Abstract BACKGROUND Patients with newly diagnosed high-grade glioma (HGG) and low Karnofsky Performance Status (KPS) often face challenges in receiving cancer-directed therapy. They are excluded from prospective trials, limiting the chance of developing novel therapeutic approaches. METHODS We retrospectively reviewed charts of patients with functional debility and newly diagnosed HGG who received radiotherapy (RT) while admitted to the inpatient service at Memorial Sloan Kettering between 2013 and 2023. Multivariable analyses were performed which associated patient demographics, KPS, histology, genetic and molecular pathology, RT duration and dose, chemotherapy, palliative/supportive care consultation, and advanced care planning documentation with overall survival (OS) and discharge location, separately. RESULTS Fifty-four patients were identified; median age was 68 years (range:21-86) and 28 (52%) were women. Median KPS was 50 (range:30-70). Per WHO 2021 criteria, 47 (87%) were glioblastoma, IDH wild-type and 7 (13%) were HGG not otherwise specified, diagnosed by biopsy in 30 (56%), subtotal resection in 23 (43%), and gross total resection in one. MGMT promoter methylation was performed in 39/54 and was hypermethylated in 15 (38%). All patients received RT and 52 (96%) with concurrent temozolomide; 47/54 (87%) completed planned RT, with the median dose of 4,005 cGy in 15 fractions. 13 (24%) received bevacizumab. The median length of stay (LOS) was 29 days (range:20-65). Only 17 (31%) had palliative care consultation prior to discharge. The median OS (mOS) from the last radiation treatment was 4.21 months (95% CI: 2.73, 6.63). In multivariable Cox and logistic regression, respectively, lower KPS remained the sole factor significantly associated with increased risk of death (p=0.004) and decreased chance of return home (p=0.040). CONCLUSION In our patient cohort, treatment was associated with prolonged LOS and poor outcomes. A clinical trial should be considered to evaluate shorter RT courses and early palliative care consultation in this patient population.
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