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J C Flickinger

Publications and source records attributed to J C Flickinger.

At least 145 records · Page 8Linked to original sources
PubMed1993

Intraparenchymal brain stem radiosurgery.

Stereotactic radiosurgery using the gamma unit has been used to manage patients with brain stem tumors or vascular malformations as an alternative to microsurgical resection. Whether associated with the pial or ependymal brain stem surface or within the brain stem parenchyma proper, radiosurgery provides relatively safe and effective management. Radiosurgery is a valuable alternative for many patients with pathologic lesions of the brain stem and may represent the only surgical option for some patients.

Adolescent↗
PubMed1992

Radiosurgery and brain tolerance: an analysis of neurodiagnostic imaging changes after gamma knife radiosurgery for arteriovenous malformations.

In order to analyze complications and the factors responsible for the development of serial imaging changes after stereotactic radiosurgery for intracranial arteriovenous malformations, we reviewed serial post-treatment magnetic resonance imaging scans in 72 patients. Median follow-up was 23 months (range 12 to 35 months). Twenty patients developed post-radiosurgical imaging changes consisting of new regions of increased T2 signal on magnetic resonance imaging in brain surrounding the arteriovenous malformation (two year actuarial incidence of 31%). Imaging changes were associated with headache or new neurological deficits in nine of these 20 (45%) and remained asymptomatic in 11 (55%). Symptoms developed in three of 13 patients with imaging changes in the cerebral cortex or cerebellum, in contrast to six of seven patients who had symptoms with imaging changes in the brainstem (p = .028). The onset of imaging changes varied from five to 18 months after radiosurgery (median, 12 months). Serial follow-up scans four to 25 months after the onset of imaging changes were available for review in 16 patients. Post-radiosurgical imaging changes completely resolved within 4 to 19 months in ten patients and have not yet completely resolved after 6 to 25 months in six patients. The projected actuarial rate for resolution of imaging changes was 88%, 19 months after onset; the median time for resolution was 14 months. Univariate analysis revealed that the development of imaging changes was significantly associated with treatment volume (p = .025), the risk predicted from the integrated logistic formula (p = .042), and the number of isocenters treated (p = .042). In multivariate analysis, volume was the only factor significantly associated with the development of imaging changes.

Adolescent↗
PubMed1992

Radiobiology of radiosurgery: Part I. The normal rat brain model.

Because limited histological information is available from clinical radiosurgical experience, animal investigations are needed to answer questions regarding the biological response of both normal and pathological tissues. To determine the radiosurgical dose-response relationship of normal brain, we irradiated the right frontal lobe of 18 rats with a single 4-mm isocenter of stereotactic irradiation using the 201-source 60Co gamma unit. Maximal single-fraction doses varied from 30 to 200 Gy (2 rats per dose). All animals were observed for 90 days, killed, and histologically examined. No animal developed neurological dysfunction during that interval, regardless of dose. Animals that received 30, 40, 50, or 60 Gy had no pathological changes. In those given 70 Gy, we found occasional shrunken neurons, and at 80 Gy, rare arteriolar wall thickening. One animal that received 100 Gy had marked capillary endothelial cell degeneration and protein extravasation in the target volume, and the other had a 4-mm diameter necrotic region. Circumscribed cerebral necrosis also was identified in all 4 rats treated with either 150 or 200 Gy; astrocytosis, edema, and microhemorrhage were noted within the surrounding 1 to 2 mm of adjacent brain, and tissue outside that volume had a more normal appearance. We constructed a dose-response relationship based on the cellular, spatial, and temporal effects of focused single-fraction irradiation of the rat brain. To determine the temporal evolution of a known necrotic lesion (200 Gy), 12 other animals were killed (2 each) 1, 7, 14, 21, 30, or 60 days after radiosurgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Radiobiology of radiosurgery: Part II. The rat C6 glioma model.

