Myosteatosis Differentially Affects the Prognosis of Non-Metastatic Colon and Rectal Cancer Patients: An Exploratory Study

Body composition performed by computed tomography (CT) impacts on cancer patients’ prognoses and responses to treatment. Myosteatosis has been related to overall survival (OS) and disease-specific survival in colorectal cancer (CRC); however, the independent impact of the association of myosteatosis with prognosis in colon cancer (CC) and rectal cancer (RC) is still unclear. CT was performed at the L3 level to assess body composition features in 227 patients with CRC. Clinical parameters were collected. Overall survival (OS) was the primary outcome, and the secondary outcome was disease-free survival (DFS). Skeletal muscle attenuation and intramuscular adipose tissue area were associated with DFS (p = 0.003 and p = 0.011, respectively) and OS (p < 0.001 and p < 0.001, respectively) in CC patients but not in RC patients. Only the skeletal muscle area was associated with better prognosis related to OS in RC patients (p = 0.009). When CC and RC were analyzed separately, myosteatosis influenced survival negatively in CC patients, worsening DFS survival (hazard ratio [HR], 2.70; 95% confidence interval [CI], 1.07–6.82; p = 0.035) and OS (HR, 5.76; 95% CI, 1.31–25.40; p = 0.021). By contrast, the presence of myosteatosis did not influence DFS (HR, 1.02; 95% CI, 0.52–2.03; p = 0.944) or OS (HR, 0.76; 95% CI, 0.33–1.77; p = 0.529) in RC patients. Our study revealed the interference of myosteatosis in the therapy and survival of patients with CC but not in those with RC, strengthening the value of grouping the two types of cancer in body composition analyses.

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Mecobalamin as a Neuroprotective Effector against Oxaliplatin-Based Chemotherapy in Colon and Rectal Cancer Patients

Care Weekly ◽

10.14283/cw.2021.2 ◽

2021 ◽

pp. 1-5

Author(s):

Li Hongyan ◽

Lu Wanting ◽

Li Fei

Keyword(s):

Rectal Cancer ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Disease Free Survival ◽

Sensory Neuropathy ◽

Control Group ◽

Placebo Control ◽

Case Group ◽

Colon And Rectal Cancer ◽

Grade 3

Palliative chemotherapy prolongs survival and improves quality of life. However, a variety of chemotherapeutics including oxaliplatin can cause severe side effects during treatments, leading to painful symptoms that might result in the interruption of cancer treatment. Although adding oxaliplatin to fluorouracil and leucovorin in adjuvant chemotherapy for colon and rectal cancer may improve disease-free survival, it also increases grade 3–4 sensory neuropathy. Our study aimed to determine whether oral Mecobalamin is neuroprotective against oxaliplatin-induced neuropathy. Forty-six stage III colon and rectal cancer patients receiving adjuvant biweekly oxaliplatin were randomized to oral Mecobalamin (1,500 mg; case group) or placebo (control group). Clinical neurological and electrophysiological evaluations were performed at baseline and after 4, 8, and 12 treatment cycles. Treatment-related toxicity was evaluated based on National Cancer Institute (NCI) criteria. After four cycles of chemotherapy, 9 of 23 patients in the control group and 8 of 23 patients in case group experienced grade 1 sensory neuropathy. After eight cycles, 13 patients experienced sensory neuropathy (grade 2–4 toxicity) in the control group; however, no patients in the case group experienced sensory neuropathy (P < 0.05). After 12 cycles, grade 2–4 sensory neuropathy was observed in 20 patients in the control group, but only in 4 patients in the case group (P < 0.05). We did not observe any significant electrophysiological changes in the case group after 4, 8, or 12 cycles of chemotherapy. Thus, we demonstrated that oral Mecobalamin reduces the incidence of neuropathy in colon and rectal cancer patients receiving oxaliplatin-based adjuvant chemotherapy.

