Berndt Wowra

Outpatient gamma knife surgery for vestibular schwannoma: definition of the therapeutic profile based on a 10-year experience

OBJECT The purpose of the study was to define the therapeutic profile of outpatient gamma knife surgery (GKS) for vestibular schwannoma (VS) by using sequential tumor volumetry to quantify changes following treatment. METHODS A total of 111 patients met the inclusion criteria. The median follow-up duration was 7 years (range 5-9.6 years). Thirty-seven patients (33%) had undergone surgery before GKS and 10 (9%) had neurofibromatosis Type 2 (NF2). The median VS volume was 1.6 cm3 (range 0.08-8.7 cm3). The actuarial 6-year tumor control rate after a single GKS treatment was 95%. Tumor swelling was observed in 43 patients (38.7%). Recurrence was significantly associated with NF2 (p < 0.003) and the reduced dose (p < 0.03) delivered to these tumors. The incidence of facial nerve neuropathy was mainly determined by surgery prior to GKS (p < 0.0001). Facial nerve radiation toxicity was mild and transient. No permanent facial nerve toxicity was observed. Trigeminal neuropathy occurred in 13 patients, and this was correlated with the VS volume (p < 0.02). The median hearing loss was -10 dB (range + 20 dB to -70 dB). The risk of hearing loss was correlated with age and transient tumor swelling (p < 0.05) but not with dose parameters or NF2. CONCLUSIONS Outpatient GKS is feasible, effective, and safe. Its therapeutic profile compares favorably with that of microsurgery.

Safety and feasibility of image-guided robotic radiosurgery for patients with limited bone metastases of prostate cancer

OBJECTIVE To determine the safety and feasibility after image-guided single fraction robotic stereotactic radiosurgery (SRS) in patients with bone metastases of prostate cancer. MATERIALS AND METHODS Forty patients with 64 bone metastases of prostate cancer were prospectively enrolled in a single center study and underwent 54 consecutive outpatient single session SRS procedures during a 4-year period. F-18 choline PET/CT in addition to standard CT imaging was done prior to SRS in all patients. Nineteen patients were under anti-androgen therapy, 8 patients had undergone chemotherapy before SRS. Overall survival and freedom from local tumor recurrence was analyzed with the Kaplan-Meier method. RESULTS Mean follow-up was 14 months (3-48 months). Seventy-five percent of patients had a single bone metastasis. The median tumor volume was 13 cc. The mean prescribed tumor dose was 20.2 Gy (16.5-22 Gy). Eight patients had died at the time point of the data analysis. The actuarial 6-months, 12-months, and 24-months local tumor control rate was 95.5% (95% CI: 83.0-98.8) as measured by MRI and PET CT imaging. The median initial PSA before SRS was 5.4 ng/dl (CI: 1.4-8.2) and dropped to 2.7 ng/dl (CI: 0.14-10) after 3 months. One case of progressive neurological deficits was documented. CONCLUSIONS This first report on single session, image-guided robotic SRS documents a safe, feasible, and patient-friendly treatment option in selected patients with bone metastases of prostate cancer.

Quality assurance in stereotactic space. A system test for verifying the accuracy of aim in radiosurgery.

A detailed quality assurance (QA) program is essential for high precision single dose irradiations. The accuracy of stereotactic radiosurgery is limited by the errors of each step in the chain for optimal treatment beginning with the diagnostic imaging and target localization leading to the dose planning and ending up with the treatment of the patient. Two main goals were followed on the way to finding a concept for a suitable and sufficient quality assurance routine. First, the chain of items in terms of a complete patient simulation should be followed and second, the stereotactic MR image data should be verified against a reference in our case stereotactic radiographic projection images. Target point verifications were performed using the so-called, unknown target method based on MRI, CT, and stereotactic projection images. A marked radiochromic film, embedded between inserts of the phantom is fixed parallel to either the xy or the xz plane of the stereotactic coordinate system. After imaging and planning, the phantom is adjusted and irradiated. At the end, the film, dyed by the radiation field around the premarked cross, is evaluated. The measured distance between the unit center point (shadow) and the localization of the marked film leads to the deviation to be minimized. This is referred to as the displacement vector. The results, evaluating 170 system tests within 5 years. show that the mean displacement vector of the complete system is 0.48 mm +/-0.23 mm (mean+/- sd). Factors having a significant influence on the overall accuracy are associated with MRI parameters. Test results based on axial images (xy plane; 0.42 mm +/- 0.24 mm) are significantly superior to coronal images (xz plane; x = 0.60 mm +/- 0.02 mm). Further on, the 3D-mpr sequence (0.40 mm +/- 0.19 mm) is significantly superior to the T1 weighted SE sequences (0.66 mm +/- 0.24 mm). Given the high mechanical accuracy of the Leksell gamma knife, the most sensitive technical factor having an influence on the overall precision of radiosurgery is the MRI study. However, using the appropriate imaging sequences and parameters the dislocation error inferred by MRI can be kept very low and restricted to the rare patient inherent distortion factors. With these precautions in mind, MRI is recommended as the imaging method of choice in radiosurgery.

