Dosimetric results from a feasibility study of a novel radiosurgical source for irradiation of intracranial metastases.

PURPOSE: A feasibility study addressing the role of a new miniature x-ray device, the Photon Radiosurgery System (PRS), for interstitial radiosurgical treatment of intracranial metastatic neoplasms, was conducted at our institution. To gain insight into the role of PRS vis-à-vis other currently available radiosurgical treatment modalities, dosimetric comparisons of Linac Radiosurgery and proton beam therapy were performed in the treatment of a small approximately spherical metastasis. METHODS AND MATERIALS: The photon radiosurgery system is a miniature, battery operated, high-voltage x-ray generator that produces low-energy x-rays with an effective energy of 10-20 keV emanating from the tip of a probe stereotactically inserted into small tumors (< 3 cm in diameter) in humans. Patients, 18 years or older, with supratentorial mass lesions less than 3 cm in diameter were eligible if they were likely to survive their systemic cancer and be capable of self-care for more than 4 months. Patients were ineligible if presenting with infratentorial lesions, contraindications for biopsy, or receipt of chemotherapy or radiotherapy within 4 weeks were ineligible. RESULTS: Fourteen patients with metastatic supratentorial lesions were treated from December 1992 to December 1993 for metastatic tumors to the brain. Single doses of 10-20 Gy were delivered to spherical targets of 10 to 35 mm in diameter. Treatment, including biopsy, pathologic review and radiation treatment, generally took less than 3 h. One patient, later found to have an ischemic stroke, developed a small hemorrhage from the biopsy that preceded interstitial irradiation. There were no other complications. Median survival was 10 months. Three locally recurrent lesions failed at 3.5, 4, and 10 months after treatment. All patients had stable or improved Karnofsky status for 2 weeks to 21 months after treatment. The PRS dosimetry appears at least as good as that obtained using 6 MV Linac or 160 MeV protons. Analyses of dose-volume histograms comparing the volumes of normal CNS tissue irradiated employing each of the respective modalities suggest a small sparing of normal tissue with PRS, as opposed to linac or protons, in this patient population with small, approximately spherical tumors. CONCLUSIONS: The PRS device provides a unique cost and time efficient procedure for providing interstitial radiation therapy immediately following histologic confirmation of malignancy in patients undergoing biopsy of intracranial lesions. The PRS treatment appears safe, and preliminary data suggest no evidence of treatment-related morbidity within the life span of the selected patient population. When treating small, spherical lesions, PRS appears to offer a modest dosimetric advantage over Linac or proton beam therapy in sparing normal tissue. These encouraging results have prompted a Phase II trial that is currently underway. Further efforts are necessary in the design of a clinically relevant trial addressing the role of fractionated external beam radiation therapy with boost vs. PRS treatment with WBRT in the treatment of single metastases.

Migraine, but not subarachnoid hemorrhage, is associated with differentially increased NPY-like immunoreactivity in the CSF.

To test whether migraine and subarachnoid hemorrhage (SAH) are associated with increased sympathetic tone, we compared the neuropeptide Y-like (NPY-LI) and chromogranin A-like immunoreactivities (LI) of cerebrospinal fluid (CSF) from migraneurs and SAH patients with those from control subjects. Increased sympathetic tone was expected to produce higher co-release of these co-stored peptides and concordant changes in their CSF levels. In addition, we investigated a possible disturbed nitric oxide homeostasis by measuring CSF nitrites (NO). More than 70% of CSF NPY-LI corresponded to the chromatographic peak (HPLC) for the intact molecule in all three groups. Migraneurs had 64% higher CSF NPY-LI, but no significant difference in CSF chromogranin A-LI, as compared to controls. In contrast, SAH patients had 74% less CSF chromogranin A-LI and a trend to lower NPY-LI, as compared to controls. No differences in CSF NO were detected among groups. These results argue against an increased sympathetic tone in patients with either migraine or SAH, and suggest that the higher CSF NPY-LI of migraneurs probably originates from central neurons. Furthermore, our findings in SAH patients argue in favor of a decreased sympathetic tone; this could be a homeostatic response to counterbalance vasoconstriction mediated by other mechanisms.

Interstitial irradiation of brain tumors, using a miniature radiosurgery device: initial experience.

