Sex differences in recovery from postoperative sarcopenia during adjuvant CAPOX therapy for colorectal cancer.

BACKGROUND: Women are predisposed to develop intolerance to cancer chemotherapy. Sarcopenia and chemotherapy are mutually related. Women are generally intolerable to chemotherapeutics such as 5-fluorouracil. Although adjuvant oxaliplatin-based chemotherapy, e.g. CAPOX is commonly used to treat colorectal cancer, its effects on patients in terms of sarcopenia and sex remain unknown. We investigated sex disparities in the impacts of CAPOX on body composition in this study. METHODS: We conducted a prospective study on diagnostic metrics used for sarcopenia in colorectal cancer patients receiving adjuvant CAPOX. Evaluations of the nutritional status by the Mini-Nutritional Assessment (MNA), gait speed, grip strength, skeletal muscle mass, fat mass, and bone mineral content using a body composition analyzer were performed in the first, fourth, and eighth cycles of CAPOX (first, second, and third measurements, respectively). RESULTS: Among 80 eligible patients, 61 completed four CAPOX cycles. The median differences in MNA, gait, grip strength, muscle mass, fat mass, and bone mineral content between the first and second measurements for men (n = 35) and women (n = 26) were + 10.5% and + 2.9% (p = 0.067), + 4.5% and - 2.6% (p = 0.16), + 1.8% and + 2.8% (p = 0.66), + 2.7% and + 1.3% (p = 0.021), + 4.5% and + 3.5% (p = 0.59), and + 3.3% and + 0.0% (p = 0.006), There were no sex differences in comparisons of the above metrics between the first and third measurements in 34 patients who completed eight CAPOX cycles (19 wen and 15 women). CONCLUSIONS: Early cycles of adjuvant CAPOX may have a negative impact on the postoperative recovery of several metrics for diagnosing sarcopenia in women.

Evaluating the efficacy of immunotherapy in gastric cancer: Insights from immune checkpoint inhibitors.

The emergence of immunotherapy, particularly immune checkpoint inhibitors (ICIs), represents a groundbreaking approach to treating gastric cancer (GC). However, the prognosis of GC patients receiving ICI treatment is influenced by various factors. This manuscript identified sarcopenia and myosteatosis as inde-pendent prognostic factors impacting the outcomes of GC patients treated with ICIs. Additionally, this study introduced a visual predictive model to estimate the prognosis of GC patients. If confirmed by further studies, this observation could provide valuable insights to propel the advancement of personalized clinical medicine and the integration of precision medicine practices.

Loss of Skeletal Muscle Mass During Neoadjuvant Chemotherapy for Pancreatic Cancer Is Related to the Continuation of S-1 Adjuvant Chemotherapy After Pancreatectomy.

BACKGROUND/AIM: Although perioperative chemotherapy has improved patient survival, sarcopenia may occur during chemotherapy owing to decreased food intake and physical strength. However, reports on the occurrence of sarcopenia and changes in body composition in patients with pancreatic cancer during neoadjuvant chemotherapy are scarce. This study aimed to determine the effect of changes in skeletal muscle mass during neoadjuvant chemotherapy on the S-1 adjuvant chemotherapy clinical course in patients who underwent perioperative chemotherapy and surgical resection. PATIENTS AND METHODS: We retrospectively enrolled 159 patients with pancreatic cancer who underwent neoadjuvant chemotherapy and surgical resection, followed by S-1 adjuvant chemotherapy. We evaluated changes in skeletal muscle mass during neoadjuvant chemotherapy using abdominal computed tomography and the SliceOmatic software. The association between the rate of change in skeletal muscle mass index (Δ%SMI) during neoadjuvant chemotherapy and the continuation of S-1 adjuvant chemotherapy was investigated. RESULTS: Eighty-eight (55.3%) patients lost skeletal muscle mass (Δ%SMI <0) during neoadjuvant chemotherapy with a significantly low S-1 adjuvant completion rate (p=0.02). Δ%SMI <0 was an independent risk factor for the continuation of S-1 adjuvant chemotherapy (hazard ratio=1.924, 95% confidence interval=1.002-3.695, p=0.049). Moreover, the lower the Δ%SMI, the lower the S-1 continuation rate (p=0.022). CONCLUSION: Loss of skeletal muscle mass during neoadjuvant chemotherapy for pancreatic cancer affected the continuation of S-1 adjuvant chemotherapy after pancreatic resection. Therefore, ameliorating loss of skeletal muscle mass during neoadjuvant chemotherapy should be carefully considered to improve the continuation rate of adjuvant chemotherapy and the survival of patients with pancreatic cancer.

