Halasz, Lia M.

Abstract Introduction Historical reservations regarding stereotactic radiosurgery (SRS) for small-cell lung cancer (SCLC) brain metastases include concerns for short-interval and diffuse central nervous system (CNS) progression, poor prognoses, and increased neurological mortality specific to SCLC histology. We compared SRS outcomes for SCLC and non-small cell lung cancer (NSCLC) where SRS is well established. Methods Multicenter first-line SRS outcomes for SCLC and NSCLC from 2000 to 2022 were retrospectively collected (n = 892 SCLC, n = 4785 NSCLC). Data from the prospective Japanese Leksell Gamma Knife Society (JLGK0901) clinical trial of first-line SRS were analyzed as a comparison cohort (n = 98 SCLC, n = 814 NSCLC). Overall survival (OS) and CNS progression were analyzed using Cox proportional hazard and Fine-Gray models, respectively, with multivariable adjustment for cofactors including age, sex, performance status, year, extracranial disease status, and brain metastasis number and volume. Mutation-stratified analyses were performed in propensity score–matched retrospective cohorts of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) positive NSCLC, mutation-negative NSCLC, and SCLC. Results OS was superior for patients with NSCLC compared to SCLC in the retrospective dataset (median OS = 10.5 vs 8.6 months; P < .001) and in the JLGK0901 dataset. Hazard estimates for first CNS progression favoring NSCLC were similar in both datasets but reached statistical significance in the retrospective dataset only (multivariable hazard ratio = 0.82, 95% confidence interval = 0.73 to 0.92, P = .001). In the propensity score–matched cohorts, there were continued OS advantages for NSCLC patients (median OS = 23.7 [EGFR and ALK positive NSCLC] vs 13.6 [mutation-negative NSCLC] vs 10.4 months [SCLC], pairwise P values < 0.001), but no statistically significant differences in CNS progression were observed in the matched cohorts. Neurological mortality and number of lesions at CNS progression were similar for NSCLC and SCLC patients. Leptomeningeal progression was increased in patients with NSCLC compared to SCLC in the retrospective dataset only (multivariable hazard ratio = 1.61, 95% confidence interval = 1.14 to 2.26, P = .007). Conclusions After SRS, SCLC histology was associated with shorter OS compared to NSCLC. CNS progression occurred earlier in SCLC patients overall but was similar in patients matched on baseline factors. SCLC was not associated with increased neurological mortality, number of lesions at CNS progression, or leptomeningeal progression compared to NSCLC. These findings may better inform clinical expectations and individualized decision making regarding SRS for SCLC patients.

Abstract Brain metastases are a challenging manifestation of renal cell carcinoma. We have a limited understanding of brain metastasis tumor and immune biology, drivers of resistance to systemic treatment, and their overall poor prognosis. Current data support a multimodal treatment strategy with radiation treatment and/or surgery. Nonetheless, the optimal approach for the management of brain metastases from renal cell carcinoma remains unclear. To improve patient care, the authors sought to standardize practical management strategies. They performed an unstructured literature review and elaborated on the current management strategies through an international group of experts from different disciplines assembled via the network of the International Kidney Cancer Coalition. Experts from different disciplines were administered a survey to answer questions related to current challenges and unmet patient needs. On the basis of the integrated approach of literature review and survey study results, the authors built algorithms for the management of single and multiple brain metastases in patients with renal cell carcinoma. The literature review, consensus statements, and algorithms presented in this report can serve as a framework guiding treatment decisions for patients. CA Cancer J Clin. 2022;72:454‐489.

Abstract Purpose: The optimal salvage treatment for malignant glioma after prior radiotherapy (RT) is not well established. Proton therapy (PT) is an attractive treatment modality for reirradiation (ReRT) of recurrent disease; however, data are limited.Methods: The prospective, multi-institutional Proton Collaborative Group (PCG) registry was queried for patients with malignant glioma who previously received RT and underwent PT-ReRT between 7/2011-10/2018. Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method and Cox proportional hazards regression analysis. Results: 109 consecutive patients were identified. Median follow-up was 11.2 months and median time interval (TI) from prior RT (median 59.3 Gy) to PT-ReRT (median 49.6 Gy) was 45.7 months. Primary histology was glioblastoma (n=62), oligodendroglioma (n=26), and astrocytoma (n=20). Median PFS and OS was 6.1 and 11.1 months, respectively. On UVA, improved PFS was associated with oligodendroglioma (HR 0.39) and astrocytoma (HR 0.55) histologies, WHO Grade III (HR 0.36), TI (HR 0.989), surgical resection (HR 0.39), and PT-ReRT dose ≥50 Gy (HR 0.59) (all p<0.03), while improved OS was associated with oligodendroglioma histology (HR 0.35), WHO grade III (HR 0.33), ECOG 0 (HR 0.47), TI (HR 0.985), and PT-ReRT dose ≥50 Gy (HR 0.58) (all p<0.04). Late Grade 3 toxicities occurred in 5.6% of patients with no attributable acute or late Grade 4-5 events.Conclusion: In the largest series of glioma PT-ReRT reported to date, retreatment appears well tolerated with acceptable outcomes and favorable toxicities compared to photon historical controls. Dose escalation achievable with PT may improve outcomes for well-selected patients.