Association Between RET Fusions and Efficacy of Pemetrexed-based Chemotherapy for Patients With Advanced NSCLC in China: A Multicenter Retrospective Study

BackgroundRearranged during transfection (RET) proto-oncogene gene fusions are rare in non–small-cell lung cancer (NSCLC). We compared the efficacy of pemetrexed-based chemotherapy with other chemotherapy regimens in patients with NSCLC with different RET fusion subtypes.Patients and MethodsA retrospective, multicenter study of patients with pathologically confirmed stage IIIB/IV lung adenocarcinomas was conducted. RET rearrangements were detected using next generation sequencing. We analyzed the clinical characteristics of patients with RET-rearranged NSCLC and the efficacy of chemotherapy regimens. We also evaluated the efficacy between groups of patients with and without KIF5B-RET–rearranged lung cancer.ResultsWe evaluated 62 patients with NSCLC and RET rearrangements, including 41 with KIF5B-RET, 15 with CCDC6-RET, and 6 with other rare fusion subtypes. Of these 62 patients, 50 had stage IIIB/IV. We also evaluated 40 patients with first-line chemotherapy information available. The median progression-free survival was significantly different between those receiving pemetrexed-based chemotherapy and those receiving other chemotherapy regimens (9.2 vs. 5.2 months; P = .007). The median progression-free survival for patients with KIF5B-RET fusion and non–KIF5B-RET fusion was not significantly different statistically (7.8 vs. 11.2 months; P = .847). For second-line chemotherapy, a statistically significant difference was found between the chemotherapy regimens (4.9 vs. 2.8 months; P = .049). Survival follow-up data were available for 38 patients with advanced NSCLC. The median overall survival was 26.4 months. The overall survival of the patients with RET-rearranged NSCLC who had received pemetrexed-based chemotherapy versus no pemetrexed-based chemotherapy was 35.2 versus 22.6 months (P = .052). No difference in survival was observed between the patients with KIF5B-RET and non–KIF5B-RET rearrangements.ConclusionsPemetrexed-based treatment should be considered first when selecting the chemotherapy regimen for patients with NSCLC and RET rearrangements.     

Cost–Utility Analysis of Pembrolizumab Versus Chemotherapy as First-Line Treatment for Metastatic Non-Small Cell Lung Cancer With Different PD-L1 Expression Levels

To evaluate the cost–utility of pembrolizumab versus chemotherapy as the first-line setting for metastatic nonsmall cell lung cancer (NSCLC) from the US health care system perspective, a Markov model was developed to compare the lifetime cost and effectiveness of pembrolizumab versus chemotherapy for untreated metastatic NSCLC, based on the clinical data derived from phase III randomized controlled trial (KEYNOTE- 042; ClinicalTrials.gov; NCT02220894). Weibull distribution was fitted to simulate the parametric survival functions. Drug costs were collected from official websites, and utility values were obtained from published literature. Total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were computed as primary output indicators. The impact of different PD-L1 expression levels on ICER was also evaluated. One-way and probabilistic sensitivity analyses were performed to assess the model uncertainty. Compared with chemotherapy, patients treated with pembrolizumab provided an additional 1.13, 1.01, and 0.59 QALYs in patients with PD-L1 expression levels of ≥50%, ≥20%, and ≥1%, with corresponding incremental cost of $53,784, $47,479, and $39,827, respectively. The resultant ICERs of pembrolizumab versus chemotherapy were $47,596, $47,184, and $68,061/QALY, in three expression levels of PD-L1, respectively, all of which did not exceed the WTP threshold of 180,000/QALY. Probability sensitivity analysis outcome supported that pembrolizumab exhibited evident advantage over chemotherapy to be cost-effective. One-way sensitivity analysis found that ICERs were most sensitive to utility value of pembrolizumab in progression survival state. All the adjustment of parameters did not qualitatively change the result. For treatment-naive, metastatic NSCLC patients with PD-L1+, pembrolizumab was estimated to be cost-effective compared with chemotherapy for all PD-L1 expression levels at a WTP threshold of $180,000/QALY in the context of the US health care system.     

