Recurrent Anaplastic Oligodendroglioma Research Articles

INNV-07. TTFIELDS TREATMENT OF GLIOSARCOMA AND RECURRENT ANAPLASTIC OLIGODENDROGLIOMA

Abstract INTRODUCTION The Optune device delivers tumor treating fields (TTFields) and is considered as a standard of care for newly diagnosed and recurrent glioblastoma patients. The efficacy of Optune in other glioma subtypes, such as gliosarcoma and anaplastic oligodendroglioma, is still unclear. In this small case series, we present the clinical, pathologic and radiographic findings of two patients who utilized Optune and had improved outcomes compared to historical controls. CASE 1 A 49 year old woman underwent resection of a right temporal lobe gliosarcoma in November 2017. She received conventional radiation therapy with concurrent temozolomide, which was complicated by significant thrombocytopenia and leukopenia. She initiated Optune as monotherapy six weeks after completing radiation, and used the device for 24 months. She still has not had a recurrence, now 3.5 years since her initial diagnosis. CASE 2 A 46 year old woman underwent resection of a right frontal lobe oligodendroglioma, WHO Grade 2, in September 2011. She received one cycle of temozolomide in April 2014, complicated by thrombocytopenia, and no further chemotherapy was administered. In November 2017, she underwent resection of a new focus of enhancement at the margin of the resection cavity, which was confirmed to have transformed to WHO Grade 3. In August 2019, a radiographic progression of an enhancing nodule was observed. She initiated Optune as monotherapy in September 2019, and since that time, has had stable disease for 18 months. Optune treatment is still ongoing. CONCLUSIONS In a case of newly diagnosed gliosarcoma, Optune monotherapy has contributed to progression-free and overall survival of 3.5 years to date. In a case of recurrent anaplastic oligodendroglioma, Optune monotherapy has achieved stable disease for at least 18 months. These cases demonstrate that Optune can be safely utilized in these glioma subtypes and contributed to improved survival outcomes in these two patients.

Phase II trial of palbociclib in recurrent RB-positive anaplastic oligodendroglioma: A Spanish group for research in neurooncology (GEINO) trial.

2038 Background: The pRB-dependent cell cycle checkpoint is altered in the vast majority of anaplastic oligodendrogliomas (AO), either by homozygous deletion or by hypermethylation of CDKN2A and/or CDKN2B, or by amplification and/or overexpression of CDK4. Palbociclib is an oral inhibitor of CDK4 and 6 that has already been shown to be highly active in breast cancer. Methods: We conducted a multicenter, open-label, phase II trial evaluating efficacy and safety of Palbociclib in patients with AO that progressed to radiotherapy and more than one chemotherapy regimen containing Temozolomide and/or Lomustine. Inclusion criteria included: histologically and molecularly confirmed grade III oligodendroglioma (WHO 2016 classification, IDH1/2 mutation and 1p/19 codeletion were mandatory), recurrence after radiotherapy and 1 or 2 chemotherapy regimens and conserved RB protein expression by immunohistochemistry (IHC). Patients were treated with Palbociclib 125 mg/daily 3 weeks on/1off. The primary objective of the study was progression-free survival at 6 months (6M-PFS). Results: Between October 2015 and September 2018, 34 patients were enrolled across ten hospitals. The study was stopped early secondary to lack of efficacy, with 74% of evaluable patients progressing within 6 months. Number of patients alive and free from progression at 6 months after the enrollment was 9 (26%) out of the first 34 patients, below the minimum number required (18 out of 40) to consider Palbociclib as an active drug in this population. With a median follow-up of 11.2 months, the median PFS was 3 months (95% CI: 2.5-3.5 months). Median overall survival (OS) was 23.1 months (95% CI: 17.2-25 months). There were no partial or complete responses and only 11 patients (32%) achieved stable disease as best response. Palbociclib was well tolerated with neutropenia (Grade 3 or 4: 40%) and thrombocytopenia (Grade 3 or 4: 15%) as the most common adverse effects (AEs). Both AEs had no significant impact since there were no episodes of febrile neutropenia or bleeding. Conclusions: Despite the good tolerance and drug exposure, Palbociclib monotherapy did not show favorable activity in recurrent AO. Clinical trial information: NCT02530320.

Efficacy of Gamma Knife Radiosurgery for Recurrent High-Grade Gliomas with Limited Tumor Volume.

