Search

Background: Adjuvant therapy with durvalumab, with or without tremelimumab, may have efficacy in patients with limited-stage small-cell lung cancer who do not have disease progression after standard concurrent platinum-based chemoradiotherapy., Methods: In a phase 3, double-blind, randomized, placebo-controlled trial, we assigned patients to receive durvalumab at a dose of 1500 mg, durvalumab (1500 mg) plus tremelimumab at a dose of 75 mg (four doses only), or placebo every 4 weeks for up to 24 months. Randomization was stratified according to disease stage (I or II vs. III) and receipt of prophylactic cranial irradiation (yes vs. no). Results of the first planned interim analysis of the two primary end points of overall survival and progression-free survival (assessed on the basis of blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1) with durvalumab as compared with placebo (data cutoff date, January 15, 2024) are reported; results in the durvalumab-tremelimumab group remain blinded., Results: A total of 264 patients were assigned to the durvalumab group, 200 to the durvalumab-tremelimumab group, and 266 to the placebo group. Durvalumab therapy led to significantly longer overall survival than placebo (median, 55.9 months [95% confidence interval {CI}, 37.3 to not reached] vs. 33.4 months [95% CI, 25.5 to 39.9]; hazard ratio for death, 0.73; 98.321% CI, 0.54 to 0.98; P = 0.01), as well as to significantly longer progression-free survival (median 16.6 months [95% CI, 10.2 to 28.2] vs. 9.2 months [95% CI, 7.4 to 12.9]; hazard ratio for progression or death, 0.76; 97.195% CI, 0.59 to 0.98; P = 0.02). The incidence of adverse events with a maximum grade of 3 or 4 was 24.4% among patients receiving durvalumab and 24.2% among patients receiving placebo; adverse events led to discontinuation in 16.4% and 10.6% of the patients, respectively, and led to death in 2.7% and 1.9%. Pneumonitis or radiation pneumonitis with a maximum grade of 3 or 4 occurred in 3.1% of the patients in the durvalumab group and in 2.6% of those in the placebo group., Conclusions: Adjuvant therapy with durvalumab led to significantly longer overall survival and progression-free survival than placebo among patients with limited-stage small-cell lung cancer. (Funded by AstraZeneca; ADRIATIC ClinicalTrials.gov number, NCT03703297.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: Cerebral radiation necrosis (RN), a severe complication of stereotactic radiotherapy (SRT), has been shown to significantly decrease patient survival time and quality of life. The purpose of this study was to analyze whether bevacizumab can prevent or reduce the occurrence of SRT-induced cerebral RN in non-small cell lung cancer (NSCLC) patients with brain metastases., Materials and Methods: We retrospectively reviewed the clinical records of NSCLC patients with brain metastases from March 2013 to June 2023 who were treated with SRT. Patients were divided into two groups: those in the bevacizumab group received SRT with four cycles of bevacizumab, and patients in the control group received SRT only. Inverse probability of treatment weighting (IPTW) was performed based on a multinomial propensity score model to balance the baseline characteristics. The chi-square test was used. A Cox model was used to evaluate overall survival (OS)., Results: A total of 80 patients were enrolled, namely, 28 patients in the bevacizumab group and 52 patients in the control group. The possibility of developing cerebral RN and/or symptomatic edema (RN/SE) was significantly decreased in patients treated with bevacizumab compared to those who did not receive bevacizumab before IPTW (p=0.036) and after IPTW (p=0.015) according to chi-square analysis. The IPTW-adjusted median OS was 47.7 months (95% CI 27.4-80.8) for patients in the bevacizumab group and 44.1 months (95% CI 36.7-68.0) (p=0.364) for patients in the control group., Conclusion: The application of bevacizumab concurrent with SRT may prevent or reduce the occurrence of cerebral RN in NSCLC patients with brain metastases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer XL declared a shared parent affiliation with the author JZ to the handling editor at the time of the review., (Copyright © 2024 Zhang, Yu, Yang, Jiang, Dong, Liu, Yu, Yu and Shi.)

Background: For the past 20 years, twice-daily thoracic radiotherapy with concurrent chemotherapy has been the treatment of choice for limited-stage small-cell lung cancer (LS-SCLC), which has a poor prognosis. We aimed to assess the efficacy and safety of high-dose, accelerated, hyperfractionated, twice-daily thoracic radiotherapy (54 Gy in 30 fractions) versus standard-dose radiotherapy (45 Gy in 30 fractions) as a first-line treatment for LS-SCLC., Methods: This open-label, randomised, phase 3 trial was performed at 16 public hospitals in China. The key inclusion criteria were patients aged 18-70 years, with histologically or cytologically confirmed LS-SCLC, who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and who were previously untreated or had received one course of cisplatin or carboplatin and etoposide. Eligible patients were randomly assigned (1:1) to receive volumetric-modulated arc radiotherapy (VMAT) of 45 Gy in 30 fractions to the gross tumour volume or VMAT with a simultaneous integrated boost of 54 Gy in 30 fractions to the gross tumour volume starting 0-42 days after the first chemotherapy course. Both groups received 10 fractions of twice-daily thoracic radiotherapy per week. The planning target volume was 45 Gy in 30 fractions in both groups. Patients with responsive disease received prophylactic cranial radiotherapy (25 Gy in 10 fractions). Randomisation was performed using a centralised interactive web response system, stratified by ECOG performance status, disease stage, previous chemotherapy course, and chemotherapy choice. The primary outcome was overall survival in the intention-to-treat population. Safety was analysed in the as-treated population. This study was registered at ClinicalTrials.gov, NCT03214003., Findings: From June 30, 2017, to April 6, 2021, 224 patients (102 [46%] females and 122 [54%] males; median age 64 years [IQR 58-68]) were enrolled and randomly assigned to the 54 Gy group (n=108) or 45 Gy (n=116) group. The median follow-up was 46 months (IQR 33-56). The median overall survival was significantly longer in the 54 Gy group (60·7 months [95% CI 49·2-62·0]) than in the 45 Gy group (39·5 months [27·5-51·4]; hazard ratio 0·55 [95% CI 0·37-0·72]; p=0·003). Treatment was tolerable, and the chemotherapy-related and radiotherapy-related toxicities were similar between the groups. The grade 3-4 radiotherapy toxicities were oesophagitis (14 [13%] of 108 patients in the 54 Gy group vs 14 [12%] of 116 patients in the 45 Gy group; p=0·84) and pneumonitis (five [5%] of 108 patients vs seven [6%] of 116 patients; p=0·663). Only one treatment-related death occurred in the 54 Gy group (myocardial infarction). The study was prematurely terminated by an independent data safety monitoring board on April 30, 2021, based on evidence of sufficient clinical benefit., Interpretation: Compared with standard-dose thoracic radiotherapy (45 Gy), high-dose radiotherapy (54 Gy) improved overall survival without increasing toxicity in a cohort of patients aged 18-70 years with LS-SCLC. Our results support the use of twice-daily accelerated thoracic radiotherapy (54 Gy) with concurrent chemotherapy as an alternative first-line LS-SCLC treatment option., Funding: Chinese Society of Clinical Oncology-Linghang Cancer Research, the Wu Jieping Medical Foundation, and Clinical Research Fund For Distinguished Young Scholars of Peking University Cancer Hospital and Beijing Municipal Administration of Hospitals Incubating Program., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Anlotinib is an antiangiogenic drug that shows good efficacy and safety in patients with advanced non-small-cell lung cancer (NSCLC). This study aimed to explore the efficacy and safety of anlotinib for consolidation therapy in patients with stage III locally advanced, unresectable NSCLC after concurrent chemoradiotherapy (cCRT). This was a randomized, parallel-controlled, open-label, multicenter, phase II trial of patients with unresectable/nonoperated NSCLC treated with cCRT. The participants were randomized 2:1 to the anlotinib or control group. The primary endpoint was progression-free survival (PFS). The secondary endpoints were the disease control rate (DCR) and overall survival. This study was terminated early due to poor recruitment. Nine and two participants were randomly assigned to the anlotinib and control groups, respectively. One participant in the control group was excluded due to taking prohibited medications before the first efficacy evaluation. In the anlotinib group, the median age was 63 (range, 37-74) years. Two participants achieved partial response, six stable disease, and one progressive disease as best response. The DCR was 88.9%. The median PFS was 11.5 months, and the 12-month PFS rate was 33.9%. All related adverse events were grade 1 or 2. Two participants had a dose adjustment during the study. The evaluable data suggest that anlotinib alone was effective and tolerable in consolidation therapy after cCRT in patients with stage III unresectable NSCLC. The results need to be confirmed by a large-sample trial. This clinical trial was registered on www.clinicaltrials.gov (NCT03743129). Registration date: 6 September 2018., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

