Loss of skeletal muscle mass during neoadjuvant treatments correlates with worse prognosis in esophageal cancer: a retrospective cohort study.
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SUBMITTER: Jarvinen T
PROVIDER: S-EPMC5809976 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundSarcopenia can contribute to negative outcomes in patients with various lung diseases. However, whether sarcopenia affects prognosis in patients with idiopathic pulmonary fibrosis (IPF) has not been reported. Simple measures of muscle mass, derived from chest computed tomography (CT), are increasingly being used to identify patients with sarcopenia. We hypothesized that skeletal muscle mass could be a predictor of prognosis in IPF patients.MethodsWe retrospectively evaluated 180 patients diagnosed with IPF between January 2010 and December 2015 at a tertiary care hospital in South Korea. We measured thoracic muscle volume by using the cross-sectional area (CSA) of the pectoralis, paraspinal, serratus, and latissimus muscles at the 4th vertebral region (T4CSA) and the erector spinae muscle (ESMCSA) at the 12th vertebral region. CT scans at the time of diagnosis were used for analysis and respective CSA were divided by height squared to normalize for stature. Survival times were estimated with the Kaplan-Meier method and compared with the log-rank test. Multivariate Cox proportional hazards models were performed to investigate relationships between clinical parameters and mortality.ResultsMale patients in the lowest quartile of T4CSA divided by height squared (m2) (T4MI) and in the lowest quartile of ESMCSA divided by height squared (m2) (T12MI) were more likely to have higher Gender-Age-Physiology Index scores (T4MI, 3.3?±?1.3 vs 4.0?±?1.6, P?=?0.012; T12MI, 3.2?±?1.3 vs 4.1?±?1.6, P?=?0.002). Male patients in the lowest quartile of T4MI exhibited a significantly lower survival rate (P?=?0.035). After multivariate Cox proportional hazards analysis, T4MI was a significant risk factor for all-cause mortality (HR, 0.955; 95% CI, 0.913-0.998; P?=?0.041), whereas T12MI was not (HR, 0.980; 95% CI, 0.856-1.121; P?=?0.766).ConclusionsLow skeletal mass normalized for stature at the level of 4th vertebrae which can be acquired by quantifying thoracic skeletal muscle on single-slice axial chest CT, may be a strong risk factor for all-cause mortality in patients with IPF.Trial registrationThe research protocol was approved by the Institutional Review Board of Severance Hospital, South Korea (IRB No.4-2018-0454).
| S-EPMC6376641 | biostudies-literature
Project description:BACKGROUNDS:The relationship between sarcopenia, characterized by loss of muscle mass and strength, and survival outcomes of esophageal cancer is controversial. This study aimed to assess the effect of sarcopenia and skeletal muscle loss on overall survival (OS) and recurrence-free survival (RFS) of esophageal cancer patients. METHODS:We retrospectively collected the medical records of 248 male patients diagnosed with squamous cell esophageal cancer and who underwent neoadjuvant chemoradiotherapy (NACRT) followed by surgery. We measured the cross-sectional area of the skeletal muscle at the L3 vertebra level using computed tomography images and calculated the skeletal muscle index (SMI). Sarcopenia was defined as SMI <52.4 cm2/m2, and excessive muscle loss was defined as SMI change <-10.0%/50 days during NACRT. Moreover, laboratory test results, such as albumin, prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) before and after NACRT, were collected. RESULTS:In the univariable Cox analysis, pre- (p = 0.689) and post-radiotherapy (RT) sarcopenia (p = 0.669) were not associated with OS. However, excessive muscle loss had a significant association with OS in both the univariable and multivariable analyses (all p = 0.001). Excessive muscle loss was also related to RFS in both the univariable (p = 0.011) and multivariable (p = 0.022) Cox analysis. Patients with excessive muscle loss had significantly lower levels of post-RT albumin (p < 0.001) and PNI (p < 0.001), higher levels of post-RT NLR (p = 0.031) and PLR (p = 0.071), larger decrease in albumin (p < 0.001) and PNI (p < 0.001) after NACRT, and larger increase in NLR (p = 0.051) and PLR (p = 0.088) after NACRT than in those with non-excessive muscle loss. CONCLUSION:Excessive muscle loss rather than pre- and post-RT sarcopenia was a significant prognostic factor for OS and RFS, and it was also related to nutritional and inflammatory markers.
