Different Doses of Clazosentan for Aneurismal Subarachnoid Hemorrhage: A Meta-Analysis of Randomized Controlled Trials.

Clazosentan therapy has been found to be effective in reducing the incidence of vasospasm after aneurismal subarachnoid hemorrhage (aSAH). The objective of this meta-analysis was to determine whether different doses of clazosentan treatment significantly reduced the incidence of delayed ischemic neurological deficits (DINDs) and new cerebral infarction (NCI). We systematically searched PubMed, Embase, Cochrane library and Medline from inception until October, 2015. All randomized controlled trials related to the functions of clazosentan in aSAH were included. Analyses were performed following the method guideline of Cochrane Back Review Group. Four randomized placebo-controlled trials met eligibility criteria and enrolled a total of 2159 patients. The meta-analysis demonstrated a significant decrease in the incidence of DINDs (relative risk, 0.49 and 95% CI, 0.33-0.73) and NCI (relative risk, 0.42 and 95% CI, 0.25-0.71) in patients treated with a high dose of clazosentan (15 mg/h) after aSAH. In addition, a high dose of clazosentan (15 mg/h) had no more effect on the incidence of adverse events than that of a low dose (1-5 mg/h). The results of the present meta-analysis show that a high dose of clazosentan significantly reduced the incidence of the vasospasm-related DINDs and NCI. Further study is required to fully understand the potential usefulness of clazosentan in patients with aSAH.

Lack of incremental value of three-dimensional measurement in assessing invasiveness for lung cancer.

OBJECTIVES: The aim of this study was to evaluate the performance of consolidation-to-tumour ratio (CTR) and the radiomic models in two- and three-dimensional modalities for assessing radiological invasiveness in early-stage lung adenocarcinoma. METHODS: A retrospective analysis was conducted on patients with early-stage lung adenocarcinoma from Guangdong Provincial People's Hospital and Shenzhen People's Hospital. Manual delineation of pulmonary nodules along the boundary was performed on cross-sectional images to extract radiomic features. Clinicopathological characteristics and radiomic signatures were identified in both cohorts. CTR and radiomic score for every patient were calculated. The performance of CTR and radiomic models were tested and validated in the respective cohorts. RESULTS: A total of 818 patients from Guangdong Provincial People's Hospital were included in the primary cohort, while 474 patients from Shenzhen People's Hospital constituted an independent validation cohort. Both CTR and radiomic score were identified as independent factors for predicting pathological invasiveness. CTR in two- and three-dimensional modalities exhibited comparable results with areas under the receiver operating characteristic curves and were demonstrated in the validation cohort (area under the curve: 0.807 vs 0.826, P = 0.059) Furthermore, both CTR in two- and three-dimensional modalities was able to stratify patients with significant relapse-free survival (P < 0.000 vs P < 0.000) and overall survival (P = 0.003 vs P = 0.001). The radiomic models in two- and three-dimensional modalities demonstrated favourable discrimination and calibration in independent cohorts (P = 0.189). CONCLUSIONS: Three-dimensional measurement provides no additional clinical benefit compared to two-dimensional.

Sublobectomy for stage IA1-2 invasive lung adenocarcinoma with consolidation tumor ratio ≤ 0.25.

BACKGROUND: Sublobectomy for early-stage non-small cell lung cancer (NSCLC) remains a matter of debate. This study aimed to discuss the feasibility of sublobectomy in patients with pathological-stage IA1-2 confirmed as pathologically invasive but radiologically noninvasive adenocarcinoma. METHODS: From 2011 to 2019, we screened clinical stage IA1-IA2 lung cancer patients who underwent surgery at the Guangdong Provincial People's Hospital (GDPH). Inclusion criteria were maximum tumor diameter of 2.0 cm or less, consolidation tumor ratio (CTR) ≤ 0.25, and pathologically confirmed invasive adenocarcinoma. Sublobectomy (segmentectomy and wedge resection) and lobectomy groups were created, and propensity scores were computed. The primary endpoints were lung cancer-specific overall survival (LCSS) and LCS- relapse-free survival (LCS-RFS) after adjusting propensity scores. RESULTS: A total of 1731 patients were screened, and 100 patients were enrolled. The lobectomy group had 51 patients and the limited resection group had 49. No cases relapsed, and two patients died from nontumor causes. For the entire cohort, the 5-year LCSS and 5-year LCS-RFS were 100% in the lobectomy and limited resection groups. When propensity scores matched, there were no differences in LCSS and LCS-RFS between the two groups (LCSS:100%, LCS-RFS 100% in lobectomy and limited resection, respectively). DISCUSSION: Sublobectomy may be curative for pathologically invasive but radiologically noninvasive adenocarcinoma at pathological stage IA1-2.

