Cardiopulmonary-related patient-reported outcomes in a randomized clinical trial of radiation therapy for breast cancer

Hilde Van Parijs, Vincent Vinh-Hung, Christel Fontaine, Guy Storme, Claire Verschraegen, Dung M Nguyen, Nele Adriaenssens, Nam P Nguyen, Olena Gorobets, Mark De Ridder, Hilde Van Parijs, Vincent Vinh-Hung, Christel Fontaine, Guy Storme, Claire Verschraegen, Dung M Nguyen, Nele Adriaenssens, Nam P Nguyen, Olena Gorobets, Mark De Ridder

Abstract

Background: Long-term prospective patient-reported outcomes (PRO) after breast cancer adjuvant radiotherapy is scarce. TomoBreast compared conventional radiotherapy (CR) with tomotherapy (TT), on the hypothesis that TT might reduce lung-heart toxicity.

Methods: Among 123 women consenting to participate, 64 were randomized to CR, 59 to TT. CR delivered 50 Gy in 25 fractions/5 weeks to breast/chest wall and regional nodes if node-positive, with a sequential boost (16 Gy/8 fractions/1.6 weeks) after lumpectomy. TT delivered 42 Gy/15 fractions/3 weeks to breast/chest wall and regional nodes if node-positive, 51 Gy simultaneous-integrated-boost in patients with lumpectomy. PRO were assessed using the European Organization for Research and Treatment of Cancer questionnaire QLQ-C30. PRO scores were converted into a symptom-free scale, 100 indicating a fully symptom-free score, 0 indicating total loss of freedom from symptom. Changes of PRO over time were analyzed using the linear mixed-effect model. Survival analysis computed time to > 10% PRO-deterioration. A post-hoc cardiorespiratory outcome was defined as deterioration in any of dyspnea, fatigue, physical functioning, or pain.

Results: At 10.4 years median follow-up, patients returned on average 9 questionnaires/patient, providing a total of 1139 PRO records. Item completeness was 96.6%. Missingness did not differ between the randomization arms. The PRO at baseline were below the nominal 100% symptom-free score, notably the mean fatigue-free score was 64.8% vs. 69.6%, pain-free was 75.4% vs. 75.3%, and dyspnea-free was 84.8% vs. 88.5%, in the TT vs. CR arm, respectively, although the differences were not significant. By mixed-effect modeling on early ≤2 years assessment, all three scores deteriorated, significantly for fatigue, P ≤ 0.01, without effect of randomization arm. By modeling on late assessment beyond 2 years, TT versus CR was not significantly associated with changes of fatigue-free or pain-free scores but was associated with a significant 8.9% improvement of freedom from dyspnea, P = 0.035. By survival analysis of the time to PRO deterioration, TT improved 10-year survival free of cardiorespiratory deterioration from 66.9% with CR to 84.5% with TT, P = 0.029.

Conclusion: Modern radiation therapy can significantly improve long-term PRO.

Trial registration: Trial registration number ClinicalTrials.gov NCT00459628 , April 12, 2007 prospectively.

Keywords: Dyspnea; Fatigue; Pain; Patient reported outcome measures; Quality of life.

Conflict of interest statement

The Radiation Oncology department of the Universitair Ziekenhuis Brussel under the direction of Guy Storme and Mark De Ridder had a research agreement with Tomotherapy Inc., Madison, WI, unrelated to the present study.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Consort 2010 flow diagram of the TomoBreast trial
Fig. 2
Fig. 2
Patient reported outcome (PRO) specific deterioration free survival
Fig. 3
Fig. 3
Patient reported outcome (PRO) specific survival free from deterioration in any of dyspnea, fatigue, pain, or physical functioning scales, by randomization arm. TT: tomotherapy. CR: conventional radiotherapy

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