HYPOCx-iRex (TCTR20210812003) A Phase II RCT: 44 Gy/20F VS 45 Gy/25F CCRT in Cervical Cancer: Six-month Post-RT Update

Abstract

Hypofractionation for definitive concurrent chemoradiation (CCRT) in locally advanced cervical cancer (LACC) may increase RT efficacy but scarce in data. Early results of HYPOCx-iRex trial at 3-mo follow-up (F/U) time showed a non-statistically significant small rise but auto-resolved acute GI toxicity of HYPO 44 Gy/20F arm compared to CVRT 45 Gy/25F arm, yet significantly retracted overall treatment time and time to brachytherapy without compromised GTV reduction or tumor response. This prespecified interim analysis at 6-mo post-RT of the first 20 patients was intended to prove non-inferior late toxicity, oncologic outcome and pattern of failure of HYPO in addition to previous ESTRO2023 abstract. Patients with LACC were enrolled since July 2021. ≥3 Pelvic LN or at/above common iliac were excluded to omit paraaortic RT. Open-label randomization was performed for IMRT/VMAT to HYPO for 44 Gy/20F to whole pelvis and 53 Gy/20F SIB to gross LN in five-day-a-week fractions, and for CVRT 45 and 55 Gy/25F, with concurrent weekly cisplatin 40 mg/m2. Target contour and planning dose of EBRT and IGABT were adapted and biologically converted from EMBRACE-II. Indirect ratio of excess dose volume (iRex; DOI: 10.5114/jcb.2020.100377) as a complimentary low-dose conformity index to D2cc-based IGABT was explored, but analysis was out of this abstract scope. Non-inferiority margin of 9% 5-yr GI toxicity difference of HYPO and CVRT with one-sided α = 0.5 and 1-β = 0.8 yielded 40-patient sample size for toxicity screening. Adopting 9% margin, analysis at 6-mo post-RT of the first 20 patients were done with descriptive and survival analysis. Twenty-nine patients with median F/U time from start of RT of 8 months were included. Non-significant difference of IGABT dose was seen. Median post-RT time were 7 months with non-significant difference in 6-mo crude, late and persistent (LAPER), or cumulative GI and GU toxicity. Unfortunately, difference of -0.07 [95% CI -0.47 to +0.32] cumulative GI toxicity exceeded margin of +0.09, but the p value is greater than 0.5 (cut-off for go or no go for phase III study). No significant oncologic outcome nor pattern of failure difference were shown. HYPO 44 Gy/20F showed trend of non-significant difference in 6-mo toxicity nor oncologic outcome. The unmet non-inferior margin should be re-evaluated at trial completion for further implementation.