Carcinoembryonic antigen-expressing oncolytic measles virus derivative in recurrent glioblastoma: a phase 1 trial.

Measles virus (MV) vaccine strains have shown significant preclinical antitumor activity against glioblastoma (GBM), the most lethal glioma histology. In this first in human trial (NCT00390299), a carcinoembryonic antigen-expressing oncolytic measles virus derivative (MV-CEA), was administered in recurrent GBM patients either at the resection cavity (Group A), or, intratumorally on day 1, followed by a second dose administered in the resection cavity after tumor resection on day 5 (Group B). A total of 22 patients received study treatment, 9 in Group A and 13 in Group B. Primary endpoint was safety and toxicity: treatment was well tolerated with no dose-limiting toxicity being observed up to the maximum feasible dose (2×107 TCID50). Median OS, a secondary endpoint, was 11.6 mo and one year survival was 45.5% comparing favorably with contemporary controls. Other secondary endpoints included assessment of viremia, MV replication and shedding, humoral and cellular immune response to the injected virus. A 22 interferon stimulated gene (ISG) diagonal linear discriminate analysis (DLDA) classification algorithm in a post-hoc analysis was found to be inversely (R = -0.6, p = 0.04) correlated with viral replication and tumor microenvironment remodeling including proinflammatory changes and CD8 + T cell infiltration in post treatment samples. This data supports that oncolytic MV derivatives warrant further clinical investigation and that an ISG-based DLDA algorithm can provide the basis for treatment personalization.

Hematologic Emergencies in the Postoperative Neurointensive Care Unit Setting: Illustrative Case Series and Differential Diagnosis.

OBJECTIVES: Investigating the development of acute thrombocytopenia, differential etiologies, and potentially the rare manifestation of disseminated intravascular coagulation after brain tumor resection of primary and secondary malignancies. MATERIALS AND METHODS: We performed a retrospective review of a case series of post-operative neurosurgical patients which developed thrombocytopenia. We applied National Library of Medicine search engine methodology using the terms disseminated intravascular coagulation and brain tumors. RESULTS: We report clinical, radiographic, and laboratory data of four Neurointensive care unit patients that developed thrombocytopenia, three with disseminated intravascular coagulation after craniotomy, and one with heparin-induced thrombocytopenia masquerading as low grade disseminated intravascular coagulation. All four patients presented with cranial lesions and underwent neurosurgical resection. Underlying disorders included: high grade glioma, stage IV lung cancer with metastases, and meningioma. One patient survived and was able to recover after several days of hospitalization, while another patient was discharged to hospice. Search results illustrated that disseminated intravascular coagulation in the presence of glioblastoma multiforme is rare (only four patients) and may be due to a release of coagulation factors like tissue plasminogen activator, treated with antifibrinolytic agents. Searching the terms disseminated intravascular coagulation and brain tumors in the National Library of Medicine search engine yielded 116 results; eight were relevant to our study. CONCLUSIONS: Correlation of thrombocytopenia after neurosurgery for glioblastoma multiforme and disseminated intravascular coagulation is rare. It is extremely challenging to manage these patients with concomitant deep vein thrombosis/pulmonary embolism and intracranial bleeding. Heparin-induced thrombocytopenia is common yet possesses a different hematological coagulation profile and has more pharmacologic options. Neurointensive care unit teams should recognize intraoperative and post-operative disseminated intravascular coagulation cases, and heparin-induced thrombocytopenia in the differential of post-operative thrombocytopenia with specific pharmacologic interventions.

Neurological Complications Associated With Anti-Programmed Death 1 (PD-1) Antibodies.

