Patient-reported health-related quality of life from a randomized phase II trial comparing standard-dose with high-dose twice daily thoracic radiotherapy in limited stage small-cell lung cancer

Kristin Toftaker Killingberg,Tarje Onsøien Halvorsen,Øystein Fløtten,Odd Terje Brustugun,Seppo W Langer,Jan Nyman,Kjersti Hornslien,Tesfaye Madebo,Tine Schytte,Signe Risum,Georgios Tsakonas,Jens Engleson,Bjørn Henning Grønberg

doi:10.1016/j.lungcan.2022.02.002

Abstract

ObjectivesIn a randomized phase II trial, twice daily (BID) thoracic radiotherapy (TRT) of 60 Gy/40 fractions improved survival compared with 45 Gy/30 fractions in limited stage small-cell lung cancer (LS SCLC). Notably, the higher dose did not cause more toxicity. Here we present health related quality of life (HRQoL) reported by the trial participants during the first 2 years. Materials and methods170 patients were randomized 1:1 to TRT of 45 Gy or 60 Gy concurrently with cisplatin/etoposide chemotherapy. The 150 patients who commenced TRT and completed a minimum of one HRQoL-questionnaire were included in the present study. Patients reported HRQoL on the European Organization for Research and Treatment of Cancer Core 30 and Lung Cancer 13 Quality of Life Questionnaires. Questionnaires were completed weeks 0, 4 (before TRT), 8 (end of TRT), 12 (response evaluation after chemoradiotherapy) and 16 (end of prophylactic cranial irradiation), then every 10 weeks year one, and every 3 months year two. Primary HRQoL endpoints were dysphagia and dyspnea. A difference in mean score of ≥10 was defined as clinically significant. ResultsMaximum dysphagia was reported on week 8, with no significant difference between treatment arms (mean scores 45 Gy: 44.2, 60 Gy: 51.1). The 60 Gy arm had more dysphagia in the convalescence period, but dysphagia scores returned to baseline levels at week 16 in both arms. For dyspnea there were no significant changes, or differences between treatment arms, at any timepoint. There were no significant differences between treatment arms for any other HRQoL-scales. ConclusionTRT of 60 Gy did not cause significantly higher maximum dysphagia, though patients on the 60 Gy arm reported more dysphagia the first 8 weeks of convalescence. The higher dose was well tolerated and is an attractive alternative to current TRT schedules in LS SCLC.Trial reg Clinicaltrials.gov NCT0204184.

Highlights

Small cell lung cancer (SCLC), accounting for 13% of lung cancer cases, is a malignancy with an aggressive clinical course [1]
Emotional functioning increased from baseline and remained stable throughout the study period (Figure 4). In this first trial comparing high-dose with standard-dose twice-daily thoracic radiotherapy in limited stage small-cell lung cancer (LS SCLC), patients reported an increase in mean scores of dysphagia from 10 points at baseline to 47 points at the end of TRT
Our study shows that there are no longer reasons for such concerns since dysphagia caused by twice daily TRT is transient

Summary

Introduction

Small cell lung cancer (SCLC), accounting for 13% of lung cancer cases, is a malignancy with an aggressive clinical course [1]. We conducted a phase II trial comparing high-dose, twice-daily (BID) TRT of 60 Gy in 40 fractions with the standard dose of 45 Gy BID in 30 fractions, and our primary analyses show that the high-dose arm achieved a significantly improved 2-year survival (primary endpoint, 74% vs 48%; p=.0005) and median overall survival (37.2 vs 22.6 months; p=.012) [7]. This is the first randomized trial of LS SCLC to show a significant survival improvement in more than 20 years. Assessed toxicity did not reveal any significant differences between the treatment arms, and the proportion of patients who experienced severe radiotoxicity was lower than in older trials and similar to other, recent trials of TRT in LS SCLC [5, 6, 8,9,10]

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