Publications by authors named "Oliver Blanck"

90 Publications

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

Radiat Oncol 2021 Apr 16;16(1):74. Epub 2021 Apr 16.

Department of Stereotactic and Functional Neurosurgery, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.

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-D, PTV-D, Lung-D, 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.
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http://dx.doi.org/10.1186/s13014-021-01805-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052812PMC
April 2021

MRI characteristics in treatment for cerebral melanoma metastasis using stereotactic radiosurgery and concomitant checkpoint inhibitors or targeted therapeutics.

J Neurooncol 2021 Mar 24. Epub 2021 Mar 24.

Institute for Neuroradiology, Johann Wolfgang Goethe-University, Theodor Stern Kai 7, 60590, Frankfurt am Main, Germany.

Introduction: Combination therapy for melanoma brain metastases (MM) using stereotactic radiosurgery (SRS) and immune checkpoint-inhibition (ICI) or targeted therapy (TT) is currently of high interest. In this collective, time evolution and incidence of imaging findings indicative of pseudoprogression is sparsely researched. We therefore investigated time-course of MRI characteristics in these patients.

Methods: Data were obtained retrospectively from 27 patients (12 female, 15 male; mean 61 years, total of 169 MMs). Single lesion volumes, total MM burden and edema volumes were analyzed at baseline and follow-up MRIs in 2 months intervals after SRS up to 24 months. The occurrence of intralesional hemorrhages was recorded.

Results: 17 patients (80 MM) received ICI, 8 (62 MM) TT and 2 (27 MM) ICI + TT concomitantly to SRS. MM-localization was frontal (n = 89), temporal (n = 23), parietal (n = 20), occipital (n = 10), basal ganglia/thalamus/insula (n = 10) and cerebellar (n = 10). A volumetric progression of MM 2-4 months after SRS was observed in combined treatment with ICI (p = 0.028) and ICI + TT (p = 0.043), whereas MMs treated with TT showed an early volumetric regression (p = 0.004). Edema volumes moderately correlated with total MM volumes (r = 0.57; p < 0.0001). Volumetric behavior did not differ significantly over time regarding lesions' initial sizes or localizations. No significant differences between groups were observed regarding rates of post-SRS intralesional hemorrhages.

Conclusion: Reversible volumetric increases in terms of pseudoprogression are observed 2-4 months after SRS in patients with MM concomitantly treated with ICI and ICI + TT, rarely after TT. Edema volumes mirror total MM volumes. Medical treatment type does not significantly affect rates of intralesional hemorrhage.
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http://dx.doi.org/10.1007/s11060-021-03744-4DOI Listing
March 2021

Stereotactic or conformal radiotherapy for adrenal metastases: Patient characteristics and outcomes in a multicenter analysis.

Int J Cancer 2021 Mar 8. Epub 2021 Mar 8.

Universitätsmedizin Mannheim, Medizinische Fakultät Mannheim, Universität Heidelberg, Klinik für Strahlentherapie und Radioonkologie, Mannheim, Germany.

To report outcome (freedom from local progression [FFLP], overall survival [OS] and toxicity) after stereotactic, palliative or highly conformal fractionated (>12) radiotherapy (SBRT, Pall-RT, 3DCRT/IMRT) for adrenal metastases in a retrospective multicenter cohort within the framework of the German Society for Radiation Oncology (DEGRO). Adrenal metastases treated with SBRT (≤12 fractions, biologically effective dose [BED10] ≥ 50 Gy), 3DCRT/IMRT (>12 fractions, BED10 ≥ 50 Gy) or Pall-RT (BED10 < 50 Gy) were eligible for this analysis. In addition to unadjusted FFLP (Kaplan-Meier/log-rank), we calculated the competing-risk-adjusted local recurrence rate (CRA-LRR). Three hundred twenty-six patients with 366 metastases were included by 21 centers (median follow-up: 11.7 months). Treatment was SBRT, 3DCRT/IMRT and Pall-RT in 260, 27 and 79 cases, respectively. Most frequent primary tumors were non-small-cell lung cancer (NSCLC; 52.5%), SCLC (16.3%) and melanoma (6.7%). Unadjusted FFLP was higher after SBRT vs Pall-RT (P = .026) while numerical differences in CRA-LRR between groups did not reach statistical significance (1-year CRA-LRR: 13.8%, 17.4% and 27.7%). OS was longer after SBRT vs other groups (P < .05) and increased in patients with locally controlled metastases in a landmark analysis (P < .0001). Toxicity was mostly mild; notably, four cases of adrenal insufficiency occurred, two of which were likely caused by immunotherapy or tumor progression. Radiotherapy for adrenal metastases was associated with a mild toxicity profile in all groups and a favorable 1-year CRA-LRR after SBRT or 3DCRT/IMRT. One-year FFLP was associated with longer OS. Dose-response analyses for the dataset are underway.
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http://dx.doi.org/10.1002/ijc.33546DOI Listing
March 2021

