The research drew on the Geriatric Assessment for Patients (GAP70+) study, a multicentre, cluster-randomized clinical trial conducted across 39 community oncology clinics affiliated with the University of Rochester Cancer Center NCI Community Oncology Research Program Research Base. Participants were aged 70 or older, had incurable stage III or IV solid tumours or lymphoma, and were scheduled to begin a new systemic treatment regimen known to carry a high risk of toxicity. From the trial’s usual care arm, the investigators collected abdominal and pelvic CT or PET/CT scans performed as part of routine care, applying strict time windows around enrollment and rigorous quality control. That process yielded 161 patients whose imaging and clinical data could be fully analysed, with a mean age of 76.6 years, nearly 61 percent male, and most carrying gastrointestinal or lung cancers.

What sets this analysis apart from the bulk of prior sarcopenia research in oncology is its adherence to a full clinical definition of the condition rather than a single imaging measurement. The European Working Group on Sarcopenia in Older People, known as EWGSOP2, defines sarcopenia using three criteria: reduced muscle strength, reduced muscle quantity and quality, and reduced physical performance. In this study, strength was assessed with a five-time chair-stand test, where a time exceeding 16.7 seconds signalled weakness. Muscle quantity was quantified from the mid-L3 lumbar vertebra slice of each CT scan using validated automatic segmentation software, producing a skeletal muscle index with sex- and BMI-specific thresholds. Muscle quality was captured through Hounsfield Unit measures of tissue density on the same scans, and physical performance was evaluated with the timed up-and-go test. Meeting the strength and quantity or quality criteria classified a patient as sarcopenic; meeting all three criteria indicated severe sarcopenia.

The prevalence figures were sobering. More than two-thirds of participants, 68.3 percent, had low muscle quantity by imaging criteria, and 56.5 percent met the full clinical definition of sarcopenia. Among those, 59 percent were classified as having severe sarcopenia. Patients with sarcopenia were on average about two years older than those without it and were significantly more likely to have diabetes. More tellingly, sarcopenia tracked closely with broader geriatric vulnerability: those with the severe form were significantly more likely to show impaired nutrition, dependence in activities of daily living and instrumental activities, recent falls and impaired cognition compared with patients whose muscles were preserved. In other words, the clinical sarcopenia label captured a constellation of ageing-related frailty that a simple muscle measurement did not.

When the researchers turned to treatment outcomes, documented through clinician-reported adverse events graded with the Common Terminology Criteria for Adverse Events, version 4.0, a nuanced picture emerged. Overall severe toxicity, defined as Grades 3 through 5, during the first three months of therapy did not differ significantly between patients with and without sarcopenia. But severe nonhematologic toxicities—a category that includes complications such as dehydration, electrolyte disturbances, infections, fatigue and pain, which frequently lead to hospitalization—were substantially more common in the sarcopenic group, affecting 64 percent versus 44 percent. In multivariable logistic regression adjusting for age, tumour site, sex, comorbidities and treatment type, sarcopenia more than doubled the odds of severe nonhematologic toxicity, with an odds ratio of 2.24. Notably, patients who suffered these severe nonhematologic events also had significantly slower chair-stand times, and each additional second on that strength test raised the odds of toxicity by roughly 15 percent.

The mortality findings were even more striking. At one year, only 46 percent of participants with sarcopenia were alive, compared with 60 percent of those without it. After statistical adjustment this difference fell just short of significance in the full cohort, but when the analysis focused on patients starting first-line chemotherapy, sarcopenia was clearly associated with poorer survival, with a hazard ratio of 2.12. For severe sarcopenia the signal was unmistakable: one-year survival was just 40 percent versus 60 percent among patients without sarcopenia, a difference that remained significant after adjustment with a hazard ratio of 2.08. The mortality gap opened early—within three months, nearly 21 percent of patients with severe sarcopenia had died, versus 7 percent of those without the condition. Crucially, when the investigators evaluated skeletal muscle index alone, stripped of the strength and performance components, no significant association with survival appeared at all.

