Prognostic factors in advanced pancreatic ductal adenocarcinoma patients-receiving second-line treatment: a single institution experience.
Adult
Aged
Aged, 80 and over
Antigens, Tumor-Associated, Carbohydrate
/ blood
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Capecitabine
/ therapeutic use
Carcinoma, Pancreatic Ductal
/ drug therapy
Clinical Decision-Making
Deoxycytidine
/ analogs & derivatives
Disease Progression
Female
Fluorouracil
/ therapeutic use
Humans
Irinotecan
/ therapeutic use
Leucovorin
/ therapeutic use
Logistic Models
Lymphocytes
/ cytology
Male
Middle Aged
Neutrophils
/ cytology
Oxaliplatin
/ therapeutic use
Oxaloacetates
/ therapeutic use
Pancreatic Neoplasms
/ drug therapy
Prognosis
Retrospective Studies
Time Factors
Gemcitabine
Advanced pancreatic ductal adenocarcinoma
Prognostic factors
Second-line treatment
Journal
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
ISSN: 1699-3055
Titre abrégé: Clin Transl Oncol
Pays: Italy
ID NLM: 101247119
Informations de publication
Date de publication:
Sep 2021
Sep 2021
Historique:
received:
01
02
2021
accepted:
08
03
2021
pubmed:
19
4
2021
medline:
15
12
2021
entrez:
18
4
2021
Statut:
ppublish
Résumé
Second-line (2L) treatments for advanced pancreatic ductal adenocarcinoma (PDAC) achieve a modest benefit at the expense of potential toxicity. In the absence of predictive factors of response, the identification of prognostic factors could help in the therapeutic decisions-making. The purpose of this study was to assess the prognostic factors associated with shorter survival in patients with advanced PDAC who received 2L treatment. We conducted a single institution retrospective study, which included all patients with advanced PDAC who received 2L treatment between September 2006 and February 2020 at La Paz University Hospital, Madrid (Spain). Significant variables in the logistic regression model were used to create a prognostic score. We included 108 patients. The median overall survival (OS) was 5.10 months (95%CI 4.02-6.17). In the multivariate analysis, time to progression (TTP) shorter than 4 months after first-line treatment (OR 4.53 [95%CI 1.28-16.00] p = 0.01), neutrophil-to-lymphocyte ratio (NLR) greater than 3 at the beginning of 2L (OR 9.07 [95%CI 1.82-45.16] p = 0.01) and CA-19.9 level higher than the upper limit of normal at the beginning of 2L (OR 7.83 [95%CI 1.30-49.97] p = 0.02) were independently associated with OS shorter than 3 months. The prognostic score classified patients into three prognostic groups (good, intermediate and poor) with significant differences in OS (p < 0.001). TTP shorter than 4 months after first-line treatment, NLR greater than 3 and CA-19.9 level higher than the upper limit of normal at the beginning of 2L were associated with shorter overall survival. We developed a prognostic score that classifies patients with advanced PDAC into three prognostic groups after progression to the first-line. This score could help in the decision-making for 2L treatment.
Sections du résumé
BACKGROUND
BACKGROUND
Second-line (2L) treatments for advanced pancreatic ductal adenocarcinoma (PDAC) achieve a modest benefit at the expense of potential toxicity. In the absence of predictive factors of response, the identification of prognostic factors could help in the therapeutic decisions-making. The purpose of this study was to assess the prognostic factors associated with shorter survival in patients with advanced PDAC who received 2L treatment.
METHODS
METHODS
We conducted a single institution retrospective study, which included all patients with advanced PDAC who received 2L treatment between September 2006 and February 2020 at La Paz University Hospital, Madrid (Spain). Significant variables in the logistic regression model were used to create a prognostic score.
