ESTRO 2022

Session Item

Sunday

May 08

11:40 - 12:40

Room D3

Highlights of Proffered Papers - Best Papers

Chair: , Germany;

Chair: , Italy

Session Code: 2320

Session Type: Proffered Papers

Track: Interdisciplinary

11:40 - 11:50

Brachytherapy Best Paper: Effect of dose and fractionation de-escalation in low-risk cervix cancer treated with EBRT and BT

Awardee: Monica Serban, Canada

Presentation Number: OC-0503

Abstract

Abstract Title:

Effect of dose and fractionation de-escalation in low-risk cervix cancer treated with EBRT and BT

Authors:

Monica Serban¹, Martin Gallois², Théo Urtubey², Remi Nout³, Astrid de Leeuw⁴, Lars Fokdal¹, Marianne Assenholt¹, Sofia Spampinato¹, Kjersti Bruheim⁵, Barbara Segedin⁶, Supriya Chopra⁷, Maximilian Schmid⁸, Nicole Nesvacil⁸, Stefan Ecker⁸, Kathrin Kirchheiner⁸, Richard Pötter⁸, Henrike Westerveld⁹, Fleur Huang¹⁰, Laura Velema¹¹, Li Tee Tan¹², Margit Valgma¹³, Hanne Mathiesen¹⁴, Jacob Lindegaard¹, Ina Jürgenliemk-Schulz⁴, Kari Tanderup¹

¹Aarhus University Hospital, Department of Oncology, Aarhus, Denmark; ²McGill University, Department of Physics, Montreal, Canada; ³Erasmus University Medical Center, Department of Radiation Oncology, Rotterdam, The Netherlands; ⁴University Medical Centre Utrecht, Department of Radiation Oncology, Utrecht, The Netherlands; ⁵The Norwegian Radiumhospital, Oslo University Hospital, Department of Oncology, Oslo, Norway; ⁶Institute of Oncology Ljubljana, Department of Radiation Oncology, Ljubljana, Slovenia; ⁷Tata Memorial Center, Department of Radiation Oncology, Mumbai, India; ⁸Medical University of Vienna, Department of Radiation Oncology, Vienna, Austria; ⁹Academisch Medisch Centrum , Department of Radiation Oncology, Amsterdam, The Netherlands; ¹⁰Cross Cancer Institute, University of Alberta, Department of Oncology, Edmonton, Canada; ¹¹Leiden University Medical Center, Department of Clinical Oncology, Leiden, The Netherlands; ¹²Addenbrooke’s NHS Trust, Department of Oncology, Cambridge, United Kingdom; ¹³North Estonia Medical Centre Foundation, Department of Oncology, Tallin, Estonia; ¹⁴Rigshospitalet, Department of Oncology, Copenhagen, Denmark

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Purpose or Objective

To simulate the effect of dose de-escalation and compressed EBRT and/or brachytherapy (BT) fractionation schedules on target and organ doses in low-risk cervix cancer.

Material and Methods

1261 patients enrolled in the EMBRACE II study were treated with 45Gy/25fx EBRT and MRI-guided BT. 312 (25%) node positive and negative patients were identified as having low-risk of local failure based on histology (squamous cell) and extent of primary tumour (T-score≤4 [1]) and used for further analysis. EBRT of 45Gy/25fx and 40Gy/20fx were combined with different BT fractionation schedules. For HDR: a) BT fractionation as applied clinically (“clinical”), b) 3fx, c) 2fx. For PDR: a) “clinical”, b) 1fx of 24 pulses. Target and OARs doses were simulated for CTV_HR D90% normalised to 90Gy and 85Gy EQD2₁₀. Differences in targets/OARs doses between modified and clinical schedules and adherence to hard/soft EMBRACE II OAR constraints [2] was evaluated.

Results

Median (IQR) tumour maximum dimension at diagnosis was 38 (32-47)mm, and CTV_HR volume at BT was 23 (18-31)cm³. Simulated target/OAR doses and the percentage of patients adhering to all OARs hard/soft constraints are presented in Table1. For clinical EBRT/BT plans, mean CTV_HRD_90% was 93Gy EQD2₁₀. Limiting CTV_HRD_90% to 90Gy (85Gy) for clinical fractionation schedules decreased OAR doses by 1-2Gy (2-5Gy), respectively, with most prominent effect seen in bladder D2cm³. Compressed BT with 3fx HDR or 1fx PDR delivering 90Gy to CTV_HR D_90% maintained on average similar OARs doses as clinical plans. However, global adherence to all OARs soft/hard constraints decreased by 7%/11%. Further CTV_HR dose de-escalation to 85Gy decreased OAR doses by 2-3.3Gy and nudged adherence to soft/hard constraints by 12%/-2%. With additional BT hypofractionation to 2fx HDR and 85Gy normalization, adherence to hard constraints dropped by 5% while physical CTV_HR D90% were high, >11Gy. EBRT of 40Gy/20fx with clinical or compressed BT schedules resulted in overall reduction in OAR doses of 0-2Gy, compared to 45Gy/25fx with corresponding BT schedules. A small percentage of patients had increased OAR doses, bladder mainly, for the 40Gy/20 EBRT schedules. Generally, CTV_IRD98% was <60Gy, mainly with 85Gy normalization and/or 40Gy/20fx EBRT.

Conclusion

Cervix cancer patients with low-risk of local recurrence can experience significantly less OAR doses if CTV_HRD_90% is kept between 85-90Gy. This opens the possibility of less burdensome and time-consuming treatment schedules. Compressing BT to 3fx HDR or 1fx PDR is most often feasible without compromising EMBRACE II constraints. EBRT schedules of 40Gy/20fx reduce on average OAR doses, except for cases where the OAR is in immediate target vicinity, receiving high dose. However, due to uncertainties regarding EQD2 calculation, dose response relationship and the potential impact of overall treatment time reduction, such changes need to be tested in prospective clinical studies.