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Gamma Knife surgery–induced meningioma

Report of two cases and review of the literature

Jason Sheehan, Chun PO Yen, and Ladislau Steiner

✓Gamma Knife surgery (GKS) is a minimally invasive neurosurgical technique. During the past 30 years, radiosurgery has been performed for a number of intracranial disorders with a generally low incidence of side effects. Although radiation-induced neoplasia following radiotherapy is well documented, there are few reports of this complication following radiosurgery.

The authors are engaged in an ongoing project in which they are studying the delayed adverse effects of radiosurgical changes in 2500 patients with arteriovenous malformations (AVMs) treated within a 30-year period. The cases of 1333 patients treated by the senior author (L.S.) have been reviewed thus far. A subset of 288 patients in this group underwent neuroimaging and participated in clinical follow up for at least 10 years.

The authors report two cases of radiosurgically induced neoplasia. In both cases the patient was treated with GKS for an AVM. Longer than 10 years after GKS, each of the patients was found to have an incidental, uniformly enhancing, dura-based mass lesion near the site of the AVM. These lesions displayed the imaging characteristics of a meningioma. Because in both cases the lesion has displayed no evidence of a mass effect, they continue to be followed using serial neuroimaging. These are the fifth and sixth cases meeting the criteria for radiation-induced neoplasms defined by Cahan, et al., in 1998.

Although radiosurgery is generally considered quite safe, the incidence of radiation-induced neoplasms is not known. These cases and the few others detailed in the literature emphasize the need for long-term neurosurgical follow-up review in patients after radiosurgery.

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Claire Olson, Chun-Po Yen, David Schlesinger, and Jason Sheehan

Object

Intracranial hemangiopericytoma is a rare CNS tumor that exhibits a high incidence of local recurrence and distant metastasis. The purpose of this study was to evaluate the role of Gamma Knife surgery (GKS) in the management of intracranial hemangiopericytomas.

Methods

In a review of the University of Virginia radiosurgery database between 1989 and 2008, the authors found recurrent or residual hemangiopericytomas after resection in 21 patients in whom radiosurgery was performed to treat 28 discrete tumors. The median age of this population was 47 years (range 31–61 years) at the time of the initial GKS. Prior treatments included embolization (6), transcranial resection (39), transsphenoidal resection (2), and fractionated radiotherapy (8). The mean prescription and maximum radiosurgical doses to the tumors were 17.0 and 40.3 Gy, respectively. Repeat radiosurgery was used to treat 13 tumors. The median follow-up period was 68 months (range 2–138 months).

Results

At last follow-up, local tumor control was demonstrated in 47.6% of the patients (10 of 21 patients) with hemangiopericytomas. Of the 28 tumors treated, 8 decreased in size on follow-up imaging (28.6%), 5 remained unchanged (17.9%), and 15 ultimately progressed (53.6%). The progression-free survival rates were 90, 60.3, and 28.7% at 1, 3, and 5 years after initial GKS. The progression-free survival rate improved to 95, 71.5, and 71.5% at 1, 3, and 5 years after multiple GKS treatments. The 5-year survival rate after radiosurgery was 81%. Prior fractionated irradiation or radiosurgical prescription dose did not correlate with tumor control. In 4 (19%) of 21 patients extracranial metastases developed.

Conclusions

Radiosurgery is a reasonable treatment option for recurrent hemangiopericytomas. Long-term close clinical and imaging follow-up is necessary because of the high probability of local recurrence and distant metastases. Repeat radiosurgery may be used to treat new or recurrent hemangiopericytomas over a long follow-up course.

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Chun-Po Yen, Joshua M. Beckman, Andrew C. Vivas, Konrad Bach, and Juan S. Uribe

OBJECTIVE

The authors investigated whether the presence of intradiscal vacuum phenomenon (IVP) results in greater correction of disc height and restoration of segmental lordosis (SL).

METHODS

A retrospective chart review was performed on every patient at the University of South Florida's Department of Neurosurgery treated with lateral lumbar interbody fusion between 2011 and 2015. From these charts, preoperative plain radiographs and CT images were reviewed for the presence of IVP. Preoperative and postoperative posterior disc height (PDH), anterior disc height (ADH), and SL were measured at disc levels with IVP and compared with those at disc levels without IVP using the t-test. Linear regression was used to evaluate the factors that predict changes in PDH, ADH, and SL.

