Explore the vast range of titles available.

IntroductionIt is useful to know the molecular subtype of lower-grade gliomas (LGG) when deciding on a treatment strategy. This study aims to diagnose this preoperatively.MethodsA deep learning model was developed to predict the 3-group molecular subtype using multimodal data including magnetic resonance imaging (MRI), positron emission tomography (PET), and computed tomography (CT). The performance was evaluated using leave-one-out cross validation with a dataset containing information from 217 LGG patients.ResultsThe model performed best when the dataset contained MRI, PET, and CT data. The model could predict the molecular subtype with an accuracy of 96.6% for the training dataset and 68.7% for the test dataset. The model achieved test accuracies of 58.5%, 60.4%, and 59.4% when the dataset contained only MRI, MRI and PET, and MRI and CT data, respectively. The conventional method used to predict mutations in the isocitrate dehydrogenase (IDH) gene and the codeletion of chromosome arms 1p and 19q (1p/19q) sequentially had an overall accuracy of 65.9%. This is 2.8 percent point lower than the proposed method, which predicts the 3-group molecular subtype directly.ConclusionsA deep learning model was developed to diagnose the molecular subtype preoperatively based on multi-modality data in order to predict the 3-group classification directly. Cross-validation showed that the proposed model had an overall accuracy of 68.7% for the test dataset. This is the first model to double the expected value for a 3-group classification problem, when predicting the LGG molecular subtype.

Seishi Ogawa, Atsushi Natsume and colleagues report analyses of large sets of sequence data of grade II and III gliomas. They find three distinct subtypes of grade II and III gliomas characterized by discrete mutation profiles and distinct clinical behaviors. Grade II and III gliomas are generally slowly progressing brain cancers, many of which eventually transform into more aggressive tumors. Despite recent findings of frequent mutations in IDH1 and other genes, knowledge about their pathogenesis is still incomplete. Here, combining two large sets of high-throughput sequencing data, we delineate the entire picture of genetic alterations and affected pathways in these glioma types, with sensitive detection of driver genes. Grade II and III gliomas comprise three distinct subtypes characterized by discrete sets of mutations and distinct clinical behaviors. Mutations showed significant positive and negative correlations and a chronological hierarchy, as inferred from different allelic burdens among coexisting mutations, suggesting that there is functional interplay between the mutations that drive clonal selection. Extensive serial and multi-regional sampling analyses further supported this finding and also identified a high degree of temporal and spatial heterogeneity generated during tumor expansion and relapse, which is likely shaped by the complex but ordered processes of multiple clonal selection and evolutionary events.

In the original publication [...]

Recent advancements have tangibly changed the cancer treatment landscape. However, curative therapy for this dreadful disease remains an unmet need. Sonodynamic therapy (SDT) is a minimally invasive anti-cancer therapy involving a chemical sonosensitizer and focused ultrasound. A high-intensity focused ultrasound (HIFU) beam is used to destroy or denature targeted cancer tissues. Some SDTs are based on unfocused ultrasound (US). In some SDTs, HIFU is combined with a drug, known as a chemical sonosensitizer, to amplify the drug’s ability to damage cancer cells preferentially. The mechanism by which US interferes with cancer cell function is further amplified by applying acoustic sensitizers. Combining multiple chemical sonosensitizers with US creates a substantial synergistic effect that could effectively disrupt tumorigenic growth, induce cell death, and elicit an immune response. Therefore, the minimally invasive SDT treatment is currently attracting attention. It can be combined with targeted therapy (double-targeting cancer therapy) and immunotherapy in the future and is expected to be a boon for treating previously incurable cancers. In this paper, we will consider the current state of this therapy and discuss parts of our research.

