Prognostic factors and sites of metastasis in unresectable locally advanced pancreatic cancer

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Abstract:
Due to differences in natural history and therapy, clinical trials of patients with advanced pancreatic cancer have recently been subdivided into unresectable locally advanced pancreatic cancer (LAPC) and metastatic disease. We aimed to evaluate prognostic factors in LAPC patients who were treated with first-line chemotherapy and describe patterns of disease progression. Patients with LAPC who initiated first-line palliative chemotherapy, 2001–2011 at the BC Cancer Agency were included. A retrospective chart review was conducted to identify clinicopathologic variables, treatment, and subsequent sites of metastasis. Kaplan–Meier and Cox-regression survival analyses were performed. A total of 244 patients were included in this study. For the majority of patients (94.3%), first-line therapy was single-agent gemcitabine. About 144 (59%) patients developed distant metastatic disease and the most frequent metastatic sites included peritoneum/omentum (42.3%), liver (41%), lungs (13.9%), and distant lymph nodes (9%). Median overall survival (OS) for the entire cohort was 11.7 months (95% CI, 10.6–12.8). Development of distant metastases was associated with significantly inferior survival (HR 3.56, 95% CI 2.57–4.93), as was ECOG 2/3 versus 0/1 (HR 1.69, 95% CI 1.28–2.23), CA 19.9 > 1000 versus ≤1000 (HR 1.59, 95% CI 1.19–2.14) and female gender, (HR 1.57, 95% CI 1.19–2.08). In this population-based study, 41% of LAPC patients treated with first-line chemotherapy died without evidence of distant metastases. Prognostic factors for LAPC were baseline performance status, elevated CA 19.9, gender, and development of distant metastasis. Results highlight the heterogeneity of LAPC and the importance of locoregional tumor control.

Keywords:
CA 19.9, LAPC, liver metastasis, locally advanced pancreatic cancer, metastatic sites, pancreatic ductal adenocarcinoma, PDAC, prognostic factors, survival

Autoři: Renata D’alpino Peixoto ^1,2; Caroline Speers ³; Colleen E. Mcgahan ⁴; Daniel J. Renouf ^1,2; David F. Schaeffer ^2,5; Hagen F. Kennecke ^1,2
Působiště autorů: Division of Medical Oncology, University of British Columbia, British Columbia Cancer Agency, Vancouver, British Columbia, Canada ¹; Pancreas Centre, Vancouver, British Columbia, Canada ²; Gastrointestinal Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, British Columbia, Canada ³; Cancer Surveillance & Outcomes, British Columbia Cancer Agency, Vancouver, British Columbia, Canada ⁴; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada ⁵
Vyšlo v časopise: Cancer Medicine 2015; 4(8)
Kategorie: Original Research
prolekare.web.journal.doi_sk: https://doi.org/10.1002/cam4.459

© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Souhrn

Keywords:
CA 19.9, LAPC, liver metastasis, locally advanced pancreatic cancer, metastatic sites, pancreatic ductal adenocarcinoma, PDAC, prognostic factors, survival

Zdroje

1. Siegel, R., J. Ma, Z. Zou, and A. Jemal.2014. Cancer statistics, 2014. CA Cancer J. Clin. 64:9–29.

2. Niederhuber, J. E., M. F. Brennan, and H. R. Menck. 1995. The National Cancer Data Base report on pancreatic cancer. Cancer 76:1671–1677.

3. Choti, M. A., E. Dixon, and D. Tyler. 2009. Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement by Callery, et al. Ann. Surg. Oncol. 16:1734–1735.

4. Van Cutsem, E., H. van de Velde, P. Karasek, H. Oettle, W. L. Vervenne, A. Szawlowski, et al. 2004. Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer.J. Clin. Oncol. 22:1430–1438.

5. Chauffert, B., F. Mornex, F. Bonnetain, P. Rougier, C. Mariette, O. Bouche, et al. 2008. Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000-01 FFCD/SFRO study. Ann. Oncol. 19:1592–1599.

6. Loehrer, P. J. Sr, Y. Feng, H. Cardenes, L. Wagner, J. M. Brell, D. Cella, et al. 2011. Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J. Clin. Oncol. 29:4105–4112.

7. Blackstock, A. W., J. E. Tepper, D. Niedwiecki, D. R. Hollis, R. J. Mayer, and M. A. Tempero. 2003. Cancer and leukemia group B (CALGB) 89805: phase II chemoradiation trial using gemcitabine in patients with locoregional adenocarcinoma of the pancreas. Int. J. Gastrointest. Cancer 34:107–116.

8. Burris, H. A. III, M. J. Moore, J. Andersen, M. R. Green, M. L. Rothenberg, M. R. Modiano, et al. 1997.Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J. Clin. Oncol. 15:2403–2413.

9. Hammel, P., F. Huguet, J.-L.V. Laethem, D. Goldstein, B. Glimelius, P. Artru, et al. , eds. 2013.Comparison of chemoradiotherapy (CRT) and chemotherapy (CT) in patients with a locally advanced pancreatic cancer (LAPC) controlled after 4 months of gemcitabine with or without erlotinib: Final results of the international phase III LAP 07 study. ASCO Annual Meeting; 2013; Chicago, Illinois. J. Clin. Oncol. 31(suppl): abstr LBA4003.

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

11. Von Hoff, D. D., T. Ervin, F. P. Arena, E. G. Chiorean, J. Infante, M. Moore, et al. 2013. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N. Engl. J. Med. 369:1691–1703.

