Body composition and treatment-related toxicity in pediatric lymphoma.

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.

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3167
Author(s):  
Takuya Yoshimura ◽  
Hajime Suzuki ◽  
Hirotaka Takayama ◽  
Shotaro Higashi ◽  
Yuka Hirano ◽  
...  

The impact of preoperative malnutrition and sarcopenia on survival in oral squamous cell carcinoma (OSCC) patients remains controversial. We investigated the effects of the preoperative nutritional status and abnormalities in body composition on the mortality of OSCC patients. A retrospective study involving 103 patients with OSCC was conducted. Disease-specific survival (DSS) according to the preoperative psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC) was evaluated. Univariate and multivariate analyses were performed to determine the predictive performance of the covariates with respect to DSS. The DSS rate in patients with high IMAC and low PMI was significantly lower than that in controls. Multivariate analysis revealed that a low preoperative Prognostic Nutritional Index (PNI) and high IMAC were independent risk factors. We demonstrated that preoperative malnutrition and abnormal body composition, such as preoperative skeletal muscle quality, are associated with DSS in OSCC patients. Our study suggests that the evaluation of preoperative malnutrition and skeletal muscle quality would be useful for predicting mortality in patients with OSCC.


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.


2018 ◽  
Vol 36 (34_suppl) ◽  
pp. 209-209
Author(s):  
Eric Roeland ◽  
Areej El-Jawahri ◽  
Nora Horick ◽  
Sandahl H Nelson ◽  
Andrea Gallivan ◽  
...  

209 Background: Given body composition predicts toxicity for patients receiving cytotoxic chemotherapy, we explored changes in body composition and biomarkers as predictors of immune-related adverse events (irAEs) and health care utilization. Methods: We conducted a longitudinal study of patients with metastatic solid tumor receiving immunotherapy (07/2014-10/2017). Eligible patients had a computed tomography (CT) scan prior to first-line immunotherapy with at least two additional CT scans at three, six or nine months after immunotherapy initiation. We analyzed body composition using cross-sectional CT scans at the third lumbar vertebra. We utilized mixed effect linear regression models to assess longitudinal changes in body composition (weight, skeletal muscle, total adipose). We examined associations of baseline body composition and biomarkers (albumin, neutrophil-lymphocyte ratio (NLR)) with the incidence of irAEs and healthcare utilization (hospitalizations/ED visits) using logistic regression. Results: Of 140 patients treated with immunotherapy, 61 met inclusion criteria. The majority (80%) received prior chemotherapy and the most common malignancies included lung (26%), head and neck (20%), and melanoma (20%). We found that one-third (n=19) experienced an irAE and colitis (53%) was the most common irAE. Patients experienced substantial weight loss over time (B= -1.88, p<0.001) with a decrease both in skeletal muscle (B= -3.08, p=0.001) and total adipose tissue (B =-50.44, p<0.001). We found greater skeletal muscle at baseline was associated with lower risk of health care utilization (OR 0.98, 95% CI: 0.965-0.998, p=0.03). We observed no association with biomarkers and/or body composition variables with irAEs or health care utilization. Conclusions: Patients with metastatic cancer receiving immunotherapy lose weight including skeletal muscle and adipose tissue. Aside from higher baseline skeletal muscle predicting less health care utilization, we did not observe any other associations between body composition changes and irAEs or health care utilization.


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.


2018 ◽  
Vol 3 (1) ◽  
Author(s):  
Rogier Leendert Charles Plas ◽  
Klaske Van Norren ◽  
Harm Van Baar ◽  
Carla Van Aller ◽  
Maarten De Bakker ◽  
...  

AbstractBackground: Chemotherapeutic treatment is regularly accompanied by side-effects. Hydrophilic chemotherapeutics such as capecitabine and oxaliplatin (CAPOX), often used in colorectal cancer treatment, predominantly accumulate in non-adipose tissues. From this we hypothesized that body composition and fat infiltration in the muscle (muscle attenuation and intermuscular-adipose-tissue [IMAT] content) are associated with chemotherapy-induced toxicities.Methods: In this retrospective observational study, we collected data from 115 colorectal cancer patients receiving adjuvant CAPOX chemotherapy between 2006 and 2015. Information on cancer characteristics were obtained from the Netherlands Cancer Registry. Diagnostic CT scans were retrieved to assess cross-sectional areas of skeletal muscle and adipose tissue at the third lumbar vertebrae. Information on dose-limiting toxicity [DLT] and relative administered dose (as % of BSA-based-planned-dose) were retrieved from medical charts. Associations between body composition, muscle quality and chemotherapy-induced toxicities were determined using Cox-regression and linear-regression analyses.Results: We found that DLT incidence was 90% in our cohort: 50% had their dose reduced, 30% their next cycle postponed, 4% a full treatment stop and 6% was hospitalized at their first DLT. Most common were reductions in oxaliplatin dose whilst keeping the capecitabine dose constant. Cox regression analysis indicated no association between body composition or muscle quality and DLT during the first treatment cycle or time to the first DLT. Multiple linear regression showed that higher IMAT-index and IMAT muscle percentage were associated with a lower relative administered dose of oxaliplatin.Conclusions: In conclusion; only IMAT, not skeletal or fat area was associated with dose-limiting toxicities among these CRC patients who received CAPOX treatment.


2020 ◽  
Author(s):  
Wenhao Zhao ◽  
Xuelian Liu ◽  
Xiangliang Liu ◽  
Haimei Yang ◽  
Wei Ji ◽  
...  

