Publications from the Li Lab

View details for DOI 10.1007/s11060-025-05405-2

View details for PubMedID 41533247

View details for PubMedCentralID 1735225

Abstract

Diffuse midline gliomas, including diffuse intrinsic pontine gliomas, represent one of the most aggressive pediatric malignancies in the central nervous system with a uniformly poor prognosis. They can be consistently identified by mutations in histone H3 K27M, which are associated with aggressive tumor biology, marked resistance to therapies, and abysmal survival. The current review critically assesses the existing application of immunotherapeutic modalities in DMGs, emphasizing biological hurdles in efficacy, translation methodologies, and prospects in attaining sustained responses.We examined preclinical and early clinical studies in DMGs for immune therapies such as peptide vaccines against H3K27M antigens, chimeric antigen receptor T-cell therapies, immune checkpoint modulation, and radioimmunotherapy. Current developments in the interface of cancer neuroscience and tumor interaction with neurons were incorporated in a manner relevant to immune suppression in the microenvironment of DMG. Although these tumors have traditionally shown poor immune reactivity because of low tumor mutational burden, immune-privileged sites, and a strongly suppressive tumor microenvironment, a variety of different immune therapeutic approaches have shown promising early efficacy. Of particular interest are neoantigen-targeted vaccines and CAR T-cell therapy using surface antigens. Preliminary findings suggest an important role for neuron-glioma synaptic and paracrine signaling in mediating tumor progression and immune evasion.Immunotherapy for DMGs is moving from a conceptual state to a translational reality. A better understanding of the realm of tumor immune-neural crosstalk, combination therapies, and immune biology in pediatric patients will be critical in addressing resistance and providing durable control for these aggressive malignancies.

View details for DOI 10.1007/s11060-025-05347-9

View details for PubMedID 41460355

View details for PubMedCentralID 9533228

View details for DOI 10.1227/neuprac.0000000000000169

View details for Web of Science ID 001577502000001

Abstract

Occipital condyle metastasis (OCM) is a rare condition characterized by severe occipital pain and neurological symptoms due to lower cranial nerve (CN) deficits, stemming from its anatomic location. Despite the widespread use of stereotactic radiosurgery (SRS) for cranial metastases, its specific impact on OCM remains underexplored. This study evaluates the efficacy and safety of CyberKnife SRS in treating OCM, focusing on occipital pain, dysfunctions of lower CNs, and local tumor control.We retrospectively analyzed cases of OCM treated with SRS at our institute from 2012 to 2023, evaluating patient demographics, presenting symptoms, treatment parameters, and outcomes.Eighteen patients (10 females) with a mean age of 64 years (SD: 10.4) were treated. Common presentations included occipital pain (44.4%) and lower CN deficits (27.8%). The median target volume was 6.95 cc (IQR: 4.64-21.2). The mean single-fraction equivalent dose was 18.7 Gy10 (SD: 1.9). Ten tumors received 15-20 Gy in 1 fraction (50%), 2 tumors received 20-28 Gy in 2 fractions (10%), 4 tumors received 27 Gy in 3 fractions (20%), and 4 tumors received 30-40 Gy in 5 fractions (20%). Based on Kaplan-Meier estimate, SRS achieved 93.8% local tumor control rate over 3 years, with a median overall survival of 13 months (95% CI: 0-32.2). Among patients presenting with symptoms, 87.5% reported occipital pain relief (P = .04), and 80% observed improvements in CN function (P = .003). Four patients experienced local recurrence.CyberKnife SRS is a promising treatment of OCM, offering significant pain relief and improvement in neurological symptoms, along with favorable local control rates. This noninvasive therapy provides a valuable alternative to surgery, potentially enhancing the quality of life for patients with limited treatment options due to this challenging condition.

