OBJECTIVE Establishing benchmarks for length of stay (LOS) may inform strategies to improve resource efficiency, decrease costs, and advance care quality. In this study, the authors characterize postoperative LOS in endoscopic skull base surgery (ESBS) and elucidate prolonging factors. METHODS A retrospective chart review was conducted at a tertiary academic center including consecutive adult patients who underwent intradural ESBS with intraoperative CSF leak during primary repair between July 2018 and March 2024. LOS, calculated as the time between the end of anesthesia until discharge from the hospital, comprised the primary outcome. Categorical and continuous independent study variables were assessed for univariate LOS association via the Mann-Whitney U-test and Kendall's tau-b correlation, respectively, and those with significant associations were included as multiple linear regression inputs. RESULTS One hundred sixty-three patients were included, with a median LOS of 4.0 (interquartile range [IQR] 2.8-5.8) days. LOS was significantly prolonged in high-flow (n = 82) compared with low-flow (n = 81) CSF leak cohorts (median 4.5 [IQR 3.9-6.5] vs 2.9 [IQR 2.1-4.7] days, p = 0.002). Defects involving the anterior cranial fossa (n = 16, median 4.6 [IQR 3.3-7.5)] days), suprasellar region (n = 94, median 4.4 [IQR 3.2-6.4] days), sella (n = 138, median 3.9 [IQR 2.8-5.8] days), or posterior cranial fossa (n = 17, median 4.5 [IQR 3.9-6.5] days) had variable LOSs. On multiple linear regression, after controlling for numerous patient, surgical, and postoperative factors, lesion diameter (B = 0.16, 95% CI 0.048-0.26), bone defect area (B = 0.008, 95% CI 0.001-0.014), anesthesia time (B = 0.015, 95% CI 0.004-0.026), bed rest length (B = 2.34, 95% CI 1.12-3.56), postoperative CSF leak (B = 11.06, 95% CI 4.11-18.01), postoperative meningitis (B = 11.79, 95% CI 4.83-18.74), postoperative stroke/hemorrhage (B = 25.25, 95% CI 18.43-32.06), and postoperative pneumonia (B = 5.59, 95% CI 0.79-10.38) independently predicted overall prolonged LOS. CONCLUSIONS With healthcare utilization receiving increased attention, mitigating factors that extend LOS are important. Extent of surgery and certain postoperative complications may constitute key factors prolonging LOS following intradural ESBS with intraoperative CSF leak. https://thejns.org/doi/abs/10.3171/2024.6.JNS232409

Background There is emerging evidence to suggest the role of induction chemotherapy (IC) in definitive management of locoregionally advanced sinonasal squamous cell carcinoma (SNSCC). We evaluated the influence of IC on survival and predictors of its use in SNSCC patients.Methods The 2004 to 2017 National Cancer Database was queried for patients with locoregionally advanced SNSCC (T4/M0). Treatments were stratified into seven groups: definitive chemoradiation (CRT), IC with definitive CRT (IC + CRT), IC + CRT with salvage surgery (IC + CRT + Sx), definitive surgery (Sx), IC with definitive surgery (IC + Sx), definitive surgery with adjuvant radiation or CRT (Sx + ATx), or IC + Sx + ATx. Cox proportional-hazards regression assessed overall survival (OS) and logistic regression identified predictors of IC.Results Of 3,162 patients, 1,088 (34.4%) were female with a mean age of 63.4 +/- 13.4 years. The 2- and 5-year OS rates were 58.6 and 42.0%, respectively. Compared with CRT, Sx + ATx (hazard ratio [HR]: 0.663; p < 0.001), IC + Sx (HR: 0.606; p = 0.005), or IC + Sx + ATx (HR: 0.468; p = 0.001) exhibited reduced mortality. Among patients who were treated with definitive surgery, those receiving IC had additional OS benefit (all p s < 0.05). Older age (odds ratio [OR]: 0.607; p < 0.001), female sex (OR: 0.759; p = 0.028), Black race (OR: 1.650; p < 0.001, T4b stage (OR: 1.674; p < 0.001), and higher N stage (OR: 1.395; p < 0.001) were predictors of IC.Conclusions IC prior to definitive surgery with or without adjuvant therapy exhibited the highest OS for locoregionally advanced SNSCC. Age, sex, race, and T/N staging were predictors of IC. Multimodal treatment regimens involving surgery as the primary modality may, therefore, provide the greatest therapeutic response.