ObjectiveThis study aims to determine whether gamma knife radiosurgery (GKR) improves survival in patients with recurrent highgrade gliomas.MethodsTwenty nine patients with recurrent high-grade glioma underwent 38 GKR. The male-to-female ratio was 10 : 19, and the median age was 53.8 years (range, 20–75). GKR was performed in 11 cases of recurrent anaplastic oligodendrogliomas, five anaplastic astrocytomas, and 22 glioblastomas. The median prescription dose was 16 Gy (range, 10–24), and the median target volume was 7.0 mL (range, 1.1–15.7). Of the 29 patients, 13 (44.8%) received concurrent chemotherapy. We retrospectively analyzed the progression-free survival (PFS) and overall survival (OS) after GKR depending on the Eastern Cooperative Oncology Group (ECOG) performance status (PS), pathology, concurrent chemotherapy, radiation dose, and target tumor volume.ResultsStarting from when the patients underwent GKR, the median PFS and OS were 5.0 months (range, 1.1–28.1) and 13.0 months (range, 1.1–75.1), respectively. On univariate analysis, the median PFS was significantly long in patients with anaplastic oligodendroglioma, ECOG PS 1, and target tumor volume less than 10 mL (p<0.05). Meanwhile, on multivariate analysis, patients with ECOG PS 1 and target tumor volume less than 10 mL showed improved PFS (p=0.043 and p=0.007, respectively). The median OS was significantly increased in patients with ECOG PS 1 and tumor volume less than 10 mL on univariate and multivariate analyses (p<0.05).ConclusionGKR could be an additional treatment option in recurrent high-grade glioma, particularly in patients with good PS and limited tumor volume.

IMCT-05COMBINABILITY OF TOCA FC AND TOCA 511 WITH CHEMOTHERAPY AND TARGETED AGENTS

Investigational Toca 511, a retroviral replicating vector, and Toca FC (extended-release flucytosine) are used in combination to target recurrent high grade glioma at resection by transducing the tumor with the gene encoding cytosine deaminase, converting flucytosine to 5-FU intratumorally. Preclinically, additive efficacy with temozolomide, lomustine and radiation therapy has been observed. Patients treated on two protocols (NCT 01156584 and NCT01470794) delivering intracranial Toca 511 and Toca FC were enrolled in a continuation protocol for extended safety observations, which allows Toca FC with investigator's choice of subsequent therapy. Exploratory safety analysis of the combinability of Toca 511 and Toca FC with concurrent subsequent therapy was conducted. Five patients received Toca FC in combination with other therapies. These patients were 37-68 years old; 4 had recurrent glioblastoma and 1 recurrent anaplastic oligodendroglioma. Concurrent therapy was administered for 2 to 10 months, including Toca FC + lomustine (1), lomustine + procarbazine (1), lomustine + bevacizumab (2), sequential bevacizumab + lomustine then bevacizumab + carboplatin (1). Patients reported adverse events (AEs) ranging from Grade 1 to Grade 3. No Toca 511- or Toca FC- related serious AEs were reported. AEs related to Toca 511 occurred in 2 patients: grade 1 fatigue, generalized aching and to Toca FC in 4 patients: grade 1 fatigue, decreased appetite, nausea, constipation, diarrhea; grade 2 heartburn, nausea, vomiting, constipation. Overall survival was 11-30+ months (2 alive as of data cut-off date). Preliminary data suggest that in combination with chemotherapy and/or bevacizumab, Toca 511 and Toca FC are tolerated with a manageable safety profile. Updates with prospectively collected data on treatment with lomustine or bevacizumab will be provided. The safety of combining Toca 511 and Toca FC with multimodality treatment will be further explored in a Phase 1b in newly diagnosed glioblastoma to begin enrollment in 2016.

Temozolomide Salvage Chemotherapy for Recurrent Anaplastic Oligodendroglioma and Oligo-Astrocytoma

