-5.

    Article  PubMed  Google Scholar 

  11. Golcher, H., T.B. Brunner, H. Witzigmann, et al., Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer: Results of the first prospective randomized phase II trial. Strahlenther Onkol, 2014.

  12. Christians, K.K., S. Tsai, A. Mahmoud, et al., Neoadjuvant FOLFIRINOX for borderline resectable pancreas cancer: a new treatment paradigm? Oncologist, 2014. 19(3): p. 266-74.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  13. Bilimoria, K.Y., D.J. Bentrem, C.Y. Ko, et al., National failure to operate on early stage pancreatic cancer. Ann Surg, 2007. 246(2): p. 173-80.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Vanderveen, K.A., R.J. Canter, D. Yin, et al., Factors affecting treatment delivery and outcomes of patients with early-stage pancreatic adenocarcinoma. Pancreas, 2011. 40(3): p. 480-2.

    Article  PubMed  Google Scholar 

  15. Riall, T.S., C.M. Townsend, Jr., Y.F. Kuo, et al., Dissecting racial disparities in the treatment of patients with locoregional pancreatic cancer: a 2-step process. Cancer, 2010. 116(4): p. 930-9.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Murphy, M.M., J.P. Simons, S.C. Ng, et al., Racial differences in cancer specialist consultation, treatment, and outcomes for locoregional pancreatic adenocarcinoma. Ann Surg Oncol, 2009. 16(11): p. 2968-77.

    Article  PubMed  Google Scholar 

  17. Cooper, A.B., A.D. Parmar, T.S. Riall, et al., Does the Use of Neoadjuvant Therapy for Pancreatic Adenocarcinoma Increase Postoperative Morbidity and Mortality Rates? J Gastrointest Surg, 2014.

  18. Corsini, M.M., R.C. Miller, M.G. Haddock, et al., Adjuvant radiotherapy and chemotherapy for pancreatic carcinoma: the Mayo Clinic experience (1975-2005). J Clin Oncol, 2008. 26(21): p. 3511-6.

    Article  PubMed  Google Scholar 

  19. Herman, J.M., M.J. Swartz, C.C. Hsu, et al., Analysis of fluorouracil-based adjuvant chemotherapy and radiation after pancreaticoduodenectomy for ductal adenocarcinoma of the pancreas: results of a large, prospectively collected database at the Johns Hopkins Hospital. J Clin Oncol, 2008. 26(21): p. 3503-10.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Yeo, C.J., R.A. Abrams, L.B. Grochow, et al., Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience. Ann Surg, 1997. 225(5): p. 621-33; discussion 633-6.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  21. Parmar, A.D., G.M. Vargas, N.P. Tamirisa, et al., Trajectory of care and use of multimodality therapy in older patients with pancreatic adenocarcinoma. Surgery, 2014. 156(2): p. 280-9.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Simons, J.P., S.C. Ng, T.P. McDade, et al., Progress for resectable pancreatic [corrected] cancer?: a population-based assessment of US practices. Cancer, 2010. 116(7): p. 1681-90.

    Article  PubMed  Google Scholar 

  23. Bilimoria, K.Y., A.K. Stewart, D.P. Winchester, et al., The National Cancer Data Base: a powerful initiative to improve cancer care in the United States. Ann Surg Oncol, 2008. 15(3): p. 683-90.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Davila, J.A., E.Y. Chiao, J.C. Hasche, et al., Utilization and determinants of adjuvant therapy among older patients who receive curative surgery for pancreatic cancer. Pancreas, 2009. 38(1): p. e18-25.

    Article  PubMed  CAS  Google Scholar 

  25. Papalezova, K.T., D.S. Tyler, D.G. Blazer, 3rd, et al., Does preoperative therapy optimize outcomes in patients with resectable pancreatic cancer? J Surg Oncol, 2012. 106(1): p. 111-8.

    Article  PubMed  Google Scholar 

  26. Sener, S.F., A. Fremgen, H.R. Menck, et al., Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985-1995, using the National Cancer Database. J Am Coll Surg, 1999. 189(1): p. 1-7.

    Article  PubMed  CAS  Google Scholar 

  27. Bilimoria, K.Y., D.J. Bentrem, C.Y. Ko, et al., Multimodality therapy for pancreatic cancer in the U.S. : utilization, outcomes, and the effect of hospital volume. Cancer, 2007. 110(6): p. 1227-34.

    Article  PubMed  Google Scholar 

  28. Sen, N., S. Falk, and R.A. Abrams, Role of chemoradiotherapy in the adjuvant and neoadjuvant settings for resectable pancreatic cancer. Clin Oncol (R Coll Radiol), 2014. 26(9): p. 551-9.

    Article  CAS  Google Scholar 

  29. Merkow, R.P., K.Y. Bilimoria, J.S. Tomlinson, et al., Postoperative complications reduce adjuvant chemotherapy use in resectable pancreatic cancer. Ann Surg, 2014. 260(2): p. 372-7.

    Article  PubMed  Google Scholar 

  30. Artinyan, A., D.A. Anaya, S. McKenzie, et al., Neoadjuvant therapy is associated with improved survival in resectable pancreatic adenocarcinoma. Cancer, 2011. 117(10): p. 2044-9.

