Revisiting prognostic factors of gliomatosis cerebri in adult-type diffuse gliomas.

PURPOSE: There is lack of comprehensive analysis evaluating the impact of clinical, molecular, imaging, and surgical data on survival of patients with gliomatosis cerebri (GC). This study aimed to investigate prognostic factors of GC in adult-type diffuse glioma patients. METHODS: Retrospective chart and imaging review was performed in 99 GC patients from adult-type diffuse glioma (among 1,211 patients; 6 oligodendroglioma, 16 IDH-mutant astrocytoma, and 77 IDH-wildtype glioblastoma) from a single institution between 2005 and 2021. Predictors of overall survival (OS) of entire patients and IDH-wildtype glioblastoma patients were determined. RESULTS: The median OS was 16.7 months (95% confidence interval [CI] 14.2-22.2) in entire patients and 14.3 months (95% CI 12.2-61.9) in IDH-wildtype glioblastoma patients. In entire patients, KPS (hazard ratio [HR] = 0.98, P = 0.004), no 1p/19q codeletion (HR = 10.75, P = 0.019), MGMTp methylation (HR = 0.54, P = 0.028), and hemorrhage (HR = 3.45, P = 0.001) were independent prognostic factors on multivariable analysis. In IDH-wildtype glioblastoma patients, KPS (HR = 2.24, P = 0.075) was the only independent prognostic factor on multivariable analysis. In subgroup of IDH-wildtype glioblastoma with CE tumors, total resection of CE tumor did not remain as a significant prognostic factor (HR = 1.13, P = 0.685). CONCLUSIONS: The prognosis of GC patients is determined by its underlying molecular type and patient performance status. Compared with diffuse glioma without GC, aggressive surgery of CE tumor in GC patients does not improve survival.

Predictive factors for overall survival in surgical cases of gliomatosis cerebri from the National Cancer Database.

Gliomatosis Cerebri (GC) is a rare, aggressive, diffusely infiltrating cerebral tumor. Prognostic indicators and management strategies are currently poorly characterized. The National Cancer Database was queried for patients with histologically confirmed GC between 2004 and 2016. Demographic, tumor, and treatment characteristics were collected, including the Charlson/Deyo score, a comorbidity index adapted from the Charleston Comorbidity Index. Allowable values for the Charlson/Deyo score are 0 (no recorded comorbidities), 1, 2, and 3+ (most severe). Factors associated with overall survival were identified via bivariate log-rank tests and multivariate stepwise Cox proportional hazards models. The query returned 108 GC patients. The median age was 60.0 years, males were predominantly affected (63%), and most patients were white (86%). While 12% of cases achieved near/gross total resection and 27% of cases achieved partial resection, most surgeries were for biopsy (61%). Treatments included radiation therapy in 64% and chemotherapy in 63% of patients. The median overall survival was 15.1 (95% confidence interval [CI] = 11.1-24.8) months. On bivariate analysis, chemotherapy improved overall survival (p = 0.01) while radiation therapy (p = 0.07) and extent of resection (p = 0.48) did not. On multivariate analysis, older patients (hazard ratio [HR] = 1.07, CI = 1.03-1.11, p < 0.01) and Charlson/Deyo scores of ≥1 versus 0 (HR = 3.47, CI = 1.40-8.60, p < 0.01) had significantly increased mortality risk following surgery. In particular, the Charlson/Deyo score is a novel prognostic factor for GC that may guide clinical and surgical decision-making for this rare, rapidly fatal tumor. Further prospective studies are warranted to clarify the effects of chemotherapy versus radiation as treatment modalities for GC.

Central nervous system neuroepithelial tumors with MN1-alteration: an individual patient data meta-analysis of 73 cases.

