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Background: Cancer cachexia is a multifactorial metabolic syndrome characterized by systemic inflammation and ongoing skeletal muscle loss resulting in weakness, poor quality of life, and decreased survival. Whereas lipid accumulation in skeletal muscle is associated with cancer cachexia as well as the prognosis of cancer patients, surprisingly little is known about the nature of the lipids that accumulate in the muscle during cachexia, and whether this is related to inflammation. We aimed to identify the types and distributions of intramyocellular lipids in patients with and without cancer cachexia., Methods: Rectus abdominis muscle biopsies were collected during surgery of patients with pancreatic ductal adenocarcinoma (n = 10 without cachexia, n = 20 cachectic without inflammation (CRP < 10 mg/L), n = 10 cachectic with inflammation (CRP ≥ 10 mg/L). L3-CT scans were analysed to assess body composition based on validated thresholds in Hounsfield units (HU). Muscle sections were stained with Oil-Red O and H&E to assess general lipid accumulation and atrophy. Untargeted lipidomic analyses were performed on laser-microdissected myotubes using LC-MS/MS. The spatial distribution of intramyocellular lipids with differential abundance between groups was visualized by mass-spectrometry imaging. Genes coding for inflammation markers and enzymes involved in de novo ceramide synthesis were studied by qPCR., Results: Muscle radiation attenuation was lower in cachectic patients with inflammation (median 24.3 [18.6-30.8] HU) as compared with those without inflammation (34.2 [29.3-38.7] HU, P = 0.033) or no cachexia (37.4 [33.9-42.9] HU, P = 0.012). Accordingly, intramyocellular lipid content was lower in non-cachectic patients (1.9 [1.6-2.1]%) as compared with those with cachexia with inflammation (5.5 [4.5-7.3]%, P = 0.002) or without inflammation (4.8 [2.6-6.0]%, P = 0.017). Intramyocellular lipid accumulation was associated with both local IL-6 mRNA levels (r s  = 0.57, P = 0.015) and systemic CRP levels (r s  = 0.49, P = 0.024). Compared with non-cachectic subjects, cachectic patients had a higher relative abundance of intramyocellular glycerophospholipids and a lower relative abundance of glycerolipids. Furthermore, increases in several intramyocellular lipids such as SM(d36:1), PC(34:1), and TG(48:1) were found in cachectic patients with inflammation and correlated with specific cachexia features. Altered intramyocellular lipid species such as PC(34:1), LPC(18:2), and TG(48:1) showed an uneven distribution in muscle sections of cachectic and non-cachectic patients, with areas featuring abundance of these lipids next to areas almost devoid of them., Conclusions: Intramyocellular lipid accumulation in patients with cachexia is associated with both local and systemic inflammation, and characterized by changes in defined lipid species such as glycerolipids and glycerophospholipids., (© 2024 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background: Cachexia-associated body composition alterations and tumor metabolic activity are both associated with survival of cancer patients. Recently, subcutaneous adipose tissue properties have emerged as particularly prognostic body composition features. We hypothesized that tumors with higher metabolic activity instigate cachexia related peripheral metabolic alterations, and investigated whether tumor metabolic activity is associated with body composition and survival in patients with non-small-cell lung cancer (NSCLC), focusing on subcutaneous adipose tissue., Methods: A retrospective analysis was performed on a cohort of 173 patients with NSCLC. 