The head and neck district represents one of the most frequent sites of cancer, and the percentage of metastases is very high in both loco-regional and distant areas. Prognosis refers to several factors: a) stage of disease; b) loco-regional relapses; c) distant metastasis. At diagnosis, distant metastases of head and neck cancers are present in about 10% of cases with an additional 20-30% developing metastases during the course of their disease. Diagnosis of distant metastases is associated with unfavorable prognosis, with a median survival of about 10 months. The aim of the present review is to provide an update on distant metastasis in head and neck oncology. Recent achievements in molecular profiling, interaction between neoplastic tissue and the tumor microenvironment, oligometastatic disease concepts, and the role of immunotherapy have all deeply changed the therapeutic approach and disease control. Firstly, we approach topics such as natural history, epidemiology of distant metastases and relevant pathological and radiological aspects. Focus is then placed on the most relevant clinical aspects; particular attention is reserved to tumours with distant metastasis and positive for EBV and HPV, and the oligometastatic P. Pisani et al. S2 concept. A substantial part of the review is dedicated to different therapeutic approaches. We highlight the role of immunotherapy and the potential effects of innovative technologies. Lastly, we present ethical and clinical perspectives related to frailty in oncological patients and emerging difficulties in sustainable socio-economical governance.

In patients with advanced unresectable squamous-cell carcinoma of the head and neck, chemotherapy alternating with radiotherapy increases the median survival and doubles the probability of survival for three years as compared with radiotherapy alone. However, since local disease cannot be controlled in over half the patients who receive the combined treatment and since almost two thirds die within three years, further improvements in management are necessary.

Between 1983 and 1986, the National Institute for Cancer Research in Genoa and affiliated institutions conducted a randomized study to compare two different ways of combining chemotherapy (CT) and radiation therapy (RT). One hundred sixteen patients were randomized to receive neoadjuvant CT followed by definitive RT (treatment arm A) or alternating CT and RT. In treatment arm A, RT consisted of 70 Gy to the involved areas and 50 Gy to the uninvolved neck at 2 Gy/fraction, five fractions per week. In treatment arm B, RT consisted of 60 Gy to involved areas and 50 Gy to the uninvolved neck in three courses of 20 Gy each, 2 Gy/fraction, ten fractions/2 weeks alternated with four courses of CT. CT consisted of vinblastine 6 mg/m2 intravenously followed 6 hours later by bleomycin 30 IU intramuscularly, day 1; methotrexate 200 mg intravenously, day 2; leucovorin rescue, day 3. CT was repeated every 2 weeks up to four courses. The same CT was used in both treatment arms of the study. Fifty-five patients were entered in treatment arm A and 61 in treatment arm B. Complete responses were 7/48 and 19/57 in treatment arms A and B, respectively (P less than 0.03). Four-year progression-free survival was 4% in treatment arm A and 12% in treatment arm B (P less than 0.02), and four-year survival was 10% in A and 22% in B (P less than 0.02). Mucosal tolerance was significantly worse in treatment arm B (P less than 0.00004). The subgroup analysis shows the major improvement of alternating CT and RT in patients with the worst prognostic characteristics.

Oxidative stress exerts major role in the pathogenesis of side effects of many antineoplastic drugs, including ototoxicity of cisplatin. In particular, increased levels of reactive oxygen species (ROS) represent one of the molecular mechanisms underlying the apoptosis of different types of hearing cells. Antioxidants and ROS scavengers may thus represent potential therapeutic options to prevent platinum-associated ototoxicity.The aim of this preliminary case-control study was to explore the efficacy of a dietary antioxidant supplement, in order to hamper the occurrences of ototoxicity in patients undergoing cisplatin chemotherapy.As results, a significant protection against cochlear toxic damage was demonstrated in patients who took the antioxidant supplement, which furthermore prevented the occurrence of hearing disorders and tinnitus. These clinical evidences were corroborated by the oxidative status of patients. After cisplatin chemotherapy, the plasma derivatives of reactive oxygen metabolites (d-ROMs) content rapidly increased in control patients, but it was maintained in those under dietary supplementation, likely because of a higher anti-ROMs potential. Indeed, an increment in rapid anti-ROMs was detected in supplemented patients, though no differences were highlighted in terms of slow anti-ROMs.In conclusion, in this preliminary report we demonstrated the feasibility of a dietary antioxidant supplementation in order to prevent the cisplatin induced hearing damage.

Objectives/Hypothesis: The need for class I and II studies on the efficacy of liberatory maneuvers in the treatment of lateral canal benign paroxysmal positional vertigo (LC-BPPV) motivated the present double-blind randomized trial on the short-term efficacy of the forced prolonged position (FPP). Study Design: Double-blind, randomized controlled trial. Methods: Two hundred twenty-one patients with unilateral LC-BPPV met the inclusion criteria for a multicentric study. Patients were randomly assigned to treatment by FPP (116 subjects) or sham treatment (105 subjects). Subjects were followed up at 24 hours with the supine roll test by blinded examiners. Results: Among the sample, 67.4% and 32.6% of the patients showed respectively geotropic and apogeotropic variant of LC-BPPV. At the 24-hour follow-up, the effectiveness of FFP compared to the sham maneuver was, respectively, 57.8% versus 12.4% (P < .0001) in the total sample, 76.9% versus 11.3% (P < .0001) in the geotropic variant group, and 60.5% versus 17.6% (P = .0003) in the apogeotropic variant group, including resolution or transformation to geotropic variant. Conclusions: FPP proved highly effective compared to the sham maneuver. The present class 2 study of the efficacy of the FPP changes the level of recommendation of the method for treating LC-BPPV into a strong one.