Importance: Neurological complications are an increasingly recognized consequence of the use of anti-programmed death 1 (PD-1) antibodies in the treatment of solid-organ tumors, with an estimated frequency of 4.2%. To date, the clinical spectrum and optimum treatment approach are not established. Objective: To investigate the frequency, clinical spectrum, and optimum treatment approach to neurological complications associated with anti-PD-1 therapy. Design, Setting, and Participants: This single-center, retrospective cohort study was conducted from either September or December 2014 (the approval dates of the study drugs by the US Food and Drug Administration) to May 19, 2016. All patients receiving anti-PD-1 monoclonal antibodies were identified using the Mayo Cancer Pharmacy Database. Patients with development of neurological symptoms within 12 months of anti-PD-1 therapy were included. Patients with neurological complications directly attributable to metastatic disease or other concurrent cancer-related treatments were excluded. Main Outcomes and Measures: Clinical and pathological characteristics, time to development of neurological symptoms, and modified Rankin Scale (mRS) score. Results: Among 347 patients treated with anti-PD1 monoclonal antibodies (pembrolizumab or nivolumab), 10 (2.9%) developed subacute onset of neurological complications. Seven patients were receiving pembrolizumab, and 3 patients were receiving nivolumab. The patients included 8 men and 2 women. Their median age was 71 years (age range, 31-78 years). Neurological complications occurred after a median of 5.5 (range, 1-20) cycles of anti-PD-1 inhibitors. Complications included myopathy (n = 2), varied neuropathies (n = 4), cerebellar ataxia (n = 1), autoimmune retinopathy (n = 1), bilateral internuclear ophthalmoplegia (n = 1), and headache (n = 1). Peripheral neuropathies included axonal and demyelinating polyradiculoneuropathies (n = 2), length-dependent neuropathies (n = 1), and asymmetric vasculitic neuropathy (n = 1). The time to maximum symptom severity varied from 1 day to more than 3 months. The median mRS score was 2.5 (range, 1-5), indicating mild to moderate disability. Five patients experienced other systemic immune-mediated complications, including hypothyroidism (n = 3), colitis (n = 2), and hepatitis (n = 1). Treatment with anti-PD-1 antibodies was discontinued in 7 patients. Treatment included corticosteroids (n = 7), intravenous immunoglobulin (n = 3), and plasma exchange (n = 1). Nine patients improved, with a median mRS score of 2 (range, 0-6). One patient with severe necrotizing myopathy died. Conclusions and Relevance: Neurological adverse events associated with anti-PD-1 therapy have a diverse phenotype, with more frequent neuromuscular complications. Although rare, they will likely be encountered with increasing frequency as anti-PD-1 therapy expands to other cancers. The time of onset is unpredictable, and evolution may be rapid and life-threatening. Prompt recognition and discontinuation of anti-PD-1 therapy is recommended. In some cases, immune rescue treatment may be required.

Orthostatic myoclonus after brain tumor radiation: Insights from two lesional cases.

INTRODUCTION: Orthostatic myoclonus (OM) is a recognized syndrome of gait unsteadiness accompanied by lower limb myoclonus provoked by the assumption of an upright posture. OM typically affects the elderly and is often associated with neurodegenerative disease. We sought to review the clinical and electrophysiologic characteristics of OM due to brain tumor treatment, the first reported lesional cases of this rare disorder. METHODS: The database of the Mayo Clinic Rochester Movement Disorders Laboratory was searched for all patients diagnosed with OM from January 2007 to December 2016. All available clinical, radiographic, and surface electromyographic data were reviewed, and patients with a history of primary or metastatic brain tumor were analyzed. RESULTS: Two patients with OM and brain tumor were identified; both had undergone tumor resection and targeted brain radiation. Both patients complained of unsteadiness while walking and recurrent falls. Tumor pathology (atypical meningioma, gliosarcoma) was centered in the frontal lobe and extended to the supplementary motor area (SMA), pre-SMA, or prefrontal cortex. Medications did not improve gait. CONCLUSION: Two cases of brain tumor-related OM suggest that degeneration of frontal motor programming circuits underlies the pathophysiology of OM.

Trochlear Schwannoma Presenting with Isolated Trigeminal Neuralgia.

BACKGROUND: Schwannomas arising from the cranial nerves controlling extraocular eye movements are very rare and usually present with some degree of diplopia. CASE PRESENTATION: We report a 50-year-old woman who presented with isolated left-sided trigeminal neuralgia of 6 months' duration. Imaging demonstrated a homogeneously enhancing mass in the left ambient cistern, and the patient was brought to the operating room for resection. A retrosigmoid approach was used, and the mass was directly visualized arising from the trochlear nerve and compressing the dorsal root entry zone of the trigeminal nerve. A gross total resection of the mass was achieved, and microvascular decompression of the trigeminal nerve was performed. The tumor was pathologically confirmed as a schwannoma. At 3-month follow-up, the patient's facial pain was resolved, and her extraocular eye movements were intact. CONCLUSIONS: A total of 32 pathology-confirmed cases of trochlear schwannoma have been previously reported in the English-language literature. Most of these tumors arose from the cisternal segment of the nerve, and most patients presented with frank trochlear nerve palsy on exam. We report the first case of trochlear schwannoma presenting with isolated trigeminal neuralgia.

