Dose-intensified stereotactic body radiotherapy for painful vertebral metastases: A randomized phase 3 trial.

BACKGROUND: The purpose of this randomised study was to determine whether dose-intensified stereotactic body radiotherapy (SBRT) for painful vertebral metastases results in increased rates of pain improvement compared with conventional external beam radiotherapy (cEBRT) (control) 6 months after treatment. METHODS: This randomized, controlled phase 3 trial was conducted between November 2016 and January 2023, when it was stopped early. Patients were eligible if they were aged 18 years or older; had one or two painful, stable, or potentially unstable vertebral metastases; and had a life expectancy of 1 year or longer according to the investigator's estimates. Patients received 48.5 grays (Gy) in 10 fractions (with epidural involvement) or 40 Gy in five fractions (without epidural involvement) in the SBRT group and 30 Gy in 10 fractions or 20 Gy in five fractions in the cEBRT group, respectively. The primary end point was an improvement in the pain score at the treated site by at least 2 points (on a visual analog scale from 0 to 10 points) at 6-month follow-up. Data were analyzed on an intention-to-treat and per-protocol basis. RESULTS: Of 214 patients who were screened for eligibility, 63 were randomized 1:1 between SBRT (33 patients with 36 metastases) and cEBRT (30 patients with 31 metastases). The median age of all patients was 66 years, and 40 patients were men (63.5%). In the intention-to-treat analysis, the 6-month proportion of patients who had metastases with pain reduction by 2 or more points was significantly higher in the SBRT group versus the control group (69.4% vs. 41.9%, respectively; two-sided p = .02). Changes in opioid medication intake relative to baseline were nonsignificant between the groups. No differences were observed in vertebral compression fracture or adverse event rates between the groups. CONCLUSIONS: Dose-intensified SBRT improved pain score more effectively than cEBRT at 6 months.

Diabetes Mellitus Is a Strong Independent Negative Prognostic Factor in Patients with Brain Metastases Treated with Radiotherapy.

BACKGROUND: Brain metastases (BM) cause relevant morbidity and mortality in cancer patients. The presence of cerebrovascular diseases can alter the tumor microenvironment, cellular proliferation and treatment resistance. However, it is largely unknown if the presence of distinct cerebrovascular risk factors may alter the prognosis of patients with BM. METHODS: Patients admitted for the radiotherapy of BM at a large tertiary cancer center were included. Patient and survival data, including cerebrovascular risk factors (diabetes mellitus (DM), smoking, arterial hypertension, peripheral arterial occlusive disease, hypercholesterolemia and smoking) were recorded. RESULTS: 203 patients were included. Patients with DM (n = 39) had significantly shorter overall survival (OS) (HR 1.75 (1.20-2.56), p = 0.003, log-rank). Other vascular comorbidities were not associated with differences in OS. DM remained prognostically significant in the multivariate Cox regression including established prognostic factors (HR 1.92 (1.20-3.06), p = 0.006). Furthermore, subgroup analyses revealed a prognostic role of DM in patients with non-small cell lung cancer, both in univariate (HR 1.68 (0.97-2.93), p = 0.066) and multivariate analysis (HR 2.73 (1.33-5.63), p = 0.006), and a trend in melanoma patients. CONCLUSION: DM is associated with reduced survival in patients with BM. Further research is necessary to better understand the molecular mechanisms and therapeutic implications of this important interaction.