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Biomedical subjects

J C Flickinger

Publications and source records attributed to J C Flickinger.

At least 127 records · Page 7Linked to original sources
PubMed1994

Facial nerve preservation and tumor control after gamma knife radiosurgery of unilateral acoustic tumors.

To assess the long-term risk of facial nerve dysfunction after unilateral acoustic tumor stereotactic radiosurgery, we retrospectively analyzed our initial experience in 98 unilateral acoustic tumor patients who were evaluated at least 2 years after treatment. This observation interval permits an analysis of both the risk of onset and the potential for recovery of facial nerve function. The overall risk of developing any degree of delayed transient or permanent postoperative facial neuropathy was 21.4% (21 of 98 patients). Only one patient undergoing radiosurgery alone had poor residual facial nerve dysfunction worse than House-Brackmann grade III. Normal facial nerve function (House-Brackmann grade 1) was preserved in 95% of patients with small tumors (10 mm or less petrous-pons dimension) and in 90% of patients who had useful hearing and normal facial function preoperatively. Normal facial function was preserved in all patients with intracanalicular acoustic tumors. The risk of delayed facial neuropathy was reduced by performing radiosurgery when tumors were small (1000 mm(3) or less), by enclosing the tumor within the 50% isodose volume, by using multiple small radiation isocenters, and by detailed identification of the tumor volume using stereotactic magnetic resonance imaging.

Journal Article↗
PubMed1994

Cerebral radioprotective effects of high-dose pentobarbital evaluated in an animal radiosurgery model.

Because pentobarbital has been shown to reduce cerebral toxicity to single-fraction whole brain irradiation in a rat model, we sought to evaluate its cerebral radioprotective effects for stereotactic radiosurgery. We hypothesized that concurrent high-dose pentobarbital anaesthesia (50 mg kg-1) during irradiation could delay or prevent the onset of radiation necrosis within the radiosurgical volume. Six rats were placed in pentobarbital or control groups, irradiated, and then evaluated at different intervals (60, 100, 150, 365 days; total = 48 animals studied). All rats had 100 Gy radiosurgery to the right frontal brain region (a threshold dose for focal necrosis at 90 days). The radioprotective effects of pentobarbital were compared to ketamine anaesthesia (control) and evaluated for observed focal necrosis, size of necrotic lesion, blood vessel alterations, and to changes in cell nuclei. There was no difference between groups in the numbers of rats with necrosis at 100 days (p = 0.72), at 150 days (p = 0.77), or at 365 days (p = 0.77); no necrosis was observed in either group at 60 days. There was no difference in the size of the necrotic lesion at 100 days (p = 1.0), at 150 days (p = 0.39), or at 365 days (p = 0.07). There was no difference between groups in observed blood vessel changes or nuclear changes at any time interval (p > 0.6). There was no animal morbidity related to radiosurgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Stereotactic options in the management of craniopharyngioma.

Multimodality stereotactic techniques were used in the management of 39 patients with craniopharyngiomas in a 12-year interval. Monocystic craniopharyngiomas were treated successfully by intracavitary beta-irradiation using 32P (96% cyst control rate). Solid tumor progression or secondary cyst formation required repeat irradiation, radiosurgery or microsurgery in selected patients. In the future, wider and earlier application of stereotactic techniques may further reduce the still unacceptable morbidity currently associated with initial radical microsurgical resection of craniopharyngiomas.

Adolescent↗
PubMed1994

Patient outcomes after stereotactic radiosurgery for "operable" arteriovenous malformations.

To define the outcomes after stereotactic radiosurgery performed for smaller volume arteriovenous malformations (AVMs) that are potentially suitable for surgical removal, we retrospectively reviewed our 4-year experience in 65 patients who declined microsurgery. All 65 patients had Spetzler-Martin Grade I or II AVMs and a minimum follow-up of 24 months (median, 29 mo). Symptomatic improvement after radiosurgery occurred in 52% of patients with seizures and in 63% of patients with headaches. The annual risk of AVM hemorrhage during the latency interval after radiosurgery was 3.7%. Five patients (7.7%) had a subsequent hemorrhage (all within 8 mo of radiosurgery); two died, and three recovered (one after hematoma evacuation and two with conservative management). Forty-seven patients (72%) returned to their previous employment status or activity level within 1 week of radiosurgery (92% within 1 yr). No patient suffered radiation-related complications. Twenty-seven (84%) of 32 patients evaluated by postradiosurgical angiography had complete AVM obliteration. Radiosurgery is an effective and less invasive management strategy for Grade I or II AVM patients who are either medically unsuitable for or unwilling to undergo surgical removal. The risk of AVM hemorrhage during the latency interval until obliteration occurs appears to be no different than the natural history of untreated AVMs. These results (including hemorrhage prevention and symptom amelioration) indicate that the conservative management of small AVMs can rarely be justified.

