David Schlesinger

Stereotactic body radiation therapy: The report of AAPM Task Group 101

Task Group 101 of the AAPM has prepared this report for medical physicists, clinicians, and therapists in order to outline the best practice guidelines for the external-beam radiation therapy technique referred to as stereotactic body radiation therapy (SBRT). The task group report includes a review of the literature to identify reported clinical findings and expected outcomes for this treatment modality. Information is provided for establishing a SBRT program, including protocols, equipment, resources, and QA procedures. Additionally, suggestions for developing consistent documentation for prescribing, reporting, and recording SBRT treatment delivery is provided.

Gamma Knife radiosurgery to the surgical cavity following resection of brain metastases.

OBJECT This study evaluated the efficacy of postoperative Gamma Knife surgery (GKS) to the tumor cavity following gross-total resection of a brain metastasis. METHODS A retrospective review was conducted of 700 patients who were treated for brain metastases using GKS. Forty-seven patients with pathologically confirmed metastatic disease underwent GKS to the postoperative resection cavity following gross-total resection of the tumor. Patients who underwent subtotal resection or who had visible tumor in the resection cavity on the postresection neuroimaging study (either CT or MR imaging with and without contrast administration) were excluded. Radiographic and clinical follow-up was assessed using clinic visits and MR imaging. The radiographic end point was defined as tumor growth control (no tumor growth regarding the resection cavity, and stable or decreasing tumor size for the other metastatic targets). Clinical end points were defined as functional status (assessed prospectively using the Karnofsky Performance Scale) and survival. Primary tumor pathology was consistent with lung cancer in 19 cases (40%), melanoma in 10 cases (21%), renal cell carcinoma in 7 cases (15%), breast cancer in 7 cases (15%), and gastrointestinal malignancies in 4 cases (9%). The mean duration between resection and radiosurgery was 15 days (range 2-115 days). The mean volume of the treated cavity was 10.5 cm3 (range 1.75-35.45 cm3), and the mean dose to the cavity margin was 19 Gy. In addition to the resection cavity, 34 patients (72%) underwent GKS for 116 synchronous metastases observed at the time of the initial radiosurgery. RESULTS The mean radiographic follow-up duration was 14 months (median 10 months, range 4-37 months). Local tumor control at the site of the surgical cavity was achieved in 44 patients (94%), and tumor recurrence at the surgical site was statistically related to the volume of the surgical cavity (p=0.04). During follow-up, 34 patients (72%) underwent additional radiosurgery for 140 new (metachronous) metastases. At the most recent follow-up evaluation, 11 patients (23%) were alive, whereas 36 patients had died (mean duration until death 12 months, median 10 months). Patients who showed good systemic control of their primary tumor tended to have longer survival durations than those who did not (p=0.004). At the last clinical follow-up evaluation, the mean Karnofsky Performance Scale score for the overall group was 78 (median 80, range 40-100). CONCLUSION Radiosurgery appears to be effective in terms of providing local tumor control at the resection cavity following resection of a brain metastasis, and in the treatment of synchronous and metachronous tumors. These data suggest that radiosurgery can be used to prevent recurrence following gross-total resection of a brain metastasis.

Long-term outcomes after Gamma Knife radiosurgery for patients with a nonfunctioning pituitary adenoma.

BACKGROUND:Nonfunctioning pituitary adenomas recur after microsurgery. Gamma Knife radiosurgery (GKRS) has been used to treat recurrent adenomas. OBJECTIVE:To evaluate the long-term rates of tumor control and development of hypopituitarism in patients with nonfunctioning pituitary adenomas after GKRS. METHODS:Forty-eight patients with a nonfunctioning pituitary adenoma treated between 1991 and 2004 at the University of Virginia were studied. All patients had more than 4 years of clinical and imaging follow-up. RESULTS:All patients underwent follow-up imaging and endocrine evaluations, with a duration ranging from 50 to 215 months (median, 80.5 months) and 57 to 201 months (median, 95 months), respectively. New hormone deficiency after GKRS occurred in 19 of 48 patients (39%). Corticotropin/cortisol deficiency developed in 8% of patients, thyroid hormone deficiency in 20.8%, gonadotropin deficiency in 4.2%, growth hormone/insulin-like growth factor 1 in 16.7%, and diabetes insipidus in 2%. Panhypopituitarism including diabetes insipidus developed in 1 patient. Overall, control of tumor volume was 83%. Tumor volume decreased in 36 patients (75%), increased in 8 patients (17%), and was unchanged in 4 patients (8%). Tumor volumes greater than 5 mL at the time of GKRS were associated with a significantly greater rate of growth (P = .003) compared with an adenoma with a volume of 5 mL or less. CONCLUSION:GKRS resulted in a high and durable rate of tumor control in patients with a nonfunctioning pituitary adenoma. A higher preoperative tumor volume was associated with an increased rate of tumor growth.