Predictors of medical school clerkship performance: a multispecialty longitudinal analysis of standardized examination scores and clinical assessments.

BACKGROUND: Evidence suggests that poor performance on standardized tests before and early in medical school is associated with poor performance on standardized tests later in medical school and beyond. This study aimed to explore relationships between standardized examination scores (before and during medical school) with test and clinical performance across all core clinical clerkships. METHODS: We evaluated characteristics of 435 students at Mayo Medical School (MMS) who matriculated 2000-2009 and for whom undergraduate grade point average, medical college aptitude test (MCAT), medical school standardized tests (United States Medical Licensing Examination [USMLE] 1 and 2; National Board of Medical Examiners [NBME] subject examination), and faculty assessments were available. We assessed the correlation between scores and assessments and determined USMLE 1 cutoffs predictive of poor performance (≤10th percentile) on the NBME examinations. We also compared the mean faculty assessment scores of MMS students vs visiting students, and for the NBME, we determined the percentage of MMS students who scored at or below the tenth percentile of first-time national examinees. RESULTS: MCAT scores correlated robustly with USMLE 1 and 2, and USMLE 1 and 2 independently predicted NBME scores in all clerkships. USMLE 1 cutoffs corresponding to poor NBME performance ranged from 220 to 223. USMLE 1 scores were similar among MMS and visiting students. For most academic years and clerkships, NBME scores were similar for MMS students vs all first-time examinees. CONCLUSIONS: MCAT, USMLE 1 and 2, and subsequent clinical performance parameters were correlated with NBME scores across all core clerkships. Even more interestingly, faculty assessments correlated with NBME scores, affirming patient care as examination preparation. USMLE 1 scores identified students at risk of poor performance on NBME subject examinations, facilitating and supporting implementation of remediation before the clinical years. MMS students were representative of medical students across the nation.

Seizures in patients with primary brain tumors: what is their psychosocial impact?

Seizures occur in most patients with primary malignant tumors and are associated with poor quality of life. To our knowledge, no previous studies have sought descriptions of quality of life in patients' own words. Patients with a history of a malignant primary brain tumor and seizures participated in semi-structured interviews, which were analyzed with qualitative methodology. Twenty-seven patients participated, most with high grade brain tumors. Most were receiving anti-seizure medication. Three distinct themes emerged: (1) the first seizure as a sentinel event, as manifested in part by how patients described their first seizure in remarkable detail ("I clearly remember the date…"); (2) seizures as inextricably tied to the brain tumor itself; for example, one patient explained how he "always wondered what was happening with my brain tumor" with each seizure; and (3) adaptation and acceptance-or lack therefore-to seizures. With respect to this third theme, patients conveyed frustration from an inability to work, to drive, and to take care of their children ("It's like you are 15 all over again.") Others described frustration with taking antiseizure medications ("I felt like an 80 year old, now taking her pills every day"). However, some patients had adapted or resigned themselves ("…so much of life is out of control-you just gotta take what you get."). These findings have future research implications but should also serve to make healthcare providers more aware of the heavy emotional burden that seizures thrust upon brain tumor patients.

Mortality and discharge to home after closed brain biopsy: analysis of 3523 cases from the State of California, 2003-2009.

