High-dose-rate brachytherapy boost for locally advanced cervical cancer: Oncological outcome and toxicity analysis of 4 fractionation schemes

Maud le Guyader; Daniel Lam Cham Kee; Brice Thamphya; Renaud Schiappa; Mathieu Gautier; Marie-Eve Chand-Fouche; Jean-Michel Hannoun-Levi

doi:10.1016/j.ctro.2021.10.005

High-dose-rate brachytherapy boost for locally advanced cervical cancer: Oncological outcome and toxicity analysis of 4 fractionation schemes

Clin Transl Radiat Oncol. 2021 Nov 6:32:15-23. doi: 10.1016/j.ctro.2021.10.005. eCollection 2022 Jan.

Authors

Maud le Guyader¹, Daniel Lam Cham Kee², Brice Thamphya³, Renaud Schiappa³, Mathieu Gautier¹, Marie-Eve Chand-Fouche¹, Jean-Michel Hannoun-Levi¹

Affiliations

¹ Department of Radiation Oncology, Antoine Lacassagne Cancer Center, University of Côte d'Azur, 33 avenue Valombrose, 06189 Nice Cedex 2, Nice, France.
² Department of Radiation Oncology, Pôle Santé République, Clermont-Ferrand, France.
³ Department of Statistics, Antoine Lacassagne Cancer Center, University of Côte d'Azur, Nice, France.

Abstract

Purpose: Brachytherapy (BT) boost after radio-chemotherapy (RCT) is a standard of care in the management of locally advanced cervical cancer (LACC). As there is no consensus on high-dose-rate (HDR) BT fractionation schemes, our aim was to report the oncological outcome and toxicity profile of four different schemes using twice-a-day (BID) HDR-BT.

Patients and methods: This was an observational, retrospective, single institution study for patients with LACC receiving a HDR-BT boost. The latter was performed with a single implant and single imaging done on day 1. The different fractionation schemes were: 7 Gy + 4x3.5 Gy (group 1); 7 Gy + 4x4.5 Gy (group 2); 3x7Gy (group 3) and 3x8Gy (group 4). Local (LFS), nodal (NFS) and metastatic (MFS) recurrence-free survival as well as progression-free survival (PFS) and overall survival (OS) were analyzed. Acute (≤6 months) and late toxicities (>6 months) were reported.

Results: From 2007 to 2018, 191 patients were included. Median follow-up was 57 months [45-132] and median EQD2₁₀D₉₀CTV_HR was 84, 82 and 90 Gy for groups 2, 3 and 4 respectively (dosimetric data missing for group 1). The 5-year LFS, NFS, MFS, PFS and OS were 85% [81-90], 83% [79-86], 70% [67-73], 61% [57-64] and 75% [69-78] respectively, with no significant difference between the groups. EQD2₁₀D₉₀CTV_HR < 85 Gy was a prognostic factor for local recurrence in univariate analysis (p = 0.045). The rates of acute/late grade ≥ 2 urinary, digestive and gynecological toxicities were 9%/15%, 3%/15% and 9%/25% respectively.

Conclusion: Bi-fractionated HDR-BT boost seems feasible with good oncological outcome and slightly more toxicity after dose escalation.

Keywords: BED, biologically effective dose; BID, twice-a-day; BMI, body-mass index; BT, brachytherapy; Brachytherapy; CT, computerized tomography; CTCAE, common terminology criteria for adverse events; CTV, clinical target volume; Cervical cancer; EBRT, external beam radiotherapy; EMBRACE, image guided intensity modulated External beam radiochemotherapy and MRI based Adaptative BRAchytherapy in locally advanced CErvical cancer; EQD2Gy, equivalent dose at 2 Gy; ESTRO, European Society for Radiotherapy and Oncology; FIGO, International Federation of Gynecology and Obstetrics; Fractionation scheme; GEC, groupe européen de curiethérapie; GTV, gross tumor volume; HDR, high-dose-rate; HIV, human immunodeficiency virus; HR, high-risk; High-dose-rate; ICRU, International Commission on Radiation Units and measurements; IGABT, image-guided adaptative brachytherapy; IMRT, intensity modulated radiotherapy; IR, intermediate-risk; LACC, locally advanced cervical cancer; LDR, low-dose-rate; LFS, local recurrence-free survival; LQ, linear quadratic; MFS, metastatic recurrence-free survival; MFU, median follow up; MRI, magnetic resonance imaging; NA, not available; NCI, national cancer institute; NFS, nodal recurrence-free survival; OAR, organs at risk; OS, overall survival; OTT, overall treatment time; PDR, pulsed-dose-rate; PET, positron emission tomography; PFS, progression-free survival; PTV, planning target volume; RCT, radio-chemotherapy; SCC, squamous cell cancer; SEER, surveillance, epidemiology and end results; pt, patient; pts, patients.