Skeletal Muscle Cross-sectional Area Research Articles

Blood flow restriction Exercise in the perioperative setting to Prevent loss of muscle mass in patients with pancreatic, biliary tract, and liver cancer: study protocol for the PREV-Ex randomized controlled trial

BackgroundPatients diagnosed with pancreatic, biliary tract, and liver cancer often suffer from a progressive loss of muscle mass. Given the considerable functional impairments in these patients, high musculoskeletal weight loads may not be well tolerated by all individuals. The use of blood-flow restricted resistance training (BFR-T) which only requires low training loads may allow for a faster recovery of muscle due to avoidance of high levels of mechanical muscle stress associated with high-load resistance exercise. This study aims to investigate whether BFR-T can prevent or slow down the loss of skeletal muscle mass and enhance the functional capacity and mental health of patients with pancreatic, biliary tract, and liver cancer.MethodsThe PREV-Ex exercise trial is a multicenter two-armed randomized controlled trial. Patients will be randomized to an exercise program consisting of home-based low-load BFR-T during a combined pre- and postoperative period for a total of 6–10 weeks (prehabilitation and rehabilitation), or to a control group. Protein supplementation will be given to both groups to ensure adequate protein intake. The primary outcomes, skeletal muscle thickness and muscle cross-sectional area, will be assessed by ultrasound. Secondary outcomes include the following: (i) muscle catabolism-related and inflammatory bio-markers (molecular characteristics will be assessed from a vastus lateralis biopsy and blood samples will be obtained from a sub-sample of patients); (ii) patient-reported outcome measures (self-reported fatigue, health-related quality of life, and nutritional status will be assessed through validated questionnaires); (iii) physical fitness/performance/activity (validated tests will be used to evaluate physical function, cardiorespiratory fitness and maximal isometric muscle strength. Physical activity and sedentary behavior (assessed using an activity monitor); (iv) clinical outcomes: hospitalization rates and blood status will be recorded from the patients’ medical records; (v) explorative outcomes of patients’ experience of the exercise program which will be evaluated using focus group/individual interviews.DiscussionIt is worthwhile to investigate new strategies that have the potential to counteract the deterioration of skeletal muscle mass, muscle function, strength, and physical function, all of which have debilitating consequences for patients with pancreatic, biliary tract, and liver cancer. The expected findings could improve prognosis, help patients stay independent for longer, and possibly reduce treatment-related costs.Trial registrationClinicalTrials.gov NCT05044065. Registered on September 14, 2021.

Body composition measures as a determinant of alpelisib-related toxicity.

e13093 Background: Body composition has emerged as an important prognostic factor in patients treated with cancer. Severe depletion of skeletal muscle, sarcopenia, has been associated with poor performance status and worse oncological outcomes. We studied patients with metastatic breast cancer receiving alpelisib, to determine if sarcopenia and additional body composition measures accounting for muscle and adiposity are associated with toxicity. Methods: A retrospective observational analysis was conducted, including 38 women with metastatic breast cancer and a PIK3CA mutation, treated with alpelisib as advanced line of therapy. Sarcopenia was determined by measuring skeletal muscle cross-sectional area at the third lumbar vertebra using computerized tomography. Various body composition metrics were assessed along with drug toxicity, dose reductions, treatment discontinuation, and hospitalizations. Results: Sarcopenia was observed in half of the patients (n=19, 50%), spanning normal weight, overweight, and obese individuals. Among the body composition measures, lower skeletal muscle density (SMD) was associated with an increased risk of treatment-related hyperglycaemia (P=0.03). Additionally, lower visceral adipose tissue (VAT) was associated with alpelisib-induced rash (P=0.04) and hospitalizations (P=0.04). Notably, alpelisib treatment discontinuation was not impacted by alpelisib toxicity. Conclusions: Body composition measures, specifically SMD and VAT may provide an opportunity to identify patients at higher risk for severe alpelisib related hyperglycemia, and cutaneous toxicity. These findings suggest the potential use of body composition assessment to predict toxicity, allowing for personalized therapeutic observation and intervention.

A randomized controlled intervention trial to study the effect of a personalized lifestyle program on cancer-related fatigue among colorectal cancer survivors: protocol for the SoFiT study.

