Neuro-oncology practice最新文献

Background: Intra-cerebrospinal fluid (CSF) chemotherapy delivered through an Ommaya reservoir is a treatment for certain patients with leptomeningeal metastasis (LM). Numerous administration strategies are advocated in the literature and are used in practice. We evaluated differences in drug delivery associated with the three most used techniques.

Methods: Consecutive patients with newly diagnosed LM underwent conventional CSF flow studies using indium-111-DTPA (n = 104). Three different administration techniques and two different radionuclide volumes were used. Techniques evaluated were administration of the radionuclide followed by repeated compression of the Ommaya bulb, administration mixed with an equal volume of CSF followed by compression, and barbotage with CSF withdrawn prior to chemotherapy injection. Residual radionuclide counts were measured in the injection syringe, butterfly needle/stopcock apparatus, and reservoir bulb after radionuclide administration. In addition, U.S. neuro-oncologists were surveyed regarding their intra-CSF chemotherapy administration techniques.

Results: For the 3 mL injection volume, 53.5%, 28.0%, and 3.14% of the radionuclide never reached the patient using the bulb compression, CSF-drug mixing followed by compression, and barbotage techniques respectively (P < .00001). For the 5 mL injection volume, the corresponding percentages were 23.3%, 18.7%, and 3.0% (P < .0001). The survey of U.S. neuro-oncologists revealed that a majority (56%) do not use a barbotage procedure for chemotherapy administration.

Conclusions: A large proportion of radionuclide injected into Ommaya reservoirs never reaches the patient unless a barbotage technique is used. This finding likely applies to intraventricular chemotherapy injections as well and may represent one easily remediable reason for the poor efficacy of intraventricular chemotherapy in patients with LM.

Background: Prolonged Diagnostic Interval (DI)s pose a challenge in childhood central nervous system (CNS) tumors. The coronavirus disease 2019 (COVID-19) pandemic altered contact with healthcare. The aim of this study was to describe DIs in children diagnosed with a CNS tumor in Denmark during the first year of the pandemic.

Methods: We performed a retrospective questionnaire study, mapping time intervals and symptoms in the diagnostic pathway. We analyzed DIs measured in days and performed descriptive analyses of symptoms and contacts with health care professionals (HCP). Comparison to a pre-COVID cohort was applied. Intervals were presented as total diagnostic interval (TDI; time from symptom onset to diagnosis); Patient Interval (PI; time from symptom onset to first contact to an HCP); and DI (time from first contact to an HCP to diagnosis).

Results: We included 25 patients (median age 8.2 years, 56% female). Median TDI: 98 days (IQR 26 210). The DI constituted the majority of TDI (median 70 days). Low-grade tumors displayed longer TDI than high-grade tumors. No significant difference in TDI was found when compared to a pre-COVID cohort (median 98 vs. 106 days). No hesitance to contact a doctor was reported by 88%, but 24% reported delays attributable to the pandemic. Patients reported more symptoms at onset, and the trajectory in the diagnostic pathways changed with fewer patients assessed by their general practitioner than pre-COVID.

Conclusions: The DI was unaltered during the COVID-19 pandemic, but changes in trajectory were reported. Results stress the ongoing need for interventions to promote timely diagnosis.

Background: The use of procarbazine in the treatment of lower-grade gliomas as part of the procarbazine, lomustine, and vincristine (PCV) regimen is frequently limited by the development of hypersensitivity reactions (HSRs), which often require dose reduction or cessation of procarbazine therapy prior to the completion of a planned treatment course. The incidence, clinical characteristics, and potential predictors of these reactions are not well defined.

Methods: We conducted a retrospective cohort study of patients with lower-grade gliomas who received PCV between January 2016 and January 2024 at a tertiary medical center. Data on patient demographics, tumor type, clinical characteristics, treatment course, and HSRs were collected. A total of 61 patients were included.

Results: The overall incidence of procarbazine-associated HSRs was 60.7% (95% CI: 48.4%-72.9%). All HSRs involved the development of rash, with 86.5% being pruritic and 21.6% involving the face. Treatments for HSRs included antihistamines (62.2%), topical corticosteroids (35.1%), and systemic corticosteroids (27.0%). Patients who experienced procarbazine-associated HSRs received significantly fewer cycles of procarbazine compared to those who did not experience HSRs (P < .001). 83.8% of patients with HSRs permanently discontinued procarbazine. Three patients with HSRs presented to the emergency department with concern for anaphylaxis, and one required treatment with epinephrine. One of 6 rechallenged patients experienced a recurrent HSR that resolved with systemic corticosteroids. The other 5 were successfully rechallenged without recurrent HSRs.

Conclusions: The high incidence of HSRs in this population, including cases of suspected anaphylaxis, should be considered carefully by clinicians when prescribing chemotherapy for glioma and warrants routine counseling and close monitoring.

Background: Although hemangioblastomas (HBs) are biologically benign, their management is often complicated, particularly in the context of von Hippel-Lindau disease (VHL). Few studies have investigated treatment outcomes of both VHL-related sporadic HBs in detail. This study assessed the clinical characteristics and neurosurgical outcomes of VHL-related and sporadic HBs using data from the nationwide Brain Tumor Registry of Japan database.

