Single-fraction image-guided robotic radiosurgery efficiently controls local prostate cancer recurrence after radical prostatectomy.

Purpose: To assess the therapeutic potential of single-fraction robotic stereotactic ablative body radiotherapy (SABR) in patients with locally recurrent prostate cancer (PC) after radical prostatectomy (RP). Materials and methods: We included 35 patients with biochemical failure after RP with single-site local recurrence in the prostate bed diagnosed by PSMA PET/CT. About 20/35 pts had previously received post-surgical adjuvant radiation therapy.High-resolution multiparametric magnetic resonance imaging (mpMRI) for exact visualization of tumor tissue was performed at 1.5 (n = 23; Siemens Magnetom Aera) or 3 Tesla (n = 12; Siemens Magnetom VIDA, Siemens Healthineers, Erlangen, Germany). Using the MRI and PET/CT dataset for planning, SABR was carried out after ultrasound-guided placement of a single gold fiducial marker at the site of tumor recurrence using a CyberKnife M6 unit (Accuray Inc., Sunnyvale, USA). Due to the high diagnostic accuracy of PSMA PET/CT and mpMRI, pre-SABR biopsy of tumor tissue was not deemed necessary. PSMA PET/CT performed in median 88 days before SABR confirmed the absence of distant metastases. MpMRI was performed at a median of 22 days prior to the intervention. SABR was performed in a single fraction with a dose of 20 (5/35), 21 (27/35) or 22 (3/35) Gy. Follow-up serum PSA was measured every 3 months thereafter. Results: Median patient age was 72 years (57-80 years) and median time from RP to SABR was 96.8 months (IQR, 69.3-160.2). Median serum PSA before SABR was 1.38 ng/mL (IQR 0.75-2.72). At 3 months, median PSA had dropped significantly in 27/35 patients to a median of 0.35 ng/mL (IQR 0.25-0.68). At 6 months, 30/35 patients showed biochemical response to SABR, while five patients were progressing: three had systemic disease on PSMA PET/CT, while two patients had rising PSA values without a visible correlate on PET/CT. The median follow-up time was 16 months. Grade 1 genitourinary (GU) toxicity was reported in 3/35 patients (9%) and grade 1 gastrointestinal (GI) toxicity in 2/35 patients (6%), respectively. Conclusion: SABR is an efficient new treatment option in the management of single-site local recurrent PC without the evidence of systemic disease; due to its very low toxicity, it is an alternative to surgical re-treatment or other focal therapies. It can significantly delay the onset of androgen deprivation therapy (ADT) in biochemical failure after radical prostatectomy.

Quality of life in the follow-up of uveal melanoma patients after enucleation in comparison to CyberKnife treatment.

PURPOSE: To compare quality of life (QoL) in patients with uveal melanoma after enucleation and stereotactic radiosurgery to that in an age-matched patient collective. METHODS: QoL was assessed in a cross-sectional survey and compared among 32 uveal melanoma patients after enucleation, 48 patients after stereotactic radiosurgery (CyberKnife(®); Accuray(®) Incorporated, Sunnyvale, CA, USA), and an age-matched control group of 35 patients, using the SF-12 Health Survey. Statistical analysis was performed with Fisher's exact test, Student's t test, one-way ANOVA analysis, Wilcoxon rank-sum (Mann-Whitney test), and ordered logistic regression for multivariate analysis. RESULTS: There was no significant difference in QoL between patients treated by stereotactic radiosurgery and the age-matched control group. After enucleation, patients presented significantly lower values in Physical Functioning (PF), Role Physical (RP), and Role Emotional (RE) compared to the radiosurgery and control group. To control for the overall QoL lowering effect of visual loss, the QoL of the patients who underwent enucleation was compared with the QoL of patients suffering severe functional loss after CyberKnife radiosurgery in a subgroup analysis, which showed no statistically significant difference. The number of comorbidities had a significant impact on QoL in multivariate analysis. CONCLUSIONS: Superior performance in PF, RP, and RE suggests that CyberKnife represents a suitable first-line therapy for uveal melanoma. In cases with painful amaurosis or vast tumor recurrence, enucleation can be performed with an acceptable QoL outcome.

