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Tumor hypoxia hampers the efficacy of radiotherapy because of its increased resistance to ionizing radiation. The aim of the present study was to estimate the potential added clinical value of the specific hypoxia tracer 18 F-fluoroazomycin arabinoside ( 18 F-FAZA) over commonly used 18 F-FDG in the treatment of advanced-stage non-small cell lung cancer (NSCLC). Methods: Eleven patients with stage III or stage IV NSCLC underwent 18 F-FDG and 18 F-FAZA PET before chemoradiotherapy. The maximum standardized uptake value (SUV max ) was used to depict 18 F-FDG uptake, and the tumorto-background (T/B) ratio and tumor fractional hypoxic volume (FHV) were used to quantify hypoxia. The spatial correlation between 18 F-FDG and 18 F-FAZA uptake values was investigated using voxel-based analysis. Partial-volume correction was applied. Results: All 11 patients showed clear uptake of 18 F-FAZA in the primary tumor. However, different patterns of 18 F-FDG and 18 F-FAZA uptake distributions were observed and varied widely among different tumors. No significant correlation was observed between 18 F-FDG SUV max and 18 F-FAZA T/B ratio (P 5 0.055). The median FHV of 1.4 was 48.4% (range, 5.0-91.5). A significant positive correlation was found between the 18 F-FAZA T/B ratio and FHV of 1.4 (P , 0.001). There was no correlation between the lesion size and FHV or between the 18 F-FDG SUV max and FHV. The pattern of tumoral 18 F-FDG uptake was rather homogeneous, whereas 18 F-FAZA uptake was more heterogeneous, suggesting that 18 F-FAZA identifies hypoxic areas within metabolically active areas of tumor. A significant correlation between 18 F-FDG SUV max and lesion size (P 5 0.002) was observed. Conclusion: 18 F-FAZA PET imaging is able to detect heterogeneous distributions of hypoxic subvolumes out of homogeneous 18 F-FDG background in a clinical setting. Therefore, 18 F-FAZA might be considered a tool for guiding dose escalation to the hypoxic fraction of the tumor. Lungcanceri s the leading cause of worldwide cancer mortality, and non-small cell lung cancer (NSCLC) accounts for 85% of all cases. At presentation, approximately 30% of patients with NSCLC have locally advanced stage III disease (1). The median overall survival for (pathologically) stage IIIA and IIIB disease is 22 and 13 mo, respectively, with corresponding 5-y overall survival rates of 24% and 9%, respectively (2). For patients with stage IV clinical disease, median overall survival is only 6 mo, and the estimated 5-y overall survival a poor 2% (2).The treatment of stage III and IV patients currently consists of either chemotherapy or combined chemoradiotherapy. Unfortunately, the efficacy of these therapies is limited because of chemoradioresistance, which can be attributed to a large extent to the presence of hypoxia (3). The hallmark of tumor hypoxia is upregulation of hypoxia-inducible factor, leading to an increased expression of hypoxia-responsive elements such as the vascular endothelial growth factor, which induces angiogenesis for growth and differentiation...

IntroductionIn randomly assigned studies with EGFR TKI only a minor proportion of patients with NSCLC have genetically profiled biopsies. Guidelines provide evidence to perform EGFR and KRAS mutation analysis in non-squamous NSCLC. We explored tumor biopsy quality offered for mutation testing, different mutations distribution, and outcome with EGFR TKI.Patient and MethodsClinical data from 8 regional hospitals were studied for patient and tumor characteristics, treatment and overall survival. Biopsies sent to the central laboratory were evaluated for DNA quality and subsequently analyzed for mutations in exons 18–21 of EGFR and exon 2 of KRAS by bidirectional sequence analysis.ResultsTumors from 442 subsequent patients were analyzed. For 74 patients (17%) tumors were unsuitable for mutation analysis. Thirty-eight patients (10.9%) had EGFR mutations with 79% known activating mutations. One hundred eight patients (30%) had functional KRAS mutations. The mutation spectrum was comparable to the Cosmic database. Following treatment in the first or second line with EGFR TKI median overall survival for patients with EGFR (n = 14), KRAS (n = 14) mutations and wild type EGFR/KRAS (n = 31) was not reached, 20 and 9 months, respectively.ConclusionOne out of every 6 tumor samples was inadequate for mutation analysis. Patients with EGFR activating mutations treated with EGFR-TKI have the longest survival.