The effect of everolimus on body composition (BC) in patients with metastatic breast cancer (MBC).

e13026 Background: BC measurement can distinguish adipose tissue distribution, as well as the quantity and quality of muscle. Dysregulation in the mammalian target of rapamycin (mTOR) signaling pathway is associated with obesity and its related diseases. Everolimus (Eve), an mTOR inhibitor, is used in combination with endocrine therapy (ET) in hormone positive, HER2 negative (HR+/HER2-) MBC. However, there is limited data on the effect of Eve on BC. We aim to assess the effect of Eve on BC in patients (pts) with HR+/HER2- MBC. Methods: Pts with HR+/HER2- MBC who received Eve and ET between 2012 and 2019 at our institution were identified. We collected information about breast cancer diagnosis and treatment, weight (wt), body mass index (BMI), and computed tomography (CT). BC measurements; including skeletal muscle area (SMA), skeletal muscle density (SMD), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and muscle adiposity (MA); were analyzed at the L3 region on CT scans using Tomovision’s SliceOmatic Version 5.0. Total adipose tissue (TAT) was defined as SAT+VAT+MA. To isolate the effect of Eve on BC we also identified a cohort of pts who received ET only. We compared change in wt, BMI, and BC before and after 3 and 6 months of therapy. Wilcoxon signed rank test was used to compare BC parameters. Results: Our study included 42 pts who received Eve plus ET; 43% were Hispanic and 33% were Black. The median number of prior ET and chemotherapy lines were 1 and 0, respectively. The cohort who received ET alone included 63 patients. Median age was 68 years (interquartile range [IQR] 56-74) for the Eve and ET group and 67 years (IQR 55-74) for the ET only group (p = 0.74). Median baseline BMI was 25.8 kg/m2 (IQR 23.1-28.2) for the Eve and ET group and 28.5kg/m2 (IQR 24.2-30.8) for ET only (p = 0.08). Visceral disease was present in 24 (57%) pts on Eve and ET and 41 (65%) pts on ET only (p = 0.54). At month 3 of treatment with Eve and ET, there was a significant decrease in wt (-2.75kg, IQR -4.53-0.40, p < 0.005), BMI (-1.15kg/m2, IQR -1.71-0.14, p < 0.01), SAT (-21.93cm2, IQR -50.13-5.08, p < 0.01), and TAT (-22.34cm2, IQR -69.89-11.98, p = 0.02), which remained statistically significant at month 6 (wt: -5.70kg, IQR –7.75-1.83, p < 0.01; BMI: -2.3kg/m2, IQR -2.83-0.72, p < 0.01; SAT: -43.00cm2, IQR -73.81-10.69, p < 0.01; TAT: -32.56cm2, IQR –92.18-9.61, p = 0.03). These findings were not seen in pts who received ET only at 3 months (wt: 0.00kg, IQR –2.65-2.38, p = 0.99; BMI: 0.00kg/m2, IQR –1.07-0.91, p = 0.94; SAT: -1.82cm2, IQR -26.10-25.15, p = 0.59; TAT: 0.71cm2, IQR -44.39-27.43, p = 0.35), with similar results at 6 months. There were no statistically significant changes in VAT, SMA, SMD, or MA in both groups at 3 or 6 months. Conclusions: Everolimus is associated with decrease in SAT, with no significant change in VAT, SMA, or SMD. Further investigation is required to determine if these changes are associated with disease outcomes or everolimus toxicities.

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Effect of cyclin-dependent kinase 4 and 6 inhibitors (CDKIs) on body composition (BC) in patients (pts) with hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer (MBC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e13033 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e13033-e13033

Author(s):

Lisa Phuong ◽

Janki Patel ◽

Nadia Baka ◽

Jessica Goldman ◽

Michael Lyudmer ◽

...

Keyword(s):