Association between exposure to organophosphate esters metabolites and sarcopenia prevalence: A cross-sectional study using NHANES data.

Organophosphate esters (OPEs) are an emerging group of environmental pollutants linked to numerous health concerns, and their increasing prevalence in the environment is alarming. However, the impact of OPEs exposure on sarcopenia, a condition characterized by muscle loss and weakness, remains unknown. In this study, the connection between urinary metabolites of OPEs and the occurrence of sarcopenia was investigated using data from the National Health and Nutrition Examination Survey (NHANES) covering a period from 2011 to 2018. The analysis found that two specific urinary metabolites, Dibutyl phosphate (DBUP) and Bis (2-chloroethyl) phosphate (BCEP), were positively correlated with an increased risk of sarcopenia. Among these metabolites, DBUP had the highest contribution to sarcopenia development according to weighted quantile sum (WQS) model analysis. Additionally, it was observed that inflammation mediated the relationship between urinary exposure to DBUP/BCEP and the prevalence of sarcopenia. Overall, this research emphasizes the role of OPEs in the progression of sarcopenia, prompting concerns regarding their potential impact on health and advocating for further prospective investigations into their correlation with the risk of developing sarcopenia.

Assessing Sarcopenia in Advanced-Stage Ovarian Cancer Patients Undergoing Neoadjuvant Chemotherapy: A Case Series.

OBJECTIVES: In ovarian and other cancers, low muscle mass and density are associated with poorer clinical outcomes. However, screening for cancer-related sarcopenia (typically defined as low muscle mass) is not routinely conducted. The European Working Group on Sarcopenia in Older People (EWGSOP) recommends an algorithm for sarcopenia screening and diagnosis in clinical settings, with sarcopenia based on muscle strength and mass, and severity on physical performance. We explored the application of the EWGSOP2 algorithm to assess sarcopenia in six ovarian cancer patients receiving neoadjuvant chemotherapy. METHODS: We assessed sarcopenia risk with the SARC-F screening questionnaire (at risk ≥4 points), muscle strength with a handgrip strength test (cut point <16 kg) and five times sit-to-stand test (cut point >15 s), muscle mass by skeletal muscle index (SMI in cm2/m2 from a single computed tomography [CT] image; cut point <38.5 cm2/m2), and physical performance with a 4-m gait speed test (cut point ≤0.8 m/s). RESULTS: Of six participants, none were identified as "at risk" for sarcopenia based on SARC-F scores. Two participants were severely sarcopenic based on EWGSOP2 criteria (had low muscle strength, mass, and physical performance), and five participants were sarcopenic based on muscle mass only. DISCUSSION: Ovarian cancer patients with low muscle mass during neoadjuvant chemotherapy may not be identified as sarcopenic based on the EWGSOP2 diagnostic algorithm. While lacking a universally accepted definition for cancer-related sarcopenia and cancer-specific recommendations for the screening, diagnosis, and treatment of sarcopenia, ovarian cancer clinicians should focus on the diagnosis and treatment of low muscle mass and density.

