1067 - Toxicity and Clinical Outcomes of Proton vs. Photon Volumetric Modulated Arc Therapy Craniospinal Irradiation for Solid Tumor Leptomeningeal Carcinomatosis

04:10pm - 04:15pm PT

Room 307/308

Presenter(s)

Gene Lamanilao, MD, MS, BS - University of California San Diego, La Jolla, CA

G. G. Lamanilao¹, B. Hostler², D. Piccioni³, J. Schulte³, R. Shatsky⁴, X. Zhang⁴, H. Orosco³, J. Steinberg⁵, V. Wu⁶, J. A. Hattangadi-Gluth¹, and K. R. Tringale¹; ¹Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, ²Department of Psychology, San Diego State University, San Diego, CA, ³Department of Neuro-Oncology, University of California San Diego, La Jolla, CA, ⁴Department of Medical Oncology, University of California San Diego, La Jolla, CA, ⁵Department of Neurosurgery, University of California San Diego, La Jolla, CA, ⁶Department of Neurology, University of California San Diego, La Jolla, CA

Purpose/Objective(s):

Craniospinal irradiation (CSI) is an effective treatment for solid tumor leptomeningeal carcinomatosis (LMC). Although proton CSI (pCSI) improves survival vs involved-field photon therapy, it is unclear if outcomes differ by modality when treating the entire neuraxis and applying modern photon techniques (volumetric modulated arc therapy [VMAT], “xCSI”). Here, we sought to compare toxicity and outcomes for solid tumor LMC treated with pCSI vs xCSI. We hypothesized that xCSI would have greater hematologic toxicity but performance status-adjusted survival outcomes would be similar.

Materials/Methods:

Patients =18y diagnosed with solid tumor LMC on MRI and/or cerebrospinal fluid (CSF) and planned for CSI to 30Gy/10fx from 2020-2025 were included. Acute (during CSI) and late (1, 3m post-CSI) hematologic toxicities were graded per CTCAE v5.0. Performance status at CSI start was defined per ECOG. Systemic and intrathecal (IT) therapy delivered pre- and post-CSI were collected. CNS progression-free (PFS) and overall (OS) survivals were calculated from CSI start with Cox proportional hazards models to account for ECOG.

Results:

Of 36 patients planned for CSI, 33 completed CSI (3 stopped during pCSI): 20 (61%) pCSI, 13 (39%) xCSI. Clinicodemographics were similar: median age was 53y (19–81; p=0.2), most were ECOG 0-1 (91% pCSI, 69% xCSI, p=0.4), and most histologies were breast (42%) or lung (36%; p=0.3). At diagnosis, 16 of 24 had neurologic symptoms (6 pCSI, 10 xCSI; p=0.5). 14 had prior CNS radiotherapy (9 pCSI, 5 xCSI; p=1.0) and 6 had prior IT chemotherapy (4 pCSI, 2 xCSI; p=1.0). After CSI, more pCSI patients received systemic therapy (92% pCSI, 46% xCSI; p=0.03) and IT use was similar (47% pCSI, 31% xCSI; p=0.6). Acute anemia (grade =1) was more common with xCSI (61% vs 20%, p=0.04) with a trend toward higher grade acute lymphopenia with xCSI (88% vs 67% grade 3-4, p=0.09). At 1m, leukopenia (grade =1) trended higher with xCSI (46% vs 10%, p=0.05). At 3m, there were no differences in toxicity. At the time of analysis, 8 (62%) xCSI and 12 (60%) pCSI were alive. Median OS was 10.7m (95% CI 4.6-NR: 10.9m pCSI, 4.6m xCSI; p=0.03). Median CNS PFS was 5.5m (95% CI 1-NR: 8.5m pCSI, 3.0 xCSI; p=0.02). There was no significant difference in ECOG-adjusted OS (HR_xCSI 1.3 [95% CI 0.9-14.9]; p=0.07) or CNS PFS (HR_xCSI 1.4 [95% CI 1.0-15.4]; p=0.05).

Conclusion:

This is the first study to compare proton vs photon VMAT CSI for patients treated to the same dose for solid tumor LMC. Here, we show that hematologic toxicity was comparable during and up to 3m post-CSI, supporting the safety of VMAT xCSI. Differences in both CNS PFS and OS were driven by patient performance status, highlighting selection bias for patients eligible for these treatment modalities. Given that VMAT is a more widely accessible CSI technique, further work is warranted to better define its role in LMC management.