Journal of Neuro-Oncology最新文献

Purpose: In patients with subtotal resection (STR) of WHO grade I skull base meningiomas, treatment strategies of adjuvant radiation versus observation with salvage radiation, if necessary, were compared using progression-free survival (PFS) and radiation failure-free survival (RFFS).

Methods: Patients with newly diagnosed WHO grade I skull base meningioma who underwent radiographically confirmed STR between 1995 and 2021 were included. PFS was measured from last treatment date. RFFS was measured from surgery date to first radiation failure. Multivariable Cox regression, adjusted for propensity score (PS) and inverse probability treatment weighted (IPTW), was performed.

Results: Of 179 patients, 25 (14.0%) received adjuvant radiation. Among 154 observed patients, 90 (58.4%) experienced tumor progression and 64 (71.1%) received salvage radiation. Observation after STR had PFS at 3, 5, and 10 years of 60.6%, 47.5%, and 26.8%, respectively. Adjuvant radiation had PFS/RFFS at 3, 5, and 10 years of 84.2%, 77.2%, and 77.2%. Salvage radiation had PFS at 3, 5, and 10 years of 96.0%, 85.0%, and 80.0%. RFFS after observation with salvage radiation, if needed, at 3, 5, and 10 years was 100%, 97.7%, and 92.8%. PS and IPTW Cox regression models, controlling for residual tumor volume, demonstrated that observation with salvage radiation significantly prolonged RFFS (HR = 0.06, p = 0.013; HR 0.08, p = 0.026, respectively) compared to adjuvant radiation. Median follow-up was 77.5 months.

Conclusion: Most patients will have tumor progression within 10 years of STR. Our data suggests that appropriately selected patients can be observed with close follow-up, reserving radiation for progression.

Purpose: We characterized the association between photon radiation dose (< 59.4 versus ≥ 59.4 Gy) and outcomes in intracranial ependymoma. We also examined factors associated with survival after relapse.

Methods: This multi-institutional retrospective study included patients age ≤ 21 years who received postoperative definitive-intent photon radiotherapy for posterior fossa ependymoma between 1997 and 2021. Clinical characteristics were obtained from medical records. Five-year overall (OS) and progression-free (PFS) survival were estimated using the Kaplan-Meier method. Factors associated with progression after radiotherapy, including dose < 59.4 versus ≥ 59.4 Gy, were analyzed using Fine and Gray's proportional subhazards model. Factors associated with post-relapse survival were explored using the Cox proportional-hazards model.

Results: We identified 45 patients meeting inclusion criteria; 48.9% received ≥ 59.4 Gy. There was no difference in 5-year OS or PFS between those who received < 59.4 Gy versus ≥ 59.4 (OS 49.0% vs. 82.9%, p = 0.11; PFS 36.4% vs. 63.9%, p = 0.08); however, there was a trend towards worse 5-year OS and PFS among patients with grade 2 ependymoma who received < 59.4 Gy (OS 48.8% vs. 88.9%, p = 0.06, PFS 40.0% vs. 83.1%, p = 0.08). Only age > 4 years at diagnosis (subdistribution hazard ratio [SHR]: 0.40, p = 0.03) was associated lower risk of progression. Following radiotherapy, 24 patients relapsed. Receipt of salvage systemic therapy was associated with worse post-relapse OS on multivariable analysis (HR = 2.84, p = 0.04).

Conclusion: Underlying biological factors such as age and molecular subtype may hold greater prognostic significance than radiation dose in pediatric ependymoma. Regardless, recurrences are common and outcomes remain poor. Further research into optimal management of relapsed disease is critical.

Purpose: Gliomas, the most prevalent type of central nervous system tumors, currently lack effective therapeutic options. Lipolysis-stimulated lipoprotein receptors (LSR) have been implicated in tumor development and progression. This study aims to investigate the influence of LSR on gliomas and elucidate the underlying mechanisms.

Methods: We analyze LSR expression in gliomas and its association with patient prognosis using bioinformatics tools. Western blotting and immunohistochemistry revealed differential expression of LSR across different grades of glioma. The effects of LSR on glioma cell proliferation and invasion are evaluated through a series of cellular assays. Subcutaneous xenografts in nude mice are utilized to assess the impact of LSR on gliomas in vivo. Additionally, western blotting is employed to detect changes in protein levels related to the FOXO3a signaling pathway following LSR overexpression.

Results: LSR expression is higher in tissues from low-grade gliomas compared to those from glioblastomas. Patients with low LSR expression exhibit poorer prognoses. Overexpression of LSR inhibit glioma cell proliferation and invasion. The protein levels of PCNA, Cyclin D1, MMP2, and MMP9 are significantly decreased in the OE-LSR group. Tumor volume is reduced in nude mice injected subcutaneously with LSR-overexpressing glioma cells. Overexpression of LSR increases nuclear FOXO3a level while reduces p-FOXO3a and p-14-3-3 levels. Knockdown of FOXO3a reverse the inhibitory effects of LSR overexpression on glioma cell proliferation and invasion.