OBJECTIVE: Closed (percutaneous) brain biopsy is an important diagnostic procedure. Information on patient outcomes after biopsy come largely from single-institution series or population-based samples that include patients treated during periods that may not reflect current neurosurgical practice. We sought to determine the rates of in-hospital mortality and discharge to home after closed brain biopsy, and predictors of these outcomes by using a large population-based hospital discharge database with near-complete case ascertainment. METHODS: All closed brain biopsies performed in nonfederal hospitals within the State of California between 2003 and 2009 were identified from a discharge database. Adult patients admitted from home were analyzed; patient-level and hospital-level factors were reviewed for predictors of in-hospital mortality and discharge to home. Logistic regression was used to determine significant predictors of outcome. RESULTS: During the 7-year period, 3523 hospitalizations, including closed brain biopsy, met our inclusion criteria. Overall in-hospital mortality rate was 3.5%, and 67.2% of hospitalizations were followed by discharge directly to home. Scheduled versus unscheduled admission and patient race were predictors of mortality in multivariate analysis. Patient age, hospital biopsy volume, scheduled versus unscheduled admission, and patient race were predictors of discharge to home. CONCLUSIONS: Closed brain biopsy is associated with a greater rate of mortality than is generally recognized. Most patients are able to return to home directly after biopsy, but the rate of discharge to home is lower at hospitals with lower procedure volumes.

Spinal cord disease in patients with cancer.

PURPOSE OF REVIEW: Spinal cord disease is not uncommon in patients with systemic cancer. Most cases are due to epidural tumor metastases with resulting cord compression, although intramedullary spinal cord metastases, radiation myelopathy, and myelopathic complications of chemotherapy must be considered. RECENT FINDINGS: Techniques for surgical decompression of the spinal cord in patients with epidural tumor have improved significantly over the past decade. Several studies have demonstrated improved neurologic outcome in a subset of patients with epidural spinal cord compression treated surgically. SUMMARY: This article outlines the clinical features, radiographic findings, and differential diagnosis of spinal cord disease in patients with cancer and describes the therapeutic approach to these patients. Early identification and treatment of patients with epidural spinal cord compression is critical to maintaining neurologic function and preserving quality of life.

Conditional probability of long-term survival in glioblastoma: a population-based analysis.

BACKGROUND: Advances in glioblastoma care have resulted in a larger proportion of patients surviving beyond 2 years after diagnosis. It is not clear how long-term survivors should be counseled with respect to future prognosis, or what factors influence that prognosis. The conditional probability of survival was evaluated from multiple time points in patients with glioblastoma, using Surveillance, Epidemiology, and End Results (SEER) data. METHODS: Patients diagnosed with glioblastoma from 1998 to 2008 who were treated with radiation-containing regimens were identified within SEER data. Conditional survival probabilities from multiple survival points were calculated. Cox proportional hazards models were constructed to identify predictors of survival from diagnosis and from 1 and 2 years after diagnosis. RESULTS: A total of 10,022 patients with glioblastoma met study inclusion criteria; median survival was 12.61 months. Conditional probability of surviving an additional 2 years ranged from 19.8% at diagnosis to 65.9% at 5 years after diagnosis. The proportion of patients surviving 12 months from time of diagnosis as well as from 6, 12, and 18 months after diagnosis was significantly higher in patients diagnosed in 2005 through 2008 than those diagnosed in 1998 through 2004. Of demographic and treatment-related factors evaluated, only age was associated with hazard of death at diagnosis and 1 and 3 years after diagnosis (P < .0001 at each time point). CONCLUSIONS: Patients surviving past 2 years from diagnosis have a relatively favorable conditional probability of survival into the future compared to newly diagnosed patients. This effect becomes more pronounced with increasing time since diagnosis. These data will assist in the counseling of glioblastoma survivors.

Pilocytic astrocytoma survival in adults: analysis of the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute.

Pilocytic astrocytoma is a WHO grade 1 brain tumor common in children. Relatively little is known about the behavior of pilocytic astrocytomas in adult patients, largely due to the rarity of pilocytic astrocytoma in this population. Some data suggest that adults share the excellent prognosis seen in children, while other reports suggest more aggressive tumor behavior in adult patients. Patients diagnosed with pilocytic astrocytoma between 1973 and 2008 were identified in the National Cancer Institute Surveillance, Epidemiology, and End Results Program database. Age-group specific survival was analyzed with overall, expected, and cancer-specific survival rates. Further survival analyses were performed with the Kaplan-Meier method and Cox Proportional Hazards models. 3,066 patients with pilocytic astrocytoma were identified, including 865 patients aged 20 years and older. Survival rates declined significantly with age, from 96.5% 60-month survival in patients 5-19 years (95% CI 95.3-97.4) to 52.9% 60-month survival in adult patients 60+ years of age (95% CI 38.4-65.5), with a corresponding decrease in relative and cancer-specific survival rates. Gross total resection was a positive prognostic indicator in adults, while patients receiving radiation had shorter survival regardless of extent of resection. Pilocytic astrocytoma is associated with higher mortality in adult patients than in children and teens, and survival decreases with increasing age in adults. The morbidity of pilocytic astrocytoma in adults provides rationale for future trials of adjuvant treatment in high-risk patients.

