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

by Selleckchem | Aug 13 2023

Background: Utero-vaginal brachytherapy (BT) is an irreplaceable care component for the curative treatment of locally advanced cervix cancer (LACC). Magnetic Resonance Imaging (MRI)-image guided adaptive BT (IGABT) using the GYN-GEC-ESTRO EMBRACE guidelines is the international care standard. Usually following chemo-radiation therapy (CRT), IGABT has high proven utility in LACC but requires significant health system resources. Timely access was disrupted by the COVID-19 pandemic which challenged us to re-design our established IGABT care pathway.

Methods: From April 2020 consecutive patients with LACC were enrolled after CRT in a single arm exploratory non-inferiority study of a modified IGABT (mIGABT) protocol. This delivered an iso-effective IGABT dose (39.3 Gy: EQD2: α/β10Gy concept) over a 24-h period during a single overnight hospitalisation.

Results: Fourteen LACC patients received mIGABT from April 2020 to March 2022. Median age was 62.5 years (37-82 years). LACC histology was primary squamous (9/14) or adeno-carcinoma (5/14). International Federation of Gynaecology and Obstetrics (FIGO) 2018 stages ranged from IB1/2 (N = 3), IIA1/IIB (5), IIIB (2), IIIC1/2 (4) with mean ± standard deviation (SD) gross tumour volume-at-diagnosis (GTV_D) of 37.7 cc ± 71.6 cc. All patients achieved complete metabolic, clinical, and cytologic cancer response with CRT and IGABT. High-risk HPV was cleared by 6-months. Complete MRI-defined cancer response before mIGABT (GTV_Fx1) was seen in 77% of cases (10/13). Only two women developed metastatic disease and one died at 12-months; 13 patients were alive without cancer at mean 20.3 ± 7.2 months follow-up. Actuarial 2-year overall survival was 93%. Compared with our pre-COVID IGABT program, overall mIGABT cost-saving in this cohort was USD 22,866. Prescribed dose covered at least 90% (D90) of the entire cervix and any residual cancer at time of BT (HRCTV_D90: high-risk clinical target volume) with 3-fractions of 8.5 Gy delivered over 24-h (22.8 ± 1.7 h). Total treatment time including CRT was 38 days. The mIGABT schedule was well tolerated and the entire cohort met EMBRACE recommended (EQD2: α/β10Gy) combined HRCTV_D90 coverage of 87.5 ± 3.7 Gy. Similarly, organ-at-risk (OAR) median: interquartile range D2cc constraints (EQD2: α/β3Gy) were EMBRACE compliant: bladder (65.9 Gy: 58.4-72.5 Gy), rectum (59.1 Gy: 55.7-61.8 Gy), and sigmoid colon (54.6 Gy: 50.3-58.9 Gy). ICRU recto-vaginal point dose was significantly higher (75.7 Gy) in our only case of severe (G4) pelvic toxicity.

Conclusions: This study demonstrated the utility of mIGABT and VMAT CRT in a small cohort with LACC. Loco-regional control was achieved in all cases with minimal emergent toxicity. Single insertion mIGABT was logistically efficient, cost-saving, and patient-centric during the COVID-19 pandemic.

Comments:

The study described the implementation and outcomes of a modified image-guided adaptive brachytherapy (IGABT) protocol, referred to as mIGABT, for the treatment of locally advanced cervical cancer (LACC) during the COVID-19 pandemic. The standard IGABT using MRI guidance was disrupted due to limited health system resources during the pandemic, leading to the need for a re-designed care pathway.

Between April 2020 and March 2022, a total of 14 LACC patients received mIGABT following chemo-radiation therapy (CRT). The median age of the patients was 62.5 years, and the majority had squamous cell carcinoma (9 out of 14) or adenocarcinoma (5 out of 14). The patients were classified based on the International Federation of Gynaecology and Obstetrics (FIGO) 2018 staging system, with a range of stages from IB1/2 to IIIC1/2. The average gross tumor volume at diagnosis was 37.7 cc.

All patients achieved a complete response to CRT and IGABT, as confirmed by metabolic, clinical, and cytologic evaluations. High-risk human papillomavirus (HPV) was cleared within 6 months. Complete cancer response, as determined by MRI before mIGABT, was observed in 77% of cases. The overall survival rate at 2 years was 93%, with 13 patients alive without cancer at a mean follow-up of 20.3 months. Only two patients developed metastatic disease, and one patient died at 12 months.

The mIGABT protocol involved delivering an iso-effective dose (39.3 Gy, equivalent dose in 2 Gy fractions with an alpha/beta ratio of 10 Gy) over a 24-hour period during a single overnight hospitalization. The prescribed dose covered at least 90% (D90) of the entire cervix and any residual cancer at the time of BT (high-risk clinical target volume, HRCTV_D90). The treatment schedule, including CRT, lasted for a total of 38 days.

The mIGABT protocol was cost-saving compared to the pre-COVID IGABT program, with a cost reduction of USD 22,866 in this cohort. The treatment was well tolerated by patients, and the overall toxicity was minimal. The dose constraints for organs at risk (OAR) were compliant with the EMBRACE guidelines, with acceptable median D2cc values for the bladder, rectum, and sigmoid colon. However, there was one case of severe pelvic toxicity (G4) observed, with a significantly higher recto-vaginal point dose (75.7 Gy) according to the International Commission on Radiation Units and Measurements (ICRU) guidelines.

In conclusion, the study demonstrated the feasibility and effectiveness of the mIGABT protocol combined with VMAT CRT in a small cohort of LACC patients. The modified protocol provided efficient and cost-saving treatment during the COVID-19 pandemic, ensuring loco-regional control with minimal emergent toxicity.