Radiosurgery in the treatment of spinal metastases: tumor control, survival, and quality of life after helical tomotherapy.

OBJECTIVEThe effectiveness and limitations of spinal radiosurgery using a helical TomoTherapy system for the treatment of spinal metastases are reviewed in this article. METHODSThis is a retrospective review of patients who underwent stereotactic radiosurgery for spinal metastases between July 2004 and December 2007. Radiographic follow-up consisted of magnetic resonance imaging to assess tumor growth control as well as pre- and posttreatment x-rays, which were used to measure changes in segmental angulation and deformity. Clinical performance was assessed using the Karnofsky Performance Scale, Oswestry Disability Index, and visual analog scale. RESULTSForty patients were treated for 110 metastatic tumors (range, 1–6 tumors per patient). The mean age at the time of radiosurgical treatment was 67 years (age range, 35–81 years). Twenty-three patients (57.5%) had undergone previous surgical resection. Pain was the most common presenting symptom, seen in 32 patients (80%). The mean Oswestry Disability Index score at presentation was 43 (range, 20–90), and the mean visual analog scale score was 6.2 (range, 0–10). The mean radiosurgical dose to the tumor was 17.3 Gy (range, 10–24 Gy). At a mean follow-up duration of 12.7 months (range, 4–32 months), decreased or stable tumor volume was seen in 90 (82%) of the tumors treated. There was improvement in pain in 34 patients (85%). The mean postradiosurgical Oswestry Disability Index score was 25 (range, 10–90), whereas the postradiosurgical visual analog scale score was 3.2 (range, 0–9). Progression of kyphosis was the most common radiographic sequela, experienced by 73% of patients alive at 12 months, with a mean change in angulation of 7.3 ± 4.5 degrees. CONCLUSIONRadiosurgery is effective as either primary or adjunctive treatment of metastatic tumors of the spine.

MR‐guided focused ultrasound surgery, present and future

MR-guided focused ultrasound surgery (MRgFUS) is a quickly developing technology with potential applications across a spectrum of indications traditionally within the domain of radiation oncology. Especially for applications where focal treatment is the preferred technique (for example, radiosurgery), MRgFUS has the potential to be a disruptive technology that could shift traditional patterns of care. While currently cleared in the United States for the noninvasive treatment of uterine fibroids and bone metastases, a wide range of clinical trials are currently underway, and the number of publications describing advances in MRgFUS is increasing. However, for MRgFUS to make the transition from a research curiosity to a clinical standard of care, a variety of challenges, technical, financial, clinical, and practical, must be overcome. This installment of the Vision 20∕20 series examines the current status of MRgFUS, focusing on the hurdles the technology faces before it can cross over from a research technique to a standard fixture in the clinic. It then reviews current and near-term technical developments which may overcome these hurdles and allow MRgFUS to break through into clinical practice.