Efficacy of PD-1/PD-L1 inhibitors against pretreated advanced cancer: a systematic review and meta-analysis.

BACKGROUND: Programmed cell death 1 (PD-1) and programmed cell death-ligand 1(PD-L1) inhibitors have captured our attention as new therapeutic options for several tumor types. Nonetheless, the differences in efficacy between PD-1/PD-L1 inhibitors and conventional treatments (chemotherapy or targeted therapy) in pretreated advanced cancer patients remain unclear. MATERIALS AND METHODS: A systematic literature search was conducted to identify phase III randomized controlled trials (RCTs)-based investigations of PD-1(nivolumab, pembrolizumab)/PD-L1 inhibitors (atezolizumab) against pretreated advanced cancer. We evaluated these trials for inclusion, assessed each study's risk of bias and selected relevant data for analysis. RESULTS: The eligibility criteria were met by 5,093 patients from 8 phase III RCTs. PD-1/PD-L1 inhibitors significantly extended overall survival relative to the conventional treatment, expressed as hazard ratio [HR] (0.72, 95% CI, 0.66 to 0.77, P < 0.001) and median month difference (2.83 months, 95% CI, 1.87 to 3.78, P < 0.001). The progression-free survival HRs favored PD-1/PD-L1 inhibitors over conventional treatment (0.88; 95% CI, 0.82 to 0.95, P = 0.002), whereas median month difference was just the opposite (-0.69 months, 95% CI, -1.14 to -0.24, P < 0.001). CONCLUSIONS: Among selected patients with pretreated advanced cancer, PD-1/PD-L1 inhibitors, compared with conventional treatments (chemotherapy or targeted therapy), were associated with improvement in overall survival (2.83 months) but not progression-free survival. These findings will be important in considering PD-1/PD-L1 inhibitors in the treatment of pretreated advanced cancer and have implications for future study design.

Meta-analysis of incidence and risk of severe adverse events and fatal adverse events with crizotinib monotherapy in patients with ALK-positive NSCLC.

BACKGROUND: Numerous clinical trials show crizotinib has promising efficacy for anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patients which trigger the substitution of traditional chemotherapy to be the current standard first-line treatment for these patients. Conversely, few reports systematically analyze toxicity of crizotinib. Hence, we performed a first meta-analysis to determine the risk of crizotinib-related severe adverse events (SAEs) and fatal adverse events (FAEs) in ALK positive NSCLC patients. MATERIALS AND METHODS: A systematic literature search was conducted through December 2016 to identify clinical trials that reported crizotinib monotherapy in ALK-positive NSCLC patients. Data on crizotinib-related SAEs and FAEs were extracted from each study and pooled to determine the overall incidence and risk. Random-effects or fixed-effects models were conducted to calculate the summary incidence, relative risk (RR), and 95% CIs on basis of the heterogeneity of included studies. RESULTS: 1,924 patients from 11 clinical trials were included. The overall incidence of SAEs and FAEs with crizotinib was 19.9% (95% CI, 14.1% to 23.7%; P < 0.001) and 1.4% (95% CI, 0.9% to 2.1%; P < 0.001), respectively. Meanwhile, Asian patients have lower incidence of SAEs (11.5%, 95% CI: 7.9% to 16.5%). However, significant differences of SAEs (RR: 0.97, 95% CI, 0.79 to 1.18; P = 0.76) and FAEs (RR: 2.24, 95% CI, 0.49 to 10.30; P = 0.30) were not detected between crizotinib monotherapy and chemotherapy. CONCLUSIONS: Crizotinib may not increase the risk of SAEs and FAEs in patients with ALK positive NSCLC compared with chemotherapy.