Observational studies suggest that a healthy diet in combination with ample physical activity is associated with a lower prevalence of cancer-related fatigue. The SoFiT trial (SoFiT: Study on Fatigue: a lifestyle intervention among colorectal cancer survivors) will assess the effect of a personalized lifestyle program on cancer-related fatigue in a randomised study.We designed a program that aims to increase adherence to lifestyle recommendations on diet and physical activity. The program was person-centred with regards to the lifestyle and personal characteristics of participants, to the determinants of behaviour of that participant, and to the preference, opportunities, and barriers of the participant.The effect of the program was tested in the SoFiT trial: a two-armed, parallel, randomized controlled trial among adult stage I-III colorectal cancer survivors, who experience cancer-related fatigue after treatment completion; intended sample size n=184. Participants randomized to the intervention group received the personalized lifestyle program. During six months, participants in the intervention group had individual sessions with a lifestyle coach of which four sessions were face-to-face and eight sessions were remote. After six months, participants randomized to the control group had access to two lifestyle coaching sessions and to the same materials that the intervention group also received.The primary endpoint of the trial is cancer-related fatigue. Secondary endpoints are: sleep quality and duration, health-related quality of life, physical performance, depression and anxiety, skeletal muscle echo intensity and cross-sectional area, and gut microbiota composition.This trial will show the effects of a personalized lifestyle program on cancer-related fatigue, and on an extensive set of secondary outcomes.

#2439 The association between vitamin D deficiency and sarcopenia in patients with pre-dialysis CKD

Abstract Background and Aims Sarcopenia is characterized by a progressive and widespread loss of skeletal muscle, leading to muscle weakness and frailty. While primary sarcopenia is linked to aging, secondary sarcopenia can independently occur, especially in chronic conditions like chronic kidney disease (CKD). Investigating sarcopenia in CKD patients has become a focal point in research due to its significant impact on the quality of life, morbidity, and mortality of these individuals. Despite reports connecting vitamin D deficiency, prevalent in CKD, to sarcopenia in the general population, there is limited information regarding the specific relationship between vitamin D and sarcopenia in CKD. This study aims to explore the association between vitamin D deficiency and sarcopenia in patients with pre-dialysis CKD. Method This cross-sectional study enrolled 569 patients with pre-dialysis chronic kidney disease (CKD), defined as having an estimated glomerular filtration rate (eGFR) less than 60 ml/min/m2. Sarcopenia was assessed using computed tomography (CT)-derived skeletal muscle index (SMI), calculated based on the cross-sectional area of skeletal muscles at the 3rd lumbar vertebra. Using Korean-specific SMI cutoffs, patients were categorized into sarcopenic and non-sarcopenic groups. Logistic regression analyses were employed to explore associations between sarcopenia and baseline variables, including active vitamin D, specifically 1,25-dihydroxyvitamin D [1,25(OH)2D] level. Results Among the 569 patients, 278 had CKD stage 3, 198 had CKD stage 4, and 93 had CKD stage 5. The prevalence of sarcopenia increased with advancing CKD stage (CKD stage 3 vs. stage 4 vs. stage 5: 20.1% vs. 31.3% vs. 41.9%, P < 0.001). Univariate logistic regression analysis revealed an association between 1,25(OH)2D levels and sarcopenia. Additionally, age, male sex, diabetes, body mass index, eGFR, urinary albumin excretion levels, and serum levels of albumin, high-sensitive C-reactive protein (hsCRP), and intact parathyroid hormone were associated with sarcopenia. In multivariable logistic regression analysis, 1,25(OH)2D levels remained independently associated with sarcopenia (per 1 pg/dl increase, odds ratio [OR]: 0.84; 95% confidence interval [CI]: 0.80–0.87, P < 0.001). Age (per 1 year increase, OR: 1.04, 95% CI: 1.02–1.07, P < 0.001), diabetes (vs. non-diabetes, OR: 2.33, 95% CI: 1.39–3.89, P = 0.001), serum albumin (per 1 mg/dl increase, OR: 0.39, 95% CI: 0.22–0.71, P = 0.0023), and hsCRP (per 1 mg/dl increase, OR: 1.91, 95% CI: 1.25–2.92, P = 0.003) were also independently associated with sarcopenia. Conclusion This study revealed an independent association between 1,25(OH)2D levels and sarcopenia derived from CT scans in pre-dialysis CKD patients. This association retained significance even after adjusting for traditional risk factors for sarcopenia, such as age, diabetes, serum albumin, and hsCRP. Further prospective studies are necessary to determine whether therapy with exogenous 1,25(OH)2D drugs can improve sarcopenia in these patients.

Sarcopenia is independently associated with mortality and recovery from dialysis in critically ill patients with sepsis-induced acute kidney injury receiving continuous renal replacement therapy.

