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Article Outline

• Impact of High-dose Chemotherapy on the Ability to Deliver Subsequent Local–Regional Radiotherapy for Breast Cancer:Analysis of Cancer and Leukemia Group B Protocol 9082Page 1305
• Multi-institutional Trial of Accelerated Hypofractionated Intensity-Modulated Radiation Therapy for Early-Stage, Oropharyngeal Cancer (RTOG 00-22)Page 1333
• Total Androgen Blockade Versus a Luteinizing Hormone–Releasing Hormone Agonist Alone in Men With High-Risk Prostate Cancer Treated With RadiotherapyPage 1439
• Activated Macrophages as a Novel Determinant of Tumor Cell Radioresponse: The Role of Nitric Oxide–Mediated Inhibition of Cellular Respiration and Oxygen SparingPage 1520

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Impact of High-dose Chemotherapy on the Ability to Deliver Subsequent Local–Regional Radiotherapy for Breast Cancer:Analysis of Cancer and Leukemia Group B Protocol 9082Page 1305 

L. B. Marks, C. Irrincione, T. J. Fitzgerald, F. Laurie, A. S. Glicksman, J. Vredenburgh, L. R. Prosnitz, E. J. Shpall, M. Crump, P. G. Richardson, M. W. Schuster, J. Ma, B. L. Peterson, L. Norton, S. Seagren, C. Henderson, D. D. Hurd, W. P. Peters, for the Cancer and Leukemia Group B, Southwest Oncology Group, and National Cancer Institute of Canada Clinical Trials Group

Chemotherapy and radiation therapy are both important treatment modalities that improve outcomes for women with breast cancer. This study demonstrates that the use of “high-dose” chemotherapy (with stem cell rescue) for breast cancer can make it difficult to complete planned subsequent local/regional radiation. While such high-dose chemotherapy is largely out-of-favor for breast cancer, there are continued efforts to assess the utility of dose enhancement/intensification for various tumors. Thus, it is important to consider the potential influences of systemic and local treatment decisions on each other, as there may be unanticipated interactions.

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Multi-institutional Trial of Accelerated Hypofractionated Intensity-Modulated Radiation Therapy for Early-Stage, Oropharyngeal Cancer (RTOG 00-22)Page 1333 

A. Eisbruch, J. Harris, A. S. Garden, C. K. S. Chao, W. Straube, P. M. Harari, G. Sanguineti, C. U. Jones, W. R. Bosch, and K. K Ang

This was a multi-institutional study of IMRT for oropharyngeal cancer in which treatment acceleration was achieved by treating the gross disease at 2.2 Gy/fraction to a total of 66 Gy, biologically thought to be equivalent to 70 Gy at 2 Gy fractions, over 6 weeks, while sub-clinical disease received 54-60 Gy. Centralized physics quality control was an essential part of the study. Tumor control rate was high and xerostomia was significantly less than in similar patients treated in previous RTOG studies. Importantly, under-dosage of the primary tumors was significantly associated with local failures.

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Total Androgen Blockade Versus a Luteinizing Hormone–Releasing Hormone Agonist Alone in Men With High-Risk Prostate Cancer Treated With RadiotherapyPage 1439 

A. Nanda, M.-H. Chen, B. J. Moran, M. H. Braccioforte, D. Dosoretz, S. Salenius, M. Katin, R. Ross, and A.V. D'amico

Although the benefits of hormonal therapy (HT) when combined with radiation therapy (RT) in select men with locally advanced or localized, high-risk prostate cancer (PC) have been well established, it is unknown whether total as compared to partial androgen blockade improves survival. This study demonstrates that after adjusting for treatment year, age, duration of HT, and known PC prognostic factors, total androgen blockade is associated with a decreased risk of PC-specific mortality when compared to a luteinizing hormone-releasing hormone (LHRH) agonist alone in men with high-risk disease treated with curative RT. These results raise the hypothesis that both a LHRH agonist and an anti-androgen may be necessary to optimize curability and require testing in a randomized trial.

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Activated Macrophages as a Novel Determinant of Tumor Cell Radioresponse: The Role of Nitric Oxide–Mediated Inhibition of Cellular Respiration and Oxygen SparingPage 1520 

H. Jiang, M. de ridder, V. N. Verovski, P. Sonveaux, B. F. Jordan, K. Law, C. Monsaert, D. L. Van den berge, D. Verellen, O. Feron, B. Gallez, and G. A. Storme

This article describes the ability of nitric oxide (NO), a diffusible immunomediator that is produced by activated macrophages, to radiosensitize mammary carcinoma cells in tumor-relevant hypoxia. Radiosensitization is tightly linked to the physiological role of NO in sparing intracellular oxygen, through down-regulation of metabolic oxygen consumption in the mitochondrial respiratory chain. This phenomenon is supposed to rescue cells from a hypoxic insult and can be alongside exploited for radiotherapeutic applications, since oxygen is a powerful natural radiosensitizer. As little as one NO-producing macrophage is enough to re-oxygenate ten neighbor tumor cells, resulting in a 2-fold radiosensitization.