Purpose To develop a European White Paper document on oropharyngeal dysphagia (OD) in head and neck cancer (HNC). There are wide variations in the management of OD associated with HNC across Europe. Methods Experts in the management of specific aspects of OD in HNC across Europe were delegated by their professional medical and multidisciplinary societies to contribute to this document. Evidence is based on systematic reviews, consensus-based position statements, and expert opinion. Results Twenty-four sections on HNC-specific OD topics. Conclusion This European White Paper summarizes current best practice on management of OD in HNC, providing recommendations to support patients and health professionals. The body of literature and its level of evidence on diagnostics and treatment for OD in HNC remain poor. This is in the context of an expected increase in the prevalence of OD due to HNC in the near future. Contributing factors to increased prevalence include aging of our European population (including HNC patients) and an increase in human papillomavirus (HPV) related cancer, despite the introduction of HPV vaccination in various countries. We recommend timely implementation of OD screening in HNC patients while emphasizing the need for robust scientific research on the treatment of OD in HNC. Meanwhile, its management remains a challenge for European professional associations and policymakers.

Background Chemoradiation or bioradiation treatment (CRT/BRT) of locally advanced head and neck squamous cell carcinoma (LAHNSCC) comes with high toxicity rates, often leading to temporary tube feeding (TF) dependency. Cachexia is a common problem in LAHNSCC. Yet changes in body composition and muscle weakness during CRT/BRT are underexplored. Strong evidence on the effect of TF on body composition during treatment is lacking. The aim of this cohort study was to assess (i) the relationship of fat‐free mass index (FFMI) and handgrip strength (HGS) with CRT/BRT toxicity and outcome, (ii) body composition in patients treated with chemoradiation (cisplatin) vs. bioradiation (cetuximab), and (iii) the effect of the current TF regime on body composition and muscle strength. Methods Locally advanced head and neck squamous cell carcinoma patients treated with CRT/BRT between January 2013 and December 2016 were included (n = 137). Baseline measurements of body composition (bioelectrical impedance analysis) and HGS were performed. Toxicity grades (Common Terminology Criteria for Adverse Events) were scored. In a subset of 69 patients, weight loss, body composition, and HGS were additionally assessed during and after CRT/BRT. TF was initiated according to the Dutch guidelines for malnutrition. Results In this cohort (68% male, mean age 59 ± 8 years), the incidence of baseline muscle wasting, defined as FFMI < P10, was 29%. Muscle wasting was present in 23 of 100 (23%) chemoradiation patients and 17 of 37 (46%) bioradiation patients (P = 0.009). Muscle‐wasted patients required more unplanned hospitalizations during CRT (P = 0.035). In the chemoradiation subset, dose‐limiting toxicity was significantly higher in wasted vs. non‐wasted patients (57% vs. 25%, P = 0.004). Median follow‐up was 32 months. Multivariate Cox regression analysis identified muscle wasting as independent unfavourable prognostic factor for overall survival [hazard ratio 2.1 (95% CI 1.1–4.1), P = 0.022] and cisplatin as favourable prognostic factor [hazard ratio 0.3 (95% CI 0.2–0.6), P = 0.001]. Weight and HGS significantly decreased during CRT/BRT, −3.7 ± 3.5 kg (P < 0.001) and −3.1 ± 6.0 kg (P < 0.001), respectively. Sixty‐four per cent of the patients required TF 21 days (range 0–59) after CRT/BRT initiation. Total weight loss during CRT/BRT was significantly (P = 0.007) higher in the total oral diet group (5.5 ± 3.7 kg) compared with the TF group (3.0 ± 3.2 kg). Loss of FFM and HGS was similar in both groups. Conclusions In LAHNSCC patients undergoing CRT/BRT, FFMI < P10 is an unfavourable prognostic factor for overall survival, treatment toxicity, and tolerance. Patients experience significant weight and FFM loss during treatment. Current TF regime attenuates weight loss but does not overcome loss of muscle mass and function during therapy. Future interventions should consider nutritional intake and additional strategies specifically targeting metabolism, loss of muscle mass, and function.

