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

On behalf of the RTT-SCLC Collaborative Group

Research output: Contribution to journalReview article

28 Citations (Scopus)

Abstract

Background: Chemotherapy (CT) combined with radiotherapy is the standard treatment of 'limited-stage' small-cell lung cancer. However, controversy persists over the optimal timing of thoracic radiotherapy and CT. Materials and methods: We carried out a meta-analysis of individual patient data in randomized trials comparing earlier versus later radiotherapy, or shorter versus longer radiotherapy duration, as defined in each trial. We combined the results from trials using the stratified log-rank test to calculate pooled hazard ratios (HRs). The primary outcome was overall survival. Results: Twelve trials with 2668 patients were eligible. Data from nine trials comprising 2305 patients were available for analysis. The median follow-up was 10 years.When all trials were analysed together, 'earlier or shorter' versus 'later or longer' thoracic radiotherapy did not affect overall survival. However, the HR for overall survival was significantly in favour of 'earlier or shorter' radiotherapy among trials with a similar proportion of patients who were compliant with CT (defined as having received 100% or more of the planned CT cycles) in both arms (HR 0.79, 95%CI 0.69-0.91), and in favour of 'later or longer' radiotherapy among trials with different rates of CT compliance (HR 1.19, 1.05-1.34, interaction test, P < 0.0001). The absolute gain between 'earlier or shorter' versus 'later or longer' thoracic radiotherapy in 5-year overall survival for similar and for different CT compliance trials was 7.7% (95% CI 2.6-12.8%) and -2.2% (-5.8% to 1.4%), respectively. However, 'earlier or shorter' thoracic radiotherapy was associated with a higher incidence of severe acute oesophagitis than 'later or longer' radiotherapy. Conclusion: '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.

Original languageEnglish (US)
Pages (from-to)1818-1828
Number of pages11
JournalAnnals of Oncology
Volume27
Issue number10
DOIs
StatePublished - Jan 1 2016

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Small Cell Lung Carcinoma
Meta-Analysis
Radiotherapy
Thorax
Drug Therapy
Survival
Esophagitis

Keywords

  • Chemotherapy compliance
  • Individual participant data meta-analysis
  • Radiotherapy timing
  • Randomized clinical trials
  • Small-cell lung cancer
  • Thoracic radiotherapy

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Impact of thoracic radiotherapy timing in limited-stage small-cell lung cancer : Usefulness of the individual patient data meta-analysis. / On behalf of the RTT-SCLC Collaborative Group.

In: Annals of Oncology, Vol. 27, No. 10, 01.01.2016, p. 1818-1828.

Research output: Contribution to journalReview article

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title = "Impact of thoracic radiotherapy timing in limited-stage small-cell lung cancer: Usefulness of the individual patient data meta-analysis",
abstract = "Background: Chemotherapy (CT) combined with radiotherapy is the standard treatment of 'limited-stage' small-cell lung cancer. However, controversy persists over the optimal timing of thoracic radiotherapy and CT. Materials and methods: We carried out a meta-analysis of individual patient data in randomized trials comparing earlier versus later radiotherapy, or shorter versus longer radiotherapy duration, as defined in each trial. We combined the results from trials using the stratified log-rank test to calculate pooled hazard ratios (HRs). The primary outcome was overall survival. Results: Twelve trials with 2668 patients were eligible. Data from nine trials comprising 2305 patients were available for analysis. The median follow-up was 10 years.When all trials were analysed together, 'earlier or shorter' versus 'later or longer' thoracic radiotherapy did not affect overall survival. However, the HR for overall survival was significantly in favour of 'earlier or shorter' radiotherapy among trials with a similar proportion of patients who were compliant with CT (defined as having received 100{\%} or more of the planned CT cycles) in both arms (HR 0.79, 95{\%}CI 0.69-0.91), and in favour of 'later or longer' radiotherapy among trials with different rates of CT compliance (HR 1.19, 1.05-1.34, interaction test, P < 0.0001). The absolute gain between 'earlier or shorter' versus 'later or longer' thoracic radiotherapy in 5-year overall survival for similar and for different CT compliance trials was 7.7{\%} (95{\%} CI 2.6-12.8{\%}) and -2.2{\%} (-5.8{\%} to 1.4{\%}), respectively. However, 'earlier or shorter' thoracic radiotherapy was associated with a higher incidence of severe acute oesophagitis than 'later or longer' radiotherapy. Conclusion: '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.",
keywords = "Chemotherapy compliance, Individual participant data meta-analysis, Radiotherapy timing, Randomized clinical trials, Small-cell lung cancer, Thoracic radiotherapy",
author = "{On behalf of the RTT-SCLC Collaborative Group} and {De Ruysscher}, D. and B. Lueza and {Le P{\'e}choux}, C. and Johnson, {D. H.} and M. O'Brien and N. Murray and S. Spiro and X. Wang and M. Takada and B. Lebeau and W. Blackstock and D. Skarlos and P. Baas and H. Choy and A. Price and L. Seymour and R. Arriagada and Pignon, {J. P.} and Rodrigo Arriagada and Paul Baas and William Blackstock and Sylvie Chevret and Hak Choy and Jeffrey Crawford and Urania Dafni and Suzanne Dahlberg and {De Ruysscher}, Dirk and Allan Hackshaw and Baktiar Hasan and Johnson, {David H.} and {Le Pechoux}, C{\'e}cile and Bernard Lebeau and James Lovato and B{\'e}ranger Lueza and Nevin Murray and Mary O'Brien and Emmanuelle Paris and Pignon, {Jean Pierre} and Madelon Pijls-Johannesma and Allan Price and Stephen Spiro and Lesley Seymour and Taro Shibata and Dimosthenis Skarlos and Minoru Takada and Veillard, {Anne Sophie} and Xiaofei Wang and {De Ruysscher}, D. and {Le Pechoux}, C. and B. Lueza",
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T1 - Impact of thoracic radiotherapy timing in limited-stage small-cell lung cancer

T2 - Usefulness of the individual patient data meta-analysis

AU - On behalf of the RTT-SCLC Collaborative Group

AU - De Ruysscher, D.

