Biopsy Of Brain Lesions Research Articles

Targeted multiplex validation of CSF proteomic biomarkers: implications for differentiation of PCNSL from tumor-free controls and other brain tumors.

Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin's lymphoma that affects brain parenchyma, eyes, cerebrospinal fluid, and spinal cord. Diagnosing PCNSL can be challenging because imaging studies often show similar patterns as other brain tumors, and stereotactic brain lesion biopsy conformation is invasive and not always possible. This study aimed to validate a previous proteomic profiling (PMID: 32610669) of cerebrospinal fluid (CSF) and develop a CSF-based proteomic panel for accurate PCNSL diagnosis and differentiation. CSF samples were collected from patients of 30 PCNSL, 30 other brain tumors, and 31 tumor-free/benign controls. Liquid chromatography tandem-mass spectrometry targeted proteomics analysis was used to establish CSF-based proteomic panels. Final proteomic panels were selected and optimized to diagnose PCNSL from tumor-free controls or other brain tumor lesions with an area under the curve (AUC) of 0.873 (95%CI: 0.723-0.948) and 0.937 (95%CI: 0.807- 0.985), respectively. Pathways analysis showed diagnosis panel features were significantly enriched in pathways related to extracellular matrices-receptor interaction, focal adhesion, and PI3K-Akt signaling, while prion disease, mineral absorption and HIF-1 signaling were significantly enriched with differentiation panel features. This study suggests an accurate clinical test panel for PCNSL diagnosis and differentiation with CSF-based proteomic signatures, which may help overcome the challenges of current diagnostic methods and improve patient outcomes.

Safety and efficacy of frameless stereotactic robot-assisted intraparenchymal brain lesion biopsies versus image-guided biopsies: a bicentric comparative study.

User-friendly robotic assistance and image-guided tools have been developed in the past decades for intraparenchymal brain lesion biopsy. These two methods are gradually becoming well accepted and are performed at the discretion of the neurosurgical teams. However, only a few data comparing their effectiveness and safety are available. Population-based parallel cohorts were followed from two French university hospitals with different surgical methods and defined geographical catchment regions (September 2019 to September 2022). In center A, frameless robot-assisted stereotactic intraparenchymal brain lesion biopsies were performed, while image-guided intraparenchymal brain lesion biopsies were performed in center B. Pre-and postoperative clinical, radiological, and histomolecular features were retrospectively collected and compared. Two hundred fifty patients were included: 131 frameless robot-assisted stereotactic intraparenchymal brain lesion biopsies in center A and 119 image-guided biopsies in center B. The clinical, radiological, and histomolecular features were comparable between the two groups. The diagnostic yield (96.2% and 95.8% respectively; p = 1.000) and the overall postoperative complications rates (13% and 14%, respectively; p = 0.880) did not differ between the two groups. The mean duration of the surgical procedure was longer in the robot-assisted group (61.9 ± 25.3 min, range 23-150) than in the image-guided group (47.4 ± 11.8 min, range 25-81, p < 0.001). In the subgroup of patients with anticoagulant and/or antiplatelet therapy administered preoperatively, the intracerebral hemorrhage > 10 mm on postoperative CT scan was higher in the image-guided group (36.8%) than in the robot-assisted group (5%, p < 0.001). In our bicentric comparative study, robot-assisted stereotactic and image-guided biopsies have two main differences (shorter time but more frequent postoperative hematoma for image-guided biopsies); however, both techniques are demonstrated to be safe and efficient.

Phase 1 Trial of Orelabrutinib in Combination with Rituximab, Methotrexate, and Dexamethasone in Patients with Newly Diagnosed Primary CNS Lymphoma Implementing Bayesian Design for Dose-Seeking

