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Concurrent chemoradiation for cervical cancer: Comparison of LDR and HDR brachytherapy.

ABSTRACT: PURPOSE:To compare clinical outcomes between low-dose-rate (LDR) brachytherapy and high-dose-rate (HDR) brachytherapy for cervical cancer patients. METHODS AND MATERIALS:All consecutive newly diagnosed cervical cancer patients undergoing pretreatment 18-fluorodeoxyglucose positron emission tomography imaging and treated with curative-intent definitive chemoradiation from 1997 to 2016 at a U.S. academic center were included. Brachytherapy boost was LDR or HDR 2D treatment planning from 1997 to 2005 and HDR with MR-based 3D planning from 2005 to 2016. Local control (LC), cancer-specific survival (CSS), and late bowel/bladder complications were evaluated. RESULTS:Tumor stages were International Federation of Gynecology and Obstetrics IB1-IIB (n = 457; 75%) and III-IVA (n = 152; 25%). Brachytherapy was LDR for 104 patients and HDR for 505 patients. Concurrent weekly cisplatin was administered to 536 patients (88%). With median followup of 9.4 years, there was no difference in LC (p = 0.24) or CSS (p = 0.50) between LDR and HDR brachytherapy. Cox multivariable regression showed that only International Federation of Gynecology and Obstetrics stage III-IVA (HR=2.4, p = 0.004) was associated with worse LC. A propensity-matched cohort (90 LDR vs. 90 HDR) was created, and the 5-year LC rates were 88% LDR and 82% HDR, p = 0.26; 5-year CSS rates were 66% LDR and 58% HDR, p = 0.19; 5-year grade ?3 bowel/bladder toxicities were 23% LDR and 16% HDR, p = 0.44. For all patients, the 5-year late toxicity in stage III-IVA patients was higher with LDR 47% vs. HDR 15%, p = 0.03, with no difference in LC, 86% and 75%, respectively (p = 0.09). CONCLUSIONS:There was no difference in LC with either LDR or HDR brachytherapy. The late complication rate was reduced with HDR and 3D-planned brachytherapy compared to LDR and 2D-planned brachytherapy.

SUBMITTER: Lin AJ

PROVIDER: S-EPMC7477730 | biostudies-literature | 2019 May - Jun

REPOSITORIES: biostudies-literature

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Concurrent chemoradiation for cervical cancer: Comparison of LDR and HDR brachytherapy.

Lin Alexander J AJ Samson Pamela P Zoberi Jacqueline J Garcia-Ramirez Jose J Williamson Jeffrey F JF Markovina Stephanie S Schwarz Julie J Grigsby Perry W PW

Brachytherapy 20190407 3

<h4>Purpose</h4>To compare clinical outcomes between low-dose-rate (LDR) brachytherapy and high-dose-rate (HDR) brachytherapy for cervical cancer patients.<h4>Methods and materials</h4>All consecutive newly diagnosed cervical cancer patients undergoing pretreatment 18-fluorodeoxyglucose positron emission tomography imaging and treated with curative-intent definitive chemoradiation from 1997 to 2016 at a U.S. academic center were included. Brachytherapy boost was LDR or HDR 2D treatment planning ...[more]

PMID: 30971370

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Project description:The purpose of this study was to evaluate adaptive daily planning for cervi-cal cancer patients who underwent high-dose-rate intracavitary brachytherapy (HDR-BT) using comprehensive interfractional organ motion measurements. This study included 22 cervical cancer patients who underwent 5 fractions of HDR-BT. Regions of interest (ROIs) including high-risk clinical tumor volume (HR-CTV) and organs at risk (OARs) were manually contoured on daily CT images. All patients were clinically treated with adaptive daily plans (ADP), which involved ROI delineation and dose optimization at each treatment fraction. Single treatment plans (SP) were retrospectively generated by applying the first treatment fraction's dwell times adjusted for decay and dwell positions of the applicator to subsequent treatment fractions. Various existing similarity metrics were calculated for the ROIs to quantify interfractional organ variations. A novel similarity (JRARM) score was established, which combined both volumetric overlap metrics (DSC, JSC, and RVD) and distance metrics (ASD, MSD, and RMSD). Linear regression was performed to determine a relationship between interfractional organ varia-tions of various similarity metrics and D2cc variations from both plans. Wilcoxon signed-rank tests were used to assess ADP and SP by comparing EQD2 D2cc (?/? = 3) for OARs. For interfractional organ variations, the sigmoid demonstrated the greatest variations based on the JRARM, DSC, and RMSD metrics. Comparisons between paired ROIs showed differences in metrics at each treatment fraction. RVD, MSD, and RMSD were found to be significantly correlated to D2cc varia-tions for bladder and sigmoid. The comparison between plans found ADP provided lower EQD2 D2cc of OARs than SP. Specifically, the sigmoid demonstrated sta-tistically significant dose variations (p = 0.015). Substantial interfractional organ motion occurs during HDR-BT based on comprehensive measurements and may significantly affect D2cc of OARs. Adaptive daily planning provides improved dose sparing for OARs compared to single planning with the extent of sparing being different among OARs.

Project description:IntroductionIn locally advanced cervical cancer, nodal, local and distant relapse continue to be significant patterns of relapse. Therefore, strategies to improve the efficacy of chemoradiation are desirable such as biological pathway modifiers and immunomodulating agents. This trial will investigate the impact of nelfinavir, a protease inhibitor that targets the protein kinase B (AKT) pathway on disease-free survival (DFS).Methods and analysisRadiosensitising effect of nelfinavir in locally advanced carcinoma of cervix is a single-centre, open-label, parallel-group, 1:1 randomised phase-III study. Patients aged over 18 years with a diagnosis of carcinoma cervix stage III are eligible for the study. After consenting, patients will undergo randomisation to chemoradiation and brachytherapy arm or nelfinavir with chemoradiation and brachytherapy arm. The primary aim of the study is to compare the difference in 3-year DFS between the two arms. Secondary aims are locoregional control, overall survival, toxicity and quality of life between the two arms. Pharmacokinetics of nelfinavir and its impact on tumour AKT, programmed cell death ligand 1, cluster of differentiation 4, cluster of differentiation 8 and natural killer 1.1 expression will be investigated. The overall sample size of 348 with 1 planned interim analysis achieves 80% power at a 0.05 significance level to detect a HR of 0.66 when the proportion surviving in the control arm is 0.65. The planned study duration is 8 years.Ethics and disseminationThe trial is approved by the Institutional Ethics Committee-I of Tata Memorial Hospital, Mumbai (reference number: IEC/0317/1543/001) and will be monitored by the data safety monitoring committee. The study results will be disseminated via peer-reviewed scientific journals, and conference presentations. Study participants will be accrued after obtaining written informed consent from them. The confidentiality and privacy of study participants will be maintained.Trial registration numberThe trial is registered with Clinical Trials Registry-India (CTRI/2017/08/009265) and ClinicalTrials.gov (NCT03256916).

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Concurrent chemoradiation for cervical cancer: Comparison of LDR and HDR brachytherapy.

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Concurrent chemoradiation for cervical cancer: Comparison of LDR and HDR brachytherapy.

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