AU - Lueza, B.

AU - Le Péchoux, C.

AU - Johnson, D. H.

AU - O'Brien, M.

AU - Murray, N.

AU - Spiro, S.

AU - Wang, X.

AU - Takada, M.

AU - Lebeau, B.

AU - Blackstock, W.

AU - Skarlos, D.

AU - Baas, P.

AU - Choy, H.

AU - Price, A.

AU - Seymour, L.

AU - Arriagada, R.

AU - Pignon, J. P.

AU - Arriagada, Rodrigo

AU - Baas, Paul

AU - Blackstock, William

AU - Chevret, Sylvie

AU - Choy, Hak

AU - Crawford, Jeffrey

AU - Dafni, Urania

AU - Dahlberg, Suzanne

AU - De Ruysscher, Dirk

AU - Hackshaw, Allan

AU - Hasan, Baktiar

AU - Johnson, David H.

AU - Le Pechoux, Cécile

AU - Lebeau, Bernard

AU - Lovato, James

AU - Lueza, Béranger

AU - Murray, Nevin

AU - O'Brien, Mary

AU - Paris, Emmanuelle

AU - Pignon, Jean Pierre

AU - Pijls-Johannesma, Madelon

AU - Price, Allan

AU - Spiro, Stephen

AU - Seymour, Lesley

AU - Shibata, Taro

AU - Skarlos, Dimosthenis

AU - Takada, Minoru

AU - Veillard, Anne Sophie

AU - Wang, Xiaofei

AU - De Ruysscher, D.

AU - Le Pechoux, C.

AU - Lueza, B.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Background: Chemotherapy (CT) combined with radiotherapy is the standard treatment of 'limited-stage' small-cell lung cancer. However, controversy persists over the optimal timing of thoracic radiotherapy and CT. Materials and methods: We carried out a meta-analysis of individual patient data in randomized trials comparing earlier versus later radiotherapy, or shorter versus longer radiotherapy duration, as defined in each trial. We combined the results from trials using the stratified log-rank test to calculate pooled hazard ratios (HRs). The primary outcome was overall survival. Results: Twelve trials with 2668 patients were eligible. Data from nine trials comprising 2305 patients were available for analysis. The median follow-up was 10 years.When all trials were analysed together, 'earlier or shorter' versus 'later or longer' thoracic radiotherapy did not affect overall survival. However, the HR for overall survival was significantly in favour of 'earlier or shorter' radiotherapy among trials with a similar proportion of patients who were compliant with CT (defined as having received 100% or more of the planned CT cycles) in both arms (HR 0.79, 95%CI 0.69-0.91), and in favour of 'later or longer' radiotherapy among trials with different rates of CT compliance (HR 1.19, 1.05-1.34, interaction test, P < 0.0001). The absolute gain between 'earlier or shorter' versus 'later or longer' thoracic radiotherapy in 5-year overall survival for similar and for different CT compliance trials was 7.7% (95% CI 2.6-12.8%) and -2.2% (-5.8% to 1.4%), respectively. However, 'earlier or shorter' thoracic radiotherapy was associated with a higher incidence of severe acute oesophagitis than 'later or longer' radiotherapy. Conclusion: '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.

AB - Background: Chemotherapy (CT) combined with radiotherapy is the standard treatment of 'limited-stage' small-cell lung cancer. However, controversy persists over the optimal timing of thoracic radiotherapy and CT. Materials and methods: We carried out a meta-analysis of individual patient data in randomized trials comparing earlier versus later radiotherapy, or shorter versus longer radiotherapy duration, as defined in each trial. We combined the results from trials using the stratified log-rank test to calculate pooled hazard ratios (HRs). The primary outcome was overall survival. Results: Twelve trials with 2668 patients were eligible. Data from nine trials comprising 2305 patients were available for analysis. The median follow-up was 10 years.When all trials were analysed together, 'earlier or shorter' versus 'later or longer' thoracic radiotherapy did not affect overall survival. However, the HR for overall survival was significantly in favour of 'earlier or shorter' radiotherapy among trials with a similar proportion of patients who were compliant with CT (defined as having received 100% or more of the planned CT cycles) in both arms (HR 0.79, 95%CI 0.69-0.91), and in favour of 'later or longer' radiotherapy among trials with different rates of CT compliance (HR 1.19, 1.05-1.34, interaction test, P < 0.0001). The absolute gain between 'earlier or shorter' versus 'later or longer' thoracic radiotherapy in 5-year overall survival for similar and for different CT compliance trials was 7.7% (95% CI 2.6-12.8%) and -2.2% (-5.8% to 1.4%), respectively. However, 'earlier or shorter' thoracic radiotherapy was associated with a higher incidence of severe acute oesophagitis than 'later or longer' radiotherapy. Conclusion: '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.

KW - Chemotherapy compliance

KW - Individual participant data meta-analysis

KW - Radiotherapy timing

KW - Randomized clinical trials

KW - Small-cell lung cancer

KW - Thoracic radiotherapy

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U2 - 10.1093/annonc/mdw263

DO - 10.1093/annonc/mdw263

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SP - 1818

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JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

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