This workshop yielded recommendations on using hypoxia measurement to identify patients who would respond best to radiation therapy, which would improve treatment planning. This represents a narrow focus, as hypoxia measurement might also prove useful in drug development and in increasing our understanding of tumor biology.

Purpose: Advanced head and neck cancer shows hypoxia that results in biological changes to make the tumor cells more aggressive and less responsive to treatment resulting in poor survival. [F-18] fluoromisonidazole (FMISO) positron emission tomography (PET) has the ability to noninvasively quantify regional hypoxia. We investigated the prognostic effect of pretherapy FMISO-PETon survival in head and neck cancer. Experimental Design: Seventy-three patients with head and neck cancer had pretherapy FMISO-PETand 53 also had fluorodeoxyglucose (FDG) PETunder a research protocol from April 1994 to April 2004. Results: Significant hypoxia was identified in 58 patients (79%). The mean FMISO tumor/ blood max (T/B max ) was 1.6 and the mean hypoxic volume (HV) was 40.2 mL. There were 28 deaths in the follow-up period. Mean FDG standard uptake value (SUV) max was 10.8.The median time for follow-up was 72 weeks. In a univariate analysis,T/B max (P = 0.002), HV (P = 0.04), and the presence of nodes (P = 0.01) were strong independent predictors. In a multivariate analysis, including FDG SUV max , no variable was predictive at P < 0.05. When FDG SUV max was removed from the model (resulting in n = 73 with 28 events), nodal status and T/B max (or HV) were both highly predictive (P = 0.02, 0.006 for node andT/B max , respectively; P = 0.02 and 0.001for node and HV, respectively).Conclusions: Pretherapy FMISO uptake shows a strong trend to be an independent prognostic measure in head and neck cancer.

Purpose: The aim of this study is to compare glucose metabolism and hypoxia in four different tumor types using positron emission tomography (PET).18 F-labeled fluorodeoxyglucose (FDG) evaluates energy metabolism, whereas the uptake of 18 F-labeled fluoromisonidazole (FMISO) is proportional to tissue hypoxia. Although acute hypoxia results in accelerated glycolysis, cellular metabolism is slowed in chronic hypoxia, prompting us to look for discordance between FMISO and FDG uptake.Experimental Design: Forty-nine patients (26 with head and neck cancer, 11 with soft tissue sarcoma, 7 with breast cancer, and 5 with glioblastoma multiforme) who had both FMISO and FDG PET scans as part of research protocols through February 2003 were included in this study. The maximum standardized uptake value was used to depict FDG uptake, and hypoxic volume and maximum tissue: blood ratio were used to quantify hypoxia. Pixel-by-pixel correlation of radiotracer uptake was performed on coregistered images for each corresponding tumor plane.Results: Hypoxia was detected in all four patient groups. The mean correlation coefficients between FMISO and FDG uptake were 0.62 for head and neck cancer, 0.47 for breast cancer, 0.38 for glioblastoma multiforme, and 0.32 for soft tissue sarcoma. The correlation between the overall tumor maximum standardized uptake value for FDG and hypoxic volume was small (Spearman r ‫؍‬ 0.24), with highly significant differences among the different tumor types (P < 0.005).Conclusions: Hypoxia is a general factor affecting glucose metabolism; however, some hypoxic tumors can have modest glucose metabolism, whereas some highly metabolic tumors are not hypoxic, showing discordance in tracer uptake that can be tumor type specific.

Purpose: Hypoxia is associated with resistance to radiotherapy and chemotherapy and activates transcription factors that support cell survival and migration.We measured the volume of hypoxic tumor and the maximum level of hypoxia in glioblastoma multiforme before radiotherapy with [ Conclusions:The volume and intensity of hypoxia in glioblastoma multiforme before radiotherapy are strongly associated with poorer TTP and survival. This type of imaging could be integrated into new treatment strategies to target hypoxia more aggressively in glioblastoma multiforme and could be applied to assess the treatment outcomes.