A Randomized Phase I/II Trial to Compare Weekly Usage with Triple Weekly Usage of Paclitaxel in Concurrent Radiochemotherapy for Patients with Locally Advanced Non-small Cell Lung Cancer

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). Conclusion 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

Clinical Study on the Prevention of Oxaliplatin-Induced Neurotoxicity with Guilongtongluofang: Results of a Randomized, Double-Blind, Placebo-Controlled Trial

Objective. Oxaliplatin-induced peripheral neurotoxicity continues to be a kind of frequent dose-limiting toxicity for many cancer patients. This study evaluated the preventive effects of Guilongtongluofang on peripheral neurotoxicity induced by oxaliplatin in patients with colorectal tumor. Patients and Methods. From May 2007 to May 2011, we conducted a randomized, double-blind, placebo-controlled trial. 120 patients of colorectal cancer treated with adjuvant oxaliplatin-based chemotherapy were randomly enrolled into the trial group and the control group. The trial group received Guilongtongluofang (at a dose of 200 mL once a day) from 3 days prior to chemotherapy. The control group received a placebo from 3 days prior to chemotherapy. Every 2-week cycle, neurotoxicity was evaluated using numeric rating scale for pain intensity and experienced relief. The primary endpoint was efficacy measurement which included oxaliplatin-induced neurotoxicity and tumor response. The differences of side effects between the two groups were also analyzed. Results. The percentage of grades 1-2 neurotoxicity was significantly lower in the trial group than that in the control group (13.3% versus 20.0%; P0.05). Conclusion. This study provides evidence that Guilongtongluofang is a promising drug for the prevention of oxaliplatin-induced neurotoxicity in patients with colorectal cancer, and it does not reduce the efficacy of oxaliplatin

Analysis of clinical and dosimetric factors associated with severe acute radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with concurrent chemotherapy and intensity-modulated radiotherapy

<p>Abstract</p> <p>Background</p> <p>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).</p> <p>Methods</p> <p>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.</p> <p>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.</p> <p>Results</p> <p>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 (<it>p </it>< 0.05). In multivariate analysis, NTCP value (<it>p </it>= 0.001) and V10 (<it>p </it>= 0.015) were the most significant factors associated with SARP. The incidences of SARP in the group with NTCP > 4.2% and NTCP ≤4.2% were 43.5% and 1.4%, respectively (<it>p </it>< 0.01). The incidences of SARP in the group with V10 ≤50% and V10 >50% were 5.7% and 29.2%, respectively (<it>p </it>< 0.01).</p> <p>Conclusions</p> <p>NTCP value and V10 are the useful indicators for predicting SARP in NSCLC patients treated with concurrent chemotherapy and IMRT.</p

Predicting progression of white matter hyperintensity using coronary artery calcium score based on coronary CT angiography—feasibility and accuracy

ObjectiveCoronary artery disease (CAD) usually coexists with subclinical cerebrovascular diseases given the systematic nature of atherosclerosis. In this study, our objective was to predict the progression of white matter hyperintensity (WMH) and find its risk factors in CAD patients using the coronary artery calcium (CAC) score. We also investigated the relationship between the CAC score and the WMH volume in different brain regions.MethodsWe evaluated 137 CAD patients with WMH who underwent coronary computed tomography angiography (CCTA) and two magnetic resonance imaging (MRI) scans from March 2018 to February 2023. Patients were categorized into progressive (n = 66) and nonprogressive groups (n = 71) by the change in WMH volume from the first to the second MRI. We collected demographic, clinical, and imaging data for analysis. Independent risk factors for WMH progression were identified using logistic regression. Three models predicting WMH progression were developed and assessed. Finally, patients were divided into groups based on their total CAC score (0 to &lt;100, 100 to 400, and &gt; 400) to compare their WMH changes in nine brain regions.ResultsAlcohol abuse, maximum pericoronary fat attenuation index (pFAI), CT-fractional flow reserve (CT-FFR), and CAC risk grade independently predicted WMH progression (p &lt; 0.05). The logistic regression model with all four variables performed best (training: AUC = 0.878, 95% CI: 0.790, 0.938; validation: AUC = 0.845, 95% CI: 0.734, 0.953). An increased CAC risk grade came with significantly higher WMH volume in the total brain, corpus callosum, and frontal, parietal and occipital lobes (p &lt; 0.05).ConclusionThis study demonstrated the application of the CCTA-derived CAC score to predict WMH progression in elderly people (≥60 years) with CAD

Effects of Thymosin Alpha-1 on Radiation-induced Pneumonitis

Background and objective Radiation-induced lung injure is one of the major factors of limitation in radiotherapy for lung cancer. Whether the use of thymosin and radiotherapy simultaneously would increase the radiationinduced lung injure is unclear. The aim of this study is to evaluate the effects of thymosin alpha-1 on radiation induced pneumonitis in mice. Methods Three groups of mice, control (C), radiation alone (RT), thymosin alpha-1 plus radiation (T+RT), were entered into the study. The weight and mortality of mice, pleural effusion, quantity of protein and cell count in the bronchoalvealar lavage (BAL) and pulmonary fibrosis score were evaluated as the outcome measures. Results The mortality ratio of the T+RT and RT groups were 3/14, 2/10, respectively. The time of death were all in the 23-24 weeks after radiotherapy. There was no pleural effusion in the T+RT group other than 2/2 occured in RT group. The quantity of protein, cell number and neutrophil number in the BAL and lung coefficient in mice of T+RT group were remarkably lower than that of RT group, but the BALF macrophages number was remarkably higher than that in RT group in the 8 weeks. The quantity of protein, cell number, neutrophil number and macrophages number in the BAL, lung coefficient, the scores of lung fibrosis in mice of T+RT group were significantly lower than that of RT group in the 24 weeks. All test data were lowest in mice of C group. And there was no obvious pulmonary fibrosis in the mice of C group. Conclusion Thymosin alpha-1 could relieve radiation-induced acute and late pulmonary injuries