Abstract
No dose volume parameter has been identified to predict late bowel toxicities in locally advanced cervical cancer (LACC) patients treated with image-guided adaptive brachytherapy. We examined the incidence of bowel toxicities according to the total reference air kerma (TRAK) in 260 LACC patients. In both univariate and multivariate analysis, late morbidity positively correlated with a TRAK ≥2 cGy (centigray) at 1 meter, emphasizing the importance of this parameter in term of late bowel morbidity. Objective: There is no validated dose volume parameter to predict late bowel toxicities in cervical cancer patients treated with image-guided adaptive brachytherapy (IGABT). We examined the incidence of bowel toxicities according to the TRAK, which is proportional to the integral dose to the patients. Material/Methods: Clinical data of 260 LACC patients treated with curative intent from 2004 to 2016 were examined. Patients received chemoradiation plus a pulse-dose rate IGABT boost. The relationship between TRAK and morbidity was assessed by Kaplan-Meier method, log-rank tests, and Cox proportional-hazards model on event-free periods. Results: Median follow-up was 5.2 years (SE (Standard Error): 0.21). Probability of survival without late bowel toxicity Grade ≥ 2 rate for patients without recurrence (n = 227) at 5 years was 66.4% (SE 3.7). In univariate analysis, bowel and/or sigmoid dose/volume parameters were not significant. Late morbidity positively correlated with active smoking, CTVHR volume >25 cm3, and a TRAK ≥2 cGy at 1 meter. In multivariate analysis, the following factors were significant: Active smoking (p < 0.001; HR: 2.6; 95%CI: 1.4–5.0), and the TRAK (p = 0.02; HR: 2.4; 95%CI: 1.2–5.0). Conclusion: TRAK was associated with late bowel toxicities probability, suggesting that the integral dose should be considered, even in the era of IGABT.
Highlights
The standard definitive treatment for locally advanced cervical cancer (LACC) relies on chemoradiation followed by a brachytherapy boost [1,2,3]
The implementation of image-guided adaptive brachytherapy (IGABT) has yielded to an increased capability to perform isodose optimization, allowing dose escalation to the clinical target volumes (CTV) while ensuring a limited dose to organs at risk (OARs), which can be accurately delineated for dose volume histograms (DVH) analysis
Despite advances in external beam radiotherapy (EBRT) techniques, including intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT), bowel toxicity remains a major issue after pelvic irradiation [9]
Summary
The standard definitive treatment for locally advanced cervical cancer (LACC) relies on chemoradiation followed by a brachytherapy boost [1,2,3]. In the last International Commission on Radiation Units (ICRU) guidelines for cervical cancer brachytherapy, consensual OARs dose/volume parameters have been proposed for treatment optimization [4]. One hypothesis is that the mobility of bowel makes its dose/volume parameters highly uncertain and the doses reported at time of image acquisition may not reflect the actual dose delivered [18,19,20]. Another hypothesis is that most frequent bowel morbidities (e.g., diarrhea) may be dependent on low doses regions [12,21,22]
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