Craniospinal irradiation for CNS leukemia: rates of response and durability of CNS control.

PURPOSE: Management of CNS involvement in leukemia may include craniospinal irradiation (CSI), though data on CSI efficacy are limited. METHODS: We retrospectively reviewed leukemia patients who underwent CSI at our institution between 2009 and 2021 for CNS involvement. CNS local recurrence (CNS-LR), any recurrence, progression-free survival (PFS), CNS PFS, and overall survival (OS) were estimated. RESULTS: Of thirty-nine eligible patients treated with CSI, most were male (59%) and treated as young adults (median 31 years). The median dose was 18 Gy to the brain and 12 Gy to the spine. Twenty-five (64%) patients received CSI immediately prior to allogeneic hematopoietic cell transplant, of which 21 (84%) underwent total body irradiation conditioning (median 12 Gy). Among 15 patients with CSF-positive disease immediately prior to CSI, all 14 assessed patients had pathologic clearance of blasts (CNS-response rate 100%) at a median of 23 days from CSI start. With a median follow-up of 48 months among survivors, 2-year PFS and OS were 32% (95% CI 18-48%) and 43% (95% CI 27-58%), respectively. Only 5 CNS relapses were noted (2-year CNS-LR 14% (95% CI 5-28%)), which occurred either concurrently or after a systemic relapse. Only systemic relapse after CSI was associated with higher risk of CNS-LR on univariate analysis. No grade 3 or higher acute toxicity was seen during CSI. CONCLUSION: CSI is a well-tolerated and effective treatment option for patients with CNS leukemia. Control of systemic disease after CSI may be important for CNS local control. CNS recurrence may reflect reseeding from the systemic space.

Prognostic value of cerebrospinal fluid tumor cell count in leptomeningeal disease from solid tumors.

PURPOSE: Treatment decisions for leptomeningeal disease (LMD) rely on patient risk stratification, since clinicians lack objective prognostic tools. The introduction of rare cell capture technology for identification of cerebrospinal fluid tumor cells (CSF-TCs), such as CNSide assay, improved the sensitivity of LMD diagnosis, but prognostic value is unknown. This study assesses the prognostic value of CSF-TC density in patients with LMD from solid tumors. METHODS: We conducted a retrospective cohort study of patients with newly diagnosed or previously treated LMD from a single institution who had CNSide assay testing for CSF-TCs from 2020 to 2023. Univariable and multivariable survival analyses were conducted with Cox proportional-hazards modeling. Maximally-selected rank statistics were used to determine an optimal cutpoint for CSF-TC density and survival. RESULTS: Of 31 patients, 29 had CSF-TCs detected on CNSide. Median (interquartile range [IQR]) CSF-TC density was 67.8 (4.7-639) TCs/mL. CSF cytology was positive in 16 of 29 patients with positive CNSide (CNSide diagnostic sensitivity = 93.5%, negative predictive value = 85.7%). Median (IQR) survival from time of CSF-TC detection was 176 (89-481) days. On univariable and multivariable analysis, CSF-TC density was significantly associated with survival. An optimal cutpoint for dichotomizing survival by CSF-TC density was 19.34 TCs/mL. The time-dependent sensitivity and specificity for survival using this stratification were 76% and 67% at 6 months and 65% and 67% at 1 year, respectively. CONCLUSIONS: CSF-TC density may carry prognostic value in patients with LMD from solid tumors. Integrating CSF-TC density into LMD patient risk-stratification may help guide treatment decisions.

Older patients with primary central nervous system lymphoma: Survival and prognostication across 20 U.S. cancer centers.