Background: Primary central nervous system lymphoma (PCNSL) is an aggressive extranodal subtype of non-Hodgkin's lymphoma (NHL). High-dose methotrexate (HD-MTX)-based regimens are the first-line treatment for PCNSL, but remain suboptimal due to response instability and short effective remission duration. Orelabrutinib is a novel, potent, highly selective BTK inhibitor with a high CSF concentration. This study aims to investigate optimal combination dose of Orelabrutinib in combination with Rituximab, Methotrexate, and Dexamethasone (ORMD) as well as safety and efficacy of the regimen. Methods: This was a phase 1, investigator-initiated, dose-escalation study of ORMD, being conducted at Huashan Hospital, Fudan University (NCT05036577). Eligible patients must have histopathologically confirmed PCNSL-DLBCL by biopsy of brain lesions and be aged 18-75 years with adequate organ functions. Patients were treated for 6-8 cycles of induction therapy with 21 days per cycle, receiving rituximab (375mg/m 2 on day 1), dexamethasone (10-15mg on d1-d4), MTX (d2, 3.5g/m 2 or 5g/m 2), and orelabrutinib (once daily, after MTX clearance, 150mg/d, or 200mg/d), followed by orelabrutinib maintenance up to one year among CR/CRu patients. The primary objective was to determine the maximum tolerated dose (MTD) of the combination of orelabrutinib and MTX with R and D and investigate the safety and tolerability of this regimen using Bayesian Optimal Interval (BOIN) waterfall design to determine rule of dose escalation and movement among dose combination matrix to identify MTD contour. DLT was defined by the occurrence of severe toxicities during the first cycle: any grade 4 hematologic toxicity, grade 3 febrile neutropenia and grade 3 thrombocytopenia with hemorrhage, or any grade 3 non-hematologic toxicity that failed to respond to supportive therapy and possibly related to orelabrutinib and/or MTX (assessed according to NCI CTCAE V5.0). The secondary objectives included ORR/CR（u） and PFS/OS. Results: From October 2021 to July 2023, the study completed enrollment of all 13 patients. The median age was 60 years, and other basic characteristics are shown in Figure 1. All the patients had completed at least one cycle of ORMD treatment and were evaluable for DLT. The median cycle of ORMD was seven (range: 2.5-8). No DLT occurred among first 3 patients in cohort 1 (Orelabrutinib: 150mg/MTX: 3.5g/m 2) and dose escalation was allowed to cohort 2 (Orelabrutinib: 200mg/MTX: 3.5g/m 2). In cohort 2, 5 patients were dosed in total, and Gr 3 lung infection was observed in patient #4 during cycle 1, was deemed as a DLT. Another four patients were enrolled in the same cohort according to BOIN design algorithm and no DLT was identified, allowing to escalate to cohort 3 (Orelabrutinib:200mg/MTX:5g/m 2). In cohort 3, 5 patients were dosed in total, and Gr 3 elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was observed in patient #9 during cycle 1, was deemed as a DLT. The causality of this AE was certain to methotrexate due to folate metabolic gene polymorphism in the assessment of the investigator. The toxicity probability from 3 dose combo cohort is 0.13, 0.13 and 0.21, all of which is below predefined threshold 0.3. So MTD is not reached and 200mg+5g/m 2 dose combo remains to be RP2D candidate. No Gr 4 AE had been observed. The most common adverse events were lymphopenia (Gr 3 in 8 case), neutropenia(Gr 3 in 2 case), Covid-19(Gr 3 in 2 case) and hyperglycemia (Gr 3 in 2 case). No atrial fibrillation or bleeding was observed by the cut-off date. ORR and CR/CRu in 12 patients possessed at least one efficacy evaluation were both 83.3%, the PFS and OS rate were 56.6% (95% CI, 29.6% ,100%) and 100%(95% CI, 100% ,100%) at 1 year. Among nine patients completed ≥6 cycles of induction therapy, ORR and CR/CRu were both 100%. PFS and OS rate were 75.0% (95% CI, 42.6% ,100%) and 100%(95% CI, 100% ,100%) at 1 year. All patients in remission achieved CR/CRu, the high rate of deep remission may be related to the addition of orelabrutinib. Conclusions: As a novel therapeutic combination of induction therapy, ORMD therapy has shown deep remission potential as well as a predictable and manageable safety profile in patients with newly diagnosed PCNSL. MTD contour not reached. The combination of this induction therapy with consolidation therapies such as ASCT deserves further investigation and may provide greater survival benefit for patients.

Stereotactic biopsy for brain lesions: Doing more with less.

Stereotactic biopsy (STB) is a potential diagnostic tool considering its minimal invasiveness, high diagnostic yield, and minimal associated complications. Over the years, various frame-based instrument systems and frameless stereotactic biopsy systems have emerged to be employed in clinical use. With this study, we intend to get more by doing less in the form of STB for the patients of doubtful intracranial lesions treated over the past 5 years. We also want to highlight the technique of performing the procedure under scalp block, which can be used as a versatile tool in many clinical scenarios. Stereotactic biopsies may be planned even in rural district-level health facilities. One-time investment to procure instruments and avail existing imaging can lead to establishing definitive diagnoses in many doubtful cases. This will result in lesser cost and early establishment of treatment. Independent risk factors determining the outcome, such as deep-seated lesions, associated edema, and intraoperative hypertension, were studied. Establishing the diagnosis helped in prognosticating the disease, explaining the natural progression of symptoms, and starting adjuvant therapy. This tissue biopsy would also help secure samples for research and molecular analysis. Twenty patients underwent STBs at our institution between January 2018 and December 2022. We retrospectively analyzed patient characteristics, tumor pathology, surgical procedures, and outcomes, including the diagnostic value and surgery-related complications. These patients were followed up, and their progression-free and overall survival were analyzed. The need for adjuvant treatment was noted and analyzed. All procedures were performed using Cosman Roberts Wells® stereotactic frame. Pre-procedure magnetic resonance scans were performed at the time of admission. Contrast-enhanced computerized tomography (CT) scan after frame application was performed to identify targets and calculate the coordinates. A post-procedure CT scan was done to confirm the accessibility of the targeted lesion. The most common location of the tumor was a deep-seated thalamic lesion. A definitive diagnosis was established in 19 patients (95%) at the first STB. The diagnoses were glioma in 55% of cases, primary central nervous system lymphoma, tuberculosis, and demyelinating disorders in 10% of each, and a metastatic brain tumor in 1 (5%). The post-operative complications were all transient except in one patient with deterioration of motor weakness. The follow-up was noted, and modes of adjuvant treatment needed in these patients were recorded. Stereotactic biopsy is a useful and effective method for achieving a definitive diagnosis and aiding in treating multifocal or small deep-seated lesions in or around eloquent regions.

