Clinical application and prospect of SBRT in treatment of oligo-metastatic NSCLC / 中华放射肿瘤学杂志

The rapid progress on immunotherapy and targeted therapy has brought long-term survival benefits for locally advanced non-small cell lung cancer (NSCLC). The oncology community has also paid more attention to the local treatment for advanced NSCLC, especially for patients with limited metastatic lesions, also known as oligo-metastasis. Many studies have reported that oligo-metastatic NSCLC patients could benefit from the combination of local and systematic treatment, and even to be cured. In recent years, with the advances in radiation technology, stereotactic body radiation therapy (SBRT) has achieved precise high-dose radiotherapy for small target tumors. Currently, SBRT has been widely applied in the treatment of inoperable early lung cancer, and its application value and safety in patients with advanced lung cancer are also being actively explored. In this article, the research status, progress and future development direction of SBRT in the treatment of oligo-metastatic NSCLC were discussed.

Analysis of failure patterns and survival after SBRT for 147 cases of T 1-2N 0M 0 stage non-small cell lung cancer / 中华放射肿瘤学杂志

Objective:To analyze the failure patterns and survival after stereotactic body radiotherapy (SBRT) in patients with T 1-2N 0M 0 non-small cell lung carcinoma (NSCLC). Methods:Clinical data of early-stage NSCLC patients who received SBRT at Zhejiang Cancer Hospital from January 2012 to September 2018 were retrospectively analyzed. The primary observed endpoint was the pattern of disease progression, which was divided into intra-field recurrence, regional lymph node recurrence and distant metastasis. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan-Meier method. Univariate analysis was conducted by log-rank test, and multivariate analysis was performed by Cox's model.Results:A total of 147 patients with 156 lesions were included. The median follow-up time was 44.0 months (16.5-95.5 months). A total of 57 patients (38.8%) progressed: 14 patients (24.5%) had recurrence with the 1-, 3-, and 5-year local recurrence rates of 2.0%, 10.9%, and 14.3%, respectively; 36 patients (63.2%) had Distant metastasis with the 1-, 3- and 5-year distant metastasis rates of 12.2%, 22.4% and 28.6%, respectively; and 7 patients (12.3%) had recurrence complicated with distant metastasis. The 3-, 5- and 7-year OS rates were 80.5%, 64.2% and 49.9% for all patients, respectively. The median OS was 78.4 months. The 3-, 5- and 7-year PFS rates were 64.8%,49.5% and 41.5%, with a median PFS of 57.9 months (95% CI: 42.3-73.5 months). Univariate and multivariate analyses showed that biologically equivalent dose and age were the factors affecting the efficacy of SBRT (both P<0.05). Conclusion:Distant metastasis is the main failure pattern in patients with T 1-2N 0M 0 NSCLC after SBRT. High-risk population should be selected for further systematic treatment to improve the efficacy.

Failure mode and long-term survival after neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma / 中华放射肿瘤学杂志

Objective:To analyze the fail mode of neoadjuvant therapy combined with surgery for locally advanced esophageal squamous cell carcinoma (ESCC) after long-term follow-up.Methods:Clinical data of consecutive 238 patients with locally advanced resectable ESCC who underwent neoadjuvant therapy combined with surgery in Zhejiang Cancer Hospital from September 2012 to October 2019 were retrospectively analyzed. The failure mode in the whole cohort was analyzed after long-term follow-up. The overall survival (OS) and disease free survival (DFS) rates were analyzed by Kaplan-Meier method. Survival differences were determined by log-rank test.Results:The pathological complete response (pCR) rate was 42.0% in 238 patients. After a median follow-up of 46.1 months, tumor progression occurred in 96 patients (40.3%), including 25 patients (10.5%) with local recurrence, 61 patients (25.6%) with distant metastases, and 10 patients (4.2%) with simultaneous local recurrence and distant metastases. The median OS and DFS were 64.7 months and 49.9 months. And the 3-, 5-, and 7-year OS and DFS rates were 70.0%, 52.8%, 36.4% and 63.5%, 42.5%, and 30.0%, respectively. The 3-, 5-, and 7-year locoregional recurrence-free survival rates and distant metastasis-free survival rates were 86.0%, 71.4%, 61.2% and 70.6%, 55.9%, 43.0%. Compared with non-pCR patients, the overall progression rate and distant metastasis rate of pCR patients were lower (26.0% vs. 50.7%, 16.0% vs. 32.6%, both P<0.05). And the 3-, 5-, and 7-year OS (83.0% vs. 60.2%, 69.7% vs. 41.7%, 50.4% vs. 27.7%, all P<0.001) and DFS rates (80.4% vs. 51.4%, 63.9% vs. 31.2%, 45.9% vs. 20.3%, all P<0.001) were significantly better in pCR patients. Conclusions:Distant metastasis is the main failure mode of patients with locally advanced ESCC after neoadjuvant therapy. Patients with postoperative pCR can achieve better long-term survival.

