Publications by authors named "Alexander Muacevic"

81 Publications

Longitudinal Changes of Quality of Life and Hearing Following Radiosurgery for Vestibular Schwannoma.

Cancers (Basel) 2021 Mar 15;13(6). Epub 2021 Mar 15.

European Cyberknife Center, 81377 Munich, Germany.

Background: Most existing publications on quality of life (QoL) following stereotactic radiosurgery (SRS) for vestibular schwannomas (VS) gather information retrospectively by conducting surveys several years after treatment. The purpose of this study is therefore to provide longitudinal QoL data and assess how changes in hearing impact QoL.

Methods: Patients completed the 12-item short-form (SF-12) health survey prior to treatment and at every follow-up visit. One hundred and seventy-five patients who had complete forms prior to treatment as well as at an early and at a late follow-up were included in the analysis. For 51 of these patients, longitudinal audiometry data were available.

Results: Median follow-up was 7.2 years. Patients experienced a significant reduction in the physical composite score (PCS, = 0.011) compared to before treatment. The mental composite score (MCS) increased significantly ( = 0.032). A decrease in PCS was not significantly correlated with an increased hearing threshold on the affected but rather on the unaffected ear (r(49) = -0.32, = 0.023).

Conclusions: It is unclear whether the decline in the PCS is due to treatment-related toxicity or the normal decline of PCS with age. Ensuring proper hearing on the untreated ear might be crucial to ensure good QoL for patients treated with SRS for VS, though this association should be confirmed in additional studies.
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http://dx.doi.org/10.3390/cancers13061315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998632PMC
March 2021

Magnetic Resonance Imaging-Based Robotic Radiosurgery of Arteriovenous Malformations.

Front Oncol 2020 9;10:608750. Epub 2021 Mar 9.

European Cyberknife Center Munich-Grosshadern, Munich, Germany.

Objective: CyberKnife offers CT- and MRI-based treatment planning without the need for stereotactically acquired DSA. The literature on CyberKnife treatment of cerebral AVMs is sparse. Here, a large series focusing on cerebral AVMs treated by the frameless CyberKnife stereotactic radiosurgery (SRS) system was analyzed.

Methods: In this retrospective study, patients with cerebral AVMs treated by CyberKnife SRS between 2005 and 2019 were included. Planning was MRI- and CT-based. Conventional DSA was not coregistered to the MRI and CT scans used for treatment planning and was only used as an adjunct. Obliteration dynamics and clinical outcome were analyzed.

Results: 215 patients were included. 53.0% received SRS as first treatment; the rest underwent previous surgery, embolization, SRS, or a combination. Most AVMs were classified as Spetzler-Martin grade I to III (54.9%). Hemorrhage before treatment occurred in 46.0%. Patients suffered from headache (28.8%), and seizures (14.0%) in the majority of cases. The median SRS dose was 18 Gy and the median target volume was 2.4 cm³. New neurological deficits occurred in 5.1% after SRS, with all but one patient recovering. The yearly post-SRS hemorrhage incidence was 1.3%. In 152 patients who were followed-up for at least three years, 47.4% showed complete AVM obliteration within this period. Cox regression analysis revealed Spetzler-Martin grade (P = 0.006) to be the only independent predictor of complete obliteration.

Conclusions: Although data on radiotherapy of AVMs is available, this is one of the largest series, focusing exclusively on CyberKnife treatment. Safety and efficacy compared favorably to frame-based systems. Non-invasive treatment planning, with a frameless SRS robotic system might provide higher patient comfort, a less invasive treatment option, and lower radiation exposure.
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http://dx.doi.org/10.3389/fonc.2020.608750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986716PMC
March 2021

Robotic assisted CyberKnife radiosurgery for the treatment of iris melanoma.

Sci Rep 2021 Mar 11;11(1):5685. Epub 2021 Mar 11.

Department of Ophthalmology, Ludwig-Maximilians University Munich, Mathildenstr. 8, 80336, Munich, Germany.

Iris melanoma is a rare form of uveal melanoma with potential metastic spread. Treatment options include surgical resection, enucleation or irradiation. We analysed visual outcome, complication appearance and management in eight patients with iris melanoma following robotic-assisted CyberKnife treatment. Consecutive patients from the Department of Ophthalmology at University of Munich were included in the study if they had an iris melanoma that was treated with CyberKnife and had a minimum follow-up of 12 months. We evaluated tumor thickness, largest diameter, visual acuity and complications. 8 patients were included in this report. The median age was 74 years (range: 53-86 years). The median follow-up was 23 months (range 12-48 months). Tumor thickness decreased from 2.1 to 1.4 mm on average. Four out of eight patients showed stable or increased visual acuity compared to visual acuity at first visit. We did not find a correlation of applied radiation volume or radiation dose on visual outcome. Radiation keratopathy was the most common complication in five patients. No recurrences were noted. Robotic-assisted radiosurgery following CyberKnife is a promising non-invasive, single session treatment option for iris melanoma with comparable results regarding recurrence rate or complications to brachytherapy and proton beam therapy. All included patients showed good visual outcome.
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http://dx.doi.org/10.1038/s41598-021-84290-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952409PMC
March 2021

Potential Clinical Significance of Overall Targeting Accuracy and Motion Management in the Treatment of Tumors That Move With Respiration: Lessons Learnt From a Quarter Century of Stereotactic Body Radiotherapy From Dose Response Models.

Front Oncol 2020 9;10:591430. Epub 2021 Feb 9.

Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, United States.

Objective: To determine the long-term normal tissue complication probability with stereotactic body radiation therapy (SBRT) treatments for targets that move with respiration and its relation with the type of respiratory motion management (tracking . compression or gating).

Methods: A PubMed search was performed for identifying literature regarding dose, volume, fractionation, and toxicity (grade 3 or higher) for SBRT treatments for tumors which move with respiration. From the identified papers logistic or probit dose-response models were fitted to the data using the maximum-likelihood technique and confidence intervals were based on the profile-likelihood method in the dose-volume histogram (DVH) Evaluator.

