LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Select appropriate multidisciplinary treatment regimens and cytoprotection for clinical trials for patients with head and neck cancer.2. Identify radiation toxicity for the head and neck, lung, and pelvic irradiated areas.3. Describe the cytoprotective effect of amifostine against radiation toxicity.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACTAfter several decades of preclinical and clinical research, the first approved radioprotective drug, amifostine, is being used in clinical practice. Amifostine has been shown to specifically protect normal tissues from damage caused by radiation and chemotherapy. An inactive prodrug, amifostine is converted to an active thiol by dephosphorylation by alkaline phosphatase in the normal endothelium. The hypovascularity and acidity of the tumor environment and the differential expression of alkaline phosphatase in normal and neoplastic tissues contribute to its cytoprotective selectivity. The cytoprotective mechanism of amifostine is complicated, involving free-radical scavenging, DNA protection and repair acceleration, and induction of cellular hypoxia. The U.S. Food and Drug Administration has approved the i.v. use of amifostine to reduce the cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer and to reduce the incidence of moderate to severe xerostomia in patients undergoing postoperative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands. Nonetheless, amifostine has potential applications in many other oncologic settings. Novel schedules and routes of administration are under investigation and may further simplify the use of amifostine, reduce any undesired effects, and considerably broaden its applications. This review summarizes the clinical experience with amifostine and provides insight into future clinical directions. The Oncologist 2007;12:738 -747

Many patients with hepatocellular carcinoma (HCC) present with advanced disease, not amenable to curative therapies such as surgery, transplantation or radiofrequency ablation. Treatment options for this group of patients include transarterial chemoembolization (TACE) and radiation therapy. Especially TACE, delivering a highly concentrated dose of chemotherapy to tumor cells while minimizing systemic toxicity of chemotherapy, has given favorable results on local control and survival. Radiotherapy, as a therapeutic modality of internal radiation therapy with radioisotopes, has also achieved efficacious tumor control in advanced disease. On the contrary, the role of external beam radiotherapy for HCC has been limited in the past, due to the low tolerance of surrounding normal liver parenchyma. However, technological innovations in the field of radiotherapy treatment planning and delivery, have provided the means of delivering radical doses to the tumor, while sparing normal tissues. Advanced and highly conformal radiotherapy approaches such as stereotactic body radiotherapy and proton therapy, evaluated for efficacy and safety for HCC, report encouraging results. In this review, we present the role of radiotherapy in hepatocellular carcinoma patients not suitable for radical treatment.

ObjectiveOral squamous cell carcinoma has a remarkable incidence worldwide and a fairly onerous prognosis, encouraging further research on factors that might modify disease outcome.Data sourcesA web-based search for all types of articles published was initiated using Medline/Pub Med, with the key words such as oral cancer, alcohol consumption, genetic polymorphisms, tobacco smoking and prevention. The search was restricted to articles published in English, with no publication date restriction (last update 2010).Review MethodsIn this review article, we approach the factors for a cytologic diagnosis during OSCC development and the markers used in modern diagnostic technologies as well. We also reviewed available studies of the combined effects of alcohol drinking and genetic polymorphisms on alcohol-related cancer risk.ResultsThe interaction of smoking and alcohol significantly increases the risk for aero-digestive cancers. The interaction between smoking and alcohol consumption seems to be responsible for a significant amount of disease.ConclusionPublished scientific data show promising pathways for the future development of more effective prognosis. There is a clear need for new prognostic indicators, which could be used in diagnostics and, therefore a better selection of the most effective treatment can be achieved.

Oral pseudomembranous candidiasis (OPC) was evaluated in 61 patients receiving head and neck radiotherapy (RT). Herpes simplex virus-1 (HSV-1) reactivation was also investigated in 14 patients. According to the agreed protocol, granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwash was administered in 46 patients with radiation-induced ulcers. Candidiasis was diagnosed in 31 patients. Candida albicans was the most frequent isolate. Multiple Candida species were isolated from the lesions of four patients. Concurrent candidiasis and radiation-induced ulcers were observed in 17 patients. Viral culture and the polymerase chain reaction disclosed the presence of HSV-1 in five patients. Twenty of the 46 patients, with initial mucositis grade II and grade III, completed RT with mucositis grade I, indicating a beneficial effect of GMCSF mouthwash, although further controlled studies are necessary to verify that. In conclusion, OPC was an important infection in patients undergoing radiotherapy. The role of HSV-1 in oral mucositis during head and neck radiotherapy needs additional study.

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A descriptive analysis was made in terms of the related radiation induced acute and late mucositis and xerostomia along with survival and tumor control rates (significance level at 0.016, bonferroni correction), for irradiation in head and neck carcinomas with either 2D Radiation Therapy (2DRT) and 3D conformal (3DCRT) or Intensity Modulated Radiation Therapy (IMRT). The mean score of grade > II xerostomia for IMRT versus 2-3D RT was 0.31 ± 0.23 and 0.56 ± 0.23, respectively (Mann Whitney, P < 0.001). The parotid-dose for IMRT versus 2-3D RT was 29.56 ± 5.45 and 50.73 ± 6.79, respectively (Mann Whitney, P = 0.016). The reported mean parotid-gland doses were significantly correlated with late xerostomia (spearman test, rho = 0.5013, P < 0.001). A trend was noted for the superiority of IMRT concerning the acute oral mucositis. The 3-year overall survival for either IMRT or 2-3DRT was 89.5% and 82.7%, respectively (P = 0.026, Kruskal-Wallis test). The mean 3-year locoregional control rate was 83.6% (range: 70–97%) and 74.4 (range: 61–82%), respectively (P = 0.025, Kruskal-Wallis). In conclusion, no significant differences in terms of locoregional control, overall survival and acute mucositis could be noted, while late xerostomia is definitely higher in 2-3D RT versus IMRT. Patients with head and neck carcinoma should be referred preferably to IMRT techniques.

Our preliminary results indicate an induction of apoptosis and inflammation in the oral mucosa in patients developing mucositis during radiotherapy for head/neck cancer.

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