Late Course Accelerated Hyperfractionated Radiotherapy Research Articles

Late-course accelerated Hyperfractionation vs. Conventional Fraction Radiotherapy under precise technology plus Concurrent Chemotherapy for Esophageal Squamous Cell Carcinoma: comparison of efficacy and side effects

Background: The accelerated reproliferation of esophageal squamous cell carcinoma (ESCC) after radiation contributes to conventional fraction radiotherapy (CFRT) failure. Late course accelerated hyperfractionated radiotherapy (LCAHFRT) can improve the long-term survival of esophageal cancer patients in China but is associated with a high rate of side effects due to the large exposure field of two-dimensional treatment and drug toxicity. Intensity-modulated radiotherapy (IMRT) can increase the tumor dose while decreasing the normal tissue dose. Therefore, we compared the outcomes and side effects of LCAHFIMRT plus concurrent chemotherapy (CT) and CFIMRT plus CT for ESCC.Methods and Materials: Between 2013 and 2016, 114 eligible patients with ESCC were recruited and randomly assigned to receive LCAHFIMRT+CT (58 patients) or CFIMRT+CT (56 patients) by a linear accelerator (6-MV X-ray) under image guidance. Two cycles of CT with cisplatin and docetaxel were also administered.Results: The complete response (CR) rates were 79.3% and 61.8% in the LCAHFIMRT+CT and CFIMRT+CT groups, respectively (P=0.041). The median duration of local control times was 31.0±1.9 months for the LCAHFIMRT+CT group and 24.0±3.3 months for the CFIMRT+CT groups,and the 1-, 2-, and 3-year local control rates were 86.2%, 63.8%, and 41.4% and 85.7%, 51.8%, and 32.1% for the LCAHFIMRT+CT and CFIMRT+CT groups (P=0.240), respectively. The median survival times were 34.0±1.1 months for the LCAHFIMRT+CT group and 28.0.0±3.7 months for the CFIMRT groups,and the 1-, 2-, and 3-year survival rates were 87.9%, 74.1%, and 44.8% and 87.5%, 60.7%, and 39.3% for the LCAHFIMRT+CT and CFIMRT+CT groups, respectively (P=0.405). The incidence of side effects was not significantly different between the two groups. Local recurrence and uncontrolled disease resulted in more deaths in the CFIMRT+CT group than in the LCAHFIMRT+CT group (58.9% vs. 39.7%) (P=0.040).Conclusion: For ESCC patients, LCAHFRT delivered by image-guided intensity-modulated techniques Plus Concurrent Chemotherapy with cisplatin and docetaxel keeps safety and high CR rate, as well as local control and long-term survival rates.

Analysis of Body Weight Loss and Influence Factors During Intensity-modulated Radiotherapy for Patients with Nasopharyngeal Carcinoma

Objective To investigate body weight loss and influence factors during intensity-modulated radiotherapy(IMRT) in patients with nasopharyngeal carcinoma(NPC).Methods To explore body weight and BMI variation and influence factors,body weight and body mass index(BMI) change analysis were done retrospectively for 57 NPC patients during IMRT.Results In 57 NPC patients treated by IMRT,the pre-radiotherapy and post-radiotherapy average body weight were(60.4±9.4)kg and(55.1±8.7)kg(P=0.0025),body weight loss ranged from 17 kg to-0.5 kg,and average BMI of pre-radiotherapy and post-radiotherapy were(22.8±3.5)kg/m2,(20.8±3.1)kg/m2(P=0.0017),ranged from 6.0 kg/m2 to-0.2 kg/m2,respectively.To the end of radiotherapy,93.0% patients lost weight at different levels,the mean percentage of weight loss was 8.4% and ranged from 23.4% to-0.7%,35.1% patients lost weight over 10% and 68.4% patients lost weight over 5.0%.Univariate multi-factor analysis of variance showed that the WHO pathological grade,AJCC6th stage,performance status(PS),concurrent chemotherapy and late course accelerated hyperfractionated radiotherapy(LCAFR) had no statistical influence on body weight and BMI loss,but patients with age older than 50 years or BMI greater than 25 kg/m2 or body weight more than 60 kg lost body weight and BMI more than others(P0.05).Linear regression analysis showed that average radiation dose weekly and the average body weight weekly were significantly negatively correlated(R2=-0.996,P0.001).Conclusion Body weight loss is widespread in NPC patients during IMRT.The age,pre-radiotherapy body weight and BMI,radiation dose maybe have more impact on body weight and BMI loss significantly rather than the gender,WHO pathological grade,AJCC6thstage,performance status,concurrent chemotherapy and late course accelerated hyperfractionated radiotherapy in NPC patients with IMRT.

