Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study

BackgroundObservational studies suggest that loss of skeletal muscle mass (SMM) is associated with chemotherapy‐related toxicity, poor quality of life, and poor survival in metastatic colorectal cancer (mCRC) patients. Little is known about the evolution of SMM during palliative systemic therapy. We investigated changes in SMM during various consecutive palliative systemic treatment regimens using repeated abdominal computed tomography scans of mCRC patients who participated in the randomized phase 3 CAIRO3 study.MethodsIn the CAIRO3 study, mCRC patients with stable disease or better after 6 cycles of first‐line treatment with capecitabine + oxaliplatin + bevacizumab (CAPOX‐B) were randomized between maintenance treatment with capecitabine + bevacizumab (CAP‐B) or observation. Upon first disease progression, in both groups, CAPOX‐B or other treatment was reintroduced until the second disease progression, which was the primary study endpoint. We analysed 1355 computed tomography scans of 450 (81%) CAIRO3 patients (64 ± 9.0 years, CAP‐B n = 223; observation n = 227) for SMM at four time points (i.e. prior to the start of pre‐randomization initial treatment, at randomization, and at first and at second disease progression) using the Slice‐o‐matic software and single slice evaluation at the lumbar 3 level. By using accepted and widely used formulas, whole body SMM was calculated. A linear mixed effects model, adjusted for relevant confounders, was used to assess SMM changes for the total group and within and between study arms.ResultsDuring 6 cycles of initial treatment with CAPOX‐B prior to randomization, SMM decreased significantly in all patients [CAP‐B arm: −0.53 kg (95% CI −1.12; −0.07) and observation arm: −0.85 kg (−1.45; −0.25)]. After randomization, SMM recovered during CAP‐B treatment by 1.32 kg (0.73; 1.90) and observation by 1.20 kg (0.63; 1.78) (median time from randomization to first disease progression 8.6 and 4.1 months for CAP‐B arm and observation arm, respectively). After first progression and during reintroduction treatment with CAPOX‐B or other treatment, SMM again decreased significantly and comparable in both arms, CAP‐B: −2.71 kg (−3.37; −2.03), and observation: −2.01 kg (−2.64; −1.41) (median time from first progression until second progression CAP‐B arm: 4.7 months and observation arm: 6.6 months).ConclusionsThis longitudinal study provides a unique insight in SMM changes in mCRC patients during palliative systemic treatment regimens, including observation. Our data show that muscle loss is reversible and may be influenced by the intensity of systemic regimens. Although studies have shown prognostic capacity for SMM, the effects of subsequent changes in SMM are unknown and may be clues for new future therapeutic interventions.

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Impact of different palliative systemic treatments on skeletal muscle mass in metastatic colorectal cancer patients

Kurk

Peeters

Dorresteijn

et al. 2018

“…Among various imaging modalities, such as dual‐energy X‐ray absorptiometry, computed tomography (CT), magnetic resonance imaging, and bioimpedance analysis, CT seems the best suited to measuring skeletal muscle mass in clinical settings, particularly in the surgical field, as CT is usually performed as part of the pre‐operative work‐up and during follow‐up. Although several studies from Western countries have proposed different cut‐offs for low skeletal muscle mass as calculated from CT,2, 3, 5 such values would differ from those in Asian populations, due to general differences in characteristics such as body size, lifestyles, and other factors. We have previously established new diagnostic criteria for low skeletal muscle mass by using the psoas muscle mass index from healthy young Asian adults, which was adopted in the Japan Society of Hepatology guidelines for sarcopenia in liver disease 13, 14.…”

Section: Introductionmentioning

confidence: 99%

Proposal for new selection criteria considering pre‐transplant muscularity and visceral adiposity in living donor liver transplantation