CyberKnife radiosurgery for the treatment of orbital metastases.

Purpose of this study is to evaluate radiographic therapy response, clinical outcome and adverse effects of CyberKnife radiosurgery in patients suffering from orbital metastases. Sixteen orbital metastases originating from different solid cancers in fourteen patients were treated by single fraction CyberKnife radiosurgery. Radiographic response and clinical outcome were evaluated. The treated tumor volume ranged from 0.2 to 35 cm3 (median 2.3 cm3, mean 7.0 cm3, SD 6 10.4 cm3, CI 0.9-9.4 cm3). The prescription dose ranged from 16.5-21 Gy (median 18 Gy, mean 18.2 Gy, SD 6 1.2 Gy, CI 17.0-18.4 Gy). A no change situation was observed in nine lesions, partial remission in four as well as complete remission in one metastasis. Tumor growth was stabilized or regressive following CyberKnife therapy in 87% of the cases. Recurrence was observed in two cases (13%). Before therapy, three patients suffered from visual disturbance and five patients reported diplopia. Six patients had no initial symptoms. After therapy, one patient indicated improvement of the present visual deficit and two patients no change. Out of the two patients with persistent diplopia, two reported improvement after therapy and three no change. No progression of symptoms was noted in any of the cases. Fourteen out of sixteen treated lesions were stable or regressive following CyberKnife radiosurgery (87%). As no serious adverse effects were reported in this series, CyberKnife therapy was shown to be of great value for local management of orbital metastases.

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 cm(3) (range 0.2-43.4 cm(3)). 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.

Combined surgical and radiosurgical treatment of symptomatic aggressive vertebral osteomyelitis.

INTRODUCTION: The surgical treatment of vertebral osteomyelitis can be complicated by severe additional diseases or the need for extensive debridement with concomitant risks. We report a case of combined surgical and radiosurgical treatment of idiopathic vertebral osteomyelitis of L4. CASE REPORT: The patient presented with progressive enlargement of the right side of the vertebral body L4 due to chronic fibrous osteomyelitis without evidence of infection, leading to compression of nerve roots L4, L5 and the dural sac with resulting radicular paresis. During decompression of the nerve roots via a dorsal approach, massive bleeding from the inflammatory vertebral body occurred, making abortion of surgery necessary. Remnant inflammatory masses of vertebral body L4 were treated by spinal robotic radiosurgery with a high tumoricidal dose of 20 Gy without clinical and radiological signs of relapse of disease in the following three years. CONCLUSION: We describe a case of the combined surgical and radiosurgical treatment of lumbar osteomyelitis with symptomatic nerve root compression. Dorsal decompression followed by spinal radiosurgery for the anterior vertebral parts with avoidance of potentially dangerous anterior spondylectomy led to a rapid improvement of paresis and pain with persistent control of vertebral inflammation and enlargement. The described case of close cooperation of surgeons and radiosurgeons offered an effective and functionality preserving treatment in this challenging case.

[Cyberknife surgery with a radio-scalpel: a new treatment option for patients with unresectable metastases]. / Cyberknife-Chirurgie mit dem Strahlenmesser: eine neue Behandlungsalternative für Patienten mit inoperablen Metastasen.

Patients with non-resectable metastases of various diseases are today treated by one of several different techniques, such as radiofrequency ablation, laser-induced thermoablation or stereotactic radiotherapy. Frequently, the employment of these therapeutic strategies is limited due to their invasiveness and treatment-associated morbidity. Furthermore, stereotactic radiotherapy is associated with a high degree of patient discomfort due to the necessary fixation of moving inner organs (lung, liver). With the development of the cyberknife radiosurgery technique, an image-guided, superselective, robot-based radiotherapy, these problems seem to be resolved. With this technique, metastases may be treated in an outpatient single-treatment setting.

Frameless single-session robotic radiosurgery of liver metastases in colorectal cancer patients.

