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Robert J. Coffey, Terrence L. Cascino and Edward G. Shaw

✓ Hemangiopericytomas of the meninges, classified previously as angioblastic meningiomas, have a propensity to recur either locally or at distant sites within the nervous system after surgical resection. Visceral metastases also develop much more commonly in these lesions than in other types of histologically benign meningiomas. The radiosurgical gamma knife was used to treat five patients with 11 meningeal hemangiopericytomas (seven new, two recurrent, and two residual tumors) after surgical resection of an initially solitary intracranial lesion. Three patients had undergone multiple craniotomies and radiation therapy before referral, and two patients underwent a second radiosurgical procedure for lesions that appeared between 5 and 13 months after the first treatment session. Dramatic tumor shrinkage occurred in most patients within 6 to 10 months after treatment. The only treatment-related morbidity in this series was a partial visual-field defect in one patient with a large falx-tentorial junction hemangiopericytoma who had previously undergone radiation therapy. Radiosurgery appears to cause dramatic early shrinkage of small and medium-sized intracranial hemangiopericytomas that have recurred or developed after previous surgery and/or radiation therapy.

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Resection for solitary brain metastasis

Role of adjuvant radiation and prognostic variables in 229 patients

Stephen R. Smalley, Edward R. Laws Jr., Judith R. O'Fallon, Edward G. Shaw and Mark F. Schray

✓ The authors reviewed 229 consecutive patients treated intramurally by resection of solitary cerebral metastasis. Patients were classified into four groups on the basis of whether a gross total resection or subtotal resection was performed and whether systemic disease was present or absent at the time of craniotomy. Group 1 had gross total resection and no systemic disease; Group 2 had subtotal resection and no systemic disease; Group 3 had subtotal resection and systemic disease; and Group 4 had gross total resection and systemic disease. All four groups were further subdivided into Subgroup A (adjuvant whole-brain radiation therapy) or Subgroup B (no adjuvant radiation). Data were collected regarding multiple patient and tumor variables for multivariate analysis. Survival data for the 46 patients in Group 1A (median 1.3 years, 2-year survival rate 41%, 5-year survival rate 21%) were markedly better than those for the 75 in Group IB (median 0.7 year, 2-year survival rate 19%, 5-year survival rate 4%). The 20 patients in Group 2A also had superior survival data (median 1.1 years, 2-year survival rate 30%, 3-year survival rate 30%) when compared with the eight patients in Group 2B (median 3 months, 1-year survival rate 0%). However, the 16 and 22 patients in Groups 3A and 4A, respectively, had no discernible differences compared to the seven and 35 patients in their Group 3B and 4B counterparts. Multivariate analyses were performed to assess the association of survival with multiple patient, disease, and treatment variables. Poor neurological status and systemic disease were significantly associated with inferior survival, while longer (> 36 months) intervals between primary diagnosis and craniotomy were significantly associated with improved survival. After adjusting for the effects of other patient, disease, and treatment characteristics, adjuvant whole-brain radiotherapy was significantly associated with improved survival times. These data support the continued use of craniotomy followed by adjuvant wholebrain radiation therapy for treatment of solitary brain metastasis. However, this aggressive therapy appears relatively contraindicated in the face of either systemic disease or substantial neurological deficit.

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Edward G. Shaw, Bernd W. Scheithauer, Judith R. O'Fallon, Henry D. Tazelaar and Dudley H. Davis

✓ Eighty-one patients with pure supratentorial oligodendrogliomas underwent surgery alone (19 patients) or surgery plus postoperative radiation therapy (63 patients) between the years 1960 and 1982. The median survival time and the 5-, 10-, and 15-year survival rates for these 82 patients were 7.1 years, 54%, 34%, and 24%, respectively; these values were significantly different from those for an age- and sex-matched normal reference population. Univariate and multivariate survival analyses were performed on 13 possible prognostic factors including: patient age and sex; presence of seizures; site, size, side, computerized tomography (CT) enhancement, grade, and calcification of the tumor; and treatment (extent of surgical resection, lobectomy, radiation dose, and radiation field). Of these factors, tumor grade as classified by the Kernohan and St. Anne-Mayo methods was most strongly associated with survival. Patients with Grade 1 or 2 tumors by either grading method had a median survival time and 5- and 10-year survival rates of approximately 9.8 years, 75%, and 46%, respectively, compared to 3.9 years, 41%, and 20% for those with Grade 3 or 4 tumors. The extent of surgical resection was also associated with survival. The 19 patients who underwent gross total resection of their tumor had a median survival time and 5- and 10-year survival rates of 12.6 years, 74%, and 59%, compared to 4.9 years, 46%, and 23%, respectively, for the 63 who had subtotal resection. When comparing the 19 patients who underwent surgery alone with the 63 who had surgery plus postoperative radiation therapy, there did not appear to be a survival benefit to be gained from the addition of postoperative radiation therapy. However, the patients who had surgery alone tended to have gross total resections and lower tumor grades. Analysis of the subset of 63 patients who underwent subtotal resection alone or with radiation therapy showed that the median survival time and 5- and 10-year survival rates were: 2 years, 25%, and 25% for the eight patients with subtotal resection alone; 4.5 years, 39%, and 20% for the 26 patients with surgery and low-dose (< 5000 cGy) radiation therapy; and 7.9 years, 62%, and 31% for the 29 patients receiving surgery and high-dose radiation therapy (≥ 5000 cGy), respectively.

