Diagnosis Of Low-grade Glioma Research Articles

NCOG-33. MTOR INHIBITORS AS ADJUVANT TARGETED THERAPY IN PEDIATRIC PATIENTS WITH PROGRESSIVE OR REFRACTORY LOW-GRADE GLIOMA: A SINGLE-CENTER RETROSPECTIVE STUDY

Abstract Low grade gliomas (LGG) represent about one-third of all pediatric central nervous system tumors, with about half having disease progression despite upfront surgery and adjuvant therapies. Current treatments for LGG progression either produce toxic side effects (i.e., radiation therapy) or do not generate durable responses. Targeted agents are an effective way of attacking tumors with identified genetic mutations, but in some cases, a complete response can be subverted by the heterogeneity of tumors. Additionally, most tumors do not carry any targetable mutations. Temsirolimus and everolimus are mTOR inhibitors that have previously been shown to be well-tolerated in early clinical studies in pediatric solid tumors. We performed a retrospective study to look at the toxicity profile of mTOR inhibitors when given in combination therapy and treatment response in patients with progressive or refractory LGG. We examined 20 patients with a diagnosis of LGG including mixed glioma and glioneuronal tumors who received treatment at our institution from 2016-2024 with targeted therapy, of which 8 patients also received temsirolimus or everolimus. Of these 8 patients, 2 had partial response, 2 had minor response, 3 had stable disease, and 1 had progressive disease. The average number of cycles received was 13.6 (range 3-24). Most observed side effects were grade 2 or less, including nausea, transaminitis, myelosuppression, diarrhea, and hyperlipidemia while grade 3/4 toxicities that required dose modification included mucositis, hyperglycemia, and hyperlipidemia. Overall, the addition of temsirolimus to treatment regimens of pediatric patients with heavily pretreated refractory LGG prolonged progression free survival by an average of 478 days with only one patient progressing while on therapy. These results demonstrate feasibility and preliminary efficacy of adding mTOR inhibitors as adjuvant therapy in this patient population. There is dire need of large prospective collaborative studies in the future.

LGG-39. REAL-LIFE STUDY OF THE EFFICACY AND TOLERANCE OF TRAMETINIB IN THE TREATMENT OF LOW-GRADE GLIOMAS IN CHILDREN WITH NEUROFIBROMATOSIS TYPE 1

Abstract BACKGROUND Low grade gliomas (LGG) are the most common brain tumors in children. Targeted therapies such as the MEK-inhibitor trametinib have revolutionized the management of pediatric LGGs. NF1 mutations generate misregulations in the RAS/MAP kinase pathway, but data on trametinib in type 1 neurofibromatosis (NF1)-related LGG are scarce. Efficacy and safety of trametinib in NF1 patients with LGG need to be further investigated. METHODS This retrospective study included patients with NF1 <18 years from two French centers having received trametinib for a relapsing/progressive LGG between March 2020 and July 2022. Treatment efficacy was assessed according to RAPNO criteria, and toxicities and therapeutic exposure were assessed using real-life data collected retrospectively up to July 2023. RESULTS The study enrolled 11 patients, the median age at LGG diagnosis was 3 (1-9) years. All patients previously received a median number of 2 (1-4) lines of chemotherapy. Median age at treatment initiation was 9 (4-13) years. Median duration of trametinib treatment was 9.3 (5.8-24) months. Progression-free survival was 91% at 6 months and 61% at 2 years. Median time to best response was 2.7 (1.1-9) months, including 5 stable diseases, 4 minor responses, and 2 partial responses. Median duration of response was 8.6 (3.7-36.2) months. Adverse events (AEs) occurred in all patients, and 64% of the patient had grade 3 AEs. Skin toxicities and paronychia were the most frequent AEs. Treatment interruption occurred in 55% of the patients, and 3 patients permanently discontinued trametinib due to treatment-related toxicities. Real therapeutic exposure was significantly shorter than theoretically expected (19.6% treatment reduction). CONCLUSION Trametinib showed promising efficacy in NF1 children with relapsing/progressive LGG. Trametinib toxicity remains challenging. Further prospective clinical trials stratified according to molecular alterations are needed to support these preliminary results.

Intraoperative magnetic resonance imaging in glioma surgery: a single-center experience.

