Prognostic factors for survival in patients with gastrointestinal stromal tumors treated with adjuvant imatinib
Keywords:
gastrointestinal stromal tumors, imatinib, prognosis, survival, non-gastric tumor location.Abstract
Introduction: Gastrointestinal stromal tumors are rare neoplasms of the gastrointestinal tract. A considerable number of cases have risk factors that cause early recurrence of the disease, therefore, adjuvant therapy with imatinib in this group of patients manages to increase the disease-free interval and overall survival.
Objective: To evaluate the prognostic factors that influence the survival of patients with gastrointestinal stromal tumors in localized stages in adjuvant treatment with imatinib.
Material and Methods: A retrospective and observational study was carried out in patients diagnosed with gastrointestinal stromal tumors who received adjuvant treatment with imatinib at the Ameijeiras Hospital between 2003 and 2020. Survival was evaluated by the Kaplan-Meier method and Cox regression was used to determine independent prognostic factors for survival.
Results: The disease-free survival rates at 2, 3, and 5 years were 84.6 %, 81.2 %, and 74.5 %, respectively. The overall survival rates at 2, 3, and 5 years were 96.6 %, 88.6 %, and 81.9 %, respectively. Patients aged >60 years, non-gastric tumor location, higher mitotic index, and presence of positive surgical margins were independent prognostic factors related to lower survival.
Conclusions: This study is the first Cuban report in the real world on the use of adjuvant imatinib. The results obtained in overall survival and disease-free survival are similar to those reported internationally.Downloads
References
1. Soriano-Lorenzo J, Lima-Pérez M, Soriano-García J, Zaldívar-Blanco K, Fleites-Calvo V. Tumores del estroma gastrointestinal. An Fac med [Internet]. 2019;80(2):214-21. Disponible en: https://doi.org/10.15381/anales.802.16418
2. Blay JY, Kang YK, Nashida T, von Mehren M. Gastrointestinal stromal tumours. Nat Rev Dis Primers [Internet]. 2021;18(7):22. Disponible en: https://doi.org/10.1038/s41572-021-00254-5
3. Von Mehren M, Joensuu H. Gastrointestinal stromal tumors. J Clin Oncol [Internet]. 2018;36(2):136-43. Disponible en: https://doi.org/10.1200/JCO.2017.74.9705
4. Li GZ, Raut CP. Targeted therapy and personalized medicine in gastrointestinal stromal tumors: drug resistance, mechanisms, and treatment strategies. Onco Targets Ther [Internet]. 2019;12:5123-33 Disponible en: https://doi.org/10.2147/OTT.S180763
5. Mei L, Du W, Idowu M, von Mehren M, Boikos SA. Advances and challenges on management of gastrointestinal stromal tumor. Front Oncol [Internet]. 2018;8:135. Disponible en: https://doi.org/10.3389/fonc.2018.00135
6. DeMatteo RP, Ballman KV, Antonescu CR, Maki RG, Pisters PW, Demetri GD. Placebo-controlled randomized trial of adjuvant imatinib mesylate following the resection of localized, primary gastrointestinal stromal tumor (GIST). Lancet [Internet]. 2009; 373(9669):1097-2104. Disponible en: https://doi.org/10.1016/S0140-6736(09)60500-6
7. DeMatteo RP, Ballman KV, Antonescu CR, Corless C, Kolesnikova V, von Mehren M. Long-term result of adjuvant imatinib mesylate in localized, high-risk, primary gastrointestinal stromal tumors (GIST) ACOSOG Z9000 (Alliance) intergroup phase 2 trial. Ann Surg [Internet]. 2013; 258(3):422-29. Disponible en: https://doi.org/10.1097/SLA.0b013e3182a15eb7
