Nitroglycerin as a radiosensitizer in non-small cell lung cancer: Results of a prospective imaging-based phase II trial. (March 2020)

• Record Type: Journal Article
• Authors: Reymen, Bart J.T.; van Gisbergen, Marike W.; Even, Aniek J.G.; Zegers, Catharina M.L.; Das, Marco; Vegt, Erik; Wildberger, Joachim E.; Mottaghy, Felix M.; Yaromina, Ala; Dubois, Ludwig J.; van Elmpt, Wouter; De Ruysscher, Dirk; Lambin, Philippe
• Is Part Of: Clinical and translational radiation oncology. Volume 21(2020)
• Page Start: 49
• Page End: 55
• Publication Date: 2020-03
• Subjects: BF blood flow -- BV blood volume -- CI confidence interval -- CoR coefficient of repeatability -- DCE-CT dynamic contrast-enhanced CT -- FHV fraction of hypoxic volume hypoxic fraction of the GTV -- GTV gross tumour volume -- GTVln gross tumour volume of the lymph nodes -- GTVp gross tumour volume of the primary tumour -- HX4 2-nitroimidazole [18F]-HX4 (flortanidazole, 3-[18F]fluoro-2-(4-((2-nitro-1Himidazol-1-yl)methyl)-1H-1, 2, 3-triazol-1-yl)-propan-1-ol) -- HX4-HF HX4 hypoxic fraction -- HX4-HV HX4 hypoxic volume -- INDAR individualized accelerated radiotherapy -- IQR interquartile range -- LRPFS loco-regional progression free survival -- MFS metastasis-free survival -- NO nitric oxide -- NSCLC non-small cell lung cancer -- OS overall survival -- PET positron emission tomography -- SUVmax maximum standardised uptake value -- SUVmean mean standardised uptake value -- TTD total tumour dose -- TBR tumour-to-blood ratio; Nitroglycerin -- HX4 -- NSCLC -- Hypoxia -- Perfusion -- Mitochondria; Cancer -- Radiotherapy -- Periodicals; Oncology -- Periodicals; Cancer -- Radiotherapy; Oncology; Radiation Oncology; Neoplasms -- radiotherapy; Translational Medical Research; Periodicals; Electronic journals; Periodicals; 616.9940642
• DOI: 10.1016/j.ctro.2019.12.002
• Languages: English
• ISSNs: 2405-6308

Abstract

Highlights: Nitroglycerin didn't improve overall survival of NSCLC patients. The toxicity of combining nitroglycerin with standard treatment was mild. Increased uptake of HX4 showed negative prognostic significance in NSCLC patients. Tumor perfusion after nitroglycerin treatment did not correlate with outcome. Abstract: Background: Nitroglycerin is proposed as an agent to reduce tumour hypoxia by improving tumour perfusion. We investigated the potential of nitroglycerin as a radio-sensitizer in non-small cell lung cancer (NSCLC) and the potential of functional imaging for patient selection. Material and methods: Trial NCT01210378 is a single arm phase II trial, designed to detect 15% improvement in 2-year overall survival (primary endpoint) in stage IB-IV NSCLC patients treated with radical (chemo-) radiotherapy and a Transiderm-Nitro 5 patch during radiotherapy. Patients underwent dynamic contrast-enhanced CTs (DCE-CT) and HX4 (hypoxia) PET/CTs before and after nitroglycerin. Secondary endpoints were progression-free survival, toxicity and the prognostic value of tumour perfusion/hypoxia at baseline and after nitroglycerin. Results: The trial stopped after a futility analysis after 42 patients. At median follow-up of 41 months, two-year and median OS were 58% (95% CI: 44–78%) and 38 months (95% CI: 22–54 months), respectively. Nitroglycerin could not reduce tumour hypoxia. DCE-CT parameters did not correlate with OS, whereas hypoxic tumours had a worse OS (p = 0.029). Changes in high-uptake fraction of HX4 and tumour blood flow were negatively correlated (r = -0.650, p = 0.022). The heterogeneity in treatment modalities and patient characteristics combined with a small sample size made further subgroup analysis of survival results impossible. Toxicity related to nitroglyerin was limited to headache (17%) and hypotension (2.4%). Conclusion: Nitroglycerin did not improve OS of NSCLC patients treated with (chemo-)radiotherapy. A general ability of nitroglycerin to reduce hypoxia was not shown.