Kotecha, Rupesh

PURPOSE Survival for patients with melanoma has recently improved. The propensity of melanoma to metastasize to the brain remains a common and serious feature of this disease. The purposes of this study were to evaluate prognostic factors for patients with newly diagnosed melanoma brain metastases (MBMs) in a large cohort treated with modern multimodal therapies, compare those results with those in prior eras, and update the Melanoma Graded Prognostic Assessment (GPA). METHODS Univariable and multivariable (MVA) analyses of prognostic factors and treatments associated with survival were performed on 1,796 patients with newly diagnosed MBM treated between January 01, 2015, and December 31, 2021, using a multi-institutional retrospective database. Multiple imputation was used to address missingness of potential predictors. Significant variables in combined MVA were used to update the Melanoma GPA. Comparisons were made with legacy cohorts. RESULTS Median survivals for cohorts A (1985-2007, n = 481), B (2006-2015, n = 823), and C (2015-2021, n = 1,796) were 6.7, 9.8, and 16.6 months and median follow-up times were 40.1, 43.6, and 48.8 months, respectively. In combined MVA, significant prognostic factors for survival were higher Karnofsky Performance Status, fewer MBMs, absence of extracranial metastases, lower serum lactate dehydrogenase, and no immunotherapy before MBM. These factors were incorporated into the updated Melanoma GPA. The combined median and 3-year survivals for patients with GPA 0-1, 1.5-2, and 2.5-4.0 were 5.4, 13.2, and 43.2 months and 12.4%, 28.8%, and 51.6%, respectively. CONCLUSION Prognostic factors have changed and survival has improved for patients with MBM but varies widely by GPA. The updated Melanoma GPA calculator (BrainMetGPA), available free online, can be used to estimate survival, individualize treatment, stratify clinical trials, guide surveillance, and augment clinical trial eligibility. Multidisciplinary treatment is essential. Trials are needed to elucidate the optimal sequencing of various therapeutic modalities.

Abstract Background There are limited data on the use of stereotactic radiosurgery (SRS) for pediatric patients. The aim of this systematic review was to summarize indications and outcomes specific to pediatric cranial SRS to inform consensus guidelines on behalf of the International Stereotactic Radiosurgery Society. Methods A systematic review, using the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses, analyzed English-language articles on SRS, published between 1989 and 2021, that included outcomes for at least 5 pediatric patients. MEDLINE database terms included tumor types and locations, and radiosurgical and age-specific terms. We excluded nonclinical reports, expert opinions, commentaries, and review articles. Meta-regressions for associations with local control were performed for medulloblastoma, craniopharyngioma, ependymoma, glioma, and arteriovenous malformation (AVM). Results Of the 113 articles identified for review, 68 met the inclusion criteria. These articles described approximately 400 pediatric patients with benign and malignant brain tumors and 5119 with AVMs who underwent cranial SRS. The rates of local control for benign tumors, malignant tumors, and AVMs were 89% (95% CI, 82%–95%), 71% (95% CI, 59%–82%), and 65% (95% CI, 60%–69%), respectively. No significant associations were identified for local control with the patient-, tumor-, or treatment-related variables. Conclusions This review is the first to summarize outcomes specific to SRS for pediatric brain tumors and AVMs. Although data reporting is limited for pediatric patients, SRS appears to provide acceptable rates of local control. We present ISRS consensus guidelines to inform the judicious use of cranial SRS for pediatric patients.