KEY POINTS
- This multicenter retrospective study included 232 women with breast cancer leptomeningeal disease treated at three US academic centers from 2005–2020. Median age at leptomeningeal disease diagnosis was 54.5 years, median Karnofsky performance status was 80%, and disease involved the brain only in 53.8%, brain and spine in 37.5%, and spine only in 8.6%.
- Radiotherapy was used in 154 patients (66.3%), accounting for 205 treatment courses. Whole-brain radiotherapy was the dominant approach, delivered to 114 patients, typically to 30 Gy in 10 fractions; only 3 patients (1.9%) received craniospinal irradiation, and no particle therapy was used.
- Prognosis remained poor: median overall survival from leptomeningeal disease diagnosis was 4.7 months (95% CI 3.9–5.5). Overall survival at 6, 12, 18, and 24 months was 41.1%, 19.7%, 11.5%, and 7.2%, respectively.
- Radiotherapy was not associated with improved survival. Restricted mean survival at 12 months was 5.6 months with radiotherapy versus 6.4 months without radiotherapy (p=0.20); at 24 months it was 6.6 versus 9.3 months (p=0.01).
- Among patients with Karnofsky performance status ≥80%, radiotherapy was associated with shorter restricted mean survival at 12 months: 6.1 versus 8.0 months (p=0.01). In time-varying multivariable models, radiotherapy was also associated with worse overall survival in high-performance-status patients with brain involvement (HR 1.74, 95% CI 1.07–2.80) and without brain involvement (HR 3.59, 95% CI 2.02–6.40); the authors emphasize that confounding by indication is likely and these associations should not be interpreted as radiotherapy causing harm.
- Systemic therapy was given to 61.6% of patients and showed the clearest survival association in those with poor performance status. In patients with Karnofsky performance status <80%, restricted mean survival at 6 months was 4.3 months with systemic therapy versus 2.6 months without it (p=0.0008), with an adjusted HR of 0.49 (95% CI 0.30–0.80).
- Radiotherapy may still provide clinically meaningful symptom palliation, which this survival-focused analysis could not adequately measure. The study also predates contemporary proton craniospinal irradiation practice: no patient received particle therapy, limiting applicability to current pCSI strategies.
CLINICAL TAKEAWAY
Radiotherapy should not be expected to prolong survival simply because breast cancer leptomeningeal disease is present, and treatment should remain driven by symptoms, disease distribution, performance status, and goals of care. These retrospective data do not argue against focal palliation or contemporary proton craniospinal irradiation, which was not represented in this cohort.