Sarcopenia upon admission to the intensive care unit (ICU) consistently correlates with adverse outcomes, including heightened mortality, in critically ill patients. This study aims to investigate the independent association of sarcopenia with both mortality and recovery from dialysis in critically ill patients with sepsis-induced acute kidney injury (SIAKI) undergoing continuous renal replacement therapy (CRRT). This retrospective study included 618 patients with SIAKI who underwent CRRT in our ICU. All patients had abdominal computed tomography (CT) scans within 3 days preceding ICU admission. The cross-sectional area of skeletal muscles at the third lumbar vertebra was quantified, and the skeletal muscle index (SMI), a normalized measure of skeletal muscle mass, was computed. Using Korean-specific SMI cutoffs, patients were categorized into sarcopenic and non-sarcopenic groups. Among the 618 patients, 301 expired within 28 days of ICU admission. Multivariable Cox regression analysis revealed that sarcopenia independently predicted 28-day mortality. Among survivors, sarcopenia was independently associated with recovery from dialysis within 28 days after ICU admission. Kaplan-Meier analysis illustrated that sarcopenic patients had a higher mortality rate and a lower rate of recovery from dialysis within 28 days after ICU admission compared to non-sarcopenic patients. This study underscores the independent association of sarcopenia, assessed via CT-derived SMI, with both mortality and recovery from dialysis in critically ill patients with SIAKI undergoing CRRT. The inclusion of sarcopenia assessment could serve as a valuable tool for physicians in effectively stratifying the risk of adverse outcomes in these patients.

Peripheral quantitative computed tomography is a valid imaging technique for tracking changes in skeletal muscle cross-sectional area.

Peripheral quantitative computed tomography (pQCT) has recently expanded to quantifying skeletal muscle, however its validity to determine muscle cross-sectional area (mCSA) compared to magnetic resonance imaging (MRI) is unknown. Eleven male participants (age: 22 ± 3 y) underwent pQCT and MRI dual-leg mid-thigh imaging before (PRE) and after (POST) 6 weeks of resistance training for quantification of mid-thigh mCSA and change in mCSA. mCSA agreement at both time points and absolute change in mCSA across time was assessed using Bland-Altman plots for mean bias and 95% limits of agreement (LOA), as well as Lin's concordance correlation coefficients (CCC). Both pQCT and MRI mCSA increased following 6 weeks of resistance training (∆mCSApQCT: 6.7 ± 5.4 cm2, p < 0.001; ∆mCSAMRI: 6.0 ± 6.4 cm2, p < 0.001). Importantly, the change in mCSA was not different between methods (p = 0.39). Bland-Altman analysis revealed a small mean bias (1.10 cm2, LOA: -6.09, 8.29 cm2) where pQCT tended to overestimate mCSA relative to MRI when comparing images at a single time point. Concordance between pQCT and MRI mCSA at PRE and POST was excellent yielding a CCC of 0.982. For detecting changes in mCSA, Bland-Altman analysis revealed excellent agreement between pQCT and MRI (mean bias: -0.73 cm2, LOA: -8.37, 6.91 cm2). Finally, there was excellent concordance between pQCT and MRI mCSA change scores (CCC = 0.779). Relative to MRI, pQCT imaging is a valid technique for measuring both mid-thigh mCSA at a single time point and mCSA changes following a resistance training intervention.

Impact of cachexia on disease recurrence and survival outcomes in endometrial cancer patients

ObjectiveCancer cachexia is progressive weight loss due to muscle/adipose tissue wasting and inadequate intake that occurs in response to malignancy. It is an independent predictor of disease recurrence and reduced survival in several cancers. However, cachexia’s relationship with gynecologic malignancy outcomes has only been examined in small studies with limited follow-up and inconsistent definitions of cachexia. This study investigated the impact of cachexia on disease recurrence and overall survival in high-risk endometrial carcinoma patients. MethodsThis retrospective cohort study examined data from patients with high-risk non-metastatic primary endometrial carcinoma treated at a single institution from 2015 to 2020. Treatment for all subjects included total hysterectomy, surgical staging, pelvic external beam radiotherapy with or without adjuvant chemotherapy. Radiation planning CT datasets were used to measure skeletal musculature at the L3 vertebral level. Skeletal muscle index (SMI) was defined as total L3 skeletal muscle cross sectional area (cm2)/height2 (m2), and cachexia was defined based on SMI. Results55 patients were eligible for analysis. Several SMI thresholds were used to define cachexia, and analysis was performed for each definition. Kaplan-Meier and Cox-proportional hazards regression analysis yielded no significant reduction in overall survival (OS) or progression-free survival (PFS) in patients with cachexia, regardless of threshold chosen. However, 4 of 13 definitions of cachexia showed significantly improved OS in patients without cachexia, relative to those with cachexia. There were no significant differences in disease recurrence. ConclusionsCachexia as defined in this study was not associated with poor outcomes in endometrial carcinoma patients based on OS, PFS, or disease recurrence.

