tbuckley/cabot-search huggingface dataset:
P18.36.A REGIONAL CENTRE EXPERIENCE OF LARGE PTV VOLUME PATIENT OUTCOMES WITH 40GY/15# RADIOTHERAPY FOR GLIOBLASTOMA MULTIFORME (GBM)
Authors: K Streatfield, J Glendenning, A Davies, S L Forner
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Glioblastoma Multiforme (GBM) are aggressive proliferative tumours, which are often large at diagnosis such that radiotherapy unavoidably treats a large percentage of brain. The required expansion margins to create the Planning Target Volume (PTV) for radiotherapy treatment, can often lead to high volumes of normal brain included. In the 40Gy/15# regimen indicated for the older patient population, and younger patients with larger treatment volumes, we sought to evaluate the effect that this had on both treatment outcomes and ability to offer further treatment at progression. MATERIAL AND METHODS A retrospective review of GBM patients of performance status 0-1, treated during 2018-2023, with 40Gy/15# ± chemotherapy at the Kent Oncology Centre. Patient demographics, histology and radiotherapy planning data, subsequent lines of treatment and survival outcomes from radiotherapy start date were extracted from the local oncology electronic system. Analysis was performed using Python and the Lifelines survival analysis library. RESULTS 58 patients fulfilled the selection criteria, with the average age of 68 (range 46-80). The Male/Female ratio was 1:1. The Median Overall Survival (mOS) for the entire population was 9.0 months and Progression Free Survival (PFS) 5.0 months. 43% of the patients received surgical intervention with biopsy only and 55% debulking. 33 (57%) of the patients were MGMT unmethylated. As a percentage of the total brain volume, mean PTV size was 27.0%, with the range of 5.1-50.4%. 20 (34%) of patients had a large PTV size, defined as ≥30% of the total brain volume. These patients had poorer mOS in comparison to smaller PTV patients, with mOS 5.0 vs 11.0 months. Similarly, PFS was 4.0 months vs 5.0 months. Within the cohort of larger PTV patients, MGMT methylation status did not influence mOS (5 months Methylated vs 4 months Unmethylated) and PFS (both groups 4 months). In the 3 patients with very large PTV sizes (&amp;gt;45%, compared to ≤45%) of total brain volume, mOS was 4.0 months vs 9.0 months, and PFS 3.0 months vs 5.0 months. Fitness to receive subsequent lines of treatment was used as a measure of functional status at progression following radiotherapy. Of the 31 patients in the entire cohort with progressive disease, 12 (39%) received 2nd line treatment. 28% of progressing patients with large PTV sizes went on to receive 2nd line treatment, compared to 38% of smaller PTV sizes. No patients with very large PTV sizes &amp;gt;45%, received 2nd line treatment. CONCLUSION Our study indicates that large volume radiotherapy treatments (≥30% of total brain volume) are associated with poorer disease control and survival outcomes. This includes a lower proportion in patients with the functional ability to receive 2nd line treatment. Evaluation in larger patient cohorts to verify these findings would assist to inform treatment discussions.