Hamaguchi

Kaido

Okumura

et al. 2018

BackgroundThe significance of pre‐operative body composition has recently attracted much attention in various diseases. However, cut‐off values for these parameters remain undetermined, and these factors are not currently included in selection criteria for recipients of living donor liver transplantation (LDLT).MethodsUsing computed tomography of 657 donors for LDLT, skeletal muscle mass, muscle quality, and visceral adiposity were evaluated by using skeletal muscle mass index (SMI), intramuscular adipose tissue content (IMAC), and visceral‐to‐subcutaneous adipose tissue area ratio (VSR). Sex‐specific cut‐offs for SMI, IMAC, and VSR were determined, and correlations with outcomes after LDLT in 277 recipients were examined with the aim of establishing new selection criteria for LDLT.ResultsOn the basis of younger donor data, we determined sex‐specific cut‐off values for low SMI, high IMAC, and high VSR (mean ± 2 standard deviations). Patients with all three factors showed the lowest survival rate after LDLT (1 year survival rate, 41.2%; P < 0.001). On multivariate analysis, low SMI (P = 0.002), high IMAC (P = 0.002), and high VSR (P = 0.001) were identified as independent risk factors for mortality after LDLT. Based on these findings, we have excluded patients showing all three factors (low SMI, high IMAC, and high VSR) as candidates for LDLT since October 2016.ConclusionsUsing cut‐off values determined from healthy donors, we have established new selection criteria for LDLT including body composition, which should improve post‐transplant outcomes.

“…Often, authors use previously published cut‐points that were originally derived using optimal stratification (e.g. Thoresen52 used the Prado53 cut‐points for skeletal muscle index, ≤38.5 cm 2 /m 2 for women and ≤52.5 cm 2 /m 2 for men, and found a low muscle mass prevalence of 39%). Regardless of the cut‐points applied or whether the linear measures were modelled continuously, we found that the linear measures method was valid compared with total L3 cross‐sectional area and associated with overall mortality.…”

Section: Discussionmentioning

confidence: 99%

Screening for low muscularity in colorectal cancer patients: a valid, clinic‐friendly approach that predicts mortality

Feliciano

Avrutin

Caan

et al. 2018

BackgroundLow skeletal muscle quantified using computed tomography (CT) scans is associated with morbidity and mortality among cancer patients. However, existing methods to assess skeletal muscle from CT are time‐consuming, expensive, and require training. Clinic‐friendly tools to screen for low skeletal muscle in cancer patients are urgently needed.MethodsWe included 807 scans from non‐metastatic colorectal cancer patients. With the digital ruler available in most radiological software, we implemented an abbreviated method to assess skeletal muscle area at the third lumbar vertebra (L3), which consisted of assessing the height and width of the psoas and paraspinal muscles and computing their combined ‘linear area’ in centimetres squared (cm2). A subset of CT scans was assessed twice by two analysts to compute intra‐rater and inter‐rater reliability. We derived cut‐points for ‘low’ linear area using optimal stratification and then calculated the sensitivity and specificity of these cut‐points relative to standard methods (total L3 cross‐sectional area assessed with Slice‐O‐Matic research software). We further evaluated the association of low linear area with death from any cause after colorectal cancer diagnosis in Cox proportional hazards models adjusting for demographics, smoking, body mass index category, and tumour characteristics.ResultsThe linear area was highly correlated with total cross‐sectional area assessed using standard methods [r = 0.92; 95% confidence interval (CI): 0.91, 0.93] overall and within subgroups defined by age, sex, and body mass index group. Intra‐rater and inter‐rater reliability were equally high (both intra‐class correlations = 0.98). Cut‐points for low linear area were sensitive (0.75; 95% CI: 0.70, 0.80) and specific (0.77; 95% CI: 0.73, 0.80) for identifying low skeletal muscle relative to the standard of total L3 cross‐sectional area. The hazard ratio and 95% CI for death associated with a low linear area were hazard ratio = 1.66; 95% CI: 1.22, 2.25.ConclusionsClinic‐friendly methods that assess linear area from CT scans are an accurate screening tool to identify low skeletal muscle among non‐metastatic colorectal cancer patients. These linear measures are associated with mortality after colorectal cancer, suggesting they could be clinically useful both to improve prognostication and to provide a practical screening tool to identify cancer patients who require nutrition or exercise intervention.