Conclusion: Low LSR expression is associated with adverse prognosis in glioma patients. By modulating FOXO3a, LSR overexpression suppresses glioma cell proliferation and invasion.

Background: The RANO classification for glioblastoma defines resection categories based on volumetric tumor assessments, aiming to standardize outcomes related to extent of resection (EOR). This study revalidates the prognostic impact of RANO classes by reconstructing individual patient data (IPD).

Methods: A systematic review and meta-analysis were performed, including three studies comprising 580 glioblastoma patients. Included studies reported or allowed conversion to RANO classes for glioblastoma resection extent, with detailed OS data and numbers at risk. Overall survival (OS) data were extracted from Kaplan-Meier survival curves, and IPD were reconstructed using Digitizelt and the R package IPDfromKM. Survival analyses were conducted using Kaplan-Meier estimates and Cox regression models.

Results: Median follow-up was 15.6 months (IQR: 10.1-28.8). Patients undergoing supramaximal resection (RANO class 1, n = 163) had the highest median OS (35.6 months; 95% CI: 30.9-40.4), significantly outperforming non-class 1 resections (median OS: 13.9 months; 95% CI: 13.0-14.7; p < 0.001). Subgroup analysis revealed superior OS for class 2a (19.0 months) over class 2b (14.1 months; p < 0.001), while class 3 and 4 resections demonstrated progressively poorer outcomes. Hazard ratios consistently favored class 1 versus all other classes (HR: 0.28; 95% CI: 0.23-0.37).

Conclusions: Supramaximal (class 1) resection provides a significant survival benefit in glioblastoma, underscoring its critical role in surgical management. The RANO classification stratifies resection outcomes effectively, supporting its use as a prognostic tool. These findings advocate for resection strategies targeting maximal tumor removal.

Purpose: To determine neurocognitive function (NCF) profiles of patients with lower grade glioma (LGG) eligible to undergo proton radiotherapy (PRT), and how these relate to clinical and radiological characteristics. PRT is offered to those patients for whom sparing of NCF is considered important given their favorable prognosis. To date it is unknown to which extent their NCF profiles are favorable as well.

Methods: A consecutive cohort of 151 LGG patients eligible for PRT according to prevailing Dutch criteria, referred between 2018 and 2023, were assessed with standardized neuropsychological tests prior to PRT. Scores were compared to norm-scores. Composite scores were calculated for the total NCF and 6 separate cognitive domains, and profiles were related to tumor location. Clinical and radiological factors characterizing overall NCF impaired patients were investigated, comparing 3 definitions for impairment.

Results: Patients had on average significantly lower NCF than their norm-group, but interindividual variability was large. For 100/151 patients (66.2%), all cognitive domains were intact, whereas 15/151 patients (9.9%) displayed multiple domain impairments. Poorer NCF was related to right-sided LGG laterality, larger PRT target volume, no Wait & Scan policy, worse neurological function and worse radiological indices (Fazekas and global cortical atrophy, respectively). LGG involvement of the left temporal and occipital lobes was associated with, respectively, lower verbal memory and processing speed.

Conclusion: Prior to PRT, the majority of selected LGG patients display favorable NCF profiles. However, a subgroup showed NCF impairments, with multiple relevant clinical and radiological covariates.

Purpose: Papillary craniopharyngioma is a rare entity, demonstrating BRAF-V600E mutations in approximately 95% of patients. Recently, a phase 2 trial of patients treated with surgery and BRAF/MEKi demonstrated 91% reduction in residual tumor volume. This study allowed for additional treatments at the discretion of the treatment team without reporting subsequent rates of endocrinopathy or visual decline. We aimed to evaluate the possibility of employing BRAF/MEKi without the need for adjuvant radiotherapy therapies.

Methods: A retrospective report of two patients treated with resection and BRAF/MEKi without additional treatment were analyzed. Patient demographics, treatment characteristics, pre- and post-treatment radiographic volumes, adverse events, and endocrinologic and visual outcomes, were recorded and analyzed.

