Transformation of low grade glioma and correlation with outcome: an NCCTG database analysis.

Glioblastomas (GBM) may originate de novo (primary), or following transformation from a lower grade glioma (secondary), and it has been postulated that these tumors may have different biological behaviors. We performed a correlative analysis involving 204 patients with glioma treated prospectively on NCCTG clinical trials. Central pathology review of tumor tissues taken at the time of initial diagnosis and at recurrence were performed in all patients. Tumors progressed from low (WHO grade 2) to high (grade 3-4) at recurrence in 45% low grade oligodendroglioma patients, in 70% with low grade oligoastrocytoma, and 74% with low grade astrocytoma (P = 0.031). Median overall survival (OS) from initial diagnosis varied by histology: oligodendroglioma, 8.8 years; (95% CI 5.7-10.2); oligoastrocytoma, 4.4 years (95% CI 3.5-5.6); astrocytoma grade 2 3.1 years (astrocytoma grade 2-4, 2.1 years) (95% CI 1.7-2.5, P < 0.001). Mean time to recurrence (TTR) also varied between patients with de novo GBM, those secondary GBM, and those that remained non-GBM at recurrence (1.1 ± 1.1 vs. 2.9 ± 1.8 vs. 4.0 ± 2.9 years, respectively, P < 0.001). Median OS from time of recurrence also varied between these three categories (0.7 years, 95% CI: 0.5-1.1 vs. 0.6 years, CI: 0.5-1.0 vs. 1.4 years, 95% CI: 1.1-2.0, respectively) (P < 0.001). At time of relapse, transformation to higher grade is frequent in low grade pure and mixed astrocytomas, but is observed in less than half of those with low grade oligodendroglioma. From time of recurrence, OS was not significantly different for those with primary versus secondary GBM, and it may thus be reasonable include patients with secondary GBM in clinical therapeutic trials for recurrent disease.

Dysembryoplastic neuroepithelial tumor and calcifying pseudoneoplasms of the neuraxis: a collision of two seizure-associated lesions.

Dysembryoplastic neuroepithelial tumor (DNET) is a benign glioneuronal neoplasm typically associated with intractable, partial complex seizures in children and young adults. The authors present a case in which a DNET in a 45-year-old male was accompanied by a so-called "calcifying pseudoneoplasm of the neural axis" (CPNA), a rare tumefactive lesion considered reactive in nature. An MRI scan of the brain revealed a right temporal lobe abnormality with characteristics of DNT but no apparent calcification. Histologically, it exhibited classic features of DNET and an overlying meningeal- based, partially ossified, chondrocalcific lesion morphologically characteristic of CPNA. The association of DNET and CPNA has not been previously reported. The literature relevant to these two seizure-associated lesions is reviewed.

Tumefactive demyelination and glioblastoma: a rare collision lesion.

OBJECTIVE: Inflammatory demyelination occasionally forms a solitary mass lesion clinically and radiographically indistinguishable from glioma, replete with enhancement and mass effect. Termed "tumefactive demyelination" it often prompts a brain biopsy. DESIGN: We undertook neuroimaging and morphologic analysis of a unifocal demyelinating lesion intimately associated with glioblastoma. MRI characteristics of the lesion were assessed as were biopsy and resection specimens by both histological and immunohistochemical methods. RESULTS: The patient, a 49-year-old woman, presented with subacute onset headaches. An MRI T1W scan revealed a hemispheric mass with centrally reduced signal and ring enhancement. T2W images showed increased central signal with a rim of reduced signal co-localized to the enhancing ring. A biopsy was initially misinterpreted as demyelination alone, given abundance of histiocytes, the presence of hypertrophic astrocytes with micronuclei ("Creutzfeldt-Peters cells"), and occasional mitoses. Upon consultative review, two histologically distinct components, one inflammatory demyelination and the other an anaplastic astrocytoma were revealed. Subsequent complete resection of the abnormality demonstrated a WHO grade IV astrocytoma (glioblastoma multiforme). CONCLUSION: Our experience underscores the importance of adequate tissue sampling during biopsy for suspected glioma, and confirms the fact that active inflammatory demyelination may coexist with a high-grade glioma. Despite detailed study, the basis for the association remains elusive.

