Malignant Meningioma Research Articles

AhR and HIF-1α Signaling Pathways in Benign Meningioma under Hypoxia.

The role of hypoxia in benign meningiomas is less clear than that in the malignant meningiomas. Hypoxia-induced transcription factor 1 subunit alpha (HIF-1α) and its downstream signaling pathways play a central role in the mechanism of hypoxia. HIF-1α forms a complex with the aryl hydrocarbon receptor nuclear translocator (ARNT) protein and can compete for ARNT with aryl hydrocarbon receptor (AhR). In this work, the status of HIF-1α- and AhR-dependent signaling pathways was investigated in World Health Organization (WHO) grade 1 meningioma and patient-derived tumor primary cell culture under hypoxic conditions. mRNA levels of HIF-1α, AhR, and of their target genes as well as of ARNT and nuclear receptor coactivator NCOA2 were determined in tumor tissues from patients in whom the tumor was promptly removed either with or without prior endovascular embolization. Using the patient-derived nonembolized tumor primary cell culture, the effects of a hypoxia mimetic cobalt chloride (CoCl2) and an activator of the AhR signaling pathway benzo(α)pyrene (B[a]P) on mRNA levels of HIF-1α, AhR, and their target genes were investigated. Our findings show active functioning of AhR signaling in meningioma tissue of patients with tumor embolization and crosstalk between HIF-1α and AhR signaling in meningeal cells under hypoxia.

P.104 Grade 3 meningioma survival, recurrence and functional outcomes in an international multicenter cohort

Background: Meningiomas are the most common intracranial tumor, graded from 1 (benign) to 3 (malignant). The aim of this study was to identify clinical features associated with overall survival (OS), progression-free survival (PFS) and functional status for malignant meningiomas. Methods: Demographic, clinical and histopathological data from grade 3 intracranial meningioma cases were identified in the clinical databases from seven sites in North America and Europe from 1991-2022. Summary statistics and Kaplan-Meier OS and PFS curves were generated. Results: We identified 108 patients, with a median age 65 years (IQR: 52, 72) and 53.7% were female. Median OS was 109 months (95% CIs: 88, 227), and 5-year OS rate was 65% (95% CIs: 56, 76). Median PFS was 38 months (95% CIs: 24, 56) and 5-year PFS rate was 37% (95% CIs: 28, 49). OS and PFS were significantly lower in patients aged ≥65 years. Median preoperative KPS score was 80 (IQR: 70, 90), postoperatively KPS was 90 (IQR: 70, 98) and 1-year follow-up KPS was 70 (IQR: 50, 80). Conclusions: This study provides robust survival, recurrence and functional data for grade 3 meningiomas in North America and Europe over a 30-year period.

The experience of living with malignant meningioma.

Meningiomas are the most common, primary intracranial tumor and most are benign. Little is known of the rare patient group living with a malignant meningioma, comprising 1-3% of all meningiomas. Our aim was to explore how patients perceived quality of daily life after a malignant meningioma diagnosis. This qualitative explorative study was composed of individual semi-structured interviews. Eligible patients (n=12) were selected based on ability to participate in an interview, from a background population of 23 patients diagnosed with malignant meningioma at Rigshospitalet from 2000 to 2021. We performed an inductive thematic analysis following Braun and Clarke's guidelines. Eight patients were interviewed. The analysis revealed 4 overarching themes: (1) perceived illness and cause of symptoms, (2) identity, roles, and interaction, (3) threat and uncertainty of the future, and (4) belief in authority. The perceived quality of daily life is negatively impacted by the disease. Patients experience a shift in self-concept and close interactions, and some struggle with accepting a new everyday life. Patients have a high risk of discordant prognostic awareness in relation to health-care professionals. We provide a much-needed patient-centered perspective of living with malignant meningioma: quality of life was affected by perception of threat and an uncertainty of the future. Perception of illness and the interpretation of the cause of symptoms varied between subjects, but a common trait was that patients' identity, roles, and interactions were affected. Shared decision-making and a strengthened continuity during follow-up could aid this rare patient group.

Recurrent Anaplastic Meningioma with Metastasis

Meningioma is the commonest primary intracranial tumor in adults, with the majority being benign. Malignant meningioma is exceedingly rare and carries a poor prognosis because of its tendency for local recurrence and distant metastasis. We present the case of a 53 years old male with anaplastic malignant meningioma, which recurred after excision and radiotherapy and later metastasised to pleura, bones and brain. Keywords: Metastatic meningioma, Anaplastic meningioma, Pleural metastasis, Intracranial tumor, Extracranial metastasis

Epidemiology and survival of non-malignant and malignant meningiomas in middle-aged females, 2004-2018.