Body composition measures as a determinant of Alpelisib related toxicity

BackgroundBody composition has emerged as an important prognostic factor in patients treated with cancer. Severe depletion of skeletal muscle, sarcopenia, has been associated with poor performance status and worse oncological outcomes. We studied patients with metastatic breast cancer receiving alpelisib, to determine if sarcopenia and additional body composition measures accounting for muscle and adiposity are associated with toxicity.MethodsA retrospective observational analysis was conducted, including 38 women with metastatic breast cancer and a PIK3CA mutation, treated with alpelisib as advanced line of therapy. Sarcopenia was determined by measuring skeletal muscle cross-sectional area at the third lumbar vertebra using computerized tomography. Various body composition metrics were assessed along with drug toxicity, dose reductions, treatment discontinuation, hospitalizations, time to treatment failure and overall survival.ResultsSarcopenia was observed in half of the patients (n = 19, 50%), spanning normal weight, overweight, and obese individuals. Among the body composition measures, lower skeletal muscle density (SMD) was associated with an increased risk of treatment-related hyperglycaemia (P = 0.03). Additionally, lower visceral adipose tissue (VAT) was associated with alpelisib-induced rash (P = 0.04) and hospitalizations (P = 0.04). Notably, alpelisib treatment discontinuation was not impacted by alpelisib toxicity.ConclusionBody composition measures, specifically SMD and VAT may provide an opportunity to identify patients at higher risk for severe alpelisib related hyperglycemia, and cutaneous toxicity. These findings suggest the potential use of body composition assessment to caution toxicity risk, allowing for personalized therapeutic observation and intervention.

One-leg standing time is a simple measure for loss of skeletal muscle mass and fat deposition in muscle: the J-SHIPP study

BackgroundsOne-leg standing time (OLST) has been frequently used physical performance measure; however, what muscular characteristics OLST represents remains uncertain.AimThis cross-sectional study aimed to investigate the association between OLST and muscle characteristics to clarify the possibility of using OLST as a physical performance measure.MethodsStudy participants comprised 1144 older adults aged 65 years or older. Computed tomography images provided mid-thigh skeletal muscle cross-sectional area and mean attenuation value. OLST was measured for a maximum of 60 s. Static postural instability was assessed using a posturography.ResultsA frequency of OLST < 20 s was increased by quartiles of muscle cross-sectional area (Q1: 33.6, Q2: 12.8, Q3: 13.6, Q4: 11.9%, P < 0.001) and mean attenuation value (Q1: 32.3, Q2: 21.7, Q3: 14.3, Q4: 7.7%, P < 0.001). Results of the multinomial regression analysis indicated that muscle cross-sectional area and mean attenuation value were independently associated with an OLST of less than 20 s. The crude odds ratio of OLST less than 20 s for the lowest quartiles of both cross-sectional area and mean attenuation value was 4.19 (95% CI: 3.01 − 5.84). The cross-sectional area of muscles with greater fat deposition was inversely associated with OLST, while that with smaller fat deposition showed a positive association with OLST, indicating why mean attenuation value and cross-sectional area were independently associated with OLST. No clear relationship was observed with static postural instability.ConclusionOLST was a simply measurable quantifiable physical measure representing the loss of muscle mass and quality in older adults.

Comparison of bioelectrical impedance analysis and computed tomography for the assessment of muscle mass in patients with gastric cancer

BackgroundLow muscle mass was significantly correlated with poor clinical outcomes in cancer patients. This study aimed to compare the differences between bioelectrical impedance analysis (BIA) and computed tomography (CT) in measuring skeletal muscle mass and detecting low muscle mass in patients with gastric cancer (GC). MethodThis cross-sectional study included a total of 302 consecutive patients diagnosed with GC at our institution from October 2021 to March 2023. CT images were analyzed at the L3 level to obtain the cross-sectional area of skeletal muscle, which was subsequently used for calculating whole-body skeletal muscle mass via the Shen equation and skeletal muscle tissue density. BIA was utilized to measure skeletal muscle mass using the manufacturer's proprietary algorithms. Skeletal muscle mass (kg) was divided by height squared (m2) to obtain skeletal muscle index (SMI, kg/m2). Pearson's correlation coefficient was performed to assess the correlation between SMI measured by BIA and CT. The agreement between the two methods was assessed using Bland-Altman analyses. The clinically acceptable agreement was defined as the 95% limits of agreement (LOA) for the percentage bias falling within ± 10%. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of BIA in identifying low muscle mass. ResultsA total of 59 patients (19.5%) were identified as having low muscle mass based on CT analysis, whereas only 19 patients (6.3%) met the criteria for low muscle mass according to BIA analysis. BIA-measured SMI showed a strong positive correlation with CT-measured SMI in all patients (r = 0.715, P < 0.001). With Bland-Altman analysis, there was a significant mean bias of 1.18 ± 0.96 kg/m2 (95% CI 1.07–1.29, P < 0.001) between SMI measured by BIA and CT. The 95% LOA for the percentage bias ranged from -7.98 to 33.92%, which exceeded the clinically acceptable range of ± 10%. A significant difference was observed in the mean bias of SMI measured by BIA and CT between patients with and without GLIM malnutrition (1.42 ± 0.91 kg/m2 versus 0.98 ± 0.96 kg/m2, P < 0.001). The cut-off values for BIA-measured SMI in identifying low muscle mass using CT as the reference were 10.11 kg/m2 for males and 8.71 kg/m2 for females (male: AUC = 0.840, 95% CI: 0.772–0.908; female: AUC = 0.721, 95% CI: 0.598–0.843). ConclusionsDespite a significant correlation, the values of skeletal muscle mass obtained BIA and CT cannot be used interchangeably. The BIA method may overestimate skeletal muscle mass in GC patients compared to CT, especially among those with GLIM malnutrition, leading to an underestimation of low muscle mass prevalence.

