Beyond sarcopenia: Characterization and integration of skeletal muscle quantity and radiodensity in a curable breast cancer population

Weinberg, Marc S.; Shachar, Shlomit Strulov; Muss, Hyman B.; Deal, Allison M.; Popuri, Karteek; Yu, Hyeon; Nyrop, Kirsten A.; Alston, Shani; Williams, Grant R.

doi:10.1111/tbj.12952

Cited by 81 publications

(79 citation statements)

References 24 publications

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“…Skeletal muscle gauge is a recently devised metric that incorporates both SMD and SMI and has already been shown to be very useful in predicting treatment‐related toxicities . Shachar et al .…”

Section: Discussionmentioning

confidence: 99%

“…The cross‐sectional areas of skeletal muscle and TAT were normalized for the patients' heights to calculate the indexes (cm 2 /m 2 ) for skeletal muscle (SMI) and TAT (TATI). SMG was calculated by multiplying SMI by SMD (SMI × SMD) . The actual units for SMG are (cm 2 tissue × average HU)/(m 2 height); for simplicity, we present them as arbitrary units …”

Section: Methodsmentioning

confidence: 99%

“…SMG was calculated by multiplying SMI by SMD (SMI × SMD). 31 The actual units for SMG are (cm 2 tissue × average HU)/(m 2 height); for simplicity, we present them as arbitrary units. 32,33 Given that the body composition varies greatly with the type and stage of the cancer, geographical regions, and ethnicities, 57,58 we defined our own cut-off values for this cohort based on previous studies with similar population sizes.…”

Section: Computed Tomography-based Body Composition Analysismentioning

confidence: 99%

“…SMD is a radiological characteristic, and skeletal muscle with low SMD is suggestive of fatty infiltration of the skeletal muscle (myosteatosis) leading to poor ‘quality’ skeletal muscle . SMI and SMD are defined independent of the other, and both are demonstrated prognostic indicators for cancer outcomes; integrating the SMI and SMD into a novel measure of skeletal muscle gauge (SMG) could lead to a more unified reporting for body composition and disease outcomes . Recently, SMG was reported as a better predictor of chemotherapy toxicities than either SMI or SMD .…”

Section: Introductionmentioning

confidence: 99%

“…30 SMI and SMD are defined independent of the other, and both are demonstrated prognostic indicators for cancer outcomes; integrating the SMI and SMD into a novel measure of skeletal muscle gauge (SMG) could lead to a more unified reporting for body composition and disease outcomes. 31 Recently, SMG was reported as a better predictor of chemotherapy toxicities than either SMI or SMD. [32][33][34] Adipose tissue content, including subcutaneous and visceral adipose tissues, has also been associated with cancer outcomes and can be assessed on CT imaging.…”

Section: Introductionmentioning

confidence: 99%

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Muscle radiodensity loss during cancer therapy is predictive for poor survival in advanced endometrial cancer

Lee

Lin

et al. 2019

J cachexia sarcopenia muscle

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Background Treatment‐related toxicities and decreased levels of patient performance during cancer therapy might contribute to body composition changes and thereby impact outcomes. However, the effect of longitudinal body composition changes on outcomes in patients with advanced endometrial cancer is unknown. This study investigated the association between body composition changes during staging surgery and adjuvant chemoradiotherapy and outcomes in patients with stage III endometrial cancer. Methods Pretreatment and post‐treatment computed tomography (CT) images of 131 patients with stage III endometrial cancer who were treated between 2008 and 2016 were analysed. All CT images were contrast enhanced and acquired according to the standardized protocol. The skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), and total adipose tissue index were measured from two sets of CT images obtained at the level of the third lumbar vertebra. The skeletal muscle gauge was calculated by multiplying SMI by SMD (SMI × SMD). Predictors of overall survival and progression‐free survival were identified using Cox regression models. Results The median follow‐up was 50.6 (range 12.1–117.0) months. Overall, body mass index (BMI) changes during treatment were 0.4% per 210 days (95% confidence interval: −0.6 to 1.4; P = 0.41), and patients experienced an average SMD loss of 2.1% per 210 days (95% confidence interval: −4.0 to −0.2; P = 0.03). Weight loss and SMD loss ≥5% were observed in 23 (17.6%) and 54 (41.2%) patients, respectively. The changes in SMD did not correlate with those in BMI (Spearman's ρ for SMD, −0.13; P = 0.13). SMD change (per 1 Hounsfield unit/210 days decrease) was independently associated with poorer overall survival (hazard ratio: 1.32, 95% confidence interval: 1.14–1.52; P < 0.001) and progression‐free survival (hazard ratio: 1.28, 95% confidence interval: 1.12–1.43; P < 0.001). Our results did not show association between survival and pretreatment myosteatosis and sarcopenia or changes in SMI and total adipose tissue index during treatment. The pretreatment skeletal muscle gauge was associated with treatment modifications such as delays, dose reductions, and discontinuation of chemotherapy. Conclusions Skeletal muscle radiodensity decreased significantly during treatment and was independently associated with poorer survival in patients with stage III endometrial cancer who underwent staging surgery and adjuvant chemoradiotherapy. SMD loss was occult and occurred independently of BMI change.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Computed Tomography-based Body Composition Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Muscle radiodensity loss during cancer therapy is predictive for poor survival in advanced endometrial cancer

