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Biomedical subjects

Mark M Souweidane

Publications and source records attributed to Mark M Souweidane.

9 recordsLinked to original sources

Patterns of failure using a conformal radiation therapy tumor bed boost for medulloblastoma.

PURPOSE: To assess the patterns of failure for patients with medulloblastoma receiving a conformal tumor bed boost rather than a boost to the entire posterior fossa. PATIENTS AND METHODS: From 1994 to 2002, 32 consecutive patients with newly diagnosed medulloblastoma treated at Memorial Sloan-Kettering Cancer Center (New York, NY) received a conformal boost to the tumor bed in conjunction with craniospinal radiation therapy. Twenty-eight patients also received chemotherapy. The median age was 9 years (range, 3 to 34 years), and the male to female ratio was 3:1. Twenty-seven patients had standard-risk disease, and five patients had high-risk disease. Craniospinal doses ranged from 23.4 to 39.6 Gy, and total tumor bed doses ranged from 54 to 59.4 Gy. RESULTS: With a median follow-up of 56 months, six patients have relapsed; five relapsed outside of the posterior fossa, and one failed within the posterior fossa, outside of the high-dose boost volume. Five-year actuarial disease-free and overall survival rates were 84% and 85%, respectively. Freedom from posterior fossa failure was 100% and 86% at 5 and 10 years, respectively. Freedom from distant failure was 84% at 5 years, with a trend for improvement when full-dose craniospinal radiation (36 to 39.6 Gy) was used compared with a reduced dose (23.4 Gy) of radiation (100% v 63%, respectively; P =.06). No other predictive variables were identified. CONCLUSION: Conformal treatment to the tumor bed allows for significant sparing of critical structures. The posterior fossa failure rate in this series is similar to that reported when the entire posterior fossa is treated. This approach should be investigated further in a phase III trial.

Adolescent↗

Prolonged convection-enhanced delivery into the rat brainstem.

OBJECTIVE: Prolonged convection-enhanced delivery was used in an attempt to achieve large volumes of distribution (V(d)) in the rat brainstem. Clinical assessment and histological analysis were performed to establish the safety of this approach. METHODS: For evaluation of V(d,), 10 rats underwent stereotactic cannula placement into the brainstem. Five rats underwent a 24-hour infusion (volume of infusion [V(i)], 200 microl), and 5 rats underwent a 7-day infusion (V(i), 2 ml) of fluorescein isothiocyanate-dextran. Serial brainstem sections were imaged with ultraviolet illumination, and V(d) was assessed. For assessment of clinical tolerance, 30 additional rats underwent chronic infusions of an isotonic saline solution into the brainstem. Serial neurological examinations were performed, followed by histological analysis after the animals' death. RESULTS: No animal demonstrated clinically recognized neurological deficits. Foci of organizing necrosis were limited to the site of infusion and cannula tract. V(d) increased linearly with increasing V(i) (range, 24.8-130.6 mm(3)). Maximal cross sectional area of fluorescence and craniocaudal extent of fluorescence increased with increasing V(i). Fluorescence was detected throughout the entire brainstem beyond the compact area of highly concentrated tracer. CONCLUSION: Prolonged convection-enhanced delivery can be applied safely in the rat brainstem with no recognized limitations of V(d) and minimal histological changes beyond the site of infusion. Chronic brainstem infusions may enhance the potential application of convection-enhanced delivery for therapeutic purposes in treating diffuse pontine gliomas.

Animals↗

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↗

Effect of hyperosmolar mannitol on convection-enhanced delivery into the rat brain stem.

INTRODUCTION: Convection-enhanced delivery (CED) can safely achieve high local infusate concentrations within the rat brain stem with predictable distribution volumes. The authors investigated the effects of co-infusion or systemic administration of hyperosmolar mannitol on distribution parameters for infusions into the rat brain stem. METHODS: Fifteen rats underwent stereotactic cannula placement into the pontine nucleus oralis (PnO) followed by infusions at a constant rate to a total volume of 1 microl. Five rats underwent infusion of fluorescein isothiocyanate (FITC)-dextran diluted in 20% mannitol. Five rats received an intraperitoneal injection of 20% mannitol 10 min prior to infusion of FITC-dextran diluted in isotonic saline. As a control group, 5 rats underwent infusion of FITC-dextran diluted in isotonic saline without mannitol administration. Serial brain sections were imaged using confocal microscopy with ultraviolet illumination, and distribution volume (Vd) was calculated by computer image analysis. Histologic analysis was performed on adjacent sections. RESULTS: Volumes of distribution were not significantly increased by co-infusion of mannitol directly into the brain stem or by systemic mannitol administration compared to infusion without mannitol. Similarly, mannitol administration by either means failed to significantly alter maximal cross-sectional area or cranio-caudal extent of fluorescence. No animal demonstrated a postoperative neurological deficit or histologic evidence of tissue disruption. CONCLUSIONS: Neither systemic administration nor co-infusion of hyperosmolar mannitol significantly affects distribution parameters for CED infusions into the rat brain stem.

Animals↗

Delayed surgical resection of central nervous system germ cell tumors.