Expression of diagnostic neuronal markers and outcome in glioblastoma.

BACKGROUND: High-grade gliomas featuring giant cells, often demonstrate immunoreactivity for neuronal markers, a finding prognostically significant according to some studies. We investigated this event in glioblastomas (GBM). METHODS: Immunoexpression for synaptophysin, neurofilament protein, neuronal nuclear antigen, chromogranin and glial fibrillary acidic protein was analysed in 82 GBM including 11 fibrillary, 8 gemistocytic, 40 giant cell and 23 small cell examples. Survival was compared between tumours exhibiting (GBMpos) or lacking (GBMneg) neuronal markers and also between tumours expressing only one vs. two or more neuronal markers. RESULTS: Forty-five of the 82 tumours (54.8%) including 5 fibrillary, 5 gemistocytic, 30 giant cell and 5 small cell GBMs expressed at least one neuronal marker, synaptophysin being the most frequent (96%). There was no statistically significant difference in survival between GBMpos and GBMneg tumours, all cytologic subtypes combined (P = 0.22). The same was true when cytologic categories were compared. When only GBMpos tumours were analysed, there was a marginally significant difference in outcome between tumours positive for one vs. multiple markers (P = 0.05). This difference was influenced primarily by giant cell GBMs among which the survival time was significantly shorter in the multiple vs. single marker category (median 123 vs. 295 days, P = 0.014). This difference was not observed in the other GBM cell types. Ultrastructurally, rare neurosecretory granules in glial filament-rich cells were identified in one of four tumours studied. CONCLUSIONS: Neuronal marker expression is a frequent feature of GBM. Its prognostic significance is limited to the giant cell GBMs expressing two or more neuronal markers, these being associated with shorter survival.

Concurrent solitary fibrous tumor and low-grade fibrillary astrocytoma of the cerebellum.

OBJECTIVE: We report the clinicopathologic features of a solitary fibrous tumor (SFT) having undergone malignant transformation and being intimately associated with a WHO Grade II astrocytoma. CLINICAL PRESENTATION: A 7-month old patient presented with delayed motor development and hydrocephalus. INTERVENTION: Histologic and immunocytologic methods were applied in the study of the tumors. Resection was initially employed and the SIOP protocol employing vincristine and carboplatin was applied upon tumor recurrence. CONCLUSION: The biologic basis for the association of SFT and astrocytoma is unknown. The complex lesion differs substantially from WHO Grade IV gliosarcoma and from gliofibroma, lesions in which the disparate elements are linked by metaplasia. Indeed, it may represent a collision tumor. Lastly, induction of the glioma by the solitary fibrous tumor, a mechanism invoked to explain the poorly understood "sarcoglioma," deserves consideration.

Intraosseous soft tissue perineurioma: report of a vertebral example.

OBJECTIVE: To describe a unique intraosseous perineurioma affecting the L2 vertebral body and pedicle of a 28-year-old female. MATERIAL: A lytic, expansive lesion virtually limited to bone was gross totally excised; only minimal epidural extension was noted. METHODS: Histologic, immunohistochemical and ultrastructural studies were performed. RESULTS: The tumor was partially encapsulated, moderately cellular, and showed classic features of benign soft tissue perineurioma, being composed of interlacing fascicles of spindle cells with undulating nuclei and long, very narrow, cytoplasmic processes. Immunohistochemistry showed reactivity for EMA, Glut-1, claudin, collagen-4 and CD34; no S-100 or neurofilament protein staining was seen to suggest an origin in nerve. CONCLUSION: Perineurioma, a tumor affecting soft tissue, and presumably nerve-unassociated, may affect bone. No prior entirely osseous examples have been reported. This tumor expands the differential diagnosis of spindle cell tumors of bone.