MN1 alteration characterizes a recently described group of neuroepithelial tumors with varied morphological features. In cIMPACT-NOW update 6, only those with astroblastoma morphology has been accepted as a newly recognized tumor type, whereas the rest of morphological variants are considered lesions sub-judice. We perform an individual patient data meta-analysis of MN1-altered neuroepithelial tumors comprising a total of 73 cases, in order to study the survival data and predictive markers for better diagnosis and management of this rare molecular entity. The 5- and 10-year progression-free survival are 38% and 0%, whereas the 5- and 10-year overall survival are 89% and 55%, respectively. Among all the morphological variants of MN1-altered tumor, astroblastoma morphology is significantly associated with an improved overall survival, emphasizing the importance of providing an integrated histologic and molecular diagnosis. Histological grading within the molecularly-defined MN1-altered astroblastoma remains controversial. In tumors with astroblastoma morphology, the odds of MN1-altered status among patients less than 15-year-old is 10.5 times that of those 15-year-old and older, and female of 9.4 times that of the male gender. Gross tumor resection appears as main treatment modality for better disease control based on observational data.

A single supratentorial high-grade neuroepithelial tumor with two distinct BCOR mutations, exceptionally long complete remission and survival.

Here, we present a patient with high-grade neuroepithelial tumors with mutations in the BCL6 corepressor BCOR (HGNET-BCOR), a rare, highly malignant brain tumor with poor prognosis. The patient underwent gross total tumor resection (GTR), high-dose chemotherapy, and, after local relapse, GTR, proton radiation, and chemotherapy. After a 7.5 year-long complete remission, the tumor recurred locally, was treated by GTR, and responded to temozolomide treatment. In addition to an internal tandem duplication in BCOR common to the majority of HGNET-BCOR cases, molecular analysis revealed a second BCOR mutation in this tumor: a frame shift mutation. The combination of these mutations was associated with relatively low BCOR expression compared to other HGNET-BCOR cases.

Genomic analysis demonstrates that histologically-defined astroblastomas are molecularly heterogeneous and that tumors with MN1 rearrangement exhibit the most favorable prognosis.

Astroblastoma (AB) is a rare CNS tumor demonstrating abundant astroblastomatous pseudorosettes. Its molecular features have not been comprehensively studied and its status as a tumor entity is controversial. We analyzed a cohort of 27 histologically-defined ABs using DNA methylation profiling, copy number analysis, FISH and site-directed sequencing. Most cases demonstrated mutually exclusive MN1 rearrangements (n = 10) or BRAFV600E mutations (n = 7). Two additional cases harbored RELA rearrangements. Other cases lacked these specific genetic alterations (n = 8). By DNA methylation profiling, tumors with MN1 or RELA rearrangement clustered with high-grade neuroepithelial tumor with MN1 alteration (HGNET-MN1) and RELA-fusion ependymoma, respectively. In contrast, BRAFV600E-mutant tumors grouped with pleomorphic xanthoastrocytoma (PXA). Six additional tumors clustered with either supratentorial pilocytic astrocytoma and ganglioglioma (LGG-PA/GG-ST), normal or reactive cerebrum, or with no defined DNA methylation class. While certain histologic features favored one genetic group over another, no group could be reliably distinguished by histopathology alone. Survival analysis between genetic AB subtypes was limited by sample size, but showed that MN1-rearranged AB tumors were characterized by better overall survival compared to other genetic subtypes, in fact, significantly better than BRAFV600E-mutant tumors (P = 0.013). Our data confirm that histologically-defined ABs are molecularly heterogeneous and do not represent a single entity. They rather encompass several low- to higher-grade glial tumors including neuroepithelial tumors with MN1 rearrangement, PXA-like tumors, RELA ependymomas, and possibly yet uncharacterized lesions. Genetic subtyping of tumors exhibiting AB histology, particularly determination of MN1 and BRAFV600E status, is necessary for important prognostic and possible treatment implications.

Leptomeningeal Gliomatosis: A Single Institution Study of 31 Patients.