Results: Pooled logistic and probit models for grade 3 or higher toxicity for aorta, chest wall, duodenum, and small bowel suggest a significant difference when live motion tracking was used for targeting tumors with move with respiration which was on the average 10 times lower, in the high dose range.

Conclusion: Live respiratory motion management appears to have a better toxicity outcome when treating targets which move with respiration with very steep peripheral dose gradients. This analysis is however limited by sparsity of rigorous data due to poor reporting in the literature.
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http://dx.doi.org/10.3389/fonc.2020.591430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900559PMC
February 2021

Robotic assisted CyberKnife radiosurgery for the treatment of choroidal metastasis.

Eye (Lond) 2021 Feb 11. Epub 2021 Feb 11.

Department of Ophthalmology, Ludwig-Maximilians University Munich, Munich, Germany.

Purpose: Choroidal metastases occur in many patients with systemic cancer and limit quality of life due to visual deterioration or pain. The limited prognosis of these patients demand treatment approaches that aim at a quick response and easy application. We evaluated a robotic assisted radiosurgery device, the CyberKnife, in the treatment of choroidal metastasis.

Methods: Following retrobulbar anaesthesia, target volume was defined by an interdisciplinary team using gadolinium-contrast-enhanced MRI, computer tomography (CT) as well as all previously obtained clinical data. Radiation was delivered in a single fraction with a CyberKnife at a radiation dose of 21 Gy with a 70% isodose. We evaluated tumour height, reflectivity, visual acuity and side effects over the course of the follow-up.

Results: A total of four patients were included in this report. Mean follow-up time was 31 months, and all patients showed decreased tumour volume and signs of fibrosis during follow-up. One patient remained stable in terms of visual acuity, two patients lost visual acuity and one patient improved and had a functional visual acuity at last follow-up. One patient developed radiation retinopathy with subsequent neovascular glaucoma that needed further management. All other patients did not show any signs of radiation induced side effects.

Conclusion: We report on the outcome of robotic CyberKnife radiosurgery in the treatment of uveal metastasis. We believe that single session, outpatient treatment delivery that can be facilitated with CyberKnife radiosurgery offer some benefits for this particularly sick group of patients.
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http://dx.doi.org/10.1038/s41433-020-01299-8DOI Listing
February 2021

Robotic Radiosurgery for Persistent Postoperative Acromegaly in Patients with Cavernous Sinus-Invading Pituitary Adenomas-A Multicenter Experience.

Cancers (Basel) 2021 Jan 31;13(3). Epub 2021 Jan 31.

European Cyberknife Center, 81377 Munich, Germany.

Background: The rates of incomplete surgical resection for pituitary macroadenomas with cavernous sinus invasion are high. In growth hormone-producing adenomas, there is a considerable risk for persistent acromegaly. Thus, effective treatment options are needed to limit patient morbidity and mortality. This multicenter study assesses the efficacy and safety of robotic radiosurgery (RRS) for patients with cavernous sinus-invading adenomas with persistent acromegaly.

Methods: Patients who underwent RRS with CyberKnife for postoperative acromegaly were eligible.

Results: Fifty patients were included. At a median follow-up of 57 months, the local control was 100%. The pretreatment insulin-like growth factor 1 (IGF-1) levels and indexes were 381 ng/mL and 1.49, respectively. The median dose and prescription isodose were 18 Gy and 70%, respectively. Six months after RRS, and at the last follow-up, the IGF-1 levels and indexes were 277 ng/mL and 1.14, as well as 196 ng/mL and 0.83, respectively ( = 0.0001 and = 0.0002). The IGF-1 index was a predictor for biochemical remission ( = 0.04). Nine patients achieved biochemical remission and 24 patients showed biochemical disease control. Three patients developed a new hypopituitarism.

Conclusions: RRS is an effective treatment for this challenging patient population. IGF-1 levels are decreasing after treatment and most patients experience biochemical disease control or remission.
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http://dx.doi.org/10.3390/cancers13030537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866786PMC
January 2021

Safety and Efficacy of Robotic Radiosurgery for Visceral and Lymph Node Metastases of Renal Cell Carcinoma: A Retrospective, Single Center Analysis.

Cancers (Basel) 2021 Feb 8;13(4). Epub 2021 Feb 8.

Department of Urology, University Hospital of Munich, 80333 Munich, Germany.

Despite rapid advances of systemic therapy options in renal cell carcinoma (RCC), local tumor or metastases treatment remains important in selected patients. Here, we assess the safety and efficacy of robotic radiosurgery (RRS) as an ablative therapy for visceral and lymph node metastases of RCC. Patients with histologically confirmed RCC and radiologically confirmed progression of visceral or lymph node metastases underwent RRS and were retrospectively analyzed. Overall survival and progression free survival were calculated by the Kaplan-Meier method and log-rank test. Sixty patients underwent RRS and were included in the analysis. Patients presented for RRS treatment with a median age at RRS treatment of 64 years (range 42-83), clear cell histology (88.3%) and favorable international metastatic renal cell carcinoma database (IMDC) risk score (58.3%). Treatment parameters differed for the number of fractions (median visceral metastases: 1, range 1-5; median lymph node metastases: 1, range 0-5; = 0.003) and prescription dose (median visceral metastases 24 Gy, range 8-26; median lymph node metastases 18 Gy, range 7-26, < 0.001). The median overall survival was 65.7 months (range: 2.9-108.6), the median progression free survival was 17.4 months (range: 2.7-70.0) and local tumor control was achieved in 96.7% of patients. Adverse events were limited to 8.3% of patients, with one grade 4 toxicity within 6 weeks after RRS therapy. RRS is a safe and effective treatment option in selected patients with metastatic RCC in a multimodal approach. Further research is warranted to confirm our findings prospectively.
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http://dx.doi.org/10.3390/cancers13040680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915686PMC
February 2021

Image-Guided Robotic Radiosurgery for the Management of Intramedullary Spinal Cord Metastases-A Multicenter Experience.

