Copenhagen, Denmark
Onsite/Online

ESTRO 2022

Session Item

Sunday
May 08
11:40 - 12:40
Room D3
Highlights of Proffered Papers - Best Papers
Esther Troost, Germany;
Umberto Ricardi, Italy
Proffered Papers
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
Monica Serban, Canada
OC-0503

Abstract

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-score4 [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 CTVHR 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 CTVHR 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 CTVHR D90% was 93Gy EQD210. Limiting CTVHR D90% 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 CTVHR D90% maintained on average similar OARs doses as clinical plans. However, global adherence to all OARs soft/hard constraints decreased by 7%/11%. Further CTVHR 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 CTVHR 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, CTVIR D98% 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 CTVHR D90% 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.