| S-EPMC7226603 | biostudies-literature
Project description:The aim of this study was to investigate whether rapid depletions of fat mass and skeletal muscle mass predict mortality in hepatocellular carcinoma (HCC) patients treated with sorafenib. This retrospective study evaluated 61 HCC patients. The cross-sectional areas of visceral and subcutaneous fat mass and skeletal muscle mass were measured by computed tomography, from which the visceral fat mass index (VFMI), subcutaneous fat mass index (SFMI), and skeletal muscle index (L3SMI) were obtained. The relative changes in these indices per 120 days (ΔVFMI, ΔSFMI, and ΔL3SMI) before and after sorafenib treatment were calculated in each patient. Patients within the 20th percentile cutoffs for these indices were classified into the rapid depletion (RD) group. Kaplan-Meier analysis revealed that with respect to ΔL3SMI (p = 0.0101) and ΔSFMI (p = 0.0027), the RD group had a significantly poorer survival. Multivariate analysis using the Cox proportional-hazards model also demonstrated that ΔL3SMI (≤-5.73 vs. >-5.73; hazard ratio [HR]: 4.010, 95% confidence interval [CI]: 1.799-8.938, p = < 0.001) and ΔSFMI (≤-5.33 vs. >-5.33; HR: 4.109, 95% CI: 1.967-8.584, p = < 0.001) were independent predictors. Rapid depletions of subcutaneous fat mass and skeletal muscle mass after the introduction of sorafenib indicate a poor prognosis.
| S-EPMC6721466 | biostudies-literature
Project description:BACKGROUND:Observational 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. METHODS:In 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. RESULTS:During 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). CONCLUSIONS:This 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.
| S-EPMC6204584 | biostudies-literature
Project description:BackgroundRisk assessment is relevant to predict postoperative outcomes in patients with gastro-oesophageal cancer. This cohort study aimed to assess body composition changes during neoadjuvant chemotherapy and investigate their association with postoperative complications.MethodsConsecutive patients with gastro-oesophageal cancer undergoing neoadjuvant chemotherapy and surgery with curative intent between 2016 and 2019 were identified from a specific database and included in the study. CT images before and after neoadjuvant chemotherapy were used to assess the skeletal muscle index, sarcopenia, and subcutaneous and visceral fat index.ResultsIn a cohort of 199 patients, the mean skeletal muscle index decreased during neoadjuvant therapy (from 51·187 to 49·19 cm2 /m2 ; P < 0·001) and the rate of sarcopenia increased (from 42·2 to 54·3 per cent; P < 0·001). A skeletal muscle index decrease greater than 5 per cent was not associated with an increased risk of total postoperative complications (odds ratio 0·91, 95 per cent c.i. 0·52 to 1·59; P = 0·736) or severe complications (odds ratio 0·66, 0·29 to 1·53; P = 0·329).ConclusionSkeletal muscle index decreased during neoadjuvant therapy but was not associated with postoperative complications.
| S-EPMC7528528 | biostudies-literature
Project description:BackgroundBone and skeletal muscle represent a single functional unit. We cross-sectionally investigated body composition, risk of fall and circulating osteocalcin (OC) isoforms in osteoporotic postmenopausal women to test the hypothesis of an involvement of OC in the bone-muscle crosstalk.Materials and methodsTwenty-nine non-diabetic, non-obese, postmenopausal osteoporotic women (age 72.4 ± 6.8 years; BMI 23.0 ± 3.3 kg/m2) underwent to: 1) fasting blood sampling for biochemical and hormone assays, including carboxylated (cOC) and uncarboxylated (uOC) osteocalcin; 2) whole-body dual energy X-ray absorptiometry (DXA) to assess total and regional body composition; 3) magnetic resonance imaging to determine cross-sectional muscle area (CSA) and intermuscular adipose tissue (IMAT) of thigh muscles; 4) risk of fall assessment through the OAK system.ResultsAppendicular skeletal muscle index (ASMMI) was low in 45% of patients. Forty percent got a low OAK score, consistent with moderate-severe risk of fall, which was predicted by low legs lean mass and increased total fat mass. Circulating cOC levels showed significantly correlated with βCTx-I, lean mass parameters including IMAT, and OAK score. Fractured and unfractured women did not differ for any of the analyzed parameters, though cOC and uOC positively correlated with legs lean mass, OAK score and bone markers only in fractured women.ConclusionsData supported the relationship between OC and skeletal muscle mass and function in postmenopausal osteoporotic women. Serum cOC, but not uOC, emerges as mediator in the bone-muscle crosstalk. Circulating cOC and uOC levels may be differentially regulated in fractured and unfractured osteoporotic women, suggesting underlying differences in bone metabolism.
| S-EPMC8133362 | biostudies-literature
Project description:BACKGROUND:Increasing evidence recognizes that DNA methylation abnormalities play critical roles in cancer development. Our previous genome-wide methylation profile showed that tumor necrosis factor-alpha-induced protein 8 like 3 (TIPE3) was hypermethylated in nasopharyngeal carcinoma (NPC). However, the relationship between TIPE3 methylation and its mRNA expression, as well as its biological roles in NPC are unknown. METHODS:Bisulfite pyrosequencing and quantitative RT-PCR were performed to quantify the TIPE3 methylation and expression levels. Kaplan-Meier curves and Cox regression analysis were used to estimate the correlation between TIPE3 methylation levels and survival in two patient cohorts collected from two hospitals (n?=?441). The MTT, colony formation, Transwell migration and invasion assays, and xenograft tumor growth and lung metastatic colonization models were used to identify the functions of TIPE3 on NPC cells. RESULTS:We found that TIPE3 CpG island (CGI) was hypermethylated and its mRNA levels were downregulated in many cancers, including NPC. TIPE3 downregulation was associated with its CGI hypermethylation. Furthermore, NPC patients with high TIPE3 CGI methylation levels had poorer clinical outcomes than those with low methylation levels. The TIPE3 CGI methylation level was an independent prognostic factor. Moreover, restoring TIPE3 expression significantly inhibited NPC cell proliferation, migration and invasion in vitro, and suppressed tumor growth and lung metastatic colonization in vivo, while silencing TIPE3 acted in an opposite way. CONCLUSIONS:TIPE3 downregulation correlates with its CGI hypermethylation in several solid cancers. TIPE3 acts as a tumor suppressor in NPC, providing a further insight into NPC progression and representing a potential prognostic biomarker for NPC.