Cancers (Basel) 2021 Jan 15;13(2). Epub 2021 Jan 15.

European Cyberknife Center, 81377 Munich, Germany.

Background: Intramedullary metastases are rare and bear a dismal prognosis. Limited data are available on the treatment of such lesions. As surgery may be the mainstay of treatment for patients with resectable and localized metastatic spread, previous case reports and case series suggest radiosurgery to be another viable treatment modality. This multicenter study analyzes the efficacy and safety of robotic radiosurgery (RRS) for intramedullary metastases.

Methods: Patients who received RRS for the treatment of at least one intramedullary metastasis were included.

Results: Thirty-three patients with 46 intramedullary metastases were treated with a median dose of 16 Gy prescribed to a median isodose of 70%. The local control was 79% after a median follow-up of 8.5 months. The median overall survival (OS) was 11.7 months, with a 12- and 24-month OS of 47 and 31%. The 12-month progression-free survival was 42% and at 24 months 25%. In addition, 57% of patients showed either an improved or stable neurological function after treatment delivery. Systemic disease progression was the main cause of death. No significant treatment-related toxicities were observed.

Conclusions: RRS appears to be a safe, time-saving and effective treatment modality for intramedullary metastases, especially for patients with unresectable lesions and high burden of disease.
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http://dx.doi.org/10.3390/cancers13020297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829974PMC
January 2021

Robotic-assisted radiosurgery for the treatment of vasoproliferative tumours.

Acta Ophthalmol 2020 Dec 6. Epub 2020 Dec 6.

Department of Ophthalmology, Ludwig-Maximilians University, Munich, Germany.

Purpose: Vasoproliferative tumours (VPT) are a rare but benign entity that can lead to severe visual acuity deterioration. There is no standard of care, and depending on the degree of clinical features, including tumour size and dissemination, visual acuity and subretinal fluid, treatment options include observation, cryotherapy and brachytherapy. Particularly in larger tumours, brachytherapy has advantages over other options, although higher radiation doses and the need for surgical application are disadvantages of this otherwise effective treatment option. CyberKnife radiosurgery might represent an alternative therapeutic option as no surgical intervention is needed and radiation doses are lower.

Methods: All patients diagnosed with vasoproliferative tumors who were treated with CyberKnife radiosurgery with a minimum follow-up time of 12 months were included in this case series. We recorded visual acuity, number of lesions, central retinal thickness with optical coherence tomography (OCT) and reflectivity using A-scan standardizes echography every three months.

Results: A total of four patients with a median age of 34 years (range: 24 - 51) who were observed over an average of 26.5 months (range: 17 - 49 months) matched our inclusion criteria. We appreciated stabilization or increase in visual acuity in all four patients and a regression in tumour thickness with subsequent increase in internal reflectivity as a marker of increasing fibrosis.

Conclusion: We observed good visual and functional outcome following CyberKnife therapy for VPT. We believe that further studies should be pursued to evaluate CyberKnife therapy for the treatment of VPT not treatable with cryo- or lasertherapy.
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http://dx.doi.org/10.1111/aos.14609DOI Listing
December 2020

Single- and Multifraction Stereotactic Radiosurgery Dose/Volume Tolerances of the Brain.

Int J Radiat Oncol Biol Phys 2020 Sep 11. Epub 2020 Sep 11.

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Purpose: As part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy investigating normal tissue complication probability (NTCP) after hypofractionated radiation therapy, data from published reports (PubMed indexed 1995-2018) were pooled to identify dosimetric and clinical predictors of radiation-induced brain toxicity after single-fraction stereotactic radiosurgery (SRS) or fractionated stereotactic radiosurgery (fSRS).

Methods And Materials: Eligible studies provided NTCPs for the endpoints of radionecrosis, edema, or symptoms after cranial SRS/fSRS and quantitative dose-volume metrics. Studies of patients with only glioma, meningioma, vestibular schwannoma, or brainstem targets were excluded. The data summary and analyses focused on arteriovenous malformations (AVM) and brain metastases.

Results: Data from 51 reports are summarized. There was wide variability in reported rates of radionecrosis. Available data for SRS/fSRS for brain metastases were more amenable to NTCP modeling than AVM data. In the setting of brain metastases, SRS/fSRS-associated radionecrosis can be difficult to differentiate from tumor progression. For single-fraction SRS to brain metastases, tissue volumes (including target volumes) receiving 12 Gy (V1) of 5 cm, 10 cm, or >15 cm were associated with risks of symptomatic radionecrosis of approximately 10%, 15%, and 20%, respectively. SRS for AVM was associated with modestly lower rates of symptomatic radionecrosis for equivalent V12. For brain metastases, brain plus target volume V20 (3-fractions) or V24 (5-fractions) <20 cm was associated with <10% risk of any necrosis or edema, and <4% risk of radionecrosis requiring resection.

Conclusions: The risk of radionecrosis after SRS and fSRS can be modeled as a function of dose and volume treated. The use of fSRS appears to reduce risks of radionecrosis for larger treatment volumes relative to SRS. More standardized dosimetric and toxicity reporting is needed to facilitate future pooled analyses that can refine predictive models of brain toxicity risks.
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http://dx.doi.org/10.1016/j.ijrobp.2020.08.013DOI Listing
September 2020

Image-guided robotic radiosurgery for glomus jugulare tumors-Multicenter experience and review of the literature.

Head Neck 2021 Jan 27;43(1):35-47. Epub 2020 Aug 27.

Department of Otorhinolaryngology and Head and Neck Surgery, Ludwig-Maximilians-University Munich, Campus Grosshadern, Munich, Germany.

Background: Glomus jugulare tumors (GJTs) are challenging to treat due to their vascularization and location. This analysis evaluates the effectiveness and safety of image-guided robotic radiosurgery (RRS) for GJTs in a multicenter study and reviews the existing radiosurgical literature.

