Integrating Anatomical, Molecular and Clinical Risk Factors in Gastrointestinal Stromal Tumor of the Stomach.
Journal
Annals of surgical oncology
ISSN: 1534-4681
Titre abrégé: Ann Surg Oncol
Pays: United States
ID NLM: 9420840
Informations de publication
Date de publication:
Oct 2021
Oct 2021
Historique:
received:
25
08
2020
accepted:
07
11
2020
pubmed:
3
3
2021
medline:
28
9
2021
entrez:
2
3
2021
Statut:
ppublish
Résumé
Adjuvant imatinib for 3 years is recommended to patients with high-risk gastrointestinal stromal tumor (GIST). Risk stratification is inaccurate, and risk assessments are further complicated by the increased use of neoadjuvant treatment. Anatomical criteria for prognostication have not been investigated. Clinical, molecular, and anatomical variables were retrospectively studied in a population-based cohort of 295 patients with gastric GIST resected between 2000 and 2018. Gastric subsite was divided into the upper, middle, and lower thirds. Growth pattern was classified as luminal, exophytic, or transmural based on imaging and surgical reports. Of 113 tumors in the upper third of the stomach, 103 (91.2%) were KIT mutated, 7 (6.2%) were PDGFRA mutated, and 104 (92.0%) harbored genotypes sensitive to imatinib. Transmural tumors were strongly associated with a high mitotic index. Five-year recurrence-free survival (RFS) was 71% for patients with transmural tumors versus 96% with luminal or exophytic tumors (hazard ratio [HR] 8.45, 95% confidence interval [CI] 3.69-19.36; p < 0.001), and, in high-risk patients, 5-year RFS was 46% for patients with transmural tumors versus 83% with luminal or exophytic tumors (HR 4.47, 95% CI 1.71-11.66; p = 0.001). Among 134 patients with tumors > 5 cm, there were 29 recurrences. Only five patients with exophytic or luminal tumors had recurrent disease, of whom four had tumor rupture. Five-year RFS for patients with exophytic/luminal tumors >5 cm without rupture was 98%. In the upper third, over 90% of tumors were sensitive to imatinib. Patients with exophytic or luminal tumors without rupture, irrespective of size, had an excellent prognosis and may not benefit from adjuvant therapy.
Sections du résumé
BACKGROUND
BACKGROUND
Adjuvant imatinib for 3 years is recommended to patients with high-risk gastrointestinal stromal tumor (GIST). Risk stratification is inaccurate, and risk assessments are further complicated by the increased use of neoadjuvant treatment. Anatomical criteria for prognostication have not been investigated.
METHODS
METHODS
Clinical, molecular, and anatomical variables were retrospectively studied in a population-based cohort of 295 patients with gastric GIST resected between 2000 and 2018. Gastric subsite was divided into the upper, middle, and lower thirds. Growth pattern was classified as luminal, exophytic, or transmural based on imaging and surgical reports.
RESULTS
RESULTS
Of 113 tumors in the upper third of the stomach, 103 (91.2%) were KIT mutated, 7 (6.2%) were PDGFRA mutated, and 104 (92.0%) harbored genotypes sensitive to imatinib. Transmural tumors were strongly associated with a high mitotic index. Five-year recurrence-free survival (RFS) was 71% for patients with transmural tumors versus 96% with luminal or exophytic tumors (hazard ratio [HR] 8.45, 95% confidence interval [CI] 3.69-19.36; p < 0.001), and, in high-risk patients, 5-year RFS was 46% for patients with transmural tumors versus 83% with luminal or exophytic tumors (HR 4.47, 95% CI 1.71-11.66; p = 0.001). Among 134 patients with tumors > 5 cm, there were 29 recurrences. Only five patients with exophytic or luminal tumors had recurrent disease, of whom four had tumor rupture. Five-year RFS for patients with exophytic/luminal tumors >5 cm without rupture was 98%.
CONCLUSIONS
CONCLUSIONS
In the upper third, over 90% of tumors were sensitive to imatinib. Patients with exophytic or luminal tumors without rupture, irrespective of size, had an excellent prognosis and may not benefit from adjuvant therapy.
Identifiants
pubmed: 33651216
doi: 10.1245/s10434-021-09605-8
pii: 10.1245/s10434-021-09605-8
pmc: PMC8460510
doi:
Substances chimiques
Antineoplastic Agents
0
Proto-Oncogene Proteins c-kit
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
6837-6845Subventions
Organisme : Radiumhospitalets Forskningsstifltelse
ID : 182007
Organisme : Kreftforeningen
ID : 5790283
Organisme : Helse Sør-Øst RHF
ID : 2019064
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021. The Author(s).
