Chemotherapy treatments induce loss of skeletal muscle and adipose tissue each of which are important prognostic indicators after a cancer diagnosis. Males and females may respond differently to drugs used to treat cancer. Given the high degree of heterogeneity in the literature, the objective of this scoping review is to evaluate the methodological variability in reporting of muscle and adipose tissue changes comparing males and females during cancer-directed treatment.

Relevant databases were searched for papers reporting longitudinal CT based body composition changes separately for males and females in solid tumors.

Of the 29 studies that met inclusion criteria, 22 were retrospective and 7 were prospective. The majority of studies reported on gastrointestinal cancers [n=24]. Among collective participants (n= 5139), 32% were females. Females were under represented in half the studies. For 21/29 studies, baseline characteristics were combined for males and females, hindering the ability to understand the effect of disease stage, chemotherapy type and co-morbidities on muscle and fat changes experienced by each sex. Multiple chemotherapy regimens were combined (n=24) and not reported in a sex-specific way (n=26).

While the literature reporting body composition changes during cancer treatment is abundant, study design and reporting is problematic and precludes metaanalysis. Disproportionate numbers of males and females, marked heterogeneity in cancer types and chemotherapy regimens evaluated within a single study collectively pose challenges in analysing the impact of specific chemotherapy regimens on muscle and adipose change by sex. Strategies to standardize this set of literature in a sex specific way are required to improve evidence synthesis.

This randomized phase-II trial (ClinicalTrials.gov identifier: NCT02767557) compared efficacy of gemcitabine/nab-paclitaxel (Gem/Nab) with or without the anti-interleukin-6 (IL-6) receptor antibody tocilizumab (Toc) for advanced pancreatic cancer (PC).

A safety cohort received Gem 1,000 mg/m2 and Nab 125 mg/m2 on days 1, 8, and 15, and Toc 8 mg/kg on day 1 for each 28-day cycle. Participants with modified Glasgow prognostic scores of 1 or 2 were randomly assigned 1:1 to receive Gem/Nab/Toc or Gem/Nab. The primary end point was the overall survival (OS) rate at 6 months (OS6). Secondary end points were progression-free survival (PFS), overall response rate (ORR), and safety. Exploratory end points were cachexia, quality of life, and biomarkers, including the cachexia-promoting protein, growth differentiation factor 15 (GDF15).

Overall, 147 patients were treated, including six safety cohort participants. The median follow-up period was 8.1 months (IQR, 4.2-13.9). OS6 was 68.6% (95% CI, 56.3 to 78.1) for the Gem/Nab/Toc group and 62.0% (49.6-72.1) for the Gem/Nab group (P = .409). OS for Gem/Nab/Toc versus Gem/Nab improved at 18 months (27.1% v 7.0%, P = .001). No differences in median OS, PFS, or ORR were observed. Incidence of grade-3+ treatment-related adverse events (TrAEs) was 88.1% for Gem/Nab/Toc and 63.4% for Gem/Nab (P < .001). Gem/Nab/Toc decreased muscle loss versus Gem/Nab, with median change +0.1013% versus -3.430% (P = .0012) at 2 months and +0.7044 versus -3.353% (P = .036) at 4 months. Incidence of muscle loss was 43.48% on Gem/Nab/Toc versus 73.52% on Gem/Nab at 2 months (P = .0045) and 41.82% versus 68.75% (P = .0062) at 4 months. GDF15 was not changed by Gem/Nab or Gem/Nab/Toc.

Although the primary end point was not met and TrAEs were increased by Toc, increased survival at 18 months and reduced muscle wasting support an anticachexia effect of IL-6 blockade independent of GDF15. Further studies could leverage these findings for precision anticachexia therapy.

To evaluate the prognostic value of quantitative imaging biomarkers derived from computed tomography (CT) and magnetic resonance imaging (MRI) for pancreatic cancer (PC), with a particular focus on body composition parameters beyond the traditional intrinsic features of the tumor.

PubMed, EMBASE, and Cochrane Library databases were searched for articles on quantitative imaging biomarkers obtained from CT or MRI in predicting PC prognosis published between January 2014 and August 2024. The Newcastle-Ottawa scale was used to assess the quality of the included studies. Survival outcomes, such as overall survival (OS) and recurrence-free survival (RFS), were evaluated. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. In case of high heterogeneity, subgroup analyses and sensitivity analyses were performed to identify potential sources of heterogeneity among the studies.

We performed a meta-analysis of ten imaging biomarkers investigated in 43 included studies. Larger tumor size, lower skeletal muscle radiodensity, lower skeletal muscle index (SMI), presence of sarcopenic obesity, lower psoas muscle index (PMI), higher visceral to subcutaneous adipose tissue area ratio, and lower visceral adipose tissue index were associated with significantly worse OS. In particular, lower SMI and lower PMI had relatively high HRs (1.65 for SMI, 95% CI 1.39-1.96, and 2.20 for PMI, 95% CI 1.74-2.78). Patients with lower SMI exhibited poorer RFS (HR 1.78, 95% CI 1.46-2.18). Subgroup analyses identified the origin region of the study and intervention type as potential factors of heterogeneity for SMI in predicting OS.

Imaging biomarkers indicating body composition at PC diagnosis may play an important role in predicting patient prognosis. Further prospective multi-center studies with large sample sizes are needed for validation and translation into clinical practice.

Neuroendocrine neoplasms (NEN) are rare tumors arising from neuroendocrine cells most commonly in the gastrointestinal-tract. In recent years, advancements in therapeutics have increased survival rates in patients with NEN leading to a greater clinical burden compared to the general population.

The aim of this single-center case-control study was to investigate the incidence of low bone mass and changes in body composition in adult patients diagnosed with gastroenteropancreatic neuroendocrine tumors (GEPNET). Enrolled participants underwent measurements of bone mineral density (BMD) at the lumbar spine (LS), femoral neck (FN), and total hip (TH) and body composition analysis with calculation of total fat-mass (TFM) and relative skeletal mass index (RSMI), by dual X-ray absorptiometry.

Ninety GEPNET patients (28 with Pancreatic-NET, 20 with small-intestine-NET, 42 with gastric-NET), and 50 age and sex-matched controls were enrolled. The mean disease duration was 5±4.4 years, the majority of patients (54/90) was classified as stage-1, and were not receiving systemic-treatment (76/90). The incidence of osteoporosis/osteopenia was threefold higher in the patients' cohort, compared to controls (OR: 3.17 95% CI 1.16-7.8, p < 0.001). Among NEN patients, gastric-NET had the lowest bone mass, especially in LS. In addition, GEPNET patients demonstrated significantly lower TFM and RSMI, compared to controls (TFM: 31.6 ± 9.6 kg vs. 38.6 ± 6.4 kg, respectively, p = 0.03; RSMI: 6.4 ± 1.1 vs. 8.2 ± 0.6, respectively, p < 0.001). Within our patients' cohort, RSMI was significantly associated with LS-BMD (rho = 0.49, p < 0.001) and TH-BMD (rho = 0.58, p < 0.001), and TFM was associated with TH-BMD (rho = 0.31, p = 0.004).

