Tumor hypoxia is a well-established biological phenomenon that affects the curability of solid tumors, regardless of treatment modality. Especially for head and neck cancer patients, tumor hypoxia is linked to poor patient outcomes. Given the biological problems associated with tumor hypoxia, the goal for clinicians has been to identify moderately to severely hypoxic tumors for differential treatment strategies. The ''gold standard'' for detecting and characterizing of tumor hypoxia are the invasive polarographic electrodes. Several less invasive hypoxia assessment techniques have also shown promise for hypoxia assessment. The widespread incorporation of hypoxia information in clinical tumor assessment is severely impeded by several factors, including regulatory hurdles and unclear correlation with potential treatment decisions. There is now an acute need for approved diagnostic technologies for determining the hypoxia status of cancer lesions, as it would enable clinical development of personalized, hypoxia-based therapies, which will ultimately improve outcomes. A number of different techniques for assessing tumor hypoxia have evolved to replace polarographic pO 2 measurements for assessing tumor hypoxia. Several of these modalities, either individually or in combination with other imaging techniques, provide functional and physiological information of tumor hypoxia that can significantly improve the course of treatment. The assessment of tumor hypoxia will be valuable to radiation oncologists, surgeons, and biotechnology and pharmaceutical companies who are engaged in developing hypoxia-based therapies or treatment strategies. Antioxid. Redox Signal. 21, 1516-1554.

Purpose:To determine the performance of positron emission mammography (PEM), as compared with magnetic resonance (MR) imaging, including the effect on surgical management, in ipsilateral breasts with cancer. Materials and Methods:Four hundred seventy-two women with newly diagnosed breast cancer who were offered breast-conserving surgery consented from September 2006 to November 2008 to participate in a multicenter institutional review board-approved, HIPAA-compliant protocol. Participants underwent contrast material-enhanced MR imaging and fl uorine 18 fl uorodeoxyglucose PEM in randomized order; resultant images were interpreted independently. Added biopsies and changes in surgical procedure for the ipsilateral breast were correlated with histopathologic fi ndings. Performance characteristics were compared by using the McNemar test and generalized estimating equations. Results:Three hundred eighty-eight women (median age, 58 years; age range, 26-93 years; median estimated tumor size, 1.5 cm) completed the study. Additional cancers were found in 82 (21%) (41%) were depicted by PEM ( P = .043). Fifty-six (14%) of the 388 women required mastectomy: 40 (71%) of these women were identifi ed with MR imaging, and 20 (36%) were identifi ed with PEM ( P , .001). Eleven (2.8%) women underwent unnecessary mastectomy, which was prompted by only MR fi ndings in fi ve women, by only PEM fi ndings in one, and by PEM and MR fi ndings in fi ve. Thirty-three (8.5%) women required wider excision: 24 (73%) of these women were identifi ed with MR imaging, and 22 (67%) were identifi ed with PEM. Conclusion:PEM and MR imaging had comparable breast-level sensitivity, although MR imaging had greater lesion-level sensitivity and more accurately depicted the need for mastectomy. PEM had greater specifi city at the breast and lesion levels. Eighty-nine (23%) participants required more extensive surgery: 61 (69%) of these women were identifi ed with MR imaging, and 41 (46%) were identifi ed with PEM ( P = .003). Fourteen (3.6%) women had tumors seen only at PEM.

PEM was more sensitive than either WBPET or PET/CT in showing index and additional ipsilateral breast tumors and remained highly sensitive for tumors smaller than 1 cm.

Use of standardized terminology to report PEM findings will facilitate effective communication of results and consistent management. A probably benign category 3 assessment carried a substantial rate of malignancy for lesions seen on PEM, and biopsy may be more appropriate than follow-up.

Contralateral cancer was found in 15 of 367 women (4.1%), with MRI showing 14 (93%). Eleven contralateral cancers (73%) were visible on PEM, but only three (20%) were recognized prospectively as suspicious. Lesions that are visible on PEM should be viewed as suspicious unless known to be benign by prior breast imaging or biopsy.