View details for DOI 10.1227/neuprac.0000000000000169

View details for PubMedID 41163734

View details for PubMedCentralID PMC12560716

Abstract

Combining focused ultrasound (FUS)-induced blood-brain barrier opening with bevacizumab (BEV) has demonstrated survival benefits in preclinical models. This study aimed to evaluate the safety and feasibility of repeated FUS-BEV treatments in patients with recurrent glioblastoma and to explore imaging and serum biomarkers in relation to disease status.This was a prospective, single-arm, open-label pilot trial. The primary end point was 6-month progression-free survival (PFS). Disease progression was assessed according to the Response Assessment in Neuro-Oncology criteria by independent radiological review. Radiological response was evaluated using fluid-attenuated inversion-recovery sequences to compare FUS-exposed vs nonexposed regions. Plasma cell-free DNA (cfDNA) concentrations were measured before and after FUS treatment.Between July 2020 and August 2023, 6 patients received a median of 14.5 sessions of biweekly FUS-BEV (10 mg/kg). The median PFS was 11 months, with a 6-month PFS rate of 66.7%. The only FUS-related adverse event was transient scalp heating (grade 1; 1.9%). A fluid-attenuated inversion recovery normalization effect emerged within 1 month after treatment. Plasma cfDNA increased significantly post-FUS, with total cfDNA rising 2.03 ± 0.76-fold, EGFR cfDNA 1.77 ± 0.76-fold, and HMBS cfDNA 1.68 ± 0.66-fold.Repeated FUS-BEV treatment is safe and feasible in patients with recurrent glioblastoma. Randomized controlled trials are warranted to confirm its therapeutic efficacy and validate imaging and liquid biopsy biomarkers.

View details for DOI 10.1227/neu.0000000000003851

View details for PubMedID 41283685

View details for DOI 10.1093/neuonc/noaf201.1765

View details for Web of Science ID 001613221000013

View details for DOI 10.1093/neuonc/noaf201.0195

View details for Web of Science ID 001613247800006

View details for DOI 10.1093/neuonc/noaf201.1782

View details for Web of Science ID 001614383800038

View details for DOI 10.1093/neuonc/noaf201.0812

View details for Web of Science ID 001612037600022

View details for DOI 10.1093/neuonc/noaf201.0044

View details for Web of Science ID 001612039700001

Abstract

Hypoglossal schwannomas (HSs) are rare benign tumors originating from Schwann cells of cranial nerve XII. While surgery has been the primary treatment, stereotactic radiosurgery (SRS) is emerging as an effective alternative. This study evaluates the clinical characteristics, treatment strategies, and outcomes of HS patients managed with SRS, resection, or observation.A retrospective analysis was conducted on the medical records of HS patients treated at the authors' institution from 1999 to 2024. Collected data included demographic, clinicopathologic, radiological, and treatment details. Outcomes evaluated were local tumor control (LTC), progression-free survival, overall survival, adverse events, symptom resolution, and hypoglossal nerve deficits. A literature review adhering to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines supplemented the analysis.The cohort included 16 patients (63% female) with 20 HS tumors. SRS was performed in 10 tumors (50%), demonstrating superior LTC (100%) over a 4- to 17-year follow-up. Symptom resolution was observed in 86% of SRS cases, and hypoglossal nerve deficits were minimized. No severe complications were reported in the SRS group, with only grade 1 adverse events noted. Resection, performed in 7 cases (35%), was associated with significant complications, including cranial nerve deficits and higher adverse event rates. The surgery group exhibited a declining LTC over time: 83% at 2 years, 63% at 4 years, and 42% at 10 years. Observation was chosen for 3 tumors (15%) with stable outcomes during follow-up.SRS provides excellent long-term control of HS with significant symptom resolution and low recurrence rates in the authors' cohort, supporting its use as a primary treatment modality in selected patients for small and medium-sized schwannomas, particularly when a minimally invasive approach is preferred.