18 F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scans obtained before treatment were used to analyze tumor metabolic activity (standardized uptake value (SUV) and SUV normalized by lean body mass (SUL)) as well as body composition variables (subcutaneous and visceral adipose tissue radiodensity (SAT/VAT radiodensity) and area; skeletal muscle radiodensity (SM radiodensity) and area). Subjects were divided into groups with high or low SAT radiodensity based on Youden Index of Receiver Operator Characteristics (ROC). Associations between tumor metabolic activity, body composition variables, and survival were analyzed by Mann-Whitney tests, Cox regression, and Kaplan-Meier analysis., Results: The overall prevalence of high SAT radiodensity was 50.9% (88/173). Patients with high SAT radiodensity had shorter survival compared with patients with low SAT radiodensity (mean: 45.3 vs. 50.5 months, p = 0.026). High SAT radiodensity was independently associated with shorter overall survival (multivariate Cox regression HR = 1.061, 95% CI: 1.022-1.101, p = 0.002). SAT radiodensity also correlated with tumor metabolic activity (SULpeak r s  = 0.421, p = 0.029; SUVpeak r s  = 0.370, p = 0.048). In contrast, the cross-sectional areas of SM, SAT, and VAT were not associated with tumor metabolic activity or survival., Conclusion: Higher SAT radiodensity is associated with higher tumor metabolic activity and shorter survival in patients with NSCLC. This may suggest that tumors with higher metabolic activity induce subcutaneous adipose tissue alterations such as decreased lipid density, increased fibrosis, or browning., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Cancer cachexia is a multifactorial syndrome characterized by body weight loss and systemic inflammation. The characterization of the inflammatory response in patients with cachexia is still limited. Lipocalin-2, a protein abundant in neutrophils, has recently been implicated in appetite suppression in preclinical models of pancreatic cancer cachexia. We hypothesized that lipocalin-2 levels could be associated with neutrophil activation and nutritional status of pancreatic ductal adenocarcinoma (PDAC) patients., Methods: Plasma levels of neutrophil activation markers calprotectin, myeloperoxidase, elastase, and bactericidal/permeability-increasing protein (BPI) were compared between non-cachectic PDAC patients (n=13) and cachectic PDAC patients with high (≥26.9 ng/mL, n =34) or low (<26.9 ng/mL, n =34) circulating lipocalin-2 levels. Patients' nutritional status was assessed by the patient-generated subjective global assessment (PG-SGA) and through body composition analysis using CT-scan slices at the L3 level., Results: Circulating lipocalin-2 levels did not differ between cachectic and non-cachectic PDAC patients (median 26.7 (IQR 19.7-34.8) vs . 24.8 (16.6-29.4) ng/mL, p =0.141). Cachectic patients with high systemic lipocalin-2 levels had higher concentrations of calprotectin, myeloperoxidase, and elastase than non-cachectic patients or cachectic patients with low lipocalin-2 levels (calprotectin: 542.3 (355.8-724.9) vs . 457.5 (213.3-606.9), p =0.448 vs . 366.5 (294.5-478.5) ng/mL, p =0.009; myeloperoxidase: 30.3 (22.1-37.9) vs . 16.3 (12.0-27.5), p =0.021 vs . 20.2 (15.0-29.2) ng/mL, p =0.011; elastase: 137.1 (90.8-253.2) vs . 97.2 (28.8-215.7), p =0.410 vs . 95.0 (72.2-113.6) ng/mL, p =0.006; respectively). The CRP/albumin ratio was also higher in cachectic patients with high lipocalin-2 levels (2.3 (1.3-6.0) as compared to non-cachectic patients (1.0 (0.7-4.2), p =0.041). Lipocalin-2 concentrations correlated with those of calprotectin ( r s =0.36, p <0.001), myeloperoxidase ( r s =0.48, p <0.001), elastase ( r s =0.50, p <0.001), and BPI ( r s =0.22, p =0.048). Whereas no significant correlations with weight loss, BMI, or L3 skeletal muscle index were observed, lipocalin-2 concentrations were associated with subcutaneous adipose tissue index ( r s =-0.25, p =0.034). Moreover, lipocalin-2 tended to be elevated in severely malnourished patients compared with well-nourished patients (27.2 (20.3-37.2) vs . 19.9 (13.4-26.4) ng/mL, p =0.058)., Conclusions: These data suggest that lipocalin-2 levels are associated with neutrophil activation in patients with pancreatic cancer cachexia and that it may contribute to their poor nutritional status., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Deng, Aberle, van Bijnen, van der Kroft, Lenaerts, Neumann, Wiltberger, Schaap, Olde Damink and Rensen.)