RESULTS
RESULTS
We included 108 patients. The median overall survival (OS) was 5.10 months (95%CI 4.02-6.17). In the multivariate analysis, time to progression (TTP) shorter than 4 months after first-line treatment (OR 4.53 [95%CI 1.28-16.00] p = 0.01), neutrophil-to-lymphocyte ratio (NLR) greater than 3 at the beginning of 2L (OR 9.07 [95%CI 1.82-45.16] p = 0.01) and CA-19.9 level higher than the upper limit of normal at the beginning of 2L (OR 7.83 [95%CI 1.30-49.97] p = 0.02) were independently associated with OS shorter than 3 months. The prognostic score classified patients into three prognostic groups (good, intermediate and poor) with significant differences in OS (p < 0.001).
CONCLUSIONS
CONCLUSIONS
TTP shorter than 4 months after first-line treatment, NLR greater than 3 and CA-19.9 level higher than the upper limit of normal at the beginning of 2L were associated with shorter overall survival. We developed a prognostic score that classifies patients with advanced PDAC into three prognostic groups after progression to the first-line. This score could help in the decision-making for 2L treatment.
Identifiants
pubmed: 33866520
doi: 10.1007/s12094-021-02589-7
pii: 10.1007/s12094-021-02589-7
doi:
Substances chimiques
Antigens, Tumor-Associated, Carbohydrate
0
Oxaloacetates
0
carbohydrate antigen 199, human
0
folfirinox
0
Oxaliplatin
04ZR38536J
Deoxycytidine
0W860991D6
Capecitabine
6804DJ8Z9U
Irinotecan
7673326042
Leucovorin
Q573I9DVLP
Fluorouracil
U3P01618RT
Gemcitabine
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1838-1846Informations de copyright
© 2021. Federación de Sociedades Españolas de Oncología (FESEO).
Références
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7–30. https://doi.org/10.3322/caac.21590 .
doi: 10.3322/caac.21590
pubmed: 31912902
pmcid: 31912902
Laquente B, Calsina-Berna A, Carmona-Bayonas A, Jiménez-Fonseca P, Peiró I, Carrato A. Supportive care in pancreatic ductal adenocarcinoma. Clin Transl Oncol. 2017;19(11):1293–302. https://doi.org/10.1007/s12094-017-1682-6 .
doi: 10.1007/s12094-017-1682-6
pubmed: 28612201
Ilic M, Ilic I. Epidemiology of pancreatic cancer. World J Gastroenterol. 2016;22(44):9694–705. https://doi.org/10.3748/wjg.v22.i44.9694 .
doi: 10.3748/wjg.v22.i44.9694
pubmed: 27956793
pmcid: 5124974
McGuigan A, Kelly P, Turkington RC, Jones C, Coleman HG, McCain RS. Pancreatic cancer: a review of clinical diagnosis, epidemiology, treatment and outcomes. World J Gastroenterol. 2018;24(43):4846–61. https://doi.org/10.3748/wjg.v24.i43.4846 .
doi: 10.3748/wjg.v24.i43.4846
pubmed: 30487695
pmcid: 6250924
Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. N Engl J Med. 2014;371(11):1039–49. https://doi.org/10.1056/NEJMra1404198 .
doi: 10.1056/NEJMra1404198
pubmed: 25207767
Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–25. https://doi.org/10.1056/NEJMoa1011923 .
doi: 10.1056/NEJMoa1011923
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. https://doi.org/10.1056/NEJMoa1304369 .
doi: 10.1056/NEJMoa1304369
Oettle H, Riess H, Stieler JM, et al. Second-line oxaliplatin, folinic acid, and fluorouracil versus folinic acid and fluorouracil alone for gemcitabine refractory pancreatic cancer: outcomes from the CONKO-003 trial. J Clin Oncol. 2014;32(23):2423–9. https://doi.org/10.1200/JCO.2013.53.6995 .
doi: 10.1200/JCO.2013.53.6995
pubmed: 24982456
Wang-Gillam A, Li C-P, Bodoky G, et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet. 2016;387(10018):545–57. https://doi.org/10.1016/S0140-6736(15)00986-1 .
