The Progression and Prospects of the Gene Expression Profiling in Ovarian Epithelial Cancer.

Ovarian cancer is one of the most common cancers with a high mortality rate among females worldwide. The understanding of the pathogenesis of the disease is highly important to provide personalized therapy to the patients. Ovarian cancer is as heterogeneous as colon and breast cancer which makes it difficult to treat. The development of gene signature is the only hope in providing targeted therapy to improve the survival of ovarian cancer patients. Malignant epithelial carcinomas are the most common cancers of the ovary with different histological and molecular subtypes and clinical behavior. The development of precursor lesions of ovarian carcinoma in the tubes and endometrium has provided a new dimension to the origin of ovarian cancers. The clinical utility of various gene signatures may not be logical unless validated. Validated gene signatures can aid the clinician in deciding the appropriate line of treatment.

Uterine preservation in low-grade endometrial stromal sarcoma.

Data on uterine preservation in the management of low grade endometrial stromal sarcoma (LGESS) is scarce due to rarity of this tumor type. Standard management of LGESS involves extrafascial hysterectomy with bilateral salpingo-oophorectomy with debulking of any extrauterine metastatic disease. High estrogen and progesterone receptor expression facilitates adjuvant hormone therapy post-surgery. LGESS frequently affects young women, thus fertility preservation is an important issue in management. Here we describe uterine preservation in two young women diagnosed with LGESS followed by GnRH analogue therapy with favorable outcome. The first case was diagnosed with recurrent endometrial polyp invading myometrium requiring wedge resection of uterus with free margins. Second case presented with a vaginal mass arising from cervix and excision was done through vaginal route. Both patients were prescribed GnRH analogue therapy for six months post-surgery and are currently on follow-up. These case reports add to literature on feasibility of uterine preservation in the management of LGESS.

Evaluation of infectious morbidity due to BTK inhibitors in indolent B-cell lymphomas: latest research findings and systematic analysis.

INTRODUCTION: Randomized clinical trials (RCTs) have suggested that BTK inhibitors (BTKis) might increase infectious disease (ID) risk. Systematic analysis of this topic as derived from RCTs and clinical practice is needed. AREAS COVERED: An extensive Medline, Embase, and Cochrane search of peer-reviewed sources reporting on ID morbidity in patients on BTKis was performed (1 January 2014 - 31 December 2013). Contribution of intrinsic immune defects in indolent B-cell lymphomas to this morbidity was carefully considered. EXPERT OPINION: Patients with indolent B-cell lymphomas display a wide range of innate and adaptive immune defects. In addition, BTKi use is linked with an increased signal of upper respiratory tract infections (URTIs) and pneumonias, mainly grade 1-2. These agents also increase the risk of rare invasive fungal infections (IFIs), mainly due to Cryptococcus and Aspergillus spp. with a peak within several months after the start of therapy. More than half of these IFIs are fatal. Research suggests a similar ID risk across 1st, 2nd and 3rd generations of BTKis, all causing B-cell dysfunction due to BTK inhibition, along with off-target functional neutrophil/macrophage alterations. Expanding the knowledge base on ID morbidity in patients on BTKis would facilitate timely diagnosis and treatment, and improve clinical outcomes.

Effectiveness and safety of the tetravalent TAK-003 dengue vaccine: a systematic review.

In Argentina, the dengue virus has experienced an increase in recent years. This study aims to conduct a systematic review to evaluate the effectiveness and safety of the TAK-003 tetravalent dengue vaccine in this context. A systematic review of randomized controlled trials comparing the effectiveness and safety of the vaccine with placebo in the general population was conducted. The search was carried out in Epistemonikos, and two researchers independently assessed the studies. Risk of bias was evaluated using the Cochrane Rob 2 tool. A meta-analysis of the results was performed, and the certainty of evidence was assessed using the GRADE methodology. We concluded, with high certainty of evidence, that the tetravalent dengue vaccine reduces severe infections (RR 0.17, 95% CI 0.12 to 0.24) and infections by the dengue virus (RR 0.40, 95% CI 0.36 to 0.45) in a population ≤17 years. The vaccine may not increase the risk of serious adverse events, although it is important to note the low certainty of evidence (RR 1.04, 95% CI: 0.69-1.55). The use of the tetravalent dengue vaccine decreases the risk of severe and non-severe dengue infections in this population. However, there is low certainty of evidence regarding the vaccine's safety. The decision to vaccinate should consider the magnitude of benefits relative to the risk of infection.