OBJECTIVE: To determine the value of delayed surgical resection in patients with central nervous system germ cell tumors who exhibit less than complete radiographic response despite declining serum and cerebrospinal fluid (CSF) tumor markers after initial chemotherapy. METHODS: We retrospectively analyzed 126 patients enrolled on two international multicenter clinical trials (the First and Second International Central Nervous System Germ Cell Tumor Studies) for patients with newly diagnosed central nervous system germ cell tumors. After at least three cycles of chemotherapy, 10 of these patients underwent delayed surgical resection owing to evidence of residual radiographic abnormalities despite declining or completely normalized serum and CSF levels of alpha-fetoprotein and human chorionic gonadotropin. RESULTS: Eight of these patients demonstrated nongerminomatous germ cell tumor elements at the time of initial diagnosis. In these patients, either serum or CSF tumor markers were elevated initially. Two patients demonstrated pure germinomas with normal levels of serum and CSF tumor markers. After chemotherapy, radiographic evaluation revealed a partial response in seven patients, a minor response in one patient, and stable disease in two patients. All 10 patients had either normal or decreasing levels of serum and CSF tumor markers before second-look surgery. At delayed surgical resection, 7 of the 10 patients underwent gross total resection, and 3 patients underwent subtotal resection of residual lesions. Pathological findings at second-look surgery demonstrated three patients to have mature teratomas, two with immature teratomas, and five with necrotic or scar tissue alone. To date, 7 of the 10 patients have had no recurrence during an average follow-up time of 36.9 months (range, 3-96 mo). Three of four patients with nongerminomatous germ cell tumors who had tumor markers that were decreased, but not normalized, before second-look surgery eventually developed tumor dissemination/progression, and they required subsequent radiation therapy despite having teratoma or necrosis/scar tissue at delayed surgery. In contrast, three of four patients with nongerminomatous germ cell tumors and completely normalized markers did not progress and did not require radiation therapy. CONCLUSION: Delayed surgical resection should be considered in patients with central nervous system germ cell tumors who have residual radiographic abnormalities and normalized tumor markers, because these lesions are likely to be teratoma or necrosis/scar tissue. However, second-look surgery should be avoided in patients whose tumor markers have not normalized completely.

Adolescent↗

Radiation myelitis in a 5-year-old girl.

Myelopathy is an uncommon complication of radiotherapy, particularly in the pediatric age group. A 5-year-old girl with acute lymphoblastic leukemia developed a severe but transient radiculopathy after intrathecal administration of methotrexate and cytarabine for an isolated central nervous system relapse. Chemotherapy was then given through an intraventricular catheter. Owing to a second central nervous system recurrence, she was treated with craniospinal radiation. The whole brain down to the level of C2 received a dose of 2400 cGy. Two months after completion of radiation, the child developed a progressive tetraparesis, and magnetic resonance imaging revealed an enhancing lesion involving the medulla and upper cervical cord. A biopsy was consistent with a treatment-related necrotizing leukoencephalopathy. This case suggests that patients who develop neurologic dysfunction when treated with methotrexate can also be particularly susceptible to radiation-related injury.

Child, Preschool↗

Convection-enhanced delivery into the rat brainstem.

OBJECT: Convection-enhanced delivery (CED) can be used safely to achieve high local infusate concentrations within the brain and spinal cord. The use of CED in the brainstem has not been previously reported and may offer an alternative method for treating diffuse pontine gliomas. In the present study the authors tested CED within the rat brainstem to assess its safety and establish distribution parameters. METHODS: Eighteen rats underwent stereotactic cannula placement into the pontine nucleus oralis without subsequent infusions. Twenty rats underwent stereotactic cannula placement followed by infusion of fluorescein isothiocyanate (FITC)-dextran at a constant rate (0.1 microl/minute) until various total volumes of infusion (V(i)s) were reached: 0.5, 1, 2, and 4 microl. Additional rats underwent FITC-dextran infusion (V, 4 microl) and were observed for 48 hours (five animals) or 14 days (five animals). Serial (20-microm thick) brain sections were imaged using confocal microscopy with ultraviolet illumination, and the volume of distribution (Vd) was calculated using computer image analysis. Histological analysis was performed on adjacent sections. No animal exhibited a postoperative neurological deficit, and there was no histological evidence of tissue disruption. The Vd increased linearly (range 15.4-55.8 mm3) along with increasing Vi, with statistically significant correlations for all groups that were compared (p < 0.022). The Va/Vi ratio ranged from 14 to 30.9. The maximum cross-sectional area of fluorescence (range 9.8-20.9 mm2) and the craniocaudal extent of fluorescence (range 2.8-5.1 mm) increased with increasing Vi. CONCLUSIONS: Convection-enhanced delivery can be safely applied to the rat brainstem with substantial and predictable V(d)s. This study provides the basis for investigating delivery of various candidate agents for the treatment of diffuse pontine gliomas.

Animals↗

Diffusion imaging in obstructive hydrocephalus.

BACKGROUND AND PURPOSE: Hydrocephalus causes transependymal resorption of spinal fluid that in turn produces periventricular interstitial edema. This study was performed to determine if diffusion imaging can demonstrate this interstitial edema in the periventricular region in patients with obstructive hydrocephalus and if it can be used to assess the treatment response. METHODS: Twenty-one patients with obstructive hydrocephalus were evaluated with MR diffusion imaging before and after treatment. The change in ventricular size was measured by using the frontal and occipital horn ratio. The signal intensity abnormalities in periventricular white matter were scored. Average diffusion constants (D(av)) in the periventricular white matter were measured before and after treatment and compared with normal values. Post-treatment resolution of MR imaging abnormalities and changes in ventricular volume were compared with changes in D(av). RESULTS: D(av) measured from periventricular white matter was increased in hydrocephalic patients compared with age-matched control subjects by a mean of 6.9% (P <.02). After treatment, D(av) decreased by an average of 6.0%: D(av) decreased in 11 patients (53%), it remained essentially unchanged in seven (33%), and it increased in three (14%). CONCLUSION: For patients with obstructive hydrocephalus, diffusion is usually increased in the periventricular white matter. Therefore, increased D(av) may be a clinically useful sign of hydrocephalus, and it may prove useful in cases with equivocal clinical or imaging findings. Measurement of D(av) may be valuable in assessing the treatment response in these patients because D(av) usually decreases toward normal levels with successful treatment.

Adolescent↗