Methods: We analyzed outcome data from 101 patients to evaluate local control (LC), changes in pretreatment deficits, and toxicity. Moreover, radiosurgical studies for GJTs have been reviewed.

Results: After a median follow-up of 35 months, the overall LC was 99%. Eighty-eight patients were treated with a single dose, 13 received up to 5 fractions. The median tumor volume was 5.6 cc; the median treatment dose for single-session treatments is 16 Gy, and for multisession treatments is 21 Gy. Fifty-six percentage of patients experienced symptom improvement or recovered entirely.

Conclusions: RRS is an effective primary and secondary treatment option for GJTs. The available literature suggests that radiosurgery is a treatment option for most GJTs.
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http://dx.doi.org/10.1002/hed.26439DOI Listing
January 2021

Vestibular Migraine Following Radiosurgery for Vestibular Schwannoma.

Cureus 2020 Jun 11;12(6):e8569. Epub 2020 Jun 11.

Otolaryngology - Head and Neck Surgery, University of California San Francisco, San Francisco, USA.

Vestibular schwannoma (VS) is associated with dizziness and vertigo during all stages of treatment. This report describes a patient who presented with a one-year history of intermittent motion sickness, dizziness, headache, imbalance, and nausea. MRI showed a right-side VS in the cerebellopontine angle and internal auditory canal. The patient elected to undergo Gamma Knife radiosurgery for treatment. Within two to three months, she continued to experience recurring dizziness, vertigo, neck stiffness, and head pressure. She was referred for neurotology evaluation, which led to a diagnosis of vestibular migraine (VM). Her vestibular reflexes were intact. Subsequently, she was treated with diet modification and low-dose venlafaxine. She reported dramatically improved dizziness and vertigo symptoms at six-month follow-up. VM is a very common cause of dizziness that should always be included in the differential diagnosis, even in VS patients.
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http://dx.doi.org/10.7759/cureus.8569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358935PMC
June 2020

Robotic CyberKnife Radiosurgery for Ciliary Body Melanoma.

Ophthalmol Retina 2020 09 20;4(9):954-956. Epub 2020 Apr 20.

Department of Ophthalmology, Ludwig-Maximilians University, Munich, Germany.

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http://dx.doi.org/10.1016/j.oret.2020.03.031DOI Listing
September 2020

Stereotactic Ablative Radiotherapy for ≥T1b Primary Renal Cell Carcinoma: A Report From the International Radiosurgery Oncology Consortium for Kidney (IROCK).

Int J Radiat Oncol Biol Phys 2020 11 17;108(4):941-949. Epub 2020 Jun 17.

Department of Radiation Oncology, London Regional Cancer Program, London, Ontario, Canada; Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.

Purpose: Patients with larger (T1b, >4 cm) renal cell carcinoma (RCC) not suitable for surgery have few treatment options because thermal ablation is less effective in this setting. We hypothesize that SABR represents an effective, safe, and nephron-sparing alternative for large RCC.

Methods And Materials: Individual patient data from 9 institutions in Germany, Australia, USA, Canada, and Japan were pooled. Patients with T1a tumors, M1 disease, and/or upper tract urothelial carcinoma were excluded. Demographics, treatment, oncologic, and renal function outcomes were assessed using descriptive statistics. Kaplan-Meier estimates and univariable and multivariable Cox proportional hazards regression were generated for oncologic outcomes.

Results: Ninety-five patients were included. Median follow-up was 2.7 years. Median age was 76 years, median tumor diameter was 4.9 cm, and 81.1% had Eastern Cooperative Oncology Group performance status of 0 to 1 (or Karnofsky performance status ≥70%). In patients for whom operability details were reported, 77.6% were defined as inoperable as determined by the referring urologist. Mean baseline estimated glomerular filtration rate (eGFR) was 57.2 mL/min (mild-to-moderate dysfunction), with 30% of the cohort having moderate-to-severe dysfunction (eGFR <45mL/min). After SABR, eGFR decreased by 7.9 mL/min. Three patients (3.2%) required dialysis. Thirty-eight patients (40%) had a grade 1 to 2 toxicity. No grade 3 to 5 toxicities were reported. Cancer-specific survival, overall survival, and progression-free survival were 96.1%, 83.7%, and 81.0% at 2 years and 91.4%, 69.2%, 64.9% at 4 years, respectively. Local, distant, and any failure at 4 years were 2.9%, 11.1%, and 12.1% (cumulative incidence function with death as competing event). On multivariable analysis, increasing tumor size was associated with inferior cancer-specific survival (hazard ratio per 1 cm increase: 1.30; P < .001).

Conclusions: SABR for larger RCC in this older, largely medically inoperable cohort, demonstrated efficacy and tolerability and had modest impact on renal function. SABR appears to be a viable treatment option in this patient population.
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http://dx.doi.org/10.1016/j.ijrobp.2020.06.014DOI Listing
November 2020

Implementation of model explainability for a basic brain tumor detection using convolutional neural networks on MRI slices.

Neuroradiology 2020 Nov 4;62(11):1515-1518. Epub 2020 Jun 4.

European CyberKnife Center, Munich, Germany.

Purpose: While neural networks gain popularity in medical research, attempts to make the decisions of a model explainable are often only made towards the end of the development process once a high predictive accuracy has been achieved.

Methods: In order to assess the advantages of implementing features to increase explainability early in the development process, we trained a neural network to differentiate between MRI slices containing either a vestibular schwannoma, a glioblastoma, or no tumor.

Results: Making the decisions of a network more explainable helped to identify potential bias and choose appropriate training data.

Conclusion: Model explainability should be considered in early stages of training a neural network for medical purposes as it may save time in the long run and will ultimately help physicians integrate the network's predictions into a clinical decision.
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http://dx.doi.org/10.1007/s00234-020-02465-1DOI Listing
November 2020

Single-session image-guided robotic radiosurgery and quality of life for glomus jugulare tumors.

Head Neck 2020 09 12;42(9):2421-2430. Epub 2020 May 12.

