Peripheral Tumor Location Predicts a Favorable Prognosis in Patients with Resected Small Cell Lung Cancer

Background. Small cell lung cancer (SCLC) is an aggressive malignancy. Surgical resection is currently only recommended for clinical stage I patients who have been carefully staged. The clinical outcomes of patients with resected SCLCs vary because the disease is highly heterogeneous, suggesting that selected patients could be considered for surgical resection depending on their clinical and/or molecular characteristics. Methods. We collected data on a retrospective cohort of 119 limited-stage SCLC patients who underwent lobectomy with mediastinal lymph node dissection from March 2013 to March 2020 at Harbin Medical University Cancer Hospital. Correlations were derived using Fisher’s exact test. Models of 2-year and 3-year survival were evaluated by deriving the area under receiver operating characteristic curves. Kaplan–Meier and Cox regression analyses were used to evaluate significant differences between the survival curves and hazard ratios. Results. The median disease-free survival (DFS) was 35.9 months (range 0.9–105.3 months), and the median overall survival (OS) was 45.2 months (range 4.8–105.3 months). Univariate analysis showed that TNM stage was significantly correlated with DFS and OS. The 2-year disease-free rates of patients with stage I, II, and III disease were 76.4%, 50.5%, and 36.1%, respectively, and the 3-year OS rates were 75.9%, 57.7%, and 34.4%, respectively. In pN + patients, multiple (or multiple-station) lymph node involvement significantly increased recurrence and reduced survival compared with patients with single or single-station metastases. Patients with peripheral SCLCs evidenced significantly better DFS and OS than did patients with central tumors. Multivariate analysis showed that TNM stage and tumor location were independently prognostic in Chinese patients with resected limited-stage SCLC. A combination of TNM stage and tumor location was helpful for prognosis. Conclusions. TNM stage and tumor location were independently prognostic in Chinese patients with resected SCLCs. Patient stratification by tumor location should inform the therapeutic strategy. The role of surgical resection for limited-stage SCLC patients must be reevaluated, as this may be appropriate for some patients

Polyphenol based hybrid nano-aggregates modified collagen fibers of biological valve leaflets to achieve enhanced mechanical, anticoagulation and anti-calcification properties

Glutaraldehyde (Glut)-crosslinked porcine pericardium and bovine pericardium are mainly consisted of collagen and widely used for the preparation of heterogenous bioprosthetic heart valves (BHV), which play an important role in the replacement therapy of severe valvular heart disease, while their durability is limited by degeneration due to calcification, thrombus, endothelialization difficulty and prosthetic valve endocarditis. Herein, we develop a novel BHV, namely, TPly-BP, based on natural tannic acid and polylysine to improve the durability of Glut crosslinked bovine pericardium (Glut-BP). Impressively, tannic acid and polylysine could form nanoaggregates via multiple hydrogen bonds and covalent bonds, and the introduction of nanoaggregates not only improved the mechanical properties and collagen stability but also endowed TPly-BP with good biocompatibility and hemocompatibility. Compared to Glut-BP, TPly-BP showed significantly reduced cytotoxicity, improved endothelial cell adhesion, a low hemolysis ratio and obviously reduced platelet adhesion. Importantly, TPly-BP exhibited great antibacterial and in vivo anti-calcification ability, which was expected to improve the in vivo durability of BHVs. These results suggested that TPly-BP would be a potential candidate for BHV. Graphical abstract: [Figure not available: see fulltext.

Somatic mutation of KIT is rare in small cell lung cancer patients from Northeast China

Studies have confirmed that protein overexpression or mutations of KIT are involved in growth and development of a variety of cancers. however, little is known about data of gene mutation and protein expression in small cell lung cancer (SCLC) patients from northeast China.The aim of study is to investigate gene mutation and protein expression in such patients with small cell lung cancer (SCLC) and analyse their clinical significance.The expression of c-Kit protein was analyzed by immunohistochemistry in 77 SCLC samples and 22 normal lung samples. KIT mutations were screened in exons 9, 11, 13, 14, 17 and 18 by DNA direct sequencing.The study showed that positive staining for c-Kit was observed in 28 of 77 SCLC patients . There was no correlations between expression of c-Kit and sex, ages, smoking status, stage. only 1 case was found to have known T801I mutation in exon 17. The median survival (13.9 months) of cases with c-Kit-positive was shorter than that (19.9 months)of cases with c-Kit-negative. The finding revealed that stages was identified as an independent predictive factor for SCLC patients.Our finding reveals that somatic mutation of KIT is rare in SCLC patients from the northeast China and there is no enough evidence comfirming KIT inhibitors for treatment in SCLC

Third‐line or above anlotinib in relapsed and refractory small cell lung cancer patients with brain metastases: A post hoc analysis of ALTER1202, a randomized, double‐blind phase 2 study

Abstract Background The prognosis of patients with small cell lung cancer (SCLC) and brain metastases (BM) was poor. This study aimed to explore the efficacy and safety of anlotinib as third‐line or above treatment in SCLC with BM. Methods This was a subgroup analysis of the ALTER1202 trial, which was a randomized, placebo‐controlled trial aimed to evaluate the role of anlotinib as third‐line treatment or above in patients with SCLC. This study included patients with BM at baseline. The efficacy and safety outcomes included progression‐free survival (PFS), overall survival (OS), central nervous system (CNS), objective response rate (ORR), CNS disease control rate (DCR), time to CNS progression, and adverse events (AEs). Results Twenty‐one and nine patients with BM were included in the anlotinib and placebo groups, respectively. The median PFS and OS were 3.8 months (95% confidence interval [CI]: 1.8–6.1) and 6.1 months (95% CI: 4.1–8.0) in the anlotinib group. Anlotinib was associated with a significant improvement in PFS (hazard ratio [HR] = 0.15, 95% CI: 0.04–0.51, p = 0.0005) and OS (HR = 0.26, 95% CI: 0.09–0.73, p = 0.0061) than placebo. Anlotinib significantly prolonged the time to CNS progression (p < 0.0001). The anlotinib group had a higher CNS DCR than placebo (95.2% vs. 22.2%, p = 0.0001). The most common grade 3 or higher AEs were increased lipase (19.0%), hypertension (14.3%), and hyponatremia (14.3%) in the anlotinib group. Conclusions Anlotinib proved to have potential CNS activity and a manageable toxicity profile in patients with SCLC and BM, significantly delaying CNS progression