Sarcopenia Predicts Prognosis in Patients with Newly Diagnosed Hepatocellular Carcinoma, Independent of Tumor Stage and Liver Function.
ABSTRACT: The purpose of this study was to demonstrate the prognostic significance of changes in body composition in patients with newly diagnosed hepatocellular carcinoma (HCC).Patients (n=178) newly diagnosed with HCC participated in the study between 2007 and 2012. Areas of skeletal muscle and abdominal fat were directly measured using a three-dimensional workstation. Cox proportional-hazards modes were used to estimate the effect of baseline variables on overall survival. The inverse probability of treatmentweighting (IPTW) method was used to minimize confounding bias.Cutoff values for sarcopenia, obtained from receiver-operating characteristic curves, were defined as skeletal muscle index at the third lumbar vertebra of ? 45.8 cm/m2 for males and ? 43.0 cm/m2 for females. Sarcopenia patients were older, more likely to be female, and had lower body mass index. Univariable analysis showed that the presence of sarcopenia and visceral to subcutaneous fat area ratio (VSR) were significantly associatedwith prognosis. The multivariable analyses revealed that VSR was predictive of overall survival. However, in the multivariable Cox model adjusted by IPTW, sarcopenia, not VSR, were associated with overall survival.The presence of sarcopenia at HCC diagnosis is independently associated with survival.
Project description:<h4>Background and aim</h4>Several reports have demonstrated that skeletal muscle mass influences mortality in patients with hepatocellular carcinoma (HCC) receiving sorafenib treatment; however, there is still controversy with regard to whether skeletal muscle and adipose tissue are associated with the prognosis in HCC patients. We examined the relationship between body composition and prognosis in HCC patients.<h4>Methods</h4>We retrospectively analyzed 82 patients with unresectable HCC receiving sorafenib treatment. The skeletal muscle area and adipose tissue area were measured by computed tomography. Patients with low skeletal muscle index (male ?36.2?cm<sup>2</sup>/m<sup>2</sup>, female ?29.6?cm<sup>2</sup>/m<sup>2</sup>) and high visceral to subcutaneous adipose tissue area ratio (VSR) (male???1.33, female???0.93) were diagnosed as low skeletal muscle mass (LSMM) and high VSR, respectively.<h4>Results</h4>A total of 16 and 34 patients were classified as LSMM and high VSR, respectively. LSMM patients frequently experienced serious adverse events (SAEs) and thus had a shorter duration of sorafenib treatment than non-LSMM patients. High VSR was a significant factor for progression-free survival. LSMM patients less frequently received additional/subsequent therapies combined with sorafenib than non-LSMM patients. Multivariate Cox hazard analysis demonstrated that LSMM was a significant factor for the duration of sorafenib treatment. The treatment duration and receiving of additional/subsequent therapies were significantly associated with overall survival (OS) but not with LSMM or high VSR.<h4>Conclusion</h4>LSMM was associated with the frequency of SAEs, treatment tolerability, and treatment duration. LSMM patients were less likely to receive additional/subsequent therapies than non-LSMM patients. Thus, LSMM could identify a subgroup of patients with poor OS.
Project description:The present study aimed to examine the impact of sarcopenia, defined as low muscle mass on computed tomography (CT), prior to sorafenib therapy on the clinical outcomes of patients with hepatocellular carcinoma (HCC) receiving sorafenib therapy. In total, 232 patients with unresectable HCC (median age, 72 years) were analyzed, and the extent of sarcopenia was assessed using CT. Cross-sectional areas (cm2) of the skeletal muscles at the third lumbar vertebra level were determined by manual outlining on the CT images. The cross-sectional areas were normalized for height [skeletal muscle index (SMI), cm2/m2]. Based on the findings of previous studies, male patients with SMI ≤36.2 cm2/m2 and female patients with SMI ≤29.6 cm2/m2 were defined as having sarcopenia. The baseline characteristics, overall survival (OS) rates, progression-free survival (PFS) rates and best treatment response of the sarcopenia group were retrospectively compared with those of the non-sarcopenia group, and the factors associated with OS and PFS were examined. Sarcopenia was observed in 151 patients (65.1%). There were 165 patients with Child-Pugh A and 67 with Child-Pugh B cirrhosis. In the sarcopenia group, the median treatment duration was 66 days, whereas in the non-sarcopenia group it was 103 days (P=0.001). The median OS time was 174 days in the sarcopenia group and 454 days in the non-sarcopenia group (P<0.0001). The median PFS was 77 days in the sarcopenia group and 106 days in the non-sarcopenia group (P=0.0131). Multivariate analysis identified sarcopenia to be an independent predictor of OS (hazard ratio, 0.365; P<0.0001). The objective response rate and disease control rate in the sarcopenia group were significantly lower, compared with those in the non-sarcopenia group (P=0.0146 and P=0.0151, respectively). In conclusion, sarcopenia may be an indicator of poor clinical course in patients with HCC receiving sorafenib.