That last result may be the study’s most important technical message. Much of the oncology literature has equated sarcopenia with low muscle quantity on imaging, treating the skeletal muscle index as a standalone prognostic marker. This analysis suggests that in older adults that approach is insufficient, because muscle mass declines physiologically with age and is not a linear proxy for what muscles can actually do. The consensus definitions that incorporate grip-equivalent strength measures and performance tests appear to identify a genuinely distinct population of patients whose functional reserve is depleted and who are therefore less able to withstand the catabolic assault of cytotoxic therapy. The authors note this contrasts with patterns seen in younger patients, in whom imaging-based muscle measures have shown stronger associations with outcomes.

The comparison with the limited prior work reinforces the point. Only one earlier study, in men with metastatic castrate-resistant prostate cancer, had evaluated treatment toxicity in older adults using a definition of sarcopenia encompassing strength, quantity and performance; it reported a prevalence of 27 percent, lower than the 57 percent seen here, likely reflecting stricter criteria that resemble the severe sarcopenia category. That study likewise linked sarcopenia to poorer survival and heightened toxicity risk. Two recent studies in gastrointestinal cancer patients that relied on muscle index alone produced inconsistent survival associations, underscoring the value of the multi-domain approach. The new analysis also benefits from real-world breadth: patients were treated in community clinics nationwide rather than tertiary referral centres, and toxicity data met the annotation standards of a randomized trial.

The limitations are worth noting. The cohort was predominantly non-Hispanic white, limiting generalizability to other populations. Scans were not mandated by the protocol, and the strict time windows that ensured data quality reduced the analysable sample. As an exploratory secondary analysis, p-values were not corrected for multiple testing, so the findings are hypothesis-generating and require confirmation in prospective cohorts. Treatment regimens and dosing were left to each patient’s oncologist rather than standardized. Even so, the clinical implications are hard to dismiss. Patients with severe sarcopenia received some of the most intensive treatments in the cohort yet had the worst survival, raising the possibility of overtreatment and suggesting that comprehensive geriatric evaluation should precede decisions about aggressive therapy.

The authors argue that sarcopenia screening should become routine in geriatric oncology, and they point to a practical path. Although CT scans are already available for nearly every cancer patient and software tools exist to quantify muscle from them, the expertise to interpret such measurements is not yet part of routine practice. The geriatric assessment, by contrast, is already recommended by ASCO guidelines and captures exactly the measures—chair-stand strength, timed up-and-go performance, falls, daily functioning—that this study linked to toxicity and death. Integrating those simple tests into treatment planning, and designing intervention trials that incorporate sarcopenia status into treatment selection and dosing, could spare the most vulnerable older adults the cruelest harms of therapy while preserving its benefits for those robust enough to tolerate it.

Subject of Research: Sarcopenia and treatment toxicity and mortality in older adults with advanced cancer

Article Title: Sarcopenia Is Associated With Severe Treatment Toxicity and Mortality in Older Adults With Advanced Cancer: A Secondary Analysis

Article References: Mattick, L. J., Mohammed, M., Li, C.-S., Tylock, R. G., Loh, K. P., Flannery, M. A., Peppone, L. J., Lin, P.-J., Goncalves, M. D., Caan, B. J., Cespedes Feliciano, E. M., Popuri, K., Beg, M. F., Bearden, J. D., Berenberg, J., Katato, K., Mustian, K. M., Mohile, S. G., & Dunne, R. F. (2026). Sarcopenia Is Associated With Severe Treatment Toxicity and Mortality in Older Adults With Advanced Cancer: A Secondary Analysis. Journal of Cachexia, Sarcopenia and Muscle, 17(5), Article e70388. https://doi.org/10.1002/jcsm.70388

Image Credits: AI Generated

DOI: 10.1002/jcsm.70388

Keywords: sarcopenia, geriatric oncology, advanced cancer, chemotherapy toxicity, muscle strength, mortality, CT body composition, EWGSOP2, geriatric assessment, cancer cachexia, older adults, clinical trial

