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.

Management of Brain Metastases from Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Breast Cancer.

In the past 5 years, the treatment options available to patients with HER2+ breast cancer brain metastasis (BCBM) have expanded. The longer survival of patients with HER2+ BCBM renders understanding the toxicities of local therapies even more important to consider. After reviewing the available literature for HER2 targeted systemic therapies as well as local therapies, we present a simplified algorithm for when to prioritize systemic therapies over local therapies in patients with HER2+ BCBM.

Control of exploration, motor coordination and amphetamine sensitization by cannabinoid CB1 receptors expressed in medium spiny neurons.

Activation of cannabinoid 1 receptors (CB1 R) modulates multiple behaviours, including exploration, motor coordination and response to psychostimulants. It is known that CB1 R expressed by either excitatory or inhibitory neurons mediates different behavioural responses to CB1 R activation, yet the involvement of CB1 R expressed by medium spiny neurons (MSNs), the neuronal subpopulation that expresses the highest level of CB1 R in the CNS, remains unknown. We report a new genetically modified mouse line that expresses functional CB1 R in MSN on a CB1 R knockout (KO) background (CB1 R(MSN) mice). The absence of cannabimimetic responses measured in CB1 R KO mice was not rescued in CB1 R(MSN) mice, nor was decreased spontaneous locomotion, impaired instrumental behaviour or reduced amphetamine-triggered hyperlocomotion measured in CB1 R KO mice. Significantly, reduced novel environment exploration of an open field and absence of amphetamine sensitization (AS) measured in CB1 R KO mice were fully rescued in CB1 R(MSN) mice. Impaired motor coordination in CB1 R KO mice measured on the Rotarod was partially rescued in CB1 R(MSN) mice. Thus, CB1 R expressed by MSN control exploration, motor coordination, and AS. Our study demonstrates a new functional roles for cell specific CB1 R expression and their causal link in the control of specific behaviors.

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.

Seasonal variation in the incidence of primary CNS lymphoma.

BACKGROUND: Primary CNS lymphoma is a rare and aggressive cancer that can develop in immunocompetent individuals, but little is known about risk factors and causes of disease. Previous studies have demonstrated seasonal patterns for lymphomas and brain tumors. This study examined the seasonal incidence pattern for primary CNSlymphoma. METHODS: A retrospective review was performed for patients diagnosed with primary CNS lymphoma from 2000 through 2018 at our tertiary referral center. A total of 156 patients were categorized based on month of symptom onset, month of diagnosis, and month of recurrence if they experienced a relapse of their disease. The distributions were then analyzed for seasonal patterns. RESULTS: There was a significant, bimodal seasonal incidence pattern based on month of symptom onset (P < .001), with peaks in July (n = 19) and December (n = 23) and troughs in March (n = 4) and September (n = 5). There were no significant differences in patients' sex, age at presentation, length of follow-up, and progression-free survival across months. There were no seasonal patterns based on month of diagnosis (P = .450) or month of disease recurrence (P = .572). CONCLUSION: The incidence of primary CNS lymphoma has bimodal peaks in midsummer and early winter, which could provide insight into causative agents and mechanisms of disease.

Clinical Imaging for Diagnostic Challenges in the Management of Gliomas: A Review.

Neuroimaging plays a critical role in the management of patients with gliomas. While conventional magnetic resonance imaging (MRI) remains the standard imaging modality, it is frequently insufficient to inform clinical decision-making. There is a need for noninvasive strategies for reliably distinguishing low-grade from high-grade gliomas, identifying important molecular features of glioma, choosing an appropriate target for biopsy, delineating target area for surgery or radiosurgery, and distinguishing tumor progression (TP) from pseudoprogression (PsP). One recent advance is the identification of the T2/fluid-attenuated inversion recovery mismatch sign on standard MRI to identify isocitrate dehydrogenase mutant astrocytomas. However, to meet other challenges, neuro-oncologists are increasingly turning to advanced imaging modalities. Diffusion-weighted imaging modalities including diffusion tensor imaging and diffusion kurtosis imaging can be helpful in delineating tumor margins and better visualization of tissue architecture. Perfusion imaging including dynamic contrast-enhanced MRI using gadolinium or ferumoxytol contrast agents can be helpful for grading as well as distinguishing TP from PsP. Positron emission tomography is useful for measuring tumor metabolism, which correlates with grade and can distinguish TP/PsP in the right setting. Magnetic resonance spectroscopy can identify tissue by its chemical composition, can distinguish TP/PsP, and can identify molecular features like 2-hydroxyglutarate. Finally, amide proton transfer imaging measures intracellular protein content, which can be used to identify tumor grade/progression and distinguish TP/PsP.