Cisplatin dose limiting toxicity and skeletal muscle mass in head and neck cancer patients: The effect of skeletal muscle mass on dose limiting toxicities and potential solutions

The research in this thesis is about the impact of low skeletal muscle mass on cisplatin dose-limiting toxicity and explores strategies to optimize treatment outcomes for head and neck squamous cell carcinoma patients undergoing chemoradiotherapy. Patients with low skeletal muscle mass have higher risk for cisplatin dose-limiting toxicity, and skeletal muscle mass further declines during therapy with chemoradiotherapy. In the prospective CISLOW study, patients with low skeletal muscle mass were randomized between weekly versus triweekly cisplatin schedules to assess whether weekly cisplatin leads to less cisplatin dose-limiting toxicity. In addition to this intervention, patients with low skeletal muscle mass were interviewed about their experiences during cisplatin-based chemoradiotherapy. Patients highlighted the life-altering nature of chemoradiotherapy, and emphasized the need for post-treatment counseling and support. Ototoxicity is a common cause of cisplatin dose-limiting toxicity, and hearing loss was associated with a low skeletal muscle index. Nephrotoxicity is another common cause of cisplatin dose-limiting toxicity. To prevent nephrotoxicity, patients receive hydration regimens around chemoradiotherapy. Shorter hydration schedules were linked to less nephrotoxicity but more ototoxicity, so exploring additional strategies to prevent both are warranted. Overall, this work highlights the importance of a multidisciplinary approach addressing both physical and psychosocial consequences of head and neck squamous cell carcinoma treatment and optimizing care to improve head and neck cancer patient outcomes.