Prognostic Analysis of NSCLC Based on the Tumor-associated Macrophages, Tumor Neo-vessels and PD-L1 Expression in Tumor Microenvironment / 中国肺癌杂志

BACKGROUND@#Tumor microenvironment is a complex and dynamic community, which plays a crucial role in tumor progression via the co-evolution of cancer cells and tumor stroma. Among them, tumor-associated macrophages (TAMs) and tumor neo-vessels are two key components in the tumor microenvironment during cancer invasion. In addition, programmed cell death ligand 1/programmed cell death ligand 1 (PD-1/PD-L1) also plays an important role in tumorigenesis and development, and the clinical strategies to block PD-1/PD-L1 pathway could have great benefits for cancer patients. This study was aimed at analyzing the quantitative expression and prognostic significance of TAMs, tumor neo-vessels and PD-L1 in tumor microenvironment and exploring the relations between the expression of above components with the patients' prognosis of non-small cell lung cancer (NSCLC).@*METHODS@#Clinico-pathological data and surgical specimens of 92 patients with NSCLC were collected, and immunohistochemistry was used to stain the expression of TAMs, tumor neo-vessels and PD-L1 on tumor tissue and peri-tumor tissues. The inverted microscopy was used to take pictures and Image-pro Plus 6.0 software was used for quantitative analysis. The clinicopathological characteristics and overall survival (OS) were analyzed.@*RESULTS@#The median OS of 92 NSCLC cases was 22.5 month. The expression of TAMs, tumor neo-vessels and PD-L1 in tumor tissue and peri-tumor tissues were not statistically significant (P>0.05). According to the cutoff of above key three components in tumor microenvironment, all the cases could be classified into high, middle and low expression groups. The survival analysis demonstrated that the OS in high expression group of TAMs (P=0.016) and PD-L1 (P=0.002) was shorter than the other two groups, respectively, with statistical significance. The OS in high tumor neo vessels group was shorter than the other two groups. However, there was no statistical significance between these three group (P=0.626). Combined with above the three components, all the cases could be classified into low, middle and high density groups. The survival analysis demonstrated that the median OS of combined high density group was shorter than the other two groups (P=0.001). Multivariate analysis by Cox regression indicated that pathological type, TAMs and PD-L1 expression were the independent prognostic factors.@*CONCLUSIONS@#The key components of TAMs and PD-L1 in tumor microenvironment are closely related to the prognosis of NSCLC patients.

Effects of hypoxia on adiponectin in tongue squamous cell carcinoma / 中国肿瘤临床

Objective: Adiponectin (APN) is an endogenous cytokine that mediates the development and progression of various tumors through its receptors (AdipoRs). The present study aimed to detect the expression and distribution of APN and its receptors (AdipoR1 and AdipoR2) in tongue squamous cell carcinoma (TSCC). Moreover, we explored whether the locoregional expression of APN was reg-ulated by HIF-1α in the hypoxic microenvironment. Methods: The expression and distribution of APN and its receptors in TSCC tissues were analyzed by immunohistochemical. Lentiviral expression vector for HIF-1α shRNA was constructed and stably transfected in TSCC cells to knock down HIF-1α expression. The mRNA and protein expression levels of APN and its receptors were detected using RT-PCR and Western blot, respectively, after hypoxic treatment. Results: The locoregional expression of APN and AdipoR1, but not AdipoR2, was upregulated at the early stages of T1, T2, and/or N0 stage, respectively, in tumor tissues compared to that in control paracancer-ous tissues (P<0.05 or P<0.01). The expression of APN and AdipoR1, but not AdipoR2, in TSCC cells was up-regulated on hypoxic treat-ment. Moreover, the expression of APN and AdipoR1 was down-regulated after shRNA knockdown of HIF-1α under hypoxia. Conclu-sions: The APN-AdipoR1 signaling pathway was activated and regulated by HIF-1α in the hypoxic environment of TSCC tissues.

Optimization of the Formula of Konjac Glucomannan-Paeonol Matrix Tablets / 医药导报

Objective To optimize the formula of konjac glucomannan-paeonol matrix tablets. Methods The formula of paeonol matrix tablets was optimized by the orthogonal design with the accumulative release rate in vitro as index, with the viscosity of konjac glucomannan ( KGM) , the amount of KGM and lactose as influence factors. Results The optimized formula was as follows:the viscosity of konjac glucomannan was 20 000 mPa·s, KGM 30%, lactose 20% and the release in vitro fit into the Higuchi equation. Conclusion The formula of the paeonol matrix tablets is reasonable and the tablets have well release effect in vitro.