RESULTS

One hundred forty patients with 247 disc levels between L-1 and L-5 were treated with lateral lumbar interbody fusion. Among all disc levels treated, the mean PDH increased from 3.69 to 6.66 mm (p = 0.011), the mean ADH increased from 5.45 to 11.53 mm (p < 0.001), and the mean SL increased from 9.59° to 14.55° (p < 0.001). Significantly increased PDH was associated with the presence of IVP, addition of pedicle screws, and lack of cage subsidence; significantly increased ADH was associated with the presence of IVP, anterior longitudinal ligament (ALL) release, addition of pedicle screws, and lack of subsidence; and significantly increased SL was associated with the presence of IVP and ALL release.

CONCLUSIONS

IVP in patients with degenerative spinal disease remains grossly underreported. The data from the present study suggest that the presence of IVP results in increased restoration of disc height and SL.

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Chun Po Yen, Jason Sheehan, Greg Patterson, and Ladislau Steiner

Object

Although considered benign tumors, neurocytomas have various biological behaviors, histological patterns, and clinical courses. In the last 15 years, fractionated radiotherapy and radiosurgery in addition to microsurgery have been used in their management. In this study, the authors present their experience using Gamma Knife surgery (GKS) in the treatment of these tumors.

Methods

Between 1989 and 2004, the authors performed GKS in seven patients with a total of nine neurocytomas. Three patients harbored five recurrent tumors after a gross-total resection, three had progression of previous partially resected tumors, and one had undergone a tumor biopsy only. The mean tumor volume at the time of GKS ranged from 1.4 to 19.8 cm3 (mean 6.0 cm3). A mean peripheral dose of 16 Gy was prescribed to the tumor margin with the median isodose configuration of 32.5%.

Results

After a mean follow-up period of 60 months, four of the nine tumors treated disappeared and four shrank significantly. Because of secondary hemorrhage, an accurate tumor volume could not be determined in one. Four patients were asymptomatic during the follow-up period, and the condition of the patient who had residual hemiparesis from a previous transcortical resection of the tumor was stable. Additionally, the patient who experienced tumor hemorrhage required a shunt revision, and another patient died of sepsis due to a shunt infection.

Conclusions

Based on this limited experience, GKS seems to be an appropriate management alternative. It offers control over the tumor with the benefits of minimal invasiveness and low morbidity rates. Recurrence, however, is not unusual following both microsurgery and GKS. Open-ended follow-up imaging is required to detect early recurrence and determine the need for retreatment.

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Peter Varady, Jason Sheehan, Melita Steiner, and Ladislau Steiner

Heading : Chun Po Yen

Object

Subtotal obliteration of cerebral arteriovenous malformations (AVMs) after Gamma Knife surgery (GKS) implies a complete angiographic disappearance of the AVM nidus but persistence of an early filling draining vein, indicating that residual shunting is still present; hence, per definition there is still a patent AVM and the risk of bleeding is not eliminated. The aim of this study was to determine the risk of hemorrhage for patients with subtotal obliteration of AVMs.

Methods

After GKS for cerebral AVMs, follow-up angiography demonstrated a subtotally obliterated lesion in 159 patients. Of these, in 16 patients a subtotally obliterated AVM developed after a second GKS was performed for the partially obliterated lesion. The mean age of these patients was 35.2 years at the time of the diagnosis of subtotally obliterated AVMs. The lesion volumes at the time of initial GKS treatment ranged from 0.1 to 11.5 cm3 (mean 2.5 cm3). The mean peripheral dose used in the 175 GKS treatments was 22.5 Gy (median 23 Gy, range 15–31 Gy). To achieve total obliteration of the AVM, 23 patients underwent a new GKS targeting the proximal end of the early filling vein. The mean peripheral dose given in these cases was 23 Gy (median 24, range 18–25 Gy).

The incidence of subtotally obliterated AVMs was 7.6% from a total of 2093 AVMs treated and in which follow-up imaging was available. The diagnosis of subtotally obliterated AVMs was made a mean of 29.4 months (range 4–178 months) after GKS. The number of patient-years at risk (from the time of the diagnosis of subtotally obliterated AVMs until either the confirmation of a total obliteration of the lesion on angiography or the time of the latest follow-up angio-graphic study that still visualized the early filling vein) was a mean of 3.9 years, ranging from 0.5 to 13.5 years, and a total of 601 patient-years. There was no case of bleeding after the diagnosis of subtotally obliterated AVMs. Of 90 patients who did not undergo further treatment and in whom follow-up angiography studies were available, the same early filling veins still filled in 24 (26.7%), and the subtotally obliterated AVMs were subsequently obliterated in 66 patients (73.3%). In 19 patients who underwent repeated GKS for subtotally obliterated AVMs and in whom follow-up angiography studies were available, the AVMs were obliterated in 15 (78.9%) and remained patent in four (21.1%).