Elective lymph node irradiation late course accelerated hyper-fractionated radiotherapy plus concurrent cisplatin-based chemotherapy for esophageal squamous cell carcinoma: a phase II study

BackgroundIn this phase II study, we evaluated the efficacy, toxicity, and patterns of failure of elective lymph node irradiation (ENI) late course accelerated hyper-fractionated radiotherapy (LCAHRT) concurrently with cisplatin-based chemotherapy (CHT) for esophageal squamous cell carcinoma (ESCC).MethodsPatients with clinical stage II-IVa (T1-4N0-1M0 or M1a) ESCC were enrolled between 2004 and 2011. Radiation therapy (RT) comprised two courses: The first course of radiation covered the primary and metastatic regional tumors and high risk lymph nodal regions, given at 2 Gy per fraction for a dose of 40 Gy. In the second course, LCAHRT was delivered to the boost volume twice a day for an additional 19.6 Gy in 7 treatment days, using 1.4 Gy per fraction. Two cycles of CHT were given at the beginning of RT.ResultsThe median age and Karnofsky performance status were 63 years and 80, respectively. The American Joint Committee on Cancer stage was II in 14 (20.6%) patients, III in 32 (47.1%), and IVa in 22 (32.3%). With a median follow-up of 18.5 months, the overall survival at 1-, 3-, 5-year were 75.5%, 46.5%, 22.7% for whole group patients, versus 78.6%, 49.4%, 39.9% for patients with stage II–III. The patterns of first failure from local recurrence, regional failure, and distant metastasis were seen in 20.6%, 17.6%, and 19.1%, respectively. The most frequent acute high-grade (≥ 3) toxicities were esophagitis and leucopenia, occurred in 26.4% and 32.4%.ConclusionsENI LCAHRT concurrently with CHT was appeared to be an effective regimen for ESCC patient with a favorable and tolerated profile. Further observation with longer time and randomized phase III trial is currently underway.Trial registrationChiCTR-TRC-09000568

Clinical observation of improved late course accelerated hyperfractionated radiotherapy with concurrent chemotherapy for locally advanced esophageal squamous cell carcinom

Objective To assess the efficacy and the adverse effects of improved late course accelerated hyperfractionated radiotherapy (LCAHRT) combined with cisplatin-based chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC).Methods 68 Patients with pathologically confirmed ESCC were enrolled.Conventional fractionation was implemented to 40 Gy/20 fractions,followed by LCAHRT delivered 2 fractions of 1.4 Gy with an interval of 6-8 hours per day to 14 fractions,thus the total dose was 59.6 Gy.Two cycles of cisplatin-based chemotherapy were administered concurrently,followed by two more cycles.The short-term efficacy of treatment,overall survival for 1-,3-,5-year,and treatment-related toxicity were evaluated.Results All patients successfully completed LCAHRT and the overall response rate was 91.6％ (62/68).The overall survival rate of 1-,3-,and 5-year was 75.5％,46.5％,22.7％,respectively.The incidence of radiation esophagitis (grade 3 or greater) was 26.4％,and no patients developed grade 3 or worse radiation pneumonitis.The radiation-induced skin injury were most of grade 0 or 1.Grade 3 of leucopenia and neutropenia were observed in 29.4％ and 7.4％ of patients,respectively,and grade 4 were both in 2.9％.During long-term follow-up,no esophageal stenosis and severe pulmonary fibrosis was developed except for two cases(2.9％)of esophageal mediastinal fistula.Conclusion Late course accelerated hyperfractionated radiotherapy combined with chemotherapy yields promising long-term survival,with lower treatment-related toxicity for patients of locally advanced esophageal squamous cell carcinoma. Key words: Esophageal neoplasms; Radiotherapy; Cisplatin; Survival rate; Adverse effects