Patients with GEPNET even at an early stage exhibit significantly lower bone, muscle and fat mass compared to the non-NET population, highlighting the importance of continuous monitoring of the musculoskeletal system in these patients.

Sarcopenia is common in patients with head and neck cancer and is suggested to be associated with decreased survival. This study aimed to investigate the relationship between changes in skeletal muscle mass during alternating chemoradiotherapy (CRT) and the prognosis of patients with nasopharyngeal carcinoma (NPC). This retrospective study included 64 patients with NPC who had undergone alternating CRT at our institution between 2005 and 2022. The skeletal muscle mass index (SMI) was measured using pre- and post-treatment computed tomography. SMI decreased in 58 patients (90.6%), with a mean change of -6.1%. Using a cutoff value of -6.0% for SMI change, 32 patients (50.0%) were categorized into the SMI loss group. The SMI loss group had a significantly lower mean overall survival (OS) than the SMI maintenance group (122.6 vs. 153.0 months; p = 0.021). Multivariate analysis identified SMI loss and prognostic nutritional index (PNI) as independent predictors of poor OS (p < 0.05). They were used to construct the nomogram of OS. In conclusion, SMI loss during alternating CRT was identified as a poor prognostic factor. These findings suggest that preserving skeletal muscle mass during alternating CRT may improve the prognosis and merits further investigation.

Background: Sarcopenia has been associated with poor outcomes in pancreatic cancer (PC). However, published results are heterogeneous in terms of study design, oncological outcomes, and sarcopenia measurements. This meta-analysis aims to evaluate the impact of computed tomography (CT)-based sarcopenia on overall survival (OS) and progression-free survival (PFS) in patients with PC, considering potential confounders such as the CT-based method and thresholds used to define sarcopenia, as well as treatment intention. Methods: We systematically searched databases for observational studies reporting hazard ratios (HRs) for OS and PFS in PC patients stratified by CT-based sarcopenia status. Random-effects models were used to calculate pooled crude and adjusted HRs (cHRs and aHRs, respectively), with subgroup analyses based on sarcopenia measurement methods, cutoff values, sarcopenia prevalence, and treatment intention. Heterogeneity was assessed using the I2 and τ2 statistics, and publication bias was evaluated using funnel plots and Egger's test. Results: Data from 48 studies were included. Sarcopenia was significantly associated with worse OS (pooled cHR = 1.58, 95% CI: 1.38-1.82; pooled aHR = 1.39, 95% CI: 1.16-1.66) and worse PFS (pooled cHR = 1.55, 95% CI: 1.29-1.86; pooled aHR = 1.31, 95% CI: 1.11-1.55). Subgroup analyses revealed significantly different, stronger associations in studies using stricter sarcopenia cutoffs (<50 cm2/m2 for males) and in patients undergoing curative treatments. Heterogeneity was substantial across analyses (I2 > 67%), but with generally low τ2 values (0.01-0.25). Egger's test indicated potential publication bias for OS (p < 0.001), but no significant bias was observed for PFS (p = 0.576). Conclusions: Sarcopenia determined by CT is an independent predictor of poor OS and PFS in PC, but this association varies depending on the cutoff used for its definition as well as on the treatment intention. Therefore, its routine assessment in clinical practice could provide valuable prognostic information, but future research should focus on standardizing sarcopenia assessment methods.

Patients with advanced-stage pancreatic ductal adenocarcinoma (PDAC) are regularly treated with FOLFIRINOX, a chemotherapy regimen based on 5-fluorouracil, irinotecan and oxaliplatin, which is associated with high toxicity. Dosing of FOLFIRINOX is based on body surface area, risking under- or overdosing caused by altered pharmacokinetics due to interindividual differences in body composition. This study aimed to investigate the relationship between body composition and treatment toxicity in advanced stage PDAC patients treated with FOLFIRINOX.

Data from patients treated at the Maastricht University Medical Centre + between 2012 and 2020 were collected retrospectively (n = 65). Skeletal muscle-, visceral adipose tissue, subcutaneous adipose tissue-, (SM-Index, VAT-Index, SAT-Index resp.) and Skeletal Muscle Radiation Attenuation (SM-RA) were calculated after segmentation of computed tomography (CT) images at the third lumbar level using a validated deep learning method. Lean body mass (LBM) was estimated using SM-Index. Toxicities were scored and grade 3-4 adverse events were considered dose-limiting toxicities (DLTs).

Sixty-seven DLTs were reported during the median follow-up of 51.4 (95%CI 39.2-63.7) weeks. Patients who experienced at least one DLT had significantly higher dose intensity per LBM for all separate cytotoxics of FOLFIRINOX. Independent prognostic factors for the number of DLTs per cycle were: sarcopenia (β = 0.292; 95%CI 0.013 to 0.065; p = 0.013), SM-Index change (% per 30 days, β = -0.045; 95%CI -0.079 to -0.011; p = 0.011), VAT-Index change (% per 30 days, β = -0.006; 95%CI -0.012 to 0.000; p = 0.040) between diagnosis and the first follow-up CT scan, and cumulative relative dose intensity >80 % (β = -0.315; 95 % CI -0.543 to -0.087; p = 0.008).

Sarcopenia and early muscle and fat wasting during FOLFIRINOX treatment were associated with treatment-related toxicity, warranting exploration of body composition guided personalized dosing of chemotherapeutics to limit DLTs.

Muscle and fat loss from cancer may have prognostic significance. Skeletal muscle and fat areas measured at L3 on a CT scan correlate with body muscle and fat mass. We wished to know if reduced skeletal muscle area or fat on diagnostic CT scans or changes from initial CT scans in patients with pancreatic cancer who died in 2018 and 2019 predicted mortality.

Electronic records of 112 patients with locally advanced or metastatic pancreatic cancer were used to extract stage, age, gender, comorbidities, weight, and height at the time of the first CT scan. Survival (in days) was defined from the first CT scan to the death date. Patients had at least one CT scan of the abdomen. I. Two trained medical students read scans independently using TeraRecon software (Durham, NC). Results were averaged, and the differences determined precision. Interclass correlation coefficient (ICC), coefficient of variation, and least significant change determined the precision between readers. Independent prognostic modeling included age and BMI.