Simultaneous anti-angiogenic therapy and single-fraction radiosurgery in clinically relevant metastases from renal cell carcinoma

Study Type – Therapy (case series)

Technical Description, Phantom Accuracy, and Clinical Feasibility for Single-Session Lung Radiosurgery Using Robotic Image-Guided Real-time Respiratory Tumor Tracking

To describe the technological background, the accuracy, and clinical feasibility for single session lung radiosurgery using a real-time robotic system with respiratory tracking. The latest version of image-guided real-time respiratory tracking software (Synchrony®, Accuray Incorporated, Sunnyvale, CA) was applied and is described. Accuracy measurements were performed using a newly designed moving phantom model. We treated 15 patients with 19 lung tumors with robotic radiosurgery (CyberKnife®, Accuray) using the same treatment parameters for all patients. Ten patients had primary tumors and five had metastatic tumors. All patients underwent computed tomography-guided percutaneous placement of one fiducial directly into the tumor, and were all treated with single session radiosurgery to a dose of 24 Gy. Follow up CT scanning was performed every two months. All patients could be treated with the automated robotic technique. The respiratory tracking error was less than 1 mm and the overall shape of the dose profile was not affected by target motion and/or phase shift between fiducial and optical marker motion. Two patients required a chest tube insertion after fiducial implantation because of pneumothorax. One patient experienced nausea after treatment. No other short-term adverse reactions were found. One patient showed imaging signs of pneumonitis without a clinical correlation. Single-session radiosurgery for lung tumor tracking using the described technology is a stable, safe, and feasible concept for respiratory tracking of tumors during robotic lung radiosurgery in selected patients. Longer follow-up is needed for definitive clinical results.

CyberKnife Radiosurgery for Malignant Spinal Tumors Characterization of Well-Suited Patients

Study Design. A prospective interventional case-series study. Objective. To provide clinical results of CyberKnife fiducial-free spinal radiosurgery. The study focused on patients with no more than 2 malignant spinal tumors. Summary of Background Data. Progress in frameless radiosurgical technology has enabled the application of radiosurgery to the spine. The CyberKnife System has been used extensively for spine radiosurgery. Until recently, the system required metallic fiducial implants for precise target tracking. Fiducial-free spinal radiosurgery with the CyberKnife has recently become possible, but until now clinical results obtained with this method had been limited. Methods. From August 2005 until October 2007, a consecutive series of 102 patients with a total of 134 malignant spinal tumors were selected for single-fraction, fiducial-free CyberKnife radiosurgery (CKRS). The study was limited to patients with a maximum of 2 tumors. Malignant primaries included breast cancer in 23 (22.6%) patients, renal cancer in 20 (19.6%) patients, gastro-intestinal cancers in 12 (11.8%) patients, prostate cancer each in 12 (11.8%) patients, lung cancer in 9 (8.9%) patients, sarcomas in 7 (6.9%) patients. A variety of other malignant tumors were found in 19 (18.6%) patients. Patients with spinal cord compression or evidence of myelopathy were excluded. The sequential neurologic status was recorded. Tumor-associated spinal pain was prospectively scored according to the visual analogue scale (VAS). Results. Of 102 individuals, 22 (21.6%) died due to progression of their systemic disease. Mean survival after CKRS was 1.4 years (CI: 1.2–1.6). Karnofsky performance score was the only independent predictor of survival after radiosurgery on log-rank test (P < 0.0001), and on Cox regression analysis (hazard ratio, 0.864, P < 0.0001, CI: 0.809–0.922). Median survival after initial tumor diagnosis was 18.4 years (CI: 15.1–23.4). Two (2%) patients suffered complications after radiosurgery; a tumor hemorrhage occurred in one, and another developed spinal instability. These and 2 other patients were stabilized by kyphoplasty. Neurotoxicity or myelopathy was not observed. Local tumor control 15 months after CKRS was 98% (95% CI: 89–99%). Tumor-associated pain was observed in 52 (51%) patients. In these patients the median pretreatment pain score of VAS = 7 (95% CI: 6–7) was significantly reduced to VAS = 1 (95% CI: 4–6) (P < 0.001) within 1 week after CKRS. Analysis of variance identified the initial pain score as the only significant variable to predict pain reduction after CKRS (P < 0.03). Pain recurrence in correlation with tumor recurrence was observed for 3 (6%) patients. Conclusion. Spinal radiosurgery with the CyberKnife technology is a nonivasive, safe, and effective treatment method for patients with 1 or 2 small spinal malignant tumors. The best benefit of the treatment can be expected in patients with good to excellent clinical condition and patients with severe tumor associated pain.