Background: The majority of patients with pancreatic cancer develops cachexia. The mechanisms underlying cancer cachexia development and progression remain elusive, although tumour-derived factors are considered to play a major role. Pancreatic tumour organoids are in vitro three-dimensional organ-like structures that retain many pathophysiological characteristics of the in vivo tumour. We aimed to establish a pancreatic tumour organoid biobank from well-phenotyped cachectic and non-cachectic patients to enable identification of tumour-derived factors driving cancer cachexia., Methods: Organoids were generated from tumour tissue of eight pancreatic cancer patients. A comprehensive pre-operative patient assessment of cachexia-related parameters including nutritional status, physical performance, body composition, and inflammation was performed. Tumour-related and cachexia-related characteristics of the organoids were analysed using histological stainings, targeted sequencing, and real-time-quantitative PCR. Cachexia-related factors present in the circulation of the patients and in the tumour organoid secretome were analysed by enzyme-linked immunosorbent assay., Results: The established human pancreatic tumour organoids presented typical features of malignancy corresponding to the primary tumour (i.e. nuclear enlargement, multiple nucleoli, mitosis, apoptosis, and mutated KRAS and/or TP53). These tumour organoids also expressed variable levels of many known cachexia-related genes including interleukin-6 (IL-6), TNF-α, IL-8, IL-1α, IL-1β, Mcp-1, GDF15, and LIF. mRNA expression of IL-1α and IL-1β was significantly reduced in organoids from cachectic vs. non-cachectic patients (IL-1α: -3.8-fold, P = 0.009, and IL-1β: -4.7-fold, P = 0.004). LIF, IL-8, and GDF15 mRNA expression levels were significantly higher in organoids from cachectic vs. non-cachectic patients (LIF: 1.6-fold, P = 0.003; IL-8: 1.4-fold, P = 0.01; GDF15: 2.3-fold, P < 0.001). In line with the GDF15 and IL-8 mRNA expression levels, tumour organoids from cachectic patients secreted more GDF15 and IL-8 compared with organoids from non-cachectic patients (5.4 vs. 1.5 ng/mL, P = 0.01, and 7.4 vs. 1.3 ng/mL, P = 0.07, respectively)., Conclusions: This novel human pancreatic tumour organoid biobank provides a valuable tool to increase our understanding of the mechanisms driving cancer cachexia. Our preliminary characterization of the secretome of these organoids supports their application in functional studies including conditioned medium approaches and in vivo transplantation models., (© 2020 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Simple Summary: Pancreatic cancer is associated with weight loss and negatively affects skeletal muscle function. It is not known whether the changes observed in skeletal muscle also occur in smooth muscle, a tissue critical for gastrointestinal functioning. In cancer-related muscle wasting, it is widely assumed that both tumor- and host-derived factors and pro-inflammatory cytokines directly target skeletal muscle. This study aimed to investigate the impact of pancreatic tumor-derived factors on smooth muscle. The results from this study show that pancreatic tumor organoid-derived factors compromise the contractile phenotype of healthy smooth muscle cells. Loss of the contractile smooth muscle cell phenotype may impair the contractile functionality of the intestinal smooth musculature and may therefore contribute to the frequently reported gastrointestinal symptoms in pancreatic cancer patients. Patients with pancreatic cancer often suffer from cachexia and experience gastrointestinal symptoms that may be related to intestinal smooth muscle cell (SMC) dysfunction. We hypothesized that pancreatic tumor organoids from cachectic patients release factors that perturb the SMC's contractile characteristics. Human visceral SMCs were exposed to conditioned medium (CM) from the pancreatic tumor organoid cultures of cachectic (n = 2) and non-cachectic (n = 2) patients. Contractile proteins and markers of inflammation, muscle atrophy, and proliferation were evaluated by qPCR and Western blot. SMC proliferation and migration were monitored by live cell imaging. The Ki-67-positive cell fraction was determined in the intestinal smooth musculature of pancreatic cancer patients. CM from the pancreatic tumor organoids of cachectic patients did not affect IL-1β, IL-6, IL-8, MCP-1, or Atrogin-1 expression. However, CM reduced the α-SMA, γ-SMA, and SM22-α levels, which was accompanied by a reduced SMC doubling time and increased expression of S100A4, a Ca2+-binding protein associated with the synthetic SMC phenotype. In line with this, Ki-67-positive nuclei were increased in the intestinal smooth musculature of patients with a low versus high L3-SMI. In conclusion, patient-derived pancreatic tumor organoids release factors that compromise the contractile SMC phenotype and increase SMC proliferation. This may contribute to the frequently observed gastrointestinal motility problems in these patients. [ABSTRACT FROM AUTHOR]