Non-conventional radiotherapy versus conventional radiotherapy for inoperable non-small-cell lung cancer: A meta-analysis of randomized clinical trials.

The aim of this study was to evaluate the efficacy and safety of non-conventional radiotherapy versus conventional radiotherapy for inoperable non-small-cell lung cancer and to conduct a meta-analysis to compare these two methods of radiotherapy for inoperable NSCLC. We included randomized controlled trials, which were compared with non-conventional radiotherapy with or without concurrent chemotherapy versus conventional radiotherapy with or without concurrent chemotherapy. Meta-analysis of 13 randomized controlled trials with a total of 2206 patients showed that the non-conventional radiotherapy group could significantly improve the objective response rate (OR 1.68, 95% confidence intervals (CI) 1.19-2.37) and overall survival of up to 1-year (OR 1.30, 95% CI 1.09-1.54), 2-year (OR 1.41, 95% CI 1.17-1.70), 3-year (OR 1.55, 95% CI 1.24-1.94), 4-year (OR 1.60, 95% CI 1.20-2.15), 5-year (OR 1.63, 95% CI 1.11-2.38); and local control rate in 1-year (OR 1.35, 95% CI 1.09-1.68), 2-year (OR 1.57, 95% CI 1.23-1.99), 3-year (OR 1.45, 95% CI 1.10-1.91) compared with the conventional radiotherapy group. With regard to the side effects, non-conventional radiotherapy was more likely to result in level III and IV radioactive esophagitis (OR 1.64, 95% CI 1.09-2.46), but there was no significant difference in the incidence of radioactive pneumonitis (OR 0.96, 95% CI 0.67-1.39). In the subgroup analysis we found late course accelerated hyperfractionated radiotherapy (LCHRT) could obviously improve 1-year OS (OR 2.29, 95% CI 1.29-4.06), 2-year OS (OR 4.22, 95% CI 2.03-8.77), 3-year OS (OR 2.49, 95% CI 1.24-5.02) and Objective response rate (OR 2.38, 95% CI 1.17-4.83). However, hyperfractionated radiotherapy (HRT) and accelerated hyperfractionated radiotherapy (AHRT) could not improve 1-, 2-, 3-year OS or OR compared with conventional fractionation radiotherapy. Our findings indicate that NCRT could improve OR, reduce the risk of death by 1-5 years, and significantly increase level III and IV radioactive esophagitis incidence. The late course accelerated hyperfractionated radiotherapy (LCAHRT) group seemed to improve compared with the AHRT and conventional radiotherapy (CRT) groups.

Evaluation of whole-course three-dimensional conformal radiotherapy combined with late-course accelerated hyperfractionated radiotherapy for esophageal carcinoma patients

Objective The aim of the study was to evaluate the therapeutic effect and safety of whole-course three-dimensional conformal radiotherapy (3DCRT) combined with late-course accelerated hyperfractionated radiotherapy (LCAFR) on patients with esophageal carcinoma.

