[Diagnosis and Management of Vestibular Schwannomas - An Interdisciplinary Challenge]. / Diagnostik und Therapie des Vestibularisschwannoms ­ eine interdisziplinäre Herausforderung.

Vestibular schwannomas expand slowly in the internal auditory canal, in the cerebellopontine angle, inside the cochlear and the labyrinth. Larger tumors can displace and compress the brainstem. With an annual incidence of 1:100 000 vestibular schwannoma represent 6-7% of all intracranial tumors. In the cerebellopontine angle they are by far the most neoplasm with 90% of all lesions located in this region. Magnetic resonance imaging (MRI), audiometry, and vestibular diagnostics are the mainstays of the clinical workup for patients harboring tumors. The first part of this paper delivers an overview of tumor stages, the most common grading scales for facial nerve function and hearing as well as a short introduction to the examination of vestibular function.Upholding or improving quality of life is the central concern in counseling and treating a patient with vestibular schwannoma. Preservation of neuronal function is essential and the management options - watchful waiting, microsurgery and stereotactic radiation - should be custom-tailored to the individual situation of the patient. Continuing interdisciplinary exchange is important to monitor treatment quality and to improve treatment results. Recently, several manuscripts and reviews have been published on the topic of vestibular schwanomma. On the occasion of the 88th annual meeting of the German Society of Oto-rhino-laryngology, Head and Neck surgery a special volume of the journal "HNO" will be printed. Hence this presentation has been designed to deviate from the traditional standard which commonly consists of a pure literature review. The current paper was conceptually woven around a series of interdisciplinary cases which outlines examples for every stage of the disease that show characteristic results for management options to date. Systematic clinical decision pathways have been deduced from our experience and from results reported in the literature. These pathways are graphically outlined after the case presentations. Important criteria for decision making are size and growth rate of the tumor, hearing of the patient and the probability of total tumor resection with preservation of hearing and facial nerve function, age and co-morbidity of the patient, best possible control of vertigo and tinnitus and last but not least the patient's preference and choice. In addition to this, the experience and the results of a given center with each treatment modality will figure in the decision making process.We will discuss findings that are reported in the literature regarding facial nerve function, hearing, vertigo, tinnitus, and headache and reflect on recent studies on their influence on the patient's quality of life. Vertigo plays an essential role in this framework since it is an independent predictor of quality of life and a patient's dependence on social welfare.Pathognomonic bilateral vestibular schwannoma that occur in patients suffering from neurofibromatosis typ-2 (NF2) differ from spontaneous unilateral tumors in their biologic behavior. Treatment of neurofibromatosis type-2 patients requires a multidisciplinary team, especially because of the multitude of separate intracranial and spinal lesions.Off-label chemotherapy with Bevacizumab can stabilize tumor size of vestibular schwannomas and even improve hearing over longer periods of time. Hearing rehabilitation in NF2 patients can be achieved with cochlea and auditory brainstem implants.

Treatment of acromegaly patients with risk-adapted single or fractionated stereotactic high-precision radiotherapy: High local control and low toxicity in a pooled series.

PURPOSE: The purpose of this work was to evaluate a prospectively initiated two-center protocol of risk-adapted stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) in patients with acromegaly. PATIENTS AND METHODS: In total 35 patients (16 men/19 women, mean age 54 years) were prospectively included in a treatment protocol of SRS [planning target volume (PTV < 4 ccm, > 2 mm to optic pathways = low risk] or SRT (PTV ≥ 4 ccm, ≤ 2 mm to optic pathways = high risk). The mean tumor volume was 3.71 ccm (range: 0.11-22.10 ccm). Based on the protocol guidelines, 21 patients were treated with SRS and 12 patients with SRT, 2 patients received both consecutively. RESULTS: The median follow-up (FU) reached 8 years with a 5-year overall survival (OS) of 87.3% [confidence interval (CI): 70.8-95.6%] and 5-year local control rate of 97.1% (CI: 83.4-99.8%). Almost 80% (28/35) presented tumor shrinkage during FU. Endocrinological cure was achieved in 23% and IGF-1 normalization with reduced medication was achieved in 40% of all patients. An endocrinological response was generally achieved within the first 3 years, but endocrinological cure can require more than 8 years. A new adrenocorticotropic hypopituitarism occurred in 13 patients (46.4%). A new visual field disorder and a new oculomotor palsy occurred in 1 patient, respectively. Patients with occurrence of visual/neurological impairments had a longer FU (p = 0.049). CONCLUSION: Our SRS/SRT protocol proved to be safe and successful in terms of tumor control and protection of the visual system. The timing and rate of endocrine improvements are difficult to predict. One has to accept an unavoidable rate of additional adrenocorticotropic hypopituitarism in the long term.

