Predictors of mortality and tumor recurrence in desmoplastic infantile ganglioglioma and astrocytoma-and individual participant data meta-analysis (IPDMA).

PURPOSE: Desmoplastic infantile astrocytoma (DIA) and desmoplastic infantile ganglioglioma (DIG) are classified together as grade I neuronal and mixed neuronal-glial tumor of the central nervous system by the World Health Organization (WHO). These tumors are rare and have not been well characterized in terms of clinical outcomes. We aimed to identify clinical predictors of mortality and tumor recurrence/progression by performing an individual patient data meta-analysis (IPDMA) of the literature. METHODS: A systematic literature review from 1970 to 2020 was performed, and individualized clinical data for patients diagnosed with DIA/DIG were extracted. Aggregated data were excluded from collection. Outcome measures of interest were mortality and tumor recurrence/progression, as well as time-to-event (TTE) for each of these. Participants without information on these outcome measures were excluded. Cox regression survival analyses were performed to determine predictors of mortality and tumor recurrence / progression. RESULTS: We identified 98 articles and extracted individual patient data from 188 patients. The cohort consisted of 58.9% males with a median age of 7 months. The majority (68.1%) were DIGs, while 24.5% were DIAs and 7.5% were non-specific desmoplastic infantile tumors; DIAs presented more commonly in deep locations (p = 0.001), with leptomeningeal metastasis (p = 0.001), and was associated with decreased probability of gross total resection (GTR; p = 0.001). Gender, age, and tumor pathology were not statistically significant predictors of either mortality or tumor recurrence/progression. On multivariate survival analysis, GTR was a predictor of survival (HR = 0.058; p = 0.007) while leptomeningeal metastasis at presentation was a predictor of mortality (HR = 3.27; p = 0.025). Deep tumor location (HR = 2.93; p = 0.001) and chemotherapy administration (HR = 2.02; p = 0.017) were associated with tumor recurrence/progression. CONCLUSION: Our IPDMA of DIA/DIG cases reported in the literature revealed that GTR was a predictor of survival while leptomeningeal metastasis at presentation was associated with mortality. Deep tumor location and chemotherapy were associated with tumor recurrence / progression.

Impact of surgery, adjuvant treatment, and other prognostic factors in the management of anaplastic ganglioglioma.

BACKGROUND/PURPOSE: Anaplastic ganglioglioma (AGG) is a rare tumor with both glial and neuronal component accounting for less than 1% of all CNS tumors with limited information about the optimum treatment and outcome of these tumors. METHOD AND MATERIALS: We did a thorough search of the PubMed with the following MesH terms: "Ganglioglioma; Anaplastic ganglioglioma; Ganglioglioma AND treatment; and Anaplastic ganglioglioma AND survival" to find all possible publications related to AGG to perform an individual patient data analysis and derive the survival outcome and optimum treatment of these tumors. RESULTS: A total of 56 articles were retrieved pertaining to AGG with 88 patients. However, a total of 40 publications found eligible with 69 patients for individual patient data analysis. Median age for the entire cohort was 16 years (range 0.2-77 years). Surgical details were available for 64 patients. A gross total or near total resection was reported in 21 cases (32.8%), subtotal resection or debulking was reported in 25 cases (39.1%). Surgical details were available for 64 patients. A gross total or near total resection was reported in 21 cases (32.8%), and subtotal resection or debulking was reported in 25 cases (39.1%). Median overall survival (OS) was 29 months [95% CI 15.8-42.2 months] with 2- and 5-year OS 61 and 39.4% respectively. CONCLUSION: AGG is associated with a dismal. Pediatric age and a gross total resection of tumor confer a better progression-free survival and OS. Hence, surgery should remain the cornerstone of therapy. However, because of modest survival, there is enough opportunity to improve survival with addition of adjuvant radiation and chemotherapy. A whole genome sequencing and molecular characterization would help to derive the best treatment option.

Brainstem gangliogliomas: prognostic factors, surgical indications and functional outcomes.

