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Arsalan Khan, Savan K Shah, Wara Naeem, Sanjib Basu, Gillian Alex, Nicole Geissen, Michael J Liptay, Christopher W. Seder
Abstract
BACKGROUND: We hypothesize that reduction in skeletal muscle volume between the time of surgery and the first postoperative surveillance CT scan is associated with recurrence in resected patients with early-stage non-small cell lung cancer (NSCLC). STUDY DESIGN: Patients who underwent lung resection for pT1-2aN0 NSCLC between 2010 and 2021 were identified. Exclusion criteria included neoadjuvant or adjuvant therapy, missing CT scan data, and steroid use. Volumetric body composition analysis was performed with Data Analysis Facilitation Suite software using preoperative and initial postoperative surveillance CT scans. A Cox proportional hazards model was used to examine the association between body composition changes and recurrence. RESULTS: Overall, 233 patients were examined, including 63% (147 of 233) women with a median BMI of 27 (interquartile range [IQR] 23 to 30) kg/m 2 , and a median tumor size of 1.6 (IQR 1.3 to 2.2) cm. Disease recurrence was observed in 14% (33 of 233), and the median time to recurrence was 15 (IQR 9 to 25) months. In patients that recurred, median skeletal muscle percent change was -3.6% (IQR -9.26 to 1.23) and 1.99% (IQR -4.6 to 11.4) in nonrecurrent patients. On univariable analysis, loss in skeletal muscle volume >1% was associated with worse disease-free survival (hazard ratio 2.93, 95% CI 1.42 to 6.04, p = 0.004). On multivariable analysis, after controlling for sex, age, race, BMI, pack years, forced expiratory volume in 1 second, histology, tumor size, number of nodes, procedure type, and comorbidities, this association persisted (hazard ratio 3.16, 95% CI 1.44 to 6.94, p = 0.004). CONCLUSIONS: Loss in skeletal muscle volume on first surveillance CT scan is associated with recurrence after resection of early-stage NSCLC.
Published on
February 18, 2025
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David da Silva Dias, Paulo Luz, Ana Fortuna, Ana Águas, Mafalda Machado, Beatriz Gosálbez, Rosa Farate, Rita Clemente Pinho, A.C. Valente, José Leão Mendes, Marta Maria Seladas, Carolina Trabulo, Paula Ravasco
Abstract
Background: Weight loss and skeletal muscle wasting are frequent in cancer and may influence treatment tolerance and outcomes. Computed tomography (CT) based body composition analysis at the third lumbar vertebra (L3) is an accurate method to quantify skeletal muscle in routine oncology care. Methods: We performed a multicenter retrospective cohort study including 202 adults with locally advanced (stage IB–III) gastric cancer treated in four Portuguese hospitals (January 2020–December 2022). Skeletal muscle area (SMA) was assessed on baseline CT at the L3 vertebral level, using Data Analysis Facilitation Suite (DAFS) software v3.11.2, and skeletal muscle index (SMI) was subsequently calculated. Patients with low muscle quantity were classified as sarcopenic (below sex-specific SMI mean). We evaluated associations with relapse-free survival (RFS), overall survival (OS), FLOT chemotherapy dose-limiting toxicities (DLTs), and postoperative complications after gastrectomy. Results: Mean age was 69 years, 65% had ECOG PS 0, 53% received FLOT chemotherapy protocol. Mean SMI was 49.6 cm2/m2 in males and 40.9 cm2/m2 in females and correlated positively, though moderately, with BMI (p < 0.01; r = 0.424). Sarcopenia was not significantly associated with RFS (p = 0.186) or OS (p = 0.168) at 30-month follow-up. Although numerical differences were observed (64% vs. 56% of patients did not relapse and 74% vs. 63% were alive, for non-sarcopenic vs. sarcopenic patients). Sarcopenia was associated with a higher risk of DLTs (p = 0.021; OR 2.56, 95% CI 1.15–5.73) and postoperative complications (p = 0.024; OR 2.16, 95% CI 1.11–4.21). Conclusions: Sarcopenia significantly increases the risk of chemotherapy toxicity and postoperative complications in locally advanced gastric cancer. However, its effect on OS and RFS was not statistically significant at 30-month follow-up. Standardization of CT-based sarcopenia cut-offs remains a major barrier to clinical implementation.
Published on
April 30, 2026
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A. G. W. Biersma, Bram van Leer, M. H. Renes, Janesh Pillay, J. Koeze
Abstract
BACKGROUND: Kidney function is associated with kidney volume. This study aims to explore automated segmentation for measuring total kidney volume (TKV) and to analyse the association between (changes in) TKV and acute kidney injury (AKI) incidence and/or severity in Intensive Care Unit (ICU) patients. METHODS: Patients were included in this retrospective pilot cohort study when at least two abdominal Computed Tomography (CT) scans were performed during ICU admission. If available, CT scans made before the ICU admission were included as a baseline scan. TKV was measured by automated segmentation of both kidneys using Data Analysis Facilitation Suite (DAFS, Voronoi Analytics Incorporated). All segmentations were visually checked and manually adjusted when necessary. ΔTKV was calculated between baseline CT and CT1 (ΔTKVCT1–baseline) and CT1 and CT2 (ΔTKVCT2–CT1). Primary outcomes were differences in kidney volume before and after manual correction and AKI incidence and severity, per the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, on the day of scanning. RESULTS: Twenty-six patients were included, of whom eighteen developed AKI during ICU admission. Analysis showed no significant differences in volumes before and after manual correction of the automated segmentations. TKV was not associated with AKI incidence or severity. Longitudinal intraindividual changes in TKV were observed. Median ΔTKVCT1–baseline was statistically significantly different for AKI versus non-AKI patients (−22 cm3 (−49–9) versus 42 cm3 (23–43), p = 0.03) and for different KDIGO stages. CONCLUSION: This study demonstrates the possibility of measuring TKV on CT in ICU patients using automated segmentation. Longitudinal intraindividual changes in TKV were observed, however, no clear association between TKV and AKI was found. CLINICAL TRIAL NUMBER: Not applicable.
Published on
March 26, 2026
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Dinh Van, Ioanna Drami, Edward T. Pring, Laura Gould, Jason Rai, George Malietzis, Phillip Lung, Vincent Chow, Karteek Popuri, Mirza Faisal Beg, Thanos Athanasiou, John T. Jenkins
Abstract
Abstract unavailable
Published on
May 13, 2025
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Zubaidah Nor Hanipah, Gabriela de O. Lemos, Sophia Ramirez, Venkata Satya Naga Arun Kousik Dhulipala, Karteek Popuri, Mirza Faisal Beg, Shengping Yang, Philip R. Schauer, Vance L. Albaugh, Steven B. Heymsfield
Abstract
BACKGROUND: Roux-en-Y gastric bypass (RYGB) is associated with substantial weight loss and improved obesity-related comorbidities. However, outcomes on body composition, particularly skeletal muscle (SM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) remain inconsistent due to limitations in measurement techniques. OBJECTIVE: Evaluate longitudinal changes in SM, VAT, and SAT volumes (cm3) following RYGB using Data Analysis Facilitation Suite (DAFS), an automated computed tomography (CT) analysis software. METHODS: In this prospective pilot study, nine female patients underwent low-dose abdominal and pelvic CT imaging at baseline, 3-, and 6-months post-RYGB. Volumetric analysis from the ninth thoracic veterbra (T9) to the sacrum was performed using DAFS. Changes in SM, VAT, and SAT were assessed using paired t-tests. RESULTS: Participants (mean ± SD; age 35 ± 9 years, BMI 48 ± 10 kg/m²) experienced substantial weight loss (14 ± 5% at 3 months, 25 ± 7% at 6 months; p < 0.001). SAT and VAT volumes decreased significantly by 21% and 27% at 3 months, and by 31% and 47% at 6 months, respectively (all p < 0.001). In contrast, SM volume showed a significant decline of 14% at month 3 (p
Published on
February 21, 2026
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Arsalan Khan, Wara Naeem, Savan K Shah, Mumtaz Ahmad Ansari, Gillian Alex, Nicole Geissen, Jun Li, Christopher W. Seder
Abstract
Background: Despite advances in treatment, approximately 20% of patients with early stage non-small cell lung cancer (NSCLC) will experience recurrence. Sarcopenia has emerged as a potential prognostic factor in lung cancer. We hypothesize that rate of skeletal muscle volume loss after lung resection is associated with disease-free survival (DFS).
Patients and methods: A retrospective analysis was conducted on 316 patients with node-negative NSCLC (≤ 4 cm) who underwent lung resection between 2010 and 2021. Those receiving neoadjuvant or adjuvant therapy or experiencing recurrence within 12 months of surgery were excluded. Skeletal muscle index (SMI) was measured preoperatively and annually for up to 5 years. Locally estimated scatterplot smoothing (LOESS) regression was used to visualize trends in SMI over time, and cut-point analysis identified the optimal slope of SMI change associated with DFS. The association between SMI slope and DFS was further evaluated using multivariable Cox proportional hazards models, adjusting for relevant demographic and clinical covariates.
Results: LOESS analysis revealed an initial plateau in SMI during the first postoperative year across all patients, followed by a marked decline in patients that recurred. The greatest loss in SMI occurred in the year immediately preceding radiographic identification of recurrence. In Cox proportional hazards analysis, patients with an SMI loss greater than 13.5 units/year had worse DFS (hazard ratio [HR] 11.97, 95% confidence interval [CI] 5.54-25.87, p
Published on
September 13, 2025
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Gupta S, Jeffrey AW, Wang Z, Adams LA, Garas G, MacQuillan G, Wallace M, Smith B, Lim WH, Francis R, Welman CJ,
Jeffrey GP
Abstract
Background and aim: Model for End-Stage Liver Disease (MELD) incorporates serum creatinine (sCr), a poor measure of renal function in cirrhotic patients. Females have higher waitlist mortality which is proposed to be due to lower muscle mass and consequent lower sCr values. This study evaluated the difference (ΔCr) between sCr and calculated creatinine (cCr) derived from measured GFR (mGFR) in cirrhosis. The effect of sex and muscle mass on ΔCr and MELD was studied for bias.
Methods: 139 cirrhotic patients assessed for liver transplantation (LT) from 2019-2024 were included. 48 living kidney donors were the controls (n=48). The CKD-EPI equation was rearranged to determine cCr as a function of mGFR. MELD, MELD-Na and MELD 3.0 scores were calculated using cCr and sCr; and the difference was ΔMELD, ΔMELD-Na and ΔMELD 3.0. Skeletal muscle index (SMI, cm2/m2) was calculated from CT images at L3 level.
Results: Mean cCr was significantly higher than mean sCr, (p
Published on
October 14, 2025
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Anlan Cao, Ijeamaka Anyene Fumagalli, Wendy Y. Chen, Adana A. M. Llanos, Charles P. Quesenberry, Bette J. Caan, Elizabeth M. Cespedes Feliciano
Abstract
Background Total adiposity measured by abdominal computed tomography (CT) at the third lumbar vertebrae (L3) has been associated with breast cancer survival, but most patients undergo chest CT. If adipose tissues at the thoracic level, including those surrounding the thoracic organs, are associated with survival, they could be used to inform care for significantly more breast cancer patients. Methods We included 2127 individuals aged 18-< 90, diagnosed with stage II-III breast cancer at Kaiser Permanente Northern California (2005–2019). Cross-sectional areas of adiposity were quantified at the fourth thoracic vertebrae (T4) and L3. Using multivariable Cox models, we estimated hazard ratios (HRs) and 95% confidence intervals to compare the strength of association of T4-level versus L3-level adiposity with all‐cause and cause-specific mortality. Results Participants were on average 56.2 years old at diagnosis. During an average follow-up of 8.2 years, 593 deaths occurred, with 100 from heart disease and 429 from breast cancer. Positive, moderate-to-strong correlations were observed between adiposity at T4 and L3. After adjusting for covariates including body mass index and muscle, higher intrathoracic and intermuscular adiposity at T4 were associated with increased all-cause (intrathoracic: HR = 1.35[1.06–1.72]; intermuscular: HR = 1.26[1.01–1.59]) and heart disease-specific mortality (intrathoracic: HR = 2.23[1.31–3.78]; intermuscular: HR = 2.25[1.37–3.68]). Greater subcutaneous adiposity at T4 showed a non-significant trend toward increased mortality (overall: HR = 1.24[0.95–1.61]; breast cancer-specific: 1.27[0.93–1.73]). These associations were not observed at L3. Conclusions Despite strong correlations with L3, adiposity at T4 was significantly associated with overall and heart disease-specific mortality, while measurements at L3 were not, possibly due to the proximity of T4 to the breast tumor and heart.