The incidence of meningioma is disparate to sex: meningiomas are more common in women than in men, especially in middle-aged women. Understanding the epidemiology and survival of middle-aged women with meningiomas would help estimate their public health impacts and optimize risk stratification. Data on middle-aged (35-54 years) female patients with meningiomas between 2004 and 2018 were obtained from the SEER database. Age-adjusted incidence rates per 100 000 population-years were calculated. Kaplan-Meier and multivariate Cox proportional hazard models were utilized in the overall survival (OS) analysis. Data from 18302 female patients with meningioma were analyzed. The distribution of patients increased with age. Most patients were White and non-Hispanic, according to race and ethnicity, respectively. Over the past 15 years, non-malignant meningiomas have shown an increasing trend; however, malignant meningiomas have shown an opposite trend. Older age, Black population, and large non-malignant meningiomas tend to have worse prognoses. Surgical resection improves OS, and the extent of resection is a critical prognostic factor. This study observed an increase in non-malignant meningiomas and a decrease in the incidence of malignant meningiomas in middle-aged females. The prognosis deteriorated with age, in Black people, and with large tumor size. Additionally, the extent of tumor excision was found to be a significant prognostic factor.

Prognostic factors and Doxorubicin involved in malignant progression of meningioma

Meningioma was the most primary intracranial tumor, but the molecular characteristics and the treatment of malignant meningioma were still unclear. Nine malignant progression-related genes based prognostic signatures were identified by transcriptome analysis between benign meningioma and malignant meningioma. The external dataset GEO136661 and quantitative Real-time Polymerase Chain Reaction were used to verify the prognostic factors. has-miR-3605-5p, hsa-miR-664b-5p, PNRC2, BTBD8, EXTL2, SLFN13, DGKD, NSD2, and BVES were closed with malignant progression. Moreover, Doxorubicin was identified by Connectivity Map website with the differential malignant progression-related genes. CCK-8 assay, Edu assay, wound healing assay, and trans-well experiment were used to reveal that Doxorubicin could inhibit proliferation, migration and invasion of IOMM-Lee Cells.

474 Incidence and Risk Factors for Perioperative Stroke Following Resection of Intracranial Tumors: A Nationwide Analysis of 30,951 Cases

INTRODUCTION: Perioperative cerebrovascular accidents (CVA) in neurosurgical patients is a serious complication that may result in permanent neurological deficits. Establishment of associated risk factors allows for mitigation of CVA risk and sequelae. METHODS: The National Surgical Quality Improvement Program (NSQIP) database was queried for cranial tumor excision cases (2015-2019, N = 30,951). Univariate and multivariable analysis of demographic data and comorbidities was used to assess predictive strength of these factors on postoperative CVA. RESULTS: CVA occurred in 1.7% of cases (N = 532). Patients with CVA, on average, were older, frailer, with increased rates of diabetes mellitus, hypertension, and weight loss. In multivariable analysis, predictors of CVA included advanced age (≥75th percentile in cohort)(OR: 1.9, 95% CI: 1.4-2.5), diabetes mellitus (OR: 1.4, 95% CI: 1.1-1.8), hypertension (OR: 1.4, 95% CI: 1.1-1.7), and weight loss (OR: 1.9, 95% CI: 1.1-3.2). Increased proportions of CVA were found among patients with primary malignant brain tumors (46.1%) and meningiomas (32.9%) when compared to all other benign brain tumors (6.6%) and secondary metastatic brain tumors (14.5%)(all p < .001). Elective surgery status was associated with decreased likelihood of CVA (OR: .74, 95% CI: .60-.91). In multivariable analysis, increasing frailty (as measured by mFI-5 and RAI-revised) was associated with increasing likelihood of CVA. CONCLUSIONS: The current study was the largest to identify preoperative risk factors for perioperative stroke after resection of intracranial tumors. Patients with advanced age, multiple comorbidities, and higher frailty scores were significantly more likely to suffer CVA. Frailty (as measured by mFI- and RAI-revised) is a valuable tool for preoperative risk stratification.

