@article {72, title = {Data from: Nitroglycerin in non-small cell lung cancer: does it impact tumor hypoxia and tumor perfusion? A window-of-opportunity clinical trial.}, year = {2016}, abstract = {

Despite preclinical evidence that nitric oxide (NO) donors influence both tumor perfusion and hypoxia, in clinical trials nitroglycerin has not been shown to improve the treatment results of all patients with non-small cell lung cancer (NSCLC). Biomarkers are therefore needed to select patients for treatment with NO donors. In this window-of-opportunity study we demonstrate the effect of nitroglycerin on hypoxia in patients using repeated hypoxia PET-imaging: we observed a reduction of hypoxia - quantified by uptake of PET tracer HX4- of varying magnitude upon application of a nitroglycerin patch in approximately two thirds of patients with hypoxic loco-regional disease.

In a quarter of patients with baseline hypoxia, the tumor and nodes become normoxic after treatment with nitroglycerin. Furthermore, through dynamic contrast enhanced CT-scans (DCE-CT) we demonstrated that this effect on hypoxic tracer uptake is negatively correlated with tumor perfusion in hypoxic tumors.

Using in vitro experiments we show that the metabolism of 2-nitroimidazoles is not influenced by nitroglycerin itself and furthermore that nitroglycerin does not inhibit mitochondrial respiration at human achievable concentrations. Therefore, 2-nitroimidazole based imaging biomarkers can be used to evaluate the nitroglycerin treatment efficacy in an individual patient.\ 

The current results do support the hypothesis that hypoxia scans and/or DCE-CT scans could form a tool to select patients for a nitroglycerin patch adjuvant to anti-cancer treatment (radiotherapy, chemotherapy, targeted agents or immunotherapy) to increase drug uptake and/or to decrease hypoxia.

An animation summarizing our results is available at https://youtu.be/udJSBYaRv9w.

Figure 1. Uptake of HX4 before and after nitoglycerin administration

A. Images of a HX4 PET/CT scan before and after nitroglycerin administration of the same patient.
B. Evolution of high-uptake fraction (HF) of HX4 after application of nitroglycerin patch in baseline hypoxic lesions. Blue = decline \> CR of HX4 (17\%), grey = stable: change \< CR.

Note: dataset was updated 2017-11-24
}, doi = {10.17195/candat.2016.07.2}, author = {Bart Reymen and Marike W. van Gisbergen and Aniek J.G. Even and Catharina M.L. Zegers and Cary Oberije and Felix Mottaghy and Marco Das and Ala Yaromina and Wouter van Elmpt and Dirk De Ruysscher and Ludwig Dubois and Philippe Lambin} }