Purpose Stereotactic radiosurgery (SRS), whole-brain radiotherapy (WBRT), and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are treatment options for brain metastases in patients with EGFR-mutant non-small-cell lung cancer (NSCLC). This multi-institutional analysis sought to determine the optimal management of patients with EGFR-mutant NSCLC who develop brain metastases and have not received EGFR-TKI. Materials and Methods A total of 351 patients from six institutions with EGFR-mutant NSCLC developed brain metastases and met inclusion criteria for the study. Exclusion criteria included prior EGFR-TKI use, EGFR-TKI resistance mutation, failure to receive EGFR-TKI after WBRT/SRS, or insufficient follow-up. Patients were treated with SRS followed by EGFR-TKI, WBRT followed by EGFR-TKI, or EGFR-TKI followed by SRS or WBRT at intracranial progression. Overall survival (OS) and intracranial progression-free survival were measured from the date of brain metastases. Results The median OS for the SRS (n = 100), WBRT (n = 120), and EGFR-TKI (n = 131) cohorts was 46, 30, and 25 months, respectively ( P < .001). On multivariable analysis, SRS versus EGFR-TKI, WBRT versus EGFR-TKI, age, performance status, EGFR exon 19 mutation, and absence of extracranial metastases were associated with improved OS. Although the SRS and EGFR-TKI cohorts shared similar prognostic features, the WBRT cohort was more likely to have a less favorable prognosis ( P = .001). Conclusion This multi-institutional analysis demonstrated that the use of upfront EGFR-TKI, and deferral of radiotherapy, is associated with inferior OS in patients with EGFR-mutant NSCLC who develop brain metastases. SRS followed by EGFR-TKI resulted in the longest OS and allowed patients to avoid the potential neurocognitive sequelae of WBRT. A prospective, multi-institutional randomized trial of SRS followed by EGFR-TKI versus EGFR-TKI followed by SRS at intracranial progression is urgently needed.

Purpose Rhabdomyosarcoma (RMS) is a pediatric sarcoma rarely occurring in adults. For unknown reasons, adults with RMS have worse outcomes. Methods We analyzed data from all patients who presented to XXXXXXXX between 1990 and 2011 with RMS diagnosed at age 16 or older. 148 patients met study criteria. Ten were excluded for lack of adequate data. Results Median age was 28 yrs. Tumor histology was: embryonal 54%, alveolar 33%, pleomorphic 12%, and NOS 2%. The tumor site was unfavorable in 67% of patients. 33 patients (24%) were low risk, 61 (44%) intermediate risk, and 44 (32%) high risk. 46% were treated on or according to a prospective RMS protocol. Five-year overall survival (OS) was 45% for non-metastatic patients. Failure rates at 5 years for non-metastatic patients were 34% locally and 42% distantly. Among patients with non-metastatic disease (n=94), significant factors associated with OS were histology, site, risk group, age, and protocol treatment. On multivariate analysis, risk group and protocol treatment were significant after adjusting for age. Five-yr OS was 54% for protocol patients vs 36% for non-protocol patients. Conclusions Survival in non-metastatic adult patients was significantly improved for those treated on RMS protocols, most of which are now open to adults.

Purpose/Objectives Radiation therapy (RT) is the principal modality in the treatment of patients with brain metastases (BM). However, given the activity of EGFR tyrosine kinase inhibitors in the central nervous system (CNS), it is uncertain whether upfront brain RT is necessary for patients with EGFR-mutant lung adenocarcinoma with BM. Methods and Materials Patients with EGFR-mutant lung adenocarcinoma and newly diagnosed BM were identified. Results 222 patients were identified. Exclusion criteria included prior erlotinib use, presence of a de novo erlotinib resistance mutation, or incomplete data. Of the remaining 110 patients, 63 were treated with erlotinib, 32 with whole-brain RT (WBRT), and 15 with stereotactic radiosurgery (SRS). Median OS for the whole cohort was 33 months. There was no significant difference in OS between the WBRT and erlotinib groups (median 35 vs. 26 months, p = .62), while patients treated with SRS had a longer OS compared with the erlotinib group (median, 64 months, p = .004). Median time to ICP was 17 months. There was a longer time to ICP in patients who received WBRT vs. erlotinib upfront (median 24 vs. 16 months, p = .04). Patients in the erlotinib or SRS group were more likely to fail intracranially as a component of first failure, while WBRT patients were more likely to fail outside the brain (p = .004). Conclusions The survival of patients with EGFR-mutant adenocarcinoma with BM is notably long, whether they receive upfront erlotinib or brain RT. We observed longer intracranial control with WBRT, even though the WBRT patients had a higher burden of intracranial disease. Despite the equivalent survival between the WBRT and erlotinib group, this study underscores the role of WBRT in producing durable intracranial control in comparison to a targeted biologic agent with known CNS activity.

4. Laryngoscope, 128:2326-2332, 2018.

While IDH mutant proneural tumors impart a better prognosis in the short-term, survival beyond 4 years does not require IDH mutation and is not dictated by a single transcriptional subclass. In contrast, MGMT methylation continues to have strong prognostic value for survival beyond 4 years. These findings have substantial impact for understanding GBM biology and progression.