Risk-adapted single or fractionated stereotactic high-precision radiotherapy in a pooled series of nonfunctioning pituitary adenomas: high local control and low toxicity.

PURPOSE: The purpose of this work was to evaluate a prospectively initiated two-center protocol of risk-adapted single-fraction (SRS) or fractionated radiotherapy (SRT) in patients with nonsecretory pituitary adenomas (NSA). PATIENTS AND METHODS: A total of 73 NSA patients (39 men/34 women) with a median age of 62 years were prospectively included in a treatment protocol of SRS [planning target volume (PTV) < 4 ccm, > 2 mm to optic pathways = low risk] or SRT (PTV ≥ 4 ccm, ≤ 2 mm to optic pathways = high risk) in two Novalis® centers. Mean tumor volume was 7.02 ccm (range 0.58-57.29 ccm). Based on the protocol guidelines, 5 patients were treated with SRS and 68 patients with SRT. RESULTS: Median follow-up (FU) reached 5 years with 5-year overall survival (OS) of 90.4 % (CI 80.2-95 %) and 5-year local control and progression-free survival rates of 100 % (CI 93.3-100 %) and 90.4 % (CI 80.2-95 %), respectively. A post-SRS/SRT new visual disorder occurred in 2 patients (2.7 %), a new oculomotor nerve palsy in one pre-irradiated patient, in 3 patients (4.1 %) a pre-existing visual disorder improved. New complete hypopituitarism occurred in 4 patients (13.8 %) and in 3 patients (25 %) with pre-existing partial hypopituitarism. Pituitary function in 26 % of patients retained normal. Patients with tumor shrinkage (65.75 %) had a significantly longer FU (p = 0.0093). Multivariate analysis confirmed correlation of new hypopituitarism with duration of FU (p = 0.008) and correlation of new hypopituitarism and tumor volume (p = 0.023). No significant influence factors for occurrence of visual disorders were found. CONCLUSION: Our SRS/SRT protocol proved to be safe and successful in terms of tumor control and protection of the visual system, especially for large tumors located close to optic pathways.

Stereotactic radiosurgery and fractionated stereotactic radiotherapy: comparison of efficacy and toxicity in 260 patients with brain metastases.

We retrospectively evaluated and compared the efficacy and the toxicity profile of stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) for the treatment of patients with brain metastases (BM). Between 2000 and 2009, 260 patients with 1-3 BM were treated using either SRS (median dose 20 Gy; n = 138) or two different FSRT dose concepts: 7 × 5 Gy (n = 61) or 10 × 4 Gy (n = 61). The median survival for SRS, 7 × 5 Gy and 10 × 4 Gy was 8, 7 and 10 months (p = 0.575), respectively, and the overall survival (OS) was 9 months. Follow-up imaging data were available in 214 of the 260 patients. The 1-year local progression-free survival (LPFS) was 73, 75 and 71 %, respectively (p = 0.191). After a mean follow-up of 28 months (range: 2.1-77 months), the rate of complete remission, partial remission, stable disease and progressive disease were 29, 40, 21 and 10 %, respectively. On multivariate analysis, RPA class I was associated with better OS and regional progression-free survival (both p < 0.001). SRS was associated with a higher toxicity rate (grade I-III) compared to the 7 × 5 Gy and 10 × 4 Gy groups (14 vs. 6 vs. 2 %, respectively; p = 0.01). Although FSRT was used for large lesions and/or lesions near critical structures, the LPFS was comparable to SRS. Importantly, FSRT presented low toxicity and appears to be an effective and safe treatment for BM not amenable to SRS. The 10 × 4 Gy fractionation scheme warrants further investigation due to its efficacy and safe toxicity profile.

Radiotherapy for brain metastases from renal cell cancer: should whole-brain radiotherapy be added to stereotactic radiosurgery?: analysis of 88 patients.