Published on
October 14, 2025
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Mushfiqus Salehin, Vincent Chow, Hyunwoo Lee, Erin Weltzien, Nguyễn Quang Long, Jia Li, Varun Akella, Bette J. Caan, Elizabeth M. Cespedes Feliciano, Da Ma, Mirza Faisal Beg, Karteek Popuri
Abstract
Background & aims: Assessing body composition using computed tomography (CT) can help predict the clinical outcomes of cancer patients, including surgical complications, chemotherapy toxicity, and survival. However, manual segmentation of CT images is labor-intensive and can lead to significant inter-observer variability. In this study, we validate the accuracy and reliability of automatic CT-based segmentation using the Data Analysis Facilitation Suite (DAFS) Express software package, which rapidly segments single CT slices.
Methods: The study analyzed single-slice images at the third lumbar vertebra (L3) level (n = 5973) of patients diagnosed with non-metastatic colorectal (n = 3098) and breast cancer (n = 2875) at Kaiser Permanente Northern California. Manual segmentation used SliceOmatic with Alberta protocol HU ranges; automated segmentation used DAFS Express with identical HU limits. The accuracy of the automated segmentation was evaluated using the DICE index, the reliability was assessed by intra-class correlation coefficients (ICC) with 95 % CI, and the agreement between automatic and manual segmentations was assessed by Bland-Altman analysis. DICE scores below 20 % and 70 % were considered failed and poor segmentations, respectively, and underwent additional review. The mortality risk associated with each tissue's area was generated using Cox proportional hazard ratios (HR) with 95 % CI, adjusted for patient-specific variables including age, sex, race/ethnicity, cancer stage and grade, treatment receipt, and smoking status. A blinded review process categorized images with various characteristics for sensitivity analysis.
Results: The mean (standard deviation, SD) ages of the colorectal and breast cancer patients were 62.6 (11.4) and 56 (11.8), respectively. Automatic segmentation showed high accuracy vs. manual segmentation, with mean DICE scores above 96 % for skeletal muscle (SKM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT), and above 77 % for intermuscular adipose tissue (IMAT), with three failures, representing 0.05 % of the cohort. Bland-Altman analysis of 5973 measurements showed mean cross-sectional area differences of -5.73, -0.84, -2.82, and -1.02 cm2 for SKM, VAT, SAT and IMAT, respectively, indicating good agreement, with slight underestimation in SKM and SAT. Reliability Coefficients ranged from 0.88 to 1.00 for colorectal and 0.95-1.00 for breast cancer, with Simple Kappa values of 0.65-0.99 and 0.67-0.97, respectively. Additionally, mortality associations for automated and manual segmentations were similar, with comparable hazard ratios, confidence intervals, and p-values. Kaplan-Meier survival estimates showed mortality differences below 2.14 %.
Conclusion: DAFS Express enables rapid, accurate body composition analysis by automating segmentation, reducing expert time and computational burden. This rapid analysis of body composition is a prerequisite to large-scale research that could potentially enable use in the clinical setting. Automated CT segmentations may be utilized to assess markers of sarcopenia, muscle loss, and adiposity and predict clinical outcomes.
Published on
August 25, 2025
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Amy Wozniak, P. O'Connor, Jared Seigal, Vasilios Vasilopoulos, Mirza Faisal Beg, Karteek Popuri, Cara Joyce, Patricia Sheean
Abstract
Rationale and objectives: Fully automated, artificial intelligence (AI) -based software has recently become available for scalable body composition analysis. Prior to broad application in the clinical arena, validation studies are needed. Our goal was to compare the results of a fully automated, AI-based software with a semi-automatic software in a sample of hospitalized patients.
Materials and methods: A diverse group of patients with Coronovirus-2 (COVID-19) and evaluable computed tomography (CT) images were included in this retrospective cohort. Our goal was to compare multiple aspects of body composition procuring results from fully automated and semi-automated body composition software. Bland-Altman analyses and correlation coefficients were used to calculate average bias and trend of bias for skeletal muscle (SM), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), intermuscular adipose tissue (IMAT), and total adipose tissue (TAT-the sum of SAT, VAT, and IMAT).
Results: A total of 141 patients (average (standard deviation (SD)) age of 58.2 (18.9), 61 % male, and 31 % White Non-Hispanic, 31 % Black Non-Hispanic, and 33 % Hispanic) contributed to the analysis. Average bias (mean ± SD) was small (in comparison to the SD) and negative for SM (-3.79 cm2 ± 7.56 cm2) and SAT (-7.06 cm2 ± 19.77 cm2), and small and positive for VAT (2.29 cm2 ± 15.54 cm2). A large negative bias was observed for IMAT (-7.77 cm2 ± 5.09 cm2), where fully automated software underestimated intramuscular tissue quantity relative to the semi-automated software. The discrepancy in IMAT calculation was not uniform across its range given a correlation coefficient of -0.625; as average IMAT increased, the bias (underestimation by fully automated software) was greater.
Conclusions: When compared to a semi-automated software, a fully automated, AI-based software provides consistent findings for key CT body composition measures (SM, SAT, VAT, TAT). While our findings support good overall agreement as evidenced by small biases and limited outliers, additional studies are needed in other clinical populations to further support validity and advanced precision, especially in the context of body composition and malnutrition assessment.
Keywords: Automated segmentation; Body composition; Computed tomography; Malnutrition; Nutrition status; SARS-CoV-2 infection.
Published on
June 11, 2025
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Chen IM, Johansen JS, Theile S, et al.
Abstract
Purpose
This randomized phase-II trial (ClinicalTrials.gov identifier: NCT02767557) compared efficacy of gemcitabine/nab-paclitaxel (Gem/Nab) with or without the anti–interleukin-6 (IL-6) receptor antibody tocilizumab (Toc) for advanced pancreatic cancer (PC).
Methods
A safety cohort received Gem 1,000 mg/m2 and Nab 125 mg/m2 on days 1, 8, and 15, and Toc 8 mg/kg on day 1 for each 28-day cycle. Participants with modified Glasgow prognostic scores of 1 or 2 were randomly assigned 1:1 to receive Gem/Nab/Toc or Gem/Nab. The primary end point was the overall survival (OS) rate at 6 months (OS6). Secondary end points were progression-free survival (PFS), overall response rate (ORR), and safety. Exploratory end points were cachexia, quality of life, and biomarkers, including the cachexia-promoting protein, growth differentiation factor 15 (GDF15).
Results
Overall, 147 patients were treated, including six safety cohort participants. The median follow-up period was 8.1 months (IQR, 4.2-13.9). OS6 was 68.6% (95% CI, 56.3 to 78.1) for the Gem/Nab/Toc group and 62.0% (49.6-72.1) for the Gem/Nab group (P = .409). OS for Gem/Nab/Toc versus Gem/Nab improved at 18 months (27.1% v 7.0%, P = .001). No differences in median OS, PFS, or ORR were observed. Incidence of grade-3+ treatment-related adverse events (TrAEs) was 88.1% for Gem/Nab/Toc and 63.4% for Gem/Nab (P
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Nobuhide Ohashi, Kazushige Koike, Kurumi Sakai, Koyo Nishiyama, Takanori Sasaki, Kazuhiro Ogi, Hironari Dehari, Nobumichi Kobayashi, Akihiro Miyazaki
Abstract
Objectives
We evaluated the accuracy of estimating the cross-sectional area (CSA) at the third lumbar
vertebra (L3) based on the CSA at the third cervical vertebra (C3) using computed
tomographic images, and we identified the sources of error and bias using the evaluation of
absolute reliability in 89 Japanese patients with oral squamous cell carcinoma.
Methods
Skeletal muscle CSA was measured at the C3 and L3 on pretreatment computed
tomographic images. We used the CSA at the C3 to estimate CSA at the L3 in an existing
prediction formula. Correlation coefficients were used to evaluate the relative reliability of
the estimate, and Bland-Altman analysis and minimum detectable change (MDC) were
used to evaluate its absolute reliability.
Results
Estimated and actual CSAs at L3 were strongly correlated (r=0.885, p
Published on
September 16, 2022
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Farzaneh Rahmani, Garrett Camps, Olesya Mironchuk, Norman Atagu, David H. Ballard, Tammie L.S. Benzinger, Vincent Chow, Sonika Dahiya, J. C. Evans, Shama Jaswal, Sara Hosseinzadeh Kassani, Da Ma, Muhammad Naeem, Karteek Popuri, Cyrus A. Raji, Marilyn J Siegel, Yifei Xu, Jingxia Liu, Mirza Faisal Beg, Michael R. Chicoine, Joseph E. Ippolito
Abstract
Background Alterations in cellular metabolism affect cancer survival and can manifest in metrics of body composition. We investigated the effects of various body composition metrics on survival in patients with glioblastoma (GBM). Methods We retrospectively analyzed patients who had an abdominal and pelvic computed tomography (CT) scan performed within 1 month of diagnosis of GBM (178 participants, 102 males, 76 females, median age: 62.1 years). Volumetric body composition metrics were derived using automated CT segmentation of adipose tissue, skeletal muscle, and aortic calcification from L1 to L5. Univariable and multivariable Cox proportional hazards models were performed separately in males and females using known predictors of GBM overall survival (OS) as covariates. A sex-specific composite score of predisposing and protective factors was constructed using the relative importance of each metric in GBM OS. Results Higher skeletal muscle volume and lower skeletal muscle fat fraction were associated with better OS in the entire dataset. A robust and independent effect on GBM OS was seen specifically for fraction of inter/intramuscular adipose tissue to total adipose tissue after correction for known survival predictors and comorbidities. Worse OS was observed with increased abdominal aortic calcification volume in both sexes. There was a significant difference in GBM OS among participants stratified into quartiles based on sex-specific composite predisposing and protective scores. Conclusion The relationship between body composition and GBM OS provides an actionable advancement toward precision medicine in GBM management, as lifestyle and dietary regimens can alter body composition and metabolism and from there GBM survival.
Published on
November 28, 2024
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Dinh Van, Ioanna Drami, Edward T. Pring, Laura E. Gould, Phillip Lung, Karteek Popuri, Vincent Chow, Mirza Faisal Beg, Thanos Athanasiou, John T. Jenkins
Abstract
Abstract Automated computed tomography (CT) scan segmentation (labelling of pixels according to tissue type) is now possible. This technique is being adapted to achieve three‐dimensional (3D) segmentation of CT scans, opposed to single L3‐slice alone. This systematic review evaluates feasibility and accuracy of automated segmentation of 3D CT scans for volumetric body composition (BC) analysis, as well as current limitations and pitfalls clinicians and researchers should be aware of. OVID Medline, Embase and grey literature databases up to October 2021 were searched. Original studies investigating automated skeletal muscle, visceral and subcutaneous AT segmentation from CT were included. Seven of the 92 studies met inclusion criteria. Variation existed in expertise and numbers of humans performing ground‐truth segmentations used to train algorithms. There was heterogeneity in patient characteristics, pathology and CT phases that segmentation algorithms were developed upon. Reporting of anatomical CT coverage varied, with confusing terminology. Six studies covered volumetric regional slabs rather than the whole body. One study stated the use of whole‐body CT, but it was not clear whether this truly meant head‐to‐fingertip‐to‐toe. Two studies used conventional computer algorithms. The latter five used deep learning (DL), an artificial intelligence technique where algorithms are similarly organized to brain neuronal pathways. Six of seven reported excellent segmentation performance (Dice similarity coefficients > 0.9 per tissue). Internal testing on unseen scans was performed for only four of seven algorithms, whilst only three were tested externally. Trained DL algorithms achieved full CT segmentation in 12 to 75 s versus 25 min for non‐DL techniques. DL enables opportunistic, rapid and automated volumetric BC analysis of CT performed for clinical indications. However, most CT scans do not cover head‐to‐fingertip‐to‐toe; further research must validate using common CT regions to estimate true whole‐body BC, with direct comparison to single lumbar slice. Due to successes of DL, we expect progressive numbers of algorithms to materialize in addition to the seven discussed in this paper. Researchers and clinicians in the field of BC must therefore be aware of pitfalls. High Dice similarity coefficients do not inform the degree to which BC tissues may be under‐ or overestimated and nor does it inform on algorithm precision. Consensus is needed to define accuracy and precision standards for ground‐truth labelling. Creation of a large international, multicentre common CT dataset with BC ground‐truth labels from multiple experts could be a robust solution.
