Stereotactic radiosurgery and radiotherapy for brainstem metastases: An international multicenter analysis.

Brainstem metastases (BSM) present a significant neuro-oncological challenge, resulting in profound neurological deficits and poor survival outcomes. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) offer promising therapeutic avenues for BSM despite their precarious location. This international multicenter study investigates the efficacy and safety of SRS and FSRT in 136 patients with 144 BSM treated at nine institutions from 2005 to 2022. The median radiographic and clinical follow-up periods were 6.8 and 9.4 months, respectively. Predominantly, patients with BSM were managed with SRS (69.4%). The median prescription dose and isodose line for SRS were 18 Gy and 65%, respectively, while for FSRT, the median prescription dose was 21 Gy with a median isodose line of 70%. The 12-, 24-, and 36-month local control (LC) rates were 82.9%, 71.4%, and 61.2%, respectively. Corresponding overall survival rates at these time points were 61.1%, 34.7%, and 19.3%. In the multivariable Cox regression analysis for LC, only the minimum biologically effective dose was significantly associated with LC, favoring higher doses for improved control (in Gy, hazard ratio [HR]: 0.86, p < .01). Regarding overall survival, good performance status (Karnofsky performance status, ≥90%; HR: 0.43, p < .01) and prior whole brain radiotherapy (HR: 2.52, p < .01) emerged as associated factors. In 14 BSM (9.7%), treatment-related adverse events were noted, with a total of five (3.4%) radiation necrosis. SRS and FSRT for BSM exhibit efficacy and safety, making them suitable treatment options for affected patients.

Entirely noninvasive outcome prediction in central nervous system lymphomas using circulating tumor DNA.

ABSTRACT: State-of-the-art response assessment of central nervous system lymphoma (CNSL) by magnetic resonance imaging is challenging and an insufficient predictor of treatment outcomes. Accordingly, the development of novel risk stratification strategies in CNSL is a high unmet medical need. We applied ultrasensitive circulating tumor DNA (ctDNA) sequencing to 146 plasma and cerebrospinal fluid (CSF) samples from 67 patients, aiming to develop an entirely noninvasive dynamic risk model considering clinical and molecular features of CNSL. Our ultrasensitive method allowed for the detection of CNSL-derived mutations in plasma ctDNA with high concordance to CSF and tumor tissue. Undetectable plasma ctDNA at baseline was associated with favorable outcomes. We tracked tumor-specific mutations in plasma-derived ctDNA over time and developed a novel CNSL biomarker based on this information: peripheral residual disease (PRD). Persistence of PRD after treatment was highly predictive of relapse. Integrating established baseline clinical risk factors with assessment of radiographic response and PRD during treatment resulted in the development and independent validation of a novel tool for risk stratification: molecular prognostic index for CNSL (MOP-C). MOP-C proved to be highly predictive of outcomes in patients with CNSL (failure-free survival hazard ratio per risk group of 6.60; 95% confidence interval, 3.12-13.97; P < .0001) and is publicly available at www.mop-c.com. Our results highlight the role of ctDNA sequencing in CNSL. MOP-C has the potential to improve the current standard of clinical risk stratification and radiographic response assessment in patients with CNSL, ultimately paving the way toward individualized treatment.

Stereotactic Therapies for Meningiomas.

Although surgery remains the mainstay of treatment for most meningiomas, radiotherapy, specifically stereotactic radiosurgery, has become more commonplace as first-line therapy for select meningioma cases, particularly small meningiomas in challenging or high-risk anatomic locations. Radiosurgery for specific groups of meningiomas have been found to provide local control rates comparable to surgery alone. In this chapter stereotactic techniques for the treatment of meningiomas such as stereotactic radiosurgery by using Gamma knife or Linear Accelerator-based techniques (modified LINAC, Cyberknife, etc.) as well as stereotactically guided implantation or radioactive seeds for brachytherapy are introduced.

Intraoperative microscopic autofluorescence detection and characterization in brain tumors using stimulated Raman histology and two-photon fluorescence.

