Biomedical subjects

Mark L Rosenblum

Publications and source records attributed to Mark L Rosenblum.

7 recordsLinked to original sources

PubMed2006

Postoperative radiosurgery for malignant spinal tumors.

OBJECTIVE: Although, as a primary therapy, radiosurgery for spinal tumors is becoming more common in clinical practice and is associated with encouraging clinical results, we wanted to evaluate outcomes after radiosurgery in a series of postoperative patients. METHODS: We examined the medical records of 18 postoperative patients who received radiosurgical treatment to their residual spinal tumors: metastatic carcinoma (10), sarcoma (3), multiple myeloma/plasmacytoma (4), and giant cell tumor (1). Marginal radiosurgical doses ranged from 6 to 16 Gy (mean, 11.4 Gy) prescribed to the 90% isodose line. All regions of the spine received treatment: 2 cervical, 15 thoracic, and 1 lumbosacral. The volume of irradiated spinal elements receiving 30, 50, and 80% of the total dose ranged from 0.51 to 11.05, 0.19 to 6.34, and 0.06 to 1.73 cm, respectively. Treatment sessions (i.e., patient in to patient out of the room) varied between 20 and 40 minutes. Follow-up ranged from 4 to 36 months (median, 7 mo). RESULTS: Even though significant doses of radiation were delivered to all regions of the spinal cord and nerve roots coincidentally involved in the treatments, only one patient in this series developed progressive symptoms possibly attributable to a toxic effect of the radiosurgery. Of those patients initially presenting with neurological deficits, 92% either remained neurologically stable or improved. CONCLUSION: Our observations suggest that radiosurgery as prescribed in this series of postoperative patients with residual spinal tumor is well-tolerated and associated with little to no significant morbidity.

Adult↗

PubMed2004

Modification of radiation injury by ramipril, inhibitor of angiotensin-converting enzyme, on optic neuropathy in the rat.

Inhibitors of angiotensin-converting enzyme (ACE) have been used to reduce radiation-induced normal tissue injury. The present study was carried out to determine whether ramipril, one of the inhibitors of ACE, would ameliorate radiation-induced brain damage, using a well-characterized optic neuropathy model in the rat, one of the most critical and radiosensitive structures in the brain. The brains of adult Fischer rats were irradiated stereotactically with 30 Gy using a single collimated beam. Six months after irradiation and 1.5 mg/kg day(-1) ramipril (started 2 weeks after irradiation), rats were assessed for optic nerve damage functionally, using visual evoked potential, and histologically. Results show that ramipril conferred significant modification of radiation injury, since rats receiving radiation alone showed a threefold lengthening in the mean peak latency in the visual evoked potential, whereas 75% of rats receiving radiation followed by ramipril had evoked potentials that resembled those of normal untreated control rats. The histology of irradiated and ramipril-treated optic nerves appeared nearly normal, while there was significant demyelination in both optic nerves of irradiated rats. The study represents the first demonstration of prophylaxis of radiation injury by a carboxyl-containing ACE inhibitor, providing a pharmacological strategy designed to reduce radiation-induced normal tissue damage.

Administration, Oral↗

PubMed2003

Meningiomas: analysis of loss of heterozygosity on chromosome 10 in tumor progression and the delineation of four regions of chromosomal deletion in common with other cancers.

