The research, published in the European Journal of Nuclear Medicine and Molecular Imaging, examined whether body composition measured on routine CT scans could predict which patients would experience early progression after PRRT. The idea rests on a growing body of evidence in oncology: it is not merely how much muscle a patient carries, but the quality of that muscle, that shapes outcomes across a striking range of cancers. Previous studies have linked fatty infiltration of muscle, a condition called myosteatosis, to poorer survival after pancreatic surgery, worse responses to chemoembolization in liver cancer, and altered activity of immunotherapies in metastatic melanoma.

Myosteatosis is best understood as muscle that has been quietly invaded by fat at the microscopic level. On a CT scan, healthy skeletal muscle appears relatively dark because it contains abundant water-dense contractile tissue. When fat infiltrates the muscle fibers, the tissue’s average density drops, which radiologists measure in Hounsfield units on the standard gray-scale of CT imaging. Crucially, researchers can extract these measurements from virtually any abdominal CT, including the CT component of a PET/CT scan that every PRRT patient already receives, simply by analyzing a slice at the level of the third and fourth lumbar vertebrae, where the psoas muscles anchor the spine.

The Munich team, led by first authors Elma Dema and Christian Dascalescu under the senior guidance of Rudolf Werner and Sophie Siegmund, screened 321 consecutive patients who underwent PRRT for somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors. Complete imaging and follow-up data were available for 301 of them. Using BMI-adjusted cut-offs for psoas muscle attenuation, the investigators defined which patients had myosteatosis at baseline, before a single radioactive dose had been administered. Their primary endpoint was deliberately stringent: early progression as seen on somatostatin receptor-targeted PET imaging after up to four consecutive treatment cycles, dichotomized as progressive disease versus disease control.

The headline result was, in one sense, a negative one. Traditional quantity-based measures of body composition, including skeletal muscle area and related indices that simply quantify how much muscle tissue surrounds the spine, showed no association whatsoever with early progression. Muscle bulk alone, it seems, tells clinicians nothing useful about whether a neuroendocrine tumor will shrug off PRRT within the first treatment window. This finding matters because muscle quantity is still the most commonly reported body composition parameter in oncology literature, often treated as a stand-in for overall nutritional reserve.

The quality-based measure told a more intriguing story. Only eight of the 301 patients, a mere 2.7 percent, met the criteria for baseline myosteatosis, yet those eight appeared to fare strikingly worse. In univariable analysis, myosteatosis was associated with roughly an eight-fold increase in the odds of early PET-based progression, with an odds ratio of 7.8 and a 95 percent confidence interval running from 1.74 to 34.78, yielding a nominal p-value of 0.0073. In a separately specified model adjusted for baseline clinical characteristics, the association held steady at an odds ratio of 8.1. But here the statistical plot thickens considerably.

When the researchers applied the Benjamini-Hochberg procedure, a standard correction that controls the false discovery rate when multiple hypotheses are tested simultaneously, the p-value drifted to 0.1073, crossing above the conventional significance threshold. The association was also attenuated when the number of completed PRRT cycles was added as a post-baseline treatment exposure variable, landing at an odds ratio of 5.7 with a confidence interval that narrowly grazed 1.0 and a p-value of 0.0538, just shy of the 0.05 benchmark. With only eight affected patients, the confidence intervals around these estimates were wide, which is the statistical signature of a hypothesis that cannot yet be called a finding.

The authors are admirably blunt about this limitation. They conclude that the results should be regarded as exploratory and hypothesis-generating, and that they do not establish any clinical utility for myosteatosis in individual risk stratification. In plain terms, no one should yet order a CT-based muscle analysis to decide who gets PRRT or how closely they should be monitored. The study also reveals a practical puzzle: myosteatosis was far rarer in this cohort than the 30 to 50 percent prevalence reported in some other cancer populations treated with PRRT, suggesting that the BMI-adjusted thresholds used here may flag only the most severe cases, or that neuroendocrine tumor patients differ fundamentally in their metabolic profiles.

Why might fat-infiltrated muscle and treatment resistance be connected at all? The mechanisms remain speculative, but several plausible pathways have been described in the wider literature. Myosteatosis is considered a marker of systemic metabolic derangement, reflecting chronic inflammation, insulin resistance, and altered mitochondrial function within muscle tissue. These same processes could plausibly influence tumor biology, modulate the delivery of radiopharmaceuticals, or shape how the body tolerates and responds to radiation. Some researchers have even proposed myosteatosis as an early and targetable biomarker of cancer prognosis, a measurable vulnerability that nutritional or exercise interventions might one day reverse before treatment begins.