Adolescent↗
PubMed1994

Stereotactic radiosurgery for acoustic nerve tumors in patients with useful preoperative hearing: results at 2-year follow-up examination.

Twenty patients with acoustic nerve tumors (mean diameter < or = 30 mm) and useful preoperative hearing were examined 2 years after stereotactic radiosurgery to determine the effectiveness of the surgery in the control of tumor growth and the preservation of cranial nerve function. Results showed tumor volume stabilization (12 cases) or reduction (seven cases) was achieved in a total of 19 patients (95%). Useful hearing (defined as Gardner and Robertson Class I or II) preservation was obtained in 100% of cases immediately postoperatively, 50% at 6 months, and 45% at both 1 and 2 years. Two years after stereotactic radiosurgery, facial nerve function was preserved in 90% of patients and 75% continued to have normal trigeminal nerve function. All patients returned to and maintained their preoperative functional status within 3 to 5 days after radiosurgery. These findings indicate that stereotactic radiosurgery with multiple isocenters and narrow radiation beams is a safe and effective management strategy for progressive acoustic nerve tumors. Auditory, facial, and trigeminal nerve function can be preserved in most patients. Prevention of further growth and preservation of cranial nerve function appear to be satisfactory goals in the current management of patients with acoustic neuromas.

Adult↗
PubMed1994

Stereotactic radiosurgery for intracranial malignancies.

Stereotactic radiosurgery has historically been used for arteriovenous malformations and benign tumors but has rather recently been used as a tool in the multimodality management of intracranial malignancies. Radiosurgery has been shown to be highly effective in the management of small metastatic brain tumors and has proven effective in controlling small brain metastases that progress after prior fractionated radiotherapy. The technique is also a reasonable, low morbidity alternative to surgical resection in the initial management of patients with solitary brain metastasis. In selected patients with small, relatively spherical, high-grade gliomas, radiosurgery appears to produce tumor control, survival, and toxicity similar to that of brachytherapy. However, compared with brachytherapy, radiosurgery has the advantage of lower initial morbidity, reduced hospital stay, reduced radiation exposure to personnel, and lower costs. Future clinical trials should further define dose-response relationships and the optimum role for radiosurgery in the management of malignant intracranial neoplasms.

Brain Neoplasms↗
PubMed1993

Tolerance of cranial nerves of the cavernous sinus to radiosurgery.

PURPOSE: Stereotactic radiosurgery is becoming a more accepted treatment option for benign, deep seated intracranial lesions. However, little is known about the effects of large single fractions of radiation on cranial nerves. This study was undertaken to assess the effect of radiosurgery on the cranial nerves of the cavernous sinus. METHODS AND MATERIALS: We examined the tolerance of cranial nerves (II-VI) following radiosurgery for 62 patients (42/62 with meningiomas) treated for lesions within or near the cavernous sinus. Twenty-nine patients were treated with a modified 6 MV linear accelerator (Joint Center for Radiation Therapy) and 33 were treated with the Gamma Knife (University of Pittsburgh). Three-dimensional treatment plans were retrospectively reviewed and maximum doses were calculated for the cavernous sinus and the optic nerve and chiasm. RESULTS: Median follow-up was 19 months (range 3-49). New cranial neuropathies developed in 12 patients from 3-41 months following radiosurgery. Four of these complications involved injury to the optic system and 8 (3/8 transient) were the result of injury to the sensory or motor nerves of the cavernous sinus. There was no clear relationship between the maximum dose to the cavernous sinus and the development of complications for cranial nerves III-VI over the dose range used (1000-4000 cGy). For the optic apparatus, there was a significantly increased incidence of complications with dose. Four of 17 patients (24%) receiving greater than 800 cGy to any part of the optic apparatus developed visual complications compared with 0/35 who received less than 800 cGy (p = 0.009). CONCLUSION: Radiosurgery using tumor-controlling doses of up to 4000 cGy appears to be a relatively safe technique in treating lesions within or near the sensory and motor nerves (III-VI) of the cavernous sinus. The dose to the optic apparatus should be limited to under 800 cGy.