To investigate the effect of intraoperative magnetic resonance imaging (Io MRI) on overall and progression-free survival (OS and PFS), on the extent of resection (EOR) in patients with glioma, and impact of the radiological diagnosis on the decision to continue the surgery when a residual mass was detected on Io MRI. The study comprised 153 glioma patients who received surgical treatment between 2013 and 2023. One-hundred twenty-five of them had Io MRI guidance during surgery. The remainder 28 patients constituted the control group who did not undergo Io MRI. All patients' age at surgery, gender, initial radiological diagnosis, primary tumor localization, EOR, last histopathological diagnosis, and the follow-up periods were recorded. The rate of tumor recurrence in Io MRI cases was significantly lower compared to the cases in the control group (p < .0001). It was decided to continue the operation in 45 Io MRI applied cases. This raised the gross total resection (GTR) rate from 33.6% to 49.6% in the Io MRI group. The frequency of GTR was significantly higher in patients with an initial radiological diagnosis of low grade glioma than those with high grade glioma. The shortest OS was seen in occipital gliomas. In this study, the convenience provided by the high-field MRI device was explored and proven both in reducing the tumor burden, increasing the PFS, and providing the surgeon with a maximal resection in the first operation.

Consensus guidelines for the management of adult low-grade gliomas for low and middle-income countries.

Low-grade gliomas (LGG) are brain tumors of glial cells origin. They are grade 1 and grade 2 tumors according to the WHO classification. Diagnosis of LGG is made through imaging, histopathological analysis, and use of molecular markers. Imaging alone does not establish the grade of the tumor and thus a histopathological examination of tissue is crucial in establishing the definite histopathological diagnosis. Clinical presentation varies according to the location and size of the tumor. Surgical resection is strongly recommended in LGG over observation to improve overall survival as surgery leads to greater benefit due to progression-free survival. Radiation has shown benefits in LGG patients in randomized controlled trials and chemotherapy with temozolomide has also shown good results. This paper covers the principles of low-grade gliomas management and summarizes the recommendations for the LMICs.

NIMG-47. LONGITUDINAL TRAJECTORIES FROM SERIAL SURVEILLANCE MRI IMAGING OF PROGRESSIVE IDH MUTANT LOW-GRADE GLIOMA PATIENTS

Abstract BACKGROUND Most patients with isocitrate dehydrogenase mutant (IDHm) low-grade glioma (LGG) undergo active MRI surveillance after initial surgery. Timely biopsy referral during surveillance is a complex trade-off between avoiding the harms of unnecessary surgery and early detection of transformation. Serial surveillance MRIs could be leveraged to develop dynamic imaging markers, yet prior research has primarily focused on the prognostication of pre-treatment images. We piloted the feasibility of an automated pipeline using patient-specific imaging trajectories. METHODS We retrospectively identified 12 progressive IDHm LGG patients and collected serial surveillance MRIs. A previously developed segmentation model was fine-tuned on a subset of T2/FLAIR images (n=49) before automated tumor segmentation was performed on all MRIs. We extracted geometric and topological tumor features, including volume, cross product, and Euler Characteristic Transform, from each MRI. We used piecewise linear regression to quantify feature trajectories and identify change points in feature growth rates. RESULTS Twelve patients received 14 biopsies/repeat resections (10 with transformation, 4 without) and 282 MRIs (median per patient: 17, range: 10-40). All biopsies/repeat resections were preceded by a change point in tumor volume trajectory, indicating an increase in tumor growth rate preceding clinician-determined MRI progression and biopsy referral. The mean increase in volume growth rate, pre to post change point, was 2.3cm3/month (SE: 0.9) in biopsies/repeat resections with transformation, compared to 1.1cm3/month (SE: 0.6) in biopsies/repeat resections without transformation. Among the ten patients with transformation, the median time from IDHm LGG diagnosis to transformation was 64.8 months (range: 38.6-141.1), and the median time between volume change point and transformation was 15.6 months (range: 4.6-28.2). DISCUSSION This pilot study suggests that feature trajectories from serial MRIs of IDHm LGG patients may advance the detection and treatment of transformed lesions by 12-18 months. Larger studies can corroborate these findings and inform clinical decision-making.

CLRM-05 ADAPTATION OF NEW CLASSIFICATION OF ASTROCYTOMA IN LOW AND MIDDLE INCOME COUNTRY- HOW SMOOTH IS THE ROAD AHEAD?

Abstract BACKGROUND The 2021 WHO CNS 5 classification made major changes with integration of immunohistochemistry, molecular profiling and sequencing in addition to histopathology to classify brain tumors. IDH mutation is mainstay for diagnosis of low grade glioma and 1p/19q testing required only to confirm oligodendroglioma but not in all cases. This integrated approach has favored prognosis, and diagnosis of disease as well as prediction of response to therapy. METHODS A retrospective study was conducted to analyze the molecular alterations in patients diagnosed with astrocytoma in 2021 in Kathmandu Cancer Center, Nepal. The demographic data were collected from the patients’ archived files from the medical record department. The patients were categorized as IDH: mutant and wild, and ATRX: retained and lost. RESULTS This study demonstrated IDH and ATRX mutation with 30.3% and 24.23% respectively. In our study, among grade 2 and 3 patients, 8 out of 11 (72.7%) were IDH mutant types. 2 patients of this group were IDH wild type, who ideally required further testing for correct classification but couldn’t be done due to financial constraints. IDH status of one patient in this group was unknown. 72.7% of the Grade 4 gliomas were IDH wild type and classified as Glioblastoma Multiforme. In 6 of the patients IDH status was unknown. Among 8 grade 2 and 3 tumors with IDH mutant, 2 had loss of ATRX and 6 had ATRX retained. Among these 6 patients only one had 1p/19q co-deletion done which was positive. Rests 5 were not properly classified. CONCLUSION In conclusion, higher percentage of IDH wild type was seen in Grade 4 gliomas. Similarly, the IDH mutant type predominated in Grade 2 and 3 gliomas. More pronounced investigations are still not feasible in low- and-middle income countries because of limited resources.