There is a paucity of large-scale data delineating outcomes and prognostication of older patients with primary central nervous system lymphoma (PCNSL). We retrospectively analyzed 539 newly-diagnosed PCNSL patients ages ≥60 years across 20 U.S. academic centers. The median age was 70 years (range 60-88); at least one geriatric syndrome was present in 46%; the median Cumulative Index Ratings Scale-Geriatrics (CIRS-G) score was 6 (range, 0-27); and 36% had impairment in activities of daily living (ADL). The most common induction regimens were high-dose methotrexate (HD-MTX) ± rituximab; methotrexate, temozolomide, rituximab (MTR); and rituximab, methotrexate, procarbazine, vincristine (R-MPV). Overall, 70% of patients achieved remission, with 14% undergoing consolidative autologous stem cell transplant (ASCT) and 24% receiving maintenance. With 58-month median follow-up, median progression-free survival (PFS) and overall survival (OS) were 17 months (95% CI 13-22 months) and 43 months (95% CI 31-56 months), respectively. Three-year PFS and OS were highest with MTR (55% and 74%, respectively). With single-agent methotrexate ± rituximab, 3-year PFS and OS were 30% (p = .0002) and 47% (p = .0072). On multivariate analysis, increasing age at diagnosis and Cooperative Oncology Group (ECOG) performance status (PS) was associated with inferior PFS; age, hypoalbuminemia, higher CIRS-G score, and ECOG PS adversely affected OS. Among patients receiving maintenance, 3-year PFS was 65% versus 45% without maintenance (p = 0.02), with 3-year OS of 84% versus 61%, respectively (p = .0003). Altogether, outcomes in older PCNSL patients appeared optimized with HD-MTX combination induction regimens and maintenance therapy. Furthermore, several prognostic factors, including geriatric measures, were associated with inferior outcomes.

Neuro-oncology Treatment Strategies for Primary Glial Tumors.

Primary brain tumors underwent reclassification in the 2021 World Health Organization update, relying on molecular findings (especially isocitrate dehydrogenase mutations and chromosomal changes in 1p, 19q, gain of chromosome 7 and loss of chromosome 10). Newer entities have also been described including histone 3 mutant midline gliomas. These updated pathologic classifications improve prognostication and reliable diagnosis, but may confuse interpretation of prior clinical trials and require reclassification of patients diagnosed in the past. For patients over seventy, multiple studies have now confirmed the utility of shorter courses of radiation, and the risk of post-operative delirium. Ongoing studies are comparing proton to photon radiation. Long term follow up of prior clinical trials have confirmed the roles and length of chemotherapy (mainly temozolomide) in different tumors, as well as the wearable novottf device. New oral isocitrate dehydrogenase inhibitors have also shown efficacy in clinical trials.

Distinct imaging patterns of pseudoprogression in glioma patients following proton versus photon radiation therapy.

PURPOSE: Criteria by the Radiologic Assessment in Neuro-Oncology (RANO) group outline the diagnosis of pseudoprogression (Ps) after photon therapy for gliomas based on timing and location. We noted that patients receiving proton therapy manifested radiographic changes that appear different than Ps after photon therapy, which could be interpreted as tumor progression. In this study, we retrospectively reviewed MR imaging after proton or photon radiation for gliomas. We propose criteria to characterize proton pseudoprogression (ProPs) as distinct from Ps seen after photons. METHODS: Post-treatment MR imaging, clinical and pathological data of low grade glioma patients were reviewed. Overall, 57 patients receiving protons were reviewed for the presence of ProPs, and 43 patients receiving photons were reviewed for any equivalent imaging changes. Data collected included the location and timing of the new enhancement, tumor grade, molecular subtype, chemotherapy received, and clinical symptoms. RESULTS: Fourteen patients (24.6%) had new enhancement following radiation therapy that was unique to treatment with protons. The mean time to development of the ProPs was 15.4 months (7-27 months). We established the following criteria to characterize ProPs: located at the distal end of the proton beam; resolves without tumor-directed therapy; and subjectively multifocal, patchy, and small (< 1 cm). In the group receiving photons, none had changes that met our criteria for ProPs. CONCLUSION: Patients who receive protons have unique imaging changes after radiation therapy. ProPs could be mistaken for tumor progression, but typically resolves on follow up. Further studies are needed to understand the radiobiology and pathophysiology underlying these imaging changes.