BACKGROUND/AIM: Secondary leptomeningeal gliomatosis (LG) is a rare and severe progression pattern of glioma. Our objective was to evaluate the characteristics and outcome of patients with LG. PATIENTS AND METHODS: We retrospectively reviewed 31 patients diagnosed with secondary LG. At the time of LG diagnosis, the median age of patients was 45 years. The histological grade was IV in 20 patients and II to III in 11 patients. As a first-line of therapy for LG, 22 patients received an oncological treatment: i) BCNU-temozolomide (TMZ) (n=15), ii) other type of chemotherapy (n=7), and iii) no treatment (supportive care) (n=9). RESULTS: Following LG diagnosis, the median progression-free survival (PFS) and overall survival (OS) were 1.8 months [95% confidence interval (CI)=0.9-2.7] and 2.1 months (95%CI=1.3-3), respectively. The univariate analyses showed an improved OS with age of less than 45 years (p<0.001), a prolonged interval from the initial glioma diagnosis (IGD) to LG diagnosis (p=0.003), BCNU-TMZ as the preferred first-line treatment for LG out of the three options (p=0.008), and Karnofsky performance status (KPS) ≥70 (p=0.012). Prolonged interval from IGD to LG diagnosis (HR=5.839) and BCNU-TMZ as the chosen first-line treatment for LG (HR=6.635) remained significant in the multivariate analyses as well. Among the 22 treated patients, the median OS was significantly higher (p=0.008) with the BCNU-TMZ treatment (5.7 months; 95%CI=4.2-7.1), compared to other types of treatment offered (2 months; 95%CI=1.1-2.9). CONCLUSION: The time interval from the IGD to the LG diagnosis is a potential prognostic factor for LG. BCNU-TMZ may be a therapeutic option in the present setting.

Prognostic Factors and Survival of Gliomatosis Cerebri: A Systematic Review and Meta-Analysis.

BACKGROUND: Gliomatosis cerebri (GC) is a fatal diffusely infiltrating glioma. Because of its rarity, only scarce evidence is available regarding outcome predictors and the proper management of GC. METHODS: Reported studies of patients with histologically confirmed GC were systematically reviewed and individual patient-level data (n = 523) extracted. Multivariable Cox proportional hazard models were fit for overall survival (OS) and progression-free survival (PFS). RESULTS: The median OS and PFS were 13 and 10 months, with 5-year rates of 18% and 13%, respectively. Age ≥65 years at diagnosis (hazard ratio for OS [HROS], 2.32; 95% confidence interval [CI], 1.62-3.31), high-grade tumor (HRPFS for grade III, 1.57; 95% CI, 1.02-2.40; HRPFS for grade IV, 1.74; 95% CI, [0.98-3.10), GC type II (HROS, 1.49; 95% CI, 1.12-1.98; HRPFS, 1.56; 95% CI, 1.04-2.34), more central nervous system (CNS) regions involved (HROS, 1.09; 95% CI, 1.01-1.18), focal neurological deficits (HROS, 1.41; 95% CI, 1.07-1.86), cerebellar symptoms (HRPFS, 2.20; 95% CI, 1.42-3.39), more symptoms at presentation (HROS, 1.21; 95% CI, 1.05-1.40), Karnofsky performance scale score <70 (HROS, 3.58; 95% CI, 1.73-7.39; HRPFS, 4.48; 95% CI, 1.39-14.4), magnetic resonance imaging contrast enhancement (HROS, 1.48; 95% CI, 1.12-1.96; HRPFS, 1.74; 95% CI, 1.18-2.55), symmetric bilateral CNS invasion (HROS, 1.42; 95% CI, 1.03-1.96), and high proliferation index (Ki-67 >5%; HROS, 2.32; 95% CI, 1.11-4.86) were independent predictors of poor outcomes. In contrast, seizure occurrence (HROS, 0.77; 95% CI, 0.60-1.00; HRPFS, 0.68; 95% CI, 0.47-0.95), isocitrate dehydrogenase 1 mutation (HROS, 0.16; 95% CI, 0.05-0.49), and O6-methylguanine-DNA-methyltransferase promoter methylation (HROS, 0.23; 95% CI, 0.09-0.59) were associated with prolonged survival. Chemotherapy and surgical resection were associated with improved outcomes, but radiotherapy, whether monotherapy or combined with chemotherapy, was not superior to chemotherapy alone. CONCLUSIONS: In the largest study to date on GC, we have identified clinical, imaging, and molecular outcome predictors that are similar to other gliomas and highlight the beneficial effect of chemotherapy and surgical resection, when feasible, on outcomes.