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Abnormal body composition in patients with adrenal adenomas

Acta Endocrinologica ◽

10.1530/eje-21-0458 ◽

2021 ◽

Author(s):

Danae Delivanis ◽

Maria Daniela Hurtado Andrade ◽

Tiffany Cortes ◽

Shobana Athimulam ◽

Aakanksha Khanna ◽

...

Keyword(s):

Skeletal Muscle ◽

Body Composition ◽

Muscle Mass ◽

Visceral Fat ◽

Cushing Syndrome ◽

Cross Sectional Study ◽

Cortisol Secretion ◽

Muscle Area ◽

Cross Sectional ◽

Skeletal Muscle Area

Objective: Increased visceral fat and sarcopenia are cardiovascular risk factors that may explain increased cardiovascular morbidity and frailty in patients with adrenal adenomas. Our objective was to compare body composition measurement of patients with adrenal adenomas to referent subjects without adrenal disease Design: Cross-sectional study, 2014-2018 Methods: Participants were adults with nonfunctioning adrenal tumor (NFAT), mild autonomous cortisol secretion (MACS) and Cushing syndrome (CS), and age, sex and body mass index 1:1 matched referent subjects without adrenal disorders. Main outcome measures were body composition measurements calculated from abdominal computed tomography imaging. Intraabdominal adipose tissue and muscle mass measurements were performed at the 3rd lumbar spine level. Results: Of 227 patients with adrenal adenomas, 20 were diagnosed with CS, 76 with MACS and 131 with NFAT. Median age was 56 years (range, 18-89), and 67% were women. When compared to referent subjects, patients with CS, MACS, and NFAT demonstrated a higher visceral fat (odds ratio (OR) of 2.2 [95% CI 0.9-6.5], 2.0 [1.3-3.2], and 1.8 [1.2-2.7] and a lower skeletal muscle area (OR of 0.01 [95% CI 0-0.09], 0.31 [0.18-0.49], and 0.3 [1.2-2.7]), respectively. For every 1 mcg/dL cortisol increase after overnight dexamethasone, visceral fat/muscle area ratio increased by 2.3 (P=0.02) and mean total skeletal muscle area decreased by 2.2cm2 (P=0.03). Conclusion: Patients with adrenal adenomas demonstrate a lower muscle mass and a higher proportion of visceral fat when compared to referent subjects, including patients with NFAT. Even a subtle abnormality in cortisol secretion may impact health of patients with adenomas.

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Impact of a ketogenic diet intervention during radiotherapy on body composition: III. An interim analysis of the KETOCOMP study

10.1101/343251 ◽

2018 ◽

Author(s):

Rainer J. Klement ◽

Gabriele Schäfert ◽

Reinhart A. Sweeney

Keyword(s):

Breast Cancer ◽

Skeletal Muscle ◽

Amino Acids ◽

Rectal Cancer ◽

Body Composition ◽

Cancer Patients ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Essential Amino Acids ◽

Ketogenic Diets

AbstractBackgroundKetogenic therapy (KT) in the form of ketogenic diets (KDs) and/or supplements that induce nutritional ketosis have gained interest as a complementary treatment for cancer patients. Besides putative anti-tumor effects, preclinical and preliminary clinical data indicate that KT could induce favorable changes in body composition of the tumor bearing host. Here we present first results of our ongoing KETOCOMP study (NCT02516501) study concerning body composition changes among rectal, breast and head & neck cancer (HNC) patients who underwent concurrent KT during standard-of-care radiotherapy (RT).MethodsEligible patients were assigned to one of three groups: (i) a standard diet group; (ii) a ketogenic breakfast group taking 50-250 ml of a medium-chain triglyceride (MCT) drink plus 10 g essential amino acids in the morning of RT days; (iii) a complete KD group supplemented with 10 g essential amino acids on RT days. Body composition was to be measured prior to and weekly during RT using 8-electrode bioimpedance analysis. Longitudinal data were analyzed using mixed effects linear regression.ResultsA total of 17 patients underwent KT during RT thus far (rectal cancer: n=6; HNC: n=6; breast cancer: n=5). All patients consuming a KD (n=14) reached nutritional ketosis and finished the study protocol with only minor problems reported. Compared to control subjects, the ketogenic intervention in rectal and breast cancer patients was significantly associated with a decline in fat mass over time (−0.3 and −0.5 kg/week, respectively), with no significant changes in skeletal muscle mass. In HNC patients, concurrent chemotherapy was the strongest predictor of body weight, fat free and skeletal muscle mass decline during radiotherapy, while KT showed significant opposite associations. Rectal cancer patients who underwent KT during neoadjuvant RT had significantly better tumor response at the time of surgery as assessed by the Dworak regression grade (median 3 versus 2, p=0.04483).ConclusionsWhile sample sizes are still small our results already indicate some significant favorable effects of KT on body composition. These as well as a putative radiosensitizing effect on rectal tumor cells need to be confirmed once the final analysis of our study becomes possible.

