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Peer-reviewedCC BY 4.0JAMA Network Open

Exercise Training During Neoadjuvant Treatment for Gastroesophageal Cancer and Tumor Surgery

  • Casper Simonsen1,2
  • Pieter de Heer3
  • Simon Nørskov Thomsen1
  • Rikke Krabek1
  • Sarah Thorsen-Streit1
  • Mark Preben Printz Lyngbæk1
  • Anna Sundberg1
  • Anne Sofie Knust Hjort1
  • Rajendra Singh Garbyal4
  • Louise Lang Lehrskov1
  • Thomas Skårup Kristensen5
  • Jens Georg Hillingsø3
8 more authors
  • Jon Kroll Bjerregaard6
  • Lene Bæksgaard6
  • Anders Tolver7
  • Lars Bo Svendsen3
  • Bente Klarlund Pedersen1
  • Camilla Qvortrup6
  • Michael Patrick Achiam3,8
  • Jesper Frank Christensen1
8 affiliations
  1. 1Centre for Physical Activity Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
  2. 2Now with Novo Nordisk A/S, Bagsværd, Gladsaxe, Denmark
  3. 3Department of Digestive Diseases, Transplantation, and General Surgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
  4. 4Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
  5. 5Department of Radiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
  6. 6Department of Oncology, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark
  7. 7Statistics and Data Analysis, Danish Cancer Institute, Copenhagen, Denmark
  8. 8Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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Abstract

Importance: Physical deterioration and disease progression during neoadjuvant treatment can preclude tumor surgery in patients with gastroesophageal cancer. Whether preoperative exercise training can increase the probability of undergoing tumor surgery remains unknown.

Objective: To compare exercise training with usual care on the likelihood of not undergoing tumor surgery with curative intent after neoadjuvant treatment for gastroesophageal cancer.

Design, Setting, and Participants: PRESET-RCT was a single-blinded, parallel-group, 2-arm, superiority randomized clinical trial. Patients with gastroesophageal adenocarcinoma scheduled to undergo treatment with curative intent, including neoadjuvant treatment, and with no contraindication to exercise training were eligible. Participants were enrolled at University Hospital Copenhagen, Rigshospitalet, Copenhagen, Denmark, from August 16, 2018, to September 23, 2022, with final follow-up on October 22, 2024. Data analysis was performed from March 2023 to May 2025.

Intervention: The participants were randomized 1:1 to preoperative exercise training from diagnosis until tumor surgery or control. The intervention consisted of twice-weekly concurrent aerobic exercise and resistance training.

Main Outcomes and Measures: The primary outcome was not undergoing tumor surgery with curative intent. The secondary outcomes were treatment tolerance and overall survival.

Results: In total, 207 participants (73.7%) were randomized and 202 were included in the modified intention-to-treat analyses (mean [SD] age, 65.3 [8.5] years; 161 [78.9%] male; 170 [83.3%] with gastroesophageal junction cancer), with 101 randomized to each group. In the exercise group, 10 (9.9%) did not undergo tumor surgery with curative intent compared with 8 (7.9%) in the control group (odds ratio, 1.28; 95% CI, 0.48-3.38; P = .62). There were no between-group differences in permanent discontinuation of neoadjuvant treatment (odds ratio, 0.81; 95% CI, 0.38-1.72) or postoperative complications (odds ratio, 1.16; 95% CI, 0.61-2.20). The overall survival rates at 3 years for the exercise and control group were 51.0% and 65.0%, respectively (hazard ratio, 1.58; 95% CI, 1.02-2.45).

Conclusion and Relevance: In this randomized clinical trial, preoperative exercise training did not increase the likelihood of undergoing tumor surgery for patients with gastroesophageal cancer. The findings do not support the use of exercise training during neoadjuvant treatment to improve surgical outcomes, and further research is needed to determine its effects on long-term outcomes.