Patterns of care and treatment outcomes of patients with astroblastoma: a National Cancer Database analysis.

AIM: To evaluate the use of chemotherapy and radiation, and their outcomes for patients with astroblastoma. PATIENTS & METHODS: This is a retrospective review of patients extracted from the National Cancer Database. We investigated overall survival (OS) using Kaplan-Meier curves. Cox proportional hazards models were used to correlate OS with risk variables and treatments. RESULTS: OS at 5 years was 79.5%. Patients with high-grade tumors were more likely to receive chemotherapy and radiation. Patients with high-grade astroblastoma who did not receive adjuvant radiation had poor survival. CONCLUSION: Patients with astroblastoma should be treated with curative intent. Radiation is likely beneficial in high-grade astroblastoma. The exact role of radiation and chemotherapy following surgical resection warrant further investigation.

Patterns of care and survival outcomes in patients with astroblastoma: an individual patient data analysis of 152 cases.

BACKGROUND: Astroblastoma (AB) is a rare tumor with significant dilemma regarding diagnostic criteria, behavior, and optimum treatment. MATERIALS AND METHODS: We searched PubMed, Google Search, and Cochrane Library for eligible studies with the following search words: astroblastoma, high-grade astroblastoma, and anaplastic astroblastoma till July 1, 2016, published in English language and collected data regarding age, sex, site of disease, pathological grade, treatment received, and survival. RESULTS: Data of 152 patients were retrieved from 63 publications. Median age was 16 years (range 0-71). Females were affected twice more frequently than male (70.3 vs. 29.7%). Tumors were most commonly located in the frontal (39%) followed by parietal lobe (26.7%). Fifty-two and 25% of the patients had headache and seizure at presentation, 76.3% of the patients underwent a gross total resection, 41 out of 89 had a high-grade tumor, and 56 patients received adjuvant radiation with a median dose of 54 Gy (range 20-72). Adjuvant chemotherapy was used in 23 patients. Temozolomide was the most common drug used in 30% of the patients. A combination of cisplatin, etoposide with vincristine, or ifosfamide was used in 17%. Median follow-up duration was 37 months (range 1-238). Median progression-free survival and OS were 36 and 184 months, respectively. Patients with a higher-grade tumor had significantly worse OS with HR 5.260 and p = 0.001. Forty patients experienced local progression. Sixty-five percent patients underwent surgery while 50% underwent radiation as salvage. CONCLUSION: AB has two distinct grades with higher-grade tumors having significantly poor survival. Maximal safe surgery followed by adjuvant radiation and temozolomide should be advocated for these tumors.

Management and Survival Patterns of Patients with Gliomatosis Cerebri: A SEER-Based Analysis.

OBJECTIVE: We used the SEER (Surveillance Epidemiology and End Results) database (1999-2010) to analyze the clinical practice patterns and overall survival in patients with gliomatosis cerebri (GC), or glioma involving 3 or more lobes of the cerebrum. METHODS: We identified 111 patients (age ≥18 years) with clinically or microscopically diagnosed GC in the SEER database. Analyses were performed to determine clinical practice patterns for these patients and whether these practices were associated with survival. RESULTS: Fifty-eight percent of the 111 patients with GC received microscopic confirmation of their diagnosis. Of the remaining patients, 40% were diagnosed via imaging or laboratory tests, and 2% had unknown methods of diagnosis. Seven percent of patients who did not have microscopic confirmation of their diagnosis received radiation therapy. Radiation therapy and surgery were not associated with survival. The only variable significantly associated with overall survival was age at diagnosis. Patients aged 18-50 years showed improved survival relative to patients aged >50 years (median survival, 11 and 6 months, respectively; P = 0.03). For patients aged >50 years, improved overall survival was observed in the post-temozolomide era (2005-2010) relative to those treated in the pre-temozolomide era (1999-2004) (median survival, 9 and 4 months, respectively; P = 0.005). CONCLUSIONS: In the SEER database, ∼40% of the patients with glioma with imaging findings of GC do not receive microscopic confirmation of their diagnosis. We propose that tissue confirmation is warranted in patients with GC, because genomic analysis of these specimens may provide insights that will contribute to meaningful therapeutic intervention.