We developed an experimental animal model to evaluate the potential role of stereotactic radiosurgery for glial neoplasms. Rats were randomized to control or treatment groups after implantation of C6 glioma cells into the right frontal region; 14 days later, 19 rats underwent stereotactic radiosurgical treatment of the induced tumor, using the 4-mm collimator of the gamma unit. Both groups were observed for up to 65 days after implantation. Treated animals had a mean survival of 39.2 days; the 22 control animals lived a mean of 29.4 days before death from tumor growth (P = 0.07). Six treated animals (32%), but only one control animal, survived the full observation period (P = 0.07). The mean tumor diameter in the control group was 9.64 mm; in the radiosurgery group, it was 6.47 mm (P = 0.001). Compared with tumors in control animals, treated tumors had a hypocellular appearance (P less than 0.001) and demonstrated cellular edema (P less than 0.005) under light microscopy, indicating a direct cytotoxic response to treatment. No difference was identified in the amount of tumor necrosis, intratumor hemorrhage, or degree of brain invasion between the two groups. Variations in the maximum treatment dose (30, 40, 50, 70, or 100 Gy) did not result in observed differences in tumor response. This in vivo rat malignant glioma model is a valuable tool to evaluate the tumoricidal effects of single-fraction, focused irradiation. Additional studies are warranted to evaluate dose-response relationships, radiation sensitizers, and use of radiosurgery with other adjuvant treatments.

Animals↗
PubMed1992

Tumor control after stereotactic radiosurgery in neurofibromatosis patients with bilateral acoustic tumors.

During a 4-year interval, 17 patients with bilateral acoustic tumors (vestibular schwannomas) underwent unilateral stereotactic radiosurgery using a multisource gamma unit; 2 patients underwent radiosurgery of both tumors in separate sessions. Eleven patients with unoperated contralateral tumors served as concurrent controls to compare the effects of radiosurgery with the natural history of acoustic tumors. After radiosurgery, the tumor control and regression rates were 89.5 and 21.1%, respectively (median neuroimaging follow-up, 1.4 years; range, 0.3-3.9). The tumor regression rate increased to 40% for patients evaluated at least 12 months after radiosurgery. In comparison to the unoperated contralateral tumors, stereotactic radiosurgery achieved tumor control, as assessed by the ultimate change in tumor size at follow-up (P, 0.012), the change in tumor size over time (P, 0.006), and tumor growth rates (P, 0.003). This study provided convincing evidence that tumor stabilization after radiosurgery (as assessed by neuroimaging) truly represented tumor control. The incidence of delayed facial neuropathy after radiosurgery compared favorably with the incidence reported after microsurgical removal. Some hearing was preserved in one-third of the patients who had preoperative hearing, including three patients who were contralaterally deaf. Stereotactic radiosurgery should be considered as a primary surgical modality for many patients with neurofibromatosis Type II.

Adolescent↗
PubMed1992

Radiotherapy of lymphoproliferative diseases of the orbit. Surveillance of 65 cases.

Sixty-five patients with lymphoproliferative disease of the orbit were treated at the Joint Radiation Oncology Center of the University of Pittsburgh. An analysis of these patients was stratified by their initial tumor histopathology: benign lymphoid hyperplasia (BLH) in 28, malignant lymphoma (ML) in 20, and lymphoid infiltrate of indeterminate histology (IH) in 17. The median follow-up was 42 months. Radiation treatment was efficacious in all three groups of patients. The actuarial local recurrence-free survival rate is 84%. Treatment programs usually consisted of 20 to 30 Gy delivered in 10 to 15 fractions. ML patients had significantly lower overall and disease-specific survival rates than IH and BLH patient (p less than or equal to 0.02). BLH patients had a significantly lower local recurrence-free survival than patients with IH and BLH (p = 0.03). There was no significant difference between the three groups of patients with regard to the subsequent development of systemic lymphoma. There were no significant differences in local (16%) or systemic (36%) relapse between patients irradiated with less than 30 Gy or greater than or equal to 30 Gy. Cataracts were detected in 46% of the patients treated with anterior-posterior fields, but none were detected in those treated with other techniques. The results of this study emphasize the importance of long-term follow-up and careful treatment planning for patients with lymphoproliferative diseases of the orbit.

