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Biomedical subjects

J C Flickinger

Publications and source records attributed to J C Flickinger.

At least 163 records · Page 9Linked to original sources
PubMed1991

Evaluation of radiosurgery techniques with cumulative dose volume histograms in linac-based stereotactic external beam irradiation.

Radiosurgery at UCSF is performed with a 6-MV linear accelerator with tertiary collimation for improved small field definition. The dose delivery to the target relative to normal tissue is influenced by the number of arcs, the arc geometry, field size, and beam energy. The impact of arc number, arc geometry, and field size on the dose distribution from 6-MV X rays in a 16 cm spherical phantom has been evaluated through the use of cumulative dose volume histograms. Dose volume histograms were calculated for a) 1-5 and 10 arcs, and b) collimator sizes of 1.25, 2.0, and 3.0 cm. Differences between techniques were found at the 5-10% level for field sizes from 1.25 to 2.0 cm. It was shown that the finite dimension of the sphere and, by extension, head diminishes the differences between techniques for the larger field sizes. The effect of treating with two isocenters is also analyzed and an approach for improving the dose distribution is presented.

Brain Diseases↗
PubMed1991

The role of radiosurgery in the management of chordoma and chondrosarcoma of the cranial base.

Despite conventional multimodality treatment (surgery and fractionated radiation therapy), recurrence and clinical progression of cranial base chordomas and chondrosarcomas are common. The malignant behavior of these tumors is a result of their critical location, locally aggressive nature, and high recurrence rate. To explore the role of radiosurgery in the treatment of these skull base neoplasms, we assessed its use in four patients with chordoma and two with chondrosarcoma. In five of the patients, radiosurgery was used as adjuvant therapy for residual or recurrent tumors after surgical debulking, and in one patient with a chordoma, it was the primary treatment. No patient received fractionated external beam radiotherapy. All tumors were less than 30 mm in diameter and were treated with 20 Gy to the tumor margin. Skull base computed tomography and magnetic resonance images were essential to define the anatomic relationships between tumor and adjacent basal structures. During follow-up (mean, 22 mo; range, 8-36 mo), we found no progression of the treated tumor volume in any patient. Neurological deficits before treatment improved in three patients; the other three patients remained in stable neurological condition. Serial follow-up imaging studies demonstrated that two patients showed reduction in tumor size and four patients had no tumor growth. In one patient, a metastatic parietal lobe chondrosarcoma developed and was treated by microsurgery. Another patient showed tumor progression outside of the radiosurgical treatment volume. Our results attest to the value of stereotactic radiosurgery as an adjuvant or primary treatment for selected patients with chordoma or chondrosarcoma and demonstrate its potential advantages over standard fractionated irradiation. Analysis of the long-term clinical and imaging effects after radiosurgery is warranted.

Adult↗
PubMed1991

Gamma knife radiosurgery of meningiomas.

Fifty patients with meningiomas were treated during the initial 30 months experience using the 201 source cobalt-60 gamma knife at the University of Pittsburgh. The most frequent site of origin was the skull base. Stereotactic radiosurgery was the primary treatment modality in 16 (32%) patients with symptomatic tumors demonstrated by neuroimaging. Thirty-six patients (72%) had undergone at least one craniotomy, and 4 patients (8%) previously had fractionated external beam radiation therapy. The proximity of cranial nerves, vascular, pituitary and brainstem structures to the often convoluted tumor mass was crucial to dose selection. Follow-up imaging studies and clinical analysis of patients were performed at 6-month intervals. The actuarial 2-year tumor control rate was 96%. Only 2 patients have shown delayed tumor growth outside the radiosurgical treatment volume. To date, stereotactic radiosurgery proved to be a relatively safe and effective therapy for selected patients with symptomatic meningiomas, either as an adjuvant treatment to prior resection, or as a primary treatment alternative for patients whose advanced age, medical condition or high-risk tumor location mitigated against surgical resection.

Adolescent↗
PubMed1991

Dose-volume considerations in radiosurgery.

Dose-volume effects are very important in radiosurgery. Functional radiosurgery illustrates brain tolerance at the extremes of small volumes and high radiation doses. The risks of radiation necrosis from radiosurgery of arteriovenous malformations (AVMs) and tumors appear to be reasonably well predicted by the integrated logistic formula and the 1% dose-volume isoeffect line for proton beam irradiation. The two main exceptions to this rule are cranial nerves, which appear to be more sensitive than the rest of the brain, and angiographically occult vascular malformations, where complications appear to occur at lower doses/volumes than in the treatment of tumors or AVMs. Further investigation is needed to better predict complications throughout the entire range of volumes, radiation doses, treatment locations and techniques presently used in stereotactic radiosurgery.

