Abstract Does prehabilitation be able to favorably impact on the pathway of head and neck cancer patients, candidate to surgery or chemoradiotherapy as primary treatment?

Head and Neck Cancer (HNC) is a rare tumor, accounted for 900,000 new cases in 2020 with the incidence in 2040 predicted to rise by 46.8%. Diagnosis is generally late, with most of the patients (about 80%) at stage III and IV. Main causes of HNC are HPV infection, smoking and alcohol abuse. Unfortunately, despite the advancement in the knowledge, there have not been significant changes in patients' treatment in the last 20 years. Surgery followed by radiotherapy (RT) +/- chemotherapy (CT) or concomitant chemo-radiotherapy (CRT) remains the standard of care for locally advanced cases.
Treatment-related acute and late toxicities represent a serious issue, deteriorating the quality of life and the well-being of cured patients. Prehabilitation (P) is a multimodal needs-based intervention dedicated to cancer patients before an acute treatment, even if recent recommendations from ASCO support P even during active cancer treatments. It aims at enhancing patient's functional capacity, physical strength and emotional resilience before undergoing a cancer treatment. P typically involves a combination of exercise training, nutritional counseling and psychological support. In addition, P seems to induce tumor shrinkage, potentially acting as "treatment sensitizer". Even if the mechanisms behind this behaviour need to be fully clarified yet, it has been hypothesized an effect by physical exercise on tumor vasculature (e.g. exercise may remodel the tumor vasculature), coupled with an enhancement of immune cells response (e.g. increasing of number of circulating memory T cells after the exercise). There are amount of growing evidence supporting the efficacy of P in breast, lung and colorectal cancer patients while very few evidences are available for HNC up to now. Most of the papers are referred to clinical reviews, and prospective data are completely lacking. Regarding the timing of P in HNC, we believe it would be feasible before acute treatments; more critical the application of P during active cancer treatments, especially considering the prolonged CRT period and the acute side effects burden. With this proposal, we would address three main points: 1) to prospectively assess the feasibility of P before and during curative treatment for HNC patients; 2) to investigate the efficacy outcomes of P; 3) to explore the cost-effectiveness of P. To answer to these questions, we have created a multidisciplinary consortium including ENT surgeons, medical oncologists, radiation oncologists, clinical nutritionist, psychologists, biologist and biomedical engineer. We have estimated to enroll in the study period 60 patients with locally advanced HNC, 30 candidates to surgery plus RT +/- CT and 30 to CRT. P will start 4 weeks before the radical treatment (i.e. surgery or CRT) and will be continued in parallel until 2 weeks after the end of the whole program of treatment (i.e. end of CRT). Specific questionaries will be employed as screening tools to assess the nutritional status, the psychological status, the performance status, the individual levels of physical activity and the overall quality of life. Wearable health devices will be provided to all enrolled patients to monitor the adherence to the P program. Collection of biological samples (blood, stool, saliva, tumor samples) will be performed for translational research purposes (e.g. microbioma, circulating immune cell populations etc.)