SDPS-08 OSSEOUS METASTASES IN H3G34-MUTANT DIFFUSE HEMISPHERIC GLIOMAS

Abstract Subset of patients with H3G34 gliomas may present with extra-CNS metastasis further complicating both diagnosis and treatment. We describe a case of a 19-year-old female presenting initially with focal motor seizure in right leg along with leg pain. MRI of the leg showed an ill-defined right distal femur expansile osteolytic lesion with central fluid signal, thick rim enhancement, endosteal scalloping, cortical invasion, and smooth enhancing periosteal reaction/soft tissue extension associated with surrounding enhancing marrow signal abnormality worrisome for lesion extension. Contrast brain MRI exhibited multiple frontal and partial lobe T2 FLAIR hyperintense lesions. The largest lesion demonstrated contrast enhancement, internal foci of restricted diffusion, and a focus of intratumoral hemorrhage. A whole-body PET/CT showed intensely FDG-avid lytic lesion in the right distal femur, with FDG activity along the biopsy tract. Hypermetabolic lytic metastases to the right femoral head and mid-sacral body were also observed. A craniotomy with brain lesion biopsy two months later indicated preliminary histopathology of malignant small round blue cell neoplasm. A biopsy from the distal right femur was non-diagnostic of malignancy but a sacral bone biopsy reported malignant small blue cell neoplasm, consistent with involvement by the patient's known cranial neoplasm. Final pathological diagnosis including molecular diagnostics was consistent with WHO grade 4 IDH-wildtype H3G34 mutant diffuse hemispheric glioma with osseous metastases. Patient was treated with chemoradiotherapy with temozolomide (TMZ). Following the sixth cycle of TMZ, MRI brain imaging was stable. Apart from holocephalic headaches, the patient had no significant medication side effects and was seizure-free. A second whole-body PET scan showed improvement and interval decrease in FDG uptake of the sacrum and right femoral head. Given the stress that patients with H3G34 can experience and the poor prognosis, it is imperative to expand our knowledge and ascertain accurate screening and diagnostic methodologies.

Stereotactic biopsy for multiple intra-axial brain lesions: impact on consequent treatment Regimen

Background and objectivesMultiple brain lesions represent a serious challenge in which biopsy is commonly the first step to help overcome patients' mental anxiety and decide the following treatment step. This study presents an effective decisional algorithm that could guide in dealing with such a challenge. We evaluate the feasibility and safety of frame-based stereotactic biopsy to obtain the histopathologic diagnosis of the multiple intra-axial brain lesions and to decide the further treatment.Patients and methodsThirty-two patients with multiple intracerebral lesions underwent stereotactic serial biopsies for brain lesions at the Neurosurgery Department, Tanta University Hospital. All the stereotactic biopsies were obtained under local anesthesia using Riechert–Mundinger (RM) system or Cosman–Roberts–Wells (CRW) system.ResultsThe histopathological diagnosis revealed multifocal malignant gliomas in 43.75% of patients (18.75% anaplastic astrocytoma and 25% multiform glioblastoma) and metastatic tumor in 37.5% of patients (all were adenocarcinoma). In addition, 12.5% had multiple brain abscesses, and 6.25% had malignant lymphoma. We reported no mortality secondary to the surgical procedure.ConclusionsStereotactic biopsy is considered the best choice to allow histopathologic diagnosis of multiple brain lesions with minimal morbidity and no mortality. Histopathologic findings gained with stereotactic procedures guided the choice of proper treatment thus eliminating the hazards associated with blind treatments.

The risk factors of hemorrhage in stereotactic needle biopsy for brain lesions in a large cohort: 10 years of experience in a single center

This study aimed to identify the risk factors for hemorrhage from a large cohort who underwent stereotactic needle biopsy for brain lesions at a single center over a 10-year period. We performed a retrospective chart review of consecutive patients who underwent stereotactic biopsy at our institute between January 2010 and December 2019. Demographic characteristics and clinical variables were collected and analyzed to identify risk factors for postbiopsy hemorrhage using the chi-square test and univariable and multivariable logistic regression analyses. A total of 3196 patients were included in this study; of these, a histological diagnosis was eventually made for 2938 (91.93%) patients. Hemorrhage occurred in 149 (4.66%) patients, and symptomatic hemorrhage occurred in 46 (1.44%) patients. In multivariable logistic regression analyses, the presence of deep-seated lesions (OR 1.272, p = 0.035), concomitant edema and enhancement on MR imaging scans (OR 1.827, p = 0.002), intraoperative hypertension without a past history (OR 1.012, p = 0.024), and the presence of high-grade glioma (OR 0.306, p = 0.003) were identified as independent predictors of hemorrhage after biopsy. Stereotactic needle biopsy is a safe and effective way to obtain tissue from brain lesions for histological diagnosis. The presence of deep-seated lesions, concomitant edema, and enhancement on MR imaging scans and the presence of high-grade glioma are independent predictors of hemorrhage after stereotactic biopsy.