Long-term results of the transmanubrial osteomuscular-sparing approach for pediatric tumors.

BACKGROUND: The complete and safe resection of pediatric cervicothoracic tumors, mostly represented by neurogenic tumors, remains a surgical challenge because of the complex anatomy of this region. The transmanubrial osteomuscular-sparing approach (TOSA) is an alternative to isolated or combined cervical and thoracic approaches enabling the control of supra-aortic vessels and nerves through the thoracic inlet. METHODS: We retrospectively reviewed the tumor characteristics, completeness of resection, morbidity, and long-term outcome of patients with cervicothoracic tumors removed by TOSA between 2000 and 2012 in our institution. RESULTS: Thirteen patients (7 males, 6 females) underwent surgery at a median age of 72 months (4-188) for neuroblastoma (n = 6), ganglioneuroblastoma (n = 3), rhabdoid tumor (n = 1), melanotic schwannoma (n = 1), chordoma (n = 1), and malignant peripheral nerve sheath tumor in one patient with type 1 neurofibromatosis. The median duration of the procedure was 215 minutes (110-315). Two children presented with postoperative chylothorax that resolved spontaneously. The median duration of hospitalization was 7 days (4-22). At a median follow-up of 39 months (2-159), four patients had died of metastatic relapse (n = 2), locoregional progression (n = 1), and chemotoxicity (n = 1). The patient with melanotic schwannoma was lost to follow-up after a local relapse at 5 months. Long-term morbidity revealed homolateral Claude-Bernard Horner sign and upper limb vasomotor dysfunction in disease-free patients due to mandatory resection of the stellate ganglia. CONCLUSIONS: TOSA is a valuable surgical approach for all cervicothoracic tumors with acceptable long-term morbidity when compared with its complexity. We can therefore recommend TOSA for tumors involving the thoracic inlet.

Incidence of neuroepithelial primary brain tumors among adult population of Emilia-Romagna Region, Italy.

Incidence of neuroepithelial Primary Brain Tumors (nPBT) varies, ranging from 7.3 to 11.6 cases/100,000/year across Europe. We present incidence and survival of nPBT in the Emilia-Romagna region (ER), Italy. This study is the largest in Southern Europe. Specialists in neurosurgery, neurology, neuroradiology, oncology, radiotherapy, genetics, and pathology of ER notified all suspected nPBT adult cases residing in ER (4,337,966 inhabitants) observed during 2009. Furthermore, through ICD-9 discharge codes, we identified and reviewed all possible cases. Neuroepithelial PBT diagnosis was based on histological or radiological findings. We included 400 incident nPBT cases, of which 102 (25%) were retrospectively identified. These latter were significantly older. The standardized incidence was 10.5/100,000/year (95% CI 9.4-11.5), higher for men. It was 9.2/100,000/year (95% CI 8.3-10.2) for astrocytic tumors, 0.6/100,000/year (95% CI 0.4-0.9) for oligodendroglial tumors, and 7.1 (95% CI 6.3-8.0) for glioblastoma (GBM). Among GBM patients, median survival was 249 days if prospectively identified vs. 132 days when identified through ICD-9 codes (p < 0.0001). The incidence of nPBT in the ER region is among the highest in the literature. Older patients were more likely to escape an active surveillance system. This should be considered when comparing incidence rates across studies, giving the increasing number of elderly people in the general population.

