Comparison of Skeletal Muscle Changes at Three Vertebral Levels Following Radiotherapy in Patients With Oropharyngeal Carcinoma.

Evaluation of skeletal muscle (SM) depletion, or sarcopenia, utilizes the cross-sectional area (CSA) of computed tomography (CT) scans at the lumbar level L3. However, alternate vertebral landmarks are used in patients with head and neck cancer due to scan unavailability. Muscle changes following radiotherapy at cervical (C3) and thoracic (T2) levels were compared to L3 in patients with oropharyngeal carcinoma. Muscle density data were derived retrospectively from diagnostic PET-CT scans at C3, T2 and L3 pretreatment, and up to six months post. CSA changes were compared to L3 in scans of 33 patients (88% male, mean age 61 (SD 8.5) years). On matched pair analysis; mean L3-CSA change -12.1 cm2 (SD 9.7, 95%CI -15.5 to -8.6, and p < 0.001), T2-CSA -30.5 cm2 (SD 34.8, 95%CI -42.8 to -18.1, and p < 0.001) and C3-CSA +2.1 cm2 (SD 4.1, 95%CI 0.63 to 3.5, and p < 0.00). No difference was found in the percentage change of T2-CSA with L3-CSA (mean -2.2%, SD 10.6, 95%CI -6.0 to 1.6, and p = 0.240), however, was significantly different to C3-CSA (mean 13.2%, SD 11.6, 95%CI 9.1 to 17.3, and p < 0.001). Results suggest SM at C3 does not change proportionately and may not be a reliable representation of whole-body SM change over time.

A prediction model for skeletal muscle evaluation and computed tomography-defined sarcopenia diagnosis in a predominantly overweight cohort of patients with head and neck cancer.

PURPOSE: This study investigates the feasibility of computed tomography (CT)-defined sarcopenia assessment using a prediction model for estimating the cross-sectional area (CSA) of skeletal muscle (SM) in CT scans at the third lumbar vertebra (L3), using measures at the third cervical level (C3) in a predominantly overweight population with head and neck cancer (HNC). METHODS: Analysis was conducted on adult patients with newly diagnosed HNC who had a diagnostic positron emission tomography-CT scan. CSA of SM in CT images was measured at L3 and C3 in each patient, and a predictive formula developed using fivefold cross-validation and linear regression modelling. Correlation and agreement between measured CSA at L3 and predicted values were evaluated using intraclass correlation coefficients (ICC) and Bland-Altman plot. The model's ability to identify sarcopenia was investigated using Cohen's Kappa (k). RESULTS: A total of 109 patient scans were analysed, with 64% of the cohort being overweight or obese. The prediction model demonstrated high level of correlation between measured and predicted CSA measures (ICC 0.954, r = 0.916, p < 0.001), and skeletal muscle index (SMI) (ICC 0.939, r = 0.883, p < 0.001). Bland-Altman plot showed good agreement in SMI, with mean difference (bias) = 0.22% (SD 8.65, 95% CI - 3.35 to 3.79%), limits of agreement (- 16.74 to 17.17%). The model had a sensitivity of 80.0% and specificity of 85.0%, with moderate agreement on sarcopenia diagnosis (k = 0.565, p = 0.004). CONCLUSION: This model is effective in predicting lumbar SM CSA using measures at C3, and in identifying low SM in a predominately overweight group of patients with HNC.

Thoracic skeletal muscle index is effective for CT-defined sarcopenia evaluation in patients with head and neck cancer.

PURPOSE: Computed tomography (CT)-defined sarcopenia, as a measurement of low skeletal muscle (SM), is a poor prognostic indicator in patients with head and neck cancer (HNC), independent of weight or nutritional status. We used SM measures at the second thoracic vertebra (T2) to determine T2-SM index (SMI) thresholds for sarcopenia, and investigate the impact of low T2-SMI on overall survival (OS), and weight loss during radiotherapy (RT). METHODS: Adult patients with newly diagnosed HNC with a diagnostic PET-CT or RT planning CT scan were included. SM was analysed at T2 and a model applied to predict SM at L3. T2-SMI thresholds for sarcopenia were established with predicted measures, stratified by BMI and sex. Impact of sarcopenia and low T2-SMI on OS and weight loss during RT was investigated. RESULTS: A total of 361 scans were analysed (84% males, 54% oropharynx tumours). Sarcopenia was found in 49%, demonstrating worse OS (p = 0.037). T2-SMI cutoff values were: females-74 cm2/m2 [area under the curve (AUC): 0.89 (95%CI 0.80-0.98)], males (BMI < 25)-63 cm2/m2 [AUC 0.93 (95%CI 0.89-0.96)], males (BMI ≥ 25)-88cm2/m2 [AUC 0.86 (95%CI 0.78-0.93)]. No difference in OS with T2-SMI categories. Lowest T2-SMI quartile of < 63 cm2/m2 demonstrated worse OS (p = 0.017). Weight loss during RT was higher in patients; who were not sarcopenic (6.2% vs 4.9%, p = 0.023); with higher T2-SMI (6.3% vs 4.9%, p = 0.014) and; in the highest quartiles (3.6% vs 5.7% vs 7.2%, p < 0.001). CONCLUSIONS: These T2-SMI thresholds are effective in assessing CT-defined sarcopenia in HNC. Further assessment of clinical application is warranted.