An evaluable sample of 104 with an average age of 67, 56 were male. Nearly half had a TNM Stage of IV (45%). The average Charlson Comorbidity index is 7.2. In those undergoing repeat scans, most were in the timeframe of 60-120 days. Changes in visceral fat in men in the unadjusted Cox proportional hazard model and reduced skeletal muscle area in the age-adjusted model of men predicted mortality. In contrast, myosteatosis in women marginally predicted improved survival. ICC's precision between readers was adequate but by least significant change would have missed subtle, clinically important changes.

Muscle loss during chemotherapy in men predicted mortality in men but not women. Precision is an important metric when measuring body composition.

Muscle loss in men during chemotherapy of pancreatic cancer predicts mortality.

Pancreatic exocrine insufficiency (PEI) is defined as a reduction in pancreatic exocrine secretion below the level that allows the normal digestion of nutrients. Pancreatic disease and surgery are the main causes of PEI. However, other conditions and upper gastrointestinal surgery can also affect the digestive function of the pancreas. PEI can cause symptoms of nutritional malabsorption and deficiencies, which affect the quality of life and increase morbidity and mortality. These guidelines were developed following the United European Gastroenterology framework for the development of high-quality clinical guidelines. After a systematic literature review, the evidence was evaluated according to the Oxford Center for Evidence-Based Medicine and the Grading of Recommendations Assessment, Development, and Evaluation methodology, as appropriate. Statements and comments were developed by the working groups and voted on using the Delphi method. The diagnosis of PEI should be based on a global assessment of symptoms, nutritional status, and a pancreatic secretion test. Pancreatic enzyme replacement therapy (PERT), together with dietary advice and support, are the cornerstones of PEI therapy. PERT is indicated in patients with PEI that is secondary to pancreatic disease, pancreatic surgery, or other metabolic or gastroenterological conditions. Specific recommendations concerning the management of PEI under various clinical conditions are provided based on evidence and expert opinions. This evidence-based guideline summarizes the prevalence, clinical impact, and general diagnostic and therapeutic approaches for PEI, as well as the specifics of PEI in different clinical conditions. Finally, the unmet needs for future research are discussed.

Patients with borderline resectable (BR) or locally advanced pancreatic cancer (LAPC) require complex management strategies. This study evaluated the prognostic significance of the perichemotherapy skeletal muscle index (SMI) and carbohydrate antigen 19-9 (CA 19-9) in patients with BRPC or LAPC treated with FOLFIRINOX.

We retrospectively evaluated 227 patients with BR or LAPC who received at least four cycles of chemotherapy between 2015 and 2020. We analysed chemotherapy response, changes in SMI (ΔSMI, %) on computed tomography (CT) and CA19-9 to determine their impact on progression-free survival (PFS) and overall survival (OS). After the early application of loco-regional treatments (LRT) within 3 months after completing four cycles of chemotherapy, the outcomes were compared between ΔSMI and CA19-9 subgroups.

Among 227 patients (median age, 60 years; 124 [54.6%] male) with 97 BR and 130 LAPC, 50.7% showed partial response (PR) to chemotherapy, 44.5% showed stable disease and 4.8% showed progressive disease (PD). Post-chemotherapy CA19-9 levels were normalized in 41.0% of patients. The high and low ΔSMI groups (based on the gender-specific cut-off of -8.6% for males and -2.9% for females) comprised 114 (50.2%) and 113 (49.8%) patients, respectively. The high ΔSMI group had poorer survival rates than the low ΔSMI group in both PFS (HR = 1.32, p = 0.05) and OS (HR = 1.74, p = 0.001). Multivariable analysis showed that ΔSMI (high vs. low; PFS, HR = 1.39, p = 0.03; OS, HR = 1.82, p < 0.001) and post-chemotherapy response (PD vs. PR/SD; PFS, HR = 18.69, p < 0.001; OS, HR = 6.19, p < 0.001) were independently associated with both PFS and OS. Additionally, the post-chemotherapy CA19-9 (≥ 37 vs. < 37; HR = 1.48, p = 0.01) was an independent predictor for PFS. Early application of LRT after chemotherapy significantly improved PFS and OS in both ΔSMI groups (all p < 0.05). However, it was not beneficial in the group with high ΔSMI and post-chemotherapy CA19-9 ≥ 37 (PFS, p = 0.39 and OS, p = 0.33).

Progressive sarcopenic deterioration after four cycles of chemotherapy was associated with poor survival outcomes in patients with BR or LAPC after FOLFIRINOX. We also investigated the optimal clinical setting for the early application LRTs using the ΔSMI and post-chemotherapy CA 19-9.

To investigate the association of skeletal muscle mass and quality with survival outcomes in patients with advanced hepatocellular carcinoma (HCC) treated with lenvatinib (LEN).

In this retrospective study, LEN-treated patients with HCC were enrolled. Sarcopenia and myosteatosis were evaluated on the basis of baseline skeletal muscle index and mean muscle attenuation, respectively, on computed tomography at the L3 level. Low skeletal muscle mass (LSMM) was determined on the basis of index value, and bioinformatics tools were used to determine reliable cutoff values. Myosteatosis was defined on the basis of mean Hounsfield unit values and predefined cutoff values. A logrank test and Cox proportional hazards model were used to compare overall survival (OS) and progression-free survival (PFS).

A total of 81 patients were included. Patients with LSMM exhibited significantly lower PFS (p = 0.003) and OS (p = 0.010) than did patients without LSMM. Patients with myosteatosis exhibited significantly lower PFS (p = 0.012) and OS (p < 0.001) than did patients without myosteatosis. In multivariate analysis adjusted for tumor extent and liver function reserve, LSMM and myosteatosis remained independent predictors of low PFS (p = 0.028, p = 0.031) and OS (p = 0.027, p = 0.001), respectively.

LSMM and myosteatosis are independent prognostic factors for PFS and OS in advanced patients with HCC who received LEN and may exert synergistic effects on these survival outcomes.

Systematic review and clinimetric analysis.

Frailty and sarcopenia predict worse surgical outcomes among spinal degenerative and deformity-related populations; this association is less clear in the context of spinal oncology. Here, we sought to identify frailty and sarcopenia tools applied in spinal oncology and appraise their clinimetric properties.

A systematic review was conducted from January 1st, 2000, until June 2022. Study characteristics, frailty tools, and measures of sarcopenia were recorded. Component domains, individual items, cut-off values, and measurement techniques were collected. Clinimetric assessment was performed according to Consensus-based Standards for Health Measurement Instruments.

