Unresectable Intermediate-Size (3–5 cm) Colorectal Liver Metastases: Stereotactic Ablative Body Radiotherapy Versus Microwave Ablation (COLLISION-XL): Protocol of a Phase II/III Multicentre Randomized Controlled Trial
Authors: van der Lei Susan , Dijkstra Madelon , Nieuwenhuizen Sanne , Schulz Hannah H. , Vos Danielle J. W. , Versteeg Kathelijn S. , Buffart Tineke E. , Swijnenburg Rutger-Jan , de Vries Jan J. J. , Bruynzeel Anna M. E. , van den Tol M. Petrousjka , Scheffer Hester J. , Puijk Robbert S. , Haasbeek Cornelis J. A. , Meijerink Martijn R. ,   and COLLISION Trial Group, Geboers Bart , Timmer Floor E. F. , Verheul Henk , Nielsen Karin , Van der Meijs Bram , Van Grieken Nicole , Van Delden Otto , Van Gulik Thomas , Besselink Mark , Tanis Pieter , Van Lienden Krijn , Burgmans Mark , Van Erkel Arian , Hartgrink Henk , Van Rijswijk Carla , Mieog Sven , Sietses Colin , Van Heek Tjarda , Diederik Arjen , Spaargaren Gert-Jan , Groot Gerie , Vink Ted , Manusama Eric , Eker Hasan , Dol Johan , Kappers Ingrid , Van der Leij Christiaan , Brans Rutger , Coolsen Mariëlle , De Jong Kees , Van Dam Ronald , Kruimer Han , Van Baardewijk Laurens , Leclercq Wouter , Futterer Jurgen , Van den Boezem Peter , Stommel Martijn , De Wilt Hans , Jenniskens Sjoerd , Arntz Mark , Janssen Jan Jaap , Torrenga Hans , Ruiter Simeon , Nijkamp Maarten , Kater Matthijs , De Jong Koert , Serafino GianPiero , Draaisma Werner , Van Geel Anne , Schreurs Hermien , Smits Maarten , Hagendoorn Jeroen , Molenaar Quintus , Bruijnen Rutger , Prevoo Warner , De Cobelli Francesco , Aldrighetti Luca , Ratti Francesca , Marra Paolo , Corte Angelo Della , Chapelle Thiery , Peeters Marc 
Published: July 2023

Background

Although microwave ablation (MWA) has a low complication rate and good efficacy for small-size (≤ 3 cm) colorectal liver metastases (CRLM), local control decreases with increasing size. Stereotactic body radiotherapy (SBRT) is gaining interest as a potential means to treat intermediate-size CRLM and might be less susceptible to increasing volume. The objective of this study is to compare the efficacy of MWA to SBRT in patients with unresectable, intermediate-size (3–5 cm) CRLM.

Methods

In this two-arm, multicentre phase II/ III randomized controlled trial, 68 patients with 1–3 unresectable, intermediate-size CRLM suitable for both MWA and SBRT, will be included. Patients will be treated with MWA or SBRT as randomised. The Primary endpoint is local tumour progression-free survival (LTPFS) at 1 year (intention-to-treat analysis). Main secondary endpoints are overall survival, overall and distant progression-free survival (DPFS), local control (LC) and procedural morbidity and mortality and assessment of pain and quality of life.

Discussion

Current guidelines lack clear recommendations for the local treatment of liver only intermediate-size, unresectable CRLM and studies comparing curative intent SBRT and thermal ablation are scarce. Although safety and feasibility to eradicate tumours ≤ 5 cm have been established, both techniques suffer from lower LTPFS and LC rates for larger-size tumours. For the treatment of unresectable intermediate-size CRLM clinical equipoise has been reached. We have designed a two-armed phase II/ III randomized controlled trial directly comparing SBRT to MWA for unresectable CRLM 3–5 cm.

Level of Evidence

Level 1, phase II/ III Randomized controlled trial.

Trial Registration: NCT04081168, September 9th 2019.

Graphical Abstract