To compare the dosimetric differences in volumetric modulated arc therapy (VMAT) and intensity modulated proton therapy (IMPT) in stereotactic body radiation therapy (SBRT) of multiple lung lesions and determine a normal tissue complication probability (NTCP) model-based decision strategy that determines which treatment modality the patient will use. A total of 41 patients were retrospectively selected for this study. The number of patients with 1-6 lesions was 5, 16, 7, 6, 3, and 4, respectively. A prescription dose of 70 Gy RBE in 10 fractions was given to each lesion. SBRT plans were generated using VMAT and IMPT. All the IMPT plans used robustness optimization with ± 3.5% range uncertainties and 5 mm setup uncertainties. Dosimetric metrics and the predicted NTCP value of radiation pneumonitis (RP), esophagitis, and pericarditis were analyzed to evaluate the potential clinical benefits between different planning groups. In addition, a threshold for the ratio of PTV to lungs (%) to determine whether a patient would benefit highly from IMPT was determined using receiver operating characteristic curves. All plans reached target coverage (V70Gy RBE ≥ 95%). Compared with VMAT, IMPT resulted in a significantly lower dose of most thoracic normal tissues. For the 1-2, 3-4 and 5-6 lesion groups, the lung V5 was 29.90 ± 9.44%, 58.33 ± 13.35%, and 81.02 ± 5.91% for VMAT and 11.34 ± 3.11% (p < 0.001), 21.45 ± 3.80% (p < 0.001), and 32.48 ± 4.90% (p < 0.001) for IMPT, respectively. The lung V20 was 12.07 ± 4.94%, 25.57 ± 6.54%, and 43.99 ± 11.83% for VMAT and 6.76 ± 1.80% (p < 0.001), 13.14 ± 2.27% (p < 0.01), and 19.62 ± 3.48% (p < 0.01) for IMPT. The D mean of the total lung was 7.65 ± 2.47 Gy RBE , 14.78 ± 2.75 Gy RBE , and 21.64 ± 4.07 Gy RBE for VMAT and 3.69 ± 1.04 Gy RBE (p < 0.001), 7.13 ± 1.41 Gy RBE (p < 0.001), and 10.69 ± 1.81 Gy RBE (p < 0.001) for IMPT. Additionally, in the VMAT group, the maximum NTCP value of radiation pneumonitis was 73.91%, whereas it was significantly lower in the IMPT group at 10.73%. The accuracy of our NTCP model-based decision model, which combines the number of lesions and PTV/Lungs (%), was 97.6%. The study demonstrated that the IMPT SBRT for multiple lung lesions had satisfactory dosimetry results, even when the number of lesions reached 6. The NTCP model-based decision strategy presented in our study could serve as an effective tool in clinical practice, aiding in the selection of the optimal treatment modality between VMAT and IMPT., Competing Interests: Conflict of Interest X.D. received industry research funding from IBA and Elekta outside the work presented here. X.D. received honoraria from IBA and Elekta speaker bureau outside the work presented here. X.D. holds a patent on particle arc therapy, and it has been licensed to IBA. All authors contributed to the article and approved the submitted version. The authors declared no potential conflicts of interest with respect to the research, author- ship, and/or publication of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the clinical impact of plan complexity on the local recurrence-free survival (LRFS) of non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT)., Methods: Data from 123 treatment plans for 113 NSCLC patients were analyzed. Plan-averaged beam modulation (PM), plan beam irregularity (PI), monitor unit/Gy (MU/Gy) and spherical disproportion (SD) were calculated. The γ passing rates (GPR) were measured using ArcCHECK 3D phantom with 2 %/2mm criteria. High complexity (HC) and low complexity (LC) groups were statistically stratified based on the aforementioned metrics, using cutoffs determined by their significance in correlation with survival time, as calculated using the R-3.6.1 packages. Kaplan-Meier analysis, Cox regression, and Random Survival Forest (RSF) models were employed for the analysis of local recurrence-free survival (LRFS). Propensity-score-matched pairs were generated to minimize bias in the analysis., Results: The median follow-up time for all patients was 25.5 months (interquartile range 13.4-41.2). The prognostic capacity of PM was suggested using RSF, based on Variable Importance and Minimal Depth methods. The 1-, 2-, and 3-year LRFS rates in the HC group were significantly lower than those in the LC group (p = 0.023), when plan complexity was defined by PM. However, no significant difference was observed between the HC and LC groups when defined by other metrics (p > 0.05). All γ passing rates exceeded 90.5 %., Conclusions: This study revealed a significant association between higher PM and worse LRFS in NSCLC patients treated with SBRT. This finding offers additional clinical evidence supporting the potential optimization of pre-treatment quality assurance protocols., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background: Oesophageal squamous cell carcinoma is one of the most commonly diagnosed carcinomas in China, and postoperative radiotherapy plays an important role in improving the prognosis of patients. Carcinomas in different locations of the oesophagus could have different patterns of lymph node metastasis after surgery., Methods: In this multicentric retrospective study, we enrolled patients with middle thoracic oesophageal squamous cell carcinomas from 3 cancer centres, and none of the patients underwent radiotherapy before or after surgery. We analysed the lymph node recurrence rates in different stations to explore the postoperative lymphatic recurrence pattern., Results: From January 1st, 2014, to December 31st, 2019, 132 patients met the criteria, and were included in this study. The lymphatic recurrence rate was 62.1%. Pathological stage (P = 0.032) and lymphadenectomy method (P = 0.006) were significant predictive factors of lymph node recurrence. The recurrence rates in the supraclavicular, upper and lower paratracheal stations of lymph nodes were 32.6%, 28.8% and 16.7%, respectively, showing a high incidence. The recurrence rate of the subcarinal node station was 9.8%, while 8.3% (upper, middle and lower) thoracic para-oesophageal nodes had recurrences., Conclusions: We recommend including the supraclavicular, upper and lower paratracheal stations of lymph nodes in the postoperative radiation field in middle thoracic oesophageal carcinomas. Subcarinal station is also potentially high-risk, while whether to include thoracic para-oesophageal or abdominal nodes needs careful consideration., (© 2024. The Author(s).)

Background: This study aims to evaluate the ability of laboratories to perform spinal muscular atrophy (SMA) genetic testing in newborns based on dried blood spot (DBS) samples, and to provide reference data and advance preparation for establishing the pilot external quality assessment (EQA) scheme for SMA genetic testing of newborns in China., Methods: The pilot EQA scheme contents and evaluation principles of this project were designed by National Center for Clinical Laboratories (NCCL), National Health Commission. Two surveys were carried out in 2022, and 5 batches of blood spots were submitted to the participating laboratory each time. All participating laboratories conducted testing upon receiving samples, and test results were submitted to NCCL within the specified date., Results: The return rates were 75.0% (21/28) and 95.2% (20/21) in the first and second surveys, respectively. The total return rate of the two examinations was 83.7% (41/49). Nineteen laboratories (19/21, 90.5%) had a full score passing on the first survey, while in the second survey twenty laboratories (20/20, 100%) scored full., Conclusions: This pilot EQA survey provides a preliminary understanding of the capability of SMA genetic testing for newborns across laboratories in China. A few laboratories had technical or operational problems in testing. It is, therefore, of importance to strengthen laboratory management and to improve testing capacity for the establishment of a national EQA scheme for newborn SMA genetic testing.

Background: Phlegm-dampness constitution is a traditional Chinese medicine constitution typically associated with essential hypertension. Previous studies have demonstrated that auricular acupuncture effectively decreases blood pressure and adjusts the constitution. However, the mechanism underlying auricular acupuncture's effect is poorly understood., Methods: A non-blinded, randomized controlled trial will be undertaken between September 2022 and May 2023. Eighty essential hypertensive patients with a phlegm-dampness constitution will be randomly allocated to one of two groups. The intervention group will receive eight weeks of auricular acupuncture and regular use of antihypertensive drugs, while the control group will only receive antihypertensive drugs. The primary outcome will be any mean differences in office systolic blood pressure. The secondary outcomes investigations will include proteins of the renin-angiotensin system, office blood pressure of different genotypes, and phlegm-dampness constitution scores., Discussion: By demonstrating how auricular acupuncture affects the renin-angiotensin system, this research will offer significant new information on the mechanism underlying the action of auricular acupuncture in hypertension. Moreover, the results will provide crucial clinical information on the associations between renin-angiotensin system gene polymorphisms and the antihypertensive effects of auricular acupuncture., Trial Registration: Registered at the chictr.org., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The study aimed to investigate the efficacy of induction immunochemotherapy before radiotherapy (RT) for patients with locally advanced or metastatic esophageal cancer., Methods: Patients with unresectable locally advanced or metastatic esophageal cancer who received induction immunochemotherapy followed by RT (ICIs + RT group) and RT alone (RT group) were retrospectively identified in two cancer centers, respectively. Propensity score matching (PSM) was used to balance the potential confounders between the two groups. Overall survival (OS), progression-free survival (PFS), and recurrence patterns were evaluated., Results: A total of 467 patients were reviewed, and 66 were matched in each group. After PSM, the 1- and 2-year OS rates were 84.6% and 57.9% in ICIs + RT group, and 71.1% and 43.0% in RT group (HR 0.60, 95% CI 0.36-1.00, p = 0.050). The absolute increase of restricted mean survival time (RMST) for OS in ICIs + RT group compared with RT group were 0.89 years (p = 0.023) at one year and 2.59 years at two years (p = 0.030). The median PFS time, 1- and 2-year PFS rates were 20.3 months, 69.3%, and 45.7% in ICIs + RT group, and 12.2 months, 51.4%, and 35.8% in RT group (HR 0.64, 95% CI 0.41-0.99, p = 0.045). The cumulative locoregional recurrence (LRR) rate was significantly lower in ICIs + RT group (1-year rate, 17.4% vs. 38.8%, p = 0.011), and distant metastasis (DM) rates were comparable (p = 0.755). Consolidation ICIs was associated with a trend of improved 1-year OS and PFS., Conclusion: Induction immunochemotherapy followed by RT might improve locoregional control and survival outcomes for patients with unresectable locally advanced or metastatic esophageal cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: This prospectively randomised, double-blinded, placebo-controlled, multicenter Phase 3 clinical trial was conducted to assess the efficacy and safety profile of nimotuzumab (nimo) plus concurrent chemo-radiotherapy (CCRT) in patients with unresectable locally advanced ESCC., Methods: Patients were randomly assigned (1:1) to receive CCRT plus nimotuzumab or placebo. The primary endpoint was overall survival (OS). In addition, interim analysis for short-term response rate was pre-defined., Results: A total of 201 patients were randomised into two groups. Eighty patients in the nimo group and eighty-two in the placebo group were evaluable. Three to six months after treatment, 26 (32.5%) patients achieved complete response (CR) in the nimo group, and 10 (12.2%) in the placebo group (P = 0.002). The ORR of the nimo group was significantly higher than the placebo group (93.8% vs. 72.0%, P < 0.001). The two groups' grade 3-5 adverse drug reactions were 11.1% vs. 10.9% (P > 0.05)., Conclusions: Nimotuzumab, in combination with chemo-radiotherapy, increased the CRR and ORR with a good safety profile. The OS is needed to be followed and finally analysed., Clinical Trial Registration: NCT02409186., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Whether supraclavicular lymph node (SCLN) metastasis in patients with oesophageal cancer belongs to regional disease is controversial, leading to heterogeneity in clinical treatment decisions. This study aimed to determine the optimal treatment for lower thoracic oesophageal cancer (LTOC) with SCLN metastasis., Methods: Patients with LTOC registered in the Surveillance, Epidemiology, and End Results database during 2010-2015 were identified. Selected patients were grouped according to disease spread as those with locoregional disease, with SCLN metastasis or with distant metastasis, as well as according to treatment modality (neoadjuvant chemoradiotherapy followed by surgery (nCRT+S group), upfront surgery ± adjuvant therapy (upfront S group) and definitive chemoradiotherapy (dCRT group)). The Cox regression analysis and inverse probability of treatment weighting (IPTW) were used to identify the optimal treatment modality for different groups., Results: Of 11,767 LTOC patients identified from the database, the 5-year overall survival (OS) rates for patients with the locoregional disease (n = 7,541), SCLN metastasis (n = 120) and distant metastasis (n = 4,106) were 28.3%, 10.0% and 3.0%, respectively (P < 0.001). Among patients with SCLN metastasis, median OS in the nCRT+S, upfront S and dCRT groups were 25, 14 and 8 months, respectively (P < 0.001). After IPTW, the nCRT+S group was still associated with better median OS compared with other groups. The multivariate analysis identified treatment modality as an independent prognostic factor for OS., Conclusions: Neoadjuvant chemoradiotherapy followed by oesophagectomy may be the optimal treatment modality for LTOC with SCLN metastasis. The findings of this study need to be validated in large prospective studies., (© 2023 Royal Australian and New Zealand College of Radiologists.)