Effectivity and safety of PD-1/PD-L1 inhibitors for different level of PD-L1-positive,advanced NSCLC: A meta-analysis of 4939 patients from randomized controlled trials

BackgroundEffective improvement for the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors had been shown in advanced non-small cell lung cancer (NSCLC) patients compared with traditional therapy. However, we do not have ample evidences to demonstrate the safety and effectivity in the treatment of PD-L1-positive, advanced NSCLC. The relation was controversial about the expression of PD-L1 and survival outcomes of PD-1/PD-L1 inhibitors.Materials and methodsElectronic databases (PubMed, EMBASE, and the Cochrane library) and major conference proceedings were systematically searched for all clinical trials in NSCLC using PD-1/PD-L1 inhibitors. Randomized controlled trials (RCTs) were included to compare PD-1/PD-L1 inhibitors with chemotherapy in advanced NSCLC patients reporting adverse events (AEs) and immune-related AEs (irAEs). The incidence, Hazard Ratio (HR), Odds Ratio (OR), and corresponding 95% confidence interval (CI) of outcomes were calculated.ResultsA total of 4939 patients from 10RCTs were included. In the group of PD-L1 ≥ 1%, PD-L1 ≥ 5%, PD-L1 ≥ 10%, PD-L1 ≥ 50%, the HR of OS is 0.31(95%CI 0.38–0.23; p < 0.0001), 0.47(95%CI 0.82–0.12; p = 0.008), 0.85(95%CI 1.17–0.53; p < 0.0001), 0.47(95%CI 0.59–0.36; p < 0.0001) respectively. The HR of PFS is 0.13(95%CI 0.01–0.24; p = 0.027), 0.31(95%CI 0.00–0.62; p < 0.0001), 0.62(95%CI 0.30–0.93; p < 0.0001), 0.40(95% CI 0.20–0.59; p < 0.0001) respectively. In terms of summary adverse events, PD-1/PD-L1 inhibitors groups had a significant lower risks in any treat-realated AEs than chemotherapy. About irAEs, PD-1/PD-L1 inhibitors groups had a significant higher risks in irAEs than chemotherapy.ConclusionPD-1/PD-L1 inhibitors are generally effected and safer than chemotherapy for patients with PD-L1-positive, advanced NSCLC. However, PD-1/PD-L1 inhibitors can generate a unique spectrum of irAEs, and even life-threatening.     

Topical Treatment of Oral Mucositis in Cancer Patients: A Systematic Review of Randomized Clinical Trials

Background and Purpose: Evidence-based protocols of topical therapy for oral mucositis (OM) induced by chemoradiotherapy (CRT) are continuously established and updated. Thus, the present systematic review aims to evaluate the scientific literature in terms of effectiveness of topical treatment of OM in cancer patients undergoing CRT.  Materials and Methods: This systematic review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Checklist. Randomized clinical trials were identified through electronic database searches on CINAHL, Cochrane Library, LILACS, Livivo, PubMed, SCOPUS, and Web of Science. Grey literature was also assessed on Google Scholar, Open Grey, and ProQuest. The risk of bias in the included studies was assessed by the Cochrane Collaboration Risk of Bias Tool. Results: Twenty-three randomized clinical trials (n=1169 patients) met the inclusion criteria. Twenty-three different topical agents were examined and categorized into five groups: analgesics (30.4%), natural agents (21.7%), other topical agents (21.7%), antimicrobial agents (17.4%), and growth factors (8.8%). Of the included studies, 50% presented a resolution of OM within 14 days. Topical natural agents yielded good results with average resolution time of 3–7 days. The included studies generally demonstrated that patients treated with mouthwashes presented superior benefits compared to the control, depending on OM severity. Conclusion: Topical agents effectively reduced the severity of OM lesions and pain intensity in patients receiving chemoradiotherapy, although the effects varied by agent type. However, the heterogeneity in the results of these topical intervention studies underscores the need for standardized clinical trial methodologies. Clinical Relevance: Topical agents were effective in patients with severe OM lesions receiving chemoradiotherapy and are a good alternative of home care in relation to pain control, reduction of inflammation and consequent improvement in quality of life.     

Complications and reoperations after surgery for 647 patients with spine metastatic disease

Background Context

Postoperative morbidity may offset the potential benefits of surgical treatment for spine metastatic disease; hence, risk factors for postoperative complications and reoperations should be taken into considerations during surgical decision-making. In addition, it remains unknown whether complications and reoperations shorten these patients' survival.

