scholarly journals Deep Learning-Based Body Composition Analysis Predicts Outcome in Melanoma Patients Treated with Immune Checkpoint Inhibitors

Diagnostics ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2314
Author(s):  
Anton Faron ◽  
Nikola S. Opheys ◽  
Sebastian Nowak ◽  
Alois M. Sprinkart ◽  
Alexander Isaak ◽  
...  

Previous studies suggest an impact of body composition on outcome in melanoma patients. We aimed to determine the prognostic value of CT-based body composition assessment in patients receiving immune checkpoint inhibitor therapy for treatment of metastatic disease using a deep learning approach. One hundred seven patients with staging CT examinations prior to initiation of checkpoint inhibition between January 2013 and August 2019 were retrospectively evaluated. Using an automated deep learning-based body composition analysis pipeline, parameters for estimation of skeletal muscle mass (skeletal muscle index, SMI) and adipose tissue compartments (visceral adipose tissue index, VAI; subcutaneous adipose tissue index, SAI) were derived from staging CT. The cohort was binarized according to gender-specific median cut-off values. Patients below the median were defined as having low SMI, VAI, or SAI, respectively. The impact on outcome was assessed using the Kaplan–Meier method with log-rank tests. A multivariable logistic regression model was built to test the impact of body composition parameters on 3-year mortality. Patients with low SMI displayed significantly increased 1-year (25% versus 9%, p = 0.035), 2-year (32% versus 13%, p = 0.017), and 3-year mortality (38% versus 19%, p = 0.016). No significant differences with regard to adipose tissue compartments were observed (3-year mortality: VAI, p = 0.448; SAI, p = 0.731). On multivariable analysis, low SMI (hazard ratio (HR), 2.245; 95% confidence interval (CI), 1.005–5.017; p = 0.049), neutrophil-to-lymphocyte ratio (HR, 1.170; 95% CI, 1.076–1.273; p < 0.001), and Karnofsky index (HR, 0.965; 95% CI, 0.945–0.985; p = 0.001) remained as significant predictors of 3-year mortality. Lowered skeletal muscle index as an indicator of sarcopenia was associated with worse outcome in patients with metastatic melanoma receiving immune checkpoint inhibitor therapy.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 633-633 ◽  
Author(s):  
Grant Richard Williams ◽  
Allison Mary Deal ◽  
Shlomit S. Shachar ◽  
Christine Marie Walko ◽  
Jai Narendra Patel ◽  
...  

633 Background: Great heterogeneity exists in the ability of adults with cancer to tolerate treatment. Variability in body composition may affect rates of metabolism of cytotoxic agents and contribute to the variable chemotherapy toxicity observed. The goal of this study was to explore the impact of body composition, in particular sarcopenia, on the pharmacokinetics of 5-fluorouracil (5FU) in a cohort of patients receiving FOLFOX +/- bevacizumab for colorectal cancer. Methods: We performed a secondary analysis of a completed multicenter trial that investigated pharmacokinetic-guided 5FU in patients receiving mFOLFOX6 +/- bevacizumab [Patel et al. The Oncologist 2014]. Computed Tomography (CT) images that were performed as part of routine care were used to for body composition analysis. Skeletal muscle area (SMA) and density (SMD) were analyzed from CT scan L3 lumbar segments using radiological software. SMA and height (m2) were used to calculate skeletal muscle index (SMI = SMA/m2). Skeletal Muscle Gauge (SMG) was created by multiplying SMI x SMD. Differences were compared using two group t-tests and fisher’s exact tests. Results: Of the 70 patients from the original study, 25 had available CT imaging. The mean age was 59, 52% female, 80% Caucasian, and 92% with either stage III or IV disease. Eleven patients (44%) had grade 3/4 toxicity, and 12 patients were identified as sarcopenic (48%) [per Martin et al. JCO 2013]. Sarcopenic patients had numerically higher first cycle 5FU AUCs compared to non-sarcopenic patients (19.3 vs. 17.3 AUC, p= 0.43) and higher grade 3/4 toxicities (50 vs 38.5%, p= 0.70). Patients with low SMG ( < 1475 AU) had higher grade 3/4 toxicities (62 vs 25%, p= 0.11) and higher hematologic toxicities (46 v 8%, p= 0.07). Conclusions: CRC patients with sarcopenia had numerically higher first cycle AUCs of 5FU and a higher incidence of severe toxicities; however, this was not statistically significant, possibly due to limited sample size. SMG, an integrated muscle measure, was more highly correlated with toxicity outcomes than either SMI or SMD alone. Further research exploring the role of body composition in pharmacokinetics is needed with a focus on alternative dosing strategies in sarcopenic patients.