En Argentina, el virus del dengue ha experimentado un aumento en los últimos años. Este estudio se propone realizar una revisión sistemática para evaluar la efectividad y seguridad de la vacuna TAK-003 tetravalente contra el dengue en este contexto. Se llevó a cabo una revisión sistemática de ensayos clínicos controlados aleatorizados que comparaban la efectividad y seguridad de la vacuna con placebo en la población general. La búsqueda se efectuó en Epistemonikos y dos investigadores evaluaron los estudios de manera independiente. El riesgo de sesgo se evaluó con la herramienta Rob 2 de Cochrane. Se realizó un metaanálisis de los resultados y la certeza en la evidencia se evaluó mediante la metodología GRADE. Concluimos, con alta certeza de evidencia, que la vacuna tetravalente contra el dengue reduce las infecciones graves (RR 0.17, IC 95% 0.12 a 0.24) e infecciones por el virus del dengue (RR 0.40, IC 95% 0.36 a 0.45) en una población de ≤17 años. La vacuna podría no incrementar el riesgo de eventos adversos serios, aunque es importante destacar la baja certeza de evidencia (RR 1.04, IC 95%: 0.69-1.55). La aplicación de la vacuna tetravalente contra el dengue disminuye el riesgo de infecciones graves y no graves por el dengue en esta población. No obstante, existe baja certeza en la evidencia en relación a la seguridad de la vacuna. La decisión de la vacunación debe considerar la magnitud de los beneficios en función del riesgo de infección.

Accurate low and high grade glioma classification using free water eliminated diffusion tensor metrics and ensemble machine learning.

Glioma, a predominant type of brain tumor, can be fatal. This necessitates an early diagnosis and effective treatment strategies. Current diagnosis is based on biopsy, prompting the need for non invasive neuroimaging alternatives. Diffusion tensor imaging (DTI) is a promising method for studying the pathophysiological impact of tumors on white matter (WM) tissue. Single-shell DTI studies in brain glioma patients have not accounted for free water (FW) contamination due to tumors. This study aimed to (a) assess the efficacy of a two-compartment DTI model that accounts for FW contamination and (b) identify DTI-based biomarkers to classify low-grade glioma (LGG) and high-grade glioma (HGG) patients. DTI data from 86 patients (LGG n = 39, HGG n = 47) were obtained using a routine clinical imaging protocol. DTI metrics of tumorous regions and normal-appearing white matter (NAWM) were evaluated. Advanced stacked-based ensemble learning was employed to classify LGG and HGG patients using both single- and two-compartment DTI model measures. The DTI metrics of the two-compartment model outperformed those of the standard single-compartment DTI model in terms of sensitivity, specificity, and area under the curve of receiver operating characteristic (AUC-ROC) score in classifying LGG and HGG patients. Four features (out of 16 features), namely fractional anisotropy (FA) of the edema and core region and FA and mean diffusivity of the NAWM region, showed superior performance (sensitivity = 92%, specificity = 90%, and AUC-ROC = 90%) in classifying LGG and HGG. This demonstrates that both tumorous and NAWM regions may be differentially affected in LGG and HGG patients. Our results demonstrate the significance of using a two-compartment DTI model that accounts for FW contamination by improving diagnostic accuracy. This improvement may eventually aid in planning treatment strategies for glioma patients.

Tumor grade and progesterone receptor status in predicting benefit of chemotherapy in high genomic risk breast cancer.