Risk factors for meningioma in postmenopausal women: results from the Iowa Women's Health Study.

Few risk factors for meningioma, aside from increasing age and female sex, have been identified. We investigated risk factors for meningioma in elderly women, a group with a high incidence. We evaluated associations of demographic, lifestyle, medical history, and anthropometric variables with risk of meningioma in the Iowa Women's Health Study (IWHS), a population-based, prospective cohort study. Risk factors were collected via questionnaires mailed in 1986 and 1992. Incident meningiomas were identified via linkages to Medicare. Cox regression models were used to examine the association of risk factors with meningioma incidence. The mean age at baseline of the 27,791 women in the analysis cohort was 69.3 years (range, 65.0-84.6 years). During 291,021 person-years of follow-up, 125 incident meningiomas were identified. After adjusting for age, lower levels of physical activity (relative risk [RR] , 0.68 for high versus low; P for trend = .039), greater body mass index (BMI; RR, 2.14 for ≥35 versus 19.5-24.9 kg/m(2); P for trend = .0019), greater height (RR, 2.04 for >66 versus ≤62 inches; P for trend = .013), and a history of uterine fibroids (RR, 1.72; 95% confidence interval, 1.19, 2.50) were positively associated with meningioma risk in multivariate analysis. BMI at age 18 and 30 years were not associated with risk. There were no associations with menstrual or reproductive factors or other medical history and lifestyle factors. Physical activity, BMI, height, and history of uterine fibroids were associated with meningioma risk in older women. The positive association with height suggests a role for early life influences on risk, whereas the associations with BMI and physical activity suggest a role for modifiable factors later in life.

Intravascular lymphoma presenting as a longitudinally-extensive myelitis: diagnostic challenges and etiologic clues.

Intravascular lymphoma is a rare disorder that commonly involves the central nervous system. Neurologic involvement may be the presenting and only manifestation. Identifying intravascular lymphoma as the cause of neurologic disease is diagnostically challenging. We report an elderly woman presenting with subacute onset paraparesis due to spinal cord involvement by an intravascular lymphoma. Progressive worsening was associated with extension of a longitudinally-extensive thoracic intramedullary spinal cord lesion. Extensive investigations failed to provide a diagnosis in life and repeated empiric therapeutic trials were unsuccessful. Diagnostic confirmation was postmortem. A longitudinally-extensive spinal cord lesion has a broad differential diagnosis. Intravascular lymphoma should be considered particularly in older individuals. The presence of coexisting hematologic abnormalities should prompt consideration of a bone marrow biopsy. Early diagnosis may direct therapy and lead to a more favorable prognosis.

Phase II NCCTG trial of RT + irinotecan and adjuvant BCNU plus irinotecan for newly diagnosed GBM.