To explore the prognostic factors and discuss the surgical indications of brainstem gangliogliomas. Twenty-one patients with brainstem ganglioglioma were surgically treated at our hospital between 2006 and 2014. The clinical, radiological, operative, and pathological findings of these patients were retrospectively reviewed. The 3-years overall survival and event-free survival (EFS) rates were 90.5 % and 68.4 %, respectively. Four patients (4/18, 22 %) experienced a recurrence with a mean recurrence-free survival of 5.5 months and a mean follow-up of 37 months. Three patients died of surgery-related complications. Three growth patterns were identified: exophytic (6/21), intrinsic (2/21), and endo-exophytic (13/21). Eight patients (8/15, 53 %) harbored a BRAF V600E mutation. All recurrent tumors were endo-exophytic, and except the one without molecular information, were BRAF V600E mutants. A Cox hazard proportion ratio model was used to identify factors influencing EFS, including sex, age, location, growth patterns, extent of resection (EOR), and BRAF V600E mutation status. On univariate analysis, none of these factors reached statistical significance. Among them, EOR and growth patterns were strongly associated with each other (Fisher's exact test, P < 0.01). A multivariate analysis demonstrated that growth patterns were the only factor associated with EFS (P = 0.02; HR 49.05; 95 % CI 1.76-1365.13). Growth patterns may be useful to select surgery candidates and predict prognosis for patients with brainstem gangliogliomas. BRAF V600E was frequently present and appeared to be associated with shorter recurrence-free survival. Studies on BRAF V600E-targeted therapy for patients with high surgical risks are needed.

BRAF(V600E) mutation is a negative prognosticator in pediatric ganglioglioma.

Gangliogliomas are typically low-grade neuroepithelial tumors seen in the pediatric and young adult populations. Despite their often bland histologic appearance, these tumors recur with varying frequencies; however, little data exist that adequately predict ganglioglioma recurrence in children. To identify potential histopathologic features predictive of recurrence-free survival, a series of 53 patients with World Health Organization (WHO) grade I gangliogliomas were evaluated, representing the largest cohort of pediatric gangliogliomas with accompanying histopathologic and survival data. Fifteen patients (28 %) exhibited disease recurrence during the study period. BRAF(V600E) immunohistochemistry was performed on 47 of these tumors. Histopathologic features associated with shorter recurrence-free survival included an absence of oligodendroglial morphology, higher glial cell density, microvascular proliferation, and the presence of a high lymphoplasmacytic inflammatory infiltrate. Eighteen tumors (38.3 %) had positive BRAF(V600E) staining, which was associated with shorter recurrence-free survival. Collectively, the combined use of histopathologic and molecular features to stratify grade I gangliogliomas into low and high-risk groups provides important information relevant to the management of children and young adults with these rare tumors.

Outcome and prognostic features in anaplastic ganglioglioma: analysis of cases from the SEER database.

Anaplastic ganglioglioma (AGG) are rare central nervous system tumours. Patient and treatment factors associated with outcome are poorly defined and limited to small retrospective case series and single case reports. Using the Surveillance, Epidemiology, and End Results (SEER) cancer registry, we investigated potential clinicopathological factors that can affect outcome in patients with anaplastic ganglioglioma. Patients with anaplastic ganglioglioma diagnosed between 1973 and 2007 were identified from the SEER database. Kaplan-Meier survival analysis and Cox models were used to examine the effect of variables on overall survival. The variables analysed included patient age at diagnosis, gender, race, tumour location, uni-focal or multi-focal tumour, surgical resection and the use of adjuvant radiotherapy. Fifty-eight patients were identified, with a median age at diagnosis of 25.5 years. Ninety-three percent of patients underwent surgery and 36% received adjuvant radiotherapy. The median overall survival was 28.5 months. The most common tumour site was the temporal lobe (27%). Univariate and multivariate analysis identified surgery and uni-focal disease as important predictors of overall survival. Adjuvant radiotherapy did not influence overall survival. This study represents the largest analysis of anaplastic ganglioglioma to date. Furthermore it also emphasises the role of national tumour databases for furthering our understanding of rare brain tumours and determining management options.

Low-grade gangliogliomas in adults: A population-based study.