ObjectiveTo evaluate the efficacy of temozolomide (TMZ) chemotherapy for recurrent anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA).MethodsA multi-center retrospective trial enrolled seventy-two patients with histologically proven AO/AOA who underwent TMZ chemotherapy for their recurrent tumors from 2006 to 2010. TMZ was administered orally (150 to 200 mg/m2/day) for 5 days per 28 days until unacceptable toxicity occurred or tumor progression was observed.ResultsTMZ chemotherapy cycles administered was median 5.3 (range, 1-41). The objective response rate was 24% including 8 cases (11%) of complete response and another 23 patients (32%) were remained as stable disease. Severe side effects (≥grade 3) occurred only in 9 patients (13%). Progression-free survival (PFS) of all patients was a median 8.0 months (95% confidence interval, 6.0-10.0). The time to recurrence of a year or after was a favorable prognostic factor for PFS (p<0.05). Overall survival (OS) was apparently differed by the patient's histology, as AOA patients survived a median OS of 18.0 months while AO patients did not reach median OS at median follow-up of 11.5 months (range 2.7-65 months). Good performance status of Eastern Cooperative Oncology Group 0 and 1 showed prolonged OS (p<0.01).ConclusionFor recurrent AO/AOA after surgery followed by radiation therapy, TMZ could be recommended as a salvage therapy at the estimated efficacy equal to procarbazine, lomustine, and vincristine (PCV) chemotherapy at first relapse. For patients previously treated with PCV, TMZ is a favorable therapeutic option as 2nd line salvage chemotherapy with an acceptable toxicity rate.

MicroRNA expression profiling in recurrent anaplastic oligodendroglioma treated with postoperative radiotherapy

In anaplastic oligodendroglioma (AO), genetic alternation was associated with clinical outcome. We explored radiation-associated up or downregulation of microRNAs (miRNAs) in AO by comparing miRNA expression profiles in newly-diagnosed AO to recurrent AO treated with postoperative radiotherapy. We identified that 23 miRNAs were upregulated and 42 miRNAs were downregulated in recurrent AO compared with newly-diagnosed AO. Especially, the expression of MiR-124, miR-128, miR-139-5p, miR-153, miR-210, miR-582-5p, and miR-96 were highly increased in the patient with recurrent AO. In contrast, MiR-1, miR-1180, miR-133b, miR-135b, miR1539, miR-193a-5p, miR-196a, miR-196b, miR-200b, miR-21*, miR-221*, miR-224, miR-24-1*, miR-31, miR-32*, miR-34a*, miR-34c-5p, miR-455-5p, miR-503, and miR-631 showed extremely decreased expression in the patient with recurrent AO. Our results provide meaningful data for miRNAs as molecular diagnosis and novel therapeutic targets in recurrent AO treated with radiotherapy.

Spinal cord anaplastic oligodendroglioma with 1p deletion: report of a relapsing case treated with temozolomide

Primary spinal cord oligodendroglial tumor is very rare, and in only one patient with spinal cord oligodendroglioma has a deletion of chromosome 1p/19q been reported. We present the case of an 18-year-old girl, who had one-year lower back pain and one-month lower limb weakness. Magnetic resonance images of the spinal cord showed an intramedullary mass from level T8 to T10, which was then radically removed. Histology revealed an anaplastic oligodendroglioma. The patient was treated with radiotherapy postoperatively. Eight months after the treatment, follow-up magnetic resonance images disclosed an enhancing intramedullary mass at level T4-T8; recurrence of the tumor was therefore diagnosed. Maximum surgical removal of the recurrent tumor was performed, diagnosis of anaplastic oligodendroglioma was made, and a chromosome 1p deletion was determined by FISH. After treatment with temozolomide for six months, the patient had a remarkable improvement of her lower limb symptoms, and complete imaging regression of the residual tumor showed no evidence of recurrence at any other sites. The most recent MRI of brain and spinal cord showed postoperative changes without evidence of tumor recurrence of the spine and oligodendrogliomatosis along the cerebral-spinal axis. To our knowledge, this is the first report of a recurrent anaplastic oligodendroglioma with 1p deletion occurring in the spinal cord. It is also the first case of the patient with recurrent intramedullary anaplastic oligodendroglioma who had a significant clinical improvement and complete imaging remission after subtotal resection then treatment with temozolomide chemotherapy.