12. Iacobuzio-Donahue, C. A., B. Fu, S. Yachida, M. Luo, H. Abe, C. M. Henderson, et al. 2009. DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J. Clin. Oncol.27:1806–1813.

13. Philip, P. A., M. Mooney, D. Jaffe, G. Eckhardt, M. Moore, N. Meropol, et al. 2009. Consensus report of the national cancer institute clinical trials planning meeting on pancreas cancer treatment. J. Clin. Oncol.27:5660–5669.

14. Moore, M. J., D. D. V. Hoff, T. J. Ervin, F. P. Arena, E. G. Chiorean, J. R. Infante, et al. , eds. 2013. Prognostic factors (PFs) of survival in a randomized phase III trial (MPACT) of weekly nab-paclitaxel (nab-P) plus gemcitabine (G) versus G alone in patients (pts) with metastatic pancreatic cancer (MPC). 2013 ASCO Annual Meeting; 2013; Chicago, Illinois. J. Clin. Oncol. 31(suppl: abstr 4059).

15. Rocha Lima, C. M., M. R. Green, R. Rotche, W. H. Miller Jr, G. M. Jeffrey, L. A. Cisar, et al. 2004. Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate. J. Clin. Oncol.22:3776–3783.

16. National Comprehensive Cancer Network, Inc. 2015. NCCN Guidelines: Pancreatic Adenocarcinoma. Version 2.2015, Fort Washington, PA, USA.

17. Seufferlein, T., J. B. Bachet, E. Van Cutsem, and P. Rougier, Group obotEGW. 2012. Pancreatic adenocarcinoma: ESMO–ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol.. 23(suppl 7):vii33–vii40.

18. Huguet, F., P. Hammel, D. Vernerey, D. Goldstein, J. L. V. Laethem, B. Glimelius, et al. , eds. 2013. Impact of chemoradiotherapy (CRT) on local control and time without treatment in patients with locally advanced pancreatic cancer (LAPC) included in the international phase III LAP 07 study. ASCO Annual Meeting; 2014; Chicago, Illinois:. J. Clin. Oncol. 32 5s (suppl; abstr 4001).

19. Vernerey, D., P. Hammel, S. Paget-Bailly, F. Huguet, J. L. V. Laethem, D. Goldstein, et al. , eds. 2014. Prognosis model for overall survival in locally advanced pancreatic cancer (LAPC): an ancillary study of the LAP 07 trial. ASCO Annual Meeting; 2014; Chicago, Illinois. J. Clin. Oncol. 32:5s (suppl; abstr 4024).

20. Hess, V., B. Glimelius, P. Grawe, D. Dietrich, G. Bodoky, T. Ruhstaller, et al. 2008. CA 19-9 tumour-marker response to chemotherapy in patients with advanced pancreatic cancer enrolled in a randomised controlled trial. Lancet Oncol. 9:132–138.

21. Maisey, N. R., A. R. Norman, A. Hill, A. Massey, J. Oates, and D. Cunningham. 2005. CA19-9 as a prognostic factor in inoperable pancreatic cancer: the implication for clinical trials. Br. J. Cancer 93:740–743.

22. Ikeda, M., S. Okada, K. Tokuuye, H. Ueno, and T. Okusaka. 2001. Prognostic factors in patients with locally advanced pancreatic carcinoma receiving chemoradiotherapy. Cancer 91:490–495.

23. Ince, A. T., K. Yildiz, B. Baysal, A. Danalioglu, O. Kocaman, M. Tozlu, et al. 2014. Roles of serum and biliary CEA, CA19-9, VEGFR3, and TAC in differentiating between malignant and benign biliary obstructions. Turk. J. Gastroenterol. 25:162–169.

24. Marrelli, D., F. Roviello, A. De Stefano, M. Farnetani, L. Garosi, A. Messano, et al. 1999. Prognostic significance of CEA, CA 19-9 and CA 72-4 preoperative serum levels in gastric carcinoma. Oncology 57:55–62.

25. Tonack, S., C. Jenkinson, T. Cox, V. Elliott, R. E. Jenkins, N. R. Kitteringham, et al. 2013. iTRAQ reveals candidate pancreatic cancer serum biomarkers: influence of obstructive jaundice on their performance. Br. J. Cancer 108:1846–1853.

26. Ballehaninna, U. K., and R. S. Chamberlain. 2012. The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: an evidence based appraisal. J. Gastrointest. Oncol. 3:105–119.

27. Ishii, H., S. Okada, H. Nose, M. Yoshimori, K. Aoki, and T. Okusaka. 1996. Prognostic factors in patients with advanced pancreatic cancer treated with systemic chemotherapy. Pancreas 12:267–271.

28.Kalser, M. H., J. Barkin, and J. M. MacIntyre. 1985. Pancreatic cancer. Assessment of prognosis by clinical presentation. Cancer 56:397–402.

29. Papadoniou, N., C. Kosmas, K. Gennatas, A. Polyzos, D. Mouratidou, E. Skopelitis, et al. 2008. Prognostic factors in patients with locally advanced (unresectable) or metastatic pancreatic adenocarcinoma: a retrospective analysis. Anticancer Res. 28:543–549.

30. Inal, A., F. T. Kos, E. Algin, R. Yildiz, V. Berk, I. Tugba Unek, et al. 2012. Prognostic factors in patients with advanced pancreatic cancer treated with gemcitabine alone or gemcitabine plus cisplatin: retrospective analysis of a multicenter study. J. Buon. 17:102–105.