View details for DOI 10.3171/2025.6.JNS242975

View details for PubMedID 41172365

Abstract

We report outcomes of repeat stereotactic radiosurgery (rSRS) to sites of tumor progression following initial SRS. Additionally, we sought to determine if, at the time of recurrence following initial SRS, surgical resection of the tumor followed by SRS (surgery + rSRS) provided benefit compared to rSRS alone.We retrospectively reviewed patients treated with rSRS for local recurrence after initial SRS. The cumulative incidences of LF and adverse radiation effect (ARE), with death as a competing risk, were estimated.From 2004 to 2022, we identified 77 patients with 429 brain metastases treated with initial SRS, of which 97 metastases were treated with rSRS for salvage of LF following initial SRS; 49 metastases had resection prior to rSRS. Of the 429 brain metastases treated with initial SRS, the cumulative incidence of LF was 12.6% [95% confidence interval (CI) 9.7-15.9] at 1 year; in 97 sites treated with rSRS, LF was 14.6% (95%CI 8.4-22.4) at 1 year. There was no significant difference (p = 0.3) in 1-year LF after surgery + rSRS [11.1% (95%CI 4.0-22.31)] versus rSRS alone [18.4% (95%CI 9.0-30.5)]. The 1-year rates of ARE were: 3.0% (95%CI 1.7-5.0%) for initial SRS (overall grade 1-4), 15.6% (95%CI 9.2-23.6) for rSRS (overall grade 1-4), and 12.6% (95%CI 6.8-20.1%) for rSRS (symptomatic grade 2-4).Given that the 1-year local progression of 15% with rSRS is similar to the 13% of initial SRS, our data do not support that tumors recurrent after initial SRS are inherently radioresistant to salvage SRS. Tumor control must be balanced by the 1-year rates of adverse radiation effect (16% overall, 13% symptomatic).

View details for DOI 10.1007/s11060-025-05201-y

View details for PubMedID 40914931

View details for PubMedCentralID 5737512

View details for DOI 10.1007/s11060-025-05178-8

View details for PubMedID 40844729

View details for PubMedCentralID 10883934

Abstract

Adenoid cystic carcinoma (ACC) is a rare, aggressive malignancy with a predilection for perineural spread and distant metastases. Given the limited but emerging evidence on the role of stereotactic radiosurgery (SRS) in managing intracranial and spinal ACC, a systematic review was deemed necessary to synthesize relevant parameters related to clinical features and management of ACC patients, SRS treatment characteristics, and clinical outcomes across published studies.This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search of the PubMed, Scopus, and Embase databases was performed to identify studies evaluating patients with histologically confirmed diagnoses of intracranial and/or spinal ACC who were treated with SRS. Additionally, a unique illustrative case was presented.A total of 129 patients and 211 lesions with ACC were identified from 16 studies published between 1992 and 2025. Patient ages ranged from 10 to 85 years. Lesions were mostly in the intracranial space (n = 194; 91.9%), followed by the spinal column (n = 17; 8.1%). Standalone SRS was administered as primary treatment in 108 lesions (57.1%). Six of eight studies documented a median prescription dose ≥ 15 Gy, while the mean calculated dose among case reports/series with individualized data was 20.8 Gy (SD = 10.4 Gy). Two of four studies recorded a median maximum tumor dose ≥ 30 Gy. Most treatment plans were delivered in a single fraction. Local tumor control (LTC) was achieved in 210/211 lesions (99.5%) over time, although 32/201 lesions eventually experienced local failure (15.9%). LTC duration ranged from 1 to 326 months, and overall survival ranged from 0 to 354 months. A 43-year-old male with concurrent intracranial and spinal ACC treated with CyberKnife SRS is presented.SRS offers favorable LTC for intracranial and spinal ACC, supporting its role as a precise, advanced radiation modality in this challenging context.

