Head and Neck Diseases

Model Pathologies

Aims

To develop personalized medicine for elderly patients suffering from head and neck cancer and facilitate the discovery of biomarkers and innovative therapeutic strategies

Leader name(s)

Pr J. Guigay
Dr E. Van Obberghen
Dr S. Chevillard

General description

The population of elderly patients with head and neck cancer (HNC) requires a complex, specific and multidisciplinary care management, based on initial comprehensive geriatric assessment due to fragility criteria. The development of personalized treatment that takes clinical and biological characteristics of this ageing population into account and incorporates the psychosocial dimensions and quality of life (QoL) is therefore a major challenge. The expertise of the specialized medical teams (IUFC, CAL, CHU-Nice, CLB) involved is recognized by head and neck and geriatric oncology groups (Unicancer, Gerico, Gortec-Gettec-Gercor) with whom collaborations exist on numerous clinical trials from phase I to III. The coordination of the ELAN project (curative or palliative personalized treatment of HNC elderly patients, after geriatric assessment) by Pr Guigay is an essential component of this WP. Clinical understanding combined with academic expertise (IBV, IRCAN, IPMC, TIRO, IRCM, IGR, IARC) and 4 advanced technical platforms provide a unique holistic therapeutic approach for this population. We intend to:

1. Develop clinical and therapeutic research geared toward elderly HNC patients and promote the availability of innovations through a CLIPP2 Unit by

  • identifying geriatric criteria to improve frailty assessment
  • targeting the immune system in elderly HNC patients
  • designing an appropriate dose-escalation Phase I study for protontherapy

2. Promote evidence based discovery and validation of novel biomarkers: predictive prognostic factors, malnutrition detection using blood samples and imaging

3. Strengthen the continuum between basic and clinical research on HN/thyroid and epithelial carcinogenesis by

  • favoring studies on human tumors from the biobank and optimizing animal models for human disease studies
  • facilitating projects involving basic scientists and clinicians
  • promoting the search for novel biomarkers and drug development
  • encouraging collaborative ancillary clinical biomarker studies

4. Develop a gerontology specific training program for professionals (academic and clinical)

Task Title
Innovative clinical research
Task Description

1.1.  Merge existing high quality clinical databases (CHUN, ELAN, PACSA study) to identify prognostic factors and to evaluate an adapted test of geriatric frailty for elderly HNC patients

Conduct:

1.2. Ambispective multicenter study assessing the impact of treatments on frailty, disabilities, comorbidities and survival

1.3. Phase I studies of new agents dedicated to elderly HNC patients (mainly immunotherapy, better tolerated than conventional agents)

1.4. Radiotherapy and combination therapy studies:

  1. Phase I/II study with an ancillary biomarker study to evaluate the combination of immune check point inhibitors with radiotherapy, in fit elderly HNC patients
  2. Phase I dose-escalation study for protontherapy
Task Improvement
  • Improve frailty assessment of HNC patients (including psychosocial environment, comorbidities)
  • Identify geriatric and clinical criteria for patient care management from a multivariate analysis
  • Improve treatment of FIT elderly patients for whom no standard exists and better understanding of antitumoral mechanisms of immunotherapy and radiotherapy combination

Reachable in 5 years

Task Title
Biomarker validation and application
Task Description

2.1. Assess tumor risk among the elderly with novel correlative biomarkers in liquid biopsies (gal-9, microRNAs)

2.2. Analyze the impact of aging on the ability to develop antibody-dependent cell-mediated cytotoxicity

2.3. Analyze the impact of aging on immune profiles in blood and tumor tissue of patients undergoing different anticancer treatments

2.4. Validate an innovative software application that assesses a quantitative imaging biomarker of body composition based on CT-scan

Task Improvement
  • Improvement of diagnosis, prognosis and treatment
  • Comprehensive reliable nutritional monitoring of elderly patients to propose surgical management and/or chemotherapy doses adaptation

Reachable in 5 years

Task Title
Basic mechanisms and biomarker discovery
Task Description

3.1. Study epigenetic heterogeneity during HNC evolution and the contribution of epigenetic alterations to HNC

3.2. Elucidate the tumor- and age-related mechanisms affecting extracellular matrix homeostasis (assembly/remodeling) and cell-matrix interactions that impact HNC progression, treatment and recurrence

3.3. Investigate tumor cell metabolism and stromal-related mechanisms involved  in tumor invasion and spread

3.4. Investigate the molecular and cellular responses of tissue-associated innate immune cells and their regulation by the HNC microenvironment

Task Improvement
  • Discover and validate new epigenetic biomarkers in HNC
  • Improve understanding of adhesion signaing in HNC
  • Develop new approaches for drug intervention that target cellular (immune cells, fibroblasts) and non-cellular (ECM) components of the tumor microenvironment

Reachable in 5 years

Task Title
Thyroid disorders and genotoxicity
Task Description

4.1. Search for genetic and epigenetic imprinting of radiation- and pollutant-induced thyroid tumors

4.2. Study the NIS sodium iodide symporter expression/function and control of iodide accumulation in normal and tumoral thyroid cells

4.3. Analyze age-dependency of microRNA and long noncoding RNA profiles in thyroid cancer

Task Improvement
  • Improve radioablation therapy and understanding of radiation-induced thyroid tumors
  • Ameliorate control of iodide accumulation in the thyroid
  • Improve diagnosis of age-related tumors with similar histology

Reachable in 5 years

Task Title
Training
Task Description

5.1. Expand the educational program of medical oncology and radiotherapy units caring for HNC patients based on ELAN project

5.2. Develop regional gerontology training for clinicians/academic researchers

Task Improvement
  • Expand the clinical and biological understanding of professionals relating to the elderly HNC patients

Reachable in 5 years