Project description:Sarcopenia has been associated with lower overall survival in patients with cirrhosis and hepatocellular carcinoma (HCC) undergoing surgical resection, TACE, TARE, or transplantation. This monocentric study evaluated the prognostic significance of sarcopenia in patients affected by HCC who received bland transarterial embolization (TAE) therapy, by analyzing its impact on survival and treatment-related complications. All consecutive patients who underwent the 1st TAE between March 1st 2011 and July 1st 2019 in our Institution were retrospectively studied. To evaluate sarcopenia, the skeletal muscle index (SMI) was calculated by normalizing the cross-sectional muscle area at the level of L3 on an abdominal CT scan prior to embolization (cm2) by patient height (m2). SMI cut-off values for sarcopenia were considered ? 39 cm2/m2 for women and ?55 cm2/m2 for men. Data about age, gender, body mass index (BMI), underlying liver disease, liver function, MELD score, Child-Pugh score, multifocal disease, performance status, previous interventions, length of stay (LOS), complications after the procedure, readmission rate within 30 days, survival time from TAE and total number and type of TAE received following the first procedure were collected. From 2011 to 2019, 142 consecutive patients underwent 305 TAEs. Observation time ranged from 1.4 to 100.5 months (median 20.1 SD = 22). Sarcopenia at baseline was present in 121 (85%) patients. Overall 87 (61.2%) patients died during follow-up with survival rates at 1-, 2-, 3-, 4-, and 5-year of 71%, 41%, 22%, 16% and 11% respectively. After multivariate analysis sarcopenia (HR = 2.22, p = 0.046), previous ablation/resection (HR = 0.51, p = 0.005) and multifocal disease (HR = 1.84, p = 0.02) were associated with reduced survival. Sarcopenia did not influence the safety of TAE in terms of LOS (2 days vs 1.5 days, p = 0.2), early complications rate (8% vs 5%, p = 0.5) and readmission rate within 30 days (7% vs 5%, p = 0.74). Sarcopenia, estimated by the L3SMI method, is an emerging prognostic factor in patients with HCC undergoing bland TAE therapy as it is associated with increased mortality, without impairing the safety of the locoregional treatment. Measures to ameliorate the SMI, such as nutritional support and physical exercise, should be evaluated in clinical trials for HCC patients receiving liver embolization to determine their impact on overall survival.
Project description:Objective:Visceral adiposity, defined as a high visceral-to-subcutaneous adipose tissue area ratio (VSR), has been shown to be associated with poor outcomes in several cancers. However, in the surgical field, the significance of visceral adiposity remains controversial. The present study investigated the impact of visceral adiposity as well as sarcopenic factors (low muscularity) on outcomes in patients undergoing hepatectomy for hepatocellular carcinoma (HCC). Patients and Methods:This retrospective study analyzed data from 606 patients undergoing hepatectomy for HCC at our institution between April 2005 and March 2016. Using preoperative plain computed tomography imaging at the level of the third lumbar vertebra, visceral adiposity, skeletal muscle mass, and muscle quality were evaluated by the VSR, skeletal muscle mass index (SMI), and intramuscular adipose tissue content (IMAC), respectively. The impact of these parameters on outcomes after hepatectomy for HCC was analyzed. Results:The overall survival rate was significantly lower among patients with a high VSR (p < 0.001) than among patients with a normal VSR. Similarly, the recurrence-free survival rate was significantly lower among patients with a high VSR (p = 0.016). A high VSR, low SMI, and high IMAC contributed to an increased risk of death (p < 0.001) and HCC recurrence (p < 0.001) in an additive manner. Multivariate analysis showed that not only preoperative low muscularity but also visceral adiposity was a significant risk factor for mortality (hazard ratio [HR] = 1.566, p < 0.001) and HCC recurrence (HR = 1.329, p = 0.020) after hepatectomy for HCC. Conclusions:Preoperative visceral adiposity, as well as low muscularity, was closely related to poor outcomes after hepatectomy for HCC. It is crucial to establish a new strategy including perioperative nutritional interventions with rehabilitation for better outcomes after hepatectomy for HCC.