Bevacizumab for recurrent alkylator‐refractory anaplastic oligodendroglioma

A retrospective evaluation of single agent bevacizumab was carried out in adults with recurrent alkylator-refractory 1p19q codeleted anaplastic oligodendrogliomas (AO) with an objective of determining progression-free survival (PFS). There is no standard therapy for alkylator-resistant AO, and hence a need exists for new therapies. Twenty-two patients aged 24 to 60 years with recurrent AO were treated. All patients had previously been treated with surgery, radiotherapy, adjuvant chemotherapy (temozolomide, 17; carmustine wafers, 4; carmustine, 1), and 1 salvage regimen (procarbazine, lomustine, and vincristine, 15; temozolomide, 6; carmustine wafers, 1). Eleven patients underwent repeat surgery. Patients were treated at second recurrence with bevacizumab, once every 2 weeks, defined as a single cycle. Neurological evaluation was performed every 2 weeks, and neuroradiographic assessment was made after the initial 2 cycles of bevacizumab and subsequently after every 4 cycles of bevacizumab. A total of 391 cycles of bevacizumab (median, 14.5 cycles; range, 2-39 cycles) were administered. Bevacizumab-related toxicity included fatigue (14 patients; 4 grade 3), leukopenia (9; 1 grade 3), anemia (5; 0 grade 3), hypertension (5; 1 grade 3), deep vein thrombosis (4; 1 grade 3), and wound dehiscence (2; 1 grade 3). Fifteen (68%) patients demonstrated a partial radiographic response, 1 (5.0%) demonstrated stable disease, and 6 (27%) demonstrated progressive disease after 2 cycles of bevacizumab. Time to tumor progression ranged from 1 to 18 months (median, 6.75 months). Survival ranged from 3 to 19 months (median, 8.5 months). Six-month and 12-month PFS were 68% and 23%, respectively. Bevacizumab demonstrated efficacy and acceptable toxicity in this cohort of adults with recurrent 1p19q codeleted alkylator-refractory AO.

CPT-11 for recurrent temozolomide-refractory 1p19q co-deleted anaplastic oligodendroglioma

A Phase II study of CPT-11 in adults with recurrent, temozolomide (TMZ)-refractory, 1p19q co-deleted, anaplastic oligodendroglioma (AO) with a primary objective of determining 6-month progression free survival (PFS). There is no standard therapy for alkylator-resistant AO. Twenty-two patients (11 men; 11 women) ages 26-65 (median 40), with radiographically recurrent AO were enrolled. All patients had previously been treated with surgery, involved-field radiotherapy, and adjuvant chemotherapy (TMZ in 15; BCNU in 6). Fifteen patients were treated at first recurrence with an alternative chemotherapy. 13 patients underwent repeat surgery. All patients were treated at either first or second recurrence with CPT-11 administered intravenously once every 3 weeks. Neurological and neuroradiographic evaluations were performed every 8-9 weeks. All patients were evaluable for toxicity and response. A total of 141 cycles of CPT-11 (median 3 cycles; range 3-18) were administered. CPT-11 related toxicity included diarrhea (14 patients; 4 grade 3), neutropenia (8; 4 grade 3), fatigue (12; 3 grade 3), and delayed nausea/vomiting (12; 3 grade 3). 5 patients (23%) demonstrated a partial radiographic response, 8 (36%) demonstrated stable disease and 9 (41%) had progressive disease following three cycles of CPT-11. Time to tumor progression ranged from 2 to 13.5 months (median: 4.5 months). Survival ranged from 3 to 21 months (median: 5.5 months). Six-month and 12-month PFS were 33% and 4.5% respectively. CPT-11 demonstrated modest efficacy (similar to other salvage glioma regimens) with acceptable toxicity in this cohort of adults with recurrent, 1p19q co-deleted AO all of whom had failed prior TMZ chemotherapy.

Anaplastic oligodendroglial tumor metastatic to the bone marrow: Molecular heterogeneity of glial neoplasms and the clinical importance of minor clones

Anaplastic oligodendrogliomas are primary brain tumors that rarely metastasize to extracranial sites. We present a case of a 37 year old man who presented at age 34 with a cystic, ring‐enhancing left parietal tumor. Partial resection revealed a synaptophysin‐positive anaplastic oligodendroglioma with a Ki‐67 labeling index of 17%; fluorescence in situ hybridization (FISH) revealed relative deletions of both chromosomes 1p and 19q. The patient subsequently received temozolomide (TMZ), radiotherapy (RT) plus TMZ, and post‐RT TMZ with continued progression of the tumor. Re‐resection 2 years later showed recurrent anaplastic oligodendroglioma with a Ki‐67 labeling index of 50% and he was started on procarbazine, lumustine, vincristine (PCV). Nine months later a third resection revealed anaplastic mixed oligo‐astrocytoma with a Ki‐67 index of 89% and loss of heterozygosity (LOH) 1p/19q. He was started on irinotecan and Avastin. Six months later he presented with night sweats and lower back pain. Bone marrow biopsy revealed a GFAP‐positive metastatic glioma histologically similar to the intracranial tumor; FISH studies revealed normal dosages of both 1p and 19q. These findings suggest that a minor clone in the primary brain tumor did not have LOH 1p and/or 19q and that this clone metastasized to the bone marrow.