Introduction: The intrinsic autofluorescence of biological tissues interferes with the detection of fluorophores administered for fluorescence guidance, an emerging auxiliary technique in oncological surgery. Yet, autofluorescence of the human brain and its neoplasia is sparsely examined. This study aims to assess autofluorescence of the brain and its neoplasia on a microscopic level by stimulated Raman histology (SRH) combined with two-photon fluorescence. Methods: With this experimentally established label-free microscopy technique unprocessed tissue can be imaged and analyzed within minutes and the process is easily incorporated in the surgical workflow. In a prospective observational study, we analyzed 397 SRH and corresponding autofluorescence images of 162 samples from 81 consecutive patients that underwent brain tumor surgery. Small tissue samples were squashed on a slide for imaging. SRH and fluorescence images were acquired with a dual wavelength laser (790 nm and 1020 nm) for excitation. In these images tumor and non-tumor regions were identified by a convolutional neural network that reliably differentiates between tumor, healthy brain tissue and low quality SRH images. The identified areas were used to define regions.of- interests (ROIs) and the mean fluorescence intensity was measured. Results: In healthy brain tissue, we found an increased mean autofluorescence signal in the gray (11.86, SD 2.61, n=29) compared to the white matter (5.99, SD 5.14, n=11, p<0.01) and in the cerebrum (11.83, SD 3.29, n=33) versus the cerebellum (2.82, SD 0.93, n=7, p<0.001), respectively. The signal of carcinoma metastases, meningiomas, gliomas and pituitary adenomas was significantly lower (each p<0.05) compared to the autofluorescence in the cerebrum and dura, and significantly higher (each p<0.05) compared to the cerebellum. Melanoma metastases were found to have a higher fluorescent signal (p<0.01) compared to cerebrum and cerebellum. Discussion: In conclusion we found that autofluorescence in the brain varies depending on the tissue type and localization and differs significantly among various brain tumors. This needs to be considered for interpreting photon signal during fluorescence-guided brain tumor surgery.

Pseudoprogression of Vestibular Schwannoma after Stereotactic Radiosurgery with Cyberknife®: Proposal for New Response Criteria.

(1) Background: Transient increase in volume of vestibular schwannomas (VS) after stereotactic radiosurgery (SRS) is common and complicates differentiation between treatment-related changes (pseudoprogression, PP) and tumor recurrence (progressive disease, PD). (2) Methods: Patients with unilateral VS (n = 63) underwent single fraction robotic-guided SRS. Volume changes were classified according to existing RANO criteria. A new response type, PP, with a >20% transient increase in volume was defined and divided into early (within the first 12 months) and late (>12 months) occurrence. (3) Results: The median age was 56 (range: 20-82) years, the median initial tumor volume was 1.5 (range: 0.1-8.6) cm3. The median radiological and clinical follow-up time was 66 (range: 24-103) months. Partial response was observed in 36% (n = 23), stable disease in 35% (n = 22) and PP in 29% (n = 18) of patients. The latter occurred early (16%, n = 10) or late (13%, n = 8). Using these criteria, no case of PD was observed. (4) Conclusion: Any volume increase after SRS for vs. assumed to be PD turned out to be early or late PP. Therefore, we propose modifying RANO criteria for SRS of VS, which may affect the management of vs. during follow-up in favor of further observation.

Use of dose-area product to assess plan quality in robotic radiosurgery.

PURPOSE: In robotic stereotactic radiosurgery (SRS), optimal selection of collimators from a set of fixed cones must be determined manually by trial and error. A unique and uniformly scaled metric to characterize plan quality could help identify Pareto-efficient treatment plans. METHODS: The concept of dose-area product (DAP) was used to define a measure (DAPratio) of the targeting efficiency of a set of beams by relating the integral DAP of the beams to the mean dose achieved in the target volume. In a retrospective study of five clinical cases of brain metastases with representative target volumes (range: 0.5-5.68 ml) and 121 treatment plans with all possible collimator choices, the DAPratio was determined along with other plan metrics (conformity index CI, gradient index R50%, treatment time, total number of monitor units TotalMU, radiotoxicity index f12, and energy efficiency index η50%), and the respective Spearman's rank correlation coefficients were calculated. The ability of DAPratio to determine Pareto efficiency for collimator selection at DAPratio < 1 and DAPratio < 0.9 was tested using scatter plots. RESULTS: The DAPratio for all plans was on average 0.95 ±â€¯0.13 (range: 0.61-1.31). Only the variance of the DAPratio was strongly dependent on the number of collimators. For each target, there was a strong or very strong correlation of DAPratio with all other metrics of plan quality. Only for R50% and η50% was there a moderate correlation with DAPratio for the plans of all targets combined, as R50% and η50% strongly depended on target size. Optimal treatment plans with CI, R50%, f12, and η50% close to 1 were clearly associated with DAPratio < 1, and plans with DAPratio < 0.9 were even superior, but at the cost of longer treatment times and higher total monitor units. CONCLUSIONS: The newly defined DAPratio has been demonstrated to be a metric that characterizes the target efficiency of a set of beams in robotic SRS in one single and uniformly scaled number. A DAPratio < 1 indicates Pareto efficiency. The trade-off between plan quality on the one hand and short treatment time or low total monitor units on the other hand is also represented by DAPratio.