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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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Clinical implications of muscle mass and quality in early-stage colorectal cancer (CRC).

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.648 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 648-648

Author(s):

Jessica Hopkins ◽

Vickie E Baracos ◽

David Bigam ◽

Dean Eurich ◽

Michael B. Sawyer

Keyword(s):

Skeletal Muscle ◽

Overall Survival ◽

Body Composition ◽

Muscle Mass ◽

Visceral Fat ◽

Cox Regression ◽

Early Stage ◽

Visceral Obesity ◽

Disease Free Survival ◽

Skeletal Muscle Index

648 Background: Body composition has emerged as a potential prognostic factor for outcomes in early-stage CRC. Specifically, muscle mass and quality and visceral fat have been shown to be related to overall survival (OS) and disease-free survival (DFS). The objective of this study was to determine associations of sarcopenia, reduced skeletal muscle radiodensity (SMR) and visceral obesity (VO) with 5-year OS and DFS. Methods: Muscle and visceral fat at the time of diagnosis were quantified in a retrospective cohort of consecutive, early-stage CRC patients (pts), identified from a prospectively collected cancer database. Skeletal muscle area on computed tomography (CT) was measured and normalized by height (m2) in order to compare skeletal muscle index (SMI) between pts. Mean SMR and visceral fat area were measured. All parameters were analyzed using Kaplan-Meier curves and univariate Cox regression. Sarcopenia was defined as SMI < 41 cm2/m2 in females and < 43 cm2/m2 in males with BMI < 25 kg/m2 and < 53 cm2/m2 with BMI > 25 kg/m2. Reduced SMR was defined as < 41 HU if BMI < 25 kg/m2 and < 33 HU if BMI > 25 kg/m2. VO was defined as VAT > 160cm2 in males and > 80cm2 in females. Results: We identified 968 pts with available CTs and anthropometric data. Prevalence of sarcopenia was 44.5% in males and 59.6% in females. Myosteatosis was present in 60.9% of pts. The mean length of follow up was 5.0 years, with 254 patients developing recurrent disease and 351 deaths. Males with sarcopenia and myosteatosis had worse overall survival (HR, 0.69, p = 0.005; HR 0.49, p < 0.001) but no difference in DFS. Presence of VO was not associated with worse OS or DFS. There was no difference in OS for females with sarcopenia or VO, but myosteatosis predicted reduced OS (HR 0.53, p = 0.004). There was no difference in DFS for females by presence of sarcopenia, myosteatosis or VO. Conclusions: Body composition, specifically sarcopenia and myosteatosis, are highly prevalent in CRC pts treated with curative intent, and their presence is associated with reduced OS. Therefore, skeletal muscle mass and radiodensity are important prognostic factors in CRC outcomes, which are easily attained in a clinical setting.

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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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Impact of Body Composition Status on 90-Day Mortality in Cancer Patients with Septic Shock: Sex Differences in the Skeletal Muscle Index

Journal of Clinical Medicine ◽

10.3390/jcm8101583 ◽

2019 ◽

Vol 8 (10) ◽

pp. 1583 ◽

Cited By ~ 2

Author(s):

Youn-Jung Kim ◽

Dong-Woo Seo ◽

Jihoon Kang ◽

Jin Won Huh ◽

Kyung Won Kim ◽

...