Introduction: Adjuvant radiotherapy is recommended for pT1b esophageal squamous cell cancer (ESCC) after endoscopic submucosal dissection (ESD). However, it is unclear whether additional radiotherapy can improve patient survival. This study aimed to evaluate the efficacy of adjuvant radiotherapy after ESD for pT1b ESCC., Methods: This was a multicenter, cross-sectional study involving 11 hospitals in China. Between January 2010 and December 2019, patients with T1bN0M0 ESCC treated with or without adjuvant radiotherapy after ESD were included. Survival between groups was compared., Results: Overall, 774 patients were screened, and 161 patients were included. Forty-seven patients (29.2%) received adjuvant radiotherapy after ESD (RT group) and 114 (70.8%) underwent ESD alone (non-RT group). There were no significant differences in overall survival (OS) and disease-free survival (DFS) between the RT and non-RT groups. Lymphovascular invasion (LVI) was the only prognostic factor. In the LVI+ group, adjuvant radiotherapy significantly improved survival (5-year OS: 91.7% vs 59.5%, P = 0.050; 5-year DFS: 92.9% vs 42.6%, P = 0.010). In the LVI- group, adjuvant radiotherapy did not improve survival (5-year OS: 83.5% vs 93.9%, P = 0.148; 5-year DFS: 84.2% vs 84.7%, P = 0.907). The standardized mortality ratios were 1.52 (95% confidence interval 0.04-8.45) in the LVI+ group with radiotherapy and 0.55 (95% confidence interval 0.15-1.42) in the LVI- group without radiotherapy., Discussion: Adjuvant radiotherapy could improve survival in pT1b ESCC with LVI+ other than LVI- after ESD. Selective adjuvant radiotherapy based on LVI status achieved survival rates similar to those of the general population., (Copyright © 2023 by The American College of Gastroenterology.)

Background: Immunotherapy has made significant advances in the treatment of extensive-stage small-cell lung cancer (ES-SCLC), but data in combination with radiotherapy are scarce. This study aims to assess the safety and efficacy of chemoimmunotherapy combined with thoracic radiotherapy in patients with ES-SCLC., Methods: This single-center retrospective study analyzed patients with ES-SCLC who received standard platinum-etoposide chemotherapy combined with atezolizumab or durvalumab immunotherapy as induction treatment, followed by consolidative thoracic radiotherapy (CTRT) before disease progression in the first-line setting. Adverse events during radiotherapy with or without maintenance immunotherapy and survival outcomes were assessed., Results: Between December 2019 and November 2021, 36 patients with ES-SCLC were identified to have received such treatment modality at one hospital. The number of metastatic sites at diagnosis was 1-4. The biological effective dose of CTRT ranged from 52 to 113 Gy. Only two patients (6%) developed grade 3 toxic effect of thrombocytopenia, but none experienced grade 4 or 5 toxicity. Four patients developed immune-related pneumonitis during the induction treatment period but successfully completed later CTRT. The rate of radiation-related pneumonitis was 8% with grades 1-2 and well tolerated. The median progression-free survival (PFS) was 12.8 months, but the median overall survival (OS) was not determined. The estimated 1-year OS was 80.2% and 1-year PFS was 53.4%., Conclusions: Immunotherapy combined with CTRT for ES-SCLC is safe and has ample survival benefit., (© 2023. The Author(s).)

Purpose: The standard dose (SD) of definitive concurrent chemoradiotherapy (dCRT) remains 50.4 Gy in patients with esophageal cancer; a higher dose, when applied with conventional radiation therapy techniques, increases toxicities without improving survival. We investigated whether a high dose of 59.4 Gy using intensity-modulated radiation therapy (IMRT) would improve survival without increasing toxicities., Methods: Patients with inoperable thoracic esophageal squamous cell carcinoma (SCC) referred for dCRT were randomly assigned (1:1) to high-dose (HD) IMRT (59.4 Gy) or SD IMRT (50.4 Gy). Chemotherapy consisted of 6 cycles of concurrent weekly paclitaxel and carboplatin and a maximum of 2 cycles of consolidation chemotherapy. Nutritional intervention was implemented for patients with malnutrition on the basis of nutritional screening. The primary endpoint was median overall survival (mOS). Analyses were by modified intention to treat., Results: Between April 30, 2016, and April 30, 2019, 167 patients were enrolled at 9 participating centers in China. Seventy-one patients in the HD and 73 patients in the SD groups were included in the analysis; 86.8% of the patients completed radiation therapy and 70.1% received 5 or 6 cycles of concurrent chemotherapy. The median follow-up was 36.0 months. The mOS was 28.1 and 26.0 months in the HD and SD arms, respectively (P = .54). A total of 7 treatment-related deaths were observed. Grade 3 or worse treatment-related toxicities were observed in 62% and 68.5% of the patients in the HD and SD arms, respectively (P = .675)., Conclusions: For patients with inoperable thoracic esophageal SCC, a dose of 59.4 Gy did not improve survival compared with the SD of dCRT using IMRT., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Most of the currently available knowledge about protein structure and function has been obtained from laboratory experiments. As a complement to this classical knowledge discovery activity, bioinformatics-assisted sequence analysis, which relies primarily on biological data manipulation, is becoming an indispensable option for the modern discovery of new knowledge, especially when large amounts of protein-encoding sequences can be easily identified from the annotation of highthroughput genomic data. Here, we review the advances in bioinformatics-assisted protein sequence analysis to highlight how bioinformatics analysis will aid in understanding protein structure and function. We first discuss the analyses with individual protein sequences as input, from which some basic parameters of proteins (e.g., amino acid composition, MW and PTM) can be predicted. In addition to these basic parameters that can be directly predicted by analyzing a protein sequence alone, many predictions are based on principles drawn from knowledge of many well-studied proteins, with multiple sequence comparisons as input. Identification of conserved sites by comparing multiple homologous sequences, prediction of the folding, structure or function of uncharacterized proteins, construction of phylogenies of related sequences, analysis of the contribution of conserved related sites to protein function by SCA or DCA, elucidation of the significance of codon usage, and extraction of functional units from protein sequences and coding spaces belong to this category. We then discuss the revolutionary invention of the "QTY code" that can be applied to convert membrane proteins into water- soluble proteins but at the cost of marginal introduced structural and functional changes. As machine learning has been done in other scientific fields, machine learning has profoundly impacted protein sequence analysis. In summary, we have highlighted the relevance of the bioinformatics-assisted analysis for protein research as a valuable guide for laboratory experiments., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: Anatomical changes occurred during the treatment course of radiation therapy for lung cancer patients may introduce clinically unacceptable dosimetric deviations from the planned dose. Adaptive radiotherapy (ART) can compensate these dosimetric deviations in subsequent treatments via plan adaption. Determining whether and when to trigger plan adaption during the treatment course is essential to the effectiveness and efficiency of ART. In this study, we aimed to develop a prediction model as an auxiliary decision-making tool for lung ART to identify the patients with intrathoracic anatomical changes that would potentially benefit from the plan adaptions during the treatment course., Methods: Seventy-one pairs of weekly cone-beam computer tomography (CBCT) and planning CT (pCT) from 17 advanced non-small cell lung cancer patients were enrolled in this study. To assess the dosimetric impacts brought by anatomical changes observed on each CBCT, dose distribution of the original treatment plan on the CBCT anatomy was calculated on a virtual CT generated by deforming the corresponding pCT to the CBCT and compared to that of the original plan. A replan was deemed needed for the CBCT anatomy once the recalculated dose distribution violated our dosimetric-based trigger criteria. A three-dimensional region of significant anatomical changes (region of interest, ROI) between each CBCT and the corresponding pCT was identified, and 16 morphological features of the ROI were extracted. Additionally, eight features from the overlapped volume histograms (OVHs) of patient anatomy were extracted for each patient to characterize the patient-specific anatomy. Based on the 24 extracted features and the evaluated replanning needs of the pCT-CBCT pairs, a nonlinear supporting vector machine was used to build a prediction model to identify the anatomical changes on CBCTs that would trigger plan adaptions. The most relevant features were selected using the sequential backward selection (SBS) algorithm and a shuffling-and-splitting validation scheme was used for model evaluation., Results: Fifty-five CBCT-pCT pairs were identified of having an ROI, among which 21 CBCT anatomies required plan adaptions. For these 21 positive cases, statistically significant improvements in the sparing of lung, esophagus and spinal cord were achieved by plan adaptions. A high model performance of 0.929 AUC (area under curve) and 0.851 accuracy was achieved with six selected features, including five ROI shape features and one OVH feature. Without involving the OVH features in the feature selection process, the mean AUC and accuracy of the model significantly decreased to 0.826 and 0.779, respectively. Further investigation showed that poor prediction performance with AUC of 0.76 was achieved by the univariate model in solving this binary classification task., Conclusion: We built a prediction model based on the features of patient anatomy and the anatomical changes captured by on-treatment CBCT imaging to trigger plan adaption for lung cancer patients. This model effectively associated the anatomical changes with the dosimetric impacts for lung ART. This model can be a promising tool to assist the clinicians in making decisions for plan adaptions during the treatment courses., (© 2022 American Association of Physicists in Medicine.)