A Multicenter, Single-Arm, Prospective Phase II Study of Orelabrutinib Combined with High-Dose Methotrexate and Rituximab Sequential Autologous Hematopoietic Stem Cell Transplantation in Newly-Dignosed Primary Central Nervous System Lymphoma

Background: Primary central nervous system lymphoma (PCNSL) is primarily large B-cell lymphoma (accounting for nearly 95% of central lymphomas). Current treatments, including surgery, chemotherapy, and whole-brain radiotherapy, often fail to achieve satisfactory results, especially in the elderly. High-dose methotrexate (MTX) based treatment is the current standard treatment, but the long-term survival rate of young patients is still less than 50% even after autologous transplantation. Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, has been tested in multiple clinical trials for PCNSL, as a single drug achieved an objective response rate (ORR) of 50-70% and a CRR of 20%-40% in relapsed and refractory PCNSL, while combination therapy can achieve an ORR of 80% and a CRR of 50%. However, ibrutinib efficacy is less than half a year and has poor selectivity. Owing to its off-target inhibition effect, the incidence of serious adverse reactions such as bleeding and atrial fibrillation in patients increases, leading to dose reduction or drug withdrawal, which makes patients unable to continue treatment. Orelabrutinib is a new-generation BTK inhibitor, that has been rationally optimized in molecular structure, which makes its binding with BTK more durable, more stable, more specific, less off-target effect, and higher BBB pass rate and better safety. In addition, a retrospective article published recently showed that obrutinib monotherapy was more effective and well-tolerated in patients with r/r PCNSL. Herein, we combined rituximab, MTX, and ibrutinib for induction therapy, finally through autologous hematopoietic stem cells consolidation therapy or lenalidomide or obrutinib maintenance treatment, to evaluate toxicity and to improve efficacy. This study is registered with Chictr.org.cn, number ChiCTR2200061485. Methods: The study is a multicenter, single-arm, prospective phase II study, conducted at Shengli Oilfield Central Hospital and Shandong Cancer Hospital. Patients diagnosed with Newly Diagnosed PCNSL by biopsy of brain lesion, systemic immunology, bone marrow, and a CSF examination, et al, and be suitable for the immunochemotherapy, were enrolled in the clinical trial. The Orelabrutinib -based ROM regimen consists of rituximab 375mg / m 2 on day 0. MTX 3.5g/m 2 on day1, and Orelabrutinib 150mg once daily on day1 to day 28. Every 28 days is a cycle of treatment. After 4-cycles of ROM induction therapy, patients who achieved CR/CRu/PR received autologous peripheral blood hematopoietic stem cell transplantation (HSCT) or the extra 2 cycles of ROM regimen as consolidation therapy. Orelabrutinib or lenalidomide monotherapy was prescribed as maintenance therapy, according to the willingness of patients until the disease progresses. The primary endpoint was the safety and efficacy of this regimen in newly diagnosed with PCNSL. Results: There were a real of 10 patients enrolled in this clinical trial, between July 2021 and May 2022. All the patients were pathologically DLBCL, including 7 non-GCB subtypes and 3 GCB subtypes. The median follow-up time was 6.5 (1-12) months up to June 30, 2022. After 4 cycles of ROM induction therapy, complete metabolic remission (CMR) was achieved in 5 patients (50%), partial response (PR) in 5 patients (50%), and the overall response rate (ORR) of induction therapy was 100% (Figure 1). Among responders, 3 (33%) received HSCT, 1 (10%) received RT and 5 (50%) received extra 2 cycles of ROM regimen as consolidation therapy. After the consolidation therapy, 90% of patients (9/10) received maintenance therapy, including 5 who received lenalidomide and 4 who received ibrutinib. The median progression-free survival (PFS) and overall survival (OS) were not achieved. The safety of Orelabrutinib -based regimens have also been evaluated. No grade 4 adverse events were observed. Grade 3 hematologic toxicity included lymphopenia in 1 case and neutropenia in 3 cases. Conclusions: Our data preliminaries indicate that ROM is efficacious and well-tolerated as a first-line regimen in newly diagnosed PCNSL and might effectively improve the survival of these patients. These combined therapies offer a potential new therapeutic strategy. More patients and longer follow-ups are necessary to confirm our conclusion. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Preliminary Result of Phase 1 Trial of Orelabrutinib in Combination with Rituximab, Methotrexate, and Dexamethasone in Patients with Newly Diagnosed Primary CNS Lymphoma Implementing Bayesian Design for Dose-Seeking