Meta-analysis of late course accelerated hyperfractionated radiotherapy combined with FP chemotherapy for esophageal carcinoma

Although there are many randomized clinical trials of late course accelerated hyperfractionated radiotherapy (LCAHFR) combined with FP chemotherapy for esophageal cancer, the efficacy and toxicity are controversial. This study was to evaluate the efficacy and toxicity of LCAHFR combined with FP chemotherapy in treating esophageal cancer. Reports of randomized clinical trials on LCAHFR combined with FP chemotherapy for esophageal cancer published between January 1999 and January 2009 were researched through Wanfang, CNKI, and PubMed databases. RevMan4.2 software was used for Meta-analysis. Twenty-one reports, including 2030 patients, were included in the meta-analysis. Of the 2030 patients, 1006 underwent LCAHFR (LCAHFR group), and 1024 underwent LCAHFR combined with FP chemotherapy (combination group). Compared with those of the LCAHFR group, the 1-, 2-, 3-, 5-years survival rates and 1-, 2-, 3-year local control rates of the combination group were significant increased, and the acute toxicity was also increased, but chronic toxicity showed no significant difference. LCAHFR combined with FP chemotherapy can improve the survival rate and the local control rate of the patients with esophageal cancer. The increased acute toxicity need to be concerned, whereas the chronic toxicity needs a long-term observation.

Comprehensive parameters in predicting radiation pneumonitis in advanced stage non-small-cell lung cancer treated with three-dimensional conformal or intensity-modulated radiation therapy

Objective To analyze relation of comprehensive parameters of the dose-volume V5,V10 and V20 with radiation pneumonitis (RP) in patients with advanced stage non-small-cell lung cancer (NSCLC) treated with three-dimensional conformal (3DCRT) or intensity-modulated radiation therapy (IMRT).Methods Data of 90 patients with histologically proved NSCLC treated with 3DCRT or IMRT between November 2006 and July 2009 were collected.The median radiation dose of 70 Gy (range, 61 - 80 Gy) was delivered with late-course accelerated hyperfractionated radiotherapy (LAHRT).The V5 ,V10 ,V20,V30 and mean lung dose (MLD) were calculated from the dose-volume histogram system.The RP was evaluated according to the common toxicity criteria 3.0(CTC 3.0).Results The range of V5 ,V10 and V20 was 36% - 98%, 27% - 78% and 19% - 54%, respectively, with a median value of 66%, 48% and 31%, respectively.The RP of grade 1,2,3,4 and 5 was observed in 29,23,5,1 and 1 patients.The V5,V10 ,V20, contralateral V10, GTV,PTV, and numbers of fields were all significantly associated with RP of ≥grade 1 (χ2=2.04, 2.05, 2.01, 4.62, 6.50, 5.61, 5.61, and P= 0.044, 0.043, 0.047, 0.030,0.010,0.020,0.020).The V5, V10, V20, V30, and MLD were all significantly associated with RP of ≥ grade 2 (χ2= 2.05,2.20,2.96,4.96,5.20, and P = 0.040,0.030,0.000,0.030,0.020).In Logistic regression analysis, GTV was the only factor significantly associated with RP of ≥ grade 1 (χ2= 4.06, P =0.044).The V20 was the only factor significantly associated with RP of ≥grade 2(χ2=9.61,P=0.002).The RP of ≥grade 2 was significantly increased when V20 was more than 31%.The RP of ≥grade 2 was significantly increased when V20, V10 and V5 were more than 31%, 48% and 66%, respectively.The RP of ≥ grade 2 was significantly increased when V20 was more than 31% and V5 was more than 66%.Conclusions The comprehensive parameters combined with V5, V10 and V20 are effective in predicting RP. Key words: Carcinoma, non-small cell lung/radiotherapy; Radiotherapy, three-dimensional conformal or intensity-modulated; Radiotherapy, late-course accelerated hyperfraction; Radiation pneumonitis; Dose volume histogram

Late course accelerated hyperfractionated radiotherapy plus concurrent chemotherapy for squamous cell carcinoma of the esophagus: A phase III randomized study