Department of Otorhinolaryngology and Head and Neck Surgery, Campus Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany.

Background: Limited data are available on the efficacy and impact on the quality of life (Qol) of single-session image-guided robotic radiosurgery (RRS) for glomus jugulare tumors (GJTs). This study investigates the role of RRS in the management of GJTs and reviews the RRS literature.

Methods: We analyzed 53 GJT patients treated with RRS to evaluate the safety, local control, clinical outcome, and Qol assessed by the SF12v2.

Results: The local control was 98% at a median follow-up of 38 months. The median tumor volume was 4.3 cc and tumors were treated with a median dose of 16.5 Gy. At the last follow-up, 35 patients had recovered from their symptoms or experienced symptom improvement. Qol analyses showed no significant decline while bodily pain significantly decreased.

Conclusions: RRS is a safe and efficient tool for the treatment of GJTs. Qol of patients after treatment is stable and tends to improve over time.
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http://dx.doi.org/10.1002/hed.26231DOI Listing
September 2020

Frameless Single Robotic Radiosurgery for Pulmonary Metastases in Colorectal Cancer Patients.

Cureus 2020 Mar 18;12(3):e7305. Epub 2020 Mar 18.

Radiosurgery, European CyberKnife Center, Munich, DEU.

Background Surgical intervention and radiation therapy are common approaches for pulmonary metastasectomy. The role of minimally invasive techniques in pulmonary metastases remains unclear. Frameless single robotic radiosurgery [CyberKnife (CK); Accuray Incorporated, Sunnyvale, CA] of pulmonary metastases in colorectal cancer (CRC) patients offers high precision local radiation therapy. Methods We analyzed the efficacy and safety of CK treatment for lung metastases in CRC in 34 patients and a total of 45 lesions. The primary endpoint was local control (LC); secondary endpoints were progression-free survival (PFS), overall survival (OS), distant control (DC), and safety-relevant events. Results Of the treated lesions, 34/45 (77.8%) decreased in size or remained unchanged [complete response (CR), partial response (PR), stable disease (SD)]; 8/45 (17.8%) lesions increased in size [progressive disease (PD)] and 2/45 (4.4%) lesions were not evaluable. Local progression was shown in 2 lesions (4.4 %). The median PFS period was six months. In a median follow-up time of 19.4 months, medium OS was 19.9 months (range: 3-61 months). Distant recurrence was observed in 21/34 patients (61.8 %). Intrapulmonary progression occurred in six patients. In 4/45 cases, fiducial placement led to a pneumothorax; three out of four patients needed chest tube insertion. No radiation-associated side effects were reported in 57.8% of patients. In 10/45 cases (22.2%), patients suffered asymptomatic radiographic changes; 7/45 cases (15.6%) reported a late onset of radiation-associated side effects. Maximal radiation-associated side effects reached the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) Grade 1. Conclusion CK treatment of pulmonary metastases is safe and well-tolerated. For metastatic colorectal cancer (mCRC) patients with pulmonary metastases and not eligible for surgery, CK radiation offers a valuable treatment option.
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http://dx.doi.org/10.7759/cureus.7305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164549PMC
March 2020

Clinical Results After Single-fraction Radiosurgery for 1,002 Vestibular Schwannomas.

Cureus 2019 Dec 16;11(12):e6390. Epub 2019 Dec 16.

Neurosurgery, Radiosurgery, European CyberKnife Center, Munich, DEU.

Background Herein, we report clinical results for patients treated with stereotactic radiosurgery (SRS) for vestibular schwannomas (VS) over a period of 10 years. Methods Clinical data and imaging follow-up were stored in a database of 1,378 patients, with 1,384 VS treated consecutively between 2005 and 2018 and analyzed retrospectively. A total of 996 patients with 1,002 tumors with at least one year of follow-up were included for analysis. Results Median follow-up was 3·6 years (1-12·5 years). The three, five, and 10-year Kaplan-Meier estimated local tumor control was 96·6%, 92·3%, and 90·8%, respectively. The median hearing loss of the affected ear as compared to its healthy counterpart was 17 dB at treatment start and increased to 23 and 29 dB at one and five years. Six patients (0·6%) developed symptomatic hydrocephalus and underwent the placement of a ventriculoperitoneal shunt. In 30 patients (3·0%), trigeminal sensory dysfunction developed, five patients (0·5%) had a mild transient weakness, and nine patients (0·9%) had a permanent facial weakness (House-Brackmann Grade > II) after SRS. Conclusion Single fraction SRS proves to be highly effective and shows low treatment-related toxicity for VS. SRS should be considered a primary treatment option for small and middle-sized VS.
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http://dx.doi.org/10.7759/cureus.6390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957120PMC
December 2019

The Emerging Role of Stereotactic Ablative Radiotherapy for Primary Renal Cell Carcinoma: A Systematic Review and Meta-Analysis.

Eur Urol Focus 2019 Nov 24;5(6):958-969. Epub 2019 Jun 24.

Division of Radiation Oncology & Cancer Imaging, Peter MacCallum Cancer Centre, and University of Melbourne, Melbourne, Australia. Electronic address:

Context: Stereotactic ablative radiotherapy (SABR) is an emerging treatment option for primary renal cell carcinoma (RCC).

Objective: To systematically review the literature on SABR for primary RCC and perform a meta-analysis evaluating local control (LC), toxicity, and renal function.

Evidence Acquisition: A PROSPERO-registered (#115573), Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA)-based systematic review of the literature was conducted (1995-2019). Studies of SABR targeting primary RCC tumors were included, while those targeting only metastases were excluded. The primary outcome was LC defined as tumor size reduction and/or absence of local progression. Secondary outcomes included toxicity (Common Terminology Criteria for Adverse Events) and renal function (change in estimated glomerular filtration rate [eGFR]). Weighted random-effect meta-analyses using the DerSimonian and Laird method were conducted for primary and secondary outcomes. The I statistic and Cochran's Q test were used to assess heterogeneity.

