Early Compared With Late Radiotherapy in Combined Modality Treatment for Limited Disease Small-Cell Lung Cancer: A London Lung Cancer Group Multicenter Randomized Clinical Trial and Meta-Analysis

2006 ◽  
Vol 24 (24) ◽  
pp. 3823-3830 ◽  
Author(s):  
Stephen G. Spiro ◽  
Lindsay E. James ◽  
Robin M. Rudd ◽  
Colin W. Trask ◽  
Jeffrey S. Tobias ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Meta Analysis ◽  
Small Cell ◽  
Combined Modality Treatment ◽  
Small Cell Lung ◽  
Limited Disease ◽  
Cancer Group ◽  
Survival Difference

Purpose To replicate an earlier National Cancer Institute of Canada (NCIC) trial that examined the effect on survival of the timing of thoracic radiotherapy (TRT) in patients with limited disease small-cell lung cancer (SCLC). Patients and Methods Patients received three cycles of cyclophosphamide, doxorubicin, and vincristine alternating with three cycles of etoposide and cisplatin. Three hundred twenty five chemotherapy- and radiotherapy-naïve patients were randomly assigned to either early TRT administered concurrently in the second cycle or late TRT administered concurrently with the sixth cycle; the dose was 40 Gy in 15 fractions over 3 weeks. Results TRT was received by 92% and 82% of patients in the early and late arms, respectively (P = .01). Sixty-nine percent of patients in the early arm received all six courses of chemotherapy compared with 80% in the late arm (P = .003). There was no evidence of a survival difference; median overall survival time was 13.7 and 15.1 months in the early and late arms, respectively (P = .23). In a meta-analysis of all eight trials that compared early and late TRT, there were three in which the proportion of patients who completed their planned chemotherapy was similar between the TRT arms (hazard ratio [HR] = 0.73; 95% CI, 0.62 to 0.86) and five in which proportionally fewer patients in the early TRT arm completed their chemotherapy (HR = 1.06; 95% CI, 0.97 to 1.17). Conclusion This study failed to show a survival advantage for early TRT with chemotherapy in limited-stage SCLC, unlike the NCIC trial. However, the results of a meta-analysis suggest that it is essential to ensure that the delivery of chemotherapy is optimal when administered with early TRT.

Time Between the First Day of Chemotherapy and the Last Day of Chest Radiation Is the Most Important Predictor of Survival in Limited-Disease Small-Cell Lung Cancer

2006 ◽  
Vol 24 (7) ◽  
pp. 1057-1063 ◽  
Author(s):  
Dirk De Ruysscher ◽  
Madelon Pijls-Johannesma ◽  
Søren M. Bentzen ◽  
André Minken ◽  
Rinus Wanders ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Survival Rate ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Important Predictor ◽  
Phase Iii ◽  
Combined Modality Treatment ◽  
Small Cell Lung ◽  
Limited Disease

Purpose To identify time factors for combined chemotherapy and radiotherapy predictive for long-term survival of patients with limited-disease small-cell lung cancer (LD-SCLC). Methods A systematic overview identified suitable phase III trials. Using meta-analysis methodology to compare results within trials, the influence of the timing of chest radiation and the start of any treatment until the end of radiotherapy (SER) on local tumor control, survival, and esophagitis was analyzed. For comparison between studies, the equivalent radiation dose in 2-Gy fractions, corrected for the overall treatment time of chest radiotherapy, was analyzed. Results The SER was the most important predictor of outcome. There was a significantly higher 5-year survival rate in the shorter SER arms (relative risk [RR] = 0.62; 95% CI, 0.49 to 0.80; P = .0003), which was more than 20% when the SER was less than 30 days (upper bound of 95% CI, 90 days). A low SER was associated with a higher incidence of severe esophagitis (RR = 0.55; 95% CI, 0.42 to 073; P < .0001). Each week of extension of the SER beyond that of the study arm with the shortest SER resulted in an overall absolute decrease in the 5-year survival rate of 1.83% ± 0.18% (95% CI). Conclusion A low time between the first day of chemotherapy and the last day of chest radiotherapy is associated with improved survival in LD-SCLC patients. The novel parameter SER, which takes into account accelerated proliferation of tumor clonogens during both radiotherapy and chemotherapy, may facilitate a more rational design of combined-modality treatment in rapidly proliferating tumors.