OUTC-07. ANALYZING PREDICTORS OF LOSS TO FOLLOW-UP AS SEEN AMONG YOUNG SURVIVORS OF CENTRAL NERVOUS SYSTEM TUMORS FOR QUALITY IMPROVEMENT INTERVENTIONS AT DANA FARBER CANCER INSTITUTE

Abstract At Dana Farber Cancer Institute, children and young adults who have completed treatment for central nervous system tumors visit the Pediatric Neuro-Oncology Outcomes Clinic (“Empower”) for survivorship visits. By attending these long-term clinic visits, survivors can receive multidisciplinary services and undergo monitoring for disease recurrence. We used descriptive statistics and chi-square tests to investigate the relationship between loss to follow-up and sociodemographic factors among Empower patients. We reviewed medical records to gather data on 200 patients who had visited the clinic between 1-1-2015 and 1-1-2020, extracting information about sex, zip code, diagnosis, treatment received, and insurance type (private vs. public). We then indicated whether each patient had been “lost to follow-up,” defined as not returning to the clinic for &amp;gt;1,000 days after the recommended follow-up date. Among the 200 patients reviewed, 46 (23%) were lost to follow-up and 154 (77%) were not lost to follow-up. With respect to race and ethnicity, individuals identifying as Black, Asian, Middle Eastern, Native Hawaiian or Pacific Islander, Hispanic or Latino, or “Other” were more likely to be lost to follow-up than patients who exclusively identified as White (21% versus 39%; p=0.036). Additionally, individuals who were lost to follow-up were more likely to have been treated for low-grade gliomas as opposed to other CNS tumors (30% versus 13.6%; p=.015). Sex, the use of chemotherapy and radiation, and insurance type did not have a significant association with loss to follow-up. An analysis of the relationship between median household income and loss to follow-up is pending. The results imply that there is a significant association between non-white race, Hispanic or Latino ethnicity, a diagnosis of low-grade glioma, and loss to follow-up. The continuation of this study can provide the groundwork for interventions targeted at supporting patients who are at an increased risk of loss to follow-up.

QOL-09. NAVIGATING DISABILITY INSURANCE FOR PATIENTS DIAGNOSED WITH LOW-GRADE GLIOMA

Abstract Central nervous system tumors and their treatments can cause neurologic, cognitive, and psychiatric symptoms that restrict a patient’s ability to work. In the United States, a diagnosis of high-grade glioma (grade 3 or 4) medically qualifies a patient for disability benefits through Social Security. Low-grade gliomas can be similarly debilitating, with at least 50% of patients presenting with one or more cognitive deficits and 80% of patients with tumor-related epilepsy. In light of these serious symptoms, it is unsurprising at least half of patients with low-grade glioma do not return to work within one year of diagnosis. Yet a diagnosis of low-grade glioma does not in and of itself qualify patients for disability benefits; the burden of proof is substantially higher. Thus, patients with low-grade glioma require special attention as they seek disability benefits. Here, we outline the process of medical documentation to support disability benefits, Security Disability Insurance (SSDI) and Supplemental Security Income (SSI). We provide a template to assist providers in facilitating the application process for patients with low-grade glioma seeking disability benefits. The provider’s role is not to simply “declare” a patient disabled, but rather to provide comprehensive documentation regarding the patient’s diagnosis, treatment, response to treatment, symptoms, and functional status in the medical record. As cognitive symptoms and seizures are two key sources of disability in low-grade glioma patients, referrals to neuropsychology and epileptology, among other sub-specialties, are key to improve patient care and bolster documentation of the patient’s symptoms in these domains. Likewise, connecting patients with social workers and disability claims representatives can assist them in navigating the complicated application process. Providers are better able to help their patients navigate the disability application process when they understand how disability evaluations work and what key information evaluators seek.

Recurrent insular low-grade gliomas: factors guiding the decision to reoperate.