PURPOSE: Loss of heterozygosity (LOH) of alleles on chromosome 10 has been reported in many cancers, leading to the identification of tumor suppressor genes on this chromosome. Several reports implicate LOH of chromosome 10 alleles in meningioma progression, but the frequency and complexity of the loss have not been well characterized. Furthermore, the location and identity of the putative tumor suppressor genes on this chromosome that contribute to meningioma progression are unknown because the currently characterized tumor suppressor genes do not appear to be involved. Therefore, this study was undertaken to (a) assess the frequency and complexity of LOH in meningioma progression, (b) map the LOH patterns of individual meningiomas to define the smallest regions of shared chromosomal deletion, and (c) compare the identified regions with chromosome 10 deletions in other cancers, and thereby initiate the localization of the putative tumor suppressor genes. EXPERIMENTAL DESIGN: We examined 11 microsatellite dinucleotide repeat loci in 208 meningiomas of all grades using laser capture microdissection and fluorescence-based detection of PCR products. RESULTS: For all markers examined, the incidence of LOH was much higher in all grades than that previously reported, with incidence and complexity of LOH increasing with tumor grade. LOH mapping identified four regions of chromosomal deletion: 10pter-D10S89, D10S109-D10S215, D10S187-D10S209, and D10S169-10qter. These deletions on chromosome 10 are shared with other cancer types. CONCLUSIONS: These results delineate chromosomal locations of putative tumor suppressor genes on chromosome 10 that likely play an early role in meningioma tumorigenesis as well as tumor progression.

Brain↗

PubMed2003

Meningiomas: loss of heterozygosity on chromosome 10 and marker-specific correlations with grade, recurrence, and survival.

PURPOSE: In a study of 208 meningiomas, we found a high incidence of loss of heterozygosity (LOH) on chromosome 10 in benign (73.4%), atypical (80.0%), and malignant (86.7%) tumors. A large percentage of the benign and atypical tumors and an increasing percentage of malignant tumors had LOH on multiple loci (43.9%, 45%, and 66.7%, respectively). The high incidence of LOH occurring early in meningioma progression suggests that LOH at individual alleles may serve as a marker of clinically relevant alterations useful for patient diagnosis, the subclassification of tumors, and/or the treatment of patients. EXPERIMENTAL DESIGN: To test this, we examined 208 sporadic and recurrent meningiomas of all grades for correlations between LOH at 11 markers on chromosome 10 and tumor location, histology, and grade and patient race, gender, age, recurrence, and survival. RESULTS: Several significant correlations were found. The data indicate that genetic differences occur not only between tumors of different grade, but also between tumors of the same grade, and therefore may be useful to define genetic subsets with clinical implications. LOH at D10S179 (P = 0.001) or D10S169 (P = 0.004) is most likely present in higher-grade meningiomas and, when present in benign tumors, may signify sampling error or a morphologically benign but biologically aggressive tumor. Furthermore, LOH at D10S209 (P = 0.06) and D10S169 (P = 0.01) may predict shorter survival and/or higher rates of recurrence, respectively, in tumors with benign or malignant histology. CONCLUSIONS: We conclude that these chromosome 10 markers deserve further testing as unfavorable prognostic indicators for meningioma patients.

Adult↗

PubMed2003

An inflatable balloon catheter and liquid 125I radiation source (GliaSite Radiation Therapy System) for treatment of recurrent malignant glioma: multicenter safety and feasibility trial.

OBJECT: In this study the authors evaluated the safety and performance of the GliaSite Radiation Therapy System (RTS) in patients with recurrent malignant brain tumors who were undergoing tumor resection. METHODS: The GliaSite is an inflatable balloon catheter that is placed in the resection cavity at the time of tumor debulking. Low-dose-rate radiation is delivered with an aqueous solution of organically bound iodine-125 (lotrex [sodium 3-(125I)-iodo-4-hydroxybenzenesulfonate]), which are temporarily introduced into the balloon portion of the device via a subcutaneous port. Adults with recurrent malignant glioma underwent resection and GliaSite implantation. One to 2 weeks later, the device was filled with Iotrex for 3 to 6 days, following which the device was explanted. Twenty-one patients with recurrent high-grade astrocytomas were enrolled in the study and received radiation therapy. There were two end points: 1) successful implantation and delivery of brachytherapy; and 2) safety of the device. Implantation of the device, delivery of radiation, and the explantation procedure were well tolerated. At least 40 to 60 Gy was delivered to all tissues within the target volume. There were no serious adverse device-related events during brachytherapy. One patient had a pseudomeningocele, one patient had a wound infection, and three patients had meningitis (one bacterial, one chemical, and one aseptic). No symptomatic radiation necrosis was identified during 21.8 patient-years of follow up. The median survival of previously treated patients was 12.7 months (95% confidence interval 6.9-15.3 months). CONCLUSIONS: The GliaSite RTS performs safely and efficiently. It delivers a readily quantifiable dose of radiation to tissue at the highest risk for tumor recurrence.