Brain↗
PubMed1991

Predicted dose-volume isoeffect curves for stereotactic radiosurgery with the 60Co gamma unit.

Mathematical models were developed to predict tolerance of brain tissue to stereotactic radiosurgery. The use of these formulas for predicting symptomatic brain necrosis from stereotactic radiosurgery with the 60Co gamma unit is discussed. Predicted dose-response curves for different collimator sizes were calculated. Dose-volume isoeffect curves for a 3% risk of brain necrosis from a single fraction radiosurgery were then derived. Dose-volume isoeffect curves for combinations of fractionated whole brain irradiation with radiosurgery boosts were also calculated. The predicted dose-volume isoeffect curves provide useful tolerance guidelines for the practice of stereotactic radiosurgery.

Brain↗
PubMed1991

Stereotactic radiosurgery of meningiomas.

Stereotactic radiosurgery has an expanding role in the management of selected intracranial tumors. In an initial 30-month experience using the 201-source cobalt-60 gamma knife at the University of Pittsburgh, 50 patients with meningiomas were treated. The most frequent site of origin was the skull base. Previously, 36 patients (72%) had undergone at least one craniotomy and four patients (8%) had received fractionated external beam radiation therapy. Stereotactic radiosurgery was the primary treatment modality in 16 patients (32%) with symptomatic tumors demonstrated by neuroimaging. Computer imaging-generated isodose plans (with one to five irradiation isocenters) for single-treatment irradiation gave optimal (greater than or equal to 50% isodose line) coverage in 44 patients (88%). The proximity of cranial nerves or vascular, pituitary, and brain-stem structures to the often convoluted tumor mass was crucial to dose selection. Serial imaging studies were evaluated in all 50 patients. Twenty-four patients were examined between 12 and 36 months after treatment; 13 (54%) showed a reduction in tumor volume while nine (38%) showed no change. Of 26 patients evaluated between 6 and 12 months after treatment, four showed a decrease in tumor size while 22 showed no change. Two patients (both with large tumors that received suboptimal irradiation) had delayed tumor growth outside the radiosurgical treatment volume. The actuarial 2-year tumor growth control rate was 96%. Between 3 and 12 months after radiosurgery, three patients developed delayed neurological deficits that gradually improved, compatible with delayed radiation injury. Although extended follow-up monitoring over many years will be necessary to fully evaluate treatment, to date stereotactic radiosurgery has proved to be a relatively safe and effective therapy for selected patients with symptomatic meningiomas, including those who failed surgical resection. Radiosurgery was an effective primary treatment alternative for those patients whose advanced age, medical condition, or high-risk tumor location mitigated against surgical resection.

Adolescent↗
PubMed1991

Stereotactic radiosurgery for arteriovenous malformations of the brain.

Stereotactic radiosurgery successfully obliterates carefully selected arteriovenous malformations (AVM's) of the brain. In an initial 3-year experience using the 201-source cobalt-60 gamma knife at the University of Pittsburgh, 227 patients with AVM's were treated. Symptoms at presentation included prior hemorrhage in 143 patients (63%), headache in 104 (46%), and seizures in 70 (31%). Neurological deficits were present in 102 patients (45%). Prior surgical resection (resulting in subtotal removal) had been performed in 36 patients (16%). In 47 selected patients (21%), embolization procedures were performed in an attempt to reduce the AVM size prior to radiosurgery. The lesions were classified according to the Spetzler grading system: 64 (28%) were Grade VI (inoperable), 22 (10%) were Grade IV, 90 (40%) were Grade III, 43 (19%) were Grade II, and eight (4%) were Grade I. With the aid of computer imaging-integrated isodose plans for single-treatment irradiation, total coverage of the AVM nidus was possible in 216 patients (95%). The location and volume of the AVM were the most important factors for the selection of radiation dose. Magnetic resonance (MR) imaging was performed at 6-month intervals in 161 patients. Seventeen patients who had MR evidence of complete obliteration underwent angiography within 3 months of imaging: in 14 (82%) complete obliteration was confirmation being 4 months (mean 17 months) after radiosurgery. The 2-year obliteration rates according to volume were: all eight (100%) AVM's less than 1 cu cm; 22 (85%) of 26 AVM's of 1 to 4 cu cm; and seven (58%) of 12 AVM's greater than 4 cu cm. Magnetic resonance imaging revealed postirradiation changes in 38 (24%) of 161 patients at a mean interval of 10.2 months after radiosurgery; only 10 (26%) of those 38 patients were symptomatic. In the entire series, two patients developed permanent new neurological deficits believed to be treatment-related. Two patients died of repeat hemorrhage at 6 and 23 months after treatment during the latency interval prior to obliteration. Stereotactic radiosurgery is an important method to obliterate AVM's, especially those previously considered inoperable. Success and complication risks are related to the AVM location and the volume treated.

