Markus Kufeld

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.

Human satellite cells have regenerative capacity and are genetically manipulable

Muscle satellite cells promote regeneration and could potentially improve gene delivery for treating muscular dystrophies. Human satellite cells are scarce; therefore, clinical investigation has been limited. We obtained muscle fiber fragments from skeletal muscle biopsy specimens from adult donors aged 20 to 80 years. Fiber fragments were manually dissected, cultured, and evaluated for expression of myogenesis regulator PAX7. PAX7+ satellite cells were activated and proliferated efficiently in culture. Independent of donor age, as few as 2 to 4 PAX7+ satellite cells gave rise to several thousand myoblasts. Transplantation of human muscle fiber fragments into irradiated muscle of immunodeficient mice resulted in robust engraftment, muscle regeneration, and proper homing of human PAX7+ satellite cells to the stem cell niche. Further, we determined that subjecting the human muscle fiber fragments to hypothermic treatment successfully enriches the cultures for PAX7+ cells and improves the efficacy of the transplantation and muscle regeneration. Finally, we successfully altered gene expression in cultured human PAX7+ satellite cells with Sleeping Beauty transposon-mediated nonviral gene transfer, highlighting the potential of this system for use in gene therapy. Together, these results demonstrate the ability to culture and manipulate a rare population of human tissue-specific stem cells and suggest that these PAX7+ satellite cells have potential to restore gene function in muscular dystrophies.

Radiosurgery of spinal meningiomas and schwannomas.

Purpose of this study is to analyze local control, clinical symptoms and toxicity after image-guided radiosurgery of spinal meningiomas and schwannomas. Standard treatment of benign spinal lesions is microsurgical resection. While a few publications have reported about radiosurgery for benign spinal lesions, this is the first study analyzing the outcome of robotic radiosurgery for benign spinal tumors, treated exclusively with a non-invasive, fiducial free, single-fraction setup. Thirty-six patients with spinal meningiomas or schwannomas were treated, utilizing a robotic radiosurgery system (CyberKnife®, Accuray Inc. Sunnyvale CA), and were followed prospectively. Medical history, histology, clinical symptoms and radiographic outcome were recorded. Thirty-nine spinal lesions were treated because of tumor recurrence, remnants after microsurgery, multiple lesions, or rejection of open surgery. Median age was 45 years (range 18–80 years). Median target volume was 3.4 cm3 (range 0.2–43.4 cm3). Histology revealed 28 schwannomas and 11 meningiomas (WHO grade I). All spinal levels were affected. Median prescription dose was 14 Gray (95% C.I. 13.4–14 Gy) to the 70% isodose. After a median follow-up of 18 months (range 6–50 months) no local tumor progression was detected. 20 lesions (51%) remained stable, 19 tumors (49%) decreased in size. One patient with schwannomatosis was treated repeatedly for three new tumor locations. Pain was the initial symptom in 16 of 25 schwannoma patients, and in 3 of 11 patients with meningiomas. Pain levels decreased in 8/19 patients. All but one patient with motor deficits remained clinically stable. No myelopathic signs where found. Single-session radiosurgery for benign spinal tumors in selected patients has proven to inhibit tumor progression within the observed period without signs of early toxicity. Radiosurgery offers an additional treatment option, if microsurgery is not feasible in cases of tumor recurrence, post-resection remnants, multiple lesions, or medical comorbidity.

