Faculty Bibliography

PURPOSE/OBJECTIVE:Stereotactic radiosurgery (SRS) is an effective alternative to microsurgical resection or embolization for definitive treatment of arteriovenous malformations (AVMs). Digital subtraction angiography (DSA) is the gold standard for pretreatment diagnosis and characterization of vascular anatomy, but requires rigid frame (skull) immobilization when used in combination with SRS. With the advent of advanced proton and image-guided photon delivery systems, SRS treatment is increasingly migrating to frameless platforms, which are incompatible with frame-based DSA. Without DSA as the primary image, target definition may be less than optimal, in some cases precluding the ability to treat with a frameless system. This article reports a novel solution. METHODS AND MATERIALS/METHODS:Fiducial markers are implanted into the patient's skull before angiography. Angiography is performed according to the standard clinical protocol, but, in contrast to the previous practice, without the rigid frame. Separate images of a specially designed localizer box are subsequently obtained. A target volume projected on DSA can be transferred to the localizer system in three dimensions, and in turn be transferred to multiple CT slices using the implanted fiducials. Combined with other imaging modalities, this "virtual frame" approach yields a highly precise treatment plan that can be delivered by frameless SRS technologies. RESULTS:Phantom measurements for point and volume targets have been performed. The overall uncertainty of placing a point target to CT is 0.4 mm. For volume targets, deviation of the transformed contour from the target CT image is within 0.6 mm. The algorithm and software are robust. The method has been applied clinically, with reliable results. CONCLUSIONS:A novel and reproducible method for frameless SRS of AVMs has been developed that enables the use of DSA without the requirement for rigid immobilization. Multiple pairs of DSA can be used for better conformality. Further improvement, including using nonimplanted fiducials, is potentially feasible.

PURPOSE/OBJECTIVE:To evaluate spectral computed tomography (CT) with metal artifacts reduction software (MARS) for reduction of metal artifacts associated with gold fiducial seeds. MATERIALS AND METHODS/METHODS:Thirteen consecutive patients with 37 fiducial seeds implanted for radiation therapy of abdominal lesions were included in this HIPAA-compliant, institutional review board-approved prospective study. Six patients were women (46%) and seven were men (54%). The mean age was 61.1 years (median, 58 years; range, 29-78 years). Spectral imaging was used for arterial phase CT. Images were reconstructed with and without MARS in axial, coronal, and sagittal planes. Two radiologists independently reviewed reconstructions and selected the best image, graded the visibility of the tumor, and assessed the amount of artifacts in all planes. A linear-weighted κ statistic and Wilcoxon signed-rank test were used to assess interobserver variability. Histogram analysis with the Kolmogorov-Smirnov test was used for objective evaluation of artifacts reduction. RESULTS:Fiducial seeds were placed in pancreas (n = 5), liver (n = 7), periportal lymph nodes (n = 1), and gallbladder bed (n = 1). MARS-reconstructed images received a better grade than those with standard reconstruction in 60% and 65% of patients by the first and second radiologist, respectively. Tumor visibility was graded higher with standard versus MARS reconstruction (grade, 3.7 ± 1.0 vs 2.8 ± 1.1; P = .001). Reduction of blooming was noted on MARS-reconstructed images (P = .01). Amount of artifacts, for both any and near field, was significantly smaller on sagittal and coronal MARS-reconstructed images than on standard reconstructions (P < .001 for all comparisons). Far-field artifacts were more prominent on axial MARS-reconstructed images than on standard reconstructions (P < .01). Linear-weighted κ statistic showed moderate to perfect agreement between radiologists. CT number distribution was narrower with MARS than with standard reconstruction in 35 of 37 patients (P < .001). CONCLUSION/CONCLUSIONS:Spectral CT with use of MARS improved tumor visibility in the vicinity of gold fiducial seeds.

