scholarly journals Impact of body composition on outcomes from anti-PD1 +/− anti-CTLA-4 treatment in melanoma

2020 ◽  
Vol 8 (2) ◽  
pp. e000821
Author(s):  
Arissa C Young ◽  
Henry T Quach ◽  
Haocan Song ◽  
Elizabeth J Davis ◽  
Javid J Moslehi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Composition ◽  
Adipose Tissue ◽  
Checkpoint Inhibitors ◽  
Lumbar Vertebrae ◽  
Composition Analysis ◽  
Muscle Area ◽  
Skeletal Muscle Index ◽  
Body Composition Analysis ◽  
Tissue Area

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.

The impact of sarcopenia on toxicity and pharmacokinetics of 5-fluorouracil (5FU) in colorectal cancer.

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 ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Skeletal Muscle ◽  
Body Composition ◽  
Secondary Analysis ◽  
Cytotoxic Agents ◽  
Composition Analysis ◽  
Muscle Area ◽  
Skeletal Muscle Index ◽  
Grade 3 ◽  
The Impact

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.

Body composition and association with treatment toxicity in patients with advanced renal cell carcinoma receiving targeted agents.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15608-e15608
Author(s):  
Kelly McCabe ◽  
Vicky Goh ◽  
Anup Vinayan ◽  
Ann Petruckevitch ◽  
Paul D. Nathan
Keyword(s):  
Skeletal Muscle ◽  
Body Composition ◽  
Adipose Tissue ◽  
Weight Change ◽  
Mtor Inhibitors ◽  
Targeted Agents ◽  
Muscle Area ◽  
Skeletal Muscle Index ◽  
Treatment Toxicity ◽  
Increased Risk

e15608 Background: Treatment toxicity may be influenced by heterogeneity in body composition. Muscle wasting in mRCC patients treated with sorafenib is associated with increased risk of toxicity (Antoun et al, 2010). We used CT analysis to investigate changes in adipose tissue and skeletal muscle in a large cohort of mRCC patients treated with a number of targeted agents and determined whether body composition was associated with treatment toxicity. Methods: A retrospective analysis of between 2-7 sequential CT scans of 112 mRCC patients was conducted. Each patient received between 1-4 courses of therapy. In total 191 treatment episodes within this population were included; 113 courses of VEGF TKIs, 22 courses of mTOR inhibitors, 36 courses of immunotherapy and 20 episodes where no treatment was given. A validated method, using L3 as a lumbar vertebral landmark, was used to measure lumbar skeletal muscle area (cm3) and adipose tissue volume (cm3). Appendicular Skeletal Muscle Index (ASMI) was calculated to determine prevalence of sarcopenia within the cohort; sarcopenia was defined as ASMI <7.26kg/m2 for males and <5.45kg/m2for females. Toxicity was assessed by Common Toxicity Criteria (CTC) scores documented in medical records. The cohort was divided into body mass index (BMI) quartiles. Results: Of the 112 participants, 74.1% of the group had a BMI >25 at their first scan. Mean weight change between first and last scan was -3.89kg (SD: ±9.09). 20.5% of the cohort were sarcopenic at baseline, increasing to 38.4% at final scan. Sarcopenia was independent of weight change and was associated with increased frequency of severe (CTC grade > 2) treatment toxicity (Pearson Chi Square Value: 12.82; p= 0.001). This effect persisted after adjusting for BMI quartile (odds ratio = 5.04; p=0.004). Changes in bone composition and correlation of body composition with clinical outcome will also be reported. Conclusions: Sarcopenia is common in mRCC patients and is associated with a significantly increased risk of severe treatment toxicity when receiving targeted agents. Sarcopenia was seen across all BMI quartiles and was not associated with weight change.

Impact of body composition on outcomes from anti-programmed death-1 (PD-1) treatment.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9516-9516 ◽  
Author(s):  
Arissa Young ◽  
Henry T. Quach ◽  
Elizabeth J. Davis ◽  
Javid Moslehi ◽  
Grant R. Williams ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Composition ◽  
Adipose Tissue ◽  
Favorable Effect ◽  
High Fat ◽  
Muscle Area ◽  
Skeletal Muscle Index ◽  
Pre Treatment ◽  
Skeletal Muscle Area ◽  
The Impact

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]

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 ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Composition ◽  
Adipose Tissue ◽  
Deep Learning ◽  
Immune Checkpoint ◽  
Composition Analysis ◽  
Skeletal Muscle Index ◽  
Checkpoint Inhibitor Therapy ◽  
Tissue Compartments ◽  
The Impact

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.