The use of alternate vertebral levels to L3 in computed tomography scans for skeletal muscle mass evaluation and sarcopenia assessment in patients with cancer: a systematic review.

Body composition measurement using diagnostic computed tomography (CT) scans has emerged as a method to assess sarcopenia (low muscle mass) in oncology patients. Assessment of skeletal muscle mass (SMM) using the cross-sectional area of a single vertebral slice (at lumbar L3) in a CT scan is correlated with whole-body skeletal muscle volume. This method is used to assess CT-defined sarcopenia in patients with cancer, with low SMM effecting outcomes. However, as diagnostic scans are based on tumour location, not all include L3. We evaluated the evidence for the use of alternate vertebral CT slices for SMM evaluation when L3 is not available. Five electronic databases were searched from January 1996 to April 2020 for studies using CT scan vertebral slices above L3 for SM measurement in adults with cancer (solid tumours). Validation with whole-body SMM, rationale for the chosen slice and sarcopenia cut-off values were investigated. Thirty-two studies were included, all retrospective and cross-sectional in design. Cervical, thoracic and lumbar slices were used (from C3 to L1), with no validation of whole-body SMM using CT scans. Alternate slices were used in lung, and head and neck cancer patients. Sarcopenia cut-off values were reported in 75 % of studies, with differing methods, with or without sex-specific values, and a lack of consensus. Current evidence is inadequate to provide definitive recommendations for alternate vertebral slice use for SMM evaluation in cancer patients. Variation in sarcopenia cut-offs warrants more robust investigation, in order for risk stratification to be applied to all patients with cancer.

The Impact of Critical Weight Loss and Reactive Feeding Tubes on Cancer-Specific Survival in Head and Neck Cancer.

Critical weight loss (CWL) continues to be a major issue in head and neck cancer (HNC) and many patients require tube feeding. We investigated the use of reactive feeding tubes (RFTs), associated CWL, and the impact on cancer-specific survival (CSS). A single-institution, retrospective audit was conducted on 460 adult HNC patients who received radiotherapy ± chemotherapy between 2005 and 2017. CSS in patients with CWL and RFTs was compared to those with no tube. Prediction analysis for RFT insertion was also performed. CWL occurred in 53% of patients, and in 88% of those with a RFT (p < 0.001). In patients with CWL, those with a RFT had worse 5 and 10-year CSS compared to those with no tube (68% and 65% vs 83% and 80% respectively, p = 0.040) in multivariate Cox regression analysis. Concurrent chemoradiotherapy combined with CWL was the strongest predictor for RFT insertion (p = 0.003). CWL, combined with having a RFT, impacts negatively on CSS. CWL may be one of the triggers for RFT insertion, however those with no tube have better CSS. This may be due to higher weight loss levels seen in those who have a RFT, and earlier insertion to prevent such losses seems indicated.

Critical Weight Loss in Patients With Oropharynx Cancer During Radiotherapy (± Chemotherapy).

Critical weight loss (CWL) defined as ≥5% in one month, is common in patients with oropharynx cancer and identification of patients at risk is challenging. We aimed to investigate if predictors of CWL in this population exist to guide nutritional intervention. Data were collected retrospectively on 134 patients who had radiotherapy (RT) ± concurrent chemotherapy (CRT) ± surgery. Body weights were collected pre-RT and during RT, with percentage weight change measured against baseline. Logistic regression was used to analyze chosen predictors. The incidence of CWL was 67% (26% of these patients experiencing ≥10% loss). Patients who had CRT experienced significantly higher weight loss (7.1% versus 4.7%; p = 0.001). Tube feeding was used in 64% of patients with CWL, the majority of tubes inserted reactively. These patients had a mean weight change of -8.8% (versus -7.1% in those with no tube) (p = 0.004). Multivariate models identified increased risk of CWL in tonsil origin tumors (p < 0.05), with CRT being the only predictor of weight loss ≥10% (p < 0.05). These patients are particularly vulnerable to CWL and the majority experience significant nutritional issues during RT, regardless of nutritional status at diagnosis. Nutritional intervention should be targeted accordingly.

Clinical predictors for reactive tube feeding in patients with advanced oropharynx cancer receiving radiotherapy ± chemotherapy.

Enteral feeding is often required for nutrition support in head and neck cancer patients when oral intake is inadequate. When to initiate the insertion of a feeding tube continues to be a debated issue in our institution. We investigated the use of reactive feeding tubes (RFTs) in patients with advanced stage oropharynx cancer (OPC). Data were retrospectively collected on 131 patients who had radiotherapy (RT) ± chemotherapy from 2005 to 2015. Predictors for RFT insertion were investigated. Weight loss during RT was compared between those with RFT versus prophylactic tubes (PFTs) versus no tube, and survival outcomes evaluated. RFTs were more likely to be needed in patients who had bilateral neck node irradiation (p = 0.001) and concurrent chemoradiotherapy (CRT) (p = 0.038). Patients with RFTs had significantly higher mean percentage weight loss during RT (9.5 ± 3.4%) (p < 0.001) when compared to those with a PFT (5.2 ± 4.7%) and those with no tube (5.4 ± 3.1%). No difference was seen in 5-year survival rates in patients who did not have a feeding tube to those who required a RFT. RFT use is frequent in OPC, although difficult to predict. CRT and bilateral neck node irradiation were found to be associated with the need for the insertion of a feeding tube during RT. These patients also experience significantly higher weight loss, therefore, prophylactic tubes may need to be considered more often in this population.