Published on
August 10, 2023
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Kwang Cheol Koh, W.K. Liu, Othman Al‐Sawaf, Corentin Richard, Kerstin Haase, Richard Scott, Selvaraju Veeriah, C. Lombardelli, Izadora Furlani, James I. MacRae, Charles Swanton, Mariam Jamal‐Hanjani
Abstract
Background
Cancer-associated cachexia (CAC) is a debilitating syndrome of fat and/or muscle loss that affects up to 80% of patients with cancer, leading to progressive functional decline, reduced treatment response and survival. Despite its morbidity, there are no globally approved therapies or standardised diagnostic criteria. The dynamic changes in body composition (BC) - subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and skeletal muscle (SKM) from early to late stage disease in patients with non-small cell lung cancer (NSCLC) is poorly understood. Here, we analyse longitudinal BC changes in patients with NSCLC in the context of tumour burden.
Methods
TRACERx is a national prospective study that follows over 800 patients with NSCLC from diagnosis to death or end of follow up. Patients are recruited with early stage, operable disease and undergo surgical resection, followed by standard of care treatment. Computed tomography (CT) imaging is performed at diagnosis, post-surgery, relapse and post-relapse. Here, we analysed BC of two cohorts: patients who relapsed and patients in remission. DAFS (Data Analysis Facilitation Suite), a deep learning pipeline is used to derive BC measurements from CT scans. Tumour volume in matched CT images were evaluated via segmentation and contouring of visualised lesions to quantify metastatic burden volumetrically.
Results
As cachexia is not well defined, two approaches were utilised to identify patients who develop CAC. (1) The threshold loss approach uses the 5th percentile of BC changes in the non-relapse cohort as the cachectic loss threshold to identify patients who develop CAC. Patients who were CAC based on this approach have worse overall survival compared to non-CAC patients. (2) The trajectory approach uses latent class mixed models to identify distinct trajectories of BC changes. In some patients, BC changes were found to track with increasing or decreasing tumour volumes and were impacted by treatment.
Conclusions
Assessing longitudinal BC may help identify patients at risk of developing CAC during treatment and disease progression and guide early intervention. Correlating this to metastatic disease burden may reveal shared biological mechanisms driving CAC and the metastatic process.
Published on
October 1, 2024
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Leo R. Brown, Maria Soupashi, Michael S. Yule, Cathleen Grossart, Donald C. McMillan, Barry Laird, Stephen J. Wigmore, Richard J. E. Skipworth
Abstract
Background: Cachexia is common in patients with oesophagogastric cancer. The syndrome is characterised by tissue wasting (muscle and fat), anorexia, and reduced physical function, which result from complex interactions between the tumour and its host. Heterogeneity in the diagnostic criteria used for cachexia has hindered their clinical utilisation. This study aimed to compare the two established cachexia definitions (Fearon’s consensus definition and the Global Leadership Initiative on Malnutrition [GLIM] criteria) and their relationships with survival in patients with oesophagogastric cancer. Methods: Consecutive patients newly diagnosed with oesophagogastric cancer (January 2019 to December 2020) were identified from a prospective regional database. Involuntary weight loss, BMI, CT body composition analyses, and neutrophil–lymphocyte ratios were recorded at clinical staging. These data were used to assess patients for cachexia according to Fearon and GLIM diagnostic criteria. The primary outcome of interest was overall survival. Results: Overall, 465 patients (66.9% male, median 71 years) were diagnosed with oesophagogastric cancer during the 2-year study period. Cachectic proportions differed between definitions (Fearon: 59.1% vs. GLIM: 44.1%), and only 49.1% of the 322 patients who met one set of diagnostic criteria were cachectic according to both. Patients who met the GLIM criteria were significantly more comorbid and had a poorer performance status; however, no such difference was evident when using the Fearon definition. Those patients who met either set of diagnostic criteria had shorter survival than those who met neither (p < 0.001). Following adjustment for confounders, GLIM-defined cachexia was more strongly associated with reduced survival (aHR: 1.57 [95% CI: 1.25–1.96], p < 0.001) than Fearon-defined cachexia (aHR: 1.41 [95% CI: 1.13–1.76], p = 0.002). Patients who only met the Fearon diagnostic criteria had prolonged survival (median: 363 days) when compared to those who met only GLIM (median: 158 days) or both definitions (median: 120 days). A secondary analysis of those patients who met the GLIM diagnostic criteria (n = 205) compared the three potential phenotypical criteria used in this definition. Only reduced muscle mass, and not low BMI or weight loss, was associated with poorer survival (aHR: 1.88 [95% CI: 1.15–3.07], p = 0.012) in this group. Conclusions: Cancer cachexia is strongly associated with shortened survival in patients with oesophagogastric cancer. Classification using the GLIM criteria provides more effective prognostication and this definition should be utilised in multidisciplinary patient care.
Published on
January 28, 2025
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Jonathan P. Bennett, Katherine L. Ford, Mario Siervo, Marı́a Cristina González, Henry C. Lukaski, Michael B. Sawyer, Marina Mourtzakis, Nicolaas E.P. Deutz, John Shepherd, Carla M. Prado
Abstract
Background and aims
Measurement of body composition using computed tomography (CT) scans may be a viable clinical tool for low muscle mass assessment in oncology. However, longitudinal assessments are often infeasible with CT. Clinically accessible body composition technologies can be used to track changes in fat-free mass (FFM) or muscle, though their accuracy may be impacted by cancer-related physiological changes. The purpose of this study was to examine the agreement among accessible body composition method with criterion methods for measures of whole-body FFM measurements and, when possible, muscle mass for the classification of low muscle in patients with cancer.
Methods
Patients with colorectal cancer were recruited to complete measures of whole-body DXA, air displacement plethysmography (ADP), and bioelectrical impedance analysis (BIA). These measures were used alone, or in combination to construct the criterion multicompartment (4C) mode for estimating FFM. Patients also underwent abdominal CT scans as part of routine clinical assessment. Agreement of each method with 4C model was analyzed using mean constant error (CE = criterion – alternative), linear regression including root mean square error (RMSE), Bland-Altman limits of agreement (LoA) and mean percentage difference (MPD). Additionally, appendicular lean soft tissue index (ALSTI) measured by DXA and predicted by CT were compared for the absolute agreement, while the ALSTI values and skeletal muscle index by CT were assessed for agreement on the classification of low muscle mass.
Results
Forty-five patients received all measures for the 4C model and 25 had measures within proximity of clinical CT measures. Compared to 4C, DXA outperformed ADP and BIA by showing the strongest overall agreement (CE = 1.96 kg, RMSE = 2.45 kg, MPD = 98.15 ± 2.38%), supporting its use for body composition assessment in patients with cancer. However, CT cutoffs for skeletal muscle index or CT-estimated ALSTI were lower than DXA ALSTI (average 1.0 ± 1.2 kg/m2) with 24.0% to 32.0% of patients having a different low muscle classification by CT when compared to DXA.
Conclusions
Despite discrepancies between clinical body composition assessment and the criterion multicompartment model, DXA demonstrates the strongest agreement with 4C. Disagreement between DXA and CT for low muscle mass classification prompts further evaluation of the measures and cutoffs used with each technique. Multicompartment models may enhance our understanding of body composition variations at the individual patient level and improve the applicability of clinically accessible technologies for classification and monitoring change over time.
Published on
May 6, 2024
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11
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Netanja I. Harlianto, Pim A. de Jong, Wouter Foppen, Edwin Bennink, Stijn Bunk, S.C. Mastbergen, Adriane D.M. Vorselaars, Mareye Voortman, M. Kloppenburg, Francisco J. Blanco, I.K. Haugen, Françis Berenbaum, Karteek Popuri, Mirza Faisal Beg, Mylène P. Jansen
Abstract
The systemic associations with knee osteoarthritis (KOA) are incompletely understood. This study explores aortic disease, musculoskeletal and organ findings in patients with KOA in relation to their symptoms or radiographic abnormalities. Full body computed tomography (CT) scans of 255 IMI-APPROACH participants were investigated using an automated analysis of multislice CT (Voronoi Health Analytics) that extracts aortic size and calcifications, and volumes and densities of bones, muscles, fat compartments and thoracic and abdominal organs. The CT measurements were primarily related to KOA as measured with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual scores and automated knee radiograph analysis of osteophytes, bone sclerosis and joint space width. The median age was 67 years, body mass index (BMI) 26.8 kg/m² and 78% were female. About half had Kellgren-Lawrence grade ≥ 2. Larger knee osteophyte area was associated with a larger aortic volume (RSpearman=0.21,P = 0.001), which can be due to elongation or dilatation. We observed an association between more symptoms and increased psoas (RSpearman=-0.23,P < 0.001) and lower leg (RSpearman=-0.23,P
Published on
February 24, 2025
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Kristen M. Beavers, Allison E. Avery, Mahalakshmi Shankaran, William J. Evans, S. Delanie Lynch, C. Liam Dwyer, Marjorie Howard, Daniel P. Beavers, Ashley A. Weaver, Leon Lenchik, Peggy M. Cawthon
Abstract
Background Traditionally, weight loss (WL) trials utilize dual energy X‐ray absorptiometry (DXA) to measure lean mass. This method assumes lean mass, as the sum of all non‐bone and non‐fat tissue, is a reasonable proxy for muscle mass. In contrast, the D 3 ‐creatine (D 3 Cr) dilution method directly measures whole body skeletal muscle mass, although this method has yet to be applied in the context of a geriatric WL trial. The purpose of this project was to (1) describe estimates of change and variability in D 3 Cr muscle mass in older adults participating in an intentional WL intervention and (2) relate its change to other measures of body composition as well as muscle function and strength. Methods The INVEST in Bone Health trial (NCT04076618), used as a scaffold for this ancillary pilot project, is a three‐armed, 12‐month randomized, controlled trial designed to determine the effects of resistance training or weighted vest use during intentional WL on a battery of musculoskeletal health outcomes among 150 older adults living with obesity. A convenience sample of 24 participants ( n = 8/arm) are included in this analysis. At baseline and 6 months, participants were weighed, ingested a 30 mg D 3 Cr tracer dose, provided a fasted urine sample 3–6 days post‐dosage, underwent DXA (total body fat and lean masses, appendicular lean mass) and computed tomography (mid‐thigh and trunk muscle/intermuscular fat areas) scans, and performed 400‐m walk, stair climb, knee extensor strength, and grip strength tests. Results Participants were older (68.0 ± 4.4 years), mostly White (75.0%), predominantly female (66.7%), and living with obesity (body mass index: 33.8 ± 2.7 kg/m 2 ). Six month total body WL was −10.3 (95% confidence interval, CI: −12.7, −7.9) kg. All DXA and computed tomography‐derived body composition measures were significantly decreased from baseline, yet D 3 Cr muscle mass did not change [+0.5 (95% CI: −2.0, 3.0) kg]. Of muscle function and strength measures, only grip strength significantly changed [+2.5 (95% CI: 1.0, 4.0) kg] from baseline. Conclusions Among 24 older adults, significant WL with or without weighted vest use or resistance training over a 6‐month period was associated with significant declines in all bioimaging metrics, while D 3 Cr muscle mass and muscle function and strength were preserved. Treatment assignment for the trial remains blinded; therefore, full interpretation of these findings is limited. Future work in this area will assess change in D 3 Cr muscle mass by parent trial treatment group assignment in all study participants.
Published on
September 5, 2023
cited by
4
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Maximilian Volk, Saeid Mirzai, Ian Persits, Kunaal S. Sarnaik, Laurie Ann Moennich, Po‐Hao Chen, John Rickard, W.H. Wilson Tang
Abstract
Background
The region of adipose deposition is an important determinant in the outcomes of patients with heart failure (HF). However, the impact of regional adiposity on HF patients undergoing cardiac resynchronization therapy (CRT) remains unclear.