Liver SBRT with active motion-compensation results in excellent local control for liver oligometastases: An outcome analysis of a pooled multi-platform patient cohort.

Radiother Oncol 2021 May 3;158:230-236. Epub 2021 Mar 3.

University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Department of Radiation Oncology, Germany.

Background: Local treatment of metastases in combination with systemic therapy can prolong survival of oligo-metastasized patients. To fully exploit this potential, safe and effective treatments are needed to ensure long-term metastases control. Stereotactic body radiotherapy (SBRT) is one means, however, for moving liver tumors correct delivery of high doses is challenging. After validating equal in-vivo treatment accuracy, we analyzed a pooled multi-platform liver-SBRT-database for clinical outcome.

Methods: Local control (LC), progression-free interval (PFI), overall survival (OS), predictive factors and toxicity was evaluated in 135 patients with 227 metastases treated by gantry-based SBRT (deep-inspiratory breath-hold-gating; n = 71) and robotic-based SBRT (fiducial-tracking, n = 156) with mean gross tumor volume biological effective dose (GTV-BED) of 146.6 Gy.

Results: One-, and five-year LC was 90% and 68.7%, respectively. On multivariate analysis, LC was significantly predicted by colorectal histology (p = 0.006). Median OS was 20 months with one- and two-year OS of 67% and 37%. On multivariate analysis, ECOG-status (p = 0.003), simultaneous chemotherapy (p = 0.003), time from metastasis detection to SBRT-treatment (≥2months; p = 0.021) and LC of the treated metastases (≥12 months, p < 0.009) were significant predictors for OS. One- and two-year PFI were 30.5% and 14%. Acute toxicity was mild and rare (14.4% grade I, 2.3% grade II, 0.6% grade III). Chronic °III/IV toxicities occurred in 1.1%.

Conclusions: Patient selection, time to treatment and sufficient doses are essential to achieve optimal outcome for SBRT with active motion compensation. Local control appears favorable compared to historical control. Long-term LC of the treated lesions was associated with longer overall survival.
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http://dx.doi.org/10.1016/j.radonc.2021.02.036DOI Listing
May 2021

In-field stereotactic body radiotherapy (SBRT) reirradiation for pulmonary malignancies as a multicentre analysis of the German Society of Radiation Oncology (DEGRO).

Sci Rep 2021 Feb 25;11(1):4590. Epub 2021 Feb 25.

Department of Radiation Oncology, University Hospital Zürich, University of Zurich, Zurich, Switzerland.

Data of thoracic in-field reirradiation with two courses of stereotactic body radiotherapy (SBRT) is scarce. Aim of this study is to investigate feasibility and safety of this approach. Patients with a second course of thoracic SBRT and planning target volume (PTV) overlap were analyzed in this retrospective, multicenter study. All plans and clinical data were centrally collected. 27 patients from 8 centers have been amenable for evaluation: 12 with non-small-cell lung cancer, 16 with metastases, treated from 2009 (oldest first course) to 2020 (latest second course). A median dose of 38.5 Gy to the 65%-isodose over a median of 5 fractions was prescribed in the first course and 40 Gy in 5 fractions for the second SBRT-course. Median PTV of the second SBRT was 29.5 cm, median PTV overlap 22 cm. With a median interval of 20.2 months between the two SBRT-courses, 1-year OS, and -LCR were 78.3% and 70.3% respectively. 3 patients developed grade 1 and one grade 2 pneumonitis. No grade > 2 toxicity was observed. Peripheral location and dose were the only factors correlating with tumor control. A second SBRT-course with PTV overlap appears safe and achieves reasonable local control.
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http://dx.doi.org/10.1038/s41598-021-83210-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907095PMC
February 2021

Interdisciplinary Clinical Target Volume Generation for Cardiac Radioablation: Multicenter Benchmarking for the RAdiosurgery for VENtricular TAchycardia (RAVENTA) Trial.

