Brain tumor research and treatment最新文献

Lynch syndrome (LS) is an autosomal dominant disorder caused by mutations in mismatch repair (MMR) genes and is also known to be associated with glioblastomas. The efficacy of immunotherapy for LS-associated glioblastomas remains unknown. Herein, we report a rare case of LS-associated glioblastoma, treated with chemotherapy using immune checkpoint inhibitors (ICI). A 41-year-old female patient presented with headaches and sensory disturbances in the right upper limb for 6 weeks. She had been treated for rectal cancer and had a family history of LS. MRI revealed two ring-enhancing lesions in the left precentral gyrus. She underwent subtotal resection, leading to a pathological diagnosis of isocitrate dehydrogenase wild-type glioblastoma. She received daily administration of (temozolomide, 75 mg/m²) and concurrent radiotherapy (60 Gy) postoperatively. However, the tumor recurred 1 year after the initial treatment. A molecular genetic study showed high microsatellite instability (MSI), and she was treated with pembrolizumab therapy. Disease progression occurred despite six cycles of pembrolizumab therapy and radiotherapy at the dose of 40 Gy. She died due to glioblastoma progression 19 months after the initial treatment. The present case demonstrates that some LS-associated glioblastomas may be resistant to ICI despite high MSI, possibly because of intratumor heterogeneity related to MMR deficiency.

Background: Glioma is caused by multiple genomic alterations. The evolving classification of gliomas emphasizes the significance of molecular testing. Next generation sequencing (NGS) offers the assessment of parallel combinations of multiple genetic alterations and identifying actionable mutations that guide treatment. This study comprehensively analyzed glioma patients using multi-gene NGS panels, providing powerful insights to inform diagnostic classification and targeted therapies.

Methods: We conducted a targeted panel-based NGS analysis on formalin-fixed and paraffin-embedded nucleic acids extracted from a total of 147 glioma patients. These samples underwent amplicon capture-based library preparation and sequenced using the Oncomine Comprehensive Assay platform. The resulting sequencing data were then analyzed using the bioinformatics tools.

Results: A total of 301 mutations, were found in 132 out of 147 tumors (89.8%). These mutations were in 68 different genes. In 62 tumor samples (42.2%), copy number variations (CNVs) with gene amplifications occurred in 25 genes. Moreover, 25 tumor samples (17.0%) showed gene fusions in 6 genes and intragenic deletion in a gene. Our analysis identified actionable targets in several genes, including 11 with mutations, 8 with CNVs, and 3 with gene fusions and intragenic deletion. These findings could impact FDA-approved therapies, NCCN guideline-based treatments, and clinical trials.

Conclusion: We analyzed precisely diagnosing the classification of gliomas, detailing the frequency and co-occurrence of genetic alterations and identifying genetic alterations with potential therapeutic targets by NGS-based molecular analysis. The high-throughput NGS analysis is an efficient and powerful tool to comprehensively support molecular testing in neurooncology.

Background: This study aimed to retrospectively assess results of intracranial meningioma surgery with or without intraoperative neuromonitoring (IONM) in a single institution.

Methods: Two cohorts (a historical cohort and a monitoring cohort) were collected for the analysis. Before IONM was introduced, a total of 107 patients underwent intracranial meningioma operation without IONM from January 2000 to December 2008 by one neurosurgeon (historical cohort). After IONM was introduced, a total of 99 patients with intracranial meningioma were operated under IONM between November 2018 and February 2023 by two neurosurgeons (monitoring cohort). A retrospective comparison was made on the complications from meningioma surgery between the two groups.

Results: In the monitoring cohort, warning signals of motor evoked potential (MEPs) or somatosensory evoked potential (SSEPs) were alarmed in 10 patients. Two of these 10 patients aborted the operation and eight of these 10 patients with warning signals underwent tumor resection. Of these eight patients, five showed postoperative morbidity. Five of 89 patients without warning signals developed neurological deficits. In the historical cohort, 14 of 107 patients showed postoperative morbidity or mortality.

Conclusion: Even after successful resection of intracranial meningiomas prior to the advent of IONM, integration of MEPs and SSEPs monitoring yielded valuable insights for surgical teams during operative procedures.

Background: For patients diagnosed with asymptomatic, non-functional pituitary incidentaloma (PI), periodic follow-up is generally proposed. However, the recommended follow-up period differs among existing guidelines and consensus is lacking. Thus, this study aimed to suggest follow-up periods for PI based on MRI characteristics.