Background: To study lymphatic recurrence distribution after radical surgery in the real world and guide clinical tumor volume delineation for regional lymph nodes during postoperative radiotherapy for lower thoracic squamous cell esophageal carcinomas., Methods: We enrolled patients who underwent radical esophagectomy, without radiation before or after surgery, at 3 cancer hospitals. Patients were classified into groups according to tumor locations. We included patients with tumors in the lower thoracic segment and analyzed the postoperative lymph node recurrence mode. A cutoff value of 10% was used to differentiate high-risk lymph node drainage areas from others., Results: We enrolled 1905 patients in the whole study series, including 652 thoracic esophageal carcinomas that met our inclusion criteria; there were 241 cases of lower thoracic esophageal carcinomas. 1st, 2nd, 4th, 7th, 8th groups of lymph nodes, according to the 8th edition of the AJCC classification, displayed as high-risk recurrence areas, representing 17.8%, 23.9%, 11.7%, 10.9% and 12.2% of lymph node recurrence. Stage III-IV tumors located in the lower segment of the thoracic esophagus showed a tendency to recur in the left gastric nodes (7.9%) and celiac nodes (10.6%)., Conclusions: According to our results, we recommended including the 4th, 7th and 8th groups of lymph nodes in the radiation field, and for patients with stage III-IV disease, the 17th and 20th groups of nodes should be irradiated during postoperative treatment. Whether including 1st/2nd groups in preventive irradiation needed more proofs., (© 2022. The Author(s).)

Background: The oesophageal carcinoma patients show high incidence of malnutrition, which negatively affects their therapy outcome. Moreover, benefits of enteral nutrition remain to be studied in details in these patients. Therefore, we set to assess the effects of enteral nutrition on the nutritional status, treatment toxicities and survival in the oesophageal carcinoma patients treated with concurrent chemoradiotherapy (CCRT)., Materials and Methods: Eligible patients were randomly assigned to either the experimental or control group. The patients in the experimental group were treated with a whole-course enteral nutrition management, while the control group were provided a unsystematic nutrition without setting intake goals for energy and protein. The primary endpoint was a change in body weight, while the secondary endpoints included nutrition-related haematological indicators, toxicities, completion rate of treatment and survival., Results: A total of 222 patients were randomised to either the experimental (n=148) or control (n=74) group. Patients in the experimental group showed significantly less decrease in body weight, serum albumin and haemoglobin levels, a lower incidence rates of grade ≥3 myelosuppression and infection, and a higher completion rate of CCRT than those in the control group. While analyses of the 2 and 3 year overall survival (OS) and progression-free survival (PFS) did not reveal differences between these groups, we observed a significantly higher OS at 1 year (83.6% vs. 70.0%). In the subgroup analysis, patients with patient-generated subjective global assessment (PG-SGA)=C were likely to have better OS and PFS with enteral nutrition., Conclusions: In EC patients treated with CCRT, enteral nutrition conferred positive effects on the nutritional status, treatment toxicities and prognosis, which mandate its inclusion in clinical practice., Clinical Trial Registration: This prospective trial has been registered with www.clinicaltrials.gov as NCT02399306., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lyu, Shi, Li, Li, Zhao, Zhu, Wang, Xing, Yang, Xie, Shen, Zhang, Zhu, Wang, Pan, Li, Lang and Shi.)

Background: A substantial proportion of patients with unresectable stage III non-small-cell lung cancer (NSCLC) cannot either tolerate or access concurrent chemoradiotherapy, so sequential chemoradiotherapy is commonly used. We assessed the efficacy and safety of sugemalimab, an anti-PD-L1 antibody, in patients with stage III NSCLC whose disease had not progressed after concurrent or sequential chemoradiotherapy., Methods: GEMSTONE-301 is a randomised, double-blind, placebo-controlled, phase 3 trial in patients with locally advanced, unresectable, stage III NSCLC, done at 50 hospitals or academic research centres in China. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 who had not progressed after concurrent or sequential chemoradiotherapy. We randomly assigned patients (2:1, using an interactive voice-web response system) to receive sugemalimab 1200 mg or matching placebo, intravenously every 3 weeks for up to 24 months. Stratification factors were ECOG performance status, previous chemoradiotherapy, and total radiotherapy dose. The investigators, trial coordination staff, patients, and study sponsor were masked to treatment allocation. The primary endpoint was progression-free survival as assessed by blinded independent central review (BICR) in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of assigned study treatment. The study has completed enrolment and the results of a preplanned analysis of the primary endpoint are reported here. The trial is registered with ClinicalTrials.gov, NCT03728556., Findings: Between Aug 30, 2018 and Dec 30, 2020, we screened 564 patients of whom 381 were eligible. Study treatment was received by all patients randomly assigned to sugemalimab (n=255) and to placebo (n=126). At data cutoff (March 8, 2021), median follow-up was 14·3 months (IQR 6·4-19·4) for patients in the sugemalimab group and 13·7 months (7·1-18·4) for patients in the placebo group. Progression-free survival assessed by BICR was significantly longer with sugemalimab than with placebo (median 9·0 months [95% CI 8·1-14·1] vs 5·8 months [95% CI 4·2-6·6]; stratified hazard ratio 0·64 [95% CI 0·48-0·85], p=0·0026). Grade 3 or 4 treatment-related adverse events occurred in 22 (9%) of 255 patients in the sugemalimab group versus seven (6%) of 126 patients in the placebo group, the most common being pneumonitis or immune-mediated pneumonitis (seven [3%] of 255 patients in the sugemalimab group vs one [<1%] of 126 in the placebo group). Treatment-related serious adverse events occurred in 38 (15%) patients in the sugemalimab group and 12 (10%) in the placebo group. Treatment-related deaths were reported in four (2%) of 255 patients (pneumonia in two patients, pneumonia with immune-mediated pneumonitis in one patient, and acute hepatic failure in one patient) in the sugemalimab group and none in the placebo group., Interpretation: Sugemalimab after definitive concurrent or sequential chemoradiotherapy could be an effective consolidation therapy for patients with stage III NSCLC whose disease has not progressed after sequential or concurrent chemoradiotherapy. Longer follow-up is needed to confirm this conclusion., Funding: CStone Pharmaceuticals and the National Key Research and Development Program of China., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests Y-LW reports advisory services for AstraZeneca, Boehringer Ingelheim, Novartis, and Takeda; personal fees from AstraZeneca, Beigene, Boehringer Ingelheim, Bristol Meyer Squibb, Eli Lilly, MSD, Pfizer, Roche, and Sanofi; grants from AstraZeneca, Boehringer Ingelheim, BMS, Hengrui, and Roche, outside of the submitted work. QZ reports honoraria from AstraZeneca, Boehringer Ingelheim, Bristol Meyer Squibb, Eli Lilly, MSD, Pfizer, Roche, and Sanofi, outside the submitted work. NC, JW, QW, RZ, and JY are employed by CStone Pharmaceuticals and NC, JW, QW, and JY declare stock ownership in the company. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Hypofractionated radiotherapy (HypoRT) has been used to pursue an alternative treatment regimen for patients with non-small-cell lung cancer (NSCLC) who are not eligible for stereotactic ablative radiotherapy (SABR), surgery or concurrent chemoradiotherapy (CCRT) and has shown good local control and safety. We analyzed the feasibility of using volumetric-modulated arc radiotherapy (VMAT) with the simultaneous integrated boost (SIB) technique to achieve high local control with few treatment-related toxicities., Patients and Methods: A total of 55 patients with stage I-IV NSCLC who were not candidates for SABR, surgery or CCRT were included in the present study. All patients received a prescribed dose of 60 to 66 Gy in 15 fractions. Local progression-free survival (LPFS), PFS, overall survival (OS), and toxicities were retrospectively analyzed., Results: Thirty-three patients (60.0%) had stage IV or recurrent disease in this study. The median follow-up time was 8 months (interquartile range: 5.0-16.3 months). The 1-year and 2-year OS rates were 84.3% and 69.9%, and the 1-year and 2-year LPFS rates were 91.0% and 63.0%. The median OS (mOS) and median LPFS (mLPFS) were not reached, and median PFS (mPFS) was 15 months. Twenty-eight (51.9%) patients had disease progression at the time of analysis. Of these, 7 (13.0%), 7 (13.0%) and 21 (38.9%) had local recurrence, locoregional failure and distant metastasis, respectively. All cases of local recurrence were found within the SIB region. Four patients had grade 2-3 pneumonitis, and 8 patients had grade 2-3 esophagitis. Patients with grade 2-3 esophagitis had significantly higher maximum dose and dose to 5 cm 3 volume to esophagus than those with grade 0-1 esophagitis. No grade 4 or higher toxicity was observed., Conclusion: The 60 to 66 Gy in 15 fractions RT regimen provides favorable local control and survival with well-tolerated toxicities. Hypofractionated VMAT+SIB is an alternative treatment option for patients with NSCLC who cannot tolerate standard definitive therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shen, Yang, Chen, Jiang, Dong, Li, Yu, Yu and Shi.)