OBJECTIVE:The purpose of this study is to determine whether complications associated with combining biopsy and percutaneous fiducial seed placement in the abdomen and pelvis exceeds that of either procedure alone or prohibits completion of the combined procedure. MATERIALS AND METHODS/METHODS:A retrospective review was performed of 188 consecutive patients who underwent CT- or ultrasound-guided placement of fiducial seeds in the abdomen or pelvis, either alone (group 1, n = 117) or with concomitant biopsy (group 2, n = 71), from October 2005 through April 2010. Complications classified according to the Society of Interventional Radiology guidelines were compared between both groups using the Z test for proportions, as were the number of seeds per patient and seed migration and technical success rates. RESULTS:One hundred eighty-eight patients underwent percutaneous placement of 533 fiducial seeds in the abdomen and pelvis. Eight patients (4.3%) had complications. Five were minor (four small hematomas and one pneumothorax) and three were major (two cases of bleeding and one of sepsis). There was no significant difference between groups with respect to minor complication rates, number of seeds placed per patient (p = 0.85), or technical success (p = 0.33). Significantly more major complications (p = 0.04) occurred in group 2, but the rate was similar to that for percutaneous biopsy alone as reported in the literature. Group 2 also had more seed migration (p = 0.02). CONCLUSION/CONCLUSIONS:Biopsy and fiducial seed placement in the abdomen and pelvis can be performed in the same session rather than separately, with a high rate of technical success and without an increased risk of complications when compared with either procedure alone.

Development of hypofractionated stereotactic radiosurgery (HSRS) has expanded the size of lesion that can be safely treated by focused radiation in a limited number of treatment sessions. However, clinical data regarding the efficacy and morbidity of HSRS in the treatment of cerebral metastasis is lacking. Here, we review our experience with CyberKnife(®) HSRS for this indication. From 2005 to 2010, we identified 37 patients with large (>3 cm in diameter) cerebral metastases resection cavity that was treated with HSRS. This constituted approximately 8% of all treated resection cavities. We reviewed dose regimens, local control, distal control, and treatment associated morbidities. Primary sites for the metastatic lesions included: lung (n = 10), melanoma (n = 12), breast (n = 9), kidney (n = 4), and colon (n = 2). All patients underwent resection of the cerebral metastasis and received 800 cGy × 3 daily fractions to the resection cavity. Of the 37 patients treated, one-year follow-up data was available for 35 patients. The median survival was 5.5 months. Actuarial local control rate at 6 months was 80%. Local failures did not correlate with prior WBRT, or tumor histology. Distant recurrence occurred in 7 of the 35 patients. Morbidities associated with HSRS totaled 9%, including radiation necrosis (n = 1, 2.9%), prolonged steroid use (n = 1, 2.9%), and new-onset seizures (n = 1, 2.9%). This study demonstrates the safety and efficacy of an 800 cGy × 3 daily fractions CyberKnife(®) HSRS regimen for irradiation of large resection cavity. The efficacy compares favorably to historical data derived from patients undergoing WBRT, SRS, or brachytherapy.

Glioblastoma Multiforme (GBM) is an aggressive primary brain neoplasm with dismal prognosis. Based on successful phase III trials, 60 Gy involved-field radiotherapy in 30 fractions over 6 weeks [Standard radiation therapy (RT)] with concurrent and adjuvant temozolomide is currently the standard of care. In this disease, age and Karnofsky Performance Status (KPS) are the most important prognostic factors. For elderly patients, clinical trials comparing standard RT with radiotherapy abbreviated to 40 Gy in 15 fractions over 3 weeks demonstrated similar outcomes, indicating shortened radiotherapy may be an appropriate option for elderly patients. However, these trials did not include temozolomide chemotherapy, and included patients with poor KPS, possibly obscuring benefits of more aggressive treatment for some elderly patients. We conducted a prospective Phase II trial to examine the efficacy of a hypofractionated radiation course followed by a stereotactic boost with concurrent and adjuvant temozolomide chemotherapy in elderly patients with good performance status. In this study, patients 65 years and older with a KPS > 70 and histologically confirmed GBM received 40 Gy in 15 fractions with 3D conformal technique followed by a 1-3 fraction stereotactic boost to the enhancing tumor. All patients also received concurrent and adjuvant temozolomide. Patients were evaluated 1 month post-treatment and every 2 months thereafter. Between 2007 and 2010, 20 patients (9 males and 11 females) were enrolled in this study. The median age was 75.4 years (range 65-87 years). At a median follow-up of 11 months (range 7-32 months), 12 patients progressed and 5 are alive. The median progression free survival was 11 months and the median overall survival was 13 months. There was no additional toxicity. These results indicate that elderly patients with good KPS can achieve outcomes comparable to the current standard of care using an abbreviated radiotherapy course, radiosurgery boost, and temozolomide.

