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Section II Techniques, Modalities, and Modifiers in Radiation Oncology

adherence to a strict regimen of oral hygiene during head and neck RT. Patients on both the drug and placebo arms were instructed to swish and gargle prior to each administration of study drug. They also maintained study diaries to help ensure adequate compliance with administration of the study drug. These interventions were not performed in the patients assigned to SOC alone. This trial provides an important foun- dation in the evaluation of new therapies for mucositis through its demonstration of the value of organized and systematic attention to the maintenance of good oral hygiene throughout a course of head and neck CRT. Summary The chemical modification of radiation response both for enhancing treatment efficacy and reducing therapy-induced toxicity remains an area of active investigation. Promising candidates identified in preclinical and early phase trials have been less successful in randomized phase III settings. Attempts to improve treatment efficacy by augmenting tumor oxygen delivery have a mixed record of success. The use of drugs that are preferentially cytotoxic to hypoxic cells holds promise, although improved tools to identify those patients most likely to benefit from targeted therapy are needed. Proof of principle for chemical radioprotection has been established in salivary glands but not elsewhere and is associated with significant tox- icity in its own right. Growth factor utilization appears to pro- tect against treatment-induced mucositis but not to an extent to change clinical practice. As radiotherapy regimens evolve and new technological advances continue to improve treat- ment delivery, investigators will continue to seek agents that optimize the therapeutic ratio. References 1. Chapman JD, Reuvers AP, Borsa J, et al. Chemical radioprotection and radiosen- sitization of mammalian cells growing in vitro. Radiat Res 1973;56(2):291–306. 2. Gray LH, Conger AD, Ebert M, et al. The concentration of oxygen dissolved in tis- sues at the time of irradiation as a factor in radiotherapy. Br J Radiol 1953;26(312): 638–648. 3. Thomlinson RH, Gray LH. The histological structure of some human lung cancers and the possible implications for radiotherapy. Br J Cancer 1955;9(4):539–549. 4. Becker A, Hansgen G, Bloching M, et al. Oxygenation of squamous cell carcinoma of the head and neck: comparison of primary tumors, neck node metastases, and normal tissue. Int J Radiat Oncol Biol Phys 1998;42(1):35–41. 5. Brizel DM, Sibley GS, Prosnitz LR, et al. Tumor hypoxia adversely affects the prog- nosis of carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 1997;38(2): 285–289. 6. Brizel DM, Dodge RK, Clough RW, et al. Oxygenation of head and neck cancer: changes during radiotherapy and impact on treatment outcome. Radiother Oncol 1999;53(2):113–117. 7. Nordsmark M, Bentzen SM, Rudat V, et al. Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study. Radiother Oncol 2005;77(1):18–24. 8. Hockel M, Knoop C, Schlenger K, et al. Intratumoral pO2 predicts survival in advanced cancer of the uterine cervix. Radiother Oncol 1993;26(1):45–50. 9. Hockel M, Schlenger K, Aral B, et al. Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res 1996; 56(19):4509–4515. 10. Fyles AW, Milosevic M, Wong R, et al. Oxygenation predicts radiation response and survival in patients with cervix cancer. Radiother Oncol 1998;48(2):149– 156. 11. Brizel DM, Scully SP, Harrelson JM, et al. Tumor oxygenation predicts for the likeli- hood of distant metastases in human soft tissue sarcoma. Cancer Res 1996;56(5): 941–943. 12. Chang CH. Hyperbaric oxygen and radiation therapy in the management of glio- blastoma. Natl Cancer Inst Monogr 1977;46:163–169. 13. Cade IS, McEwen JB. Clinical trials of radiotherapy in hyperbaric oxygen at Portsmouth, 1964–1976. Clin Radiol 1978;29(3):333–338. 14. CadeIS,McEwenJB,DischeS,etal.Hyperbaricoxygenandradiotherapy:aMedical Research Council trial in carcinoma of the bladder. Br J Radiol 1978;51(611): 876–878. 15. Sealy A, Hockly J, Shepstone B. The treatment of malignant melanoma with cobalt and hyperbaric oxygen. Clin Radiol 1974;25(2):211–215. 16. Watson ER, Halnan KE, Dische S, et al. Hyperbaric oxygen and radiotherapy: a MedicalResearchCounciltrialincarcinomaofthecervix. BrJRadiol 1978;51(611): 879–887. 17. Henk JM. Late results of a trial of hyperbaric oxygen and radiotherapy in head and neck cancer: a rationale for hypoxic cell sensitizers? Int J Radiat Oncol Biol Phys 1986;12(8):1339–1341. 18. Henk JM, Kunkler PB, Smith CW. Radiotherapy and hyperbaric oxygen in head and neck cancer. Final report of first controlled clinical trial. Lancet 1977;2(8029): 101–103. 19. Horsman MR, Brown JM, Hirst VK, et al. Mechanism of action of the selective tumor radiosensitizer nicotinamide. Int J Radiat Oncol Biol Phys 1988;15(3):685–690.

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