Comparative Evaluation of the Possibilities of Radiomic Аnalysis of Magnetic Resonance Imaging in the Differential Diagnostics of Primary Extra-Axial Intracranial Tumors

Purpose of the study. Comparing magnetic resonance imaging (MRI) abilities in differential diagnostic of three types of primary extra‑ axial brain tumors (benign and malignant meningiomas, and neuromas) based on standard semiotics and radiomic features.Patients and methods. Retrospective research included 66 patients with primary extra‑a xial tumors who were divided into two groups: the instructional (39 patients) and the valid (27 patients). MRI was used towards all patients before surgery. The one method of statistical modeling – discriminant analysis – was used to compare the abilities of differential diagnostic based on semiotic features and radiomic parameters.Results. The features of tumor semiotics MRI didn’t allow to differentiate effectively benign and malignant meningiomas. Several parameters were certainly varied for all those tumor types (neuromas, benign and malignant meningiomas). The modelling based on the discriminant analysis demonstrated that radiomic features can be used for primary extra‑a xial tumors differential diagnostic. The area of the radiomic model ROC‑curve took 0.86 which exceeds the result of the model based on semiotic features (AUC 0.78).Conclusion. The best results of the tumors classification by radiomic model demonstrate expediency to continue research the primary extra‑ axial tumors differential diagnostic with support of histogram and textural parameters of MRI imaging.

Prevalence and Influence of Frailty on Hospital Outcomes After Surgical Resection of Spinal Meningiomas

Frailty has been shown to affect patient outcomes after medical and surgical interventions. The Hospital Frailty Risk Score (HFRS) is a growing metric used to assess patient frailty using International Classification of Diseases, Tenth Revision codes. The goal of this study was to investigate the impact of frailty, assessed by HFRS, on health care resource utilization and outcomes in patients undergoing surgery for spinal meningiomas. A retrospective cohort study was performed using the 2016-2019 National Inpatient Sample database. Adult patients with benign or malignant spinal meningiomas, identified using International Classification of Diseases, Tenth Revision, Clinical Modification codes, were stratified by HFRS: low frailty (HFRS <5) and intermediate-high frailty (HFRS ≥5). Patient demographics, hospital characteristics, comorbidities, procedural variables, adverse events, length of stay (LOS), discharge disposition, and cost of admission were assessed. Multivariate regression analysis was used to identify predictors of increased LOS, discharge disposition, and cost. Of the 3345 patients, 530 (15.8%) had intermediate-high frailty. The intermediate-high cohort was significantly older (P < 0.001). More patients in the intermediate-high cohort had ≥3 comorbidities (P < 0.001). In addition, a greater proportion of patients in the intermediate-high cohort experienced ≥1 perioperative adverse events (P < 0.001). Intermediate-high patients experienced greater mean LOS (P < 0.001) and accrued greater costs (P < 0.001). A greater proportion of intermediate-high patients had nonroutine discharges (P < 0.001). On multivariate analysis, increased HFRS (≥5) was independently associated with extended LOS (adjusted odds ratio [aOR], 3.04; P < 0.001), nonroutine discharge (aOR, 1.98; P= 0.006), and increased costs (aOR, 2.39; P= 0.004). Frailty may be associated with increased health care resource utilization in patients undergoing surgery for spinal meningiomas.

Competing Risk Model to Determine the Prognostic Factors and Treatment Strategies for Adult Patients with Malignant Meningioma: a SEER Population-Based Study

Competing Risk Model to Determine the Prognostic Factors and Treatment Strategies for Adult Patients with Malignant Meningioma: a SEER Population-Based Study

Competing Risk Model to Determine the Prognostic Factors and Treatment Strategies for Adult Patients with Malignant Meningioma: a SEER Population-Based Study

Competing Risk Model to Determine the Prognostic Factors and Treatment Strategies for Adult Patients with Malignant Meningioma: a SEER Population-Based Study

Malignant Meningioma: Two Cases Observed at the Hospital Center of Soavinandriana, Antananarivo