doi: 10.1016/S0140-6736(15)00986-1
pubmed: 26615328
Demols A, Peeters M, Polus M, Marechal R, Gay F, Monsaert E, Hendlisz A, Van Laethem JL. Gemcitabine and oxaliplatin (GEMOX) in gemcitabine refractory advanced pancreatic adenocarcinoma: a phase II study. Br J Cancer. 2006;94(4):481–5. https://doi.org/10.1038/sj.bjc.6602966 .
doi: 10.1038/sj.bjc.6602966
pubmed: 16434988
pmcid: 2361170
Yoo C, Hwang JY, Kim JE, Kim TW, Lee JS, Park DH, Lee SS, Seo DW, Lee SK, Kim MH, Han DJ, Kim SC, Lee JL. A randomised phase II study of modified FOLFIRI.3 vs modified FOLFOX as second-line therapy in patients with gemcitabine-refractory advanced pancreatic cancer. Br J Cancer. 2009;101(10):1658–63. https://doi.org/10.1038/sj.bjc.6605374 .
doi: 10.1038/sj.bjc.6605374
pubmed: 19826418
pmcid: 2778540
Xiong HQ, Varadhachary GR, Blais JC, Hess KR, Abbruzzese JL, Wolff RA. Phase 2 trial of oxaliplatin plus capecitabine (XELOX) as second-line therapy for patients with advanced pancreatic cancer. Cancer. 2008;113(8):2046–52. https://doi.org/10.1002/cncr.23810 .
doi: 10.1002/cncr.23810
pubmed: 18756532
Berk V, Ozdemir N, Ozkan M, Aksoy S, Turan N, Inal A, Balakan O, Yasar N, Unal OU, Benekli M, Durnali A, Colak D, Sonmez OU. XELOX vs. FOLFOX4 as second line chemotherapy in advanced pancreatic cancer. Hepatogastroenterology. 2012;59:2635–9. https://doi.org/10.5754/hge12181 .
doi: 10.5754/hge12181
pubmed: 22534542
Zaniboni A, Aitini E, Barni S, Ferrari D, Cascinu S, Catalano V, Valmadre G, Ferrara D, Veltri E, Codignola C, Labianca R. FOLFIRI as second-line chemotherapy for advanced pancreatic cancer: a GISCAD multicenter phase II study. Cancer Chemother Pharmacol. 2012;69:1641–5. https://doi.org/10.1007/s00280-012-1875-1 .
doi: 10.1007/s00280-012-1875-1
pubmed: 22576338
Oettle H, Arnold D, Esser M, Huhn D, Riess H. Paclitaxel as weekly second-line therapy in patients with advanced pancreatic carcinoma. Anticancer Drugs. 2000;11(8):635–8. https://doi.org/10.1097/00001813-200009000-00006 .
doi: 10.1097/00001813-200009000-00006
pubmed: 11081455
Maeda S, Motoi F, Onogawa T, Morikawa T, Shigeru O, Sakata N, Takadate T, Naitoh T, Rikiyama T, Katayose Y, Egawa S, Unno M. Paclitaxel as second-line chemotherapy in patients with gemcitabine-refractory pancreatic cancer: a retrospective study. Int J Clin Oncol. 2011;16(5):539–45. https://doi.org/10.1007/s10147-011-0220-8 .
doi: 10.1007/s10147-011-0220-8
pubmed: 21455624
Cereda S, Reni M. Weekly docetaxel as salvage therapy in patients with gemcitabine-refractory metastatic pancreatic cancer. J Chemother. 2008;20(4):509–12. https://doi.org/10.1179/joc.2008.20.4.509 .
