Patients with solid tumor brain metastases that progress after whole-brain radiation have limited options. This prospective trial investigated the efficacy, safety, and tolerability of bevacizumab as salvage therapy in this population. Eligible patients received bevacizumab 10 mg/kg intravenously every 2 weeks until progression. The primary endpoint was radiologic response using Response Assessment in Neuro-Oncology (RANO) criteria. The secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response, and safety. Quality of life (QOL) was studied using the Functional Assessment of Cancer Therapy-Brain (FACT-Br) scale. Twenty-seven patients were enrolled, with twenty-four having evaluable data for response. The majority of histologies (n = 21, 78%) were breast cancer. The remaining histologies were non-small-cell lung cancer (n = 4, 15%), neuroendocrine cancer (n = 1, 3%), and papillary fallopian serous adenocarcinoma (n = 1, 3%). Eighteen patients had radiologic response, with two patients demonstrating partial response (8.33%) and sixteen patients demonstrating stable disease (66.7%). The median duration of response was 203 days. PFS at 6 months was 46%, median PFS was 5.3 m, and median OS was 9.5 m. Treatment was well tolerated, with six patients experiencing grade 3 lymphopenia and hypertension. There was one grade 3 thromboembolism. QOL was not negatively impacted. Bevacizumab is a safe and feasible salvage treatment with durable response and favorable overall survival for patients with progressive brain metastases after whole-brain radiation.

BACKGROUND: Existing evidence demonstrates that radiotherapy and antiangiogenic drugs have synergistic antitumour effects and may be a promising treatment option for patients with solid tumour. Thus, we performed a phase II trial to evaluate the efficacy and safety of whole-brain radiotherapy (WBRT) combined with anlotinib for multiple brain metastases (BMs) from non-small cell lung cancer (NSCLC) without targetable driver mutations.
METHODS: Patients with multiple BMs (⩾3) from NSCLC without targetable driver mutations who failed to respond to at least first-line chemotherapy were enrolled. Eligible patients received WBRT (30 Gy/10 f, 5 f/week) and anlotinib (12 mg/day, day 1-14 of 21 days per cycle, 2 cycles) until disease progression or treatment intolerance. The primary endpoint was intracranial objective response rate (iORR) and secondary endpoints included intracranial progression-free survival (iPFS), disease control rate (DCR), overall survival (OS), and safety.
RESULTS: Between April 2019 and March 2021, 21 patients were enrolled in the trial, of which 12 were aged ⩾60 years (57.1%), 13 were men (61.9%), 7 had an Eastern Cooperative Oncology Group Performance Status score of 0 to 1 (81.0%), 18 had adenocarcinoma (85.7%), and 11 had ⩾6 BMs (52.4%). Of the 21 evaluable patients, the iORR was 66.7% (1 complete response + 13 partial response [PR]), and 28.6% (7PR) had extracerebral lesions. The DCRs for intracerebral and extracerebral lesions were 90.5% and 81.0%, respectively. The iPFS and OS were 10.3 months (95% confidence interval [CI]: 0-24.8 months) and 13.4 months (95% CI: 0-27.9 months), respectively. The most frequently observed toxicities were loss of appetite (61.9%), hypertension (52.4%), fatigue (47.6%), diarrhoea (28.6%), vomiting (19.0%), dizziness (42.9%), and headache (33.3%). None of the patients developed grade 4 or higher grade adverse reactions.
CONCLUSIONS: Anlotinib combined with WBRT is effective and well tolerated in patients with multiple BMs (⩾3) from NSCLC without targetable driver mutations. Therefore, further validation studies are required.Clinical trial registration number: ChiCTR 1900027769.

OBJECTIVE: The aim of this study was to analyze the survival of patients with brain metastases treated with best supportive care or additional whole-brain radiotherapy (WBRT), in order to confirm results from the prospective randomized QUARTZ study, which suggested prolonged survival after WBRT (5 fractions of 4 Gy) if favorable prognostic factors were present (age younger than 60 years, graded prognostic assessment score 2.5-3 points).
METHODS: We performed a retrospective single institution analysis of 76 patients with favorable prognosis. In contrast to the QUARTZ trial, inclusion was not limited to patients with non-small cell lung cancer (NSCLC). Furthermore, a cohort treated with higher total doses of WBRT was included (10 fractions of 3 Gy).
RESULTS: All patients were younger than 60 years or had a graded prognostic assessment score of 2.5-3. The median survival was significantly shorter after best supportive care (1.2 months; 3.2 months after WBRT with 5 fractions of 4 Gy and 3.9 months after 10 fractions of 3 Gy). Also, in multivariate analyses, survival was significantly better after WBRT. Further favorable prognostic factors included better performance status, no or limited extracranial metastases and primary tumor other than gastrointestinal.
CONCLUSIONS: In line with the QUARTZ trial results, WBRT prolonged survival in patients with favorable prognostic features.