A comparison of cisplatin cumulative dose and cisplatin schedule in patients treated with concurrent chemo-radiotherapy in nasopharyngeal carcinoma

IntroductionThree-weekly cisplatin dose is accepted for standard treatment for concurrent chemo-radiotherapy in nasopharyngeal carcinoma. However, different chemotherapy schedules are presented in the literature.ObjectiveWe intend to compare toxicity and outcomes of high dose 3-weekly cisplatin versus low dose weekly-cisplatin and cumulative dose of cisplatin in the patients with nasopharyngeal carcinoma.Methods98 patients were included in the study, between 2010 and 2018. Cumulative doses of cisplatin (≥200 mg/m² and <200 mg/m²) and different chemotherapy schedules (weekly and 3-weekly) were compared in terms of toxicity and survival. Besides prognostic factors including age, gender, T category, N category and radiotherapy technique were evaluated in uni-multivariate analysis.ResultsMedian follow-up time 41.5 months (range: 2–93 months). Five year overall survival, local relapse-free survival, regional recurrence-free survival and distant metastasis-free survival rates were; 68.9% vs. 90.3% (p = 0.11); 66.2% vs. 81.6% (p = 0.15); 87.3% vs. 95.7% (p = 0.18); 80.1% vs. 76.1% (p = 0.74) for the group treated weekly and 3 weekly, respectively. There was no statistically significant difference between groups. Five year overall survival, local relapse-free survival, regional recurrence-free survival and distant metastasis-free survival rates were; 78.2% vs. 49.2% (p = 0.003); 75.8% vs. 47.9% (p = 0.055); 91% vs. 87.1% (p = 0.46); 80% vs. 72.2% (p = 0.46) for the group treated ≥200 mg/m² and <200 mg/m² cumulative dose cisplatin. There was statistically significant difference between groups for overall survival and there was close to being statistically significant difference between groups for local relapse-free survival. Age, gender, T category, N category, chemotherapy schedules were not associated with prognosis in the uni-variety analysis. Radiotherapy technique and cumulative dose of cisplatin was associated with prognosis in uni-variate analysis (HR = 0.21; 95% CI: 0.071–0.628; p = 0.005 and HR = 0.29; 95% CI: 0.125–0.686; p = 0.003, respectively). Only cumulative dose of cisplatin was found as an independent prognostic factor in multivariate analysis (HR = 0.36; 95% CI: 0.146–0.912; p = 0.03). When toxicities were evaluated, such as hematological toxicity, dermatitis, mucositis, nausea and vomiting, there were no statistically significant differences between cumulative dose of cisplatin groups (<200 mg/m² and ≥200 mg/m²) and chemotherapy schedules (3-weekly and weekly). But malnutrition was statistically significant higher in patients treated with 3-weekly cisplatin compared with patients treated with weekly cisplatin (p = 0.001).ConclusionA cisplatin dose with ≥200 mg/m² is an independent prognostic factor for overall survival. Chemotherapy schedules weekly and 3-weekly have similar outcomes and adverse effects. If patients achieve ≥200 mg/m² dose of cumulative cisplatin, weekly chemotherapy schedules may be used safely and effectively in nasopharyngeal carcinoma patients.     

The comparison of animal models for premature ovarian failure established by several different source of inducers

The objective of this study was to compare premature ovarian failure animal models established by several different source of inducers. Female ICR mice, KM mice, and SD rats were treated by cyclophosphamide at 120 mg/kg, busulfan at 12 mg/kg, cisplatin at 3 or 4 mg/kg, 4-vinylcyclohexene diepoxide at 160 mg/kg, 35% galactose food pellet, and tripterygium glycosides at 50 mg/kg, respectively. Parameters were analyzed by body weight, serum concentration level of related hormones, ovarian and uterine pathological examination. The results indicated the body weight of mice increased very slowly following single dose of cyclophosphamide (p < 0.05) with damaged ovary; repeated doses of cisplatin could induce body weight significantly decreased (p < 0.01) with a rising trend of serum LH concentration, declining tendency of serum E2 concentration and injured ovary and uterus; 4-vinylcyclohexene diepoxide also hindered the mice growing (p < 0.05) with damaged ovary and uterus; the body weight of mice feed by 35% galactose food pellet increased slowly (p < 0.05) with dramatically higher serum concentration level of galactose, albumin, and total protein (p < 0.001) and injured ovary. Busulfan and tripterygium glycosides did not present obvious evidences. In conclusion, the inducers presented their respective features in such animal models and should be appropriately applied in preventive methods.