Microsatellite Instability and Effectiveness of Adjuvant Treatment in pT1N1 Gastric Cancer: A Multicohort Study.


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:
Dec 2021
Historique:
received: 18 01 2021
accepted: 12 04 2021
pubmed: 18 8 2021
medline: 18 11 2021
entrez: 17 8 2021
Statut: ppublish

Résumé

Microsatellite status is a prognostic biomarker in advanced gastric cancer. This retrospective study aimed to investigate the usefulness of microsatellite status in predicting prognosis and response to adjuvant treatment in pT1N1 gastric cancer. Among 875 patients who underwent radical gastrectomy for pT1N1 gastric cancer at two tertiary hospitals, 838 with available microsatellite instability (MSI) data were included and classified into two groups according to microsatellite status: microsatellite stable (MSS) and MSI-high (MSI-H). Recurrence-free survival rate and risk factors for tumor recurrence were analyzed. Of 838 gastric cancer patients, 100 (11.9%) were MSI-H and 307 (36.6%) received adjuvant treatment. During median follow-up of 70 months, 42 (5.0%) patients experienced gastric cancer recurrence; hematogenous recurrences were the most common (45.2%). Recurrence-free survival was similar in the MSS and MSI-H groups (p = 0.27), and adjuvant treatment did not show an oncological benefit over surgery alone for pT1N1 gastric cancer (p = 0.53). On univariate analysis, age, operation period, and Lauren classification were significantly associated with tumor recurrence, while adjuvant treatment and MSI status were not associated with tumor recurrence. On multivariate analysis, MSI status was not associated with tumor recurrence, and adjuvant treatment worsened the tumor recurrence risk [hazard ratio (HR) 2.373, 95% confidence interval (CI) 1.125-5.006, p = 0.023). MSI status may not be a prognostic factor for tumor recurrence or a predictor of response to adjuvant treatment in pT1N1 gastric cancer patients. Considering that the effect of adjuvant treatment to decrease the risk of tumor recurrence is not clear, it may not be indicated in pT1N1 patients.

Sections du résumé

BACKGROUND BACKGROUND
Microsatellite status is a prognostic biomarker in advanced gastric cancer. This retrospective study aimed to investigate the usefulness of microsatellite status in predicting prognosis and response to adjuvant treatment in pT1N1 gastric cancer.
PATIENTS AND METHODS METHODS
Among 875 patients who underwent radical gastrectomy for pT1N1 gastric cancer at two tertiary hospitals, 838 with available microsatellite instability (MSI) data were included and classified into two groups according to microsatellite status: microsatellite stable (MSS) and MSI-high (MSI-H). Recurrence-free survival rate and risk factors for tumor recurrence were analyzed.
RESULTS RESULTS
Of 838 gastric cancer patients, 100 (11.9%) were MSI-H and 307 (36.6%) received adjuvant treatment. During median follow-up of 70 months, 42 (5.0%) patients experienced gastric cancer recurrence; hematogenous recurrences were the most common (45.2%). Recurrence-free survival was similar in the MSS and MSI-H groups (p = 0.27), and adjuvant treatment did not show an oncological benefit over surgery alone for pT1N1 gastric cancer (p = 0.53). On univariate analysis, age, operation period, and Lauren classification were significantly associated with tumor recurrence, while adjuvant treatment and MSI status were not associated with tumor recurrence. On multivariate analysis, MSI status was not associated with tumor recurrence, and adjuvant treatment worsened the tumor recurrence risk [hazard ratio (HR) 2.373, 95% confidence interval (CI) 1.125-5.006, p = 0.023).
CONCLUSION CONCLUSIONS
MSI status may not be a prognostic factor for tumor recurrence or a predictor of response to adjuvant treatment in pT1N1 gastric cancer patients. Considering that the effect of adjuvant treatment to decrease the risk of tumor recurrence is not clear, it may not be indicated in pT1N1 patients.

Identifiants

pubmed: 34401986
doi: 10.1245/s10434-021-10084-0
pii: 10.1245/s10434-021-10084-0
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

8908-8915

Informations de copyright

© 2021. Society of Surgical Oncology.