Patient reported outcomes after navigated minimally invasive hybrid lumbar interbody fusion (nMIS-HLIF) using cortical bone trajectory screws.

Prospective observational study. To evaluate patient-reported outcomes after navigation-guided minimally invasive hybrid lumbar interbody fusion (nMIS-HLIF) for decompression and fusion in degenerative spondylolisthesis (Meyerding grade I-II). Posterior lumbar interbody fusion (PLIF) and transforaminal lumbar interbody fusion (TLIF) are well-known standard procedures for lumbar spinal fusion. nMIS-HLIF is a navigation-guided combined percutaneous and open procedure that combines the advantages of PLIF and TLIF procedures for the preparation of a single-port endoscopic approach. 33 patients underwent nMIS-HLIF. Core outcome measure index (COMI), oswestry disability index (ODI), numeric rating scale (NRS) back, NRS leg, and short form health-36 (SF-36) were collected preoperatively and at follow-up of 6 weeks, 3 months, 6 months, and 1 year. The impact of body mass index (BMI) was also analyzed. Computed tomography reconstruction was used to assess realignment and verify fused facet joints and vertebral bodies at the 1-year follow-up. 28 (85%) completed the 1-year follow-up. The median BMI was 27.6 kg/m2, age 69 yrs. The mean reduction in listhesis was 8.4% (P < .01). BMI was negatively correlated with listhesis reduction (P = .032). The improvements in the NRS back, NRS leg, ODI, and COMI scores were significant at all times (P < .001-P < .01). The SF-36 parameters of bodily pain, physical functioning, physical component summary, role functioning/physical functioning, and social functioning improved (P < .003). The complication rate was 15.2% (n = 5), with durotomy (n = 3) being the most frequent. To reduce the complication rate and allow transitioning to a fully endoscopic approach, expandable devices have been developed. The outcomes of nMIS-HLIF are comparable to the current standard open and minimally invasive techniques. A high BMI hinders this reduction. The nMIS-HLIF procedure is appropriate for learning minimally invasive dorsal lumbar stabilization. The presented modifications will enable single-port endoscopic lumbar stabilization in the future.

Differentiation of Intracerebral Tumor Entities with Quantitative Contrast Attenuation and Iodine Mapping in Dual-Layer Computed Tomography.

Purpose: To investigate if quantitative contrast enhancement and iodine mapping of common brain tumor (BT) entities may correctly differentiate between tumor etiologies in standardized stereotactic CT protocols. Material and Methods: A retrospective monocentric study of 139 consecutive standardized dual-layer dual-energy CT (dlDECT) scans conducted prior to the stereotactic needle biopsy of untreated primary brain tumor lesions. Attenuation of contrast-enhancing BT was derived from polyenergetic images as well as spectral iodine density maps (IDM) and their contrast-to-noise-ratios (CNR) were determined using ROI measures in contrast-enhancing BT and healthy contralateral white matter. The measures were correlated to histopathology regarding tumor entity, isocitrate dehydrogenase (IDH) and MGMT mutation status. Results: The cohort included 52 female and 76 male patients, mean age of 59.4 (±17.1) years. Brain lymphomas showed the highest attenuation (IDM CNR 3.28 ± 1,23), significantly higher than glioblastoma (2.37 ± 1.55, p < 0.005) and metastases (1.95 ± 1.14, p < 0.02), while the differences between glioblastomas and metastases were not significant. These strongly enhancing lesions differed from oligodendroglioma and astrocytoma (Grade II and III) that showed IDM CNR in the range of 1.22−1.27 (±0.45−0.82). Conventional attenuation measurements in DLCT data performed equally or slightly superior to iodine density measurements. Conclusion: Quantitative attenuation and iodine density measurements of contrast-enhancing brain tumors are feasible imaging biomarkers for the discrimination of cerebral tumor lesions but not specifically for single tumor entities. CNR based on simple HU measurements performed equally or slightly superior to iodine quantification.