2020 ◽  
Vol 8 (2) ◽  
pp. e000821
Author(s):  
Arissa C Young ◽  
Henry T Quach ◽  
Haocan Song ◽  
Elizabeth J Davis ◽  
Javid J Moslehi ◽  
...  

BackgroundImmune checkpoint inhibitors (ICIs) have transformed treatment for melanoma, but identifying reliable biomarkers of response and effective modifiable lifestyle factors has been challenging. Obesity has been correlated with improved responses to ICI, although the association of body composition measures (muscle, fat, etc) with outcomes remains unknown.MethodsWe performed body composition analysis using Slice-o-matic software on pretreatment CT scans to quantify skeletal muscle index (SMI=skeletal muscle area/height2), skeletal muscle density (SMD), skeletal muscle gauge (SMG=SMI × SMD), and total adipose tissue index (TATI=subcutaneous adipose tissue area + visceral adipose tissue area/height2) of each patient at the third lumbar vertebrae. We then correlated these measures to response, progression-free survival (PFS), overall survival (OS), and toxicity.ResultsAmong 287 patients treated with ICI, body mass index was not associated with clinical benefit or toxicity. In univariable analyses, patients with sarcopenic obesity had inferior PFS (HR 1.4, p=0.04). On multivariable analyses, high TATI was associated with inferior PFS (HR 1.7, p=0.04), which was particularly strong in women (HR 2.1, p=0.03). Patients with intermediate TATI and high SMG had the best outcomes, whereas those with low SMG/high TATI had inferior PFS and OS (p=0.02 for both PFS and OS).ConclusionsBody composition analysis identified several features that correlated with improved clinical outcomes, although the associations were modest. As with other studies, we identified sex-specific associations that warrant further study.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9516-9516 ◽  
Author(s):  
Arissa Young ◽  
Henry T. Quach ◽  
Elizabeth J. Davis ◽  
Javid Moslehi ◽  
Grant R. Williams ◽  
...  

9516 Background: Obesity is associated with improved outcomes in melanoma patients (pts) treated with PD-1, whereas low muscle mass, known as sarcopenia, has been associated with poor outcomes in many cancers. We sought to assess the impact of body composition on PD-1 outcomes. Methods: We analyzed pre-treatment CT scans at the L3 slice using Slice-o-matic software (Tomovision V. 5.0) to determine skeletal muscle, visceral adipose, and subcutaneous adipose tissue parameters for 104 pts with metastatic melanoma who received PD-1 monotherapy. We assessed sarcopenia using skeletal muscle index (SMI=skeletal muscle area/m2). We also quantified total adipose tissue index (TATI), and skeletal muscle gauge (SMG = SMI x skeletal muscle density [SMD]). We stratified pts into high/low groups using previously published cutoffs and assessed toxicity (tox), progression-free and overall survival (PFS/OS), and response rate (RR) by group. Results: Sarcopenia (low SMI) was negatively associated with any tox (39% vs. 60%, p=0.04) but not OS, PFS, or RR. Adiposity (TATI) was not associated with outcomes. By contrast, SMG was significantly associated with OS (median 35.5 vs. 16.0m, p=0.01 for high vs. low SMG). Interestingly, when incorporating TATI with SMG, we found that high SMG/high TATI pts (high muscle/high fat) have superior clinical outcomes (Table). Notably, low SMG/high TATI pts (low muscle/high fat) had seemingly the worst outcomes. Conclusions: We found that high SMG, a measure incorporating muscle area and density, was associated with improved OS in PD1 treated pts. Further, pts with high adiposity and high SMG had superior outcomes, potentially identifying the population responsible for the favorable effect of obesity in these pts. Validation and combination treated cohorts will be presented. [Table: see text]


2019 ◽  
Vol 32 (Supplement_2) ◽  
Author(s):  
Doganay Emre ◽  
R Boshier Piers ◽  
J Halliday Laura ◽  
Thomas Rob ◽  
E Low Donald ◽  
...  