Background: Primary central nervous system lymphoma (PCNSL) is an aggressive extranodal subtype of diffuse large B-cell lymphoma (DLBCL). High-dose methotrexate (HD-MTX)-based regimen is the first-line treatment of PCNSL, with or without the anti-CD20 antibody rituximab, remaining to be suboptimal due to unstable response and short effective remission time. Genetic alterations often occur in the chronic active B-cell receptor signaling featured by MYD88 and CD79B which mediate the response to BTK inhibition (BTKi) in PCNSL. Orelabrutinib is a novel, potent, highly selective BTK inhibitor with a high CSF concentration. This study aims to investigate optimal combination dose of Orelabrutinib in combination with Rituximab, Methotrexate, and Dexamethasone (ORMD) as well as safety and efficacy of the regimen. Methods: This was a phase 1, investigator-initiated, dose-escalation study of ORMD, being conducted at Huashan Hospital, Fudan University (ClinicalTrials.gov identifier: NCT05036577). It was planned to enroll 12-15 patients with newly diagnosed PCNSL to the regimen of orelabrutinib and MTX combined with the fixed dose of rituximab(R) and dexamethasone(D). Eligible patients must have histopathologically confirmed PCNSL-DLBCL by biopsy of brain lesions and be aged 18-75 years with adequate organ functions. Patients were treated for 6-8 cycles of induction therapy with 21 days per cycle, receiving rituximab (375mg/m2 on day 1), dexamethasone (10-15mg on d1-d4), MTX (d2, 3.5g/m2 or 5g/m2), and orelabrutinib (once daily, after MTX clearance, 150mg/d, or 200mg/d), followed by orelabrutinib maintenance up to one year among CR/CRu patients. The primary objective was to determine the maximum tolerated dose (MTD) of the combination of orelabrutinib and MTX with R and D and investigate the safety and tolerability of this regimen using Bayesian Optimal Interval (BOIN) waterfall design to determine rule of dose escalation and movement among dose combination matrix to identify MTD contour. DLT was defined by the occurrence of severe toxicities during the first cycle: any grade 4 hematologic toxicity, grade 3 febrile neutropenia and grade 3 thrombocytopenia with hemorrhage, or any grade 3 non-hematologic toxicity that failed to respond to supportive therapy and possibly related to orelabrutinib and/or MTX (assessed according to NCI CTCAE V5.0). The secondary objectives included ORR/CR(u) and PFS/OS. Baseline tissue/CSF samples and sequential CSF/plasma samples were collected for targeted NGS and pharmacokinetics evaluation as exploratory objectives. Results: Eight patients were enrolled from October 2021 to June 2022 as the preliminary analysis set. The median age was 62 year (range: 43-73) and six patients were male. All the patients with histologically confirmed DLBCL (6 non-GCB subtypes and 2 GCB subtypes) had completed at least one cycle of ORMD treatment and were evaluable for DLT. The median cycle of ORMD was one (range: 1-7). No DLT occurred among first three patients in cohort 1 (Orelabrutinib: 150mg/MTX: 3.5g/m2) and dose escalation was allowed to cohort 2 (Orelabrutinib: 200mg/MTX: 3.5g/m2). In cohort 2, 5 patients were dosed in total, and Gr 3 lung infection was observed in patient #4 during cycle 1, was deemed as a DLT. Another four patients were enrolled in the same cohort according to BOIN design algorithm and no DLT was identified, allowing to escalate to cohort 3 (Orelabrutinib:200mg/MTX:5g/m2). No Gr 4 AE had been observed. The most common adverse events were lymphopenia (Gr 3 in 4 case) and hyperglycemia (Gr 3 in 1 case). No atrial fibrillation, hypertension, or bleeding was observed by the cut-off date. The study is ongoing. Further results will be updated as data becomes mature. Conclusions: ORMD regimen preliminarily demonstrated predictable and manageable safety profile in newly diagnosed PCNSL patients with 200mg/d orelabrutinib and 3.5g/m2 MTX to date. MTD contour not reached and further evaluation continues. Longer follow-up is needed regarding efficacy, biomarker, and more safety data Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Outcome of Image-Guided Surgical Biopsy of Brain Lesions: A Single Centre Experience

Abstract AIMS The aim of this study was to quantify the accuracy of surgical biopsy for brain lesions using different image-guidance techniques, in our tertiary neurosurgical centre. METHOD Retrospective data was collected from electronic and paper patient notes. Data collected included: age, sex, comorbidities, pre-operative functional images, surgeon grade, biopsy method, number of targets, number of samples, result from frozen section and fixed sample histopathology, complications, and length of stay. Methods of biopsy included: ultrasound-guided, frame-based biopsy and frameless Brainlab guided biopsy (free-hand, Varioguide and registration tool -guided). RESULTS A percentage of 11.5% of cases (total = 52) were US-guided biopsy. Navigated frameless biopsies comprised 76.9% of all cases. In these cases, 42.3% of cases were guided by the registration tool, 23% used a fixed “Varioguide” instrument alignment tool and 11.5% were completed using the free-hand method. Overall accuracy of biopsy for all cases was 82.69%. Accuracy rates of different frameless methods were: 81.8% for Brainlab registration- guided biopsy, 66.7% for Brainlab Varioguide biopsy and 100% for Brainlab free-hand frameless biopsies. The percentage of complications was 5.8%. CONCLUSION In our centre, the accuracy of image-guided surgical biopsy for brain lesions was as high as 82.69% with a low complication rate of 5.8%. The Brain lab free-hand technique had the highest diagnostic yield and safety amongst all frameless stereotactic techniques.