PURPOSE: To evaluate the role of stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT) for the treatment of brain metastases in patients with renal cell cancer (RCC). PATIENTS AND METHODS: 88 patients were treated with either SRS (n = 51) or SRS + WBRT (n = 17) for one to three lesions, or with WBRT (n = 20) for more than three brain metastases. Overall survival (OS), intracerebral control (IC) and local control (LC) were retrospectively analyzed. Six potential prognostic factors were assessed: age, gender, number of brain metastases, extracerebral metastases, recursive partitioning analysis (RPA) class, and interval from tumor diagnosis to irradiation. RESULTS: The median times for OS, IC, and LC from the time of diagnosis were 11, 9, and 10 months. The median OS times for SRS, SRS + WBRT, and WBRT were 12, 16, and 2 months. Addition of WBRT to the SRS improved IC (p = 0.032) but not OS (p = 0.703). On multivariate analyses, improved OS was associated with the absence of extracerebral metastases (p < 0.001) and RPA class (p = 0.04), and IC with treatment (p = 0.019). SRS provided a 1-year, 2-year, and 3-year LC probability of 81%, 78%, and 55%, respectively. No association between LC and any of the potential prognostic factors was observed. The results of the subgroup analyses, regarding treatment modality, were similar to the entire cohort, particularly for RPA class I patients. CONCLUSION: Addition of WBRT to SRS offers better IC and should be considered for RCC patients with one to three brain metastases, especially in RPA class I group. SRS offers excellent LC rates, while WBRT should be reserved for patients with multiple metastases and poor prognosis.

Comparison of stereotactic radiosurgery and fractionated stereotactic radiotherapy of acoustic neurinomas according to 3-D tumor volume shrinkage and quality of life.

BACKGROUND AND PURPOSE: Stereotactic radiosurgery (SRS) and also fractionated stereotactic radiotherapy (SRT) offer high local control (LC) rates (> 90%). This study aimed to evaluate three-dimensional (3-D) tumor volume (TV) shrinkage and to assess quality of life (QoL) after SRS/SRT. PATIENTS AND METHODS: From 1999 to 2005, 35/74 patients were treated with SRS, and 39/74 with SRT. Median age was 60 years. Treatment was delivered by a linear accelerator. Median single dose was 13 Gy (SRS) or 54 Gy (SRT). Patients were followed up > or = 12 months after SRS/SRT. LC and toxicity were evaluated by clinical examinations and magnetic resonance imaging. 3-D TV shrinkage was evaluated with the planning system. QoL was assessed using the questionnaire Short Form-36. RESULTS: Median follow-up was 50/36 months (SRS/SRT). Actuarial 5-year freedom from progression/overall survival was 88.1%/100% (SRS), and 87.5%/87.2% (SRT). TV shrinkage was 15.1%/40.7% (SRS/SRT; p = 0.01). Single dose (< 13 Gy) was the only determinant factor for TV shrinkage after SRS (p = 0.001). Age, gender, initial TV, and previous operations did not affect TV shrinkage. Acute or late toxicity (> or = grade 3) was never seen. Concerning QoL, no significant differences were observed after SRS/SRT. Previous operations and gender did not affect QoL (p > 0.05). Compared with the German normal population, patients had worse values for all domains except for mental health. CONCLUSION: TV shrinkage was significantly higher after SRT than after SRS. Main symptoms were not affected by SRS/SRT. Retrospectively, QoL was neither affected by SRS nor by SRT.

LINAC stereotactic radiosurgery for trigeminal neuralgia -retrospective two-institutional examination of treatment outcomes.