[Sarcopenia and immune-related toxicity in patients with malignant melanoma undergoing immune checkpoint inhibition]. / Die Bedeutung von Sarkopenie für die immunvermittelte Toxizität bei Patienten mit malignem Melanom unter einer Immuncheckpoint-Inhibition.

BACKGROUND AND OBJECTIVES: Sarcopenia is the generalized loss of muscle strength, mass, and function. The aim was to investigate whether pretherapeutic sarcopenia, as determined by the psoas muscles, affects therapy-mediated toxicity in patients with malignant melanoma undergoing immunotherapy. PATIENTS AND METHODS: Measurement of psoas musculature was performed pretherapeutically using computed tomography at the level of the third lumbar vertebra in the axial plane in 75 patients between January 2011 and December 2020. Sarcopenia was defined using the psoas muscle index (PMI). Immune-related toxicity was retrospectively assessed. RESULTS: Treatment-related toxicity was recorded in 33 of the 75 patients (44%). Of these, 16 patients (36.2%) experienced dose-limiting severe events (DLT). Pretherapeutic sarcopenia was identified in 25 patients (33.3%). Comparative analysis showed that the patients with a DLT had lower PMI values compared with the patient group without a DLT (4.65 ± 1.33 vs. 5.79 ± 1.67 cm2m-2, p = 0.015) (odds ratio = 0.60, 95% confidence interval 0.40-0.92, p = 0.02). CONCLUSIONS: Pretherapeutic sarcopenia measured based on the psoas muscle is not a significant predictor of immune-mediated toxicity in patients with malignant melanoma treated with immune checkpoint inhibitors. Patients with DLT have lower values for the psoas muscle parameters PMI compared to the group of patients without DLT.

Sarcopenia as a Predictive Factor for Carboplatin Toxicity in Patients with Advanced Non-Small Cell Lung Cancer.

Sarcopenia in cancer patients often negatively impacts various outcomes. Carboplatin, a first-line chemotherapy for non-small cell lung cancer (NSCLC), is dosed based on body weight, which doesn't account for sarcopenia. This study evaluated the association between sarcopenia and carboplatin-related toxicity in NSCLC patients. Patients with locally advanced or metastatic NSCLC treated with carboplatin were included. Toxicity events during the first two cycles of treatment were recorded. Sarcopenia was assessed using pretreatment computed tomography scans analyzed with Slice-O-Matic V4.2 software, defining sarcopenia as a skeletal muscle index (SMI) of <52.4 cm2/m2 for men and <38.5 cm2/m2 for women. Among 146 patients, 52% had sarcopenia. Hematological toxicity occurred in 71.2% of all patients and 77.6% of those with sarcopenia. The fat-free mass index (FFMI) was independently associated with hematological toxicity and dose-limiting toxicity (DLT), which was observed in 55.5% of patients. Sarcopenia significantly correlates with hematological toxicity and DLT during carboplatin treatment in NSCLC patients. Given its prevalence and noninvasive detection, further research is needed to understand its impact on treatment outcomes.

Association of sarcopenia with severe chemotherapy toxicities and survival in patients with advanced gastric cancer.

