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Biomedical subjects

Mark Rosenblum

Publications and source records attributed to Mark Rosenblum.

13 recordsLinked to original sources
PubMed2008

Brainstem primitive neuroectodermal tumors (bstPNET): results of treatment with intensive induction chemotherapy followed by consolidative chemotherapy with autologous hematopoietic cell rescue.

We have evaluated the response rate and survival utilizing intensified chemotherapy followed by myeloablative chemotherapy with autologous hematopoietic cell rescue (AuHCR) and adjuvant radiation therapy in six young children with newly diagnosed brainstem primitive neuroectodermal tumors (bstPNET). Following maximum surgical resection of the tumor, patients received high dose induction chemotherapy including vincristine, cisplatin, cyclophosphamide, and etoposide. Eligible patients received a single cycle of myeloablative chemotherapy followed by AuHCR. Two patients survive at least 32 months with stable disease. This approach provides an alternative for young patients with bstPNET who in prior reports have had a uniformly fatal prognosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2007

Partial volume tolerance of the spinal cord and complications of single-dose radiosurgery.

BACKGROUND: Spine radiosurgery causes a rapid dose fall-off within the spinal cord. The tolerance of partial volume of the spinal cord may determine the extent of clinical application. The study analyzed the partial volume tolerance of the human spinal cord to single fraction radiosurgery. METHODS: A total of 230 lesions with spine metastases in 177 patients were treated with radiosurgery with single fraction of 8 to 18 Gy, prescribed to the 90% isodose line that encompassed the target volume. Spinal cord volume was defined as 6 mm above and below the radiosurgery target volume. Spinal cord dose was calculated from the radiation dose/spinal cord volume histogram and correlated with clinical/neurological status and radiographic studies. Median follow-up was 6.4 months (range, 0.5-49 months). The 1-year survival rate was 49%. RESULTS: The average spinal cord volume defined at the treated spinal segment was 5.9 +/- 2.2 mL. The average dose to the 10% spinal cord volume was 9.8 +/- 1.5 Gy, calculated from the dose-volume histogram in the group of 18 Gy prescribed dose. The spinal cord volume that received higher than 80% of the prescribed dose was 0.07 +/- 0.10 mL, which represented 1.3 +/- 1.8% of the cord volume. Among the 86 patients who survived longer than 1 year there was 1 case of radiation-induced cord injury after 13 months of radiosurgery. There were no other cases of spinal cord sequelae. CONCLUSIONS: Whereas the maximum spinal cord tolerance to single-dose radiation is not known, partial volume tolerance of the human spinal cord is at least 10 Gy to 10% of the spinal cord volume defined as 6 mm above and below the radiosurgery target.

Adolescent↗
PubMed2006

High-resolution global genomic survey of 178 gliomas reveals novel regions of copy number alteration and allelic imbalances.

Primary brain tumors are the fourth leading cause of cancer mortality in adults under the age of 54 years and the leading cause of cancer mortality in children in the United States. Therapy for the most common type of primary brain tumors, gliomas, remains suboptimal. The development of new and more effective treatments will likely require a better understanding of the biology of these tumors. Here, we show that use of the high-density 100K single-nucleotide polymorphism arrays in a large number of primary tumor samples allows for a much higher resolution survey of the glioma genome than has been previously reported in any tumor type. We not only confirmed alterations in genomic areas previously reported to be affected in gliomas, but we also refined the location of those sites and uncovered multiple, previously unknown regions that are affected by copy number alterations (amplifications, homozygous and heterozygous deletions) as well as allelic imbalances (loss of heterozygosity/gene conversions). The wealth of genomic data produced may allow for the development of a more rational molecular classification of gliomas and serve as an important starting point in the search for new molecular therapeutic targets.

Alleles↗
PubMed2005

Direct infiltration of brainstem glioma along the cranial nerves.