8. Casali PG, Le Cesne A, Poveda A, Kotasek D, Rutkowski P, Hohenberg P, et al. Time to definitive failure to the first tyrosine kinase inhibitor in localized GI stromal tumors treated with imatinib as an adjuvant:a European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Intergroup randomized trial in collaboration with the Australasian Gastro-Intestinal Trials Group, UNICANCER, French Sarcoma Group, Italian Sarcoma Group and Spanish Group for Research on Sarcoma. J Clin Oncol [Internet]. 2015; 33(36):4276-83. Disponible en: https://doi.org/10.1200/JCO.2015.62.4304
9. Joensuu H, Eriksson M, Sundby Hall K, Hartmann JT, Pink D, Schutte J, et al. One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. JAMA [Internet]. 2012; 307(12):1265-72. Disponible en: https://doi.org/10.1001/jama.2012.347
10. Joensuu H, Eriksson M, Sundby K, Reichardt A, Hermes B, Schütte J, et al. Survival outcomes associated with 3 years vs 1 year of adjuvant imatinib for patients with high-risk gastrointestinal stromal tumors: an analysis of a randomized clinical trial after 10-year follow-up. JAMA [Internet]. 2020;307(12):1265-72. Disponible en: https://doi.org/10.1001/jamaoncol.2020.2091
11. Casali PG, Blay JY, Abecassis N, Bajpai J, Bauer S, Biagini R, et al. Gastrointestinal stromal tumors: ESMO-EURACAN-GENTURIS clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol [Internet]. 2018;29(Suppl4):iv68-iv78. Disponible en: https://doi.org/10.1016/j.annonc.2021.09.005
12. NCCN Clinical Practice Guidelines in Oncology. Gastrointestinal stromal Tumor (GISTs). Version 1.2022 [Internet]. EE UU: NCCN; 2022. [Citado 10/01/2022]. Disponible en: http://www.nccn.org/guidelines
13. Poveda A, García del Muro X, López Guerrero JA, Martínez V, Romero I, Serrano C, et al. GEIS Guidelines for gastrointestinal sarcomas (GIST). Cancer Treat Rev [Internet]. 2017;55:107-19. Disponible en: https://dx.doi.org/10.1016/j.ctrv.2016.11.011
14. Landi B, Blay JY, Bonvalot S, Breasseur M, Coindre JM, Emile JF, et al. Gastrointestinal stromal tumours (GISTs): French Intergroup Clinical Practice Guidelines for diagnosis, treatment and follow-up (SNFG•, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO). Dig Liver Dis [Internet]. 2019;51(9):1223-31. Disponible en: https://doi.org/10.1016/j.dld.2019.07.006
15. Raut C, Espat J, Maki RG, Araújo DM, Trent J, Williams TF, et al. Efficacy and tolerability of 5-year adjuvant imatinib treatment for patients with resected intermediate or high risk primary gastrointestinal stromal tumor: the PERSIST-5 clinical trial. JAMA Oncol [Internet]. 2018;4(12):e184060. Disponible en: https://doi.org/10.1001/jamaoncol.2018.4060
16. Rutkowski P, Bylina E, Lugowska I, Teterycz P, Klimczak A, Streb J, et al. Treatment outcome in older patients with advanced gastrointestinal stromal tumors (GIST). J Geriatr Oncol [Internet]. 2018;9(5):520-5. Disponible en: https://doi.org/10.1016/j.jgo.2018.03.009
17. Kramer K, Knippschild U, Mayer B, Bögelspacher K, Spatz H, Henne-Bruns D, et al. Impact of age and gender on tumor related prognosis in gastrointestinal stromal tumors (GIST). BMC Cancer [Internet]. 2015;15:57. Disponible en: https://doi.org/10.1186/s12885-015-1054-y
18. Corless Cl, Ballman KV, Antonescu CR, Kolesnikova V, Maki RG, Pisters PW, et al. Pathologic and molecular features correlate with long-term outcome after adjuvant therapy of resected primary GI stromal tumor: the ACOSOG Z9001 trial. J Clin Oncol [Internet]. 2014;32(15):1563-70. Disponible en: https://doi.org/10.1200/JCO.2013.51.2046
19. Joensuu H, Eriksson M, Hall KS, Hartmann JT, Pink D, Schütte J. Risk factors for gastrointestinal stromal tumor recurrence in patients treated with adjuvant imatinib. Cancer [Internet]. 2014; 120(15):2325-33. Disponible en: https://doi.org/10.1002/cncr.28669
