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We have recently published the first results of a randomized trial comparing high-dose with standard dose twice-daily thoracic radiotherapy (TRT) in limited stage small cell lung cancer (LS SCLC) (NCT02041845). In this trial, patients received four courses of platinum/etoposide chemotherapy and were randomized to receive twice-daily TRT of 45 Gy/30 fractions or 60 Gy/40 fractions. Patients in the high-dose arm achieved a significantly higher 2-year survival (primary endpoint) (74.2% vs. 48.1%; p=0.001) and longer median overall survival (37.2 vs. 22.6 months; p=0.012). Notably, there was not more radiotherapy related toxicity in the high-dose arm. This is the first randomized trial to show a survival benefit in LS SCLC for more than 20 years. There was no difference in distribution of TNM-stage of disease between the treatment arms (Table 1), but it has been questioned whether there was an imbalance in tumor- and irradiated volumes. In a follow-up PhD-project we will analyze all radiotherapy treatment plans and baseline CT and PET-CT images in order to assess tumor volumes, irradiation of surrounding normal tissue, and feasibility of the high-dose of 60 Gy/40 fractions also for patients that received the standard dose. To our knowledge, this PhD-project is the first detailed analysis of 3-dimensional dose distributions in a randomized trial of TRT in LS SCLC. Here we present the first results of target volume evaluation.

Radiotherapy treatment plans (3D) were collected for all 166 patients who commenced TRT, imported into RayStation radiotherapy treatment planning system (v. 9Bsp1, ©RaySearch Laboratories) and standardized for automatic extraction of data. The total planning target volume (PTV, ICRU83) was chosen for the analysis, as it was the most consistent volume delineated across all hospitals. The PTVs, as defined in the trial protocol, included gross tumor volume, margins for subclinical disease, tumor motion and technical uncertainties. Wilcoxon rank sum test was used to analyze volume differences between the treatment arms.

Volume distributions of PTVs for the treatment arms, sorted in decreasing order, are shown in Figure 1A with the corresponding boxplot shown in Figure 1B. There were no significant differences in volumes of PTV between treatment arms (Wilcoxon rank sum, p = 0.50). Mean and median values with corresponding measures of spread are shown in Table 1. Notably, some of the patients with the largest PTVs received 60 Gy. The proportion of radiotherapy treatment plans made by using modern inverse treatment planning techniques such as VMAT and IMRT were also well balanced between the treatment arms (Table 1).

Treatment arms in our randomized trial of high-dose versus standard dose twice-daily TRT in LS SCLC were well balanced with respect to both volumes of PTV and treatment planning techniques.