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P Y Wen

Publications and source records attributed to P Y Wen.

At least 19 recordsLinked to original sources
PubMed2006

Pilot study of the combination of EGFR and mTOR inhibitors in recurrent malignant gliomas.

Malignant gliomas are frequently characterized by amplification of the epidermal growth factor receptor (EGFR) and loss of PTEN tumor suppressor gene. Twenty-eight heavily pretreated patients with recurrent malignant gliomas were administered EGFR inhibitors (gefitinib or erlotinib) in combination with the mTOR (mammalian target of rapamycin) inhibitor sirolimus. The regimens were reasonably well tolerated. Nineteen percent of patients experienced a partial response and 50% had stable disease. Six-month progression-free survival for glioblastoma patients was 25%.

Adult↗
PubMed2001

Gliomas arising in organ transplant recipients: an unrecognized complication of transplantation?

Reported are six cases of glioma, diagnosed in the last 10 years, arising in organ transplant recipients. Five transplant recipients developed glioblastoma, and one developed oligodendroglioma. None had other risk factors for glioma. Gliomas must be considered in the differential diagnosis of space-occupying lesions in transplant recipients. Although these cases may represent coincidence, the putative HIV-glioma association suggests a pathogenetic link to immunosuppression.

Aged↗
PubMed2000

Brain metastases.

Brain metastases are an increasingly common complication in patients with systemic cancer. The optimal treatment for each patient depends on careful evaluation of several factors: the location, size, and number of brain metastases; the patient's age, general condition, and neurologic status; and the extent of systemic cancer to name a few. For patients with a single brain metastasis and limited systemic disease, the standard treatment is surgical resection followed by whole brain radiation therapy. In patients with a small, single metastasis, stereotactic radiosurgery is probably comparable to surgery. Patients with several metastases (up to three) and controlled systemic disease can be treated with whole-brain radiation and stereotactic radiosurgery. Patients with multiple metastases (more than three) are generally treated with whole-brain radiation alone. Radiosurgery is effective in treating patients with a limited number of recurrent brain metastases and stable systemic diseases. Surgery may have a role in patients with a large symptomatic recurrent lesion producing mass effect. Reirradiation and chemotherapy may have a limited role in patients with multiple recurrent metastases.

Adrenal Cortex Hormones↗
PubMed2000

Systemic metastasis in glioblastoma may represent the emergence of neoplastic subclones.

Glioblastomas only rarely metastasize to sites outside the central nervous system, for reasons that are poorly understood. We report the clinicopathological and molecular genetic findings in 6 patients with metastatic glioblastoma. Four patients were under the age of 32 and all but 1 patient died within 2 yr of diagnosis. The number of metastases ranged from 1 to 3. At the time of death, 3 patients had apparent tumor control at their primary site. We evaluated DNA from both primary and metastatic glioblastomas for genetic alterations commonly found in glioblastomas: TP53 mutations, CDKN2A/p16 deletions, EGFR amplification, and allelic loss of chromosomes 1p, 10q and 19q. Four of 6 cases had TP53 mutations and only single cases had EGFR amplification, CDKN2A/p16 deletions, or allelic loss of 1p, 10q and 19q; 2 cases had no detectable genetic alterations. In 2 cases, the primary and metastatic tumors had identical genotypes. Remarkably, however, 2 cases had different TP53 alterations in the primary and metastatic lesions, or among the metastatic tumors, which suggests that some metastatic deposits may represent emergence of subclones that were not necessarily dominant in the primary tumor. The present observations and a review of the recent literature demonstrate that metastatic glioblastomas tend to occur in younger adults who do not follow long clinical courses, and may be characterized by TP53 mutations and differential clonal selection.

Adult↗
PubMed2000

Phase II trial of the antiangiogenic agent thalidomide in patients with recurrent high-grade gliomas.