INTRODUCTION: Due to advanced chemotherapy regimens, patients presenting with residual liver metastases of colorectal cancer (CRC) has increased. Surgery of residual metastases enhances overall survival, but surgical resection is often limited. Less invasive techniques have been invented to enhance local disease control. We investigated in a selected patient cohort local control of liver metastasis from CRC using robotic radiosurgery. METHODS AND MATERIALS: In this study patients with colorectal liver metastases were prospectively followed after having been treated with single-session radiosurgery using a robotic image-guided device and real-time tumour tracking. The primary end-point was local control (LC); secondary end-points were toxicity, progression-free survival (PFS) and overall survival (OS). Extrahepatic metastases were excluded using a whole body (PET-CT: positron emission tomography computed tomography). Follow up was done by liver MRI every 3 months post-treatment. RESULTS: Fourteen patients (median age 65 years), with a total of 19 colorectal liver metastases were treated with 24 Gy in one fraction. Median follow up was 16.8 months. A one-year LC rate of 87% and a median PFS of 9.2 months were reached. DISCUSSION: Frameless robotic image-guided radiosurgery with real-time tumour tracking as an effective treatment for patients with colorectal liver metastases. This technique enhances the possibilities of multidisciplinary oncological concepts.

[Interventional oncology for lung tumors]. / Interventionelle Onkologie bei Lungentumoren.

Lung tumors and pulmonary metastases together are the most common cause of cancer-related death in men and the second most frequent in women. Up to now, surgical resection has remained the gold standard in the treatment of pulmonary tumors, being the only treatment option that was potentially curative and offered the possibility of a significant increase in life expectancy after successful therapy. Over the past decade, percutaneous radiofrequency ablation (RFA) has gained worldwide acceptance in the treatment of primary and secondary tumors of the liver with curative intent, so that indications for RFA have been extended to embrace tumors in other organs, e.g. the lung. Since the first case results were described, the number of publications dealing with the treatment of lung tumors using thermal ablative therapies has increased significantly. The aims of the present article are to give a short overview of emerging therapies such as cyberknife surgery and also, especially, to describe the indications for and technique of RFA, to discuss the ideal method of follow-up, and to highlight possible complications of the therapy and the current results of RFA of primary and secondary lung tumors. In addition, the value of combining RFA with other therapy modes (especially chemotherapy and radiation therapy)is briefly treated.

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.

Functional outcome after gamma knife treatment in vestibular schwannoma.

Radiosurgery (RS) is a noninvasive, ambulatory special neurosurgical procedure for the treatment of vestibular schwannoma (VS). We treated 123 patients with unilateral schwannomas between 1994 and 2000 at the gamma knife (GK) center in Munich using a primary stereotactic procedure. These patients were followed up until June 2004 in respect to audiological, neurological, neurootological and radiological features before and after radiosurgical intervention. The actual tumor control rate of 8.2 years (mean) after GK surgery for all patients and a single treatment was calculated to be 96.7%. The impairment of hearing was on average 18% after GK, ranking from 0% gain of hearing loss up to 90%. Facial nerve function, graded according to the House-Brackmann scale, deteriorated in none of the patients; 5.8% reported a trigeminal neuralgia. Tinnitus developed in 4.1% of the patients after RS; 13.3% had vertigo for the first time after the treatment, age apparently being a predisposing factor. Radiosurgical treatment for VS is an alternative to microsurgery (MS). It is associated with a lower rate of facial and trigeminal neuropathy, postoperative complications and hospital stay. The hearing preservation rate is equivalent to MS.

Image guided interstitial laser thermotherapy: a canine model evaluated by magnetic resonance imaging and quantitative autoradiography.

