Systematic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited-stage small-cell lung cancer

Multidisciplinary Thoracic Oncology Program, Lineberger Comprehensive Cancer Center, Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Journal of Clinical Oncology (Impact Factor: 18.43). 01/2005; 22(23):4837-45. DOI: 10.1200/JCO.2004.01.178
Source: PubMed


We employed meta-analytic techniques to evaluate early (E) versus late (L) timing of thoracic radiation therapy (RT) in limited-stage small-cell lung cancer (LS-SCLC). In addition, we assessed the impact of radiation fractionation and chemotherapeutic regimen on timing.
Randomized trials published after 1985 addressing timing of RT relative to chemotherapy in LS-SCLC were included. Trials were analyzed by risk ratio (RR), risk difference, and number-needed-to-treat methods.
Overall survival (OS) RRs for all studies were 1.17 at 2 years (95% CI, 1.02 to 1.35; P = .03) and 1.13 at 3 years (95% CI, 0.92 to 1.39; P = .2), indicating a significantly increased 2-year survival for ERT versus LRT patients and suggestive of a similar trend at 3 years. Subset analysis of studies using hyperfractionated RT revealed OS RR for ERT versus LRT of 1.44 (95% CI, 1.17 to 1.77; P = .001) and 1.39 (95% CI, 1.02 to 1.90; P = .04) at 2 and 3 years, respectively, indicating a survival benefit of ERT versus LRT. Studies using once-daily fractionation showed no difference in 2- and 3-year OS RRs for ERT compared with LRT. Studies using platinum-based chemotherapy had OS RRs of 1.30 (95% CI, 1.10 to 1.53; P = .002) and 1.35 (95% CI, 1.07 to 1.70; P = .01) at 2 and 3 years, respectively, favoring ERT. Studies using nonplatinum-based chemotherapy regimens had nonsignificant differences in OS.
A small but significant improvement in 2-year OS for ERT versus LRT in LS-SCLC was observed, similar to the benefit of adding RT to chemotherapy or prophylactic cranial irradiation. A greater difference was evident for hyperfractionated RT and platinum-based chemotherapy.

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    • "Indeed, a randomized phase 3 clinical trial have recently showed that in LD-SCLC thoracic radiotherapy starting in the third cycle of chemotherapy seemed to be non inferior to thoracic radiotherapy administered concurrently with the first cycle of chemotherapy in terms of complete response rate (36% vs 38%, respectively), and it had a more favorable profile with regard to neutropenic fever (10.2% vs 21.6%, p = 0.02) [17]. Therefore, in the strategy of combined treatment for LD-SCLC, it is important to plan early thoracic radiotherapy (possibly with the first-cycle of chemotherapy, but no later than the third cycle), to combine platinum-based chemotherapy and to ensure that the delivery of chemotherapy is optimal when administered with concurrent thoracic radiotherapy [17] [18] [19]. As a result of the combined treatment, the risk of a thoracic recurrence decreases and brain metastasis becomes one of the main types of relapse, with a cumulative incidence at 2 years higher than 50% [20]. "
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    • "The timing of TRT in combined chemoradiotherapy has been controversial in several respects. Some argue that TRT should be started simultaneously with chemotherapy [7,10-12], while others claim that a delay of TRT (1-2 cycles) from the beginning of chemotherapy provides similar or better outcomes [13]. One rationale for the former argument is that a simultaneous start of TRT decreases the tolerance of chemotherapy, thereby reducing local relapse and distance metastasis. "
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    • "According to the recently meta-analyses [29], the CCRT itself can decrease locoregional progression and improve overall survival in NSCLC. (3) The start of thoracic radiotherapy in the limited-stage SCLC patients was all within 2 cycles of chemotherapy in our study, which was proved to be favorable in survival than the late start of radiotherapy [30]. "
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