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Background A prospective phase II study showed that Endostar combined with concurrent chemoradiotherapy (CCRT) can improve overall survival (OS) in patients with inoperable locally advanced non-small cell lung cancer (NSCLC). This study aimed to retrospectively compare the 5-year survival rates of patients with inoperable locally advanced NSCLC who received a combination of Endostar and CCRT to that of patients receiving CCRT. Methods Treatment-naive patients with inoperable locally advanced NSCLC who had long-term follow-up data were included in this study. Patients in CCRT + Endostar group were treated with Endostar plus radical CCRT, and patients in CCRT group received radical CCRT. For patients with a radiation dose ≥60 Gy, Kaplan-Meier method was used for survival analysis, and Cox proportional-hazards regression model was used for univariate analysis. Results A total of 104 participants were included in the CCRT + Endostar group with 89 participants included in the CCRT group. There were 88 (84.6%) and 74 (83.1%) male patients, respectively. The median follow-up times of two groups were 73.6 (95% CI: 65.6 to 81.7 months) and 66.3 months (95% CI: 52.7 to 79.9 months), respectively. The median overall survival (OS) was 29.7 (95% CI: 22.8 to 36.6 months) and 21.3 months (95% CI: 15.9 to 26.7 months), respectively. Conclusions This study showed that the 5-year survival of those patients who received the combination treatment of Endostar and radical CCRT was significantly superior to those who received radical CCRT.

// Yujin Xu 1, 2 , Xiao Zheng 1, 2 , Xue Bai 3 , Pu Li 3 , Honglian Ma 1, 2 , Jin Wang 1, 2 , Xiao Hu 1, 2 and Ming Chen 1, 2 1 Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, 310022, China 2 Zhejiang Provincial Key Laboratory of Radiation Oncology, Hangzhou, 310022, China 3 Department of Radiation Physics, Zhejiang Cancer Hospital, Hangzhou, 310022, China Correspondence to: Ming Chen, email: chenming@zjcc.org.cn Keywords: non-small cell lung cancer, integrated boost intensity-modulated radiotherapy, local control, overall survival Received: March 03, 2017 Accepted: March 31, 2017 Published: April 13, 2017 ABSTRACT Objectives: To evaluate the clinical efficacy and toxicity of simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) for patients with locally advanced non-small cell lung cancer (NSCLC). Results: All patients completed definitive radiotherapy and 74 (85.1%) patients administrated platinum-based chemotherapy. The median radiation dose was 50.4Gy to PTV and 64.4 Gy simultaneously to the PGTV. The overall response rate (ORR) was 57.5% (50/87). The median duration of follow up was 24.6 months. The 1, 2, 3-year local control rate was 79.0%, 66.1%, and 60.5%, respectively. The 1, 2, 3-year overall survival (OS) rate was 89.7%, 56.7%, and 30.6%, respectively. Subgroup analysis showed that the median OS in concurrent chemoradiation (CCRT) was much better than non-CCRT (35.7 vs. 26.4 months) (HR: 0.52, 95% CI: 0.32–0.95, P = 0.033). Twenty-two (25.3%) patients experienced acute grade 3 esophagitis and 10 (11.5%) experienced acute grade ≥ 3 radiation pneumonitis. There were 2 (2.6%) late grade 3 pulmonary toxicity and no late grade ≥ 3 esophageal toxicity was observed. Materials and Methods: A total of 87 patients with locally advanced NSCLC who received SIB-IMRT from Jan. 2009 to Dec. 2012 in our hospital were retrospectively analyzed. Male accounted for 88.5%, with a median age of 61 years old. The SIB-IMRT plans were designed to deliver 50.4–64.0 Gy in 28–33 fractions (1.8–2.1 Gy/fraction) to PTV while simultaneously delivering 60.0–74.3 Gy in 28–33 fractions (2.0–2.5 Gy/fraction) to PGTV. Conclusions: SIB-IMRT, especially with concurrent chemotherapy, appears to be an effective and safe option to treat patients with locally advanced NSCLC. More prospective clinical studies should be warranted.

