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.

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Extra efficiency is possible, but it is difficult to predict when favorable conditions exist. If a factorial design is used, potential efficiency gains should be weighed against potential loss of power to arrive at the correct conclusion under possible scenarios of interest.

Breast-sparing therapy was used in the minority of women subsequently accrued to two national adjuvant breast cancer studies, even though this cohort and their referring surgeons represented a select population. Although multiple concrete factors were independent predictors of lower lumpectomy rates, prospective research is needed into how patients and their physicians approach the mastectomy versus lumpectomy decision.

Kinetic analysis is used to extract metabolic information from dynamic positron emission tomography (PET) uptake data. The theory of indicator dilutions, developed in the seminal work of Meier and Zierler (1954), provides a probabilistic framework for representation of PET tracer uptake data in terms of a convolution between an arterial input function and a tissue residue. The residue is a scaled survival function associated with tracer residence in the tissue. Nonparametric inference for the residue, a deconvolution problem, provides a novel approach to kinetic analysis-critically one that is not reliant on specific compartmental modeling assumptions. A practical computational technique based on regularized cubic B-spline approximation of the residence time distribution is proposed. Nonparametric residue analysis allows formal statistical evaluation of specific parametric models to be considered. This analysis needs to properly account for the increased flexibility of the nonparametric estimator. The methodology is illustrated using data from a series of cerebral studies with PET and fluorodeoxyglucose (FDG) in normal subjects. Comparisons are made between key functionals of the residue, tracer flux, flow, etc., resulting from a parametric (the standard twocompartment of Phelps et al. 1979) and a nonparametric analysis. Strong statistical evidence against the compartment model is found. Primarily these differences relate to the representation of the early temporal structure of the tracer residence-largely a function of the vascular supply network. There are convincing physiological arguments against the representations implied by the compartmental approach but this is the first time that a rigorous statistical confirmation using PET data has been reported. The compartmental analysis produces suspect values for flow but, notably, the impact on the metabolic flux, though statistically significant, is limited to deviations on the order of 3%-4%. The general advantage of the nonparametric residue analysis is the ability to provide a valid kinetic quantitation in the context of studies where there may be heterogeneity or other uncertainty about the accuracy of a compartmental model approximation of the tissue residue.