Spinal radiosurgery - efficacy and safety after prior conventional radiotherapy

BackgroundConventional external beam radiotherapy is a standard procedure for treatment of spinal metastases. In case of progression spinal cord tolerance limits further radiotherapy in pre-irradiated areas. Spinal stereotactic radiotherapy is a non-invasive option to re-treat pre-irradiated patients. Nevertheless, spinal radiosurgery results in relevant dose deposition within the myelon with potential toxicity. Aim of the study was to retrospectively analyse the efficacy and feasibility for salvage radiosurgery of spinal metastases.MethodsDuring a period of 4 years (2005-2009) 70 lesions in 54 patients were treated in 60 radiosurgery sessions and retrospectively analysed. Clinical (pain, sensory and motor deficit) and radiological (CT/MRI) follow-up data were collected prospectively after radiosurgery. Pain - as main symptom - was classified by the Visual Analogue Scale (VAS) score. Every patient received single session radiosurgery after having been treated first-line with conventionally fractionated radiotherapy. Kaplan-Meier method and life tables were used to analyse freedom from local failure and overall survival.ResultsAt a median follow-up of 14.5 months the actuarial rates of freedom from local failure at 6/12/18 months were 93%, 88% and 85%, respectively. The median radiosurgery dose was 1 × 18 Gy (range 10-28 Gy) to the median 70% isodose. The VAS score of patients with pain (median 6) dropped significantly (median 4, p = 0.002). In 6 out of 7 patients worse sensory or motor deficit after SRS was caused by local or distant failures (diagnosed by CT/MRI). One patient with metastatic renal cell carcinoma developed a progressive complete paraparesis one year after the last treatment at lumbar level L3. Due to multiple surgery and radiosurgery treatments at the lumbar region and further local progression, the exact reason remained unclear. Apart from that, no CTC grade III or higher toxicity has been observed.ConclusionsBy applying spinal radiosurgery relevant radiation doses can be limited to small parts of the myelon. This prevents myelopathic side effects and makes it an effective and safe treatment option for well-suited patients. Especially for previously irradiated patients with local failure or pain salvage SRS represents a valuable treatment option with high local control rates, low toxicity and significant pain reduction.

Dosimetric comparison of different treatment modalities for stereotactic radiosurgery of meningioma

The original version of this article unfortunately contained mistakes. The name of Constantin Tulaesca is misspelled, it should be Constantin Tuleasca. The correct affiliation of C. Tuleasca and M. Levivier should be: Lausanne University Hospital, Neurosurgery Service and Gamma Knife Center; University of Lausanne, Faculty of Biology and Medicine On the third page, Subtitle “Patient population”, lines 18 and 19: “Gamma Knife planning and optimalisation was performed by Thierry Gevaert” should be: “Gamma Knife planning and optimalisation was performed by Marc Levivier”.

Functional brain mapping of patients with arteriovenous malformations using navigated transcranial magnetic stimulation: first experience in ten patients

BackgroundIntracranial arteriovenous malformations (AVM) are known to be potent inductors of functional plasticity, and their vasculature makes standard functional imaging difficult. Here we conducted functional mapping of both primary motor cortex and speech related areas in patients with AVM using navigated transcranial magnetic stimulation (nTMS), which has been recently proven as a reliable noninvasive modality of preoperative functional brain mapping.MethodnTMS mapping was performed in ten patients with unruptured intracranial AVMs located in or near eloquent areas. Motor mapping was conducted for six patients with AVMs near the rolandic region, and speech mapping was performed for four patients with left perisylvian AVMs. After the examination, all patients were treated with surgery, radiosurgery or observed with best medical treatment on case-by-case basis.ResultsMotor mapping allowed for delineation of the primary motor cortex, even if the anatomy was severely obscured by the AVM in all cases with rolandic AVMs. No plastic relocation of the primary motor cortex was observed. Repetitive stimulation of the left ventral precentral gyrus led to speech impairments in all four cases that underwent speech mapping. Right hemispheric involvement was observed in one out of four cases and potentially indicated plastic changes. No side effects were observed.ConclusionnTMS allowed for detailed delineation of eloquent areas even within hypervascularized cortical areas. Our observations indicate that nTMS functional mapping is feasible not only in tumorous brain lesions, but also in AVMs.

Advances in fiducial-free image-guidance for spinal radiosurgery with CyberKnife - a phantom study