Abstract Purpose: The tolerance of patients withdiffuse large B cell lymphoma(DLBCL) receiving CHOP±R regimen was significantly different, and grade 3~4 hematologic toxicity after chemotherapy in some patients resulted in prolonged hospital stay, increased risk of infection, delayed treatment, and directly or indirectly affected short-term efficacy and long-term prognosis. Lean body mass(LBM)and L3 skeletal muscle index (L3SMI)obtained from abdominal CT of DLBCL patients were analyzed to determine whether they could be used as independent predictors of hematological toxicity of CHOP± R regimen in DLBCL patients.Methods: The patients with DLBCL who underwent CHOP±R regimen at the Cancer Center of the First Hospital of Jilin University from January 2015 to November 2018 were retrospectively analyzed. The abdominal CT of the patient was analyzed by sliceOmatic5.0 software. The third lumbar disc planar imaging was selected, and two consecutive images were taken to calculate LBM and L3SMI. Single factor and multivariate analysis were performed on the correlation of LBM, L3SMIand chemotherapy-related grade 3~4 hematologic toxicity. The ROC curve was drawn to investigate the predictive value of various human indicators on the hematologic toxicity of grade 3~4 related to chemotherapy.Results: The L3 skeletal muscle index is associated with the occurrence of grade 3~4 hematologic toxicity (leukocyte and neutropenia) in patients with diffuse large B-cell lymphoma treated with CHOP±R regimen. Those with lower L3SMI are prone to grade 3~4 hematologic toxicity.LBM is associated with the occurrence of grade 3~4 hematologic toxicity (leukopenia) in patients with diffuse large B-cell lymphoma treated with CHOP±R regimen. This with lower LBM is prone to grade 3~4 hematologic toxicity.The L3 skeletal muscle index can be used as an independent predictor of grade 3~4 hematologic toxicity (leukocyte and neutropenia) in patients with diffuse large B-cell lymphoma treated with CHOP ± R regimen. The cut-off value can be defined as 39.91 cm2/m2.Conclusion: We can draw the following conclusions:The L3 skeletal muscle index is associated with the occurrence of grade 3~4 hematologic toxicity (leukocyte and neutropenia) in patients with diffuse large B-cell lymphoma treated with CHOP±R regimen. Those with lower L3SMI are prone to grade 3~4 hematologic toxicity.LBM is associated with the occurrence of grade 3~4 hematologic toxicity (leukopenia) in patients with diffuse large B-cell lymphoma treated with CHOP±R regimen. This with lower LBM is prone to grade 3~4 hematologic toxicity.The L3 skeletal muscle index can be used as an independent predictor of grade 3~4 hematologic toxicity (leukocyte and neutropenia) in patients with diffuse large B-cell lymphoma treated with CHOP ± R regimen. The cut-off value can be defined as 39.91 cm2/m 2.


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.


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.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6537-6537
Author(s):  
Grant Richard Williams ◽  
Chen Dai ◽  
Carson Foster ◽  
Mustafa Al-Obaidi ◽  
Christian Harmon ◽  
...  

6537 Background: Despite recent cancer advances, racial disparities in outcomes persist. Our objective was to examine racial differences in GA impairments, HRQOL, and body composition metrics as a novel way to understand outcome disparities in older adults with GI malignancies. Methods: The CARE registry at the University of Alabama at Birmingham (UAB) is an ongoing prospective cohort study that consecutively enrolls older adults (≥60y) with GI malignancies. The CARE registry utilizes a patient-reported GA that measures a broad range of aging-related health issues. HRQOL is measured using PROMIS Global-10. Computed-Tomography (CT) images are procured to measure skeletal muscle index (SMI) and skeletal muscle density (SMD) from the L3 cross-section. For this study, we examined the adjusted odds ratio (aOR) for racial differences in GA impairments, HRQOL, sarcopenia (defined as men BMI < 25, SMI ≤43 cm2/m2; men BMI ≥25, SMI < 53 cm2/m2; women SMI < 41 cm2/m2), and myosteatosis (defined as BMI < 25, < 41 Hounsfield Units [HU]; BMI ≥25, < 33 HU), adjusting for age, sex, education, cancer type, cancer stage, and comorbidity. Results: We included 448 patients with GI malignancies, with self-reported race as White or Black, a completed GA and available CT imaging +/- 60 days of GA completion. Mean age at enrollment was 70±7.2y, 58% were male and 25% were Black. Primary cancer diagnoses included colorectal cancer (33%), pancreatic cancer (25%), and other GI malignancies (52%). Black participants had lower education (high school or < 54% vs. 38%, p< 0.01) and were less likely to be married (55% vs 71%, p< 0.01). Black participants reported more limitations in activities of daily living (aOR = 2.0 (95% confidence level [CI] 1.01-3.9, p= 0.03) and frailty (aOR = 1.9, 95% CI 1.1-3.3, p= 0.02). Similarly, Black participants reported lower HRQOL (physical: β coefficient, -2.7; p= 0.03; mental: β coefficient, -2.4; p= 0.03). Conversely, Black participants were less likely to have sarcopenia (aOR = 0.5, 95% CI 0.3-0.9, p= 0.02) and myosteatosis (aOR = 0.12, 95% CI 0.02-0.8, p= 0.02). Conclusions: Differences in frailty, HRQOL, and body composition between Black and White participants present the first step towards understanding disparities in cancer outcomes amongst older adults.


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