Purpose: To identify cytokines in plasma that may predict objective response and progression-free survival (PFS) in patients with locally advanced non-small cell lung cancer (NSCLC) treated with chemoradiotherapy., Materials and Methods: From April 2016 to May 2017, thirty-one patients with locally advanced inoperable/unresectable NSCLC were included, and treated with concurrent chemoradiotherapy (CCRT). No immune checkpoint inhibitors were administered after CCRT. Plasma from each patient was collected before radiotherapy, and 25 cytokines in the plasma were measured by Luminex or U-PLEX assays. Logistic regression and COX regression were performed to identify the predictive factors for objective response and PFS, respectively. Kaplan-Meier survival analysis was used to compare the PFS between the groups., Results: High levels of IL-13 and TNF-α, and low levels of ICAM-1, IFN-γ, and soluble PD-L1 (sPD-L1) were significantly associated with objective response ( P < 0.05). High levels of IL-8, CCL5, and CXCL3 also showed a trend toward association with objective response ( P < 0.1). The combination of cytokines (IL-8 and ICAM-1, or TNF-α and sPD-L1) improved predictive accuracy. Univariate analysis identified IL-8 and ICAM-1 as potential markers to predict PFS. Multivariate analysis suggested that high level of IL-8 ( P =0.010) and low level of ICAM-1 ( P =0.011) correlated significantly with a longer PFS., Conclusion: IL-8 and ICAM-1 in plasma have the potential to predict objective response and PFS in patients with locally advanced NSCLC underwent chemoradiotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sui, Jiang, Teng, Mi, Li, Shi, Yu, Li, Dong, Yang, Yu and Wang.)

Background: There is no consensus on the therapeutic approach to ECOG 2 patients with locally advanced non-small-cell lung cancer (LA-NSCLC), despite the sizable percentage of these patients in clinical practice. This study focused on the efficacy, toxicity and the optimal chemotherapy regimen of CCRT in ECOG 2 patients in a phase III trial., Methods: Patients capable of all self-care with bed rest for less than 50% of daytime were classified as ECOG 2 subgroup. A subgroup analysis was performed for ECOG 2 patients recruited in the phase III trial receiving concurrent EP (etoposide + cisplatin)/PC (paclitaxel + carboplatin) chemotherapy with intensity-modulated radiation therapy (IMRT) or three-dimensional conformal external beam radiation therapy (3D-CRT)., Results: A total of 71 ECOG 2 patients were enrolled into the study. Forty-six (64.8%) patients were treated with IMRT technique. The median overall survival (OS) and progression free survival (PFS) for ECOG 2 patients were 16.4 months and 9 months, respectively. No difference was observed in treatment compliance and toxicities between ECOG 2 patients and ECOG 0-1 patients. Within the ECOG 2 group (31 in the EP arm and 40 in the PC arm), median OS and 3-year OS were 15.7 months and 37.5% for the EP arm, and 16.8 months and 7.5% for the PC arm, respectively (p = 0.243). The incidence of grade ≥ 3 radiation pneumonitis was higher in the PC arm (17.5% vs. 0.0%, p = 0.014) with 5 radiation pneumonitis related deaths, while the incidence of grade 3 esophagitis was numerically higher in the EP arm (25.8% vs. 10.0%, p = 0.078)., Conclusions: CCRT provided ECOG 2 patients promising outcome with acceptable toxicities. EP might be superior to PC in terms of safety profile in the setting of CCRT for ECOG 2 patients. Prospective randomized studies based on IMRT technique are warranted to validate our findings., Trial Registration: ClinicalTrials.gov registration number: NCT01494558. (Registered 19 December 2011).

Background: Stereotactic body radiotherapy (SBRT) is the standard care for inoperable early stage non-small cell lung cancer (NSCLC). The purpose of our study was to investigate whether a prediction model based on cone-beam CT (CBCT) plus pretreatment CT radiomics features could improve the prediction of tumor control and lung toxicity after SBRT in comparison to a model based on pretreatment CT radiomics features alone., Methods: A total of 34 cases of stage I NSCLC patients who received SBRT were included in the study. The pretreatment planning CT and serial CBCT radiomics features were analyzed using the imaging biomarker explorer (IBEX) software platform. Multivariate logistic regression was conducted for the association between progression-free survival (PFS), lung toxicity and features. The predictive capabilities of the models based on CBCT and CT features were compared using receiver operating characteristic (ROC) curves., Results: Five CBCT features and two planning CT features were correlated with disease progression. Six CBCT features and two planning CT features were related to lung injury. The ROC curves indicated that the model based on the CBCT plus planning CT features might be better than the model based on the planning CT features in predicting lung injury. The other ROC curves indicated that the model based on the planning CT features was similar to the model based on the CBCT plus planning CT features in predicting disease progression., Conclusions: Both pretreatment CT and CBCT radiomics features could predict disease progression and lung injury. A model with CBCT plus pretreatment CT radiomics features might improve the prediction of lung toxicity in comparison with a model with pretreatment CT features alone., Key Points: Significant findings of the study: A model with cone-beam CT radiomics features plus pre-treatment CT radiomics features might improve the prediction of lung toxicity after SBRT in stage I NSCLC patients., What This Study Adds: In the prediction of PFS and lung toxicity in early-stage NSCLC patients treated with SBRT, CBCT radiomics could be another effective method., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: There is no consensus on the definition or recommended radiotherapy treatment of ultracentral non-small cell lung cancer (NSCLC). Here, we report our institution's experience in treating ultracentral lung cancer patients with stereotactic ablative radiotherapy (SABR) of 60 Gy in eight fractions., Methods: We retrospectively reviewed the outcomes of 21 ultracentral NSCLC patients treated with 60 Gy SABR in eight fractions. We defined ultracentral lung cancer as the planning target volume (PTV) directly abutting or overlapping central structures, including the proximal bronchial tree, heart, and great vessels but not the esophagus. The Kaplan-Meier method was used to estimate overall survival (OS), progression-free survival (PFS) and local control (LC). Toxicity was scored per the CTCAE v4.03., Results: The median follow-up time was 15 months, and the median OS was 15 months. The one- and two-year OS rates were 87.5% and 76.6%, respectively. The one- and two-year PFS rates were 71.1% and 64.0%, respectively. The one- and two-year LC rates were 92.9% and 92.9%, respectively. The rate of grade 2 treatment-related toxicities was 19.1%. There was no grade ≥ 3 treatment-related toxicity., Conclusion: SABR of 60 Gy in eight fractions is feasible for ultracentral NSCLC., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: The standard treatment for locally advanced non-small cell lung cancer (NSCLC) is radiotherapy concurrent with chemotherapy, but the survival was not satisfied. With the development of intensity modulated radiotherapy, simultaneous integrated boost technique (SIB) becomes the research direction of locally advanced NSCLC. The aim of this study is to investigate the efficacy and safety of SIB intensity modulated radiotherapy technique for locally advanced NSCLC., Methods: We retrospectively reviewed the clinical data of locally advanced NSCLC who were treated with radiotherapy by SIB technique in Peking University Cancer Hospital from June 2015 to December 2018. Kaplan-Meier method was used for analysis., Results: Ninty-three patients were included in the analysis. After a median follow-up of 34.23 months, 3-year overall survival (OS), progression-free survival (PFS), local-recurrence free survival (LRFS) and metastasis free survival (MFS) rates were 53.0%, 37.0%, 50.5% and 50.5%, respectively. The incidence of grade ≥3 esophagitis was 5.4%. There were 2 (2.2%) patients experiencing grade ≥3 radiation-related pneumonia., Conclusions: Radiation with SIB intensity modulated radiotherapy technique is effective and safe for patients with locally advanced NSCLC.