Abstract Aims This study characterises changes in body composition and physical performance during neoadjuvant therapy in the context of prehabilitation before oesophago-gastric resection. Background & Methods Neoadjuvant therapy has deleterious effects on functional capacity and may lead to a decline in physical fitness and skeletal muscle mass. This is a retrospective review of oesophago-gastric cancer patients undergoing prehabilitation. Assessment of body composition (skeletal muscle, visceral and subcutaneous adipose tissue) was performed from L3 axial CT images acquired at the time of diagnosis and after neoadjuvant therapy. Results 42 patients (33M, 65.7±11.1) met the inclusion criteria. Patients body weight (81.8±21.3 kg vs. 81.3±21 kg, p=0.668) and BMI (27.9±7.2 kg/m2 vs. 27.8±7.0 kg/m2, p=0.648) did not change significantly between the study time points. There was no significant difference between estimated lean body mass (39.2±13.2 vs. 38.3±10.1; 95%CI -2.5 to 4.3 p=0.592) and fat mass (30.6±15.4 vs. 28.6±14.0; 95%CI -1.7 to 5.7, p=0.284). Skeletal muscle index significantly decreased (46.5±9.9 to 43.1±9.8; 95%CI 2.1 to 4.6, p<0.001). Patients who were adherent to the prehabilitation programme had a significantly higher skeletal muscle index compared to noncompliant patients (47.4±10.4 vs. 40.2±8.9; 95%CI 1.5 to 13.5, p=0.016). Patients who achieved a higher MET-minutes were less likely to be sarcopenic (F(1,40 = 6.1, p = 0.018)).There was no decline in physical performance (Median IQR; VO2max ml kg−1min−1) during neoadjuvant therapy (17.5 [14-19.3] vs. 17.5 [13.3-19.3]; p=0.164). Conclusion this is the first study to report variations in parameters of body composition in patients undergoing a prehabilitation programme. Findings suggest that prehabilitation may be a useful adjunct in limiting the extent of sarcopenia and patient deconditioning during neoadjuvant therapy.


Author(s):  
Oktay Aktepe ◽  
Ahmet Gürkan Erdemir ◽  
Gurkan Guner ◽  
Deniz Can Güven ◽  
Suayib Yalcin ◽  
...  

Background: To explore the clinical significance of baseline volumetric body composition parameters evaluated with computerized tomography (CT) and their changes after 3-4 months from treatment initiation of targeted therapy in patients with metastatic renal cell carcinoma (mRCC). Method: This study included 108 Caucasian mRCC patients (Male/Female: 77/31) treated with targeted therapy. Volumetric body composition parameters including total adipose tissue index (TATI), subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI) and skeletal muscle index (SMI) values were depicted from CT images at third lumbar vertebra level through volumetric measurement software. Kaplan-Meier method and the long test were used for estimation of progression free survival (PFS) and overall survival (OS). Univariate and multivariate analyses were done to determine the associations between clinic-pathologic variables including VBC and survival outcomes. Results: The median PFS and OS of all patients were 11 months and 46 months in patients respectively. After adjustment for the variables including international mRCC database consortium (IMDC) risk score, only a high skeletal muscle index (SMI) was associated with better PFS (HR: 0.975, P=0.015). The independent predictors for OS were VATI (HR 1.005, P=0.024), SATI (HR: 0.976, P=0.019) and TATI (HR: 0.982, P=0.035) in addition to IMDC risk score. Conclusion: Our findings revealed that while SMI was the only significant determinant parameter for PFS among VBC parameters, TATI, VATI, and SATI were determined as independent predictors for OS in addition to IMDC risk score.


2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 525-525
Author(s):  
Karan Kumar Arora ◽  
Caroline Kato ◽  
Kunnal Batra ◽  
Michael Russell Mullane ◽  
Thomas E. Lad ◽  
...  