Irinotecan has radiosensitizing effects and shows synergism with nitrosoureas. We performed a Phase II study of RT and irinotecan, followed by BCNU plus irinotecan in newly-diagnosed GBM. The MTD for patients receiving enzyme-inducing anticonvulsants (EIAC) was as follows: irinotecan 400 mg/m(2)/week on Days 1, 8, 22 and 29 during RT, followed by BCNU 100 mg/m(2) Day 1, and irinotecan, 400 mg/m(2) on Days 1, 8, 22 and 29, every 6 weeks. The MTD for non-EIAC patients was as follows: irinotecan 125 mg/m(2)/week on Days 1, 8, 22 and 29 during RT, followed by BCNU 100 mg/m(2) Day 1 and irinotecan 75 mg/m(2) Days 1, 8, 22 and 29, every 6 weeks. Median OS was 10.8 mos. (95% CI: 7.7-14.9); OS at 12 months was 44.6% (95% CI: 33.3-59.8) and PFS 6 was 28.6% (95% CI: 18.9-43.2). Patients went off treatment due to adverse events (7%), refusal (11%), progressive disease (48%), death (9%), and other (9%); 16% completed protocol treatment. Survival was similar in patients with variant (6/7 or 7/7) and wild-type (6/6) UGT1A1*28 genotypic alleles. Grade 3-4 toxicity was more common in non-EIAC patients with variant alleles. SN-38 C(max) and AUC in EIAC patients receiving 400 mg/m(2) irinotecan were 20.9 ng/ml and 212 ng/ml h, and in non-EIAC patients receiving 125 mg/m(2), 15.5 ng/ml and 207 ng/ml h. SN-38 AUC varied by UGT1A1*28 status in non-EIAC patients. This regimen was not significantly active and radiosensitization was not observed. Non-EIAC patients with UGT1A1*28 variant alleles appear particularly sensitive to toxicity from irinotecan.

Occult malignancy in patients with suspected paraneoplastic neurologic syndromes: value of positron emission tomography in diagnosis.

OBJECTIVE: To determine the value of positron emission tomography (PET) in diagnosing occult malignancies in patients with paraneoplastic neurologic syndromes (PNSs) at Mayo Clinic's site in Rochester, MN. PATIENTS AND METHODS: We retrospectively reviewed the medical charts of all 107 patients who underwent PET from January 1, 2000, to July 31, 2006, for the indication of suspected PNS. Three patients did not meet inclusion criteria. PET results were considered positive if increased fludeoxyglucose F 18 uptake indicated malignancy (24 patients). Results from computed tomography were interpreted as positive if any suspect lesion was consistent with malignancy (26 patients). RESULTS: One hundred four patients with PNS were identified from the PET central database; 73 patients had at least 1 positive result for paraneoplastic antibody, and 31 had antibody-negative PNS. Malignancy was confirmed pathologically in 10 patients, of whom 8 had positive PET results. There were 2 cases of confirmed malignancy (fallopian tube adenocarcinoma and spindle cell uterine carcinoma) for which PET results were negative. Two patients with positive PET results declined biopsy. Computed tomography was able to identify 3 of the 10 malignancies detected. Five cases of malignancy were detected only by PET. All patients with confirmed malignancy had positive results for at least 1 paraneoplastic antibody. One patient with positive results for PNS antibody and negative PET results was diagnosed as having small cell carcinoma on a follow-up PET scan after 27 months. PET had sensitivity, specificity, positive predictive value, and negative predictive value of 80%, 67%, 53%, and 88%, respectively. CONCLUSION: PET scan was shown to be more sensitive than computed tomography for detecting occult malignancy (confirmed by positive test results for autoantibody) among patients with suspected PNS. The greatest clinical utility of PET could be in its high negative predictive value.

Phase I/II trial of pyrazoloacridine and carboplatin in patients with recurrent glioma: a North Central Cancer Treatment Group trial.