Adolescent↗
PubMed1992

Stereotactic radiosurgery: current spectrum and results.

Stereotactic radiosurgery has an important role as primary or adjuvant therapy for selected cerebral vascular malformations and brain tumors. Over the next decade, both extended clinical experience, basic radiobiologic studies, and improvements in dose planning are expected to enhance its overall efficacy and safety.

Adult↗
PubMed1992

Stereotactic radiosurgery for acoustic tumors.

Stereotactic radiosurgery is an important alternative treatment for carefully selected patients with acoustic tumors. We perform radiosurgery under local anesthesia, and 91% of our patients have been discharged from the hospital within 24 hours after treatment. All returned to their preoperative level of function or employment within 5 to 7 days after treatment. Our current tumor control rate is 97%, but reduction in tumor size, judged by strict, objective criteria, was achieved in only 23%. Our actuarial rate of useful hearing preservation after radiosurgery is 38% at 1 year. Three tumors increased in size after treatment. Only one of the three demonstrated increased mass effect on surrounding brain structures by neuroimaging criteria. No increase has led to worsened clinical symptoms or has required surgical excision at this point in follow-up. The 1-year rates for developing new facial or trigeminal neuropathies after radiosurgery were 30% and 33%, respectively. Cranial neuropathies had a delayed onset, with the median onset occurring after 5 to 6 months. The vast majority were partial at onset, and most improved over time. Communicating hydrocephalus requiring ventriculoperitoneal shunts developed after radiosurgery in four patients. Eight patients developed increased signal within adjacent brain parenchyma on T2-weighted MR imaging, consistent with edema or blood-brain barrier breakdown. It is unlikely that stereotactic radiosurgery using the gamma knife will obviate the need for microsurgical removal performed by skilled and experienced microsurgeons. However, radiosurgery is a safe and effective treatment for patients whose medical problems make surgery unacceptably dangerous, those with bilateral tumors or a tumor in their only hearing ear, those who have recurrent tumor despite surgical resection, or patients who refuse microsurgical excision.

Adolescent↗
PubMed1992

Gamma knife surgery for sellar and suprasellar tumors.

Recent advances in neuroimaging, coupled with stereotactic delivery of ionizing radiation, permit precise, single-treatment irradiation of various intracranial tumors. This article describes the authors' experience with the 201-source 60Co gamma knife. Initial results indicate a potential therapeutic role for radiosurgery in controlling tumor growth and hormone hypersecretion in most patients. The authors believe that radiosurgery should be considered for small pituitary adenomas when prior microsurgery has failed to control tumor growth. Radiosurgery is a primary treatment alternative for patients who are elderly, medically infirm, or refuse microsurgical removal. Further follow-up is necessary to evaluate the long-term tumor control rate, hormonal effects, and tolerance of surrounding critical structures to stereotactic radiosurgery.

Adenoma↗
PubMed1992

The role of radiosurgery in the treatment of malignant brain tumors.

Most studies describing the results of radiosurgery have concentrated on the definitive treatment of small, histologically benign lesions such as vascular malformations, acoustic neurinomas, and pituitary adenomas. More recently, the role of radiosurgery using the gamma knife or LINAC-based systems to treat malignant neoplasms has become better defined. Most solitary metastases, ependymomas, well-circumscribed (on imaging studies) AAs, and a few glioblastomas (and other tumors) have responded dramatically to radiosurgery. Provided that the tumor volume was small (less than or equal to 14 cm3; 30-mm diameter), radiosurgery safely has caused tumor disappearance, shrinkage, or stabilization, regardless of prior surgery, conventional fractionated irradiation, or tumor radioresistance. For patients with recurrent or persistent, small, malignant intracranial tumors, radiosurgical treatment has obviated the need for prolonged hospitalization and has eliminated the risks associated with general anesthesia and open craniotomy.

Adolescent↗
PubMed1992

Dose prescription and dose-volume effects in radiosurgery.