Perioperative Risk Assessment of Patients with Gliomatosis Cerebri.

BACKGROUND: Gliomatosis cerebri is a rare diffusely infiltrating malignant glial neoplasm. Presenting symptoms include seizures, neurologic deficits, and frequently symptoms related to increased intracranial pressure (ICP). Surgical intervention, including brain biopsy, may induce worsening of these neurologic symptoms. We reviewed our database to identify prognostic and risk factors for perioperative deterioration specifically associated with elevated ICP. METHODS: Between 2006 and 2014, 78 patients were treated for gliomatosis cerebri. Ten patients required perioperative emergent treatment for elevated ICP. The clinical course and outcome of these 10 patients (study group) were characterized and compared with the remaining 68 patients. RESULTS: The study group patients developed life-threatening symptoms of increased ICP and required urgent decompressive craniectomy (n = 5 urgent decompressive craniectomy after biopsy, n = 2 urgent decompressive craniectomy on admission) or aggressive medical therapy (n = 3). Demographic and clinical variables were similar in both groups. In patients with severe symptoms of increased ICP, enhancing tumor volume was significantly greater than in asymptomatic patients. Radiologic evidence of obliteration of the basal cisterns and herniation was more common in symptomatic patients. The proliferation index in the biopsy specimens of tumors was also significantly higher in patients with symptomatic ICP elevation. CONCLUSIONS: Clinical symptoms and radiologic appearance suggestive of elevated ICP at presentation, volume of contrast enhancement, and high Ki-67 proliferation index may predict the need for aggressive rapid treatment to control ICP in a small but significant subset of patients with GC. Further studies are needed to clarify the biologic basis for the unusual clinical course in these tumors.

Primary Leptomeningeal Gliomatosis in Children and Adults: A Morphological and Molecular Comparative Study With Literature Review.

BACKGROUND: Primary leptomeningeal gliomatosis (PLG) is a poorly recognized tumor of the central nervous system. OBJECTIVE: To describe the histopathological, immunohistochemical, and molecular features of PLG. METHODS: Results of our multicentric retrospective study of 6 PLG cases (3 pediatric and 3 adult) were compared with literature data. RESULTS: The mean age was 54.7 years for adults and 8.7 years for children, with 3 males and 3 females. Clinical symptoms were nonspecific. Cerebrospinal fluid analyses showed a high protein level often associated with pleocytosis but without neoplastic cells. On neuroimaging, diffuse leptomeningeal enhancement and hydrocephalus were observed, except in 1 case. PLG was mostly misinterpreted as infectious or tumoral meningitis. The first biopsy was negative in 50% of cases. Histopathologically, PLG cases corresponded to 1 oligodendroglioma without 1p19q codeletion and 5 astrocytomas without expression of p53. No immunostaining for IDH1R132H and no mutations of IDH1/2 and H3F3A genes were found. Overall survival was highly variable (2-82 months) but seems to be increased in children treated with chemotherapy. CONCLUSION: This study shows the difficulties of PLG diagnosis. The challenge is to achieve an early biopsy to establish a diagnosis and to begin a treatment, but the prognosis remains poor. PLG seems to have a different molecular and immunohistochemical pattern compared with intraparenchymal malignant gliomas.

An individual patient data meta-analysis on characteristics and outcome of patients with papillary glioneuronal tumor, rosette glioneuronal tumor with neuropil-like islands and rosette forming glioneuronal tumor of the fourth ventricle.

