Preoperative patient-reported physical health-related quality of life predicts short-term postoperative outcomes in brain tumor patients.

BACKGROUND: Patient-reported outcome measures (PROMs) are increasingly used to assess patients' perioperative health. The PROM Information System 29 (PROMIS-29) is a well-validated global health assessment instrument for patient physical health, though its utility in cranial neurosurgery is unclear. OBJECTIVE: To investigate the utility of preoperative PROMIS-29 physical health (PH) summary scores in predicting postoperative outcomes in brain tumor patients. METHODS: Adult brain tumor patients undergoing resection at a single institution (January 2018-December 2021) were identified and prospectively received PROMIS-29 surveys during pre-operative visits. PH summary scores were constructed and optimum prediction thresholds for length of stay (LOS), discharge disposition (DD), and 30-day readmission were approximated by finding the Youden index of the associated receiver operating characteristic curves. Bivariate analyses were used to study the distribution of low (z-score≤-1) versus high (z-score>-1) PH scores according to baseline characteristics. Logistic regression models quantified the association between preoperative PH summary scores and post-operative outcomes. RESULTS: A total of 157 brain tumor patients were identified (mean age 55.4±15.4 years; 58.0% female; mean PH score 45.5+10.5). Outcomes included prolonged LOS (24.8%), non-routine discharge disposition (37.6%), and 30-day readmission (19.1%). On bivariate analysis, patients with low PH scores were significantly more likely to be diagnosed with a high-grade tumor (69.6% vs 38.85%, p=0.010) and less likely to have elective surgery (34.8% vs 70.9%, p=0.002). Low PH score was associated with prolonged LOS (26.1% vs 22%, p<0.001), nonroutine discharge (73.9% vs 31.3%, p<0.001) and 30-day readmission (43.5% vs 14.9%, p=0.003). In multivariate analysis, low PH scores predicted greater LOS (odds ratio [OR]=6.09, p=0.003), nonroutine discharge (OR=4.25, p=0.020), and 30-day readmission (OR=3.93, p=0.020). CONCLUSION: The PROMIS-29 PH summary score predicts short-term postoperative outcomes in brain tumor patients and may be incorporated into prospective clinical workflows.

Molecular characterization of gliosarcoma reveals prognostic biomarkers and clinical parallels with glioblastoma.

PURPOSE: Gliosarcoma is a rare histopathological variant of glioblastoma, but it is unclear whether distinct clinical or molecular features distinguish it from other glioblastomas. The purpose of this study was to characterize common genomic alterations of gliosarcoma, compare them to that of glioblastoma, and correlate them with prognosis. METHODS: This was a single-institution, retrospective cohort study of patients seen between 11/1/2017 to 1/28/2024. Clinical and genomic data were obtained from the medical record. Results were validated using data from AACR Project GENIE (v15.1-public). RESULTS: We identified 87 gliosarcoma patients in the institutional cohort. Compared to a contemporary cohort of 492 glioblastoma, there was no difference in overall survival, though progression free survival was inferior for patients with gliosarcoma (p = 0.01). Several of the most-commonly altered genes in gliosarcoma were more frequently altered than in glioblastoma (NF1, PTEN, TP53), while others were less frequently altered than in glioblastoma (EGFR). CDKN2A/CDKN2B/MTAP alterations were associated with inferior survival on univariate Cox (HR = 5.4, p = 0.023). When pooled with 93 patients from the GENIE cohort, CDKN2A/B (HR = 1.75, p = 0.039), RB1 (HR = 0.51, p = 0.016), LRP1B (p = 0.050, HR = 2.0), and TSC2 (HR = 0.31, p = 0.048) alterations or loss were significantly associated with survival. These effects remained when controlled for age, sex, and cohort of origin with multivariate Cox. CONCLUSION: Gliosarcoma has a similar overall survival but worse response to treatment and different mutational profile than glioblastoma. CDKN2A/B loss and LRP1B alterations were associated with inferior prognosis, while RB1 or TSC2 alterations were associated with improved outcomes. These findings may have implications for clinical management and therapeutic selection in this patient population.

Impact of upfront adjuvant chemoradiation on survival in patients with molecularly defined oligodendroglioma: the benefits of PCV over TMZ.