Computed tomography evaluation of skeletal muscle quality and quantity in people with morbid obesity with and without metabolic abnormality.

We investigated the differences in quantity and quality of skeletal muscle between metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) individuals using abdominal CT. One hundred and seventy-two people with morbid obesity who underwent bariatric surgery and 64 healthy control individuals participated in this retrospective study. We divided the people with morbid obesity into an MHO and MUO group. In addition, nonobese metabolic healthy people were included analysis to provide reference levels. CT evaluation of muscle quantity (at the level of the third lumbar vertebra [L3]) was performed by calculating muscle anatomical cross-sectional area (CSA), which was normalized to patient height to produce skeletal muscle index (SMI). Muscle quality was assessed as skeletal muscle density (SMD), which was calculated from CT muscle attenuation. To characterize intramuscular composition, muscle attenuation was classified into three categories using Hounsfield unit (HU) thresholds: -190 HU to -30 HU for intermuscular adipose tissue (IMAT), -29 to +29 HU for low attenuation muscle (LAM), and +30 to +150 HU for normal attenuation muscle (NAM). People with morbid obesity comprised 24 (14%) MHO individuals and 148 (86%) MUO individuals. The mean age of the participants was 39.7 ± 12.5 years, and 154 (65%) participants were women. MUO individuals had a significantly greater total skeletal muscle CSA than MHO individuals in the model that adjusted for all variables. Total skeletal muscle SMI, SMD, NAM index, LAM index, and IMAT index did not differ between MHO and MUO individuals for all adjusted models. Total skeletal muscle at the L3 level was not different in muscle quantity, quality, or intramuscular composition between the MHO and MUO individuals, based on CT evaluation. MHO individuals who are considered "healthy" should be carefully monitored and can have a similar risk of metabolic complications as MUO individuals, at least based on an assessment of skeletal muscle.

CT sarcometry in the prediction of postoperative complications in patients with gastric cancer: Retrospective cohort study

Aim. Computed tomographic preoperative assessment of sarcopenia in patients with gastric cancer as a part of combined treatment and the study of the relationship between sarcopenia and postoperative complications.&#x0D; Materials and methods. We analyzed retrospectively the data of 65 patients with morphologically verified diagnosis of stage IIA–IIIC gastric cancer. All patients at stage I of the combined treatment received neoadjuvant chemotherapy (NCT) according to the FLOT regimen, and then a gastrectomy with D2 lymph node dissection was performed. Computed tomography (CT) scans were performed before NCT initiation and 3.5 to 5 weeks after NCT completion for preoperative staging and assessment of tumor response. Using the obtained CT data, CT sarcometry was performed by calculating the cross-sectional area of skeletal muscles at the LIII vertebra level and the “skeletal-muscular index”. Postoperative complications were assessed using the Clavien–Dindo classification. Non-parametric comparison methods were used to assess the significance of differences between groups and subgroups (Wilcoxon T-test, Pearson χ2 test). Differences were considered statistically significant at p0.05.&#x0D; Results. We analyzed the incidence of sarcopenia in the examined patients before the NCT and immediately before the surgery. Sarcopenia was noted in 41 (63.1%) of 65 patients before NCT and in 50 (76.9%) patients after NCT, which indicates its high prevalence in patients with stomach cancer and the adverse effect of NCT on the muscular status of patients (76.9% versus 63.1%). Postoperative complications were diagnosed in 12 of 65 patients (18.5%). The rate of postoperative complications in patients with and without sarcopenia was not statistically significantly different (p=0.392); however, complications of Clavien–Dindo grade ≥IIIb occurred only in patients with sarcopenia (p0.001).&#x0D; Conclusion. According to our data, NCT in gastric cancer aggravates preoperative nutritional disorders. CT, as a standard method of staging and assessing the tumor response to NCT for gastric cancer, provides a tool to assess the state of muscle mass in patients before and after NCT. Preoperative sarcopenia is a risk factor for severe postoperative complications in patients with gastric cancer after gastrectomy.

Is assessment of skeletal muscle mass useful to predict time-to-awake in awake craniotomies?