BACKGROUND: Low-grade gangliogliomas (GGs) are rare tumors of the central nervous system in adults. This study aims to define their characteristics, prognostic factors, and the impact of different treatment patterns on survival. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to investigate the potential clinicopathological factors of low-grade GGs in adult patients (age ≥18 years). Kaplan-Meier method and Cox regression model were utilized to evaluate the associations between variables and overall survival (OS). RESULTS: A total of 703 adult patients diagnosed with low-grade GGs were identified between 2004 and 2016, with a median follow-up period of 60.0 months. The median age at diagnosis was 32.0 years, with 50.1% of patients being male, 84.2% white people, and 40.2% of married status. The predominant tumor site was located in temporal lobe (38.8%). The median OS time for the whole cohort was not reached. The 5- and 10-year OS rates for patients underwent gross total resection (GTR) were 92.5% and 87.2%, respectively. Univariate and multivariate analysis showed age, gender, tumor site, and treatment pattern were significant factors for OS. The employment of adjuvant radiotherapy (RT) and/or chemotherapy would significantly shorten OS time. CONCLUSIONS: This is the largest retrospective study of adult low-grade GGs up to date. Younger age, female gender, temporal lobe location, and GTR indicated better survival. Adjuvant RT and/or chemotherapy should not be considered after whatever surgery in adult patients with low-grade GGs, unless the malignant transformation has been confirmed.

Prognostic Role of BRAF Mutation in Low-Grade Gliomas: Meta-analysis.

OBJECTIVE: Newly emerged molecular markers in gliomas provide prognostic values beyond the capabilities of histologic classification. BRAF mutation, especially BRAF V600E, is common in a subset of gliomas and may represent a potential prognostic marker. The aim of our study is to investigate the potential use of BRAF mutations on the prognosis of low-grade glioma patients. METHODS: Four electronic databases were searched for potential articles including PubMed, Web of Science, Embase, and Cochrane. Data of hazard ratio (HR) for overall survival and progression-free survival were directly obtained from original papers or indirectly estimated from the Kaplan-Meier curve. A random effect model weighted by inverse variance method was used to calculate the pooled HR. From 483 articles, we finally included 8 articles with 698 glioma patients for the final analysis. The overall estimates showed that BRAF V600E was associated with an improved overall survival in glioma patients (HR = 0.64; 95% confidence interval = 0.45-0.92). RESULTS: Results for progression-free survival, however, were not statistically significant (HR = 0.97; 95% confidence interval = 0.7-1.36). In subgroup analyses, BRAF V600E showed its effect in improving survival in pediatric patients but did not have prognostic value in adult. Our meta-analysis provides evidence that BRAF mutation has a favorable prognostic impact in low-grade gliomas, and its prognostic value might be dependent on patient age. CONCLUSIONS: This mutation can be used as a prognostic factor in low-grade glioma, but additional studies are required to clarify its prognostic value taking into account other confounding factors.

A national perspective of adult gangliogliomas.

Gangliogliomas (GG) are rare tumors of the nervous system. Patient characteristics and clinical outcomes of low and high-grade GG have been difficult to elucidate in the adult population. This study aims to further elaborate on GG treatment and overall survival utilizing a larger cohort than previously published. The USA National Cancer Database was utilized to evaluate adult (age 18years and older) patients diagnosed with GG between 2004 and 2006. Descriptive statistics and Kaplan-Meier overall survival estimates were provided. A total of 198 adult GG patients were diagnosed between 2004 and 2006. Of these, 181 (91.4%) were low-grade and 17 (8.6%) high-grade GG. Overall, the median age was 36years; approximately 50% of patients were female, and 86.5% Caucasian. Most patients (59%) had near/gross total resection. Radiation and chemotherapy were prescribed in 18 (9.1%) and 11 (5.7%) patients, respectively. Radiation (64.7% versus 3.9%, p<.0001) and chemotherapy (47.1% versus 1.7%, p<.0001) were more frequently given to patients with high-grade tumors than low-grade. The median overall survival of high-grade GG was 44.4months (95% confidence interval [CI]: 10.5-92.5) while the corresponding estimate for low-grade tumors was not reached. Older age (hazard ratio [HR] 1.72, 95% CI: 1.26-2.34) and high tumor grade (HR 3.91, 95% CI: 1.43-10.8) were found to be associated with poor survival. Adult GG have a temporal lobe predilection and overall gross total resection rate of 59%. Older patients with high-grade tumors had an increased hazard of mortality. High-grade GG were significantly more likely to be treated with radiation therapy and chemotherapy.

The Brain Symptom and Impact Questionnaire in brain metastases patients: a prospective long-term follow-up study.