BACKGROUND: In this pooled 2-center series LINAC radiosurgery (SRS) has been applied as a treatment option for a subset of refractory trigeminal neuralgia (TN) patients. This study approached to retrospectively assess the efficacy and safety of LINAC SRS and to provide a brief overview addressed to the technical development from frame-based towards frameless robotic SRS. METHODS: From 2001 to 2017 n = 55 patients (pts) were treated, n = 28 were female (51%), mean age: 66 years (range 36-93 years); TN etiology: 37 classic TN, 15 multiple sclerosis (MS)-related TN, 2 symptomatic TN, and 1 atypical TN. Previous treatment was present in n = 35 (63.6%) pts. (some multiple or combined) with n = 23 microsurgical vascular decompression and n = 17 percutaneous retrogasserian rhizotomy. A 6 MV LINAC (4-5 mm collimators) was applied in all pts. (n = 26 framebased - n = 29 frameless robotic). The dorsal root entry zone (DREZ) was targeted in n = 35 cases and the retrogasserian target in n = 20 pts. with a homogeneous dose for the entire study cohort (90 Gy). SRS outcome was measured using the Barrow Neurological Institute (BNI) score for pain and hypaesthesia and statistically evaluated by univariate and multivariate analyzes. RESULTS: Mean follow-up (FU) was 30 months (2 lost FU); the total rate of post SRS BNI pain I-IIIa (=painfree w or w/o medication) was 69% (88% for the classic TN pts), 29% (38.8% classic TN) were classified as BNI pain I-II (=painfree w/o medication). A BNI hypaesthesia II-III was present in 9.4% (n = 5) and BNI hypaesthesia IV in n = 2. Between groups analysis demonstrated no correlation of SRS responsiveness with age, gender, MS- or not MS-associated TN, previous surgery, framebased/frameless robotic SRS. DREZ targeting significantly better suppressed TN compared to RG targeting (p = 0.01). Additionally, a statistical trend for a better BNI pain outcome (p = 0.07) along with a significant increase in BNI hypaesthesia (p = 0.01) was found when using a larger partial trigeminal 70 Gy volume. CONCLUSION: Our retrospective analysis support LINAC SRS as an effective and safe treatment option in TN. Frameless robotic SRS of TN is safe when using a dedicated LINAC system. A target definition closer to the brainstem and tendencially a larger target volume were associated with a better outcome for pain.

Diagnostics and therapy of vestibular schwannomas - an interdisciplinary challenge.

Vestibular schwannomas (VS) expand slowly in the internal auditory canal, in the cerebellopontine angle, inside the cochlear and the labyrinth. Larger tumors can displace and compress the brainstem. With an annual incidence of 1:100,000 vestibular schwannoma represent 6-7% of all intracranial tumors. In the cerebellopontine angle they are by far the most neoplasm with 90% of all lesions located in this region. Magnetic resonance imaging (MRI), audiometry, and vestibular diagnostics are the mainstays of the clinical workup for patients harboring tumors. The first part of this paper delivers an overview of tumor stages, the most common grading scales for facial nerve function and hearing as well as a short introduction to the examination of vestibular function. Upholding or improving quality of life is the central concern in counseling and treating a patient with vestibular schwannoma. Preservation of neuronal function is essential and the management options - watchful waiting, microsurgery and stereotactic radiation - should be custom-tailored to the individual situation of the patient. Continuing interdisciplinary exchange is important to monitor treatment quality and to improve treatment results. Recently, several articles and reviews have been published on the topic of vestibular schwannoma. On the occasion of the 88th annual meeting of the German Society of Oto-Rhino-Laryngology, Head and Neck surgery a special volume of the journal "HNO" will be printed. Hence this presentation has been designed to deviate from the traditional standard which commonly consists of a pure literature review. The current paper was conceptually woven around a series of interdisciplinary cases that outline examples for every stage of the disease that show characteristic results for management options to date. Systematic clinical decision pathways have been deduced from our experience and from results reported in the literature. These pathways are graphically outlined after the case presentations. Important criteria for decision making are size and growth rate of the tumor, hearing of the patient and the probability of total tumor resection with preservation of hearing and facial nerve function, age and comorbidity of the patient, best possible control of vertigo and tinnitus and last but not least the patient's preference and choice. In addition to this, the experience and the results of a given center with each treatment modality will figure in the decision making process. We will discuss findings that are reported in the literature regarding facial nerve function, hearing, vertigo, tinnitus, and headache and reflect on recent studies on their influence on the patient's quality of life. Vertigo plays an essential role in this framework since it is an independent predictor of quality of life and a patient's dependence on social welfare. Pathognomonic bilateral vestibular schwannomas that occur in patients suffering from neurofibromatosis typ-2 (NF2) differ from spontaneous unilateral tumors in their biologic behavior. Treatment of neurofibromatosis type-2 patients requires a multidisciplinary team, especially because of the multitude of separate intracranial and spinal lesions. Off-label chemotherapy with Bevacizumab can stabilize tumor size of vestibular schwannomas and even improve hearing over longer periods of time. Hearing rehabilitation in NF2 patients can be achieved with cochlear and auditory brainstem implants.