Background: Although extensive resection improves the prognosis of gliomas, it risks impairing critical brain functions. Photodynamic therapy (PDT) utilizing talaporfin sodium (TS) targets tumor cells upon light activation. Despite its approval in Japan, TS application remains restricted, and factors influencing its efficacy are unclear. We aimed to identify TS efficacy determinants to optimize treatment outcomes. Methods: Data from 171 patients with grade 4 glioma who underwent surgery and PDT at Tokyo Women’s Medical University Hospital between January 2017 and March 2024 were retrospectively analyzed. Clinical variables evaluated included age, sex, genotype, Karnofsky Performance Status (KPS), serum albumin (Alb) levels, MIB-1 expression levels, and medication history. TS concentrations in tumor tissues were quantitatively assessed in 82 patients (41 primary, 41 recurrent). Survival outcomes were analyzed. RNA-seq was performed on the three highest and three lowest TS concentration samples with significant TS concentration variations to investigate corresponding gene expression changes. Results: Multivariate analysis identified KPS (hazard ratio [95% confidence interval]: 0.96 [0.93–0.99], p = 0.01) and Alb (3.68 [1.05–13.76], p = 0.047) as independent prognostic factors. In recurrent cases, higher TS concentrations were significantly associated with improved survival (p = 0.0454). RNA-seq analysis indicated decreased expression of ACTB and PDPN genes in samples with lower TS concentrations, suggesting potential resistance mechanisms. Conclusions: TS concentration is a critical determinant of PDT efficacy, especially in recurrent glioma, highlighting its prognostic significance. Alb may affect treatment outcomes by mediating TS binding. RNA-seq findings imply that low TS concentrations may suppress immune and stress response-related genes, potentially diminishing PDT sensitivity.

Introduction Tumor recurrence patterns after resection of intracranial low-grade gliomas (LGG) generally remain obscured. The objective of the present retrospective study was their multifaceted analysis, evaluation of associated factors, and assessment of impact on prognosis. Methods Study group comprised 81 consecutive adult patients (46 men and 35 women; median age, 37 years) with recurrent diffuse astrocytomas (DA; 51 cases) and oligodendrogliomas (OD; 30 cases). The median length of follow-up after primary surgery was 6.7 years. Results Early (within 2 years after primary surgery) and non-early (> 2 years after primary surgery) recurrence was noted in 23 (28%) and 58 (72%) cases, respectively. Fast (≤ 6 months) and slow ( > 6 months) radiological progression of relapse was noted in 31 (38%) and 48 (59%) cases, respectively. Tumor recurrence was local and non-local in 71 (88%) and 10 (12%) cases, respectively. Recurrence patterns have differed in OD, IDH1 -mutant DA, and IDH wild-type DA. Early onset, fast radiological progression, and non-local site of relapse had statistically significant negative impact on overall survival of patients and were often associated with malignant transformation of the tumor (38 cases). However, in subgroup with extent of resection ≥ 90% (56 cases) no differences in recurrence characteristics were found between 3 molecularly defined groups of LGG. Conclusions Recurrence patterns after resection of LGG show significant variability, differ in distinct molecularly defined types of tumors, and demonstrate definitive impact on prognosis. Aggressive resection at the time of primary surgery may result in more favorable characteristics of recurrence at the time of its development.

IntroductionTumor Treating Fields (TTFields; antimitotic treatment) delivers low-intensity, intermediate-frequency, alternating electric fields through skin-applied transducer arrays. TTFields (200 kHz) was FDA-approved in glioblastoma (GBM), based on the phase 3 EF-11 (recurrent GBM, rGBM) and EF-14 (newly diagnosed GBM, ndGBM) trials. The most common TTFields-related adverse event (AE) in both trials was array-associated skin irritation. We now report on TTFields-related AEs in the real-world, clinical practice setting.MethodsUnsolicited, post-marketing surveillance data from TTFields-treated patients (October 2011–February 2019) were retrospectively analyzed using MedDRA v21.1 preferred terms, stratified by region (US, EMEA [Europe, Middle East, Africa], Japan), diagnosis (ndGBM, rGBM, anaplastic astrocytoma/oligodendroglioma, other brain tumors), and age (< 18 [pediatric], 18–64 [adults], ≥ 65 [elderly]; years of age).ResultsOf 11,029 patients, 53% were diagnosed with ndGBM and 39% were diagnosed with rGBM at any line of disease recurrence. Most were adults (73%), 26% were elderly, and the male-to-female ratio was ~ 2:1 (close to published ratios of typical GBM populations). The most commonly reported TTFields-related AE was array-associated skin reaction, occurring in patients with ndGBM (38%), rGBM (29%), anaplastic astrocytoma/oligodendroglioma (38%), and other brain tumors (31%); as well as 37% of pediatric, 34% of adult, and 36% of elderly patients. Most skin AEs were mild/moderate and manageable. Other TTFields-related AEs in patients with ndGBM/rGBM included under-array heat sensation (warmth; 11%, 10%, respectively) and electric sensation (tingling; 11%, 9%, respectively), and headache (7%, 6%, respectively).ConclusionsThis TTFields safety surveillance analysis in > 11,000 patients revealed no new safety concerns, with a favorable safety profile comparable with published TTFields/GBM trials. The safety profile remained consistent among subgroups, suggesting feasibility in multiple populations, including elderly patients.

