Predictors of Normal Tissue Response From the Microenvironment in Radiotherapy for Prostate and Head-and-neck Cancer

The main idea behind MICRO-LEARNER is to provide new insights about the response of healthy tissues to radiation by using information from the micro-environment obtained by biological measurements and imaging. This new knowledge will be included in current available predictive models of radio-induced toxicity, thus allowing to add unique biological characteristics of patients to dosimetry and treatment/clinical related variables. MICRO-LEARNER focuses on prostate cancer (PCa) and head-and-neck cancer (HNCa). For both cancers, radiotherapy is effectively used as curative treatment, in single modality or within a multidisciplinary approach including surgery (PCa) and/or chemotherapy (HNCa). Prediction and reduction of radio-induced side effects are becoming a priority: for PCa, high survival rates should be accompanied by a very low rate of moderate/severe toxicities; for HNCa, there is the need to tailor radiation dose according to disease recurrence risk profile. The shared aim of both cancers is to balance the improvement in outcome with a well-tolerated toxicity profile. Recent research indicates that the intestinal/salivary bacteria are strongly suspected of being very important in mediating the response to inflammation and lesions. Although their balance deeply changes during radiotherapy, studies done so far in the field of the microbiota-host relationship in radiotherapy have not addressed their role in insurgence of radiation toxicity. In this study, the investigators will assess how microbial populations evolve and how this influences the host and radiation induced toxicity in a significant number of patients. Moreover, the individual response at the tissue microstructure level, through analysis of images with advanced bioengineering techniques, will be determined. Results from this research, besides suggesting new ways to predict patients at risk of relevant side-effects, may also suggest possible treatments to change the baseline microbiota of patients at high risk or to modify it during therapy, in order to mitigate toxicity. Understanding the microbiota-radiotherapy interaction may thus lead to novel, effective and inexpensive ways of assessing and managing complications of cancer treatment.

Sex

All

Minimum age

18 Years

Inclusion Criteria (PCa patients in discovery and validation cohorts):

* Patients with histologically confirmed diagnosis of PCa candidate to exclusive or post-surgical radiotherapy, in both case it can be associated to hormone therapy
* Prognostic risk included in the very low, low, intermediate or high risk classes following the NCCN Clinical Practice Guidelines in Oncology and patients with oligometastatic disease treated with curative doses to the prostate (≥70 Gy at 2 Gy per fraction)
* Written informed consent to the study

Exclusion Criteria (PCa patients in discovery and validation cohorts):

* Previous pelvic radiotherapy
* Autoimmune disease (scleroderma,Chron's disease and ulcerative colitis), chronic kidney disease requiring dyalis
* Patients with malignant neoplasm in treatment with local or systemic therapies, except for patients with PCa and skin cancers
* Refusal to accept the study participation modalities

Inclusion Criteria (HNCa patients in discovery and validation cohorts):

* ECOG PS ≤ 3
* Histologically confirmed diagnosis of squamous cell carcinoma of the head and neck (oral cavity, pharynx, larynx, paranasal sinuses and nasal cavity, salivary glands)
* Non-metastatic stage III-IV cancer of the pharinx, larynx according to AJCC VII edition. Patients with stage III-IV cancer of salivary glands o paranasal sinuses. Patients with stage I-II cancer of pharinx and larynx only if neck lymph nodes or oral mucosa are included in the irradiated volume
* Indication to exclusive or post-surgical radiotherapy (associated or not to systemic therapy according to internal guidelines)
* Written informed consent to the study

Exclusion Criteria (HNCa patients in discovery and validation cohorts):

* Previous head and neck radiotherapy
* Connective tissue disease (lupus erythematosus or scleroderma) or other concomitant head and neck cancers, except for in situ skin cancers not requiring radiotherapy or systemic therapies.
* Refusal to accept the study participation modalities

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