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Biomedical subjects

Eric Lis

Publications and source records attributed to Eric Lis.

At least 19 recordsLinked to original sources

Recurrent ependymoma treated with high-dose tamoxifen in a peripubertal female: Impact on tumor and the pituitary-ovarian axis.

Due to high rates of recurrence, the prognosis of childhood ependymoma remains guarded. Anecdotal evidence suggests that tamoxifen may have a role in the treatment of these tumors. We present a case of a child with recurrent ependymoma treated with tamoxifen who showed tumor regression on two separate occasions. However, treatment with tamoxifen resulted in the development of large ovarian cysts associated with supraphysiological plasma concentrations of estradiol.

Child↗

A phase II trial of thalidomide and cyclophosphamide in patients with recurrent or refractory pediatric malignancies.

BACKGROUND: Previous clinical and pre-clinical research has demonstrated synergy between anti-angiogenic agents and cytotoxic chemotherapy. This trial was undertaken to investigate whether the combination of cyclophosphamide and thalidomide would be active against pediatric tumors. PROCEDURE: Patients with pediatric malignancies who had no remaining conventional therapeutic options were recruited from January 1999 to May 2001. They received thalidomide (6-12 mg/kg po every day; maximum daily dose 800 mg) and cyclophosphamide (1,200 mg/m2 IV every 28 days). RESULTS: Twenty-seven patients were enrolled on the study. Seventeen were male and 10 were female. Median age at the time of registration was 15 years (range 1-54 years). The median number of prior treatment regimens was four. Twenty-one patients were evaluable for response; 1 had a partial response (Hodgkin disease), 1 demonstrated stable disease (neuroendocrine tumor), and 19 had progressive disease. The most common toxicities were hematological (leukocytopenia and neutropenia) and gastrointestinal. One patient experienced a grade 3 rash. Fatigue and daytime somnolence were variable. No peripheral neuropathy was observed. CONCLUSION: The combination of thalidomide and cyclophosphamide as described herein has a modest and tolerable toxicity profile but little evidence of efficacy.

Adolescent↗

A Phase II study of SU5416 in patients with advanced or recurrent head and neck cancers.

BACKGROUND: SU5416 (semaxanib) is a synthetic small molecule inhibitor of the tyrosine kinase domain of vascular endothelial growth factor receptor 2 (VEGFR2). This Phase II study was conducted to determine the safety and efficacy of SU5416 in patients with recurrent or metastatic head and neck cancers. PATIENTS AND METHODS: This was an open label, single arm, Phase 2 study for patients who had received no more than 2 cytotoxic regimens. Thirty-five patients received intravenous SU5416 (145 mg/m(2)) twice per week by intravenous catheter. Radiologic imaging for response assessment was planned at the conclusion of each 8 week cycle. Serum VEGF levels and power Doppler ultrasound tumor imaging were explored as potential surrogate markers for SU5416 activity. RESULTS: Thirty-two patients had received prior radiotherapy, including 18 patients who received prior concurrent chemoradiotherapy. Twelve patients had received prior chemotherapy in the recurrent disease setting. Thirty-one patients were evaluable for response. There was one partial response and one minor response. The median number of 8-week cycles received was 1 (range 1-4). Median overall survival was 6.25 months. The most common > or = grade 3 toxicity was headache (31%). There was one fatal carotid artery hemorrhage. Fatigue, nausea, and vomiting were common grade 1-2 adverse events. Power Doppler ultrasound demonstrated decreased tumor vascularity in 5 of 7 patients. CONCLUSIONS: Treatment with SU5416 in patients with head and neck cancers is feasible, but objective responses are rare. Studies evaluating more potent anti-angiogenic agents in this disease are of interest.

Adult↗

Concurrent cetuximab, cisplatin, and concomitant boost radiotherapy for locoregionally advanced, squamous cell head and neck cancer: a pilot phase II study of a new combined-modality paradigm.