Improving alloreactive CTL immunotherapy for malignant gliomas using a simulation model of their interactive dynamics.

Glioblastoma (GBM), a highly aggressive (WHO grade IV) primary brain tumor, is refractory to traditional treatments, such as surgery, radiation or chemotherapy. This study aims at aiding in the design of more efficacious GBM therapies. We constructed a mathematical model for glioma and the immune system interactions, that may ensue upon direct intra-tumoral administration of ex vivo activated alloreactive cytotoxic-T-lymphocytes (aCTL). Our model encompasses considerations of the interactive dynamics of aCTL, tumor cells, major histocompatibility complex (MHC) class I and MHC class II molecules, as well as cytokines, such as TGF-beta and IFN-gamma, which dampen or increase the pro-inflammatory environment, respectively. Computer simulations were used for model verification and for retrieving putative treatment scenarios. The mathematical model successfully retrieved clinical trial results of efficacious aCTL immunotherapy for recurrent anaplastic oligodendroglioma and anaplastic astrocytoma (WHO grade III). It predicted that cellular adoptive immunotherapy failed in GBM because the administered dose was 20-fold lower than required for therapeutic efficacy. Model analysis suggests that GBM may be eradicated by new dose-intensive strategies, e.g., 3 x 10(8) aCTL every 4 days for small tumor burden, or 2 x 10(9) aCTL, infused every 5 days for larger tumor burden. Further analysis pinpoints crucial bio-markers relating to tumor growth rate, tumor size, and tumor sensitivity to the immune system, whose estimation enables regimen personalization. We propose that adoptive cellular immunotherapy was prematurely abandoned. It may prove efficacious for GBM, if dose intensity is augmented, as prescribed by the mathematical model. Re-initiation of clinical trials, using calculated individualized regimens for grade III-IV malignant glioma, is suggested.

Temozolomide treatment for newly diagnosed anaplastic oligodendrogliomas: a clinical efficacy trial

Chemotherapy with alkylating agents is of proven efficacy in recurrent anaplastic oligodendroglioma (AO) with reported response rates ranging between 50% and 70%. The response of newly diagnosed AO to initial treatment with temozolomide (TMZ) has not yet been reported. This study evaluated the response and time to tumor progression of newly diagnosed AO initially treated with TMZ. Twenty patients with a median age of 47 (range: 26-65) received a median of 14 (range: 3-24) cycles of TMZ as their first modality of therapy following diagnosis of AO. Treatment was given every 28 days for 5 days at a starting dose of 200 mg/m2/d and was continued for 24 cycles unless toxicity or tumor progression required withdrawal of TMZ. MRI evaluations were repeated every 8 weeks and scales of Karnofsky performance status (KPS) and of neurological function were used to assess clinical response. Clinical improvement was observed in 60% of the patients with statistically significant gain measured by KPS and the neurologic function scales. The objective response rate was 75%, and median time to tumor progression was 24 months. Maximal objective response was reached within a median of 6 months (range: 3-12). Tumors with 1p loss had longer progression free survival compared to tumors without deletions (PFS at 24 months: 1p LOH = 100%, 1p intact = 20%; P = 0.057). TMZ was well tolerated with only two events of grade 3/4 hematological toxicity. Newly diagnosed AO demonstrates a high rate of response to initial therapy with TMZ, similar to the response reported for PCV combination therapy. Further studies are needed to determine the optimal duration of treatment and whether radiotherapy should immediately follow chemotherapy.

Multicentre phase II study of imatinib mesylate in patients with recurrent anaplastic oligodendroglioma (AOD)/mixed oligoastrocytoma (MOA) and anaplastic astrocytoma (AA)/low grade astrocytoma (LGA): An EORTC New Drug Development Group (NDDG) and Brain Tumor Group (BTG) study

1517 Background: Autocrine activation of PDGFα&β receptors yields strong mitogenic effects and activates tumor angiogenesis in malignant gliomas. Preclinical data showed tumor growth inhibition of ...

Temozolomide chemotherapy in recurrent oligodendroglioma.

The authors determined the tolerance, response rate, and duration of recurrent anaplastic oligodendroglioma in 30 patients to temozolomide given orally at 150 to 200 mg/m2 on days 1 through 5 in cycles of 28 days. Nine patients responded: 7 of 27 patients (26%) treated with temozolomide after prior PCV chemotherapy and 2 of 3 chemotherapy-naive patients (both complete response). Median time to progression in responding patients was 13 months. Temozolomide shows promise and has an acceptable safety profile in recurrent anaplastic oligodendroglial tumors. Patients not responding to PCV may respond to temozolomide.