A single-center retrospective analysis of outcome measures and consolidation strategies for relapsed and refractory primary CNS lymphoma.

BACKGROUND: Relapsed or refractory primary CNS lymphoma (rrPCNSL) is a rare and challenging malignancy for which better evidence is needed to guide management. METHODS: We present a retrospective cohort of 66 consecutive patients with rrPCNSL treated at the University of Washington between 2000 and 2020. Immunosuppressed and secondary CNS lymphoma patients were excluded. RESULTS: During a median follow-up of 40.5 months from initial diagnosis, median OS for relapsed disease was 14.1 (0.2-88.5) months and median PFS was 11.0 (0.2-73.9) months. At diagnosis (r2 = 0.85, p < 0.001), first relapse (r2 = 0.69, p < 0.001), multiple relapses (r2 = 0.97, p < 0.001) PFS was highly correlated with OS. In contrast, there was no correlation between the duration of subsequent progression-free intervals. No difference in PFS or OS was seen between CSF or intraocular relapse and parenchymal relapse. Patients reinduced with high-dose methotrexate-based (HD-MTX) regimens had an overall response rate (ORR) of 86.7%. Consolidation with autologous stem cell transplant (ASCT) was associated with longer PFS compared to either no consolidation (p = 0.01) and trended to longer PFS when compared to other consolidation strategies (p = 0.06). OS was similarly improved in patients consolidated with ASCT compared with no consolidation (p = 0.04), but not compared with other consolidation (p = 0.22). Although patients receiving ASCT were younger, KPS, sex, and number of recurrences were similar between consolidation groups. A multivariate analysis confirmed an independent effect of consolidation group on PFS (p = 0.01), but not OS. CONCLUSIONS: PFS may be a useful surrogate endpoint which predicts OS in PCNSL. Consolidation with ASCT was associated with improved PFS in rrPCNSL.

Radiation Necrosis from Stereotactic Radiosurgery-How Do We Mitigate?

OPINION STATEMENT: Intracranial stereotactic radiosurgery (SRS) is an effective and convenient treatment for many brain conditions. Data regarding safety come mostly from retrospective single institutional studies and a small number of prospective studies. Variations in target delineation, treatment delivery, imaging follow-up protocols and dose prescription limit the interpretation of this data. There has been much clinical focus on radiation necrosis (RN) in particular, as it is being increasingly recognized on follow-up imaging. Symptomatic RN may be treated with medical therapy (such as corticosteroids and bevacizumab) with surgical resection being reserved for refractory patients. Nevertheless, RN remains a challenging condition to manage, and therefore upfront patient selection for SRS remains critical to provide complication-free control. Mitigation strategies need to be considered in situations where the baseline risk of RN is expected to be high-such as large target volume or re-irradiation. These may involve reduction in the prescribed dose or hypofractionated stereotactic radiation therapy (HSRT). Recently published guidelines and international meta-analysis report the benefit of HSRT in larger lesions, without compromising control rates. However, careful attention to planning parameters and SRS techniques still need to be adhered, even with HSRT. In cases where the risk is deemed to be high despite mitigation, a combination approach of surgery with or without post-operative radiation should be considered.

Leptomeningeal Metastases.

OPINION STATEMENT: Treatment options for leptomeningeal metastases are expanding with greater tolerability and efficacy than in the past. Improved knowledge of molecular subtypes of some cancers can guide in choosing more effective therapeutic options; however, physicians should be mindful that these molecular types can be different in the central nervous system compared to the rest of the body. This is particularly true in breast and lung cancer, in which some patients now can live for many months or even years after diagnosis of leptomeningeal metastases. Options for intrathecal therapies are expanding, but physicians should be mindful that this is a passive delivery system that relies on normal CSF flow, so therapies will not penetrate bulky or parenchymal disease sites, especially in the presence of abnormal CSF flow. When chemotherapeutic options are lacking or unsuccessful, focal radiosurgery which can provide symptomatic relief and proton craniospinal radiation remain effective options. Hopefully more formal studies will be conducted in the future to verify which treatments are indeed most effective for particular types of cancer.