PURPOSE:Randomized trials have found that patients with locoregionally advanced p16+ oropharyngeal squamous cell carcinoma (OPSCC) do not benefit from treatment deintensification, even among favorable risk groups. Although various methods have been used to identify candidates for treatment deintensification, the optimal approach is unknown. METHODS AND MATERIALS:We conducted a multi-institutional cohort study of 444 patients with previously untreated p16+ OPSCC undergoing definitive radiation therapy with or without systemic therapy between 2009 and 2022. We compared the following 2 approaches for identifying candidates for deintensification: (1) favorable versus unfavorable risk, using NRG-HN005 eligibility criteria, and (2) low versus high relative risk of cancer events, using the Head and Neck Cancer Intergroup predictive classifier ("omega score"). We tested differences in outcomes and systemic therapy allocation by risk group using multivariable Cox models, competing event models, and logistic regression, and compared characteristics of hypothetical deintensification trials using the 2 approaches. Progression-free survival events were defined as cancer recurrence (locoregional or distant) or death from any cause. RESULTS:Median follow-up time was 52 months; 120 patients (27.0%) were favorable risk; a different 120 patients had low omega score; 28 patients (6.3%) met both criteria; 184 patients (41.4%) had discordant classification. On ordinal logistic regression, decreasing omega score was associated with a statistically significantly lower odds of receiving intensive therapy (normalized odds ratio, 0.37 per SD; 95% CI, 0.24-0.57), with a greater magnitude than favorable risk group (odds ratio, 0.66; 95% CI, 0.44-0.99). Among patients receiving cisplatin and/or platinum-based induction (n = 374), favorable risk was associated with significantly improved progression-free survival (hazard ratio, 0.59; 95% CI, 0.36-0.99), whereas lower omega score was associated with a significantly decreased relative hazard for cancer events (relative hazard ratio, 0.18; 95% CI, 0.070-0.46). In simulations, selecting patients with low omega scores increased the efficiency of hypothetical noninferiority trials. CONCLUSIONS:Considering patients' relative risk of cancer events can help define optimal populations for treatment deintensification in p16+ OPSCC.

In 2018, Medicare introduced new codes to the Endoscopic Sinus Surgery (FESS) and balloon sinus dilation (BSD) families of Current Procedural Terminology (CPT) codes. Using the Medicare Part B National Summary Data File from 2010 to 2022, an interrupted time-series analysis examined trends in volume and reimbursements before and after 2018. Prior to 2018, volume and reimbursements for FESS grew at a mean rate of 2.5% +/- 2.2% per year and 6.9% +/- 6.6% per year, respectively, before reimbursements decreased significantly in 2018 by -13.9% (P = .014), leading to a stabilization of volume (growth of 0.72%, P = .602). Volume and reimbursements for BSD saw rapid growth from 2011 to 2015 which plateaued prior to the introduction of bundled codes and did not appear to change significantly in 2018 (-0.6%, P = .306 and 11.9%, P = .392, respectively). In addition to concurrent devaluation of FESS and BSD codes, bundling appears to have further contributed to falling reimbursements in rhinology.