Keyword(s):

Skeletal Muscle ◽

Septic Shock ◽

Body Composition ◽

Cancer Patients ◽

Proportional Hazards Model ◽

Lumbar Vertebra ◽

Cox Proportional Hazards Model ◽

Muscle Area ◽

Skeletal Muscle Index ◽

Male Patients

Abnormalities in body composition are associated with poor prognosis in cancer patients. We investigated the association between body composition and 90-day mortality in cancer patients who developed septic shock. We included consecutive septic shock patients with active cancer from 2010 to 2017. The muscle area at the level of the third lumbar vertebra was measured by computed tomography upon emergency department admission and adjusted by height squared, yielding the Skeletal Muscle Index (SMI). Hazard ratios (HRs) and 95% confidence intervals (CIs) for 90-day mortality were estimated using a Cox proportional hazards model. Among 478 patients, the prevalence of muscle depletion was 87.7%. Among markers of body composition, the SMI only differed significantly between non-survivors and survivors (mean, 35.48 vs. 33.32 cm2/m2; P = 0.002) and was independently associated with lower 90-day mortality (adjusted HR, 0.970; P = 0.001). The multivariable-adjusted HRs (95% CI) for 90-day mortality comparing quartiles 2, 3, and 4 of the SMI to the lowest quartile were 0.646 (0.916–1.307), 0.620 (0.424–0.909), and 0.529 (0.355–0.788), respectively. The associations were evident in male patients, but not in female patients. The SMI was independently associated with 90-day mortality in cancer patients with septic shock. The graded association between the SMI and 90-day mortality was observed in male patients.

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Feasibility and Preliminary Efficacy of a 10-Week Resistance and Aerobic Exercise Intervention During Neoadjuvant Chemoradiation Treatment in Rectal Cancer Patients

Integrative Cancer Therapies ◽

10.1177/1534735418781736 ◽

2018 ◽

Vol 17 (3) ◽

pp. 952-959 ◽

Cited By ~ 7

Author(s):

Favil Singh ◽

Daniel A. Galvão ◽

Robert U. Newton ◽

Nigel A. Spry ◽

Michael K. Baker ◽

...

Keyword(s):

Quality Of Life ◽

Skeletal Muscle ◽

Rectal Cancer ◽

Body Composition ◽

Aerobic Exercise ◽

Cancer Patients ◽

Neoadjuvant Chemoradiation ◽

Leg Press ◽

Chemoradiation Treatment

Background: Neoadjuvant chemoradiation treatment (CRT) in rectal cancer patients is associated with a reduction in physical capacity, lean mass and increased fatigue. As a countermeasure to these treatment-related adverse effects, we examined the feasibility and preliminary efficacy of a 10-week exercise program during CRT. Methods: Ten rectal cancer patients (7 men, aged 27-70 years, body mass index = 26.4 ± 3.8 kg/m2) receiving CRT undertook supervised resistance and aerobic exercise twice weekly. Assessments were undertaken pre- and post-intervention for upper and lower body muscle strength by 1-RM, muscle endurance, physical performance tests, body composition by dual X-ray absorptiometry, quality of life, and fatigue. Results: There was a significant loss in appendicular skeletal muscle (−1.1 kg, P = .012), and fat mass (−0.8 kg, P = .029) following CRT. Despite the loss in skeletal muscle, leg press ( P = .030) and leg extension ( P = .046) strength improved by 27.2% and 22.7%, respectively, and leg press endurance by 76.7% ( P = .007). Changes in strength were accompanied by improved performance ( P < .05) in 6-m fast walking speed (6.9%) and dynamic balance as determined by the 6-m backwards walk (15.5%). There was minimal change in quality of life and fatigue, and no adverse events related to training. Conclusions: Exercise during neoadjuvant CRT appears to be feasible and well tolerated in rectal cancer patients and may enhance physical function while minimizing adverse changes in body composition and cancer-related fatigue. These initial findings need to be confirmed in randomized controlled trials.

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