Reoperation has been established as an effective therapeutic strategy in recurrent diffuse low-grade gliomas (LGGs). Insular gliomas represent a specific surgical challenge because of the surrounding vascular and functional structures. The aim of this study was to investigate the main clinicoradiological factors guiding the decision to reoperate on recurrent insular LGGs (ILGGs). In this retrospective consecutive series, the authors screened all patients operated on for an ILGG in their institution who further presented with a tumor regrowth without the development of contrast enhancement. They compared patients who were subsequently offered a reoperation under awake mapping at recurrence or who underwent reoperation after adjuvant treatment had reduced the volume of the initial tumor recurrence (with a proven pathological diagnosis of LGG after the second surgery) to patients who were not selected for a reoperation. The first group (reoperated group; n = 20) included all recurrent ILGG patients who underwent second resection, and the second group (nonreoperated group; n = 60) included patients who did not undergo reoperation but underwent adjuvant oncological treatment. Factors significantly associated with reoperation were extent of resection (EOR) at first surgery (91.9% vs 89.7%, p = 0.014), residual tumor volume (9.5 ± 7.1 mL [range 0-30 mL] vs 6.3 ± 7.3 mL [range 0-30 mL], p = 0.02) at first surgery and left temporopolar infiltration at the time of tumor recurrence (Liebermeister statistical analysis, 4293 voxels survived false discovery rate correction with p < 0.05; maximal z-statistic = 6.50). Infiltration of the anterior perforated substance at tumor recurrence was significantly anticorrelated to reoperation (179 voxels survived false discovery rate correction with p < 0.05; minimal z-statistic = -4.33). The mean EOR was 83.7% at reoperation with a 90% survival rate at last follow-up (9.3 ± 3.8 years), low postsurgical morbidity (Karnofsky Performance Status score ≥ 80 in 95% of patients), a high rate of postoperative professional resumption (95%), and seizure control in 57.1% of patients. In selected patients with recurrent ILGG without radiographic evidence of malignant transformation, reoperation with intraoperative awake mapping is associated with favorable oncological outcomes and a low postsurgical morbidity. A greater EOR and a lower residual tumor volume at first surgery were significantly associated with reoperation. Patients who benefited from a second surgery typically had a recurrent pattern within cortical areas (such as the temporopolar region), while other patients typically presented with a deeper infiltrative pattern within the anterior perforated substance and the surrounding white matter pathways. Such original findings may be helpful to select the optimal indications of reoperation in recurrent ILGG.

Navigating disability insurance in the American healthcare system for the low-grade glioma patient.

In the United States, diagnosis of grade 3 or 4 glioma qualifies patients for Social Security disability benefits. Low-grade gliomas (LGGs) can be similarly debilitating, with at least 31% of patients presenting with cognitive deficits and 80% with tumor-related epilepsy. A diagnosis of LGG does not in and of itself qualify patients for disability benefits; the burden of proof is substantially higher. We outline the American healthcare system process of medical documentation to support disability benefits, Social Security Disability Insurance (SSDI) and Supplemental Security Income (SSI). We provide a template to assist providers in facilitating the application process for patients with LGG. The provider's role is not to simply "declare" a patient disabled, but to provide comprehensive documentation regarding diagnosis, treatment, disease status, symptoms, and functional status in the medical record. As cognitive symptoms and seizures are 2 key sources of disability in LGG patients, selective referrals to neuropsychology and epileptology may improve patient care and bolster documentation of the patient's symptoms in these domains. Likewise, connecting patients with social workers and disability claims representatives can assist them in navigating the complicated application process. We provide an extensive review for patient eligibility in the United States to receive disability. We map a comprehensive care process that may have relevance to multiple regions outside the United States. Providers are better able to help their patients navigate the disability application process when they understand how to address physical and cognitive changes for thorough care of their patient.

OS07.7.A Rate and type of recurrence of lower-grade gliomas submitted to functional neurosurgical approach: the impact of the extent of resection

