Quality of Life Is Associated With Survival in Patients With Gastric Cancer: Results From the Randomized CRITICS Trial

Authors:
Romy M. van Amelsfoort Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam;

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Iris Walraven Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam;
Department for Health Evidence, Radboud University Medical Center, Nijmegen;

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Jacobien Kieffer Department of Psychosocial Research and Epidemiology, and

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Edwin P.M. Jansen Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam;

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Annemieke Cats Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam;

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Nicole C.T. van Grieken Department of Pathology, VU University Medical Center, Amsterdam;

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Elma Meershoek-Klein Kranenbarg Department of Surgical Oncology, Leiden University Medical Center, Leiden;

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Hein Putter Department of Surgical Oncology, Leiden University Medical Center, Leiden;

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Johanna W. van Sandick Department of Surgical Oncology, and

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Karolina Sikorska Department of Biostatistics, Netherlands Cancer Institute, Amsterdam; and

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Cornelis J.H. van de Velde Department of Pathology, VU University Medical Center, Amsterdam;

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Neil K. Aaronson Department for Health Evidence, Radboud University Medical Center, Nijmegen;

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Marcel Verheij Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam;
Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands.

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on behalf of the CRITICS Investigators
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Background: The evaluation of health-related quality of life (HRQoL) in clinical trials has become increasingly important because it addresses the impact of treatment from the patient’s perspective. The primary aim of this study was to investigate the effect of postoperative chemotherapy and chemoradiotherapy (CRT) after neoadjuvant chemotherapy and surgery with extended (D2) lymphadenectomy on HRQoL in the CRITICS trial. Second, we investigated the potential prognostic value of pretreatment HRQoL on event-free survival (EFS) and overall survival (OS). Patients and Methods: Patients in the CRITICS trial were asked to complete HRQoL questionnaires (EORTC Quality-of-Life Questionnaire-Core 30 and Quality-of-Life Questionnaire gastric cancer–specific module) at baseline, after preoperative chemotherapy, after surgery, after postoperative chemotherapy or CRT, and at 12 months follow-up. Patients with at least 1 evaluable questionnaire (645 of 788 randomized patients) were included in the HRQoL analyses. The predefined endpoints included dysphagia, pain, physical functioning, fatigue, and Quality-of-Life Questionnaire-Core 30 summary score. Linear mixed modeling was used to assess differences over time and at each time point. Associations of baseline HRQoL with EFS and OS were investigated using multivariate Cox proportional hazards analyses. Results: At completion of postoperative chemo(radio)therapy, the chemotherapy group had significantly better physical functioning (P=.02; Cohen’s effect size = 0.42) and less dysphagia (P=.01; Cohen’s effect size = 0.38) compared with the CRT group. At baseline, worse social functioning (hazard ratio [HR], 2.20; 95% CI, 1.36–3.55; P=.001), nausea (HR, 1.89; 95% CI, 1.39–2.56; P<.001), worse WHO performance status (HR, 1.55; 95% CI, 1.13–2.13; P=.007), and histologic subtype (diffuse vs intestinal: HR, 1.94; 95% CI, 1.42–2.67; P<.001; mixed vs intestinal: HR, 2.35; 95% CI, 1.35–4.12; P=.003) were significantly associated with worse EFS and OS. Conclusions: In the CRITICS trial, the chemotherapy group had significantly better physical functioning and less dysphagia after postoperative treatment. HRQoL scales at baseline were significantly associated with EFS and OS.

Submitted December 11, 2020; final revision received April 7, 2021; accepted for publication May 3, 2021.

Author contributions: Study concept and design: Jansen, Cats, Meershoek-Klein Kranenbarg, Putter, van de Velde, Aaronson, Verheij. Data research: van Amelsfoort, Walraven, Kieffer, Jansen, Aaronson, Verheij. Writing – original draft: van Amelsfoort. Writing – review and editing: Walraven, Kieffer, Jansen, Cats, van Grieken, Meershoek-Klein Kranenbarg, Putter, van Sandick, Sikorska, van de Velde, Aaronson, Verheij. Final manuscript approval: All authors.

Disclosures: The authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: This work was supported by funding from KWF Kankerbestrijding, the Dutch Colorectal Cancer group, and F. Hoffmann-La Roche.

Correspondence: Marcel Verheij, MD, PhD, Department of Radiation Oncology, Radboud University Medical Center, Geert Grooteplein 32, 6500 HB Nijmegen, the Netherlands. Email: Marcel.Verheij@radboudumc.nl

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