Otamendi-Lopez, Andrea

BACKGROUND AND OBJECTIVES: Degenerative spine disease is a leading cause of disability, with increasing prevalence in the older patients. While age has been identified as an independent predictor of outcomes, its predictive value is limited for similar older patients. Here, we aimed to determine the most predictive frailty score of adverse events in patients aged 80 and older undergoing instrumented lumbar fusion. METHODS: We proceeded with a multisite (3 tertiary academic centers) retrospective review including patients undergoing instrumented fusion aged 80 and older from January 2010 to present. A composite end point encompassing 30-day return to operating room, readmission, and mortality was created. We estimated the area under the receiver operating characteristic curve for frailty scores (Modified Frailty Index-5 [MFI-5], Modified Frailty Index-11 [MFI-11], and Charlson Comorbidity Index [CCI]) in relation to that composite score. In addition, we estimated the association between each score and the composite end point by means of logistic regression. RESULTS: A total of 153 patients with an average age of 85 years at the time of surgery were included. We observed a 30-day readmission rate of 11.1%, reoperation of 3.9%, and mortality of 0.6%. The overall rate of the composite end point at 30 days was 25 (15.1%). The AUC for MFI-5 was 0.597 (0.501-0.693), for MFI-11 was 0.620 (0.518-0.723), and for CCI was 0.564 (0.453-0.675). The association between the scores and composite end point did not reach statistical significance for MFI-5 (odds ratio [OR] = 1.45 [0.98-2.15], P = .061) and CCI (OR = 1.13 [0.97-1.31], P = .113) but was statistically significant for MFI-11 (OR = 1.46 [1.07-2.00], P = .018). CONCLUSION: This is the largest study comparing frailty index scores in octogenarians undergoing instrumented lumbar fusion. Our findings suggest that while MFI-11 score correlated with adverse events, the predictive ability of existing scores remains limited, highlighting the need for better approaches to identify select patients at age extremes.

OBJECTIVE Chordomas are rare tumors that often recur regardless of surgery with negative margins and postoperative radiotherapy. The predictive accuracy of widely used immunohistochemical (IHC) markers in addressing the recurrence of skull base chordomas (SBCs) is yet to be determined. This study aimed to investigate IHC markers in the prediction of recurrence after SBC resection with adjuvant radiation therapy. METHODS The authors reviewed the records of patients who had treatment for SBC between January 2017 and June 2021 across the Mayo Clinic in Minnesota, Florida, and Arizona. Exclusion criteria included patients who had no histopathology or recurrence as an outcome. Histopathological markers included cytokeratin A1/A3 only, epithelial membrane antigen (EMA), S100 protein, pan-cytokeratin, IN1, GATA3, CAM5.2, OSCAR, and chondroid. Information from patient records was abstracted, including treatment, clinical and radiological follow-up duration, demographics, and histopathological factors. Decision tree and random forest classifiers were trained and tested to predict the recurrence based on unseen data using an 80/20 split. RESULTS A total of 38 patients with a diagnosis of SBC who underwent resection (gross-total resection: 42.1%; and subtotal resection: 57.9%) and radiation therapy were extracted from the medical records. The mean patient age was 48.2 (SD 19.6) years; most patients were male (n = 23; 60.5%) and White (n = 36; 94.7%). Pan-cytokeratin was associated with an increased risk of postoperative recurrence (OR 14.67, 95% CI 2.44–88.13; p = 0.00517) after resection and adjuvant radiotherapy. The decision tree analysis found pan-cytokeratin–positive tumors to have a 78% chance of being classified as a recurrence, with an accuracy of 75%. The distribution of minimal depth in the prediction of postoperative recurrence indicates that the most important variables were pan-cytokeratin, followed by cytokeratin A1/A3 and EMA. CONCLUSIONS The authors’ machine learning algorithm identified pan-cytokeratin as the largest contributor to recurrence among other IHC markers after SBC resection. Machine learning may facilitate the prediction of outcomes in rare tumors, such as chordomas.