Results: Two patients underwent subtotal resection followed by BRAF/MEKi without adjuvant treatment. Mean length of BRAF therapy was 21.4 months and MEKi therapy was 12.94 months. Mean preoperative nodule volume was 0.33 cm [3] and 2.29 cm [3] and cystic volume was 5.04 cm [3] and 6.18 cm [3] in case 1 and case 2, respectively. Neither patient received radiation. Grade 3 cardiotoxicity developed in case 1 after 6.5 months, with function recovering completely following discontinuation of MEKi. BRAF therapy was discontinued electively after 23.5 months. The second patient remains on dual inhibition therapy without toxicity. For these cases, post-treatment nodule volumes are 0.07 cm [3] (98.4% reduction) and 0.04 cm [3] (99.2% reduction), respectively, and cystic volume 0.0 cm [3] in both patients. Progression free survival is 100% with a mean follow up of 36-months.

Conclusions: Utilizing surgery and BRAF/MEKi without adjuvant radiation, we demonstrate excellent disease control with reversible toxicity. Avoiding additional treatments may spare vital functions and unnecessary procedures.

Purpose: Chordomas are rare malignant tumors arising from the embryological notochord that present most frequently in the lumbosacral spine, followed by the skull base, with an overall 1/1,000,000 incidence. These tumors and their treatment significantly affect quality of life (QOL) due to intricate anatomical locations and aggressive treatment regimens. Despite these challenges, there are currently no disease-specific patient-reported outcome (PRO) surveys for chordomas. We aimed to develop a tool to assess QOL in patients with skull base chordomas (sbCs).

Methods: Twenty-seven patients who underwent sbC resection were interviewed on QOL throughout their care. Grounded-theory analysis of interview transcripts generated 7 themes. We developed an initial survey with 79 items from existing general and anatomic-specific QOL assessment tools addressing these themes. Ten chordoma providers and 10 new patients completed an anonymous Qualtrics survey, rating items' relevance on a 5-point Likert scale to validate survey content. An a priori cutoff of > 3.0 was used for significant relevance. Mean relevance scores for each item were compared between providers and patients as well as between skull base respondents and 5 control patients with lumbar spine and sacral chordomas, using two-sided Mann-Whitney U-tests.

Results: Seventy-four items reached the relevance threshold. These were consolidated to create the final 42-item Skull Base Chordoma Patient Reported Outcome Survey (sbCPROS). Providers significantly overvalued items related to the themes of pain (73%), sleep changes (60%), and sensory & motor symptoms (43%) relative to patients. Ten items were more relevant to skull base patients than patients with spinal tumors (p < 0.05).

Conclusion: The authors developed a novel patient-centered, disease-specific PRO instrument to assess change in QOL for sbC patients over time. sbCPROS may provide significant insight into the delivery of high quality care for patients with sbCs and guide patient-physician discussions about care decision-making.

Purpose: The purpose of this systematic review and meta-analysis was to compare tinnitus outcomes following microsurgery and stereotactic radiosurgery for vestibular schwannoma.

Methods: The databases MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Ovid), SCOPUS, CINAHL (EBSCO), and Web of Science were searched for studies comparing microsurgery and radiosurgery treatment, and reporting tinnitus outcomes. Longitudinal tinnitus assessment with pre-treatment evaluation was required for inclusion. Fractionated radiotherapy treatment was excluded. Newcastle-Ottawa scale was used to assess the quality of the included studies. A separate random-effects meta-analysis was performed for the continuous, binary and ordinal tinnitus outcomes, with pooled effects described as a standardised mean difference or a log odds ratio as appropriate.

Results: Thirteen studies involving 5814 patients were included in the review; 4 were prospective studies, and the rest were retrospective cohort studies. The median follow-up duration in the microsurgery and radiosurgery groups was 39.5 months and 41.1 months, respectively. Studies were diverse with respect to inclusion criteria and method of tinnitus outcome assessment. Only 4 studies reported tinnitus scores using tinnitus questionnaires, while others used Likert scale, visual analogue scale, binary (present or absent) scale or ordinal (improved, same or worse) scale. Four studies reported better tinnitus outcomes after microsurgery than radiosurgery. However, the overall quality of the studies was low, and most did not control for important confounders, such as age, tumour characteristics, and hearing impairment. Meta-analysis of continuous and binary tinnitus outcomes showed no difference between the interventions (standardised mean difference = -0.04, 95% CI -0.37 to 0.28, p = 0.80; log odds ratio = 0.32, 95% CI -1.11 to 1.74, p = 0.66). Meta-analysis of tinnitus outcomes on an ordinal scale showed microsurgery increased the odds of reporting improved tinnitus compared to radiosurgery (log odds ratio = 0.83, 95% CI 0.01 to 1.64, p = 0.045). Heterogeneity between the studies was high for all outcome measures (I² > 56%).

Conclusion: Meta-analyses of tinnitus outcomes were largely inconclusive, except when tinnitus was reported as an ordinal outcome, which favoured microsurgery. However, due to the low quality of studies and high heterogeneity, no definitive conclusions could be drawn favouring either treatment.