Adolescent↗
PubMed1990

Stereotactic radiosurgery of small intracranial tumors: neuropathological correlation in three patients.

The mechanism by which radiosurgery can stop the growth of some tumors is poorly understood, in part because postmortem neuropathological findings in patients have been reported only rarely. To define further the effects of radiosurgery, we present the correlation among clinical, neuroimaging, and neuropathological data in three patients with different intracranial tumors who died between 2 and 39 weeks after radiosurgery. The target volumes in two patients with malignant tumors showed sharply demarcated coagulative necrosis. In the third patient, who had a benign acoustic nerve tumor, neuropathological examination found intratumoral hemorrhage and cyst formation, but no necrosis. Radiosurgery appears to cause acute necrosis of malignant cells, although its effectiveness may be limited by the infiltrative nature of some tumors. In benign tumors, necrosis following radiosurgery is relatively delayed, and may not be required for growth arrest.

Adenocarcinoma↗
PubMed1990

Use of normalized total dose to represent the biological effect of fractionated radiotherapy.

There are currently a number of radiobiological models to account for the effects of dose fractionation and time. Normalized total dose (NTD) is not another new model but is a previously reported, clinically useful form in which to represent the biological effect, determined by any specific radiobiological dose-fractionation model, of a course of radiation using a single set of standardized, easily understood terminology. The generalized form of NTD reviewed in this paper describes the effect of a course of radiotherapy administered with nonstandard fractionation as the total dose of radiation in Gy that could be administered with a given reference fractionation such as 2 Gy per fraction, 5 fractions per week that would produce an equivalent biological effect (probability of complications or tumor control) as predicted by a given dose-fractionation formula. The use of normalized total dose with several different exponential and linear-quadratic dose-fraction formulas is presented.

Humans↗
PubMed1990

Radiosurgery and the double logistic product formula.

The double logistic product formula is proposed as a method for predicting the probability of developing brain necrosis after high dose irradiation of small target volumes as used in stereotactic radiosurgery. Dose-response data observed for the production of localized radiation necrosis for treating intractable pain with the original Leksell gamma unit were used to choose the best fitting parameters for the double logistic product formula. This model can be used with either exponential or linear quadratic formulas to account for the effects of dose, fractionation and time in addition to volume. Dose-response predictions for stereotactic radiosurgery with different sized collimators are presented.

Brain↗
PubMed1990

Shielding requirements on-site loading and acceptance testing on the Leksell gamma knife.

On August 14, 1987, the first stereotactic radiosurgical procedure using the gamma knife was performed in North America. Located in a self-contained radiosurgical suite in the basement of Presbyterian-University Hospital in Pittsburgh, Pennsylvania. This device uses 201 highly focused beams 60Co for the single-treatment closed-skull irradiation of brain lesions localized by stereotactic techniques (radiosurgery). One hundred and fifty-two patients with intracranial arteriovenous malformations or brain tumors were treated in the first year of operation. The Presbyterian University Hospital of Pittsburgh gamma knife is the first such unit in which the 60Co sources were loaded on-site. This effort required us to solve some difficult and unusual problems encountered during site preparation, delivery, and loading of the unit in a busy hospital setting. The solutions developed enabled installation and use of the gamma knife with minimal disruption of hospital activities while maintaining acceptable levels of exposure to radiation. Environmental surveys performed during the loading of the 201 radioactive sources (total, 219 TBq) confirmed that on-site loading is possible and practical. Our experience in the design, construction, and implementation of the first North American gamma knife supports the practicality and safety of on-site loading and may be of value in the planning and development of future gamma knife installations.

Brain Neoplasms↗
PubMed1990

Megavoltage external beam irradiation of craniopharyngiomas: analysis of tumor control and morbidity.