OPINION STATEMENT:Significant advancements have been made in the treatment of locally advanced head and neck cancer, predominantly driven by the integration of concurrent chemotherapy with radiation therapy as a standard of care for many patients. The most heavily investigated chemotherapeutic is cisplatin, yet many patients are ineligible for cisplatin due to the presence of pre-existing medical comorbidities. Moreover, given the toxicity profile of cisplatin, identifying which patients stand to benefit from cisplatin is challenging, which is particularly evident in older patients. Efforts to better risk-stratify patients based on age, performance status, and the degree of pre-existing comorbidities are ongoing and have been increasingly utilized in national clinical trials. In parallel, exploration into alternative systemic agents, including novel targeted therapies and immunotherapies, in cisplatin-ineligible patients are rapidly expanding. Cumulatively, identifying appropriate treatment paradigms in patients who harbor contraindications to cisplatin can not only improve clinical outcomes but also critically mitigate detrimental adverse effects.

Objective: To determine characteristics most strongly associated with risk for aspiration events among head and neck cancer (HNC) patients undergoing curative intent treatment.Materials and methods: This was a retrospective, cross-sectional study of 106 patients with previously untreated HNC who received definitive or postoperative radiation therapy (RT) +/- systemic therapy with curative intent. Patients who received post-treatment videofluoroscopic swallow study (VFSS) between 2018-2021 were included. Using ordinal multivariable logistic regression, we modeled the effects of age (>60 years vs. <= 60 years), sex, body mass index (BMI) (>20 kg/m2 vs. <= 20 kg/m2), American Joint Committee on Cancer 8th edition stage (I-II vs. III-IVB), treatment with cisplatin (vs. other or no systemic therapy), post-operative status, primary site (oral cavity vs. P16+ oropharynx vs. P16- Mucosal Site vs. other), and quantitative VFSS measures on Penetration-Aspiration Scale (PAS) score.Results and conclusion: On ordinal multivariable logistic regression, age >60 years (odds ratio (OR): 3.91, 95% confidence interval (CI): 1.29, 11.9), advanced stage (stage III-IVB) (OR: 3.13, 95% CI: 1.23, 7.79), pharyngeal constriction ratio (PCR) >0.25 (OR: 3.65, 95% CI: 1.14, 11.7), and bolus clearance ratio (BCR) > 0.10 (OR: 3.42, 95% CI: 1.20, 9.75) were found to be significant risk factors for higher PAS scores. Patients with >= 2 pretreatment risk factors had statistically significant increased risk for post-treatment aspiration (OR 2.52, 95% CI: 1.31, 4.86) on ordinal logistic regression. This model could be useful to direct high-risk patients toward interventions designed to reduce risk of aspiration events.

Craniopharyngiomas are uncommon benign sellar and parasellar tumors with high overall survival (OS) and recurrence rates. Treatment is often surgical but may include adjuvant therapies. The impact of adjuvant therapy and surgical approach have been evaluated, however, facility volume and type have not. The purpose of this study is to analyze the influence of facility volume and type on treatment modalities, extent of surgery and survival of craniopharyngioma. The 2004–2016 National Cancer Database (NCDB) was queried for patients diagnosed with craniopharyngioma. Facilities were classified by type (academic vs. non-academic) and low-volume center (LVC) (Treating < 8 patients over the timeline) versus high-volume center (HVC), (Treating ≥ 8 patients over the timeline). Differences in treatment course, outcomes, and OS by facility type were assessed. 3730 patients (51.3

