A non-small cell lung cancer (NSCLC) patient with leptomeningeal metastasis harboring rare epidermal growth factor receptor (EGFR) mutations G719S and L861Q benefited from doubling dosage of osimertinib: a case report.

Leptomeningeal metastasis (LM) is a rare but lethal complication of advanced non-small cell lung cancer (NSCLC) that has a devastating impact on patient survival and quality of life. Osimertinib, an irreversible tyrosine kinase inhibitor, is approved as a therapy for advanced NSCLC with epidermal growth factor receptor (EGFR) mutation. However, the efficacy and optimal dosage of osimertinib in the treatment of NSCLC patients with LM who harbor uncommon EGFR mutations have yet to be fully investigated. Herein, we report a case of an advanced NSCLC patient with LM carrying EGFR G719S and L861Q, who was successfully treated by osimertinib at 160 mg. The patient initially presented with clear cell renal carcinoma and renal metastatic adenocarcinoma, and underwent right nephrectomy. At 2 months after nephrectomy, he developed a disturbance of consciousness and was subsequently diagnosed with NSCLC with LM by meningeal biopsy pathology and cerebrospinal fluid (CSF) cytology. Next-generation sequencing detected the rare EGFR mutations G719S and L861R in the meningeal biopsy tissues. The patient was then administered osimertinib at 80 mg quaque die (QD); after 1 month of treatment, his symptoms were alleviated. However, two months later, he experienced epileptic episode. Subsequently, the osimertinib dosage was doubled to 160 mg QD. After 1 month of treatment, the patient achieved central nervous system (CNS) response, and at the time of this manuscript's submission, he had maintained stable disease (SD) for more than 1 year. To our knowledge, this study provides the first clinical evidence that the administration of osimertinib at 160 mg once daily can achieve an encouraging, durable response in an NSCLC patient with LM carrying EGFR G719S and L861Q.

T2 Fluid-Attenuated Inversion Recovery Resection for Glioblastoma Involving Eloquent Brain Areas Facilitated Through Awake Craniotomy and Clinical Outcome.

BACKGROUND: Despite evidence that a greater extent of resection (EOR) improves survival, the role of extended resection based on magnetic resonance imaging (MRI) fluid-attenuated inversion recovery (FLAIR) in the prognosis of glioblastoma (GBM) remains controversial. This study aims to investigate the role of additional resection of FLAIR-detected abnormalities and its influence on clinical outcomes of patients with GBM. METHODS: Forty-six patients with newly diagnosed GBM involving eloquent brain areas were included. Surgeries were performed using awake craniotomy (AC) or AC combined with sodium fluorescein (SF) guidance. Following total removal of the contrast-enhancing tumor area, the EOR of FLAIR abnormalities was dichotomized to identify the best separation threshold for progression-free survival (PFS), overall survival (OS), and 30-day postoperative neurologic function of patients with GBM. RESULTS: The threshold for removal of FLAIR abnormalities affecting survival was determined to be 25%. The median OS and PFS were shorter in the group with FLAIR resection <25% compared with the group with FLAIR resection ≥25% (12 months vs. 26 months; P = 0.001 and 6 months vs. 15 months; P = 0.016, respectively). Univariate and multivariate analyses identified tumor location within or near the eloquent brain areas and the 25% threshold for FLAIR EOR as independent factors affecting OS and PFS. CONCLUSIONS: Identifying a feasible threshold for the resection of FLAIR abnormalities is valuable in improving the survival of patients with GBM. Extended resection of GBM involving eloquent brain areas was safe when using a combination of AC and SF-guided surgery.

Bevacizumab rescue therapy extends the survival in patients with recurrent malignant glioma.

OBJECTIVE: We retrospectively studied the efficacy of bevacizumab as salvage therapy for recurrent malignant glioma with a focus on the overall survival (OS). METHODS: Patients who received a therapy other than surgery for recurrent malignant glioma were included. Efficacy was evaluated using MRI. Neurological function was evaluated using the Response Assessment in Neuro-Oncology (RANO). The survival rate was calculated using the Kaplan-Meier method. RESULTS: Fifty-one patients with recurrent glioma (31 grade III, 20 grade IV) were included. Among them, 22 subjects (43.1%) received bevacizumab. The median OS was 10.2 months (range, 1 to 27 months). Patients receiving bevacizumab had comparable OS (a median of 9.9 vs. 10.0 months) and similar 6-month survival rate (43% vs. 34%) to those who did not receive bevacizumab. A subgroup analysis failed to notice any significant difference in grade III glioma patients receiving bevacizumab vs. those who did not. The median survival was significantly longer at 8.9 months (range, 4 to 13 months) in grade IV glioma patients receiving bevacizumab than in those who did not (5.6 months, range, 2 to 7 months, P=0.042). The 6-month survival rate was higher (83%) in those who received bevacizumab than in those who did not (47%, P=0.046). No grade 3/4 adverse events were observed in any patient. CONCLUSIONS: Bevacizumab, as a rescue therapy, provides a survival benefit for recurrent grade IV glioma.