P27.32.B V-REX RANDOMIZED TRIAL
Authors: D Dhayalan
Journal: Neuro-Oncology (2024)

Abstract IMPORTANCE Current guidelines for treating small- to medium-sized vestibular schwannoma recommend either upfront radiosurgery or waiting to treat until tumor growth has been detected radiographically. OBJECTIVE To determine whether upfront radiosurgery provides superior tumor volume reduction to a wait-and-scan approach for small- to medium-sized vestibular schwannoma. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of 100 patients with a newly diagnosed (&amp;lt;6 months) unilateral vestibular schwannoma and a maximal tumor diameter of less than 2 cm in the cerebellopontine angle as measured on magnetic resonance imaging. INTERVENTIONS Participants were randomized to receive either upfront radiosurgery (n = 50) or to undergo a wait-and-scan protocol, for which treatment was given only upon radiographically documented tumor growth (n = 50). Participants underwent 5 annual study visits consisting of clinical assessment, radiological examination, audiovestibular tests, and questionnaires. MAIN OUTCOMES AND MEASURES The primary outcome was the ratio between tumor volume at the trial end at 4 years and baseline (V4:V0). There were 26 prespecified secondary outcomes, including patient-reported symptoms, clinical examinations, audiovestibular tests, and quality-of-life outcomes. Safety outcomes were the risk of salvage microsurgery and radiation-associated complications. RESULTS Of the 100 randomized patients, 98 completed the trial and were included in the primary analysis (mean age, 54 years; 42% female). In the upfront radiosurgery group, 1 participant (2%) received repeated radiosurgery upon tumor growth, 2 (4%) needed salvage microsurgery, and 45 (94%) had no additional treatment. In the wait-and-scan group, 21 patients (42%) received radiosurgery upon tumor growth, 1 (2%) underwent salvage microsurgery, and 28 (56%) remained untreated. For the primary outcome of the ratio of tumor volume at the trial end to baseline, the geometric mean V4:V0 was 0.87 (95% CI, 0.66-1.15) in the upfront radiosurgery group and 1.51 (95% CI, 1.23-1.84) in the wait-and-scan group, showing a significantly greater tumor volume reduction in patients treated with upfront radiosurgery (wait-and-scan to upfront radiosurgery ratio, 1.73; 95% CI, 1.23-2.44; P =.002). Of 26 secondary outcomes, 25 showed no significant difference. No radiation-associated complications were observed. CONCLUSION AND RELEVANCE Among patients with newly diagnosed small- and medium-sized vestibular schwannoma, upfront radiosurgery demonstrated a significantly greater tumor volume reduction at 4 years than a wait-and-scan approach with treatment upon tumor growth. These findings may help inform treatment decisions for patients with vestibular schwannoma, and further investigation of long-term clinical outcomes is needed.
P18.12.B CLINICAL, MOLECULAR, AND TRANSCRIPTOMIC FEATURES ASSOCIATED WITH SEIZURES AT ONSET IN PATIENTS WITH GLIOBLASTOMA
Authors: J Rossi, A Picca, C Carpentier, A Dridi Aloulou, B Mathon, F Bielle, B Donati, E Froio, S Serra, A Ciarrocchi, A Pisanello, F Valzania, K Hoang-Xuan, M Sanson
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Seizures occur in up to 60% of patients with glioblastoma (GBM), revealing the tumor in 25-30% of cases. The understanding of the tumor biology associated with epilepsy as the presenting symptom remains limited. Moreover, despite growing preclinical evidence of a link between epileptogenesis and tumorigenesis, the prognostic role of seizures at onset remains debated, partly due to study heterogeneity. MATERIAL AND METHODS We leveraged a homogeneous cohort of WHO 2021 GBM patients from our Institution with available clinical, molecular, and transcriptomic data. We retrospectively queried clinical records to identify the presence and characteristic of seizures at disease onset. RESULTS in our cohort of 231 GBM patients, 36% presented with seizures: of them, 47% were focal, 11% focal with impaired awareness, and 42% generalized. We did not observe significant differences in terms of age, sex, type of surgery, and tumor localization between the two groups. Patients presenting with seizures had a higher Karnofsky Performance Status score (median KPS: 90 vs. 80, p&amp;lt;0.01) and tended to have a less frequently mutated TERT promoter (86% vs. 94%, p=0.07). Seizures at onset were not associated with overall survival neither in univariate (HR 1.10, C.I. 0.83 - 1.46, p=0.50) nor in multivariate Cox regression analysis (HR 1.16, C.I. 0.86 - 1.57, p= 0.33). Differences in terms of gene expression will be assessed on 3’ RNA sequencing data. CONCLUSION Despite the presence of seizures at diagnosis was associated with higher performance status and a distinct molecular profile, it does not predict survival.