Late course accelerated hyperfractionated (LCAF) radiotherapy (RT) is as effective as standard chemoradiotherapy for nonsurgical management of locally advanced esophageal squamous cell carcinoma (SCC). We have evaluated further the efficacy of concurrent LCAF RT and chemotherapy. In all, 111 eligible patients with esophageal SCC were randomized to receive LCAF alone (LCAF) or concurrent LCAF and chemotherapy (LCAT+CT) between March 1998 and July 2000. All patients received conventional fractionation irradiation of 1.8 Gy per day, to a dose of 41.4 Gy/23 fractions in 4-5 weeks, followed by accelerated hyperfractionated irradiation using reduced fields, 1.5 Gy/fractions twice a day, to a dose of 27 Gy in 18 days. Thus, the total dose was 68.4 Gy/41 fractions in 44 days. Fifty-four patients in the LCAF+CT arm had an additional four cycles of chemotherapy using cisplatin 25 mg/m(2) daily and fluorouracil (5-FU) 600 mg/m(2) daily on Days 1-3 every 4 weeks starting on the same day that LCAF was delivered. The median survival was 23.9 months (95% confidence [CI], 20.1-27.7) for the LCAF arm and 30.8 months (95% CI, 17.6-44.1) for the LCAF+CT arm, respectively. Survival rates at 1, 3, and 5 years of the LCAF arm were 77%, 39%, and 28%, respectively, while those of the LCAF+CT arm were 67%, 44%, and 40%, respectively (p = 0.310). Grades 3 and 4 acute toxicities occurred in 46% and 25% of the patients in the LCAF arm and the LCAF+CT arm, respectively; 6% of the patients in the combined arm had Grade 5 acute toxicities, whereas none was noted in the LCAF alone arm. Late course accelerated hyperfractionation was effective for locally advanced esophageal SCC. There was a trend toward better survival among patients who received intensified treatment with concurrent chemotherapy. Further randomized studies with a larger number of patients should be carried out, but additional measures must be taken to reduce the higher mortality rate due to chemotherapy-related acute toxicities.

Late-course accelerated hyperfractionated radiotherapy for localized esophageal carcinoma

Purpose To evaluate the long-term survival results and patterns of failure for localized carcinoma of the esophagus receiving late-course accelerated hyperfractionated (LCAF) radiotherapy (RT). Methods and materials We studied 201 patients with histologically confirmed squamous cell carcinoma of the esophagus who were treated with LCAF RT between August 1994 and January 2000. The design of the radiation fields was based on the diagnosis by computed tomography and barium examination. All patients received conventionally fractionated RT at 1.8 Gy/d, five fractions weekly for the first two-thirds of treatment to a dose of about 41.4 Gy in 23 fractions within 4–5 weeks. This was followed by LCAF RT using reduced fields, 1.5 Gy/fraction twice daily with a 6-h interval between fractions, to a dose of about 27 Gy within 9 days. Thus, the total dose was 68.4 Gy in 41 fractions within 44 days. Results The incidence of Grade 3–5 acute radiation-induced bronchitis was 4.0% (8 cases), 3.0% (6 cases), and 0%, respectively. The incidence of Grade 3–5 acute radiation-induced esophagitis was 14.9% (30 cases), 0.5% (1 case), and 0%. Ten patients (5%) died of late complications. The 1-year, 3-year, and 5-year overall survival rate was 73%, 34%, and 26%, respectively. The 1-year, 3-year, and 5-year local control rate was 77%, 58%, and 56%, respectively. The main site of first failure was locoregional failure and distant metastasis (including lymph node metastasis from regional recurrence). Of 201 patients, 77 (38.4%) had local disease alone or with distant metastasis as the first failure, and 70 patients (34.9%) had distant metastasis and/or lymph node metastasis alone or with local failure as the first failure. Conclusion The LCAF regimen offers similar local control and survival to standard chemotherapy plus RT, such as was delivered in the Radiation Therapy Oncology Group studies 85-01 and 94-05.