Twenty-two studies were included (42 514 patients). Seventeen studies utilized 6 frailty tools; the three most employed were the Metastatic Spine tumor Frailty Index (MSTFI), Modified Frailty Index-11 (mFI-11), and the mFI-5. Eight studies utilized measures of sarcopenia; the three most common were the L3-Total Psoas Area (TPA)/Vertebral Body Area (VBA), L3-TPA/Height2, and L3-Spinal Muscle Index (L3-Cross-Sectional Muscle Area/Height2). Frailty and sarcopenia measures lacked or had uncertain content and construct validity. Frailty measures were objective except the Johns-Hopkins Adjusted Clinical Groups. All tools were feasible except the Hospital Frailty Risk Score (HFRS). Positive predictive validity was observed for the HFRS and in select studies employing the mFI-5, MSTFI, and L3-TPA/VBA. All frailty tools had floor or ceiling effects.

Existing tools for evaluating frailty and sarcopenia among patients undergoing surgery for spinal tumors have poor clinimetric properties. Here, we provide a pragmatic approach to utilizing existing frailty and sarcopenia tools, until more clinimetrically robust instruments are developed.

Infectious complications (ICs) have been reported as major causes of postoperative mortality in patients with cancer. However, to the best of our knowledge, the impact of ICs after gastrectomy on non-gastric cancer-related deaths (NGCDs) remains unexplored. The present study aimed to identify the impact of ICs after gastrectomy on NGCDs. A retrospective analysis of 712 patients with gastric cancer who underwent curative gastrectomy was conducted. The participants were categorized into IC and non-IC groups based on the incidence of postoperative IC. Clinicopathological factors and non-gastric cancer-related survival (NGCS) rates were compared between groups. Further NGCD and associated risk factor analyses were performed in a background factor-adjusted cohort using multivariate analysis. Among the 712 patients, 112 developed ICs (Clavien-Dindo classification grade ≥II). In the entire cohort, the IC group had a significantly worse 5-year cumulative incidence of NGCD (17.8 vs. 10.6%; Gray's P=0.021) compared with the non-IC group. Although a number of clinicopathological factors differed between the groups, including patient background, operative factors and tumor factors, the risk factors for NGCD identified in the multivariate analysis were older age, low prognostic nutritional index, low skeletal muscle index and Charlson comorbidity index ≥1, excluding IC incidents. The IC group exhibited more background factors contributing to NGCDs, suggesting a potential increase in NGCD regardless of IC incidence.

This study investigates the relationship between 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) metabolic parameters, clinicopathological characteristics, and sarcopenia in patients with pancreatic ductal adenocarcinoma (PDAC) and evaluates their prognostic roles.

The primary tumor's maximum standard uptake (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) values, as well as clinicopathological factors, were evaluated retrospectively. Computed tomography (CT) was used to assess the skeletal muscle index (SMI). Sarcopenia was defined based on SMI calculated at the third lumbar vertebra (L3). SMI cut-off values ​​for sarcopenia were accepted as 44.77 cm2/m2 for men and 32.50 cm2/m2 for women. The primary endpoint was the overall survival (OS). OS data were analyzed by the Kaplan-Meier method and compared using the log-rank test. To identify predictive factors for sarcopenia, multivariable logistic regression was used following univariable logistic regression. Cox proportional hazards regression analyses were used to find predictors of OS.

Of the 86 patients included in the study, 37 (43%) were diagnosed with sarcopenia. Compared with non-sarcopenic patients, sarcopenia was observed in older patients (P=0,028) and patients with lower body mass index (BMI) (p=0,001). Age and BMI independently predicted sarcopenia. Univariate analysis identified sarcopenia, advanced stage, and higher primary tumor TLG as significant predictors of overall survival. Multivariate Cox regression analysis revealed that the advanced tumor stage (p=0.017) and higher TLG (p=0,042) independently predicted OS. The median OS was 9.4 months in non-sarcopenic patients and 5.0 months in sarcopenic patients (p=0,021).

In this study cohort, advanced-stage disease and higher primary tumor TLG were identified as independent predictors of OS in patients with PDAC. Additionally, we emphasize the importance of incorporating [18F]FDG PET/CT-derived sarcopenia assessments into the prognostic evaluation and clinical management of PDAC patients. While sarcopenia was associated with shorter OS in univariate analysis, it was not an independent predictor in multivariate analysis.

Temporal muscle thickness (TMT) serves as an indicator of sarcopenia and holds predictive value for various cancers. This study aims to evaluate the prognostic significance of TMT for high-grade glioma patients. A retrospective review of 172 high-grade glioma patients from January 2015 to December 2022 was conducted. TMT value was measured based on contrast-enhanced T1-weighted magnetic resonance images before surgery. Pearson analysis was used to evaluate potential correlations. Cox regression analysis was performed to evaluate overall survival for high-grade glioma patients. In our study, the cutoff value of TMT was determined as 7.4 mm. TMT value was not a significant prognostic predictor for high-grade glioma patients (hazard ratio [HR]: 1.151, 95% confidence interval [CI]: 0.9299-1.424, p = 0.196). World Health Organization (WHO) VI and high body mass index (BMI) value were significantly associated with poorer survival outcomes (HR: 2.6689, 95% CI: 1.5729-4.528, p < 0.001; HR: 1.120, 95% CI: 1.0356-1.211, p = 0.005). TMT did not show a significant association with other factors (p > 0.05). Notably, age demonstrated a significant difference between the thicker and thinner groups (p = 0.019). Our study revealed that WHO grade and BMI demonstrated significant prognostic value for survival outcomes. Consequently, TMT does not appear to be a significant or applicable predictor in patients with high WHO grades.

Associations of body mass index (BMI) with survival in pancreatic ductal adenocarcinoma (PDA) have substantial variability in literature, potentially due to heterogeneous patient populations and retrospective analyses. Additionally, BMI may inadequately describe body composition (ie, morphomics; including subcutaneous and visceral fats, muscle, and fascia), which might have independent biological roles and associations with survival.

To study the associations of BMI and morphomics with survival and metabolomics in metastatic PDA.

This cohort study prospectively collected patient data, imaging, and serum on the phase 3 trial (Avenger500), which investigated the efficacy and safety of 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) versus modified FOLFIRINOX plus devimistat. The randomized trial accrued 528 patients with chemotherapy-naive, metastatic PDA from Europe, Israel, Korea, and the US between 2018 and 2020. In the present study, per-protocol patients with L1 to L4, T10 to T12 vertebral levels were evaluated. Data analysis occurred from January 2023 to April 2024.

Patient data were collected by clinical staff. Morphomics were analyzed from baseline imaging. Metabolites were extracted from baseline serum.

A multifaceted statistical approach evaluated associations of BMI and morphomics with progression-free survival (PFS) and overall survival (OS). Associations of morphomics with metabolites were also studied.