Awake craniotomy is the gold standard for the resection of brain lesions near eloquent areas. For the commonly used asleep-awake-asleep technique, the patient must be awake and fully cooperative as soon as possible after discontinuation of anesthetics. A shorter emergence time is essential to decrease the likelihood of adverse events. Previous research found no relationship between body mass index (BMI) and time-to-awake for intravenous anesthesia with propofol, which is a lipophilic agent. As BMI cannot differentiate between fat and muscle tissue, we hypothesize that skeletal muscle mass, particularly when combined with BMI, may better predict time-to-awake from propofol sedation. We aimed to evaluate the relationship between skeletal muscle mass and the time-to-awake in patients undergoing awake craniotomy, as well as the interaction between skeletal muscle mass and BMI. In 260 patients undergoing an awake craniotomy, we used preoperative magnetic resonance imaging to assess temporalis muscle and cross-sectional skeletal muscle area of the masseter muscles and at level of the third cervical vertebra. Time-to-awake was dichotomized as ≤20 and >20 minutes. No association between various measures of skeletal muscle mass and time-to-awake was observed, and no interaction between skeletal muscle mass and BMI was found (all P > .05). Likewise, patients with a high BMI and low skeletal muscle mass (indicating an increased proportion of fat tissue) did not have a prolonged time-to-awake. Skeletal muscle mass did not predict time-to-awake in patients undergoing awake craniotomy, neither in isolation nor in combination with a high BMI.

Prognostic significance of body mass index in small-cell lung cancer: Exploring the relationship with skeletal muscle status.

We investigated the prognostic significance of body mass index in small-cell lung cancer and explored whether skeletal muscle status affects the body mass index-survival relationship. This retrospective study evaluated data from patients who underwent platinum-etoposide chemotherapy for small-cell lung cancer between March 2010 and December 2021. Skeletal muscle status was assessed using non-contrast computed tomography images of baseline positron-emission tomography-computed tomography, with the skeletal muscle index defined as the cross-sectional area of skeletal muscle divided by height squared, and the average attenuation values of skeletal muscle. Cox proportional hazards regression analysis was used to determine the correlations of body mass index, skeletal muscle metrics, and overall survival. We analysed the data of 1146 Asian patients (1006 men and 140 women, with a median age of 67years [interquartile range: 61-72years]), including 507 and 639 patients with limited and extensive disease, respectively. Being underweight, defined as a body mass index <18.5kg/m2 , was associated with shorter overall survival, independent of clinical covariates in both the limited-disease (hazard ratio, 1.77; 95% confidence interval, 1.01-3.09) and extensive-disease (hazard ratio, 1.71; 95% confidence interval, 1.18-2.48) groups. The prognostic value of being underweight remained significant after additional adjustment for skeletal muscle index and attenuation in both limited-disease (hazard ratio, 1.96; 95% confidence interval, 1.09-3.51) and extensive-disease (hazard ratio, 1.75; 95% confidence interval, 1.17-2.61) groups. Being underweight is an independent poor prognostic factor for shorter overall survival in Asian patients with small-cell lung cancer, regardless of skeletal muscle status.

Relationship of Sarcopenia to Tolerance of Chemotherapy During Definitive Treatment of Primary Anal Squamous Cell Carcinoma

Primary therapy for anal squamous cell carcinoma consists of definitive radiation with concurrent chemotherapy, most commonly 5-fluorouracil and mitomycin-C. This regimen is associated with significant cutaneous, hematologic, and gastrointestinal toxicity. Sarcopenia, or low skeletal muscle mass, has been described as an adverse prognostic factor and predictor of poor tolerance to therapy across a range of malignancies, including breast, gynecologic and head and neck cancers. Here, we sought to determine if the presence of sarcopenia at the initiation of therapy is associated with increased rates of toxicity and poorer tolerance of definitive treatment for primary anal squamous cell carcinoma. This was a review of patients treated with curative intent for anal squamous cell carcinoma at a single academic medical center between 2007 and 2017, median follow up was 38 months. Analysis was limited to patients receiving definitive radiation with concurrent chemotherapy. Sarcopenia was objectively defined, using previously validated methods, as a skeletal muscle index (SMI) <41 cm2/m2 for female patients regardless of body mass index (BMI); for male patients sarcopenia was defined as SMI<43cm2/m2 for BMI<25 and <53 cm2/m2 for BMI >25. SMI calculations were performed using the average skeletal muscle cross sectional areas of two sequential axial CT slices at the L3 vertebral level obtained from radiation planning computed tomography scans. The image analysis was performed by a single trained observer using Sliceomatic software with a Hounsfield unit threshold of -29 to 150 to define skeletal muscle. Sarcopenia as a predictor for treatment toxicity was analyzed using Chi-Square testing. Overall survival and progression free survival were compared with 2-sample t tests. Sixty-one patients were included in the analysis with 49% meeting criteria for sarcopenia. Stage did not differ although sarcopenic patients were significantly more elderly than those without sarcopenia (mean 72 vs 58 years, p<0.001). Patients with sarcopenia were significantly more likely to have chemotherapy breaks, chemotherapy dose reductions, and incomplete chemotherapy courses compared to non-sarcopenic patients (33.3% vs 9.7%; p = 0.02). Sarcopenia was not predictive of more radiation treatment breaks, hematologic toxicity, progression free survival or overall survival. Sarcopenia is predictive of reduced tolerance to chemotherapy among patients receiving definitive combined modality therapy for primary anal carcinoma. We found no association between sarcopenia and tolerance of radiation therapy or survival outcomes.

