Predictive factors for survival and correlation to toxicity in advanced Stage III non-small cell lung cancer patients with concurrent chemoradiation

Abstract

Objective: Concurrent chemoradiotherapy is the standard treatment for locally advanced Stage III non-small cell lung cancer in patients with a good performance status and minimal weight loss. This study aimed to define subgroups with different survival outcomes and identify correlations with the radiation-related toxicities. Methods: We retrospectively reviewed 381 locally advanced Stage III non-small cell lung cancer patients with a good performance status or weight loss of <10% who received concurrent chemoradiotherapy between 2004 and 2011. Three-dimensional conformal radiotherapy was administered once daily, combined with weekly chemotherapy. The Kaplan-Meier method was used for survival comparison and Cox regression for multivariate analysis. Multivariate analysis was performed using all variables with P values <0.1 from the univariate analysis. Results: Median survival of all patients was 24 months. Age > 75 years, the diffusion lung capacity for carbon monoxide ≤80%, gross tumor volume ≥100 cm 3 and subcarinal nodal involvement were the statistically significant predictive factors for poor overall survival both in univariate and multivariate analyses. Patients were classified into four groups according to these four predictive factors. The median survival times were 36, 29, 18 and 14 months in Groups I, II, III and IV, respectively (P < 0.001).Rates of esophageal or lung toxicity ≥Grade 3 were 5.9, 14.1, 12.5 and 22.2%, respectively. The radiotherapy interruption rate differed significantly between the prognostic subgroups; 8.8, 15.4, 22.7 and 30.6%, respectively (P = 0.017). Conclusion: Severe toxicity and interruption of radiotherapy were more frequent in patients with multiple adverse predictive factors. To maintain the survival benefit in patients with concurrent chemoradiotherapy, strategies to reduce treatment-related toxicities need to be deeply considered.

Concurrent chemoradiotherapy with weekly nedaplatin versus radiotherapy alone in elderly patients with non-small-cell lung cancer

“…Gandara DR and Chansky K demonstrated that cisplatin and S-1 with concurrent TRT in unresectable stage III NSCLC patients undergone grade 3/4 leukopenia in 50%, neutropenia in 25%, pneumonitis in 26% of patients [26]. A Japanese study reported that cisplatin or carboplatin, paclitaxel and docetaxel with concurrent RT resulted in an incidence of 13% acute grade 3/4 pneumonitis toxicity and 13% grade 3/4 esophageal toxicity in stage III elderly NSCLC patients [27]. The consequences of our trial are considered remarkably lower toxicity than these three investigations.…”

Multidisciplinary team approach for the management of patients with locally advanced non-small cell lung cancer: searching the evidence to guide the decision

“…A retrospective study showed that age >75 years (p = 0.009), diffusion lung capacity for carbon monoxide (DL CO ) ≤80% (p = 0.011), and gross tumor volume (GTV) ≥ 100 cm 3 (p = 0.001) were statistically significant factors. Severe esophageal and lung toxicity and interruption of RT were more frequent in patients with multiple adverse prognostic factors [14]. …”

“…There remain controversial results regarding age factors (Table 3). Several studies have reported that CCRT could benefit appropriately selected elderly patients [14,16]. In a subgroup analysis of elderly patients (≥75 years), the median survival time was 31 months for those with adequate pulmonary function (DL CO > 80%), with a small tumor volume (GTV < 100 cm 3 ).…”

“…In a subgroup analysis of elderly patients (≥75 years), the median survival time was 31 months for those with adequate pulmonary function (DL CO > 80%), with a small tumor volume (GTV < 100 cm 3 ). Although the number of elderly patients (n = 11) was too small to verify the statistical significance of these findings, it appears that elderly patients (≥75 years) with no adverse risk factors may benefit from CCRT [14]. Heterogeneity of the older cancer patient population requires a carefully tailored approach that considers individual frailty.…”

The Impact of Staging by Positron-Emission Tomography on Overall Survival and Progression-Free Survival in Patients With Locally Advanced NSCLC

“…[3][4][5] However, there is a need for more effective and less toxic regimens as the 5-year survival rates remain low (approximately 14% for stage IIIA and 5% for stage IIIB NSCLC). 2,6 In the PROCLAIM phase 3 trial, concurrent pemetrexed plus cisplatin and thoracic radiotherapy (TRT) followed by consolidation pemetrexed (arm A) in stage IIIA/B inoperable NSCLC did not show superior survival versus a standard concurrent chemoradiotherapy with consolidation (etoposide; arm B). 7 Both treatment arms had longer than expected median overall survival (OS) compared to historical data.…”