Abstract PD4-01: Response according to revised RANO criteria is associated with overall survival in breast cancer patients with leptomeningeal metastasis

Abstract Introduction: Leptomeningeal metastasis (LM) is a severe complication of many solid tumors generally associated with dismal prognosis. Limited therapeutic options are available in this setting and assessment of response to treatment currently lacks validated tools. In 2017, the Response Assessment in Neuro-Oncology (RANO) LM Working Group proposed a standardized scorecard to aid in the evaluation of MRI findings in LM, which was revised and simplified in a subsequent 2019 version. To date, the prognostic impact of response to treatment evaluated according to these criteria has not been assessed in breast cancer (BC). In this study, we aim to validate this tool in a multicentric cohort of BC patients (pts) diagnosed with LM.Methods: Pts with LM from BC diagnosed at Istituto Oncologico Veneto (Padova, Italy) and Montpellier Regional Cancer Institute (Montpellier, France) between December 2005 and June 2018 were identified. Clinicopathological characteristics were collected from medical charts. Baseline and follow-up MRI scans were centrally reviewed by a dedicated radiologist and response assessment was evaluated according to the 2019 revised RANO LM response criteria (Le Rhun E. et al., Neuro-Oncology 2019).Results: A total of 225 pts diagnosed with BC-related LM were identified; among these, 142 had an available baseline brain MRI imaging and were included in the present study. Among these 142 pts, 78 had a positive cerebrospinal fluid (CSF) cytology and were classified as type I according to EANO-ESMO classification (41 type IA, 9 type IB, 28 type IC); for 64 pts CSF cytology was negative (N=25) or not performed (N=39), and were classified as type II (28 type IIA, 4 type IIB, 32 type IIC). At the time of last follow-up, 138 out of 142 pts had died and median overall survival (OS) from baseline MRI was 5.0 months (95% CI 3.4-6.7). Presence/absence of positive CSF cytology did not impact OS (median OS 5.3 versus 5.2 months, log-rank p=0.406). A total of 60 pts (positive/negative/not done CSF cytology: N=36/9/15) had an evaluable follow-up MRI imaging, with drop-off mainly due to deteriorating performance status or death. In this selected subgroup of pts, a longer OS was observed (median OS 15.2 months; 95% CI 9.5-21.0). Treatment administered for BC-related LM was heterogeneous and several pts received more than one treatment modality: systemic chemotherapy (N=44), endocrine therapy (N=27), HER2-targeted treatment (N=16), intrathecal chemotherapy (N=37) and radiotherapy (N=24). Response to treatment at time of first disease re-evaluation by brain MRI imaging was as follows: complete response for 2 pts, partial response for 12 pts, stable disease for 33 pts, and progression of disease for 13 pts. Response according to 2019 RANO criteria was significantly associated with OS (p=0.029, Table 1). Conclusions: Response assessment in pts with LM is challenging. In our study, the 2019 RANO revised response score was associated with OS in patients with LM from BC, thus validating these criteria in a real-world cohort. Response according to 2019 RANO LM criteriaMedian OS (months)OS 95% CI (months)Univariate Cox Hazard RatioUnivariate Cox Hazard Ratio 95% CIp-valueComplete Response31.1NE-NE0.100.01-0.780.028Partial Response16.10.0-37.40.410.17-0.970.043Stable Disease17.98.3-27.50.450.22-0.910.026Progression of Disease9.55.9-13.1Ref.Ref.Ref. Citation Format: Gaia Griguolo, Vittoria Aldegheri, Michele Bottosso, Francesca Caumo, Stéphane Pouderoux, Federica Miglietta, William Jacot, Maria Vittoria Dieci, Amélie Darlix, Valentina Guarneri. Response according to revised RANO criteria is associated with overall survival in breast cancer patients with leptomeningeal metastasis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD4-01.