Case report: Use of 68Ga-DOTATATE-PET for treatment guidance in complex meningioma disease.

Currently, contrast-enhanced MRI is the method of choice for treatment planning and follow-up in patients with meningioma. However, positron emission tomography (PET) imaging of somatostatin receptor subtype 2 (SSTR2) expression using 68Ga-DOTATATE may provide a higher sensitivity for meningioma detection, especially in cases with complex anatomy or in the recurrent setting. Here, we report on a patient with a multilocal recurrent atypical meningioma, in which 68Ga-DOTATATE PET was considerably helpful for treatment guidance and decision-making.

Accuracy of Robotic and Frame-Based Stereotactic Neurosurgery in a Phantom Model.

Background: The development of robotic systems has provided an alternative to frame-based stereotactic procedures. The aim of this experimental phantom study was to compare the mechanical accuracy of the Robotic Surgery Assistant (ROSA) and the Leksell stereotactic frame by reducing clinical and procedural factors to a minimum. Methods: To precisely compare mechanical accuracy, a stereotactic system was chosen as reference for both methods. A thin layer CT scan with an acrylic phantom fixed to the frame and a localizer enabling the software to recognize the coordinate system was performed. For each of the five phantom targets, two different trajectories were planned, resulting in 10 trajectories. A series of five repetitions was performed, each time based on a new CT scan. Hence, 50 trajectories were analyzed for each method. X-rays of the final cannula position were fused with the planning data. The coordinates of the target point and the endpoint of the robot- or frame-guided probe were visually determined using the robotic software. The target point error (TPE) was calculated applying the Euclidian distance. The depth deviation along the trajectory and the lateral deviation were separately calculated. Results: Robotics was significantly more accurate, with an arithmetic TPE mean of 0.53 mm (95% CI 0.41-0.55 mm) compared to 0.72 mm (95% CI 0.63-0.8 mm) in stereotaxy (p < 0.05). In robotics, the mean depth deviation along the trajectory was -0.22 mm (95% CI -0.25 to -0.14 mm). The mean lateral deviation was 0.43 mm (95% CI 0.32-0.49 mm). In frame-based stereotaxy, the mean depth deviation amounted to -0.20 mm (95% CI -0.26 to -0.14 mm), the mean lateral deviation to 0.65 mm (95% CI 0.55-0.74 mm). Conclusion: Both the robotic and frame-based approach proved accurate. The robotic procedure showed significantly higher accuracy. For both methods, procedural factors occurring during surgery might have a more relevant impact on overall accuracy.

Oncologic Outcome and Immune Responses of Radiotherapy with Anti-PD-1 Treatment for Brain Metastases Regarding Timing and Benefiting Subgroups.