Sarcopenia and altered body composition following abiraterone acetate (AA) and corticosteroid (C) treatment in men with castration-refractory prostate cancer (CRPC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15134-e15134
Author(s):  
Deborah Mukherji ◽  
Carmel Jo Pezaro ◽  
Diletta Bianchini ◽  
Nina Tunariu ◽  
Amy Mulick Cassidy ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Composition ◽  
Prognostic Factor ◽  
Muscle Mass ◽  
Median Duration ◽  
Visceral Fat ◽  
Muscle Area ◽  
Skeletal Muscle Index ◽  
Advanced Malignancy ◽  
Total Fat

e15134 Background: Sarcopenia, or skeletal muscle wasting, is an independent prognostic factor in advanced malignancy (Prado Lancet Onc 2008). Decreased muscle and increased fat are recognized side effects of androgen deprivation therapy. AA is a CYP17 inhibitor administered with corticosteroids (C), approved for treatment of advanced CRPC. AA reduces circulating androgens to ‘super-castrate’ levels; we hypothesized that AA + C would impact body composition. Methods: We retrospectively evaluated 54 CRPC pts treated on a Phase I/II trial. Pts received AA alone followed by combination AA + C on biochemical progression. CT scans at baseline, on AA alone and on AA + C were analyzed. Cross-sectional areas of fat and muscle were measured on 3 consecutive images at L4 using OsiriX 4.0. Muscle area was used to calculate skeletal muscle index (SMI); sarcopenia was defined as SMI <52.4 cm2/m2. Data were analyzed using t-tests and Kaplan-Meier analysis with overall survival (OS) measured from day 1 of AA. Results: Median duration on AA alone was 7.4 months (m; range 1.4-37.5); median duration on concurrent AA + C was 7.4m (range 0.9-46.2). Body composition did not change between two pre-treatment scans (n=29; median 3m apart). On AA alone there was a decrease in total fat (-8.5%, p=0.0001), visceral fat (-9.8%, p=0.0015) and muscle mass (-3.9%, p=0.0023) with a significant decrease in mean body mass index (BMI; -3.4 %, p=0.0118). Conversely AA + C was associated with increased total fat (+15.1%, p<0.0001) and visceral fat (+21.4%, p<0.0001) but no further change in muscle mass. Mean BMI significantly increased on the addition of C, returning to baseline levels (p< 0.0001). Overall, 13 pts (24%) were sarcopenic prior to commencing AA compared to 22 (41%) at the end of treatment. Pts who were sarcopenic at baseline had significantly reduced OS: 26.1m (95%CI 16.6 – 41) vs 46.5m (95%CI 28.6 – 57.5, p=0.0253). Conclusions: Treatment with AA alone resulted in decreased fat and muscle. AA + C increased body fat without further alteration in muscle mass. Changes in BMI did not reflect changes in body composition. Sarcopenia at baseline was a negative prognostic factor in this population.

scholarly journals Association between CT-Measured Abdominal Skeletal Muscle Mass and Pulmonary Function

2019 ◽  
Vol 8 (5) ◽  
pp. 667 ◽  
Author(s):  
Eun Kyung Choe ◽  
Young Lee ◽  
Hae Yeon Kang ◽  
Seung Ho Choi ◽  
Joo Sung Kim
Keyword(s):  
Skeletal Muscle ◽  
Lung Function ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Lumbar Vertebrae ◽  
Forced Expiratory Volume ◽  
The Body ◽  
Muscle Area ◽  
Skeletal Muscle Index ◽  
Clinical Records

A relationship between lung function and sarcopenia has been suggested. This study aimed to evaluate the association between lung function and abdominal skeletal muscle mass, as measured by computed tomography (CT). The clinical records of 1907 subjects (1406 males, mean age 53.1 ± 9.2 years), who underwent routine health check-ups, including spirometry and abdominal CT, were retrospectively reviewed. The CT-measured skeletal muscle index (SMICT, cm2/(kg/m2) was defined as the skeletal muscle area of the third lumbar vertebrae (L3) level that is normalized by the body mass index. The mean values of forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) gradually increased as the SMICT quartiles increased (all p for trend < 0.05). The proportions of subjects with less than 80% of the predicted FVC (%) and predicted FEV1 (%) significantly decreased as the SMICT quartiles increased (all p for trend < 0.05). The β regression coefficients for FVC and FEV1 significantly increased as the SMICT quartiles increased after adjusting for other confounding variables (p for trend < 0.05). This study showed that abdominal muscle mass, which was precisely measured by CT, independently affected lung function proportionally after adjusting for confounding factors in relatively healthy adults.