PURPOSE: Oligodendroglioma is an adult-type diffuse glioma defined by 1p/19q codeletion and IDH1/2 mutation. Treatment includes surgery followed by observation alone in select low-grade tumors, or combination radiation and chemotherapy with procarbazine, lomustine, and vincristine (PCV) or temozolomide (TMZ). While prospective studies investigating treatments for molecularly defined oligodendrogliomas are ongoing, this retrospective study analyzes the relationship between adjuvant regimens and progression-free survival (PFS). METHODS: Adults with IDH-mutant, 1p/19q codeleted oligodendroglioma (WHO grade 2 or 3) who underwent surgery between 2005 and 2021 were identified. Clinical data, disease characteristics, treatment, and outcomes were collected. RESULTS: A total of 207 patients with grade 2 and 70 with grade 3 oligodendrogliomas were identified. Median (IQR) follow-up was 57 (87) months. Patients with grade 3 tumors who received adjuvant radiation and PCV had longer median PFS (> 110 months) than patients who received radiation and TMZ (52 months, p = 0.008) or no adjuvant chemoradiation (83 months, p = 0.03), which was not seen in grade 2 tumors (p = 0.8). In multivariate analysis, patients who received PCV chemotherapy (Relative Risk [95% CI] = 0.24[0.05-1.08] and radiotherapy (0.46[0.21-1.02]) trended towards longer PFS, independently of grade. CONCLUSION: Adjuvant radiation and PCV are associated with improved PFS over radiation with TMZ in patients with grade 3 molecularly defined oligodendrogliomas, and all-grade patients treated with PCV trended towards decreased risk of recurrence and progression. These results highlight the importance of ongoing clinical trials investigating these treatments.

Management and Molecular Characterization of Intraventricular Glioblastoma: A Single-Institution Case Series.

While the central nervous system (CNS) tumor classification has increasingly incorporated molecular parameters, there is a paucity of literature reporting molecular alterations found in intraventricular glioblastoma (IVGBM), which are rare. We present a case series of nine IVGBMs, including molecular alterations found in standardized next-generation sequencing (NGS). We queried the clinical charts, operative notes, pathology reports, and radiographic images of nine patients with histologically confirmed IVGBM treated at our institution (1995-2021). Routine NGS was performed on resected tumor tissue of two patients. In this retrospective case series of nine patients (22% female, median (range) age: 64.3 (36-85) years), the most common tumor locations were the atrium of the right lateral ventricle (33%) and the septum pellucidum (33%). Five patients had preoperative hydrocephalus, which was managed with intraoperative external ventricular drains in three patients and ventriculoperitoneal shunts in one patient. Hydrocephalus was managed with subtotal resection of a fourth ventricular IVGBM in one patient. The most common surgical approach was transcortical intraventricular (56%). Gross total resection was achieved in two patients, subtotal resection was achieved in six patients, and one patient received a biopsy only. Immunohistochemistry for IDH1 R132H mutant protein was performed in four cases and was negative in all four. Genetic alterations common in glioblastoma, IDH-wildtype, were seen in two cases with available NGS data, including EGFR gene amplification, TERT promoter mutation, PTEN mutation, trisomy of chromosome 7, and monosomy of chromosome 10. Following surgical resection, four patients received adjuvant chemoradiation. Median survival among our cohort was 4.7 months (IQR: 0.9-5.8 months). Management of IVGBM is particularly challenging due to their anatomical location, presentation with obstructive hydrocephalus, and fast growth, necessitating prompt intervention. Additional studies are needed to better understand the genetic landscape of IVGBM compared to parenchymal glioblastoma and may further elucidate the unique pathophysiology of these rare tumors.

Multiplatform molecular analyses refine classification of gliomas arising in patients with neurofibromatosis type 1.

Gliomas arising in the setting of neurofibromatosis type 1 (NF1) are heterogeneous, occurring from childhood through adulthood, can be histologically low-grade or high-grade, and follow an indolent or aggressive clinical course. Comprehensive profiling of genetic alterations beyond NF1 inactivation and epigenetic classification of these tumors remain limited. Through next-generation sequencing, copy number analysis, and DNA methylation profiling of gliomas from 47 NF1 patients, we identified 2 molecular subgroups of NF1-associated gliomas. The first harbored biallelic NF1 inactivation only, occurred primarily during childhood, followed a more indolent clinical course, and had a unique epigenetic signature for which we propose the terminology "pilocytic astrocytoma, arising in the setting of NF1". The second subgroup harbored additional oncogenic alterations including CDKN2A homozygous deletion and ATRX mutation, occurred primarily during adulthood, followed a more aggressive clinical course, and was epigenetically diverse, with most tumors aligning with either high-grade astrocytoma with piloid features or various subclasses of IDH-wildtype glioblastoma. Several patients were treated with small molecule MEK inhibitors that resulted in stable disease or tumor regression when used as a single agent, but only in the context of those tumors with NF1 inactivation lacking additional oncogenic alterations. Together, these findings highlight recurrently altered pathways in NF1-associated gliomas and help inform targeted therapeutic strategies for this patient population.

Radiotherapy for meningiomas.

Meningiomas are the most common primary central nervous system neoplasm. Despite promising recent progress in elucidating the genomic landscape and underlying biology of these histologically, molecularly, and clinically diverse tumors, the mainstays of meningioma treatment remain maximal safe resection and radiation therapy. The aim of this review of meningioma radiotherapy is to provide a concise summary of the history, current evidence, and future for application of radiotherapy in meningioma treatment.