Background: Cancer cachexia is a multifactorial syndrome characterized by body weight loss and systemic inflammation. The characterization of the inflammatory response in patients with cachexia is still limited. Lipocalin-2, a protein abundant in neutrophils, has recently been implicated in appetite suppression in preclinical models of pancreatic cancer cachexia. We hypothesized that lipocalin-2 levels could be associated with neutrophil activation and nutritional status of pancreatic ductal adenocarcinoma (PDAC) patients. Methods: Plasma levels of neutrophil activation markers calprotectin, myeloperoxidase, elastase, and bactericidal/permeability-increasing protein (BPI) were compared between non-cachectic PDAC patients (n=13) and cachectic PDAC patients with high (≥26.9 ng/mL, n=34) or low (<26.9 ng/mL, n=34) circulating lipocalin-2 levels. Patients' nutritional status was assessed by the patient-generated subjective global assessment (PG-SGA) and through body composition analysis using CT-scan slices at the L3 level. Results: Circulating lipocalin-2 levels did not differ between cachectic and noncachectic PDAC patients (median 26.7 (IQR 19.7-34.8) vs. 24.8 (16.6-29.4) ng/mL, p=0.141). Cachectic patients with high systemic lipocalin-2 levels had higher concentrations of calprotectin, myeloperoxidase, and elastase than noncachectic patients or cachectic patients with low lipocalin-2 levels (calprotectin: 542.3 (355.8-724.9) vs. 457.5 (213.3-606.9), p=0.448 vs. 366.5 (294.5-478.5) ng/mL, p=0.009; myeloperoxidase: 30.3 (22.1-37.9) vs. 16.3 (12.0-27.5), p=0.021 vs. 20.2 (15.0-29.2) ng/mL, p=0.011; elastase: 137.1 (90.8-253.2) vs. 97.2 (28.8-215.7), p=0.410 vs. 95.0 (72.2-113.6) ng/mL, p=0.006; respectively). The CRP/albumin ratio was also higher in cachectic patients with high lipocalin-2 levels (2.3 (1.3-6.0) as compared to non-cachectic patients (1.0 (0.7-4.2), p=0.041). Lipocalin-2 concentrations correlated with those of calprotectin (rs=0.36, p<0.001), myeloperoxidase (rs=0.48, p<0.001), elastase (rs=0.50, p<0.001), and BPI (rs=0.22, p=0.048). Whereas no significant correlations with weight loss, BMI, or L3 skeletal muscle index were observed, lipocalin-2 concentrations were associated with subcutaneous adipose tissue index (rs=-0.25, p=0.034). Moreover, lipocalin-2 tended to be elevated in severely malnourished patients compared with well-nourished patients (27.2 (20.3-37.2) vs. 19.9 (13.4-26.4) ng/mL, p=0.058). Conclusions: These data suggest that lipocalin-2 levels are associated with neutrophil activation in patients with pancreatic cancer cachexia and that it may contribute to their poor nutritional status. [ABSTRACT FROM AUTHOR]

Background: Cancer cachexia is characterized by a negative energy balance, muscle and adipose tissue wasting, insulin resistance, and systemic inflammation. Because of its strong negative impact on prognosis and its multifactorial nature that is still not fully understood, cachexia remains an important challenge in the field of cancer treatment. Recent animal studies indicate that the gut microbiota is involved in the pathogenesis and manifestation of cancer cachexia, but human data are lacking. The present study investigates gut microbiota composition, short‐chain fatty acids (SCFA), and inflammatory parameters in human cancer cachexia. Methods: Faecal samples were prospectively collected in patients (N = 107) with pancreatic cancer, lung cancer, breast cancer, or ovarian cancer. Household partners (N = 76) of the patients were included as healthy controls with similar diet and environmental conditions. Patients were classified as cachectic if they lost >5% body weight in the last 6 months. Gut microbiota composition was analysed by sequencing of the 16S rRNA V4 gene region. Faecal SCFA levels were quantified by gas chromatography. Faecal calprotectin was assessed with enzyme‐linked immunosorbent assay. Serum C‐reactive protein and leucocyte counts were retrieved from medical records. Results: Cachexia prevalence was highest in pancreatic cancer (66.7%), followed by ovarian cancer (25%), lung cancer (20.8%), and breast cancer (17.3%). Microbial α‐diversity was not significantly different between cachectic cancer patients (N = 33), non‐cachectic cancer patients (N = 74), or healthy controls (N = 76) (species richness P = 0.31; Shannon effective index P = 0.46). Community structure (β‐diversity) tended to differ between these groups (P = 0.053), although overall differences were subtle and no clear clustering of samples was observed. Proteobacteria (P < 0.001), an unknown genus from the