Methods: Between 2007 and 2023, 245 patients who were diagnosed with PI were retrospectively assessed. Their mean clinical and neuroradiological follow-up periods were 74.2 and 27.3 months, respectively. Their baseline clinical and neuroradiological characteristics were analyzed. These 245 patients were divided into two groups: those with PI size progression and those without PI size progression. Additionally, neuroradiological features of each group were analyzed according to presumptive diagnoses of PI.

Results: PI size increased in 33 of 245 patients. For the remaining 212 patients, PI size decreased or stayed unchanged. Of the 33 patients with PI size progression, ten underwent surgery. Stalk deviation (p<0.001) and lesion enhancement (p=0.001) were significantly more observed in those with PI size progression than in those without PI size progression. MRI morphological factors were not related to changes in PI size in the presumptive Rathke's cleft cyst group. In the presumptive pituitary adenoma group, absence of tumor enhancement (p<0.001) and stalk deviation (p<0.001) were significantly associated with tumor reduction and progression, respectively.

Conclusion: Our findings support an additional guideline for patients with asymptomatic non-functional PI without stalk deviation and enhancement. For these patients, the clinical and neuroradiological follow-up periods could be reduced.

Differential diagnosis of focal brainstem lesions detected on MRI is challenging, especially in young children. Formerly, brainstem gliomas were classified mainly based on MRI features and location. However, since 2016, the World Health Organization's brainstem lesion classification requires tissue biopsy to reveal molecular characteristics. Although modern techniques of stereotactic or navigation-guided biopsy ensure accurate biopsy of the lesion with safety, biopsy of brainstem lesions is still generally not performed. Here, we report a focal brainstem lesion mimicking brainstem glioma in a 9-year-old girl. Initial MRI, MR spectroscopy, and ¹¹C-methionine positron emission tomography (PET) features suggested low-grade glioma or diffuse intrinsic pontine glioma. However, repeated MR spectroscopy, perfusion MRI, and ¹⁸fluorodeoxyglucose PET findings suggested that it was more likely a non-tumorous lesion. As the patient presented not with a neurological manifestation but with precocious puberty, the attending oncologist chose to observe with regular follow-up MRI. The pontine lesion with high signal intensity on T2-weighted MRI regressed from the 6-month follow-up and became invisible on the 1.5-year follow-up MRI. We reviewed brainstem glioma-mimicking lesions in the literature and discussed the key points of differential diagnosis.

With advancements in systemic cancer therapies, the incidence and diagnosis of brain metastases (BMs) have increased, necessitating updated clinical practice guidelines. There also were developments in neurosurgical and radiotherapeutic modalities for intracranial lesions, as well as advances in immune and targeted therapies for BMs of systemic cancers. Recently, the ASCO-SNO-ASTRO and EANO-ESMO have published clinical guidelines for BMs from solid tumors. The ASCO-SNO-ASTRO guidelines, published in 2021, underwent a systematic literature review and critical evaluation by their Expert Panel, addressing the key questions in various therapies such as surgery, radiotherapy, and systemic therapy for the recommendations. Similarly, the EANO-ESMO guidelines, also published in 2021, involved a selection of relevant literature by expert authors, with final references confirmed through consensus, focusing on prevention, diagnosis, therapy, and follow-up. This review aims to provide an overview of the recent clinical practice guidelines for BMs from solid tumors, based on these two recently developed guidelines.

A 27-year-old male patient, previously diagnosed with Hodgkin lymphoma (HL), presented with gait disturbance. Brain MRI showed a 4.5 cm mass lesion in the right occipital lobe, suggesting either intracranial involvement of HL or a potential meningioma. Despite high-dose methotrexate and steroid treatment, the patient's symptoms persisted, and imaging showed an enlarging mass, leading to surgical intervention. Histopathological examination confirmed central nervous system (CNS) involvement of HL. Postoperatively, the patient underwent whole-brain radiotherapy and demonstrated marked clinical improvement. Our literature review from 1980 to 2023 identified only 46 cases of intracranial HL (IC-HL), underscoring its rarity. Lymphomas represent 2.2% of brain tumors, with 90%-95% being diffuse large B-cell lymphoma (DLBCL). In contrast, the incidence of CNS-HL patients is a mere 0.02%. Notably, IC-HL and intracranial DLBCL have differences in their typical locations and treatment strategies. Unlike DLBCL, which predominantly appears in the supratentorial region (87%), IC-HL is found there in 61.5% of cases. Additionally, 33.3% of IC-HL cases occur in the cerebellum, with 43.5% associated with posterior circulation regions. Furthermore, while biopsy followed by chemotherapy induction is a common strategy for DLBCL, 81.8% of IC-HL cases underwent surgical resection, and only 18.1% had a biopsy alone. The distinct characteristics of IC-HL tumors, including their larger size, attachment to the dura, and fibrotic nature with clear boundaries, might account for the preference for surgical intervention. The unique features of IC-HL compared to DLBCL highlight the need for distinct considerations in diagnosis and management.

