Impact of thoracic radiotherapy timing in limited-stage small-cell lung cancer: usefulness of the individual patient data meta-analysis

Ruysscher, Dirk De; Lueza, Béranger; Wang, X.; Baas, Paul; Choy, Hak; Arriagada, R.; Blackstock, William; Chevret, Sylvie; Crawford, Jeffrey; Dafni, Urania; Dahlberg, Suzanne E.; Hackshaw, Allan; Hasan, Baktiar; Johnson, David H.; Péchoux, C. Le; Lebeau, B.; Lovato, James; Murray, Nevin; O’Brien, Mary; Paris, Emmanuelle; Pignon, Jean‐Pierre; Pijls‐Johannesma, Madelon; Price, Allan; Spiro, Stephen; Seymour, Lesley; Shibata, Taro; Skarlos, Dimosthenis; Takada, Minoru; Veillard, Anne-Sophie; Wang, Xiaofei

doi:10.1093/annonc/mdw263

Cited by 90 publications

(63 citation statements)

References 36 publications

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“…These results, together with several meta-analyses and systematic overviews, support the use of short overall radiotherapy treatment time to avoid early cancer cell repopulation. 7 , 8 , 9 , 10 , 11 One of the systematic overviews also identified that time from the start of any treatment to completion of radiotherapy is a key variable in predicting outcome. 20 Although not significant, 2-year overall survival was slightly higher in the twice-daily group than in the once-daily group, which could possibly be a result of improved delivery of treatment in the twice-daily group, with more patients receiving full-dose radiotherapy, the optimal planned number of fractions, and treatment delivered over the optimal treatment time.…”

Section: Discussionmentioning

confidence: 99%

“…Subsequently, meta-analyses of clinical trials investigating the optimal timing and sequencing of chemoradiotherapy have shown an advantage for early concurrent thoracic radiotherapy. 7 , 8 , 9 , 10 , 11 Furthermore, twice-daily radiotherapy was superior to once-daily radiotherapy in the landmark Intergroup 0096 study. 4 In that study, patients were randomly assigned to receive either 45 Gy once-daily (1·8 Gy per fraction) for 5 weeks or 45 Gy twice-daily (1·5 Gy per fraction) for 3 weeks.…”

Section: Introductionmentioning

confidence: 99%

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Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial

Faivre-Finn

Snee

Ashcroft

et al. 2017

The Lancet Oncology

426

385

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SummaryBackgroundConcurrent 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.MethodsThe 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.FindingsBetween 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) an...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial

Faivre-Finn

Snee

Ashcroft

et al. 2017

The Lancet Oncology

426

385

View full text Add to dashboard Cite

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“…35 More recently, De Ruysscher published another meta-analysis of IPD from 12 trials (2668 patients) reporting improved 5-year survival in the early concurrent CRT vs. late concurrent CRT arm. 36 In LS-SCLC, previous randomised trials have reported median survivals of 18-24 months and 40%-50% 2-year survival rates. 28,31,[37][38][39] Previously, the preponderance of evidence has reported no consistent survival benefit from administration of supplementary chemotherapeutic agents or other platinum-based combination regimens, increased dose density and intensity and maintenance chemotherapy.…”

Section: Introductionmentioning

confidence: 98%

Treatment Response and Prophylactic Cranial Irradiation Are Prognostic Factors in a Real-life Limited-disease Small-cell Lung Cancer Patient Cohort Comprehensively Staged With Cranial Magnetic Resonance Imaging

Eze

Roengvoraphoj

Niyazi

et al. 2017

Clinical Lung Cancer

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“…However, the optimal dose and schedule of thoracic RT has not been definitively established and different factors such as, performance status (PS), pulmonary function, target volume, comorbidities, and centre resources may underlie their election. Early concurrent CTRT has demonstrated better local control and survival results when compared to sequential treatment administration [12][13][14] at the cost of a higher rate of oesophageal toxicity. With respect to fractionation, both once-daily and twice-daily radiotherapy with cisplatin and etoposide have been evaluated in LS-SCLC.…”

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confidence: 99%

SEOM clinical guidelines for the treatment of small-cell lung cancer (SCLC) (2019)

et al. 2020

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Small-cell lung cancer (SCLC) accounts for 15% of lung cancers. Only one-third of patients are diagnosed at limited stage. The median survival remains to be around 15-20 months without significative changes in the strategies of treatment for many years. In stage I and IIA, the standard treatment is the surgery followed by adjuvant therapy with platinum-etoposide. In stage IIB-IIIC, the recommended treatment is early concurrent chemotherapy with platinum-etoposide plus thoracic radiotherapy followed by prophylactic cranial irradiation in patients without progression. However, in the extensive stage, significant advances have been observed adding immunotherapy to platinum-etoposide chemotherapy to obtain a significant increase in overall survival, constituting the new recommended standard of care. In the second-line treatment, topotecan remains as the standard treatment. Reinduction with platinum-etoposide is the recommended regimen in patients with sensitive relapse (≥ 3 months) and new drugs such as lurbinectedin and immunotherapy are new treatment options. New biomarkers and new clinical trials designed according to the new classification of SCLC subtypes defined by distinct gene expression profiles are necessary.

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Impact of thoracic radiotherapy timing in limited-stage small-cell lung cancer: usefulness of the individual patient data meta-analysis

Abstract: 'Earlier or shorter' delivery of thoracic radiotherapy with planned CT significantly improves 5-year overall survival at the expense of more acute toxicity, especially oesophagitis.

Cited by 90 publications

References 36 publications

Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial

Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial

Treatment Response and Prophylactic Cranial Irradiation Are Prognostic Factors in a Real-life Limited-disease Small-cell Lung Cancer Patient Cohort Comprehensively Staged With Cranial Magnetic Resonance Imaging

SEOM clinical guidelines for the treatment of small-cell lung cancer (SCLC) (2019)

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