ONC201 (Dordaviprone) in Recurrent H3 K27M-Mutant Diffuse Midline Glioma.

PURPOSE: Histone 3 (H3) K27M-mutant diffuse midline glioma (DMG) has a dismal prognosis with no established effective therapy beyond radiation. This integrated analysis evaluated single-agent ONC201 (dordaviprone), a first-in-class imipridone, in recurrent H3 K27M-mutant DMG. METHODS: Fifty patients (pediatric, n = 4; adult, n = 46) with recurrent H3 K27M-mutant DMG who received oral ONC201 monotherapy in four clinical trials or one expanded access protocol were included. Eligible patients had measurable disease by Response Assessment in Neuro-Oncology (RANO) high-grade glioma (HGG) criteria and performance score (PS) ≥60 and were ≥90 days from radiation; pontine and spinal tumors were ineligible. The primary end point was overall response rate (ORR) by RANO-HGG criteria. Secondary end points included duration of response (DOR), time to response (TTR), corticosteroid response, PS response, and ORR by RANO low-grade glioma (LGG) criteria. Radiographic end points were assessed by dual-reader, blinded independent central review. RESULTS: The ORR (RANO-HGG) was 20.0% (95% CI, 10.0 to 33.7). The median TTR was 8.3 months (range, 1.9-15.9); the median DOR was 11.2 months (95% CI, 3.8 to not reached). The ORR by combined RANO-HGG/LGG criteria was 30.0% (95% CI, 17.9 to 44.6). A ≥50% corticosteroid dose reduction occurred in 7 of 15 evaluable patients (46.7% [95% CI, 21.3 to 73.4]); PS improvement occurred in 6 of 34 evaluable patients (20.6% [95% CI, 8.7 to 37.9]). Grade 3 treatment-related treatment-emergent adverse events (TR-TEAEs) occurred in 20.0% of patients; the most common was fatigue (n = 5; 10%); no grade 4 TR-TEAEs, deaths, or discontinuations occurred. CONCLUSION: ONC201 monotherapy was well tolerated and exhibited durable and clinically meaningful efficacy in recurrent H3 K27M-mutant DMG.

Paraneoplastic Neurologic Syndromes.

OBJECTIVE: Progress is ongoing in understanding paraneoplastic neurologic disorders, with new syndromes and antibodies being described and more detailed evidence available to guide workup for diagnosis and treatment to improve outcomes. Many excellent reviews have summarized the molecular features of different antibodies, but this article emphasizes the clinical features of each syndrome that may help guide initial diagnosis and treatment, which often should occur before an antibody or cancer is found to confirm the diagnosis. LATEST DEVELOPMENTS: Recent findings include updated diagnostic criteria with validated sensitivity and specificity, discovery of novel antibodies, and clinical findings that increase the likelihood of an underlying paraneoplastic disorder. Suggestive syndromes that have been recently identified include faciobrachial dystonic seizures and pilomotor auras in anti-leucine-rich glioma inactivated protein 1 encephalitis, extreme delta brush on EEG in N-methyl-d-aspartate (NMDA)-receptor encephalitis, déjà vu aura in anti-glutamic acid decarboxylase 65 (GAD65) encephalitis, and sleep disturbances in several disorders. In addition, there is confirmed utility of brain positron emission tomography (PET) and CSF markers, including carcinoembryonic antigen and oligoclonal bands, as well as improved tests for the presence of leptomeningeal cancer cells in CSF. Associations of cancer immunotherapies with paraneoplastic syndromes and herpes simplex virus encephalitis (and COVID-19) with NMDA-receptor encephalitis have been described. ESSENTIAL POINTS: All neurologists should be aware of advances regarding paraneoplastic neurologic syndromes, as patients can present with a wide variety of neurologic symptoms and earlier diagnosis and treatment can improve outcomes.