Brain metastasis of thyroid adenoid cyst carcinoma: Unusual case report

Background: Cerebral metastasis from Adenoid cyst Carcinoma (ACC) remains extremely rare. Case description: 62-year-old female, with a history of thyroidectomy for goiter surgery associated with left cervical lymphadenopathy five years ago. She presented a decrease in visual acuity at 6/10 in the right eye. Brain MRI revealed an intra-conical right orbital lesion process associated with a right frontal cerebral lesion process, three other osteolytic lesions of the cranial vault, lung metastases, and hepatic metastasis. Thyroid ACC with Antibody Anti CD117+ after stereotaxic biopsy of brain lesion was retained by the pathologist. She underwent radiotherapy and chemotherapy management. At 6 months follow-up, the cerebral and liver localisations didn’t progress, unfortunately, the lung mass was progressed from 4 cm to 6 cm. Conclusion: Multiple brain metastasis from ACC of the thyroid is extremely rare. Diagnosis and Management could present some challenges for surgeons and oncologists Keywords: Adenoid cyst carcinoma; Thyroid; Brain metastasis; CD117; Stereotaxic biopsy.

A preliminary study of the diagnostic efficacy and safety of the novel boring biopsy for brain lesions

Existing methods for biopsy of intraparenchymal brain lesions, including stereotactic biopsy and open block biopsy, have advantages and disadvantages. We propose a novel biopsy method, called “boring biopsy,” which aims to overcome the drawbacks of each conventional method. This method is less invasive and allows obtaining continuous specimens of sufficient volume. We aimed to assess the feasibility and efficacy of using boring biopsy for intraparenchymal brain lesions. We included 26 consecutive patients who underwent boring biopsy for intraparenchymal lesions. Columnar continuous specimens from the surface of the normal brain tissue to the tumor margin and the center of the lesion were obtained using the boring biopsy method. We used a catheter introducer with original modifications to create a cylindrical biopsy tool for surgery. Columnar continuous specimens were successfully obtained. Histopathological diagnosis was based on cellular changes and differentiation from normal tissues to the core of the lesion and established in all cases. No permanent deficits, major adverse outcomes, or deaths were observed. This novel technique may improve diagnostic accuracy and reduce invasiveness associated with brain biopsy. This method may become the next standard procedure, particularly in some cases where histological evaluation is paramount, and conventional biopsy methods are not suitable.

Ibrutinib in Combination with Rituximab and High-Dose Methotrexate in Newly Diagnosed Primary Central Nervous System Lymphoma Patients

Ibrutinib in combination with rituximab and high-dose methotrexate in newly diagnosed primary central nervous system lymphoma patientsYixian Guo, Xiaoxi Lan, Xiaoli Chang, Guoxiang Wang, Dongmei Zou, Li Su, Wanling SunDepartment of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. ChinaCorresponding author: Wanling Sun, M.D. & Ph.D.Email: wanlingsun@xwhosp.orgBackground: Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphoma. Most PCNSL are pathologically classified as diffuse large B-cell lymphoma (DLBCL). In addition to the importance of high-dose systemic methotrexate (HD-MTX), there is no consensus on the optimal composition of induction and consolidation therapy for newly diagnosed PCNSL. BTK inhibitors are the second-line recommended choice in relapsed of refractory cases. In this study, we described our institutional experience with the oral BTK inhibitor, ibrutinib, combined with rituximab and HD-MTX (I-RM regimen) in newly diagnosed PCNSL. This study is registered with Chictr.org.cn, number ChiCTR1900027811.Methods: The study was a phase 1, investigator-initiated, clinical trial being conducted at Xuanwu Hospital, Capital Medical University . Patients definitely diagnosed as PCNSL-DLBCL by biopsy of brain lesion, systemic imageology, bone marrow and CSF examination, et al, and be suitable for the immunochemotherapy,were enrolled the clinical trial. The next-generatioin sequencing of the lesion tissue were used to detect hot spot mutations evolved in B cell lymphoma. The ibrutinib-based I-RM regimen consists of rituximab 375mg / m 2 on day 0, MTX 3.5g/m 2 on day1, and ibrutinib 560mg once daily starting from plasma MTX concentration <0.1umol/L to day 28, every 28 days is a cycle of treatment. After 4 cycles of I-RM induction therapy, patients who achieved CR/CRu/PR received autologous peripheral blood hematopoietic stem cell transplantation (HSCT) or the extra 2 cylces of I-RM regimen as consolidation therapy. Ibrutinib or lenalidomide monotherapy was prescribed as maintenance therapy, according to the willingness of patients until the disease progresses. The primary end point was the safety and efficacy of this regimen in newly diagnosed PCNSL.Results:There were totally16 patients enrolled in this clinical trial, between April 2018 and December 2020 (Table 1). All the patients were pathologically DLBCL, including 14 non-GCB subtypes and 2 GCB subtypes. The commonest hot spot mutations were PIM1 (68.75%), MYD88 (43.75%), and CD79B (37.50%). The median follow-up time was 24.5 (6-37) months up to June 30, 2021. After 4-cycles of I-RM induction therapy, CR were achieved in 8 patients (50%), PR in 7 patients (44%), and progressive disease in one patients(6%) who quit the clinical trial and transferred to other regimen，and the ORR of induction therapy was 94%. Among 15 responsers, 5 (33%) received HSCT and 10 (67%) received extra 2 cylces of I-RM regimen as consolidation therapy. After the consolidation therapy, 93% patients (14/15) received maintenance therapy, including 6 received lenalidomide and 8 received ibrutinib. Relapse happened in 2 patients during the maintenance therapy, including 1 death due to the progressed disease (Table 2). The median PFS and OS were not achieved, and the estimated 3-year OS and PFS were 88.9% and 86.5%, respectively (Figure 1). No grade 4 adverse event was observed. The grade 3 hematologic toxicities included lymphopenia in 3 cases and neutropenia in 1 case .The grade 3 non-hematologic toxicities including hypertension in 1 case and increased serum creatinine in 1 case.Conclusions: Our data preliminarily indicates that I-MR is active and safe as a first-line regimen in newly diagnosed PCNSL and might effectively improve the survival of these patients. More patients and longer follow-up are needed to confirm our conclusion. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Factors affecting diagnostic yield in stereotactic biopsy for brain lesions: a 5-year single-center series.

