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Abstract

BACKGROUND:

Concurrent chemoradiotherapy is the standard of care in limited-stage small-cell lung cancer, but the optimal radiotherapy schedule and dose remains controversial. The aim of this study was to establish a standard chemoradiotherapy treatment regimen in limited-stage small-cell lung cancer.

METHODS:

The CONVERT trial was an open-label, phase 3, randomised superiority trial. We enrolled adult patients (aged ≥18 years) who had cytologically or histologically confirmed limited-stage small-cell lung cancer, Eastern Cooperative Oncology Group performance status of 0-2, and adequate pulmonary function. Patients were recruited from 73 centres in eight countries. Patients were randomly assigned to receive either 45 Gy radiotherapy in 30 twice-daily fractions of 1·5 Gy over 19 days, or 66 Gy in 33 once-daily fractions of 2 Gy over 45 days, starting on day 22 after commencing cisplatin-etoposide chemotherapy (given as four to six cycles every 3 weeks in both groups). The allocation method used was minimisation with a random element, stratified by institution, planned number of chemotherapy cycles, and performance status. Treatment group assignments were not masked. The primary endpoint was overall survival, defined as time from randomisation until death from any cause, analysed by modified intention-to-treat. A 12% higher overall survival at 2 years in the once-daily group versus the twice-daily group was considered to be clinically significant to show superiority of the once-daily regimen. The study is registered with ClinicalTrials.gov (NCT00433563) and is currently in follow-up.

FINDINGS:

Between April 7, 2008, and Nov 29, 2013, 547 patients were enrolled and randomly assigned to receive twice-daily concurrent chemoradiotherapy (274 patients) or once-daily concurrent chemoradiotherapy (273 patients). Four patients (one in the twice-daily group and three in the once-daily group) did not return their case report forms and were lost to follow-up; these patients were not included in our analyses. At a median follow-up of 45 months (IQR 35-58), median overall survival was 30 months (95% CI 24-34) in the twice-daily group versus 25 months (21-31) in the once-daily group (hazard ratio for death in the once daily group 1·18 [95% CI 0·95-1·45]; p=0·14). 2-year overall survival was 56% (95% CI 50-62) in the twice-daily group and 51% (45-57) in the once-daily group (absolute difference between the treatment groups 5·3% [95% CI -3·2% to 13·7%]). The most common grade 3-4 adverse event in patients evaluated for chemotherapy toxicity was neutropenia (197 [74%] of 266 patients in the twice-daily group vs 170 [65%] of 263 in the once-daily group). Most toxicities were similar between the groups, except there was significantly more grade 4 neutropenia with twice-daily radiotherapy (129 [49%] vs 101 [38%]; p=0·05). In patients assessed for radiotherapy toxicity, was no difference in grade 3-4 oesophagitis between the groups (47 [19%] of 254 patients in the twice-daily group vs 47 [19%] of 246 in the once-daily group; p=0·85) and grade 3-4 radiation pneumonitis (4 [3%] of 254 vs 4 [2%] of 246; p=0·70). 11 patients died from treatment-related causes (three in the twice-daily group and eight in the once-daily group).

INTERPRETATION:

Survival outcomes did not differ between twice-daily and once-daily concurrent chemoradiotherapy in patients with limited-stage small-cell lung cancer, and toxicity was similar and lower than expected with both regimens. Since the trial was designed to show superiority of once-daily radiotherapy and was not powered to show equivalence, the implication is that twice-daily radiotherapy should continue to be considered the standard of care in this setting.

FUNDING:

Cancer Research UK (Clinical Trials Awards and Advisory Committee), French Ministry of Health, Canadian Cancer Society Research Institute, European Organisation for Research and Treatment of Cancer (Cancer Research Fund, Lung Cancer, and Radiation Oncology Groups).​ 

Author information

Faivre-Finn C1, Snee M2, Ashcroft L3, Appel W4, Barlesi F5, Bhatnagar A6, Bezjak A7, Cardenal F8, Fournel P9, Harden S10, Le Pechoux C11, McMenemin R12, Mohammed N13, O'Brien M14, Pantarotto J15, Surmont V16, Van Meerbeeck JP17, Woll PJ18, Lorigan P19, Blackhall F19; CONVERT Study Team.

1 Division of Molecular and Clinical Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; Department of Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester, UK. Electronic address: corinne.finn@christie.nhs.uk.

2 St James Institute of Oncology, Leeds, UK.

3 Manchester Academic Health Science Centre Trials Co-ordination Unit, The Christie NHS Foundation Trust, Manchester, UK.

4 Rosemere Cancer Centre, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK.

5 Multidisciplinary Oncology & Therapeutic Innovations Department, Aix Marseille Univ, Assistance Publique Hôpitaux de Marseille, Marseille, France.

6 Department of Clinical Oncology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.

7 Canadian Cancer Trials Group, Princess Margaret Cancer Center, Toronto, ON, Canada.

8 GECP, Department of Medical Oncology, Institut Català'Oncologia, L'Hospitalet (Barcelona), Barcelona, Spain.

9 GFPC, Département d'Oncologie Médicale, Institut de Cancérologie Lucien Neuwirth, Saint-Étienne, France.

10 Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.

11 Département d'Oncologie Radiothérapie, Gustave Roussy Cancer Campus, Villejuif, France.

12 Northern Centre for Cancer Care, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.

13 Beatson West of Scotland Cancer Centre, NHS Greater Glasgow and Clyde, Glasgow, UK.

14 Department of Medicine, Royal Marsden NHS Foundation Trust, Surrey, UK.

15 Division of Radiation Oncology, University of Ottawa, Ottawa, ON, Canada.

16 Department of Respiratory Medicine/Thoracic Oncology, Ghent University Hospital, Ghent, Belgium.

17 Thoracic Oncology, Antwerp University Hospital, Antwerp, Belgium.

18 Department of Oncology & Metabolism, University of Sheffield, Sheffield, UK.

19 Division of Molecular and Clinical Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.