The authors describe a case of a low-grade brainstem glioma extending along the cranial nerves without any evidence of leptomeningeal spread. The tumor extended directly along the VII-VIIIth cranial nerve complex and also along the trigeminal nerve, which is quite an unusual characteristic of the glial tumors.

Adult↗
PubMed2004

The use of trastuzumab in the treatment of hormone refractory prostate cancer; phase II trial.

PURPOSE: To investigate the efficacy and toxicity of the antibody to the HER-2/neu receptor (trastuzumab, Herceptin) in the treatment of advanced hormone-refractory prostate cancer (HRPC). MATERIALS AND METHODS: Eighteen patients with HRPC were recruited for this phase II trial in which they received trastuzumab for 12 weeks or until disease progression or unacceptable toxicity was documented. HER-2 receptor overexpression was evaluated using immunohistochemistry (IHC) and dual-color fluorescence in-situ hybridization (FISH) assays. RESULTS: Trastuzumab as a single agent demonstrated little efficacy in treating HRPC. Two patients demonstrated stable disease based on a decrease in PSA level to less than 50% of baseline. No patient demonstrated a regression of radiographic bony or soft tissue metastatic disease. The medication was well tolerated in 16 patients (89%), and 2 patients (11%) had to be hospitalized for cardiac complications. CONCLUSIONS: Trastuzumab (Herceptin) as a single agent demonstrated poor efficacy in treating HRPC. Based on promising results in treating breast cancer with regimens using Herceptin and cytotoxic agents, a similar combination approach might demonstrate better efficacy in treating HRPC.

Antibodies, Monoclonal↗
PubMed2004

A phase I open-label, dose-escalation, multi-institutional trial of injection with an E1B-Attenuated adenovirus, ONYX-015, into the peritumoral region of recurrent malignant gliomas, in the adjuvant setting.

ONYX-015 is an oncolytic virus untested as a treatment for malignant glioma. The NABTT CNS Consortium conducted a dose-escalation trial of intracerebral injections of ONYX-015. Cohorts of six patients at each dose level received doses of vector from 10(7) plaque-forming units (pfu) to 10(10) pfu into a total of 10 sites within the resected glioma cavity. Adverse events were identified on physical exams and testing of hematologic, renal, and liver functions. Efficacy data were obtained from serial MRI scans. None of the 24 patients experienced serious adverse events related to ONYX-015. The maximum tolerated dose was not reached at 10(10) pfu. The median time to progression after treatment with ONYX-015 was 46 days (range 13 to 452 + days). The median survival time was 6.2 months (range 1.3 to 28.0 + months). One patient has not progressed and 1 patient showed regression of interval-increased enhancement. With more than 19 months of follow-up, 1/6 recipients at a dose of 10(9) and 2/6 at a dose of 10(10) pfu remain alive. In 2 patients who underwent a second resection 3 months after ONYX-015 injection, a lymphocytic and plasmacytoid cell infiltrate was observed. Injection of ONYX-015 into glioma cavities is well tolerated at doses up to 10(10) pfu.

Adenoviridae↗
PubMed2004

Associations among magnetic resonance spectroscopy, apparent diffusion coefficients, and image-guided histopathology with special attention to radiation necrosis.