Treatment of Cerebral Arteriovenous Malformations with Radiosurgery or Hypofractionated Stereotactic Radiotherapy in a Consecutive Pooled Linear Accelerator Series.

OBJECTIVE: To review outcomes after linear accelerator stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (hfSRT) of arteriovenous malformations (AVMs) from a consecutive and pooled series of 2 Novalis centers and to analyze the influence of AVM size, Spetzler-Martin (SM) grade, pretreatment, and hemorrhagic versus nonhemorrhagic presentation. A subgroup analysis of A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA)-eligible patients also was performed. METHODS: Prospectively collected treatment and outcome data were supplemented by retrospectively collected follow-up data for 93.8% of all patients. A total of 129 patients with AVM had SRS or hfSRT between 2000 and 2014 with the same linear accelerator system in 2 centers. Data analysis included initial presentation, SM grade, occlusion rates assessed by magnetic resonance and/or digital subtraction angiography, neurologic and therapeutic complications, and pretreatments. Statistical analysis was performed for patient demographic data and for factors potentially influencing outcome. RESULTS: Initial presentation was hemorrhage in 43.8% or seizures/neurologic deficits in 46.2%. The series included 6 SM grade I (5%), 26 SM II (21.5%), 55 SM III (45.5%), 28 SM IV (23%), and 6 SM V cases (5%). Pre-embolization was used in 36 patients (29.8%), 8 patients had previous surgery (6.6%), and 6 patients were irradiated before elsewhere (5%); 5 patients (4.2%) received multimodal pretreatment. Mean follow-up was 43 months. The occlusion rate for the total series was 71.1%, for SM I/II cases 80.6%, and 67.4% for the SM ≥ subgroup. The occlusion rate was 75.0% for the small volume (<4 cc) and 55.6% for the large volume (>10 cc) subgroup. There was no statistical difference between the occlusion rate of patients with or without pretreatment if taken all modalities together (72.7% and 69.7%, respectively). There was only a trend of a belated occlusion of pre-embolized AVMs. The occlusion rate for hemorrhagic AVM was with 77.4% better than for nonhemorrhagic (66.2%) or ARUBA-eligible AVMs (64.8%) but without reaching statistical significance. Neurologic deterioration was seen in 13.2% of the patients. There were 2 re-bleedings within 17-18 months (1.7%), 1 of them without a new neurologic deficit and total occlusion after re-SRS. One patient with pre-existing epilepsy died a sudden unexpected death (mortality rate: 0.8%). CONCLUSIONS: Overall SRS and hfSRT are valuable therapy options, especially in symptomatic patients with AVM, with a low rate of morbidity and mortality and an acceptable overall complete occlusion rate of >70% and >80% for SM I/II AVMs.

Significance of different conformity indices for evaluation of radiosurgery treatment plans for vestibular schwannomas.

OBJECT: There are various kinds of conformity parameters currently in use, although several of them are limited and reflect only target volume coverage or normal tissue overdosage. Indices are reviewed with the goal of determining those that are most significant for the evaluation of radiosurgery treatment plans for patients with vestibular schwannoma, based on the authors' experience at the Novalis Shaped Beam Surgery Center. METHODS: Fifty-five radiosurgery plans for patients with vestibular schwannomas (VSs) have been evaluated. In this paper the conformation number (CN) and dose-related CN (dCN) are evaluated, and a penalty for underdosed target volumes and overdosed normal tissue is incorporated. A strategy is discussed to apply these indices (CN and dCN) to define the optimal prescription isodose (PI). For a given radiosurgery treatment plan, permitting partial target underdosage may offer an improvement of the CN. Variations of different conformation indices have been calculated for varying prescription levels--for example, an isodose plan. The resulting graph for the CN is discussed in detail to illustrate its use in defining the optimal PI level. For the 55 cases of VSs reported on, the median CNmax result was 0.78. CONCLUSIONS: It is possible to achieve highly conformal dose distributions with Novalis radiosurgical system. The CN is the parameter of choice when evaluating radiosurgery treatment plans and scoring possible treatment plans. It takes into account both target underdosage and normal tissue overdosage and offers a valuable scoring parameter while avoiding false-perfect scores.