AIMS: To assess the ability of the Brain Metastases Symptom and Impact Questionnaire (BASIQ) in evaluating symptoms and impact on daily life. PATIENTS & METHODS: Patients with brain metastases completed BASIQ, Functional Assessment of Cancer Therapy-General, FACT-Brain at baseline and at 1, 2 and 3 months follow-ups. RESULTS: Thirty-six patients completed all follow-ups. BASIQ correlated well (r ≥ 0.40) with FACT subscales, except for social/family and emotional wellbeing. Linear regression analysis found no significant changes in quality of life (QOL) over time in both the BASIQ and FACT scales. Therefore, the two questionnaires coincide as both detected nonchanges. CONCLUSION: The ability of the BASIQ in evaluating symptoms and impact on over longer assessment periods was supported by the FACT questionnaires.

Atypical pediatric ganglioglioma is common and associated with a less favorable clinical course.

OBJECT Ganglioglioma (GG) is commonly recognized as a low-grade tumor located in the temporal lobe, often presenting with seizures. Most are amenable to complete resection and are associated with excellent oncological outcome. The authors encountered several GGs in various locations, which seem to have a less favorable clinical course than GGs in the temporal lobe. METHODS The authors performed a single-center retrospective review of all children with a histological diagnosis of GG who were treated at Children's Hospital Colorado between 1997 and 2013. Each tumor was categorized by 2 pediatric neuroradiologists as typical or atypical based on preoperative MRI appearance. Typical lesions were cortically based, within a single cerebral lobe, well-circumscribed, and solid or mixed solid/cystic. The treatment and clinical course of each patient was analyzed. RESULTS Thirty-seven children were identified, with a median age at presentation of 8.2 years and median follow-up of 38.0 months. Eighteen tumors (48.6%) were typical and 19 (51.4%) were atypical. All typical lesions presented with seizures, whereas no atypical lesions did so. Sixteen (88.9%) typical lesions were located in the temporal lobe. In the atypical group, tumor location was variable, including 11 (57.9%) in the brainstem. Death during follow-up was statistically more common in the atypical group (31.6% vs 0%, p = 0.02). Gross-total resection (GTR) was achieved for 15 of 16 typical tumors (93.8%), compared with 3 atypical tumors (15.8%, p < 0.0001). Presentation with seizure or non-brainstem location were each associated with survival (p = 0.02 and 0.004, respectively). The presence of mutation in BRAF exon 15 did not differ between the 2 groups. CONCLUSIONS Pediatric GG with typical imaging features is associated with excellent rates of GTR and overall survival. Atypical GG is commonly encountered, less amenable to GTR, and associated with a worse outcome. This may relate to anatomical or biological characteristics and merits further investigation.

Intramedullary gangliogliomas: histopathologic and molecular features of 25 cases.

Gangliogliomas are uncommon glioneuronal tumors, which usually arise in the cerebral hemispheres and occasionally in the brain stem. Gangliogliomas occurring in the spinal cord are extremely rare. In this study, we analyzed the clinical, histopathologic, and molecular features of 25 spinal gangliogliomas. The cases included in our series affected mostly children and young adults (15 males and 10 females; mean age, 20 years; median age, 14 years; age range, 1-72 years) and were predominantly localized in the cervical and thoracic spine. From the clinical point of view (detailed follow-up available for 9 pediatric cases; mean follow-up: 2 years 10 months; range, 3 months to 5 years 10 months), most patients showed stable disease after subtotal resection. Radiotherapy was rarely used as adjuvant treatment. Histologically, gangliogliomas (WHO grade I) (21 cases) showed features largely similar to their supratentorial counterparts. Anaplastic gangliogliomas (World Health Organization grade III) (4 cases) showed features of anaplasia (including high cellularity and increased mitotic and proliferation activity). From a molecular point of view, only 2 tumors (2/19, 11%) harbored a BRAF(V600E) mutation. In conclusion, although spinal gangliogliomas display histologic and clinical features similar to their supratentorial counterparts, they show a relatively low frequency of BRAF(V600E) mutations, alteration otherwise common in hemispheric and brain stem gangliogliomas.

Role of [(11)C] methionine positron emission tomography in the diagnosis and prediction of survival in brain tumours.