Methods
A retrospective cohort analysis was conducted on 95 patients from a single-center study, assessing post-CRT outcomes. Multi-slice body composition measurements of chest computed tomography before CRT placement were used for adipose quantification. Patients were stratified based on subcutaneous adiposity, intramuscular adiposity, and hepatic steatosis.
Results/Conclusion
Subcutaneous adiposity correlated with higher CRT response rates (44.4 % in subcutaneous adiposity vs 16.7 % in subcutaneous adipopenia, p = 0.009), while intramuscular adiposity was associated with increased pre-frailty (adjusted OR 14.17, 95 % CI 2.24–89.57, p = 0.005). The higher response to CRT in patients with subcutaneous adiposity may be secondary to preferred subcutaneous over ectopic adipose fat deposition, which is potentially protective against cardiomyocyte dysfunction. Thus, intramuscular adiposity could potentially serve as a prognostic tool for frailty in HF patients.
Published on
September 27, 2024
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0
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Maria F. Gomez, Daniel Jeong, Scott Pitcher, Stephanie Hogue, Mark Friedman, Seth Felder, Xuefeng Wang, Erin M. Siegel, Doratha A. Byrd
Abstract
Objectives: Colorectal cancer (CRC) is the second overall leading cause of cancer death in the United States. Body composition may influence CRC prognosis by regulating inflammation, insulin sensitivity, and microbial-modulated metabolism. We used a novel computer tomography (CT)-based approach to investigate associations of body composition with overall survival among 121 CRC patients.
Methods: We included patients with colon (40%) or rectum (60%) cancer stages I-IV (III-IV 65%), 58% male, median age 56, who had surgery at Moffitt Cancer Center from 1995-2020. We estimated visceral (VF), subcutaneous (SF) fat, and skeletal muscle mass (SKM) using the Data Analysis Facilitation Suite (DAFS) 3.5 platform to segment standard of care CT images. Respective body composition metric volumes were generated from axial CT images between the top of the 10th thoracic vertebral body to the bottom of the 5th lumbar vertebral body. Standard single-slice body composition metric areas were also obtained using the axial CT image through the mid-3rd lumbar vertebra(cm2). We normalized the SKM area by dividing it by height (m2). We used multivariate Cox proportional hazard regressions to estimate associations of body composition metrics with overall survival. Models were adjusted for sex, age at diagnosis, stage, and tumor site.
Results: Overall, all three single-slice CT body composition metrics were strongly positively correlated with overall survival. Single-slice mid-L3 Visceral and subcutaneous fat areas were associated with worse survival. For the cross-sectional area of VF and SF (cm2), the hazard ratios (HRs) and 95% confidence intervals (CIs) comparing the highest relative to lowest tertiles were HR=2.37 (95% CI= 1.04-5.36; P-Trend=0.04) and HR= 3.36 (95%CI=1.44-7.86; P-Trend= 0.01), respectively. Associations of the SKM index and volumetric metrics with survival were weaker and closer to null.
Conclusions: Our study suggests that pretreatment CT metrics of body composition reflecting visceral and subcutaneous fat may be associated with poorer CRC survival, potentially informing clinical decision-making and interventional strategies. These associations should be further studied in large, diverse populations with measured prognostic biomarkers.
Published on
June 29, 2024
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0
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Ijeamaka Anyene Fumagalli, Sidney Le, Peter D. Peng, Patricia Kipnis, Jean‐Louis Vincent, Bette J. Caan, Vincent Chow, Mirza Faisal Beg, Karteek Popuri, Elizabeth M. Cespedes Feliciano
Abstract
Importance Prior studies demonstrated consistent associations of low skeletal muscle mass assessed on surgical planning scans with postoperative morbidity and mortality. The increasing availability of imaging artificial intelligence enables development of more comprehensive imaging biomarkers to objectively phenotype frailty in surgical patients. Objective To evaluate the associations of body composition scores derived from multiple skeletal muscle and adipose tissue measurements from automated segmentation of computed tomography (CT) with the Hospital Frailty Risk Score (HFRS) and adverse outcomes after abdominal surgery. Design, Setting, and Participants This retrospective cohort study used CT imaging and electronic health record data from a random sample of adults who underwent abdominal surgery at 20 medical centers within Kaiser Permanente Northern California from January 1, 2010, to December 31, 2020. Data were analyzed from April 1, 2022, to December 1, 2023. Exposure Body composition derived from automated analysis of multislice abdominal CT scans. Main Outcomes and Measures The primary outcome of the study was all-cause 30-day postdischarge readmission or postoperative mortality. The secondary outcome was 30-day postoperative morbidity among patients undergoing abdominal surgery who were sampled for reporting to the National Surgical Quality Improvement Program. Results The study included 48 444 adults; mean [SD] age at surgery was 61 (17) years, and 51% were female. Using principal component analysis, 3 body composition scores were derived: body size, muscle quantity and quality, and distribution of adiposity. Higher muscle quantity and quality scores were inversely correlated ( r = −0.42; 95% CI, −0.43 to −0.41) with the HFRS and associated with a reduced risk of 30-day readmission or mortality (quartile 4 vs quartile 1: relative risk, 0.61; 95% CI, 0.56-0.67) and 30-day postoperative morbidity (quartile 4 vs quartile 1: relative risk, 0.59; 95% CI, 0.52-0.67), independent of sex, age, comorbidities, body mass index, procedure characteristics, and the HFRS. In contrast to the muscle score, scores for body size and greater subcutaneous and intermuscular vs visceral adiposity had inconsistent associations with postsurgical outcomes and were attenuated and only associated with 30-day postoperative morbidity after adjustment for the HFRS. Conclusions and Relevance In this study, higher muscle quantity and quality scores were correlated with frailty and associated with 30-day readmission and postoperative mortality and morbidity, whereas body size and adipose tissue distribution scores were not correlated with patient frailty and had inconsistent associations with surgical outcomes. The findings suggest that assessment of muscle quantity and quality on CT can provide an objective measure of patient frailty that would not otherwise be clinically apparent and that may complement existing risk stratification tools to identify patients at high risk of mortality, morbidity, and readmission.
Published on
April 10, 2024
cited by
16
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Othman Al‐Sawaf, Jakob Weiss, Marcin Skrzypski, Jie Min Lam, Takahiro Karasaki, Francisco Zambrana, Andrew Kidd, Alexander M. Frankell, Thomas B.K. Watkins, Carlos Martínez‐Ruiz, Clare Puttick, James R. Black, Ariana Huebner, Maise Al Bakir, Mateo Sokač, Susie M. Collins, Selvaraju Veeriah, Neil Magno, Cristina Naceur‐Lombardelli, Paulina Prymas, Antonia Toncheva, Sophia Ward, Nick Jayanth, Roberto Salgado, Christopher P. Bridge, David C. Christiani, Raymond H. Mak, Camden Bay, Michael H. Rosenthal, Naveed Sattar, Paul Welsh, Ying Liu, Norbert Perrimon, Karteek Popuri, Mirza Faisal Beg, Nicholas McGranahan, Allan Hackshaw, Danna M. Breen, Stephen O’Rahilly, Nicolai J. Birkbak, Hugo J.W.L. Aerts, Thomas B.K. Watkins, Nicolai J. Birkbak, Hugo J.W.L. Aerts, J.F. Lester, Amrita Bajaj, Apostolos Nakas, Azmina Sodha-Ramdeen, Keng Ang, Mohamad Tufail, Mohammed Fiyaz Chowdhry, Molly Scotland, Rebecca Boyles, Sridhar Rathinam, Claire Wilson, Domenic Marrone, Sean Dulloo, Dean A. Fennell, Gurdeep Matharu, Jacqui Shaw, Joan Riley, Lindsay Primrose, Ekaterini Boleti, Heather Cheyne, Mohammed Khalil, Shirley Richardson, Tracey Cruickshank, Gillian Price, Keith M. Kerr, Sarah Benafif, Kayleigh Gilbert, Babu Naidu, Akshay J. Patel, Aya Osman, Christer Lacson, Gerald Langman, Helen Shackleford, Madava Djearaman, Salma Kadiri, Gary Middleton, Angela Leek, Jack Davies Hodgkinson, Nicola Totten, Ángeles Montero, Elaine Smith, Eustace Fontaine, Felice Granato, Helen Doran, Juliette Novasio, Kendadai Rammohan, Leena Dennis Joseph, Paul N. Bishop, Rajesh Shah, Stuart Moss, Vijay Joshi, Philip Crosbie, Fábio Gomes, Kate Brown, Mathew Carter, Anshuman Chaturvedi
Abstract
Cancer-associated cachexia (CAC) is a major contributor to morbidity and mortality in individuals with non-small cell lung cancer. Key features of CAC include alterations in body composition and body weight. Here, we explore the association between body composition and body weight with survival and delineate potential biological processes and mediators that contribute to the development of CAC. Computed tomography-based body composition analysis of 651 individuals in the TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study suggested that individuals in the bottom 20th percentile of the distribution of skeletal muscle or adipose tissue area at the time of lung cancer diagnosis, had significantly shorter lung cancer-specific survival and overall survival. This finding was validated in 420 individuals in the independent Boston Lung Cancer Study. Individuals classified as having developed CAC according to one or more features at relapse encompassing loss of adipose or muscle tissue, or body mass index-adjusted weight loss were found to have distinct tumor genomic and transcriptomic profiles compared with individuals who did not develop such features. Primary non-small cell lung cancers from individuals who developed CAC were characterized by enrichment of inflammatory signaling and epithelial-mesenchymal transitional pathways, and differentially expressed genes upregulated in these tumors included cancer-testis antigen MAGEA6 and matrix metalloproteinases, such as ADAMTS3. In an exploratory proteomic analysis of circulating putative mediators of cachexia performed in a subset of 110 individuals from TRACERx, a significant association between circulating GDF15 and loss of body weight, skeletal muscle and adipose tissue was identified at relapse, supporting the potential therapeutic relevance of targeting GDF15 in the management of CAC.
Published on
April 1, 2023
cited by
90
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Ijeamaka Anyene, Bette J. Caan, Grant R. Williams, Karteek Popuri, Leon Lenchik, Smith Giri, Vincent Chow, Mirza Faisal Beg, Elizabeth M. Cespedes Feliciano
Abstract
Abstract Background Computed tomography (CT) scans are routinely obtained in oncology and provide measures of muscle and adipose tissue predictive of morbidity and mortality. Automated segmentation of CT has advanced past single slices to multi‐slice measurements, but the concordance of these approaches and their associations with mortality after cancer diagnosis have not been compared. Methods A total of 2871 patients with colorectal cancer diagnosed during 2012–2017 at Kaiser Permanente Northern California underwent abdominal CT scans as part of routine clinical care from which mid‐L3 cross‐sectional areas and multi‐slice T12–L5 volumes of skeletal muscle (SKM), subcutaneous adipose (SAT), visceral adipose (VAT) and intermuscular adipose (IMAT) tissues were assessed using Data Analysis Facilitation Suite, an automated multi‐slice segmentation platform. To facilitate comparison between single‐slice and multi‐slice measurements, sex‐specific z‐scores were calculated. Pearson correlation coefficients and Bland–Altman analysis were used to quantify agreement. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for death adjusting for age, sex, race/ethnicity, height, and tumour site and stage. Results Single‐slice area and multi‐slice abdominal volumes were highly correlated for all tissues (SKM R = 0.92, P < 0.001; SAT R = 0.97, P < 0.001; VAT R = 0.98, P < 0.001; IMAT R = 0.89, P < 0.001). Bland–Altman plots had a bias of 0 (SE: 0.00), indicating high average agreement between measures. The limits of agreement were narrowest for VAT ( 0.42 SD) and SAT ( 0.44 SD), and widest for SKM ( 0.78 SD) and IMAT ( 0.92 SD). The HRs had overlapping CIs, and similar magnitudes and direction of effects; for example, a 1‐SD increase in SKM area was associated with an 18% decreased risk of death (HR = 0.82; 95% CI: 0.72–0.92), versus 15% for volume from T12 to L5 (HR = 0.85; 95% CI: 0.75–0.96). Conclusions Single‐slice L3 areas and multi‐slice T12–L5 abdominal volumes of SKM, VAT, SAT and IMAT are highly correlated. Associations between area and volume measures with all‐cause mortality were similar, suggesting that they are equivalent tools for population studies if body composition is assessed at a single timepoint. Future research should examine longitudinal changes in multi‐slice tissues to improve individual risk prediction.