Anaplastic astroblastoma-sarcoma in neurofibromatosis Type 1.

Astroblastoma is a distinctive brain tumor when its histologic features occur in pure form. More often, the tumor pattern is seen to emerge in infiltrative astrocytic tumors. The former are rare. Astroblastoma as a de novo component of gliosarcoma has not previously been described. Furthermore, astroblastoma has only once been reported to occur in the setting of neurofibromatosis Type I (NF1), a condition more often associated with pilocytic and diffuse or infiltrative astrocytic tumors. Herein, we describe a unique case of anaplastic de novo astroblastoma-sarcoma, in essence a variant of gliosarcoma, occurring in a 50-year-old female with documented NF1. Genetic study (fluorescence in situ hybridization) demonstrated no chromosomal losses or gains. Testing for abnormalities of chromosomes 7, 9, 10, 12, 17, 19 and 20, including the EGFR, p16, PTEN, MDM2 and NF1 gene regions, we found the tumor to exhibit a deletion of PTEN, monosomy 17 and gains of chromosomes 19 and 20q. The latter alterations, having been reported in astroblastoma, were noted in both tumor components, thus confirming the common origin of the glial and sarcomatous elements.

Oncocytic choroid plexus carcinoma: case report.

Herein, we report an unusual choroid plexus carcinoma with extensive oncocytic transformation. A 13-month-old girl presented with acute lethargy which quickly progressed to coma. A CT scan of the head revealed impending herniation due to hemorrhage within an intracranial tumor. An MRI scan showed a large, partly cystic and highly vascular left lateral ventricular mass. A near total resection was achieved. Microsections revealed a WHO Grade III choroid plexus carcinoma with extensive oncocyti c transformation. A minor portion of the moderately to poorly differentiated tumor exhibited classical microscopic features of choroid plexus carcinoma, including marked nuclear atypia, brisk mitotic activity (78/10 HPF), a high MIB-1 labeling index (44%) and zones of necrosis. In contrast, the large, eosinophilic, cytologically malignant but granular-appearing oncocytes comprising the majority of the lesion showed scant (1/10 HPF) mitotic activity and only a low MIB-1 labeling index (5%). A subsequent recurrence at 1 year consisted entirely of non-oncocytic tumor. Choroid plexus carcinoma with oncocytic transformation has not been previously reported. The remarkable extent of this alteration and its clinical significance remains to be determined.

Endoglin and CD-34 immunoreactivity in the assessment of microvessel density in normal pituitary and adenoma subtypes.

UNLABELLED: Vascularization is a prerequisite of tumor growth, invasion and metastasis. In the present work, microvessel density was assessed by quantitating using two different endothelial cell biomarkers, endoglin (CD-105) and CD-34. Fifty endocrinologically active and 36 clinically nonfunctioning pituitary adenomas, all surgically resected, as well as 10 autopsy-derived normal adenohypophyses were investigated by immunohistochemistry. The results showed that in every pituitary adenoma type endoglin, an assumed biomarker of proliferating endothelial cells, immunostained fewer vessels than CD-34 which revealed immunopositivity in all capillaries. Differences in endoglin versus CD-34 immunoexpression indicate varying degrees of vascularity in pituitary adenoma subtypes. The low levels of endoglin immunoexpression in pituitary tumors exposed to long-acting somatostatin analogs and dopamine agonists are consistent with the view that these agents inhibit angiogenesis. KEYWORDS: immunohistochemistry, endoglin, CD34, microvascular density, angiogenesis, pituitary.

Clinical and radiographic spectrum of pathologically confirmed tumefactive multiple sclerosis.