The use of the second thoracic vertebral landmark for skeletal muscle assessment and computed tomography-defined sarcopenia evaluation in patients with head and neck cancer.

BACKGROUND: The cross-sectional area (CSA) of skeletal muscle (SM) at the third lumbar vertebra (L3) is used to determine computed tomography (CT)-defined sarcopenia. We investigated the feasibility of SM assessment at the second thoracic vertebra (T2) in patients with head and neck cancer (HNC). METHODS: Diagnostic PET-CT scans were used to develop a prediction model for L3-CSA using T2-CSA. Effectiveness of the model and cancer-specific survival (CSS) were investigated. RESULTS: Scans of 111 patients (85% male) were evaluated. The predictive formula: L3-CSA (cm2 ) = 174.15 + [0.212 × T2-CSA (cm2 )] - [40.032 × sex] - [0.928 × age (years)] + [0.285 × weight (kg)] had good correlation r = 0.796, ICC = 0.882 (p < 0.001). SM index (SMI) mean difference (bias) was -3.6% (SD 10.2, 95% CI -8.7% to 1.3%). Sensitivity (82.8%), specificity (78.2%), with moderate agreement (ƙ = 0.540, p < 0.001). Worse 5-year CSS with lower quartile T2-SMI (51%, p = 0.003). CONCLUSIONS: SM at T2 can be effectively used for CT-defined sarcopenia evaluation in HNC.

The effectiveness of skeletal muscle evaluation at the third cervical vertebral level for computed tomography-defined sarcopenia assessment in patients with head and neck cancer.

BACKGROUND: Computed tomography (CT)-defined sarcopenia is a prognostic indicator in head and neck cancer (HNC), with the gold standard for muscle evaluation using cross-sectional area (CSA) at the third lumbar vertebra (L3). We compared methods using CSA at the third cervical vertebra (C3). METHODS: Muscle CSA was measured at L3, and CSA at C3 was used to estimate L3 CSA using a prediction model. Agreement and sarcopenia diagnosis were evaluated. RESULTS: Good correlation was found between measured and estimated CSA (101 scans; r = 0.86, p < 0.001). CSA mean difference (bias) 9.99 cm2 , (SD = 20.3 cm2 ). Skeletal muscle index bias 5.85% (SD = 13.4%), 95% limits of agreement (LoA) (-20.4 to 32.1%, r = 0.29), exceeded clinically accepted limits of 5%. Sarcopenia was diagnosed in 26%-(L3), 45%-(C3), with weak agreement (ƙ = 0.368, 95% confidence interval, 0.192-0.544, p < 0.001) (sensitivity 79.2%, specificity 66.7%). CONCLUSION: Agreement between measures was weak. Widespread LoA, proportional bias, and sarcopenia misclassification indicates that estimates using C3 cannot replace actual measures at L3.

The impact of HPV status on weight loss and feeding tube use in oropharyngeal carcinoma.

OBJECTIVES: It has been well established that patients with oropharyngeal carcinoma are at high nutritional risk, with significant weight loss and tube feeding common. Human papillomavirus (HPV)-associated disease has led to a change in the "typical" presentation and nutritional profile of this population. The aim of our study was to determine whether the need for a feeding tube, and weight loss during radiotherapy (RT) in patients with oropharyngeal carcinoma differed with HPV status. MATERIALS AND METHODS: Patients who received curative RT ±â€¯chemotherapy from January 2011 to January 2016 were included (n = 100). We retrospectively evaluated feeding tube use and timing of insertion (prophylactic vs reactive), percentage weight loss during RT and the prevalence of critical weight loss (CWL) ≥5%. RESULTS: HPV-positive patients had significantly higher weight loss during RT compared to the rest of the cohort (8.4% vs 6.1%, 95%CI 0.8-3.9, p = 0.003). CWL was observed in 86% and in a higher proportion with HPV-positive disease (93%, p = 0.011). Conditional probability modelling analysis revealed, with 74% accuracy, concurrent chemoradiotherapy and HPV-positive status were predictors of CWL when comparing HPV-positive patients to HPV-negative (96%, p = 0.001 and 98%, p = 0.012 respectively). More HPV-positive patients required feeding tubes (n = 43, 63%, p = 0.05), most being reactive (n = 27, 63%). All patients with reactive tubes experienced CWL. CONCLUSION: The high incidence of CWL in patients with HPV-positive oropharyngeal carcinoma is of concern. Tube feeding continues to be a necessary nutritional intervention in this population and predicting who will require a tube is challenging. Larger, prospective cohort studies are required.