The research team followed 42 adults diagnosed with ALS according to the El Escorial criteria, all attending a nutrition consultation within the hospital’s multidisciplinary ALS unit between March 2023 and May 2025. The cohort, 36 percent of whom were women, had a mean age of 66.1 years, and slightly more than half had bulbar onset disease. Over the follow-up period, 19 of the 42 patients died, corresponding to a mean survival of about 21 months from the baseline nutritional assessment. The researchers deliberately set out to test whether a practical, integrated assessment of muscle health, combining body composition measured by bioelectrical impedance, handgrip dynamometry, ultrasound imaging, and a formal sarcopenia diagnosis, could add prognostic information that conventional clinical markers miss.

The technical backbone of the study was a 50-kilohertz phase-sensitive impedance analyzer, used to derive a panel of body composition parameters including body cell mass, body cell mass index, fat mass, total body water, and the appendicular skeletal muscle mass index, or ASMI, which expresses the muscle mass of the arms and legs divided by height squared. Following the Global Leadership Initiative on Malnutrition criteria, low muscle mass was defined as an ASMI below 7.0 kilograms per square meter in men and below 6.0 in women. Sarcopenia was diagnosed according to the EWGSOP2 framework, requiring the coexistence of low muscle strength, assessed by handgrip thresholds of less than 27 kilograms in men and 16 kilograms in women, and low muscle mass. Each patient also underwent ultrasound imaging of the quadriceps rectus femoris and abdominal adiposity measurements, and completed the Short Physical Performance Battery.

At baseline, the differences between patients who would survive the follow-up period and those who would not were striking, and they were not the differences clinicians might expect. Body mass index did not differ significantly between the two groups, nor did the prevalence of malnutrition reach statistical significance, although it trended higher among nonsurvivors. What separated the groups was muscle. Survivors had significantly higher body cell mass, higher body cell mass index, and a markedly higher ASMI, averaging 6.94 kilograms per square meter compared with 5.80 in nonsurvivors. Survivors also retained substantially stronger grips, averaging 25.45 kilograms versus 17.67 kilograms, and had lost far less weight in the preceding months. Sarcopenia was present in nearly 28 percent of nonsurvivors but only about 5 percent of survivors, a fivefold difference that immediately flagged the condition as a candidate marker of lethal trajectory.

When the team ran univariate logistic regression models, every BIVA-derived muscle mass parameter emerged as a protective factor against mortality. Each additional kilogram of body cell mass reduced the odds of death by roughly 16 percent, and the effect of ASMI was even more pronounced: an odds ratio of 0.29, meaning higher appendicular muscle mass was associated with a 71 percent reduction in the odds of dying during follow-up. Handgrip strength also predicted survival in unadjusted models, while ultrasound-derived measures of quadriceps morphology, phase angle, hydration status, and most regional fat depots did not. Interestingly, greater leg subcutaneous fat thickness was associated with lower mortality odds, hinting at the still-debated protective role of energy reserves in this hypermetabolic disease.

The critical question, of course, was whether ASMI simply echoed information already captured by age, functional status, disease duration, and site of onset. To test this, the investigators built a series of adjusted multivariable models. The result was remarkably consistent: lower ASMI remained independently associated with mortality after adjustment for the ALSFRS-R score, for age, for disease duration, and for onset type, with odds ratios ranging from 0.28 to 0.37 across individual models and remaining significant at 0.33 when age, functional score, and onset type were combined. Only in the fully saturated model including all covariates simultaneously, where the small number of 19 deaths stretched the statistical limits, did the association narrow to a borderline, nonsignificant result, a caveat the authors themselves emphasize in framing their conclusions as exploratory.