Abstract Background In the last decade, different published studies enlightened the extent-of-resection (EOR) as an independent factor for progression-free-survival (PFS) in patients with lower-grade gliomas (LGG). Aim of this study was to evaluate the impact of resections extending beyond FLAIR MRI abnormalities (supratotal), and eventual predictive factors and characteristics of recurrences. Material and Methods We retrospectively analysed 460 patients submitted to surgery between 2007 and 2016 with a presumptive diagnosis of LGG, i.e., harbouring a mass lesion with no enhancement on contrast-administered T1-weighted MRI-sequences. All resections were performed according to functional boundaries determined by brain mapping/monitoring technique, without any patient or tumor a priori selection. The EOR was defined by analyzing pre- and post-operative volumetric FLAIR images. Results The median pre-operative tumor volume was 43,7 cm3. A supratotal resection (SPR) was achieved in 31.4%, a gross-total (GTR) in 41.1%, a subtotal (STR) in 27.5%. WHO grade II/III gliomas were diagnosed in 347 cases (319 IDH-mutant, 28 IDH-wildtype). Median follow-up was 60 months. SPR versus other EOR was associated to increased PFS (log rank test, p=.000) and malignant PFS (p=.000). Data were confirmed also after IDH status stratification. Rate of immediate and permanent post-op deficits among different EOR were comparable. Pre-op tumor volume, parietal and insular sites, eloquent location and dominant hemisphere tumors, and astrocytoma histology were associated to recurrence (p&amp;lt;.05). In 95.1% of cases recurrences were peri-cavitary. Lesions invading the corpus callosum presented minor rate of relapse; recurrences were most frequently diffuse and at distant sites. After SPR most common radiological appearance of recurrence was solid, while after GTR and STR percentages of solid and diffuse patterns were similar. Occurrence of distant recurrences, away from the resection cavity, were most associated to SPR. Conclusion Our preliminary data suggests the dramatic impact in LGG of resections extending beyond FLAIR abnormalities on PFS and malignant PFS and on the characteristics of tumor recurrence.

Efficacy of MR diffusion kurtosis imaging for differentiating low-grade from high-grade glioma before surgery: A systematic review and meta-analysis

BackgroundAccurate discrimination and diagnosis of low-grade glioma (LGG) and high-grade glioma (HGG) before surgery is clinically important because it affects the patient’s outcome and guides the clinicians to select appropriate management. The aim of this study was to evaluate the diagnostic performance of diffusion kurtosis imaging (DKI) for differentiating LGG from HGG. MethodsA literature search of the PubMed, Web of Science, Cochrane Library and EMBASE databases was conducted up to December 15, 2020. Studies that evaluated the diagnostic performance of DKI for differentiating LGG from HGG were selected. Retrieved hits were evaluated by the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Summary sensitivity and specificity were determined, and the data analysis was performed using Stata 14.0 and Review Manager 5.3. ResultsThirteen studies with 705 patients were included. The individual sensitivity and specificity of the 13 studies varied from 71% to 100% for sensitivity and 73–100% for specificity. The pooled sensitivity of DKI was 88% (95% confidence interval [CI], 83–91%), and the pooled specificity was 91% (95% CI, 86–95%). The area under the summary receiver operating characteristic curve was 0.93 (95% CI, 0.90–0.95). The pooled diagnostic odds ratio of DKI was 64.85 (95% CI 38.52–109.19). The levels of heterogeneity for sensitivity and specificity across the included studies were high (I2 =66%) and mild (I2 =47.04%), respectively. The multiple subgroup analyses were driven by DKI technique and study region. ConclusionsDKI demonstrated a high diagnostic performance for differentiation of LGG from HGG.

Transition From Diencephalic Syndrome to Hypothalamic Obesity in Children With Suprasellar Low Grade Glioma: A Case Series.

BackgroundChildren with suprasellar low grade glioma (LGG) frequently develop problems to maintain their body weight within the normal range, due to hypothalamic dysfunction. Hypothalamic damage may result in the diencephalic syndrome (DS), characterized by underweight or failure to thrive, but also in hypothalamic obesity (HO). Children with LGG presenting with DS at young age often develop HO later in life. The underlying pathophysiology for this change in body mass index (BMI) is not understood. Previous hypotheses have focused on the tumor or its treatment as the underlying cause. To better understand its etiology, we aimed to relate changes in BMI over time in children with suprasellar LGG presenting with DS to age, tumor progression, treatment, and endocrine function. We hypothesize that the development of HO in children with LGG presenting with DS is related to maturation status of the hypothalamus at time of injury and thus age.MethodsIn this retrospective case series, all cases diagnosed in the Netherlands with suprasellar located LGG, currently treated or followed, with a history of DS developing into HO were included.ResultsIn total, 10 children were included. Median age at LGG diagnosis was 1.5 years (range 0.4–5.5), median BMI SDS was −2.64. The children developed overweight at a median age of 4.5 years (2.2–9.8). The median total difference in BMI SDS between underweight and obesity was +5.75 SDS (4.5–8.7). No association could be found between transition of DS to HO and onset of a pituitary disorder (present in 70.0%), surgery, chemotherapy, or tumor behavior. Two had developed central precocious puberty (CPP), both while having underweight or normal weight.ConclusionThe shift from DS to HO in children with hypothalamic LGG may be associated with age and not to tumor behavior, treatment characteristics or pituitary function. The development of CPP in these children seems not to be related to obesity. Our findings may indicate that the clinical picture of hypothalamic dysfunction reflects the maturation state of the hypothalamus at time of lesioning. Future prospective studies are needed to better understand underlying causative mechanisms of the morbid changes in body weight.

Association of Low-Grade Glioma Diagnosis and Management Approach with Mental Health Disorders: A MarketScan Analysis 2005-2014.