The objective of this study is to determine the factors that are associated with the diagnostic yield of stereotactic brain biopsy. A retrospective analysis was performed on 50 consecutive patients who underwent stereotactic brain biopsies in a single institute from 2014 to 2019. Variables including age, gender, lesion topography and characteristics, biopsy methods, and surgeon's experience were analyzed along with diagnostic rate. This study included 31 male and 19 female patients with a mean age of 48.4 (range: 1-76). Of these, 25 underwent frameless brain-suite stereotactic biopsies, 15 were frameless Portable Brain-lab® stereotactic biopsies and 10 were frame-based CRW® stereotactic biopsies. There was no statistical difference between the diagnostic yield of the three methods. The diagnostic yield in our series was 76%. Age, gender, and biopsy methods had no impact on diagnostic yield. Periventricular and pineal lesion biopsies were significantly associated with negative diagnostic yield (p = 0.01) whereas larger lesions were significantly associated with a positive yield (p = 0.01) with the mean volume of lesions in the positive yield group (13.6cc) being higher than the negative yield group (7cc). The diagnostic yields seen between senior and junior neurosurgeons in the biopsy procedure were 95% and 63%, respectively (p = 0.02). Anatomical location of the lesion, volume of the lesion, and experience of the surgeon have significant impacts on the diagnostic yield in stereotactic brain biopsy. There was no statistical difference between the diagnostic yield of the three methods, age, gender, and depth of lesion.

Early experience of stereotactic biopsy of brain lesion in tertiary centre of Nepal

Background &#x0D; Stereotactic surgery or stereotaxy is a minimally invasive form of surgical intervention which makes use of a three-dimensional coordinate system to locate small targets inside the body and to perform on them some action such as ablation, biopsy, lesion, injection, stimulation, implantation, radiosurgery (SRS), etc. Though it was developed a long time ago as a useful adjunct to brain lesions evaluation, use in Nepal is quite recent.&#x0D; Materials and Methods&#x0D; The study included eight patients who underwent frame based stereotactic biopsy and pathological evaluation of specimen at National Academy of Medical Sciences (NAMS).&#x0D; Results &#x0D; Out of eight patients the results were positive in seven patient and negative in one patient.&#x0D; &#x0D; &#x0D; &#x0D; Conclusions&#x0D; The basic advantages of stereotaxy were realized in our cases with minimal morbidity and no mortality. Craniotomy for biopsy could be avoided.&#x0D; &#x0D; &#x0D; &#x0D;

Stereotactic Biopsy in The Diagnosis of Small Brain Lesion

Background: Stereotactic neurosurgery involves mapping the brain in a three-dimensional coordinate system. With the help of MRI and CT scans and 3D computer workstations, neurosurgeons are able to accurately target any area of the brain especially deep seated and brain stem.&#x0D; Objectives: Stereotactic brain biopsy is a minimally invasive procedure that uses this technology to obtain samples of brain tissue for diagnostic purpose of multiple brain disorder where start to any medication was impossible or no response to any medical management for long term.&#x0D; Materials and Methods: Twenty-five patients underwent stereotactic biopsy of brain lesions using“KOMAI” Stereotactic frame system and were enrolled.&#x0D; Results: Of the 25 cases, positive tissue biopsy was found in 20 cases. In 5 patients, biopsy showed gliotic brain tissue or normal brain tissue. There was no post-operative new deficits or mortality seen.&#x0D; Conclusion: Stereotaxy is minimally invasive procedure having no complication. So, before starting any medication blindly stereotactic tissue diagnosis can help a lot in many medical and surgical diseases.&#x0D; J Bangladesh Coll Phys Surg 2021; 39(1): 24-35

Regarding “The Safety and Efficacy of Frame-Based Stereotactic Biopsy of Brain Lesion”

Regarding “The Safety and Efficacy of Frame-Based Stereotactic Biopsy of Brain Lesion”

