Neoadjuvant Chemoradiotherapy and Surgery for Esophageal Squamous Cell Carcinoma Versus Definitive Chemoradiotherapy With Salvage Surgery as Needed: The Study Protocol for the Randomized Controlled NEEDS Trial
Magnus Nilsson
(1, 2)
,
Halla Olafsdottir
(1)
,
Gabriella Alexandersson von Döbeln
,
Fernanda Villegas
,
Giovanna Gagliardi
,
Mats Hellström
,
Qiao-Li Wang
,
Hemming Johansson
(3)
,
Val Gebski
(4)
,
Jakob Hedberg
,
Fredrik Klevebro
,
Sheraz Markar
(5, 1)
,
Elizabeth Smyth
(6)
,
Pernilla Lagergren
(2)
,
Ghazwan Al-Haidari
,
Lars Cato Rekstad
,
Eirik Kjus Aahlin
,
Bengt Wallner
,
David Edholm
,
Jan Johansson
(7)
,
Eva Szabo
,
John Reynolds
,
Cs Pramesh
,
Naveen Mummudi
,
Amit Joshi
,
Lorenzo Ferri
,
Rebecca Ks Wong
,
Chris O’callaghan
,
Jelena Lukovic
,
Kelvin Kw Chan
,
Trevor Leong
,
Andrew Barbour
,
Mark Smithers
,
Yin Li
,
Xiaozheng Kang
,
Feng-Ming Kong
,
Yin-Kai Chao
,
Tom Crosby
,
Christiane Bruns
,
Hanneke van Laarhoven
,
Mark van Berge Henegouwen
,
Richard van Hillegersberg
,
Riccardo Rosati
,
Guillaume Piessen
(8, 9)
,
Giovanni de Manzoni
,
Florian Lordick
1
Karolinska Institutet [Stockholm]
2 Karolinska University Hospital [Stockholm]
3 Department of Oncology
4 The University of Sydney
5 Imperial College London
6 CUH - Cambridge University Hospitals - NHS
7 Center for Alzheimer Research
8 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
9 CANTHER - Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277
2 Karolinska University Hospital [Stockholm]
3 Department of Oncology
4 The University of Sydney
5 Imperial College London
6 CUH - Cambridge University Hospitals - NHS
7 Center for Alzheimer Research
8 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
9 CANTHER - Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277
Gabriella Alexandersson von Döbeln
- Function : Author
Fernanda Villegas
- Function : Author
Giovanna Gagliardi
- Function : Author
Mats Hellström
- Function : Author
Qiao-Li Wang
- Function : Author
Jakob Hedberg
- Function : Author
Fredrik Klevebro
- Function : Author
Ghazwan Al-Haidari
- Function : Author
Lars Cato Rekstad
- Function : Author
Eirik Kjus Aahlin
- Function : Author
Bengt Wallner
- Function : Author
David Edholm
- Function : Author
Eva Szabo
- Function : Author
John Reynolds
- Function : Author
Cs Pramesh
- Function : Author
Naveen Mummudi
- Function : Author
Amit Joshi
- Function : Author
Lorenzo Ferri
- Function : Author
Rebecca Ks Wong
- Function : Author
Chris O’callaghan
- Function : Author
Jelena Lukovic
- Function : Author
Kelvin Kw Chan
- Function : Author
Trevor Leong
- Function : Author
Andrew Barbour
- Function : Author
Mark Smithers
- Function : Author
Yin Li
- Function : Author
Xiaozheng Kang
- Function : Author
Feng-Ming Kong
- Function : Author
Yin-Kai Chao
- Function : Author
Tom Crosby
- Function : Author
Christiane Bruns
- Function : Author
Hanneke van Laarhoven
- Function : Author
Mark van Berge Henegouwen
- Function : Author
Richard van Hillegersberg
- Function : Author
Riccardo Rosati
- Function : Author
Giovanni de Manzoni
- Function : Author
Florian Lordick
- Function : Author
Abstract
Background The globally dominant treatment with curative intent for locally advanced esophageal squamous cell carcinoma (ESCC) is neoadjuvant chemoradiotherapy (nCRT) with subsequent esophagectomy. This multimodal treatment leads to around 60% overall 5-year survival, yet with impaired post-surgical quality of life. Observational studies indicate that curatively intended chemoradiotherapy, so-called definitive chemoradiotherapy (dCRT) followed by surveillance of the primary tumor site and regional lymph node stations and surgery only when needed to ensure local tumor control, may lead to similar survival as nCRT with surgery, but with considerably less impairment of quality of life. This trial aims to demonstrate that dCRT, with selectively performed salvage esophagectomy only when needed to achieve locoregional tumor control, is non-inferior regarding overall survival, and superior regarding health-related quality of life (HRQOL), compared to nCRT followed by mandatory surgery, in patients with operable, locally advanced ESCC. Methods This is a pragmatic open-label, randomized controlled phase III, multicenter trial with non-inferiority design with regard to the primary endpoint overall survival and a superiority hypothesis for the experimental intervention dCRT with regard to the main secondary endpoint global HRQOL one year after randomization. The control intervention is nCRT followed by preplanned surgery and the experimental intervention is dCRT followed by surveillance and salvage esophagectomy only when needed to secure local tumor control. A target sample size of 1200 randomized patients is planned in order to reach 462 events (deaths) during follow-up. Clinical Trial Registration www.ClinicalTrials.gov , identifier: NCT04460352.