View details for DOI 10.1007/s11060-025-05175-x

View details for PubMedID 40699525

View details for PubMedCentralID 11782928

Abstract

BACKGROUND AND OBJECTIVES: Paragangliomas (PGLs) are rare neuroendocrine tumors which frequently occur in the head and neck. Mutations in subunits of the succinate dehydrogenase complex (SDHx) account for approximately 50% of hereditary PGLs and are associated with increased rates of malignancy, recurrence, and multifocality. While the use of stereotactic radiosurgery (SRS) for PGLs has expanded, there is a lack of data correlating genetic background with outcomes in this distinct patient population. We aimed to evaluate the safety and efficacy of SRS, specifically long-term local control and treatment-related complications, for management of the 3 major subtypes of SDHx-related PGL.METHODS: Patients with confirmed SDHx-related PGL who underwent SRS at a single institution were retrospectively reviewed. Lesions were stratified based on location and affected SDHx gene. Primary endpoints were local control, overall survival, and symptom improvement. The secondary endpoint was treatment-related adverse events. To contextualize our results, a review of prior studies assessing SRS for head and neck PGL was performed.RESULTS: Five female and 2 male patients with SDHx mutations received SRS for 10 total PGLs during the study period. Median age at PGL diagnosis was 32years (range: 16-56), with a median age at SRS treatment of 45.5years (range: 18-59). The cohort included 2 SDHB, 1 SDHC, and 4 SDHD patients. Subtotal resection was performed for 3 of 10 lesions prior to SRS. The glomus jugulare was the most common anatomic site, followed by the carotid body and glomus vagale. Treatment volume and maximum diameter ranged from 0.3 to 30.8cm3 and 11 to 50mm, respectively. Median marginal dose was 21Gy (range: 16-25). Median follow-up was 164, 160, and 21.8months for SDHB, SDHC, and SDHD patients, respectively, with an aggregate local control rate of 100%. Symptom improvement occurred in 80% of cases with preoperative symptoms. A single patient experienced a post-SRS adverse event, late dysphagia, requiring additional treatment. Our systematic review included 9 large SRS studies reporting a total of 593 patients. Median follow-up ranged from 35 to 102months, while the median local control rate was 94.8%.CONCLUSION: To our knowledge, this represents the first analysis correlating genetic subtype of SDHx-related PGL with SRS treatment outcomes. SRS appears to provide durable local control with minimal side effects across the 3 major subtypes of SDHx-related PGL, comparable to prior reports without genetically-defined cohorts. This reaffirms its applicability as a treatment strategy for this hereditary condition.

View details for DOI 10.1016/j.jocn.2025.111387

View details for PubMedID 40513256

View details for DOI 10.1227/neuprac.0000000000000141

View details for Web of Science ID 001487521400001

Abstract

Male breast cancer (MBC) is very rare, and previous reports of brain metastases (BM) from MBC are limited. To date, the genetic characteristics of MBC with BM have not been explored. In addition, there is only a single case report documenting the use of stereotactic radiosurgery (SRS) for MBC BM. The aim of this study was to summarize genetic alterations associated with BM in patients with MBC and evaluate the safety and efficacy of SRS in this population.Four male patients with a total of 20 MBC BMs treated with SRS were retrospectively reviewed. We defined treatment response as complete response, partial response, stable disease, and local progression (LP), per Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The Kaplan-Meier method was used to estimate cumulative incidence rate of LP.The median overall survival was 16.3 months (95% confidence interval: 1.4-31.3 months). The mean age at treatment was 59 years (IQR: 56-60.5 years). Three patients had estrogen receptor-positive lesions, whereas one patient had triple-negative disease. Three patients had notable pathogenic alterations (including in AURKA, BRCA1, BRCA2, CCND1, CHEK2, ERBB2, FLT3, RAF1, and SPINK1). The median lesion size was 5.7 mm (IQR: 3.9-8.6 mm). The median delivered dose was 23 Gy (IQR: 22-24 Gy). Follow-up imaging at 3 months showed a reduction in median lesion size (3.3 mm). The percentage of lesions which were classified as complete response:partial response:stable disease:LP was 0%:45%:55%:0%, respectively. Cumulative 6-month and 12-month local control rates were 100% and 100%, respectively. Only one lesion demonstrated LP at the last follow-up (15 months).This is the first report of genetic profiling of MBC with BM and excellent SRS outcomes. The receptor status and genetic alterations across our patients with MBC BM suggest heterogeneity in disease. Larger studies are needed to further explore MBC BM characteristics and treatment outcomes.