OBJECTIVE: In patients with malignant glioma previously treated with surgery, radiation, and chemotherapy, clinical and radiographic signs of recurrent disease often require differentiation between radiation necrosis and recurrent tumor. Published work suggests that although magnetic resonance spectroscopy (MRS) can reliably differentiate pure tumor, pure necrosis, and spectroscopically normal tissues, it may not be particularly helpful because most patients have mixed histological findings comprised of necrosis and tumor. To improve our clinical ability to discriminate among these histological entities, we have analyzed MRS in conjunction with apparent diffusion coefficient (ADC) sequences derived from magnetic resonance imaging. METHODS: In 18 patients, spectroscopic and diffusion-weighted images were obtained before surgery for suspected recurrent neoplastic disease. Spectral data for pure tumor, pure necrosis, and mixed tumor and necrosis were derived from 65 spectroscopic observations in patients with previously treated gliomas (n = 16) and metastatic tumors (n = 2). Spectral data for choline (Cho), N-acetylaspartate (NAA), creatine (Cr), and lipid-lactate were analyzed separately and in conjunction with ADCs in all patients (15 observations of pure tumor, 33 observations of pure necrosis, and 13 observations of mixed tumor and necrosis). Histological specimens were obtained stereotactically at the time of surgery (<48 h after image acquisition) for recurrent disease and digitally co-registered with MRS data. RESULTS: ADC values for pure tumor, pure necrosis, and mixed tumor and necrosis were 1.30, 1.60, and 1.42, respectively. Cho/NAA less than 0.20, NAA/normal Cr greater than 1.56, and NAA/Cho greater than 1.32 increase the odds that a tissue biopsy will be pure necrosis versus mixed tumor and necrosis. Although various values of all MRS ratios analyzed may provide positive correlations for histopathological differentiation of tissue between that of pure tumor and that of pure necrosis, the addition of ADC values to only NAA/Cho and NAA/normal Cr increases the odds of correct differentiation between pure tumor and pure necrosis. The addition of ADC values does not provide additional information beyond that of MRS in distinguishing specimens of mixed tumor and necrosis from either pure tumor or pure necrosis. CONCLUSION: It has been demonstrated that MRS ratio analysis may allow for the clinical discrimination between specimens of pure tumor and pure necrosis, and the addition of ADC data into this analysis may enhance this specific differentiation. However, although a trend toward correlation between ADC values and the various histopathological features was noted, the direct addition of ADC data does not seem to allow further discrimination, beyond that provided by MRS, among specimens of mixed tumor and necrosis and either pure tumor or pure necrosis.

Adult↗
PubMed2004

Patterns of failure after single-dose radiosurgery for spinal metastasis.

OBJECT: Single-dose radiosurgery for solitary spinal metastases can achieve rapid and durable pain control. This study was conducted to determine the patterns of failure after spinal radiosurgery. METHODS: Forty-nine patients with 61 solitary spinal metastases underwent radiosurgery between May 2001 and May 2003. Single-dose radiosurgery (10-16 Gy) was delivered only to the involved spinal segments. The authors undertook a retrospective review of clinical notes, including patient questionnaires and radiological studies (computerized tomography or magnetic resonance imaging), to analyze patterns of failure following radiosurgery with regard to the pain and tumor control. Complete and partial pain relief was achieved in 85% of the lesions treated. Relapse of pain at the treated site was noted in 7%. Radiologically, lesions progressively metastasized to the immediately adjacent spines in 5%. These patients also had progressive primary and/or other systemic metastatic diseases. CONCLUSIONS: Spine-related pain control/reduction was excellent. Tumor recurrence at the treated segment and progression to the immediately adjacent region were rare. The results support the use of spinal radiosurgery as an effective treatment option for solitary spinal metastasis.

Adult↗
PubMed2004

Image-guided procedures for intensity-modulated spinal radiosurgery. Technical note.

Radiosurgery for brain tumors has been well established in the radiation oncology and neurosurgery fields. Radiosurgery of extracranial tumors such as those involving the spine is, however, still in the early stage because of difficulties in patient immobilization and organ motion. The authors describe an image-guided procedure for intensity-modulated spinal radiosurgery that was developed at Henry Ford Hospital.

Algorithms↗
PubMed2003

Image-guided and intensity-modulated radiosurgery for patients with spinal metastasis.