Breast Cancer ◽

Skeletal Muscle ◽

Adipose Tissue ◽

Metastatic Breast ◽

Median Number ◽

Breast Cancer Prognosis ◽

Cancer Prognosis ◽

Muscle Area ◽

Hormone Receptor Positive ◽

The Impact

e13033 Background: CDKIs with endocrine therapy (ET) is first-line treatment in HR+/HER2- MBC. Mouse models have shown that CDKIs prevent pRB phosphorylation in the mediobasal hypothalamus, a pathway hyper-activated in diet-induced obesity; and CDKIs lead to fat mass decrease without significant effect on lean mass. We aimed to assess the impact of CDKIs on weight (wt) and BC in pts with HR+/HER2- MBC. Methods: We identified pts with HR+/HER2- MBC who received CDKIs and ET from 2015-2018. To isolate the effect of CDKIs on BC, we identified another cohort of pts who only received ET. Body mass index (BMI), wt, and computed tomography (CT) records were reviewed. BC was analyzed at L3 on CT scans using Tomovision’s SliceOmatic v5.0 and included skeletal muscle area (SMA), skeletal muscle density (SMD), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and muscle adiposity (MA). Total adipose tissue (TAT) was defined as SAT+VAT+MA. BC changes at 3 and 6 months of therapy were evaluated using paired t-tests. Results: There were 107 pts who received CDKI plus ET - 43% were Black, and 41% were Hispanic. CDKIs used were palbociclib (85%), abemaciclib (9%), and ribociclib (6%). ETs used were letrozole (47%), fulvestrant (39%), anastrozole (12%), and exemestane (2%). Median number of prior chemo and ET lines was 0 (range 0-5). 63 pts received ET alone. There was no difference in age (63 vs. 65 years, p = 0.26), BMI (28.80 vs. 28.12kg/m2, p = 0.48), and visceral disease (69% vs. 65%, p = 0.64) between CDKI plus ET and ET alone group. At month 3 of CDKI plus ET, there was a significant decrease in wt (-0.30kg, Interquartile range [IQR] -2.55-0.95, p = 0.02), BMI (-0.12kg/m2, IQR -1.06-0.46, p = 0.02), SAT (-8.05cm2, IQR -32.58-14.74, p = 0.01), and TAT (-8.51cm2, IQR -50.42-17.84, p < 0.01), with similar results at month 6. These findings were not seen in pts on ET only at 3 months (wt: 0.00kg, IQR -2.65-2.38, p = 0.98; BMI: 0.00kg/m2, IQR -1.07-0.91, p = 0.93; SAT: -2.97cm2, IQR -26.10-25.15, p = 0.60; TAT: -0.58cm2, IQR -44.39-27.43, p = 0.18), or at 6 months. There were no significant changes in VAT, SMA, SMD, or MA in both groups at 3 or 6 months. In the CDKI plus ET group, baseline wt (74.64 vs. 72.72kg, p = 0.60), BMI (29.21 vs. 27.88kg/m2, p = 0.31), and SAT (280.29 vs. 252.75cm2, p = 0.31) were not significantly different for those who did or did not develop grade 3/4 toxicities. We obtained similar results when stratifying toxicities into hematological- and GI-related events. Conclusions: CDKIs are associated with decrease in BMI and SAT with no significant effect on VAT, SMA, or SMD. Given the known effect of obesity on breast cancer prognosis, CDKIs may have an additional effect on breast cancer prognosis by modulating body fat. Further studies are required to determine if decrease in SAT is associated with breast cancer outcomes or toxicities in pts on CDKIs.

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Skeletal muscle area and density as predictors of chemotherapy toxicity and outcomes in metastatic breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.15_suppl.1021 ◽

2016 ◽

Vol 34 (15_suppl) ◽

pp. 1021-1021

Author(s):

Shlomit Strulov Shachar ◽

Allison Mary Deal ◽

Marc Weinberg ◽

Kirsten A Nyrop ◽

Grant Richard Williams ◽

...

Keyword(s):

Breast Cancer ◽

Skeletal Muscle ◽

Metastatic Breast Cancer ◽

Metastatic Breast ◽

Muscle Area ◽

Chemotherapy Toxicity ◽

Skeletal Muscle Area

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Methallotionein expression and outcome in patients with metastatic breast cancer (MBC).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.1085 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 1085-1085

Author(s):

Jorge Arturo Rios-Perez ◽

Sameem Abedin ◽

Margaret Quinn Rosenzweig ◽

Su Yon Jung ◽

Rohit Bhargava ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Metastatic Breast ◽

