151751-Najiba-Chargi

425 Summarizing discussion and future perspectives in Chapter 9 , a study is presented which investigated the predictive impact of arterial calcifi- cation and low skeletal muscle mass for the occurrence of pharyngocutaneous fistula forma- tion in 224 patients undergoing laryngectomy. Arterial calcifications were a common finding in patients undergoing laryngectomy, with only 1.3% percent of patients having no arterial calcification present and 7.1% of patients having at most mild arterial calcifications present. Arterial calcifications at several locations, most notably of the descending aorta and the origo of the brachiocephalic arteries, were significantly associated with pharyngocutaneous fistula formation. A higher total arterial calcification score was also significantly associated with pharyngocutaneous fistula formation. Moderate to severe arterial calcification at the location of the descending aorta was more often present in patients with low skeletal muscle mass as compared to patients without low skeletal muscle mass (p<0.01). At the other locations, no significant difference was observed. Inmultivariable logistic regression analysis, both the total arterial calcification score (OR 1.05, p<0.05) and low skeletal muscle mass (OR 1.86, p<0.05) were independently associated with the formation of pharyngocutaneous fistula. Besides surgery, head and neck cancer patients, especially those with locally advanced cancer, are treated with (chemo- or bio)radiotherapy. Therefore, Part III of this thesis presents the predictive and prognostic impact of low skeletal musclemass in head and neck cancer patients treated with (chemo- or bio)radiotherapy. Chapter 10 presents a study in 343 patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who were treated with cisplatin-based chemoradiotherapy. The predictive value of low skeletal muscle mass for cisplatin dose-limiting toxicity was investigated. Dose-limiting toxicity was defined as any toxicity resulting in a cisplatin dose-reduction of ≥ 50%, a treatment delay of ≥4 days or a termination of treatment after the first or second cycle of cisplatin. Majority of these patients had low skeletal muscle mass before treatment (58%). Also, a large percentage of patients (44.9%) experienced dose-limiting toxicities. Low skeletal muscle mass was predictive factor for cisplatin-dose limiting toxicity (HR 1.8, p<0.05). Chapter 11 presents a study in 156 local- ly advanced HNSCC patients who were treated with cisplatin-based chemoradiotherapy in the Antoni van Leeuwenhoek hospital, Amsterdam. In this cohort, the predictive impact of low skeletal muscle mass on cisplatin-dose limiting toxicity was also investigated. Similar percentage of patients (54.9%) were diagnosed with low skeletal musclemass. For this cohort, cisplatin dose-limiting toxicity was defined as any toxicity resulting in receiving a cumulative cisplatin dose below 200mg/m 2 , the prescribed cumulative cisplatin dose in cisplatin-based chemoradiotherapy is 300mg/m 2 . Compared to the previous study in chapter 10, a smaller percentage of patients (24.2% versus 44.9%) experienced cisplatin dose-limiting toxicity. Nev - ertheless, low skeletal muscle mass was a significant predictor (HR 4.0, p<0.05) for cispla - tin-dose limiting toxicity. Not all patients with locally advanced head and neck cancer are physically fit to undergo cisplatin-based chemoradiotherapy, mainly due to comorbidities such as vascular diseases and kidney diseases. Chapter 12 presents a study in 91 cisplatin-un- fit patients who received cetuximab-based bioradiotherapy to evaluate the predictive impact for dose-limiting toxicities in this group of HNSCC patients. A higher percentage of patients with low skeletal muscle mass (74.7%) was found in this study compared to the cisplatin-fit 21