Introduction: Meningiomas are tumors formed by arachnoid cells, typically attached to the inner surface of the dura mater. Malignant forms are rare and no case has been reported in the Malagasy literature. The objective of our study is to report two Malagasy cases of malignant meningioma and to discuss the epidemiological and anatomical-clinical particularities of this tumor. Observation: The first patient, a 41-year-old woman, presented with a rapidly progressive intracranial hypertension syndrome. The patient had undergone surgery two years earlier for a grade II meningioma and had no family history of meningioma, neurofibromatosis, or personal history of brain irradiation or head trauma. Her brain scan showed a heterogeneous polylobed left parieto-occipital mass with a meningeal implantation base. The anatomopathological examination of the samples revealed a malignant meningioma. The second patient was a 33-year-old man, operated for grade I meningioma eleven months before admission, with no other personal or family history. The patient was hospitalized for tumor recurrence with signs of intracranial hypertension. The brain computed tomography (CT) scan showed a heterogeneous extra-axial tumor in right temporo-parietal lobe. Surgical excision was performed. On histological examination, a proliferation of tumor cells of meningothelial appearance with papillary architecture was observed, leading to the diagnosis of malignant meningioma. Conclusion: Malignant meningioma is a rare and serious entity. The clinical manifestations are nonspecific and imaging may mimic a low-grade meningioma. The diagnosis of certainty is histological and is based on essentially morphological criteria. The latter condition the overall survival of the patient and the therapeutic conduct.

Resection of Anaplastic Meningioma via Combined Craniofacial Approach

Introduction: Meningiomas are common and mostly benign intracranial tumors but may show a histological progression to malignancy. The mechanism of malignant transformation remains unclear. Malignant meningiomas usually bear a high recurrence rate and unfavorable prognosis; hence, multiple surgical resections are required for the treatmentCase Presentation: A 41-year-old woman with a prior history of craniotomy at another center six years ago with Meningioma Grade 1 presented to our institution with new neurological symptoms. The magnetic resonance image demonstrated a large frontal base mass that extended to the nasal cavity with diffuse contrast enhancement and extensive surrounding edema. A craniofacial approach combined with a bifrontal approach was performed in multistage tumor resection. The tumor and the infiltrated dura were radically removed. The histopathology demonstrated an Anaplastic Meningioma. The patient also underwent radiation therapy.Conclusion: Treatment of recurrent meningioma with anaplastic histology remains challenging because recurrence rates remain high with a poor prognosis.

Safety and efficacy of salvage therapy with laser interstitial thermal therapy for malignant meningioma refractory to cesium-131 brachytherapy: illustrative case.

Anaplastic meningioma are rare, cancerous tumors of the central nervous system that often require multimodal therapy for tumor control. Both laser interstitial thermal therapy (LITT) and brachytherapy with implanted cesium-131 metallic seeds have demonstrated efficacy in the treatment of recurrent and resistant anaplastic meningioma; however, their safety as a dual therapy has never been reported. In this report, the authors present a case of a 53-year-old female who received LITT in combination with brachytherapy after surgical and radiation treatment options had been exhausted. The authors discuss the unique safety concern of thermal injury with this treatment combination and demonstrate their method for the safe administration of these treatments together. Furthermore, the authors provide a review of the literature on LITT as an emerging therapy for anaplastic meningioma. The use of LITT in combination with brachytherapy remains an option for salvage therapy in patients with recurrent meningioma that provides durable local control of tumor.

SPDR-5 ESTABLISHMENT OF A CONTINUOUS CULTURE METHOD FOR MENINGIOMAS AND THE EFFECTS OF THE GREM2-BMP SIGNALLING PATHWAY ON PROLIFERATION AND ANGIOGENESIS

Abstract Purpose Meningiomas are closely related to osteogenesis, including calcification and hyperostosis at the site of attachment. Signaling pathways involved in tumor formation and extension of meningioma have not yet been elucidated. Treatment options include surgical removal and radiotherapy, but there are no reports of effective drug treatment. This is due to the difficulty of culturing non-malignant meningiomas, which has made basic experiments difficult. In this study, we established a continuous culture method for meningiomas and investigated the signaling pathways involved in meningioma growth. Methods 67 consecutive cases of meningiomas treated in our department for three years from Apr, 2019 to March, 2022. Primary continuous culture was performed by modifying the conditional reprogramming (CR) method. Sixty-four cases were studied, excluding three cases in which culture was abandoned due to contamination. The mean age was 62.6 years, Grade 3 (6%), Grade 2 (14%) and Grade 1 (80%). These were used to observe morphology, proliferation and genetic analysis involved in angiogenesis. Results 1) Sustained culture lasted an average of 150 days with no differences between Grades; 2) Inhibition of BMP signaling involved in osteogenesis suppressed cell proliferation regardless of Grade, and the IC50 of the inhibitor suggested the involvement of the receptor ALK3; 3) We identified GREM2 as upstream regulator of BMP signals 4) GREM2 is highly expressed in menigotherial meningiomas and immunostaining showed strong expression around whole and calcified areas. 5) GREM2 expression is negatively correlated with MIB-1 L.I., so overexpression of GREM2 in malignant meningioma cells decreased ID, which is involved in proliferation downstream of BMP signaling, and increased angiogenic factor VEGFA, which is involved in proliferation. Conclusion A method for the continuous culture of meningiomas was established. Using this experimental system, we identified the involvement of the GREM2-BMP signaling pathway in proliferation and angiogenesis in meningiomas as well as calcification.