Adult↗

PubMed2002

Correlations between magnetic resonance spectroscopy and image-guided histopathology, with special attention to radiation necrosis.

OBJECTIVE: The differentiation of tumor recurrence from radiation necrosis in patients with malignant gliomas who have been treated previously remains a challenge. Magnetic resonance imaging, single-photon emission computed tomography, and positron emission tomography cannot provide definitive histopathological insight. Multivoxel proton magnetic resonance spectroscopic imaging ((1)H MRSI) may be reliable in guiding the clinical management of untreated patients; however, its value in managing previously treated patients remains unclear. METHODS: Twenty-seven patients who had been treated previously with surgery, radiotherapy, and chemotherapy and reoperated for clinical and/or radiographic signs that caused suspicion for recurrent disease were studied. Tissues were categorized into four groups: spectroscopically normal, pure tumor, mixed tumor and radiation necrosis, and pure radiation necrosis. Spectral data for choline (Cho), lipid-lactate (Lip-Lac), N-acetylaspartate, and creatine (Cr) were analyzed as Cho/normal Cr (nCr), Lip-Lac/Cho, Lip-Lac/nCr, N-acetylaspartate/Cho, N-acetylaspartate/nCr, and Cho/normal Cho (nCho). Stereotactic biopsies were obtained within 48 hours of (1)H MRSI and were directly correlated digitally with (1)H MRSI data. Logistic regression analysis was performed on the basis of data obtained from 99 (1)H MRSI observations to determine whether the (1)H MRSI ratios varied according to tissue category. RESULTS: (1)H MRSI ratios were found to distinguish pure tumor from pure necrosis. The odds of a biopsy's being pure tumor and having either a Cho/nCr value greater than 1.79 or a Lip-Lac/Cho value less than 0.75 are seven times the odds of that biopsy's being pure necrosis (odds ratio, 7.00; P = 0.0136). The odds of a biopsy's being pure necrosis and having either a Cho/nCr value less than 0.89 or a Cho/nCho value less than 0.66 are six times the odds of that biopsy's being pure tumor (odds ratio, 5.71; P = 0.0329). The odds of a biopsy's being pure necrosis and having either a Lip-Lac/Cho value greater than 1.36 or a Lip-Lac/nCr value greater than 2.84 are more than five times the odds of the biopsy's being pure tumor (odds ratio, 5.25; P = 0.0322). In addition, although only marginally significant, Lip-Lac/Cho and Lip-Lac/nCr ratios distinguish pure tumor from pure necrosis. No values suggested that mixed specimens could be distinguished in a statistically significant way from either pure tumor or pure necrosis. CONCLUSION: The data that we gathered suggest that metabolite ratios derived on the basis of (1)H MRSI spectral patterns do allow reliable differential diagnostic statements to be made when the tissues are composed of either pure tumor or pure necrosis, but the spectral patterns are less definitive when tissues composed of varying degrees of mixed tumor and necrosis are examined.

Adult↗

PubMedDate not supplied

Developing a brain tumor center.

The development of a multidisciplinary brain tumor center requires many steps, from selection of leaders to garnering institutional support, growing the clinical neuro-oncology business, and building multidisciplinary involvement especially with the tumor board. Key clinicians and researchers need to be recruited to develop the academic enterprise, and acquiring external endorsement and philanthropy support can be critical factors in maintaining institutional support and in meeting special needs of the center. The process of managing money, space and support personnel, and the maintenance of the overall program are important as well. Our views on building a brain tumor center reflect our specific situation in developing and growing the Hermelin Brain Tumor Center at Henry Ford Hospital in Detroit and hence might not be precisely applicable to the development of centers elsewhere.

Academic Medical Centers↗