• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6263-6267
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• 2014

Background: It is standard treatment to combine chemotherapy (CT) and thoracic radiotherapy (TRT) in treating patients with limited stage small cell lung cancer (LS-SCLC). However, optimal timing of TRT is unclear. We here evaluated the survival impact of early versus late TRT in patients with LS-SCLC. Materials and Methods: Follow-up was retrospectively analyzed for seventy consecutive LS-SCLC patients who had successfully completed chemo-TRT between January 2006 and January 2012. Patients received TRT after either 1 to 2 cycles of CT (early TRT) or after 3 to 6 cycles of CT (late TRT). Survival and response rates were evaluated using the Kaplan-Meier method and comparisons were made using the multivariate Cox regression test. Results: Median follow-up was 24 (5 to 57) months. Carboplatin+etoposide was the most frequent induction CT (59%). Median overall, disease free, and metastasis free survivals in all patients were 15 (5 to 57), 5 (0 to 48) and 11 (3 to 57) months respectively. Late TRT was superior to early TRT group in terms of response rate (p=0.05). 3 year overall survival (OS) rates in late versus early TRT groups were 31% versus 17%, respectively (p=0.03). Early TRT (p=0.03), and incomplete response to TRT (p=0.004) were negative predictors of OS. Significant positive prognostic factors for distant metastasis free survival were late TRT (p=0.03), and use of PCI (p=0.01). Use of carboplatin versus cisplatin for induction CT had no significant impact on OS (p=0.634), DFS (p=0.727), and MFS (p=0.309). Conclusions: Late TRT appeared to be superior to early TRT in LS-SCLC treatment in terms of complete response, OS and DMFS. Carboplatin or cisplatin can be combined with etoposide in the induction CT owing to similar survival outcomes.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.903-915
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• 1996

Background: Combination chemotherapy is now considered to be the cornerstone of small cell lung cancer (SCLC). management but the optimal management of limited SCLC is not well defined. The role of thoracic radiotherapy (TRT) is less well established. Recent meta-analyses reports revealed that TRT combined with chemotherapy produce "good" local control and prolonged survival. But other reports that survival was not changed. The liming, dose, volume and fractionation for TRT with the combined chemotherapy of SCLC remains unsettled. In this study, we analyzed the effects according to the timing of thoracic radiotherapy in limited SCLC. Method: All fifty one patients received cytoxan, adriamycin and vincristine(CAV) alternating with etoposide and cisplatin(VPP) every 3 weeks for 6 cycles were randomized prospectively into two groups: concurrent and sequential. 27 patients received 4500cGy in 30 fractions(twice daily 150cGy fractional dose) over 3 weeks 10 the primary site concurrent with the first cycle of VPP(concurrent gorup). 24 patients received 4000 to 5000cGy over 5 or 6 weeks after completion of sixth cycles of chemotherapy(sequential group). Results: 1. Response rates and response duration : Response rates were not significantly different between two groups(p=0.13). But response duration was superior in the concurrent group(p=0.03). 2. Survival duration was nor different between two groups(p=0.33). 3. Local control rate was superior in the concurrent group(p=0.00). 4. Side effects and toxicities: Hematologic toxicities, especially leukopenia, infection and frequency of radiation esophagitis were higher in the concurrent group (p=0.00, 0.03, 0.03). Conclusion: The concurrent use of TRT with chemotherapy failed to improve the survival of limited stage SCLC patients compared with the sequential use of TRT but response duration and local control rate were superior in the concurrent group. Frequency of radiation esophagitis, life threatening hematologic toxicities and infection were more frequent in the concurrent group than sequential group. So, the selection of an optimal schedule of chemotherapy combined with TRT that would lead to a major increase in survival with minimal toxicity is remained to be validated in large scale study in the future.

• Radiation Oncology Journal
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• v.37 no.3
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• pp.185-192
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• 2019

Purpose: The effectiveness of thoracic radiation therapy (TRT) in extensive-stage small cell lung cancer (ES-SCLC) patients is increasingly reported, but there is no definite consensus on its application. The aim of this study was to identify factors associated with better outcomes of TRT among patients with ES-SCLC, focusing on whether a higher TRT dose could improve treatment outcome. Materials and Methods: The medical records of 85 patients with ES-SCLC who received TRT between January 2008 and June 2017 were retrospectively reviewed. Eligibility criteria were a biological effective dose with α/β = 10 (BED) higher than 30 Gy₁₀ and completion of planned radiotherapy. Results: During a median follow-up of 5.3 months, 68 patients (80.0%) experienced disease progression. In univariate analysis, a BED >50 Gy₁₀ was a significant prognostic factor for overall survival (OS; 40.8% vs. 12.5%, p = 0.006), progression-free survival (PFS; 15.9% vs. 9.6%, p = 0.004), and intrathoracic PFS (IT-PFS; 39.3% vs. 20.5%, p = 0.004) at 1 year. In multivariate analysis, a BED >50 Gy₁₀ remained a significant prognostic factor for OS (hazard ratio [HR] = 0.502; 95% confidence interval [CI], 0.287-0.876; p = 0.015), PFS (HR = 0.453; 95% CI, 0.265-0.773; p = 0.004), and IT-PFS (HR = 0.331; 95% CI, 0.171-0.641; p = 0.001). Response to the last chemotherapy was also associated with better OS in both univariate and multivariate analysis. Conclusion: A TRT dose of BED >50 Gy₁₀ may be beneficial for patients with ES-SCLC. Further studies are needed to select patients who will most benefit from high-dose TRT.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.291-301
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• 1998