Multisession CyberKnife radiosurgery for optic nerve sheath meningiomas

Optic nerve sheath meningiomas (ONSMs) are benign lesions originating from the dural sheath of the optic nerve. Progressive growth can lead to gradual loss of vision and exophthalmos. Loss of vision following microsurgical resection is not uncommon, and although stereotactic fractionated radiotherapy can be a safe alternative to control tumor growth and preserve vision, it may also lead to complications. Frame-based stereotactic radiosurgery has only been rarely used because single-fraction high-dose treatments of intrinsic optic nerve lesions may induce unacceptably high toxicity. New frameless radiosurgery devices such as the robotic CyberKnife, an image-guided radiosurgery system, can provide the extremely tight conformality and submillimetric accuracy of frame-based systems combined with the possibility of delivering radiation in several sessions. In the present report the authors review the clinical presentation and management of ONSMs and describe their preliminary experience using multisession radiosurgery to treat these lesions.

Stereotaktische Konvergenzbestrahlung großer uvealer Melanome mit dem Gamma-Knife

ZusammenfassungHintergrund. Wir berichten über unsere 3-Jahres-Ergebnisse mit der stereotaktischen Konvergenzbestrahlung (Gamma-Knife) bei großen und ungünstig gelegenen uvealen Melanomen. Patienten und Methode. Seit 1997 wurden 100 Patienten (51 männlich, 49 weiblich) nach einem standardisierten Protokoll behandelt (ambulante Einzeitbestrahlung, Maximaldosis 50 Gy,Tumorranddosis mindestens 25 Gy, ausschließlich Retrobulbäranästhesie zur Bulbusfixation).Bei keinem Patienten war auf Grund der Lokalisation und/oder der Tumorgröße eine Brachytherapie mit Ru-106-Applikator möglich.Am hinteren Pol waren 61 Tumoren (61%) lokalisiert,21 Tumoren (21%) lagen ausschließlich chorioidal in der mittleren Peripherie, und 18 Tumoren (18%) lagen anterior und bezogen den Ziliarkörper mit ein. Alle Patienten wurden regelmäßig ophthalmologisch und neuroradiologisch nachuntersucht. Für 73 Patienten lagen 1-, für 33 Patienten 2- und für 17 Patienten 3-Jahres-Nachbeobachtungsdaten vor. Ergebnisse. Zwei der 100 Patienten erlitten ein Tumorrezidiv.Vor der Bestrahlung (100 Patienten) betrug die maximale apikale Tumorhöhe (MAH) median 7,8 mm (95% KI 2,9–12,5 mm).Nach 1 Jahr (73 Patienten) betrug die MAH median 5,7 mm (95% KI 2,4–10,2 mm),nach 2 Jahren (33 Patienten) median 4,3 mm (95% KI 2,2–8,8 mm) und nach 3 Jahren (15 Patienten) median 4,6mm (95% KI 2,4–8,5 mm).Alle Differenzen zur MAH der jeweiligen Patienten vor Bestrahlung waren statistisch signifikant (zweiseitiger gepaarter t-Test). Innerhalb des 1. Jahres nach Bestrahlung mussten 7 Patienten wegen eines schmerzhaften Sekundärglaukoms enukleiert werden.Innerhalb des 2. Jahres nach Bestrahlung mussten 2 Patienten (1 Tumorrezidiv,1 Sekundärglaukom) und innerhalb des 3. Jahres ein weiterer Patient (Tumorrezidiv) enukleiert werden. Schlussfolgerung. Unsere 3-Jahres-Ergebnisse zeigen, dass die stereotaktische Konvergenzbestrahlung mit dem Gamma-Knife bei 98% der Patienten mit großen und ungünstig gelegenen uvealen Melanomen in der Lage ist, eine lokale Tumorkontrolle zu induzieren. Das Risiko für eine Sekundärenukleation ist im 1. Jahr nach Bestrahlung am höchsten, aber insgesamt bei diesen großen Tumoren mit 10% als niedrig anzusehen. Die sehr gute lokale Tumorkontrollrate veranlasste uns, bei den nachfolgend behandelten Patienten die Maximaldosis auf 40 Gy(Tumorranddosis mindestens 20 Gy) zu reduzieren.AbstractBackground. We report the results over 3 years with stereotactic radiosurgery using the Gamma Knife for large and unsuitably located uveal melanomas. Patients and methods. A total of 100 patients (51 male, 49 female) have been treated since 1997 following a standardised treatment protocol (outpatient single-shottreatment, maximum dose 50 Gy,tumour margin dose min.25 Gy, retrobulbar anaesthesia alone for globe fixation).The localisation and/or dimension of the tumours did not allow radiation brachytherapy with Ru106 plaques.Of the tumours 18 were located in the ciliary body, 61 were located at the posterior pole, and 21 were located in the mid-periphery. All patients were followed and tested ophthalmologically and neuroradiologically at regular intervals. The 1-year follow-up data were available for 73 patients, 2-year follow-up data for 33 patients and 3-year follow-up-data for 17 patients. Results. Before therapy the maximum apical tumour height (MAH) was median 7.8 mm (95% CI 2.9–12.5 mm): 1 year after treatment (73 patients) the MAH was median 5.7 mm (95% KI 2.4–10.2 mm),2 years after treatment (33 patients) the MAH was median 4.3 mm (95% KI 2.2–8.8 mm),and 3 years after treatment (17 patients) the MAH was median 4.6 mm (95% KI 2.4–8.5 mm).All differences to the MAH of the corresponding patients before treatment were statistically significant (paired t-test). Within the first year after treatment seven patients were enucleated due to a painful secondary glaucoma,within the second year after radiation two patients (one tumour recurrence, and one secondary glaucoma) and within the third year one more patient (tumour recurrence) was enucleated. Conclusions. Our 3-year results demonstrate that radiosurgery using the Gamma Knife is beneficial in achieving a local tumour control in 98% of eyes with large and unsuitably located uveal melanomas. The risk for a secondary enucleation is highest in the first year after treatment with a favourable overall rate of 10%. Due to the excellent local tumour control rate we decreased the maximum dose to 40 Gy (min.tumour margin dose 20 Gy) in the subsequently treated patients.