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Kern J. Minehan, Edward G. Shaw, Bernd W. Scheithauer, Dean L. Davis and Burton M. Onofrio

✓ Seventy-nine patients underwent surgery, with or without radiation therapy, for astrocytoma of the spinal cord. There were 43 tumors (54%) classified as pilocytic astrocytoma and 25 (32%) as diffuse fibrillary astrocytoma. Eleven tumors (14%) could not be classified other than as astrocytoma, “type not otherwise specified.” The 10-year overall survival rate for all 79 patients was 50% but significantly differed by histological type: 81% for patients with pilocytic astrocytoma compared to 15% for those with diffuse fibrillary astrocytoma. Tumor grade by the Kernohan, et al., or St. Anne—Mayo methods was also a significant predictor of survival in patients with diffuse fibrillary astrocytoma. The extent of surgical resection (biopsy vs. subtotal resection vs. gross total resection) did not significantly impact survival among patients with pilocytic or nonpilocytic astrocytomas of the spinal cord, although there was a trend toward poorer survival in patients undergoing some degree of resection as opposed to biopsy. Postoperative radiation therapy improved survival but did so more for diffuse fibrillary astrocytoma than pilocytic astrocytoma.

In this series, histological type was the most significant predictor of survival in patients with astrocytoma of the spinal cord. The survival rate was highest in patients who underwent biopsy followed by postoperative radiation therapy.

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Interim report on the radiosurgical treatment of cerebral arteriovenous malformations

The influence of size, dose, time, and technical factors on obliteration rate

Yoshihiro Yamamoto, Robert J. Coffey, Douglas A. Nichols and Edward G. Shaw

✓ During the authors' initial 4-year experience with radiosurgery using the Leksell cobalt-60 gamma unit, they treated 121 patients with cerebral arteriovenous malformations (AVMs). The radiosurgical dose to the margin of the nidus was 20 Gy for lesions less than 2.0 cm in diameter (volume ≤ 4.2 cm3); 18 Gy for malformations 2.1 to 3.0 cm in diameter (volume 4.2–14.1 cm3); and 16 Gy for malformations greater than 3.0 cm (volume > 14.1 cm3). Fifty-one patients underwent follow-up angiography between 1 and 3 years after treatment, and complete obliteration of the nidus was confirmed in 38 (74.5%) of these patients. Thirty-two (74.4%) of 43 AVMs with volumes of 10 cm3 or less and six (75%) of eight larger AVMs (volume 11–30 cm3) showed complete obliteration. Analysis of the time course of AVM nidus shrinkage and obliteration showed that most of the radiosurgically induced effect had occurred by 36 months after treatment. Retrospective analysis of the dose plans for 10 AVMs that were not obliterated by 36 months after gamma knife radiosurgery at the authors' institution (eight cases) or elsewhere (two cases) revealed that six AVMs had not been covered completely by the prescribed isodose. Six (5%) of the 121 patients developed neurological deficits as a direct result of radiosurgical treatment.

The authors infer from these data that malformations up to 30 cm3 in volume (approximately 4.0 cm in average diameter) can be treated effectively with an acceptably low complication rate using a radiosurgical dose of 16 Gy to the margin of the nidus. The obliteration rate for the larger malformations that were treated with a dose of 16 to 18 Gy appears to be similar to that for smaller ones treated with 18 to 20 Gy. As more experience accrues using radiosurgery to treat AVMs, patient selection criteria and the variables associated with successful obliteration of the nidus should become more clearly defined.