Lee

Lin

et al. 2019

J cachexia sarcopenia muscle

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Skeletal muscle gauge as a prognostic factor in patients with colorectal cancer

et al. 2021

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Background Although skeletal muscle index (SMI) and radiodensity (SMD) are well‐known prognostic factors, the clinical impact of the integrated measure, known as skeletal muscle gauge (SMG), has been limited in patients with colorectal cancer (CRC). Patients and Methods A total of 727 and 268 patients with CRC at two tertiary centers were included and allocated into the training and test sets, respectively. Preoperative slice computed tomography images of the third lumbar area were evaluated for SMI and SMD. SMG was calculated as SMI × SMD and expressed as an arbitrary unit (AU). The optimal cutoff SMG value was determined to maximize the overall survival (OS) difference between the groups with respect to sex in the training set. The multivariate Cox proportional hazard model evaluated the association of its clinical significance. Results With regard to SMG, 1640 and 1523 AU were identified as cutoff values for males and females, respectively. The patients with low SMG values showed significantly worse 5‐year OS than those with high SMG values in the two datasets (both p < 0.001). In the multivariate analysis, low SMG was identified as an independent poor prognostic factor of OS in the training set (hazard ratio 2.18, 95% confidence interval 1.43–3.32, p < 0.001) and test set (hazard ratio 1.79, 95% confidence interval 1.07–3.00, p = 0.025), whereas SMI and SMD were not. Conclusion SMG acts synergistically to improve its prognostic predictive accuracy as compared with SMI or SMD alone in patients with CRC. Additional research is warranted to define its significance in different ethnic groups.

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Percentile‐based averaging and skeletal muscle gauge improve body composition analysis: validation at multiple vertebral levels

Marquardt

Roeland

Seventer

et al. 2021

J cachexia sarcopenia muscle

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Background Skeletal muscle metrics on computed tomography (CT) correlate with clinical and patient-reported outcomes. We hypothesize that aggregating skeletal muscle measurements from multiple vertebral levels and skeletal muscle gauge (SMG) better predict outcomes than skeletal muscle radioattenuation (SMRA) or -index (SMI) at a single vertebral level. Methods We performed a secondary analysis of prospectively collected clinical (overall survival, hospital readmission, time to unplanned hospital readmission or death, and readmission or death within 90 days) and patient-reported outcomes (physical and psychological symptom burden captured as Edmonton Symptom Assessment Scale and Patient Health Questionnaire) of patients with advanced cancer who experienced an unplanned admission to Massachusetts General Hospital from 2014 to 2016. First, we assessed the correlation of skeletal muscle cross-sectional area, SMRA, SMI, and SMG at one or more of the following thoracic (T) or lumbar (L) vertebral levels: T5, T8, T10, and L3 on CT scans obtained ≤50 days before index assessment. Second, we aggregated measurements across all available vertebral levels using percentile-based averaging (PBA) to create the average percentile. Third, we constructed one regression model adjusted for age, sex, sociodemographic factors, cancer type, body mass index, and intravenous contrast for each combination of (i) vertebral level and average percentile, (ii) muscle metrics (SMRA, SMI, & SMG), and (iii) clinical and patient-reported outcomes. Fourth, we compared the performance of vertebral levels and muscle metrics by ranking otherwise identical models by concordance statistic, number of included patients, coefficient of determination, and significance of muscle metric. ResultsWe included 846 patients (mean age: 63.5 ± 12.9 years, 50.5% males) with advanced cancer [predominantly gastrointestinal (32.9%) or lung (18.9%)]. The correlation of muscle measurements between vertebral levels ranged from 0.71 to 0.84 for SMRA and 0.67 to 0.81 for SMI. The correlation of individual levels with the average percentile was 0.90-0.93 for SMRA and 0.86-0.92 for SMI. The intrapatient correlation of SMRA with SMI was 0.21-0.40. PBA allowed for inclusion of 8-47% more patients than any single-level analysis. PBA outperformed single-level analyses across all comparisons with average ranks 2.6, 2.9, and 1.6 for concordance statistic, coefficient of determination, and significance (range 1-5, μ = 3), respectively. On average, SMG outperformed SMRA and SMI across outcomes and vertebral levels: the average rank of SMG was 1.4, 1.4, and 1.4 for concordance statistic, coefficient of determination, and significance (range 1-3, μ = 2), respectively. Conclusions Multivertebral level skeletal muscle analyses using PBA and SMG independently and additively outperform analyses using individual levels and SMRA or SMI.

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Beyond sarcopenia: Characterization and integration of skeletal muscle quantity and radiodensity in a curable breast cancer population

Cited by 81 publications

References 24 publications

Muscle radiodensity loss during cancer therapy is predictive for poor survival in advanced endometrial cancer

Muscle radiodensity loss during cancer therapy is predictive for poor survival in advanced endometrial cancer

Skeletal muscle gauge as a prognostic factor in patients with colorectal cancer

Percentile‐based averaging and skeletal muscle gauge improve body composition analysis: validation at multiple vertebral levels

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