Progression Free Survival ◽

Breast Cancer Diagnosis ◽

Rank Test ◽

Cancer Tissue ◽

Breast Cancer Patients ◽

Development Of Resistance ◽

Bivalent Metal Ions

1085 Background: Platinum-based agents are important components of therapy of metastatic breast cancer (MBC) and triple negative breast cancer. Their use can be limited by development of resistance. Metallothioneins (MT) are low molecular weight proteins believed to bind bivalent metal ions such as platinum and zinc. MT expression has been associated with decreased survival in breast cancer patients. A proposed mechanism confers resistance to platinum-based agents by their inactivation or limitation of their activity by MT binding. Methods: MT expression in 99 women with MBC (selected at random from our database of 800 women with MBC) was determined from primary breast cancer tissue (n=80) or metastatic tissue n=19). MT expression was determined by immunohistochemistry, and graded as negative, weak, moderate or strong. Clinical data was obtained through our database and supplemented by chart review. Overall survival from breast cancer diagnosis (OS), progression free survival for first metastastic regimen (PFS), and time from first metastasis to death or last update (metastatic survival, MS), were calculated through December 2011 using the log rank test. Results: Consistent with prior studies, moderate to strong MT expression was associated with decreased 5-year OS (p=.03). There was no correlation between MT expression and PFS or MS in this cohort. Surprisingly, MT expression at any degree was strongly associated with better MS in patients with MBC that received carboplatin-based regimens in the first line (n=25, p=.0005) or at any line (n=41, p=.0437). Conclusions: Consistent with prior studies, MT expression was associated with decreased survival in patients with MBC. Surprisingly, MT expression was associated with longer MS in patients with MBC that received carboplatin. These findings are inconsistent with the hypothesis that MT expression causes chemoresistance to platinum based agents in patients with metastatic breast cancer. Further studies are needed to elucidate the mechanisms behind these findings.

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

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e17030 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e17030-e17030 ◽

Cited By ~ 1

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.

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Differences in body composition between patients with early or metastatic breast cancer (BC).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e21707 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e21707-e21707

Author(s):

Shlomit Strulov Shachar ◽

Allison Mary Deal ◽

Marc Weinberg ◽

Grant Richard Williams ◽

Kirsten A Nyrop ◽

...

Keyword(s):

Skeletal Muscle ◽

Body Composition ◽

Body Mass ◽

Metastatic Cancer ◽

Metastatic Breast ◽

Linear Regression Models ◽

Muscle Area ◽

Age Related ◽

Skeletal Muscle Area ◽

The Impact

e21707 Background: There is growing evidence in oncology that skeletal muscle (SM) loss, known as sarcopenia, can be identified from routine computed tomography (CT) imaging and used to predict increased chemotherapy toxicity, mortality, and other adverse clinical outcomes (Shachar-EJC, 2016, Shachar-CCR, 2016). The contributions of age-related and cancer-related loses in SM at diagnosis remains poorly understood. This study compares CT-derived measures of SM at the time of diagnosis in patients with early BC (EBC) versus metastatic BC (MBC) patients to investigate the impact of metastatic cancer on SM. Methods: Body composition measures were compared between patients with EBC receiving adjuvant chemotherapy and MBC initiating first line palliative chemotherapy. Measures were derived from analysis CT scans of L3 lumbar segments using radiological software (ABACS). Measures include: skeletal muscle area (SMA), density (SMD), index (SMI = SMA/height ^2), and integrated density (SMID = SMI x SMD). Sarcopenia was defined as SMI < 41(Martin-JCO, 2013). Lean body mass (LBM) was calculated (kg) = [(L3 Muscle measured by CT (cm2) × 0.3) + 6.06]) (Prado-CCR, 2009). Body surface area (BSA) was calculated using the Mosteller formula. T-tests (continuous) and Chi-squared tests (categorical) compared variables between groups; multivariable linear regression models controlled for age and body mass index (BMI). Results: MBC patients (n = 40) were older than EBC (n = 151) (56 vs 49 years, p < 0.001). Mean BMI and BSA were similar in both groups (29.0 vs 28.8, p = 0.84; 1.87 vs 1.86 m2, p = 0.55). After adjusting for age and BMI, SMI (41.3 vs 44.7 cm2/m2, p = 0.009), SMD (29.8 vs 36.4 Hounsfield Units, p < 0.0001), SMG (1250 vs 1612, p < 0.0001), and LBM (39.3 vs 41.9 kg, p = 0.024) were significantly lower in the MBC group. The MBC group included significantly more sarcopenic patients (58% vs 31%, p = 0.0016). Conclusions: Although BMI and BSA were similar in EBC and MBC patients, SM measures showed significant differences. MBCs had lower LBM, SMI, and SMD. More advanced BC was associated with higher proportions of sarcopenia. Further research is needed to explore interventions in sarcopenic patients in order improve outcomes in women with both EBC and MBC.

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Comparison between skeletal muscle and adipose tissue measurements with high-dose CT and low-dose attenuation correction CT of 18F-FDG PET/CT in elderly Hodgkin lymphoma patients: a two-centre validation

British Journal of Radiology ◽

10.1259/bjr.20200672 ◽

2021 ◽

pp. 20200672

Author(s):

Domenico Albano ◽

Luca Camoni ◽

Roberto Rinaldi ◽

Alessandra Tucci ◽

Vittorio Ruggero Zilioli ◽

...