BACKGROUND: Not all eligible breast cancer (BC) patients could afford the expensive test of 21-gene recurrence score (RS) assay. This study aimed to identify clinicopathological factors associated with high-risk RS and examine whether these factors correlate with the benefit of chemotherapy. RESEARCH DESIGN AND METHODS: Patients diagnosed with early-stage BC, node-negative, and estrogen receptor-positive disease were identified from the Surveillance, Epidemiology, and End Results Oncotype DX database. RESULT: We included 74,605 patients. Those with higher grade (p < 0.001) and progesterone receptor-negative (PR Neg) (p < 0.001) had the highest odds of a high-risk RS. Among them, 3.2%, 10.1%, 39.1%, 18.6%, 41.6%, and 80.1% had high-risk RS tumors in PR-positive (PR Pos)/well-differentiated (G1), PR Pos/moderately differentiated (G2), PR Pos/poorly and/or undifferentiated (G3), PR Neg/G1, PR Neg/G2, and PR Neg/G3 groups, respectively. Receipt of chemotherapy was associated with improved breast cancer-specific survival (p = 0.010) and overall survival (p < 0.001) in high-risk RS cohort. However, there were no survival benefits from chemotherapy in patients with PR Neg/G3 disease and other groups after stratification by grade and PR status (all p ≥ 0.05). CONCLUSION: Our study aids in refining patient selection for the RS testing, which is crucial given its economic implications. However, 21-gene RS remains pivotal for treatment decision-making.

The relationship between gadolinium enhancement and [18 F]fluorothymidine uptake in brain lesions with the use of hybrid PET/MRI.

BACKGROUND: To evaluate and compare the diagnostic power of [18F]FLT-PET with ceMRI in patients with brain tumours or other focal lesions. METHODS: 121 patients with suspected brain tumour or those after brain tumour surgery were enroled in this retrospective study (61 females, 60 males, mean age 37.3 years, range 1-80 years). All patients underwent [18F]FLT-PET/MRI with gadolinium contrast agent application. In 118 of these patients, a final diagnosis was made, verified by histopathology or by follow-up. Agreement between ceMRI and [18F]FLT-PET of the whole study group was established. Further, sensitivity and specificity of ceMRI and [18F]FLT-PET were calculated for differentiation of high-grade vs. low-grade tumours, high-grade vs. low-grade tumours together with non-tumour lesions and for differentiation of high-grade tumours from all other verified lesions. RESULTS: [18F]FLT-PET and ceMRI findings were concordant in 119 cases (98%). On closer analysis of a subset of 64 patients with verified gliomas, the sensitivity and specificity of both PET and ceMRI were identical (90% and 84%, respectively) for differentiating low-grade from high-grade tumours, if the contrast enhancement and [18F]FLT uptake were considered as hallmarks of high-grade tumour. For differentiation of high-grade tumours from low-grade tumours and lesions of nontumorous aetiology (e.g., inflammatory lesions or post-therapeutic changes) in a subgroup of 93 patients by visual evaluation, the sensitivity of both PET and ceMRI was 90%, whereas the specificity of PET was slightly higher (61%) compared to ceMRI (57%). By receiver operating characteristic analysis, the sensitivity and specificity were 82% and 74%, respectively, when the threshold of SUVmax in the tumour was set to 0.9 g/ml. CONCLUSION: We demonstrated a generally very high correlation of [18F]FLT accumulation with contrast enhancement visible on ceMRI and a comparable diagnostic yield in both modalities for differentiating high-grade tumours from low-grade tumours and lesions of other aetiology.

Neuronavigation in glioma resection: current applications, challenges, and clinical outcomes.

Background: Glioma resection aims for maximal tumor removal while preserving neurological function. Neuronavigation systems (NS), with intraoperative imaging, have revolutionized this process through precise tumor localization and detailed anatomical navigation. Objective: To assess the efficacy and breadth of neuronavigation and intraoperative imaging in glioma resections, identify operational challenges, and provide educational insights to medical students and non-neurosurgeons regarding their practical applications. Methods: This systematic review analyzed studies from 2012 to 2023 on glioma patients undergoing surgical resection with neuronavigation, sourced from MEDLINE (PubMed), Embase, and Web of Science. A database-specific search strategy was employed, with independent reviewers screening for eligibility using Rayyan and extracting data using the Joanna Briggs Institute (JBI) tool. Results: The integration of neuronavigation systems with intraoperative imaging modalities such as iMRI, iUS, and 5-ALA significantly enhances gross total resection (GTR) rates and extent of resection (EOR). While advanced technology improves surgical outcomes, it does not universally reduce operative times, and its impact on long-term survival varies. Combinations like NS + iMRI and NS + 5-ALA + iMRI achieve higher GTR rates compared to NS alone, indicating that advanced imaging adjuncts enhance tumor resection accuracy and success. The results underscore the multifaceted nature of successful surgical outcomes. Conclusions: Integrating intraoperative imaging with neuronavigation improves glioma resection. Ongoing research is vital to refine technology, enhance accuracy, reduce costs, and improve training, considering various factors impacting patient survival.

