Search

BACKGROUND: This study aims to investigate the relationship between cancer cachexia and oropharyngeal dysphagia (OD) in patients with head and neck cancer (HNC) prior to chemoradiotherapy or bioradiotherapy (CRT/BRT).METHODS: A prospective cohort study with patients with HNC undergoing CRT/BRT (2018-2021) was conducted. Body composition and skeletal muscle function were evaluated using bioelectrical impedance analysis, handgrip strength, and the short physical performance battery (SPPB). The M. D. Anderson Dysphagia Inventory (MDADI), Eating Assessment Tool (EAT)-10 questionnaire, and patient characteristics were collected. A standardized videofluoroscopic swallowing study was offered to patients.RESULTS: Sixty-six patients were included. Twenty-six patients scored EAT-10 ≥ 3 and seventeen were cachectic. ACE-27 score >1, cachexia, abnormal SPPB-derived repeated chair-stand test, lower MDADI scores, and higher overall stage grouping showed potential predictive value (p ≤ 0.10) for EAT-10 ≥ 3. Using multivariable regression analysis, only cachexia remained a significant predictor of EAT-10 ≥ 3 (HR 9.000 [95%CI 2.483-32.619], p = 0.001).CONCLUSION: Cachexia independently predicted the presence of patient-reported OD.

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 P < .001), and a strong association in the patients at risk of sarcopenia (Spearman’s rho 0.678, P 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.

Purpose Prior to radiotherapy combined with chemotherapy (CRT) or biotherapy (BRT) for oropharyngeal squamous cell carcinoma (OPSCC), teeth with poor prognosis that pose a risk for post-RT osteoradionecrosis (ORN) are removed. The effect of tooth loss on body weight loss and tube feeding (TF) dependency during CRT/BRT is unknown. This study aimed to evaluate the effect of incomplete dentition, tooth extractions prior to CRT/BRT, and the subsequent loss of functional units on (1) weight loss during CRT/BRT and (2) the need for TF during CRT/BRT for OPSCC. Methods OPSCC patients treated with CRT/BRT between 2013 and 2016 were included in this retrospective cohort study. Dental status was determined during the dental assessment at first visit and after tooth extractions prior to the start of CRT/BRT. Weight loss during CRT/BRT was scored dichotomously, comparing weight loss > 5% to stable or increased weight. Potential factors associated with weight loss were identified, including patient, tumor, and treatment characteristics. Results Seventy-seven OPSCC patients were included. Forty patients (52%) experienced weight loss > 5% during CRT/BRT. Extractions were performed in 66% of the OPSCC patients. The mean number of extracted teeth was 4.1 ± 5.6 per patient. Tooth extractions prior to CRT/BRT were associated with weight loss > 5% during CRT/BRT (HR 1.130 (95% CI 1.011–1.262), p = 0.031). None of the dental status-related parameters showed any significant associative value for TF during CRT/BRT. Conclusions Pre-CRT/BRT tooth extractions intended to reduce the risk of ORN, are a risk factor for weight loss during CRT/BRT for OPSCC. Trial registration number This study was approved by the medical ethics committee of the MUMC + (METC 2020–1589) on July 28, 2020.

BackgroundMetabolic dysfunction and cancer cachexia are associated with poor cancer prognosis, yet the molecular mechanisms causing cancer-induced metabolic dysfunction and cachexia remain to be defined. A key link between metabolic- and muscle mass-regulation is adenosine monophosphate-activated protein kinase (AMPK). As AMPK could be a potential treatment, it is important to determine the function for AMPK in cancer-associated metabolic dysfunction and cachexia. Here we determined the function of AMPK in cancer-associated metabolic dysfunction, insulin resistance, and cachexia.MethodsIn vastus lateralis muscle biopsies from pre-cachectic and cachectic patients with Non-Small-Cell Lung Carcinoma (NSCLC), AMPK signaling and expression were examined by immunoblotting. To investigate the role of muscle AMPK, male mice overexpressing a dominant-negative AMPKα2 (kinase-dead) specifically in striated muscle (mAMPK-KD) were inoculated with Lewis Lung Carcinoma (LLC) cells. In a subsequent cohort, male LLC-tumor-bearing mice were treated with/without 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) to activate AMPK for 13 days. Littermate mice were used as control. Metabolic phenotyping of mice was performed via indirect calorimetry, body composition analyses, glucose- and insulin tolerance tests, tissue-specific 2-deoxy- glucose (2-DG) uptake, and immunoblotting.ResultsIn muscle from patients with NSCLC, we found increased expression of AMPK subunits α1, α2, β2, γ1, and γ3; ranging from +27% to +79% compared to healthy control subjects. AMPK subunit expression correlated with indices of cachexia, including cross sectional area and weight loss. Tumor-bearing mAMPK-KD mice presented increased fat loss as well as glucose and insulin intolerance. LLC in mAMPK-KD mice displayed lower insulin-stimulated 2-DG uptake in skeletal muscle (quadriceps; −35%, soleus; −49%, EDL; −48%) and the heart (−29%) compared to non-tumor-bearing mice. In skeletal muscle, mAMPK-KD abrogated the tumor-induced increase in phosphorylation of TBC1D4thr642. Additionally, protein expression of TBC1D4 (+26%), pyruvate dehydrogenase (PDH, +94%), and PDH-kinases (PDKs, +45% to +100%), and glycogen synthase (+48%) were increased in skeletal muscle of tumor-bearing mice in an AMPK-dependent manner. Lastly, chronic AICAR treatment elevated hexokinase-II protein expression and normalized phosphorylation of p70S6Kthr389 (mTORC1 substrate) and ACCser212 (AMPK substrate) and rescued the cancer-induced insulin intolerance.ConclusionsUpregulated protein expression of AMPK subunits observed in skeletal muscle of (pre)cachectic patients with non-small-cell lung carcinoma. This seemed protective inferred by AMPK-deficient tumor-bearing mice being highly prone to developing metabolic dysfunction, which included the AMPK-dependent regulation of several proteins involved in glucose metabolism. These observations highlight the potential for targeting AMPK to counter cancer-associated metabolic dysfunction and cachexia.Abstract Figure