BACKGROUND:Solitary fibrous tumors (SFTs) of the central nervous system are uncommon. Their biological features remain largely unknown; hence, the clinical management and prognosis is often challenging due to the lack of comprehensive data. For this reason, we present two cases of large SFTs to illustrate a comprehensive review. METHODS:THIS WAS A RETROSPECTIVE ANALYSIS OF TWO PATIENTS: a 65-year-old male with a left parietooccipital lesion and a 70-year-old female with a right parietal convexity mass. RESULTS:Gross total resection was performed in the male patient with no recurrence 30 months after resection. The second patient received stereotactic radiosurgery for what was initially thought to be a parafalcine meningioma; however, continued growth 1 year later prompted an open resection, with pathology indicative of an SFT. The tumor recurred the following year requiring repeat resection. Unfortunately, due to the aggressive nature of the lesion, the patient eventually succumbed to tumor burden a year later. CONCLUSION/CONCLUSIONS:Based on the literature review, the sometimes observed aggressive growth pattern, and also, the potential for malignant transformation, we recommend complete resection of SFTs with close sequential follow-up.

PURPOSE/OBJECTIVE:When patients show progression after conventional fractionated radiation for spine metastasis, further radiation and surgery may not be options. Stereotactic body radiotherapy (SBRT) has been successfully used in treatment of the spine and may be applicable in these cases. We report the use of SBRT for 60 consecutive patients (81 lesions) who had radiological progressive spine metastasis with epidural involvement after previous radiation for spine metastasis. METHODS AND MATERIALS/METHODS:SBRT was used with fiducial and vertebral anatomy-based targeting. The radiation dose was prescribed based on the extent of spinal canal involvement; the dose was 8 Gy×3=24 Gy when the tumor did not touch the spinal cord and 5 to 6 Gyx5=25 to 30 Gy when the tumor abutted the cord. The cord surface received up to the prescription dose with no hot spots in the cord. RESULTS:The median overall survival was 11 months, and the median progression-free survival was 9 months. Overall, 93% of patients had stable or improved disease while 7% of patients showed disease progression; 65% of patients had pain relief. There was no significant toxicity other than fatigue. CONCLUSIONS:SBRT is feasible and appears to be an effective treatment modality for reirradiation after conventional palliative radiation fails for spine metastasis patients.

PURPOSE/OBJECTIVE:Stereotactic body radiotherapy (SBRT) has been used successfully to treat patients with locally advanced pancreas cancer. However, many patients develop metastatic disease soon after diagnosis and may receive little benefit from such therapy. We therefore retrospectively analyzed a planned strategy of initial chemotherapy with restaging and then treatment for those patients with no evidence of metastatic progression with SBRT. METHODS AND MATERIALS/METHODS:Forty-seven patients received gemcitabine (1,000 mg/m(2) per week for 3 weeks then 1 week off) until tolerance, at least six cycles, or progression. Patients without metastases after two cycles were treated with SBRT (tolerance-based dose of 24-36 Gy in 3 fractions) between the third and fourth cycles without interrupting the chemotherapy cycles. RESULTS:Eight of the 47 patients (17%) were found to have metastatic disease after two cycles of gemcitabine; the remaining 39 patients received SBRT. The median follow-up for survivors was 21 months (range, 6-36 months). The median overall survival for all patients who received SBRT was 20 months, and the median progression-free survival was 15 months. The local control rate was 85% (33 of 39 patients); and 54% of patients (21 of 39) developed metastases. Late Grade III toxicities such as GI bleeding and obstruction were observed in 9% (3/39) of patients. CONCLUSION/CONCLUSIONS:For patients with locally advanced pancreas cancer, this strategy uses local therapy for those who are most likely to benefit from it and spares those patients with early metastatic progression from treatment. SBRT delivers such local therapy safely with minimal interruption to systemic chemotherapy, thereby potentially improving the outcome in these patients.