Abducens Nerve↗
PubMed1993

Potential human error in setting stereotactic coordinates for radiosurgery: implications for quality assurance.

PURPOSE: The error frequency in setting stereotactic coordinates for gamma knife radiosurgery was investigated to determine what quality assurance safeguards are necessary. METHODS AND MATERIALS: A prospective study of 200 consecutive isocenter settings for gamma knife radiosurgery was analyzed to identify the frequency of spontaneous errors in setting and checking stereotactic coordinates (corrected prior to treatment). An additional 25 coordinate errors were introduced at random among the next 200 consecutive isocenter settings to provide additional data on identification of errors. RESULTS: Stereotactic coordinates required resetting in 12% (24/200) of the isocenters treated due to errors of 0.25-0.50 mm (8%) and 1-20 mm (4%). This comprised 2.2% (26/1200) of the individual coordinate settings. The frequency of these errors was significantly related to the specific directional coordinate set (p = 0.0004) and experience (p = 0.016). Errors were identified by 83.5% (91/109) of the observers checking the settings (60.0% of 0.25 mm errors, 94.6% of errors > or = 0.5 mm, p = 0.0000). Verification of stereotactic coordinates by two observers reduces the probability of an undetected error > or = 0.25 mm to 1/1,392 and to 1/154,712 for errors > or = 1 mm. CONCLUSION: Errors in setting stereotactic coordinates are common (12% prior to checking) but are corrected with a high degree of confidence by a quality assurance policy requiring coordinate verification by a minimum of two observers.

Calibration↗
PubMed1993

Cranial nerve length predicts the risk of delayed facial and trigeminal neuropathies after acoustic tumor stereotactic radiosurgery.

PURPOSE: To test the hypothesis that length of cranial nerve irradiated is a major factor predicting the risk of cranial nerve injury following radiosurgery and to identify any other significant related treatment factors. METHODS AND MATERIALS: Ninety-two patients (93 acoustic tumors) were treated with a 201 source Cobalt-60 gamma unit from 1987 to 1990 and prospectively followed. The range of minimum tumor dose was 12-20 Gy and maximum dose 24-50 Gy. Univariate and multivariate analyses were used to evaluate any correlations between tumor measurements and treatment factors, with the development of trigeminal and facial neuropathies following radiosurgery. RESULTS: The risks of trigeminal and facial neuropathy following radiosurgery were associated with the pon-petrous distance and mid porous transverse tumor diameters respectively (anatomically related to the irradiated length of cranial nerves V and VII respectively) in both univariate (p = .002 for V and p = .026 for VII) and multivariate (p = .004 for V and p = .055 for VII) analyses. Tumor volume, other tumor measurements, maximum dose, minimum tumor dose, and tumor dose inhomogeneity were not significantly related to either trigeminal or facial neuropathy in univariate and multivariate analyses. CONCLUSION: Within a minimum tumor dose range of 12-20 Gy, the incidence of delayed trigeminal or facial neuropathy depended more on the estimated length of nerve irradiated than the tumor dose or tumor volume. In the future, the risk of delayed facial or trigeminal cranial neuropathy may be reduced significantly by performing radiosurgery when the tumor still has both a small mid-porous transverse diameter and a small pons-petrous distance.

Facial Neuralgia↗
PubMed1993

Radiosurgery for vascular malformations of the brain stem.

The challenges associated with microsurgery of vascular malformations located in the midbrain, pons and medulla have promoted the development of alternative therapeutic techniques. To assess the efficacy and safety of radiosurgery in the management of brain stem vascular malformations we reviewed our 5-year experience in 50 patients evaluated between 4 and 51 months (mean, 25 months) after radiosurgery. Twenty-eight patients (56%) underwent gamma unit radiosurgery for symptomatic arteriovenous malformations (AVMs), and 22 patients (44%) for angiographically occult vascular malformations (AOVMs). Patients varied in age from 7 to 76 years (mean, 39 years). Forty-one patients (82%) had from 1 to 5 hemorrhages prior to gamma knife radiosurgery. Ten (20%) had one or two prior unsuccessful operations, and 37 (74%) presented with a neurological deficit. Of the patients with AVMs, 6 were considered Spetzler Grade III, and 22 (79%) Grade VI (inoperable: major component within the brain stem parenchyma). Forty-four malformations (88%) were adjacent to or within the midbrain and pons; the remainder involved the medulla. Average malformation diameters varied from 6 to 30.4 m (mean, 20.6; mean volume 4614 mm3). The minimal radiation dose to the margin of the malformations ranged from 12 to 25.6 Gy (mean, 18.9 Gy). Of the 28 patients with AVMs, 8 had follow-up angiograms at a minimum of 2-years after radiosurgery (or sooner if their MRIs suggested obliteration). Of these patients, 7 (88%) showed complete obliteration of their malformations. No patients with AOVMs rehemorrhaged if more than 15 months elapsed after radiosurgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Gamma knife radiosurgery for acoustic tumors: multivariate analysis of four year results.