BACKGROUND: Sarcopenia or skeletal muscle depletion is a poor prognostic factor for gastric cancer (GC). However, existing cutoff values of skeletal muscle index (SMI) for defining sarcopenia have been found to have limitations when clinically applied. This study aimed to determine the optimal cutoff for SMI to predict severe toxicities of chemotherapy and overall survival (OS) in patients with advanced GC. METHODS: Patients with metastatic gastric adenocarcinoma who received first-line palliative chemotherapy between January 2014 and December 2021 at Queen Mary Hospital, Hong Kong, were included in this study. The SMI was determined via a pre-chemotherapy computed tomography scan. Optimal cutoff points of SMI were identified by recursive partitioning analysis. Univariate and multivariate analyses evaluating risk factors of severe chemotherapy toxicities and OS were also performed. RESULTS: A total of 158 patients (male: 108 (68.4%), median age: 65.3) were included. The SMI cutoff to define low SMI was ≤33 cm2/m2 for males and ≤28 cm2/m2 for females; 30 patients (19.0%) had low SMI. Patients with low SMI had a higher incidence of hematological toxicities (63.3% vs 32.0%, P = .001) and non-hematological toxicities (66.7% vs 36.7%, P = .003). Multivariable analysis indicated that low SMI and low serum albumin (≤28 g/L) were independent predictive factors of hematological toxicity, while low SMI and neutrophil-lymphocyte ratio ≥5 were predictive factors of non-hematological toxicity. Moreover, patients with low SMI had a significantly shorter OS (P = .011), lower response rate to chemotherapy (P = .045), and lower utilization of subsequent lines of treatment (P < .001). CONCLUSIONS: Using pre-chemotherapy SMI cutoff (≤33 cm2/m2 for males and 28 cm2/m2 for females) one can identify individuals with a higher risk of severe chemotherapy toxicities and worse prognosis.

Health effect of multiple air pollutant mixture on sarcopenia among middle-aged and older adults in China.

BACKGROUND: As the global aging process accelerates, the health challenges posed by sarcopenia among middle-aged and older adults are becoming increasingly prominent. However, the available evidence on the adverse effects of air pollution on sarcopenia is limited, particularly in the Western Pacific region. This study aimed to explore relationships of multiple air pollutants with sarcopenia and related biomarkers using the nationally representative database. METHODS: Totally, 6585 participants aged over 45 years were enrolled from the China Health and Retirement Longitudinal Study (CHARLS) in 2011 and 3443 of them were followed up until 2015. Air pollutants were estimated from high-resolution satellite-based spatial-temporal models. In the cross-sectional analysis, we used generalized linear regression, unconditional logistic regression analytical and restricted cubic spline (RCS) methods to assess the single-exposure and non-linear effects of multiple air pollutants on sarcopenia and related surrogate biomarkers (serum creatinine and cystatin C). Several popular mixture analysis techniques such as Bayesian kernel machine regression (BKMR), weighted quantile sum (WQS) regression, and quantile-based g-computation (Qgcomp) were further used to examinate the combined effects of multiple air pollutants. Logistic regression was used to further analyze the longitudinal association between air pollution and sarcopenia. RESULTS: Each interquartile range increase in PM2.5, PM10 and NO2 was significantly associated with an increased risk of sarcopenia, with adjusted odds ratios (aORs) of 1.09 [95 % confidence interval (CI): 1.01, 1.20], 1.24 (95 % CI: 1.14, 1.35) and 1.18 (95 % CI: 1.08, 1.28), respectively. Our findings also showed that five air pollutants were significantly associated with the sarcopenia index. In addition, employing a mixture analysis approach, we confirmed significant combined effects of air pollution mixtures on sarcopenia risk and associated biomarkers, with PM10 and PM2.5 identified as major contributors to the combined effect. The results of the exposure-response (E-R) relationships, subgroup analysis, longitudinal analysis and sensitivity analysis all showed the unfavorable impact of air pollution on sarcopenia risk and related vulnerable populations. CONCLUSIONS: Single-exposure and co-exposure to multiple air pollutants were positively associated with sarcopenia among middle-aged and older adults in China. Our study provided new evidence that air pollution mixture was significantly associated with sarcopenia related biomarkers.

Body composition measures as a determinant of Alpelisib related toxicity.