EXTH-91. GALECTIN-3 INHIBITOR PAIRED WITH FOCAL LOW-INTENSITY NONINVASIVE TDCS CAN ACHIEVE MAXIMAL THERAPEUTIC BENEFIT IN CLINICALLY RELEVANT MENINGIOMA MOUSE MODELS

Abstract Atypical and anaplastic meningiomas (WHO Grade 2 and WHO Grade 3 respectively) represent a subgroup of meningiomas that tend to have higher rates of recurrence with associated’s higher morbidity and mortality than the more common WHO Grade 1 meningiomas. Our laboratory data demonstrated that galectin-3 (Gal-3), a multifunctional β-galactoside-binding protein, is highly expressed in these meningioma subtypes as compared to normal brain tissue. However, the root of the profoundly immunosuppressive tumor microenvironment in meningioma cells is not fully understood. To address this, we used a Gal-3 inhibitor TD 139 paired with low-intensity non-invasive transcranial direct current stimulation (tDCS) to suppress tumor growth and enhance the immune response in the preclinical model. Treatment of tDCS (50 mV/mm for 30 min) followed by 1 mM of TD139 induced cell death in anaplastic meningioma in vitro human triple co-culture model but has no effect on mouse cortical neurons. Furthermore, we demonstrated that inhibiting of Gal-3 expression significantly decreased the protein levels of urokinase-type plasminogen activator receptor as well as phosphorylation of Akt and upregulates Bax expression. Treatment with TD139 (1mg/kg per day for 14 days) with tDCS [350 μA (1 x 30 min/day) for 7 times (within 14 Days) showed a significantly (∼60%) decrease in MGS2 atypical meningioma tumor growth in orthotopic allograft model (at Day 41). The percent survival of tumor-bearing mice treated with TD139 and tDCS was significantly higher than an untreated tumor or single treatment. Following TD139 plus tDCS treatment, our results demonstrated significant meningioma cell death via a decrease in NDRG4 (Meningioma marker) and were associated with downregulation of Ki-67 in treated tumors. Based on our substantial preliminary data, we believe that this proposed translational work has the potential to be an effective combinational modality form of treatment for atypical and malignant meningiomas.

RADT-30. RADIATION INDUCED MENINGIOMA IN BACKGROUND OF CHILDHOOD CRANIAL IRRADIATION: A CASE SERIES

Abstract BACKGROUND Cranial irradiation as part of prophylactic (PCI) or radical treatment for childhood malignancies can be associated with late consequences such as radiotherapy induced meningioma. METHODS We are reporting 5 such patients treated at our institute. RESULTS Case 1: 24y female received PCI for Acute Lymphoblastic Leukemia at the age of 2, and developed right frontal meningioma which was resected and pathology confirmed grade 2 atypical meningioma. It was treated with radiotherapy 60Gy/30fr and 2 year follow up scans remain stable. Case 2: 31y male received PCI as a child, and developed parieto-occipital meningioma which was excised multiple times. Pathology revealed Grade 2 atypical meningioma and was treated with radiotherapy 60Gy/30fr. Follow up scans 3.5 yrs later remain stable.Case3: 37y male received PCI at the age of 3, and developed multiple site meningiomas which were excised. Pathology showed likely Grade 2 meningioma. The sphenoid wing lesion progressed 2 years later, was re-excised and treated recently with radiotherapy 60Gy/30fr. Case 4: 52y female treated with radiotherapy for retinoblastoma at the age of 6-8 wks, developed left sphenoid wing meningioma which was resected and pathology revealed malignant meningioma. Radiotherapy 60Gy/30fr was recently completed.Case 5: 24y female treated with radiotherapy for medulloblastoma at the age of 5, developed meningiomas at multiple sites. Over the span of 10 years the frontal and clinoid lesions increased in size, and were treated with SRS/SRT recently. CONCLUSION All patients had background of cranial radiation and developed meningioma with latency period ranging 19 to 52 years. It is not possible to make an inference on gender, site of meningioma or craniaI dose correlation because of small number of cases and lack of data on dose. Further research is needed on how to prevent secondary malignancies in such patients and on standard of care for secondary meningiomas.