OBJECTIVE: [(11)C] methionine (MET) positron-emission tomography (PET) is a useful diagnostic and therapeutic tool in neuro-oncology. The aim of this study was to evaluate the relationship between MET uptake and the histopathological grade in both primary brain tumours and brain metastases. A secondary goal was to assess the relationship between MET uptake and patients' survival after surgery. METHODS: We reviewed a consecutive series of 43 PET studies performed at our institution. Out of the 43 patients studied, 35 harboured primary brain tumours (3 grade I, 12 grade II, 7 grade III and 13 grade IV) and 8 patients had brain metastases. We measured the tumour/cortex ratio (T/C ratio) on each PET study and we investigated the correlations among the tracer uptake, tumour grade, tumour type, MRI parameters and outcome. RESULTS: The mean T/C ratio was 1.8 ± 0.9 for benign lesions and low grade gliomas (grade I and II) and 2.7 ± 1 for high grade gliomas (grade III and IV). In brain metastases it was 2.5 ± 0.7, with a significant difference in MET uptake between low and high grades gliomas (P=0.03). There was no statistically significant difference among all different histologic types. We found that both contrast enhancement and perfusion studies correlate with MET uptake in brain tumours. Moreover, in Kaplan-Meier curves, the T/C ratio adversely affects long term survival in patients with brain tumours (P=0.01). CONCLUSIONS: MET PET appears to be useful in diagnosis and evaluation of potential malignancy in brain tumours. MET uptake is also related with the overall survival in patients with brain tumours. Nevertheless, further studies are needed in order to define its possible clinical implications in identifying patients at high risk of tumour progression or resistance to therapy.

Cortical architectural abnormalities and MIB1 immunoreactivity in gangliogliomas: a study of 60 patients with intracranial tumors.

Gangliogliomas are generally low grade neoplasms composed of mixtures of neoplastic glial and neuronal elements whose origin and exact nature are still controversial. We studied a series of 60 intracranial gangliogliomas looking for coexistent cortical architectural abnormalities (cortical dysplasia, microdysgenesis) and to determine if tumor behavior correlates with MIB1 (marker of cellular proliferation) labeling. The patients included 34 males and 26 females who ranged in age from 6 months to 55 years (mean 20 years). Thirty-eight tumors (63%) were located in the temporal lobe and 6 (10%) in the frontal lobe. Fifty-four patients (90%) presented with seizures (most with intractable epilepsy) and the duration of seizures ranged from 1 to 38 years (mean 14 years). In all cases, the predominant glioma component resembled a low grade fibrillary astrocytoma. In 14 tumors (23%), an oligodendroglial component was present. In one case, the glial component resembled an anaplastic astrocytoma. The tumors were characterized variously by perivascular chronic inflammation (N = 45, 75%), vascular proliferation (N = 36, 60%), granular bodies (N = 54, 90%), binucleated neurons (N = 36, 60%), calcification (N = 28, 47%), and cystic degeneration (N = 26, 43%). Meningeal involvement by tumor was observed in five (8%) cases. In 38 patients, sufficient tissue was resected to evaluate for the presence of concomitant cortical architectural abnormalities. Cortical architectural abnormalities were identified near to but clearly separate from the tumor in 19 (50%) patients. Only four patients including the anaplastic tumor died with tumor progression. MIB1 indices (positive tumor cells/1,000 tumor cells counted) in 54 cases ranged from 0 to 10.2 (mean 1.1 +/- 1.0).(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic value positron emission tomography with [18F]fluoro-2-deoxy-D-glucose in the low-grade glioma.

OBJECTIVE: The natural history of the supratentorial low-grade glioma (LGG) of the adult is variable, and its malignant transformation is hardly predictable. Because positron emission tomography with [18F]fluoro-2-deoxy-D-glucose (FDG) has prognostic value in high-grade gliomas, this study was designed to search for a possible relationship between glucose metabolism and risk of malignant evolution in LGGs. METHODS: Positron emission tomography with FDG was performed in 28 patients with LGGs (22 at the time of diagnosis and 6 after the diagnosis). A metabolic grading system based on the visual inspection of the positron emission tomographic images was used. RESULTS: In 19 patients, no area of FDG uptake higher than in the white matter was detected (metabolic Grade 1). All of those patients were alive at the end of the follow-up period. Only one of the patients presented a histological modification 7 months after the diagnosis. Nine patients presented areas of increased FDG uptake (metabolic Grade 2 or 3). Those areas were found in the tumor area in eight patients and in an area of radionecrosis in one. Of the nine patients with FDG "hot spots," six died, two had recurrence but were alive at the end of the follow-up period, and the patient with radionecrosis had no signs of recurrence. CONCLUSIONS: The presence of areas of increased FDG uptake in a histologically proven LGG predicts, in most cases, a deleterious evolution. This metabolic feature, detectable with a noninvasive procedure, may provide a clue to cellular changes, announcing malignant transformation in a tumor that retains the histological features of an LGG. Protocols with aggressive therapeutic strategies in this situation should be considered for evaluation.