The optimal use of radiosurgery as a treatment technique requires thorough planning, including careful fitting of the high-dose treatment volume to the target volume, and an understanding of the effects of high-dose single-fraction irradiation on both the target volume and the surrounding normal brain. The integrated logistic formula appears to be useful as an aid for predicting the risks of complications from radiosurgery, but greater understanding of the radiation tolerance for all the different areas of the brain (particularly the cranial nerves) is needed. The risk of developing MR imaging-defined changes after radiosurgery for AVMs was significantly related to predictions from the integrated logistic formula. The obliteration rate of AVMs after radiosurgery was volume dependent. Our assessment of the integrated logistic formula to date also indicates that it provides a reasonable guide for predicting complications in the radiosurgical treatment of meningiomas and in the treatment of solitary brain metastases using a combination of fractionated whole-brain irradiation and radiosurgery. The formula did not adequately predict complications in the treatment of AOVMs, however. In the treatment of acoustic tumors, the risks of injury to cranial nerves V, VII, and VIII clearly varied with treatment volume. Further data are needed to fully understand the therapeutic dose-response functions and volume effects for the obliteration of AVMs, the prevention of rebleeding from AOVMs, and growth arrest of meningiomas and acoustic neuromas.

Brain Neoplasms↗
PubMed1992

Radiobiologic models for radiosurgery.

A series of initial radiobiologic investigations have been performed using three animal models. The baboon model proved to be a valuable technique to assess the in vivo radiobiologic response of single-fraction irradiation doses delivered to the primate brain stem. Multimodality neurodiagnostic testing, including CT, MR imaging, xenon-enhanced CT, evoked potential studies, and analysis of CSF myelin basic protein levels, all of which eventually were correlated with neuropathologic examination, enabled detection of lesions produced with high-dose (150 Gy) radiosurgery as early as 6 weeks. Within the first 6 months after radiosurgery, lower doses (20 Gy, 50 Gy) did not result in clinically or neurodiagnostically detectable lesions. The rat arteriovenous fistula model permits analysis of the delayed histopathologic effects of radiosurgery on an experimentally created fistula designed to mimic an AVM. The rat C6 glioma model is designed to evaluate the effect of radiosurgery in an infiltrative tumor that simulates a human malignant brain tumor. These studies are intended eventually to increase our knowledge about the safety and efficacy of radiosurgery in both the normal and tumor-implanted brains. We believe that such fundamental studies ultimately will improve our ability to reach the goals of radiosurgery: to destroy the target and spare the surrounding brain. Eventually, it may become feasible to achieve these goals by combining radiosurgical technique with both radiation sensitizers (for the treated volume) and brain protectors.

Animals↗
PubMed1992

Stereotactic radiosurgery of brain vascular malformations.

Stereotactic radiosurgery using the gamma unit was performed in 251 patients with brain vascular malformations in a 3-year interval. Our efforts include the identification of factors related to both success and complications, including analysis of the malformation location, volume, and dose used. Radiosurgery is a valuable alternative treatment for many patients with brain vascular malformations, including those currently believed to be poor surgical candidates.

Adolescent↗
PubMed1991

Radiation therapy for primary carcinoma of the extrahepatic biliary system. An analysis of 63 cases.

From 1976 to 1988, 63 patients received radiation therapy for primary cancers of the extrahepatic biliary system (eight gallbladder and 55 extrahepatic biliary duct). Twelve patients underwent orthotopic liver transplantation. Chemotherapy was administered to 13 patients. Three patients underwent intraluminal brachytherapy alone (range, 28 to 55 Gy). Sixty patients received megavoltage external-beam radiation therapy (range, 5.4 to 61.6 Gy; median, 45 Gy), of whom nine received additional intraluminal brachytherapy (range, 14 to 45 Gy; median, 30 Gy). The median survival of all patients was 7 months. Sixty patients died, all within 39 months of radiation therapy. One patient is alive 11 months after irradiation without surgical resection, and two are alive 50 months after liver transplantation and irradiation. Symptomatic duodenal ulcers developed after radiation therapy in seven patients but were not significantly related to any clinical variable tested. Extrahepatic biliary duct cancers, the absence of metastases, increasing calendar year of treatment, and liver transplantation with postoperative radiation therapy were factors significantly associated with improved survival.