Background: Thymic carcinomas (TCs) are rare aggressive tumors with no standard first-line treatment. This study was conducted to determine the optimal chemotherapy regimen for advanced TC., Methods: This retrospective study included 67 patients treated for stage IV TC in 2006-2015. The primary endpoints were the objective response rate (ORR) and progression-free survival (PFS) with different chemotherapy regimens. Multivariate Cox regression analysis was used to identify factors associated with PFS, including metastatic status, radiotherapy post-chemotherapy, primary lesion resection before chemotherapy, and chemotherapy regimen., Results: A total of 36 patients received a paclitaxel-platinum regimen, 31 received a gemcitabine-platinum regimen, 14 underwent primary lesion resection, and 33 underwent radiotherapy. ORR was 31% (11/36) and 29% (9/31) in the paclitaxel-platinum and gemcitabine-platinum groups, respectively (P = 0.890). Median PFS, one-year PFS rate, and two-year PFS rate were 7.0 months, 26%, and 6% with paclitaxel-platinum treatment and 12 months, 48%, and 24% with gemcitabine-platinum treatment (log-rank P = 0.030). Median PFS, one-year PFS rate, and two-year PFS rate were 18.0 months, 57%, and 33% with surgical resection and 7.3 months, 31%, and 7% without resection (log-rank P = 0.030). Median PFS, one-year PFS rate, and two-year PFS rate were 13.0 months, 52%, and 20% with radiotherapy and 4.3 months, 22%, and 7% without radiotherapy (log-rank P = 0.001). In multivariate analysis, metastatic status (hazard ratio [HR], 0.33, P = 0.004), surgical resection (HR, 0.32; P = 0.004), and radiotherapy (HR, 0.32; P < 0.001) were associated with superior PFS., Conclusions: Both gemcitabine-platinum and paclitaxel-platinum regimens were efficacious for advanced TC. Primary lesion resection and radiotherapy may also benefit selected patients., (© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Advances in the field of genome engineering demand the development of efficient non-viral transfection agents capable of delivering multiple distinct nucleic acids efficiently to cells (co-transfection). However, current delivery methods result in lower co-transfection efficiency than single plasmid transfections, and the efficiency decreases further with increasing numbers of plasmids. The development of a high-throughput methodology is required for the validation of co-transfection platforms to facilitate independent tracking of not only the multiple DNA plasmids during transfection but also the localisation of transfection agents. This is pivotal to determine the bottlenecks in achieving high transfection efficiencies at various stages of the cell internalisation and plasmid expression process. Herein we demonstrate that this can be achieved using a facile methodology in which quantum dots (QDs) are used to label two different plasmid DNA assemblies that are delivered to cells simultaneously using a dendronised polymer system. Multispectral confocal imaging can be used to separate signals from each polyplex as well as the expressed fluorescent reporter proteins to determine whether co-transfection difficulties result from poor internalisation or the inability of DNA to escape from polyplexes. The results demonstrate the utility of this facile approach to label polyplexes without interfering with gene expression, and enable high-throughput screening of transfection reagents for achieving optimal co-transfection., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Association between the epithelial growth factor receptor (EGFR) mutation and the expression of breast cancer 1 (BRCA1) and receptor-associated protein 80 (RAP80) in non-small cell lung cancer (NSCLC) was studied. From September 2014 to September 2016, 51 patients with NSCLC who were hospitalized in Department of Thoracic Surgery in The Affiliated Jiangyin Hospital of Southeast University Medical College and underwent biopsy or operation were selected. The pathological changes of lung tissue were detected by hematoxylin and eosin histopathological staining. The fluorescent expression of BRCA1 and RAP80 protein in the two groups was determined by immunofluorescence staining. Reverse transcriptase polymerase chain reaction method and western blot analysis were used to detect BRCA1 and RAP80 mRNA and protein expression. Then the EGFR gene mutation was detected and analyzed. The results show that non-small cell lung cancer has an association with smoking. Compared with the control, the lung tissue structure of the NSCLC group was damaged. The protein fluorescence expression of BRCA1 and RAP80 in non-small cell lung cancer group was significantly increased. The expression of BRCA1 and RAP80 mRNA and protein in NSCLC group was significantly increased. The difference in expression of BRCA1 and RAP80 in the control and the non-small cell lung cancer group was statistically significant (P<0.05). EGFR gene mutations detected 14 of the 51 patients with genetic mutations. Non-small cell lung cancer and smoking have certain relevance, and BRCA1 and RAP80 expression in the development and progression of NSCLC has a close relationship. EGFR mutation in non-small cell lung cancer significantly related to the mutation of EGFR and BRCA1 and RAP80 gene expression plays an important role in the diagnosis and treatment of NSCLC.

Purpose: Stereotactic ablative body radiotherapy (SABR) represents an exciting, tolerable, and highly effective form of radiotherapy. Ongoing investigations into the interactions between radiotherapy and the immune system have uncovered new mechanisms that can be exploited to improve efficacy. We determined whether baseline or posttreatment immune parameters could predict disease control and toxicity in stage I non-small-cell lung cancer (NSCLC) patients treated with SABR., Patients and Methods: Peripheral blood samples were collected from 62 patients 24 hours before treatment and within 4 weeks after treatment for lymphocyte subset count analysis. All peripheral blood samples were analyzed by flow cytometry. Associated parameters were evaluated to determine their association with progression-free survival (PFS) and symptomatic radiation pneumonitis (grade 2 or higher). The survival rates were estimated with Kaplan-Meier and multivariable analyses using binary logistic regression analysis or a Cox proportional hazards model., Results: At a median follow-up time of 36.0 months, the PFS rates for years 1, 2, and 3 were 91.0%, 82.5%, and 48.9%, respectively. The multivariable logistic regression analysis showed that only proportion of lung receiving 20 Gy of radiotherapy (odds ratio = 1.41; 95% confidence interval, 1.05-1.87; P = .023) and mean lung dose (odds ratio = 2.02; 95% confidence interval, 1.16-3.53; P = .016) were associated with symptomatic radiation pneumonitis (grade 2 or higher). Moreover, the immune parameters had no predictive value. In the multivariable Cox regression analysis, an elevated posttreatment cytotoxic CD8 + T-cell level was an independent prognostic factor for longer PFS in stage I NSCLC (hazard ratio, 1.16; 95% confidence interval, 1.01-1.28; P = .01)., Conclusion: A higher posttreatment cytotoxic CD8 + T-cell level was predictive of better PFS in stage I NSCLC patients receiving SABR. Thus, enhancing tumor antigen-specific cellular immunity by combining radiotherapy and immunotherapy might be a crucial strategy for improving survival in these patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Coriolus versicolor (CV) contains high levels of bioactive compounds, including the glucan (1→6)-α-D-glucopyranosyl. However, there is a lack of data regarding the potential effect of this CV glucan (CVG) on the stimulation of cytokine production. The present study evaluated the effect of CVG on the stimulation of cytokine production in sarcoma-180-bearing mice. Mice were treated with three doses of CVG (40, 100 or 200 mg/kg body weight) for nine days, after which serum levels of cytokines, namely interleukin (IL)-2, -4, -6, -10, -17A and interferon (IFN)-α and -γ, were investigated by ELISA. CVG significantly promoted the secretion of IL-2, -4, -6, -10, -17A and IFN-α and -γ at the doses of 100 (P<0.05) and 200 (P<0.01) mg/kg, but not at 40 mg/kg (P>0.05), when compared with cyclophosphamide treatment, as a positive control. Additionally, cytokine production associated with T helper (Th)2 and Th17 cells was enhanced compared with that of Th1 cytokines, and the immunomodulatory function of CVG appeared to be IL-10-dependent. These results demonstrate that CVG may stimulate the production of cytokines and serve as a Th2/IL-10-dependent immunomodulator, and thus has promise in supporting cancer therapies.

Purpose: In patients with esophageal cancer (EC), intensity modulated radiation therapy (IMRT) improves dose sparing to the heart and lung, with some evidence showing clinical benefit. Herein, we report our cumulative clinical experience with the use of IMRT for EC., Methods and Materials: This is a retrospective analysis of 587 patients with nonmetastatic EC who were treated consecutively with IMRT from January 2004 to June 30, 2013. All patients with stage I-IVA (American Joint Committee on Cancer 2002) received concurrent chemoradiation therapy either preoperatively or definitively. The Kaplan-Meier method was used to compute overall survival (OS) and locoregional recurrence-free survival and disease-free survival. The Common Terminology Criteria for Adverse Events, Version 4.0 were used to grade acute and subacute complications., Results: The median radiation dose was 50.4 Gy in 28 daily fractions. As of July 2015, the median follow-up was 31.4 months (range, 2.9-130.7 months) for all patients and 61.8 months (range, 7.7-130.7 months) for survivors. The median OS was 38.9 months, and the 1-, 3-, and 5-year OS rates were 86.7%, 51.8%, and 41.2%, respectively. The 1-, 3-, and 5-year locoregional recurrence-free survival rates were 77.6%, 68.2%, and 66.1%, respectively, and the 1-, 3-, and 5-year disease-free survival rates were 58.6%, 43.7%, and 41.4%, respectively. Outcomes for both trimodality and bimodality treated patients were better than the outcomes reported in the literature. Eight patients (1.4%) experienced grade ≥3 pneumonitis, and 74 patients (13%) developed grade ≥3 esophagitis. For patients who underwent surgery, the most common postoperative complications were pneumonia (9.6%), anastomotic leakage (11.1%), and atrial fibrillation (12.5%)., Conclusions: This is the largest, single institutional study to date on the long-term outcomes of treatment with IMRT for EC. For photon-based radiation therapy, IMRT yields excellent outcomes and should be considered for the treatment of EC.