Simple SummaryLow-grade gliomas (LGGs) comprise 13–16% of glial tumors. As survival for LGG patients has been improving, it is important to consider the effects of diagnosis and treatment on mental health. The aims of this retrospective cohort study were to determine the incidence, prevalence, and risk factors of mental health disorders (MHD) in LGG patients. In our analysis including 20,432 LGG patients, we identified an MHD prevalence of 60.9%. Of those with no history of prior MHD, 16.9% of LGG patients developed a new onset of MHD within 12 months of LGG diagnosis. Risk factors included female gender, ages 35–54, presence of seizures, and first-line surgical treatment. Therefore, proactive surveillance and counseling surrounding MHDs are recommended among LGG patients. Impact of surgery on brain networks affecting mood should also be considered.Low-grade gliomas (LGGs) comprise 13–16% of glial tumors. As survival for LGG patients has been gradually improving, it is essential that the effects of diagnosis and disease progression on mental health be considered. This retrospective cohort study queried the IBM Watson Health MarketScan® Database to describe the incidence and prevalence of mental health disorders (MHDs) among LGG patients and identify associated risk factors. Among the 20,432 LGG patients identified, 12,436 (60.9%) had at least one MHD. Of those who never had a prior MHD, as documented in the claims record, 1915 (16.7%) had their first, newly diagnosed MHD within 12 months after LGG diagnosis. Patients who were female (odds ratio (OR), 1.14, 95% confidence intervals (CI), 1.03–1.26), aged 35–44 (OR, 1.20, 95% CI, 1.03–1.39), and experienced glioma-related seizures (OR, 2.19, 95% CI, 1.95–2.47) were significantly associated with MHD incidence. Patients who underwent resection (OR, 2.58, 95% CI, 2.19–3.04) or biopsy (OR, 2.17, 95% CI, 1.68–2.79) were also more likely to develop a MHD compared to patients who did not undergo a first-line surgical treatment. These data support the need for active surveillance, proactive counseling, and management of MHDs in patients with LGG. Impact of surgery on brain networks affecting mood should also be considered.

Psychiatric symptoms in children with low-grade glioma and craniopharyngioma: A systematic review

The presentation of psychiatric symptoms in pediatric low-grade brain tumors is challenging because this can delay proper diagnosis and treatment. We performed a systematic review of psychiatric presenting symptoms of low-grade brain tumors in pediatric patients. We searched the PubMed and Web of Science databases of studies published in English from 1977 until 2019 reporting patients aged ≤21 years at the time of tumor diagnosis who exhibited psychiatric/behavioral symptoms before diagnosis of low-grade glioma (LGG), pilocytic astrocytoma (PA), or craniopharyngioma (CP). Our systematic search strategy coupled each tumor type with patient age and presenting symptoms by using different variations of the search terms “childhood” and “psychiatric symptoms” or “behavioral symptoms.” We identified six unique articles that met our inclusion criteria in the LGG search, 27 in the PA search, and 32 in the CP search. Six patients were included in the LGG articles (age range, 3–16 years), 75 in the PA articles (age range, 0.5–21 years), and 87 in the CP articles (age range, 0.67–21 years). The most common presenting symptoms included eating disorders (n = 64) and behavioral changes (n = 49). Our findings demonstrate the need to establish clear criteria for neuroimaging indications for pediatric patients exhibiting eating disorders.

Risk of secondary neoplasms after external-beam radiation therapy treatment of pediatric low-grade gliomas: a SEER analysis, 1973-2015.

Although past studies have associated external-beam radiation therapy (EBRT) with higher incidences of secondary neoplasms (SNs), its effect on SN development from pediatric low-grade gliomas (LGGs), defined as WHO grade I and II gliomas of astrocytic or oligodendrocytic origin, is not well understood. Utilizing a national cancer registry, the authors sought to characterize the risk of SN development after EBRT treatment of pediatric LGG. A total of 1245 pediatric patient (aged 0-17 years) records from 1973 to 2015 were assembled from the Surveillance, Epidemiology, and End Results (SEER) database. Univariable and multivariable subdistribution hazard regression models were used to evaluate the prognostic impact of demographic, tumor, and treatment-related covariates. Propensity score matching was used to balance baseline characteristics. Cumulative incidence analyses measured the time to, and rate of, SN development, stratified by receipt of EBRT and controlled for competing mortality risk. The Fine and Gray semiparametric model was used to estimate future SN risk in EBRT- and non-EBRT-treated pediatric patients. In this study, 366 patients received EBRT and 879 did not. Forty-six patients developed SNs after an LGG diagnosis, and 27 of these patients received EBRT (OR 3.61, 95% CI 1.90-6.95; p < 0.001). For patients alive 30 years from the initial LGG diagnosis, the absolute risk of SN development in the EBRT-treated cohort was 12.61% (95% CI 8.31-13.00) compared with 4.99% (95% CI 4.38-12.23) in the non-EBRT-treated cohort (p = 0.013). Cumulative incidence curves that were adjusted for competing events still demonstrated higher rates of SN development in the EBRT-treated patients with LGGs. After matching across available covariates and again adjusting for the competing risk of mortality, a clear association between EBRT and SN development remained (subhazard ratio 2.26, 95% CI 1.21-4.20; p = 0.010). Radiation therapy was associated with an increased risk of future SNs for pediatric patients surviving LGGs. These data suggest that the long-term implications of EBRT should be considered when making treatment decisions for this patient population.

