Neuro-oncology practice最新文献

Recent interest has been in using mIDH inhibitors in patients with IDH-mutant gliomas. This review paper summarizes the indications, side effects, recommended dosing, and management for patients on ivosidenib and vorasidenib.

The isocitrate dehydrogenase (IDH) inhibitor, vorasidenib, may offer a promising new treatment option for patients with IDH-mutant gliomas. However, the indefinite nature of this targeted therapy raises significant financial concerns. High costs of targeted cancer therapies, often exceeding $150 000 annually, contribute to financial toxicity, characterized by medical debt, income loss, and psychological stress, and place stress on health systems. This review analyzes the drug approval and pricing mechanisms in various countries and their impact on healthcare costs and patient access, focusing specifically on the impacts in neuro-oncology. The United States employs a market-driven approach resulting in higher drug prices, while most countries, such as the United Kingdom, Germany, France, Italy, Japan, South Africa, and Brazil, use negotiated pricing and health technology assessment to manage costs. The financial burden of expensive medications affects patient adherence and quality of life, with many cancer patients facing substantial out-of-pocket expenses and potential treatment abandonment, and many more unable to access these drugs altogether. Vorasidenib's introduction, while potentially improving patient outcomes, may exacerbate financial toxicity unless mitigated by patient access programs and cost-management strategies. As neuro-oncology treatment paradigms evolve, understanding the economic implications of new therapies is essential to ensure equitable access and optimize patient care.

The clinical efficacy of isocitrate dehydrogenase (IDH) inhibitors in the treatment of patients with grade 2 IDH-mutant (mIDH) gliomas is a significant therapeutic advancement in neuro-oncology. It expands treatment options beyond traditional radiation therapy and cytotoxic chemotherapy, which may lead to significant long-term neurotoxic effects while extending patient survival. The INDIGO study demonstrated that vorasidenib, a pan-mIDH inhibitor, improved progression-free survival for patients with grade 2 mIDH gliomas following surgical resection or biopsy compared to placebo and was well tolerated. However, these encouraging results leave a wake of unanswered questions: Will higher-grade mIDH glioma patients benefit? When is the appropriate timing to start and stop treatment? Where does this new treatment option fit in with other treatment modalities? In this study, we review the limited data available to start addressing these questions, provide a framework of how to discuss these gaps with current patients, and highlight what is needed from the neuro-oncology community for more definitive answers.

Background: Despite recent significant advances, the treatment of elderly patients with primary central nervous system lymphoma (PCNSL) is still challenging due to comorbidities, poor baseline performance status (PS), and drug toxicities. There are proposals to use high-dose cytarabine (HD-araC) in these patients.

Methods: Our retrospective study aimed to assess the efficacy and toxicity of HD-araC as an upfront treatment for patients with PCNSL who are ineligible for high-dose methotrexate (HD-MTX).

Results: We identified 12 consecutive patients with newly diagnosed PCNSL (out of a total of 68) who received first-line treatment with HD-araC, with or without rituximab (R). Most of them had poor PS and relevant comorbidities. Six patients received this treatment upfront, while the other six received it after discontinuing HD-MTX-(based) therapy. Treatment with HD-araC resulted in poor outcome, limited response, and severe hematological and infectious complications. Patients who had previously received at least one cycle of HD-MTX appeared to have slightly better outcomes, highlighting the importance of HD-MTX in the treatment of PCNSL.

Conclusion: Our case series showed limited efficacy and substantial toxicity of (R)-HD-araC in patients with PCNSL ineligible for HD-MTX. This treatment should be omitted in elderly/frail patients to avoid further compromising their quality of life.

According to the 2021 World Health Organization classification of CNS tumors, gliomas harboring a mutation in isocitrate dehydrogenase (mIDH) are considered a distinct disease entity, typically presenting in adult patients before the age of 50 years. Given their multiyear survival, patients with mIDH glioma are affected by tumor and treatment-related symptoms that can have a large impact on the daily life of both patients and their caregivers for an extended period of time. Selective oral inhibitors of mIDH enzymes have recently joined existing anticancer treatments, including resection, radiotherapy, and chemotherapy, as an additional targeted treatment modality. With new treatments that improve progression-free and possibly overall survival, preventing and addressing daily symptoms becomes even more clinically relevant. In this review we discuss the management of the most prevalent symptoms, including tumor-related epilepsy, cognitive dysfunction, mood disorders, and fatigue, in patients with mIDH glioma, and issues regarding patient's health-related quality of life and caregiver needs in the era of mIDH inhibitors. We provide recommendations for practicing healthcare professionals caring for patients who are eligible for treatment with mIDH inhibitors.