Background: Concurrent twice-daily radiotherapy with chemotherapy of EP regimen is one of the current standard treatments for limited-stage small cell lung cancer. However, the safely tolerated dose of standard chemotherapy for Chinese patients is not decided. This study was to evaluate the toxicity and the maximum tolerated dose (MTD) of etoposide and cisplatin concurrent with thoracic radiation therapy for patients with limited-stage small cell lung cancer., Methods: Patients with histologically proven limited-stage small cell lung cancer (LS-SCLC) were eligible. The patients underwent thoracic radiotherapy (45 Gy, 1.5 Gy bid, 30 fractions for 3 weeks) delivered concurrently with etoposide (100 mg/m2 iv, days 1-3) and cisplatin dose escalating from the two levels ( 70 mg/m2 and 75 mg/m2 on d1). The primary endpoints were hematologic toxicities during treatment. The secondary endpoints were non-hematologic toxicities, overall survival (OS) and progression-free survival (PFS). According to Common Terminology Criteria for Adverse Events 4.0 (CTC-AE 4.0), maximum tolerant dosage (MTD) was defined as the highest safely tolerated dose at which no more than one patient out of six experiences dose-limiting toxicity (Grades 4 hematologic), with the next higher dose having at least two out of six patients experience dose-limiting toxicity., Results: From January 2013 to August 2016, 20 patients were enrolled in this study. The median age was 49.5 (30-68). After the first 6 patients were enrolled in Arm 1 (70 mg/m2 on d1), one patient had Grade 4 neutropenia. Another 14 patients were enrolled in Arm 2 (75 mg/m2 on d1), one patient had Grade 4 neutropenia. The MTD was determined to be etoposide (100 mg/m2 iv, d1-d3) and cisplatin dose (75 mg/m2 on d1). 4 patients had ≥Grade 3 neutropenia and 1 patients had ≥Grade 3 acute esophagitis in Arm 1. 10 patients had ≥Grade 3 neutropenia and no patient had ≥Grade 3 acute esophagitis in Arm 2. All patients with a median follow-up time was 9.0 months, median OS and PFS were not achieved, 1-year OS and PFS were 91% and 61%, respectively., Conclusions: The MTD of RT with concurrent chemotherapy of EP regimen for patients with LS-SCLC was etoposide (100 mg/m2 iv, d1-d3) and cisplatin dose (75 mg/m2 on d1).
.

Background: Twice-daily radiation concurrent with chemotherapy is one of the standard methods for limited-stage small cell lung cancer. The study was to evaluate the feasibility of chemotherapy concurrent with dose-escalating twice-daily radiotherapy by simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) approach in patients with limited-stage small cell lung cancer., Methods: Patients with limited-stage small cell lung cancer were included, treated with twice-daily radiotherapy by SIB-IMRT concurrent with chemotherapy of etoposide plus cisplatin. Dose escalation was conducted by "classical" 3+3 methods with three patients enrolled in each dose level. The therapeutic gross tumor volume (GTV) was treated according to three consecutive dose levels i.e., 45 Gy at 1.5 Gy twice daily, 50 Gy at 1.67 Gy twice daily and 54 Gy at 1.8 Gy twice daily. The planning target volume (PTV) received a dose of 45 Gy delivered in 30 fractions of 1.5 Gy. The primary endpoints were acute toxicities. The secondary endpoints included overall survival (OS), progression-free survival (PFS) and loco-regional failure-free survival (LRFFS) at 1-year of follow-up., Results: Twenty men and six women were included. The median age was 52 (30-68) months. 12 patients experienced grade 2 acute esophagitis, and 1 patient developed grade 3 acute esophagitis. Only 3 patients developed Grade 2 pneumonitis. Grade 3 or higher radiation-related pneumonia was not observed. None died of treatment-related causes. With median follow-up of 11.2 months (3.2-36.2 months), 1-year OS, PFS and LRFFS were 89.0%, 51.0% and 85.0%, respectively., Conclusions: Dose escalation for twice-daily radiation concurrent with chemotherapy in LS-SCLC has been safely achieved up to 54 Gy for GTV using SIB-IMRT technique.

Purpose: To develop and validate a set of atlases for auto-contouring cardiac substructures., Methods: Eight radiation oncologists manually and independently delineated 15 cardiac substructures from noncontrast CT images of 6 patients by referring to their respective fused contrast CT images. Individual contours were fused together for each structure, edited by 2 physicians, and became atlases to delineate other 6 patients. The auto-delineated contours of the 6 additional patients became templates for manual contouring. These 12 patients with well-defined contours composed the final atlases for multi-atlas segmentation., Results: The average time for manually contouring the 15 cardiac substructures was about 40min. Inter-observer variability was small for the heart, the chambers, and the aorta compared with that for other structures that were not clearly distinguishable in CT images. The mean dice similarity coefficient and mean surface distance of auto-segmented contours were within one standard deviation of expert contouring variability. Good agreement between auto-segmented and manual contours was observed for the heart, the chambers, and the great vessels. Independent validation on other 19 patients showed reasonable agreement for the heart chambers., Conclusions: A set of cardiac atlases was created for auto-contouring from noncontrast CT images. The accuracy of auto-contouring for the heart, chambers, and great vessels was validated for potential clinical use., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC) but is associated with poor chest tumor control. Here, we report results of a randomized phase 3 study comparing two CCRT regimens in improving chest tumor control by low-dose paclitaxel chemoradiation for LA-NSCLC., Methods: Due to the logistics of local referral pattern, the study was designed to enroll patients with stage III LA-NSCLC who had completed 2-4 cycles of full-dose chemotherapy. One hundred thirty four were randomized to either Arm 1 [paclitaxel at 15 mg/m 2 , three times per week (Monday, Wednesday, and Friday) for 6 weeks, n  = 74] or Arm 2 (weekly paclitaxel at 45 mg/m 2 for 6 weeks, n  = 60). Chest radiotherapy was 60-70 Gy in standard fractionation. Response rate was the primary endpoint, with recurrence-free survival (RFS) as the secondary endpoint., Results: From March 2006 to February 2013, 71 patients completed Arm 1 treatment and 59 completed Arm 2 treatment. The response rate for Arm 1 was significantly higher (83.1%) than Arm 2 (54.2%) ( p =0.001). RFS was superior in Arm 1: median 14.6 vs. 9.4 months, p  = 0.005, Hazard ratio (HR) 1.87 [95% confidence interval (CI) 1.20, 2.90]. Overall survival was not significantly different: median 32.6 months in Arm 1 vs. 31.3 months in Arm 2, p  = 0.91, HR 0.97 (95% CI 0.55, 1.70). Toxicity was significantly lower in Arm 1 for Grade 3 and 4 leukopenia/neutropenia ( p  < 0.001)., Conclusion: Pulsed low-dose paclitaxel CCRT resulted in significantly better RFS and tumor response rate, and less hematologic toxicities than weekly CCRT for LA-NSCLC.

High level evidence from randomized studies comparing stereotactic ablative radiotherapy (SABR) to surgery is lacking. Although the results of pooled analysis of two randomized trials for STARS and ROSEL showed that SABR is better tolerated and might lead to better overall survival than surgery for operable clinical stage I non-small cell lung cancer (NSCLC), SABR, however, is only recommended as a preferred treatment option for early stage NSCLC patients who cannot or will not undergo surgery. We, therefore, are waiting for the results of the ongoing randomized studies [Veterans affairs lung cancer surgery or stereotactic radiotherapy in the US (VALOR) and the SABRTooth study in the United Kingdom (SABRTooths)]. Many retrospective and case control studies showed that SABR is safe and effective (local control rate higher than 90%, 5 years survival rate reached 70%), but there are considerable variations in the definitions and staging of lung cancer, operability determination, and surgical approaches to operable lung cancer (open vs video-assisted). Therefore, it is difficult to compare the superiority of radiotherapy and surgery in the treatment of early staged lung cancer. Most studies demonstrated that the efficacy of the two modalities for early staged lung cancer is equivalent; however, due to the limited data, the conclusions from those studies are difficult to be evidence based. Therefore, the controversies will be focusing on the safety and invasiveness of the two treatment modalities. This article will review the ongoing debate in light of these goals.

Background and Objective: Osteosarcoma is the most frequent primary cancer of bone. The incidence is higher in adolescents. Large improvement, though, has been made in the treatment of osteosarcoma under the framework of multidisciplinary team, an important prognostic factor for osteosarcoma is pulmonary metastasis. Surgical resection of lung metastases is widely accepted as the optimal modality in osteosarcoma patients. Undoubtedly, surgical resection of lung metastases is widely accepted as the optimal modality in osteosarcoma patients. However, since current conceptions within the surgical approach to lung metastasectomy involve multidisciplinary collaboration, which are highly variable,there is not neither consensus nor standardized practice patterns. We conduct a survey aiming to reveal areas of consistency in current clinical practice on lung metastasectomy among Chinese osteosarcoma high volume centers., Methods: A questionnaire survey specific to the nationwide high volume centers of osteosarcoma was conducted from September 2015 to November 2015. Analyses were stratified by hospital, working duration, case volume and medical discipline., Results: Of 150 invited physicians, 105 participated, resulting in an overall response rate of 70%. Forty-one percent of the responded physicians agreed with the statement that orthopedic oncology should play a predominant role in the multidisciplinary team. More than 64% of respondents chose metastasectomy as the preferred local control approach, and up to 78.1% of respondents recommended pulmonary metastasectomy for patients. Compared with orthopedic surgeons, other physicians were significantly more likely to report not advocating pulmonary metastasectomy in their practice (OR(others)=0.02; 95%CI: 0.00-0.22; P=0.001), and thoracic surgeons were more likely to decide metastasectomy according to indications rather than the number limit of metastases (OR(thoracic surgeons)=20.93; 95%CI: 2.05-213.64; P=0.001). For the most preferred radiographic evaluation option, approximately 83% of respondents reported diagnostic use of computed tomography (CT). More than 70% of respondents reported that chest CT follow-up should be 3 months after the primary site resection; approximately 68% deemed the diagnostic accuracy of CT about 90%; most respondents (92%) recommended the extrapulmonary imaging evaluation simultaneously. Around 46% of respondents reported that survival duration longer than 6 months after pulmonary metastasectomy is beneficial., Conclusion: This study offers new information about the variability in the reported management of pulmonary metastatic osteosarcoma in China, reflecting the deficiencies in unified practice patterns. The results of this survey also provide baseline data for future research and for the development of international guidelines.