18F-FET and 18F-choline PET-CT in patients with MRI-suspected low-grade gliomas: a pilot study

AimTo investigate the diagnostic accuracy of O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET) and fluoromethyl-(18F)-dimethyl-2-hydroxyethyl-ammonium chloride (18F-FCH) computed tomography (CT) in patients with primary low-grade gliomas (LGG).MethodsThe study enrolled patients with magnetic resonance imaging (MRI)-suspected LGG. Patients underwent both 18F-FET and 18F-FCH positron emission tomography (PET)-CT. Brain PET-CT was performed according to standard protocol – 20 minutes after intravenous injection of 185 MBq of 18F-FET and 185 MBq of 18F-FCH PET. Surgery and pathohistological diagnosis were performed in the next two weeks.ResultsWe observed significantly better concordance between tumor histology and 18F-FET PET (weighted Kappa 0.74) compared with both 18F-FCH (weighted Kappa 0.15) and MRI (weighted Kappa 0.00). Tumor histology was significantly associated with 18F-FET (odds ratio 12.87; 95% confidence interval [CI], 0.49-333.70; P = 0.013, logistic regression analysis). Receiver operating characteristic curve analysis comparing 18F-FCH (area under the curve [AUC] 0.625, 95% CI 0.298-0.884) and 18F-FET (AUC 0.833, 95% CI 0.499-0.982) showed better diagnostic properties of 18F-FET (AUC difference 0.208, 95% CI -0.145 to 0.562, P = 0.248).ConclusionPerforming PET-CT in patients with newly diagnosed LGG should be preceded by a selection of an appropriate radiopharmaceutical. 18F-FET seems to be more accurate than 18F-FCH in the LGG diagnosis.

Doubling Recruitment of Pediatric Low-grade Glioma within Two Decades does not change Outcome - Report from the German LGG Studies.

Successive multicenter studies for pediatric low-grade glioma (LGG) in Germany were accompanied by a doubling of annual recruitment over 2 decades. We investigated whether this increase conveyed a change of epidemiologic characteristics or survival. Participating centers reported 4634 patients with the radiologic/histologic diagnosis of LGG (1996-2018), rising from 109 to 278/year. Relating these numbers to all pediatric CNS tumors registered at the German Childhood Cancer Registry, the LGG fraction and annual crude incidence rates increased (32% to 51%; 0.94 to 2.12/100,000 children/adolescents<15 years). The consecutive LGG studies recruited 899 (HIT-LGG 1996), 1592 (SIOP-LGG 2004), and 1836 (LGG-registry) patients with similar distribution of tumor-sites, histology, and dissemination. 5-year overall survival was 96%-98% at median observation time of 8.1 years. Acknowledging unequal follow-up periods, 589/899 (66%), 1089/1582 (69%), and 1387/1836 (76%) patients remained under observation, while 1252/4317 received adjuvant treatment with decreasing frequency of front-line radiotherapy from 16% to 5%. Pediatric LGG incidence rates in Germany are now comparable to other European countries. The rise in patient numbers followed implementation of standard-of-care treatment protocols, but did not result in relevant changes of epidemiologic or clinical parameters or survival. Shifts in patient distribution between treatment arms reflect growing acceptance of the LGG therapy algorithm. In den vergangenen 20 Jahren hat sich die jährliche Patientenrekrutierung in den aufeinanderfolgenden multizentrischen Studien für pädiatrische niedrig-gradige Gliome (LGG) in Deutschland verdoppelt. Wir haben untersucht, ob sich mit dieser Zunahme auch epidemiologische Merkmale oder das Überleben verändert haben. Zwischen 1996 und 2018 meldeten die teilnehmenden Zentren insgesamt 4634 Patienten mit der radiologischen/histologischen Diagnose eines LGG. Die Zahl stieg von anfangs 109 bis 278 Patienten pro Jahr. Gleichzeitig stieg der Anteil der LGGs an allen am Deutschen Kinderkrebsregister gemeldeten pädiatrischen Hirntumoren von 32 auf 51%, die jährliche Inzidenz erhöhte sich von 0,94 auf 2,12/100 000 Kinder/Jugendliche<15 Jahre. Die aufeinanderfolgenden LGG-Studien rekrutierten 899 (HIT-LGG 1996), 1592 (SIOP-LGG 2004) und 1836 (LGG-Register) Patienten mit vergleichbarer Verteilung von Tumorsitz, Histologie und Disseminierung. Das 5-Jahres-Überleben lag bei einer medianen Nachbeobachtungszeit von 8,1 Jahren zwischen 96 und 98%. Unter Berücksichtigung der ungleich langen Follow-up-Zeit wurden 589/899 (65,5%), 1089/1582 (68,8%) und 1387/1836 (75,5%) Patienten bislang beobachtet, während 1252/4317 eine adjuvante Therapie erhielten. Dabei sank der Anteil der primären Radiotherapie von 16 auf 5%. Die Rekrutierung pädiatrischer LGG ist dank Implementierung verbindlicher Therapiestandards in Deutschland gestiegen, ohne zu relevanten Veränderungen epidemiologischer oder klinischer Merkmale oder des Überlebens zu führen. Die Inzidenz ist mit anderen europäischen Ländern vergleichbar. Verschiebungen der Patientenzuteilung zwischen den Therapiearmen spiegeln die zunehmende Akzeptanz des LGG-Therapie-Algorithmus wider.