OBJECTIVE: This report describes the clinical evaluation of a novel stereotactic radiosurgical device for interstitial irradiation of malignant brain tumors. METHODS: Fourteen patients with cerebral lesions less than 3.5 cm in greatest diameter were treated with a single fraction of stereotactic interstitial irradiation (average, 12.5 Gy). Clinical evaluation, Karnofsky Performance Scale ratings, and neuroimaging studies were obtained at 6-week intervals postoperatively to assess treatment response. Reduction or stabilization of tumor size on follow-up imaging was accepted as local control, whereas tumor enlargement indicated local failure. INSTRUMENTATION: This battery-powered miniature x-ray generator device produces low-energy x-ray photons that are attenuated rapidly within tissue. A dose decline rate proportional to 1/r3 yields extremely sharp dose fall-off curves with minimal exposure to surrounding tissue. Dose rates of 200 cGy per minute are possible, allowing for the administration of 12.5 Gy to a lesion 3 cm in diameter in less than 1 hour. RESULTS: Local control (stabilization or reduction in lesion size) was obtained in 10 of the 13 patients with tumors with follow-up of 1.5 to 36 months (mean, 12 mo). Of three patients with radiographic progression, recurrence was symptomatic in only one. All patients tolerated the procedure well, and most patients were discharged home the day after treatment. No new neurological deficits were noted after biopsy and irradiation. CONCLUSIONS: Preliminary experience with this novel radiosurgical device has demonstrated its feasibility and safety. Clinical efficacy of this technique is now under investigation in an international multicenter study.

A revisit of MRI analysis for synovial sarcoma.

We evaluated magnetic resonance imaging (MRI) findings of synovial sarcomas in 22 patients, and the most common MRI findings were oval and well-defined nodular masses with heterogeneous intermediate signal intensity (SI) on T1 weighted images (WI), high SI on T2-WI and heterogeneous contrast enhancement. A cystic component was seen in 77%, intratumoral hemorrhage in 73%, and calcification in three monophasic sarcomas. Metastases were noted in lung (mostly biphasic type), lymph node, and bone. Posttreatment changes revealed diffusely increased S1 on T2-W1 and slightly diffuse contrast enhancement with feathery appearance. Morphology and MR signal characteristics assist in synovial sarcoma management.

Imaging and clinical spectrum of rhabdomyosarcoma in children.

We retrospectively analyzed the MRI findings of rhabdomyosarcoma (RMSA) in 23 patients to evaluate its role in staging and management. Heterogeneous signal abnormalities were noted in the sarcoma lesions with significant contrast enhancement. Seven head and neck cases showed direct bone invasion and destruction; only one had distant bony metastasis. Metastasis was noted in the lymph nodes, lung, bone, abdominoperitoneum, and head and neck soft tissue. MRI findings of RMSA are most helpful in staging and assessing therapeutic response.

Diabetic complete external ophthalmoplegia.

A 69-year-old diabetic patient taking oral hypoglycemic drugs and with no systemic complications presented a right peripheral facial palsy, and 2 months later a complete right external ophthalmoplegia with sparing of the pupillary function. Clinical, radiologic, and other laboratory investigation ruled out compressive, infectious, and inflammatory etiology. Four months later, after achieving good metabolic control, there was almost complete recovery of the ophthalmoplegia without signs of aberrant regeneration of the third nerve. Diabetes is proposed as the etiology of this case. A possible anatomic substrate is presented to explain the findings.

Therapy for paraneoplastic neurologic syndromes in six patients with protein A column immunoadsorption.

BACKGROUND: Paraneoplastic neurologic syndromes, although rare, cause significant morbidity and mortality. They are thought to be immunologically mediated, but to date those involving the central nervous system (CNS) have not been particularly responsive to immunologic therapy. The use of the novel immunomodulator, protein A immunoadsorption, was explored to address this question. METHODS: Six patients with neurologic paraneoplastic syndromes were treated with this technique, using the "off line" method. Two hundred fifty ml of plasma was perfused through a column containing protein A covalently attached to a silica matrix. The plasma was then returned to the patient. RESULTS: Five of the patients responded to the therapy, with complete and durable responses in three patients with opsoclonus-myoclonus, objective, though transient, improvement in one patient with paraneoplastic brainstem encephalitis associated with a Merkel cell tumor, and stabilization and partial improvement in one patient with paraneoplastic limbic encephalitis. The patient without response developed a cutaneous vasculitis after the second treatment, and therapy was discontinued. CONCLUSIONS: This therapy appears beneficial for a number of paraneoplastic syndromes, most dramatically in the opsoclonus/myoclonus syndrome.