OBJECTIVE: To determine the applicability and safety of a new canine model suitable for correlative magnetic resonance imaging (MRI) studies and morphological/pathophysiological examination over time after interstitial laser thermotherapy (ILTT) in brain tissue. MATERIAL AND METHODS: A laser fibre (Diode Laser 830 nm) with an integrated temperature feedback system was inserted into the right frontal white matter in 18 dogs using frameless navigation technique. MRI thermometry (phase mapping i.e. chemical shift of the proton resonance frequency) during interstitial heating was compared to simultaneously recorded interstitial fiberoptic temperature readings on the border of the lesion. To study brain capillary function in response to ILTT over time quantitative autoradiography was performed investigating the unidirectional blood-to-tissue transport of carbon-14-labelled alpha amino-isobutyric acid (transfer constant K of AIB) 12, 36 hours, 7, 14 days, 4 weeks and 3 months after ILTT. RESULTS: All laser procedures were well tolerated, laser and temperature fibres could be adequately placed in the right frontal lobe in all animals. In 5 animals MRI-based temperature quantification correlated strongly to invasive temperature measurements. In the remaining animals the temperature fibre was located in the area of susceptibility artifacts, therefore, no temperature correlation was possible. The laser lesions consisted of a central area of calcified necrosis which was surrounded by an area of reactive brain tissue with increased permeability. Quantitative autoradiography indicated a thin and spherical blood brain barrier lesion. The magnitude of K of AIB increased from 12 hours to 14 days after ILTT and decreased thereafter. The mean value of K of AIB was 19 times (2 times) that of normal white matter (cortex), respectively. CONCLUSION: ILTT causes transient, highly localised areas of increased capillary permeability surrounding the laser lesion. Phase contrast imaging for MRI thermomonitoring can currently not be used for reliable temperature readings in vivo. The suggested new canine model proved to be safe, accurate, easy to use, and provides clinical, radiographic, pathological and physiological correlations.

Stereotactic radiosurgery without radiation therapy providing high local tumor control of multiple brain metastases from renal cell carcinoma.

The aim of this study was to analyse treatment effects after stereotactic radiosurgery (SRS) without whole brain radiation therapy (WBRT) as primary treatment for patients harboring brain metastases of renal cell carcinoma (RCC). During an 8-year period, 85 patients with 376 brain metastases from RCC underwent 134 outpatient SRS procedures. 65 % of all patients had multiple brain metastases. The median tumor volume was 1.2 cm (3) (range: 0.1 - 14.2 cm (3)). Mean prescribed tumor dose was 21.2 (+/- 3.2) Gy. Local/distant tumor recurrences were treated by additional SRS in cases of stable systemic disease. Overall median survival was 11.1 months after SRS. The local tumor control rate after SRS was 94 %. Most patients (78 %) died because of systemically progressing cancer. A KPS > 70 and RTOG class I were related to prolonged survival time. Patients of the RTOG groups I, II and III survived for 24.2 months, 9.2 months and 7.5 months, respectively. There was no permanent morbidity after SRS. 11 patients (12.9 %) showed transient radiogenic complications and 3 patients (3.5 %) died because of intratumoral bleedings after SRS. Stereotactic radiosurgery alone achieves excellent local tumor control rates for patients with small brain metastases from renal cell carcinoma.

[MRI-assisted thermometry for regional hyperthermia and interstitial laser thermotherapy]. / MRT-gestützte Thermometrie in der regionalen Tiefenhyperthermie und interstitiellen Laserthermotherapie.

PURPOSE: To demonstrate the potential of quantitative MRI-assisted thermometry for the treatment of tumor patients with regional hyperthermia (RHT) and interstitial laser thermotherapy (ILTT). METHODS: Two patients and seven tissue samples were investigated using the T1-relaxation time and the chemical shift of the proton resonance frequency (PRF) as temperature sensitive MRI-parameters at 0.2 and 1.5 T. Thermotherapy was applied using either a dedicated MRI-hyperthermia hybrid system or a temperature controlled laser with 830 nm. RESULTS: Both patients were treated successfully showing clinical benefit. T1 and PRF are depending on the applied thermotherapy method and on the MR-system suitable for MRI-assisted thermometry. The clinical application based on phantom results is not necessarily adequate. CONCLUSION: Clinical application and phantom experiments of RHT and ILTT show the potential of MRI-assisted thermometry for further improvement of both minimal invasive thermotherapy methods. Further investigations concerning optimization of the MRI-techniques, the influence of perfusion or the determination of threshold values are necessary.

Quality assurance in stereotactic radiosurgery/radiotherapy according to DIN 6875-1.