While immune checkpoint inhibitors (ICIs) in combination with radiotherapy (RT) are widely used for patients with brain metastasis (BM), markers that predict treatment response for combined RT and ICI (RT-ICI) and their optimal dosing and sequence for the best immunogenic effects are still under investigation. The aim of this study was to evaluate prognostic factors for therapeutic outcome and to compare effects of concurrent and non-concurrent RT-ICI. We retrospectively analyzed data of 93 patients with 319 BMs of different cancer types who received PD-1 inhibitors and RT at the University Hospital Cologne between September/2014 and November/2020. Primary study endpoints were overall survival (OS), progression-free survival (PFS), and local control (LC). We included 66.7% melanoma, 22.8% lung, and 5.5% other cancer types with a mean follow-up time of 23.8 months. Median OS time was 12.19 months. LC at 6 months was 95.3% (concurrent) vs. 69.2% (non-concurrent; p = 0.008). Univariate Cox regression analysis detected following prognostic factors for OS: neutrophil-to-lymphocyte ratio NLR favoring <3 (low; HR 2.037 (1.184−3.506), p = 0.010), lactate dehydrogenase (LDH) favoring ≤ULN (HR 1.853 (1.059−3.241), p = 0.031), absence of neurological symptoms (HR 2.114 (1.285−3.478), p = 0.003), RT concept favoring SRS (HR 1.985 (1.112−3.543), p = 0.019), RT dose favoring ≥60 Gy (HR 0.519 (0.309−0.871), p = 0.013), and prior anti-CTLA4 treatment (HR 0.498 (0.271−0.914), p = 0.024). Independent prognostic factors for OS were concurrent RT-ICI application (HR 0.539 (0.299−0.971), p = 0.024) with a median OS of 17.61 vs. 6.83 months (non-concurrent), ECOG performance status favoring 0 (HR 7.756 (1.253−6.061), p = 0.012), cancer type favoring melanoma (HR 0.516 (0.288−0.926), p = 0.026), BM volume (PTV) favoring ≤3 cm3 (HR 1.947 (1.007−3.763), p = 0.048). Subgroups with the following factors showed significantly longer OS when being treated concurrently: RT dose <60 Gy (p = 0.014), PTV > 3 cm3 (p = 0.007), other cancer types than melanoma (p = 0.006), anti-CTLA4-naïve patients (p < 0.001), low NLR (p = 0.039), steroid intake ≤4 mg (p = 0.042). Specific immune responses, such as abscopal effects (AbEs), pseudoprogression (PsP), or immune-related adverse events (IrAEs), occurred more frequently with concurrent RT-ICI and resulted in better OS. Other toxicities, including radionecrosis, were not statistically different in both groups. The concurrent application of RT and ICI, the ECOG-PS, cancer type, and PTV had an independently prognostic impact on OS. In concurrently treated patients, treatment response (LC) was delayed and specific immune responses (AbE, PsP, IrAE) occurred more frequently with longer OS rates. Our results suggest that concurrent RT-ICI application is more beneficial than sequential treatment in patients with low pretreatment inflammatory status, more and larger BMs, and with other cancer types than melanoma.

The Role of Stereotactic Radiosurgery in the Management of Foramen Magnum Meningiomas-A Multicenter Analysis and Review of the Literature.

BACKGROUND: Foramen magnum meningiomas (FMMs) represent a considerable neurosurgical challenge given their location and potential morbidity. Stereotactic radiosurgery (SRS) is an established non-invasive treatment modality for various benign and malignant brain tumors. However, reports on single-session or multisession SRS for the management and treatment of FMMs are exceedingly rare. We report the largest FMM SRS series to date and describe our multicenter treatment experience utilizing robotic radiosurgery. METHODS: Patients who underwent SRS between 2005 and 2020 as a treatment for a FMM at six different centers were eligible for analysis. RESULTS: Sixty-two patients met the inclusion criteria. The median follow-up was 28.9 months. The median prescription dose and isodose line were 14 Gy and 70%, respectively. Single-session SRS accounted for 81% of treatments. The remaining patients received three to five fractions, with doses ranging from 19.5 to 25 Gy. Ten (16%) patients were treated for a tumor recurrence after surgery, and thirteen (21%) underwent adjuvant treatment. The remaining 39 FMMs (63%) received SRS as their primary treatment. For patients with an upfront surgical resection, histopathological examination revealed 22 World Health Organization grade I tumors and one grade II FMM. The median tumor volume was 2.6 cubic centimeters. No local failures were observed throughout the available follow-up, including patients with a follow-up ≥ five years (16 patients), leading to an overall local control of 100%. Tumor volume significantly decreased after treatment, with a median volume reduction of 21% at the last available follow-up (p < 0.01). The one-, three-, and five-year progression-free survival were 100%, 96.6%, and 93.0%, respectively. Most patients showed stable (47%) or improved (21%) neurological deficits at the last follow-up. No high-grade adverse events were observed. CONCLUSIONS: SRS is an effective and safe treatment modality for FMMs. Despite the paucity of available data and previous reports, SRS should be considered for selected patients, especially those with subtotal tumor resections, recurrences, and patients not suitable for surgery.

Radiomics outperforms semantic features for prediction of response to stereotactic radiosurgery in brain metastases.