Published on
September 2, 2022
cited by
52
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Shlomi Peretz, Rivka Kessner, Yael Bar, Amir Sonnenblick, Shir Lerner, Ariella Deutsch-Lukatsky, Karteek Popuri, Mirza Faisal Beg, Shlomit Strulov Shachar
Abstract
Body composition is an important predictor in cancer patients, with skeletal muscle loss and high adiposity associated with poorer prognosis. This study evaluated how body composition affects treatment efficacy in 48 women with metastatic breast cancer receiving trastuzumab deruxtecan. Using computed tomography, skeletal muscle, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were assessed within 60 days before initiating treatment. High SAT and VAT areas were significantly associated with a higher likelihood of dose reductions (Odds Ratio [OR] = 5.34, p = .032 and OR = 5.52, p = 0.032, respectively). Higher SAT areas correlated with a lower objective response rate (OR = 0.22, p = 0.047). Medium SAT and low/medium VAT densities increased the risk of dose reductions. A body mass index over 25 kg/m2 was linked to higher dose reductions (OR = 4.97, p = 0.016). These findings emphasize the need for personalized treatment strategies based on body composition.
Published on
April 25, 2025
cited by
5
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Leo R. Brown, Georgina G Thomson, Ellen Gardner, Siobhan Chien, Josh McGovern, Ross D. Dolan, Stephen T. McSorley, Matthew Forshaw, Donald C. McMillan, Stephen J. Wigmore, Andrew Crumley, Richard J. E. Skipworth
Abstract
Background Features of cancer cachexia adversely influence patient outcomes, yet few currently inform clinical decision-making. This study assessed the value of the cachexia index (CXI), a novel prognostic marker, in patients for whom neoadjuvant chemotherapy and surgery for oesophagogastric cancer is planned. Methods Consecutive patients newly diagnosed with locally advanced (T3–4 or at least N1) oesophagogastric cancer between 1 January 2010 and 31 December 2015 were identified through the West of Scotland and South-East Scotland Cancer Networks. CXI was calculated as (L3 skeletal muscle index) × (serum albumin)/(neutrophil lymphocyte ratio). Sex-stratified cut-off values were determined based on the area under the curve (AUC), and patients were divided into groups with low or normal CXI. Primary outcomes were disease progression during neoadjuvant chemotherapy and overall survival (at least 5 years of follow-up). Results Overall, 385 patients (72% men, median age 66 years) were treated with neoadjuvant chemotherapy for oesophageal (274) or gastric (111) cancer across the study interval. Although patients with a low CXI (men: CXI below 52 (AUC 0.707); women: CXI below 41 (AUC 0.759)) were older with more co-morbidity, disease characteristics were comparable to those in patients with a normal CXI. Rates of disease progression during neoadjuvant chemotherapy, leading to inoperability, were higher in patients with a low CXI (28 versus 12%; adjusted OR 3.07, 95% c.i. 1.67 to 5.64; P < 0.001). Low CXI was associated with worsened postoperative mortality (P = 0.019) and decreased overall survival (median 14.9 versus 56.9 months; adjusted HR 1.85, 1.42 to 2.42; P < 0.001). Conclusion CXI is associated with disease progression, worse postoperative mortality, and overall survival, and could improve prognostication and decision-making in patients with locally advanced oesophagogastric cancer.
Published on
April 1, 2024
cited by
18
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Setarah Mohammad Nader, S. Tyler Jines, Christopher D. Collier, Teresa A. Zimmers, Rafat Abonour, Sherif S. Farag, Mohammad Abu Zaid, Kelvin P. Lee, Attaya Suvannasankha
Abstract
Introduction: Cancer-associated cachexia is associated with poor survival rates in several cancer types. Multiple Myeloma (MM) preferentially occurs in the elderly and is the most common cancer that causes lytic bone metastasis causing bone pain, fractures, mobility limitations, and falls. Cachexia is projected to be common in myeloma but has not been fully studied. Myeloma treatments including corticosteroids, radiation and alkylators cause muscle loss, while novel immunotherapy is tumor-specific but their impact on cachexia is unknown. We characterize the changes in body composition in patients with relapsed/refractory myeloma treated with BCMA bispecific antibody teclistamab and determine the association between body composition with treatement response and overall survival. Methods: 49 MM patients treated with teclistamab between 2000 and 2021 were included. All were with relapsed/refractory disease after > 4 lines of therapy and received an approved dose and schedule of teclistamab. The response assessment was according to IMWG criteria. Body weight, body mass index (BMI), tumor burden, and organ function were assessed at baseline and post-treatment. Standard-of-care abdominopelvic CT or PET/CT scans at baseline and at last known follow up were analyzed with Data Analysis Facilitation Suite (DAFS) software to quantify skeletal muscle (SKM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). Differences between groups were tested using the χ 2 test or paired t-test. Progression free survival (PFS) and overall survival (OS) from the start of teclistamab to progression and death or last follow-up, respectively, were analyzed by the Kaplan-Meier method. Comparisons were made with the log-rank test. Results: Patient characteristics are detailed in Table 1. Based on the WHO definition, 2% were underweight, 16% were normal weight, 19% were overweight and 13% were obese, at baseline. The baseline mean SKM was 105.6 ± 27.8 (Male 122.0 ± 25.3, female 93.4 ± 23.5). SAT and VAT varied widely. Median SAT was 196.5 (range 48.3-558.6), and median VAT was 136.6 (33.09-448.1). Of 32 patients in the obese group, 16 (50%) patients had SKM that was below the mean SKM of the group. Baseline SAT and VAT, but not SKM were correlated with BMI. Twenty-seven of the 49 patients had paired imaging. The absolute changes in skeletal muscle and adipose tissue compartments are shown in Table 2. A majority of patients had a decline in SKM, SAT and VAT post-treatment: mean SKM decrease was 8.9 cm 2 ( p ≤ 0.01), mean SAT decreased 24.3 cm 2 ( p = 0.02) and mean VAT decreased 27.4 cm 2 ( p = 0.03), while BMI and weight were unchanged. Nineteen of 27 (70%) subjects responded to therapy. The changes in SKM, VAT, and SAT loss did not differ significantly between responders and non-responders. 38.8% of patients (19/49) had died by the end of the follow-up. Median follow-up duration was 2.8 years, overall survival was 1.7 years and PFS was 0.9 years. Baseline SKM, SAT, and VAT did not correlate with PFS or OS, but a decline in SMK significantly correlated with a shorter OS (p=0.04); 7/18 patients with decreased SKM and 2/9 patients with unchanged or increased SKM died. Response correlated strongly with overall survival (p=0.002). Conclusions: Body composition analysis of standard CT images may provide clinically relevant information for patients with advanced myeloma. Sarcopenia was common despite high BMI, and a further decline in skeletal muscle mass correlated with shorter survival, regardless of response to tumor-specific immunotherapy. Anthropometric changes should be validated in larger patient cohorts and included in future clinical trials. Further efforts should focus on the maintenance of muscle and visceral adipose tissue in this patient population.
Published on
November 2, 2023
cited by
1
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Star Ye, Christian Harmon, Nadia M. Anabtawi, Clare Ubersax, Abigail Tucker, Gaurav Goyal, Lauren Shea, Mayur Narkhede, Amitkumar Mehta, Purnima Singh, Grant R. Williams, Ravi Bhatia, Smith Giri
Abstract
Introduction: Chemo-immunotherapy with R-CHOP is the standard of care for newly diagnosed DLBCL of all ages leading to high cure rates although treatment-related toxicities are significant among older adults. Prior studies have shown that pre-treatment skeletal muscle mass and/or density can identify older adults at risk of adverse treatment outcomes. We sought to construct a risk-prediction model for severe treatment-related toxicities among older adults with DLBCL receiving chemotherapy by incorporating clinico-demographic features and skeletal muscle mass measurements. Methods: We conducted a single institutional retrospective review of all adults ≥60y with newly diagnosed DLBCL receiving R-CHOP-based regimens between 1/2015 and 2/2021. We extracted baseline clinico-demographic variables (age, sex, race, albumin, ECOG performance status [PS], Charlson comorbidity index [CCI], stage, Revised International Prognostic Index score, growth factor use) and treatment intensity (dose at 1st cycle). Dose reduction was defined as any pre-planned reduction in or elimination of doxorubicin from standard CHOP-based regimens during cycle 1 of treatment. The primary outcome of interest was grade ≥3 treatment-related toxicity (using CTCAE v5.0) or mortality occurring within 30 days after each cycle. Treatment response was defined by Lugano criteria. Skeletal muscle area (SMA) and skeletal muscle density (SMD) were measured with mid-L3 computed tomography images using Data Analysis Facilitation Suite (DAFS) software (Voronoi Analytics, Canada) and was manually verified. Using forward stepwise binary logistic regression models (entry p <0.10, removal p 80y population in which 86% received ≥50% doxorubicin reduction. Over half (57%) experienced grade ≥3 toxicity (50% hematologic toxicity, 36% non-hematologic toxicity). Dose delays (16%), reductions (18%), or discontinuations (15%) were frequent, and over a third (39%) of patients had unplanned hospitalizations during their treatment course. Treatment-related mortality was
Published on
November 15, 2022
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0
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Rusha Bhandari, Kyuwan Lee, Xinyi Du, Stéphane Albanese, Meagan Echevarria, Caitlyn Estrada, Alexander Flores, Aleksi Iukuridze, David Iukuridze, J. E. Kim, Lanie Lindenfeld, Stephanie Rodarte, Nathan Salce, F. Lennie Wong, Saro H. Armenian
Abstract
Background Low muscle mass is associated with adverse outcomes following hematopoietic cell transplantation (HCT). Computed tomography (CT) is a gold standard approach to measuring skeletal muscle but is associated with radiation exposure and no longer routinely performed in all patients before HCT. Alternative methods are needed for early identification, intervention, and serial evaluation of low muscle mass after HCT. Optimal methods should be portable and readily accessible. We thus evaluated the correlation between quadriceps muscle ultrasound (US), whole‐body bioelectrical impedance analysis (BIA), and muscle CT in patients planned to undergo HCT. Methods This study included 71 consecutive patients ≥18 years who underwent first HCT between 2020 and 2024. Pearson correlation examined the relationship between skeletal muscle measurements of cross‐sectional area (CSA) from CT images at the third lumbar vertebra (L3), whole‐body skeletal muscle mass (SMM) from BIA, and CSA from quadriceps muscle US. Results Median age at evaluation was 52.6 years (range: 18.6–76.6). CT‐derived L3 skeletal muscle CSA positively correlated with quadriceps muscle US CSA ( r = 0.73; P < 0.0001) and BIA SMM ( r = 0.92; P < 0.0001). Quadriceps muscle US and BIA SMM were also positively correlated ( r = 0.74; P < 0.0001). Positive correlations were consistent across body mass index (BMI) and age categories. Conclusions Quadriceps muscle US and whole‐body BIA offer reliable alternatives to estimate skeletal muscle without radiation exposure. US is more readily available, allowing for detailed phenotypic evaluation of individual muscles and identification of muscle compromise that may occur following HCT. This can enable development and monitoring of tailored and targeted interventions to improve muscle health and HCT outcomes.
Published on
April 26, 2025
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0
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Ying Wang, Rafael A. Fujita, N. Fujisawa, Janessa Laskin, Pat G. Camp, Sarah Yeo, Gillian V. H. Smith, Kendra Zadravec, Kelly MacKenzie, Kristin L. Campbell
Abstract
Introduction
Exercise can mitigate declines in physical function for patients with cancer, but in-person exercise programs for patients with advanced lung cancer often face low recruitment and retention. This prospective study assessed the feasibility of virtual exercise for patients with advanced lung cancer.
Methods
Mitigation of decline with Virtual Exercise (MoVE) with Lung Cancer was a prospective, single-arm, feasibility study. Patients with advanced lung cancer undergoing systemic therapy in British Columbia, Canada participated in a 12-week group exercise program delivered twice weekly via Zoom. Feasibility measures included accrual, recruitment rate, attendance, adherence, attrition, adverse events, and group belongingness. Efficacy was assessed via effect on physical function, cardiovascular fitness, body composition, and quality of life (QoL).
