Total Reference Air Kerma is Associated with Late Bowel Morbidity in Locally Advanced Cervical Cancer Patients Treated with Image-Guided Adaptive Brachytherapy

J Clin Med. 2019 Jan 21;8(1):125. doi: 10.3390/jcm8010125.

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.

Keywords: bowel; cervical cancer; dose-volume parameters; image-guided adaptive brachytherapy; morbidity; normal tissue complication probability; sigmoid; total reference air kerma.