View details for DOI 10.1227/neuprac.0000000000000141

View details for PubMedID 41163992

View details for PubMedCentralID PMC12560722

View details for DOI 10.1200/JCO.2025.43.16_suppl.1614

View details for Web of Science ID 001509470000001

Abstract

We performed a dose escalation trial of hypofractionated stereotactic radiosurgery (SRS) to determine the maximum tolerated dose (MTD) of 3-fraction SRS for brain metastases resection cavities.Following surgical resection of a brain metastasis, patients were enrolled by SRS treatment volume onto 2 arms: Arm 1=4.2-14.1 cm3, approximating a 2-3 cm diameter sphere, and Arm 2=14.2-33.5 cm3 or a 3-4 cm sphere equivalent. Dose escalation levels were 24, 27, 30, and 33 Gy in 3 consecutive-day fractions, with 6 patients at each dose level in a 6 + 6 trial design. Dose-limiting toxicity (DLT) was defined as either acute (within 30 days of SRS) Grade 3-5 CNS toxicity and/or late Grade 3-5 radiation necrosis occurring at any subsequent timepoint. The MTD was defined as the highest dose where 0-1 out of 6 or 0-3 out of 12 had a DLT.From 2009 to 2014, 48 evaluable patients were enrolled. One (2%) patient had acute G3 toxicity; dose escalation proceeded to 33 Gy. No MTD was reached. Overall, 14 (29%) of 48 patients had G1-4 late radiation necrosis; G1 in 4(8%), G2 in 6(13%), G3 in 2(4%), and G4 in 2(4%). At the 33 Gy dose level, any grade necrosis was 58% in all 12 patients, 83% in the 6 patients on the larger volume Arm 2; no G3-4 necrosis occurred in smaller Arm 1 targets. With a median overall survival of 24 months (95% Confidence Interval (CI) 18-35), the 1-year cumulative incidence rates were: 10% (95%CI 3.8-21) for local progression, 48% (95%CI 33-61) for distant intracranial progression, and 13% (95%CI 5-24) for radiation necrosis. Nodular meningeal disease occurred in 15% (7 of 48) of patients.Grade 3-4 toxicity was 8% and no MTD was reached with dose-escalation to 33 Gy in 3 fractions. However, with a 58% incidence of G1-4 radiation necrosis at the 33 Gy level and 33% G3-4 necrosis at 30 Gy on Arm 2, a 3-fraction dose of 27-30 Gy for targets 2 to 3 cm and 27 Gy for targets 3 to 4 cm may provide the optimal balance between toxicity and tumor control. A dose of 33 Gy is reserved for cavities less than 3 cm where tumor control may benefit from higher doses.