Of the 528 initial patients, 476 (median [IQR] age, 63 [56-68] years; 280 male [58.8%]; median [IQR] BMI, 25.0 [22.1-25.9]) were evaluable for the present study. BMI (obese [≥30] compared with normal [18.5-24.9]) was not associated with OS (hazard ratio [HR], 0.90; 95% CI, 0.67-1.22; P for trend = .33). More subcutaneous fat was associated with longer OS (HR, 0.62; 95% CI, 0.41-0.94; P for trend = .02). Higher visceral fat density was associated with shorter PFS (HR, 1.74; 95% CI, 1.23-2.48; P for trend = .002) and OS (HR, 1.50; 95% CI, 1.12-2.00; P for trend = .008). A higher muscle-to-fascia ratio was associated with longer PFS (HR, 0.58; 95% CI, 0.40-0.84; P for trend = .005) and OS (HR, 0.56; 95% CI, 0.41-0.75; P for trend = 1.7 × 10-4). Subcutaneous fat was positively associated with long-chain fatty acid metabolism including pristanic acid, decanoylcarnitine, decenoylcarnitine, and octanoylcarnitine. Muscle-to-fascia was positively associated with metabolites including acetylcarnosine (β = 0.34; 95% CI, 0.21-0.47; P = 1.27 × 10-6).

In cohort study of patients with metastatic PDA, BMI was not associated with survival. Higher visceral fat density, subcutaneous fat area, and muscle-to-fascia ratio were associated with survival independent of BMI. The latter 2 were associated with higher levels of animal product metabolism. These findings could represent novel focuses for prognostication and intervention to improve survival of patients with PDA.

Introduction: Sarcopenia, a condition characterized by a loss of skeletal muscle mass, is increasingly recognized as a significant factor influencing patient outcomes in pancreatic cancer (PC). This systematic review and meta-analysis aimed to estimate the prevalence of sarcopenia in patients with PC using computed tomography and to explore how different measurement methods and cut-off values impact such prevalence. Materials and Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a comprehensive search of PubMed, Web of Science, and EMBASE databases was performed, identifying 48 observational studies involving 9063 patients. Results: The overall pooled prevalence of sarcopenia was 45% (95% CI, 40-50%), but varied significantly by the method used: 47% when measured with the skeletal muscle index and 33% when assessed with the total psoas area. In addition, in studies using SMI, sarcopenia prevalence was 19%, 45%, and 57% for cutoff values <40 cm2/m2, 40-50 cm2/m2, and >50 cm2/m2, respectively. Moreover, the prevalence was higher in patients receiving palliative care (50%) compared to those treated with curative intent (41%). High heterogeneity was observed across all analyses, underscoring the need for standardized criteria in sarcopenia assessment. Conclusions: Our findings highlight the substantial variability in sarcopenia prevalence, which could influence patient outcomes, and stress the importance of consensus in measurement techniques to improve clinical decision making and research comparability.

Sarcopenia has been identified as a risk factor for perioperative adverse events. Several studies have shown that tomographic assessment of muscle mass can be an appropriate indicator of sarcopenia associated with morbidity and mortality. The aim of the study was to determine the association between height-adjusted area of ​​the pectoral and erector spinae muscles (haPMA and haESA) and perioperative morbidity and mortality in thoracic surgery.

Retrospective cohort study. Measurement of muscle areas was performed by tomography. The outcomes were 30-day mortality and postoperative morbidity. The discriminative capacity of the muscle areas was evaluated with an analysis of ROC curves and the Youden index was used to establish a cut-off point. The raw morbidity and mortality risk was determined and adjusted for potential confounders.

A total of 509 patients taken to thoracic surgery were included. The incidence of 30-day mortality was 7.3%. An association was found between muscle areas and 30-day mortality and pneumonia, with adequate discriminative power for mortality (AUC 0.68 for haPMA and 0.67 for haESA). An haPMA less than 10 and haESA less than 8.5 cm2/m2 were identified as a risk factor for 30-day mortality with an adjusted OR of 2.34 (95%CI 1.03-5.15) and 2.22 (95%CI 1.10-6.04) respectively.

Sarcopenia, defined as low muscle area in the pectoral and erector spinae muscles, is associated with increased morbidity and mortality in patients undergoing thoracic surgery.

This study aimed to investigate the predictive capacity of lymphocyte subpopulations, sarcopenia and myosteatosis for clinical outcomes in patients who underwent gastric cancer surgery. Additionally, the prognostic significance of CD3+/CD4+ cells in conjunction with myosteatosis was explored.

A cohort of 190 patients with gastric cancer who underwent surgery and received computed tomography scans between July 2016 and December 2017 at our institution was examined. Complete clinical information and peripheral lymphocyte subpopulations were available for all patients. A comprehensive array of statistical methodologies was employed to scrutinize variances in both clinical and pathological characteristics among patients, with the aim of identifying autonomous prognostic determinants requisite for the development of a nomogram. Subsequent assessment of the predictive efficacy of the nomogram was conducted via calibration curve analysis.

The study comprised a cohort of 190 participants, encompassing 126 males (66.32%) and 64 females (33.68%), with a mean age of 58.47 (±11.37) years. Patients were stratified into three groups based on CD3+/CD4+ cells and myosteatosis, with 24 in Group 1, 87 in Group 2 and 79 in Group 3. Notably, patients in the third group exhibited significantly shorter progression-free survival (PFS) (hazard ratio [HR] = 0.208, P < 0.001) and overall survival (OS) (HR = 0.193, P < 0.001). The subset of peripheral blood lymphocytes exhibited elevated levels of CD3+/CD4+ cells (HR = 2.485, P < 0.001) and heightened CD4+/CD8+ ratios (HR = 1.705, P = 0.038), whereas diminished CD19+ cell counts (HR = 0.210, P = 0.032) correlated with improved OS in patients. The individuals presenting with sarcopenia (HR = 4.089, P = 0.023) and myosteatosis (HR = 2.857, P < 0.001) displayed reduced OS. The multivariate Cox regression analysis showed that pathological tumour-node-metastasis stage, CD19+ cells, sarcopenia and CD3+/CD4+ cell-myosteatosis were identified as independent prognostic factors for PFS and OS in patients. The constructed nomograms for PFS and OS yielded C-index values of 0.839 (95% confidence interval [CI]: 0.798-0.880) and 0.836 (95% CI: 0.792-0.879), respectively. The calibration analysis demonstrated that the nomograms accurately predicted the 3- and 5-year survival rates of PFS and OS in patients.