Trial Registration: ClinicalTrials.gov Identifier: NCT03490565

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Cite

BibTeXRIS
BibTeX
@article{simonsen2026exercise,
  title = {{Exercise Training During Neoadjuvant Treatment for Gastroesophageal Cancer and Tumor Surgery}},
  author = {Casper Simonsen and Pieter de Heer and Simon Nørskov Thomsen and Rikke Krabek and Sarah Thorsen-Streit and Mark Preben Printz Lyngbæk and Anna Sundberg and Anne Sofie Knust Hjort and Rajendra Singh Garbyal and Louise Lang Lehrskov and Thomas Skårup Kristensen and Jens Georg Hillingsø and Jon Kroll Bjerregaard and Lene Bæksgaard and Anders Tolver and Lars Bo Svendsen and Bente Klarlund Pedersen and Camilla Qvortrup and Michael Patrick Achiam and Jesper Frank Christensen},
  journal = {JAMA Network Open},
  year = {2026},
  month = oct,
  doi = {10.1001/jamanetworkopen.2026.40136},
  url = {https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2855920},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Exercise Training During Neoadjuvant Treatment for Gastroesophageal Cancer and Tumor Surgery
AU  - Casper Simonsen
AU  - Pieter de Heer
AU  - Simon Nørskov Thomsen
AU  - Rikke Krabek
AU  - Sarah Thorsen-Streit
AU  - Mark Preben Printz Lyngbæk
AU  - Anna Sundberg
AU  - Anne Sofie Knust Hjort
AU  - Rajendra Singh Garbyal
AU  - Louise Lang Lehrskov
AU  - Thomas Skårup Kristensen
AU  - Jens Georg Hillingsø
AU  - Jon Kroll Bjerregaard
AU  - Lene Bæksgaard
AU  - Anders Tolver
AU  - Lars Bo Svendsen
AU  - Bente Klarlund Pedersen
AU  - Camilla Qvortrup
AU  - Michael Patrick Achiam
AU  - Jesper Frank Christensen
PY  - 2026
DA  - 2026/10/28
JO  - JAMA Network Open
DO  - 10.1001/jamanetworkopen.2026.40136
UR  - https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2855920
AB  - Importance: Physical deterioration and disease progression during neoadjuvant treatment can preclude tumor surgery in patients with gastroesophageal cancer. Whether preoperative exercise training can increase the probability of undergoing tumor surgery remains unknown.  Objective: To compare exercise training with usual care on the likelihood of not undergoing tumor surgery with curative intent after neoadjuvant treatment for gastroesophageal cancer.  Design, Setting, and Participants: PRESET-RCT was a single-blinded, parallel-group, 2-arm, superiority randomized clinical trial. Patients with gastroesophageal adenocarcinoma scheduled to undergo treatment with curative intent, including neoadjuvant treatment, and with no contraindication to exercise training were eligible. Participants were enrolled at University Hospital Copenhagen, Rigshospitalet, Copenhagen, Denmark, from August 16, 2018, to September 23, 2022, with final follow-up on October 22, 2024. Data analysis was performed from March 2023 to May 2025.  Intervention: The participants were randomized 1:1 to preoperative exercise training from diagnosis until tumor surgery or control. The intervention consisted of twice-weekly concurrent aerobic exercise and resistance training.  Main Outcomes and Measures: The primary outcome was not undergoing tumor surgery with curative intent. The secondary outcomes were treatment tolerance and overall survival.  Results: In total, 207 participants (73.7%) were randomized and 202 were included in the modified intention-to-treat analyses (mean [SD] age, 65.3 [8.5] years; 161 [78.9%] male; 170 [83.3%] with gastroesophageal junction cancer), with 101 randomized to each group. In the exercise group, 10 (9.9%) did not undergo tumor surgery with curative intent compared with 8 (7.9%) in the control group (odds ratio, 1.28; 95% CI, 0.48-3.38; P = .62). There were no between-group differences in permanent discontinuation of neoadjuvant treatment (odds ratio, 0.81; 95% CI, 0.38-1.72) or postoperative complications (odds ratio, 1.16; 95% CI, 0.61-2.20). The overall survival rates at 3 years for the exercise and control group were 51.0% and 65.0%, respectively (hazard ratio, 1.58; 95% CI, 1.02-2.45).  Conclusion and Relevance: In this randomized clinical trial, preoperative exercise training did not increase the likelihood of undergoing tumor surgery for patients with gastroesophageal cancer. The findings do not support the use of exercise training during neoadjuvant treatment to improve surgical outcomes, and further research is needed to determine its effects on long-term outcomes.  Trial Registration: ClinicalTrials.gov Identifier: NCT03490565
SN  - 2574-3805
ER  -