The new DIN ('Deutsche Industrie-Norm') 6875-1, which is currently being finalised, deals with quality assurance (QA) criteria and tests methods for linear accelerator and Gamma Knife stereotactic radiosurgery/radiotherapy including treatment planning, stereotactic frame and stereotactic imaging and a system test to check the whole chain of uncertainties. Our existing QA program, based on dedicated phantoms and test procedures, has been refined to fulfill the demands of this new DIN. The radiological and mechanical isocentre corresponded within 0.2 mm and the measured 50% isodose lines were in agreement with the calculated ones within less than 0.5 mm. The measured absorbed dose was within 3%. The resultant output factors measured for the 14-, 8- and 4-mm collimator helmet were 0.9870 +/- 0.0086, 0.9578 +/- 0.0057 and 0.8741 +/- 0.0202, respectively. For 170 consecutive tests, the mean geometrical accuracy was 0.48 +/- 0.23 mm. Besides QA phantoms and analysis software developed in-house, the use of commercially available tools facilitated the QA according to the DIN 6875-1 with which our results complied.

Clinical quality standards for gamma knife radiosurgery--the Munich protocol.

The clinical quality standards for outpatient gamma knife radiosurgery as developed in the German Gamma Knife Center Munich during the last ten years are described. The following aspects have been taken into account: appropriate patient selection, standardised treatment cycle, acquisition of high-quality stereotactic MR images, the integrated therapeutic concept, dose conformity and dose level, patient follow-up, quality control and scientific data analysis. Particular emphasis has been put on the importance of the interdisciplinary treatment concept by subspecialised experts. The results of the Munich concept in consideration of the described quality standards verifies that gamma knife radiosurgery is a safe and effective treatment option for well selected indications.

Gamma knife radiosurgery for nonfunctioning pituitary adenomas.

The efficacy of gamma knife radiosurgery (GKS) for non-functioning pituitary adenomas (NPAs) has been assessed. Sixty patients with NPA were treated by GKS. Complete neurological and endocrinological follow-up information was available for 51 patients. Follow-up examinations included stereotactic magnetic resonance imaging for sequential measurements of the NPA volume. The median dose to the tumor margin was 16.5 Gy (range 11-20 Gy). The mean prescription isodose was 50% (range 45-75%). All patients underwent surgery for NPA before GKS. Fractionated radiotherapy was not applied. Median follow up after GKS was 21,7 months. Actuarial recurrence-free survival was 95% after three years with respect to a single GKS and 100% for patients who underwent repeated GKS. No neurological side effects were detected. Two patients developed new partial pituitary insufficiency after radiosurgery. Postoperative GKS for residual or recurrent small fragments of NPAs is an effective and safe treatment option. The follow-up examination for NPAs should include tumor volumetric analysis.

Results of outpatient gamma knife radiosurgery for primary therapy of acoustic neuromas.

Stereotactic radiosurgery (SRS) has been recognized as a non-invasive alternative to surgery for the treatment of acoustic neuromas. Purpose of the current study was to define the impact of outpatient gamma knife radiosurgery (GKS) for patients with unilateral sporadic acoustic neuromas treated within ten years. Follow-up images were analyzed using tumor volume measurements. 219 patients with sporadic acoustic neuromas were treated by GKS as primary therapy. Patients with NF-2 tumors were excluded. Patients were eligible for GKS up to a size limit of 12.5 cm3. The median follow up time was 6 years after radiosurgery. The local tumor control rate was high (97%). Cranial nerve morbidities were comparably low. 10% of the patients developed hearing loss after radiosurgery and one patient experienced a transient facial neuropathy (0.5%). Transient trigeminal neuropathy developed in 12 patients (5%) and was found to be dependent on the tumor size before treatment. Outpatient gamma knife radiosurgery is a safe and effective treatment method for selected patients with sporadic vestibular schwannomas.

Special indications in gamma knife surgery.

Pilocytic astrocytoma (PA) represent a rare indication for Gamma Knife Surgery. Mostly small remnants after surgical debulking are treated. The prognosis depends on specific variants of biological and clinical criteria. In this regard we differentiated two groups of tumors; the so-called 'typical' tumors with a histological grading of WHO Grade I, no prior fractionated radiotherapy and no cystic component and the so called 'atypical' tumors with either a malignant transformation, previous fractionated radiotherapy and/or cystic components. The outcome after GKS was much more favourable for typical PA than for atypical. In typical cases a high tumor control with a very low risk of side effects can be achieved.