Int J Radiat Oncol Biol Phys 2021 Jan 27. Epub 2021 Jan 27.

I. Medizinische Klinik, Universitätsklinikum Mannheim and German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, Mannheim, Germany.

Purpose: Cardiac radioablation is a novel treatment option for therapy-refractory ventricular tachycardia (VT) ineligible for catheter ablation. Three-dimensional clinical target volume (CTV) definition is a key step, and this complex interdisciplinary procedure includes VT-substrate identification based on electroanatomical mapping (EAM) and its transfer to the planning computed tomography (PCT). Benchmarking of this process is necessary for multicenter clinical studies such as the RAVENTA trial.

Methods And Materials: For benchmarking of the RAVENTA trial, patient data (epicrisis, electrocardiogram, high-resolution EAM, contrast-enhanced cardiac computed tomography, PCT) of 3 cases were sent to 5 university centers for independent CTV generation, subsequent structure analysis, and consensus finding. VT substrates were first defined on multiple EAM screenshots/videos and manually transferred to the PCT. The generated structure characteristics were then independently analyzed (volume, localization, surface distance and conformity). After subsequent discussion, consensus structures were defined.

Results: VT substrate on the EAM showed visible variability in extent and localization for cases 1 and 2 and only minor variability for case 3. CTVs ranged from 6.7 to 22.9 cm, 5.9 to 79.9 cm, and 9.4 to 34.3 cm; surface area varied from 1087 to 3285 mm, 1077 to 9500 mm, and 1620 to 4179 mm, with a Hausdorff-distance of 15.7 to 39.5 mm, 23.1 to 43.5 mm, and 15.9 to 43.9 mm for cases 1 to 3, respectively. The absolute 3-dimensional center-of-mass difference was 5.8 to 28.0 mm, 8.4 to 26 mm, and 3.8 to 35.1 mm for cases 1 to 3, respectively. The entire process resulted in CTV structures with a conformity index of 0.2 to 0.83, 0.02 to 0.85, and 0.02 to 0.88 (ideal 1) with the consensus CTV as reference.

Conclusions: Multicenter efficacy endpoint assessment of cardiac radioablation for therapy-refractory VT requires consistent CTV transfer methods from the EAM to the PCT. VT substrate definition and CTVs were comparable with current clinical practice. Remarkable differences regarding the degree of agreement of the CTV definition on the EAM and the PCT were noted, indicating a loss of agreement during the transfer process between EAM and PCT. Cardiac radioablation should be performed under well-defined protocols and in clinical trials with benchmarking and consensus forming.
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http://dx.doi.org/10.1016/j.ijrobp.2021.01.028DOI Listing
January 2021

Application of the RATING score: In regards to Hansen et al.

Radiother Oncol 2021 May 22;158:309-310. Epub 2021 Jan 22.

Department of Radiation Oncology, University Medical Center Schleswig-Holstein, Kiel, Germany.

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http://dx.doi.org/10.1016/j.radonc.2020.12.040DOI Listing
May 2021

Metastasis directed stereotactic radiotherapy in NSCLC patients progressing under targeted- or immunotherapy: efficacy and safety reporting from the 'TOaSTT' database.

Radiat Oncol 2021 Jan 6;16(1). Epub 2021 Jan 6.

Department of Radiation Oncology, University Hospital Zürich, Rämistrasse 100, 8091, Zürich, Switzerland.

Background: Metastasis directed treatment (MDT) is increasingly performed with the attempt to improve outcome in non-small cell lung cancer (NSCLC) patients receiving targeted- or immunotherapy (TT/IT). This study aimed to assess the safety and efficacy of metastasis directed stereotactic radiotherapy (SRT) concurrent to TT/IT in NSCLC patients.

Methods: A retrospective multicenter cohort of stage IV NSCLC patients treated with TT/IT and concurrent (≤ 30 days) MDT was established. 56% and 44% of patients were treated for oligoprogressive disease (OPD) or polyprogressive disease (PPD) under TT/IT, polyprogressive respectively. Survival was analyzed using Kaplan-Meier and log rank testing. Toxicity was scored using CTCAE v4.03 criteria. Predictive factors for overall survival (OS), progression free survival (PFS) and time to therapy switch (TTS) were analyzed with uni- and multivariate analysis.

