To report the feasibility, efficacy, and toxicity of stereotactic body radiotherapy (SBRT) for the treatment of portal vein tumor thrombosis (PVTT) and/or inferior vena cava tumor thrombosis (IVCTT) in patients with advanced hepatocellular carcinoma (HCC). Forty-one patients treated with SBRT using volumetric modulated arc therapy (VMAT) for HCC with PVTT/IVCTT between July 2010 and May 2012 were analyzed. Of these, 33 had PVTT and 8 had IVCTT. SBRT was designed to target the tumor thrombosis and deliver a median total dose of 36 Gy (range, 30–48 Gy) in six fractions during two weeks. The median follow-up was 10.0 months. At the time of analysis, 15 (36.6%) achieved complete response, 16 (39.0%) achieved partial response, 7 (17.1%) patients were stable, and three (7.3%) patients showed progressive disease. No treatment-related Grade 4/5 toxicity was seen within three months after SBRT. One patient had Grade 3 elevation of bilirubin. The one-year overall survival rate was 50.3%, with a median survival of 13.0 months. The only independent predictive factor associated with better survival was response to radiotherapy. VMAT-based SBRT is a safe and effective treatment option for PVTT/IVCTT in HCC. Prospective randomized controlled trials are warranted to validate the role of SBRT in these patients.

Recently, immune checkpoint inhibitors have shown survival advantage over chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC). This meta-analysis was conducted to gather and analyze the available evidence (Evidence level I; Randomized Controlled Trials) comparing efficacy and safety of anti-programmed cell death-1 (PD1)/programmed cell death ligand 1 (PD-L1) therapies and chemotherapy in the treatment of advanced NSCLC. A search strategy was devised to identify the randomized controlled trials (RCTs) using electronic databases of PubMed, Cochrane Library, and Web of Science. Hazard ratios or odds ratios obtained for overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment related adverse events (TRAEs) were analyzed using fixed effect model or random effects model. Additionally, subgroup analysis was also performed. A total of seven RCTs (n = 3867) were identified and selected for inclusion in this meta-analysis. Anti-PD1/PD-L1 therapies (nivolumab, pembrolizumab, atezolizumab) resulted in better OS (HR 0.72 [95% confidence interval [CI] 0.63, 0.82; P < .00001]), PFS (HR 0.84 [95% CI 0.72, 0.97; P < .02]), and ORR (odds ratio [OR] 1.52 [95% CI 1.08, 2.14; P < .02]) in comparison to chemotherapy in advanced NSCLC. Improved safety was observed with anti-PD1/PD-L1 therapies (OR 0.31 [95%CI 0.26, 0.38; P < .00001]). Subgroups analysis revealed Eastern Cooperative Oncology Group Performance Status (ECOG PS) 1 (HR 0.76 [95%CI 0.62, 0.93; P = .007]), squamous cell type (HR 0.76 [95% CI 0.63, 0.92; P = .005]), current/former smoker (HR 0.76 [95% CI 0.63, 0.92; P = .005]), epidermal growth factor receptor (EGFR) wild type (HR 0.67 [95% CI 0.60, 0.76; P < .00001]), Kirsten rat sarcoma oncogene mutation (KRAS) mutant (HR 0.60 [95% CI 0.39, 0.93; P < .02]), and absence of central nervous system (CNS) metastases (HR 0.71 [95% CI 0.63, 0.80; P < .00001]) were associated with better overall survival. Anti-PD1/PD-L1 therapies are safe and effective treatment option in advanced non-small cell lung cancer and can be recommended selectively.

Background: ALK inhibitors have shown positive advance in the treatment of ALK+ NSCLC. They have achieved better results in prolonging the progression free survival and improving quality of life in comparison to chemotherapy. We have assembled the evidence related to the efficacy and safety of these agents in the treatment of ALK positive NSCLC. Materials and Methods: A comprehensive search was conducted using electronic databases of PubMed, Medline and Cochrane Library to identify the studies involving comparison of ALK inhibitors to chemotherapy and Next generation ALK inhibitors to crizotinib. PFS was the primary outcome while other outcomes like ORR, adverse events, quality of life and OS were also analyzed and compared. Hazard ratios and odds ratios obtained were analyzed using fixed effect or random effects model in Review Manager Software. Results: A total of 12 studies (n = 3,297) met the criteria for inclusion in this review and meta-analysis. ALK inhibitors including crizotinib, ceritinib and alectinib revealed significantly better PFS (HR 0.42 [0.35, 0.50; p < 0.00001]), ORR (Overall OR 6.59 [4.86, 8.94; p < 0.00001] as compared to chemotherapy in the first line as well as second line treatment settings. Intracranial response rate was better with ALK inhibitors (ceritinib and alectinib) as compared to chemotherapy OR 6.51 [2.86, 14.83; p < 0.00001]. No significant increase in grade 3 or 4 adverse events was observed with crizotinib (OR 1.21 [0.82, 1.77; p = 0.34]) or ceritinib (OR 1.49 [0.86, 2.57; p = 0.17]) when compared to chemotherapy individually. Quality of life indicators assessed were significantly improved with ALK inhibitors. Next generation agents (ceritinib, alectinib and brigatinib) revealed significant improvement in PFS (HR 0.50 [0.43, 0.57; p < 0.00001]), ORR (OR 1.57 [1.21, 2.04; p = 0.0006]) in comparison to crizotinib. Next generation agents (Alectinib and brigatinib) yielded better response intra-cranially than crizotinib in terms of objective response rate (OR 5.87 [3.49, 9.87; p < 0.00001]) and time to CNS progression (HR 0.25 [0.13, 0.46; p < 0.0001]). Alectinib by far resulted in fewer adverse events than chemotherapy or crizotinib. Conclusions: Overall ALK inhibitors are safe and effective treatment option in ALK+ non-small cell lung cancer. Of the ALK inhibitors, Next generation agents in particular alectinib and brigatinib are safer and more effective intra-cranially and can be preferred as first option.

BACKGROUND: The increasing incidence of radiation‐induced sarcoma (RIS) has become a significant problem that can limit long‐term survival. The objective of the current study was to analyze the clinicopathologic characteristics, treatment outcomes, and prognostic factors of RIS after radiotherapy for nasopharyngeal carcinoma (NPC).METHODS: Institutional electronic medical records of patients with NPC who received definitive radiotherapy between February 1964 and 2003 were reviewed. Fifty‐three patients who developed RIS and fulfilled the study criteria were included.RESULTS: The median follow‐up after a diagnosis of RIS was 15.5 months (range, 0.4‐90.3 months), and the median latency between radiotherapy for NPC and an RIS diagnosis was 9.3 years (range, 3.2‐26.6 years). Fibrosarcoma was the most frequent histologic type observed, followed by osteosarcoma, and malignant fibrous histiocytoma. The 3‐year overall survival (OS) rate for 49 patients who received treatment was 32.4%, and the median survival was 21.2 months (95% confidence interval, 8.7‐33.8 months). The median OS was 41.3 months, 8.4 months, and 11 months for the complete resection group, the incomplete resection group, and the chemotherapy group, respectively (P<.0001). The only independent predictive factor that was associated with better OS was complete surgical resection.CONCLUSIONS: This retrospective study confirmed the rarity and poor prognosis of RIS in patients with NPC. Complete surgical resection was a significant prognostic factor for survival. The authors concluded that long‐term follow‐up is necessary for the early detection of RIS in patients with NPC. Cancer 2010. © 2010 American Cancer Society.