Effects of two different paradigms of electrical stimulation exercise on cardio-metabolic risk factors after spinal cord injury. A randomized clinical trial.

To examine the combined effects of neuromuscular electrical stimulation-resistance training (NMES-RT) and functional electrical stimulation-lower extremity cycling (FES-LEC) compared to passive movement training (PMT) and FES-LEC in adults with SCI on (1) oxygen uptake (VO2), insulin sensitivity and glucose disposal in adults with SCI; (2) Metabolic and inflammatory biomarkers; (3) skeletal muscle, intramuscular fat (IMF) and visceral adipose tissue (VAT) cross-sectional areas (CSAs). Thirty-three participants with chronic SCI (AIS A-C) were randomized to 24 weeks of NMES-RT + FES or PMT + FES. The NMES-RT + FES group underwent 12 weeks of evoked surface NMES-RT using ankle weights followed by an additional 12 weeks of progressive FES-LEC. The control group, PMT + FES performed 12 weeks of passive leg extension movements followed by an additional 12 weeks of FES-LEC. Measurements were performed at baseline (BL; week 0), post-intervention 1 (P1; week 13) and post-intervention 2 (P2; week 25) and included FES-VO2 measurements, insulin sensitivity and glucose effectiveness using the intravenous glucose tolerance test; anthropometrics and whole and regional body composition assessment using dual energy x-ray absorptiometry (DXA) and magnetic resonance imaging to measure muscle, IMF and VAT CSAs. Twenty-seven participants completed both phases of the study. NMES-RT + FES group showed a trend of a greater VO2 peak in P1 [p = 0.08; but not in P2 (p = 0.25)] compared to PMT + FES. There was a time effect of both groups in leg VO2 peak. Neither intervention elicited significant changes in insulin, glucose, or inflammatory biomarkers. There were modest changes in leg lean mass following PMT + FES group. Robust hypertrophy of whole thigh muscle CSA, absolute thigh muscle CSA and knee extensor CSA were noted in the NMES-RT + FES group compared to PMT + FES at P1. PMT + FES resulted in muscle hypertrophy at P2. NMES-RT + FES resulted in a decrease in total VAT CSA at P1. NMES-RT yielded a greater peak leg VO2 and decrease in total VAT compared to PMT. The addition of 12 weeks of FES-LEC in both groups modestly impacted leg VO2 peak. The addition of FES-LEC to NMES-RT did not yield additional increases in muscle CSA, suggesting a ceiling effect on signaling pathways following NMES-RT. identifier NCT02660073.

Sarcopenia assessed by computed tomography or magnetic resonance imaging is associated with the loss of response to biologic therapies in adult patients with Crohn's disease.

Sarcopenia occurs in patients with Crohn's disease (CD). However, the association between sarcopenia and loss of response (LOR) to biologic agents remains unclear. This study explored such an association in CD patients. This retrospective study included 94 CD patients who received biologic therapy. The skeletal muscle cross-sectional area at the third lumbar was assessed by computed tomography or magnetic resonance imaging for sarcopenia evaluation. A LOR was defined by fecal calprotectin (FC) < 250 μg/g or >50% reduction from baseline levels or other factors, such as the used agent being replaced by other biologic agents. The association between sarcopenia and LOR was assessed by logistic regression analysis. LOR was observed in 54 patients (57.4%). The prevalence of sarcopenia in the LOR group was higher than that in response group (70.4% vs. 40.0%, p = 0.003). Sarcopenia (odds ratio [OR] = 3.89, 95% confidence interval [CI]: 1.31-11.54), Montreal L1 type (OR = 0.20, 95% CI: 0.06-0.60), perianal lesions (OR = 4.08, 95% CI: 1.31-12.70), and monocytes percentage (OR = 1.27, 95% CI: 1.02-1.57) at baseline were independent associated factors for LOR. Sarcopenia was also associated with LOR in patients who received infliximab (OR = 3.31, 95% CI: 1.11-9.87). Montreal L1 type, perianal lesions, and monocytes percentage (Model 1), and with additional consideration of sarcopenia (Model 2), were developed to predict LOR. Model 2 showed better performance than Model 1 (area under the curve [AUC] 0.82 vs. 0.75). Sarcopenia was associated with the LOR to biological agents or infliximab in adult patients with CD.