Lymphocyte subsets, including CD3+/CD4+ cells, CD4+/CD8+ ratio and CD19+ cells, are indicative of clinical prognosis in gastric cancer surgery patients. Body composition parameters, such as sarcopenia and myosteatosis, are also associated with the patient's prognosis. The combination of CD3+/CD4+ cells with myosteatosis demonstrates enhanced prognostic value, enabling the identification of patients at high risk of post-operative metastasis and recurrence.

Neuroendocrine neoplasms (NENs) are slow-growing tumors. Sarcopenia is defined as the loss of muscle mass, strength, and physical performance. First-line NEN therapy is somatostatin analogs, which could be responsible for malabsorption conditions, such as pancreatic exocrine insufficiency (EPI) with underlying sarcopenia.

Evaluate the prevalence of sarcopenia in patients with NENs at diagnosis and during follow-up.

A retrospective single-center study was conducted, including patients with advanced intestinal NENs G1/G2 (excluded pancreatic NENs). CT scans were analyzed at diagnosis and after 6 months of therapy, and the skeletal muscle index was assessed.

A total of 30 patients (F:M = 6:24) were enrolled, with the following primary tumor sites: 25 in the ileum, 1 stomach, 2 jejunum, and 2 duodenum. At diagnosis, 20 patients (66.6%) showed sarcopenic SMI values, and 10 patients (33.3%) showed non-sarcopenic SMI values. At follow-up, three more patients developed sarcopenic SMI values. Statistical significance in relation to the presence of sarcopenia was found in the group of patients with carcinoid syndrome (p = 0.0178), EPI (p = 0.0018), and weight loss (p = 0.0001).

Sarcopenia was present in 2/3 of the patients with advanced intestinal NENs at the diagnosis and during the follow-up. It is reasonable to consider this condition to improve clinical outcomes.

Sarcopenia has the potential to impact the postoperative results and extended prognosis of various types of tumors. Nevertheless, the specific impact of sarcopenia on the postoperative results and long-term survival of pancreatic cancer (PC) following pancreaticoduodenectomy (PD) remains inadequately elucidated. This study investigates the significance of sarcopenia according to various Asian standards on postoperative complications and long-term prognosis in PC patients who have undergone PD.

This retrospective study systematically analyzed patients with PC who underwent PD from January 2015 to December 2022. Sarcopenia was diagnosed by the skeletal muscle index (SMI) obtained by the skeletal muscle area normalized for height squared on the third lumbar vertebra on computed tomography (CT) images. Univariate and multivariate logistic regression analysis were performed to analyze the correlation between sarcopenia and postoperative complications, while Cox regression analysis was utilized to explore the influence of sarcopenia on overall survival (OS) and recurrence-free survival (RFS) in PC patients after PD.

We enrolled 162 patients with PC after PD (92 males and 70 females, mean age: 63.78 ± 10.27 years), including 83 and 79 patients with sarcopenia and non-sarcopenia, respectively. Compared with non-sarcopenia patients, sarcopenia exhibited higher rates of recurrence rate (75% versus 59%, p = 0.039). Univariate and multivariate logistic regression analysis showed that sarcopenia did not affect the incidence of complications in patients with PC after PD in three Asian sarcopenia criteria. Multivariate Cox regression analysis indicated that sarcopenia was an independent risk factor for OS (hazard ratio [HR]: 2.49, 95% confidence interval [CI]: 1.73-3.60, p < 0.001) and RFS(hazard ratio [HR]: 1.70, 95%confidence interval [CI]: 1.12-2.50, p = 0.012) of PC patients with PD in Japanese Society of Hepatology criteria. Meanwhile, according to the Asian pancreatic cancer population standard, sarcopenia is an independent risk factor affecting the long-term OS (hazard ratio [HR]: 2.59, 95% confidence interval [CI]: 1.80-3.70, p < 0.001) and RFS (hazard ratio [HR]: 2.00, 95% confidence interval [CI]: 1.36-3.00, p < 0.001) of PC after PD. While sarcopenia is recognized as a risk factor for OS (hazard ratio [HR]: 1.81, 95% confidence interval [CI]: 1.08-3.10, p = 0.025) in PC patients based on the Fujiwara criteria, it is not found to be associated with RFS (hazard ratio [HR]: 1.60, 95% confidence interval [CI]: 0.90-3.00, p = 0.10). The model based on sarcopenia and clinical characteristics has high predictive ability for OS and RFS.

Various Asian diagnostic criteria do not link sarcopenia with postoperative complications in PC patients after PD. Nevertheless, sarcopenia remains a significant independent risk factor for long-term survival, and its combination with clinical characteristics can aid clinicians in predicting long-term survival outcomes.

To evaluate whether sarcopenia, diagnosed by magnetic resonance imaging (MRI) protocol, constitutes a prognosis-associated risk factor in patients with hepatocellular carcinoma (HCC) after hepatectomy.

One hundred and ninety-three patients who underwent hepatectomy for HCC were retrospectively enrolled. The areas of the total skeletal muscle (SM) and psoas muscle (PM) were evaluated at the third lumbar vertebra in the preoperative MR images, and divided by the square of height in order to obtain the skeletal muscle index (SMI) and psoas muscle mass index (PMI). Sarcopenia was diagnosed respectively on the definitions based on the SMI or PMI. The potential of muscle-defined sarcopenia as a prognostic factor for overall survival (OS) and recurrence-free survival (RFS) was investigated in these patients.

The areas of SM and PM, and SMI and PMI were significantly higher in the men than in the women (all p < 0.05). Notably, SMI-defined sarcopenia displayed a significant sex difference (p = 0.003), while PMI-defined sarcopenia did not (p = 0.370). Through univariate and multivariate analyses, PMI-defined sarcopenia remained an independent predictor for OS and RFS (HR = 3.486, 95% CI: 1.700-7.145, p = 0.001 and HR = 1.993, 95% CI: 1.246-3.186, p = 0.004), even after adjusting for other clinical variables. Moreover, Kaplan-Meier analysis demonstrated significantly poorer OS and RFS for patients with sarcopenia defined by using PMI, but not SMI, compared to those without sarcopenia (p < 0.001 and p = 0.006, respectively).

MRI-derived, sarcopenia defined by using PMI, not SMI, may serve as a significant risk factor for RFS and OS in patients with HCC after hepatectomy.

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.

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.

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.

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.

Sarcopenia and myosteatosis have been associated with a poor prognosis for several cancers. The albumin-myosteatosis gauge (AMG) is a novel integrated measure proposed to assess myosteatosis along with serum albumin level as a surrogate of systemic inflammation and malnutrition. The aim of this study was to investigate the prognostic value of AMG in patients with advanced pancreatic ductal adenocarcinoma (PDAC).