Enterobacteriaceae family (P < 0.01), and Veillonella (P < 0.001) were more abundant among cachectic cancer patients. Megamonas (P < 0.05) and Peptococcus (P < 0.001) also showed differential abundance. Faecal levels of all SCFA tended to be lower in cachectic cancer patients, but only acetate concentrations were significantly reduced (P < 0.05). Faecal calprotectin levels were positively correlated with the abundance of Peptococcus, unknown Enterobacteriaceae, and Veillonella. We also identified several correlations and interactions between clinical and microbial parameters. Conclusions: This clinical study provided the first insights into the alterations of gut microbiota composition and SCFA levels that occur in cachectic cancer patients and how they are related to inflammatory parameters. These results pave the way for further research examining the role of the gut microbiota in cancer cachexia and its potential use as therapeutic target. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia is the loss of skeletal muscle mass and function that occurs with advancing age and certain diseases. It is thought to have a negative impact on survival in cancer patients. Routine computed tomography imaging is often used to quantify skeletal muscle in cancer patients. Sarcopenia is defined by a low skeletal muscle index (SMI). Skeletal muscle radiation attenuation (SMRA) is used to define muscle quality. The primary aim of this meta‐analysis was to study the association between sarcopenia or SMRA and overall survival (OS) or complications in patients with ovarian cancer. Methods: Medline, Embase, CINAHL, and PEDro databases were searched from inception to 15 February 2019. Studies evaluating the prognostic effect of SMI and SMRA on ovarian cancer survival or surgical complications were included. Risk of bias and study quality were evaluated with the Quality in Prognosis Studies Instrument (QUIPS) according to the modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Results: The search strategy yielded 4262 hits in all four databases combined. Ten and eight studies were included for qualitative and quantitative analysis, respectively. Meta‐analysis revealed a significant association between the SMI and OS [0.007; hazard ratio (HR): 1.11, 95% confidence interval (CI): 1.03–1.20]. SMRA was also significantly associated with OS (P < 0.001; HR: 1.14, 95% CI: 1.08–1.20). Association between the SMI and surgical complications had borderline statistical significance (0.05; HR: 1.23, 95% CI: 1.00–1.52). The risk of bias assessed with QUIPS was high in all studies. The quality of the evidence was very low. Conclusions: Whereas our meta‐analysis indicated that a low SMI and low SMRA are associated with survival in ovarian cancer patients, the low quality of the source data precludes drawing definitive conclusions. [ABSTRACT FROM AUTHOR]

Background Cancer cachexia and skeletal muscle wasting are related to poor survival. In this study, quantitative body composition measurements using computed tomography (CT) were investigated in relation to survival, post-operative complications, and surgical site infections in surgical patients with cancer of the head of the pancreas. Methods A prospective cohort of 199 patients with cancer of the head of the pancreas was analysed by CT imaging at the L3 level to determine (i) muscle radiation attenuation (average Hounsfield units of total L3 skeletal muscle); (ii) visceral adipose tissue area; (iii) subcutaneous adipose tissue area; (iv) intermuscular adipose tissue area; and (v) skeletal muscle area. Sex-specific cut-offs were determined at the lower tertile for muscle radiation attenuation and skeletal muscle area and the higher tertile for adipose tissues. These variables of body composition were related to overall survival, severe post-operative complications (Dindo-Clavien ≥ 3), and surgical site infections (wounds inspected daily by an independent trial nurse) using Cox-regression analysis and multivariable logistic regression analysis, respectively. Results Low muscle radiation attenuation was associated with shorter survival in comparison with moderate and high muscle radiation attenuation [median survival 10.8 (95% CI: 8.8-12.8) vs. 17.4 (95% CI: 14.7-20.1), and 18.5 (95% CI: 9.2-27.8) months, respectively; P < 0.008]. Patient subgroups with high muscle radiation attenuation combined with either low visceral adipose tissue or age <70 years had longer survival than other subgroups ( P = 0.011 and P = 0.001, respectively). Muscle radiation attenuation was inversely correlated with intermuscular adipose tissue ( rp = −0.697, P < 0.001). High visceral adipose tissue was associated with an increased surgical site infection rate, OR: 2.4 (95% CI: 1.1-5.3; P = 0.027). Conclusions Low muscle radiation attenuation was associated with reduced survival, and high visceral adiposity was associated with an increase in surgical site infections. The strong correlation between muscle radiation attenuation and intermuscular adipose tissue suggests the presence of ectopic fat in muscle, warranting further investigation. CT image analysis could be implemented in pre-operative risk assessment to assist in treatment decision-making. