1 / 32

Translational research in head and neck cancer: preoperative chemotherapy in oral cavity cancer based on disease molec

MSO young investigator and Salvatore Venuta Prize. Translational research in head and neck cancer: preoperative chemotherapy in oral cavity cancer based on disease molecular profiling. Paolo Bossi. Medical Oncology Head and Neck Unit Fondazione IRCCS Istituto Nazionale Tumori Milano. INT.

portia
Download Presentation

Translational research in head and neck cancer: preoperative chemotherapy in oral cavity cancer based on disease molec

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. MSO young investigator and Salvatore Venuta Prize Translational research in head and neck cancer: preoperative chemotherapy in oral cavity cancer based on disease molecular profiling. Paolo Bossi Medical Oncology Head and Neck Unit Fondazione IRCCS Istituto Nazionale Tumori Milano INT

  2. Head and Neck Cancer: a challenging field • Most “visible” cancers • - They affect social functions • More frequent in socially-deprived people

  3. Multidisciplinary work MEDICALONCOLOGY SURGERY NUTRITION RADIOLOGY MULTIDISCIPLINARY MOLECULAR BIOLOGY RADIOTHERAPY ASCO-ESMO Consensus on Quality Cancer Care

  4. Ongoing studies on Translational Research… • Microarray analysis of preTx Nasopharyngeal Cancer  Radioresistance Profile? • HPV negative oropharyngeal cancer:biomolecular prognostic factors • Role of cytokine profile and growth factors in serum and drainage fluids

  5. Oral Cavity Squamous Cell Cancer–OCSCC- • The sixth most common cancer worldwide • Visible? Parallel with colon cancer: 36% rate of early stage detection • Overall Survivaldepending on stage:

  6. State of the art Treatment “The ultimate goal of treatment is to eradicate the cancer, preserve or restore form and function, minimize the sequelae of treatment and finally prevent any subsequent new primary cancers” STAGE III-IV: optimal surgery, followed by radio(chemo)therapy

  7. Phase II study of preoperative TPF chemotherapy in locally advanced resectable OCSCC • Aim of the study: • to improve survival of OCSCC through a molecular profiled selected treatment

  8. BACKGROUND –Induction PF study Journal ofClinicalOncology 2003

  9. 198 patients enrolled2 treatment arms: 1) CT (CDDP-5FU) surgery+/- RT2) surgery+/- RT no different postoperative morbidity no difference in survival BACKGROUND - Induction PF study

  10. Less mandibulectomy and postoperative RTin chemotherapy treated arm BACKGROUND - Induction PF study

  11. - Pathologic Response Rate similar to Radiological-Clinical one- Pathologic Complete Response (pCR) obtained in 27% of the patients treated with induction CT BACKGROUND - Induction PF study

  12. Overall Survival according to response to chemotherapy p = 0.03

  13. NEXT STEP NEXT STEP  need for effective antiblastic treatment with a biological tumor selection  To spare toxic treatment to whom is not expected to optimally respond

  14. NEXT STEP: TPF better than PF

  15. NEXT STEP: predictive factors • p53 in Head and Neck Cancer • TP53 mutations recognized prognostic factor (disruptive mut and non functional protein in particular) • Predictive role of p53 in response to chemotherapy

  16. NEXT STEP: predictive factors

  17. p53 translational research

  18. NEXT STEP: predictive factors • Beta-Tubulin in Head and Neck Cancer

  19. Ongoing phase II study of preoperative TPF • INCLUSION CRITERIA • - Hystologically proved primary OCSCC • - Stage T2 (> 3 cm)-T3, N1-N3 and T4a any N • WHO performance status < 1 • - Availability of Formalin Fixed Paraffin Embedded biopsy of the tumour • - Radiological imaging with MRI pre-therapy

  20. Ongoing phase II study of preoperative TPF • EXCLUSION CRITERIA • - Prior antitumor therapy for head & neck cancer • - Previous OCSCC to less than 2 cm from primary • - Screening laboratory values • Weight loss > 20% in previous 3 months • - Technical unresectability defined as: T4b staging or N ulcerating the skin or encasing internal carotid

  21. Ongoing phase II study of preoperative TPF STUDY DESIGN Patient Selection and Informed Consent Diagnostic Biopsy and Molecular Analysis non functional p53 and high B-Tub Patient non eligible functional p53 or high B-Tub 3 cycles of TPF chemotherapy Surgery Postoperative (chemo)radiation

  22. Ongoing phase II study of preoperative TPF PRIMARY ENDPOINT To increase rate of pCR to 50% of the patients treated with induction chemotherapy Sample Size: type I error of 10% for a mono-lateral test, power of 95% (beta=5%), plus 10% drop-out rate = 64 patients to be enrolled

  23. Ongoing phase II study of preoperative TPF • SECONDARY ENDPOINT • Early functional response evaluation • by DWI and DCE MRI • Comparison between (DWI - DCE) MRI • response and pathological response • Functional Imaging as possible predictor of early response • and for the measurement of drug effects on tumour (micro)vascularity and capillary permeability.

  24. Ongoing phase II study of preoperative TPF • SECONDARY ENDPOINT • Percentage of patient receiving postop • radiotherapy and chemotherapy • Progression free survival and overall survival • Second primary tumour incidence

  25. Ongoing phase II study of preoperative TPF • STRENGHT • Molecular profiled driven treatment • Prospective trial in specialized Centers • Centralized pathologic, molecular and • radiologic evaluation • Trial potentially opening new scenarios in • personalized treatment

  26. Ongoing phase II study of preoperative TPF • WEAKNESS • Only 2 molecular alteration as predictor of • response • Trial based on adding therapy, not on “removing” part of it (need for larger trial)

  27. Ongoing phase II study of preoperative TPF • CONCLUSIONS • Results foreseen within 2012 • Looking for increase in OS, through new therapeutic strategy • Towards an individualized treatment approach • The importance of multidisciplinary work and translational research

More Related