Predictive Evolution Factors of Incidentally Discovered Suspected Low-Grade Gliomas: Results From a Consecutive Series of 101 Patients.

Incidentally discovered suspected diffuse low-grade gliomas (LGGs) on brain imaging pose a challenge to neurosurgeons. Modern surgical series of LGGs favor early prophylactic surgery with a maximal extent of resection. However, some nonevolutive lesions may mimic LGGs on magnetic resonance imaging (MRI). To determine objective criteria to advocate surgical resection of an incidentally discovered suspected LGG based upon MRI findings. The prospective cohort of patients referred to our institution for an incidental finding suggestive of LGG was retrospectively reviewed. Stable lesions underwent systematic serial MRI follow-up, while evolutive lesions underwent prophylactic surgery under awake conditions. Initial clinico-radiological features were compared between stable and evolutive lesions in order to determine predictive criteria of further evolution. Among 101 patients referred for surgical resection of incidentally discovered suspected LGG in our center, 19 patients (18.8%) had nonevolutive MRI lesions after a mean follow-up of 46.9±34.9 mo. Insular topography (P=.003), higher mean volume at discovery (19.2vs 5.2 cm3, P<.001), and adjacent sulcal effacement (P=.001) were associated with evolutive lesions. Histopathological diagnosis of LGG was confirmed in all surgical cases. Increasing volume is an effective predictor of LGG diagnosis in incidental MRI findings, as all patients who subsequently underwent surgery had confirmed histopathological diagnosis of diffuse glioma. Approximately 18.8% of incidental findings were stable over time. Insular topography, adjacent sulcal effacement, and volume greater than 4.5 cm3 were predictive of further radiological progression. These significant elements will help neurosurgeons to define personalized strategies in this complex setting of incidental discovery.

Patterns of Interaction Between Diffuse Low-Grade Glioma and Pregnancy: An Institutional Case Series

The occurrence of pregnancy in patients with low-grade glioma (LGG) constitutes a unique therapeutic challenge. Owing to the rarity of cases, there is a dearth of information in existing literature. We retrospectively identified all patients with a diagnosis of LGG and pregnancy at some point during their illness. Clinical course and obstetrical outcomes were reviewed. A volumetric analysis of tumor growth rate in association with pregnancy was performed. Of 15 women identified, 13 (86.7%) had a prepregnancy LGG diagnosis. Of the 2 patients in whom LGG was diagnosed during pregnancy, one underwent upfront surgery, and the other had watchful waiting with resection after 60 weeks. Nine patients (60.0%) remained asymptomatic during pregnancy, while 5 (33.3%) experienced recurrence of seizures. There was one case of transformation of an astrocytoma to glioblastoma during the third trimester, which was resected emergently. In 10 cases, progression occurred after pregnancy at a median interval of 24.2 months (interquartile range 6.6-37.5 months), with progression within 6 months of delivery in 2 cases. Mean (SD) growth rate during pregnancy was 7.8 (22.2) mm/year compared with 0.62 (1.12) mm/year before pregnancy and 0.29 (1.18) mm/year after pregnancy; the difference did not reach statistical significance (P= 0.306). Pregnancy was associated with clinical deterioration in one third of patients. No significant change in growth rate was identified. Time to progression and malignant dedifferentiation were unaffected. Patients with LGG wishing to pursue pregnancy should be counseled regarding the risk of complications, and if pregnancy is pursued, close neurological and obstetrical follow-up is recommended.