Radiomics has been applied to predict recurrence in several disease sites, but current approaches are typically restricted to analyzing tumor features, neglecting nontumor information in the rest of the body. The purpose of this work was to develop and validate a model incorporating nontumor radiomics, including whole-body features, to predict treatment outcomes in patients with previously untreated locoregionally advanced cervical cancer. Methods: We analyzed 127 cervical cancer patients treated definitively with chemoradiotherapy and intracavitary brachytherapy. All patients underwent pretreatment whole-body F-18-FDG PET/CT. To quantify effects due to the tumor itself, the gross tumor volume (GTV) was directly contoured on the PET/CT image. Meanwhile, to quantify effects arising from the rest of the body, the planning target volume (PTV) was deformably registered from each planning CT to the PET/CT scan, and a semiautomated approach combining seed-growing and manual contour review generated whole-body muscle, bone, and fat segmentations on each PET/CT image. A total of 965 radiomic features were extracted for GTV, PTV, muscle, bone, and fat. Ninety-five patients were used to train a Cox model of disease recurrence including both radiomic and clinical features (age, stage, tumor grade, histology, and baseline complete blood cell counts), using bagging and split-sample-validation for feature reduction and model selection. To further avoid overfitting, the resulting models were tested for generalization on the remaining 32 patients, by calculating a risk score based on Cox regression and evaluating the c-index (c-index > 0.5 indicates predictive power). Results: Optimal performance was seen in a Cox model including 1 clinical biomarker (whether or not a tumor was stage III-IVA), 2 GTV radiomic biomarkers (PET gray-level size-zone matrix small area low gray level emphasis and zone entropy), 1 PTV radiomic biomarker (major axis length), and 1 whole-body radiomic biomarker (CT bone root mean square). In particular, stratification into high- and low-risk groups, based on the linear risk score from this Cox model, resulted in a hazard ratio of 0.019 (95% CI, 0.004, 0.082), an improvement over stratification based on clinical stage alone, which had a hazard ratio of 0.36 (95% CI, 0.16, 0.83). Conclusion: Incorporating nontumor radiomic biomarkers can improve the performance of prognostic models compared with using only clinical and tumor radiomic biomarkers. Future work should look to further test these models in larger, multiinstitutional cohorts.

Zimberelimab is a novel, fully human anti-PD-1 monoclonal antibody with high affinity and selectivity for PD-1. The objective of this study (NCT03972722) was to evaluate zimberelimab, a novel, anti-programmed cell death protein 1 monoclonal antibody, in patients with programmed death ligand-1-positive recurrent or metastatic cervical cancer that had progressed after first- or subsequent-line platinumcontaining standard chemotherapy.

Alpha-klotho is a single-pass membrane protein primarily expressed by the kidneys. Klotho deficiency in chronic kidney disease contributes to an accelerated aging phenotype. We report here development of [89Zr]DFO-anti-klotho positron emission tomography (PET) imaging as a novel non-invasive method for assessing whole-body alpha-klotho distribution. Rat monoclonal anti-mouse klotho antibody was reacted with SCN-Bn-deferoxamine (DFO) and was radiolabeled using Zirconium-89. In vitro testing of [89Zr]DFO-anti-mKlotho was done in a distal convoluted tubule kidney cell line and with 40-micron whole kidney sections from C57BL/6J mice. Competitive binding was assessed in co-incubation studies with unlabeled anti-mKlotho antibody. For in vivo testing, C57BL/6J mice were injected retro-orbitally with [89Zr]DFO-anti-mKlotho and were scanned using Inveon PET/CT. Autoradiographs of kidney sections were obtained post-imaging on select animals. Radiochemical yield of [89Zr]DFO-anti-mKlotho was >70% and radiochemical purity was confirmed by iTLC. Specific binding in the kidney cell line was reduced by 60% in the presence of unlabeled anti-mKlotho. In the PET/CT scans, initial uptake of [89Zr]DFO-anti-mKlotho was observed in the intestines and liver. Selective retention of radioactivity was observed in the kidneys in the subsequent 24, 48, and 72 hrs scans with cortical binding of [89Zr]DFO-anti-mKlotho clearly visualized. Sites of lower alpha-klotho expression were not visualized. In summary, we have successfully synthesized [89Zr]DFO-anti-mKlotho and our initial in vitro and in vivo studies in mice demonstrate selective binding in the kidney cortex, which is known to express high levels of alpha-klotho. PET imaging promises to be a novel tool for in vivo evaluation of alpha-klotho distribution.