PURPOSE: Novel therapeutic agents in the treatment of recurrent gliomas are urgently needed. Pyrazoloacridine (PZA), a rationally synthesized acridine derivative, has shown promising antitumor activity against glioma lines in combination with platinum compounds. This phase I/II trial of the PZA/carboplatin combination in recurrent glioma patients consisted of two phase I studies (studies 1 and 2) and a phase II trial (study 3). The objectives of studies 1 and 2 were to (a) assess the safety and toxicity and to establish the phase II dose of the pyrazoloacridine/carboplatin combination for recurrent glioma patients on P450 inducing anticonvulsants, and (b) to confirm the phase II dose for patients not on P450 inducing anticonvulsants. The primary objectives of study 3 were to determine the efficacy of the pyrazoloacridine/carboplatin combination in patients with recurrent gliomas, to further assess the toxicity of the combination, and to evaluate the impact of enzyme-inducing anticonvulsants on the pyrazoloacridine metabolism. EXPERIMENTAL DESIGN: Both carboplatin and pyrazoloacridine were administered intravenously every 28 days. Treatment was continued until unacceptable toxicity, tumor progression or patient withdrawal. RESULTS: 14 patients were treated in the two phase I studies and 32 patients in the phase II trial. The phase II dose of the combination was PZA 400 mg/m(2) and carboplatin AUC of 5 every 28 days. Neutropenia (4 patients) and dyspnea (1 patient) was the dose limiting toxicity in the phase I studies. In the phase II trial, the most frequent toxicity was myelosuppression with grade 3 and 4 hematologic adverse events being observed in 22 and 19% of the patients, respectively. The antitumor activity of this regimen was limited; the response rate in the phase II trial was 0%, (95% CI:0-11%) while 12 of the 32 patients (38%) had stable disease with a median duration of 2 months. The percentage of phase II patients who were progression free at three months was 22% and at six months was 16%. Median survival from study entry was 5.0 months for phase I patients and 5.8 months for phase II patients. Pharmacokinetic analysis performed in 8 phase I patients demonstrated no significant impact of the enzyme-inducing anticonvulsants on the pharmacokinetics of pyrazoloacridine. CONCLUSIONS: The phase II dose of the pyrazoloacridine/carboplatin combination is pyrazoloacridine 400 mg/m(2) in combination with carboplatin AUC of 5. Antitumor activity in patients with recurrent gliomas was limited. Initial disease stabilization occurred in approximately 38% of the patients, with median duration of 2 months. Enzyme-inducing anticonvulsants did not affect the pyrazoloacridine metabolism.

Cognitive function after radiotherapy for supratentorial low-grade glioma: a North Central Cancer Treatment Group prospective study.

PURPOSE: To evaluate the effects of cranial radiotherapy (RT) on cognitive function in patients with supratentorial low-grade glioma. METHODS AND MATERIALS: Twenty adult patients with supratentorial low-grade glioma were treated with 50.4 Gy (10 patients) or 64.8 Gy (10 patients) localized RT. The patients then were evaluated with an extensive battery of psychometric tests at baseline (before RT) and at approximately 18-month intervals for as long as 5 years after completing RT. To allow patients to serve as their own controls, cognitive performance was evaluated as change in scores over time. All patients underwent at least two evaluations. RESULTS: Baseline test scores were below average compared with age-specific norms. At the second evaluation, the groups' mean test scores were higher than their initial performances on all psychometric measures, although the improvement was not statistically significant. No changes in cognitive performance were seen during the evaluation period when test scores were analyzed by age, treatment, tumor location, tumor type, or extent of resection. CONCLUSIONS: Cognitive function was stable after RT in these patients evaluated prospectively during 3 years of follow-up. Slight improvements in some cognitive areas are consistent with practice effects attributable to increased familiarity with test procedures and content.

Choroid plexus papillomas: a single institutional experience.

OBJECTIVE: To determine the long-term outcome of resected choroid plexus papillomas (CPPs). METHODS: Medical records and histologic specimens were reviewed for 41 patients (19 male, 22 female; median age, 36 years; range, 6 months to 74 years) with CPP seen between 1974 and 2000. Tumor locations were as follows: 76%, fourth ventricle; 17%, lateral ventricle, and 7%, third ventricle. Fifty-six percent had a gross total resection (GTR) and 44% had a subtotal resection (STR). Median follow-up was 6.5 years. RESULTS: Five-year local control, distant brain control, and overall survival were 84%, 92%, and 97%, respectively. Comparison of GTR and STR at 5 years showed a significant increase in local control (100% vs. 68%; P = 0.04) but not in overall survival (100% vs. 94%). Even after STR, only 50% of patients required a subsequent resection for recurrence. Addition of radiation therapy to initial STR did not seem to influence outcomes. At first relapse, GTR was accomplished in 1 patient, and only STR was accomplished in the others. Addition of radiation therapy to STR in our study led to disease control in half the patients treated, and STR alone led to disease control in only a quarter of the patients. Second relapses were treated palliatively with radiation therapy. CONCLUSIONS: Surgical resection is the treatment of choice for CPPs. After initial STR, reoperations for recurrence are required only half the time. Therefore, there seems to be no role for radiation therapy after initial STR. For STRs at first relapse, local control outcome is poor.