e14062 Background: Adult medulloblastoma (AM) is a rare disease and represents 1 % of CNS tumors with an incidence of 0.6 per million per year. Usually arise in the cerebellar hemisphere or dorsal brainsteam. Four molecular subgroups are widely recognized and SHH subgroup are common in AM. Treatment options are usually extrapolated from pediatrics experience, and involve surgical resection followed by radiotherapy +/- chemotherapy. Methods: We conducted a retrospective cohort study in patients with medulloblastoma aged ≥18 years at a tertiary institution in Mexico City. We aim to describe clinical and treatment patterns predicting OS and PFS in an adult cohort of medulloblastomas. Kaplan Meier and Log-rank methods were used for survival analysis. Cox proportional hazard model was used for multivariate analysis. Results: Between 2010 and 2022, 78 patients met the criteria for this study. The median age was 28 years (range 18-62) and 64.1% were men. A total of 75.6% had ECOG 0-1. The desmoplastic was the most frequent histologic variant (35.9%). Surgical resection was performed in 93.6% with R0 resection in 49.3% (n=36), while 76.9% (n=61) underwent ventriculoperitoneal shunt (VPS). A total of 70 pts (89.7%) received adjuvant radiotherapy (RT), and the median time to initiation was 18 weeks. Adjuvant and concurrent chemotherapy were received in 53.8% and 12.8%, respectively. One-third of patients did not receive chemotherapy. Vincristine, cisplatin, and cyclophosphamide was the most common combination chemotherapy regimen (28.5%). PFS and OS in the entire cohort were 27.9 months (mo) (95% CI 9.9-45.9) and 124.3 mo (95% CI 52.8-59.8), respectively. OS in patients with ECOG 0-1 was better with 144.8 mo compared with 51.5 mo for ECOG 2-3 (p<0.001). Patients receiving adjuvant RT survived significantly longer (124.3 mo) than patients without radiation (18.8 mo). Other factors associated with survival were time to RT initiation ≤18 weeks vs >18 weeks (not reached vs 59.1 mo, p=0.018) and VPS insertion (144.8 mo vs 46.5 mo, p=0.023). Multivariate analysis identified performance status such as ECOG 2-3 (HR 2.93; 95% CI 1.3-6.6, p=0.009) and VPS (HR 0.39; 95% CI 0.16-0.93, p=0.034) as independent prognostic factors for OS. Conclusions: in this large cohort of Adult Medulloblastoma, we identified ventriculoperitoneal shunt and performance status as the most important factors related with better survival outcomes.

OBJECTIVE Chordomas are rare tumors from notochordal remnants and account for 1%–4% of all primary bone malignancies, often arising from the clivus and sacrum. Despite margin-negative resection and postoperative radiotherapy, chordomas often recur. Further, immunohistochemical (IHC) markers have not been assessed as predictive of chordoma recurrence. The authors aimed to identify the IHC markers that are predictive of postoperative long-term (≥ 1 year) chordoma recurrence by using trained multiple tree-based machine learning (ML) algorithms. METHODS The authors reviewed the records of patients who had undergone treatment for clival and spinal chordomas between January 2017 and June 2021 across the Mayo Clinic enterprise (Minnesota, Florida, and Arizona). Demographics, type of treatment, histopathology, and other relevant clinical factors were abstracted from each patient record. Decision tree and random forest classifiers were trained and tested to predict long-term recurrence based on unseen data using an 80/20 split. RESULTS One hundred fifty-one patients diagnosed and treated for chordomas were identified: 58 chordomas of the clivus, 48 chordomas of the mobile spine, and 45 chordomas sacrococcygeal in origin. Patients diagnosed with cervical chordomas were the oldest among all groups (58 ± 14 years, p = 0.009). Most patients were male (n = 91, 60.3%) and White (n = 139, 92.1%). Most patients underwent resection with or without radiation therapy (n = 129, 85.4%). Subtotal resection followed by radiation therapy (n = 51, 33.8%) was the most common treatment modality, followed by gross-total resection then radiation therapy (n = 43, 28.5%). Multivariate analysis showed that S100 and pan-cytokeratin are more likely to predict the increase in the risk of postoperative recurrence (OR 3.67, 95% CI 1.09–12.42, p= 0.03; and OR 3.74, 95% CI 0.05–2.21, p = 0.02, respectively). In the decision tree analysis, a clinical follow-up > 1897 days was found in 37% of encounters and a 90% chance of being classified for recurrence (accuracy = 77%). Random forest analysis (n = 500 trees) showed that patient age, type of surgical treatment, location of tumor, S100, pan-cytokeratin, and EMA are the factors predicting long-term recurrence. CONCLUSIONS The IHC and clinicopathological variables combined with tree-based ML tools successfully demonstrated a high capacity to identify recurrence patterns with an accuracy of 77%. S100, pan-cytokeratin, and EMA were the IHC drivers of recurrence. This shows the power of ML algorithms in analyzing and predicting outcomes of rare conditions of a small sample size.