PURPOSE: Cetuximab is a chimeric monoclonal antibody that targets the epidermal growth factor receptor. Cetuximab has activity in squamous cell carcinoma and enhances both chemotherapy and radiotherapy. We conducted a pilot phase II study of a new combined-modality paradigm of targeted therapy (cetuximab) with chemoradiotherapy. PATIENTS AND METHODS: Eligible patients had stage III or IV, M0, squamous cell head and neck cancer. Treatment included concomitant boost radiotherapy (1.8 Gy/d weeks 1 to 6; boost: 1.6 Gy 4 to 6 hours later weeks 5 to 6; 70 Gy total to gross disease), cisplatin (100 mg/m2 intravenously weeks 1 and 4), and cetuximab (400 mg/m2 intravenously week 1, followed by 250 mg/m2 weeks 2 to 10). RESULTS: Twenty-two patients were enrolled (median age, 57 years; range, 41 to 72 years; median Karnofsky status, 90%; range, 70% to 90%; oropharynx primary tumor, 59% of patients; T4, 36%; N2/3, 77%; stage IV disease, 86%). One patient did not receive study treatment because of an ineligible diagnosis. The severity of expected, acute toxicities was typical of concurrent cisplatin and radiotherapy alone. Grade 3 or 4 cetuximab-related toxicities included acne-like rash (10%) and hypersensitivity (5%). However, the study was closed for significant adverse events, including two deaths (one pneumonia and one unknown cause), one myocardial infarction, one bacteremia, and one atrial fibrillation. With a median follow-up of 52 months, the 3-year overall survival rate is 76%, the 3-year progression-free survival rate is 56%, and the 3-year locoregional control rate is 71%. CONCLUSION: This regimen is not currently recommended outside of the clinical trial setting. Further investigation of its safety profile is needed. However, preliminary efficacy is encouraging, and further development of this targeted combined-modality paradigm is warranted.

Adult↗

Intradiploic cerebrospinal fluid fistulas of iatrogenic origin. Report of two cases.

Intradiploic cerebrospinal fluid (CSF) collections represent a rare complication of either head trauma or neurosurgical procedures. Their formation is thought to depend partly on violation of the meninges and the inner cortical bone abutting the neuraxis. The authors present two pediatric cases involving diploic CSF collections following neurosurgical interventions. In the first case, a CSF fistula was found within the occipital bone and the petrous portion of the temporal bone 9 years after a suboccipital craniectomy. The second case features the extremely rare occurrence of a CSF fistula within a thoracic vertebra, 9 years after a laminectomy. Both patients underwent successful surgical procedures for repair of the fistulas.

Adolescent↗

Temozolomide plus thalidomide in patients with brain metastases from melanoma: a phase II study.

BACKGROUND: Temozolomide plus thalidomide is a promising oral combination regimen for the treatment of metastatic melanoma. The current Phase II study examined the efficacy and safety of this combination in chemotherapy-naive patients with brain metastases. METHODS: Patients with histologically confirmed metastatic melanoma and measurable brain metastases received temozolomide (75 mg/m2 per day for 6 weeks with a 2-week break between cycles) plus concomitant thalidomide (200 mg/day escalating to 400 mg/day for patients < 70 years or 100 mg/day escalating to 250 mg/day for patients > or = 70 years). The primary end point was tumor response in the brain assessed every 8 weeks. RESULTS: Twenty-six patients with a median age of 60 years were treated. All patients had progressive brain metastases: 16 were symptomatic and 25 had extensive extracranial metastases. Eight patients had received whole-brain radiotherapy, 4 had received stereotactic radiotherapy, and 8 had received craniotomy with resection of hemorrhagic lesions. Fifteen patients completed > or = 1 cycle (median, 1 cycle; range, 0-4 cycles), and 11 discontinued treatment before completing 1 cycle (7 for intracranial hemorrhage, 2 for pulmonary embolism, 1 for deep vein thrombosis, and 1 for Grade 3 rash). Of 15 patients assessable for response, 3 had a complete or partial response (12% intent to treat) and 7 had minor response or stable disease in the brain. However, 5 of these 10 patients had disease progression at extracranial sites. The median survival period was 5 months for all 26 patients and 6 months for the 15 assessable patients. CONCLUSIONS: Temozolomide plus thalidomide was an active oral regimen for patients with brain metastases from malignant melanoma.

Adult↗

Intensity-modulated radiotherapy for head-and-neck rhabdomyosarcoma.