The time-to-event analyses sharpened the picture considerably. Receiver operating characteristic analysis identified an optimal ASMI cut-off of 6.74 kilograms per square meter, achieving 88 percent sensitivity and 65 percent specificity for predicting mortality, with an area under the curve of 0.81, the highest discriminative performance of any muscle-related parameter tested. In Cox proportional hazards models adjusted for age and ALSFRS-R, patients falling below the ASMI cut-off faced nearly a fivefold increase in the risk of death, while those below the body cell mass index threshold of 7.20 carried more than a threefold elevated risk. But the most dramatic finding belonged to sarcopenia itself: patients meeting the combined criteria faced a hazard ratio of 17.19 for mortality, the single strongest predictor identified in the entire study.

Why would muscle mass outperform both BMI and, after adjustment, even grip strength as a prognostic signal? The authors argue that ASMI captures something fundamental about the neurogenic and metabolic burden of ALS. Progressive motor neuron loss triggers denervation, muscle fiber atrophy, mitochondrial dysfunction, oxidative stress, and chronic low-grade inflammation, all amplified by the hypermetabolism and reduced intake that characterize the disease. A shrinking muscle reservoir thus integrates, in a single measurable quantity, the downstream consequences of neurodegeneration, metabolic derangement, and nutritional decline. This may explain why several patients in the cohort displayed normal BMI alongside depressed body cell mass, a body composition pattern invisible to scales and tape measures. Muscle depletion, the study suggests, can run well ahead of overt weight loss and before malnutrition criteria are formally met.

The divergence between grip strength and muscle mass carries its own mechanistic interest. When handgrip strength was evaluated in a domain-based model that accounted for ASMI, it lost its independent association with mortality, suggesting that its prognostic power is largely mediated by the amount of muscle available to generate force. In ALS, strength is further complicated by denervation patterns, motor unit dysfunction, and compensatory reinnervation, so a patient can transiently preserve force even as muscle is wasting away. A single handgrip measurement probes one upper-limb muscle group; ASMI reflects the whole-body appendicular reserve. The authors interpret this hierarchy as a call for comprehensive morphofunctional assessment rather than reliance on any isolated strength metric.

The clinical implications could be immediate. Unlike computed tomography or dual-energy X-ray absorptiometry, which have previously linked low muscle mass to shorter ALS survival but carry cost, radiation, and accessibility barriers, bioelectrical impedance and handgrip dynamometry are inexpensive, safe, and easily repeatable at the bedside. The findings support incorporating muscle mass screening into routine ALS care from the moment of diagnosis, potentially triggering earlier nutritional surveillance, optimized protein and energy intake, and individualized rehabilitation. They also open the door to using ASMI and sarcopenia status as stratification or enrichment tools in clinical trials, matching patients with distinct prognostic profiles to appropriate study arms. The authors caution that their single-center cohort of 42 patients with 19 deaths cannot confirm causality, that impedance equations were not specifically validated in ALS, and that larger multicenter cohorts are needed. But if the findings hold, the humble measurement of limb muscle mass may become one of the most quietly powerful numbers in the care of people facing this devastating disease.

Subject of Research: The prognostic value of appendicular skeletal muscle mass and sarcopenia for survival in patients with amyotrophic lateral sclerosis

Article Title: Appendicular Skeletal Muscle Mass and Sarcopenia as Prognostic Markers in Amyotrophic Lateral Sclerosis

Article References: Zarco‐Martín, M. T., Andreo‐López, M. C., Yagui‐Beltrán, M. S., & Fernández‐Soto, M. L. (2026). Appendicular Skeletal Muscle Mass and Sarcopenia as Prognostic Markers in Amyotrophic Lateral Sclerosis. Journal of Cachexia, Sarcopenia and Muscle, 17(5), Article e70378. https://doi.org/10.1002/jcsm.70378

Image Credits: AI Generated

DOI: 10.1002/jcsm.70378

Keywords: amyotrophic lateral sclerosis, sarcopenia, appendicular skeletal muscle mass, bioelectrical impedance vector analysis, handgrip strength, prognosis, survival, body composition, malnutrition, EWGSOP2, motor neuron disease, muscle wasting