Background It is not well known to what extent effectiveness of treatment with immune checkpoint inhibitors in stage IV non‐small‐cell lung cancer (NSCLC) is influenced by weight loss and changes in body composition. Therefore, the goal of this study was to evaluate body composition changes in relation to early weight change and overall survival (OS) in stage IV NSCLC patients treated with second‐line nivolumab. Methods All patients with stage IV NSCLC, who were treated with second‐line nivolumab between June 2015 and December 2018 at Maastricht University Medical Center, were evaluated. Skeletal muscle mass (SMM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were assessed at the first lumbar level on computed tomography images obtained before initiation of nivolumab and at week 6 of treatment. The contribution of changes in body weight (defined as >2% loss), SMM, VAT, and SAT to OS was analysed by Kaplan–Meier method and adjusted for clinical confounders in a Cox regression analysis. The results from the study cohort were validated in another Dutch cohort from Erasmus Medical Center, Rotterdam. Results One hundred and six patients were included in the study cohort. Loss of body weight of >2% at week 6 was an independent predictor for poor OS (hazard ratio 2.39, 95% confidence interval 1.51–3.79, P < 0.001) when adjusted for gender, >1 organ with metastasis, pretreatment hypoalbumenaemia, and pretreatment elevated C‐reactive protein. The result was confirmed in the validation cohort (N = 62). Loss of SMM as a feature of cancer cachexia did not significantly predict OS in both cohorts. Significant (>2%) weight loss during treatment was reflected by a significant loss of VAT and SAT, while loss of SMM was comparable between weight‐stable and weight‐losing patients. Conclusions Weight loss, characterized by loss of subcutaneous and visceral adipose tissues, at week 6 of treatment with nivolumab, is a significant poor prognostic factor for survival in patients with Stage IV NSCLC.

Background Previous studies have recognized temporal muscle thickness (TMT) as a prognostic marker in glioblastoma, but clinical implementation is hampered due to studies’ heterogeneity and lack of established cutoff values. The aim of this study was to assess the validity of recent proposed sex-specific TMT cutoff values in a real-world population of genotyped primary glioblastoma patients. Methods We measured TMT in preoperative MR images of 328 patients. Sex-specific TMT cutoff values were used to divide patients in ‘at risk of sarcopenia’ or ‘normal muscle status’. Kaplan-Meier analyses and stepwise multivariate Cox-Regression analyses were used to assess the association with overall survival (OS) and progression free survival (PFS). The association with occurrence of complications and discontinuation of glioblastoma treatment was investigated using odds ratios (OR). Results Patients at risk of sarcopenia had a significantly higher risk of progression and death than patients with normal muscle status, which remained significant in the multivariate analyses (OS HR=1.437; 95%CI: 1.046-1.973; p=0.025 and PFS HR=1.453; 95%CI: 1.037-2.036; p=0.030). Patients at risk of sarcopenia also had a significantly higher risk of early discontinuation of treatment (OR=2.45; 95%CI: 1.011-5.952; p=0.042) and a significantly lower chance of receiving second line treatment (OR=0.23; 95%CI: 0.09-0.60; p=0.001). There was no association with the occurrence of complications. Conclusions Our study confirms external validity of the use of proposed sex-specific TMT cutoff values as an independent prognostic marker in newly diagnosed glioblastoma patients. This simple, noninvasive marker could improve patient counselling and aid in treatment decision processes or trial stratification.

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Background: Cancer cachexia is highly prevalent in advanced non-small cell lung cancer (NSCLC) and locally advanced head and neck squamous cell carcinoma (LAHNSCC), and compromises treatment tolerance and overall survival (OS). NSCLC and LAHNSCC patients share similar risk factors, and receive comparable anti-cancer treatment regimens. The aim of this study was to determine the predictive value of body composition assessed by bioelectrical impedance analysis (BIA) and handgrip strength (HGS) (baseline and early changes during therapy) on OS in NSCLC and LAHNSCC patients treated with platinum-based chemoradiotherapy (CRT) or cetuximab-based bioradiotherapy (BRT). To elucidate potential underlying determinants of early changes in body composition and HGS, specific (fat and fat free) mass loss patterns of squamous NSCLC (sNSCLC) were compared to human papilloma virus negative (HPV–) LAHNSCC patients treated with CRT.Methods: Between 2013 and 2016, BIA and HGS were performed at baseline and after 3 weeks of CRT/BRT in LAHNSCC and NSCLC patients treated with curative intent.Results: Two hundred thirty-three patients were included for baseline measurements. Fat free mass index (FFMI) and HGS&lt;10th percentile of reference values at baseline were both prognostic for poor OS in NSCLC and LAHNSCC [HR 1.64 [95%CI 1.13–2.39], p = 0.01 and HR 2.30 [95%CI 1.33–3.97], p = 0.003, respectively], independent of Charlson Comorbidity Index, cancer site, and gross tumor volume. Early fat mass (FM) loss during CRT was predictive for poor OS in sNSCLC (n = 64) [HR 3.80 [95%CI 1.79–8.06] p ≤ 0.001] but not in HPV– LAHNSCC (n = 61). In patients with significant weight loss (&gt;2%) in the first 3 weeks of CRT (sNSCLC n = 24, HPV– LAHNSCC n = 23), the FM change was −1.4 ± 14.5% and −8.7 ± 9.0% in sNSCLC and HPV– LAHNSCC patients, respectively (p &lt; 0.05). Fat fee mass change was −5.6 ± 6.3% and −4.0 ± 4.3% for sNSCLC and HPV– LAHNSCC, respectively (p = 0.31).Conclusion: FFMI and HGS&lt;10th percentile at baseline are independent prognostic factors for poor OS in NSCLC and LAHNSCC patients treated with CRT/BRT. The specific composition of mass loss during first 3 weeks of CRT significantly differs between sNSCLC and HPV– LAHNSCC patients. Early FM loss was prognostic in sNSCLC only.