Temporalis muscle thickness predicts early relapse and short survival in primary CNS lymphoma.

Background: Most patients with primary CNS lymphoma (PCNSL) achieve durable remission whereas a minority die in the first year. Sarcopenia is a powerful predictor of mortality in the brain and systemic cancers. Temporalis muscle thickness (TMT) is a validated radiographic measure of sarcopenia. We hypothesized that patients with thin TMT at diagnosis would have early progression and short survival. Methods: Two blinded operators retrospectively measured TMT in 99 consecutive brain MRIs from untreated patients with PCNSL. Results: We generated a receiver operator characteristic curve and chose a single threshold defining thin TMT in all patients as <5.65 mm, at which specificity and sensitivity for 1-year progression were 98.4% and 29.7% and for 1-year mortality were 97.4% and 43.5% respectively. Those with thin TMT were both more likely to progress (P < .001) and had higher rates of mortality (P < .001). These effects were independent of the effect of age, sex, and Eastern Cooperative Oncology Group performance status in a cox regression. Memorial Sloan Kettering Cancer Center score did not predict progression-free survival or overall survival as well as TMT. Patients with thin TMT received fewer cycles of high-dose methotrexate and were less likely to receive consolidation but neither variable could be included in the Cox regression due to violation of the proportional hazards assumption. Conclusions: We conclude that PCNSL patients with thin TMT are at high risk for early relapse and short survival. Future trials should stratify patients by TMT to avoid confounding.

EBV-positive PCNSL in older patients: incidence, characteristics, tumor pathology, and outcomes across a large multicenter cohort.

The objective of this multicenter retrospective study was to examine the incidence, patient characteristics, pathology, and outcomes associated with Epstein-Barr virus (EBV)-related CNS lymphoma (CNSL) in older patients. Among 309 CNSL patients aged ≥60, 11.7% had EBV + tumors of which 72.2% were solid organ transplant (SOT)-related post-transplant lymphoproliferative disorders (PTLD). Younger age, SOT or autoimmune disease, and immunosuppressive treatment correlated highly with EBV-positivity. EBV + tumors were associated with absent C-MYC and BCL6 expression. EBV + PTLD was more likely to be associated with the absence of CD5 expression. EBV + non-PTLD had better median OS (not reached) compared to EBV + PTLD (10.8 months) and EBV-negative patients (43 months). Multivariable Cox regression analysis showed that age, performance status, and PTLD were negative predictors of OS. EBV status and immunosuppressive treatment were not correlated with OS. Our findings merit further investigation of EBV + PCNSL tumors and EBV-directed therapies.

Use of recombinant tissue plasminogen activator in cancer patients with acute stroke.

People with cancer may be at increased risk for stroke, especially of cardioembolic and large vessel origin. Some clinicians are reluctant to use recombinant tissue plasminogen activator (rTPA) in the cancer population due to safety concerns. We conducted a retrospective review of patients who received rTPA for acute stroke at an academic cancer center. We report six patients with cancer treated with rTPA at our institution, four of whom had early neurologic recovery. Only one of our six patients suffered minor bleeding as a complication of rTPA. Acute stroke in patients with cancer may be treated with rTPA, and active cancer should not be considered an absolute contraindication to rTPA use.

Identifying the palliative care needs of patients living with cerebral tumors and metastases: a retrospective analysis.

Primary tumors and metastatic involvement of the central nervous system (CNS) lead to a multitude of symptoms and care needs. Patients and caregivers struggle with physical and psychological impairments, a shortened life expectancy and diverse palliative care needs. This study assesses the symptom burden and palliative care needs of patients with primary brain tumors and with metastatic brain tumors requiring inpatient hospital care. It is a retrospective analysis of patients with primary CNS tumors or cerebral metastases over a 6 month period. The data analysed included physical symptom burden and end of life care decisions such as health care proxy, transition to hospice and do-not-resuscitate orders. Hundred and sixty eight patients were included. The most common symptoms were gait impairment (65.5 %), cognitive/personality change (61.9 %), motor deficits (58.3 %), seizures (57.1 %) and delirium (27.4 %). Of the patients that died, 79 % had an appointed health care proxy, 79 % had hospice discussions, 70 % had a do-not-resuscitate order and 24 % received cancer directed therapy in the last month of life. There is a role for more aggressive palliative care support in patients living with primary or metastatic brain tumors.

