Ann Hepatobiliary Pancreat Surg.  2018 Nov;22(4):386-396. 10.14701/ahbps.2018.22.4.386.

Recent treatment patterns and survival outcomes in pancreatic cancer according to clinical stage based on single-center large-cohort data

• Lee DH
• Jang JY
• Kang JS
• Kim JR
• Han Y
• Kim E
• Kwon W
• Kim SW

• KMID: 2427371
• DOI: http://doi.org/10.14701/ahbps.2018.22.4.386

Abstract

BACKGROUNDS/AIMS
We performed a retrospective, single-center cohort study to evaluate the impact of various treatment modalities and recent changes in treatment modalities, including the increased application of chemotherapy, on survival in patients with pancreatic cancer.
METHODS
All patients with pancreatic cancer who were diagnosed and treated at Seoul National University Hospital between January 2007 and December 2014 were registered in a prospective clinical database and included in this retrospective study. All patients' radiologic imaging diagnoses were re-reviewed according to the National Cancer Center Network guidelines. The patients were divided into four groups according to their clinical stage, and each clinical stage group was further divided into four groups according to treatment modality.
RESULTS
Overall, 475 (28.9%) patients had resectable pancreatic cancer, 129 (7.8%) patients borderline resectable pancreatic cancer, 384 (23.3%) patients locally advanced pancreatic cancer, and 658 (40.0%) patients metastatic pancreatic cancer. Among the patients with borderline resectable pancreatic cancer, the median survival was significantly longer in the neoadjuvant therapy (NAT)+surgery groups (24 months) than the surgery without NAT (16 months) group (p=0.049). A multivariate survival analysis revealed that compared with the surgery group, the 5-year mortality risk was decreased by 35% in the NAT+surgery group (24 vs. 20 months, p=0.045).
CONCLUSIONS
This retrospective cohort study showed that the rates of resectable and surgically treatable pancreatic cancer were 29.1% and 32.2%, which are higher than those reported previously, and aggressive NAT for select advanced-stage patients could lead to better survival outcomes.

Keyword

Neoadjuvant therapy; Survival rate; Pancreas neoplasms

MeSH Terms

Cohort Studies
Diagnosis
Drug Therapy
Humans
Mortality
Neoadjuvant Therapy
Pancreatic Neoplasms*
Prospective Studies
Retrospective Studies
Seoul
Survival Rate

Figure

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  Fig. 1 Overall survival according to clinical stage and treatment.

Reference

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015; 65:5–29.

2. Tran KT, Smeenk HG, van Eijck CH, Kazemier G, Hop WC, Greve JW, et al. Pylorus preserving pancreaticoduodenectomy versus standard Whipple procedure: a prospective, randomized, multicenter analysis of 170 patients with pancreatic and periampullary tumors. Ann Surg. 2004; 240:738–745.

3. Jung KW, Won YJ, Oh CM, Kong HJ, Lee DH, Lee KH. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2014. Cancer Res Treat. 2017; 49:292–305.

4. Tempero MA, Malafa MP, Behrman SW, Benson AB 3rd, Casper ES, Chiorean EG, et al. Pancreatic adenocarcinoma, version 2.2014: featured updates to the NCCN guidelines. J Natl Compr Canc Netw. 2014; 12:1083–1093.

5. Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011; 364:1817–1825.

6. Liu GF, Li GJ, Zhao H. Efficacy and toxicity of different chemotherapy regimens in the treatment of advanced or metastatic pancreatic cancer: a network meta-analysis. J Cell Biochem. 2018; 119:511–523.

7. Varadhachary GR, Tamm EP, Abbruzzese JL, Xiong HQ, Crane CH, Wang H, et al. Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy. Ann Surg Oncol. 2006; 13:1035–1046.

8. Callery MP, Chang KJ, Fishman EK, Talamonti MS, William Traverso L, Linehan DC. Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement. Ann Surg Oncol. 2009; 16:1727–1733.

9. Katz MH, Marsh R, Herman JM, Shi Q, Collison E, Venook AP, et al. Borderline resectable pancreatic cancer: need for standardization and methods for optimal clinical trial design. Ann Surg Oncol. 2013; 20:2787–2795.

10. 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.

11. Goonetilleke KS, Siriwardena AK. Systematic review of carbohydrate antigen (CA 19-9) as a biochemical marker in the diagnosis of pancreatic cancer. Eur J Surg Oncol. 2007; 33:266–270.

12. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009; 45:228–247.

13. Wittekind C, Compton CC, Greene FL, Sobin LH. TNM residual tumor classification revisited. Cancer. 2002; 94:2511–2516.

14. Washington MK, Berlin J, Branton PA, Burgart LJ, Carter DK, Compton CC, et al. Protocol for the examination of specimens from patients with carcinoma of the perihilar bile ducts. Arch Pathol Lab Med. 2010; 134:e19–e24.

15. National Cancer Institute (NIH). Surveillance, Epidemiology, and End Results Program (SEER) Summary staing manual 2018. Bethesda: NIH;2018. cited 2018 May 2. Available from: https://seer.cancer.gov/tools/ssm/SSM2018-DIGESTIVE-AND-HEPATOBILIARY-SYSTEMS.pdf.

16. Katz MH, Pisters PW, Evans DB, Sun CC, Lee JE, Fleming JB, et al. Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg. 2008; 206:833–846.

17. Vauthey JN, Dixon E. AHPBA/SSO/SSAT consensus conference on resectable and borderline resectable pancreatic cancer: rationale and overview of the conference. Ann Surg Oncol. 2009; 16:1725–1726.

18. Gillen S, Schuster T, Meyer Zum, Friess H, Kleeff J. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med. 2010; 7:e1000267.

19. Katz MH, Shi Q, Ahmad SA, Herman JM, Marsh Rde W, Collisson E, et al. Preoperative modified FOLFIRINOX treatment followed by capecitabine-based chemoradiation for borderline resectable pancreatic cancer: alliance for clinical trials in oncology trial A021101. JAMA Surg. 2016; 151:e161137.

20. Tzeng CW, Balachandran A, Ahmad M, Lee JE, Krishnan S, Wang H, et al. Serum carbohydrate antigen 19-9 represents a marker of response to neoadjuvant therapy in patients with borderline resectable pancreatic cancer. HPB (Oxford). 2014; 16:430–438.

21. Evans DB, George B, Tsai S. Non-metastatic pancreatic cancer: resectable, borderline resectable, and locally advanced-definitions of increasing importance for the optimal delivery of multimodality therapy. Ann Surg Oncol. 2015; 22:3409–3413.

22. Kim HS, Jang JY, Han Y, Lee KB, Joo I, Lee DH, et al. Survival outcome and prognostic factors of neoadjuvant treatment followed by resection for borderline resectable pancreatic cancer. Ann Surg Treat Res. 2017; 93:186–194.

23. Dalah E, Tai A, Oshima K, Hall WA, Erickson B, Li XA. PET-based treatment response assessment for neoadjuvant chemoradiation in pancreatic adenocarcinoma: an exploratory study. Transl Oncol. 2018; 11:1104–1109.

24. Sakane M, Tatsumi M, Hori M, Onishi H, Tsuboyama T, Nakamoto A, et al. Volumetric parameters of 2-deoxy-2-[18F] fluoro-d-glucose positron emission tomography/computed tomography can predict histopathologic treatment response after neoadjuvant chemoradiotherapy in pancreatic adenocarcinoma. Eur J Radiol. 2017; 94:64–69.

25. Murakami Y, Uemura K, Sudo T, Hashimoto Y, Kondo N, Nakagawa N, et al. Prognostic impact of normalization of serum tumor markers following neoadjuvant chemotherapy in patients with borderline resectable pancreatic carcinoma with arterial contact. Cancer Chemother Pharmacol. 2017; 79:801–811.

26. Versteijne E, van Eijck CH, Punt CJ, Suker M, Zwinderman AH, Dohmen MA, et al. Preoperative radiochemotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC trial): study protocol for a multicentre randomized controlled trial. Trials. 2016; 17:127.

27. Heinrich S, Pestalozzi B, Lesurtel M, Berrevoet F, Laurent S, Delpero JR, et al. Adjuvant gemcitabine versus NEOadjuvant gemcitabine/oxaliplatin plus adjuvant gemcitabine in resectable pancreatic cancer: a randomized multicenter phase III study (NEOPAC study). BMC Cancer. 2011; 11:346.

28. Motoi F, Kawaguchi K, Aoki T, Kudo K, Yabuuchi S, Fukase K, et al. [Efficacy of neoadjuvant chemotherapy for resectable pancreatic carcinoma]. Gan To Kagaku Ryoho. 2013; 40:1632–1632. Japanese.