Development of a Streamlined, Non-invasive Robotic Radiosurgery Method for Treatment of Uveal Melanoma

To analyze the feasibility and safety of frameless, image-guided robotic radiosurgery against uveal melanoma, we developed a streamlined procedure that is completed within 3 hours under retrobulbar anesthesia without immobilization. Twenty patients (10 men and 10 women) with medium (3–5-mm prominence) and large (>5-mm prominence) unilateral uveal melanomas were treated with a frameless robotic radiosurgery system. Median age was 61 years (range 32–78 years). All patients underwent a single-session procedure beginning with retrobulbar anaesthesia, followed by computerized tomography (CT) scanning that was used in the generation of a treatment plan, and then the delivery of a radiosurgical tumor dose between 18 and 22 Gy to the 70% isodose line. Three-dimensional treatment planning was aimed at securing the optical lens and the optic disc as much as possible. Follow-up occurred at 3, 6, 12, and 18 months after the radiosurgery with clinical, ultrasound, and CT studies. We were able to treat all patients in the frameless setup within 3 hours. In five patients with lateral and dorsal tumors, the dose to the optic lens could be kept below 2 Gy. The clinical response was evaluated for the first seven patients treated with a follow-up of at least 6 months. No local recurrences occurred with any of the clinically evaluated patients for a mean 13-month follow-up (range 6–22 months). Maximum median apical tumor height according to standardized A-scan ultrasound evaluations decreased from 7.7 to 5.6 mm (p < 0.1). The median reflectivity increased from 41% to 70% (p < 0.01). None of the patients developed a secondary glaucoma during the short-term follow-up period. Frameless, single-session, image-guided robotic radiosurgery is a feasible, safe and comfortable treatment option for patients with uveal melanoma. Longer follow-up and analysis of a larger patient series is required for definitive clinical recommendations.

Treatment of brain metastases in renal cell carcinoma: radiotherapy, radiosurgery, or surgery?

Metastases from renal cell carcinoma raise specific therapeutic problems because they are relatively unresponsive to whole brain radiation therapy and tend to bleed. Recently, stereotactically guided high-precision irradiation as a single dose application (radiosurgery) showed promising treatment results for selected patients with brain metastases from renal cell carcinoma. Radiosurgery appears attractive due to its low risk and minimal invasiveness. Multiple lesions can be treated at the same time and retreatments can be performed for local or distant recurrences.