PURPOSE: To determine the preliminary results of intensity-modulated radiotherapy (IMRT) for head-and-neck rhabdomyosarcoma. METHODS AND MATERIALS: Twenty-eight patients underwent IMRT as a part of multimodality therapy. Twenty-one tumors were parameningeal, three were orbital, and four were in other sites. The median age was 8 years (range, 1-29 years). Most (89%) had Group III disease. Intracranial extension was present in 71% of parameningeal tumors. A 1.5-cm margin was used, and the median dose was 50.4 Gy (range, 30-55.8 Gy). RESULTS: The actuarial 3-year survival rate for patients with parameningeal tumors was 65%. The 3-year actuarial freedom from failure rate was 95% locally, 90% in regional nodes, 88% in the central nervous system, and 80% at distant sites. No failures occurred among patients with orbit tumors; a single central nervous system failure occurred in 1 patient with a lip/cheek tumor. Disease-free survival was significantly worse for patients with alveolar histologic features (p = 0.01). Acute radiation toxicity was similar to that reported by the Intergroup Rhabdomyosarcoma Study Group. Late radiation toxicity was recorded and was mild. CONCLUSION: IMRT with image fusion results in outstanding local control despite the use of a reduced margin. However, survival among patients with alveolar histologic findings or intracranial extension remains unacceptably low.

Adolescent↗

Nonconvulsive status epilepticus in patients with cancer: imaging abnormalities.

BACKGROUND: Convulsive status epilepticus may cause reversible neuroimaging abnormalities. These cortical changes have been reported rarely in association with nonconvulsive status epilepticus. OBJECTIVE: To describe patients with cancer who had reversible magnetic resonance (MR) imaging abnormalities from nonconvulsive status epilepticus and whose altered mental status and MR imaging findings were initially considered to result from a structural lesion related to their underlying tumor. DESIGN: Retrospective study. SETTING: Department of Neurology at Memorial Sloan-Kettering Cancer Center, New York, NY. PATIENTS: Eight patients with a diagnosis of nonconvulsive status epilepticus who underwent MR imaging. RESULTS: Enhancing cortical abnormalities were observed on MR images in 4 (50%) of 8 patients with cancer who had impaired mental status and an electroencephalogram demonstrating seizure activity. Follow-up MR images showed neuroimaging improvement or resolution in all patients. CONCLUSIONS: Cortical enhancement on MR images in patients with cancer who have altered mental status may be due to nonconvulsive status epilepticus and not recurrent or metastatic tumor. If electroencephalography is not immediately available at initial evaluation, a trial of anticonvulsant therapy deserves consideration.

Adult↗

Imaging therapeutic response in human bone marrow using rapid whole-body MRI.

Whole-body imaging of therapeutic response in human bone marrow was achieved without introduced contrast agents using diffusion-weighted echo-planar magnetic resonance imaging of physiologic water. Bone marrow disease was identified relative to the strong overlying signals from water and lipids in other anatomy through selective excitation of the water resonance and generation of image contrast that was dependent upon differential nuclear relaxation times and self-diffusion coefficients. Three-dimensional displays were generated to aid image interpretation. The geometric distortion inherent in echo-planar imaging techniques was minimized through the acquisition of multiple axial slices at up to 12 anatomic stations over the entire body. Examples presented include the evaluation of therapeutic response in bone marrow during cytotoxic therapy for leukemia and metastatic prostate cancer and during cytokine administration for marrow mobilization prior to stem cell harvest.

Bone Marrow↗

Brain metastases in hepatoblastoma.

Brain metastases from hepatoblastomas are rare. We report a 2-year-old male who developed multiple hemorrhagic intracranial metastases. Previous reports indicate that brain metastases are an almost uniformly fatal complication of hepatoblastoma, although one long-term survivor has been described. In a child with known hepatoblastoma, the development of neurologic signs or symptoms should lead to the performance of a brain imaging study to exclude the possibility of intracranial extension of the disease.

Biopsy↗

Single-stage posterolateral transpedicular approach for resection of epidural metastatic spine tumors involving the vertebral body with circumferential reconstruction: results in 140 patients. Invited submission from the Joint Section Meeting on Disorders of the Spine and Peripheral Nerves, March 2004.