In order to evaluate the results of radiosurgery for acoustic tumors and to identify optimum treatment parameters, an analysis of tumor control, as well as incidences of hearing loss, facial and trigeminal neuropathies was undertaken. Between August 1987 and August 1991, 134 patients with 136 acoustic tumors received stereotactic gamma knife radiosurgery at the University of Pittsburgh. Median follow-up was 24 months (range: 6-56 months). Tumor volumes ranged from 0.10 to 17.00 cm3 (median = 2.75 cm3). From one to ten isocenters were utilized per tumor treated (median = 3). Minimum tumor doses varied from 12 to 20 Gy (median = 17 Gy). The 4-year actuarial tumor control rate was 89.2 +/- 6.0%. Some degree of hearing (by pure tone audiometry) was preserved in 71.0 +/- 4.4% of patients. The actuarial rates for preservation of either pretreatment hearing level or useful hearing were 34.4 +/- 6.6% and 35.1 +/- 97% respectively. Respectively, the actuarial incidences of postradiosurgery facial and trigeminal neuropathies were 29.0 +/- 4.4% and 32.9 +/- 4.5%, respectively. No significant factors affecting tumor control were identified. Multivariate analysis identified a significantly increased risk of hearing loss in patients with neurofibromatosis (p = 0.0003) as well as decreased risks of facial and trigeminal neuropathies with both decreasing tumor diameter (p = 0.001) and increasing number of isocenters treated (p = 0.003). Radiosurgery is a safe and effective treatment for acoustic neuromas with acceptable morbidity that may be lowered by the use of multiple isocenter treatment techniques and by earlier treatment of small tumors.

Adolescent↗
PubMed1993

Stereotactic radiosurgery of cavernous sinus meningiomas as an addition or alternative to microsurgery.

To evaluate the response of cavernous sinus meningiomas to stereotactic radiosurgery, we reviewed our 54-month experience with 34 patients. All patients underwent radiosurgery with a 201-source cobalt-60 gamma unit. Twenty-eight patients (82%) had previous histological confirmation of a meningioma (1 to 5 cranial base craniotomies per patient); 6 (18%) were treated on the basis of neuroimaging criteria alone. The single-fraction radiation tumor margin dose (10 to 20 Gy) was designed to conform to the irregular tumor volumes in all patients. The maximum radiation dose to the optic nerve or tract was reduced to 9 Gy in 31 patients. No patient had tumor growth (100% tumor control) during the follow-up interval (median, 26 mo). Tumor regression was observed in 56% of patients imaged at an average of 18 months. Eight patients (24%) improved clinically at follow-up examinations. Four patients developed new or worsened cranial nerve deficits during the follow-up interval; two had subsequent full improvement. No patient developed an endocrinopathy or new extraocular muscle paresis. Stereotactic radiosurgery, using multiple isocenter dosimetry facilitated by the gamma unit, is an accurate, safe, and effective technique to prevent the growth of tumors involving the cavernous sinus. Despite the proximity of such tumors to adjacent cranial nerves, complications were rare. The maximum length of hospital stay was 36 hours, and all patients returned to their preoperative employment status within 3 to 5 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Preservation of cranial nerve function after radiosurgery for nonacoustic schwannomas.

Microsurgical resection is the primary management approach for patients with intracranial schwannomas. Recent studies have demonstrated that stereotactic radiosurgery is an effective therapeutic modality for patients with acoustic schwannomas. To define the role of radiosurgery in the management of patients with nonacoustic schwannomas, we reviewed the results of gamma unit stereotactic radiosurgery in six patients with trigeminal and five patients with jugular foramen region schwannomas. No patient with a trigeminal schwannoma demonstrated tumor growth during a mean follow-up of 21 months (range, 7-35 mo), whereas one patient with a jugular foramen region schwannoma had an increase in tumor size 7 months after radiosurgery. No new cranial nerve or brain stem deficits were noted in either patient group after radiosurgery. In this early experience, radiosurgery proved an effective primary or adjuvant technique for selected patients with schwannomas of the trigeminal, glossopharyngeal, or vagus nerves. Using our described method, the safety of radiosurgery was demonstrated on the brain stem, regional cranial nerves, and especially those cranial nerves intimately associated with the tumor.