Primary motor cortex (M1) infarctions sometimes cause sensory impairment. Because sensory signals play a vital role in motor control, sensory impairment compromises the recovery and rehabilitation of motor disability. However, the neural mechanism of the sensory impairment is poorly understood. We show that sensory processing in mouse primary somatosensory cortex (S1) was impaired in the acute phase of M1 infarctions and recovered in a layer-specific manner in the subacute phase. This layer-dependent recovery process and the anatomical connection pattern from M1 to S1 suggested that functional connectivity from M1 to S1 plays a key role in the sensory processing impairment. A simulation study demonstrated that the loss of inhibition from M1 to S1 in the acute phase of M1 infarctions could impair sensory processing in S1, and compensation for the inhibition could recover the temporal coding. Consistently, the optogenetic activation of M1 suppressed the sustained response in S1. Taken together, we revealed how focal stroke in M1 alters the cortical network activity of sensory processing, in which inhibitory input from M1 to S1 may be involved.

Transcranial magnetic stimulation (TMS) is used for the mapping of brain motor functions. The complexity of the brain deters determining the exact localization of the stimulation site using simplified methods (e.g., the region below the center of the TMS coil) or conventional computational approaches. This study aimed to present a high-precision localization method for a specific motor area by synthesizing computed non-uniform current distributions in the brain for multiple sessions of TMS. Peritumoral mapping by TMS was conducted on patients who had intra-axial brain neoplasms located within or close to the motor speech area. The electric field induced by TMS was computed using realistic head models constructed from magnetic resonance images of patients. A post-processing method was implemented to determine a TMS hotspot by combining the computed electric fields for the coil orientations and positions that delivered high motor-evoked potentials during peritumoral mapping. The method was compared to the stimulation site localized via intraoperative direct brain stimulation and navigated TMS. Four main results were obtained: 1) the dependence of the computed hotspot area on the number of peritumoral measurements was evaluated; 2) the estimated localization of the hand motor area in eight non-affected hemispheres was in good agreement with the position of a so-called “hand-knob”; 3) the estimated hotspot areas were not sensitive to variations in tissue conductivity; and 4) the hand motor areas estimated by this proposal and direct electric stimulation (DES) were in good agreement in the ipsilateral hemisphere of four glioma patients. The TMS localization method was validated by well-known positions of the “hand-knob” in brains for the non-affected hemisphere, and by a hotspot localized via DES during awake craniotomy for the tumor-containing hemisphere. •A high-precision localization method is proposed for preoperative TMS.•The method has a good agreement with direct cortical stimulation.•Hotspot predicted by the proposed method is more accurate than nTMS.•The number of measurements required during preoperative mapping may be reduced.•Accurate localization may benefit neurosurgical decision-making in the surgery strategy.

PurposeAwake craniotomy (AC) with intraoperative mapping is the best approach to preserve neurological function for glioma surgery in eloquent or near eloquent areas, but whether AC improves the extent of resection (EOR) and overall survival (OS) is controversial. This study aimed to compare the long-term clinical outcomes of glioma resection under AC with those under general anesthesia (GA).MethodsData of 335 patients who underwent surgery with intraoperative magnetic resonance imaging for newly diagnosed gliomas of World Health Organization (WHO) grades II-IV between 2000 and 2013 were reviewed. EOR and OS were quantitatively compared between the AC and GA groups after 1:1 propensity score matching. The two groups were matched for age, preoperative Karnofsky performance status (KPS), tumor location, and pathology.ResultsAfter propensity score matching, 91 pairs were obtained. The median EOR was 96.1% (interquartile range [IQR] 7.3) and 97.4% (IQR 14.4) in the AC and GA groups, respectively (p = 0.31). Median KPS score 3 months after surgery was 90 (IQR 20) in both groups (p = 0.384). The median survival times were 163.3 months (95% confidence interval [CI] 77.9–248.7) and 143.5 months (95% CI 94.4–192.7) in the AC and GA groups, respectively (p = 0.585).ConclusionEven if the glioma was within or close to the eloquent area, AC was comparable with GA in terms of EOR and OS. In case of difficulties in randomizing patients with eloquent or near eloquent glioma, our propensity score-matched analysis provides retrospective evidence that AC can obtain EOR and OS equivalent to removing glioma under GA.