Project description:Background: Sarcopenia is gaining attention as a poor prognostic factor for various types of malignancies. This study evaluated the prevalence and prognostic significance of sarcopenia and its association with survival in hepatocellular carcinoma (HCC) patients who underwent radiotherapy (RT) to the primary site. Materials and Methods: Between January 2009 and November 2016, 156 patients with HCC that underwent RT to the liver were retrospectively studied. Sarcopenia was defined as an L3 skeletal muscle index of <49 cm2/m2 for men and <41 cm2/m2 for women as proposed by Korean-specific cut-off value. Sarcopenia was identified pre- and post-RT (within 3 months from the end of RT). Results: Pre-RT sarcopenia occurred in 99 (63.5%) patients and was significantly associated with higher levels of protein induced by vitamin K absence or antagonist-II (PIVKA-II), lower percentage of overweight/obesity (body-mass index), higher percentage of previous systemic chemotherapy, and lower total RT dose. At a median follow-up of 9.3 months, median overall survival (OS) was significantly lower in patients with pre-RT sarcopenia than in those without (7.1 vs. 15.3 months, p < 0.001). In multivariate analysis [reporting hazard ratio (HR): 95% confidence interval (CI)], albumin-bilirubin score (2.35: 1.33-4.17; p = 0.003), total dose (0.44: 0.27-0.71; p = 0.001), and pre-RT sarcopenia (2.38: 1.53-3.70; p < 0.001) were independent OS prognostic factors. Among patients without pre-RT sarcopenia, 20 newly developed sarcopenia after RT and showed significantly lower OS compared to those without sarcopenia after RT (n = 35) (median 14.1 vs. 17.5 months, p = 0.018). Multivariate logistic regression analysis [reporting odds ratio (OR)] demonstrated older age (310.190; p = 0.007), Child-Pugh classification B or C (15.239; p = 0.047), higher alpha-fetoprotein (128.486; p = 0.008), higher PIVKA-II (118.536; p = 0.027), and larger planning target volume (51.310; p = 0.026) as significant factors for newly developed post-RT sarcopenia. Conclusion: Newly developed sarcopenia after RT, as well as pre-RT sarcopenia, were associated with poor survival for HCC patients who underwent RT to the liver. This result suggests the possibility that early intervention such as nutritional support and exercise therapies before and during RT could prevent muscle wasting and may be effective in improving the prognosis of HCC patients.
Project description:Sarcopenia is a surrogate marker of patient frailty that estimates the physiologic reserve of an individual patient. We sought to investigate the impact of sarcopenia on short- and long-term outcomes in patients having undergone surgical intervention for primary hepatic malignancies.Ninety-six patients who underwent hepatic resection or liver transplantation for HCC or ICC at the John Hopkins Hospital between 2000 and 2013 met inclusion criteria. Sarcopenia was assessed by the measurement of total psoas major volume (TPV) and total psoas area (TPA). The impact of sarcopenia on perioperative complications and survival was assessed.Mean age was 61.9 years and most patients were men (61.4 %). Mean adjusted TPV was lower in women (23.3 cm(3)/m) versus men (34.9 cm(3)/m) (P?<?0.01); 47 patients (48.9 %) had sarcopenia. The incidence of a postoperative complication was 40.4 % among patients with sarcopenia versus 18.4 % among patients who did not have sarcopenia (P?=?0.01). Of note, all Clavien grade ?3 complications (n?=?11, 23.4 %) occurred in the sarcopenic group. On multivariable analysis, the presence of sarcopenia was an independent predictive factor of postoperative complications (OR?=?3.06). Sarcopenia was not associated with long-term survival (HR?=?1.23; P?=?0.51).Sarcopenia, as assessed by TPV, was an independent factor predictive of postoperative complications following surgical intervention for primary hepatic malignancies.