Methods: Patients with HB who underwent surgery between 2001 and 2008 were included. Clinical and radiological findings, including preoperative and postoperative Karnofsky Performance Status (KPS) scores, were evaluated. Factors associated with improved postoperative KPS were identified using univariate and multivariate analyses. Postoperative outcomes were evaluated using the Kaplan-Meier method.

Results: A total of 443 patients (68 with VHL) were analyzed, with a median follow-up duration of 57 months, and gross total resection (GTR) was achieved in 81% of patients. Compared to sporadic HB, VHL-related HB was associated with perioperative complications (P = .020), shorter recurrence-free survival (P < .001), and the formation of de novo lesions (P < .001). GTR significantly correlated with improved postoperative KPS (P = .002) after adjusting for disease etiology and overall survival (OS) (P < .001) in VHL-related HBs, as analyzed by the Kaplan-Meier method.

Conclusions: The prognosis was worse for VHL-related HBs than for sporadic HBs; however, GTR was associated with improved OS, even in VHL-related HBs. Surgical resection is of the utmost importance in treating HB, regardless of the etiology.

Background: The use of CDKN2A/B deletions in the current WHO CNS classification (5th edition, 2021), has led to some ambiguity in patient management. Further clinical studies are required to fully ascertain the clinical impact of CDKN2A/B deletions in this patient cohort and their optimal management. To this end, we conducted a multi-center retrospective cohort study and patterns of care survey to explore real-world outcomes in CDKN2A/B homozygously (HoD) and heterozygously deleted (HeD) IDH mutant tumours.

Methods: Demographic and clinical data were compiled for patients with IDH-mutant astrocytomas across multiple oncology centers and databases. Findings were supplemented with patterns of care survey circulated to Australian neuro-oncology centers and neuro-pathologists.

Results: Patients were divided into the following cohorts: CDKN2A/B HoD (n = 12), CDKN2A/B HeD (n = 16) and non-CDKN2A/B deleted (n = 41). The CDKN2A/B HoD cohort had a median overall survival (OS) of 4.57 years, however, median OS was not yet reached for any of the other cohorts. The 5-year OS for the HoD cohort was % compared to 88% in the HeD cohort and 88% in the non-CDKN2A deleted cohort (Log-Rank P = .012). Respondents to our patterns of care survey preferred concurrent radiotherapy-temozolomide therapy followed by adjuvant temozolomide for CDKN2A/B HoD IDH-mutant astrocytomas regardless of the morphologic grade.

Conclusion: This exploratory study supports the importance of molecular profiling in glioma diagnoses and the prognostic utility of current classification systems. However future research into the optimal therapy for these patients is needed in prospective studies.

Background: Despite a generally poor prognosis of patients with brain metastases of colorectal cancer (CRC-BM), local treatment of BM might be beneficial in selected patients. The aim of this study was to characterize patient and clinicopathological characteristics of CRC-BM and to identify patients who benefit most from local treatment of CRC-BM.

Methods: In this retrospective cohort study, clinicopathological characteristics, including treatment response and survival, were collected from 100 patients who were treated for CRC-BM at the Netherlands Cancer Institute between 2001 and 2021. All analyses were performed using SPSS.

Results: Median overall survival (OS) from CRC diagnosis and diagnosis of BM was 47.3 and 5.2 months, respectively. Median brain metastasis-free interval (BMFI) was 39.0 months. Median OS of patients with metachronous extracranial metastases (ECM) and subsequent BM was 5.7 months compared to 2.8 months in patients with synchronous ECM and subsequent BM (P = .08). In the latter group, the diameter of BM and liver metastases negatively influenced survival. OS of patients with CRC-BM improved over time (9.0 vs 4.0 months in 2016-2021 vs 2001-2015, respectively (P = .002)) and was better in patients able to receive systemic therapy after diagnosis of CRC-BM compared to patients who did not (19.4 months vs 4.7 months; P = .005).

Conclusions: Although the development of BM in patients with CRC is a late event resulting in a poor prognosis, outcome improved over time. OS was significantly longer in patients who still have systemic treatment options. This can be taken into account in the decision for local treatment of patients with CRC-BM.

Background: Individuals with glioma endorse high fear of cancer recurrence or progression (FCR), yet existing interventional studies for FCR exclude glioma patients. Components of existing FCR interventions are not entirely translatable to those with glioma as they were designed for non-central nervous system (non-CNS) cancer populations with less risk for recurrence, minimal-to-no neurologic sequelae, and different sources of worry.

Methods: A two-stage Phase I ORBIT Model process was employed: Phase Ia included consultation with international FCR experts and two advisory boards toward the development of an intervention targeting FCR in neuro-oncology. Recommendations resulted in a 6-module mindfulness-based cognitive-existential intervention: FearLess in Neuro-Oncology. Phase Ib included a quasi-experimental pilot trial of telehealth FearLess in patients (n = 6), caregivers (n = 6), and patient-caregiver dyads (n = 10) with a primary aim of assessing feasibility/acceptability and an exploratory aim of characterizing change in FCR and other psychological outcomes.

