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

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.

Safety and efficacy of single insertion accelerated MR-image guided brachytherapy following chemo–radiation in locally advanced cervix cancer: modifying our EMBRACE during the COVID pandemic

“…and Patient 2 (16.5 cc.). Mean (SD) TRAK (total reference air-kerma rate at 1 m) was also acceptable/low at 0.0034 Gy (0.0016) and well within the 0.02 Gy associated with significant late bowel morbidity by Bockel et al [ 45 ].…”

“…TRAK (≥ 0.02 Gy), residual HRCTV (> 25 cc. ), and prior “active smoking” have been identified as risk factors for emergent bowel toxicity in a large multivariate analysis by Bockel et al [ 45 ]. Although a prior tobacco smoker (10–20 pack-years), her EBRT was well within EMBRACE dose-volume D95 guidelines for extended-field radiation therapy (< 3500 cc): PTV V43Gy (2407.3 cc).…”

Excess dose-related parameters (Vex, Rex, and iRex): novel predictors and late toxicity correlations in cervical cancer image-guided adaptive brachytherapy

“…There was no significant correlation between ISV and GI toxicity. In previous studies, which have reported significant correlation [ 10 , 11 , 12 ], ISV or TRAK and toxicity correlation may have been confused by the dose outside target, not the whole dose volume.…”

“…In a retrospective series of 642 cervical cancer cases, a dose volume defined by the half product of height, width, and thickness (HWT), demonstrated significant correlations with rectal and soft tissue complications [ 10 ]. Total reference air kerma (TRAK), on which ISVs are based, was shown to correlate with morbidity [ 11 , 12 ]. For ISV, a large retrospective study of 1,253 patients failed to demonstrate any correlation between 60 and 160 Gy ISVs and tumor control [ 13 ].…”

Iodine-125 brachytherapy suppresses tumor growth and alters bone metabolism in a H1299 xenograft mouse model

“…The continuous development of novel cancer treatments has led to an increase in the use of brachytherapy (also known as internal radiation therapy), as a complementary technique to conventional surgery approaches, such as chemotherapy and radiotherapy. This approach has been used in the treatment of a variety of malignant tumors, such as bladder cancer, cervical carcinoma, oral cancer and lung cancer [6][7][8][9][10] . At present, I-125 seeds are used in numerous applications due to a high killing radius and relative biological effect.…”