Identification of two distinct deleted regions on the short arm of chromosome 1 and rare mutation of the CDKN2C gene from 1p32 in oligodendroglial tumors.

Oligodendroglial tumors frequently show allelic losses on the short arm of chromosome 1. To narrow down the putative tumor suppressor gene site(s) on 1p, we have investigated 35 oligodendrogliomas and 10 mixed gliomas (oligoastrocytomas) for loss of heterozygosity (LOH) at 21 highly polymorphic loci on chromosome 1 (19 loci on 1p and 2 loci on 1q). LOH at loci on 1p was found in 30 of the 45 tumors (67%). Two distinct regions of common allelic loss were identified: a distal region between D1S76 and D1S253 at 1p36.3, and a proximal region between D1S482 and D1S2743 at 1p34-p35. We also analyzed our tumor series for genetic alterations and expression of the cyclin dependent kinase inhibitor gene CDKN2C (p18INK4c) from 1p32. We found 1 recurrent anaplastic oligodendroglioma that carried a somatic CDKN2C mutation at codon 113 (GAA ==> TAA: Glu ==> Stop). The remaining 44 tumors of our series showed neither coding sequence mutations nor homozygous deletions of CDKN2C. Investigation of 35 tumors by differential reverse transcription-PCR revealed expression of CDKN2C transcripts in all instances. Our data thus provide evidence for more than a single oligodendroglioma-associated tumor suppressor gene on 1p and implicate CDKN2C as a candidate tumor suppressor gene altered in a low fraction of oligodendroglial tumors.

The treatment of anaplastic oligodendrogliomas and mixed gliomas.

We evaluated the treatment outcome of 17 patients with anaplastic oligodendroglioma and 17 patients with anaplastic mixed oligodendroglioma-astrocytoma. In the anaplastic oligodendroglioma group, eight patients were treated at the time of the initial admission with radiotherapy and adjuvant chemotherapy, and nine patients were treated at the time of recurrence with salvage chemotherapy. Three patients for whom adjuvant chemotherapy was not successful were also treated with chemotherapy at the time of recurrence. In the initial group, one patient had complete response, three had partial responses, and 4 had stable disease (response and stable disease, 100%), but all except one progressed within 10 months. Of the 12 patients who received chemotherapy during recurrence, there was 1 complete response, 2 partial responses, and 6 stable disease (response and stable disease, 75%), with long response duration and long survival (15-132+ mo). In the anaplastic mixed oligodendroglioma-astrocytoma group, 12 patients were treated at the time of the initial admission and 6 patients treated at the time of recurrence. The initial treatment resulted in two complete responses, three partial responses, and seven stable disease (response and stable disease, 100%), with most responses lasting longer than 12 months. The treatment of the patients with recurrent disease resulted in one partial response and five stable disease (response and stable disease, 100%), with a median time to progression of 6 months. These results suggest that aggressive treatment is beneficial for recurrent anaplastic oligodendrogliomas and mixed gliomas as well as initial mixed gliomas but may offer only minimal advantage over conventional radiotherapy for the initial treatment of anaplastic oligodendrogliomas.

Successful chemotherapy for newly diagnosed aggressive oligodendroglioma

We treated 3 patients with newly diagnosed aggressive oligodendroglioma with chemotherapy prior to radiotherapy and observed responses. All had residual or progressive tumor following initial surgery. We used a combination called PCV-3 because recurrent anaplastic oligodendroglioma responds predictably to this regimen. Chemotherapy for response induction followed by radiotherapy for consolidation is feasible and effective initial treatment for this tumor.

Differential effects of isoflurane on SEP recorded over parietal and frontal scalp.

We evaluated the effects of different concentrations of isoflurane on short-latency somatosensory evoked potentials recorded over the parietal and frontal scalp in 14 patients during general anesthesia at stable end-tidal concentrations between 0% and 2.5%. At concentrations between 0% and 1%, there was a marked discrepancy between the amplitude of the parietal N20, which remained stable, and the striking increase of the frontal P22. At concentrations above 1.5%, the parietal N20 disappeared in 6 patients whereas the P22 was clearly identified in 12. The central conduction time increased significantly whereas the spinal conduction was not delayed by increasing levels of isoflurane. These results show that isoflurane anesthesia is a useful pharmacologic model to demonstrate the independence of the N20 recorded over the parietal scalp and the P22 recorded over the frontal scalp.