From 1971 to 1985, 21 patients received megavoltage external beam radiation therapy at the University of Pittsburgh for control of craniopharyngioma. Minimum tumor doses prescribed to the 95% isodose volume ranged between 51.3 to 70.0 Gy. Median total dose was 60.00 Gy and median dose per fraction was 1.83 Gy. Three deaths occurred from intercurrent disease and no deaths from tumor progression. Actuarial overall survival was 89% and 82% at 5 and 10 years. Actuarial local control was 95% at 5 and 10 years. Radiation related complications included one patient with optic neuropathy, one with brain necrosis, and one that developed optic neuropathy followed by brain necrosis. The high dose group of patients who received a NSD or Neuret equivalent of greater than 60 Gy at 1.8 Gy per fraction had a significantly greater risk of radiation complications (p = .024). The actuarial risk at 5 years for optic neuropathy was 30% and brain necrosis was 12.5% in the high dose group. Tumor control in the high dose group was not shown to be significantly better. Any possible benefit in tumor control in treating patients with craniopharyngioma with doses above 60 Gy at 1.8 Gy per fraction appears to be offset by the increased risk of radiation injury.

Adolescent↗
PubMed1990

Estimation of complications for linear accelerator radiosurgery with the integrated logistic formula.

Radiosurgery techniques permit high doses of single fraction irradiation to be administered to small volumes of tumor with relative sparing of surrounding brain tissue. The tolerance of surrounding normal brain tissue to dose distributions from linear accelerator radiosurgery with different collimator sizes is an important factor that must be estimated by anyone using these treatment techniques. The exponential and linear quadratic versions of the integrated logistic formula were used to estimate the probability of brain necrosis at different doses for radiosurgical dose distributions administered by a 6 MV linear accelerator with a 5 arc technique for collimator sizes from 12.5 to 30 mm in diameter. Dose-volume isoeffect curves for a 3% risk of brain necrosis from linear accelerator radiosurgery were then calculated. These curves approximate those calculated for gamma knife radiosurgery and a published 1% dose-volume isoeffect line predicted for proton beam irradiation. Similar dose-volume isoeffect curves were calculated for single fraction radiosurgery boosts administered after 30 Gy of whole brain irradiation in 12 fractions. The integrated logistic formula appears to be a useful tool for estimating tolerance and providing guidelines for prescribing radiation doses for linear accelerator radiosurgery.

Brain Diseases↗
PubMed1990

Treatment planning for gamma knife radiosurgery with multiple isocenters.

Many arteriovenous malformations and tumors suitable for radiosurgical treatment have non-spherical or irregular shapes. Forty-eight percent of the first 156 patients treated with the gamma unit at the University of Pittsburgh required treatment with two or more isocenters to optimize dose distributions. Dose distributions for combining gamma knife treatments to two or more isocenters were systematically investigated. High speed computerized dosimetry was performed using specially developed software and dose distributions were confirmed with film densitometry. We have developed guidelines for treatment to two or more isocenters which help reduce treatment planning time, and facilitate selection of treatment doses and optimum dose distributions. These guidelines include maintaining an account of the distances between all isocenters, using a catalogue of sample two-isocenter isodose plans, comparing dose volume histograms, and calculating complication probabilities using the integrated logistic formula.

Cobalt Radioisotopes↗
PubMed1990

Physics of gamma knife approach on convergent beams in stereotactic radiosurgery.

The Presbyterian-University Hospital of Pittsburgh installed the first clinically designated Leksell gamma knife in the U.S. in August 1987. Gamma knife radiosurgery involves stereotactic target localization with the Leksell frame and subsequent closed-skull single-treatment session irradiation of a lesion with multiple highly focused gamma ray beams produced from 60Co sources. The hemispherical array of sources, the large number of small-diameter beams, and the steep dose gradients surrounding a targeted lesion make physical characterization of the radiation field complex. This paper describes the physical features and the operation of the gamma knife as well as the calibration procedures of the very small, well-collimated beams. The results of studies using in-phantom ion chamber, diode, film, and lithium fluoride thermoluminescent dosimetry were all in close agreement. Both single-beam and multiple-beam dose profiles were measured and reported for the interchangeable helmets, which have 4-, 8-, 14-, and 18-mm-diameter collimators. We also describe the dose calculation and treatment planning algorithm in the treatment planning system. Measurements of the accuracy of mechanical and radiation alignment are also performed and discussed.

Brain Diseases↗
PubMed1990

Treatment volume shaping with selective beam blocking using the Leksell gamma unit.

The Leksell gamma unit at the University of Pittsburgh uses 201 highly focused 60Co beams arranged in a hemispherical array. Selective beam blocking can be used to modify the treatment volume into ellipsoid shapes oriented in different directions to match better the shape of the target volume. Dose distributions for different blocking patterns were calculated using specially developed computerized 3-D treatment planning software. The changes in dose distribution with different blocking patterns predicted by computer were verified by film densitometry. Techniques for using selective beam blocking to match more closely the treatment volume to the intended target volume have the potential of reducing the likelihood of complications for radiosurgery with the Leksell gamma unit and need to be further developed.

Brain Neoplasms↗