Purpose: To evaluate the clinical efficacy and toxicity of simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) in patients with esophageal squamous cell carcinoma (ESCC) in Chinese population. Patients and Methods: Patients with ESCC, who received SIB-IMRT from September 2011 to January 2013 were retrospectively analyzed. The SIB-IMRT plans were designed to deliver primary gross tumor volume at 60–64.4 Gy in 28–30 fractions, and planning target volume at 50.4–56 Gy in 28–30 fractions. Treatment-related toxicities were estimated based on Common Terminology Criteria for Adverse Events version 4.0, and tumor response after the treatment was estimated according to Response Evaluation Criteria in Solid Tumors version 1.0. Overall survival (OS), locoregional progression-free survival (LPFS), and progression-free survival (PFS) were estimated with Kaplan–Meier. Results: All patients completed definitive radiotherapy, 54 (78.3%) received combined chemotherapy, of which 31 (44.9%) were concurrent chemoradiotherapy and 23 (33.3%) were sequential chemotherapy. The objective response rate is 82.6% (56/69), with complete response 11 (15.9%), partial response 45 (65.2%), stable disease 8 (11.6%), and progressive disease 5 (7.2%). The 1-, 2- and 3-year LPFS was 74.4%, 57.8%, and 55.6%, respectively. The 1-, 2- and 3-year PFS was 62.3%, 41.0%, and 34.2%, respectively, and the 1-, 2-, and 3-year OS was 73.8%, 57.4%, and 41.0%, respectively, with a median OS of 27.1 months (4.5–54.9 m). For those who received concurrent chemotherapy, the 1-, 2-, and 3-year OS was 75.9%, 69.0%, and 55.2%, respectively, better than those who had sequential chemotherapy or radiotherapy alone (χ2 = 3.115, P = 0.078). Radiation esophagitis occurred in 63.8% and 14.5% with Grade 2 and 3, respectively. No patients occurred ≥ Grade 3 radiation pneumonia. Conclusions: It is safe and effective using SIB-IMRT technology to treat patients with ESCC. More prospective clinical studies should be needed.

The function of postoperative radiotherapy (PORT) in patients with completely resected pathologically N2 (pN2) non-small cell lung cancer (NSCLC) remains controversial due to a lack of prospective studies. The present study aimed to evaluate the efficacy of PORT in completely resected pN2 NSCLC when using modern radiation techniques, and to determine the associations between clinicopathological factors and PORT and survival rates. Following patient selection, 246 out of 269 consecutive patients with pN2 NSCLC were enrolled in the present study, with 88 patients having received postoperative chemotherapy (POCT) and PORT, 90 having received adjuvant chemotherapy, 1 having received adjuvant radiotherapy and the remaining 67 having received no adjuvant therapy. Overall survival (OS), local recurrence-free survival (LRFS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. The median age of the patients was 59 years, overall, 175 (71.1%) of the patients were male and the median radiation dose was 50.4 Gy. The median follow-up duration was 38.3 months. The 1-, 3- and 5-year OS rates were 98.9, 71.3 and 54.9%, and 93.0, 58.4 and 36.7% (P=0.011) in the PORT and non-PORT group, respectively. The 1-, 3- and 5-year LRFS rates were 95.5, 84.6 and 78.0%, and 86.6, 70.6 and 52.8% (P

Purpose Accurate staging of mediastinal lymph nodes metastases is critical for determining the application of stereotactic body radiation therapy (SBRT) for patients with early stage non-small cell lung cancer (NSCLC). In this multicenter study the accuracy of 18 F-FDG PET/CT to detect lymph node metastases was evaluated for early stage NSCLC. Materials and methods The data from the patients with stage1 NSCLC who received preoperative 18 F-FDG PET/CT staging and radical surgery was retrospectively reviewed of five centers from February 2004 to August 2010. The lymph node metastases were confirmed histopathologically after radical surgery. And the sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated for PET/CT staging. Results Two hundred patients were enrolled. The sensitivity, specificity, accuracy, PPV and NPV for lymph node metastases on PET/CT were 44%, 83%, 78%, 29% and 91%, respectively. There were eight and 19 cases positive for lymph node metastases with central ( n =62) and peripheral ( n =138) NSCLC ( P> 0.05), respectively. Conclusion 18 F-FDG PET/CT was specific in N 0 staging for T 1–2 NSCLC. The NPV was about 91% in clinical N 0 patients, suggested that 18 F-FDG PET/CT may help to accurately stage N 0 patients and thus identify patients for SBRT.

A proportion of patients with locally advanced non-small-cell lung cancer (NSCLC) may benefit from anti-angiogenic therapy combined with concurrent chemoradiotherapy; however, effective prognostic biomarkers are required for prognosis. In this study, we aimed to establish whether inflammation-based factors offer a prognostic benefit in terms of response rate (RR) and overall survival (OS) in stage III NSCLC patients treated by endostar with concurrent chemoradiotherapy (CCRT). We retrospectively investigated an unselected cohort of stage III NSCLC patients, who were treated by combined endostar and CCRT. The log-rank test was used to analyze the association between each clinical variable and OS. Cox regression models were fitted to identify risk factors associated with OS. A total of 82 patients with stage III NSCLC were treated with a combination of endostar and CCRT and 78 patients were included in the data analysis. A total of 13 patients achieved a complete response, 49 achieved a partial response, 6 had stable disease, 8 had progressive disease and 2 patients could not be evaluated. The median progression-free survival of the entire group was 10.50 months (95% CI: 6.298-14.702), while the median OS was 22.83 months (95% CI: 19.156-26.504). On χ2test analysis, the neutrophil-to-lymphocyte ratio (NLR) exerted a significant effect on RR (P=0.048). The univariate analysis identified the factors associated with OS, including NLR (P=0.004) and monocyte count (P=0.001), whereas the multivariate analysis confirmed NLR [P=0.043, hazard ratio (HR)=0.502] and monocyte count (P=0.011, HR=0.387) as independent prognostic factors for OS. Our results indicated that, in patients with stage III NSCLC treated by a combination of endostar and CCRT, pre-treatment elevated NLR and monocyte number are negatively associated with OS.