For the field of nuclear medicine, the study is a careful lesson in statistical humility and a genuine invitation to dig deeper. Early progression after PRRT occurs in roughly 8 percent of patients, and identifying this minority before therapy would allow clinicians to consider intensified surveillance, alternative sequencing, or combination approaches for those at highest risk. The Munich data suggest that the search should move beyond how much muscle a patient has and toward the finer architecture of that muscle, ideally with larger, prospective cohorts and standardized measurement protocols. Until then, the radioactive missile remains a remarkably effective weapon, even if the secrets of the rare patients it fails are still written, faintly, in their own flesh.

Subject of Research: Association between CT-based body composition and early progression after peptide receptor radionuclide therapy in gastroenteropancreatic neuroendocrine tumors

Article Title: Baseline body composition and early PRRT outcome in GEP-NETs: an exploratory analysis

Article References: Dema, E., Dascalescu, C., Holzgreve, A., Cyran, C. C., Widjaja, L., Gildehaus, F. J., Herr, F. L., Spitzweg, C., Auernhammer, C. J., Ingrisch, M., Brendel, M., Ricke, J., Werner, R. A., & Siegmund, S. C. (2026). Baseline body composition and early PRRT outcome in GEP-NETs: an exploratory analysis. European Journal of Nuclear Medicine and Molecular Imaging. https://doi.org/10.1007/s00259-026-08182-w

Image Credits: AI Generated

DOI: 10.1007/s00259-026-08182-w

Keywords: PRRT, neuroendocrine tumors, body composition, myosteatosis, lutetium-177, PET/CT, sarcopenia, radiomics, nuclear medicine, cachexia, psoas muscle, tumor progression

The study, led by Hye Ju Yeo and Ha Lim Kim of Pusan National University Yangsan Hospital in South Korea, together with colleagues including Woo Hyun Cho, examined 1,107 adults with sepsis who had undergone abdominal CT imaging as part of their clinical care. Rather than relying on height and weight, the team deployed an automated segmentation pipeline built on the nnU-Net framework, a self-configuring deep learning architecture that has become a standard tool for biomedical image analysis, supplemented by the TotalSegmentator software capable of delineating more than one hundred anatomic structures in a single scan. The algorithms measured the cross-sectional areas of subcutaneous adipose tissue, the fat layer beneath the skin, and visceral adipose tissue, the fat packed around internal organs, at the level of the third and fourth lumbar vertebrae, a standard landmark in body composition research.

The technical rationale for this approach is straightforward. Body mass index cannot distinguish between fat stored under the skin and fat stored deep within the abdomen, yet these two depots behave in profoundly different ways biologically. Subcutaneous adipose tissue acts largely as a passive energy reservoir and, in some contexts, appears metabolically protective, sequestering lipids away from the liver, muscle, and bloodstream. Visceral adipose tissue, by contrast, drains directly into the portal circulation, is richly innervated and hormonally active, and is strongly associated with insulin resistance, systemic inflammation, and adverse outcomes across a range of acute and chronic illnesses. The idea that these depots might carry opposite prognostic signals during sepsis is not new, but measuring them reliably has traditionally required painstaking manual tracing of CT images, which is impractical at scale.

Among the 1,107 patients in the cohort, 300, or 27.1 percent, died within 28 days of their sepsis diagnosis during the index hospitalization. When the researchers fed their imaging-derived measurements into Cox proportional hazards models adjusted for clinically selected covariates, a clear and internally consistent picture emerged. Greater subcutaneous adipose tissue area was associated with lower mortality, with an adjusted hazard ratio of 0.83 per one standard deviation increase, a statistically significant protective association. Obesity itself, defined here as a body mass index of 25 kilograms per square meter or higher in keeping with thresholds commonly used in Asian populations, was also associated with lower mortality, with an adjusted hazard ratio of 0.62. But the most telling variable was the ratio of visceral to subcutaneous fat: patients with a higher VAT/SAT ratio had significantly higher mortality, with an adjusted hazard ratio of 1.14 per standard deviation increase.

That pattern reframes the obesity paradox in mechanistic terms. It suggests that what has appeared to be a survival advantage of obesity in sepsis may actually reflect the composition of body fat rather than its total quantity. A patient whose excess weight is dominated by subcutaneous fat may be metabolically better buffered against the catabolic storm of critical illness than a leaner patient whose fat is disproportionately visceral. The finding aligns with a growing body of work. A 2016 study in Critical Care Medicine by Pisitsak and colleagues found that an increased visceral-to-subcutaneous adipose tissue ratio in septic patients was associated with adverse outcomes, and subsequent research suggested that the survival benefit of a low ratio depends on the balance of LDL cholesterol clearance versus production during infection. Population-level analyses in the UK Biobank have similarly shown that abdominal fat distribution outperforms traditional anthropometric indices in predicting sepsis outcomes.