Conclusions

The fact that none of the patients with subtotally obliterated AVMs suffered a rupture is not compatible with the assumption of an unchanged risk of hemorrhage for these lesions, and implies that the protection from re-bleeding in patients with subtotal obliteration is significant. Subtotal obliteration does not necessarily seem to be a stage of an ongoing obliteration. At least in some cases it represents an end point of this process, with no subsequent obliteration occurring. This observation requires further confirmation by open-ended follow-up imaging.

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Editorial

Arteriovenous malformations

Douglas Kondziolka

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Dale Ding, Zhiyuan Xu, Ian T. McNeill, Chun-Po Yen, and Jason P. Sheehan

Object

Parasagittal and parafalcine (PSPF) meningiomas represent the second most common location for intracranial meningiomas. Involvement of the superior sagittal sinus or deep draining veins may prevent gross-total resection of these tumors without significant morbidity. The authors review their results for treatment of PSPF meningiomas with radiosurgery.

Methods

The authors retrospectively reviewed the institutional review board–approved University of Virginia Gamma Knife database and identified 65 patients with 90 WHO Grade I parasagittal (59%) and parafalcine (41%) meningiomas who had a mean MRI follow-up of 56.6 months. The patients' mean age was 57 years, the median preradiosurgery Karnofsky Performance Status score was 80, and the median initial tumor and treatment volumes were 3 and 3.7 cm3, respectively. The median prescription dose was 15 Gy, isodose line was 40%, and the number of isocenters was 5. Kaplan-Meier analysis was used to determine progression-free survival (PFS). Univariate and multivariate Cox regression analyses were used to identify factors associated with PFS.

Results

The median overall PFS was 75.6 months. The actuarial tumor control rate was 85% at 3 years and 70% at 5 years. Parasagittal location, no prior resection, and younger age were found to be independent predictors of tumor PFS. For the 49 patients with clinical follow-up (mean 70.8 months), the median postradiosurgery Karnofsky Performance Status score was 90. Symptomatic postradiosurgery peritumoral edema was observed in 4 patients (8.2%); this group comprised 3 patients (6.1%) with temporary and 1 patient (2%) with permanent clinical sequelae. Two patients (4.1%) died of tumor progression.

Conclusions

Radiosurgery offers a minimally invasive treatment option for PSPF meningiomas, with a good tumor control rate and an acceptable complication rate comparable to most surgical series.

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Dale Ding, Chun-Po Yen, Zhiyuan Xu, Robert M. Starke, and Jason P. Sheehan

Object

The appropriate management of unruptured intracranial arteriovenous malformations (AVMs) remains controversial. In the present study, the authors evaluate the radiographic and clinical outcomes of radiosurgery for a large cohort of patients with unruptured AVMs.

Methods

From a prospective database of 1204 cases of AVMs involving patients treated with radiosurgery at their institution, the authors identified 444 patients without evidence of rupture prior to radiosurgery. The patients' mean age was 36.9 years, and 50% were male. The mean AVM nidus volume was 4.2 cm3, 13.5% of the AVMs were in a deep location, and 44.4% were at least Spetzler-Martin Grade III. The median radiosurgical prescription dose was 20 Gy. Univariate and multivariate Cox regression analyses were used to determine risk factors associated with obliteration, postradiosurgery hemorrhage, radiation-induced changes, and postradiosurgery cyst formation. The mean duration of radiological and clinical follow-up was 76 months and 86 months, respectively.

Results

The cumulative AVM obliteration rate was 62%, and the postradiosurgery annual hemorrhage rate was 1.6%. Radiation-induced changes were symptomatic in 13.7% and permanent in 2.0% of patients. The statistically significant independent positive predictors of obliteration were no preradiosurgery embolization (p < 0.001), increased prescription dose (p < 0.001), single draining vein (p < 0.001), radiological presence of radiation-induced changes (p = 0.004), and lower Spetzler-Martin grade (p = 0.016). Increased volume and higher Pittsburgh radiosurgery-based AVM score were predictors of postradiosurgery hemorrhage in the univariate analysis only. Clinical deterioration occurred in 30 patients (6.8%), more commonly in patients with postradiosurgery hemorrhage (p = 0.018).

Conclusions

Radiosurgery afforded a reasonable chance of obliteration of unruptured AVMs with relatively low rates of clinical and radiological complications.

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Chun Po Yen, Jason Sheehan, Greg Patterson, and Ladislau Steiner

Object

The authors review imaging and clinical outcomes in patients with metastatic brainstem tumors treated using Gamma Knife surgery (GKS).