Evidence Synthesis: From 2386 PubMed entries and 924 meeting abstracts, 26 studies were identified (11 prospective trials), including 383 tumors in 372 patients, most of whom were deemed inoperable. Weighted averages (ranges) of median follow-up, median age, and mean tumor size were 28.0 (5.8-79.2)mo, 70.4 (62-83)yr, and 4.6 (2.3-9.5)cm, respectively. RCC histology was confirmed in 78.9% of patients who underwent pretreatment biopsy. Dose fractionation varied, but 26Gy in one fraction and 40Gy in five fractions were most common. The random-effect estimates for LC, grade 3-4 toxicity, and post-SABR eGFR change were 97.2% (95% confidence interval [CI]: 93.9-99.5%, I=20%), 1.5% (95% CI: 0-4.3%, I=0%), and -7.7ml/min (95% CI: -12.5 to -2.8, I=2%), respectively, and heterogeneity was minimal. Six patients with pre-existing renal dysfunction (2.9%) required dialysis.

Conclusions: Renal SABR is locally effective and associated with low toxicity rates for primary RCC, despite treatment of larger tumors in older, mostly medically inoperable patients.

Patient Summary: Stereotactic ablative radiotherapy is a high-precision, noninvasive radiation treatment requiring few outpatient visits, and represents a safe and effective management option for primary renal cell carcinoma.
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http://dx.doi.org/10.1016/j.euf.2019.06.002DOI Listing
November 2019

Long-term outcome in orbital meningiomas: progression-free survival after targeted resection combined with early or postponed postoperative radiotherapy.

J Neurosurg 2019 Jun 14:1-11. Epub 2019 Jun 14.

Departments of1Neurosurgery.

Objective: In meningiomas involving the orbit and optic canal, surgery is the mainstay of therapy. However, radical resection is often limited to avoid functional damage, so multidisciplinary treatment concepts are implemented. Data on the timing and value of early postoperative radiotherapy (PORT) are scarce. This retrospective study analyzes outcomes in patients who underwent targeted resection alone or in combination with early PORT.

Methods: Patients undergoing resection of orbit-associated WHO grade I meningiomas from January 1999 to December 2013 who presented to the authors' department at least twice for follow-up were included. Clinical and radiological findings were analyzed retrospectively. Patients were stratified into two cohorts: follow-up with MRI scans at regular intervals, i.e., the watch and wait (W&W) group, and a PORT group receiving PORT within 6 months after surgery in addition to MRI follow-up. Patients in the W&W group were scheduled for treatment when tumor progression was detected by imaging.

Results: One hundred twenty-two patients were included. The mean follow-up was 70 months. The most common symptoms at presentation were visual disturbances; 87.7% of patients received Simpson grade II-III targeted partial resection. Twenty-three patients received PORT, and 99 patients were regularly observed with MRI scans (W&W group). Tumor recurrence/progression occurred significantly later (76.3 vs 40.7 months) and less frequently in the PORT group (13%) than in the W&W group (46.5%). Cases of recurrence were diagnosed an average of 39 months after initial surgery in both groups. PORT patients demonstrated significantly less visual impairment at last follow-up.

Conclusions: These results indicate that receiving PORT early after targeted partial resection might help to postpone tumor recurrence and the need for additional treatment, while preserving or even improving visual outcome.
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http://dx.doi.org/10.3171/2019.3.JNS181760DOI Listing
June 2019

Correction: CyberKnife Radiosurgery in Recurrent Brain Metastases: Do the Benefits Outweigh the Risks?

Cureus 2019 03 5;11(3):c18. Epub 2019 Mar 5.

Radiosurgery, European CyberKnife Center Munich, Munich, DEU.

[This corrects the article DOI: 10.7759/cureus.3741.].
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http://dx.doi.org/10.7759/cureus.c18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400328PMC
March 2019

CyberKnife Radiosurgery in Recurrent Brain Metastases: Do the Benefits Outweigh the Risks?

Cureus 2018 12 17;10(12):e3741. Epub 2018 Dec 17.

Radiosurgery, European CyberKnife Center Munich, Munich, DEU.

Introduction Local treatment concepts are in high demand in the salvage treatment of recurrent brain metastases. Still, their risks and benefits are scarcely characterized. In this study, we analyzed the outcome and risk-/benefit-ratio of salvage CyberKnife (Accuray Incorporated, Sunnyvale, California, US) radiosurgery in the treatment of recurrent brain metastases after whole brain radiotherapy (WBRT). Materials and methods Seventy-six patients with 166 recurrent brain metastases and a multimodal pretreatment were retrospectively investigated. All patients underwent salvage CyberKnife radiosurgery (single fraction, reference dose: 17-22 Gy). Study endpoints were post-recurrence survival (PRS) after salvage treatment as well as local and distant tumor control rates. Central nervous system (CNS) toxicity was assessed according to the toxicity criteria of the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer (RTOG/EORTC)). Results The population was homogenous regarding its demographic parameters. All patients had a history of WBRT prior to salvage CyberKnife radiosurgery. PRS was 13.3 months (10.4 - 16.2 months), one-year local and distant tumor control rates were 87% (95% CI: 75-99) and 38% (95% CI: 23-52), respectively. Eighteen patients suffered from RTOG/EORTC grade I/II toxicity. No toxicity-related risk factors were identified. Discussion This study found indicative survival and tumor control rates as well as a favorable risk/benefit ratio regarding radiotoxicity in salvage CyberKnife radiosurgery. These results point to a proactive therapeutic strategy based on appropriate patient selection instead of therapeutic nihilism.
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http://dx.doi.org/10.7759/cureus.3741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384047PMC
December 2018

Stereotactic Radiotherapy as a Treatment Option for Renal Tumors in the Solitary Kidney: A Multicenter Analysis from the IROCK.

J Urol 2019 06;201(6):1097-1104

Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre and University of Melbourne , Melbourne , Australia.