PURPOSE: Little progress has been made in the treatment of adult high-grade gliomas over the last two decades, thus necessitating a search for novel therapeutic strategies. Malignant gliomas are vascular or angiogenic tumors, which leads to the supposition that angiogenesis inhibition may represent a potentially promising strategy in the treatment of these tumors. We present the results of a phase II trial of thalidomide, a putative inhibitor of angiogenesis, in the treatment of adults with previously irradiated, recurrent high-grade gliomas. PATIENTS AND METHODS: Patients with a histologic diagnosis of anaplastic mixed glioma, anaplastic astrocytoma, or glioblastoma multiforme who had radiographic demonstration of tumor progression after standard external-beam radiotherapy with or without chemotherapy were eligible. Patients were initially treated with thalidomide 800 mg/d with increases in dose by 200 mg/d every 2 weeks until a final daily dose of 1,200 mg was achieved. Patients were evaluated every 8 weeks for response by both clinical and radiographic criteria. RESULTS: A total of 39 patients were accrued, with 36 patients being assessable for both toxicity and response. Thalidomide was well tolerated, with constipation and sedation being the major toxicities. One patient developed a grade 2 peripheral neuropathy after treatment with thalidomide for nearly a year. There were two objective radiographic partial responses (6%), two minor responses (6%), and 12 patients with stable disease (33%). Eight patients were alive more than 1 year after starting thalidomide, although almost all with tumor progression. Changes in serum levels of basic fibroblastic growth factor (bFGF) were correlated with time to tumor progression and overall survival. CONCLUSION: Thalidomide is a generally well-tolerated drug that may have antitumor activity in a minority of patients with recurrent high-grade gliomas. Future studies will better define the usefulness of thalidomide in newly diagnosed patients with malignant gliomas and in combination with radiotherapy and chemotherapy. Additionally, studies will be needed to confirm the potential utility of changes in serum bFGF as a marker of antiangiogenic activity and/or glioma growth.

Adult↗
PubMed1999

Assessing suspected spinal cord compression: a multidisciplinary outcomes analysis of 342 episodes.

The object of this work was to evaluate the assessment and document the outcomes of cancer patients with suspected spinal cord compression (SCC). In a retrospective cohort study of 342 episodes of suspected SCC in cancer patients evaluated by computed tomography (CT) of the spine, a multidisciplinary team of neurologists, radiologists, and oncologists assessed the impact of varying the anatomical criterion for SCC and including new SCC diagnosed shortly after definitive radiographical imaging. We developed a logistic regression model to identify independent clinical predictors of SCC, including the natural history of the underlying cancer as well as neurological and radiological risk factors. Management of suspected SCC infrequently involved neurology consultation (21% of episodes). The frequency of SCC increased more than four-fold when the definition was expanded to include epidural cancer rather than spinal cord displacement only (36% vs. 8%), and 90-day clinical follow-up identified few new lesions not evident on definitive imaging studies. Clinical information about the course of cancer (documentation and duration of metastatic cancer) added independent predictive information to that yielded by neurological assessment and prior imaging studies in a multiple regression model. The a priori predicted risk of SCC, which ranged from 4% to 87% in this study, may vary enough to affect treatment strategies, although our population may have excluded very-low-risk patients. Consistent anatomical definitions of SCC, clinical follow-up of definitive imaging studies and the addition of information on the natural history of cancer to traditional neurological and radiographical evaluation may all improve clinical assessment of suspected SCC in cancer patients.

Adolescent↗
PubMed1999

Allergic skin reactions to anticonvulsant medications in patients receiving cranial radiation therapy.

PURPOSE: Erythema multiforme and Stevens-Johnson syndrome have been associated with anticonvulsant medications (AEDs) in patients with brain tumors receiving cranial irradiation. AEDs are also known to cause mild drug rashes. The incidence of these complications has not been well studied among patients with brain tumors. We reviewed the records of patients with brain tumors treated with cranial radiation and AEDs to assess the frequency of both severe and mild skin reactions. METHODS: Retrospective review of 289 radiotherapy records of consecutively treated patients from 1988 to 1993. RESULTS: Only one of 289 patients developed erythema multiforme. Milder rashes, however, occurred in 18% of exposures to AEDs including 22% of exposures to phenytoin, compared with the expected rate of 5-10%. Most of the mild drug rashes occurred before the initiation of radiotherapy, suggesting that radiation was not the cause of these reactions. CONCLUSIONS: Severe skin rashes are rare among patients with brain tumors receiving radiation therapy and AEDs. There is, however, an increased frequency of mild drug rashes among patients with brain tumors that does not appear related to radiation.