525 Background: Exposure to cytotoxic chemotherapy (CC) has been observed to be associated with significant changes in body composition, namely marked lean muscle mass losses, with implications for treatment-related toxicity and oncologic outcomes. However, prior studies predominately include elderly patients who, a priori, are at risk for sarcopenia or severe skeletal muscle deficiency. To date, the impact of CC on body composition in young men with testicular cancer remains undefined. Methods: A retrospective analysis of 19 patients with metastatic testicular cancer treated with CC was performed (2015-17). Lumbar skeletal muscle index (SMI), visceral (VAI), subcutaneous (SCAI), and intramuscular adipose (IMAI) indices (cm2/m2), as well as fat-free mass (FFM, kg) and fat mass (FM, kg) were calculated using cross-sectional soft tissue area measurements on pre- and post-CC computed tomography (CT) axial scans and compared using paired Wilcoxon Signed Rank Tests. Results: Median age was 29 years. According to the NHANES FMI-based classification, 5 (26.3%), 9 (47.4%), 4 (21.1%), and 1 (5.3%) patients had normal, excess, class I, and class II obesity, respectively. Median pre- and post-CC BMI was 27.7 vs. 29.6 kg/m2(p = 0.03). Median pre- and post-CC SMI, VAI, SAI, and IAI were 63.5 vs 57.8 (p = 0.14), 19.9 vs 30.8 (p = 0.01), 47.9 vs 58.2 (p = 0.03), and 3.0 vs 5.2 (p = 0.002), respectively. Median muscle density pre- and post-CC were 47.0 vs 43.6 HU (p = 0.002). Pre- and post-chemotherapy FFM were 21.5 vs 19.5 kg, representing an overall median loss of 2.8%, (IQR -10.1, +4.7; Range -49.5 - +16.3; p = 0.14). Conversely, pre- and post-CC FM were 6.6 vs 7.5 kg, representing an overall median gain of 13.3% (IQR -3.3, +17.0; -24.9 - +50; p = 0.01). Median time between imaging assessments was 121 days. Specific median measures of adiposity each increased significantly, such that VIA increased by 29% (p = 0.01), SCAI increased by 39.7% (p = 0.03), and IMIA increased by 39.7% (p = 0.002). Conclusions: While lean muscularity remained stable, we observed significant increases in total body adipose mass with decreased muscle density in this consecutive case series of testicular cancer patients following CC.


2021 ◽  
Author(s):  
Brandon Whitcher ◽  
Marjola Thanaj ◽  
Madeleine Cule ◽  
Yi Liu ◽  
Nicolas Basty ◽  
...  

Longitudinal studies provide unique insights into the impact of environmental factors and lifespan issues on health and disease. Here we investigate changes in body composition in 3,088 free-living participants, part of the UK Biobank in-depth imaging study. All participants underwent neck-to-knee MRI scans at baseline and after approximately two years (re-imaging). Image-derived phenotypes for each participant were extracted using a fully-automated image processing pipeline, including volumes of several tissues and organs: liver, pancreas, spleen, kidneys, total skeletal muscle, iliopsoas muscle, visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT), as well as fat and iron content in liver, pancreas and spleen. Overall, no significant changes were observed in BMI, body weight, or waist circumference over the scanning interval, despite some large individual changes. A significant decrease in grip strength was observed, coupled to small, but statistically significant, decrease in all skeletal muscle measurements. Significant increases in VAT and intermuscular fat in the thighs were also detected in the absence of changes in BMI, waist circumference and ectopic-fat deposition. Adjusting for disease status at baseline did not have an additional impact on the changes observed. In summary, we show that even after a relatively short period of time significant changes in body composition can take place, probably reflecting the obesogenic environment currently inhabited by most of the general population in the United Kingdom.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22503-e22503
Author(s):  
Aman Wadhwa ◽  
Kandice Barnett ◽  
Chen Dai ◽  
Joshua Richman ◽  
Andrew Michael McDonald ◽  
...  