Atypical imaging features of multiple sclerosis lesions include size >2 cm, mass effect, oedema and/or ring enhancement. This constellation is often referred to as 'tumefactive multiple sclerosis'. Previous series emphasize their unifocal and clinically isolated nature, however, evolution of these lesions is not well defined. Biopsy may be required for diagnosis. We describe clinical and radiographic features in 168 patients with biopsy confirmed CNS inflammatory demyelinating disease (IDD). Lesions were analysed on pre- and post-biopsy magnetic resonance imaging (MRI) for location, size, mass effect/oedema, enhancement, multifocality and fulfilment of Barkhof criteria. Clinical data were correlated to MRI. Female to male ratio was 1.2 : 1, median age at onset, 37 years, duration between symptom onset and biopsy, 7.1 weeks and total disease duration, 3.9 years. Clinical course prior to biopsy was a first neurological event in 61%, relapsing-remitting in 29% and progressive in 4%. Presentations were typically polysymptomatic, with motor, cognitive and sensory symptoms predominating. Aphasia, agnosia, seizures and visual field defects were observed. At follow-up, 70% developed definite multiple sclerosis, and 14% had an isolated demyelinating syndrome. Median time to second attack was 4.8 years, and median EDSS at follow-up was 3.0. Multiple lesions were present in 70% on pre-biopsy MRI, and in 83% by last MRI, with Barkhof criteria fulfilled in 46% prior to biopsy and 55% by follow-up. Only 17% of cases remained unifocal. Median largest lesion size on T2-weighted images was 4 cm (range 0.5-12), with a discernible size of 2.1 cm (range 0.5-7.5). Biopsied lesions demonstrated mass effect in 45% and oedema in 77%. A strong association was found between lesion size, and presence of mass effect and/or oedema (P < 0.001). Ring enhancement was frequent. Most tumefactive features did not correlate with gender, course or diagnosis. Although lesion size >5 cm was associated with a slightly higher EDSS at last follow-up, long-term prognosis in patients with disease duration >10 years was better (EDSS 1.5) compared with a population-based multiple sclerosis cohort matched for disease duration (EDSS 3.5; P < 0.001). Given the retrospective nature of the study, the precise reason for biopsy could not always be determined. This study underscores the diagnostically challenging nature of CNS IDDs that present with atypical clinical or radiographic features. Most have multifocal disease at onset, and develop RRMS by follow-up. Although increased awareness of this broad spectrum may obviate need for biopsy in many circumstances, an important role for diagnostic brain biopsy may be required in some cases.

Spindle cell oncocytoma of the adenohypophysis: report of a case with marked cellular atypia and recurrence despite adjuvant treatment.

Spindle cell oncocytoma (SCO) of the adenohypophysis is a recently defined pituitary tumor mimicking a non-functioning macroadenoma and composed of mitochondrion rich tumor cells, positive for S-100, vimentin, epithelial membrane antigen and galectin-3 but lacking cytokeratins, pituitary hormones, and neuroendocrine markers. Derivation from pituitary folliculostellate cells (FSCs) has been suggested based upon immunohistochemical and ultrastructural characteristics shared by SCO and FSCs. 10 cases of SCO have been reported to date; of these, 8 underwent a benign clinical course and 2 recurred. We report a case of SCO with typical histologic and immunohistochemical features in addition to marked cellular pleomorphism and nuclear atypia. It showed slow regrowth over a 30-month period of follow-up despite combined surgical and radiotherapy. Despite the benign course of most reported cases, additional experience with longer follow-up are needed to assess clinical, histopathologic, and proliferative indices and their relevance to optimal therapy for this rare pituitary tumor.

Plurihormonal gonadotroph cell pituitary adenoma: report of a unique case.