374. RADIOGRAPHICALLY-DETERMINED FRAILTY IS ASSOCIATED WITH IMPAIRED GASTRIC CONDUIT PERFUSION DURING ESOPHAGECTOMY

Abstract Background Frailty is considered a preoperative risk factor for complications after esophagectomy while impaired gastric conduit perfusion is associated with anastomotic leaks. Patients with impaired conduit perfusion may be candidates for gastric ischemic preconditioning, a surgical procedure performed prior to definitive esophagectomy to improve gastric conduit perfusion. The aim of this study was to investigate the association between radiographic determinants of frailty (morphomics) and gastric conduit perfusion assessed during esophagectomy. Methods Patients undergoing an esophagectomy with a cervical esophagogastric anastomosis (2015–2021) were included. Preoperative CT scans were processed using semiautomated algorithms (MATLAB; MathWorks, MA) to assess skeletal muscle (cross-sectional area, Martin’s criteria), subcutaneous fat (cross-sectional area, decreased when below the cut-off) and bone mineral density (decreased when below the cut-off). Indocyanine green perfusion was assessed intraoperatively (SPY Elite; Stryker, MI) and Ingress Index was calculated (standardized perfusion at the evaluated point). The morphomic index (MI), as an indicator of frailty, was determined using the number of decreased morphomic factors present (0–3). Multiple linear regression was used to analyze the data. Results One hundred and thirty-six patients were evaluated, with 25 patients developing anastomotic leaks (18.4%). Morphomic indices (MIs) of 2 or 3 were independently associated with reduced Ingress Index (p = 0.019 and 0.004, Table). In a sub-analysis for MI, MIs of 2 or 3 were associated with higher age (p = 0.029), lower BMI (p = 0.003), and cardiovascular disease (myocardial infarction, chronic heart failure, and vascular disease, p = 0.017). Other patient demographic factors including age, sex, and comorbidities did not affect Ingress Index. Conclusion Higher Morphomic Index (indicating lower than normal radiographic measures) were associated with impaired gastric conduit perfusion. More patients will be needed to investigate whether increased MI also is associated with development of anastomotic leaks. These findings may be useful in risk stratification and preoperative decision making in patients undergoing esophagectomy. Patients with MI of 2 or higher should be considered for gastric ischemic preconditioning.

Development and Validation of an Automated Image-Based Deep Learning Platform for Sarcopenia Assessment in Head and Neck Cancer

Sarcopenia is an established prognostic factor in patients with head and neck squamous cell carcinoma (HNSCC); the quantification of sarcopenia assessed by imaging is typically achieved through the skeletal muscle index (SMI), which can be derived from cervical skeletal muscle segmentation and cross-sectional area. However, manual muscle segmentation is labor intensive, prone to interobserver variability, and impractical for large-scale clinical use. To develop and externally validate a fully automated image-based deep learning platform for cervical vertebral muscle segmentation and SMI calculation and evaluate associations with survival and treatment toxicity outcomes. For this prognostic study, a model development data set was curated from publicly available and deidentified data from patients with HNSCC treated at MD Anderson Cancer Center between January 1, 2003, and December 31, 2013. A total of 899 patients undergoing primary radiation for HNSCC with abdominal computed tomography scans and complete clinical information were selected. An external validation data set was retrospectively collected from patients undergoing primary radiation therapy between January 1, 1996, and December 31, 2013, at Brigham and Women's Hospital. The data analysis was performed between May 1, 2022, and March 31, 2023. C3 vertebral skeletal muscle segmentation during radiation therapy for HNSCC. Overall survival and treatment toxicity outcomes of HNSCC. The total patient cohort comprised 899 patients with HNSCC (median [range] age, 58 [24-90] years; 140 female [15.6%] and 755 male [84.0%]). Dice similarity coefficients for the validation set (n = 96) and internal test set (n = 48) were 0.90 (95% CI, 0.90-0.91) and 0.90 (95% CI, 0.89-0.91), respectively, with a mean 96.2% acceptable rate between 2 reviewers on external clinical testing (n = 377). Estimated cross-sectional area and SMI values were associated with manually annotated values (Pearson r = 0.99; P < .001) across data sets. On multivariable Cox proportional hazards regression, SMI-derived sarcopenia was associated with worse overall survival (hazard ratio, 2.05; 95% CI, 1.04-4.04; P = .04) and longer feeding tube duration (median [range], 162 [6-1477] vs 134 [15-1255] days; hazard ratio, 0.66; 95% CI, 0.48-0.89; P = .006) than no sarcopenia. This prognostic study's findings show external validation of a fully automated deep learning pipeline to accurately measure sarcopenia in HNSCC and an association with important disease outcomes. The pipeline could enable the integration of sarcopenia assessment into clinical decision making for individuals with HNSCC.

Estimation of the Skeletal Muscle Cross-Sectional Area of the Lower Extremity Using Structured Light Three-Dimensional Scanning Technology

Estimation of the Skeletal Muscle Cross-Sectional Area of the Lower Extremity Using Structured Light Three-Dimensional Scanning Technology