Cranial Nerve Neoplasms↗
PubMed1993

The radiobiology of human acoustic schwannoma xenografts after stereotactic radiosurgery evaluated in the subrenal capsule of athymic mice.

An experimental model with xenograft transplantation into the subrenal capsule of athymic (nude) mice was used to evaluate the early response of human acoustic schwannomas to stereotactic radiosurgery. After xenograft placement, 45 mice underwent radiosurgery with single doses of 10, 20, or 40 Gy using a 201-source 60Co gamma unit (4-mm collimator, single isocenter, 80% isodose line). The 45 radiosurgery-treated xenografts were compared with 15 untreated xenografts and 15 xenografts in mice that underwent "sham radiosurgery." All five study groups were matched for the following pretreatment variables: patient of origin, animal weight, average xenograft diameter, and percentage of xenograft surface vascularity. Immediately prior to sacrifice of the mice all xenografts were evaluated in situ to determine the average tumor diameter, tumor volume, and percentage of surface vascularity. Mice were sacrificed 2 weeks, 1 month, or 3 months after radiosurgery. Blinded histological review was performed by an independent neuropathologist. Tumor volume was reduced 33.6% after 2 weeks (p = 0.023) and 45% after 3 months (p = 0.018) in the 40-Gy radiosurgery group. Tumor volume was reduced by 46.2% after 1 month (p = 0.0002) and 35.2% after 3 months (p = 0.032) in the 20-Gy radiosurgery group. An average volume reduction of 16.4% was observed after 3 months (p = 0.17) in the 10-Gy radiosurgery group. At 3 months after surgery, tumor surface vascularity was reduced by an average of 19.7% (p = 0.043) in the 40-Gy radiosurgery group and 5.8% (p = 0.12) in the 20-Gy radiosurgery group and was unchanged in the 10-Gy radiosurgery group and both control groups. Histological examination demonstrated a higher incidence of hemosiderin deposits (p = 0.026) and vascular mural hyalinization (p = 0.032) in radiosurgery xenografts versus control. The subrenal capsule xenograft in nude mice was an excellent model for studying the in vivo radiobiology of acoustic schwannomas after radiosurgery. Both cellular and vascular effects could be assessed serially in situ and the model was stable even 4 months after transplantation. Additional studies investigating radiobiology over periods better approximating the time course of clinical neuroimaging changes (6 to 12 months) are warranted.

Animals↗
PubMed1993

Stereotactic radiosurgery for cerebral metastatic melanoma.

To determine local tumor control rates and survival of patients with melanoma metastases to the brain, the authors reviewed the results of 23 consecutive patients with a total of 32 tumors (19 patients had a solitary tumor and four had multiple tumors) who underwent adjuvant stereotactic radiosurgery. Tumor locations included the cerebral hemisphere (24 cases), brain stem (four cases), basal ganglia (two cases), and cerebellum (two cases). Fifteen patients had associated cranial symptomatology and eight had incidental metastases. All patients had tumors of 3 cm or less in diameter (mean tumor volume 2.5 cu cm), and all received fractionated whole-brain radiation therapy (30 Gy) in addition to radiosurgery (mean tumor margin dose 16 Gy). Nineteen patients were managed with both modalities at the time of diagnosis; four underwent radiosurgery 3 to 12 months after fractionated whole-brain radiotherapy. The mean patient follow-up period was 12 months (range 3 to 38 months). After radiosurgery, eight patients improved, 13 remained stable, and two deteriorated. One patient subsequently required craniotomy because of intratumoral hemorrhage; this patient and three others are living 13 to 38 months after radiosurgery. Nineteen patients died, 18 from progression of their systemic disease and one from another hemorrhage into a new brain metastasis. The local tumor control rate was 97%. Only two patients subsequently developed new intracranial metastases. The median survival period after diagnosis was 9 months (range 3 to 38 months). The authors believe that stereotactic radiosurgery coupled with fractionated whole-brain irradiation is an effective management strategy for cerebral metastases from a melanoma. Multi-institutional trials are warranted to confirm that stereotactic radiosurgery results equal or surpass the outcome achieved with craniotomy and tumor resection.

Adult↗