Resection vs. coagulation of dural attachment in patients with spinal meningioma: an updated systematic review and meta-analysis.

BACKGROUND: The Simpson grading scale assumes dural resection (grade I) is more effective against recurrence than coagulation (grade II). However, the results of recent studies have raised doubts about this effectiveness in spinal meningiomas. Therefore, we aimed to perform a meta-analysis comparing outcomes between Simpson grades I and II in spinal meningiomas. METHODS: According to the PRISMA statement, we systematically searched PubMed, EMBASE, and Web of Science for studies involving patients with spinal meningiomas who underwent Simpson grades I, II, III, or IV. Outcomes were radiological tumor recurrence, postoperative neurological deficits, and procedure-related complications. RESULTS: We included 54 studies with a total of 3334 patients. Simpson grades I, II, III, and IV were performed in 674 (20%), 2205 (66%), 254 (8%), and 201 (6%) patients, respectively. The follow-up ranged from 9 to 192 months, and 95.4% of all tumors were WHO grade 1. There was no difference in radiological tumor recurrence (OR 0.80, 95% CI: 0.46-1.36, P = 0.41; I2 = 0%), postoperative neurological deficits (OR 0.74, 95% CI: 0.32-1.75, P = 0.50; I2 = 0%) or procedure-related complications (OR 2.22, 95% CI: 0.80-6.13, P = 0.12; I2 = 3%) between Simpson grades I and II. Furthermore, no significant difference in postoperative neurological deficits or procedure-related complications was detected when comparing all Simpson's to each other. However, radiological tumor recurrences in Simpson I and II were significantly lower than in III and IV, with Simpson III outperforming IV (OR 0.19, 95% CI: 0.09-0.40, P < 0.01; I2 = 0%). CONCLUSION: Simpson grade I is not more effective than grade II in any outcome, although both are superior to III and IV in tumor recurrence. Our results might suggest that dural coagulation is preferable over resection when the latter carries a higher risk of complications.

Ten-year changes of periodontitis grading using direct and indirect evidence: a retrospective evaluation.

OBJECTIVE: To evaluate two methods for assessing the changes in periodontitis grading in patients undergoing supportive periodontal therapy (SPT) ten years (T10) after retrospective baseline (BL) grading. MATERIALS AND METHODS: The periodontitis grade of 51 SPT-patients was assessed using indirect evidence as the primary criterion for periodontitis progression at BL and T10 (radiographic bone loss/age index, periodontitis phenotype). Grading at T10 was also performed using the direct evidence for periodontitis progression (clinical attachment loss over the previous five years). The use of indirect evidence for periodontal progression at BL and T10 was defined as method 1 (M1) to assess the changes in periodontitis grading. The use of indirect evidence at BL and direct evidence at T10 was defined as method 2 (M2). Changes in periodontitis grading using M1 and M2 were evaluated (Wilcoxon signed-rank test). Agreement between M1 and M2 was assessed (Cohen's kappa). RESULTS: Indirect BL-grading revealed five grade B and 46 grade C patients. The indirect grading at T10 revealed 17 grade B and 34 grade C patients. The direct T10-grading classified all patients as grade C. M1 led to an overall improvement in periodontitis grading after ten years of SPT (p=0.00297), whereas M2 led to a deterioration (p=0.0369). The comparison between M1 and M2 showed that they lead to different results in terms of grading (Cohen's Kappa=0.116208). CONCLUSIONS: Periodontitis grading may change during SPT. Using indirect or direct evidence as the primary grading criterion during SPT may lead to different results.

Validity test of small cell lung cancer (SCLC) graded prognostic assessment and proposal of a new index for patients with brain metastases from SCLC.