20. Zhao R, Wang Y, Huang Y, Cui Y, Xia L, Chen Y, et al. Adjuvant imatinib for patiens wih high risk gastrointestinal stromal tumors: a retrospective cohort study. Sci Rep [Internet]. 2017;7(1):16834. Disponible en: https://doi.org/10.1038/s41598-017-17266-5
21. Lin JX, Chen QF, Zheng CH, Li P, Xie JW, Wang JB, et al. Is 3-year duration of adjuvant imatinib mesylate treatment sufficient for patients with high-risk gastrointestinal stromal tumor? A study based on long-term follow-up. J Cancer Res Clin Oncol [Internet]. 2017;143(4):727-34. Disponible en: https://doi.org/10.1007/s00432-016-2334-x
22. Soriano JL, Lima M, Fleites V, Domínguez C, González M, Fernández LT, et al. Características clínicas y patológicas de pacientes con tumores estromales gastrointestinales en Cuba. Acta Médica. [Internet]. 2021 [Citado 11/1/2022];22(1):e141. Disponible en: http://www.revactamedica.sld.cu/index.php/act/article/view/141/0
23. Zhang H, Liu Q. Prognostic indicators for gastrointestinal stromal tumors: a review. Transl Oncol [Internet]. 2020;13(10):100812. Disponible en: https://doi.org/10.1016/j.tranon.2020.100812
24. Zhou Y, Hu W, Chen P, Abe M, Shi L, Tan SY, et al. Ki67 is a biological marker of malignant risk of gastrointestinal stromal tumors. Medicine [Internet]. 2017;96(34):e7911. Disponible en: http://dx.doi.org/10.1097/MD.0000000000007911
25. Zhao WY, Wang M, Zhang ZZ, Wang CJ, Lin TL, Shen YY. Prognostic value of Ki67 index in gastrointestinal stromal tumor. Int J Clin Exp Pathol. 2015;7(5):2298-304.
26. Boukovinas I, Kotsakis A, Androulakis N, Aravantinos G, Michalaki V, Christodoulou C, et al. Recurrence-free survival and safety of imatinib in patients with gastrointestinal stromal tumor (GIST) in Grece. Anticancer Res [Internet]. 2020;40(1):435-41. Disponible en: https://doi.org/10.21873/anticanres.13971
27. Lei C, Zhao B, Wang Q, Ge L, Wang H. Imatinib therapy after resection of high-risk gastrointestinal stromal tumors in Chinese patients: a median follow-up of 48 months. JBUON. 2018;25(2):460-7.
28. McCarter M, Antonescu CR, Bllman KV, Maki RG, Pister PW, Demetri GD, et al. Microscopically positive margins for primary gastrointestinal stromal tumors: analysis of risk factors and tumor recurrence. J Am Coll Surg [Internet]. 2012;215(1):53-9. Disponible en: https://doi.org/10.1016/j.jamcollsurg.2012.05.008
29. Gronchi A, Bonvalot S, Poveda A, Kotasek D, Rutkwoski P, Hohenberg P, et al. Quality of surgery and outcome in localized gastrointestinal stromal tumors treated within an international intergroup randomized clinical trial of adjuvant imatinib. JAMA Surg [Internet]. 2020; 155(6):e200397. Disponible en: https://doi.org/10.1001/jamasurg.2020.0397
30. Lu J, Dai Y, Zheng HL, Xie JW, Wang JB, Lin JX, et al. What is the appropriated duration of adjuvant imatinib mesylate treatment for primary gastrointestinal stromal tumors classified according to the strict definition of tumor rupture? Medicine [Internet]. 2019;98(3):e14177. Disponible en: https://doi.org/10.1097/MD.0000000000014177
31. Joensuu H, Wardelmann E, Sihto H, Eriksson M, Sundby Hall K, Reichardt A. Effect of KIT and PDGFRA mutations on survival in patients with gastrointestinal stromal tumors treated with adjuvant imatinib: an exploratory analysis of a randomized clinical trial. JAMA Oncol [Internet]. 2017; 3(5):602-9. Disponible en: https://doi.org/10.1001/jamaoncol.2016.5751
32. Vicenzi B, Napolitano A, Fiocco M, Mir O, Rutkowski P, Blay JY, et al. Adjuvant imatinib in GIST patients harboring exon 9 KIT mutations: results from a multi-institutional European retrospective study. Clin Cancer Res [Internet]. 2022;14;28(8):1672-9. Disponible en: https://doi.org/10.1158/1078-0432.CCR-21-1665.
Download PDF