P14.22.B THE ROLE OF AMINO ACID PET IN RADIOTHERAPY TARGET VOLUME DELINEATION FOR ADULT-TYPE DIFFUSE GLIOMAS: A SYSTEMATIC LITERATURE REVIEW
Authors: P Horsley, D L Bailey, G Schembri, E Hsiao, J Drummond, M F Back
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Amino acid positron-emission tomography (AA-PET) is an emerging tool to complement magnetic resonance imaging (MRI) in glioma management. This purpose of this review was to summarise the existing literature examining use of early post-operative AA-PET for radiotherapy target volume delineation. MATERIAL AND METHODS A systematic search of the MEDLINE and EMBASE databases was conducted using search terms related to PET, amino acid tracers, radiotherapy and gliomas. Eligible studies included those with 20 or more patients that examined post-operative AA-PET prior to adjuvant radiotherapy and reported outcomes related to radiotherapy target volumes, relationship of PET-defined volumes to patterns of failure and/or outcomes of PET-guided radiotherapy. RESULTS The search yielded 534 unique studies for abstract and title screening, 71 of which proceeded to full-text review and 20 met eligibility criteria for inclusion. In all studies, the diagnosis for either all or the majority of included patients was glioblastoma. Eight studies compared PET- to MRI-derived target volumes with the consistent finding that the volumes were complementary. Seven studies related PET-derived volumes to the location of subsequent failure and consistently found AA-PET to be a strong predictor of failure location. Three studies reported outcomes of AA-PET-guided radiotherapy at standard doses. Survival outcomes were similar to trials in which radiotherapy volumes were generated based on MRI alone. Four studies reported outcomes following AA-PET-guided dose-escalated radiotherapy using a variety of regimens with mixed results with respect to patterns of failure and survival. We hypothesise that substantial differences in biologically effective dose (BED) and target volume delineation strategies between studies may have influenced the observed differences in outcomes. CONCLUSION Post-operative AA-PET is a promising complementary tool to MRI for radiotherapy target volume delineation, with potential benefits requiring further validation including margin reduction, reduced geographical miss and facilitation of dose-escalation. Prospective dose-escalation trials using the combination of MRI and AA-PET for target volume delineation seem warranted with close attention to BED of the chosen radiation schedule. Focused research in the setting of grade 2-3 and IDH-mutant gliomas is lacking.
P18.11.A CLINICAL OUTCOMES OF GLIOBLASTOMA MULTIFORME TREATED WITH HYPOFRACTIONATED (40GY/15 FRACTIONS) RADIOTHERAPY: THE WESSEX EXPERIENCE
Authors: E Khoury, E Clarke, J Ching, S Main
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND IDH wildtype Glioblastoma Multiforme (GBM) is the most common and aggressive form of primary brain malignancy. Hypofractionated cranial irradiation with 40Gy in 15 fractions is commonly used for those over the age of 65 or with a worse performance status. The Perry regimen (2017) provided evidence for the combination of chemotherapy (concurrent + adjuvant) with short course radiotherapy. This study provides a real world experience of short course radiotherapy in a UK tertiary centre. MATERIAL AND METHODS A retrospective observational study based on electronic patient records March 2016-May 2022 in a large UK tertiary centre (N=77). All patients received 40Gy in 15 fractions ± concurrent/adjuvant temozolomide chemotherapy. Overall Survival (OS) and Progression Free Survival (PFS) were assessed using Kaplan Meier methodology and Cox proportional hazards modeling with the R language for statistical programming. Subgroup analysis of those &amp;gt;600 days survival was performed using chi squared. RESULTS The median age 72 (33-84). Patients were selected due to age &amp;gt;70 years or due to performance status of 2. All completed radiotherapy, 44 (57.1%) were MGMT promoter methylated, 57 (74%) received concurrent chemotherapy, 42 (54.5%) received adjuvant chemotherapy, 33 (42.9%) followed a Perry regimen. Median OS (mOS) for the whole cohort is 11.3 months (95%CI:9-13.7 months) and PFS 8.17 months (95%CI:5.43-12.7). On univariate analysis adjuvant chemotherapy (p=0.0068) predicts survival and MGMT promoter methylation status trends towards this (0.063). Concurrent chemotherapy and extent of resection do not. On Cox proportional hazard modeling, adjuvant chemotherapy independently predicts survival (Hazard ratio 0.55, p=0.019), age, concurrent chemotherapy, performance status, extent of resection and MGMT methylation status do not. In those aged over 65 (N=62), mOS 9.67months (95%CI:8.47-13.37). Only adjuvant chemotherapy predicts survival (p=0.0067) in this cohort. In those with MGMT promoter methylation, mOS 13.4 months (95%CI:9.3-18.47). Use of concurrent and adjuvant chemotherapy has a significant impact on survival: 19.67 months vs 8.5 months (p=0.00078). Over a quarter of patients (25.9%) survive &amp;gt;600 days. The chi-squared test was used to compare differences in groups with OS&amp;gt;600 days (n=20) and OS&amp;lt;600 days (n=57). No significant differences could be identified. CONCLUSION This data shows comparable survival outcomes with reference to the Perry regimen (2017). In this cohort, the most important factor in predicting survival was adjuvant chemotherapy rather than: extent of resection, age, performance status, MGMT methylation status and concurrent chemotherapy. Over a quarter of patients survived &amp;gt;600days. In this cohort it has not been possible to delineate factors which may explain this. Further work is needed to investigate this.