BACKGROUND: Brain metastases show different patterns of contrast enhancement, potentially reflecting hypoxic and necrotic tumor regions with reduced radiosensitivity. An objective evaluation of these patterns might allow a prediction of response to radiotherapy. We therefore investigated the potential of MRI radiomics in comparison with the visual assessment of semantic features to predict early response to stereotactic radiosurgery in patients with brain metastases. PATIENTS AND METHODS: In this retrospective study, 150 patients with 308 brain metastases from solid tumors (NSCLC in 53% of patients) treated by stereotactic radiosurgery (single dose of 17-20 Gy) were evaluated. The response of each metastasis (partial or complete remission vs. stabilization or progression) was assessed within 180 days after radiosurgery. Patterns of contrast enhancement in the pre-treatment T1-weighted MR images were either visually classified (homogenous, heterogeneous, necrotic ring-like) or subjected to a radiomics analysis. Random forest models were optimized by cross-validation and evaluated in a hold-out test data set (30% of metastases). RESULTS: In total, 221/308 metastases (72%) responded to radiosurgery. The optimal radiomics model comprised 10 features and outperformed the model solely based on semantic features in the test data set (AUC, 0.71 vs. 0.56; accuracy, 69% vs. 54%). The diagnostic performance could be further improved by combining semantic and radiomics features resulting in an AUC of 0.74 and an accuracy of 75% in the test data set. CONCLUSION: The developed radiomics model allowed prediction of early response to radiosurgery in patients with brain metastases and outperformed the visual assessment of patterns of contrast enhancement.

Impact of prescription isodose level and collimator selection on dose homogeneity and plan quality in robotic radiosurgery.

PURPOSE: In stereotactic radiosurgery (SRS), prescription isodoses and resulting dose homogeneities vary widely across different platforms and clinical entities. Our goal was to investigate the physical limitations of generating dose distributions with an intended level of homogeneity in robotic SRS. METHODS: Treatment plans for non-isocentric irradiation of 4 spherical phantom targets (volume 0.27-7.70 ml) and 4 clinical targets (volume 0.50-5.70 ml) were calculated using Sequential (phantom) or VOLOTM (clinical) optimizers (Accuray, Sunnyvale, CA, USA). Dose conformity, volume of 12 Gy isodose (V12Gy) as a measure for dose gradient, and treatment time were recorded for different prescribed isodose levels (PILs) and collimator settings. In addition, isocentric irradiation of phantom targets was examined, with dose homogeneity modified by using different collimator sizes. RESULTS: Dose conformity was generally high (nCI ≤ 1.25) and varied little with PIL. For all targets and collimator sets, V12Gy was highest for PIL ≥ 80% and lowest for PIL ≤ 65%. The impact of PIL on V12Gy was highest for isocentric irradiation and lowest for clinical targets (VOLOTM optimization). The variability of V12Gy as a function of collimator selection was significantly higher than that of PIL. V12Gy and treatment time were negatively correlated. Plans utilizing a single collimator with a diameter in the range of 70-80% of the target diameter were fastest, but showed the strongest dependence on PIL. CONCLUSION: Inhomogeneous dose distributions with PIL ≤ 70% can be used to minimize dose to normal tissue. PIL ≥ 90% is associated with a marked and significant increase in off-target dose exposure. Careful selection of collimators during planning is even more important.

Frame-based stereotactic implantation of cystoventricular shunts for treating acquired intracerebral cysts.

OBJECTIVE: The treatment of symptomatic, progressive or recurrent acquired intracerebral cysts is challenging, especially when they are localized in eloquent structures. In addition to resection, endoscopic fenestration, or stereotactic puncture, the implantation of a cystoventricular shunt by stereotactic guidance (SCVS) has been reported as a minimally invasive procedure; however, only scarce data are available regarding its feasibility and efficacy. Here, the authors evaluated the feasibility and efficacy of frame-based SCVS in patients with acquired intracranial cysts. METHODS: In this single-center retrospective analysis, the authors included all patients with acquired intracerebral cysts treated by SCVS following a standardized prospective protocol between 2012 and 2020. They analyzed clinical symptoms, complications, and radiological outcome with regard to cyst volume reduction by 3D volumetry. RESULTS: Thirty-four patients (17 females and 17 males; median age 44 years, range 5-77 years) were identified. The median initial cyst volume was 11.5 cm3 (range 1.6-71.6 cm3), and the mean follow-up was 20 months (range 1-82 months). At the last follow-up, 27 of 34 patients (79%) showed a cyst volume reduction of more than 50%. Initial symptoms improved or resolved in 74% (n = 25) and remained stable in 24% (n = 8). No permanent clinical deterioration after treatment was observed. The total complication rate was 5.9%, comprising transient neurological deterioration (n = 1) and ventriculitis (n = 1). There were no deaths. The overall recurrence rate was 11.8%. CONCLUSIONS: In this study, SCVS proved to be a safe, minimally invasive, and effective treatment with reliable long-term volume reduction, resulting in clinical improvement and a minor complication rate.