Références

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.
doi: 10.3322/caac.21492
Hong S, Won YJ, Park YR, Jung KW, Kong HJ, Lee ES, et al. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2017. Cancer Res Treat. 2020;52(2):335–50.
doi: 10.4143/crt.2020.206
Gastric cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology
Korean practice guideline for gastric cancer 2018: an evidence-based, multi-disciplinary approach. J Gastric Cancer. 2019;19(1):1-48.
jp JGCAjkk-ma. Japanese gastric cancer treatment guidelines 2018. Gastric Cancer. 2020:1-21.
Kim SM, An JY, Lee J, Sohn TS, Kim S. Adjuvant chemotherapy versus chemoradiotherapy versus surgery alone for early gastric cancer with one or two lymph node metastasis. Ann Surg Oncol. 2018;25(6):1616–24.
doi: 10.1245/s10434-018-6434-5
Shin HB, An JY, Lee SH, Choi YY, Kim JW, Sohn SS, et al. Is adjuvant chemotherapy necessary in pT1N1 gastric cancer? BMC Cancer. 2017;17(1):1–7.
doi: 10.1186/s12885-016-3022-6
Cancer Genome Atlas Research N. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513(7517):202-9.
Cristescu R, Lee J, Nebozhyn M, Kim KM, Ting JC, Wong SS, et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med. 2015;21(5):449-U217.
doi: 10.1038/nm.3850
Cheong JH, Yang HK, Kim H, Kim WH, Kim YW, Kook MC, et al. Predictive test for chemotherapy response in resectable gastric cancer: a multi-cohort, retrospective analysis. Lancet Oncol. 2018;19(5):629–38.
doi: 10.1016/S1470-2045(18)30108-6
Smyth EC, Wotherspoon A, Peckitt C, Gonzalez D, Hulkki-Wilson S, Eltahir Z, et al. Mismatch repair deficiency, microsatellite instability, and survival: an exploratory analysis of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial. JAMA Oncol. 2017;3(9):1197–203.
doi: 10.1001/jamaoncol.2016.6762
Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet. 2012;379(9813):315–21.
doi: 10.1016/S0140-6736(11)61873-4
Noh SH, Park SR, Yang HK, Chung HC, Chung IJ, Kim SW, et al. Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial. Lancet Oncol. 2014;15(12):1389–96.
doi: 10.1016/S1470-2045(14)70473-5
Choi YY, Kim H, Shin SJ, Kim HY, Lee J, Yang HK, et al. Microsatellite instability and programmed cell death-ligand 1 expression in stage II/III gastric cancer: post hoc analysis of the CLASSIC randomized controlled study. Ann Surg. 2019;270(2):309–16.
doi: 10.1097/SLA.0000000000002803
Pietrantonio F, Raimondi A, Choi YY, Kang W, Langley RE, Kim YW, et al. MSI-GC-01: Individual patient data (IPD) meta-analysis of microsatellite instability (MSI) and gastric cancer (GC) from four randomized clinical trials (RCTs). Am Soc Clin Oncol. 2019.
Suraweera N, Duval A, Reperant M, Vaury C, Furlan D, Leroy K, et al. Evaluation of tumor microsatellite instability using five quasimonomorphic mononucleotide repeats and pentaplex PCR. Gastroenterology. 2002;123(6):1804–11.
doi: 10.1053/gast.2002.37070
Bacher JW, Flanagan LA, Smalley RL, Nassif NA, Burgart LJ, Halberg RB, et al. Development of a fluorescent multiplex assay for detection of MSI-High tumors. Dis Markers. 2004;20(4–5):237–50.
doi: 10.1155/2004/136734
Roh CK, Choi YY, Choi S, Seo WJ, Cho M, Jang E, et al. Single patient classifier assay, microsatellite instability, and Epstein-Barr virus status predict clinical outcomes in stage II/III gastric cancer: results from CLASSIC trial. Yonsei Med J. 2019;60(2):132–9.
doi: 10.3349/ymj.2019.60.2.132
Smalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, et al. Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 2012;30(19):2327–33.
doi: 10.1200/JCO.2011.36.7136
Wang J, Dang P, Raut CP, Pandalai PK, Maduekwe UN, Rattner DW, et al. Comparison of a lymph node ratio-based staging system with the 7th AJCC system for gastric cancer: analysis of 18,043 patients from the SEER database. Ann Surg. 2012;255(3):478–85.
doi: 10.1097/SLA.0b013e31824857e2
Li P, Huang C-M, Zheng C-H, Russo A, Kasbekar P, Brennan MF, et al. Comparison of gastric cancer survival after R0 resection in the US and China. J Surg Oncol. 2018;118(6):975–82.
doi: 10.1002/jso.25220
Strong VE, Song KY, Park CH, Jacks LM, Gonen M, Shah MA, et al. Comparison of disease-specific survival in the United States and Korea after resection for early-stage node-negative gastric carcinoma. J Surg Oncol. 2013;107(6):634–40.
doi: 10.1002/jso.23288
Wang SC, Yeu Y, Hammer STG, Xiao S, Zhu M, Hong C, et al. Hispanic/Latino patients with gastric adenocarcinoma have distinct molecular profiles including a high rate of germline CDH1 variants. Cancer Res. 2020;80(11):2114–24.
doi: 10.1158/0008-5472.CAN-19-2918
Lin SJ, Gagnon-Bartsch JA, Tan IB, Earle S, Ruff L, Pettinger K, et al. Signatures of tumour immunity distinguish Asian and non-Asian gastric adenocarcinomas. Gut. 2015;64(11):1721–31.
doi: 10.1136/gutjnl-2014-308252
Muro K, Van Cutsem E, Narita Y, Pentheroudakis G, Baba E, Li J, et al. Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with metastatic gastric cancer: a JSMO-ESMO initiative endorsed by CSCO, KSMO, MOS, SSO and TOS. Ann Oncol. 2019;30(1):19–33.
doi: 10.1093/annonc/mdy502
Muro K, Chung HC, Shankaran V, Geva R, Catenacci D, Gupta S, et al. Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial. Lancet Oncol. 2016;17(6):717–26.
doi: 10.1016/S1470-2045(16)00175-3
Llosa NJ, Cruise M, Tam A, Wicks EC, Hechenbleikner EM, Taube JM, et al. The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discov. 2015;5(1):43–51.
doi: 10.1158/2159-8290.CD-14-0863

Auteurs

Namkee Oh (N)

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Hyunki Kim (H)

Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.

Kyoung-Mee Kim (KM)

Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Jae-Ho Cheong (JH)

Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.

Jeeyun Lee (J)

Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Sung Hoon Noh (SH)

Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.

Tae Sung Sohn (TS)

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Yoon Young Choi (YY)

Department of Surgery, Yonsei University College of Medicine, Seoul, Korea. biosurgeon98@chamc.co.kr.
Department of Surgery, CHA Ilsan Hospital, CHA University School of Medicine, Ilsan, Gyeonggi-do, Korea. biosurgeon98@chamc.co.kr.

Ji Yeong An (JY)

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. jar319.an@samsung.com.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH