WHO Tumor Research Articles

LET-7a and LET-7b as Potential Signatures for Glioma Recurrence, Regardless of WHO Tumor Grade.

Micro RNAs (miRs; miRNAs) are small, non-coding RNA segments that influence gene expression. To do this, they bind to corresponding mRNA segments and inhibit the subsequent protein translation. Currently, about 200 transcripts are thought to be regulated by a single miRNA. Dysregulated miRNAs can act as tumor promoters as well as tumor suppressors. The aim of this study was to verify miR-LET-7a and miR-LET-7b as a signature for glioma recurrence detection by analyzing their expression in glioma tissue. Only patients with two or more recurrences of glioma (n=25) were included in the study (tissue samples, n=89). Tissue was obtained during neurosurgical procedures and shock-frozen in liquid nitrogen. The patient cohort (female:male=12:13) had an average age of 35 years when first diagnosed (primary tumor: 13 WHO grade II, 7 WHO grade III and 5 WHO grade IV) and 48 years in the fifth relapse. Quantitative real-time polymerase chain reaction was performed to analyze miRNA expression. miR-151a-3p was used as an internal reference. Expression of miR-LET-7a and miR-LET-7b was significantly lower in the first recurrence than in the primary tumor. The expression of miR-LET-7a and -7b significantly decreased with increasing tumor grade. The strongest down-regulation was found between WHO grade III and IV. In paired samples in which tumor grade did not change between the primary and the first recurrence, the expression of both miRNAs remained significantly lower in the recurrent than in the primary tumor. miR-LET-7a and miR-LET-7b represent a potential signature for glioma recurrence regardless of WHO grade.

Prognostic significance of collagen content in solitary fibrous tumors of the central nervous system.

We aimed to explore the prognostic significance of collagen content in solitary fibrous tumors (SFTs) of the central nervous system (CNS) and preliminarily investigate its relationship with magnetic resonance imaging (MRI) features of SFTs. Collagen content was identified using Masson's trichrome staining, and quantitatively assessed. Radiomic methods were applied to extract quantitative MRI features of SFTs, which were then analyzed in relation to collagen content. The collagen content in CNS SFTs was categorized into high- and low-content groups, with a cutoff value of 6%. Survival analysis indicated a positive correlation between collagen content and overall survival (OS). In multivariate Cox regression analysis, incorporating factors such as mitosis, necrosis, Ki67, and collagen content and other indicators, collagen content emerged as an independent prognostic factor. Collagen content demonstrated a negative correlation with tumor histological phenotype, Ki67, WHO grade, mitosis, necrosis, and brain invasion. Additionally, the signal intensity of SFTs on T2-weighted imaging (T2WI) decreased with increasing collagen content. Radiomics analysis identified 1,702 features from each patient's region of interest, with 12 features showing significant differences between the high and low collagen content groups. Among the quantitative parameters and radiomic models, the combined T1- and T2WI models exhibited the highest diagnostic performance. These findings suggest that collagen content is an independent prognostic risk factor for OS. Furthermore, combined radiomic models based on T1-and T2WI sequences may offer a more comprehensive, objective, and accurate assessment of collagen content in CNS SFTs.

EPID-05. THE INCREASED RISK OF MENINGIOMA AMONG INDIVIDUALS WHO ARE NON-HISPANIC BLACK IS MAGNIFIED AMONG MALES AND AMONG THOSE DIAGNOSED WITH GRADE 2-3 TUMORS

Abstract BACKGROUND Demographic factors associated with elevated meningioma incidence include older age, female sex, and Black race. There are limited data exploring how meningioma risk in Black persons varies across the lifespan, interacts with sex, and differs by tumor grade. METHODS The Central Brain Tumor Registry of the United States (CBTRUS) is a population-based registry combining data from the CDC’s National Program of Cancer Registries and NCI’s Surveillance, Epidemiology and End Results Program, covering the entire U.S. population. Meningioma diagnoses from CBTRUS (2004-2019) were used to calculate incidence rate ratios (IRRs) for non-Hispanic Black individuals (NHB) as compared to non-Hispanic White individuals (NHW) across 10-year age intervals, and stratified by sex and WHO tumor grade (grade 1 versus grades 2/3, combined). RESULTS From 2004-2019, a total of 53,890 NHB individuals and 322,373 NHW individuals were diagnosed with a primary meningioma. The NHB to NHW IRR was elevated, beginning in the third decade of life (IRR=1.19; 95%CI: 1.11-1.28), peaking in the seventh decade (IRR=1.29; 95%CI: 1.26-1.31), and persisting throughout the lifespan. The IRR peaked in the seventh decade of life across strata of tumor grade, but, within this age group, NHB race/ethnicity was associated with substantially higher risk of grade 2/3 tumors (IRR=1.59; 95%CI: 1.48-1.70) than grade 1 tumors (IRR=1.27; 95%CI: 1.24-1.29). Meningioma risk was elevated in NHB females compared to NHW females (IRR=1.16; 95%CI: 1.15-1.18) and among NHB males compared to NHW males (IRR=1.22; 95%CI: 1.19-1.25), revealing synergistic interaction between NHB race/ethnicity and male sex (PInteraction=0.001). CONCLUSIONS This study identifies an elevated risk of meningioma in NHB relative to NHW, beginning shortly after puberty and continuing across the lifespan. NHB race/ethnicity conferred higher risk of meningioma among men than among women, and higher risk of developing WHO grade 2/3 than grade 1 tumors. These results highlight meningioma as a major potential source of racial disparities in neuro-oncology.

PATH-01. SELLAR SOLITARY FIBROUS TUMORS WHO GRADE II AND III: MIMICS OF NON-FUNCTIONING PITUITARY ADENOMAS

Abstract Solitary fibrous tumors WHO grade II and III (SFTs II/III) are rare mesenchymal neoplasia accounting for 0.4% of primary central nervous system tumors. SFTs II/III located in the sella turcica region are even rarer and, since the first case described in 1983, only 21 case reports of sellar/suprasellar SFTs II/III (ssSFTs II/III) have been described to this day. We aim to analyze ssSFTs II/III and to demonstrate that can be differentiated from non-functioning pituitary adenomas through pathological examination alone. We analyzed 20 case reports of ssSFTs II/III identified through PubMed and Google searches and a new unpublished case presented at Emory University. ssSFTs II/III are equally represented in both sexes, with 11 cases over 21 occurring in females and the mean age of onset at 46 years old. Clinically, ssSFTs II/III present with compression symptoms related to the tumor location. Headache, visual field defects, and anterior hypopituitarism-related symptoms are frequent chief complaints. As such, almost all cases of ssSFTs II/III had a pre-biopsy working diagnosis of non-functioning pituitary adenomas. The differentiation between SFTs II/III and pituitary adenomas based on imaging findings remains challenging, and surgical biopsies are necessary for a definitive diagnosis. ssSFTs II/III surgical reports describe a unifying trait of a highly vascular tumor adherent to the dura that bleeds profusely after resection. These characteristics are less consistent with a pituitary adenoma. The genetic hallmark of SFTs at all anatomical sites is paracentric inversions at 12q13, fusing the NAB2 and STAT6 genes, with consequent overexpression of STAT6. Pituitary adenomas lack this genetic signature. ssSFTs II/III have an overlapping presentation and similar imaging findings of pituitary adenomas, but different management and prognosis. Hence, it is crucial to include ssSFTs II/III among the pre-biopsy differential of sellar/suprasellar masses identified on imaging. Pathology confirmation is required to guide therapy.

Utility and Safety of 5-ALA Guided Surgery in Pediatric Brain Tumors: A Systematic Review.

Background: 5-Aminolevulinic acid-guided surgery for adult gliomas has been approved by the European Medicines Agency and the US Food and Drug Administration, becoming a reliable tool for improving gross total resection rates and patient outcomes. This has led several medical centers to explore the off-label use of 5-ALA in the resection of pediatric brain tumors, assessing its efficacy and safety across various tumor types. However, given the differences between children and adults, the appropriateness of 5-ALA use in pediatric populations has not yet been fully established. Methods: We collected eligible publications from Embase, Scopus, PubMed, and Proquest, ultimately selecting 27 studies. Data extraction and retrospective analysis of 249 surgical cases were conducted to determine the current efficacy and safety of 5-ALA in pediatric brain tumors. The fluorescence rate and utility stratified by several clinical features, including WHO grade, tumor classification, and tumor location, were analyzed. Results: Most studies suggest that 5-ALA can enhance tumor identification in high-grade tumors, including glioblastomas and anaplastic astrocytomas. Changes in survival or recurrence rates associated with 5-ALA-guided resection have not been reported. None of the cases reported significant postoperative complications related to the use of 5-ALA. Conclusions: 5-ALA can aid in the resection of high-grade gliomas in pediatric patients. The efficacy of 5-ALA in low-grade gliomas and other tumors may require enhancement with additional tools or modified administration protocols. The safety of 5-ALA has reached a preliminary consensus, although further randomized controlled trials and data on survival and molecular characteristics are needed.

Impact of molecular classification on prognosis in children and adolescents with spinal ependymoma: Results from the HIT-MED database

Abstract Background Ependymomas of the spinal cord are rare among children and adolescents, and the individual risk of disease progression is difficult to predict. This study aims at evaluating the prognostic impact of molecular typing of pediatric spinal cord ependymomas. Methods Eighty-three patients with spinal ependymomas ≤22 years registered in the HIT-MED database between 1992 and 2022 were included. Forty-seven tumors were analyzed by DNA methylation array profiling. In six cases, HOXB13 and MYCN proteins were detected as surrogate markers for specific methylation classes. Ten patients had NF2-related schwannomatosis. Results With a median follow-up time of 4.9 years (y), 5y- and 10y-overall survival (OS) were 100% and 86%, while 5y- and 10y-progression-free survival (PFS) were 65% and 54%. Myxopapillary ependymoma (SP-MPE, n=32, 63%) was the most common molecular type followed by spinal ependymoma (SP-EPN, n=17, 33%) and MYCN-amplified ependymoma (n=2, 4%). One case could not be molecularly classified, and one was reclassified as anaplastic pilocytic astrocytoma. 5y-PFS did not significantly differ between SP-MPE and SP-EPN (65% versus 78%, p=0.64). MYCN-amplification was associated with early relapses (<2.3y) in both cases and death in one patient. Patients with SP-MPE subtype B (n=9) showed a non-significant trend for better 5y-PFS compared to subtype A (n=18; 86% versus 56%, p=0.15). The extent of resection and WHO tumor grades significantly influenced PFS in a uni- and multivariate analysis. Conclusions Molecular typing of pediatric spinal ependymomas aids to identify very-high-risk MYCN-amplified ependymomas. Further insights into the molecular heterogeneity of spinal ependymomas are needed for future clinical decision-making.

Grade-stratified meningioma risk among individuals who are Non-Hispanic black and interactions with male sex.

Meningioma risk factors include older age, female sex, and African-American race. Limited data explore how meningioma risk in African-Americans varies across the lifespan, interacts with sex, and differs by tumor grade. The Central Brain Tumor Registry of the United States (CBTRUS) is a population-based registry covering the entire U.S. population. Meningioma diagnoses from 2004-2019 were used to calculate incidence rate ratios (IRRs) for non-Hispanic Black individuals (NHB) compared to non-Hispanic white individuals (NHW) across 10-year age intervals, and stratified by sex and by WHO tumor grade in this retrospective study. 53,890 NHB individuals and 322,373 NHW individuals with an intracranial meningioma diagnosis were included in analyses. Beginning in young adulthood, the NHB-to-NHW IRR was elevated for both grade 1 and grade 2/3 tumors. The IRR peaked in the seventh decade of life regardless of grade, and was higher for grade 2/3 tumors (IRR = 1.57; 95% CI: 1.46-1.69) than grade 1 tumors (IRR = 1.27; 95% CI: 1.25-1.30) in this age group. The NHB-to-NHW IRR was elevated in females (IRR = 1.17; 95% CI: 1.16-1.18) and was further elevated in males (IRR = 1.28; 95% CI: 1.26-1.30), revealing synergistic interaction between NHB race/ethnicity and male sex (PInteraction=0.001). Relative to NHW individuals, NHB individuals are at elevated risk of meningioma from young adulthood through old age. NHB race/ethnicity conferred greater risk of meningioma among men than women, and greater risk of grade 2/3 tumors. Population-level differences in meningioma incidence and tumor behavior suggest potential disparities in the geographic, socioeconomic, and racial distribution of meningioma risk factors within the U.S.

Intracranial Solitary Fibrous Tumor in a 25-Year-Old Woman

<p><strong>Introduction:</strong> Intracranial solitary fibrous tumors (ISFTs) are extremely rare spindle cell tumors originating from dendritic mesenchymal cells expressing CD34 antigens that are usually benign, although malignant transformation had been reported. The knowledge of natural course and prognostic factors of ISFTs is still limited and the tumor is easily misdiagnosed.</p><p><strong>Case Presentation:</strong> An intra-cranial extra-axial tumor tissue resection from a 25-year-old woman was evaluated in the Surgical Pathology Laboratory. Histologic findings (cellular spindle cell tumor with ‘patternless’ pattern, staghorn blood vessels and <5 mitoses per 10 hpf) and immunophenotype (positive for CD34, weakly and focally positive for STAT6) suggested a diagnosis of intracranial solitary fibrous tumor WHO Grade II.</p><p><strong>Discussion:</strong> ISFTs have very low incidence in the CNS and are difficult to distinguish radiologically from meningiomas, thus post operative pathological examination and immunohistochemistry markers evaluations are the mainstay for diagnosis. ISFT is associated with NAB2-STAT6 gene fusion and may exhibits a wide spectrum of histological features. STAT6 immunohistochemistry is considered as one of the most sensitive diagnostic methods, while the evaluation of CD34 expression can be used as alternative diagnostic method despite having lower sensitivity.</p>

Preoperative prediction of CNS WHO grade and tumour aggressiveness in intracranial meningioma based on radiomics and structured semantics

Preoperative identification of intracranial meningiomas with aggressive behaviour may help in choosing the optimal treatment strategy. Radiomics is emerging as a powerful diagnostic tool with potential applications in patient risk stratification. In this study, we aimed to compare the predictive value of conventional, semantic based and radiomic analyses to determine CNS WHO grade and early tumour relapse in intracranial meningiomas. We performed a single-centre retrospective analysis of intracranial meningiomas operated between 2007 and 2018. Recurrence within 5 years after Simpson Grade I-III resection was considered as early. Preoperative T1 CE MRI sequences were analysed conventionally by two radiologists. Additionally a semantic feature score based on systematic analysis of morphological characteristics was developed and a radiomic analysis were performed. For the radiomic model, tumour volume was extracted manually, 791 radiomic features were extracted. Eight feature selection algorithms and eight machine learning methods were used. Models were analysed using test and training datasets. In total, 226 patients were included. There were 21% CNS WHO grade 2 tumours, no CNS WHO grade 3 tumour, and 25 (11%) tumour recurrences were detected in total. In ROC analysis the best radiomic models demonstrated superior performance for determination of CNS WHO grade (AUC 0.930) and early recurrence (AUC 0.892) in comparison to the semantic feature score (AUC 0.74 and AUC 0.65) and conventional radiological analysis (AUC 0.65 and 0.54). The combination of human classifiers, semantic score and radiomic analysis did not markedly increase the model performance. Radiomic analysis is a promising tool for preoperative identification of aggressive and atypical intracranial meningiomas and could become a useful tool in the future.

Is it Cellulitis Again? Erythema Concerning for Infection in Children With High-Risk Solid Tumors Who Have a Gastrostomy Tube.

Proper nutrition is known to hasten healing, reduce treatment-related morbidity, and improve outcomes. Children with high-risk solid tumors often have gastrostomy tubes (GTs) placed for supplemental nutrition during cancer therapy. Gastrostomy tubes, however, are not without risks, and many patients develop erythema concerning for infection at the stoma site. Gastrostomy complications are described in the literature, but knowledge regarding this topic is limited. In this retrospective descriptive study, the authors reviewed 3 years of clinical data regarding pediatric patients with solid tumors who had GTs at a pediatric medical center. Descriptive statistics were used to describe the incidence of erythema concerning for infection, identify factors most likely to be associated with this complication, and understand how erythema impacts the completion of cancer therapy. In a sample of 58 children with high-risk solid tumors who had GTs placed between 2018 and 2021, 53% developed erythema concerning for infection. More subjects who experienced episodes of GT erythema had neuroblastoma (48%), tubes placed after the start of cancer therapy (74%), and erythema during periods of neutropenia (71%). Only one subject experienced a treatment delay due to GT erythema. Despite the rate of GT erythema among study subjects, most completed cancer therapy without delay related to this complication. Additionally, the incidence of stoma site erythema was notably less when tubes were placed prior to the start of cancer therapy. Therefore, the authors recommend GT placement prior to therapy start when possible and further attention be paid to this complication during cancer therapy.

Elevated meningioma risk among individuals who are Non-Hispanic Black is strongest for grade 2-3 tumors and synergistically modified by male sex.

Meningioma risk factors include older age, female sex, and African-American race. There are limited data exploring how meningioma risk in African-Americans varies across the lifespan, interacts with sex, and differs by tumor grade. The Central Brain Tumor Registry of the United States (CBTRUS) is a population-based registry covering the entire U.S. population. Meningioma diagnoses from 2004-2019 were used to calculate incidence rate ratios (IRRs) for non-Hispanic Black individuals (NHB) compared to non-Hispanic white individuals (NHW) across 10-year age intervals, and stratified by sex and by WHO tumor grade. 53,890 NHB individuals and 322,373 NHW individuals with an intracranial meningioma diagnosis were included in analyses. Beginning in young adulthood, the NHB-to-NHW IRR was elevated for both grade 1 and grade 2/3 tumors. The IRR peaked in the seventh decade of life regardless of grade, and was higher for grade 2/3 tumors (IRR=1.57; 95% CI: 1.46-1.69) than grade 1 tumors (IRR=1.27; 95% CI: 1.25-1.30) in this age group. The NHB-to-NHW IRR was elevated in females (IRR=1.17; 95% CI: 1.16-1.18) and further elevated in males (IRR=1.28; 95% CI: 1.26-1.30), revealing synergistic interaction between NHB race/ethnicity and male sex (P Interaction =0.001). Relative to NHW individuals, NHB individuals are at elevated risk of meningioma from young adulthood through old age. NHB race/ethnicity conferred higher risk of meningioma among men than women, and higher risk of developing WHO grade 2/3 tumors. Results identify meningioma as a significant source of racial disparities in neuro-oncology and may help to improve preoperative predictions of meningioma grade.

Perioperative Management of Neuroanesthesia in Patients with Supratentorial Tumors Who Have Excised Tumors Using Neuroprotection Technique and Total Intravenous Anesthesia

Background: Neuroanesthesia management presents a unique challenge for anesthesiologists. They must provide an optimal surgical condition without worsening the patient's neurological deficits. Therefore, we need drugs with neuroprotective abilities. This case report explains the perioperative management of neuroanesthesia in patients with supratentorial tumors who have excised tumors using a neuroprotection technique and total intravenous anesthesia (TIVA). Case: A 43-year-old female patient with space-occupying process cerebri with the differential diagnosis of meningioma frontotemporal dextra, post trepanation frontal sinistra tumor excision, edema cerebri, and hydrocephalus on ventriculoperitoneal shunt. On physical examination, Glasgow coma scale E3M6Vaphasia, aphasia and left hemiparesis were found. She underwent a tumor excision procedure with total intravenous anesthesia modified with neuroprotection techniques and total intravenous anesthesia techniques using 300 mg thiopental, 2 mg midazolam, 150 µg fentanyl, 80 mg lidocaine, and 50 mg rocuronium. Intraoperative anesthesia management was carried out by administering propofol 50 mg/hour, fentanyl 50 µg/hour, and atracurium 15 mg/hour. Conclusion: Total intravenous anesthesia is a complete general anesthesia method used in all intravenous agents, where the benefits of this method are used in neurosurgery, including accelerating the patient's return from the effects of anesthesia, faster recovery of cognitive function, as well as reducing intracranial pressure and the risk of ischemia.

Value of long non-coding RNA HAS2-AS1 as a diagnostic and prognostic marker of glioma

BackgroundGlioma presents high incidence and poor prognosis, and therefore more effective treatments are needed. Studies have confirmed that long non-coding RNAs (lncRNAs) basically regulate various human diseases including glioma. It has been theorized that HAS2-AS1 serves as an lncRNA to exert an oncogenic role in varying cancers. This study aimed to assess the value of lncRNA HAS2-AS1 as a diagnostic and prognostic marker for glioma. MethodsThe miRNA expression data and clinical data of glioma were downloaded from the TCGA database for differential analysis and survival analysis. In addition, pathological specimens and specimens of adjacent normal tissue from 80 patients with glioma were used to observe the expression of HAS2-AS1. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic ability and prognostic value of HAS2-AS1 in glioma. Meanwhile, a Kaplan–Meier survival curve was plotted to evaluate the survival of glioma patients with different HAS2-AS1 expression levels. ResultsHAS2-AS1 was significantly upregulated in glioma tissues compared with normal tissue. The survival curves showed that overexpression of HAS2-AS1 was associated with poor overall survival (OS) and progression-free survival (PFS). Several clinicopathological factors of glioma patients, including tumor size and WHO grade, were significantly correlated with HAS2-AS1 expression in tissues. The ROC curve showed an area under the curve (AUC) value of 0.863, indicating that HAS2-AS1 had good diagnostic value. The ROC curve for the predicted OS showed an AUC of 0.906, while the ROC curve for predicted PFS showed an AUC of 0.88. Both suggested that overexpression of HAS2-AS1 was associated with poor prognosis. ConclusionsNormal tissues could be clearly distinguished from glioma tissues based on HAS2-AS1 expression. Moreover, overexpression of HAS2-AS1 indicated poor prognosis in glioma patients. Therefore, HAS2-AS1 could be used as a diagnostic and prognostic marker for glioma.

Abstract 1006: Revitalizing the accrual of women and minorities: Unique drivers of therapeutic clinical trial enrollment for underrepresented patients with diffuse glioma

Abstract Introduction: Despite the enactment of the 1993 NIH Revitalization Act to improve accrual of women and minorities in clinical trials, these groups remain underrepresented. This study aims to uncover drivers of therapeutic clinical trial enrollment that are unique to women and minority patients with low- and high-grade glioma. Methods: Adult glioma patients who received care from the UCSF Brain Tumor Center between 1997-2017 were identified in a prospective registry. Dividing the cohort into subgroups by gender and NIH-designated minority status, factors associated with therapeutic clinical trial enrollment on univariate logistic regression (p<0.2) were selected for multivariate logistic regression. Results: There were 351 trial participants (41% women, 12% minority) and 627 non-trial participants (44% women, 17% minority). Among women only, seizure at presentation (OR 2.10, p=0.008) was associated with increased odds of trial enrollment. In contrast, among men only, higher median household income (OR 1.09 per $10,000 increase, p=0.006), higher WHO tumor grade (OR 1.89, p=0.045), and occupational status according to the International Standard Classification of Occupations [professionals (e.g., physicians) vs managers (e.g., supervisory positions), OR 2.87, p=0.043] were associated with increased odds of trial enrollment. Among both women and men, lack of insurance (women: OR 0.49, p=0.02; men: OR 0.55, p=0.031) and no treatment with chemotherapy (women: OR 0.18, p=0.001; men: OR 0.34, p=0.002) were associated with decreased odds of clinical trial enrollment, whereas higher KPS (women: 90 vs <80, OR 3.16, p=0.003; men: 90 vs <80, OR 3.15, p=0.002) was associated with increased odds of trial enrollment. Among NIH-designated minority patients, older age (OR 0.66 per 10-year increase, p=0.033) and non-English preferred language (OR: 0.30, p=0.035) were associated with decreased odds of trial enrollment on univariate analysis, but not on multivariate analysis. Among non-minority patients, lack of insurance (OR 0.58, p=0.008) and no chemotherapy treatment (OR 0.25, p<0.001) were associated with decreased odds of trial enrollment, whereas seizure at presentation (OR 1.80, p=0.001), higher neighborhood household income (OR 1.07 per $10,000 increase, p=0.004), higher WHO grade (4 vs 2-3, OR 1.86, p=0.015), higher KPS (90 vs <80, OR 3.21, p<0.0001), and lower extent of tumor resection (80-89% vs 100%, OR 2.16, p=0.047) were associated with increased odds of trial enrollment. Conclusion: Drivers of trial enrollment differed for women and minority patients with glioma. Non-English-speaking minority patients may face additional barriers to trial enrollment requiring targeted interventions. Our findings can revitalize and tailor efforts to recruit women and minority patients to therapeutic clinical trials in neuro-oncology. Citation Format: Mulki Mehari, Gayathri Warrier, Sheantel Reihl, Abraham Dada, Aymen Kabir, Mikias Negussie, Cesar Nava Gonzales, Ugonma Chukwueke, Alyx Porter, Shawn Hervey-Jumper. Revitalizing the accrual of women and minorities: Unique drivers of therapeutic clinical trial enrollment for underrepresented patients with diffuse glioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1006.

Exploring prognostic factors and treatment strategies for long-term survival in pleomorphic xanthoastrocytoma patients

Pleomorphic xanthoastrocytomas (PXA) are rare, accounting for < 1% of all astrocytomas. Literature on the clinical course and treatment outcomes of PXAs is limited. The study aimed to determine prognosis and treatment strategies for PXAs. Patients who had PXAs surgery between 2000–2021 were retrospectively analyzed for demographics and radiological characteristics. Initial and salvage treatment outcomes were recorded. Overall, 40 and 9 patients had grade 2 and 3 PXAs; their 5-year progression-free survival (PFS) rates were 75.8% and 37.0%, respectively (p = 0.003). Univariate analysis revealed that strong T1 enhancement (p = 0.036), infiltrative tumor margins (p < 0.001), peritumoral edema (p = 0.003), WHO grade (p = 0.005), and gross total resection (p = 0.005) affected the PFS. Multivariate analysis revealed that the WHO grade (p = 0.010) and infiltrative tumor margins (p = 0.008) influenced the PFS. The WHO grade (p = 0.027) and infiltrative tumor margins (p = 0.027) also affected the overall survival (OS). Subgroup analysis for grade 2 PXAs revealed no significant associations between adjuvant radiation therapy and the PFS and OS. This study highlighted the heterogeneous nature of PXAs and its impact on patient prognosis. Infiltrative tumor margins emerged as a key prognostic factor. Our findings have emphasized the prognostic relevance of radiological features and the need for larger studies on comprehensive management.

Astrocytomas of the spinal cord.

Tumors of astrocytic origin represent one of the most frequent entities among the overall rare group of spinal cord gliomas. Initial clinical symptoms are often unspecific, and sensorimotor signs localizing to the spinal cord occur with progressing tumor growth. On MRI, a hyperintense intrinsic spinal cord signal on T2-weighted sequences with varying degrees of contrast enhancement raises suspicion for an infiltrative neoplasm. Blood and CSF analysis serves to exclude an infectious process, nutritional deficits, or metabolic disorders. When such other differential diagnoses have been ruled out, a neuropathological tissue-based analysis is warranted to confirm the diagnosis of a spinal cord astrocytoma and guide further patient management. As such, maximal safe resection forms the basis of any treatment. Meticulous preoperative planning is necessary to weigh the potential improvement in survival against the risk of functional deterioration. Intraoperative neuromonitoring and ultrasound may aid in achieving a more extensive resection. Depending on the assigned WHO tumor grade spanning from grade 1 to grade 4, the use of radiotherapy and chemotherapy might be indicated but also wait-and-scan approaches appear reasonable in tumors of lower grade. Close imaging follow-up is necessary given that recurrence inevitably occurs in astrocytomas of grades 2-4. Prognosis is so far dictated by tumor grade and histopathological findings, but also by age and clinical performance of the patient. Targeted therapies resting upon an in-depth tissue analysis are emerging in recurrent tumors, but no prospective study is available so far given the rarity of spinal cord astrocytomas.

Quality of surveillance in patients with completely resected gastroenteropancreatic neuroendocrine tumors.

591 Background: The incidence and prevalence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are increasing worldwide. Surgery remains the only curative modality. Because of limited data on patterns of recurrence, real-world surveillance practices and duration vary widely. In 2018, the Commonwealth Neuroendocrine Tumour Research Collaboration (CommNETs) published consensus surveillance guidelines for patients with completely resected GEP-NETs. Our aim was to assess adherence to the CommNETs guidelines for surveillance practices for this patient population at our center. Methods: We conducted a retrospective cohort study of patients with GEP-NETs seen for a new patient appointment at Princess Margaret Cancer Centre (PMCC) from 2019-2022. Patients were included if they had a completely resected GEP-NET and followed on surveillance at our center. Demographic and tumor characteristics, surveillance practices, and clinical outcomes were abstracted. Summary statistics and a descriptive comparison of surveillance practices were completed. Results: Out of the 374 new patient appointments, 87 met the inclusion criteria. The main reasons for exclusion were metastatic disease at presentation (n=128), primary tumor not resected (n=58), and patients not followed at PMCC (n=49) so their surveillance practices cannot be determined from our records. The primary tumor sites were pancreatic (n=50, 57%), appendiceal (n=15, 17%), small bowel (n=11, 13%), rectal (n=10, 12%), and colon (n=1, 1%). Thirty-eight patients (44%) had stage 1 disease, 21 patients (24%) had stage 2, and 28 patients (32%) had stage 3. Forty-six patients (53%) had a WHO tumor grade of 1, 36 patients (41%) had grade 2, and 5 patients (6%) had grade 3. The median duration of follow-up was 18.2 months. Adherence to ordering the recommended surveillance investigations was 23% (20/87). Within the adherent cases, there was a higher number of appendiceal, WHO grade 1, and stage 1 tumors. Sixty-six patients (76%) had at least one test that was not recommended by the guidelines. The most frequent unnecessary tests were CT chest in all patient groups and CT pelvis in pancreatic NETs (Table). Six patients were lost to follow up and none discharged from surveillance. Conclusions: Adherence to the CommNETs consensus guidelines was low at our center, suggesting the guidelines had a minor impact on surveillance practices and providing an area for improvement in process of care and resource utilization. [Table: see text]

Progress in diagnosing and treating thyroid squamous cell carcinoma under the 5th edition of WHO classification.