BACKGROUND: Radiosurgery can deliver a single, large radiation dose to a localized tumor using a stereotactic approach and hence, requires accurate and precise delivery of radiation to the target. Of the extracranial organ targets, the spine is considered a suitable site for radiosurgery, because there is minimal or no breathing-related organ movement. The authors studied spinal radiosurgery in patients with spinal metastases to determine its accuracy and precision. METHODS: The spinal radiosurgery program was based on an image-guided and intensity-modulated, shaped-beam radiosurgical unit. It is equipped with micromultileaf collimators for beam shaping and radiation intensity modulation and with a noninvasive, frameless positioning device that uses infrared, passive marker technology together with corroborative image fusion of the digitally reconstructed image from computed tomography (CT) simulation and orthogonal X-ray imagery at the treatment position. These images were compared with the port films that were taken at the time of treatment to determine the accuracy of the isocenter position. Clinical feasibility was tested in 10 patients who had spinal metastasis with or without spinal cord compression. The patients were treated with fractionated external beam radiotherapy followed by single-dose radiosurgery as a boost (6-8 grays) to the most involved portion of the spine or to the site of spinal cord compression. RESULTS: The accuracy for the isocenter was within 1.36 mm +/- 0.11 mm, as measured by image fusion of the digitally reconstructed image from CT simulation and the port film. Clinically, the majority of patients had prompt pain relief within 2-4 weeks of treatment. Complete and partial recovery of motor function also was achieved in patients with spinal cord compression. The radiation dose to the spinal cord was minimal. The maximum dose of radiation to the anterior edge of the spinal cord within a transverse section, on average, was 50% of the prescribed dose. There was no acute radiation toxicity detected clinically during the mean follow-up of 6 months. CONCLUSIONS: Image-guided, shaped-beam spinal radiosurgery is accurate and precise. Rapid clinical improvement of pain and neurologic function also may be achieved. The results indicate the potential of spinal radiosurgery in the treatment of patients with spinal metastasis, especially those with solitary sites of spine involvement, to increase the prospects of long-term palliation.

Feasibility Studies↗
PubMed2002

Radiosurgical treatment for Ewing's sarcoma of the lumbar spine: case report.

STUDY DESIGN: Case report. OBJECTIVES: The objective of this study was to document the long-term follow-up of a single case. SUMMARY OF BACKGROUND DATA: Radiosurgery is potentially a useful therapeutic option for spinal tumors. The authors present the unusual case of a patient with recurrent extraosseous Ewing's sarcoma of the lumbar spine, who experienced excellent clinical, radiographic, and oncologic response without complications after treatment with dedicated Novalis Shaped Beam Radiosurgery (Brain Lab, Inc.). METHODS: Observational. RESULTS: We observed excellent clinical and oncologic control at 1-year posttreatment. CONCLUSION: Radiosurgery may be a valuable treatment option for recurrent spinal tumors.

Bone Neoplasms↗
PubMed2002

A technique of intensity-modulated radiosurgery (IMRS) for spinal tumors.

This study is to demonstrate the feasibility of spinal radiosurgery using an image-guided intensity-modulated radiosurgical (IMRS) procedure. A dedicated Novalis shaped beam surgery unit equipped with a built-in micro-multileaf collimator (mMLC) with a single 6 MV photon beam was used. Each patient was simulated in the supine position using an AcQsim CT simulator with infrared sensitive markers for localization. A variety of different treatment plans were developed, but the most common plan was the use of seven coplanar intensity-modulated beams to minimize radiation to critical organs such as the spinal cord and kidneys. An automatic localization device based on infrared and video cameras was used to guide the initial patient setup. Two keV x-ray imaging systems were used to identify potential deviations from the planned isocenter. A total of 25 patients with spinal tumors have been treated using this procedure with a single prescription dose ranging from 6 to 12 Gy. The final verification images indicated that the average isocenter deviation from the planned isocenter was within 2 mm. The phantom verification of isocenter doses indicated that the average deviation of measured isocenter doses from the planned isocenter doses for all patients treated with intensity-modulated beams was less than 2%. Film dose measurement in a phantom study demonstrated good agreement of above 50% isodose lines between the planned and measured results. Preliminary experience shows that precision delivery of high dose radiation could be administered to the planned target volume while the dose to the critical organs is kept within tolerable limits.

Computer Simulation↗