Low SER versus high SER thoracic radiotherapy in the management of limited-stage small cell lung cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18170-18170
Author(s):  
K. Lee ◽  
S. Lee ◽  
S. Lee ◽  
J. Kim ◽  
C. Shin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Rational Design ◽  
Cox Model ◽  
Small Cell ◽  
Combined Modality Treatment ◽  
Thoracic Radiotherapy ◽  
Small Cell Lung ◽  
Limited Disease

18170 Background: Patients with small-cell lung cancer account for about 20% of all lung cancer patients, with only one third of the patients presenting with limited disease. Although the combinations of chemo and radiation therapy have improved the prognosis substantially, the optimal chemoradiotherapy remains controversial in LD-SCLC. There are many reports that the overall duration of the chemoradiotherapy package is the most relevant predictor of the outcome. Therefore we tested SER beginning with the start of any treatment until the end of radiotherapy in patients with LD-SCLC. Methods: We enrolled the patients who were diagnosed as SCLC histologically in Korea University Medical Center from 2003 to 2006. All of them presented with limited disease. We divided them into two groups; the low SER (within 60 days of SER) and the high SER group (over 60 days). The patients were treated with thoracic radiotherapy and platinum based topoisomerase inhibitor. Overall survival was analyzed with a Cox model adjusted for performance and the chemotherapy regimen. Results: Of 29 patients, 16 patients were in low SER and 13 patients were in high SER. Low SER, as compared with high SER, significantly prolonged survival rate (p=0.028). We evaluated the radiation effect by the time between the start of chemotherapy and the start of radiotherapy, below 30 days and above 30 days, but there were no statistically comparable difference in there survival time between the two groups (p=0.176). The survival times of the patients were increased by 3.094 times in the low SER (95% C.I, 1.083 to 8.840, p=0.028) and by 6.901 times in ECOG groups 0 or 1 compared with group 2 (95% C.I, 1.563 to 30.468, p=0.018). There were no statistically significant increases in the side effects: pneumonitis, esophagitis, and BM suppressions. Conclusions: The cumulative survival of the patients in the low SER group is higher than for patients in the high SER group. The SER may facilitate a more rational design of combined-modality treatment in rapidly proliferating tumors. [Table: see text] No significant financial relationships to disclose.

Efficacy and Safety of Antigen-specific Immunotherapy in the Treatment of Patients with Non-small-cell Lung Cancer: A Systematic Review and Meta-analysis

2019 ◽  
Vol 19 (3) ◽  
pp. 199-209 ◽  
Author(s):  
Bing-Di Yan ◽  
Xiao-Feng Cong ◽  
Sha-Sha Zhao ◽  
Meng Ren ◽  
Zi-Ling Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Specific Immunotherapy ◽  
Meta Analysis ◽  
Small Cell ◽  
Efficacy And Safety ◽  
Small Cell Lung

Background and Objective: We performed this systematic review and meta-analysis to assess the efficacy and safety of antigen-specific immunotherapy (Belagenpumatucel-L, MAGE-A3, L-BLP25, and TG4010) in the treatment of patients with non-small-cell lung cancer (NSCLC). </P><P> Methods: A comprehensive literature search on PubMed, Embase, and Web of Science was conducted. Eligible studies were clinical trials of patients with NSCLC who received the antigenspecific immunotherapy. Pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated for overall survival (OS), progression-free survival (PFS). Pooled risk ratios (RRs) were calculated for overall response rate (ORR) and the incidence of adverse events. </P><P> Results: In total, six randomized controlled trials (RCTs) with 4,806 patients were included. Pooled results showed that, antigen-specific immunotherapy did not significantly prolong OS (HR=0.92, 95%CI: 0.83, 1.01; P=0.087) and PFS (HR=0.93, 95%CI: 0.85, 1.01; P=0.088), but improved ORR (RR=1.72, 95%CI: 1.11, 2.68; P=0.016). Subgroup analysis based on treatment agents showed that, tecemotide was associated with a significant improvement in OS (HR=0.85, 95%CI: 0.74, 0.99; P=0.03) and PFS (HR=0.70, 95%CI: 0.49, 0.99, P=0.044); TG4010 was associated with an improvement in PFS (HR=0.87, 95%CI: 0.75, 1.00, P=0.058). In addition, NSCLC patients who were treated with antigen-specific immunotherapy exhibited a significantly higher incidence of adverse events than those treated with other treatments (RR=1.11, 95%CI: 1.00, 1.24; P=0.046). </P><P> Conclusion: Our study demonstrated the clinical survival benefits of tecemotide and TG4010 in the treatment of NSCLC. However, these evidence might be limited by potential biases. Therefore, further well-conducted, large-scale RCTs are needed to verify our findings.

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