Gangliogliomas: experience with 34 patients and review of the literature.

Ganglioglioma is an uncommon central nervous system tumor. The role of adjuvant postoperative radiation therapy is undefined. The authors retrospectively reviewed the clinicopathologic features and results of therapy for 34 patients with ganglioglioma treated at the University of California at Los Angeles. There were 18 women and 16 men. Median age was 18 years. Twenty-five tumors were low grade. Twenty-one patients underwent gross total resection. Three patients received adjuvant radiotherapy. The 4-year actuarial progression free and overall survival rates were 67% and 75%, respectively. The median time to progression was 14 months and all relapses were local. Factors significantly influencing progression-free or overall survival according to univariate analysis included degree of resection and tumor grade. Survival and relapse were not significantly influenced by any factor according to multivariate analysis. The progression-free survivals after gross total resection of low- and high-grade tumors were 78% and 75%, respectively. Respective rates after subtotal resection were 63% and 25%. Review of the literature demonstrates no role for radiotherapy after total resection of ganglioglioma or after partial removal of low-grade tumor. Radiation therapy appears to reduce the relapse rate after partial removal of high-grade lesions. A dose in excess of 5,000 cGy is necessary for ganglioglioma.

Clinicopathological analysis of pilocytic astrocytomas and gangliogliomas in children.

We present here a clinico-pathological analysis of 58 pilocytic astrocytomas (PA) and 11 gangliogliomas (GG) based on an analysis of neuronal markers (GFAP, SYN, NFP) in these two groups of neoplasms. During the retrospective review of 58 cases recognized primarily as PA, 11 verified neoplasms demonstrated strong reaction for SYN or NFP or for both antibodies. These cases were reclassified as gangliogliomas. None of 11 tumors recognized as GG were further reclassified as PA. The overall 5-year survival was 88.89% in PA and 70.00% in GG group.

Clinical and prognostic features of adult patients with gangliogliomas.

BACKGROUND: Gangliogliomas (GGs) represent <1% of primary brain tumors in adults. Little is known regarding prognostic features, clinical characteristics, or the impact of treatment on patient outcomes. METHODS: Our neuro-oncology longitudinal database was screened for patients with GG from 1992 to 2012. Sixty-seven patients (age >18 y) were identified. RESULTS: Sixty-two patients presented with low-grade GG and 5 with anaplastic GG. The median age at diagnosis was 29 years. With a median follow-up of 4.7 years after the initial diagnosis, 23 patients had progressive disease. Range of time to progression was 0.2-20 years. Nine patients with low-grade GG progressed to a malignant tumor. The median overall survival (OS) for all patients was not reached. The 2-, 5-, and 10-year OS for patients with low-grade GG were 100%, 88% (95% confidence interval [CI]: 73%, 95%), and 84% (95% CI: 67%, 93%), respectively. Factors identified by univariate analysis that were significantly associated with OS were age, KPS, extent of resection (EOR), and grade. Factors on univariate analysis that were significantly associated with progression-free survival were grade and EOR. On multicovariate Cox regression, lower tumor grade and younger age were significant factors for longer OS. EOR is a significant factor for progression-free survival. CONCLUSIONS: While GG has excellent prognosis, malignant histologic grade, older age, and diagnosis with biopsy could indicate worse prognosis. The late nature and high rate of progression emphasize the importance of long-term follow-up. The role of chemotherapy and radiation therapy for incompletely resected low-grade GG remains unclear.

Greater extent of resection improves ganglioglioma recurrence-free survival in children: a volumetric analysis.