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Stephen J. McGirr, Michael J. Ebersold, Bernd W. Scheithauer, Lynn M. Quast and Edward G. Shaw

✓ The medical records and histological specimens from 26 patients with choroid plexus papillomas operated on at one institution were reviewed retrospectively. Four patients died perioperatively, and 21 of the remaining 22 patients were followed through March, 1986; the patient lost to follow-up review was last seen 14 years postoperatively. Of the 14 patients who underwent gross total removal of their tumor, one had a recurrence at 11 years postoperatively and two died in the perioperative period. Of the 12 patients who underwent subtotal removal of their tumor, two died in the perioperative period. The two patients who did not have radiation therapy postoperatively are free of apparent disease at 6 and 8 years after their operation. Eight patients underwent radiation therapy after subtotal removal of their tumor; four of these remain alive and well, and four have died of progressive disease.

The role of irradiation in the treatment of subtotally resected lesion remains controversial, but this therapy is thought to be indicated for recurrent disease after a surgical excision that is as complete as possible. Histopathologically, the presence of occasional mitotic figures, microscopic infiltration, ependymal differentiation, or mild to moderate atypia was not correlated with likelihood of complete resectability or tendency to recurrence.

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Peter A. Forsyth, Terrence L. Cascino, Edward G. Shaw, Bernd W. Scheithauer, Judith R. O'Fallon, James C. Dozier and David G. Piepgras

✓ Fifty-one patients with intracranial chordomas who were surgically treated between 1960 and 1984 were studied. Median patient age was 46 years, and 73% presented with diplopia or headache. Nineteen tumors were classified as the “chondroid” type. The extent of surgical removal was a biopsy in 11 patients and subtotal removal or greater in 40. Thirty-nine patients received postoperative radiation therapy. At the time of analysis, 17 patients were alive, and the estimated 5- and 10-year survival rates were 51% and 35%, respectively, for the group of 51 patients. Univariate analysis showed that: 1) patients undergoing resection lived longer (the 5-year survival rate was 36% for the 11 biopsy patients compared with 55% for the 40 patients who had resection; 2) patients who underwent postoperative radiotherapy tended to have longer disease-free survival times; and 3) overall and disease-free survival data were the same for patients with chondroid tumors and those with typical chordomas. Multivariate analysis showed that: 1) age was the factor most strongly associated with longer overall and disease-free survival; 2) diplopia was associated with longer survival; and 3) tumoral mitotic activity tended to be associated with shorter disease-free survival. One tumor metastasized to the cervical cord, and two tumors underwent anaplastic transformation. These data suggest that the prognosis in patients with chordomas is unfavorable, young age is the single factor most strongly associated with longer survival, surgical resection is beneficial, and postoperative radiotherapy may prolong disease-free survival.

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Daniela Lombardi, Bernd W. Scheithauer, Fredric B. Meyer, Glenn S. Forbes, Edward G. Shaw, Donna J. Gibney and Jerry A. Katzmann

✓ Twenty-one intracranial subependymomas were reviewed with regard to presentation, diagnosis, operative findings, and long-term follow-up data. The histopathological features were critically reviewed, and deoxyribunucleic acid analysis was performed by flow cytometry. The patients' mean age was 48.5 years (range 32 to 72 years). In 14 cases the tumor was located in the fourth ventricle, in six within a lateral ventricle, and in one in the third ventricle with extension into the lateral ventricle. Radiographic characteristics included isodensity with minimal enhancement on computerized tomography, frequent dystrophic calcification, and isointensity on T1-weighted or slight hyperintensity on T2-weighted magnetic resonance images. The predominant histological features in all cases were those of classic subependymoma. Nonetheless, pathological examination showed a minor (< 20%) ependymoma component in five cases, significant cytological atypia in seven, mitoses in 11, endothelial prominence in four, and focal hemorrhage-associated necrosis in two. Flow cytometry revealed a diploid pattern in 12 patients, tetraploidy in two, and aneuploidy in one.

Two patients died in the perioperative period. Of the remaining 19, 12 underwent gross total resection (two of whom received postoperative irradiation) and seven underwent subtotal resection (five of whom received irradiation). None of the 12 non-irradiated patients developed tumor progression or died of direct tumor-related causes. Of the seven irradiated patients, follow-up imaging studies demonstrated their tumors to be radioresponsive, particularly with doses of 5000 cGy or greater. Despite the presence of cytological atypia and mitotic activity in the majority of cases, the prognostic effects of such factors as tumor location and the extent of surgical resection outweighed those of the standard histopathological parameters. Routine postoperative irradiation is not recommended, but should be reserved for cases with a symptomatic residual or recurrent subependymomas following surgery.