OBJECT: Patients with metastatic spine tumors often have multicolumn involvement and high-grade epidural compression, requiring circumferential decompression and instrumentation. Secondary medical and oncological issues add morbidity to combined approaches. The authors present their experience in using the single-stage posterolateral transpedicular approach (PTA) to decompress the spine circumferentially and to place instrumentation. METHODS: From September 1997 to February 2004, 140 patients with spine metastases underwent the PTA. Magnetic resonance imaging revealed high-grade spinal cord compression in 120 patients (86%) and lytic vertebral body destruction in all patients. Preoperatively 84 patients (60%) received radiotherapy directed to the involved level and 42 (30%) underwent tumor embolization. Following circumferential decompression, all patients underwent anterior reconstruction with polymethylmethacrylate and Steinmann pins, and posterior segmental fixation. The median operative time was 5.1 hours, the median blood loss was 1500 ml, and the median hospital stay was 9 days. Ninety-six percent of the patients experienced postoperative pain improvement and improvement in or stabilization of neurological status. In 51 nonambulatory patients with poor Eastern Cooperative Oncology Group grades, 75% regained the ability to walk. One month postoperatively 90% of patients achieved good-to-excellent performance scores. The overall median patient survival time was 7.7 months. Patients with colon and lung carcinomas had significantly shorter survival times. Major operative complications occurred in 20 patients (14.3%). Wound complications occurred in 16 patients (11.4%), but this was not correlated with preoperative radiation treatment. CONCLUSIONS: The PTA allows circumferential epidural tumor decompression and the placement of anterior and posterior spinal column instrumention. Immediate spinal stability is achieved without the use of brace therapy. This technique achieved a high success rate for pain palliation, neurological preservation, and functional improvement, while avoiding the morbidity associated with combined approaches.

Adult↗

Percutaneous CT-guided biopsy of osseous lesion of the spine in patients with known or suspected malignancy.

BACKGROUND AND PURPOSE: CT-guided spinal biopsy (CTGSB) is considered a safe and accurate procedure. Our goal was to determine the accuracy of a CTGSB of osseous spinal lesions in patients with known or suspected underlying malignancy in reference to major variables such as the radiographic appearance of the biopsied lesion and its location within the spinal column. METHODS: We retrospectively reviewed results of 410 consecutive percutaneous CTGSB procedures of osseous spinal lesions. Biopsy was determined to be adequate if diagnostic tissue was obtained (n = 401) or unsatisfactory (n = 9) if only blood without cellular elements was present on final pathologic-cytologic examination. RESULTS: The level of spinal biopsy was cervical in nine patients (2%), thoracic in 123 (31%), lumbar in 164 (42%), and sacral in 96 (25%). The overall diagnostic accuracy of CTGSB was 89%, with a false-negative rate of 11%. Biopsy of lytic lesions yielded an accurate diagnosis in 93% (220 of 236). Despite technical challenges inherent to biopsy of sclerotic lesions, diagnostic accuracy was 76% (63 of 83), although more importantly, 24% (20 of 83) of the results in sclerotic lesions were falsely negative. CONCLUSION: CTGSB of osseous spinal lesions is an important tool in the workup of patients with known or suspected underlying neoplastic disease. However, a negative result must be confirmed with either close follow-up or, preferably, open biopsy, especially in cases of sclerotic lesions for which diagnostic accuracy is decreased and the false-negative rate is high.

Adolescent↗

Advances in imaging in the postoperative patient with a rising prostate-specific antigen level.