BACKGROUND AND PURPOSE: In 2007, the WHO classification of brain tumors was extended by three new entities of glioneuronal tumors: papillary glioneuronal tumor (PGNT), rosette-forming glioneuronal tumor of the fourth ventricle (RGNT) and glioneuronal tumor with neuropil-like islands (GNTNI). Focusing on clinical characteristics and outcome, the authors performed a comprehensive individual patient data (IPD) meta-analysis of the cases reported in literature until December 2012. METHODS: PubMed, Embase and Web of Science were searched for peer-reviewed articles reporting on PGNT, RGNT, and GNTNI using predefined keywords. RESULTS: 95 publications reported on 182 patients (PGNT, 71; GNTNI, 26; RGNT, 85). Median age at diagnosis was 23 years (range 4-75) for PGNT, 27 years (range 6-79) for RGNT, and 40 years (range 2-65) for GNTNI. Ninety-seven percent of PGNT and 69% of GNTNI were located in the supratentorial region, 23% of GNTNI were in the spinal cord, and 80% of RGNT were localized in the posterior fossa. Complete resection was reported in 52 PGNT (73%), 36 RGNT (42%), and 7 GNTNI (27%) patients. Eight PGNT, 3 RGNT, and 12 GNTNI patients were treated with chemo- and/or radiotherapy as the primary postoperative treatment. Follow-up data were available for 132 cases. After a median follow-up time of 1.5 years (range 0.2-25) across all patients, 1.5-year progression-free survival rates were 52±12% for GNTNI, 86±5% for PGNT, and 100% for RGNT. The 1.5-year overall-survival were 95±5%, 98±2%, and 100%, respectively. CONCLUSIONS: The clinical understanding of the three new entities of glioneuronal tumors, PGNT, RGNT and GNTNI, is currently emerging. The present meta-analysis will hopefully contribute to a delineation of their diagnostic, therapeutic, and prognostic profiles. However, the available data do not provide a solid basis to define the optimum treatment approach. Hence, a central register should be established.

Patterns of presentation and failure in patients with gliomatosis cerebri treated with partial-brain radiation therapy.

BACKGROUND: The patterns of lobar involvement, optimal treatment, and disease course among patients with gliomatosis cerebri (GC) have not been fully characterized. The current study evaluates the clinical presentations and outcomes for patients with GC treated with radiation therapy (RT) at our institution. METHODS: A total of 26 patients (25 with follow-up) with GC were diagnosed and treated between January 2004 and June 2012. Inclusion criteria consisted of brain magnetic resonance imaging and neuroradiology confirmation of contiguous involvement of ≥ 3 lobes/lobar equivalents with preservation of neural architecture. Patients were treated with either partial-brain RT to involved tumor (25 patients) or whole-brain RT (1 patient). The median RT dose was 54.0 Gray. The median follow-up was 17.3 months. RESULTS: The median age of the patients at the time of diagnosis was 57 years. Twenty-one patients (81%) and 5 patients (19%) had 3 to 6 and ≥ 7 involved lobes/lobar equivalents, respectively. The median progression-free survival and overall survival were 7.4 months and 14.9 months, respectively. Fifteen patients experienced radiographic disease progression after partial-brain RT, 14 of whom (93%) developed infield disease recurrence. On univariate analysis, higher tumor grade and type II GC (with focal mass) were associated with a poorer progression-free survival. The extent of lobar involvement and chemotherapy were not associated with overall survival. CONCLUSIONS: Even with partial-brain RT, nearly all disease recurrences were infield and clinical outcomes were similar to previous GC series, thereby suggesting that whole-brain RT is not necessary for this patient population. A greater number of involved lobes did not correlate with inferior outcomes. Further studies are necessary to establish more uniform and optimal treatments for this rare disease.

Exclusive radiotherapy for gliomatosis cerebri: long-term follow-up at a single institution.

