Leonel Varela Cagetti

The influence of time and implants in high-dose rate image-guided adaptive brachytherapy for locally advanced cervical cancer

To compare the clinical outcomes of two different schedules of modern image-guided adaptive brachytherapy (IGABT) in patients underwent chemoradiotherapy (CCRT) and high-dose rate (HDR) brachytherapy (BT) for locally advanced cervical cancer treated (LACC) METHODS AND MATERIALS: Data from medical records of all consecutive patients with histologically proven cervical cancer (FIGO 2018 stage IB-IVA) treated by HDR-BT after CCRT at our institution between 2016 and 2021 were reviewed. Two hundred and 8 patients with LACC FIGO 2018 stages (IB 20.7%; II 26.5%, III 51%, IVA 1.9%) underwent brachytherapy at our institution. Depending on initial clinical features of disease and the clinical response to CCRT, HDR-BT was delivered with one implant (BT1i) or two implants (BT2i) in 39% and 61% of patients respectively. FIGO stages (≥IIB) were 63% vs. 78% for BT1i and BT2i patient group respectively. Combined brachytherapy technique [endocavitary/interstitial (IC/IS)] was required in 14.8% vs. 68.5% for BT1i and BT2i respectively. With a median follow-up of 32.5 months (95% confidence interval, [29.7-35.8]), local relapse was observed in sixteen patients: 8 patients (3.8%) had local (exclusive) relapse and 8 patients (3.8%) had locally persistent and progressive disease, without significant difference for each BT modality group (p = 0.27), even if BT2i group had more aggressive initial disease. The estimated 3-year disease free survival and overall survival for the entire population was 69% (95% confidence interval, [62-75%]) and 88% (95% confidence interval, [82-92%]) respectively. There was a significant difference in the incidence of global toxicity grade G≥2 in favour to the BT2i group (p = 0.026). HDR brachytherapy delivered with a long time interval between fractions, two implants, and combined IC/IS brachytherapy is the best way to ensure local control and to perform IGABT with low toxicity, even in advanced stages of disease.

Lessons from radiochemotherapy and modern image-guided adaptive brachytherapy followed by hysterectomy

To analyze the clinical outcomes and the safety of radiochemotherapy (RCT) and image-guided adaptive brachytherapy (IGABT) and to evaluate the impact of hysterectomy (HT) as completion of treatment for cervical cancer. 145 patients with locally advanced cervical cancer were treated at our institution. Patients underwent RCT and IGABT, then hysterectomy (HT) as completion of treatment was performed, with the exception of patients with surgical contraindications, para aortic metastatic disease or patients who refused surgery. Clinical outcomes and morbidity were retrospectively reviewed in both groups. Local relapse free survival (LRFS), pelvic relapse free survival (PRFS) and overall survival (OS) were analyzed. Completion HT was performed in 90 (62.1%) patients. Complete histological response and microscopic disease were found in 77 patients (85.6%). Local relapse was observed in 14 patients (9.6%) without differences between completion HT group and the definitive RCT and IGABT group (Odds Ratio OR = 1.73 [0.57-5.23], p = 0.33). The estimated 3-year LRFS and PRFS for the entire population were respectively 90% [84%-94%] and 93% [87%-96%], with no significant differences between them (respectively Hazard Ratio HR = 0.57 [0.20-1.64], p = 0.30 and HR = 0.37 [0.10-1.31], p = 0.12). The estimated 3-year OS rate for the whole population was 84% [75%-91%] with no significant differences between groups (HR = 0.81 [0.32-2.06], p = 0.65). Regarding morbidity, grade ≥ 2 vaginal toxicity was more frequent in the definitive RCT and IGABT group (43.6% vs 26.7%, p = 0.04). All grade 4 toxicity events were reported in the completion HT group. Due to high severe toxicity, RCT and IGABT with dose escalation followed by completion hysterectomy don't seem compatible. No benefit and increased severe late morbidity were observed. Combined intracavitary/interstitial technique is mandatory in large target volume at brachytherapy.