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Thomas B. Crotty, Bernd W. Scheithauer, William F. Young Jr., Dudley H. Davis, Edward G. Shaw, Gary M. Miller and Peter C. Burger

✓ Two distinct clinicopathological variants of craniopharyngioma exist: the classic adamantinomatous type and a recently described papillary form that predominates in adults and reportedly behaves in a less aggressive manner. The present study describes the clinicopathological features of 48 patients with papillary craniopharyngioma treated at the Mayo Clinic between 1910 and 1994. An additional four tumors were found to have histological features of both adamantinomatous and papillary craniopharyngioma. Whereas adamantinomatous tumors typically occur in adolescent patients, the mean age of the 48 patients (23 males and 25 females) with papillary craniopharyngioma was 44.7 years (range 10 to 74 years). Presenting clinical features included visual impairment (84%), headache (68%), and pituitary insufficiency (anterior 42%; posterior 27%). Preoperative computerized tomography (CT) and magnetic resonance (MR) imaging in 17 patients typically revealed a noncalcified, partially cystic mass that enhanced peripherally and contained mural nodules (67%). Many (41%) of the lesions involved or extended into the third ventricle on imaging. At first surgery, gross total tumor removal was achieved in 17 patients (36%) and subtotal resection in 30 patients (64%) in whom tumor resection was attempted. Tumor recurrence was noted in two patients who underwent gross total removal. Tumor-free survival rates of 100% and 78% were obtained in patients who underwent gross total and subtotal resection at initial surgery, respectively. Postoperative radiation therapy was beneficial to patients having undergone a subtotal resection, with an increase in tumor-free survival from 26% to 86%.

Aside from well-documented morphological distinctions, papillary craniopharyngiomas differ from adamantinomatous tumors in several important respects. These include the almost exclusive occurrence of papillary tumors in adulthood and their more uniform appearance on both CT and MR imaging. However, a preliminary analysis of our data suggests there are no significant differences between the two lesions with respect to resectability, efficacy of radiation therapy, and overall survival.

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Peter A. Forsyth, Patrick J. Kelly, Terrence L. Cascino, Bernd W. Scheithauer, Edward G. Shaw, Robert P. Dinapoli and Elizabeth J. Atkinson

✓ Fifty-one patients with supratentorial glioma treated with external beam radiotherapy (median dose 59.5 Gy) who then demonstrated clinical or radiographic evidence of disease progression underwent stereotactic biopsy to differentiate tumor recurrence from radiation necrosis. The original tumor histological type was diffuse or fibrillary astrocytoma in 21 patients (41%), oligodendroglioma in 13 (26%), and oligoastrocytoma in 17 (33%); 40 tumors (78%) were low-grade (Kernohan Grade 1 or 2). The median time to suspected disease progression was 28 months. Stereotactic biopsy showed tumor recurrence in 30 patients (59%), radiation necrosis in three (6%), and a mixture of both in 17 (33%); one patient (2%) had a parenchymal radiation-induced chondroblastic osteosarcoma. The tumor type at stereotactic biopsy was similar to the original tumor type and was astrocytoma in 24 patients (47%), oligodendroglioma in eight (16%), oligoastrocytoma in 16 (31%), unclassifiable in two (4%), and chondroblastic osteosarcoma in one patient (2%). At biopsy, however, only 19 tumors (37%) were low grade (Kernohan Grade 1 or 2). Subsequent surgery confirmed the stereotactic biopsy histological findings in eight patients. Follow-up examination showed 14 patients alive with a median survival of 1 year for the entire group. Median survival times after biopsy were 0.83 year for patients with tumor recurrence and 1.86 years for patients with both tumor recurrence and radionecrosis; these findings were significantly different (p = 0.008, log-rank test). No patient with radiation necrosis alone died. Other factors associated with reduced survival were a high proportion of residual tumor (p = 0.024), a low proportion of radionecrosis (p < 0.001), and a Kernohan Grade of × or 4 (p = 0.005).

In conclusion, in patients with previously irradiated supratentorial gliomas in whom radionecrosis or tumor recurrence was clinically or radiographically suspected, results of stereotactic biopsy could be used to differentiate tumor recurrence, radiation necrosis, a mixture of both lesions, or radiation-induced neoplasm. In addition, biopsy results could predict survival rates.