Purpose: Stereotactic ablative radiotherapy is an emerging treatment for renal cell carcinoma. Our study objective was to evaluate this therapy in patients with a solitary kidney, focusing on oncologic and renal function outcomes.

Materials And Methods: We pooled individual patient data from 9 IROCK (International Radiosurgery Oncology Consortium for Kidney) institutions in Germany, Australia, the United States of America, Canada and Japan. Median followup was 2.6 years. Baseline characteristics and outcomes were compared between the solitary and bilateral kidney cohorts. Predictors of renal function after stereotactic ablative radiotherapy were assessed by logistic regression modeling.

Results: A total of 81 patients with a solitary kidney underwent stereotactic ablative radiotherapy. Mean age was 67.3 years and 97.5% of patients had good performance status, including ECOG (Eastern Cooperative Oncology Group) 0-1 or KPS (Karnofsky Performance Status) 70% or greater. Median tumor diameter was 3.7 cm (IQR 2.5-4.3) and 37% of tumors were 4 cm or greater. The 138 patients in the bilateral cohort harbored larger tumors and were older (p <0.001) with a lower baseline estimated glomerular filtration rate (p = 0.024). After stereotactic ablative radiotherapy in the solitary kidney cohort the mean ± SD estimated glomerular filtration rate decrease was -5.8 ± 10.8 ml per minute (-9%). No patient with a solitary kidney required dialysis. After stereotactic ablative radiotherapy a tumor size of 4 cm or greater was associated with an estimated glomerular filtration rate decrease of 15 ml per minute or greater (OR 4.2, p = 0.029). At 2 years the rates of local control, and progression-free, cancer specific and overall survival in the solitary cohort were 98.0%, 77.5%, 98.2% and 81.5%, respectively. There was no significant difference in renal function or oncologic outcomes between the cohorts (p >0.05).

Conclusions: In this analysis of the IROCK database stereotactic ablative radiotherapy in patients with a solitary kidney had an acceptable impact on renal function and achieved excellent oncologic outcomes, similar to those in patients with bilateral kidneys. Thus, stereotactic ablative radiotherapy represents a viable treatment option in patients with renal cell carcinoma in a solitary kidney.
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http://dx.doi.org/10.1097/JU.0000000000000111DOI Listing
June 2019

An interdisciplinary consensus on the management of bone metastases from renal cell carcinoma.

Nat Rev Urol 2018 08;15(8):511-521

Department of Urology, Ludwig-Maximilians University Munich, Munich, Germany.

Bone is a major site of haematogenous tumour cell spread in renal cell carcinoma (RCC), and most patients with RCC will develop painful and functionally disabling bone metastases at advanced disease stages. The prognosis of these patients is generally poor and the treatment is, therefore, aimed at palliation. However, RCC-associated bone metastases can be curable in select patients. Current data support a multimodal management strategy that includes wide resection of lesions, radiotherapy, systemic therapy, and other local treatment options, which can improve quality of life and survival. Nevertheless, the optimal approach for metastatic bone disease in RCC has not yet been defined and practical recommendations are rare. To improve the management and outcomes of patients with RCC and bone metastases, the International Kidney Cancer Coalition and the interdisciplinary working group on renal tumours of the German Cancer Society convened a meeting of experts with a global perspective to perform an unstructured review and elaborate on current treatment strategies on the basis of published data and expertise. The panel formulated recommendations for the diagnosis and treatment of patients with RCC and metastasis to the bone. Furthermore, the experts summarized current challenges and unmet patient needs that should be addressed in the future.
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http://dx.doi.org/10.1038/s41585-018-0034-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136176PMC
August 2018

Population description and clinical response assessment for spinal metastases: part 2 of the SPIne response assessment in Neuro-Oncology (SPINO) group report.

Neuro Oncol 2018 08;20(9):1215-1224

Department of Radiation Oncology, University of Toronto, Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada.

Background: Approximately 40% of metastatic cancer patients will develop spinal metastases. The current report provides recommendations for standardization of metrics used for spinal oncology patient population description and outcome assessment beyond local control endpoints on behalf of the SPIne response assessment in Neuro-Oncology (SPINO) group.

Methods: The SPINO group survey was conducted in order to determine the preferences for utilization of clinician-based and patient-reported outcome measures for description of patients with spinal metastases. Subsequently, ClinicalTrials.gov registry was searched for spinal oncology clinical trials, and measures for patient description and outcome reporting were identified for each trial. These two searches were used to identify currently used descriptors and instruments. A literature search was performed focusing on the measures identified in the survey and clinical trial search in order to assess their validity in the metastatic spinal tumor patient population. References for this manuscript were identified through PubMed and Medline searches.

Results: Published literature, expert survey, and ongoing clinical trials were used to synthesize recommendations for instruments for reporting of spinal stability, epidural tumor extension, neurological and functional status, and symptom severity.

Conclusions: Accurate description of patient population and therapy effects requires a combination of clinician-based and patient-reported outcome measures. The current report provides international consensus recommendations for the systematic reporting of patient- and clinician-reported measures required to develop trials applicable to surgery for spinal metastases and postoperative spine stereotactic body radiotherapy (SBRT).
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http://dx.doi.org/10.1093/neuonc/noy047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071663PMC
August 2018

A Suspected Vestibular Schwannoma with Uncharacteristic Growth Dynamic and Symptom Severity: A Case Report.

Cureus 2018 Jan 5;10(1):e2024. Epub 2018 Jan 5.

Radiosurgery, European CyberKnife Center Munich.