Methods

Between March 1989 and March 2005, 53 patients (24 men and 29 women) with metastatic brainstem lesions underwent GKS. The metastatic deposits were located in the midbrain in eight patients, the pons in 42, and the medulla oblongata in three. Lung cancer was the most common primary malignancy, followed by breast cancer, melanoma, and renal cell carcinoma. The mean volume of the metastatic deposits at the time of treatment was 2.8 cm3 (range 0.05–21 cm3). The prescription doses varied from 9 to 25 Gy (mean 17.6 Gy).

Imaging follow-up studies were not completed in 16 patients, because of the short-term survival in 11 and patient refusal in five. Of the remaining 37 patients, who underwent an imaging follow-up evaluation at a mean of 9.8 months (range 1–25 months), the tumors disappeared in seven, shrank in 22, remained unchanged in three, and grew in five. All but one of 18 patients with asymptomatic brainstem deposits remained free of symptoms. In 35 patients with symptomatic brainstem deposits, neurological symptoms improved in 21, remained stable in 11, and worsened in three. At the time of this study, 10 patients were alive, and their survival ranged from 3 to 52 months after treatment. Thirty-four patients died of extracranial disease, three of the progressing metastatic brainstem lesion, and six of additional progressing intracranial deposits in other parts of the brain. The overall median survival period was 11 months after GKS. In terms of survival, the absence of active extracranial disease was the only favorable prognostic factor. Neither previous whole-brain radiation therapy nor a single brainstem metastasis was statistically related to the duration of survival.

Conclusions

Compared with allowing a metastatic brainstem lesion to take its natural course, GKS prolongs survival. The risks associated with such treatment are low. The severity of systemic diseases largely determines the prognosis of metastases to the brainstem.

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Dale Ding, Chun-Po Yen, Robert M. Starke, Zhiyuan Xu, and Jason P. Sheehan

Object

Ruptured intracranial arteriovenous malformations (AVMs) are at a significantly greater risk for future hemorrhage than unruptured lesions, thereby necessitating treatment in the majority of cases. In a retrospective, single-center study, the authors describe the outcomes after radiosurgery in a large cohort of patients with ruptured AVMs.

Methods

From an institutional review board–approved, prospectively collected AVM radiosurgery database, the authors identified all patients with a history of AVM rupture. They analyzed obliteration rates in all patients in whom radiological follow-up data were available (n = 639). However, to account for the latency period associated with radiosurgery, only those patients with more than 2 years of radiological follow-up and those with earlier AMV obliteration were included in the analysis of prognostic factors related to obliteration and complications. This resulted in a cohort of 565 patients with ruptured AVMs for whom data were analyzed; these patients had a median radiological follow-up of 57 months and a median age of 29 years. Twenty-one percent of the patients underwent preradiosurgery embolization. The median volume and prescription dose were 2.1 cm3 and 22 Gy, respectively. The Spetzler-Martin grade was III or higher in 56% of patients, the median radiosurgery-based AVM score was 1.08, and the Virginia Radiosurgery AVM Scale (RAS) score was 3 to 4 points in 44%. Survival and regression analyses were performed to determine obliteration rates over time and predictors of obliteration and complications.

Results

In the overall population of 639 patients with ruptured AVMs, the obliteration rate was 11.1% based on MRI only (71 of 639 patients), 56.0% based on angiography (358 of 639), and 67.1% based on combined modalities (429 of 639 patients). In the cohort of patients with 2 years of follow-up or an earlier AVM obliteration, the cumulative obliteration rate was 76% and the actuarial obliteration rates were 41% and 64% at 3 and 5 years, respectively. Multivariate analysis identified the absence of preradiosurgery embolization (p < 0.001), increased prescription dose (p = 0.001), the presence of a single draining vein (p = 0.046), no postradiosurgery-related hemorrhage (p = 0.007), and lower Virginia RAS score (p = 0.020) as independent predictors of obliteration. The annual risk of a hemorrhage occurring during the latency period was 2.0% and the rate of hemorrhage-related morbidity and mortality was 1.6%. Multivariate analysis showed that decreased prescription dose (p < 0.001) and multiple draining veins (p = 0.003) were independent predictors of postradiosurgery hemorrhage. The rates of symptomatic and permanent radiation-induced changes were 8% and 2.7%, respectively. In the multivariate analysis, a single draining vein (p < 0.001) and higher Virginia RAS score (p = 0.005) were independent predictors of radiation-induced changes following radiosurgery.

Conclusions

Radiosurgery effectively treats ruptured AVMs with an acceptably low risk-to-benefit ratio. For patients with ruptured AVMs, favorable outcomes are more likely when preradiosurgical embolization is avoided and a higher prescription dose can be delivered.