This review provides an overview of the current state of pediatric brain tumor imaging, emphasizing the role of various imaging sequences and highlighting the advantages of standardizing protocols for pediatric brain tumor imaging in diagnosis and treatment response evaluation. Basic anatomical sequences such as pre- and post-contrast 3D T1-weighted, T2-weighted, fluid-attenuated inversion recovery, T2*-weighted, and diffusion-weighted imaging (DWI), are fundamental for assessing tumor location, extent, and characteristics. Advanced techniques like DWI, diffusion tensor imaging, perfusion imaging, magnetic resonance spectroscopy, and functional MRI offer insights into cellularity, vascularity, metabolism, and function. To enhance consistency and quality, standardized protocols for pediatric brain tumor imaging have been recommended by expert groups. Special considerations for pediatric patients, including the minimization of anesthesia exposure and gadolinium contrast agent usage, are essential to ensure patient safety and comfort. Staying up-to-date with diagnostic imaging techniques can contribute to improved communication, outcomes, and patient care in the field of pediatric neurooncology.

We report a patient with whole neuroaxis dissemination of a sporadic supratentorial hemangioblastoma (HB) for more than 15 years. A 68-year-old female patient presented with severe radiating pain in the right leg. Gadolinium-enhanced lumbar spine MRI showed an intradural mass (2.5 cm in diameter) at the L4 level. The patient had been severely disabled for 22 years after a previous intraventricular brain tumor resection. At that time, the diagnosis was angioblastic meningioma, which was thought to be incorrect. At 14 years after the brain surgery, gamma knife radiosurgery was performed three times for newly developed or recurred supratentorial and infratentorial tumors in the cerebrospinal fluid pathway. The patient underwent lumbar spinal surgery, and a gross total removal of the mass was performed, which confirmed the histopathological diagnosis of HB. We reexamined the old histopathological specimen of the intraventricular tumor from 20 years ago and changed the diagnosis from angioblastic meningioma to supratentorial HB. Six months after spinal surgery, the patient underwent a second spinal surgery and brain surgery, and the histopathological diagnosis was HB following both surgeries, which was the same following the first spinal surgery. Here, we report a sporadic supratentorial HB patient who showed cranial and spinal disseminations for more than two decades along with a literature review.

Background: Thallium-201 single-photon emission computed tomography/computed tomography (SPECT/CT) brain scan is an imaging modality which can be done to differentiate between malignant and nonmalignant lesions among patients with nonconclusive findings on conventional neuroimaging. This study describes the results of thallium-201 SPECT/CT brain imaging and relate it to histopathologic and/or clinical findings and evaluate the value of thallium-201 SPECT/CT brain imaging in differentiating malignant from nonmalignant lesions.

Methods: This is a retrospective case series study of 10 patients with cerebral lesions who underwent thallium-201 SPECT/CT brain imaging in a hospital in the Philippines from 2010 to 2021.

Results: A total of 10 patients underwent thallium-201 SPECT/CT brain scan. Six had negative results while 4 had positive results. All of the patients who had positive results were found to have malignancy, whether recurrent or newly diagnosed. All of the patients with negative scan were found to have either an infectious and inflammatory disease and responded to treatment albeit in different degrees. Two of the 10 patients underwent biopsy whose results were consistent with the thallium-201 SPECT/CT brain scan results.

Conclusion: Thallium-201 brain scan combined with SPECT and SPECT/CT has been demonstrated to be useful in distinguishing malignant from nonmalignant lesions and is more cost-effective versus other imaging techniques. The findings in this study support the role of thallium scintigraphy in the diagnosis of patients with brain lesions most significantly when there is a need to differentiate between a malignant and benign condition.