View details for DOI 10.1016/j.ijrobp.2025.03.015

View details for PubMedID 40089071

Abstract

For patients with spine metastases, stereotactic radiosurgery (SRS) provides excellent local control and pain response. Despite increasing use of this treatment modality, there is no consensus on the optimal dose and fractionation of spine SRS for efficacy and toxicity. We have initiated a single-center phase III randomized trial that compares two dose regimens with similar biological equivalent dose (BED) to determine the isolated effect of SRS fractionation on local control.Patients with one to three cervical, thoracic, or lumbar spine metastases spanning no more than two contiguous vertebral levels in need of radiation will be eligible for enrollment. Patients will be assigned 1:1 to receive either 22 Gy in 1 fraction or 28 Gy in 2 fractions. Biased coin randomization will be used to randomly assign patients while balancing the following stratifying variables between the two treatment arms at baseline: gastrointestinal histology (yes/no), paraspinal tissue extension (yes/no), epidural compression (low-/high-grade), and number of sites treated (one to three). The primary endpoint is one-year local control, defined per Spine Response Assessment in Neuro-Oncology (SPINO) criteria. The secondary endpoints include patient-reported health-related quality of life (HRQOL), pain associated with the treated site, vertebral compression fracture (VCF), and two-year local control. Patients will be followed for these outcomes at one to two weeks, one month, three months, and six months after treatment, and every six months thereafter until 24 months after treatment. While on the study, patients will receive routine co-interventions as clinically indicated.The studies published thus far comparing the single- and multi-fraction SRS are lacking long-term local control outcomes and are limited by selection bias as well as single-fraction arms with higher BED, which is correlated with improved local control. Our study will isolate the effect of fractionation by comparing one-year local control in patients treated with single- and multi-fraction SRS with equivalent BED. We anticipate that the results of this, as well as secondary endpoints such as pain response, adverse effects, and quality of life will provide much-needed guidance regarding optimal dose and fractionation for both maximizing local control and minimizing toxicity.NCT#06173401. Approved by Stanford Scientific Review Committee (study ID: BRN0060) on 9/12/2023 and Stanford Institutional Review Board (study ID: IRB-72248) on 11/14/2023.

View details for DOI 10.1186/s12885-025-13655-6

View details for PubMedID 39984889

View details for PubMedCentralID PMC11846292

Abstract

Glioblastoma (GBM) is a highly aggressive brain tumor with poor prognosis and high recurrence rates. The complex immune microenvironment of GBM is highly infiltrated by tumor-associated microglia and macrophages (TAM). TAMs are known to be heterogeneous in their functional and metabolic states and can transmit either protumoral or antitumoral signals to glioma cells. Here, we performed bulk RNA sequencing and single-cell RNA sequencing on samples from patients with GBM, which revealed increased ATP synthase expression and oxidative phosphorylation activity in TAMs located in the tumor core relative to the tumor periphery. Both in vitro and in vivo models displayed similar trends of augmented TAM mitochondrial activity, along with elevated mitochondrial fission, glucose uptake, mitochondrial membrane potential, and extracellular ATP (eATP) production by TAMs in the presence of GBM cells. Tumor-secreted factors, including GM-CSF, induced the increase in TAM eATP production. Elevated eATP in the GBM microenvironment promoted glioma growth and invasion by activating the P2X purinoceptor 7 (P2X7R) on glioma cells. Inhibition of the eATP-P2X7R axis attenuated tumor cell viability in vitro and reduced tumor size and prolonged survival in glioma-bearing mouse models. Overall, this study revealed elevated TAM-derived eATP in GBM and provided the basis for targeting the eATP-P2X7R signaling axis as a therapeutic strategy in GBM. Significance: Glioblastoma-mediated metabolic reprogramming in tumor-associated microglia increases ATP secretion that supports cancer cell proliferation and invasion by activating P2X7R, which can be inhibited to attenuate tumor growth.