BACKGROUND: Body composition has emerged as an important prognostic factor in patients treated with cancer. Severe depletion of skeletal muscle, sarcopenia, has been associated with poor performance status and worse oncological outcomes. We studied patients with metastatic breast cancer receiving alpelisib, to determine if sarcopenia and additional body composition measures accounting for muscle and adiposity are associated with toxicity. METHODS: A retrospective observational analysis was conducted, including 38 women with metastatic breast cancer and a PIK3CA mutation, treated with alpelisib as advanced line of therapy. Sarcopenia was determined by measuring skeletal muscle cross-sectional area at the third lumbar vertebra using computerized tomography. Various body composition metrics were assessed along with drug toxicity, dose reductions, treatment discontinuation, hospitalizations, time to treatment failure and overall survival. RESULTS: Sarcopenia was observed in half of the patients (n = 19, 50%), spanning normal weight, overweight, and obese individuals. Among the body composition measures, lower skeletal muscle density (SMD) was associated with an increased risk of treatment-related hyperglycaemia (P = 0.03). Additionally, lower visceral adipose tissue (VAT) was associated with alpelisib-induced rash (P = 0.04) and hospitalizations (P = 0.04). Notably, alpelisib treatment discontinuation was not impacted by alpelisib toxicity. CONCLUSION: Body composition measures, specifically SMD and VAT may provide an opportunity to identify patients at higher risk for severe alpelisib related hyperglycemia, and cutaneous toxicity. These findings suggest the potential use of body composition assessment to caution toxicity risk, allowing for personalized therapeutic observation and intervention.

Doxorubicin causes cachexia, sarcopenia, and frailty characteristics in mice.

While chemotherapy treatment can be lifesaving, it also has adverse effects that negatively impact the quality of life. To investigate the effects of doxorubicin chemotherapy on body weight loss, strength and muscle mass loss, and physical function impairments, all key markers of cachexia, sarcopenia, and frailty. Seventeen C57/BL/6 mice were allocated into groups. 1) Control (n = 7): mice were exposed to intraperitoneal (i.p.) injections of saline solution. 2) Dox (n = 10): mice were exposed to doxorubicin chemotherapy cycles (total dose of 18 mg/kg divided over 15 days). The body weight loss and decreased food intake were monitored to assess cachexia. To assess sarcopenia, we measured muscle strength loss using a traction method and evaluated muscle atrophy through histology of the gastrocnemius muscle. To evaluate physical function impairments and assess frailty, we employed the open field test to measure exploratory capacity. Doxorubicin administration led to the development of cachexia, as evidenced by a significant body weight loss (13%) and a substantial decrease in food intake (34%) over a 15-day period. Furthermore, 90% of the mice treated with doxorubicin exhibited sarcopenia, characterized by a 20% reduction in traction strength (p<0,05), a 10% decrease in muscle mass, and a 33% reduction in locomotor activity. Importantly, all mice subjected to doxorubicin treatment were considered frail based on the evaluation of their overall condition and functional impairments. The proposed model holds significant characteristics of human chemotherapy treatment and can be useful to understand the intricate relationship between chemotherapy, cachexia, sarcopenia, and frailty.

The correlation of sarcopenia and adverse events of imatinib therapy postoperatively in gastrointestinal stromal tumor through computed tomography quantitative body composition.

PURPOSE: This study aimed to investigate the correlation between sarcopenia and adverse events (AEs) of postoperative imatinib therapy through computed tomography (CT) quantitative body composition for intermediate- and high-risk gastrointestinal stromal tumors (GISTs). METHODS: The study retrospectively analyzed the clinical data of 208 patients with intermediate- and high-risk GIST treated surgically and treated with imatinib afterward at the First Affiliated Hospital of Wenzhou Medical University between October 2011 and October 2021. Images of preoperative CT scans within 1 month were used to determine the body composition of the patients. On the basis of the L3 skeletal muscle index, patients were classified into sarcopenia and nonsarcopenia groups. In 2 groups, AEs related to imatinib were analyzed. RESULTS: The proportion of AEs related to imatinib in the sarcopenia group was higher, and this disparity had a significant statistical significance (P = .013). Sarcopenia was significantly associated with hemoglobin reduction compared with nonsarcopenia (P = .015). There was a significant difference between the sarcopenia group and the nonsarcopenia group in the ratio of severe AEs (grades 3-4). Hemoglobin content (odds ratio [OR], 0.981; 95% CI, 0.963-1.000; P = .045), sex (OR, 0.416; 95% CI, 0.192-0.904; P = .027), and sarcopenia (OR, 5.631; 95% CI, 2.262-14.014; P < .001) were the influential factors of imatinib severe AEs in patients with intermediate- and high-risk GIST within 1 year after imatinib treatment. CONCLUSION: Patients with preoperative sarcopenia have a higher incidence and severity of AEs during adjuvant imatinib therapy.