Background and purpose: We performed a validity test of a recently-reported, small cell lung cancer (SCLC) graded prognostic assessment (GPA) system for SCLC patients with brain metastases (BMs). Thereafter, we created a new prognostic index, the SCLC Grade, for such patients. Materials and methods: We studied 508 SCLC patients selected from among nearly 7000 consecutive patients undergoing gamma knife SRS for BMs since 1998. Results: In the SCLC GPA, there were no median survival time (MST) differences among pairs of the neighboring subgroups. Therefore, the 508 patients were randomly divided into the two series, i.e., a test (340 patients) and a validity (168) series. In the test series, five factors were identified by univariable analyses as favoring longer survival (rounded lower 95 % CI of the HR was at least 1.3): Sex, Karnofsky Performance Status, tumor numbers, primary tumor status and extracerebral metastases. This new index is the sum of scores (0 and 1) of these five factors: SCLC-Grade 4-6 (score of 4, 5 or 6), 2-3 (2 or 3), and 0-1 (0 or 1). This new system showed highly statistically significant MST differences among subclasses. Next, this SCLC-Grade was applied to the verification series. Consistent results were obtained, i.e., there were highly statistically significant MST differences among subclasses. Conclusions: Our validity test results for the SCLC GPA demonstrated this system to not precisely reflect the outcomes of SCLC patients with BMs. Our results suggest the herein-proposed SCLC-Grade to have superior prognostic value.

Multi-omics reveals the impact of cancer-associated fibroblasts on the prognosis and treatment response of adult diffuse highest-grade gliomas.

Background: Cancer associated fibroblasts (CAF), an important cancer-promoting and immunosuppressive component of the tumor immune microenvironment (TIME), have recently been found to infiltrate adult diffuse highest-grade gliomas (ADHGG) (gliomas of grade IV). Methods: Gene expression and clinical data of ADHGG patients were obtained from the CGGA and TCGA databases. Consensus clustering was used to identify CAF subtypes based on CAF key genes acquired from single-cell omics and spatial transcriptomomics. CIBERSORT, ssGSEA, MCPcounter, and ESTIMATE analyses were used to assess the TIME of GBM. Survival analysis, drug sensitivity analysis, TCIA database, TIDE and cMap algorithms were used to compare the prognosis and treatment response between patients with different CAF subtypes. An artificial neural network (ANN) model based on random forest was constructed to exactly identify CAF subtypes, which was validated in a real-world patient cohort of ADHGG. Results: Consensus clustering classified ADHGG into two CAF subtypes. Compared with subtype B, patients with ADHGG subtype A had a poorer prognosis, worse responsiveness to immunotherapy and radiotherapy, higher CAF infiltration in TIME, but higher sensitivity to temozolomide. Furthermore, patients with subtype A had a much lower proportion of IDH mutations. Finally, the ANN model based on five genes (COL3A1, COL1A2, CD248, FN1, and COL1A1) could exactly discriminate CAF subtypes, and the validation of the real-world cohort indicated consistent results with the bioinformatics analyses. Conclusion: This study revealed a novel CAF subtype to distinguish ADHGG patients with different prognosis and treatment responsiveness, which may be helpful for accurate clinical decision-making of ADHGG.

Preoperative bedside test indicators as predictors of difficult video laryngoscopy in obese patients: a prospective observational study.

Purpose: The aim of this study was to identify factors associated with difficult video laryngoscopy in obese patients. Methods: A total of 579 obese patients undergoing elective laparoscopic weight loss surgery were intubated with a single-lumen endotracheal tube using a video laryngoscopy under general anesthesia, and the patients were divided into two groups based on the Cormack-Lehane classification (difficult video laryngoscopy defined as ≥ 3): the easy video laryngoscopy group and the difficult video laryngoscopy group. Record the general condition of the patient, bedside testing indicators related to the airway, Cormack-Lehane classification during intubation, and intubation failure rate. Results: The findings of this study show that the incidence of difficult video laryngoscopy in obese patients is 4.8%. Multivariate logistic regression analysis indicated that body mass index was significantly associated with difficult video laryngoscopy (OR = 1.082, 95% CI [1.033-1.132], P < 0.001). Conclusion: For Chinese obese patients without known difficult airways, the incidence of difficult video laryngoscopy is 4.8%. Body mass index is associated factors for the occurrence of difficult video laryngoscopy, with an increased risk observed as body mass index rise.