Results: Phase Ia results supported an individual- or dyadic-level intervention with an emphasis on the inclusion of caregivers, a focus on individuals affected by malignant gliomas, and strategies to address glioma-specific FCR hypervigilance symptoms. Our phase Ib trial demonstrated adequate rates of enrollment, measure completion, retention, and satisfaction; however, screening rates (successful screening of those interested) were lower among caregivers.

Conclusion: Findings support continued optimization of FearLess in Neuro-Oncology. Targeted recruitment strategies are needed to reach caregivers, who engaged with and benefitted from the intervention, but were difficult to enroll and retain when not participating as a dyad. Participants reported high perceived benefit and utility of the strategies learned in the intervention.

Background: Glioblastoma (GBM) is the most aggressive primary brain neoplasm in adults, characterized by high recurrence and poor post-recurrence survival. Validated quality indicators (QIs) have been used to assess the quality of care in many cancer populations, now providing clinicians, researchers, and healthcare policymakers with evidence-based metrics to enhance patient outcomes. In contrast, few glioblastoma-specific QIs have been described and their impact and meaningfulness are yet to be determined.

Methods: A scoping review was conducted of described QIs for adult patients with GBM. The literature was screened for relevance, and eligible QIs were evaluated and grouped into 5 domains: pre-intervention, surgical, postsurgical, supportive care, and recurrence/survival.

Results: A total of 80 articles were retrieved, with 12 of these studies meeting inclusion criteria. Twenty-six QIs were identified across the 5 care domains. Evidence linking these QIs directly to improved survival or quality of life is variable. Some QIs have solid evidence of impact (eg, accurate tissue diagnosis), while others are based on reasonably assumed benefits rather than robust evidence (eg, early palliative care referral). Frail or older patients and those with recurrent GBM are subsets with the least high-quality QIs.

Conclusions: Current QIs potentially provide valuable benchmarks to assess and optimize care in adults with glioblastoma, but many are yet to be supported by high-quality clinical evidence, with greater gaps in some patient populations. Further research is required to define and validate QIs that robustly assess quality of care, supporting urgent efforts to improve patient outcomes for this poor prognosis of cancer.

Neuro-oncology researchers and clinicians rely mostly on subjective measures to evaluate physical functioning (PF) and predict survival in primary brain tumor (PBT) patients. Exploring alternative clinical outcome assessment (COA) measures may identify more objective measures that better quantify PF in PBT patients. A scoping review was conducted to identify studies related to PF measures used in PBT patients. Using the PRISMA-SCRA guideline 3 databases (PubMed, Web of Science, and Cochrane Library) were searched on January 25, 2024. Reviewers performed an independent review of titles, abstracts, and full text using covidence systematic review software and a standardized Microsoft Excel form for extracting data. 1093 publications were identified; 49 studies met eligibility criteria. Studies used a variety of PF measures evaluated at different time points, ranging from preintervention to 3 years or more postintervention. 39 PF COA measures were identified. Of the 39, 3 clinician-reported measures (ClinRO) [KPS, ECOG, and FIM] are validated for PBT. Many measures found are standardized for other neurological diseases including performance (PerfO) and patient-reported outcome (PRO) measures. Validation of additional COA types (PerfO and PRO) that are complementary to the ClinRO measures already validated for the PBT population should be established. Measures of interest should include the evaluation of walking due to its clinical relevance and indication for overall PF.

Background: Current World Health Organization (WHO) 2021 classification of adult-type diffuse gliomas includes three main diagnostic entities with different prognosis and treatment algorithm: glioblastoma IDH wild-type, astrocytoma IDH mutant, and oligodendroglioma IDH mutant/1p-19q co-deleted. For IDH mutant gliomas, it is well known that administering postoperative chemo-radiation based on risk factors such as age, extent of resection, and WHO grading significantly improves disease control and overall survival. However, whether the use of chemotherapy may be considered safe in special populations such as orthotopic liver transplant recipients (TRs) is still not fully understood.

Case summary: Here, we report the case of a 56-year-old patient diagnosed with central nervous system WHO grade 2 oligodendroglioma IDH mutant/1p-19q co-deleted and medical history of orthotopic liver transplantation for HCV-related cirrhosis, subsequent HCV infection relapse and on therapy with immunosuppressive agents (tacrolimus plus everolimus). After radiation therapy, benefits and risks of chemotherapy were carefully assessed in terms of drug-to-drug interactions, additive immune-suppression, potential hepatic toxicity, and possibility of organ rejection. The patient successfully received a full course of standard-schedule temozolomide for 12 cycles, with no adverse events to be reported. Notably, imaging findings consistent with treatment-related changes were observed during chemotherapy cycles, managed with appropriate diagnostic workflow and no treatment interruption.

Conclusion: This case study described for the first time safe administration of temozolomide-based chemotherapy in an orthotopic TR, sharing potential insights for best managing such a rare clinical scenario.