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Over-expression of ki 67 and vascular endothelial growth factor (VEGF) is a frequent finding in squamous cell carcinoma (SCC) of the oral mucosa. The expression of VEGF and ki 67 proteins was studied in a cohort of 87 patients with primary, previously untreated SCC of the tongue, using computerized image analysis (CIA) in order to determine the potential prognostic significance of these factors. Immunohistochemical analysis was performed with monoclonal anti-ki 67 (MIB 1) and anti-VEGF antibodies. A digital image analysis assay was applied for the evaluation of the results. Using CIA, VEGF over-expression was observed in 24/87 (27.5%) of the examined cases and this finding correlated to the stage of the disease (p = 0.05). ki 67 was over-expressed in 49/87 (56.3%) of the cases and correlated to the size of the tumors (p = 0.05). Cox regression analysis showed that there was no prognostic significance associating VEGF protein expression to survival status of the examined patients (p = 0.77), whereas ki 67 over-expression was strongly correlated to poor prognosis (p = 0.017). The size of the primary tumors was also strongly correlated to survival status of the patients (p = 0.024), whereas stage of disease showed a borderline statistical significance (p = 0.091). (C) 2008 Elsevier Ltd. All rights reserved.

Patients with head and neck squamous cell carcinoma (HNSCC) are at considerable risk for death, with 5-year relative survival rates of approximately 60%. The profound multifaceted deficiencies in cell-mediated immunity that persist in most patients after treatment may be related to the high rates of treatment failure and second primary malignancies. Radiotherapy and chemoradiotherapy commonly have severe acute and long-term side effects on immune responses. The development of immunotherapies reflects growing awareness that certain immune system deficiencies specific to HNSCC and some other cancers may contribute to the poor long-term outcomes. Systemic cell-mediated immunotherapy is intended to activate the entire immune system and mount a systemic and/or locoregional antitumor response. The delivery of cytokines, either by single cytokines, for example, interleukin-2, interleukin-12, interferon- 𝛾 , interferon- 𝛼 , or by a biologic mix of multiple cytokines, such as IRX-2, may result in tumor rejection and durable immune responses. Targeted immunotherapy makes use of monoclonal antibodies or vaccines. All immunotherapies for HNSCC except cetuximab remain investigational, but a number of agents whose efficacy and tolerability are promising have entered phase 2 or phase 3 development.

Salivary gland carcinomas are a rare and clinically diverse group of neoplasms among which mucoepidermoid carcinomas (MEC) are reported to be the most frequently encountered. During the years 1994-2004 18 patients with MEC were treated in our Department. All patients underwent surgery with a curative intent, and in 11 of them treatment was supplemented by radiotherapy. Follow up ranged from 6 to 120 months. Twelve (66.6%) MECs originated from the major salivary glands with the majority located in the parotid. Histologically, 50% of tumors were classified as tow grade, 28% as intermediate and 22% as high-grade MECs. Positive surgical margins were documented in six cases (33%) and all in tumors of high or intermediate histological grade. All these patients received adjuvant radiotherapy and one developed local recurrence. Local recurrence occurred in two more patients with histologically free margins. Both received postoperative radiotherapy. Distant metastases were documented in four patients all between 14 and 24 months after surgical treatment. An association between local recurrence and distant metastasis might be suggested since all patients with local recurrences subsequently developed distant metastases. The 5-year overall disease specific survival rate was 85%. Statistical multivariate analysis demonstrated that the factor that significantly correlated with overall survival was the histological grade of tumors (Log Rank test: p = 0.013). A trend towards poorer survival was observed in patients aged over 50 years. Our results also suggested a potential benefit of postoperative radiotherapy for patients with positive margins. (c) 2006 Elsevier Ltd. All rights reserved.

Encouraging results have recently been reported in patients (pts) with locally advanced unresectable, squamous cell carcinoma of the head and neck (SCCHN) when induction chemotherapy (IC) is used and followed by radiotherapy (RT). The present study assessed the therapeutic response of an aggressive regimen consisting of clocetaxel (TXT), cisplatin (CDDP) and 5-fluorouracil (5-Fu) as IC and concurrent with RT in pts with locally advanced (stages III and IV) SCCHN. 42 pts (35 male and 7 female) with a mean age of 58 years suffering from stages III and IV (Mo) SCCHN were included to this organ preservation phase II clinical trial. The site of the primary tumors was the anterior mouth in 9 pts, base of tongue and oropharynx in 12, middle third of the face in 8 and larynx in 13. The performance status of the pts was 0-1 according to WHO and above 80% according to Karnofsky classification. IC consisted of TXT (40 mg/m(2)), CDDP (40 mg/m(2)) and 5-Fu (350 mg/m2) every two weeks (wks) for a total of four courses and repeated, coupled with RT (66-68 cGys total dose fractionated at 200 Gy per day, 5 days a week), for up to seven wks. In total, pts received eight courses of chemotherapy (CT) at the end of RT treatment. Pts were evaluated at the end of IC, after RT and every six wks thereafter. 41 pts were eligible for evaluation after IC (one died from myocardial infarction) and 39 after completion of treatment (two died during RT). Statistical multivariate analysis was performed using SPSS (11) package. Complications from IC and RT were evaluated according to WHO criteria and included mucositis Grade (Gr) IV in 10% of the pts, Gr III in 50%, Gr II in 20%. Anemia presented in 40% of the pts with Gr II, 40% with Gr I, neutropenia 17% with Gr IV, 20% with Gr III, 30% with Gr II, thrombocytopenia 3% with Gr III, 10% with Gr I and xerostomia up to Gr II in 70% of the pts. The response rate (RR) after IC was complete response (CR) for 10 pts (24.4%), partial response (PR) for 22 (53.7%) and no response (NR) for 9 (21.9%). At the end of the treatment the RR in the intention-to-treat population were CR for 25 pts (64.1%), and PR for 14 (35.9%). Follow up ranges from 18 to 56 months (mts). 14 pts died during follow-up time. The mean survival time is 41 mts and the median 40. 2 pts with CR developed local recurrence and two distant metastases, whereas all pts with PR developed progressive disease (PD) and all but two are dead from disease. It is evident from this phase II study that TXT-CDDP-5Fu based IC followed by the same regimen coupled with RT improves local control. Pts that showed CR after IC continued to maintain disease status during RT (P-value = 0.0181). In pts with SD concurrent RT did not alter dramatically disease outcome. Patients who showed complete response after both IC and RT presented a four-year survival rate of 74% compared to a 30% to partial responders (P-value = 0.0001). Results are encouraging and further study of the toxicity and follow-up is needed to validate treatment effectiveness. (c) 2005 Elsevier Ltd. All rights reserved.