Metabolic rewiring in glioblastoma (GBM) is linked to intra- and extracellular pH regulation. In this study, we sought to characterize the role of melatonin on intracellular pH modulation and metabolic consequences to identify the mechanisms of action underlying melatonin oncostatic effects on GBM tumor initiating cells. GBM tumor initiating cells were treated at different times with melatonin (1.5 and 3.0 mM). We analyzed melatonin’s functional effects on GBM proliferation, cell cycle, viability, stemness, and chemo-radiosensitivity. We then assessed the effects of melatonin on GBM metabolism by analyzing the mitochondrial and glycolytic parameters. We also measured the intracellular and extracellular pH. Finally, we tested the effects of melatonin on a mouse subcutaneous xenograft model. We found that melatonin downregulated LDHA and MCT4, decreasing lactate production and inducing a decrease in intracellular pH that was associated with an increase in ROS and ATP depletion. These changes blocked cell cycle progression and induced cellular death and we observed similar results in vivo. Melatonin’s cytotoxic effects on GBM were due, at least in part, to intracellular pH modulation, which has emerged as a newly identified mechanism, providing new insights into the oncostatic effect of melatonin on GBM.

Abstract OBJECTIVE: The present study aimed to investigate postoperative swallowing disorders in patients diagnosed with CM I after decompression neurosurgery.METHODS: We selected 54 patients after decompression neurosurgery procedure for CM I from January 2017 to December 2019. We evaluated the speech-language assessment (CSLSA) 24-hours after post-surgical extubation. CSLSA observed aspects of posture, sensitivity, tone, and extra- and intraoral mobility of the FAO and visualizing the functions of breathing, phonation, articulation, chewing, and swallowing. We correlated the severity of the dysphagia and the presence of associated malformations in the CM I patients.RESULTS: In our study, 39 patients were female (mean age 41.3±47.1 years). Thirty-seven patients had associated malformations (p=0.0243): 21 patients syringomyelia, 11 basilar invagination and 5 syringomyelia and basilar invagination. Dysphagia was present in 37 of the cases (68.5%;p=0.0016). Dysphonia in 13 (24.1%;p=0.4785) and dysarthria in 3 (5.6%;p=0.0042). We observed in the CSLSA: orofacial hypomobility (29-patients–53.7%;p=0.0204), orofacial hyposensitivity (26-patients–48.1%; p=0.3023), reduced GAG reflex (24 patients–44.5%;p=0.1041), ineffective cough (19 patients–35.2%;p=0.0022), ineffective saliva swallowing (18-patients–33.3%;p=0.0396), dyspnea (13-patients–24.1%;p=0.4785), orofacial hypotonia (11-patients–20.4%;p=0.0004), altered cervical auscultation (10-patients–18.5%;p=0.0003), and dysarthria (3-patients–9.3%;p=0.0042). The presence of associated malformations significantly influenced the appearance of swallowing disorders, the severity of oropharyngeal dysphagia, the post-surgical complications (17-patients–31.5%;p<0.001), and the clinical outcomes (p=0.0029) of patients with CM type I. CONCLUSION: Decompressive neurosurgery for CM I had low rates of post-surgical complications overall. However, there was a high incidence of dysphagia. The presence of associated malformations is related with poorer prognosis and greater severity of oropharyngeal dysphagia in patients with CM I.