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PREDICTORS OF PATHOLOGICAL TUMOR RESPONSE IN GASTRIC CANCER PATIENTS AFTER NEOADJUVANT THERAPY
Marcus Kodama Ramos2, Marina Pereira2, Amir Z. Charruf2, André R. Dias2, Osmar K. Yagi2, Sheila F. Faraj3, Guilherme L. Pereira2, Evandro S. Mello3, Bruno Zilberstein1, Ivan Cecconello1, Ulysses Ribeiro*1,2
1Gastroenterology, University of São Paulo, Sao Paulo, SP, Brazil; 2Gastroenterology, Sao Paulo Cancer Institute of Hospital das Clinicas - ICESP-HCFMUSP, Sao Paulo, SP, Brazil; 3Pathology, University of Sao Paulo Medical School, Sao Paulo, SP, Brazil
Background: Neoadjuvant chemotherapy (NACT) has been a pre-operative treatment option for patients with advanced gastric cancer (GC). Although the histologic tumor regression after NACT may be related to overall survival, the complete tumor response has seldom been achieved. Thus, clinicopathological characteristics can be utilized to evaluate the effect of NACT, and may be a useful tool to identify responsive patients.
Objective: the aim of this study was to identify clinical or pathologic predictive factors for pathologic tumor response and tumor downstaging after neoadjuvant therapy for GC patients.
Methodology: We retrospectively reviewed all patients who underwent R0 resection after receiving NACT for GC between 2009 and 2015 from a prospective collected database. Histopathological response to the treatment was graded from 0% to 100% and the clinicopathological characteristics were assessed to identify predictors of tumor response. A threshold of 50% histopathological response was used for analysis.
Results: NACT was performed in 45 patients. Cisplatin-irinotecan therapy was used in 64.4% of patients and 11 (24.4%) tumors were located in the proximal stomach. Ten (22.2%) patients demonstrated a tumor regression of at least 50% and one patient had complete response. The mean number of lymph node retrieved was 38.1 and 66.7% patients had lymph node metastasis (LNM). Lower neutrophil-lymphocyte ratio (NLR) (p=0.035), diffuse/mixed Lauren type (p=0.007), lower depth of tumor invasion (p=0.043) and non-cisplatin-irinotecan therapy (p=0.01) were found to be factors associated with >50% of response by univariate analyses. A slight tendency of poorly differentiated tumors respond better to NACT than differentiated type was observed (p=0.05). There was no significant difference regarding the presence of mucin, calcification and/or necrosis and the tumor response. Multivariate analysis identified NLR and diffuse/mixed tumors as independent predictors of pathologic response. Median follow-up for all patients was 26.5 months and recurrence-free survival (RFS) rate was 74.3% and 60% for patients with >50% and <50% of response, respectively (p=0.08). RFS was significantly different in patients without LNM compared to patients who have LNM (100% vs. 55.2%, p=0.01), and in patients with fibroinflammatory/inflammatory stroma infiltration compared to patients with only fibrotic stroma (80% vs. 53.3%, p=0.015).
Conclusion: Lauren diffuse/mixed type and lower NLR are independently predictors of tumor response. Few GC demonstrate histologic response, and these clinical variables may offer insight into patient selection and treatment response evaluation after NACT.
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