e22503 Background: Body composition is an emerging predictor of toxicity and survival in older adults with cancer ( Shachar, Eur J Can, 2016); however, its role in pediatric cancer is not known. We examined body composition (using computed-tomography [CT] scans at the 3rd lumbar level) in children with lymphoma (Hodgkin [HL] and non-Hodgkin [NHL]) at cancer diagnosis and examined its association with treatment-related toxicities. Methods: We constructed a retrospective cohort of 87 consecutive children (HL: n = 45; NHL: n = 42) diagnosed between 2000 and 2015 (2-21y at diagnosis) with pretreatment abdominal CT scans. Body composition was assessed using sliceOmatic (TomoVision) and included skeletal muscle index (SMI, cm2/m2), skeletal muscle density (SMD: Hounsfield units [HU]), and height-adjusted total adipose tissue (hTAT: sum of visceral, intramuscular and subcutaneous adipose tissue, cm2/m2). For the analysis, we used skeletal muscle gauge (SMG = SMI x SMD, expressed per 1000 in arbitrary units [AU]) and hTAT. Sociodemographics, disease and treatment details, as well as toxicities (CTCAE v5) were abstracted from medical records. Proportion of chemotherapy cycles with grade 4 hematologic or grade 3-4 non-hematologic toxicities were calculated (percent toxicity). Generalized linear regression models were constructed to examine associations between body composition metrics and toxicities, adjusting for age at diagnosis, gender, race/ethnicity and lymphoma subtype. Results: Median age at diagnosis was 12.9y (range, 2-18.5y); 60.9% males; 60.4% non-Hispanic white. Median BMI%ile was 62 (0-99), median SMG was 2.2AU (0.9-3.7) and median hTAT was 20.1 cm2/m2 (0.04-226.7). Overall, the mean percent toxicity for grade 4 hematologic and grade 3-4 non-hematologic toxicity was 38.9% (±32.6) and 31.4% (±32.6) respectively. Correlation was poor between SMG and BMI%ile ( R2= 0.04), SMG and hTAT ( R2= -0.01) and moderate between hTAT and BMI%ile ( R2= 0.4). SMG was significantly associated with grade 4 hematologic percent toxicity ( β= -18, P= 0.007) after adjusting for hTAT and cancer type. BMI%ile was not associated with grade 4 hematologic percent toxicity ( β= -0.09, P= 0.5). Non-hematologic percent toxicity was not associated with BMI%ile, hTAT or SMG. Conclusions: In this first study of its kind, we find that children with poorer muscle quality are more likely to experience grade 4 hematologic toxicities. These findings form the basis for larger studies to incorporate body composition when developing prediction models for chemotherapy-related toxicity and disease outcomes.


Author(s):  
H. van Baar ◽  
M. J. L. Bours ◽  
S. Beijer ◽  
M. van Zutphen ◽  
F. J. B. van Duijnhoven ◽  
...  

Abstract Purpose Persistent fatigue among colorectal cancer (CRC) patients might be associated with unfavorable body composition, but data are sparse and inconsistent. We studied how skeletal muscle index (SMI), skeletal muscle radiodensity (SMR), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) at diagnosis are associated with fatigue up to 24 months post-diagnosis in stage I–III CRC patients. Methods SMI, SMR, VAT, and SAT were assessed among 646 CRC patients using pre-treatment computed tomography images. Fatigue at diagnosis, at 6, and 24 months post-diagnosis was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. The association of SMI, SMR, VAT, and SAT with fatigue (yes/no) was assessed using confounder-adjusted restricted cubic spline analyses. Results Prevalence of fatigue at diagnosis was 18%, at 6 months 25%, and at 24 months 12%. At diagnosis, a significant (p = 0.01) non-linear association of higher levels of SAT with higher prevalence of fatigue was observed. Lower levels of SMR were linearly associated with higher prevalence of fatigue at 6 months post-diagnosis (overall association p = 0.02). None of the body composition parameters were significantly associated with fatigue at 24 months. Conclusion Having more SAT was associated with more fatigue at diagnosis, while low levels of SMR were associated with more fatigue at 6 months post-diagnosis. Implications for Cancer Survivors Our results suggest that it may be interesting to investigate whether interventions that aim to increase SMR around the time of diagnosis may help to lower fatigue. However, more knowledge is needed to understand the mechanisms behind the association of SMR with fatigue.


Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1061
Author(s):  
Min-Kyu Kang ◽  
Jung-Hun Baek ◽  
Young-Oh Kweon ◽  
Won-Young Tak ◽  
Se-Young Jang ◽  
...  

Adipose tissue and skeletal muscle is associated with non-alcoholic fatty liver disease (NAFLD). This study evaluates the association between body composition and histologic severity in patients with NAFLD. Using the cross-sectional CT images at the level of L3 vertebra and the histologic findings of 178 patients with biopsy-proven NAFLD, we analyzed the correlation of the histologic findings to the skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI), which is defined as the body composition area (cm2) by height squared (m2). The clinical and laboratory features with body composition were analyzed to determine the risk factors for advanced fibrosis. The VATI significantly increased in severe non-alcoholic steatohepatitis (NASH) or advanced fibrosis. In addition, the VATI was correlated with the NAFLD activity score (NAS) and the fibrosis stage. In multivariate analyses, age (odds ratio (OR), 1.09; 95% confidence interval (CI), 1.02–1.19; p = 0.025), severe NASH (OR, 8.66; 95% CI, 2.13–46.40; p = 0.005), and visceral adiposity (OR, 6.77; 95% CI, 1.81–29.90; p = 0.007) were independently associated with advanced fibrosis in patients with NAFLD. Visceral adiposity is correlated with the histologic severity of NAFLD, which is independently associated with advanced fibrosis.


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