Patients with advanced PDAC treated with chemotherapy between 2013 and 2022 were evaluated. Skeletal muscle radiodensity (SMD) and skeletal muscle index (SMI) were calculated using computed tomography at the level of the L3 vertebra. The AMG was defined as albumin x SMD and expressed as an arbitrary unit (AU). Patients were first categorized by sex-specific quartiles and then dichotomized at the sex-specific median value of the AMG.

A total of 196 patients were included. The median age (interquartile range) was 62 (54-67), and 128 (65.3%) were male. With regard to AMG, 142.86 and 114.15 AU were identified as cutoff values for males and females, respectively. In multivariable analyses, lower AMG values (G1-G2 vs. G3-G4) (HR: 1.61, 95% CI 1.17-2.21, p = 0.003), higher ECOG performance score (> 0 vs. 0) (HR: 1.51, 95% CI 1.10-2.06, p = 0.009) and metastatic disease (vs. locally advanced) (HR: 1.88, 95% CI 1.27-2.79, p = 0.001) were associated with OS.

The study findings suggest the prognostic value of AMG in patients with advanced PDAC undergoing first-line chemotherapy. Further studies are warranted to validate these findings and assess potential predictive role of AMG in guiding treatment selection.

Sarcopenia is an important prognostic factor for cancer patients. The aim of this study was to assess the ability of sarcopenia to predict recurrent biliary obstruction (RBO) in patients with unresectable cancer after EUS-guided biliary drainage (EUS-BD).

The study enrolled 113 patients who underwent EUS-BD using the self-expandable metal stent (SEMS) for unresectable malignant biliary obstruction (MBO) between April 2016 and December 2021 at Wakayama Medical University Hospital. The skeletal muscle index at the third lumbar spine level (L3) was calculated from computed tomography images. We analyzed the cumulative incidence of RBO at 180 days after stent insertion. Univariate and multivariate analyses were performed to identify variables significantly associated with RBO.

Seventy-six patients were assigned to the sarcopenia group, and 37 were assigned to the non-sarcopenia group. The 180-day cumulative incidence of RBO was 11% in the non-sarcopenia group and 29% in the sarcopenia group (p = 0.034). The time to RBO was significantly shorter for the sarcopenia group (p = 0.028; Gray's test). Multivariate analyses identified sarcopenia as an independent prognostic factor for RBO (present vs absent; HR 4.61; 95% CI 1.76-12.10, p = 0.001). The rates of biliary sludge/food impaction were significantly higher in the sarcopenia group for the causes of RBO (p = 0.048). There were no significant differences between the sarcopenia and the non-sarcopenia groups with respect to related EUS-BD adverse events.

Sarcopenia is an independent indicator of RBO in patients with MBO who receive EUS-BD with SEMS.

Despite the prognostic relevance of cachexia in pancreatic cancer, individual body composition has not been routinely integrated into treatment planning. In this multicenter study, we investigated the prognostic value of sarcopenia and myosteatosis automatically extracted from routine computed tomography (CT) scans of patients with advanced pancreatic ductal adenocarcinoma (PDAC).

We retrospectively analyzed clinical imaging data of 601 patients from three German cancer centers. We applied a deep learning approach to assess sarcopenia by the abdominal muscle-to-bone ratio (MBR) and myosteatosis by the ratio of abdominal inter- and intramuscular fat to muscle volume. In the pooled cohort, univariable and multivariable analyses were carried out to analyze the association between body composition markers and overall survival (OS). We analyzed the relationship between body composition markers and laboratory values during the first year of therapy in a subgroup using linear regression analysis adjusted for age, sex, and American Joint Committee on Cancer (AJCC) stage.

Deep learning-derived MBR [hazard ratio (HR) 0.60, 95% confidence interval (CI) 0.47-0.77, P < 0.005] and myosteatosis (HR 3.73, 95% CI 1.66-8.39, P < 0.005) were significantly associated with OS in univariable analysis. In multivariable analysis, MBR (P = 0.019) and myosteatosis (P = 0.02) were associated with OS independent of age, sex, and AJCC stage. In a subgroup, MBR and myosteatosis were associated with albumin and C-reactive protein levels after initiation of therapy. Additionally, MBR was also associated with hemoglobin and total protein levels.

Our work demonstrates that deep learning can be applied across cancer centers to automatically assess sarcopenia and myosteatosis from routine CT scans. We highlight the prognostic role of our proposed markers and show a strong relationship with protein levels, inflammation, and anemia. In clinical practice, automated body composition analysis holds the potential to further personalize cancer treatment.

Several studies have suggested that sarcopenia is associated with an increased treatment toxicity in patients with cancer. The aim of this study is to evaluate the relationship between sarcopenia and anthracycline-related cardiotoxicity.

Patients who received anthracycline-based chemotherapy between 2014 and 2018 and had baseline abdominal CT and baseline and follow-up echocardiography after anthracycline treatment were included. European Society of Cardiology ejection fraction criteria and American Society of Echocardiography diastolic dysfunction criteria were used for definition of cardiotoxicity. Sarcopenia was defined on the basis of skeletal muscle index (SMI) and psoas muscle index (PMI) calculated on CT images at L3 and L4 vertebra levels.

A total of 166 patients (75 men and 91 women) were included. Sarcopenia was determined in 33 patients (19.9%) according to L3-SMI, in 17 patients (10.2%) according to L4-SMI and in 45 patients (27.1%) according to PMI. 27 patients (16.3%) developed cardiotoxicity. PMI and L3-SMI were significantly associated with an increased risk of cardiotoxicity (L3-SMI: HR=3.27, 95% CI 1.32 to 8.11, p=0.01; PMI: HR=3.71, 95% CI 1.58 to 8.73, p=0.003).

This is the first study demonstrating a significant association between CT-diagnosed sarcopenia and anthracycline-related cardiotoxicity. Routine CT scans performed for cancer staging may help clinicians identify high-risk patients in whom closer follow-up or cardioprotective measures should be considered.

Parameters to adapt individual treatment strategies for patients with pancreatic ductal adenocarcinoma (PDAC) are urgently needed. The present study aimed to evaluate body composition parameters as predictors of overall survival (OS) in PDAC patients.

Measurements of body composition parameters were performed on computed tomography scans at diagnosis. Height-standardized and Body Mass Index- and sex-adjusted regression formulas deriving cut-offs from a healthy population were used. The Kaplan-Meier method with the log-rank test was performed for survival analysis. Independent prognostic factors were identified with uni- and multivariable Cox regression analyses.

In total, 354 patients were analyzed. In a multivariable Cox model, besides tumor stage and resection status, only myosteatosis (HR 1.53; 95% CI 1.10-2.14, p = 0.01) was an independent prognostic factor of OS among body composition parameters. Subgroup analyses revealed that the prognostic impact of myosteatosis was higher in patients ≤68 years of age, with advanced tumor stages and patients without curative intended resection.