Assessing the Malignancy Risk of a Meningioma by Its Location.

Meningiomas represent 30% of primary intracranial tumors. The current incidence is up to 4.5 cases per 100,000 habitants worldwide. Although there is no prognostic difference among benign histopathological subtypes, atypical meningiomas and malignant meningiomas (WHO grade II and III respectively) may extend to the adjacent brain parenchyma, dura mater, and osseous tissue with a recurrence score (21-49%). This manuscript analyzes the malignancy risk according to neoplastic localization through a logistic retrospective analysis from a total sample of 452 patients with grade I, II, and III (WHO) meningiomas. Detailed data collection through a three-year retrospective analysis (January 2008 to December 2011) was applied at Mexico's National Neurology and Neurosurgery Institute including patients with intracranial or spinal-cord meningioma, preoperative imaging study availability and post-surgical histopathological diagnosis. Formal written consent was not required with a waiver by the appropriate national research ethics committee in accordance with the provisions of the regulations of the general health law of Mexico. Convexity lesions displayed an increased risk of malignancy turning for non-benign meningiomas with an odds ratio of 3.1 (95% CI 1.6 to 5.7, p=0.0002) meanwhile skull-base meningiomas present an inverse risk with an odds ratio of 0.4 (95% CI 0.2 to 0.9, p=0.02), as well as spinal-cord meningiomas with an odds ratio of 0.3 (95% CI 0.1 to 0.9). Skull base and spinal cord meningiomas usually have benign behavior, meanwhile grade II or III meningiomas within this location are rare. The present work provides an additional criterion for decision making, according to the meningioma's location.

Granular clinical history and outcome in 51 patients with primary and secondary malignant meningioma.

WHO grade III meningiomas, also known as malignant meningiomas (MMs), are rare, and the heterogenous clinical course in patients with MM is not well described. To characterize the clinical course of patients with MM, granular clinical data were gathered from 51 patients treated at the Department of Neurosurgery and Radiation Oncology, Rigshospitalet, in Copenhagen, Denmark, between 2000 and 2020. The authors investigated outcome and timing in terms of 1) tumor progression and grade transformation in patients previously diagnosed with WHO grade I or II meningiomas (patients with a secondary MM [sMM]); 2) performance status and complications following surgery; and 3) transition to noncurative treatment and ultimately death. Complications, time between recurrences, and outcome (modified Rankin Scale [mRS] score) for every surgery were analyzed, both malignant and premalignant. Of the 51 patients, 24 (47%) had an sMM. The time to WHO grade III transformation in the sMM group varied widely (median 5.5 years, range 0.5-22 years), but after transformation to a WHO grade III tumor, patients with an sMM and those with a primary MM (pMM) did not differ significantly in overall survival and cumulative risk of progression. Median overall survival for all 51 patients was 4.2 years (95% CI 2.6-7.2 years). Time from the decision to shift from curative to noncurative treatment until death was 3.8 months and the 30-day mortality rate following surgery was 11.8%. From a cumulative number of 151 surgeries, 10 surgeries were followed by improvement on the mRS, mRS score was unchanged in 70, and it worsened in 71. The MM was the underlying cause of death in 30 of 31 patients who had died at the end of follow-up. Together, these findings clearly show a significant morbidity and mortality from the disease itself and from the treatment. These findings warrant studies of prognostic factors for earlier support and adjuvant measures in MM and identify a need for better palliative strategies in this patient group.

Boron Neutron Capture Therapy: Clinical Application and Research Progress.

Boron neutron capture therapy (BNCT) is a binary modality that is used to treat a variety of malignancies, using neutrons to irradiate boron-10 (10B) nuclei that have entered tumor cells to produce highly linear energy transfer (LET) alpha particles and recoil 7Li nuclei (10B [n, α] 7Li). Therefore, the most important part in BNCT is to selectively deliver a large number of 10B to tumor cells and only a small amount to normal tissue. So far, BNCT has been used in more than 2000 cases worldwide, and the efficacy of BNCT in the treatment of head and neck cancer, malignant meningioma, melanoma and hepatocellular carcinoma has been confirmed. We collected and collated clinical studies of second-generation boron delivery agents. The combination of different drugs, the mode of administration, and the combination of multiple treatments have an important impact on patient survival. We summarized the critical issues that must be addressed, with the hope that the next generation of boron delivery agents will overcome these challenges.