| S-EPMC6137889 | biostudies-literature
Project description:BackgroundBody composition measures may predict outcomes of cancer surgery. Whereas low muscle mass shown on preoperative computed tomography (CT) scans has been associated with worse outcomes after surgery for pancreatic cancer, less consideration has been given to low muscle attenuation, reflecting poor muscle quality. Studies relating muscle mass and muscle attenuation with outcomes for patients with periampullary, nonpancreatic cancer are lacking.MethodsSkeletal muscle mass and attenuation were assessed in 166 consecutive patients undergoing pancreatoduodenectomy (PD) for periampullary, nonpancreatic cancer at a single center between 2000 and 2012. The skeletal muscle index (SMI) was calculated from cross-sectional muscle area on preoperative CT imaging at the third lumbar vertebra level (L3) and normalized for height. The skeletal muscle attenuation index (MAI) was calculated by measuring the average Hounsfield units of the total muscle area at the L3 level. Overall survival (OS) and the rate of major postoperative complications (Clavien-Dindo ?3) were extracted from prospectively maintained databases.ResultsLow SMI was present in 78.3 % and low MAI in 48.8 % of the patients. The multivariate analysis showed lymph node metastasis [hazard ratio (HR) 1.8; 95 % confidence interval (CI) 1.1-2.9], microscopic radicality (HR 2.0; 95 % CI 1.2-3.4), and low MAI (HR 2.0; 95 % CI 1.2-3.3), but not low SMI to be significantly associated with decreased OS. Low MAI (HR 1.9; 95 % CI 1.0-3.8) was the only independent risk factor for major postoperative complications.ConclusionSkeletal muscle quality, but not muscle mass, predicted survival and major complications after PD for periampullary, nonpancreatic cancer. Preoperative CT-derived body composition measures may stratify patients into risk categories and support shared decision making.
| S-EPMC5179584 | biostudies-literature
Project description:We have previously reported that the expression of mitochondrial deacetylase SIRT3 is high in the slow oxidative muscle and that the expression of muscle SIRT3 level is increased by dietary restriction or exercise training. To explore the function of SIRT3 in skeletal muscle, we report here the establishment of a transgenic mouse model with muscle-specific expression of the murine SIRT3 short isoform (SIRT3M3). Calorimetry study revealed that the transgenic mice had increased energy expenditure and lower respiratory exchange rate (RER), indicating a shift towards lipid oxidation for fuel usage, compared to control mice. The transgenic mice exhibited better exercise performance on treadmills, running 45% further than control animals. Moreover, the transgenic mice displayed higher proportion of slow oxidative muscle fibers, with increased muscle AMPK activation and PPAR? expression, both of which are known regulators promoting type I muscle fiber specification. Surprisingly, transgenic expression of SIRT3M3 reduced muscle mass up to 30%, likely through an up-regulation of FOXO1 transcription factor and its downstream atrophy gene MuRF-1. In summary, these results suggest that SIRT3 regulates the formation of oxidative muscle fiber, improves muscle metabolic function, and reduces muscle mass, changes that mimic the effects of caloric restriction.
| S-EPMC3893254 | biostudies-literature
Project description:Skeletal muscle mass is regulated by a complex array of signaling pathways. TGF-?-activated kinase 1 (TAK1) is an important signaling protein, which regulates context-dependent activation of multiple intracellular pathways. However, the role of TAK1 in the regulation of skeletal muscle mass remains unknown. Here, we report that inducible inactivation of TAK1 causes severe muscle wasting, leading to kyphosis, in both young and adult mice.. Inactivation of TAK1 inhibits protein synthesis and induces proteolysis, potentially through upregulating the activity of the ubiquitin-proteasome system and autophagy. Phosphorylation and enzymatic activity of AMPK are increased, whereas levels of phosphorylated mTOR and p38 MAPK are diminished upon inducible inactivation of TAK1 in skeletal muscle. In addition, targeted inactivation of TAK1 leads to the accumulation of dysfunctional mitochondria and oxidative stress in skeletal muscle of adult mice. Inhibition of TAK1 does not attenuate denervation-induced muscle wasting in adult mice. Finally, TAK1 activity is highly upregulated during overload-induced skeletal muscle growth, and inactivation of TAK1 prevents myofiber hypertrophy in response to functional overload. Overall, our study demonstrates that TAK1 is a key regulator of skeletal muscle mass and oxidative metabolism.
| S-EPMC5821216 | biostudies-literature