Prospective biomarker study in newly diagnosed glioblastoma: Cyto-C clinical trial.

BACKGROUND: Glioblastoma (GBM) has a 5-year survival rate of 3%-5%. GBM treatment includes maximal resection followed by radiotherapy with concomitant and adjuvant temozolomide (TMZ). Cytochrome C oxidase (CcO) is a mitochondrial enzyme involved in the mechanism of resistance to TMZ. In a prior retrospective trial, CcO activity in GBMs inversely correlated with clinical outcome. The current Cyto-C study was designed to prospectively evaluate and validate the prognostic value of tumor CcO activity in patients with newly diagnosed primary GBM, and compared to the known prognostic value of MGMT promoter methylation status. METHODS: This multi-institutional, blinded, prospective biomarker study enrolled 152 patients with newly diagnosed GBM who were to undergo surgical resection and would be candidates for standard of care. The primary end point was overall survival (OS) time, and the secondary end point was progression-free survival (PFS) time. Tumor CcO activity and MGMT promoter methylation status were assayed in a centralized laboratory. RESULTS: OS and PFS did not differ by high or low tumor CcO activity, and the prognostic validity of MGMT promoter methylation was confirmed. Notably, a planned exploratory analysis suggested that the combination of low CcO activity and MGMT promoter methylation in tumors may be predictive of long-term survival. CONCLUSIONS: Tumor CcO activity alone was not confirmed as a prognostic marker in GBM patients. However, the combination of low CcO activity and methylated MGMT promoter may reveal a subgroup of GBM patients with improved long-term survival that warrants further evaluation. Our work also demonstrates the importance of performing large, multi-institutional, prospective studies to validate biomarkers. We also discuss lessons learned in assembling such studies.

Primary central nervous system lymphoma: is there still a role for radiotherapy?

PURPOSE OF REVIEW: Adding high-dose methotrexate to whole-brain radiotherapy improves survival in primary central nervous system lymphoma. However, the high neurotoxicity rates observed, especially in the elderly, raised interest in exploring other alternatives such as reduced-dose radiotherapy and chemotherapy-only treatments. RECENT FINDINGS: Phase II studies suggested that omitting radiotherapy decreases progression-free survival (PFS) but not overall survival. A randomized phase III trial testing chemotherapy with/without radiation found similar results. However, interpretation of that trial has been difficult because of the chemotherapy regimen used (methotrexate with/without ifosfamide), intrinsic methodological problems and lack of neuropsychological evaluation. It also remains unclear whether chemotherapy-only treatments could ultimately result in worse cognitive outcomes in comparison with combined chemotherapy and radiotherapy because the higher rates of relapses could result in additional neurotoxicity from salvage treatments and brain damage by relapsing tumor. Given differences in relapses and neurotoxicity rates according to age, it is also unclear how results apply to younger versus older patients. SUMMARY: Given the lack of better data, omitting radiotherapy currently seems a justifiable choice in routine practice, particularly in the elderly, but the question remains unsettled. Ongoing studies are investigating other consolidation options, including reduced-dose radiotherapy and high-dose chemotherapy with stem-cell rescue, aiming at improving disease control and decreasing neurotoxicity.

Herpes simplex encephalitis in patients with cancer.