Adolescent↗
PubMed1999

Treatment of patients with primary glioblastoma multiforme with standard postoperative radiotherapy and radiosurgical boost: prognostic factors and long-term outcome.

OBJECT: To assess the value of stereotactic radiosurgery (SRS) as adjunct therapy in patients suffering from glioblastoma multiforme (GBM), the authors analyzed their experience with 78 patients. METHODS: Between June 1988 and January 1995, 78 patients underwent SRS as part of their initial treatment for GBM. All patients had undergone initial surgery or biopsy confirming the diagnosis of GBM and received conventional external beam radiotherapy. Stereotactic radiosurgery was performed using a dedicated 6-MV stereotactic linear accelerator. Thirteen patients were alive at the time of analysis with a median follow-up period of 40.8 months. The median length of actuarial survival for all patients was 19.9 months. Twelve- and 24-month survival rates were 88.5% and 35.9%, respectively. Patient age and Radiation Therapy Oncology Group (RTOG) class were significant prognostic indicators according to univariate analysis (p < 0.05). Twenty-three patients aged younger than 40 years had a median survival time of 48.6 months compared with 55 older patients who had 18.2 months (p < 0.001). Patients in this series fell into RTOG Classes III (27 patients), IV (29 patients), or V (22 patients). Class III patients had a median survival time of 29.5 months following diagnosis; this was significantly longer than median survival times for Classes IV and V, which were 19.2 and 18.2 months, respectively (p = 0.001). Only patient age (< 40 years) was a significant prognostic factor according to multivariate analysis. Acute complications were unusual and limited to exacerbation of existing symptoms. There were no new neuropathies secondary to SRS. Thirty-nine patients (50%) underwent reoperation for symptomatic necrosis or recurrent tumor. The rate of reoperation at 24 months following SRS was 54.8%. CONCLUSIONS: The addition of a radiosurgery boost appears to confer a survival advantage to selected patients.

Actuarial Analysis↗
PubMed1999

Management of brain metastases.

Brain metastases are the most common type of brain tumor in adults and are an increasingly important cause of morbidity and mortality in cancer patients. In recent years, important advances have been made in the diagnosis and management of brain metastases. These advances include the widespread use of magnetic resonance imaging (MRI), enabling small metastases to be detected; the introduction of stereotactic radiosurgery; and the performance of studies that have clarified the role of surgery and postoperative radiation therapy for single brain metastases. As a result, most patients receive effective palliation, and the majority do not die from their brain metastases. However, further studies are needed to define the optimal role of conventional treatments and to develop more effective novel therapies.

Brain Neoplasms↗
PubMed1998

Transgene expression in malignant glioma using a replication-defective adenoviral vector containing the Egr-1 promoter: activation by ionizing radiation or uptake of radioactive iododeoxyuridine.

One approach to improving the specificity of gene therapy involves using radiosensitive promoters to activate gene expression selectively in the radiation field. In this study, we evaluated the ability of irradiation to regulate the transcription of a recombinant replication-defective adenovirus vector, Ad.Egr-1/lacZ, containing the radiation-inducible Egr-1 promoter driving the beta-galactosidase reporter gene in glioma cells. Transcripts of the Egr-1 gene in human and rat glioma cells were induced following irradiation with as little as 2 Gy. This dose was 10-fold less than previously reported, and comparable to doses of irradiation used clinically in standard fractionated radiotherapy for brain tumors. When 9L rat gliosarcoma cells were infected with Ad.Egr-1/lacZ in vitro and exposed to 2 Gy of external beam irradiation, there was a threefold increase in beta-galactosidase expression. Irradiation of intracerebral 9L tumors infected with the Ad.Egr-1/lacZ virus, using either external beam radiotherapy (2 Gy) or the thymidine analog 5-iodo-2'-deoxyuridine radiolabeled with the Auger electron emitter iodine-125 ([125I]IdUrd), also resulted in increased beta-galactosidase activity of the tumor cells. These results indicate that the use of viral vectors containing radiation-inducible promoters represents a novel therapeutic approach that enables gene therapy to be spatially and temporally regulated by ionizing radiation. These findings also support a potential role for radiation-inducible promoters in the treatment of malignant brain tumors.

