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

ABSTRACT 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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    • "On subset analysis of studies that used hyperfractionated TRT, treatment with early versus late TRT revealed a survival benefit, but not when once-daily TRT was employed. Likewise, the survival benefit for early versus late TRT was observed uniquely in studies using platinum-based chemotherapy, which was not notable in studies using nonplatinum-based chemotherapy (Fried et al., 2004). Results of the available studies and metaanalyses suggested an interaction between TRT and chemotherapy and, accelerated tumor cell repopulation was postulated to be triggered by the first dose of any effective cytotoxic agent (De Ruysscher et al., 2006). "
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    • "In 2 metaanalyses , the addition of definitive thoracic radiation to chemotherapy was found to significantly improve overall survival in patients with LS-SCLC [32] [33] . Subsequent studies demonstrated that early thoracic radiotherapy (initiated within the first 2 cycles of chemotherapy) afforded further overall survival benefit when compared with late radiotherapy [34] . Although a large randomized trial has demonstrated an added survival gain with hyperfractionated (twice a day) thoracic radiotherapy, this strategy remains controversial and confirmatory trials are ongoing [35] . "
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