Results
Twenty-seven patients were enrolled (median age = 66 years). Most had adenocarcinoma (92 %) and were on targeted therapy (73 %). Recruitment rate was 61 %, attrition 4 %, attendance 87 %, and adherence 96 %. Significant improvements were seen in gait speed (Z = 2.759, p = 0.006), 30-second chair stand (Z = 3.810, p < 0.001), 30-second bicep curl (Z = 4.209, p
Published on
February 3, 2025
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0
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Ian Persits, Saeid Mirzai, Kunaal S. Sarnaik, Maximilian Volk, James Yun, Serge C. Harb, Rishi Puri, Samir Kapadia, Amar Krishnaswamy, Po‐Hao Chen, Grant W. Reed, W.H. Wilson Tang
Abstract
Low muscle mass (LMM) is associated with worse outcomes in various clinical situations. Traditional frailty markers have been used for preoperative risk stratification in patients who underwent transcatheter aortic valve replacement (TAVR). However, preoperative imaging provides an opportunity to directly quantify skeletal muscle mass to identify patients at higher risk of procedural complications. We reviewed all TAVR recipients from January to December 2018 and included subjects with preprocedural chest computed tomography. Multi-slice automated measurements of skeletal muscle mass were made from the ninth to twelfth thoracic vertebrae and normalized by height squared to obtain skeletal muscle index (cm2/m2). LMM was defined as the lowest gender-stratified skeletal muscle index tertile. Strength testing was collected during pre-TAVR evaluation. Primary outcome was a composite of perioperative complications, 1-year rehospitalization, or 1-year mortality. In our cohort, 238 patients met inclusion criteria, and 80 (33.6%) were identified to have LMM. Patients with LMM were older with lower body mass index, decreased grip strength, lower hemoglobin A1c, and higher N-terminal pro-brain natriuretic peptide. They had greater rates of the composite outcome and 2-year all-cause mortality, which remained significant on multivariable adjustment (hazard ratio 1.71, 95% confidence interval 1.05 to 2.78, p = 0.030 and hazard ratio 2.31, 95% confidence interval 1.02 to 5.24, p = 0.045, respectively) compared with patients without LMM; there was no significant difference in 5-year all-cause mortality. In conclusion, LMM was associated with an increase in the primary composite outcome and 2-year all-cause mortality in TAVR recipients. Using automatic muscle processing software on pre-TAVR computed tomography scans may serve as an additional preoperative risk stratification tool.
Published on
March 1, 2024
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6
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Prasanna Santhanam, Roshan Dinparastisaleh, Karteek Popuri, Mirza Faisal Beg, Stanley M. Chen Cardenas, Amir H. Hamrahian
Abstract
Abstract Determination of body composition (the relative distribution of fat, muscle, and bone) has been used effectively to assess the risk of progression and overall clinical outcomes in different malignancies. Sarcopenia (loss of muscle mass) is especially associated with poor clinical outcomes in cancer. However, estimation of muscle mass through CT scan has been a cumbersome, manually intensive process requiring accurate contouring through dedicated personnel hours. Recently, fully automated technologies that can determine body composition in minutes have been developed and shown to be highly accurate in determining muscle, bone, and fat mass. We employed a fully automated technology, and analyzed images from a publicly available cancer imaging archive dataset (TCIA) and a tertiary academic center. The results show that adrenocortical carcinomas (ACC) have relatively sarcopenia compared to benign adrenal lesions. In addition, functional ACCs have accelerated sarcopenia compared to non-functional ACCs. Further longitudinal research might shed further light on the relationship between body component distribution and ACC prognosis, which will help us incorporate more nutritional strategies in cancer therapy.
Published on
May 28, 2024
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3
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Katherine L. Ford, Michael B. Sawyer, Sunita Ghosh, Claire F. Trottier, Ilana Roitman Disi, Jacob C. Easaw, K. Mulder, Sheryl Koski, Kathryn N. Porter Starr, C. W. Bales, Jann Arends, Mario Siervo, Nicolaas E.P. Deutz, Carla M. Prado
Abstract
Background
Low muscle mass (MM) predicts unfavorable outcomes in cancer. Protein intake supports muscle health, but oncologic recommendations are not well characterized. The objectives of this study were to evaluate the feasibility of dietary change to attain 1.0 or 2.0 g/kg/day protein diets, and the preliminary potential to halt MM loss and functional decline in patients starting chemotherapy for stage II-IV colorectal cancer.
Patients and methods
Patients were randomized to the diets and provided individualized counseling. Assessments at baseline, 6 weeks, and 12 weeks included weighed 3-day food records, appendicular lean soft tissue index (ALSTI) by dual-energy X-ray absorptiometry to estimate MM, and physical function by the Short Physical Performance Battery (SPPB) test.
Results
Fifty patients (mean ± standard deviation: age, 57 ± 11 years; body mass index, 27.3 ± 5.6 kg/m2; and protein intake, 1.1 ± 0.4 g/kg/day) were included at baseline. At week 12, protein intake reached 1.6 g/kg/day in the 2.0 g/kg/day group and 1.2 g/kg/day in the 1.0 g/kg/day group (P = 0.012), resulting in a group difference of 0.4 g/kg/day rather than 1.0 g/kg/day. Over one-half (59%) of patients in the 2.0 g/kg/day group maintained or gained MM compared with 44% of patients in the 1.0 g/kg/day group (P = 0.523). Percent change in ALSTI did not differ between groups [2.0 g/kg/day group (mean ± standard deviation): 0.5% ± 4.6%; 1.0 g/kg/day group: −0.4% ± 6.1%; P = 0.619]. No differences in physical function were observed between groups. However, actual protein intake and SPPB were positively associated (β = 0.37; 95% confidence interval 0.08-0.67; P = 0.014).
Conclusion
Individualized nutrition counselling positively impacted protein intake. However, 2.0 g/kg/day was not attainable using our approach in this population, and group contamination occurred. Increased protein intake suggested positive effects on MM and physical function, highlighting the potential for nutrition to attenuate MM loss in patients with cancer. Nonetheless, muscle anabolism to any degree is clinically significant and beneficial to patients. Larger trials should explore the statistical significance and clinical relevance of protein interventions.
Published on
June 26, 2024
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8
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Michelle V. Dietz, Karteek Popuri, Lars A.L. Janssen, Mushfiqus Salehin, Da Ma, Vincent Chow, Hyunwoo Lee, Cornelis Verhoef, Eva V. E. Madsen, Mirza Faisal Beg, Jeroen L.A. van Vugt
Abstract
Introduction
Body composition evaluation can be used to assess patients’ nutritional status to predict clinical outcomes. To facilitate reliable and time-efficient body composition measurements eligible for clinical practice, fully automated computed tomography segmentation methods were developed. The aim of this study was to evaluate automated segmentation by Data Analysis Facilitation Suite in an independent dataset.
Materials and methods
Preoperative computed tomography images were used of 165 patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy from 2014 to 2019. Manual and automated measurements of skeletal muscle mass (SMM), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and intramuscular adipose tissue (IMAT) were performed at the third lumbar vertebra. Segmentation accuracy of automated measurements was assessed using the Jaccard index and intra-class correlation coefficients.
Results
Automatic segmentation provided accurate measurements compared to manual analysis, resulting in Jaccard score coefficients of 94.9 for SMM, 98.4 for VAT, 99.1 for SAT, and 79.4 for IMAT. Intra-class correlation coefficients ranged from 0.98 to 1.00. Automated measurements on average overestimated SMM and SAT areas compared to manual analysis, with mean differences (±2 standard deviations) of 1.10 (–1.91 to 4.11) and 1.61 (–2.26 to 5.48) respectively. For VAT and IMAT, automated measurements on average underestimated the areas with mean differences of –1.24 (–3.35 to 0.87) and –0.93 (–5.20 to 3.35), respectively.
Conclusions
Commercially available Data Analysis Facilitation Suite provides similar results compared to manual measurements of body composition at the level of third lumbar vertebra. This software provides accurate and time-efficient body composition measurements, which is necessary for implementation in clinical practice.
Published on
October 5, 2024
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6
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Aron Bode, Christan Bury, Mariana Luís, Lindsey Russell
Abstract
Objectives: Pancreatic adenocarcinoma leads to significant nutritional challenges due to altered digestion and appetite, making nutrition support crucial to avoid severe malnutrition. As the disease progresses, individuals often experience muscle wasting and decreased physical performance, necessitating nutrition assessment and intervention. The use of CT by registered dietitians has provided quantitative evaluation of body tissues to monitor outcomes.
Methods: Here we present a case of a 70 yr old female with stage IIA pancreatic adenocarcinoma complicated by small bowel perforation with Whipple and end ileostomy with subsequent weight loss leading to parenteral nutritional (PN) support. She had limited oral intake due to high ostomy output and abdominal pain. Multiple CT scans were completed, which were used to assess body composition. The CT scans revealed significant muscle loss and worsening body composition (29.6% decrease) from her baseline to when PN was initiated. PN as her main source of nutrition at the time led to improvement of her skeletal muscle mass (44.3% increase) as measured by an artificial intelligence program, Voronoi Data Analysis Facilitation Suite, Version 3.9.1. Of note she did not develop any infectious complications from PN. Upon withdrawal of nutrition support, she experienced a decrease in her muscle mass, but not as severe (11.4% decrease).
Results: This case highlights the dynamic nature of skeletal muscle mass changes in response to targeted nutritional and physical interventions. The initial decline in muscle mass followed by a significant increase during the nutrition intervention period, and subsequent decrease post-intervention, provide valuable insights into the effectiveness and limitations of such approaches in managing muscle mass. Finally, the worsening of muscle mass post withdrawal of nutritional support suggests the need for ongoing monitoring and nutritional assessment.
Conclusions: Assessing body composition accurately through the course of disease can provide a more comprehensive assessment of nutritional status. Understanding the changes in body composition can aid in the development of personalized nutrition strategies for maintaining and improving muscle mass in similar clinical scenarios.
Published on
May 1, 2025
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0
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Smith Giri, Christian Harmon, Daniel L. Hess, Elizabeth M. Cespedes Feliciano, Ijeamaka Anyene Fumagalli, Bette J. Caan, Leon Lenchik, Karteek Popuri, Vincent Chow, Mirza Faisal Beg, Ravi Bhatia, Grant R. Williams
Abstract
Background Older adults with cancer are at an increased risk of treatment related toxicities and early death. Routinely collected clinico‐demographic characteristics inadequately explain this increased risk limiting accurate prognostication. Prior studies have suggested that altered body composition and frailty are independently associated with worse survival among older adults with cancer; however, their combined influence remains unclear. Methods We used data from a single‐institution prospective cohort study of older adults (≥ 60 years) who underwent geriatric assessment (GA) at the time of initial consultation with a medical oncologist from September 2017 to December 2020 and available baseline abdominal computed tomography within 60 days of GA. Using multi‐slice CT images from T12 to L5 level, we assessed volumetric measures of skeletal muscle (SMV), visceral adipose tissue (VATV), subcutaneous adipose tissue (SATV) and averaged skeletal muscle density (SMD), computing sex‐specific z for each measure. Frailty was measured using a 44‐item frailty index using the deficit accumulation approach. Primary outcome of interest was overall survival (OS) defined as time from GA to death or last follow up. We used multivariable Cox regression model to study the independent association between the above four body composition measurements and OS adjusted for baseline confounders and frailty. Results We included 459 patients with a mean age of 69.7 ± 7.5 years, 60% males and 77% non‐Hispanic Whites. Most had colorectal (27%) or pancreatic cancer (20%) and 48% had stage IV disease. Over a median follow up of 39.4 months, 209 patients (46%) died. In multivariable Cox regression models adjusted for age, sex, race, cancer type, cancer stage and frailty, skeletal muscle volume (HR 0.74; 95% CI 0.58–0.96; p = 0.02, per 1 SD increment) was independently associated with OS. The addition of body composition variables to baseline clinico‐demographic variables and frailty led to a slightly improved model discrimination. Conclusions SMV is independently associated with OS among older adults with newly diagnosed gastrointestinal cancers. Capturing body composition measurements in oncology practice may provide additional prognostic information for older adults with cancer above and beyond what is captured in routine clinical assessment including frailty.