Bile Duct Neoplasms↗
PubMed1991

Radiosurgery of acoustic neurinomas.

Eighty-five patients with acoustic neurinomas underwent stereotactic radiosurgery with the gamma unit at the University of Pittsburgh (Pittsburgh, PA) during its first 30 months of operation. Neuroimaging studies performed in 40 patients with more than 1 year follow-up showed that tumors were smaller in 22 (55%), unchanged in 17 (43%), and larger in one (2%). The 2-year actuarial rates for preservation of useful hearing and any hearing were 46% and 62%, respectively. Previously undetected neuropathies of the trigeminal (n = 12) and facial nerves (n = 14) occurred 1 week to 1 year after radiosurgery (median, 7 and 6 months, respectively), and improved at median intervals of 13 and 8 months, respectively, after onset. Hearing loss was significantly associated with increasing average tumor diameter (P = 0.04). No deterioration of any cranial nerve function has yet developed in seven patients with average tumor diameters less than 10 mm. Radiosurgery is an important treatment alternative for selected acoustic neurinoma patients.

Adolescent↗
PubMed1991

Solitary brain metastasis: radiosurgery in lieu of microsurgery in 32 patients.

Thirty-two consecutive patients with 34 small brain metastases underwent boost stereotactic radiosurgery using the first North American Gamma Unit between May 1988 and July 1990. The majority of tumors (n = 24; 71%) were considered resistant to conventional, fractionated irradiation (malignant melanoma, n = 13; non-small cell lung carcinoma, n = 7; renal cell carcinoma, n = 4). During the follow-up period (median = 10 months; range = 1.5-15 months) no patient suffered a complication of radiosurgical treatment, and no patient died from a radiosurgically-treated metastasis. Shrinkage or growth-arrest was documented in 20 of 23 patients (87%) available for follow-up. Median survival after treatment was 10 months.

Adolescent↗
PubMed1991

Radiosurgery for solitary brain metastases using the cobalt-60 gamma unit: methods and results in 24 patients.

To define the role of stereotactic radiosurgery in the treatment of metastatic brain tumors we treated 24 consecutive patients (20 men, 4 women) with the 201-source 60Co gamma unit between May 1988 and March 1990. The primary tumors included malignant melanoma (n = 10), non-small cell lung carcinoma (n = 6), renal cell carcinoma (n = 3), colorectal carcinoma (n = 1), oropharyngeal carcinoma (n = 1), and adenocarcinoma of unknown origin (n = 3). All tumors were less than or equal to 3.0 cm in greatest diameter. Twenty patients received a planned combination of 30-40 Gy whole brain fractionated irradiation and a radiosurgical "boost" of 16-20 Gy to the tumor margins; one patient refused conventional fractionated irradiation. Three patients with recurrent, persistent, or new non-small cell lung carcinomas had radiosurgical treatment 12-20 months after receiving 30-42.5 Gy whole-brain external beam irradiation. Stereotactic computed tomographic imaging was used for target coordinate determination and imaging-integrated dose planning. All tumors were enclosed by the 50-90% isodose shell using one (n = 22), two (n = 1), or three (n = 1) irradiation isocenters. During this 23-month period (median follow-up of 7 months) no patient died from progression of a radiosurgically-treated brain metastasis. Ten patients died of systemic disease (n = 8) or remote central nervous system metastasis (n = 2) between 1 week and 10 months after radiosurgery. One patient had tumor progression and underwent craniotomy and tumor excision 5 months after radiosurgery. To date, median survival after radiosurgery has been 10 months; 1-year survival was 33.3%. Stereotactic radiosurgery eliminated the surgical and anesthetic risks associated with craniotomy and resection of solitary brain metastases. Radiosurgery also effectively controlled the growth of tumors considered "resistant" to conventional irradiation.

Adult↗