Prognostic significance of hypoxic PET using (18)F-FAZA and (62)Cu-ATSM in non-small-cell lung cancer.

Abstract

Tumor hypoxia is believed to have a strong correlation with the resistance to chemoradiotherapy. Noninvasive evaluation of hypoxic status in tumors using molecular imaging has the potential to characterize the tumor aggressiveness. We evaluated the clinical usefulness of newly-developed tumor hypoxic positron emission tomography (PET) tracers in localized non-small-cell lung cancer (NSCLC). Forty-seven patients with localized NSCLC received either or both hypoxic PETs using the tracers: (18)F-fluoroazomycin arabinoside ((18)F-FAZA) (n=45) and/or (62)Cu-diacetyl-bis (N4)-methylsemithiocarbazone ((62)Cu-ATSM) (n=22). All received (18)F-fluorodeoxyglucose ((18)F-FDG) PET tracer (n=47). We examined the correlation between uptake of three PET tracers and clinicopathological factors, and evaluated their impacts on survival after treatment retrospectively. A couple of commonly-identified unfavorable factors such as presence of vascular invasion and pleural invasion was significantly correlated with higher uptake of these hypoxic agents as well as that of (18)F-FDG. Larger tumor diameter, high neutrophil-to-lymphocyte ratio and advanced pathological stage were also associated with accumulation of hypoxic PETs ((18)F-FAZA, p<0.01; (62)Cu-ATSM, p<0.04), but not with that of (18)F-FDG. The patients with a higher accumulation had significantly poorer overall survival [(18)F-FAZA, HR (hazard ratio), 9.50, p<0.01; (62)Cu-ATSM, HR, 4.06, p<0.05] and progression free survival ((18)F-FAZA, HR, 5.28, p<0.01, (62)Cu-ATSM, HR, 2.72, p<0.05). Both (18)F-FAZA and (62)Cu-ATSM PET provide useful information regarding tumor aggressiveness and prediction of survival among NSCLC patients. We believe these hypoxic PETs could contribute to the establishment of the optimally individualized treatment of NSCLC.