Published on
December 23, 2024
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4
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Leo R. Brown, Maria Soupashi, Michael S. Yule, Danielle Clyde, Ellen Gardner, Charlotte Smith, Ahmed Dhaif, Barry Laird, Stephen J. Wigmore, Richard J.E. Skipworth
Abstract
Background Single‐slice computed tomography (CT) body composition has been studied extensively for prognostication in patients with cancer. New software packages can also provide multi‐slice volumetric measurements, but the clinical utility of these remains under explored. This study aimed to evaluate the agreement between single‐ and multi‐slice body composition analyses in patients with oesophagogastric cancer and to explore the association between these measures and overall survival. Methods Consecutive patients with newly diagnosed oesophagogastric (OG) cancer were identified through the prospectively maintained regional database of the South East Scotland Cancer Network across a 2‐year study period. CT body composition analyses were undertaken using scans collected during routine clinical care. Single‐slice (cross‐sectional area at mid L3) and multi‐slice (volume between T12 and L4) measurements were compared for skeletal muscle (SKM), subcutaneous adipose (SAT), visceral adipose (VAT) and intermuscular adipose (IMAT). Agreement between sex‐stratified z‐scores was quantified using Pearson correlation coefficients and Bland–Altman analyses. Cox proportional hazard modelling was used to estimate the effect of these measures on overall survival. Results Overall, 504 patients (67.9% male, median 72 years) were newly diagnosed with OG cancer during the study period. Single‐ and multi‐slice (mean: 169 slices) measurements correlated highly for SKM (R: 0.97, p < 0.001), SAT (R: 0.98, p < 0.001), VAT (R: 0.97, p < 0.001), SKM radiodensity (R: 0.93, p < 0.001) and IMAT (R: 0.88, p < 0.001). Bias on Bland–Altman analysis was 0.00 for all tissue measurements. Limits of agreement (LoA) were narrowest for SAT (±0.43), VAT (±0.46) and SKM (±0.48), but slightly wider for SKM radiodensity (±0.73) and IMAT (±0.96). Adipose tissue ‘outliers’ (those where agreement between single‐ and multi‐slice z‐scores was outside the LoA) had a higher median weight and body mass index (BMI), suggestive of poorer agreement in patients with obesity. Sensitivity analysis, excluding those with BMI > 30, narrowed the LoA for SKM, VAT, SAT and IMAT. Direction and magnitudes of observed effect sizes for overall survival were all highly comparable, with hazard ratios for each tissue type varying by ≤ 0.04 between single‐ and multi‐slice adjusted estimates. Conclusions Single‐slice and multi‐slice CT assessments provide highly correlated tissue measurements amongst patients with OG cancer. Associations between these measurements and overall survival were also comparable across both types of body composition analysis. Agreement between single‐ and multi‐slice measurements of adiposity is worse in patients with obesity, suggesting single‐slice analyses may less accurately reflect the quantity or distribution of adipose tissue in this patient group.
Published on
December 26, 2024
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ITARU HASHIMOTO, KEISUKE KOMORI, SHIZUΝE ONUMA, Hayato Watanabe, Hideaki Suematsu, Shinsuke Nagasawa, Kazuki Kano, Taiichi Kawabe, Toru Aoyama, Tsutomu Hayashi, Yamada Takanobu, Tsutomu Sato, Aya Saito, Takashi Ogata, Haruhiko Cho, Takaki Yoshikawa, Yasushi Rino, Takashi Oshima
Abstract
Background The postoperative impact of short‐term changes in skeletal muscle loss (SML) and adipose tissue loss (ATL) on treatment outcomes is unclear in patients with gastric cancer (GC). We investigate the role of SML and ATL at 1 month after surgery in determining postoperative survival and recurrence rates in patients with GC. Methods We analyzed 540 patients with GC and assessed their skeletal muscle mass, visceral fat mass, and subcutaneous fat mass using computed tomography scans preoperatively and 1 month postoperatively. Patients were categorized into high and low groups based on their levels of SML, visceral ATL (v‐ATL), and subcutaneous ATL (s‐ATL). Additionally, they were classified into three groups (high ATL, intermediate ATL, and low ATL) based on their v‐ATL and s‐ATL measurements. Results Patients with higher v‐ATL and s‐ATL had lower overall survival (OS) and recurrence‐free survival (RFS) rates. High ATL was an independent prognostic factor for decreased OS (hazard ratio [HR] 2.27; 95% confidence interval [CI] 1.16–4.42; and P = 0.02) and RFS (HR 2.51; 95% CI 1.34–4.71; and P = 0.004) rates. Conclusion A reduction in adipose tissue volume shortly after surgery (1 month) could potentially indicate an increased risk of recurrence and mortality in patients with GC.
Published on
November 14, 2024
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0
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Mateusz Malik, Maciej Michalak, Barbara Radecka, Marek Gełej, Aleksandra Jackowska, Emilia Filipczyk−Cisarż, Katarzyna Hetman, Małgorzata Foszczyńska‐Kłoda, Beata Kania-Zembaczyńska, Danuta Mańka, Marlena Orlikowska, Hanna Rogowska-Droś, Lubomir Bodnar
Abstract
Sarcopenia is common in metastatic colorectal cancer (mCRC), increases the risk of treatment-related toxicity and reduces survival. Trifluridine/tipiracil (TT) chemotherapy significantly improved survival in refractory mCRC patients, but the prognostic and predictive role of pretherapeutic sarcopenia and variation in the skeletal muscle index (SMI) during this treatment has not been investigated so far. In this retrospective, observational study, clinical data on mCRC patients treated with TT at six cancer centres in Poland were collected. Computed tomography (CT) scans acquired at the time of initiation of TT (CT1) and on the first restaging (CT2), were evaluated. SMI was assessed based on the skeletal muscle area (SMA) at the level of the third lumbar vertebra. Progression-free survival (PFS) and overall survival (OS) were calculated from the treatment start. Neither initial sarcopenia nor ≥5% skeletal mass loss (SML) between CT1 and CT2 had a significant effect on PFS in treated patients (p = 0.5526 and p = 0.1092, respectively). In the multivariate analysis, reduced OS was found in patients with ≥5% SML (HR: 2.03 (1.11–3.72), p = 0.0039). We describe the prognostic role of sarcopenia beyond second line treatment and analyze other factors, such as performance status, tumor histological differentiation or carcinoembryonic antigen level that could predict TT treatment response.
Published on
October 30, 2021
cited by
10
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Ijeamaka Anyene Fumagalli, Erica T. Warner, Adana A. M. Llanos, Charles P. Quesenberry, Wendy Y. Chen, Bette J. Caan, Elizabeth M. Cespedes Feliciano
Abstract
Abstract Background The disproportionate burden of obesity among Black women may contribute to disparities in breast cancer survival; yet, associations of body mass index (BMI), a proxy for total adiposity, are inconsistent. Methods To examine racial/ethnic differences in body composition and evaluate associations with breast cancer–specific and all‐cause mortality, this study identified 3898 women 18 to <90 years old, diagnosed in 2005–2019 with stage II‐III breast cancer at Kaiser Permanente Northern California. The authors measured subcutaneous, visceral, and intermuscular adipose tissue area from computed tomography scans. Results Body composition differed by race: compared to other race/ethnicity groups, Black women had higher skeletal muscle and subcutaneous adipose, but lower visceral adipose tissues, whereas Asian/Pacific Islander women had lower intermuscular and subcutaneous adipose tissue. BMI was not significantly associated with mortality in any group. Among Black women, higher subcutaneous adipose tissue was associated with breast cancer–specific mortality (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.02–1.52) and all adipose tissue measures were associated with increased all‐cause mortality (intermuscular HR, 1.26; 95% CI, 1.09–1.46; subcutaneous HR, 1.25; 95% CI, 1.05–1.48; and visceral HR, 1.32; 95% CI, 1.03–1.68, respectively). By contrast, only increased intermuscular adipose tissue was associated with all‐cause mortality among White women (HR, 1.08; 95% CI, 1.00–1.16), with null associations for Hispanic and Asian/Pacific Islander women. Conclusions BMI obscures variation in body composition, particularly for Black women, who have more subcutaneous adipose and skeletal muscle but less visceral adipose tissue at higher BMIs. These findings from routine imaging highlight opportunities for tailored lifestyle interventions to improve survivorship and mitigate disparities.
Published on
June 6, 2025
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Lauren K. Park, Kian‐Huat Lim, J. L. Volkman, Mina Abdiannia, Hannah Johnston, Zack Nigogosyan, Marilyn J. Siegel, Janet B. McGill, Alexis M. McKee, Maamoun Salam, Rong M. Zhang, Da Ma, Karteek Popuri, Vincent Chow, Mirza Faisal Beg, William G. Hawkins, Linda R. Peterson, Joseph E. Ippolito
Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Thus, there is an urgent need for safe and effective novel therapies. PDAC's excessive reliance on glucose metabolism for its metabolic needs provides a target for metabolic therapy. Preclinical PDAC models have demonstrated that targeting the sodium-glucose co-transporter-2 (SGLT2) with dapagliflozin may be a novel strategy. Whether dapagliflozin is safe and efficacious in humans with PDAC is unclear.
Methods: We performed a phase 1b observational study (ClinicalTrials.gov ID NCT04542291; registered 09/09/2020) to test the safety and tolerability of dapagliflozin (5 mg p.o./day × 2 weeks escalated to 10 mg p.o./day × 6 weeks) added to standard Gemcitabine and nab-Paclitaxel (GnP) chemotherapy in patients with locally advanced and/or metastatic PDAC. Markers of efficacy including Response Evaluation Criteria in Solid Tumors (RECIST 1.1) response, CT-based volumetric body composition measurements, and plasma chemistries for measuring metabolism and tumor burden were also analyzed.
Results: Of 23 patients who were screened, 15 enrolled. One expired (due to complications from underlying disease), 2 dropped out (did not tolerate GnP chemotherapy) during the first 4 weeks, and 12 completed. There were no unexpected or serious adverse events with dapagliflozin. One patient was told to discontinue dapagliflozin after 6 weeks due to elevated ketones, although there were no clinical signs of ketoacidosis. Dapagliflozin compliance was 99.4%. Plasma glucagon increased significantly. Although abdominal muscle and fat volumes decreased; increased muscle-to-fat ratio correlated with better therapeutic response. After 8 weeks of treatment in the study, partial response (PR) to therapy was seen in 2 patients, stable disease (SD) in 9 patients, and progressive disease (PD) in 1 patient. After dapagliflozin discontinuation (and chemotherapy continuation), an additional 7 patients developed the progressive disease in the subsequent scans measured by increased lesion size as well as the development of new lesions. Quantitative imaging assessment was supported by plasma CA19-9 tumor marker measurements.
Conclusions: Dapagliflozin is well-tolerated and was associated with high compliance in patients with advanced, inoperable PDAC. Overall favorable changes in tumor response and plasma biomarkers suggest it may have efficacy against PDAC, warranting further investigation.
Published on
May 18, 2023
cited by
23
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Ian Persits, Saeid Mirzai, Kunaal S. Sarnaik, Maximilian Volk, James Yun, Serge C. Harb, Rishi Puri, Samir Kapadia, Amar Krishnaswamy, Po‐Hao Chen, Grant Reed, W.H. Wilson Tang
Abstract
Background: Skeletal muscle mass (SMM) plays a crucial role in risk assessment in transcatheter aortic valve replacement (TAVR) candidates, yet it remains underutilized. Traditional methods focus on weakness or performance but omit SMM. This study compared traditional and novel markers of sarcopenia and frailty in terms of their ability to predict adverse outcomes post-TAVR.
Methods: Three risk models were evaluated for the composite outcome of perioperative complications, 1-year rehospitalization, or 1-year mortality: (1) sarcopenia by combining low muscle mass (LMM) and weakness/performance assessed by hand grip strength or gait speed; (2) frailty by an Adapted Green score; and (3) frailty by the Green-SMI score incorporating LMM by multilevel opportunistic pre-TAVR thoracic CT segmentation.
