Analysis of Once-Daily Thoracic Radiotherapy Dose According to the Underlying Lung Disease in Patients with Limited-Stage Small Cell Lung Cancer Undergoing Concurrent Chemoradiotherapy

Abstract

In the treatment of concurrent chemoradiotherapy (CCRT) in limited-stage small cell lung cancer, the optimal once-daily radiotherapy (RT) dose/fractionation remain unclear although it is the most frequently used. Therefore, this study aimed to compare the treatment outcomes and toxicities of modest dose RT (≤54 Gy) with those of standard dose RT (>54 Gy) and investigate the benefit of the high dose based on patient factors. Materials and MethodsSince 2004, our institution has gradually increased the thoracic RT dose. Among the 225 patients who underwent CCRT, 84 patients (37.3%) received >54 Gy. Because the patients treated with RT > 54 Gy were not randomly assigned, propensity score matching (PSM) was performed. ResultsThe proportion of patients treated with >54 Gy increased over time (p=0.014). Multivariate analysis revealed that the overall tumor stage and dose > 54 Gy (hazard ratio 0.65, p=0.029) were independent prognostic factors for overall survival (OS). PSM confirmed that thoracic RT doses of >54 Gy showed significantly improved progression-free survival (3-year 42.7% vs 24.0%, p < 0.001) and OS (3-year 56.2% vs 38.5%, p=0.003). Sensitivity analysis also showed that 60 Gy resulted in better survival than 54 Gy. However, in patients with underlying lung disease, OS benefit from >54 Gy was not observed but considerable rates of severe pulmonary toxicities were observed (p=0.001). ConclusionOur analysis supports that the 60 Gy RT dose should be considered in the once-daily regimen of CCRT for limited-stage small cell lung cancer without underlying lung disease, but RT dose > 54 Gy did not seem to benefit for patients with chronic obstructive pulmonary disease or interstitial lung disease. Further study is needed to validate these results.

Outcome of dose-escalated intensity-modulated radiotherapy for limited disease small cell lung cancer

“…However, few studies have compared the once-daily regimen [ 18 , 19 ] for dose escalation. Kim et al [ 18 ] showed a 3-year OS of 53.6% in the dose-escalated group irradiated with >54 Gy, and Tomita et al [ 19 ] showed a median OS equal to 41.0 months in the standard fractionation group (≥54 Gy). In the current study, we reveal that the use of a once-daily regimen with IMRT achieves a median OS of more than 3 years, with acceptable toxicity in all patients.…”

“…In our institution, we employ dose escalation in selective patients with consideration for their age, performance, other morbidities, and dose constraints for normal organs. Among the few studies that have compared once-daily regimens, one showed no significant difference in complications based on 54 Gy [ 26 ] and another study showed better PFS and OS based on the same dose [ 18 ]. Therefore, we set a dose that was slightly higher than this as the standard and converted it into BED 10 considering the diversity of the dose per fraction.…”

“…ly group and 70 Gy once-daily groups, respectively (p = 0.498). However, few studies have compared the once-daily regimen [18,19] for dose escalation. Kim et al [18] showed a 3-year OS of 53.6% in the dose-escalated group irradiated with > 54 Gy, and Tomita et al [19] showed a median OS equal to 41.0 months in the standard fractionation group ( ≥ 54 Gy).…”

The Dose/Fractionation Debate in Limited-Stage Small Cell Lung Cancer

“…The results showed that, after propensity matching, compared to the ≤54 Gy (BED10) ConvTRT group, the >54 Gy (BED10) ConvTRT group demonstrated significant improvements in three-year progression-free survival and overall survival rates (42.7% and 56.2%, respectively, both p < 0.001 and 0.003). According to the survival curves [9], the two-year overall survival rate was 61% for the ≤54 Gy ConvTRT group, while it was 72% for the >54 Gy ConvTRT group (as shown in Figure 1). The most common dose fractions in this propensity-matched study were 54 Gy/27 Fx (n = 120, accounting for 53.3%, BED10 = 49.54 Gy) and 60 Gy/30 Fx (n = 70, accounting for 31.1%, BED10 = 55.5 Gy).…”

“…Eleven patients died from treatment-related causes (3 in the twice-daily group, 8 in the once-daily group). A propensity scores matching analysis [9] was used to study the survival efficacy among different doses of ConvTRT treatment regimens. The results showed that, after propensity matching, compared to the ≤54 Gy (BED10) ConvTRT group, the >54 Gy (BED10) ConvTRT group demonstrated significant improvements in three-year progression-free survival and overall survival rates (42.7% and 56.2%, respectively, both p < 0.001 and 0.003).…”