Leptomeningeal carcinomatosis and brain metastases in gastroesophageal carcinoma: A real-world analysis of outcomes, clinical and pathologic characteristics.

person Thais Baccili Cury Megid Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada info_outline Thais Baccili Cury Megid, Zeynep Baskurt, Lucy Xiaolu Ma, Carly C. Barron, Marie-Philippe Saltiel, Abdul Rehman Farooq, Raymond Woo-Jun Jang, Eric Xueyu Chen, Rebecca KS Wong, Aruz Mesci, Hiroko Aoyama, Yvonne Bach, Xin Wang, Patrick Veit-Haibach, Ben X Wang, Sangeetha Kalimuthu, James Cotton, Elena Elimova

Authors person Thais Baccili Cury Megid Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada info_outline Thais Baccili Cury Megid, Zeynep Baskurt, Lucy Xiaolu Ma, Carly C. Barron, Marie-Philippe Saltiel, Abdul Rehman Farooq, Raymond Woo-Jun Jang, Eric Xueyu Chen, Rebecca KS Wong, Aruz Mesci, Hiroko Aoyama, Yvonne Bach, Xin Wang, Patrick Veit-Haibach, Ben X Wang, Sangeetha Kalimuthu, James Cotton, Elena Elimova Organizations Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, University of Toronto, Toronto, ON, Canada, University Health Network, Toronto, ON, Canada, Princess Margaret Cancer Centre, Toronto, ON, Canada, Joint Division of Medical Imaging (JDMI), University Health Network, Toronto, ON, Canada, Princess Margaret Hospital, Toronto, ON, Canada, Toronto General Hospital, University Health Network, Toronto, ON, Canada Abstract Disclosures Research Funding No funding received None. Background: Brain metastasis (BM) and Leptomeningeal Carcinomatosis (LC) are uncommon complications in gastroesophageal carcinoma (GEC) patients (pts). These patients have a poor prognosis and are challenging to study. We described the clinicopathologic features and outcomes in the largest real-world cohort of CNS metastasis in GEC pts. Methods: We conducted a single-center retrospective study of GEC pts treated at the Princess Margaret Cancer Centre from 2007 to 2021 who developed BM. Clinicopathologic characteristics and treatment modalities were reviewed. Survival was calculated from the date of BM or LC diagnosis until date of death/last follow-up using the Kaplan-Meier method. A multivariable Cox proportional hazards regression model was used to examine the association of baseline covariates and survival. Results: Of 3283 consecutive pts with GEC, 101 (3.08%) were diagnosed with BM and 20 with LC (0.61%). Most pts with BM were male (75.3%), non-Asian (93%), with a primary gastroesophageal junction tumor (47%) and adenocarcinoma histology (86%). Among pts with known HER2 status (N= 48), 60% were HER2 positive (defined as IHC 3+ or IHC 2+/FISH+). All patients with LC had adenocarcinoma histology; most were signet-ring subtype (85%), poorly differentiated (80%) histology and only 15% (2/13) were HER2 positive. Median survival was 0.8; 3.8; and 7.7 months (mo) in BM pts treated with palliative care only, radiation only and surgery followed by radiation, respectively (p< 0.001). In LC, median survival was 0.7 mo in pts who had palliative care only (7/20) and 2.7 mo for those (13/20) who had whole brain radiation therapy (WBRT) (p .008). Multivariate analysis showed a higher probability of death in patients with number of BM ≥4 (p 0.02) and predicted superior survival in patients who received radiation and surgery followed by radiation (p 0.02). Conclusions: This is the most comprehensive summary of clinicopathologic characteristics and survival in patients with GEC and BM and LC disease to date. Biomarker analysis reveals an enriched frequency of HER2 expression in BM, while this is uncommon in pts with LC. BM pts who were treated with surgery followed by radiation had a significantly improved OS. WBRT benefited patients with LC over palliative care alone. These findings add to our understanding for the management of this understudied population with poor survival. BM pts Median Survival (months) (95%CI) Palliative Care 0.76 (0.20, 4.26) Radiation (WBRT/SRS) 3.8 (2.16, 5.85) Surgery followed by Radiation 7.71 (5.76, 16.45) p value < 0.001 LC pts Palliative Care 0.7 (0, 1.58) WBRT 2.7 (1.35, 6.0) p < 0.008