Caleigh S Roach, Belen Wertheimer, Khushi H Shah, Victor M Lu, Ashish H Shah, Ricardo J Komotar
Preoperative risk stratification in neurosurgery typically uses body mass index (BMI), albumin, or frailty as single-marker predictors. We assessed whether a composite phenotype predicts outcomes after cranial neuro-oncologic surgery and whether effects differ by tumor histology. A retrospective analysis of 27,057 patients undergoing craniotomy for meningioma, malignant glioma, or brain metastasis was performed using the American College of Surgeons National Surgical Quality Improvement Program database (2016-2023). The composite phenotype incorporated BMI and serum albumin: adequately nourished, obese-replete, sarcopenic-obese, and cachectic-malnourished. Outcomes included major 30-day morbidity, 30-day mortality, failure to rescue (FTR), and non-home discharge. Associations were estimated using inverse probability of treatment weighting (IPTW), histology-stratified analyses, and interaction testing. Compared with adequately nourished patients, sarcopenic-obese and cachectic-malnourished phenotypes conferred elevated odds of major 30-day morbidity (IPTW odds ratio [OR] 1.47 and 1.60, respectively) and 30-day mortality (OR 2.28 and 1.96). Obese-replete showed no mortality increase (OR 1.06) and reduced FTR (OR 0.76), most pronounced in the metastasis cohort (OR 0.58). Phenotype effects differed by histology for mortality (interaction p = 0.044) and non-home discharge (p = 0.009), with sarcopenic obesity conferring a 3.61-fold mortality increase among meningioma patients. The composite phenotype achieved discrimination comparable to but not exceeding serum albumin alone (area under the curve [AUC] 0.75 vs. 0.76 for mortality). A biomarker-defined nutritional phenotype separated distinct high-risk subgroups but did not improve discrimination beyond serum albumin alone, with histology-specific effects. These findings support histology-aware nutritional phenotyping for preoperative risk communication and hypothesis generation rather than superior prediction.