The analysis of one of the largest Caucasian cohorts to date, demonstrated myosteatosis to be an independent prognostic factor of OS in PDAC. To improve outcomes, prospective trials aiming to investigate the utility of an early assessment of myosteatosis with subsequent intervention by dieticians, sports medicine physicians, and physiotherapists are warranted.

Circulating adiponectin and leptin have been associated with risk of pancreatic cancer. However, the relationship between long-term exposure to these adipokines in the prediagnostic period with patient survival has not been investigated.

Adipokine levels were measured in prospectively collected samples from 472 patients with pancreatic cancer. Because of sex-specific differences in adipokine levels, associations were evaluated separately for men and women. In a subset of 415 patients, we genotyped 23 SNPs in adiponectin receptor genes (ADIPOR1 and ADIPOR2) and 30 SNPs in the leptin receptor gene (LEPR).

Adiponectin levels were inversely associated with survival in women [HR, 1.71; 95% confidence interval (CI), 1.15-2.54]; comparing top with bottom quartile but not in men (HR, 0.89; 95% CI, 0.46-1.70). The SNPs rs10753929 and rs1418445 in ADIPOR1 were associated with survival in the combined population (per minor allele HR, 0.66; 95% CI, 0.51-0.84, and HR, 1.33; 95% CI, 1.12-1.58, respectively). Among SNPs in LEPR, rs12025906, rs3790431, and rs17127601 were associated with survival in the combined population [HRs, 1.54 (95% CI, 1.25-1.90), 0.72 (95% CI, 0.59-0.88), and 0.70 (95% CI, 0.56-0.89), respectively], whereas rs11585329 was associated with survival in men only (HR, 0.39; 95% CI, 0.23-0.66; Pinteraction = 0.0002).

High levels of adiponectin in the prediagnostic period were associated with shorter survival among women, but not among men with pancreatic cancer. Several polymorphisms in ADIPOR1 and LEPR are associated with patient survival.

Our findings reveal the association between adipokine signaling and pancreatic cancer survival and demonstrate the importance of examining obesity-associated pathways in relation to pancreatic cancer in a sex-specific manner.

Objective The effect of sarcopenia on the prognosis of patients undergoing chemotherapy for unresectable pancreatic ductal adenocarcinoma remains largely unexplored. In this retrospective study, we investigated the relationship between sarcopenia and the prognosis of patients receiving first-line nanoparticle albumin-bound paclitaxel plus gemcitabine for unresectable pancreatic ductal adenocarcinoma. Methods We enrolled 251 patients with unresectable metastatic or locally advanced pancreatic ductal adenocarcinoma who had received chemotherapy between January 2015 and December 2020 at Kitasato University Hospital. Univariate and multivariate analyses were performed using the stratified Cox proportional hazards model to determine variables significantly associated with the progression-free and overall survival. Propensity score matching was performed to mitigate selection bias effects. Results In the propensity score-matched cohort, the progression-free and overall survival were not significantly different between the sarcopenia and non-sarcopenia groups (p=0.335, and 0.679 respectively). The skeletal muscle index decreased by 4.4% and 6.5% in the sarcopenia and non-sarcopenia groups, respectively, during the early treatment phase (p=0.084). There were no significant differences between groups with regard to major adverse events or drug toxicity occurrences. Both the progression-free and overall survival were significantly shorter in the skeletal muscle index loss group than in the non-skeletal muscle index loss group (p=0.026 and 0.045, respectively). Conclusion Skeletal muscle index loss during the initial treatment phase may be an early marker for the long-term prognosis of patients receiving nanoparticle albumin-bound paclitaxel plus gemcitabine as first-line treatment for unresectable pancreatic ductal adenocarcinoma.

Pancreatic cancer is despite modern diagnostic tools and treatment regimen associated with poor outcome. Many patients show cachexia and sarcopenia.

In a retrospective analysis the SMI (cm²/m²) was measured by determining the skelettal muscle area in a computed tomography image at lumbar vertebrae 3. Further clinical parameters were measured to determine the outcome.

The mean survival after diagnosis in the population with sarcopenia was significantly lower (14,4 vs 17,7 months, p=0,046). Significantly shorter survival was also seen for higher age (p=0,006), no tumor resection (p=0,004), metastases (p=0,002) and high CA19-9 level (p=0,002) CONCLUSION: Sarcopenia is an indipendant prognostic factor in patients with pancreatic cancer. SMI should be measured clinical practice and further studies are necessary to asses a potential therapeutic strategy.

Investigators are increasingly measuring skeletal muscle (SM) and adipose tissue (AT) change during cancer treatment to understand impact on patient outcomes. Recent meta-analyses have reported high heterogeneity in this literature, representing uncertainty in the resulting estimates. Using the setting of palliative-intent chemotherapy as an exemplar, we aimed to systematically summarize the sources of variability among studies evaluating SM and AT change during cancer treatment and propose standards for future studies to enable reliable meta-analysis. Studies that measured computed tomography-defined SM and/or AT change in adult patients during palliative-intent chemotherapy for solid tumours were included, with no date or geographical limiters. Of 2496 publications screened by abstract/title, 83 were reviewed in full text and 38 included for extraction, representing 34 unique cohorts across 8 tumour sites. The timing of baseline measurement was frequently defined as prior to treatment, while endpoint timing ranged from 6 weeks after treatment start to time of progression. Fewer than 50% specified the actual time interval between measurements. Measurement error was infrequently discussed (8/34). A single metric (cm2 /m2 , cm2 or %) was used to describe SM change in 18/34 cohorts, while multiple metrics were presented for 10/34 and no descriptive metrics for 6/34. AT change metrics and sex-specific reporting were available for 10/34 cohorts. Associations between SM loss and overall survival were evaluated in 24 publications, with classification of SM loss ranging from any loss to >14% loss over variable time intervals. Age and sex were the most common covariates, with disease response in 50% of models. Despite a wealth of data and effort, heterogeneity in study design, reporting and statistical analysis hinders evidence synthesis regarding the severity and outcomes of SM and AT change during cancer treatment. Proposed standards for study design include selection of homogenous cohorts, clear definition of baseline/endpoint timing and attention to measurement error. Standard reporting should include baseline SM and AT by sex, actual scan interval, SM and AT change using multiple metrics and visualization of the range of change observed. Reporting by sex would advance understanding of sexual dimorphism in SM and AT change. Evaluating the impact of tissue change on outcomes requires adjustment for relevant covariates and concurrent disease response. Adoption of these standards by researchers and publishers would alter the current paradigm to enable meta-analysis of future studies and move the field towards meaningful application of SM and AT change to clinical care.