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 into “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 = .025 and PFS HR = 1.453; 95%CI: 1.037–2.036; P = .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 = .042) and a significantly lower chance of receiving second-line treatment (OR = 0.23; 95%CI: 0.09–0.60; P = .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 counseling and aid in treatment decision processes or trial stratification.

Prior to radiotherapy combined with chemotherapy (CRT) or biotherapy (BRT) for oropharyngeal squamous cell carcinoma (OPSCC), teeth with poor prognosis that pose a risk for post-RT osteoradionecrosis (ORN) are removed. The effect of tooth loss on body weight loss and tube feeding (TF) dependency during CRT/BRT is unknown. This study aimed to evaluate the effect of incomplete dentition, tooth extractions prior to CRT/BRT, and the subsequent loss of functional units on (1) weight loss during CRT/BRT and (2) the need for TF during CRT/BRT for OPSCC.OPSCC patients treated with CRT/BRT between 2013 and 2016 were included in this retrospective cohort study. Dental status was determined during the dental assessment at first visit and after tooth extractions prior to the start of CRT/BRT. Weight loss during CRT/BRT was scored dichotomously, comparing weight loss 5% to stable or increased weight. Potential factors associated with weight loss were identified, including patient, tumor, and treatment characteristics.Seventy-seven OPSCC patients were included. Forty patients (52%) experienced weight loss 5% during CRT/BRT. Extractions were performed in 66% of the OPSCC patients. The mean number of extracted teeth was 4.1 ± 5.6 per patient. Tooth extractions prior to CRT/BRT were associated with weight loss 5% during CRT/BRT (HR 1.130 (95% CI 1.011-1.262), p = 0.031). None of the dental status-related parameters showed any significant associative value for TF during CRT/BRT.Pre-CRT/BRT tooth extractions intended to reduce the risk of ORN, are a risk factor for weight loss during CRT/BRT for OPSCC.This study was approved by the medical ethics committee of the MUMC + (METC 2020-1589) on July 28, 2020.

e18027 Background: Response rates of immune checkpoint inhibitor (ICI) therapy for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) are relatively low. This study evaluates the predictive and prognostic value of weight loss and changes in body composition prior to and during ICI therapy in R/M HNSCC. Methods: This retrospective multicenter cohort study enrolled ninety-eight patients. Patient, tumor and treatment characteristics were retrieved from health records, including neutrophil and platelet-lymphocyte-ratio (NLR and PLR). Cachexia was defined according to the international consensus (Fearon et al. 2011). Skeletal muscle (SM), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) were evaluated on baseline and follow-up computed tomography scans at the third lumbar vertebrae level. Univariable and multivariable regression analysis were performed for six months progression free survival (PFS6m) and overall survival (OS). Results: Thirty-four patients (35%) experienced significant early weight loss (> 2%) during the first six weeks of therapy. This subgroup presented a significantly higher NLR and PLR at baseline. NLR and PLR were significantly correlated with VAT and SAT index. Independent predictors of PFS6m were lower world health organization performance status (WHO PS) (HR 0.16 [95% CI 0.04-0.54] p = 0.003), higher baseline SAT index (HR 1.045 [95% CI 1.02-1.08] p = 0.003), and early weight loss < 2% (HR 0.85 [95% CI 0.74-0.98] p = 0.03). WHO PS and baseline cachexia in combination with > 2% early weight loss were independent predictors of OS (HR 2.09 [95% CI 1.11-3.92] p = 0.02, HR 2.18 [95% CI 1.13-4.21] p = 0.02). Conclusions: The combination of cachexia at baseline and weight loss during the first six weeks of ICI therapy is associated with worse OS in HNSCC patients treated with ICI therapy. Patients with early weight loss during ICI treatment show an increase in systemic inflammation. The mechanism of how adipose tissue interferes with ICI response needs further investigation.