BACKGROUND: Gangliogliomas are rare, low-grade, glial-neural tumors that are most often found in children. They can recur with varying frequency; yet few data are available that adequately predict such events. OBJECTIVE: To review our institution's large series of gangliogliomas in children and identify clinical features that predict recurrence-free survival. METHODS: Clinical records were retrospectively reviewed from 1990 to 2011. Fifty-three children were identified, and pertinent clinical features were analyzed against survival data to categorize lesions at high risk of recurrence. RESULTS: Fifteen children (28%) experienced a recurrence during the study period with a median time to recurrence of 8.8 months and a mean follow-up of 4.2 years. The 5-year recurrence-free survival rate was 70.5%, whereas the overall survival rate was 98.1%. Older age at diagnosis (P = .02), seizure history (P < .001), supratentorial tumor location (P < .001), and greater extent of surgical resection (P < .001) were all associated with improved recurrence-free survival on univariate analysis. Extent of surgical resection was the only clinical variable that retained its significance in multivariate models (P = .01). Patients who received 94% or greater volumetric extent of resection had prolonged recurrence-free survival compared with those individuals who received a less than 94% resection (P = .02). CONCLUSION: Attention to specific clinical variables, most notably the extent of surgical resection, can further stratify grade I gangliogliomas into low- and high-risk groups among children. Although 100% resection should remain an operative goal for surgically accessible gangliogliomas, a thorough yet subtotal resection may improve recurrence-free survival.

The role of postoperative radiotherapy for the treatment of gangliogliomas.

BACKGROUND: Because of their rarity, no prospective studies have been performed regarding gangliogliomas. The optimal treatment regimen is unclear. In this study, the authors compared 4 therapies for local control (LC) and overall survival (OS) in patients with ganglioglioma. METHODS: In 402 patients with ganglioglioma, outcomes were compared for patients who underwent gross total resection alone (GTR) (n = 188), GTR plus radiotherapy (GTR + RT) (n = 21), subtotal resection alone (STR) (n = 113), and STR plus RT (STR + RT (n = 80). Age, sex, tumor site, and histologic grade also were investigated. Subgroup analyses were performed for both low-grade and high-grade tumors. RESULTS: The 10-year LC rates were 89% after GTR, 90% after GTR + RT, 52% after STR, and 65% after STR + RT (P < .001); and the 10-year OS rates were 95%, 95%, 62%, and 74%, respectively (P < .001). After STR, irradiation significantly improved LC (P = .004) but not OS (P = .22). After GTR, irradiation did not significantly improve LC (P = .23) or OS (P = .29). On multivariate analyses, LC and OS were associated with therapy and pathologic grade, and OS also was associated with tumor site. In low-grade tumors, STR + RT resulted in better LC (P = .016) but not better OS (P = .18); and, after GTR, LC (P = .28) and OS (P = 1.0) were not improved with postoperative radiotherapy. In high-grade tumors, STR + RT resulted in better LC (P = .016) but not better OS (P = .41); after GTR, LC (P = .56) and OS (P = .61) were not improved with irradiation. CONCLUSIONS: According to this review, GTR should be performed whenever safely possible and does not require postoperative irradiation. If only STR is achieved, then RT improves LC of both low-grade and high-grade tumors and, thus, should be considered seriously.

Predictors of tumor progression among children with gangliogliomas. Clinical article.

OBJECT: Few reports describe the outcome and prognostic factors for children with gangliogliomas. The objective of this report was to describe the progression-free survival (PFS) for children with low-grade gangliogliomas and identify risk factors for tumor progression. METHODS: A retrospective study was performed in children with low-grade gangliogliomas who were evaluated and treated in the neuro-oncology department between 1986 and 2006 to determine risk factors for subsequent tumor progression. RESULTS: A total of 38 children with newly diagnosed gangliogliomas were included in this report. Thirty-four children were treated with surgery alone, 3 with subtotal resection and radiation therapy, and 1 with subtotal resection and chemotherapy. The follow-up ranged from 4 months to 15.8 years (mean 5.7+/-4.2 years [+/-SD]). Seven children have experienced tumor progression, and 1 child died after his tumor subsequently underwent malignant transformation. The 5-year PFS was calculated to be 81.2% using Kaplan-Meier survival analysis. Initial presentation with seizures (p=0.004), tumor location in the cerebral hemisphere (p=0.020), and complete tumor resection (p=0.035) were associated with prolonged PFS. Further analysis of the above significant variables by a Cox regression model identified initial presentation with seizures as being associated with prolonged PFS (p=0.028). CONCLUSIONS: The PFS and overall survival of children with gangliogliomas are good. Tumors located in the cerebral hemispheres, the achievement of total resection, and seizures at presentation were associated with prolonged PFS. Cox regression analysis identified presenting symptoms including seizures as significant predictive factors of PFS. Prospective studies with larger numbers of children are needed to define the significant factors of tumor progression.