Survival outcomes of stages II-IV gastric cancer: A 13-year single center experience.
Authors: Ahmed Nabil Mohamed Hassan, Muaz Alsabbagh Alchirazi, Hadil Zureigat, Bridget Adcock, Aastha Dhakal, Naveen Rehman, Moath Albliwi, Ali Mushtaq, Monica Lee, Sara F Haddad, Heya Batah, Emily Craig Zabor, Bassam N. Estfan, Kanika G. Nair, Suneel Deepak Kamath, Smitha S. Krishnamurthi, Wen Wee Ma, Alok A. Khorana, Michael J. McNamara, Moaath Khader Mustafa Ali
Journal: Journal of Clinical Oncology (2025)

e16091 Background: The management of locoregional and metastatic gastric cancers (Ga-Ca) has significantly changed, particularly with the introduction of anti-HER2 drugs and immunotherapy (IT). This study aims to describe outcomes of locoregional (stages II-IVA) and metastatic (IVB) Ga-Ca. Methods: This retrospective study included adult Pts (diagnosed with stages II-IV Ga-Ca, treated at Cleveland Clinic from 1/2010 - 12/2022. We excluded Pts who had Siewert classification 1+2 and Pts who did not receive systemic therapy. Data included demographics, clinical variables (ECOG, BMI, comorbidities), tumor stage, and all treatment modalities. Overall survival (OS) and progression-free survival (PFS) were calculated from diagnosis or treatment, as appropriate. Multivariable Cox proportional hazards models (CPH) were used to adjust for covariates. Results: Key baseline variables and survival outcomes are summarized in Table 1. In the locoregional disease (n = 194), 80 (41%), 102 (53%) and 12 (6.2%) had stages II, III and IVA, respectively. 78% had gastrectomy and 51% had radiation (RT). Pts received: Definitive chemoradiation (CRT) (n = 51, 31%), preoperative CRT + gastrectomy (18, 12%), adjuvant chemotherapy (CTX) + gastrectomy (45, 31%), pre/peri-operative CTX + gastrectomy (31, 21%) and other modalities. In preoperative CRT + gastrectomy, 7 Pts received carboplatin + paclitaxel (39%) and 7 received cisplatin + fluorouracil (39%). In the adjuvant group, 49% received FOLFOX. In pre/peri-operative group, 55% received FLOT. On multivariable CPH, compared to definitive CRT, pre/peri-operative CTX + gastrectomy was associated with improved OS (HR 0.52, P = 0.04) but not adjuvant + gastrectomy (HR 0.82, P = 0.4) or preoperative CRT + gastrectomy (HR 0.86, P = 0.6). Stages III &amp; IVA had worse OS than stage II (P &lt; 0.01). In metastatic disease (i.e., stage IVB), CTX with palliative RT was administered in 35 Pts (21%) and systemic therapy alone in 131 Pts (79%). Systemic therapy included: FOLFOX/ XELOX (n = 86, 52%), anti-HER2 therapy (8, 4.8%) and IT ± CTX (10, 6%). CTX with palliative RT was not associated with improved OS compared to systemic therapy alone (HR 1.23, 95%CI 0.83-1.83, P = 0.3). On multivariable CPH, IT ± CTX was associated with improved OS compared to FOLFOX/ XELOX (HR 0.4, 95%CI 0.18-0.9, P = 0.01). The combined benefit of modern regimens (IT ± CTX AND anti-HER2 + CTX vs . CTX) resulted in a 54% decrease in mortality (HR 0.46., 95%CI 0.24-0.9, P = 0.01). Conclusions: In this study, pre/peri-operative CTX + gastrectomy significantly improved OS in locoregional Ga-Ca. For metastatic Ga-Ca, modern systemic therapies, including IT and anti-HER2 treatments, demonstrated superior OS compared to conventional CTX regimens. Characteristic Stage II-IVAN=194 Stage IVBN=166 Median Age, yrs (IQR) 65 (57, 74) 66 (55, 74) Male 70% 68% White 75% 78% Never smoker 34% 41% Median follow-up, months 71 23 2-year OS 63% 19% Response rate 81% 54%