Phase II Study of a Radiotherapy Total Dose Increase in Hypoxic Lesions Identified by ¹⁸F-Misonidazole PET/CT in Patients with Non–Small Cell Lung Carcinoma (RTEP5 Study)

Abstract

See an invited perspective on this article on page 1043.This multicenter phase II study investigated a selective radiotherapy dose increase to tumor areas with significant 18 F-misonidazole ( 18 F-FMISO) uptake in patients with non-small cell lung carcinoma (NSCLC). Methods: Eligible patients had locally advanced NSCLC and no contraindication to concomitant chemoradiotherapy. The 18 F-FMISO uptake on PET/CT was assessed by trained experts. If there was no uptake, 66 Gy were delivered. In 18 F-FMISO-positive patients, the contours of the hypoxic area were transferred to the radiation oncologist. It was necessary for the radiotherapy dose to be as high as possible while fulfilling dose-limiting constraints for the spinal cord and lungs. The primary endpoint was tumor response (complete response plus partial response) at 3 mo. The secondary endpoints were toxicity, disease-free survival (DFS), and overall survival at 1 y. The target sample size was set to demonstrate a response rate of 40% or more (bilateral a 5 0.05, power 1-b 5 0.95). Results: Seventy-nine patients were preincluded, 54 were included, and 34 were 18 F-FMISO-positive, 24 of whom received escalated doses of up to 86 Gy. The response rate at 3 mo was 31 of 54 (57%; 95% confidence interval [CI], 43%-71%) using RECIST 1.1 (17/34 responders in the 18 F-FMISO-positive group).

FDG and FMISO PET-guided dose escalation with intensity-modulated radiotherapy in lung cancer

“…In a phase II study (NCT01576796, RTEP5 study), we used 18 F-miso to identify and delineate hypoxic areas within the 18 FDG-defined Gross Target Volume (GTV) [ 7 ]. The total radiotherapy dose was safely increased in 24 out of 34 patients with 18 F-miso uptake.…”

Nitroglycerin as a radiosensitizer in non-small cell lung cancer: Results of a prospective imaging-based phase II trial

“…FDG-PET, DCE-CT imaging parameters and total GTV did not correlate with survival in this cohort, but patients with baseline hypoxic primary tumours had a worse prognosis than patients with normoxic tumours. Other nitro-imidazole based PET tracers, FMISO, FAZA and FETNIM [13][14][15][16], already showed to be prognostic in NSCLC, but this is the first prospective trial to find this correlation for HX4. Whether this is independent of other factors (such as GTV or pathology) should be investigated in larger cohorts, since the limited number of patients with baseline hypoxia precludes extensive multivariate analysis.…”

Oxygen-enhanced MRI Is Feasible, Repeatable, and Detects Radiotherapy-induced Change in Hypoxia in Xenograft Models and in Patients with Non–small Cell Lung Cancer

“…Furthermore, perfused Oxy-R may guide radiotherapy dose intensification (dose painting; refs. 45,46) and has unique potential for clinical applications such as real-time adaptive radiotherapy on MR Linac systems (47). For each of these applications, large studies are required to qualify the prognostic value of perfused Oxy-R as a biomarker of hypoxia and its ability to predict therapy response.…”