Purpose : A retrospective study was conducted comparing single daily fraction (SDF) thoracic radiotherapy (TRT) with twice daily (BID) TRT to determine the potential benefit of BID TRT in limited-stage small cell lung cancer (SCLC). Endpoints of the study were response. survival, pattern of failure, and acute toxicity. Materials and Methods : Between November 1989 to December 1996, 78 patients with histologically proven limited-stage SCLC were treated at the Department of Therapeutic Radiology, Chungnam National University Hospital. Of these, 9 were irradiated for palliative intent, and 1 had recurrent disease. Remaining 68 patients were enrolled in this study. There were 26 patients with a median age of 58 years, and 22 (85$\%$) ECOG performance score of less than 1 in SDF TRT. There were 42 patients with a median age of 57 years, and 36 (86$\%$) ECOG performance score of less than 1 in BID TRT By radiation fractionation regimen, there were 26 in SDF TRT and 42 in BID TRT. SDF TRT consisted of 180 cGy, 5 days a week. BID TRT consisted of 150 cGy BID, 5 days a week in 13 of 42 and 120 cGy BID, in 29 of 42. And the twice daily fractions were separated by at least 4 hours. Total radiotherapy doses were between 5040 and 6940 cGy (median, 5040 cGy) in SDF TRT and was between 4320 and 5100 cGy (median, 4560 cGy) in BID TRT. Prophylactic cranial irradiation (PCI) was recommended for patients who achieved a CR. The recommended PCI dose was 2500 cGy/10 fractions. Chemotherapy consisted of CAV (cytoxan 1000 mg/$m^2$, adriamycin 40 mg/$m^2$, vincristine 1 mg/$m^2$) alternating with VPP (cisplatin 60 mg/$m^2$, etoposide 100 mg/$m^2$) every 3 weeks in 25 (96$\%$) of SDF TRT and in 40 (95$\%$) of BID TRT. Median cycle of chemotherapy was six in both group. Timing for chemotherapy was sequential in 23 of SDF TRT and in 3 BID TRT, and concurrent in 3 of SDF TRT and in 39 of BID TRT Follow-up ranged from 2 to 99 months (median, 14 months) in both groups. Results : Of the 26 SDF TRT, 9 (35$\%$) achieved a complete response (CR) and 14 (54$\%$) experienced a partial response (PR). Of the 42 BID TRT, 18 (43$\%$) achieved a CR and 23 (55$\%$) experienced a PR. There was no significant response difference between the two arms (p=0.119). Overall median and 2-year survival were 15 months and 26.8$\%$, respectively. The 2-year survivals were 26.9$\%$ and 28$\%$ in both arm, respectively (p=0.51). The 2-rear survivals were 35$\%$ in CR and 24.2$\%$ in PR, respectively. The grade 2 to 3 esophageal toxicities and grade 2 to 4 neutropenias were more common in BID TRT (p=0.028 0.003). There was no difference in locoregional and distant metastasis between the two arms (p=0 125 and 0.335, respectively). The most common site of distant metastasis was the brain. Conclusion : The median survival and 2-year survival were 17 months and 20.9$\%$ in SDF TRT with sequential chemotherapy, and 15 months and 28$\%$ in BID TRT with concurrent chemotherapy, respectively. We did not observe a substantial improvement of long-term survival in the BID TRT with concurrent chemotherapy compared with standard schedules of SDF TRT with sequential chemotherapy. The grade 2 to 3 esophageal toxicities and glade 2 to 4 neutropenias were more common in BID TRT with concurrent chemotherapy. Although the acute toxicities were more common in BID TRT with concurrent chemotherapy than SDF TRT with sequential chemotherapy, a concurrent chemotherapy and twice daily TRT was feasible. However further patient accrual and long-term follow up are needed to determine the potential benefits of BID TRT in limited-stage SCLC.

• Radiation Oncology Journal
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• v.27 no.3
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• pp.133-139
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• 2009

Purpose: This study was designed to analyze the outcome and toxicity of thoracic radiation therapy (TRT) and chemotherapy for patients who suffer with limited-stage small-cell lung cancer (LS-SCLC). Materials and Methods: We retrospectively studied 35 patients with LS-SCLC. TRT was administered once daily (1.8 to 2 Gy per fraction) and it was directed to the primary tumor for a total 50 to 66 Gy in 6 to 7 weeks. The patients received four cycles of etoposide plus cisplatin. TRT was begun on day 1 of the first cycle of chemotherapy in the concurrent arm and after the fourth cycle in the sequential arm. Results: The median progression-free survival time was 16.5 months (95% confidence interval [CI], 9.0 to 24.1 months) for the sequential arm, and 26.3 months (95% CI, 16.6 to 35.9 months) for the concurrent arm. The 2-year progression-free survival rate was 16.0 percent for the sequential arm and 50.0 percent for the concurrent arm (p=0.0950 by log-rank test). Leukopenia was more severe and more frequent in the concurrent arm than in the sequential arm. However, severe esophagitis was infrequent in both arms. The radiotherapy was interrupted more frequently in the concurrent arm than in the sequential arm due to hematologic toxicities (p=0.001). Conclusion: This study suggests that concurrent TRT with etoposide plus cisplatin is more effective for the treatment of LS-SCLC than sequential TRT. However, there is a significant increase in the risk of toxicities, and radiotherapy was frequently interrupted in the concurrent arm due to hematologic toxicities.