Perioperative Antibiotic Prophylaxis Duration in Patients Undergoing Cystectomy With Urinary Diversion
Authors: Maria C. Thurnheer, Astrid Schürmann, Markus Huber, Jonas Marschall, Patrick Y. Wuethrich, Fiona C. Burkhard
Journal: JAMA Network Open (2024)

Importance Perioperative antibiotic prophylaxis (PAP) reduces the incidence of surgical site infections (SSIs). Guidelines recommend 24 hours or less of PAP for cystectomy with urinary diversion; however, evidence specifying optimal PAP duration for this surgery is lacking, and prolonged administration of PAP is common practice. Objective To establish noninferiority of 24-hour PAP vs extended-duration PAP in preventing SSIs within 90 days after cystectomy with urinary diversion. Design, Setting, and Participants This single-center, noninferiority randomized clinical trial was performed from April 18, 2018, to August 18, 2022, in patients aged older than 18 years undergoing elective open cystectomy with urinary diversion. Exclusion criteria were contraindications to administered drugs and inability to follow study procedures. Intervention PAP administered for 24 hours (24-hour PAP group) vs PAP until all catheters and stents were removed (extended PAP group). Main Outcome and Measures The primary end point was the rate of SSI, and the secondary end points included all-cause mortality, both within 90 days after surgery. Noninferiority of the 24-hour PAP treatment was assessed by comparing the 90% CI (corresponding to a significance level of α = .05) with the predefined noninferiority margin of 10%. Results A total of 95 patients were randomly assigned to the 24-hour PAP group (median [IQR] age, 69.3 [63.1-76.8] years; 66 males [69.5%]) and 98 to the extended PAP group (median [IQR] age, 69.5 [60.8-75.5] years; 68 males [69.4%]). Patients in the 24-hour PAP group received PAP for a median of 1 day (IQR, 1-1 day), and patients in the extended PAP group received PAP for a median of 8 days (IQR, 7-10 days). No significant differences in SSIs occurring within 90 days were found (24-hour PAP group, 8 patients [8.4%]; extended PAP group, 12 patients [12.2%]; P = .53). The risk difference for 90-day cumulative SSI incidence was −3.8% (90% CI, −11.1% to 3.4%), establishing noninferiority of 24-hour PAP vs extended PAP to prevent SSI. Mortality was not significantly different between groups. Conclusions and Relevance The findings of this randomized clinical trial demonstrate noninferiority of 24-hour PAP vs extended-duration PAP in preventing SSIs within 90 days after cystectomy with urinary diversion and may contribute to antibiotic stewardship efforts in urology. Trial Registration ClinicalTrials.gov Identifier: NCT03305627
Missing School Days Following Sport-Related Concussion in High School Athletes
Authors: Tracey Covassin, Alyssa M. Pollard-McGrandy, Lilian A. Klein, Douglas J. Wiebe, Abigail C. Bretzin
Journal: JAMA Network Open (2024)

Importance Sport-related concussions (SRC) can significantly impact students’ attendance and academic performance, highlighting the importance of gradual return-to-learn protocols for recovery. Understanding the association between missed school days and recovery, especially across genders, is vital for effective concussion management in high school athletes. Objectives To describe missed school days in high school athletes with SRC and to determine associations between missed school days and authorized clearance to return to competition; secondarily, to determine whether school days missed differed by gender. Design, Setting, and Participants Cohort study among student athletes participating in athletics sponsored by the Michigan High School Athletic Association (MHSAA) during academic years 2015 to 2023. SRC was a participant eligibility criterion and was defined as a head injury during participation in a MHSAA-sanctioned event. Data were analyzed from August 2015 to June 2023. Exposures Primary exposure was missed school days; additional exposures included gender, year of season, concussion history, event type, sport level, contact level, and athletic trainer involvement. Main Outcome and Measure The primary outcome was time to full unrestricted clearance following SRC. Results The analysis included a total of 20 934 individuals with SRC (13 869 boys [66.25%]). Gender (χ 2 3 = 167.40; P &amp;amp;lt; .001), season (χ 2 21 = 57.41; P &amp;amp;lt; .001), event type (χ 2 3 = 99.29; P &amp;amp;lt; .001), sport level (χ 2 9 = 68.15; P &amp;amp;lt; .001), contact level (χ 2 6 = 56.73; P &amp;amp;lt; .001), and initial evaluation (χ 2 3 = 147.13; P &amp;amp;lt; .001) were independently associated with missed school days. Athletes took a median (IQR) of 11 (7-16) days to return to full unrestricted clearance. Relative to no missed school days, there was a significant mean increase of 57% (incidence rate ratio, 1.57; 95% CI, 1.52-1.62) in time to full unrestricted clearance for 3 or more missed school days. The estimated mean days to return to sport were 12.15 (95% CI, 12.00-12.30) for 0 missed school days, 12.68 (95% CI, 12.39-12.96) for 1 missed school day, 15.47 (95% CI, 15.06-15.87) for 2 missed school days, and 19.08 (95% CI, 18.55-19.62) for 3 or more missed school days. Conclusions and Relevance This cohort study found that high school athletes typically missed 2 or fewer school days after SRC, suggesting that concussion management teams adhered to current recommendations of 24 to 48 hours of initial rest. The dose association, with more missed school days associated with slower return to play, suggests athletes’ missing more school days (eg, ≥3) may be associated with severity of concussion and warrant additional support to return to school and/or sport.
Current Burden of and Geographic Disparities in Liver Mortality and Access to Liver Transplant
Authors: Nicolas S. Rinella, William Charlton, Gautham Reddy, Paige McLean Diaz, Michael R. Charlton
Journal: JAMA Network Open (2024)

Importance Liver disease is a leading cause of mortality in the US. Liver transplant can be a lifesaving procedure for patients with severe liver disease. Objective To assess temporal trends and geographic variance in liver-related mortality (LRM) and liver transplant in the US. Design, Setting, and Participants In this cohort study, the frequencies and geographic variance of LRM in 2018 and 2021 were obtained in a cross-sectional analysis of the Underlying Cause of Death data available on the Centers for Disease Control and Prevention’s Epidemiologic Research database. The number of livers donated and transplanted according to the state of residence of each donor and recipient were obtained from the United Network for Organ Sharing. Main Outcomes and Measures Liver-related mortality in 2018 and 2021, overall and by state, as well as the liver transplant rate according to state of residence of recipient and donor. Results Overall LRM in the US was 93 418 in 2021, with a crude rate of 28.1 per 100 000 individuals, an increase of 19.1% compared with rates seen immediately prior to the COVID-19 pandemic in 2018 (77 282 [23.6 per 100 000 individuals]). Liver-related mortality in 2021 varied several-fold between states, from 18.4 per 100 000 individuals per year in Utah to 65.9 per 100 000 individuals per year in New Mexico. The mean number of liver-related deaths per transplant from all donor sources (in state and out of state) was 7.2 in the lowest LRM quintile compared with 21.5 in the highest (95% CI, 12.1-16.6; SE, 1.1; P &amp;amp;lt; .001). Ten states had no liver transplant center. Paradoxically, residents of states with the highest LRM had a much lower rate of liver transplant (at any location) from organs procured from in-state residents than states with the lowest LRM quintile (13.0% vs 35.2% in-state donors; 95% CI, 14.1%-30.3%; SE, 3.9%; P &amp;amp;lt; .001). Conclusions and Relevance This study suggests that rates of LRM have increased dramatically since the COVID-19 pandemic and vary several-fold between states. Rates of liver transplant are paradoxically lowest among residents living in states with the highest LRM. These findings highlight apparent geographic disparities in access to liver transplant that allocation policy cannot address.
Early Maternal Prenatal Cannabis Use and Child Developmental Delays
Authors: Lyndsay A. Avalos, Nina Oberman, Stacey E. Alexeeff, Lisa A. Croen, Meghan N. Davignon, Sara R. Adams, Deborah Ansley, Christina D. Chambers, Kristin Steuerle, Kelly C. Young-Wolff
Journal: JAMA Network Open (2024)

Maternal prenatal cannabis use is associated with adverse neonatal health effects, yet little is known about its association with child developmental outcomes.