Dataset Information

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.

SUBMITTER: De Ruysscher D

PROVIDER: S-EPMC5035783 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Publications

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

De Ruysscher D D Lueza B B Le Péchoux C C Johnson D H DH O'Brien M M Murray N N Spiro S S Wang X X Takada M M Lebeau B B Blackstock W W Skarlos D D Baas P P Choy H H Price A A Seymour L L Arriagada R R Pignon J-P JP

Annals of oncology : official journal of the European Society for Medical Oncology 20160719 10

<h4>Background</h4>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.<h4>Materials and methods</h4>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 stratif ...[more]

PMID: 27436850

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Project description:ObjectiveThe purpose of this study was to assess whether thoracic radiotherapy (TRT) combined with chemotherapy (CHT) showed promising anti-tumour activity in extensive-stage small cell lung cancer (ES-SCLC), to explore practice patterns for the radiation time and dose/fractionation and to identify prognostic factors for patients who would benefit from CHT/TRT.MethodsA total of 492 ES-SCLC patients were included from January 2010 to March 2019, 244 of whom received CHT/TRT. Propensity score matching was performed to minimize bias between the CHT/TRT and CHT-alone groups. Patients in the CHT/TRT group were categorized into four subgroups based on the number of induction CHT cycles. For effective dose fractionation calculations, we introduced the time-adjusted biological effective dose (tBED). Categorical variables were analysed with chi-square tests and Fisher's exact tests. Kaplan-Meier curves were generated to estimate survival rates using the R-project. Multivariate prognostic analysis was performed with Cox proportional hazards models.ResultsPatients who received CHT/TRT experienced improved overall survival (OS) (18.1 vs 10.8 months), progression-free survival (PFS) (9.3 vs 6.0 months) and local recurrence-free survival (LRFS) (12.0 vs 6.6 months) before matching, with similar results after matching. In the CHT/TRT group, the median LRFS times for the groups based on the radiation time were 12.7, 12.0, 12.0, and 9.0 months, respectively. Early TRT had a tendency to prolong PFS (median 10.6 vs 9.8 vs 9.0 vs 7.7 months, respectively, p = 0.091) but not OS (median 17.6 vs 19.5 vs 17.2 vs 19.0 months, respectively, p = 0.622). Notably, patients who received TRT within 6 cycles of CHT experienced prolonged LRFS (p = 0.001). Regarding the radiation dose, patients in the high-dose group (tBED > 50 Gy) who achieved complete response and partial response (CR and PR) to systemic therapy had relatively short OS (median 27.1 vs 22.7, p = 0.026) and PFS (median 11.4 vs 11.2, p = 0.032), but the abovementioned results were not obtained after the exclusion of patients who received hyperfractionated radiotherapy (all p > 0.05).ConclusionCHT/TRT could improve survival for ES-SCLC patients. TRT performed within 6 cycles of CHT and hyperfractionated radiotherapy (45 Gy in 30 fractions) may be a feasible treatment scheme for ES-SCLC patients.

Project description:Controversies exists with regard to target volumes as far as thoracic radiotherapy (TRT) is concerned in the multimodality treatment for limited-stage small cell lung cancer (LSCLC). The aim of this study is to prospectively compare the local control rate, toxicity profiles, and overall survival (OS) between patients received different target volumes irradiation after induction chemotherapy.LSCLC patients received 2 cycles of etoposide and cisplatin (EP) induction chemotherapy and were randomly assigned to receive TRT to either the post- or pre-chemotherapy tumor extent (GTV-T) as study arm and control arm, CTV-N included the positive nodal drainage area for both arms. One to 2 weeks after induction chemotherapy, 45 Gy/30 Fx/19 d TRT was administered concurrently with the third cycle of EP regimen. After that, additional 3 cycles of EP consolidation were administered. Prophylactic cranial irradiation (PCI) was administered to patients with a complete response.Thirty-seven and 40 patients were randomly assigned to study arm and control arm. The local recurrence rates were 32.4% and 28.2% respectively (P = 0.80); the isolated nodal failure (INF) rates were 3.0% and 2.6% respectively (P = 0.91); all INF sites were in the ipsilateral supraclavicular fossa. Medastinal N3 disease was the risk factor for INF (P = 0.02, OR = 14.13, 95% CI: 1.47-136.13). During radiotherapy, grade I, II weight loss was observed in 29.4%, 5.9% and 56.4%, 7.7% patients respectively (P = 0.04). Grade 0-I and II-III late pulmonary injury was developed in 97.1%, 2.9% and 86.4%, 15.4% patients respectively (P = 0.07). Median survival time was 22.1 months and 26.9 months respectively. The 1 to 3-year OS were 77.9%, 44.4%, 37.3% and 75.8%, 56.3%, 41.7% respectively (P = 0.79).The preliminary results of this study indicate that irradiant the post-chemotherapy tumor extent (GTV-T) and positive nodal drainage area did not decrease local control and overall survival while radiation toxicity was reduced. But the current sample size has not met designed requirements, and further investigation is warranted before final conclusions could be drawn.

Dataset Information

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

Background

Materials and methods

Results

Conclusion

Publications

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

Similar Datasets

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