Keyword(s):

Skeletal Muscle ◽

Adipose Tissue ◽

Fdg Pet ◽

Low Dose ◽

High Dose ◽

Muscle Area ◽

Pet Ct ◽

Skeletal Muscle Area ◽

Fdg Pet Ct ◽

Subcutaneous Adipose

Objectives: High-dose CT (HDCT) is considered the gold-standard imaging for the measurements of skeletal muscle area (SMA), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and intramuscular adipose tissue (IMAT) areas in the abdomen. These parameters may reflect sarcopenia, which can have a prognostic impact in several oncological diseases. The aim of this study was to compare the agreement of measurements of SMA, VAT, SAT and IMAT areas between HDCT and low-dose CT (LDCT) of 18-fludeoxyglucose positron emission tomography (18F-FDG PET)/CT in elderly patients affected by Hodgkin lymphoma (HL). Methods: We retrospectively included 90 patients affected by HL who underwent baseline 18F-FDG-PET/CT and HDCT within a mean interval of 7 days. HDCT and LDCT images were analysed by two blinded observers using segmentation software (Slice-O-Matic, Tomovision) to quantify the areas. HDCT and LDCT measurements were compared using Bland–Altman plots and Passing-Bablock regression analyses. Pearson correlation coefficient (r) was used to correlate measurements from the two imaging modalities. Results: Comparison of HDCT and LDCT data demonstrated a strong correlation for measurement of VAT(r = 0.942, p < 0.0001), SAT (r = 0.894, p < 0.0001) and SMA (r = 0.934, p < 0.0001). Instead considering IMAT, correlation was good but less significant (r = 0.742). The mean difference between the two methods was found to be very small, with a difference of 1% for SAT,+6.1% for VAT,+2.5% for SMA and −1.9% for IMAT. Conclusion: LDCT of PET/CT is a safe, accurate and precise method for the measurements of skeletal muscle area, visceral and subcutaneous adipose tissue. Their measurements are reproducible and correlate closely with HDCT. Advances in knowledge: LLDCT of PET/CT is a safe and accurate method for the measurements of SMA, VAT and SAT; their measurements are closely correlated with HDCT. LDCT can be considered an accurate alternative tool for measuring abdominal fat and muscles in the clinical practice.

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

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.9516 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 9516-9516 ◽

Cited By ~ 3

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]

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Characterizing Muscle Phenotype and Prognosis in Patients with Multiple Myeloma

Proceedings of IMPRS ◽

10.18060/24807 ◽

2020 ◽

Vol 3 ◽

Author(s):

Shannon Zhou ◽

Libbie Silverman ◽

Andrew Young ◽

David Roodman ◽

Attaya Suvannasankha ◽

...

Keyword(s):

Skeletal Muscle ◽

Multiple Myeloma ◽

Muscle Mass ◽

Lumbar Vertebrae ◽

University Hospital ◽

Muscle Quality ◽

Rank Test ◽

Muscle Area ◽

Skeletal Muscle Index ◽

Skeletal Muscle Area

Background/Objective: Low muscle mass (myopenia), poor muscle quality, myosteatosis, and muscle loss are associated with mortality in solid tumors. However, their impact in hematological malignancies remains unclear. We sought to determine how muscle phenotype relates to survival in patients with multiple myeloma. Methods: We performed a retrospective review of patients with multiple myeloma treated at Indiana University Hospital from 2012-2016. Total skeletal muscle area (SMA) (cm2) and radiodensity were measured on baseline (closest to diagnosis) and last CT scans at the third lumbar vertebrae area. SMA was normalized to height (SMA cm2/m2) to define skeletal muscle index (SKMI). Myopenia was defined as (SKMI) <52.4 cm2/m2 (men) and <38.5 cm2/m2 (women). Myosteatosis and obesity were defined per published BMI-specific cutoffs. Difference in survival between groups was estimated using log rank test. Results: Of 455 patients with multiple myeloma, 137 had more than one CT scan; 42 of these have been assessed to date. Half (21/42) were myopenic. Myopenia was equally prevalent across BMI categories and showed no association with survival. More than half of patients displayed myostetatosis; however, this was not associated with survival. Obesity and myopenic obesity were likewise not correlated with survival. Below-median baseline SKMI correlated with mortality, HR 2.721 (95% CI, 1.160-5.564: P=0.0129). As well, below-median final SMA correlated with mortality, HR 2.381 (95% CI, 1.094-5.181, P=0.0213). On average patients lost .7129% of SMA (95% CI; -6.072%-4.646%). Females had higher mortality, HR 2.355 (95% CI 0.9895-5.604, P=0.0215). Conclusion and Potential Impact: Although this study represents a fraction of treated patients to date, myopenia was prevalent among patients at diagnosis of multiple myeloma. Low muscle mass and sex appear to be important prognostic factors for survival. Additional measurements as well as univariate and multivariate analyses are necessary to verify these findings and identify additional factors that contribute to survival in multiple myeloma.

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