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with cancer often suffer from severe weight loss as a result of the wasting of skeletal muscle and fat tissue. This has a strong negative impact on the patient's prognosis and quality of life. Inflammation is thought to contribute to weight loss in cancer. To enable the future targeting of inflammation in patients with cancer who experience weight loss, we set out to characterize an important pro-inflammatory component of the immune system: the complement system. The blood levels of several elements of the complement system were analyzed in patients with and without weight loss and inflammation. We found that complement factors were activated specifically in patients with both weight loss and inflammation. Since complement inhibitory drugs are already on the market, these findings may open new opportunities for treating inflammation-mediated weight loss in patients with cancer. Systemic inflammation is thought to underlie many of the metabolic manifestations of cachexia in cancer patients. The complement system is an important component of innate immunity that has been shown to contribute to metabolic inflammation. We hypothesized that systemic inflammation in patients with cancer cachexia was associated with complement activation. Systemic C3a levels were higher in cachectic patients with inflammation (n = 23, C-reactive protein (CRP) ≥ 10 mg/L) as compared to patients without inflammation (n = 26, CRP < 10 mg/L) or without cachexia (n = 13) (medians 102.4 (IQR 89.4–158.0) vs. 81.4 (IQR 47.9–124.0) vs. 61.6 (IQR 46.8–86.8) ng/mL, respectively, p = 0.0186). Accordingly, terminal complement complex (TCC) concentrations gradually increased in these patient groups (medians 2298 (IQR 2022–3058) vs. 1939 (IQR 1725–2311) vs. 1805 (IQR 1552–2569) mAU/mL, respectively, p = 0.0511). C3a and TCC concentrations were strongly correlated (rs = 0.468, p = 0.0005). Although concentrations of C1q and mannose-binding lectin did not differ between groups, C1q levels were correlated with both C3a and TCC concentrations (rs = 0.394, p = 0.0042 and rs = 0.300, p = 0.0188, respectively). In conclusion, systemic inflammation in patients with cancer cachexia is associated with the activation of key effector complement factors. The correlations between C1q and C3a/TCC suggest that the classical complement pathway could play a role in complement activation in patients with pancreatic cancer. [ABSTRACT FROM AUTHOR]

Decrease in skeletal muscle index (SMI) during neoadjuvant chemotherapy (NACT) has been associated with worse outcome in patients with advanced ovarian cancer. To validate these findings, we tested if a decrease in SMI was a prognostic factor for a homogenous cohort of patients who received NACT in the randomized phase 3 OVHIPEC-trial. CT-scans were performed at baseline and after two cycles of neoadjuvant chemotherapy in stage III ovarian cancer patients. The SMI (skeletal muscle area in cm2 divided by body surface area in m2) was calculated using SliceOMatic software. The difference in SMI between both CT-scans (ΔSMI) was calculated. Cox-regression analyses were performed to analyze the independent effect of a difference in SMI (ΔSMI) on outcome. Log-rank tests were performed to plot recurrence-free (RFS) and overall survival (OS). The mean number of adverse events per patient were compared between groups using t -tests. Paired CT-scans were available for 212 out of 245 patients (87%). Thirty-four of 74 patients (58%) in the group with a decrease in ΔSMI and 73 of 138 of the patients (53%) in the group with stable/increase in ΔSMI had died. Median RFS and OS did not differ significantly (p = 0.297 and p = 0.764) between groups. Patients with a decrease in SMI experienced more pre-operative adverse events, and more grade 3–4 adverse events. Decreased SMI during neoadjuvant chemotherapy was not associated with worse outcome in patients with stage III ovarian cancer included in the OVHIPEC-trial. However, a strong association between decreasing SMI and adverse events was found. • Longitudinal CT-scans were assessed for body composition alterations during neoadjuvant chemotherapy (NACT). • A decrease in skeletal muscle index during NACT was not predictive for recurrence-free survival or overall survival. • A decrease in skeletal muscle index was associated with more pre-treatment and pre-operative reported adverse events. [ABSTRACT FROM AUTHOR]