Local recurrence remains a major obstacle to achieving cure of many locally advanced solid tumors treated with definitive radiation therapy. The microen-vironment of solid tumors is hypoxic compared with normal tissue, and this hypoxia is associated with decreased radiosensitivity. Recent preclinical data also suggest that intratumoral hypoxia, particularly in conjunction with an acid microenvironment, may be directly or indirectly mutagenic. Investigations of the prognostic significance of the pretreatment oxygenation status of tumors in patients with head and neck or cer-vical cancer have demonstrated that increased hypoxia, typically designated in these studies as pO 2 levels below 2.5-10 mm Hg, is associated with decreased local tumor control and lower rates of disease-free and overall survival. Hypoxia-directed therapies in the radiation oncology setting include treatment using hyperbaric oxygen, fluosol infusion, carbogen breathing, and electron-affinic and hypoxic-cell sensitizers. These interventions have shown the potential to increase the effectiveness of curative-intent radiation therapy, demonstrating that the strategy of overcoming hypoxia may be a viable and important approach. Anemia is common in the cancer population and is suspected to contribute to intratu-moral hypoxia. A review of the literature reveals that a low hemoglobin level before or during radiation therapy is an important risk factor for poor locoregional disease control and survival, implying that a strong correlation could exist between anemia and hypoxia (ulti-mately predicting for a poor outcome). While having a low hemoglobin level has been shown to be detrimental, it is unclear as to exactly what the threshold for "low" should be (studies in this area have used thresholds ranging from 9-14.5 g/dl). Optimal hemoglobin and pO 2 thresholds for improving outcomes may vary across and within tumor types, and this is an area that clearly The Oncologist 2002;7:492-508 www.TheOncologist.com The Oncologist ® LEARNING OBJECTIVES After completing this course, the reader will be able to: 1. Discuss the prognostic significance of intratumoral hypoxia and low hemoglobin levels in patients receiving curative-intent radiation for head and neck or cervical cancer. 2. Describe the potential relationship between anemia and intratumoral hypoxia in patients with solid tumors. 3. List possible interventions for improving intratumoral oxygenation and radiosensitivity in the radiation oncology setting. Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com

Most patients treated in Z0011 received tangential RT alone, and some received no RT at all. Some patients received directed nodal irradiation via a third field. Further research is necessary to determine the optimal RT approach in patients with low-volume axillary disease treated with SLND alone.

Primary systemic therapy (PST) or neoadjuvant therapy is used in nonmetastatic breast cancer to treat systemic disease earlier, decrease tumor bulk ideally to a complete pathological response (pCR), and reduce the extent of surgery. The multitude of clinical trials using PST in breast cancer patients has not proven the fundamental hypotheses of improved overall survival and disease-free survival that drove the investigation of PST. The other potential advantages of PST, which include increasing the rate of breast-conserving surgery and predicting outcome to a particular chemotherapy regimen, are also not conclusively established. We examined the published literature on PST for breast cancer and predominantly focused our review on data from large, randomized clinical trials comparing primary systemic chemotherapy with adjuvant chemotherapy, different primary systemic chemotherapy regimens, primary systemic chemotherapy with hormonal therapy, and different preoperative hormonal therapies. Although the optimal neoadjuvant chemotherapy regimen has not been established, a combination of four cycles of an anthracycline followed by four cycles of a taxane appears to produce the highest pCR rate (22%-31%). In patients with HER-2-positive breast cancer, concurrent use of neoadjuvant trastuzumab with an anthracycline-taxane combination has produced provocative results that require further confirmatory studies. Preoperative hormonal therapy is associated with low pCR rates and should be reserved for patients who are poor candidates for systemic chemotherapy. The optimal management of patients with residual disease after the administration of maximum neoadjuvant therapy remains to be defined. The surgical approach, including the role of sentinel node biopsy and delivery of radiation therapy after PST in breast cancer patients, is evolving. Ongoing clinical trials will help identify the subset of patients who would most benefit from the use of PST, establish the most effective PST regimen, and determine the optimal multidisciplinary approach in the management of breast cancer. The Oncologist 2006;11:574-589 Learning ObjectivesAfter completing this course, the reader will be able to:1. Describe the rationale for using primary systemic therapy (PST) in the treatment of nonmetastatic breast cancer.2. Discuss the pathologic complete response (pCR) rate as a surrogate marker of PST benefit.3. Select the most appropriate regimen for a patient with breast cancer considered for PST.4. Explain the role of sentinel node biopsy and delivery of radiation therapy after PST in breast cancer patients.Access and take the CME test online and receive 1 AMA PRA category 1 credit at CME.TheOncologist.com CME CME This material is protected by U.S.