Results: In this study we included 184 eligible patients from January to December of 2018, (96.7%) of which were balloon expandable valves. The three risk models identified 22.8% patients as sarcopenic, 63.6% as frail by the Adapted Green score, and 53.8% as frail by the Green-SMI score. There were higher rates of the composite outcome in patients with sarcopenia (54.8%) and frailty (41.9% with the Adapted Green and 50.5% with the Green-SMI score) compared to their nonsarcopenic (30.3%) and nonfrail counterparts (25.4% with the Adapted Green and 18.8% with the Green-SMI score). Sarcopenia and frailty by Green-SMI, but not by the Adapted Green, were associated with higher risks of the composite outcome on multivariable adjustment (HR 2.2 [95% CI: 1.25-4.02], P = .007 and HR 3.4 [95% CI: 1.75-6.65], P
Published on
July 18, 2024
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2
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Jason Rai, Edward T. Pring, Katrina Knight, Henry S. Tilney, Judy Gudgeon, Mark Gudgeon, Fiona Taylor, Laura E. Gould, Joel Wong, Stefano Andreani, Dinh V.C., Ioanna Drami, Phillip Lung, Thanos Athanasiou, Campbell S.D. Roxburgh, John T. Jenkins
Abstract
Background Accurate preoperative risk assessment for major colorectal cancer (CRC) surgery remains challenging. Body composition (BC) and cardiopulmonary exercise testing (CPET) can be used to evaluate risk. The relationship between BC and CPET in patients undergoing curative CRC surgery is unclear. Methods Consecutive patients undergoing CPET prior to CRC surgery between 2010 and 2020 were identified between two different UK hospitals. Body composition phenotypes such as sarcopenia, myosteatosis, and visceral obesity were defined using widely accepted thresholds using preoperative single axial slice CT image at L3 vertebrae. Relationships between clinicopathological, BC, and CPET variables were investigated using linear regression analysis. Results Two hundred eighteen patients with stage I–III CRC were included. The prevalence of sarcopenia, myosteatosis, and visceral obesity was 62%, 33%, and 64%, respectively. The median oxygen uptake at anaerobic threshold (VO2 at AT) was 12.2 mL/kg/min (IQR 10.6–14.2), and oxygen uptake at peak exercise (VO2 peak) was 18.8 mL/kg/min (IQR 15.4–23). On univariate linear regression analysis, male sex ( P < 0.001) was positively associated with VO2 at AT. While ASA grade ( P < 0.001) and BMI ( P = 0.007) were negatively associated with VO2 at AT, on multivariate linear regression analysis, these variables remained significant ( P < 0.05). On univariate linear regression analysis, male sex ( P < 0.001) was positively associated with VO2 peak, whereas age ( P < 0.001), ASA grade ( P < 0.001), BMI ( P = 0.003), sarcopenia ( P = 0.015), and myosteatosis ( P < 0.001) were negatively associated with VO2 peak. On multivariate linear regression analysis age ( P < 0.001), ASA grade ( P < 0.001), BMI ( P < 0.001), and sarcopenia ( P = 0.006) were independently and negatively associated with VO2 peak. Conclusions The novel finding that sarcopenia is independently associated with reduced VO2 peak performance in CPET supports the supposition that reduced muscle mass relates to poor physical function in CRC patients. Further work should be undertaken to assess whether sarcopenia diagnosed on CT can act as suitable surrogate for CPET to further enhance personalized risk stratification.
Published on
June 26, 2024
cited by
5
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Leo R. Brown, Michael I. Ramage, Ross D. Dolan, Judith Sayers, Nikki Bruce, Lachlan Dick, Sharukh Sami, Donald C. McMillan, Barry Laird, Stephen J. Wigmore, Richard J. E. Skipworth
Abstract
This study aimed to longitudinally assess CT body composition analyses in patients who experienced anastomotic leak post-oesophagectomy. Consecutive patients, between 1 January 2012 and 1 January 2022 were identified from a prospectively maintained database. Changes in computed tomography (CT) body composition at the third lumbar vertebral level (remote from the site of complication) were assessed across four time points where available: staging, pre-operative/post-neoadjuvant treatment, post-leak, and late follow-up. A total of 20 patients (median 65 years, 90% male) were included, with a total of 66 computed tomography (CT) scans analysed. Of these, 16 underwent neoadjuvant chemo(radio)therapy prior to oesophagectomy. Skeletal muscle index (SMI) was significantly reduced following neoadjuvant treatment (p < 0.001). Following the inflammatory response associated with surgery and anastomotic leak, a decrease in SMI (mean difference: −4.23 cm2/m2, p < 0.001) was noted. Estimates of intramuscular and subcutaneous adipose tissue quantity conversely increased (both p < 0.001). Skeletal muscle density fell (mean difference: −5.42 HU, p = 0.049) while visceral and subcutaneous fat density were higher following anastomotic leak. Thus, all tissues trended towards the radiodensity of water. Although tissue radiodensity and subcutaneous fat area normalised on late follow-up scans, skeletal muscle index remained below pre-treatment levels.
Published on
April 30, 2023
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2
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Arsalan Khan, Savan K Shah, Sanjib Basu, Gillian Alex, Jun Li, Christopher W. Seder, Nicole Geissen
Abstract
Background: In non-small cell lung cancer, reduced adipose cross-sectional area at the L3 vertebral level is associated with worse survival, however its association with occult nodal disease (OND) in patients with clinically node negative (cN0) non-small cell lung cancer remains unknown.
Methods: Patients who underwent lung resection with guideline-concordant nodal staging between 2010-2021 were identified from an institutional database. Occult nodal disease was defined as patients who were cN0 and pathologically node-positive (pN+). Thoracic volumetric body composition analysis of preoperative chest CTs was performed from T1-T12 using Data Analysis Facilitation Suite. Patients in the lowest tertile of each adiposity index were compared to the rest of the cohort for rates of OND. Univariable and multivariable logistic regression/Cox proportional hazards analyses were used to examine associations with OND and disease-free survival, respectively.
Results: A total of 224 patients met inclusion criteria, of which 55% (123/224) were female, with a median body mass index of 27 kg/m2 (interquartile range [IQR] 23-31), and median tumor size of 2.8 cm (IQR 1.8-4.8). Occult nodal disease was identified in 26% (58/224) and recurrence in 25% (57/224) of patients. Upon univariable analysis in 123 female patients, OND was associated with epicardial adipose index (odds ratio [OR] 2.86, 95% confidence interval [CI] 1.23-6.62, p = 0.014) and thoracic subcutaneous adipose index (OR 2.38, 95% CI 1.03-5.5, p = 0.043) in females. Upon multivariable analysis, this association persisted for thoracic subcutaneous adipose index (OR 6.32, 95% CI 1.65-24.18, p = 0.007) and epicardial adipose index (OR 2.96, 95% CI 1.05-8.28, p = 0.039) in females.
Conclusions: Reduced thoracic subcutaneous and epicardial adipose volume is associated with OND in females.
Published on
June 3, 2025
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0
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N Fries, Angeliki Kotti, Mischa Woisetschläger, Anna Spångéus
Abstract
Background: Sarcopenia is a skeletal muscle disease primarily associated with ageing and progressive muscle decline and increases the risk of falls. The purpose of the present study was to investigate risk factors, including sarcopenia, for severe falls compared to non-severe falls. In addition, we wanted to explore possible associations between sarcopenia, bone mineral density (BMD), adipose tissue as well as clinical scores assessing frailty, nutritional status, and fall risk.
Methods: This retrospective cohort study included 101 older patients that had experienced a fall incident during in-patient care at a geriatric ward between 2018 and 2020. The fall incidents were categorized into severe or non-severe falls. Clinical data, including risk assessment scores were retrospectively obtained from the participants' medical records. Body composition, including skeletal muscle quantity (SKM), adipose tissues, and BMD were assessed from abdominal CT-scans performed for any reason maximal 6 months before or after the fall. Skeletal muscle index ratio (SMI-ratio) was calculated using SKM cm2/height m2 and divided with previous described cut off values for sarcopenia. An SMI ratio
Published on
February 1, 2025
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2
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Olesya Mironchuk, Andrew L. Chang, Farzaneh Rahmani, Kaitlyn Portell, Elena Núñez, Zack Nigogosyan, Da Ma, Karteek Popuri, Vincent Chow, Mirza Faisal Beg, Jingqin Luo, Joseph E. Ippolito
Abstract
Clinically, the body mass index remains the most frequently used metric of overall obesity, although it is flawed by its inability to account for different adipose (i.e., visceral, subcutaneous, and inter/intramuscular) compartments, as well as muscle mass. Numerous prior studies have demonstrated linkages between specific adipose or muscle compartments to outcomes of multiple diseases. Although there are no universally accepted standards for body composition measurement, many studies use a single slice at the L3 vertebral level. In this study, we use computed tomography (CT) studies from patients in The Cancer Genome Atlas (TCGA) to compare current L3-based techniques with volumetric techniques, demonstrating potential limitations with level-based approaches for assessing outcomes. In addition, we identify gene expression signatures in normal kidney that correlate with fat and muscle body composition traits that can be used to predict sex-specific outcomes in renal cell carcinoma.
Published on
November 6, 2024
cited by
3
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Giorgio Raia, Maria Del Grande, Ilaria Colombo, Marta Nerone, Lucia Manganaro, Maria Luisa Gasparri, Andrea Papadia, Filippo Del Grande, Stefania Rizzo
Abstract
Background: The primary objective of this study was to assess the associations of computed tomography (CT)-based whole-body composition values with overall survival (OS) and progression-free survival (PFS) in epithelial ovarian cancer (EOC) patients. The secondary objective was the association of body composition with chemotherapy-related toxicity. Methods: Thirty-four patients (median age 64.9 years; interquartile range 55.4–75.4) with EOC and thorax and abdomen CT scans were included. Clinical data recorded: age; weight; height; stage; chemotherapy-related toxicity; and date of last contact, progression and death. Automatic extraction of body composition values was performed by dedicated software. Sarcopenia was defined according to predefined cutoffs. Statistical analysis included univariate tests to investigate associations of sarcopenia and body composition with chemotoxicity. Association of body composition parameters and OS/PFS was evaluated by log-rank test and Cox proportional hazard model. Multivariate models were adjusted for FIGO stage and/or age at diagnosis. Results: We found significant associations of skeletal muscle volume with OS (p = 0.04) and PFS (p = 0.04); intramuscular fat volume with PFS (p = 0.03); and visceral adipose tissue, epicardial and paracardial fat with PFS (p = 0.04, 0.01 and 0.02, respectively). We found no significant associations between body composition parameters and chemotherapy-related toxicity. Conclusions: In this exploratory study, we found significant associations of whole-body composition parameters with OS and PFS. These results open a window to the possibility to perform body composition profiling without approximate estimations.
Published on
May 4, 2023
cited by
3
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Arsalan Khan, Wara Naeem, Mumtaz Ahmad Ansari, Oluwamuyiwa W Adebayo, Savan K Shah, Gillian Alex, Nicole Geissen, Jun Li, Christopher W. Seder
Abstract
Background: Sarcopenia has emerged as a prognostic biomarker in lung cancer, yet the optimal radiological metric for its assessment remains debated. Skeletal Muscle Gauge (SMG), a composite of muscle volume and density, may offer superior prognostic utility compared with individual measures.
Patients and methods: We retrospectively analyzed 343 patients who underwent lung resection for clinical stage I-IIB NSCLC between 2010 and 2021 and had a preoperative positron emission tomography (PET) scan. Volumetric body composition metrics, skeletal muscle index, skeletal muscle area, skeletal muscle density (SMD), and SMG were derived from automated segmentation using PET scans followed by normalization. Associations with overall survival was assessed using Cox proportional hazards analyses. Predictive accuracy was evaluated using the concordance index. Optimal SMG cutoff was determined by maximally selected rank statistics.
Results: SMG and SMD were independently associated with overall survival after adjustment for clinical and tumor characteristics. SMG and SMD demonstrated the highest prognostic accuracy (C-index 0.743 and 0.710, respectively). No linear relationship was observed between skeletal muscle metrics and BMI, underscoring the limitation of BMI in detecting sarcopenia. SMG values < 87,816 AU were associated with significantly worse survival in both sexes (HR 2.34, 95% CI 1.48-3.69; p
Published on
October 15, 2025
cited by
1
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