View details for DOI 10.1158/0008-5472.CAN-24-0018

View details for PubMedID 39618248

View details for DOI 10.1093/neuonc/noae165.0626

View details for Web of Science ID 001362477700002

Abstract

While genetic testing of tumors is commonly used to inform the selection of systemic therapies, there is limited evidence for the application of radiotherapy for brain cancer. Recent studies have shown that Kelch-like ECH-associated protein 1 (KEAP1), a key regulator of cellular responses to oxidative and electrophilic stress, is associated with radioresistance in multiple cancer types. Several studies have reported the clinical significance of KEAP1 mutation in brain metastasis; however, the effect of KEAP1 mutations on radioresponse in meningioma has never been reported.The authors present the case of a 40-year-old female with a KEAP1 mutation-positive atypical meningioma that was initially treated with resection followed by intensity-modulated radiation therapy (IMRT). Recurrence was observed at 15 months, requiring reoperation and adjuvant stereotactic radiosurgery (SRS). An excellent treatment response was observed at 7 months post-SRS with an improvement in reported symptoms, although bevacizumab was required for the resolution of radiation necrosis observed 2 months post-SRS.To the authors' knowledge, this is the first report of KEAP1-mutant meningioma, including its clinical course after comprehensive management. Notably, treatment included multimodal radiotherapy with IMRT followed by SRS. SRS led to an excellent treatment response at the 7-month follow-up. However, radiation necrosis developed after both radiotherapy treatments, suggesting that radiological modification can be beneficial in patients with KEAP1 mutations. https://thejns.org/doi/10.3171/CASE24387.

View details for DOI 10.3171/CASE24387

View details for PubMedID 39250830

Abstract

Regulatory T cells (Tregs) are important players in the tumor microenvironment. However, the mechanisms behind their immunosuppressive effects are poorly understood. We found that CCR6-CCL20 activity in tumor-infiltrating Tregs is associated with greater glycolytic activity and ablation of Ccr6 reduced glycolysis and lactic acid production while increasing compensatory glutamine metabolism. Immunosuppressive activity towards CD8+ T cells was abrogated in Ccr6-/- Tregs due to reduction in activation-induced glycolysis. Furthermore, Ccr6-/- mice exhibited improved survival across multiple tumor models compared to wildtype mice, and Treg and CD8+ T-cell depletion abrogated the improvement. In addition, Ccr6 ablation further promoted the efficacy of anti-PD-1 therapy in a preclinical glioma model. Follow-up knockdown of Ccl20 with siRNA also demonstrated improvement in antitumor efficacy. Our results unveil CCR6 as a marker and regulator of Treg-induced immunosuppression and identify approaches to target the metabolic determinants of Treg immunosuppressive activity.

View details for DOI 10.1158/2326-6066.CIR-24-0230

View details for PubMedID 39133127

Abstract

Cultural competence is important in approaching serious illness communication with diverse patients about goals of care. Culture colors patients' perspectives on many healthcare issues, including end-of-life care, and impacts how clinicians make decisions with patients. Communication about serious neurological illnesses can be additionally challenging due to disease impact on patients' cognition and decision-making abilities. We aim to understand provider experiences regarding cross-cultural serious neurological illness communication with diverse patients and families.Using non-stratified purposive and snowball sampling, we conducted semi-structured interviews with 17 multidisciplinary participants, including neurosurgeons, neurologists, and social workers, who provide care for patients diagnosed with serious neurological disorders, at three hospital settings between 2021 and 2022. We used standard qualitative content analysis methods with dual review.Five themes reflected provider perspectives about serious neurological illness communication with diverse patients and families. Theme 1: providers recognize that patients' personal biases and lived experiences impact attitudes about healthcare and communication. Theme 2: challenges in communication can arise when providers miss chances to identify important cultural values. Theme 3: understanding how to engage with family members is important for effective communication about serious neurological illness. Theme 4: providers want to accommodate patients. Theme 5: cultivating trust builds a strong patientprovider partnership, even when racial or cultural discordance is present.Our study highlights elements of cross-cultural communication and opportunities for providers to approach diverse patients and families within a racial or culturally discordant context. Effective communication, fostered through respecting individual experiences and variation, eliciting cultural perspectives, engaging family, and cultivating trust reflects processes and learned skills required of highquality teams caring for patients with serious neurological conditions.