OBJECTIVE AND IMPORTANCE: Pituitary adenomas producing primarily FSH and to a lesser extent GH, LH, alpha-subunit, TSH and PRL without clinical or laboratory evidence of increased hormone release have not previously been reported. Our aim was to obtain some insight into the possible cytogenesis of this unusual tumor. CLINICAL PRESENTATION: A 65-year-old woman presented with headaches. Magnetic resonance imaging (MRI) demonstrated a sellar mass. Pituitary hormone assays showed normal blood levels. The tumor was removed by the transsphenoidal approach. RESULT: By light microscopy, the adenoma was chromophobic, weakly PAS-positive, and immunoreactive mainly for FSH (85%) and to a lesser extent for GH (30%), LH (15%), alpha-subunit (3%), TSH (2%), and PRL (1%). Although double immunostaining showed hormone reactivities to be localized largely in separate distinct cells, the tumor was ultrastructurally monomorphous, i.e., consisted of a single-cell type, resembling gonadotrophs. CONCLUSION: The cytogenesis of plurihormonal pituitary adenomas is not fully understood. Further investigations are required to clarify the basis for their plurihormonality despite an ultrastructural gonadotroph phenotype.

Ganglioglioma of the neurohypophysis.

The normal infundibulum and neurohypophysis consist entirely of neuronal processes, the neuronal cell bodies of which lie within the supraoptic and paraventricular nuclei of the hypothalamus and supportive glial cells or pituicytes. The finding of neurons within the neurohypophysis is exceedingly rare, as are ganglion cell tumors at this site. In this paper, we report a ganglion cell tumor of the neurohypophysis found incidentally at autopsy. Despite chronic hypertension and the finding of some vasopressin immunoreactivity in lesional neurons, the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was excluded on the basis of normal serum sodium levels. The morphologic and immunohistochemical features of the tumor are presented, cytogenetic considerations are discussed, and literature regarding neuronal lesions of the pituitary gland is reviewed.

Infiltrative chordoid meningioma of the pineal region: a study of 2 cases.

OBJECTIVE: Meningiomas involving the pineal region are rare. Herein we describe two cases of chordoid meningioma with histologic evidence of pineal gland infiltration. MATERIALS AND METHODS: Clinical histories were abstracted from chart review and consultation letters. HE-stained slides were reviewed in both cases. Selected immunohistochemical stains were performed. RESULTS: the patients included a 44-year-old male and a 37-year-old female who presented with symptoms of intracranial tumor referable to the pineal region. On magnetic resonance imaging (MRI), both lesions demonstrated heterogeneous contrast enhancement. Histologically, the tumors were characterized by strands and cords ofmeningothelial cells arranged in a mucinous stroma. In addition, obvious meningothelial cytology as well as focal osseous metaplasia (Case 1), and transitional histology (Case 2) were also noted. Tumor cells demonstrated EMA and focal S100 protein immunoreactivity, but lacked cytokeratin AE1/AE3 and glial fibrillary acidic protein (GFAP) staining. Synaptophysin and neurofilament protein highlighted the overrun pineal gland parenchyma. MIB1-proliferative index was 8.4 and 20.1%, respectively. CONCLUSIONS: Chordoid meningioma, although rare, may occur in the pineal region. The differential diagnosis of this meningioma subtype in this location is discussed.

Benign metastasizing leiomyomatosis with massive brachial plexus involvement mimicking neurofibromatosis type 1.

We report the case of a patient who presented with right arm and shoulder pain due to compression of the infraclavicular brachial plexus due to benign metastasizing leiomyomatosis (BML). She was initially and had been repeatedly misdiagnosed as having neurofibromatosis type 1 (NF 1). The diagnosis of BML was not obvious due to its rare nature, the patient's not detailing the specifics of her gynecologic history of having undergone resection of a large uterine leiomyoma and followed by disseminated pelvic leiomyomatous nodules, histologic misinterpretation of an extrauterine lesion of the spine and the brachial plexus as a neurofibroma and the radiologic diagnosis of lung nodules as being "non-specific" in nature. In addition and importantly, no clinical, radiographic or histologic features of NF 1 were present. Although a rare condition, BML should be considered in the differential diagnosis of NF and in patients having a history of uterine leiomyoma. The remarkable, selective involvement of the brachial plexus in this case is unexplained.