Radiomics for prediction of radiation-induced lung injury and oncologic outcome after robotic stereotactic body radiotherapy of lung cancer: results from two independent institutions.

OBJECTIVES: To generate and validate state-of-the-art radiomics models for prediction of radiation-induced lung injury and oncologic outcome in non-small cell lung cancer (NSCLC) patients treated with robotic stereotactic body radiation therapy (SBRT). METHODS: Radiomics models were generated from the planning CT images of 110 patients with primary, inoperable stage I/IIa NSCLC who were treated with robotic SBRT using a risk-adapted fractionation scheme at the University Hospital Cologne (training cohort). In total, 199 uncorrelated radiomic features fulfilling the standards of the Image Biomarker Standardization Initiative (IBSI) were extracted from the outlined gross tumor volume (GTV). Regularized models (Coxnet and Gradient Boost) for the development of local lung fibrosis (LF), local tumor control (LC), disease-free survival (DFS) and overall survival (OS) were built from either clinical/ dosimetric variables, radiomics features or a combination thereof and validated in a comparable cohort of 71 patients treated by robotic SBRT at the Radiosurgery Center in Northern Germany (test cohort). RESULTS: Oncologic outcome did not differ significantly between the two cohorts (OS at 36 months 56% vs. 43%, p = 0.065; median DFS 25 months vs. 23 months, p = 0.43; LC at 36 months 90% vs. 93%, p = 0.197). Local lung fibrosis developed in 33% vs. 35% of the patients (p = 0.75), all events were observed within 36 months. In the training cohort, radiomics models were able to predict OS, DFS and LC (concordance index 0.77-0.99, p < 0.005), but failed to generalize to the test cohort. In opposite, models for the development of lung fibrosis could be generated from both clinical/dosimetric factors and radiomic features or combinations thereof, which were both predictive in the training set (concordance index 0.71- 0.79, p < 0.005) and in the test set (concordance index 0.59-0.66, p < 0.05). The best performing model included 4 clinical/dosimetric variables (GTV-Dmean, PTV-D95%, Lung-D1ml, age) and 7 radiomic features (concordance index 0.66, p < 0.03). CONCLUSION: Despite the obvious difficulties in generalizing predictive models for oncologic outcome and toxicity, this analysis shows that carefully designed radiomics models for prediction of local lung fibrosis after SBRT of early stage lung cancer perform well across different institutions.

Cyberknife® hypofractionated stereotactic radiosurgery (CK-hSRS) as salvage treatment for brain metastases.

PURPOSE: The introduction of hypofractionated stereotactic radiosurgery (hSRS) extended the treatment modalities beyond the well-established single-fraction stereotactic radiosurgery and fractionated radiotherapy. Here, we report the efficacy and side effects of hSRS using Cyberknife® (CK-hSRS) for the treatment of patients with critical brain metastases (BM) and a very poor prognosis. We discuss our experience in light of current literature. METHODS: All patients who underwent CK-hSRS over 3 years were retrospectively included. We applied a surface dose of 27 Gy in 3 fractions. Rates of local control (LC), systemic progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan-Meier method. Treatment-related complications were rated using the Common Terminology Criteria for Adverse Events (CTCAE). RESULTS: We analyzed 34 patients with 75 BM. 53% of the patients had a large tumor, tumor location was eloquent in 32%, and deep seated in 15%. 36% of tumors were recurrent after previous irradiation. The median Karnofsky Performance Status was 65%. The actuarial rates of LC at 3, 6, and 12 months were 98%, 98%, and 78.6%, respectively. Three, 6, and 12 months PFS was 38%, 32%, and 15%, and OS was 65%, 47%, and 28%, respectively. Median OS was significantly associated with higher KPS, which was the only significant factor for survival. Complications CTCAE grade 1-3 were observed in 12%. CONCLUSION: Our radiation schedule showed a reasonable treatment effectiveness and tolerance. Representing an optimal salvage treatment for critical BM in patients with a very poor prognosis and clinical performance state, CK-hSRS may close the gap between surgery, stereotactic radiosurgery, conventional radiotherapy, and palliative care.

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

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 (p = 0.0001 and p = 0.0002). The IGF-1 index was a predictor for biochemical remission (p = 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.