Case reports and animal models suggest that chemotherapy, corticosteroids and radiotherapy (RT) may increase the risk of herpes simplex encephalitis (HSE). We retrospectively examined cases of HSE at an academic hospital devoted to cancer care. Patients were identified by positive herpes simplex virus (HSV) polymerase chain reaction (PCR) in cerebrospinal fluid (CSF) or by brain pathology. There were seven patients with HSE over a 12 year period, four of whom had received cranial RT. During this time, a total of 997 patients were treated with cranial RT, suggesting a greater incidence than the expected risk of two to four cases per million people per year in the general population. Five patients had recently received chemotherapy and three were on dexamethasone. MRI findings were typical; four patients had bilateral anterior temporal lesions and three had unilateral-temporal lesions. Four patients had a normal CSF white blood cell count, three of whom had prior RT and dexamethasone. Four patients were positive for HSV-1, and two for HSV-2. One patient had a negative CSF PCR for HSV, but autopsy confirmed active HSE. Though still rare, the risk of HSE may be increased in patients with cancer, especially in those receiving cranial RT. MRI findings were typical, but CSF white blood cell count was normal in four patients and one had negative CSF testing, suggesting that CSF results may be misleading in this population.

Overview of prognostic factors in adult gliomas.

Gliomas represent the majority of malignant central nervous system tumors, with the most aggressive subtype, glioblastoma, accounting for almost 57% of this entity. Type of glioma and its incidence can vary depending on the age of presentation. In turn, outcomes can vary significantly based on the actual type of glioma (histologically and molecularly) and age of the patient, as well as various tumor specific factors such as size, location, comorbidities, etc. In the last decade we have been able to identify key molecular features that have provided us with greater insight into the behavior of these tumors, but the spectrum of treatment options remains limited. In addition, ultimate causes of death in patients with gliomas are variable and stochastic in nature. Given these complicated factors, prognostication for gliomas remains extremely difficult. This review aims to discuss prognostication in low grade versus high grade gliomas, variability in treatment of these tumors, clinical features of poor prognosis, and differences in prognostic understanding between patients, caregivers, and providers. We will also make some general recommendations where appropriate on how to approach this subject from a palliative care perspective.

Distinguishing and treating depression, anxiety, adjustment, and post-traumatic stress disorders in brain tumor patients.

Cancer patients often suffer from psychiatric disorders as a result of their disease and its treatment. Rates of depression, anxiety, adjustment, and post-traumatic stress disorders are particularly high for individuals with cancer and differentiating between these conditions is important for providing both appropriate and high-quality care. Patients with primary and metastatic brain tumors are particularly susceptible to psychiatric morbidities as a result of direct neuropsychiatric effects from the tumor itself, as well as psychological distress stemming from their diagnosis, prognosis, or treatment. However, these morbidities are often underdiagnosed, misdiagnosed, and undertreated. Many tools exist for screening, diagnosing, and treating psychiatric disorders in brain tumor patients, and palliative care settings are well suited to both identify and treat psychiatric disorders in brain tumor patients. This review summarizes our current knowledge of psychiatric disorders in patients in patients with brain tumors, highlights the susceptibility of brain tumor patients to psychiatric conditions, provides recommendations for differentiating and treating these conditions, and emphasizes the need for further research. The goal of this review is to inform healthcare providers of the opportunities to address psychiatric morbidities in patients with primary and metastatic brain tumors, particularly in palliative care settings, and identify areas in need of additional research.

Legal assistance in dying for people with brain tumors.

The number of countries and states that have legalized assistance in dying under various names (Medical Assistance in Dying, Death with Dignity, etc.) has continued to grow in recent years, allowing this option for more patients. Most of these laws include restrictions for eligibility based on a terminal diagnosis and estimated prognosis, as well as asking certifying providers to attest to the cognitive and psychiatric competence and capacity of patients requesting access. Some laws also require that patients must be able to 'self-administer' the regimen, though details vary. Such determinations can be vague and difficult to clearly apply to patients with neurologic conditions and primary or metastatic brain tumors. There is currently a lack of rigorous studies guiding providers on how to apply these important legal criteria to this special and common patient population. As access to legal assistance in dying expands, more research is needed on how to ethically apply the laws and guide patients, families and providers through the process.