Ambient air pollution exposure and the risk of probable sarcopenia: A prospective cohort study.

BACKGROUND: Sarcopenia is characterized by decreased muscle mass and strength, posing threat to quality of life. Air pollutants are increasingly recognized as risk factors for diseases, while the relationship between the two remains to be elucidated. This study investigated whether exposure to ambient air pollution contributes to the development of sarcopenia. METHODS: We employed the data from the UK Biobank with 303,031 eligible participants. Concentrations of PM2·5, NO2, and NOx were estimated. Cox proportional hazard regression models were applied to investigate the associations between pollutants and sarcopenia. RESULTS: 30,766 probable sarcopenia cases was identified during the follow-up. We observed that exposure to PM2.5 (HR, 1.232; 95% CI, 1.053-1.440), NO2 (HR, 1.055; 95% CI, 1.032-1.078) and NOx (HR, 1.016; 95% CI, 1.007-1.026) were all significantly associated with increased risk for probable sarcopenia for each 10 µg/m3 increase in pollutant concentration. In comparison with individuals in the lowest quartiles of exposure, those in the upper quartiles had significantly increased risk of probable sarcopenia. Sarcopenia-related factors, e.g., reduced lean muscle mass, diminished walking pace, and elevated muscle fat infiltration ratio, also exhibited positive associations with exposure to ambient air pollution. On the contrary, high level physical activity significantly mitigated the influence of air pollutants on the development of probable sarcopenia. CONCLUSIONS: Air pollution exposure elevated the risk of developing sarcopenia and related manifestations in a dose-dependent manner, while physical activity maintained protective under this circumstance. Efforts should be made to control air pollution and emphasize the importance of physical activity for skeletal muscle health under this circumstance.

Sarcopenia among treated cancer patients before and after neoadjuvant chemotherapy: a systematic review and meta-analysis of high-quality studies.

BACKGROUND: Neoadjuvant chemotherapy, used to shrink tumors before surgery, is increasingly applied in clinical practice. However, retrospective studies indicate that it may increase sarcopenia rates and consequently result in an elevated occurrence rate of postoperative severe complications such as severe surgical incision infection, severe respiratory failure, and severe postoperative hemorrhage, especially in the elderly population. Currently, no systematic analysis examines the association between neoadjuvant chemotherapy and sarcopenia. This study aims to fill this gap with a comprehensive meta-analysis focused on this critical aspect of the field. METHODS: A systematic literature search was conducted in the PubMed and Web of Science databases from their inception to January 2024. The included studies encompassed patients who received neoadjuvant chemotherapy and underwent computed tomography (CT) scans both before and after treatment to calculate skeletal muscle index (SMI) or categorize them for the presence of sarcopenia. The determination of sarcopenia status was based on well-established and validated threshold criteria. Data extraction was performed independently by two reviewers. A meta-analysis was employed to estimate the pooled odds ratio (OR) and its corresponding 95% confidence interval (95% CI) to assess the risk of neoadjuvant chemotherapy-induced muscle reduction. RESULTS: In the 14 studies with complete categorical variable data, comprising 1853 patients, 773 patients were identified as having sarcopenia before neoadjuvant treatment and 941 patients had sarcopenia after neoadjuvant therapy. The OR and its 95% CI was calculated as 1.51 [1.31, 1.73]. Among these, 719 patients had digestive system cancer, with 357 patients having sarcopenia before neoadjuvant treatment and 447 patients after, resulting in an OR of 1.74 [1.40, 2.17]. In the remaining 1134 patients with non-digestive system cancers, 416 were identified as having sarcopenia before neoadjuvant treatment, and 494 patients had sarcopenia after, with an OR of 1.37 [1.15, 1.63]. Additionally, in seven studies with complete continuous variable data, including 1228 patients, the mean difference in the change of SMI before and after neoadjuvant treatment was - 1.13 [- 1.65, - 0.62]. After excluding low-quality small-sample studies with fewer than 50 patients, the same trend was observed in the analysis. CONCLUSION: The risk of muscle reduction significantly increases in cancer patients after neoadjuvant chemotherapy and digestive system cancers tend to have a higher risk of developing sarcopenia post-treatment compared to non-digestive system cancers.