Squamous cell carcinoma of the thyroid (SCCT) is a rare thyroid gland malignancy, with only a few hundred cases reported in the literature, mostly as case reports or small sample studies. In the previous WHO classification, squamous cell carcinoma of the thyroid was defined as a carcinoma composed entirely of squamous cells without differentiated carcinoma components. It was once included in the WHO tumor classification separately. However, the 2022 WHO classification of squamous cell carcinoma of the thyroid was reclassified as a morphologic subtype of anaplastic thyroid carcinoma (ATC). The squamous cell carcinoma pattern is similar to the other histologic types of ATC, but the phenotype associated has a poorer prognosis. The typical clinical manifestation of this condition is a cervical mass, accompanied by indications and symptoms of compression on adjacent structures such as the esophagus and trachea in advanced stages. Secondary squamous cell carcinoma of the thyroid may occur due to the spread of squamous carcinoma of the larynx or esophagus or distant metastases from other sites. Diagnosis of squamous cell carcinoma of the thyroid includes neck Ultrasound (US), Computed Tomography (CT) or Magnetic Resonance Imaging (MRI), puncture tissue biopsy, and full endoscopy to identify metastatic lesions from the nasopharynx, oropharynx, hypopharynx, larynx, esophagus, or bronchi and to help with the initial staging of the tumor. Current treatment modalities include surgery, radiotherapy, chemotherapy, or a combination. Because of the poor prognosis of patients with this disease, the short survival period, usually less than one year, and the difficulty of preoperative diagnosis, this article reviews the epidemiological features, origin, clinical features, pathological features, and differential diagnosis to improve the diagnosis and treatment of this disease by clinicians.

Pivotal Role of FBXW4 in Glioma Progression and Prognosis.

Glioma stands as one of the most formidable brain tumor types, with patient outcomes remaining bleak even in the face of advancements in treatment modalities. FBXW4, a constituent of the F-box and WD repeat domain-containing protein family, is recognized for its participation in diverse cellular activities, including those related to tumor dynamics. Yet, the therapeutic relevance and specific role of FBXW4 in the context of glioma are not well defined. This study aims to elucidate the functional dynamics and significance of FBXW4 in glioma cases. This research undertook a comprehensive analysis of FBXW4's expression patterns and clinical relevance in glioma by harnessing data from the TCGA and GTEx databases. The investigation revealed a distinct downregulation of FBXW4 in glioma tissues compared to normal brain counterparts, with a pronounced correlation between FBXW4 levels and disease severity. Intriguingly, FBXW4 expression inversely related to WHO tumor grades, with the most advanced grade IV gliomas exhibiting the lowest FBXW4 levels, whereas grade II tumors demonstrated the highest. Cases presenting with IDH1/2 mutations or 1p/19q codeletions were also associated with elevated FBXW4 levels. Furthermore, diminished FBXW4 expression aligned with an increased risk of mortality. The findings suggest that FBXW4 holds promise as a prognostic marker and a potential therapeutic avenue in glioma management. Nonetheless, future research is imperative to decode the intricate signaling pathways involving FBXW4 and to understand its broader clinical ramifications in glioma treatment paradigms.

Evaluation of the effect of PET/CT Fluorodeoxyglucose inclusion on mortality and survival in operated thymoma patients.

In recent years, the use of fluorodeoxyglucose PET-computed tomography (PET-CT) has become widespread to evaluate the diagnosis, metabolism, stage and distant metastases of thymoma. In this study, it was aimed to investigate the connection of malignancy potential, survival and maximum standardized uptake value (SUV max ) measured by PET-CT before surgery according to the histological classification of the WHO in patients operated for thymoma. In addition, the predictive value of the Glasgow prognostic score (GPS) generated by C-reactive protein (CRP) and albumin values on recurrence and survival was investigated and its potential as a prognostic biomarker was evaluated. Forty-five patients who underwent surgical resection for thymoma and were examined with PET-CT in the preoperative period between January 2010 and January 2022 were included in the study. The relationship between WHO histological classification, tumor size and SUV max values on PET-CT according to TNM classification of retrospectively analyzed corticoafferents were evaluated. Preoperative albumin and CRP values were used to determine GPS. The cutoff value for SUV max was found to be 5.65 in the patients and the overall survival rate of low-risk (<5.65) and high-risk (>5.65) patients was compared according to the SUV max threshold value (5.65) and found to be statistically significant. In addition, the power of PET/CT SUV max value to predict mortality (according to receiver operating characteristics analysis) was statistically significant ( P = 0.048). Survival expectancy was 127.6 months in patients with mild GPS (O points), 96.7 months in patients with moderate GPS (1 point), and 25.9 months in patients with severe GPS (2 points). PET/CT SUV max values can be used to predict histological sub-type in thymoma patients, and preoperative SUV max and GPS are parameters that can provide information about survival times and mortality in thymoma patients.