ESCMID/EUCIC clinical guidelines on preoperative decolonization and targeted prophylaxis in patients colonized by multidrug-resistant Gram-positive bacteria before surgery.

SCOPE: The aim of these guidelines is to provide recommendations on decolonization and perioperative antibiotic prophylaxis (PAP) in multidrug-resistant Gram-positive bacteria (MDR-GPB) adult carriers before inpatient surgery. METHODS: These European Society of Clinical Microbiology and Infectious Diseases (ESCMID)/European Committee on Infection Control (EUCIC) guidelines were developed following the systematic review of published studies targeting methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), methicillin-resistant coagulase-negative staphylococci (MR-CoNS) and pan-drug-resistant (PDR)-GPB. Critical outcomes were the occurrence of surgical site infections (SSIs) caused by the colonizing MDR-GPB and SSIs-attributable mortality. Important outcomes included the occurrence of SSIs caused by any pathogen, hospital-acquired infections, all-cause mortality, and adverse events associated with the interventions, including resistance development to the agents used and incidence of Clostridioides difficile infections. The last search of all databases was performed on November 1st, 2023. The level of evidence and strength of each recommendation were defined according to the GRADE approach. Consensus of a multidisciplinary expert panel was reached for the final list of recommendations. Antimicrobial stewardship considerations were included. RECOMMENDATIONS: The guideline panel reviewed the impact of decolonization, targeted PAP, and combined interventions (e.g., decolonization and targeted PAP) on the risk of SSIs and other outcomes in MDR-GPB carriers, according to the type of bacteria and type of surgery. We recommend screening for S. aureus (SA) before high-risk operations, such as cardiothoracic and orthopedic surgery. Decolonization with intranasal mupirocin with or without chlorhexidine bathing is recommended in patients colonized with SA before cardiothoracic and orthopedic surgery and suggested in other surgeries. Addition of vancomycin to standard prophylaxis is suggested for MRSA carriers in cardiothoracic surgery, orthopedic surgery, and neurosurgery. Combined interventions (e.g., decolonization and targeted prophylaxis) are suggested in MRSA carriers undergoing cardiothoracic and orthopedic surgery. No recommendation could be made regarding screening, decolonization, and targeted prophylaxis for VRE due to the lack of data. No evidence was retrieved for MR-CoNS and PDR-GPB. Careful consideration of the laboratory workload and involvement of antimicrobial stewardship as well as infection control teams are warranted before implementing screening procedures or performing changes in PAP policy. Future research should focus on novel decolonizing techniques, on the monitoring of resistance to decolonizing agents and PAP regimens, and on standardized combined interventions in high-quality studies.

Predicting Complete versus Incomplete Long-Term Functional Independence after Acute AIS Grade D Spinal Cord Injury: A Prospective Cohort Study.

Background: The proportion of patients with American Spinal Injury Association Impairment Scale (AIS) grade D traumatic spinal cord injuries (tSCI) is increasing. Although initial motor deficits can be relatively mild, some individuals fail to recover functional independence. Objectives: This study aims to identify factors associated with failure to reach complete functional independence after AIS grade D tSCI. Methods: An observational prospective cohort study was conducted at a level 1 trauma center specialized in SCI care. A prospective cohort of 121 individuals with an AIS-D tSCI was considered. The baseline characteristics, length of acute stay, need for inpatient rehabilitation, and 12-month functional status were assessed. Univariate and classification and regression tree (CART) analyses were performed to identify factors associated with reaching complete versus incomplete functional independence (defined as perfect total SCIM III score at 12-month follow-up). Results: There were 69.3%, 83.3%, and 61.4% individuals reaching complete independence in self-care, respiration/sphincter management, and mobility, respectively. A total of 64 individuals (52%) reached complete functional independence in all three domains. In the CART analysis, we found that patients are more likely to achieve complete functional independence when they have a baseline motor score ≥83 (65% individuals) and if they present fewer medical comorbidities (70% individuals if Charlson Comorbidity Index [CCI] ≤4). Conclusion: About half of individuals with AIS grade D tSCI can expect complete long-term functional independence. It is important to recognize early during acute care individuals with baseline motor score <83 or a high burden of comorbidities (CCI ≥5) to optimize their rehabilitation plan.