Références
Casali PG, Abecassis N, Aro HT, et al. Gastrointestinal stromal tumours: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29(Suppl 4):iv68–78.
doi: 10.1093/annonc/mdy095
Nishida T. Asian consensus guidelines for gastrointestinal stromal tumor: what is the same and what is different from global guidelines. Transl Gastroenterol Hepatol. 2018;3:11.
doi: 10.21037/tgh.2018.01.07
National Comprehensive Cancer Network Guidelines. NCCN Clinical Practice Guidelines in Oncology: Soft Tissue Sarcoma; 2020. www.nccn.org/professionals/physician_gls/f_guidelines.asp . Accessed 10 July 2020.
Miettinen M, Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol. 2006;23(2):70–83.
doi: 10.1053/j.semdp.2006.09.001
Joensuu H. Risk stratification of patients diagnosed with gastrointestinal stromal tumor. Hum Pathol. 2008;39(10):1411–9.
doi: 10.1016/j.humpath.2008.06.025
Rutkowski P, Bylina E, Wozniak A, et al. Validation of the Joensuu risk criteria for primary resectable gastrointestinal stromal tumour—the impact of tumour rupture on patient outcomes. Eur J Surg Oncol. 2011;37(10):890–6.
doi: 10.1016/j.ejso.2011.06.005
Khoo CY, Chai X, Quek R, Teo MCC, Goh BKP. Systematic review of current prognostication systems for primary gastrointestinal stromal tumours. Eur J Surg Oncol. 2018;44(4):388–94.
doi: 10.1016/j.ejso.2017.12.006
Rutkowski P, Gronchi A, Hohenberger P, et al. Neoadjuvant imatinib in locally advanced gastrointestinal stromal tumors (GIST): the EORTC STBSG experience. Ann Surg Oncol. 2013;20(9):2937–43.
doi: 10.1245/s10434-013-3013-7
Wozniak A, Rutkowski P, Schoffski P, et al. Tumor genotype is an independent prognostic factor in primary gastrointestinal stromal tumors of gastric origin: a European multicenter analysis based on ConticaGIST. Clin Cancer Res. 2014;20(23):6105–16.
doi: 10.1158/1078-0432.CCR-14-1677
Joensuu H, Vehtari A, Riihimäki J, et al. Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis of pooled population-based cohorts. Lancet Oncol. 2012;13(3):265–74.
doi: 10.1016/S1470-2045(11)70299-6
Florindez J, Trent J. Low frequency of mutation testing in the United States: an analysis of 3866 GIST patients. Am J Clin Oncol. 2020;43(4):270–8.
doi: 10.1097/COC.0000000000000659
Emory TS, Sobin LH, Lukes L, Lee DH, O’Leary TJ. Prognosis of gastrointestinal smooth-muscle (stromal) tumors: dependence on anatomic site. Am J Surg Pathol. 1999;23(1):82–7.
doi: 10.1097/00000478-199901000-00009
Marrelli D, Polom K, de Manzoni G, Morgagni P, Baiocchi GL, Roviello F. Multimodal treatment of gastric cancer in the west: where are we going? World J Gastroenterol. 2015;21(26):7954–69.
doi: 10.3748/wjg.v21.i26.7954
Ghidini M, Petrelli F, Tomasello G. Right versus left colon cancer: resectable and metastatic disease. Curr Treat Options Oncol. 2018;19(6):31.
doi: 10.1007/s11864-018-0544-y
Fletcher CDM, Bridge JA, Hagendoorn PCW, Mertens F, editors. WHO classification of tumours of soft tissue and bone. WHO/IARC: classifications of tumors, 4th ed. Lyon: IARC; 2013.
Hølmebakk T, Hompland I, Bjerkehagen B, et al. Recurrence-free survival after resection of gastric gastrointestinal stromal tumors classified according to a strict definition of tumor rupture: a population-based study. Ann Surg Oncol. 2018;25(5):1133–9.
doi: 10.1245/s10434-018-6353-5
Boye K, Berner J-M, Hompland I, et al. Genotype and risk of tumour rupture in gastrointestinal stromal tumor. Br J Surg. 2018;105(2):e169–75.
doi: 10.1002/bjs.10743
Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up. Am J Surg Pathol. 2005;29(1):52–68.
doi: 10.1097/01.pas.0000146010.92933.de