Vestibular schwannomas are mostly sporadic, neuroectodermal, benign tumors of the myelin-forming cells of the vestibulocochlear nerve. Typical initial symptoms of vestibular schwannomas often include unilateral hearing loss, tinnitus, vertigo, and headaches. As schwannomas characteristically show a slow growth rate and various symptoms, different therapeutic approaches are possible, ranging from a watchful waiting strategy to radiation therapy and neurosurgical tumor removal. In addition, these treatment options should be evaluated carefully and assigned individually to the patients' needs and symptoms while respecting the feasibility and possible outcome of the chosen treatment. We present a 69-year-old patient with an atypical, severe symptom constellation and tumor growth dynamic. The planned treatment of the schwannoma with radiosurgery revealed an unforeseen change of focus. Most notably, this case emphasizes the importance of a thorough radiological and patient-orientated assessment.
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http://dx.doi.org/10.7759/cureus.2024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837235PMC
January 2018

Pooled analysis of stereotactic ablative radiotherapy for primary renal cell carcinoma: A report from the International Radiosurgery Oncology Consortium for Kidney (IROCK).

Cancer 2018 03 20;124(5):934-942. Epub 2017 Dec 20.

Cyberknife Center, University of Munich Hospitals, Munich, Germany.

Background: Stereotactic ablative radiotherapy (SABR) is an emerging therapy for primary renal cell carcinoma. The authors assessed safety, efficacy, and survival in a multi-institutional setting. Outcomes between single-fraction and multifraction SABR were compared.

Methods: Individual patient data sets from 9 International Radiosurgery Oncology Consortium for Kidney institutions across Germany, Australia, the United States, Canada, and Japan were pooled. Toxicities were recorded using Common Terminology Criteria for Adverse Events, version 4.0. Patient, tumor, and treatment characteristics were stratified according to the number of radiotherapy fractions (single vs multiple). Survival outcomes were examined using Kaplan-Meier estimates and Cox proportional-hazards regression.

Results: Of 223 patients, 118 received single-fraction SABR, and 105 received multifraction SABR. The mean patient age was 72 years, and 69.5% of patients were men. There were 83 patients with grade 1 and 2 toxicity (35.6%) and 3 with grade 3 and 4 toxicities (1.3%). The rates of local control, cancer-specific survival, and progression-free survival were 97.8%, 95.7%, and 77.4%, respectively, at 2 years; and they were 97.8%, 91.9%, and 65.4%, respectively, at 4 years. On multivariable analysis, tumors with a larger maximum dimension and the receipt of multifraction SABR were associated with poorer progression-free survival (hazard ratio, 1.16 [P < .01] and 1.13 [P = .02], respectively) and poorer cancer-specific survival (hazard ratio, 1.28 [P < .01] and 1.33 [P = .01], respectively). There were no differences in local failure between the single-fraction cohort (n = 1) and the multifraction cohort (n = 2; P = .60). The mean ( ± standard deviation) estimated glomerular filtration rate at baseline was 59.9 ± 21.9 mL per minute, and it decreased by 5.5 ± 13.3 mL per minute (P < .01).

Conclusions: SABR is well tolerated and locally effective for treating patients who have primary renal cell carcinoma and has an acceptable impact on renal function. An interesting observation is that patients who receive single-fraction SABR appear to be less likely to progress distantly or to die of cancer. Cancer 2018;124:934-42. © 2017 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.31156DOI Listing
March 2018

Radiotherapy for renal cell carcinoma: renaissance of an overlooked approach.

Nat Rev Urol 2017 Sep 20;14(9):549-563. Epub 2017 Jun 20.

Department of Radiation Oncology, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356043, Seattle, Washington 98195-6043, USA.

Conventional radiotherapy previously had a limited role in the definitive treatment of renal cell carcinoma (RCC), owing to the disappointing outcomes of several trials and the perceived radioresistance of this type of cancer. In this context, radiotherapy has been relegated largely to the palliation of symptoms in patients with metastatic disease, with variable rates of response. Following the availability of newer technologies that enable safe delivery of high-dose radiotherapy, stereotactic ablative radiotherapy (SABR) has become increasingly used in patients with RCC. Preclinical evidence demonstrates that RCC cells are sensitive to ablative doses of radiotherapy (≥8-10 Gy). Trials in the setting of intracranial and extracranial oligometastases, as well as primary RCC, have demonstrated excellent tumour control using this approach. Additionally, an awareness of the capacity of high-dose radiation to stimulate antitumour immunity has resulted in novel combinations of SABR with immunotherapies. Here we describe the historical application of conventional radiotherapy, the current biological understanding of the effects of radiation, and the clinical evidence supporting the use of ablative radiotherapy in RCC. We also explore emerging opportunities to combine systemic targeted agents or immunotherapies with radiation. Radiotherapy, although once an overlooked approach, is moving towards the forefront of RCC treatment.
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http://dx.doi.org/10.1038/nrurol.2017.87DOI Listing
September 2017

Robotic Radiosurgery for Adrenal Gland Metastases.

Cureus 2017 Mar 26;9(3):e1120. Epub 2017 Mar 26.

Chief Medical Physicist, European CyberKnife Center Munich.

Introduction: The purpose of this study was to investigate the safety and efficacy of CyberKnife (CK) robotic radiosurgery for treatment of adrenal metastases.

Methods: We performed a retrospective analysis of 23 patients with adrenal metastases who had been treated with CK between October 2006 and December 2015. Fifteen patients received chemotherapy prior to radiosurgery, all patients underwent computer tomography (CT) fluoroscopically guided percutaneous placement of one to three gold fiducials into the adrenal gland. Nineteen patients were selected for single-fraction radiosurgery with a median dose of 22 Gy, four patients were treated in three fractions with a median dose of 13.5 Gy.

Results: Median follow-up time was 23.6 months. Four patients (17%) experienced local relapse during the evaluation period with a mean time of 19 months to tumor progression. The actuarial local tumor control rate was 95% after one year and 81% after two years. Three of the four patients with local recurrence were retreated with CK radiosurgery. Dynamic tumor tracking enabled accurate treatment with correlation errors less than 2 mm, despite extensive respiration-induced target motion up to 22 mm. Apart from nausea directly after treatment in five patients, we observed no early or late treatment-related side effects.

Conclusions: Single fraction robotic radiosurgery for adrenal gland metastases is a safe and effective treatment option for patients who are not eligible for surgical resection.
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http://dx.doi.org/10.7759/cureus.1120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5406171PMC
March 2017