Increasing Tumor Volume Is Predictive of Poor Overall and Progression-Free Survival: Secondary Analysis of the Radiation Therapy Oncology Group 93-11 Phase I-II Radiation Dose-Escalation Study In Patients With Inoperable Non-Small-Cell Lung Cancer

Purpose Patients with non–small-cell lung cancer (NSCLC) in the Radiation Therapy Oncology Group (RTOG) 93-11 trial received radiation doses of 70.9, 77.4, 83.8, or 90.3 Gy. The locoregional control and survival rates were similar among the various dose levels.We investigated the effect of the gross tumor volume (GTV) on the outcome. Methods and Materials The GTV was defined as the sum of the volumes of the primary tumor and involved lymph nodes. The tumor response, median survival time (MST), and progression-free survival (PFS) were analyzed separately for smaller (≤45 cm3) vs. larger (\u3e45 cm3) tumors. Results The distribution of the GTV was as follows: ≤45 cm3 in 79 (49%) and \u3e45 cm3 in 82 (51%) of 161 patients. The median GTV was 47.3 cm3. N0 status and female gender were associated with better tumor responses. Patients with smaller (≤45 cm3) tumors achieved a longer MST and better PFS than did patients with larger (\u3e45 cm3) tumors (29.7 vs. 13.3 months, p \u3c 0.0001; and 15.8 vs. 8.3 months, p \u3c 0.0001, respectively). Increasing the radiation dose had no effect on the MST or PFS. On multivariate analysis, only a smaller GTV was a significant prognostic factor for improved MST and PFS (hazard ratio [HR], 2.12, p = 0.0002; and HR, 2.0, p = 0.0002, respectively). The GTV as a continuous variable was also significantly associated with the MST and PFS (HR, 1.59, p \u3c 0.0001; and HR, 1.39, p \u3c 0.0001, respectively). Conclusions Radiation dose escalation up to 90.3 Gy did not result in improved MST or PFS. The tumor responses were greater in node-negative patients and women. An increasing GTV was strongly associated with decreased MST and PFS. Future radiotherapy trials patients might need to use stratification by tumor volume. Int. J. Radiation Oncology Biol. Physics, Volume 70, No. 2, pp. 385-390, 200

Articles Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial

Summary Background Dabrafenib, an inhibitor of mutated BRAF, has clinical activity with a manageable safety profi le in studies of phase 1 and 2 in patients with BRAF V600 -mutated metastatic melanoma. We studied the effi cacy of dabrafenib in patients with BRAF V600E -mutated metastatic melanoma