Project description:BACKGROUND:Sarcopenia, defined as decreased skeletal muscle mass, is prevalent and associated with poor prognosis in various solid tumors. This study aimed to determine the prognostic role of sarcopenia in patients with advanced gastric cancer (AGC). METHODS:This retrospective study consisted of 140 consecutive patients who underwent palliative chemotherapy for AGC. A cross-sectional area of muscle at the level of the third lumbar vertebra (L3) was measured using baseline computed tomography (CT) scans. Sarcopenia was defined as a L3 skeletal muscle index of ? 49 cm2/m2 for men and ? 31 cm2/m2 for women using Korean-specific cutoffs. We compared the overall survival (OS) and clinical characteristics of patients with and without sarcopenia. RESULTS:The median age was 67 years, and 133 (95%) patients had metastatic disease. Sarcopenia was present in 67 patients (47.9%) and was significantly related to male sex (p < 0.001) and low body mass index (p = 0.002). Patients with sarcopenia had a significantly shorter OS than those without sarcopenia (median, 6.8 months vs. 10.3 months, respectively; p = 0.033). In the multivariable analysis, sarcopenia was an independent prognostic factor of poor OS (hazard ratio, 1.51, p = 0.029); no response to chemotherapy (p < 0.001), no second-line chemotherapy (p < 0.001), metastatic sites ? 3 (p < 0.001), and low serum albumin level (p = 0.033) were also independent prognostic factors of poor OS. CONCLUSION:Sarcopenia, as determined by baseline CT, can be used to predict poor prognosis in AGC patients treated with palliative chemotherapy.
Project description:Cancer causes muscle mass loss, which is associated with a poor prognosis. Chemotherapy may also reduce muscle mass. We investigated skeletal muscle mass change during palliative chemotherapy for advanced gastric cancer (AGC) and its association with treatment outcomes. We retrospectively reviewed 111 consecutive AGC patients who underwent first-line palliative chemotherapy. Skeletal muscle area was measured before and after chemotherapy at the third lumbar vertebra level using computed tomography scans. We compared skeletal muscle index (SMI), body mass index (BMI), and body weight changes to chemotherapy response and survival. The 80 male and 31 female patients' median age was 65 (range 31-87) years, and 46.8% had sarcopenia at baseline. Median pre-chemotherapy to post-chemotherapy SMI, BMI, and body weight decreases were -?4.5 cm2/m2 (-?11.3%) (P?<?0.001); -?0.7 kg/m2 (-?3.2%) (P?<?0.001); and -?2.0 kg (-?3.5%) (P?<?0.001), respectively. Median SMI decreases for patients with objective response, stable disease, and disease progression were -?4.0 cm2/m2 (range -?20.1?~?9.5); -?4.5 cm2/m2 (range -?19.8?~?0.8); and -?3.8 cm2/m2 (range: -?17.6?~?0.1), respectively. Response to chemotherapy was not associated with SMI decrease (P?=?0.463). In multivariable analysis, sarcopenia at baseline (HR 1.681; 95% CI 1.083-2.609, P?=?0.021), decreased SMI (HR 1.620; 95% CI 1.041-2.520; P?=?0.032) were significant poor prognostic factors for survival. Skeletal muscle mass decreased significantly during chemotherapy in AGC patients, but was not associated with chemotherapy response. Decreased SMI was a poor prognostic factor in AGC patients during first-line palliative chemotherapy.
Project description:BACKGROUND:Incidence and mortality of pancreatic ductal adenocarcinoma (PDAC) are on the rise. Sarcopenia and sarcopenic obesity have proven to be prognostic factors in different types of cancers. In the context of previous findings, we evaluated the impact of body composition in patients undergoing surgery in a national pancreatic center. METHODS:Patient's body composition (n = 133) was analyzed on diagnostic CT scans and defined as follows: Skeletal muscle index ?38.5 cm2/m2 (women), ?52.4 cm2/m2 (men); obesity was classified as BMI ?25kg/m2. RESULTS:Sarcopenia showed a negative impact on overall survival (OS; 14 vs. 20 months, p = 0.016). Sarcopenic patients suffering from obesity showed poorer OS compared to non-sarcopenic obese patients (14 vs. 23 months, p = 0.007). Both sarcopenia and sarcopenic obesity were associated with sex (p<0.001 and p = 0.006; males vs. females 20% vs. 38% and 12% vs. 38%, respectively); sarcopenia was further associated with neoadjuvant treatment (p = 0.025), tumor grade (p = 0.023), weight loss (p = 0.02) and nutritional depletion (albumin, p = 0.011) as well as low BMI (<25 kg/m2, p = 0.038). Sarcopenic obese patients showed higher incidence of major postoperative complications (p<0.001). In addition, sarcopenia proved as an independent prognostic factor for OS (p = 0.031) in the multivariable Cox Regression model. CONCLUSION:Patients with sarcopenia and sarcopenic obesity undergoing resection for PDAC have a significantly shorter overall survival and a higher complication rate. The assessment of body composition in these patients may provide a broader understanding of patients' individual condition and guide specific supportive strategies in patients at risk.
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.