Purpose Reduced temporal muscle thickness (TMT) has recently been postulated as a prognostic imaging marker and an objective tool to assess patients frailty in glioblastoma. Our aim is to investigate the correlation of TMT and systemic muscle loss to confirm that TMT is an adequate surrogate marker of sarcopenia in newly diagnosed glioblastoma patients. Methods TMT was assessed on preoperative MR-images and skeletal muscle area (SMA) was assessed at the third lumbar vertebra on preoperative abdominal CT-scans. Previous published TMT sex-specific cut-off values were used to classify patients as ‘patient at risk of sarcopenia’ or ‘patient with normal muscle status’. Correlation between TMT and SMA was assessed using Spearman’s rank correlation coefficient. Results Sixteen percent of the 245 included patients were identified as at risk of sarcopenia. The mean SMA of glioblastoma patients at risk of sarcopenia (124.3 cm2, SD 30.8 cm2) was significantly lower than the mean SMA of patients with normal muscle status (146.3 cm2, SD 31.1 cm2, P < .001). We found a moderate association between TMT and SMA in the patients with normal muscle status (Spearman’s rho 0.521, P < .001), and a strong association in the patients at risk of sarcopenia (Spearman’s rho 0.678, P < .001). Conclusion Our results confirm the use of TMT as a surrogate marker of total body skeletal muscle mass in glioblastoma, especially in frail patients at risk of sarcopenia. TMT can be used to identify patients with muscle loss early in the disease process, which enables the implementation of adequate intervention strategies.

Background & aims: Malnutrition in head and neck cancer (HNC) patients is associated with increased morbidity and mortality. The purpose of this study is two-fold: to identify the risk of malnutrition in patients with oropharyngeal dysphagia (OD) secondary to HNC, and to determine the relationship between the risk of malnutrition versus tumor characteristics, treatment modality, time interval (between the end of oncological treatment and swallowing assessment date), level of oral intake, body mass index (BMI), aspiration, pharyngeal pooling, and OD-related quality of life (QoL). Methods: The Short Nutritional Assessment Questionnaire (SNAQ) was used to screen patients for the risk of malnutrition. Patients underwent a standardized swallowing examination protocol including an endoscopic evaluation of swallowing. Results: Seventy-five dysphagic HNC patients were included. Forty-eight percent of the patients presented a high risk of malnutrition using SNAQ. The majority of the patients (81.3%) was on a total oral diet. Moreover, BMI did not appear to be a reliable measure to screen for malnutrition as a normal BMI was often associated with an increased risk of malnutrition on the SNAQ. In contrast, patients who were underweight or overweight did not show an association with a high risk of malnutrition. With the exception of BMI, no other patient and tumor characteristics were found to be associated with the risk of malnutrition.Conclusions: This study emphasizes the importance of early nutritional screening in dysphagic HNC patients, as almost half of these patients presented a high risk of malnutrition. Malnutrition screening using SNAQ can identify HNC patients with OD who are at risk of malnutrition and subsequently need to be referred to a dietician for additional nutritional assessment, diagnosis of malnutrition, and nutritional support, even when their BMI is within normal range.