Hemorrhage Risk of Cerebral Arteriovenous Malformations Before and During the Latency Period After Gamma Knife Radiosurgery

Background and Purpose— To evaluate the hemorrhage rates of cerebral arteriovenous malformations (AVM) and the risk factors of hemorrhage before and after Gamma Knife radiosurgery (GKS). Methods— The annual hemorrhage rate was calculated as the number of hemorrhages divided by the patient-years at risk. Characteristics of patients and AVM related to hemorrhagic or nonhemorrhagic presentation were evaluated by logistic regression. Risk factors predicting AVM hemorrhage during the period from the diagnosis to GKS of AVM and during the latency period after radiosurgery were evaluated using Cox regression hazards model. Results— The annual hemorrhage rate before GKS was 2.0% assuming patients were at risk for hemorrhage since their birth. The hemorrhage rate calculated between the diagnosis and GKS of AVM was 6.6% and reduced to 2.5% after GKS until obliteration of the AVM. Although small and deep nidi and those with deep and single draining veins tended to present themselves with hemorrhage, only nidi with single draining veins and those ruptured before were more likely to bleed once the AVM had been diagnosed. These factors no longer predisposed the nidus to a rupture after radiosurgery and the only predicting factor for hemorrhage was a low radiosurgical prescription dose to the margin of nidus. Conclusions— The AVM hemorrhage rate seems to reduce after GKS. After radiosurgery, none of the patients or nidus-related risk factors remained relevant to the occurrence of hemorrhage. The nidus treated with a high radiosurgical dose is less likely to bleed.

Hypopituitarism after stereotactic radiosurgery for pituitary adenomas.

BACKGROUND Studies of new-onset Gamma Knife stereotactic radiosurgery (SRS)-induced hypopituitarism in large cohort of pituitary adenoma patients with long-term follow-up are lacking. OBJECTIVE We investigated the outcomes of SRS for pituitary adenoma patients with regard to newly developed hypopituitarism. METHODS This was a retrospective review of patients treated with SRS at the University of Virginia between 1994 and 2006. A total of 262 patients with a pituitary adenoma treated with SRS were reviewed. Thorough endocrine assessment was performed immediately before SRS and in regular follow-ups. Assessment consisted of 24-hour urine free cortisol (patients with Cushing disease), serum adrenocorticotropic hormone, cortisol, follicle-stimulating hormone, luteinizing hormone, insulin-like growth factor-1, growth hormone, testosterone (men), prolactin, thyroid-stimulating hormone, and free T(4). RESULTS Endocrine remission occurred in 144 of 199 patients with a functioning adenoma. Tumor control rate was 89%. Eighty patients experienced at least 1 axis of new-onset SRS-induced hypopituitarism. The new hypopituitarism rate was 30% based on endocrine follow-up ranging from 6 to 150 months; the actuarial rate of new pituitary hormone deficiency was 31.5% at 5 years after SRS. On univariate and multivariate analyses, variables regarding the increased risk of hypopituitarism included suprasellar extension and higher radiation dose to the tumor margin; there were no correlations among tumor volume, prior transsphenoidal adenomectomy, prior radiation therapy, and age at SRS. CONCLUSION SRS provides an effective and safe treatment option for patients with a pituitary adenoma. Higher margin radiation dose to the adenoma and suprasellar extension were 2 independent predictors of SRS-induced hypopituitarism.

Stereotactic Radiosurgery for Acromegaly

CONTEXT The role of stereotactic radiosurgery (SRS) in acromegaly is being assessed. OBJECTIVE We evaluated the efficacy and safety of SRS for patients with acromegaly. Prognostic factors related to outcomes were also analyzed. DESIGN This was a retrospective study of patients treated with SRS at the University of Virginia; the data were collected from 1989 to 2012, with a median follow-up of 61.5 months. PATIENTS A total of 136 patients underwent SRS for acromegaly. Diagnosis of acromegaly was based on the combination of clinical features and biochemical assessment, including the serum GH level and age- and gender-matched serum IGF-1 level. All patients underwent a complete endocrine evaluation, neuroimaging study, and ophthalmic examinations before SRS. MAIN OUTCOME MEASURES After withdrawal of GH- or IGF-1-altering medications, patients who had an oral glucose tolerance test GH of < 1.0 ng/mL or normal IGF-1 were considered in remission. Post-radiosurgical hypopituitarism was defined as a decrease in one or more hormones below normal. RESULTS With a median follow-up of 61.5 months, 65.4% of the patients achieved remission. The mean time to remission was 27.5 months. The actuarial remission rates at 2, 4, 6, and 8 years after radiosurgery were 31.7, 64.5, 73.4, and 82.6%, respectively. Favorable prognostic factors for remission included a higher margin radiation dose, higher maximum dose, and lower initial IGF-1 level. New pituitary hormone deficiency occurred in 43 patients (31.6%); two patients (1.5%) developed panhypopituitarism. Corresponding risk factors for new pituitary hormone deficiency were a margin dose > 25 Gy and tumor volume > 2.5 mL. Other complications included an adverse radiation effect in one patient, visual deterioration in four, and new oculomotor nerve palsy in one. CONCLUSION SRS affords a reasonable rate of endocrine remission in patients with acromegaly and generally does so with a low rate of adverse effects.