Sarcopenia is associated with leukopenia in urothelial carcinoma patients who receive tislelizumab combined with gemcitabine and cisplatin therapy.

BACKGROUND: In the era of combination therapy, there has been limited research on body composition. Specific body composition, such as sarcopenia, possesses the potential to serve as a predictive biomarker for toxic effects and clinical response in patients with urothelial carcinoma (UC) undergoing tislelizumab combined with gemcitabine and cisplatin (T + GC). MATERIALS AND METHODS: A total of 112 UC patients who received T + GC were selected at the Affiliated Hospital of Xuzhou Medical University from April 2020 to January 2023. Baseline patient characteristics and detailed hematological parameters were collected using the electronic medical system and laboratory examinations. The computed tomography images of patients were analyzed to calculate psoas muscle mass index (PMI). We evaluated the association between sarcopenia (PMI < 4.5 cm2/m2 in men; PMI < 3.3 cm2/m2 in women) and both hematological toxicity and tumor response. RESULTS: Overall, of the 112 patients (65.2% male, median age 56 years), 43 (38.4%) were defined as sarcopenia. Patients with sarcopenia were notably older (p = 0.037), more likely to have hypertension (p = 0.009), and had poorer ECOG-PS (p = 0.027). Patients with sarcopenia were more likely to develop leukopenia (OR 2.969, 95% CI 1.028-8.575, p = 0.044) after receiving at least two cycles of T + GC. However, these significant differences were not observed in thrombocytopenia and anemia. There were no significant differences in the tumor response and grade 3-4 hematological toxicity between patients with sarcopenia and those without sarcopenia. CONCLUSIONS: Patients with sarcopenia were more likely to develop leukopenia after receiving T + GC. There were no notable alterations observed in relation to anemia or thrombocytopenia. No significant difference was found between the sarcopenia group and non-sarcopenia group in terms of tumor response and grade 3-4 hematological toxicity.

Visceral obesity and sarcopenia as predictors of efficacy and hematological toxicity in patients with metastatic breast cancer treated with CDK 4/6 inhibitors.

PURPOSE: We aimed to investigate whether visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and skeletal muscle area (SMA) index are predictive for efficacy and hematological toxicity in ER + HER2-metastatic breast cancer (BC) patients who received CDK 4/6 inhibitors. METHODS: This retrospective cohort study analyzed 52 patients who were treated with CDK 4/6 inhibitors between January 2018 and February 2021. The values of VAT, SAT, SMA indices and hematological parameters were noted before the start, at the third and sixth months of this treatment. The skeletal muscle area (SMA) and adipose tissue measurements were calculated at the level of the third lumbar vertebra. A SMA-index value of <40 cm2/m2 was accepted as the threshold value for sarcopenia. RESULTS: Patients with sarcopenia had a worse progression-free survival (PFS) compared to patients without sarcopenia (19.6 vs. 9.0 months, p = 0.005). Patients with a high-VAT-index had a better PFS (20.4 vs. 9.3 months, p = 0.033). Only the baseline low-SMA- index (HR: 3.89; 95% CI: 1.35-11.25, p = 0.012) and baseline low-VAT-index (HR: 2.15; 95% CI: 1.02-4.53, p = 0.042) had significantly related to poor PFS in univariate analyses. The low-SMA-index was the only independent factor associated with poor PFS (HR: 3.99; 95% CI: 1.38-11.54, p = 0.011). No relationship was observed between body composition parameters and grade 3-4 hematological toxicity. CONCLUSION: The present study supported the significance of sarcopenia and low visceral adipose tissue as potential early indicators of poor PFS in patients treated with CDK 4/6 inhibitors.