    Article  PubMed  Google Scholar 

Download references

Funding

Supported by grants from the Cancer Prevention Research Institute of Texas Grant # RP140020 , UTMB Clinical and Translational Science Award #UL1TR000071, NIH T-32 Grant # 5T32DK007639, and AHRQ Grant # 1R24HS022134.

Author information

Authors and Affiliations

  1. Department of Surgery, University of Arizona, Banner-University Medical Center, 1501 N Campbell Dr, Rm 4327b, PO Box 245131, Tucson, AZ, 85274-5131, USA

    Francesca Dimou, Abhishek D. Parmar, Nina P. Tamirisa & Taylor S. Riall

  2. Department of Surgery, University of California, San Francisco-East Bay, Oakland, CA, USA

    Abhishek D. Parmar & Nina P. Tamirisa

  3. American Cancer Society, Atlanta, GA, USA

    Helmneh Sineshaw & Ahmedin Jemal

Authors
  1. Francesca Dimou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Helmneh Sineshaw
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Abhishek D. Parmar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nina P. Tamirisa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ahmedin Jemal
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Taylor S. Riall
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Taylor S. Riall.

Additional information

Primary Discussant

Dr. Stephen W. Behrman, M.D. (Memphis, TN):

Dr. Dimou and her colleagues confirm that multimodality therapy is superior to single modality treatment in early stage pancreatic cancer. Sadly, when viewed through the lens of this population-based study, the picture of our compliance to this principle is not very flattering. Utilizing the National Cancer Database, the authors demonstrate a promising 40 % increased odds of receiving multimodality therapy from 2004 to 2011, but still only 35 % of almost 40,000 patients received combined modality treatment. These types of studies, unfortunately, often leave too much unsaid in terms of the vagaries that might determine why and whether the individual patient receives one type of treatment or another or whether they may not receive treatment at all. Having said so, the pulse of this study suggests we could raise the bar on survival from pancreatic cancer in this country if we just worked better as a team. I have the following questions:

1. Prior studies have demonstrated that advanced age is independently associated with morbidity and death following pancreatectomy and that serious complications increase the likelihood of not receiving adjuvant therapy by over 2-fold in this cohort. In your study, 45 % of those greater than age 76 received no treatment and only 15 % received multimodality treatment. Did you try to tease that out a bit further? Was there any data on post-operative complications (or perhaps length of stay or readmission as a surrogate)? What about ECOG status prior to initiation or completion of neoadjuvant therapy or prior to starting adjuvant therapy in these older patients?

2. Do you have any information on those that received neoadjuvant therapy in terms of how many progressed and thus did not have surgery or those that might have had deterioration in their performance status especially those in older populations where multimodality therapy was less often utilized?

3. While the use of multimodality therapy was higher in NCI-designated centers, those receiving neoadjuvant therapy were in the minority. Was the number having surgery following neoadjuvant therapy higher in NCI designated centers than other settings?

This manuscript is very well written and analyzed, and I would like to thank the program committee for the opportunity to discuss this fine work.

Closing Discussant

Dr. Dimou:

Dr. Behrman, thank you for your comments. Of the 4202 patients 76 and older, only 38 % who underwent surgery as the initial treatment modality received adjuvant chemotherapy within 6 months, which is less than the 63 % for the 17,431 patients in the overall cohort who had surgery first. While the National Cancer Database (NCDB) does not have information on post-operative complications or ECOG performance status, we are certain that postoperative complications combined with the lack of physiologic reserve in the older population lead to decreased rates. Data from the NSQIP pancreatectomy project demonstrated that older patients have similar complication rates, but are more likely to fail to rescue, suggesting that once they have complications, they are less likely to recover. However, it may also be that many older patients are not offered or choose not to have adjuvant therapy.

To answer your second question, the NCDB lacks information on progression of disease and performance status. The NCDB does, however, report on reasons for not undergoing treatment, including contraindications and patient refusal. Clear contraindications and refusal were only coded in 5 % of the entire cohort and does not fully describe the reasons for lack of treatment within the entire cohort, especially older patients. We suspect there is an element of physician nihilism, but also acknowledge the possibility that patient choice and subtle contraindications (or good patient selection) are not captured.

It is important to note that patients classified as having neoadjuvant therapy were only placed in this treatment group if they received both chemotherapy prior to resection and surgical resection. If they never received resection, patients were placed in the chemotherapy only category and not classified as neoadjuvant. We did an analysis of all patients who got chemotherapy as the initial treatment modality, recognizing that this is not always given with neoadjuvant intent. Only 17 % of patients who had chemotherapy first went on to surgical resection. At NCI-designated cancer centers, 30 % of patients who received initial chemotherapy went on to surgical resection. Likewise, NCI-designated centers were more likely to have patients undergo both surgical resection and adjuvant chemotherapy compared to other treatment facilities, and overall, more likely to provide some sort of treatment to patients compared to other treatment centers.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dimou, F., Sineshaw, H., Parmar, A.D. et al. Trends in Receipt and Timing of Multimodality Therapy in Early-Stage Pancreatic Cancer. J Gastrointest Surg 20, 93–103 (2016). https://doi.org/10.1007/s11605-015-2952-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-015-2952-7

Keywords

Search

Navigation