151751-Najiba-Chargi

209 Systemic therapy: skeletal muscle mass and chemoradiotherapy DISCUSSION Low SMM is associated with an increase in chemotherapy related toxicity and CDLT in a variety of cancer types. Our study also shows this relationship in HNSCC patients treated with primary CRT with high-dose cisplatin. Patients with low SMM had a trifold risk of experiencing CDLT compared to patients with normal SMM in this study. Although patients with low SMM did not have a decreased OS, patients who experienced CDLT did have a significantly decreased OS. This study adds to the mounting evidence that there is a clear relationship between low SMM and the occurrence of CDLT in HNSCC patients treated with high dose cisplatin. 9,16,21,22 Platinum-based chemotherapy is routinely used in the curative treatment of LA-HNSCC to enhance the antitumor effect of radiation. Several treatment schemes and dosing levels are available for platinum-based chemotherapy in HNSCC. Level 1 evidence is available for the improvement of locoregional control and overall survival with concurrent CRT with three three-weekly cycles of high dose cisplatin at a dose level of 100mg/m 2 BSA. 2 Despite irrefut- able efficacy, the toxicity of treatment with high dose cisplatin is a well-known problem in daily clinical practice. Early chemotherapy termination due to unacceptable toxicity occurs in approximately 30% of patients and is associated with a marked decrease in overall survival (52% versus 72% in 3-year survival) as well as increase in long-termmorbidity of treatment. In recent years, several large clinical trials have investigated de-escalation strategies with weekly low-dose cisplatin or cetuximab as radiosensitizer in HNSCC, but these trials concluded that concurrent CRT with high-dose cisplatin remains the preferred treatment option with the highest survival benefit. 23–25 There is an evident clinical need for improved risk assessment in patients planned for high- dose cisplatin treatment. Several risk factors for cisplatin toxicity are already established absolute contra-indications, such as a decreased renal function with an eGFR <60, severe hearing loss or poor functional WHO-status. Better knowledge on relative contraindications is needed to identify patients whomay benefit frommodified treatments. Low SMM is a radio - logical biomarker that may aid in the identification of those patients at high risk of cisplatin related toxicity that would otherwise not have been identified. 26 Over the last decade, the body composition of cancer patients has been researched exten - sively using diagnostic computer tomography (CT) imaging. 27 Recent retrospective studies in a variety of cancer types have shown an association between low SMM, sometimes termed sarcopenia, and the occurrence of chemotherapeutic toxicity and CDLT. 10 Several hypothesis have been proffered. One hypothesis behind this relationship is that most (hydrophilic) chemo - therapy, including cisplatin, mainly distributes into the fat-free body mass, of which skeletal muscle mass is the largest contributor. 11,28 Patients with low SMM and normal or high fat mass may receive a relatively higher dose of chemotherapy than is anticipated using a standard dosing regimen based on BSA. Previous research has shown that drug dosing based on BSA 11