Pituitary corticotroph hyperplasia preceding adenoma in a patient with Nelson's syndrome.

We report the case of a 42-year-old woman with Cushing's disease and Nelson's syndrome. When she was 17 years old, transsphenoidal surgery was performed. A detailed morphologic study demonstrated nodular hyperplasia of corticotroph cells but no adenoma. Following a long-lasting remission (14 years), Cushing's disease recurred. After an unsuccessful second transsphenoidal surgery, Cushing's disease persisted and both adrenals were removed (at the age of 34). Subsequently the patient developed Nelson's syndrome. The pituitary tumor proved to be a corticotroph adenoma; it was removed by the transsphenoidal approach (at the age of 42). Although in most patients Cushing's disease is due to an ACTH-secreting pituitary corticotroph adenoma which precedes the manifestation of Nelson's syndrome, our case indicates not only that corticotroph hyperplasia may cause Cushing's disease but that it may exist before the development of Nelson's syndrome after the removal of both adrenals. Our study supports the view that protracted stimulation of corticotrophs resulting from the elimination of the negative inhibitory feedback effect by corticosteroids plays a role in adenoma initiation.

PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme.

BACKGROUND: Survival of patients with anaplastic astrocytoma is highly variable. Prognostic markers would thus be useful to identify clinical subsets of such patients. Because specific genetic alterations have been associated with glioblastoma, we investigated whether similar genetic alterations could be detected in patients with anaplastic astrocytoma and used to identify those with particularly aggressive disease. METHODS: Tissue specimens were collected from 174 patients enrolled in Mayo Clinic Cancer Center and North Central Cancer Treatment Group clinical trials for newly diagnosed gliomas, including 63 with anaplastic astrocytoma and 111 with glioblastoma multiforme. Alterations of the EGFR, PTEN, and p53 genes and of chromosomes 7 and 10 were examined by fluorescence in situ hybridization, semiquantitative polymerase chain reaction, and DNA sequencing. All statistical tests were two-sided. RESULTS: Mutation of PTEN, amplification of EGFR, and loss of the q arm of chromosome 10 were statistically significantly less common in anaplastic astrocytoma than in glioblastoma multiforme (P =.033, P =.001, and P<.001, respectively), and mutation of p53 was statistically significantly more common (P<.001). Univariate survival analyses of patients with anaplastic astrocytoma identified PTEN (P =.002) and p53 (P =.012) mutations as statistically significantly associated with reduced and prolonged survival, respectively. Multivariate Cox analysis of patients with anaplastic astrocytoma showed that PTEN mutation remained a powerful prognostic factor after adjusting for patient age, on-study performance score, and extent of tumor resection (hazard ratio = 4.34; 95% confidence interval = 1.82 to 10.34). Multivariate classification and regression-tree analysis of all 174 patients identified EGFR amplification as an independent predictor of prolonged survival in patients with glioblastoma multiforme who were older than 60 years of age. CONCLUSION: PTEN mutation and EGFR amplification are important prognostic factors in patients with anaplastic astrocytoma and in older patients with glioblastoma multiforme, respectively.

Localization of common deletion regions on 1p and 19q in human gliomas and their association with histological subtype.