PURPOSE: To evaluate the efficacy of radiotherapy and factors affecting the prognosis of gliomatosis cerebri. METHODS: Twenty-eight patients with pathologically confirmed gliomatosis cerebri underwent radiotherapy between August 1988 and September 2003. The median age of the patients was 39 years (range 18-67). Performance status was good (ECOG score ≤2) in 23 patients (82 %). The extent of radiotherapy was partial brain in 17 patients, whole brain in 2 patients, and whole brain followed by partial brain in 9 patients. The median radiation dose was 55.8 Gy (range 46.8-70.4). The median duration of follow-up was 136 months for survivors (range 39-191). RESULTS: The median overall and progression-free survival times of all patients were 20 and 11 months, respectively. When initial response to radiotherapy was grouped as improved, stationary, and aggravated, the median overall survival times in patients with improved, stationary, and aggravated responses were 76, 20, and 7 months, respectively (p = 0.0129). However, radiation parameters such as dose and irradiation volume had no impact on overall survival. On multivariate analysis, both performance status and initial response to radiotherapy were significant prognostic factors affecting overall survival (p = 0.0249 and 0.0065, respectively). CONCLUSIONS: This study showed that gliomatosis cerebri could be effectively treated with radiotherapy and that initial response to radiotherapy was a significant prognostic factor affecting the survival.

Clinical significance and limitations of repeat resection for pediatric malignant neuroepithelial tumors: clinical article.

OBJECT: Maximized tumor resection and minimized surgical morbidity are extremely important in the treatment of children with malignant neuroepithelial tumors. However, the indications for repeat surgery for these tumors remain unclear. The present study investigated the clinical significance and limitations of repeat resection for these tumors. METHODS: This study included 61 consecutive pediatric patients with malignant neuroepithelial tumor, histologically diagnosed as WHO Grades III and IV. All patients were initially treated between January 1997 and March 2011 and had follow-up of more than 2 years. The number of surgeries, presence of leptomeningeal dissemination, survival, WHO grade, and Eastern Cooperative Oncology Group performance status before and after surgery were retrospectively reviewed. RESULTS: Repeat resections were performed for 21 patients (34.4%). Eastern Cooperative Oncology Group performance status was not aggravated by surgery, even after multiple operations. The 5-year survival rates of patients who received single and repeat surgery were 58.6% and 38.7%, respectively (p = 0.12). The mean interval between initial surgery and leptomeningeal dissemination detection was 331 ± 108 days in the single-surgery group and 549 ± 122 days in the repeat-surgery group (p = 0.19). The median survival time after leptomeningeal dissemination was 580 days in the single-surgery group and 890 days in the repeat-surgery group (p = 0.74). CONCLUSIONS: Repeat resection with minimized surgical morbidity is an effective method to achieve better local control of pediatric malignant neuroepithelial tumors. Leptomeningeal dissemination was a leading cause of death, but repeat surgery did not increase the frequency of death.

Gliomatosis cerebri: clinical characteristics, management, and outcomes.

Gliomatosis cerebri is a rare diffusely infiltrating primary neoplastic glial process of the brain. Our objective is to review clinical presentation, management, and outcome in a large single institution series of gliomatosis cerebri patients. 54 consecutive gliomatosis cerebri cases presenting to Mayo Clinic Rochester between 1991 and 2008 were retrospectively reviewed. Inclusion criteria included involvement of at least three cerebral lobes, lack of a single discrete mass and pathological confirmation of diffuse glioma. Median overall survival (OS) was 18.5 months. Age, gender, presenting symptoms, and contrast enhancement did not correlate significantly with survival, though there was a trend toward decreased overall survival in patients above the median age of 46 years. Karnofsky performance score <70 was associated with poor OS (median 9.5 vs. 20.5 months, p = 0.02). Higher histologic grade was associated with poor progression-free survival (PFS; median for WHO grades II, III, and IV: 21.5, 6.5, and 4 months; p = 0.03) and OS (median 34, 15.5, and 8.5 months; p < 0.05). Radiation therapy was strongly associated with better prognosis (PFS 16.5 vs. 4.5 months, p < 0.01; OS 27.5 vs. 6.5, p < 0.01), but chemotherapy was not. Gliomatosis cerebri patients have a poor prognosis. Lower KPS upon presentation and higher histologic grade predict decreased survival. Surgery's role is limited beyond biopsy for diagnostic purposes. Radiotherapy appears beneficial, although selection bias could be present in this retrospective study. Chemotherapy's value is not as clear but this must be interpreted with caution given variable treatment regimens in this series.