OBJECTIVE:Surgical resection of skull base tumors can be associated with significant morbidity. In cases where the risks outweigh the benefits, radiation therapy can offer an alternative means to effectively control tumor growth. However, the optimal dose regime for radiation therapy remains controversial. The objective of this study was to assess the neurological outcome, local control rate and morbidity associated with a 5-fraction regime of hypofractionated stereotactic radiotherapy (HSRT) for benign skull base tumors. METHODS:Twenty-six patients presenting with two of the most prevalent benign skull base tumors were included in the study. The tumors comprised 16 meningiomas and 10 acoustic neuromas. All patients exhibited preserved cranial nerve function prior to treatment, and a detailed audiological assessment was performed pre- and post-treatment for those patients with acoustic neuroma. Stereotactic radiosurgery was administered with the frameless CyberKnife Robotic Radiosurgery System. In each case, a 5-fraction HSRT regime was used: a dose of 5 Gy × 5 = 25 Gy to 6 Gy × 5 = 30 Gy was prescribed for skull base meningiomas, and 5 Gy × 5 = 25 Gy was prescribed for acoustic neuromas. RESULTS:The clinical and radiographic median follow-up was 22 months (range: 6-54 months). Radiological assessment showed local control in all 26 tumors (100%), and in 5/26 patients (20%) the tumor showed a decrease in size. Cranial nerve function was preserved in all cases thus far studied; however, 28% of patients had transient Grade II side effects, including fatigue, headaches, unsteadiness and transient subjective worsening of hearing. In two of these patients, the period of transient worsening of hearing was associated with a temporary increase in the size of the tumor on control T2 MR images, consistent with radiation-induced edema. One patient had transient decrease in visual acuity from treatment-related edema. At the last follow-up, 3/16 patients with meningiomas (19%) and 2/10 with acoustic neuromas (20%) showed a decrease in tumor volume and improvement in hearing. CONCLUSION/CONCLUSIONS:A 5-fraction stereotactic radiotherapy regime, as used in this study, seems to be effective for local control of benign skull base tumors in this early follow-up evaluation. Neurological function preservation is excellent with this short regime in the early post-treatment period, but long-term follow-up is crucial for validation.

PURPOSE/OBJECTIVE:Patients with nonmetastatic locally advanced unresectable pancreatic cancer have a dismal prognosis. Conventional concurrent chemoradiotherapy requires 6 weeks of daily treatment and can be arduous. We explored the safety and effectiveness of a 3-day course of hypofractionated stereotactic body radiotherapy (SBRT) followed by gemcitabine in this population. PATIENTS AND METHODS/METHODS:A total of 36 patients with nonmetastatic, locally advanced, unresectable pancreatic cancer with ≥12 months of follow-up were included. They received three fractions of 8, 10, or 12 Gy (total dose, 24-36 Gy) of SBRT according to the tumor location in relation to the stomach and duodenum, using fiducial-based respiratory motion tracking on a robotic radiosurgery system. The patients were then offered gemcitabine for 6 months or until tolerance or disease progression. RESULTS:With an overall median follow-up of 24 months (range, 12-33), the local control rate was 78%, the median overall survival time was 14.3 months, the median carbohydrate antigen 19-9-determined progression-free survival time was 7.9 months, and the median computed tomography-determined progression-free survival time was 9.6 months. Of the 36 patients, 28 (78%) eventually developed distant metastases. Six patients (17%) were free of progression at the last follow-up visit (range, 13-30 months) as determined by normalized tumor markers with stable computed tomography findings. Nine Grade 2 (25%) and five Grade 3 (14%) toxicities attributable to SBRT occurred. CONCLUSION/CONCLUSIONS:Hypofractionated SBRT can be delivered quickly and effectively in patients with nonmetastatic, locally advanced, unresectable pancreatic cancer with acceptable side effects and minimal interference with gemcitabine chemotherapy.