Animals↗
PubMed1998

Survival results from a phase I study of etanidazole (SR2508) and radiotherapy in patients with malignant glioma.

PURPOSE: To report the survival results from a previous Phase I study of etanidazole (ETA) and radiotherapy in patients with glioblastoma multiforme (GBM n = 50) or anaplastic astrocytoma (AA n = 19) and examine survival according to age, Karnofsky performance status (KPS), and implant status. PATIENTS AND METHODS: In a previous Phase I study, 70 previously untreated patients (median age 49) with malignant gliomas were accrued. One patient was excluded from analysis because pathology was unverifiable. All had KPS > or = 70. Prior to initiation of treatment, patients were stratified according to whether they were candidates for interstitial implantation. The implant patients (IMP n = 14) received accelerated fractionation radiotherapy (XRT) 2 Gy BID (6 hours apart) to 40 Gy in 2 weeks with ETA 2 gm/m2 x 6 doses, a 2 week break, and then interstitial implant for an additional 50 Gy (4-7 days) with a continuous infusion of ETA over 90-96 hours. There were 55 patients treated on two sequentially conducted non-implant arms. These patients started with accelerated fractionation XRT 2 Gy BID (6 hours apart) to 40 Gy in 2 weeks with ETA 2 gm/m2 x 4-5 doses/week. Non-IMP1 arm (n = 41) received a 2-week break before standard fractionated boost XRT of 2 Gy/day for 2 weeks to a total dose of 60 Gy with ETA. Non-IMP2 arm (n = 14) did not have the 2-week break. All patients had plasma pharmacokinetic monitoring of ETA. Subsequent follow-up study provided information regarding long-term survival status of this group of patients. The Phase I toxicity evaluation was conducted according to the RTOG toxicity scale and was found well tolerated in both groups. Overall actuarial survival was plotted for all patients, by histologic group, and by implant status. Subset analyses of GBM patients by age (< or = 49 or > 49 years), KPS (< or = 80 or > 80) and implant versus non-implant were also performed. RESULTS: Median survival of GBM patients was 1.1 years and that of anaplastic astrocytoma patients was 3.1 years (p = 0.0001). In GBM patients, KPS > 80, implanted patients, and age < or = 49 were factors found not to be associated with a statistically improved survival. CONCLUSION: The results of survival in this Phase I etanidazole study of patients with anaplastic astrocytoma are comparable to the results from other studies using bromodeoxyuridine, iododeoxyuridine, or procarbazine, lomustine (CCNU), and vincristine. The use of etanidazole with accelerated radiotherapy does not appear to improve survival in patients with glioblastoma multiforme compared to those treated with conventional therapies.

Adult↗
PubMed1998

Neurologic emergencies in cancer patients.

Neurologic emergencies are common among cancer patients and their incidence is increasing as patients live longer as a result of improved antineoplastic therapy. This article reviews acute neurologic complications in cancer patients. Among those complications reviewed are brain metastases, epidural spinal cord compression, leptomeningeal metastases, cerebrovascular disorders, complications of antineoplastic therapy, and paraneoplastic syndromes.

Antineoplastic Agents↗
PubMed1998

Suspected spinal cord compression in breast cancer patients: a multidisciplinary risk assessment.

Breast cancer is the most common cause of metastatic epidural spinal cord compression (SCC) in women, and this condition results in significant neurologic dysfunction and morbidity. Prior studies of patients with suspected SCC did not employ multivariate analysis techniques, often included persons with a wide variety of malignancies, and generally focused on identifying associated neurologic and radiologic features. We therefore conducted a study examining a more comprehensive set of potential clinical risk factors in breast cancer patients with suspected SCC. We retrospectively analysed 123 episodes of suspected SCC among 93 breast cancer patients evaluated by spine computed tomography (CT) scanning. Multiple logistic regression analysis was employed to identify independent predictors of SCC. Clinically significant metastatic epidural cancer was defined as thecal sac compression (TSC), which occurred in 33 episodes (27%). Four independent predictors of TSC were identified and included oncologic features (known bone metastases > or = 2 years, metastatic disease at initial diagnosis) in addition to neurologic and radiologic features (objective weakness, vertebral compression fracture on spine radiograph). These four predictors stratified episodes into subgroups with widely varying risks of TSC, ranging from 12% (0 risk factors) to 85% (> or = 3 risk factors). These results suggest that the evaluation of breast cancer patients with suspected SCC should include clinical information about their disease course in addition to neurologic examination and prior imaging studies. If confirmed, these predictors may help clinicians assess risk in this patient population.