Background and Objective: With the rapid development of technology, stereotactic radiotherapy has been widely used. In a cohort of medically operable non-small cell lung cancer patients receiving stereotactic body radiation therapy (SBRT) survival rates "potentially equivalent to those of surgery" have been reported. Removing the field flattening filter, Clinac is capable of delivering dose rates much higher than conventional linac as well as reducing the treatment time. The goals of this work were to report safety and efficacy of SBRT treatment using a flattening filter-free model for non-small cell lung cancer (NSCLC) with small lesions., Methods: From December 2011 to December 2013, 31 NSCLC patients who were T1-2N0M0, solitary pulmonary recurrence after surgery, and stage IV with oligo metastasis were enrolled, receiving SBRT treatment (60 Gy/8 f or 48 Gy/4 f) applying a flattening filter-free model., Results: Compared with conventional technique, flattening filter-free model shortened the treating time with equivalent target dose and normal tissue dose. The median follow-up time is 19.4 mo. The 1-yr local control, regional control, distant control, progression free survival and overall survival rates were 96.8%, 96.8%, 83.9%, 77.4% and 96.8%. The most common side effects were radiation pneumonitis (29% grade 1, 3.2% grade 2) and chest pain (12.9% grade 1, 6.5% grade 2)., Conclusions: The use of flattening filter-free model in SBRT for small lesions of NSCLC patients is safe and effective. Long time follow-up and additional studies are still needed to validate our conclusions.

Purpose: To analyze the feasibility of omitting clinical target volume (CTV) for limited small cell lung cancer treated with chemotherapy and intensity modulated radiotherapy., Methods and Materials: 89 patients were treated from January 1, 2008 to August 31, 2011, 54 cases were irradiated with target volume without CTV, and 35 cases were irradiated with CTV. Both arms were irradiated post chemotherapy tumor extent and omitted elective nodal irradiation; dose prescription was 95% PTV56-63 Gy/28-35 F/5.6-7 weeks., Results: In the arm without CTV and arm with CTV, the local relapse rates were 16.7% and 17.1% (p = 0.586) respectively. In the arm without CTV, of the 9 patients with local relapse, 6 recurred in-field, 2 recurred in margin, 1 recurred out of field. In the arm with CTV, of the 6 patients with local relapse, 4 recurred in-field, 1 recurred in margin, 1 recurred out of field. The distant metastases rates were 42.6% and 51.4% (p = 0.274) respectively. Grade 3-4 hematological toxicity and radiation esophagitis had no statistically significant, but grade 3-4 radiation pneumonia was observed in only 7.4% in the arm without CTV, compared 22.9% in the arm with CTV (p = 0.040). The median survival in the arm without CTV had not reached, compared with 38 months in the with CTV arm. The l- years, 2- years, 3- years survival rates of the arm without CTV and the arm with CTV were 81.0%, 66.2%, 61.5% and 88.6%, 61.7%, 56.6% (p = 0.517). The multivariate analysis indicated that the distant metastases (p = 0.000) and PCI factor (p = 0.004) were significantly related to overall survival., Conclusions: Target delineation omitting CTV for limited-disease small cell lung cancer received IMRT was feasible. The distant metastases and PCI factor were significantly related to overall survival.

Background and Objective: The presence of epidermal growth factor receptor (EGFR) mutations is predictive of a better response to EGFR tyrosine kinase inhibitors (EGFR-TKIs) and initial chemotherapy in advanced non-squamous non-small cell lung cancer (NSCLC). The aim of this study is to analyze the association between the EGFR mutations and the outcome of combined chemoradiotherapy in stage III non-squamous NSCLC., Methods: Patients with stage III non-squamous NSCLC whose EGFR mutation status had been identified were retrospectively analyzed. The response of 87 patients to combined chemoradiotherapy, the two-year survival rate, and the response of 128 patients to initial chemotherapy were evaluated., Results: The response rate to combined chemoradiotherapy was 84.6% (33/39) in EGFR mutation-positive patients, significantly higher than the 56.3% (27/48) response rate in EGFR mutation-negative patients (P=0.004). Two-year survival rates were 53.8% and 50% in EGFR mutation-positive and mutation-negative patients, respectively. There was no significant difference in the overall survival for both patient groups. The overall response rate to initial chemotherapy was 34.5% (19/55) in EGFR mutation-positive patients, compared with the 21.9% (16/73) response rate in EGFR mutation-negative patients., Conclusions: EGFR mutation-positive status can predict better response to combined chemoradiotherapy, but is not associated with overall survival in patients with stage III non-squamous NSCLC.

Background and Objective: Although the guidelines of the National Comprehensive Cancer Network of USA recommend that the standard therapy for locally advanced non-small cell lung cancer (LANSCLC) is concurrent chemoradiotherapy. There is ongoing controversy about the treatment regimen which combines chemotherapy concurrently with radiotherapy. The aim of this study is to compare weekly usage with triple weekly usage of paclitaxel in concurrent radiochemotherapy for patients with LANSCLC, and to obtain the best paclitaxel regimen in the concurrent radiochemotherapy., Methods: From April 2006 to April 2009, some LANSCLC patients in multicenter were randomly divided into weekly usage (45 mg/m², 1 times/week, a total of 270 mg/m² in six weeks) and triple weekly usage (15 mg/m², 3 times/week, a total of 270 mg/m² in six weeks) group of paclitaxel by a random number table. All patients were treated with 3D radiotherapy, and 95% planning target volume (PTV) received a prescription dose of (60-70) Gy/(30-35)times/(6-7)weeks, (1.8-2.0) Gy/fraction. Then the side effects, response and overall survival rate were compared between two groups of patients., Results: Thirty-eight LANSCLC patients were enrolled. Weekly usage and triple weekly usage group were 20 and 18 patients, respectively. In the triple weekly usage group, the side effects were 12 patients had radiation esophagitis of I-II degree, 1 patient had radiation esophagitis of III degree, 2 patients had radiation pneumonitis of I degree, 1 patient had radiation pneumonitis of II degree, 1 patient had radiation pneumonitis of III degree and died of respiratory failure, 2 patients developed weight loss of I degree. In the weekly usage group, the side effects were 11 patients had radiation esophagitis of I-III degree, 6 patients had radiation pneumonitis of II-III degree, 2 patients developed weight loss of I degree, 6 patients developed leucopenia of III-IV degree. The response rate of two groups was 88.8% and 50.0%, respectively (P=0.026). 1-year survival rate of two groups was 79% and 67%, respectively (P=0.607)., Conclusions: Although the preliminary results did not show the merits of survival in triple weekly usage, but preliminary results show that triple weekly usage was more safe and effective than weekly usage of paclitaxel in concurrent radiochemotherapy for patients with LANSCLC.

Background: To evaluate the association between the clinical, dosimetric factors and severe acute radiation pneumonitis (SARP) in patients with locally advanced non-small cell lung cancer (LANSCLC) treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT)., Methods: We analyzed 94 LANSCLC patients treated with concurrent chemotherapy and IMRT between May 2005 and September 2006. SARP was defined as greater than or equal 3 side effects and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The clinical and dosimetric factors were analyzed. Univariate and multivariate logistic regression analyses were performed to evaluate the relationship between clinical, dosimetric factors and SARP., Results: Median follow-up was 10.5 months (range 6.5-24). Of 94 patients, 11 (11.7%) developed SARP. Univariate analyses showed that the normal tissue complication probability (NTCP), mean lung dose (MLD), relative volumes of lung receiving more than a threshold dose of 5-60 Gy at increments of 5 Gy (V5-V60), chronic obstructive pulmonary disease (COPD) and Forced Expiratory Volume in the first second (FEV1) were associated with SARP (p < 0.05). In multivariate analysis, NTCP value (p = 0.001) and V10 (p = 0.015) were the most significant factors associated with SARP. The incidences of SARP in the group with NTCP > 4.2% and NTCP 50% were 5.7% and 29.2%, respectively (p < 0.01)., Conclusions: NTCP value and V10 are the useful indicators for predicting SARP in NSCLC patients treated with concurrent chemotherapy and IMRT.

Objective: To evaluate the toxicity and the maximum tolerated dose (MTD) of paclitaxel concurrently with three-dimensional (3D) conformal radiotherapy for patients with locally advanced non-small cell lung cancer (LANSCLC) after 2-3 cycles of induction chemotherapy., Research Design and Methods: Patients with histologically proven stage III non-small cell lung cancer (NSCLC) were eligible. Induction chemotherapy regimen included cisplatin (40 mg/m2) on days 1 and 2, and vinorelbine (25 mg/m2) on days 1 and 8 every 3 weeks for 2 or 3 cycles, followed a month later by continual three-dimensional (3D) conformal radiotherapy (60 Gy in 30 fractions for 6 weeks) delivered concurrently with paclitaxel dose escalating from the lowest level, 15 mg/m2, twice weekly, 6 weeks in all, to the highest level, 15 mg/m2, three times a week, 6 weeks in all., Main Outcome Measures: The MTD was defined as the highest safely tolerated dose at which no more than one patient out of six experiences dose-limiting toxicity, with the next higher dose having at least two out of six patients experience dose-limiting toxicity (DLT)., Results: Twenty-three patients were enrolled in this study. The maximum tolerated dose of paclitaxel during 3D-conformal radiotherapy was not reached at 15 mg/m2, three times a week, 6 weeks in all, a level which has been recommended for Caucasian patients with LANSCLC without induction chemotherapy. The overall response rate of induction chemotherapy alone was 47.8% (0% complete remission, 47.8% partial remission, 39.1% stable disease, 13% progressive disease) and that of induction chemotherapy plus concurrent treatment was 78.3% (18/23), including 8.7% (2/23) complete remissions. None of the patients died as a result of toxicity. The median survival time was 23.0 months., Conclusions: 15 mg/m2 of paclitaxel, three times a week, concurrently with 3D-conformal radiotherapy for patients with locally advanced NSCLC after 2 or 3 cycles of induction chemotherapy is a safe and effective dose, according to our preliminary study.