The Safety and Efficacy of Frame-Based Stereotactic Biopsy of Brain Lesion

Background Radiological imaging techniques provide early detection of neurological diseases, but they do not always provide an adequate diagnosis. With the help of stereotactic biopsy techniques, it is possible to access deep-brain lesions safely and with high precision, being crucial in the elaboration of therapeutic strategies and prevents unnecessary neurosurgical interventions. Aim To evaluate the safety, diagnostic yields, and associated mortality and morbidity of computed tomography-guided stereotactic biopsy for intracranial lesions. Materials and Methods A retrospective study of all pathologically diagnosed intracranial biopsies, between 2010 and 2016 in Baghdad Neurosurgical Teaching Hospital, was conducted. Stereotactic biopsies were performed by using the Leksell stereotactic frame in 116 patients. Medical charts, radiological studies, and postoperative complications were reviewed, and then the information was analyzed. Results A total of 116 patients underwent stereotactic surgery procedures. Patients consisted of 66 females and 50 males, ages ranging from 7 to 74 years (mean 44.4 ± 19.35 years). General anesthesia was used in 88 patients. The rest were performed under local anesthesia. The overall diagnostic yield was 98.3%. Complications were observed in 8.6% of the cases, with morbidity 5.1% of the cases, and the overall mortality rate was 3.4%. These results are comparable to other reports. Other clinical, radiological, or histological variables were not associated with an increased risk of complications. Conclusion Our findings support that frame-based stereotactic biopsy is a relatively safe and valuable technique that allows the neurosurgeon to obtain tissue samples for histopathological diagnosis of most of the intracranial mass lesions.

Expressive aphasia caused by &lt;em&gt;Streptococcus intermedius &lt;/em&gt;brain abscess in an immunocompetent patient

BackgroundBrain abscess is an uncommon but life-threatening infection. It involves a focal, intracerebral infection that begins in a localized area of cerebritis and develops into a collection of pus, surrounded by a well-vascularized capsule. Brain abscess still poses a significant problem in developing countries but rarely in developed countries. Predisposing factors vary in different parts of the world. With the introduction of antibiotics and imaging studies, the mortality rate has decreased between 5% and 15%. If left untreated it may lead to serious neurologic sequelae. The temporal lobe abscess can be caused by conditions like sinusitis, otitis media, dental infections, and mastoiditis if left untreated or partially treated. Additionally, in neurosurgical procedures like craniotomy, the external ventricular drain can get infected, leading to abscess formation.Case presentationWe present the case study of an elderly female patient who presented with expressive aphasia caused by brain abscess, secondary to Streptococcus intermedius infection. The 72-year-old female with a medical history of hypertension came to hospital for evaluation with word-finding difficulty, an expressive aphasia that began a few days prior to presentation. Computed tomography of the head showed a left temporal lobe mass-like lesion, with surrounding vasogenic edema. The patient was empirically started on courses of antibiotics. The next day, she was subjected to magnetic resonance imaging of the brain, which showed a left temporal lobe septated rim-enhancing mass lesion, with bright restricted diffusion and diffuse surrounding vasogenic edema consistent with abscess. The patient was also seen by the neurosurgery department and underwent stereotactic, left temporal craniotomy, with drainage, and resection of abscess. Tissue culture grew S. intermedius sensitive to ampicillin sulbactam. Subsequently her expressive aphasia improved.ConclusionBrain abscess has a high mortality, however a significant proportion of patients with appropriately treated abscess recover completely and can survive without significant neurologic damage. Advanced imaging modalities may yield more accurate methods of differentiation of mass lesions in the brain. Biopsy of brain lesion with early initiation of appropriate antibiotics will change the outcome.

General Anesthesia Versus Local Anesthesia in Stereotactic Biopsies of Brain Lesions: A Prospective Randomized Study

Stereotactic biopsy of brain lesions with unknown entities is a common neurosurgical procedure to obtain tumor tissue. Pathologists can then provide an exact diagnosis on which further therapy, such as resection, radiotherapy, or chemotherapy, can be based. These procedures can be performed under local or general anesthesia. In this prospective study, we aim to show whether stress levels are higher for patients who undergo stereotactic biopsy under local or general anesthesia. Between January 2013 and December 2014, we screened 157 patients. Of these, 43 were included and evaluated in this study. Twenty-one patients gave their written consent and were randomized for either local or general anesthesia. A Post Traumatic Stress Score (PTSS) questionnaire was filled out by the patients preoperatively and postoperatively. Also, patients who did not agree to randomization had an opportunity to fill out the PTSS questionnaire. Twenty-two patients agreed only to fill out the stress-level questionnaire but refused randomization. These patients were evaluated as a subgroup. Scores achieved in the PTSS were compared by using the Fisher exact test. Among the randomized patients, 9 underwent the procedure under local anesthesia and 12 under general anesthesia. Median PTSS was 24 preoperatively in the patients who received local anesthesia versus 20 among the patients with general anesthesia (P= 0.37; Fisher exact test). Postoperatively, PTSS was 29.5 in median for patients with local anesthesia versus 23 for patients with general anesthesia (P= 0.30; Fisher exact test). Postoperatively, the PTSS showed a median increase of 5.5 points in the LA and 3 points in the GA group (P= 0.87; Fisher exact test). P values of 0.05 and lower were considered statistically significant. The willingness of patients to undergo randomization in this setting was low (13.3%). Within this highly selective group of patients, there was no significant difference for stress levels in patients who underwent stereotactic biopsy under local anesthesia versus general anesthesia. However, median values indicate a trend for higher stress-level values for patients undergoing local anesthesia.