View details for DOI 10.21037/apm-24-37

View details for PubMedID 39129523

Abstract

Tumor-infiltrating lymphocyte (TIL) hypofunction contributes to the progression of advanced cancers and is a frequent target of immunotherapy. Emerging evidence indicates that metabolic insufficiency drives T cell hypofunction during tonic stimulation, but the signals that initiate metabolic reprogramming in this context are largely unknown. Here, we found that Meteorin-like (METRNL), a metabolically active cytokine secreted by immune cells in the tumor microenvironment (TME), induced bioenergetic failure of CD8+ T cells. METRNL was secreted by CD8+ T cells during repeated stimulation and acted via both autocrine and paracrine signaling. Mechanistically, METRNL increased E2F-peroxisome proliferator-activated receptor delta (PPARδ) activity, causing mitochondrial depolarization and decreased oxidative phosphorylation, which triggered a compensatory bioenergetic shift to glycolysis. Metrnl ablation or downregulation improved the metabolic fitness of CD8+ T cells and enhanced tumor control in several tumor models, demonstrating the translational potential of targeting the METRNL-E2F-PPARδ pathway to support bioenergetic fitness of CD8+ TILs.

View details for DOI 10.1016/j.immuni.2024.07.003

View details for PubMedID 39111315

Abstract

Plasmacytoma, a rare plasma cell disorder, often presents as a solitary or multiple tumors within the bone marrow or soft tissues, typically associated with multiple myeloma. Extramedullary plasmacytomas (EMPs), particularly those located in the external auditory canal (EAC), are exceedingly rare and pose significant treatment challenges given their location, anatomical complexity, and high risk of recurrence.The authors report the case of a 72-year-old male with a history of multiple myeloma, presenting with recurrent left EAC plasmacytoma. After initial conventional radiotherapy for the lesion, a recurrence was documented in 7 years. The patient subsequently underwent stereotactic radiosurgery, which proved successful, leading to complete resolution of the lesion without any long-term adverse effects or radiation-related complications over a 45-month period.This case is a unique instance of utilizing stereotactic radiosurgery for recurrent EMP in the EAC, highlighting its potential as an effective approach in managing complex plasmacytomas.

View details for DOI 10.3171/CASE2479

View details for PubMedID 38710109

View details for PubMedCentralID PMC11076403

Abstract

PURPOSE: Hope is important in serious illnesses, as it has been linked to patient quality of life. We aimed to determine factors associated with lower hope scores among patients with central nervous system (CNS) disease or bone metastases.METHODS: The Adult Dispositional Hope Scale (AHS) is a 12-item questionnaire that measures hope through two qualities: agency (goal-directed energy) and pathways (plan to meet goals). Total scores range from 8 to 64, with higher scores reflecting higher agency and pathways thinking. We prospectively collected scores from patients seen in two radiation oncology clinics at our institution from 10/2022 to 4/2023. The method of least squares to fit general linear models and Pearson's correlation coefficients (PCC) was used to determine relationships between AHS score and socioeconomic and disease factors.RESULTS: Of the 197 patients who responded, median age was 60.5 years (range 16.9-92.5 years), most patients were male (60.9%), white (59.4%), and had malignant disease (59.4%). Median overall AHS score was 54 (range 8-64), and median pathway and agency thinking scores were 27 (range 4-32) and 27 (range 4-32), respectively. Patients who needed an interpreter compared to those who did not had significantly lower overall AHS scores (mean score 45.4 versus 51.2, respectively; p=0.0493) and pathway thinking scores (mean score 21.5 versus 25.7, respectively; p=0.0085), and patients with poorer performance status had significantly worse overall AHS scores (PCC=-0.2703, p=0.0003).CONCLUSION: Patients with CNS disease or bone metastases requiring the use of an interpreter had lower AHS scores, highlighting the possible association of language barriers to hope. Addressing patient language barriers and further studies on the possible association of language barriers to hope may improve hope, quality of life and outcomes among these patients.

View details for DOI 10.1016/j.ijrobp.2023.11.056

View details for PubMedID 38056777

View details for DOI 10.21037/jtd-23-1483

View details for PubMedID 38090286

View details for PubMedCentralID PMC10713290