The Impact of Skeletal Muscle Depletion on Head and Neck Squamous Cell Carcinoma

Nishikawa, Daisuke; Hanai, Nobuhiro; Suzuki, Hitomi; Koide, Yusuke; Beppu, Shintaro; Hasegawa, Yasuhisa

doi:10.1159/000485515

Cited by 62 publications

(93 citation statements)

References 26 publications

(28 reference statements)

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“…The present study also showed that pretreatment muscle wasting is an independent prognostic factor for OS in LAHNSCC patients. Kaplan–Meier and Cox regression analyses showed a significantly worse OS in patients with pretreatment muscle wasting, which is consistent with previous studies …”

Section: Discussionsupporting

confidence: 92%

Disease‐induced and treatment‐induced alterations in body composition in locally advanced head and neck squamous cell carcinoma

Willemsen

Hoeben

Lalisang

et al. 2019

J cachexia sarcopenia muscle

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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.

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Section: Discussionsupporting

confidence: 92%

Disease‐induced and treatment‐induced alterations in body composition in locally advanced head and neck squamous cell carcinoma

Willemsen

Hoeben

Lalisang

et al. 2019

J cachexia sarcopenia muscle

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“…Second, adjustment for confounders resulted in a minimal change of the estimated RR. Last, the relation between low muscle mass and functional impairment later on (ie, tube dependency) is biologically plausible, and analogous effects of low skeletal muscle mass have been observed for other clinical and functional outcomes of HNC treatment …”

Section: Discussionmentioning

confidence: 71%

“…In several cancer types, pretreatment sarcopenia is associated with inferior treatment outcomes including postoperative complications and treatment‐related toxicity . Recent studies confirm this association in head and neck cancer (HNC) with regard to treatment outcomes (ie, chemotherapy dose‐limiting toxicity) and survival after concomitant chemoradiotherapy (CRT) and postoperative complications including pharyngocutaneous fistula after total laryngectomy . There is a paucity of information, however, on the influence of sarcopenia on functional outcomes.…”

Section: Introductionmentioning

confidence: 99%

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Sarcopenia, a strong determinant for prolonged feeding tube dependency after chemoradiotherapy for head and neck cancer

et al. 2019

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Background Sarcopenia might be a relevant lead for optimization of the condition of patients with head and neck cancer (HNC) before chemoradiotherapy (CRT) to prevent long‐term functional swallowing impairment, such as feeding tube dependency. Methods Regression analyses were performed to assess the association between skeletal muscle mass index (SMI), as a measure of sarcopenia, and prolonged (>90 days) feeding tube dependency in 128 patients with HNC treated with primary CRT. Results Sixty‐one patients (48%) became prolonged feeding tube‐dependent. Lower SMI increased the risk of prolonged feeding tube dependency in multivariable analysis (risk ratio 1.08; 95% confidence interval 1.02‐1.14, P = .01) adjusted for body mass index, abnormal diet, and socioeconomic status. Conclusions Sarcopenia contributes to the risk of prolonged feeding tube dependency of patients with HNC treated with primary CRT. As sarcopenia might be a modifiable factor prior to treatment, it should be explored as a target for pretreatment patients' condition.

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“…Prevalence of sarcopenia in our cohort is 48.2% and thus in line with previous published prevalence. CT‐derived sarcopenia has been previously related to chemotherapy dose‐limiting toxicity and worsened survival and is aggravated trough (chemo)radiotherapy in HNC patients . However, despite being a significant problem, other associations of CT‐determined sarcopenia in HNC patients are underreported in literature.…”

Section: Discussionmentioning

confidence: 99%

CT‐measured skeletal muscle mass used to assess frailty in patients with head and neck cancer

Zwart

Hoorn

Ooijen

et al. 2019

J cachexia sarcopenia muscle

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Background Skeletal muscle depletion or sarcopenia is related to multiple adverse clinical outcome. However, frailty questionnaires are currently applied in the daily practice to identify patients who are potentially (un)suitable for treatment but are time consuming and straining for patients and the clinician. Screening for sarcopenia in patients with head and neck cancer (HNC) could be a promising fast biomarker for frailty. Our objective was to quantify sarcopenia with pre‐treatment low skeletal muscle mass from routinely obtained neck computed tomography scans at level of third cervical vertebra in patients diagnosed with HNC and evaluate its association with frailty. Methods A total of 112 HNC patients with Stages III and IV disease were included from a prospective databiobank. The amount of skeletal muscle mass was retrospectively defined using the skeletal muscle index (SMI). Correlation analysis between SMI and continuous frailty data and the observer agreement were analysed with Pearson's r correlation coefficients. Sarcopenia was present when SMI felt below previously published non‐gender specific thresholds (<43.2 cm2/m2). Frailty was evaluated by Geriatrics 8 (G8), Groningen Frailty Indicator, Timed Up and Go test, and Malnutrition Universal Screening Tool. A univariate and multivariate logistic regression analysis was performed for all patients and men separately to obtain odds ratios (ORs) and 95% confidence intervals (95% CIs). Results The cohort included 82 men (73%) and 30 women (27%), with a total mean age of 63 (±9) years. The observer agreement for cross‐sectional measurements was excellent for both intra‐observer variability (r = 0.99, P < 0.001) and inter‐observer variability (r = 0.98, P < 0.001). SMI correlated best with G8 frailty score (r = 0.38, P < 0.001) and did not differ per gender. Sarcopenia was present in 54 (48%) patients, whereof 25 (46%) men and 29 (54%) women. Prevalence of frailty was between 5% and 54% depending on the used screening tool. The multivariate regression analysis for all patients and men separately isolated the G8 questionnaire as the only independent variable associated with sarcopenia (OR 0.76, 95% CI 0.66–0.89, P < 0.001 and OR 0.76, 95% CI 0.66–0.88, P < 0.001, respectively). Conclusions This is the first study that demonstrates that sarcopenia is independently associated with frailty based on the G8 questionnaire in HNC patients. These results suggest that in the future, screening for sarcopenia on routinely obtained neck computed tomography scans may replace time consuming frailty questionnaires and help to select the (un)suitable patients for therapy, which is highly clinically relevant.

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The Impact of Skeletal Muscle Depletion on Head and Neck Squamous Cell Carcinoma

Cited by 62 publications

References 26 publications

Disease‐induced and treatment‐induced alterations in body composition in locally advanced head and neck squamous cell carcinoma

Disease‐induced and treatment‐induced alterations in body composition in locally advanced head and neck squamous cell carcinoma

Sarcopenia, a strong determinant for prolonged feeding tube dependency after chemoradiotherapy for head and neck cancer

CT‐measured skeletal muscle mass used to assess frailty in patients with head and neck cancer

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