The image‐guided CyberKnife radiosurgery system is capable of tracking spinal targets without fiducial implants. Recently, a new version of this fiducial‐free image guidance modality (“enhanced Xsight spine tracking”) has been introduced. We assessed the accuracy of this novel technique versus its precursor in a comparative phantom study. The CyberKnife consists of a 6 MV linac on a six‐axis robot and a stereoscopic kV image guidance system. An anthropomorphic head‐and‐neck phantom with a cervical spine section was mounted on the linac nozzle. The robotic manipulator was used to precisely move the phantom to defined positions in the CyberKnife workspace. Multiple stereoscopic images were acquired at different translational and rotational positions. The enhanced Xsight spine tracking readouts were recorded and compared to the nominal phantom position. These tests were repeated with the original Xsight spine tracking version to analyze potential differences. Enhanced Xsight spine tracking correctly reported translational offsets with an RMS error of less than 0.4 mm. Yaw and roll rotations were detected with an accuracy of 0.2°, 0.25°. Pitch offsets were slightly underestimated, with up to 0.3° for an offset of ± 2°. Nominal X (left‐right) translational offsets were partially misinterpreted as roll (0.2° at a 10 mm offset). Apart from this, no correlation between rotational and translational directions was found. In comparison, the original Xsight spine tracking showed identical results for translations, but larger systematic and statistical errors for rotations. Enhanced Xsight spine tracking measurably improves precision in fiducial‐free spinal radiosurgery with the CyberKnife. PACS number: 87.53.Ly

Papillary tumor of the pineal region with anaplastic small cell component

Papillary tumor of the pineal region (PTPR) is a rare brain tumor mainly affecting young adults [1, 2]. The histopathology of PTPR is characterized by loose papillary structures and tumor cells forming broad perivascular pseudorosettes showing cytokeratin expression. Little is known on the biology of PTPR, whose clinical course is often characterized by recurrences [1, 2]. Accordingly, PTPR can be classified as WHO grade II or III, but definitive histopathological grading criteria are lacking. Even though PTPR may show mitotic activity, necroses and solid growth, cases with poorly differentiated highly malignant areas have not yet been described. We therefore report the case of a PTPR with an anaplastic small cell component. A 59-year-old woman with signs and symptoms of hydrocephalus underwent an MRI-scan, which showed a contrast enhancing third ventricular mass measuring 17 9 14 9 11 mm (Fig. 1). Intraoperatively, gross total resection was thought to be achieved. On histopathological examination, the tumor showed loose papillary structures and tumor necroses as well as broad perivascular pseudorosettes characteristic of PTPR (Fig. 2a, c). In addition, however, there were also less differentiated areas with solid growth, high cellularity and small blue and round cells (Fig. 2b, d). In the latter, mitotic activity was markedly increased (4–6 mitoses per HPF). On immunohistochemical staining, the majority of tumor cells in both tumor components expressed cytokeratin (MNF116, Fig. 2e, f) as well as S-100 protein. Few tumor cells also expressed synaptophysin. Tumor cells stained negative for glial fibrillary acidic protein, epithelial membrane antigen, neuron-specific nuclear protein, neuron-specific enolase, neurofilament and thyroid transcription factor 1 (TTF1). The Ki67/MIB1 proliferation index accounted for 15–20 % in the papillary tumor component (Fig. 2g), but was more markedly increased in the anaplastic small cell areas (up to 50 %) (Fig. 2h). Imaging studies performed 2 months postoperatively revealed tumor progression (Fig. 1c). The patient was treated using a dedicated robotic LINAC for radiosurgical treatments in a single session of 30 min. The target volume of 1.2 cm was covered 99.9 % with a minimal dose of 17 Gy prescribed to the 85 % isodose line, resulting in a maximum dose of 24.3 Gy. Eighty-five individually calculated beams were used to cover the target with special regard to a steep dose gradient around the target lesion. Stereotactic radiation resulted in a marked decrease in tumor size (Fig. 1d). Six months post-operatively, the patient is alive and well. PTPR may show increased mitotic activity, compact solid growth and may also undergo malignant progression [2, 3]. PTPR featuring an anaplastic small cell component, however, have not yet been described; the present case S. Heim W. Paulus M. Hasselblatt (&) Institute of Neuropathology, University Hospital Münster, Pottkamp 2, 48149 Münster, Germany e-mail: hasselblatt@uni-muenster.de

Cyberknife radiosurgery of a renal pelvis tumor to avoid renal dialysis

Transitional cell cancer (TCC) in the renal pelvis is usually treated by nephro-ureterectomy. In functional or anatomical singular renal units, consecutive chronic hemodialysis will be needed. We present a patient treated by image-guided robotic radiosurgery for definitive tumor control of a T2G3 recurrent transitional cell cancer of the renal pelvis in a singular renal unit after nephro-ureterectomy of the contralateral kidney. Categories: Radiation Oncology, Urology