Purpose: Late radiation toxicity is a major dose-limiting factor in curative cancer radiation therapy. Previous studies identified several risk factors for late radiation toxicity, including both... Show morePurpose: Late radiation toxicity is a major dose-limiting factor in curative cancer radiation therapy. Previous studies identified several risk factors for late radiation toxicity, including both dose-volume factors and genetic predisposition. Herein, we investigated the contribution of genetic predisposition, particularly compared with dose-volume factors, to the risk of late radiation toxicity in patients treated with highly conformal radiation therapy. Methods and Materials: We included 179 patients with prostate cancer who underwent treatment with curative external beam radiation therapy between 2009 and 2013. Toxicity was graded according to the Common Terminology Criteria for Adverse Events version 4.0. Transcriptional responsiveness of homologous recombination repair genes and g-H2AX foci decay ratios (FDRs) were determined in ex vivo irradiated lymphocytes in a previous analysis. Dose-volume parameters were retrieved by delineating the organs at risk (OARs) on CT planning images. Associations between risk factors and grade >= 2 urinary and were performed using the highest toxicity grade recorded during the follow-up per patient. Results: The median follow-up period was 31 months. One hundred and one patients (56%) developed grade >2 late radiation toxicity. Cumulative rates for urinary and bowel grade >2 late toxicities were 46% and 17%, respectively. In the multivariable analysis, factors significantly associated with grade >2 late toxicity were transurethral resection of the prostate (P = .013), y-H2AX FDR <3.41 (P = .008), and rectum V70 >11.52% (P = .017). Conclusions: Our results suggest that impaired DNA double-strand break repair in lymphocytes, as quantified by y-H2AX FDR, is the most critical determining factor of late radiation toxicity. The limited influence of dose-volume parameters could be due to the use of increasingly conformal techniques, leading to improved dose-volume parameters of the organs at risk. = 2021 Elsevier Inc. All rights reserved. Show less
Purpose: The purpose of this study was to determine survival, local and distant control, toxicity, and prognostic factors in patients with stage III non-small cell lung cancer (NSCLC) treated with... Show morePurpose: The purpose of this study was to determine survival, local and distant control, toxicity, and prognostic factors in patients with stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiation therapy (CCRT).Methods and Materials: Consecutive patients with stage IIIA and IIIB NSCLC (N = 154) staged with (18) F-fluorodeoxyglucose positron emission tomography/ computed tomography were retrospectively selected (2005-2015). CCRT consisted of daily low-dose cisplatin (6 mg/m(2)) combined with 24 fractions of 2.75 Gy to a total dose of 66 Gy.Results: During a median follow-up period of 22 months (range, 1-92 months) the median overall survival was 36 months. The 1-, 2-, 3-, and 5-year survival rates were 79% (95% confidence interval [CI], 73%-86%), 61% (95% CI, 54%-70%), 52% (95% CI, 43%-60%), and 40% (95% CI, 31%-51%), respectively. The local relapse-free survival at 5 years was 55% (95% CI, 44%-69%). Metastasis-free survival at 5 years was 53% (95% CI, 44%-65%). The incidence of severe gastrointestinal disorders (grade 3-5) was 11%, among which grade 3 radiation esophagitis was 8.4%. The incidence of severe respiratory, thoracic, and mediastinal disorders (grade 3-5) was 8.4%, among which grade 3 radiation pneumonitis was 1.3%. Predictors of overall survival were lymph node gross tumor volume (GTV) (hazard ratio [HR], 1.007; 95% CI, 1.000-1.012) and sex (HR, 0.500; 95% CI, 0.320-0.870) in favor of women. Although lymph node GTV was a predictor of treatment toxicity (HR, 1.010; 95% CI, 1.000-1.013), tumor GTV was the predictor for distant metastasis during follow-up (HR, 1.002; 95% CI, 1.0011.003).Conclusions: CCRT with daily low-dose cisplatin for locally advanced stage III NSCLC resulted in promising overall survival (3-year survival rate of 52% and 5-year survival rate of 40%) with low toxicity. Lymph node GTV, tumor GTV, and sex were predictors of overall survival, treatment toxicity, and distant metastasis. (C) 2018 The Authors. Published by Elsevier Inc. Show less
Geijsen, E.D.; Reijke, T.M. de; Koning, C.C.; Vording, P.J.Z.V.S.; Rosette, J.J. de la; Rasch, C.R.; ... ; Crezee, J. 2015
Purpose: Despite intravesical therapy with immunotherapy or chemotherapy intermediate and high risk nonmuscle invasive bladder cancer is associated with a high risk of recurrence and progression to... Show morePurpose: Despite intravesical therapy with immunotherapy or chemotherapy intermediate and high risk nonmuscle invasive bladder cancer is associated with a high risk of recurrence and progression to muscle invasive bladder carcinoma. While intravesical hyperthermia combined with mitomycin C has proved effective to treat nonmuscle invasive bladder cancer, there is less experience with invasive regional 70 MHz hyperthermia and mitomycin C. Therefore, we examined the safety and feasibility of this treatment combination for intermediate and high risk nonmuscle invasive bladder cancer.Materials and Methods: Between 2009 and 2011, 20 patients with intermediate and high risk nonmuscle invasive bladder cancer were treated with intravesical mitomycin C (40 mg) combined with regional hyperthermia. Treatment consisted of 6 weekly sessions followed by a maintenance period of 1 year with 1 hyperthermia-mitomycin C session every 3 months. Regional hyperthermia was administered using a 70 MHz phased array system with 4 antennas. Toxicity was scored using CTC (Common Toxicity Criteria) 3.0.Results: The records of 18 of 20 patients could be analyzed. Median followup was 46 months. Of the 18 patients 15 (83%) completed the induction period of 6 treatments. Four patients (22%) discontinued treatment because of physical complaints without exceeding grade 2 toxicity. Toxicity scored according to CTC 3.0 was limited to grade 1 in 43% of cases and grade 2 in 14%. Mean T90 and T50 bladder temperatures were 40.6C and 41.6C, respectively. The 24-month recurrence-free survival rate was 78%.Conclusions: Treatment with regional hyperthermia combined with mitomycin C in patients with intermediate and high risk nonmuscle invasive bladder cancer is feasible with low toxicity and excellent bladder temperatures. Show less
Koning, C.C.E.; Blank, L.E.C.M.; Koedooder, C.; Os, R.M. van; Kar, M. van de; Jansen, E.; ... ; Pieters, B.R. 2012