The stratified analyses added further texture, though with appropriate statistical caution. In exploratory models stratified by body mass index category, the protective association of subcutaneous fat was most pronounced among underweight patients, where greater subcutaneous adipose tissue area carried an adjusted hazard ratio of 0.37, meaning a substantially lower hazard of death. Conversely, among patients with obesity, a higher visceral-to-subcutaneous ratio was associated with a markedly elevated mortality risk, with an adjusted hazard ratio of 1.48. In other words, not all obesity is created equal: a patient with obesity whose fat is predominantly subcutaneous may carry a very different prognosis from one whose obesity is visceral-dominant. The authors were careful to note, however, that formal interaction tests between these imaging measures and body mass index category did not reach statistical significance, with P values of 0.145 and 0.127, meaning the apparent effect modification could reflect chance and requires confirmation in larger, independent cohorts.

The study also interrogated skeletal muscle, a dimension of body composition that has gained increasing attention in critical care. Sarcopenia, the loss of muscle mass and function, is common in critically ill patients and has been linked to worse long-term outcomes, partly because sepsis itself induces profound muscle wasting through disrupted autophagy and mitochondrial dysfunction. The team quantified psoas muscle measures at the same lumbar level, including the psoas muscle index, a conventional marker of muscle quantity. Strikingly, muscle size itself did not retain an independent association with mortality after adjustment. What did survive the statistical scrutiny was muscle quality: a higher proportion of low-attenuation muscle, which reflects fatty infiltration of the muscle and is a radiographic signature of myosteatosis, was associated with higher mortality, with an adjusted hazard ratio of 1.14. A joint phenotype combining a high visceral-to-subcutaneous ratio with a low psoas muscle index, which the investigators had hypothesized might identify particularly high-risk patients, was not significant after adjustment.

These findings carry real implications for how risk is characterized in the intensive care unit. Abdominal CT scans are already obtained routinely in many sepsis patients to search for the infectious source, meaning the raw imaging data needed for automated body composition analysis often exists before anyone thinks to use it prognostically. A pretrained deep learning pipeline can extract these measurements in seconds without manual labor, and the underlying software is publicly available, making the approach reproducible and potentially deployable as a clinical decision-support tool. If validated externally, a VAT/SAT ratio or a low-attenuation muscle fraction could complement, and in some cases correct, the crude signal provided by body mass index, helping clinicians identify high-risk patients who would be missed by conventional anthropometry, including visceral-dominant patients with obesity and sarcopenic patients of normal weight.

The authors and independent commentators are quick to emphasize the study’s limitations. It was a single-center, retrospective cohort, which raises the possibility of selection bias, since only patients who happened to receive abdominal CT imaging could be included. The subgroup findings, however compelling, rest on exploratory analyses with non-significant interaction tests, and the skeletal muscle results in particular require external validation before they can inform practice. Residual confounding by illness severity, nutritional status, and chronic disease cannot be excluded in any observational design. Still, the convergence of this work with prior mechanistic and epidemiological evidence, and the elegance of using artificial intelligence to turn diagnostic scans that already exist into prognostic information that costs nothing extra, marks a meaningful step forward. The obesity paradox in sepsis has long been an embarrassment to simple models of body size and disease; deep learning analysis of where the body stores its fat may finally explain what the scale never could.

Subject of Research: Deep learning–based CT analysis of abdominal fat distribution and its association with 28-day mortality in sepsis patients

Article Title: Deep learning–derived abdominal adiposity phenotypes and 28-day mortality in sepsis

Article References: Yeo, H. J., Kim, H. L., Kim, K., Jang, J. H., Choi, E., Seol, H. Y., Lee, S. E., & Cho, W. H. (2026). Deep learning–derived abdominal adiposity phenotypes and 28-day mortality in sepsis. International Journal of Obesity. https://doi.org/10.1038/s41366-026-02220-1

Image Credits: AI Generated

DOI: 10.1038/s41366-026-02220-1

Keywords: sepsis, obesity paradox, visceral adipose tissue, subcutaneous adipose tissue, deep learning, nnU-Net, body composition, computed tomography, 28-day mortality, psoas muscle, myosteatosis, critical care