Xstrahl in action: Hypoxia imaging predicts radiotherapy response in esophageal adenocarcinoma xenografts
Esophageal cancer patients are mostly diagnosed in a locally advanced stage and treated with neoadjuvant chemoradiation followed by surgery. Prognosis is poor and response to treatment is highly variable. Identification of predictive imaging biomarkers is an important challenge.
Tumor hypoxia is an attractive predictive factor as it has been correlated with chemoresistance, radioresistance, invasiveness, propensity to metastasize, genomic instability and worse prognosis in different solid tumors.
In their research “Hypoxia imaging with 18F-FAZA PET/CT predicts radiotherapy response in esophageal adenocarcinoma xenografts” Melsens E, De Vlieghere E, Descamps B, Vanhove C, Kersemans K, De Vos F, Goethals I, Brans B, De Wever O, Ceelen W and Pattyn P, aimed to predict radiotherapy response by imaging tumor hypoxia with 18F-FAZA PET/CT in an esophageal adenocarcinoma mouse model. Additionally, they investigated the radiosensitizing effect of the hypoxia modifier nimorazole in vitro and in vivo.
Using in vitro MTS cell proliferation assays tests were performed under normoxic and hypoxic conditions: control (100 μL PBS), nimorazole, irradiation (5, 10 or 20 Gy) with or without nimorazole. In vivo, subcutaneous xenografts were induced in nude mice, and treatment was given daily for 5 consecutive days. 18F-FAZA PET/CT was performed before treatment and tumor to background ratios were calculated. Relative tumor growth was calculated and tumor sections were examined histologically (hypoxia, proliferation).
A T/B ≥ 3.59 on pre-treatment 18F-FAZA PET/CT was predictive for worse radiotherapy response (sensitivity 92.3%, specificity 71.4%). Radiation was less effective in hypoxic tumors (T/B ≥ 3.59) compared to normoxic tumors (T/B < 3.59) (P = 0.0025). In vitro, pre-treatment with nimorazole significantly decreased hypoxic radioresistance (P < 0.01) while in vivo, nimorazole enhanced the efficacy of radiotherapy to suppress cancer cell proliferation in hypoxic tumor areas (Ki67, P = 0.064), but did not affect macroscopic tumor growth.
It was therefore concluded that tumor tissue hypoxia as measured with 18F-FAZA PET/CT is predictive for radiotherapy response in an EAC xenograft model. However, the radiosensitizing effect of nimorazole