Effects of androgen deprivation therapy on elderly men with high-risk prostate cancer: PROSARC observational study.

INTRODUCTION: Prostatic carcinoma (PC) is a frequent neoplasm in elderly patients. Although androgen deprivation is associated with survival benefits, it is also related to adverse effects such as osteoporosis, frailty, or sarcopenia, which can negatively affect the patient's quality of life. This study aims to quantify and evaluate the prevalence of osteoporosis, frailty, or sarcopenia in elderly PC patients before and after androgen deprivation. We present data from an interim analysis. MATERIALS AND METHODS: PROSARC is a national (Spain) prospective observational study (May-2022-May-2025) still in progress in 2 hospitals. It includes patients with high-risk PC, aged ≥70 years, non-candidates for local treatment and scheduled to start androgen deprivation therapy. The following variables are analyzed: comorbidity, frailty (Fried frailty phenotype criteria), osteoporosis, sarcopenia (EWGSOP2), fat mass and muscle mass, before treatment and after 6 months of follow-up. RESULTS: A 6-month follow-up was completed by 12/25 included patients (mean age, 84 years), with a high baseline prevalence of pre-frailty/frailty (67.7%), sarcopenia (66.7%) and osteoporosis (25%). Treatment did not significantly alter these variables or comorbidity. We observed changes in body mass index (p=0.666), decreased mean value of appendicular muscle mass (p=0.01) and increased percentage of fat mass (p=0.012). CONCLUSION: In patients with high-risk PC, advanced age and a considerable prevalence of osteoporosis, frailty and sarcopenia, androgen deprivation (ADT; 6 months) produces decreased muscle mass without impact on the incidence of the known adverse effects of androgen deprivation.

Varying Impact of Lenvatinib or Sorafenib Therapy on Skeletal Muscle Loss in Patients with Hepatocellular Carcinoma.

INTRODUCTION: Lenvatinib and sorafenib are key therapeutic agents for hepatocellular carcinoma (HCC). However, there are no useful biomarkers for selecting molecular-targeted agents (MTAs). Skeletal muscle volume is associated with the clinical outcomes in these patients. We investigated the effects of lenvatinib and sorafenib on the skeletal muscles of patients with HCC. METHODS: We evaluated the impact of skeletal muscle changes over a 3-month period for each MTA (n = 117; lenvatinib/sorafenib, 45/72). The skeletal muscle mass index (SMI) was measured at the third lumbar vertebra. Furthermore, we evaluated the direct effect of each MTA on primary human skeletal muscle cells by estimating muscle protein synthesis using western blot analysis. RESULTS: The median change in SMI was -0.7% (p = 0.959) and -5.9% (p < 0.001) for the lenvatinib and sorafenib groups, respectively. Sorafenib had a greater effect on skeletal muscle loss than lenvatinib (p < 0.001). Additionally, SMI significantly decreased in the sorafenib group regardless of initial skeletal muscle volume (p < 0.001), whereas no significant differences were observed in the lenvatinib group. Sorafenib therapy (odds ratio [OR], 2.98; p = 0.023) and non-muscle depletion (OR, 3.31; p = 0.009) were associated with a decreased SMI. In vitro analysis showed that sorafenib negatively affected muscle synthesis compared to lenvatinib. CONCLUSIONS: Sorafenib may have a more negative effect on skeletal muscle than lenvatinib.