Imaging prostate cancer continues to represent a clinical challenge for both primary and recurrent disease. In the evaluation of the persistent/recurrent/metastatic prostate cancer, knowledge of cancer location (local v distant), size, and extent are essential in order to design a treatment, tailored to each patient's needs. There are evidence-based guidelines for the use of imaging in assessing the presence of distant spread of prostate cancer. Radionuclide bone scans and computed tomography (CT), magnetic resonance imaging (MRI), and/or positron emission tomography (PET) supplement clinical and biochemical evaluations (prostate-specific antigen [PSA]) for suspected metastatic disease to bones and lymph nodes. There is no consensus about the use of imaging in the evaluation of local tumor recurrence. The use of ultrasound has been limited to biopsy guidance of the prostatic bed, or percutaneous biopsy of enlarged lymph nodes detected on CT or MRI. The use of MRI is evolving. Recent studies indicate that the use of MRI provides valuable information in the evaluation of local tumor recurrence, and nodal and bony metastases. In a patient post-radiation therapy, the method of combining MRI anatomic information with MR spectroscopic metabolic information is evolving. Another modality offering information about anatomy and metabolism of the local disease is PET/CT. The value of PET/CT at present is controversial, but new studies exploring the role of PET/CT in aggressive prostate cancer are promising.

Bone Neoplasms↗

Primary leptomeningeal primitive neuroectodermal tumor.

Leptomeningeal metastases are a common complication of medulloblastomas and other primitive neuroectodermal tumors (PNETs). Much rarer are PNETs apparently arising in the leptomeninges. An 8-year-old boy presented with headache and vomiting, due to neoplastic meningitis from primary neuroectodermal tumor without an identifying mass. After craniospinal irradiation and chemotherapy (carboplatin, vincristine, cyclophosphamide and lomustine) the boy was in remission for 14 months, then suffered several relapses despite various chemotherapy regimens. After the initial presentation of 3.5 years the boy began to suffer from prolonged refractory non-convulsive status epilepticus and later expired from progression of primary leptomeningeal PNET.

Antineoplastic Combined Chemotherapy Protocols↗

Results of preoperative embolization for metastatic spinal neoplasms.

OBJECT: Arterial embolization reduces blood loss in patients undergoing surgery for hypervascular spinal tumors. The objectives of this study were twofold: 1) to evaluate the role of magnetic resonance (MR) imaging in predicting tumor vascularity and 2) to assess the effectiveness of preoperative embolization in devascularizing these tumors. METHODS: Fifty-one patients with metastatic spinal neoplasms underwent angiography, preoperative embolization, and excision of the lesion between 1995 and 2000. The MR imaging studies were correlated with tumor vascularity on angiograms. Embolization was angiographically graded on a five-point scale ranging from no embolization (Grade A) to total embolization (Grade E). The embolization grade was correlated with intraoperative blood loss. The mean age was 57 years, the male/female ratio was 1.2:1, and back pain was present in all patients. Metastatic renal cell carcinoma (30 cases) and thoracic spine involvement (33 cases) were most frequent. The positive predictive value of MR imaging in determining tumor vascularity was 77%, whereas the negative predictive value was 21%. Total embolization (Grade E) was achieved in 34 patients. A shared vascular pedicle between a radiculomedullary artery (RMA) and a tumor diminished the likelihood of complete embolization (p = 0.02). Small asymptomatic cerebellar infarctions were demonstrated in two cases. The mean intraoperative blood loss was 2,586 ml. Following Grade D or E embolization, intraoperative bleeding was largely related to unembolized epidural veins. CONCLUSIONS: Tumor histology and MR imaging findings are predictive of hypervascularity, however, hypervascular tumors may not be detected by standard MR imaging sequences. Superselective catheterization permits Grade D or E embolization in 80% of patients. Shared blood supply with an RMA is the most important factor precluding complete embolization.

Angiography↗

Methotrexate leukoencephalopathy presenting as Klüver-Bucy syndrome and uncinate seizures.

Methotrexate causes several biochemical changes that impact the nervous system. The neurotoxicity usually affects the cerebral white matter, causing a leukoencephalopathy that can be chronic and progressive with cognitive decline. A 15-year-old male developed olfactory seizures and behavioral abnormalities (hypersexuality, placidity, and memory disturbances) compatible with partial Klüver-Bucy syndrome after treatment for central nervous system leukemia with intraventricular methotrexate. A magnetic resonance imaging study revealed evidence of white matter disease affecting both temporal lobes. A brain biopsy revealed a necrotizing encephalopathy compatible with methotrexate-related white matter injury. It may be prudent to verify normal cerebrospinal fluid dynamics before the administration of intraventricular methotrexate in children with a history of central nervous system leukemia.

Adolescent↗