Clinicopathological features and outcomes of parenchymal rejection in liver transplant biopsies.

AIMS: The aim of this study was to perform a comprehensive retrospective analysis of liver transplant biopsies with parenchymal rejection (PR) at our institution, including histological features, laboratory values and follow-up biopsies, and to compare PR with portal-based acute cellular rejection (ACR). METHODS AND RESULTS: Biopsies from 173 patients were evaluated (retrospective database search 1990-2017), including 49 isolated PR, 35 PR with portal ACR (PR/ACR), 34 mild ACR and 52 moderate ACR cases. The rise and fall of serum liver enzymes was calculated as a measure of acute liver injury and response to immunotherapy, respectively. Isolated PR was associated with delayed-onset acute rejection (P < 0.001), as well as younger age (P = 0.004), and showed a similar rise in liver enzymes to mild ACR. PR/ACR and moderate ACR showed the highest elevations in transaminases (P < 0.05). Isolated PR on an initial biopsy was associated with recurrent episodes of PR (P = 0.01), chronic ductopaenic rejection (P = 0.002) and chronic vascular rejection (P = 0.017). Immunohistochemistry for C4d was performed, and strong C4d staining of venules was only detected in one severe isolated PR case (one of three, 33%) and one moderate ACR case (one of 20, 5%). CONCLUSIONS: Isolated PR represents a form of late acute rejection with distinct clinical and histological features. There is value in reporting PR in liver transplant biopsies to identify patients at higher risk of developing recurrent PR and chronic rejection. Standardisation of terminology and histological criteria of PR can help in uniform reporting and ensure appropriate management.

Tuberculum sellae meningiomas: grading scale to assess surgical outcomes using the transcranial versus transsphenoidal approach.

OBJECTIVE Tuberculum sellae meningiomas (TSMs) are surgically challenging tumors that can severely impair vision. Debate exists regarding whether the transcranial (TC) or endoscopic transsphenoidal (TS) approach is best for resecting these tumors, and there are few large series comparing these approaches. METHODS A retrospective chart review was performed at 2 academic centers comparing TC and TS approaches with respect to vision, extent of resection, recurrence, and complications. The authors report surgical outcomes and propose a simple preoperative tumor grading scale that scores tumor size (1-2), optic canal invasion (0-2), and arterial encasement (0-2). The authors performed univariate, multivariate, and recursive partitioning analysis (RPA) to evaluate outcomes. RESULTS The TSMs were resected in 139 patients. The median follow-up was 29 months. Ninety-five (68%) cases were resected via a TC and 44 (32%) via a TS approach. Tumors treated via a TC approach had a higher tumor (p = 0.0007), artery (p < 0.0001), and total score (p = 0.0012) on the grading scale. Preoperative visual deficits were present in 87% of patients. Vision improved in 47%, stayed the same in 35%, declined in 10%, and was not recorded in 8%. The extent of resection was 65% gross-total resection, 23% near-total resection (95%-99% resection), and 12% subtotal resection (< 95%). A lower tumor score was significantly associated with better or stable vision postoperatively (p = 0.0052). The RPA confirmed low tumor score as the key predictor of postoperative visual improvement or stability. Multivariate analysis and RPA demonstrate that lower canal score (p < 0.0001) and TC approach (p = 0.0019) are associated with gross-total resection. Complications occurred in 20 (14%) patients, including CSF leak (5%) and infection (4%). There was no difference in overall complication rates between TC and TS approaches; however, the TS approach had more CSF leaks (OR 5.96, 95% CI 1.10-32.04). The observed recurrence rate was 10%, and there was no difference between the TC and TS approaches. CONCLUSIONS Tuberculum sellae meningiomas can be resected using either a TC or TS approach, with low morbidity and good visual outcomes in appropriately selected patients. The simple proposed grading scale provides a standard preoperative method to evaluate TSMs and can serve as a starting point for selection of the surgical approach. Higher scores were associated with worsened visual outcomes and subtotal resection, regardless of approach. The authors plan a multicenter review of this grading scale to further evaluate its utility.

Pan-cancer copy number variant analysis identifies optimized size thresholds and co-occurrence models for individualized risk-stratification.

Chromosome instability leading to accumulation of copy number gains or losses is a hallmark of cancer. Copy number variant (CNV) signatures are increasingly used for clinical risk-stratification, but size thresholds for defining CNVs are variable and the biological or clinical implications of CNV size heterogeneity or co-occurrence patterns are incompletely understood. Here we analyze CNV and clinical data from 565 meningiomas and 9,885 tumors from The Cancer Genome Atlas (TCGA) to develop tumor-and chromosome-specific CNV size-dependent and co-occurrence models for clinical outcomes. Our results reveal prognostic CNVs with optimized size thresholds and co-occurrence patterns that refine risk-stratification across a diversity of human cancers.