Background: To address the lack of access to supportive cancer care resources, the purpose of this study was to examine the feasibility of a tailored exercise program for neuro-oncology patients.

Methods: Patients with a primary brain tumor diagnosis, >18 years, and able to consent in English were recruited at 2 tertiary cancer centers in Alberta. Recruitment occurred via the electronic medical record as well as self-referral. A 12-week, tailored exercise intervention with health coaching was delivered in both one-on-one and group-based formats, either in-person or online. Measures of feasibility included tracking referral, enrollment, intervention completion and adherence, measurement completion, fidelity, participant satisfaction, and safety. Participant-reported outcomes and functional fitness were assessed at baseline and 12 weeks. Objective physical activity was tracked via a Garmin activity tracker.

Results: Recruitment occurred between April 2021-December 2022. N = 70 patients enrolled in the study and n = 51 completed the intervention. The referral rate was 31%, the enrollment rate was 66%, and intervention completion and adherence rates were 82.3% and 89.7%. At baseline and 12 weeks, measurement completion rates were 100% and 77.4% for patient-reported outcomes, and 98.4% and 75.8% for functional fitness. The average wear-time for the activity tracker was 72.8%. Fidelity of intervention delivery was 100% for exercise sessions and 87.8% for health coaching. Overall participant satisfaction was 86.5%. No major and 4 minor adverse events occurred.

Conclusions: Delivery of a tailored neuro-oncology exercise program with referral included via the electronic medical record is feasible. Future work is needed to optimize tailored programming as well as to address factors critical for implementation into standard cancer care.

Clinical trials registration: NCT04831190 (https://clinicaltrials.gov/ct2/show/NCT04831190).

We report a case of a 10-year-old male with a right frontal diffuse pediatric-type high-grade glioma (HGG), H3-wild-type (WT), and IDH-WT, diagnosed at the age of 9 years, who underwent gross total resection, 60 Gy focal proton radiation in 30 fractions to the resection cavity with concurrent temozolomide followed by maintenance chemotherapy with temozolomide and lomustine. One month after completion of maintenance chemotherapy, he developed subcutaneous swelling in the right temporal region and was treated with antibiotics for presumed lymphadenitis. Two months later, he developed a recurrent painless right parietal soft tissue mass that failed to respond to antibiotic therapy. This prompted evaluation by MRI which revealed new enhancing masses in the cerebellum and extracranial soft tissue mass in the right temporal region. He underwent gross total resection of both masses. Pathologic analysis confirmed both masses as recurrent HGG. Molecular markers, however, differed between the 2 sites of recurrence. He proceeded to complete hypofractionated proton therapy at sites of recurrence. Three months later, he was found to have tumor dissemination into the spine and brain for which he received proton therapy to the whole spine and brain. Due to the presence of CDK4 amplification at diagnosis and both sites of tumor recurrence, he then received palliative treatment with the CDK4/6 inhibitor, abemaciclib, for the final 5 months of his life. Since extracranial HGG is a rare presentation, with few cases reported in the pediatric population, we report this case and review previously published literature.

Background: Low-grade gliomas (LGG) are among the most frequently occurring tumors in adolescent and young adult (AYA) patients (aged 18-39 years old at primary diagnosis). These tumors have a variable prognosis, presenting challenges for patients in shaping their future. This study aimed to identify the age-specific experiences and needs of AYA patients with LGG in their daily lives.

Methods: In-depth interviews were conducted with AYA patients diagnosed with LGG. Thematic analysis was performed to derive the age-specific codes, looking for overarching themes and sub-themes.

Results: Sixteen patients participated in this study. The cognitive symptoms of the disease (including difficulty concentrating, memory issues, and speech problems) are invisible to others but caused significant disruptions in many domains that were particularly important to AYA patients (eg, employment, family life, and autonomy). Additionally, the uncertainty regarding their life expectancy led to difficulties in making decisions about the future. They also perceived a lack of control over their future and the time they had left.

Conclusions: LGG have a significant impact on AYA patients. However, this impact is not fully understood by others close to them. The results highlight the importance of providing these patients with appropriate peer support, interventions tailored to both their disease and life phase, utilizing a multidisciplinary approach, and maintaining a focus on long-term support for these patients. It is crucial to provide AYA care for these patients within the neurology department, as LGG involve both tumor- and age-specific problems.