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BackgroundMelanoma brain metastases (BMs) are associated with poor prognosis and are the main cause of mortality in melanoma patients. BRAF inhibitors have shown intracranial activity in both treatment-naïve and previously treated BM patients. We aimed to investigate if there was any difference in response of BRAF inhibitors in these two cohorts.Materials and MethodsElectronic database search included PubMed, Medline, and Cochrane library until March 2021 for studies with desired comparative outcomes. Outcomes of interest that were obtained for meta-analysis included intracranial response rate as the primary outcome and survival and safety outcomes as the secondary outcomes. Review Manager version 5.4 was used for data analysis.ResultsThree studies comprising 410 BRAF-mutated melanoma patients with BMs were included according to eligibility criteria. The comparative cohort included patients with treatment-naïve BMs (TN cohort; n = 255) and those who had progressive disease after receiving local brain treatment for BMs (PT cohort; n = 155). Meta-analysis revealed that BRAF inhibitors (vemurafenib and dabrafenib) and BRAF/MEK inhibitor combination (dabrafenib and trametinib) induced significantly higher intracranial disease control (OR 0.58 [95% CI: 0.34, 0.97], p = 0.04) and a trend toward improved progression-free survival (PFS) (HR 1.22 [95% CI: 0.98, 1.52], p = 0.08) in the PT cohort as compared to the TN cohort. Overall survival was not significantly different between the cohorts (HR 1.16 [95% CI: 0.89, 1.51], p = 0.28). Subgroup analysis revealed that PFS was significantly improved (HR 1.67 [95% CI: 1.06, 2.62], p = 0.03), and a trend toward improved OS (HR 1.62 [95% CI: 0.95, 2.75], p = 0.08) was achieved in patients receiving BRAF/MEK inhibitor combination and patients with BRAFv600K mutation receiving dabrafenib alone. No increase in overall adverse events (AEs), grade 3/4 AEs, and severe adverse events (SAEs) was observed between the cohorts.ConclusionsBRAF inhibitors (plus MEK inhibitor) may achieve better intracranial disease stability in BRAF-mutant melanoma patients who have received previous local treatment for BMs.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/), identifier CRD42020185984.

ObjectivesTo discriminate viable tumors from benign periablational enhancement (BPE) in early stage after radiofrequency ablation (RFA) is a major confounding problem. The goal of this study is to evaluate quantitative assessment and diagnostic value of CT perfusion between viable tumors and BPE after RFA in the rabbit liver VX2 tumor model, with pathological results as the standard.MethodsTwenty-eight VX2 liver tumors were treated with RFA, on days 1, 3, 7, and 14, seven rabbits were randomly chosen for CT perfusion and performed pathology examinations immediately. The perfusion parameters along with the profile of time-density curves (TDCs) and pseudo-color images of the parameters were observed in both BPE and viable tumors, then compared with the pathology results. The perfusion parameters included blood flow (BF), blood volume (BV), time to peak (TTP), permeability (P), arterial liver perfusion (ALP), portal venous perfusion (PVP) and hepatic perfusion index (HPI).ResultsA total of 26/28 rabbits successfully underwent CT perfusion, while 6/26 lesions were confirmed to be viable tumors. The TDCs of BPE were mainly speed-up platform curves (15/26), while the viable tumors showed mainly speed-up speed-down (3/6) and speed-up platform (2/6) curves. The PVP values were significantly higher, and the HPI values were significantly lower for BPE at all time points than viable tumors (P < 0.05). Both of PVP value and HPI value have high efficiency for the differential diagnosis of the viable tumors and BPE at each time point. These characteristics of CT perfusion parameters were consistent with pathological changes.ConclusionsThe TDCs, PVP and HPI have the potential to indicate BPE and viable tumors effectively early after RFA treatment, the results were highly consistent with pathology. CT perfusion has advantages with great efficacy in monitoring the therapeutic effect early after RFA treatment.

BackgroundRadiation therapy (RT) is the mainstay of brain metastases (BMs), and anti-PD-1 blockade has led to intracranial responses in non-small cell lung carcinoma (NSCLC) patients with BMs.ObjectiveThis study aimed to evaluate the efficacy and safety of adding anti-PD-1 blockade to RT in the management of NSCLC patients with BM in terms of survival outcome.Materials and MethodsWe retrospectively reviewed 70 NSCLC patients with BMs who were treated with whole brain radiation therapy (WBRT) between January 2016 and January 2021. Of the 70 patients, 29 additionally received anti-PD-1 therapy within 30 days of WBRT initiation. Baseline characteristics of the patients and efficacy outcomes such as progression-free survival (PFS) and overall survival (OS) were statistically compared using SPSS v26. Results were obtained using the Chi-square test/Fisher exact test, t-test, Kaplan-Meier, and Cox regression survival analyses.ResultsThe median survival for the entire cohort was 24 months (95% CI, 19.5–28.5). The median survival times for WBRT alone and WBRT plus anti-PD-1 therapy cohorts were 20 months (95% CI, 11.6–28.3) and 27 months (95% CI, 19.5–28.5), respectively (p=0.035). There was no statistical difference in PFS for the treatment cohorts (median PFS for WBRT alone: 7 months vs. 12 months for WBRT plus anti-PD-1, p=0.247). In EGFR wild-type subgroup (n=31), both PFS (p=0.037) and OS (p=0.012) were significantly improved. Only the treatment group (WBRT plus anti-PD-1) was a significant predictor of OS on univariate and multivariate analyses (p=0.040). There were no significant differences in adverse events among the treatment groups.ConclusionsNSCLC patients with BM receiving additional anti-PD-1 therapy may derive better OS than WBRT alone without any increase in adverse events. Prospective well-designed studies are warranted to validate and elucidate the additive effects of the two modalities in this group of patients.

Background: Hypofractionated radiotherapy (HFR) is sometimes used in the treatment of glioblastoma multiforme (GBM). The efficacy and safety of HFR is still under investigation. The aim of this systematic review and meta-analysis was to provide a comprehensive summary of the efficacy and safety of HFR, and to compare the efficacy and safety of HFR and conventional fraction radiotherapy (CFR) for the treatment of patients with GBM, based on the results of randomized controlled trials (RCTs).Methods: A literature search was conducted to identify Phase II and III trials o comparing the efficacy and safety of HFR and CFR. Study selection, data extraction, and quality assessment, were conducted by two independent researchers. The analysis was performed using RevMan 5.3 and Stata 12.0.Results: Sixteen Phase II and III trials were included in the systematic review, and four RCTs were included in the meta-analysis. Participants treated with HRF and CRF had comparable overall survival (OS) (hazard ratio [HR]: 0.94, 95% confidence interval [CI]: 0.72–1.22, P = 0.64) and progression-free survival (PFS) (HR: 1.09, 95% CI: 0.60–1.95, P = 0.79), and similar rates of adverse events. However, in participants aged >70 years, those who received HFR had a higher OS than those who received CFR (HR: 0.59, 95% CI: 0.37–0.93, P = 0.02).Conclusions: HRF is efficacious and safe for the treatment of GBM. In individuals aged >70 years, treatment with HRF is superior to CFR in terms of OS. The role of HFR in the treatment of GBM in younger individuals and those with good prognostic factors requires further research.