Regulator of G protein signaling 5 (RGS5) belongs to the R4 subfamily of RGS proteins, a family of GTPase activating proteins, which is dynamically regulated in various biological processes including blood pressure regulation, smooth muscle cell pathology, fat metabolism and tumor angiogenesis. Low-expression of RGS5 was reported to be associated with tumor progression in lung cancer. In the present study, we examined the potential roles of RGS5 in human lung cancer cells by overexpressing RGS5 in the cancer cells and further explored the underlying molecular mechanisms. The RGS5 gene was cloned and transfected into the human lung cancer cell lines A549 and Calu-3. The cells were tested for apoptosis with flow cytometry, for viability with MTT, for mobility and adhesion capacity. The radiosensitization effect of RGS5 was measured by a colony formation assay. The mechanisms of RGS5 functioning was also investigated by detection of protein expression with western blot analysis, including PARP, caspase 3 and 9, bax, bcl2, Rock1, Rock2, CDC42, phospho-p53 (Serine 15) and p53. The present study demonstrated that RGS5 overexpression remarkably induced apoptosis in human lung cancer cells, which was suggested to be through mitochondrial mechanisms. Overexpression of RGS5 resulted in significantly lower adhesion and migration abilities of the lung cancer cells (P

Purpose To determine whether the standard uptake value (SUV) of the primary lesion can predict mediastinal lymph node metastasis in clinical stage IA non–small-cell lung cancer (NSCLC). Materials and Methods At 5 centers, patients with clinical stage IA NSCLC from February 2004 to August 2010 were analyzed retrospectively. Data from Shandong Cancer Hospital and from the Cancer Hospital Affiliated to Harbin Medical University were used as a testing set, and data from the other 3 institutions were used as the validation set. Final diagnosis was established based on the histopathologic examination. Results Data from 144 patients were collected for the study. The primary results in our study showed that maximal SUV (SUVmax) of primary tumor might be a predictor of lymph node metastasis (χ 2 = 10.424; P = .001) and the best cutoff value was 7.25 ( P = .029). For the testing set, lymph node metastasis rates in low-grade group (SUVmax 7.25) were 5% (2/43) and 36% (9/25) ( P = .001) For the total data set, lymph node metastasis rate was 7% (6/93) in low-grade group (SUVmax 7.25) (χ 2 = 10.424; P = .001). A multivariate analysis revealed that no factors were applied to predict the probability of metastasis. But the analysis showed a weak correlation between SUVmax and nodal status ( r = 0.21; P = .011) with bivariate correlation. Conclusion Analysis of our data suggested that fluorine-18 fluorodeoxyglucose SUVmax of the primary tumor might be a predictor of lymph node involvement in stage IA NSCLC. The rate of mediastinal lymph node metastasis of patients with a lower fluorine-18 fluorodeoxyglucose positron emission tomography–computed tomography SUVmax might be relatively low, which provides more evidence for clinical procedures of clinical stage IA NSCLC.

Background Hypoxic tumor cells can reduce the efficacy of radiation. Antiangiogenic therapy may transiently "normalize" the tumor vasculature to make it more efficient for oxygen delivery. The aim of this study is to investigate whether the recombinant human endostatin (endostar) can create a "vascular normalization window" to alleviate hypoxia and enhance the inhibitory effects of radiation therapy in human nasopharyngeal carcinoma (NPC) in mice. Methodology/principal findings Transient changes in morphology of tumor vasculature and hypoxic tumor cell fraction in response to endostar were detected in mice bearing CNE-2 and 5-8F human NPC xenografts. Various treatment schedules were tested to assess the influence of endostar on the effect of radiation therapy. Several important factors relevant to the angiogenesis were identified through immunohistochemical staining. During endostar treatment, tumor vascularity decreased, while the basement membrane and pericyte coverage associated with endothelial cells increased, which supported the idea of vessel normalization. Hypoxic tumor cell fraction also decreased after the treatment. The transient modulation of tumor physiology caused by endostar improved the effect of radiation treatment compared with other treatment schedules. The expressions of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2), MMP-9, and MMP-14 decreased, while the level of pigment epithelium-derived factor (PEDF) increased. Conclusions Endostar normalized tumor vasculature, which alleviated hypoxia and significantly sensitized the function of radiation in anti-tumor in human NPC. The results provide an important experimental basis for combining endostar with radiation therapy in human NPC.