Allelic alterations of chromosomes 1 and 19 are frequent events in human diffuse gliomas and have recently proven to be strong predictors of chemotherapeutic response and prolonged survival in oligodendrogliomas (Cairncross et al., 1998; Smith et al., submitted). Using 115 human diffuse gliomas, we localized regions of common allelic loss on chromosomes 1 and 19 and assessed the association of these deletion intervals with glioma histological subtypes. Further, we evaluated the capacity of multiple modalities to detect these alterations, including loss of heterozygosity (LOH), fluorescence in situ hybridization (FISH), and comparative genomic hybridization (CGH). The correlation coefficients for detection of 1p and 19q alterations, respectively, between modalities were: 0.98 and 0.87 for LOH and FISH, 0.79 and 0.60 for LOH and CGH, and 0.79 and 0.53 for FISH and CGH. Minimal deletion regions were defined on 19q13.3 (D19S412-D19S596) and 1p (D1S468-D1S1612). Loss of the 1p36 region was found in 18% of astrocytomas (10/55) and in 73% (24/33) of oligodendrogliomas (P < 0.0001), and loss of the 19q13.3 region was found in 38% (21/55) of astrocytomas and 73% (24/33) of oligodendrogliomas (P = 0.0017). Loss of both regions was found in 11% (6/55) of astrocytomas and in 64% (21/33) of oligodendrogliomas (P < 0.0001). All gliomas with LOH on either 1p or 19q demonstrated loss of the corresponding FISH probe, 1p36 or 19q13.3, suggesting not only locations of putative tumor suppressor genes, but also a simple assay for assessment of 1p and 19q alterations as diagnostic and prognostic markers.

Effective chemotherapy for advanced CNS embryonal tumors in adults.

PURPOSE: Embryonal tumors of the CNS include, among others, medulloblastoma, cerebral neuroblastoma, pineoblastoma, and primitive neuroectodermal tumors (PNETs). Almost all data on the treatment of embryonal CNS tumors are derived from the pediatric population, since these tumors are uncommon in adulthood. The purpose of this study was to examine the rate and duration of response to chemotherapy of advanced embryonal CNS tumors in adults. PATIENTS AND METHODS: We retrospectively studied all adult (> 18 years of age) patients with advanced embryonal tumors of the CNS who received chemotherapy at our institution between 1976 and 1994. Seventeen consecutive patients were treated with regimens that contained either nitrosourea or cisplatin or both sequentially, with no patients having received the combination of nitrosourea and cisplatin concurrently. RESULTS: In patients who received cisplatin-based chemotherapy, responses were observed in 84.5% (26% complete response [CR] rate), 10.5% remained stable, and 5% progressed. The median time to progression was 18 months for patients who had a CR, 6 months for those with partial response (PR), and 10 months for stable patients. Among patients who received nitrosourea-based chemotherapy, PR was observed in 27%, 36.5% remained stable, and 36.5% progress. The median time to progression was 6 months for patients who had a PR and 6.5 months for stable patients. CONCLUSION: In adults with advanced embryonal CNS tumors, conventional-dose intravenous cisplatin-based chemotherapy regimens are able to produce responses in the majority of the patients (84.5%), even as second- or third-line regimens. Nitrosourea-based regimens less frequently produce responses (27%).

Phase III comparative evaluation of PCNU and carmustine combined with radiation therapy for high-grade glioma.

PURPOSE: We performed a randomized trial to compare survival distributions and toxicity of radiation therapy (RT) and PCNU with those of RT and carmustine (BCNU) in patients with malignant glioma. PATIENTS AND METHODS: A total of 346 patients with histologically verified supratentorial grade 3 and grade 4 astrocytoma were studied. After surgery, patients were randomly assigned to receive RT 60 Gy in 30 fractions and either PCNU 100 mg/m2 or BCNU 200 mg/m2 every 7 weeks for 1 year and every 10 weeks for the second year. RT and chemotherapy were started within 72 hours of randomization and usually on the same day. Of 334 assessable patients, 72% had partial or radical resection and 71% had grade 4 tumors. Median age was 59 years, and 85% had performance scores of 0 to 2 (Eastern Cooperative Oncology Group [ECOG]). The follow-up duration of 51 living patients ranged from 10.3 to 63.2 months, with a median of 36.2 months. RESULTS: The median survival duration in each group was 47 weeks, and median time to progression was 28 weeks. PCNU produced significantly more leukopenia and thrombocytopenia, whereas BCNU produced significantly more nausea, vomiting, and irritation. CONCLUSION: PCNU has no therapeutic advantage at this dose and schedule and does not warrant further study as a single agent for patients with high-grade glioma.