Personalised post-operative radiochemotherapy in head and neck cancer
Every year about 180000 patients develop head and neck cancer. Despite of state-of-the-art therapy in combination with surgery and adjuvant radiochemotherapy the recurrence rate after 2 years is more than 30%. At the same time big heterogeneity of the recurrence risk can be found within the high-risk group of p16 negative, R1-resected, extracapsular affection of lymph nodes.
This high recurrence risk faces a serious therapeutic morbidity and a long-term mortality that are caused by persistent swallowing disorders and aspiration. Despite the obvious demand of biological stratification no parameters for personalised post-operative radiochemotherapy are defined for decision on escalation of high-risk patients and de-escalation of low-risk patients. So far no multi-parametric models exist for stratification of personalised post-operative radiochemotherapy in head and neck cancer. Such a systems biology approach is not feasible with conventional methods; it needs the collaboration within a consortium with expertise in high-throughput data associated with clinical results.
The overall goal of this project is – in cooperation with different research areas of the ZPM, like High-Throughput Methods or Functional and Molecular Imaging - to prove the clinical feasibility of a patient based integration of complex, multiparametric, tumor associated data (NGS, radio biological tests of intrinsic radiation sensitivity, functional multiparametric MR/PET, radioomics) to evaluate concrete, clinical approaches towards personalised medicine.
- Recruting of patients for a clinical phase II study for personalised post-operative radiochemotherapy in head and neck cancer
- Analysis of the post-operative, radiotherapeutic target volume via pre-operative functional MR/PET imaging, individual for each patient depending on tumor localization and resistance (clinical end-point: 2-year recurrence rate)
- Development of radiation plans on the multiparametric analysis of the PET/MR data
- Analysis of the cellular radiation sensitivity with ex-vivo tumor samples (collected at surgery)
- Mutaion analysis via NGS panel sequencing of ca. 300 oncological relevant genes and detection of copy number variations (CNVs) via microarray analysis (in cooperation with the Institute of Medical Genetics and Applied Genomics)
- Development of a systems biology model by integration of the data into a multiparametric „Tumor Control Probability“ (TCP) model (in cooperation with the QBiC)
- Development of a robust „decision support system“ for personalised treatment of head and neck cancer