doi: 10.1179/joc.2008.20.4.509
pubmed: 18676234
Hosein PJ, de Lima Jr LG, Pastorini VH, Gomez C, Macintyre J, Zayas G, Reis I, Montero AJ, Merchan JR, Rocha Lima CM. A phase II trial of nab-Paclitaxel as second-line therapy in patients with advanced pancreatic cancer. Am J Clin Oncol. 2013;36(2):151–6. https://doi.org/10.1097/COC.0b013e3182436e8c .
doi: 10.1097/COC.0b013e3182436e8c
pubmed: 22307213
Boeck S, Wilkowski R, Bruns CJ, Issels RD, Schulz C, Moosmann N, Laessig D, Haas M, Golf A, Heinemann V. Oral capecitabine in gemcitabine-pretreated patients with advanced pancreatic cancer. Oncology. 2007;73:221–7. https://doi.org/10.1159/000127413 .
doi: 10.1159/000127413
pubmed: 18424886
Kulke MH, Blaszkowsky LS, Ryan DP, Clark JW, Meyerhardt JA, Zhu AX, Enzinger PC, Kwak EL, Muzikansky A, Lawrence C, Fuchs CS. Capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer. J Clin Oncol. 2007;25(30):4787–92. https://doi.org/10.1200/JCO.2007.11.8521 .
doi: 10.1200/JCO.2007.11.8521
pubmed: 17947726
Bodoky G, Timcheva C, Spigel DR, La Stella PJ, Ciuleanu TE, Pover G, Tebbutt NC. A phase II open-label randomized study to assess the efficacy and safety of selumetinib (AZD6244 [ARRY-142886]) versus capecitabine in patients with advanced or metastatic pancreatic cancer who have failed first-line gemcitabine therapy. Invest New Drugs. 2012;30:1216–23. https://doi.org/10.1007/s10637-011-9687-4 .
doi: 10.1007/s10637-011-9687-4
pubmed: 21594619
O’Reilly EM, Niedzwiecki D, Hall M, Hollis D, Bekaii-Saab T, Pluard T, Douglas K, Abou-Alfa GK, Kindler HL, Schilsky RL, Goldberg RM. A Cancer and Leukemia Group B phase II study of sunitinib malate in patients with previously treated metastatic pancreatic adenocarcinoma (CALGB 80603). Oncologist. 2010;15:1310–9. https://doi.org/10.1634/theoncologist.2010-0152 .
doi: 10.1634/theoncologist.2010-0152
pubmed: 21148613
pmcid: 3227926
Schrag D, Archer L, Wang X, Romanus D, Mulcahy M, Goldberg R, Kindler H. A patterns-of-care study of post-progression treatment (Rx) among patients (pts) with advanced pancreas cancer (APC) after gemcitabine therapy on Cancer and Leukemia Group B (CALGB) study #80303. J Clin Oncol. 2007;25(18):4524.
doi: 10.1200/jco.2007.25.18_suppl.4524
Walker EJ, Ko AH. Beyond first-line chemotherapy for advanced pancreatic cancer: an expanding array of therapeutic options? World J Gastroenterol. 2014;20(9):2224–36. https://doi.org/10.3748/wjg.v20.i9.2224 .
doi: 10.3748/wjg.v20.i9.2224
pubmed: 24605022
pmcid: 3942828
Rahma OE, Duffy A, Liewehr DJ, Steinberg SM, Greten TF. Second-line treatment in advanced pancreatic cancer: a comprehensive analysis of published clinical trials. Ann Oncol. 2013;24(8):1972–9. https://doi.org/10.1093/annonc/mdt166 .
doi: 10.1093/annonc/mdt166
pubmed: 23670093
pmcid: 3718508
Concato J, Feinstein AR, Holford TR. The risk of determining risk with multivariable models. Ann Intern Med. 1993;118:201–10. https://doi.org/10.7326/0003-4819-118-3-199302010-00009 .
doi: 10.7326/0003-4819-118-3-199302010-00009
pubmed: 8417638
Hastie T, Tibshirani R, Friedman J, editors. The elements of statistical learning: data mining, inference, and prediction. New York: Springer; 2009.
Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982;143(1):29–36. https://doi.org/10.1148/radiology.143.1.7063747 .
doi: 10.1148/radiology.143.1.7063747
Sinn M, Dälken L, Striefler JK, Bischoff S, Schweitzer N, Pelzer U, Dörken B, Riess H, Stieler JM. Second-line treatment in pancreatic cancer patients: who profits?–results from the CONKO Study group. Pancreas. 2016;45(4):601–5. https://doi.org/10.1097/MPA.0000000000000533 .
doi: 10.1097/MPA.0000000000000533
pubmed: 26646276
Herrmann C, Abel U, Stremmel W, Jaeger D, Herrmann T. Short time to progression under first-line chemotherapy is a negative prognostic factor for time to progression and residual survival under second-line chemotherapy in advanced pancreatic cancer. Oncology. 2007;73(5–6):335–9. https://doi.org/10.1159/000134477 .
doi: 10.1159/000134477
pubmed: 18497506
Zhou Y, Wei Q, Fan J, Cheng S, Ding W, Hua Z. Prognostic role of the neutrophil-to-lymphocyte ratio in pancreatic cancer: a meta-analysis containing 8252 patients. Clin Chim Acta. 2018;479:181–9. https://doi.org/10.1016/j.cca.2018.01.024 .
doi: 10.1016/j.cca.2018.01.024
pubmed: 29407690
Yang JJ, Hu ZG, Shi WX, Deng T, He SQ, Yuan SG. Prognostic significance of neutrophil to lymphocyte ratio in pancreatic cancer: a meta-analysis. World J Gastroenterol. 2015;21(9):2807–15. https://doi.org/10.3748/wjg.v21.i9.2807 .
doi: 10.3748/wjg.v21.i9.2807
pubmed: 25759553
pmcid: 4351235
Cetin S, Dede I. Prognostic value of the neutrophil-to-lymphocyte ratio and carbohydrate antigen 19–9 in estimating survival in patients with metastatic pancreatic cancer. J Cancer Res Ther. 2020;16(4):909–16. https://doi.org/10.4103/jcrt.JCRT_366_19 .
doi: 10.4103/jcrt.JCRT_366_19
pubmed: 32930139
Boeck S, Haas M, Laubender RP, Kullmann F, Klose C, Bruns CJ, Wilkowski R, Stieber P, Holdenrieder S, Buchner H, Mansmann U, Heinemann V. Application of a time-varying covariate model to the analysis of CA 19–9 as serum biomarker in patients with advanced pancreatic cancer. Clin Cancer Res. 2010;16(3):986–94. https://doi.org/10.1158/1078-0432.CCR-09-2205 .
doi: 10.1158/1078-0432.CCR-09-2205
pubmed: 20103662
Lee JE, Lee HS, Chung MJ, et al. Analysis of clinical predictive factors affecting the outcome of second-line chemotherapy for gemcitabine-refractory advanced pancreatic cancer. Gut Liver. 2020;14(1):135–43. https://doi.org/10.5009/gnl18419 .
doi: 10.5009/gnl18419
pubmed: 30974927
Vienot A, Beinse G, Louvet C, et al. Overall survival prediction and usefulness of second-line chemotherapy in advanced pancreatic adenocarcinoma. J Natl Cancer Inst. 2017;109:10. https://doi.org/10.1093/jnci/djx037 .
doi: 10.1093/jnci/djx037
Chiorean EG, Von Hoff DD, Tabernero J, et al. Second-line therapy after nab-paclitaxel plus gemcitabine or after gemcitabine for patients with metastatic pancreatic cancer [published correction appears in Br J Cancer. 2016 Oct25; 115(9):e13]. Br J Cancer. 2016;115(2):188–94. https://doi.org/10.1038/bjc.2016.185 .
doi: 10.1038/bjc.2016.185
pubmed: 27351217
pmcid: 4947701