Sarcopenia as a predictor of survival in patients with epithelial ovarian cancer (EOC) receiving platinum and taxane-based chemotherapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17030-e17030 ◽  
Author(s):  
Stuart-Allison Moffat Staley ◽  
Katherine Tucker ◽  
Meredith Newton ◽  
Michelle Ertel ◽  
Yingao Zhang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Skeletal Muscle ◽  
Lumbar Vertebrae ◽  
Advanced Ovarian Cancer ◽  
Metastatic Breast ◽  
Survival Outcomes ◽  
Muscle Area ◽  
Skeletal Muscle Index ◽  
Kaplan Meier ◽  
Skeletal Muscle Area

e17030 Background: Severe skeletal muscle loss (sarcopenia) is associated with poor cancer outcomes, including reduced survival and increased treatment toxicity. This relationship has recently been demonstrated in women with metastatic breast cancer, but there is a paucity of data regarding this correlation in women with EOC. Thus, our goal was to evaluate if sarcopenia, as assessed by computed tomography (CT) morphometric measurements, was associated with worse survival outcomes in EOC patients undergoing primary platinum and taxane-based chemotherapy. Methods: EOC patients diagnosed between 06/2000 and 02/2017 who received treatment with platinum and taxane-based chemotherapy were included. CT abdominal images closest to the time of diagnosis were retrospectively evaluated for skeletal muscle area at the 3rd lumbar vertebrae. Measurements were obtained with use of TomoVision® radiological software (SliceOmatic – version 5.0, Quebec, Canada). Sarcopenia was defined as Skeletal Muscle Index (SMI = SMA/height2) ≤ 41. Data analysis included Kaplan-Meier plots to assess survival, and descriptive statistics was utilized to describe characteristics between the two groups. Results: 201 EOC patients were evaluated. Sixty-four percent (128/201) met criteria for sarcopenia (SMI ≤ 41) at time of diagnosis. Seventy-six percent of patients were diagnosed with Stage III or IV disease, with high-grade serous as the most common histology (74%). Median age at diagnosis was 61 years. Approximately one third were obese. Body mass index was greater in the SMI > 41 group compared to the SMI ≤ 41 group (31.3 vs 26.3, p < 0.001). There was no difference in the prevalence of chronic conditions, including diabetes, coronary artery disease, hypertension, chronic kidney disease, or tobacco use, between the two groups. The mean overall survival did not differ between patients with SMI > 41 and SMI ≤ 41 (36.5 vs 40.8 months, p = 0.4, respectively). Conclusions: Based on this patient cohort, sarcopenia was not associated with worse survival outcomes in EOC patients receiving first-line platinum and taxane-based chemotherapy. Further prospective studies are needed to explore other diagnostics that may allow us to provide improved accuracy and individualization in the care of women with advanced ovarian cancer.

scholarly journals Impact of Body Composition on the Risk of Hepatocellular Carcinoma Recurrence After Liver Transplantation

2019 ◽  
Vol 8 (10) ◽  
pp. 1672
Author(s):  
Karolina Grąt ◽  
Ryszard Pacho ◽  
Michał Grąt ◽  
Marek Krawczyk ◽  
Krzysztof Zieniewicz ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Skeletal Muscle ◽  
Liver Transplantation ◽  
Body Composition ◽  
Adipose Tissue ◽  
Visceral Fat ◽  
Recurrence Free Survival ◽  
Muscle Area ◽  
Free Survival ◽  
Hcc Recurrence

Background: Body composition parameters are reported to influence the risk of hepatocellular carcinoma (HCC) recurrence after liver resection, yet data on patients undergoing liver transplantation are scarce. The aim of this study was to evaluate the impact of the amount of abdominal adipose tissue and skeletal muscles on the risk of HCC recurrence after liver transplantation. Methods: This was a retrospective observational study performed on 77 HCC patients after liver transplantation. Subcutaneous fat area (SFA), visceral fat area, psoas muscle area and total skeletal muscle area were assessed on computed tomography on the level of L3 vertebra and divided by square meters of patient height. The primary outcome measure was five-year recurrence-free survival. Results: Recurrence-free survival in the entire cohort was 95.7%, 90.8%, and 86.5% after one, three, and five years post-transplantation, respectively. SFA was significantly associated with the risk of HCC recurrence (p = 0.013), whereas no significant effects were found for visceral fat and skeletal muscle indices. The optimal cut-off for SFA for prediction of recurrence was 71.5 cm2/m2. Patients with SFA < 71.5 cm2/m2 and ≥71.5 cm2/m2 exhibited five-year recurrence-free survival of 96.0% and 55.4%, respectively (p = 0.001). Conclusions: Excessive amount of subcutaneous adipose tissue is a risk factor for HCC recurrence after liver transplantation and may be considered in patient selection process.

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