Adult↗
PubMed1998

Immune parameters affecting adenoviral vector gene therapy in the brain.

Gene therapy utilizing replication deficient adenoviral vectors represents a potentially promising approach to the treatment of brain tumors. Limited duration of systemic transgene expression and inefficient transduction following repeat systemic vector administration secondary to an effective anti-vector immune response limits the potential application of first generation adenoviral vectors. Whether host immune responses will significantly limit the use of these vectors within the immunopriviledged environment of the central nervous system remains to be elucidated. Following a single intravenous injection of a beta-galactosidase expressing adenoviral vector (Ad.CMV-betagal), we found maximal betagal transgene expression in systemic sites (i.e. liver) at day 4, with almost complete disappearance by day 7. In contrast, significant beta-galactosidase activity was seen for greater than 28 days following a single intracerebral inoculum of virus. Rechallenge experiments demonstrated complete protection against repeat systemic vector administration, whereas intracerebral transgene expression was not affected by prior systemic or intracerebral exposure to adenoviruses. These data suggest that systemic anti-adenoviral vector immune responses are attenuated within the central nervous system and may not pose as significant a problem for the treatment of brain tumors as for other systemic indications.

Adenoviruses, Human↗
PubMed1998

5-[125I]iodo-2'-deoxyuridine in the radiotherapy of brain tumors in rats.

UNLABELLED: Glial neoplasms of the human central nervous system have defied treatment, in part because of the limited selectivity of available cytotoxic agents. The thymidine analog 5-iodo-2'-deoxyuridine radiolabeled with the Auger electron emitter 125I (125IUdR) is highly toxic to dividing cells when it is deoxyribonucleic acid incorporated, but it is relatively innocuous when located outside the nucleus. Previous studies have shown that 125IUdR has significant antineoplastic potential against mammalian cells in vitro and direct administration of 125IUdR is effective therapy for ovarian ascites tumors in mice and neoplastic meningitis in rats. Studies using external gamma imaging and autoradiography have also shown that direct intratumoral administration of 123IUdR/125IUdR into intracerebral 9L gliosarcomas in rats results in selective uptake of the radionuclide into tumor cells. Based on these encouraging results, we have evaluated the therapeutic potential of 125IUdR in rats bearing intracerebral 9L gliosarcomas. METHODS: Iodine-125-IUdR was infused intracerebrally over a 2-day period into rats bearing 1-day-old 9L tumors and over a 6-day period into animals with 9-day-old 9L tumors; equimolar concentrations of 127IUdR were infused into control animals. Tumor growth was monitored by contrast-enhanced 1H MRI and animal survival was followed over time. RESULTS: Intracerebral tumors (3-7 mm) were readily detected by MRI. Tumor-bearing rats treated with 127IUdR succumbed within 17-24 days, whereas tumor-bearing animals treated with 125IUdR survived significantly longer, and 10%-20% of the animals were cured of tumors. CONCLUSION: These data substantiate the antineoplastic potential of 5-[125I]iodo-2'-deoxyuridine and indicate that it may be a useful agent for the therapy of solid tumors that are accessible to direct radiopharmaceutical administration.

Animals↗
PubMed1997

Comparison of uptake of 99mTc-alkylisonitriles in the rat 9L gliosarcoma tumor model.

The accumulation of three 99mTc(I) alkyl isonitriles was compared in vitro and in vivo using 9L gliosarcoma cells. In vitro, the uptake of 99mTc-EIBI and 99mTc-EPI was higher than that of 99mTc-MIBI. In vivo, however, there was no difference in the tumor concentration at 15 or 60 min postinjection and only a small difference at 24 h. The differences in uptake observed in vitro are apparently offset in vivo by differences in delivery of the tracers to the tumor.

Animals↗