Gamma Knife surgery for arteriovenous malformations in children.

OBJECT The aim of this study was to evaluate the long-term imaging and clinical outcomes of intracranial arteriovenous malformations (AVMs) in children treated with Gamma Knife surgery (GKS). METHODS Between 1989 and 2007, 200 patients with AVMs who were 18 years of age or younger were treated at the University of Virginia Health System. Excluding 14 patients who had not reached 2-year follow-up, 186 patients comprised this study. Hemorrhage was the most common presenting symptom leading to the diagnosis of AVMs (71.5%). The mean nidus volume was 3.2 cm(3) at the time of GKS, and a mean prescription dose of 21.9 Gy was used. RESULTS After initial GKS, 49.5% of patients achieved total angiographic obliteration. Forty-one patients whose AVM nidi remained patent underwent additional GKS. The obliteration rate increased to 58.6% after a second or multiple GKS. Subtotal obliteration was achieved in 9 patients (4.8%). Forty-nine patients (26.3%) still had a patent residual nidus. In 19 patients (10.2%), obliteration was confirmed on MR imaging only. Ten patients had 17 hemorrhages during the follow-up period. The hemorrhage rate was 5.4% within 2 years after GKS and 0.8% between 2 and 5 years. Six patients developed neurological deficits along with the radiation-induced changes. Two patients developed asymptomatic meningiomas 10 and 12 years after GKS. After a mean clinical follow-up of 98 months, less than 4% of patients had difficulty attending school or developing a career. CONCLUSIONS Gamma Knife surgery offers a reasonable chance of obliteration of an AVM in pediatric patients. The incidence of symptomatic radiation-induced changes is relatively low; however, long-term clinical and imaging follow-up is required to identify delayed cyst formation and secondary tumors.

Gamma Knife surgery for parasellar meningiomas: long-term results including complications, predictive factors, and progression-free survival.

OBJECT Stereotactic radiosurgery serves as an important primary and adjuvant treatment option for patients with many types of intracranial meningiomas. This is particularly true for patients with parasellar meningiomas. In this study, the authors evaluated the outcomes of Gamma Knife surgery (GKS) used to treat parasellar meningiomas. METHODS The study is a retrospective review of the outcomes in 138 patients with meningiomas treated at the University of Virginia from 1989 to 2006; all patients had a minimum follow-up of 24 months. There were 31 men and 107 women whose mean age was 54 years (range 19-85 years). Eighty-four patients had previously undergone resection. The mean pre-GKS tumor volume was 7.5 ml (range 0.2-54.8 ml). Clinical and radiographic evaluations were performed, and factors related to favorable outcomes in each case were assessed. RESULTS The mean follow-up duration was 84 months (median 75.5 months, range 24-216 months). In 118 patients (86%), the tumor volume was unchanged or had decreased at last follow-up. Kaplan-Meier analysis demonstrated radiographic progression-free survival at 5 and 10 years to be 95.4% and 69%, respectively. Fourteen patients (10%) developed new cranial nerve palsies following GKS. Factors associated with tumor control included younger age, a higher isodose, and smaller tumor volume. A longer follow-up duration was associated with either a decrease or increase in tumor volume. Fourteen patients (10%) experienced new or worsening cranial nerve deficits after treatment. Factors associated with this occurrence were larger pretreatment tumor volume, lower peripheral radiation dose, lower maximum dose, tumor progression, and longer follow-up. CONCLUSIONS Gamma Knife surgery offers an acceptable rate of tumor control for parasellar meningiomas and accomplishes this with a low incidence of neurological deficits. Radiological control after radiosurgery is more likely in those patients with a smaller tumor volume and a higher prescription dose.