The variable histogenesis and biology of selected bland fibroblastic lesions of the breast - pitfalls in the differential diagnostics and optimal therapeutic approach (three case reports).

Presented are three casuistics of seemingly identical breast lesions which even by adopting advanced laboratory techniques may represent diagnostic challenge. Microscopic features of some bland spindle cell lesions of different histogenesis (epithelial or mesenchymal) are misleading and a potential source of unaware errors, which might affect optimal therapeutic strategy. In the setting of three diverse entities (low-grade spindle cell metaplastic carcinoma, desmoid fibromatosis and phyllodes tumor) is documented both demanding diagnostic algorithm and revealing molecular landscape on one side as well as evolving predictive/prognostic parameters on the other one. Close interdisciplinary cooperation is inevitable for accurate interpretation/understanding of revealed diagnostic facts which is required for adjustment of competent rational and individualized therapy.

Advances in the Treatment of Pediatric Low-Grade Gliomas.

PURPOSE OF REVIEW: Pediatric low-grade gliomas (pLGGs) often result in significant long-term morbidities despite high overall survival rates. This review aims to consolidate the current understanding of pLGG biology and molecular features and provide an overview of current and emerging treatment strategies. RECENT FINDINGS: Surgical resection remains a primary treatment modality, supplemented by chemotherapy and radiotherapy in specific cases. However, recent advances have elucidated the molecular underpinnings of pLGGs, revealing key genetic abnormalities such as BRAF fusions and mutations and the involvement of the RAS/MAPK and mTOR pathways. Novel targeted therapies, including MEK, BRAF and pan-RAF inhibitors, have shown promise in clinical trials, demonstrating significant efficacy and manageable toxicity. Understanding of pLGGs has significantly improved, leading to more personalized treatment approaches. Targeted therapies have emerged as effective alternatives, potentially reducing long-term toxicities. Future research should focus on optimizing therapy sequences, understanding long-term impacts, and ensuring global accessibility to advanced treatments.

A perioperative study of Safusidenib in patients with IDH1-mutated glioma.

This is a single arm, open label perioperative trial to assess the feasibility, pharmacokinetics and pharmacodynamics of treatment with safusidenib following biopsy, and prior to surgical resection in patients with IDH1 mutated glioma who have not received radiation therapy or chemotherapy. Fifteen participants will receive treatment in two parts. First, biopsy followed by one cycle (28 days) of safusidenib, an orally available, small molecular inhibitor of mutated IDH1, then maximal safe resection of the tumor (Part A). Second, after recovery from surgery, safusidenib until disease progression or unacceptable toxicity (Part B). This research will enable objective measurement of biological activity of safusidenib in patients with IDH1 mutated glioma. Anti-tumor activity will be assessed by progression free survival and time to next intervention.Clinical Trial Registration: NCT05577416 (ClinicalTrials.gov).

Adult low-grade gliomas (aLGG) are primary brain cancers, defined by mutations in IDH1 or IDH2. When the IDH gene becomes abnormal (mutated), production of a metabolite that causes cancer cells to grow is increased. These tumors grow slowly but invade the normal functioning brain, making them nearly impossible to cure. The current standard of care treatment includes surgery, followed by radiation therapy and chemotherapy, the timing of which depends on the risk of cancer regrowth. Some patients may be suitable for monitoring with MRI scans alone, however recurrences will inevitably occur. Recently developed targeted mutant IDH inhibitors for aLGG patients may be beneficial both at diagnosis and recurrence. Notably, early treatment prior to radiation therapy and chemotherapy delays growth of aLGG and the need for subsequent radiation therapy and chemotherapy. Nevertheless, most patients will eventually suffer further tumor growth and the optimal timing and sequencing of these therapies remains an area of active research. This research investigates the mutant IDH1 inhibitor safusidenib. The researchers are conducting an innovative clinical trial where patients with aLGG, who have not received radiation therapy or chemotherapy, are treated with safusidenib following a biopsy and prior to surgical removal of their tumor. In this study they investigate whether this trial design is safe and feasible, and how safusidenib works; with the goal to better understand the optimal use of IDH inhibitors for patients with aLGG.