Phase IIB Randomized, Placebo Controlled Trial of Pioglitazone for Oral Premalignant Lesions: An InterConsortium Collaborative Study. This is an inter-consortium collaboration between two Consortium Lead Organizations (CLO), MD Anderson Cancer Center (MDACC), Houston, TX and University of Wisconsin Paul P. Carbone Comprehensive Cancer Center (UWCCC), Madison, WI with a total of 11 participating clinical sites. (USA cancer Centers (Memorial Sloan-Kettering Cancer Center, New York, NY; University of Minnesota, Minneapolis, MN; University of Wisconsin, Madison, WI; Columbia University Medical Center, New York, NY; Weill Medical College of Cornell University, New York, NY; UT MD Anderson Cancer Center, Houston, TX; University of Iowa, Iowa City, IA; University of Alabama-Birmingham, Birmingham, AL; University of Maryland, Baltimore, MD; Roswell Park Cancer Institute, Buffalo, NY) and in Europe the IEO. The central hypothesis of this protocol is that the PPAR gamma agonist pioglitazone (Actos®) may have activity against tobacco-related intraepithelial neoplasia (IEN) in humans, and this activity may be suggested by clinical or histologic response to pioglitazone treatment of oral premalignant lesions (OPL), namely dysplastic oral leukoplakia, hyperplastic leukoplakia in high risk locations (dorsal, lateral or ventral tongue or floor of
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the mouth) or erythroplakia of any histology. So, the primary objective of this Phase IIB randomized, placebocontrolled trial is to assess the efficacy of pioglitazone 45 mg qd given for 24 weeks in subjects with oral premalignant lesions. Efficacy will be assessed by the proportion of subjects who show complete or partial responses in either clinical or histological outcomes based on the final response evaluation at 24 weeks and the following definitions. If either the clinical or histologic parameters indicate progression, then by default, overall response will be classified as progressive disease. The IEO is supposed to include 9 patients in two years. The study started in March 2011 and as of 31/12/2011, 6 patients underwent randomisation. Radiotherapy vs Transoral Robotic Surgery (TORS) in Stage I-II oropharyngeal cancers: a radomised trial Randomised trial. This ia a multicentric phase III pilot study coordinated by the IEO Head and Neck Division. Criteria of inclusion are patients not previously treated with a cT1 – cT2 cN0 squamous cell carcinoma of tonsil and cT1 cN0 of the base of the tongue and posterior pharyngeal wall. Stage II cancers of the latter sites are not included because there is not yet enough technical and oncological experience in robotic surgery of such a large neoplasias in these regions. Patients randomised in the surgical arm will be closely checked in the 1st year for evaluating possible progression of the disease on the neck. In case of development of nodal metastases they will undergo a neck dissection. The aim of the study is to compare 5-year loco-regional control achieved by transoral robotic surgery vs Radiotherapy alone; second aim is to evaluate how many patients treated by TORS spare neck dissection and post-operative radiotherapy, and third aim is to compare quality of life and function preservation in the 2 arms. The study will randomise 50 patients in each arm in 2 years. It is granted by ROL (Oncological Web of the Regione Lombardia). It started in December 2011 Role of human papillomavirus infection and other co-factors in the aetiology of head and neck cancer in Europe and India. (Retrospective and Prospective multicentric study granted by the CEE VII Framework). Human papillomavirus (HPV) is responsible for approximately 25% of head and neck cancer (HNC) worldwide and appears to be associated with a better response to treatment and improved prognosis. Evidence suggests that HPV-induced HNC has steadily increased in the USA and some European countries in
the last decades. However, whether this is a worldwide phenomenon and specific risk factors are associated with it remains to be proven. In addition, little is known on the natural history and risk factors of oral HPV infection. HPVAHEAD network aims to address these and other unanswered questions on HNC aetiology and epidemiology with a focus on the role of HPV. We will assemble and analyze a large collection of plasma/ sera and HNC tissues from 42 centres in 16 European countries as well as HNC tissues from 7 Indian centres together with epidemiological and clinical data. HPV status in human specimens will be evaluated by different assays in central laboratories. Epidemiological studies will be conducted to establish the overall proportion and type distribution of HPVpositive HNC at different anatomical sites in European and Indian regions as well as the time trend of the proportion of HPV-positive HNC in recent decades. Using the follow-up information on HNC patients, we will further investigate whether HPV positivity confers a better prognosis and survival. We will also conduct a study in HPV-vaccinated and non-vaccinated women in order to determine risk factors and natural history of oral HPV infections. In addition, we will search for new surrogate markers for oral HPV infection to facilitate novel screening strategies. Finally, the HPV-AHEAD consortium aims to transfer technology to Indian centres as well as to develop several strategies for the training of European and Indian researchers in infections and cancers. This study will provide important insights for the screening, diagnosis, treatment and prophylaxis of HPV-associated HNC in Europe, India and elsewhere. This proposal will be focused on the elucidation of the role of HPV types and other environmental risk factors in HNC in Europe and in India. In particular, the proposal will (i) improve our understanding of the role of HNC aetiology in geographical regions with different incidence rates, (ii) lead to the identification of the clinically most useful HPV markers and new biomarkers for different types of HNC, which both can be used for screening and/or therapy strategies, (iii) provide new insights on the natural history of HPV oral infection and its diagnosis, on HNC prognosis and survival by HPV status, and (iv) determine whether prophylactic HPV vaccine may have an impact on oral HPV infections. The study will take 3 years and started in October, 2011. In the first year about 500 slides of patients operated on for an oral cancer at IEO will be evaluated for HPV and DOK1 expression.
Research Activities
to treatments. The aim of our study is to prospectively collect baseline data from both pathological specimens, FDG PET and functional MRI exams in order to correlate these parameters with response to non surgical treatment and clinical outcome (in terms of Overall Survival and Disease Free Survival) in patients with locally advanced head and neck squamous cell carcinoma. This project is organized in tasks: Task 1: The aim of this task is to evaluate, on the initial biopsy specimen, the expression as well as the prognostic and predictive value of some biomarkers potentially involved in treatment failure: ERCC1, CD105, p16INK4,p53 VEGFR, PTEN. All these biomarkers will be evaluated with immuno-histochemical analysis. Task 2-3: The aim of these tasks is to evaluate the predictive and prognostic value of radiological and nuclear medicine parameters. A baseline functional MRI (DCE- and DWI-MRI) and an FDG-PET will be performed before starting the radio-chemotherapy treatment regimens and objective parameters will be collected. Data from baseline pathological specimens, functional MRI and FDG-PET exams will be analyzed and correlated with the response to treatment and patient clinical outcome.
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