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Background:
RTOG0617 found higher radiation dose does not benefit patients with unresectable stage III non-small cell lung cancer (NSCLC). To investigate the potential benefit of individual isotoxic dose escalation based on normal tissue constraints (NTC), hypothesizing that high-dose radiation therapy would be superior to standard-dose in concurrent chemoradiotherapy for unresectable stage III NSCLC.

Methods:
Data from two prospective clinical trials were merged for analysis. Individually prescribed radiation doses were calculated based on NTC. Patients with total radiation doses ≥66 Gy were assigned to the high-dose group (H-D, ≥66 Gy), and all other patients were assigned to the standard-dose group (S-D, <66 Gy). Intensity modulated radiation therapy plans were optimized to minimize the volumes of organs at risk exposed to radiation. The primary endpoint was overall survival.

Results:
From March 2006 to September 2012, 140 patients were enrolled and assigned to one of two groups: 71 patients into the H-D group and 69 patients into the S-D group. The median survival time (MST) was significantly higher in the H-D group (33.5 months) than in the S-D group (17 months), (p < 0.0001). Overall 5-year survival rates were significantly higher in the H-D group than in the S-D group (38.0% vs. 12.3%). Median progression-free survival was 19 months in the H-D group and 11 months in the S-D group (p < 0.0001). No difference in severe (grade 3–5) toxic effects was noted between the two groups.

Conclusions:
The dose-escalated radiation concurrent with chemotherapy showed an significant advantage in MST and survival rates over standard-dose. This individualized isotoxic dose chemoradiotherapy strategy may be a promising method for unresectable stage III NSCLC patients.

Clinical trial identification:


Legal entity responsible for the study:
Shandong Cancer Hospital

Funding:
This study was supported in part by National Nature Science Foundation of China (Grant NO. 81530060), and The National Key Research and Development Plan (Grant NO. 2016YFC0105106).

Disclosure:
All authors have declared no conflicts of interest.

Background:
RTOG 0617 identified cardiac dose-volume metrics as independent predictors of survival for locally advanced NSCLC patients following chemoradiotherapy with conventional and dose escalated regimes. Accelerated radiotherapy schedules such as continuous hyperfractionated accelerated radiotherapy (CHART) are widespread in the UK. In this single-centre retrospective analysis, we study the impact of cardiac dosimetry on survival of early stage and locally advanced patients radically treated with accelerated radiotherapy.

Methods:
We reviewed the records of all stage I-III NSCLC patients treated at our institution with radical accelerated radiotherapy (CHART, 54 Gy/36# over 12 days; hypofractionated, 55 Gy/20# over 4 weeks) between 2010 and 2015. Patient demographics, tumour characteristics, survival and dosimetric data were recorded. Cardiac dosimetric parameters included heart V5, V30, V33, V50, V67, V100 and mean dose. The impact of these metrics on survival was assessed using Cox regression.

Results:
We identified 563 patients treated of whom 294 had cardiac dosimetric data for analysis. For these patients, 55% were male with a mean age of 72. The percentage of patients with stage I, II and III disease were 33%, 16% and 51%, respectively. 60% had a WHO performance status of 0–1. 124 received CHART and 171 received hypofractionated radiotherapy. 2 year overall survival was 48% with a median overall survival of 22.5 months. On univariate analysis, gender, stage, tumour recurrence, PTV volume and all cardiac dosimetric parameters were significantly associated with survival. However, multivariate analysis identified only PTV volume and heart V30, V33, V50 and mean dose as independent predictors of survival with mean heart dose being the most predictive (HR = 1.027, 95% CI = 1.002–1.053, p = 0.032).

Conclusions:
We identified several cardiac dosimetric parameters as independent predictors of survival following accelerated radiotherapy. Consequently, minimising cardiac dose may improve outcomes and warrants further study.

Clinical trial identification:


Legal entity responsible for the study:
Weston Park Hospital

Funding:
Sheffield Hospital Charity

Disclosure:
All authors have declared no conflicts of interest.

Background:
The survival advantage of radiotherapy (RT) for patients with stage IV non-small cell lung cancer (NSCLC) has not been adequately evaluated.

Methods:
We analyzed stage IV NSCLC patients enrolled from the Surveillance, Epidemiology, and End Results (SEER) registry through January 2010 to December 2012. Propensity score (PS) analysis with 1:1 nearest neighbor matching method was used to ensure well-balanced characteristics of all comparison groups by histological types and metastatic sites. Kaplan-Meier and Cox proportional hazardous model were used to evaluate the overall survival (OS) and cancer-specific survival (CSS).

Results:
There was a trend towards improved OS and CSS using radiotherapy to stage IV NSCLC patients for any metastatic sites and for any histological types except AD. Radiotherapy significantly improved the survival of NSCLC patients with metastasis to brain (P < 0.001), especially for adenocarcinoma (AD) (P < 0.001). For stage IV lung cancer patients with squamous cell carcinoma (SQC), radiotherapy for any metastatic sites could universally improve the OS (P < 0.001) and CSS (P < 0.001). In particular, radiotherapy also was associated with improved OS (P < 0.001) and CSS (P = 0.012) for stage IV patients with metastases of two or more site, i.e., poly-metastatic disease. Furthermore, for those stage IV SQC patients without metastasis, radiotherapy, most likely to the primary site, also significantly improved the survival (P < 0.001).

Conclusions:
The results support the idea that radiotherapy might improve the survival of patients with metastatic NSCLC in a PS-matched patient cohort from the large SEER database. It is prudent to carefully select patients for radiotherapy in metastatic NSCLC.

Clinical trial identification:


Legal entity responsible for the study:
Dr. Zhenming Fu, Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China

Funding:
National Science Foundation of China (NSFC)

Disclosure:
All authors have declared no conflicts of interest.

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