UNASSIGNED: Non-small-cell lung cancer (NSCLC) is a global public health problem, and brain is a common metastatic site in advanced NSCLC. Currently, whole-brain radiotherapy (WBRT) remains a major treatment for brain metastases, while EGFR-tyrosine kinase inhibitor (TKI) is the standard treatment for advanced NSCLC harboring EGFR mutations, which is also effective for brain metastases. However, whether EGFR-TKIs plus radiotherapy is superior to EGFR-TKIs alone for the treatment of advanced EGFR-mutant NSCLS with brain metastases remains controversial. This study aimed to compare the efficacy of concurrent EGFR-TKIs and WBRT vs EGFR-TKI alone in a retrospective cohort of advanced EGFR-mutant NSCLS with brain metastases.
UNASSIGNED: The medical records of 104 treatment-naïve, advanced EGFR-mutant NSCLC patients with brain metastases were retrospectively reviewed, and there were 56 patients undergoing concurrent EGFR-TKI and WBRT, and 48 patients given EGFR-TKI alone, including 20 cases with salvage WBRT upon brain metastasis progression. The survival prognosis was compared between the two cohorts.
UNASSIGNED: The baseline clinicopathologic factors were balanced between the two cohorts. After a median follow-up of 23 months, 35.6% of the study subjects survived. Concurrent EGFR-TKI and WBRT significantly improved the median intracranial PFS (iPFS) compared with EGFR-TKI alone (17.7 vs 11.0 months, P=0.015); however, no significant difference was seen in median overall survival between the two cohorts (28.1 vs 24.0 months, P=0.756). In addition, the median iPFS was found to significantly vary in the number of brain metastases (≤3 vs>3 metastases: 18.0 vs 12.5 months, P=0.044). Subgroup analysis showed that concurrent EGFR-TKI and WBRT improved median iPFS compared with EGFR-TKI alone in patients with more than three brain metastases (P=0.001); however, no significant difference was observed between the two regimens in patients with three or less brain metastases (P=0.526).
UNASSIGNED: Our data demonstrate that concurrent EGFR-TKI and WBRT achieves longer iPFS than EGFR-TKI alone in advanced EGFR-mutant NSCLC with brain metastases. In advanced EGFR-mutant NSCLC with three or less brain metastases, EGFR-TKI alone may be an option as a first-line therapy.

OBJECTIVE: This prospective, randomized, controlled and open-label clinical trial sought to evaluate the tolerability and efficacy of the FTD regimen (fotemustine, teniposide and dexamethasone) compared to HD-MA therapy (high-dose methotrexate plus cytarabine) and to elucidate some biomarkers that influence outcomes in patients with newly diagnosed primary CNS lymphoma.
METHODS: Participants were stratified by IELSG risk score (low versus intermediate versus high) and randomly assigned (1:1) to receive four cycles of FTD or HD-MA regimen. Both regimens were administered every 3 weeks and were followed by whole-brain radiotherapy. The primary endpoints were overall response rate (ORR), progression-free survival (PFS) and overall survival (OS).
RESULTS: Between June 2012, and June 2015, 52 patients were enrolled, of whom 49 patients were randomly assigned and analyzed. Of the 49 eligible patients, no significant difference was observed in terms of ORR between FTD (n = 24) and HD-MA (n = 25) groups (88% versus 84%, respectively, P = 0.628). Neither the 2-year PFS nor the 3-year OS rate differed significantly between FTD and HD-MA groups (37% versus 39% for 2-year PFS, P = 0.984; 51% versus 46% for 3-year OS, P = 0.509; respectively). The HD-MA group showed more serious neutropenia (P = 0.009) than the FTD group. High Bcl-6 expression correlated with longer OS (P = 0.038).
CONCLUSIONS: FTD chemotherapy appeared to be safe and effective for PCNSL patients. High Bcl-6 expression correlated with longer survival.