Results: MDT of 192 lesions in 108 patients was performed between 07/2009 and 05/2018. Concurrent TT/IT consisted of EGFR/ALK-inhibitors (60%), immune checkpoint inhibitors (31%), VEGF-antibodies (8%) and PARP-inhibitors (1%). 2y-OS was 51% for OPD and 25% for PPD. After 1 year, 58% of OPD and 39% of PPD patients remained on the same TT/IT. Second progression after MDT was oligometastatic (≤ 5 lesions) in 59% of patients. Severe acute and late toxicity was observed in 5.5% and 1.9% of patients. In multivariate analysis, OS was influenced by the clinical metastatic status (p = 0.002, HR 2.03, 95% CI 1.30-3.17). PFS was better in patients receiving their first line of systemic treatment (p = 0.033, HR 1.7, 95% CI 1.05-2.77) and with only one metastases-affected organ (p = 0.023, HR 2.04, 95% CI 1.10-3.79). TTS was 6 months longer in patients with one metastases-affected organ (p = 0.031, HR 2.53, 95% CI 1.09-5.89). Death was never therapy-related.

Conclusions: Metastases-directed SRT in NSCLC patients can be safely performed concurrent to TT/IT with a low risk of severe toxicity. To find the ideal sequence of the available multidisciplinary treatment options for NSCLC and determine what patients will benefit most, a further evaluated in a broader context within prospective clinical trials is needed continuation of TT/IT beyond progression combined with MDT for progressive lesions appears promising but requires prospective evaluation.

Trial Registration: retrospectively registered.
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http://dx.doi.org/10.1186/s13014-020-01730-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788768PMC
January 2021

A Review of Cardiac Radioablation (CR) for Arrhythmias: Procedures, Technology, and Future Opportunities.

Int J Radiat Oncol Biol Phys 2021 Mar 5;109(3):783-800. Epub 2020 Nov 5.

ACRF ImageX Institute, University of Sydney, Sydney, Australia.

Purpose: Cardiac radioablation (CR), a new treatment for cardiac arrhythmias such as ventricular tachycardia and atrial fibrillation, has had promising clinical outcomes to date. There is consequent desire for rapid clinical adoption. However, CR presents unique challenges to radiation therapy, and it is paramount that clinical adoption be performed safely and effectively. Recent reviews comprehensively detail patient selection, clinical history, treatment outcomes, and treatment toxicities but only briefly mention the technical aspects of CR. To address this knowledge gap, this review collates currently available knowledge regarding CR technology choice and procedural details to help inform and guide clinics considering implementing their own CR program, to aid technique standardization, and to highlight areas that require further development or verification.

Methods And Materials: Original preclinical and clinical scientific articles that sufficiently detailed CR technical aspects, including pretreatment electrophysiology and imaging, motion analysis and management techniques, treatment planning, and/or treatment delivery, were identified within a comprehensive literature search.

Results: Nineteen preclinical and 18 clinical scientific articles sufficiently detailed the technical aspects of CR treatment deliveries on live subjects. The technical aspects of these scientific articles were diverse: Preclinical treatments have been performed with brachytherapy, photons, protons, and carbon ions, and clinical treatments have been performed with photons using conventional, robotic, and magnetic resonance imaging guided systems. Other technical aspects demonstrated similar variability.

Conclusions: This review summarizes the technical aspects and procedural details of preclinical and clinical CR treatment deliveries and highlights the complexity and current variability of CR. There is need for standardized procedural reporting to aid multicenter and multiplatform evaluation and potential for significant technological improvements in imaging, planning, delivery, and monitoring to maximize the clinical outcomes for selected patients with arrhythmia.
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http://dx.doi.org/10.1016/j.ijrobp.2020.10.036DOI Listing
March 2021

Mitigation of motion effects in pencil-beam scanning - Impact of repainting on 4D robustly optimized proton treatment plans for hepatocellular carcinoma.

Z Med Phys 2020 Oct 29. Epub 2020 Oct 29.

West German Proton Therapy Centre Essen, Am Mühlenbach 1, 45147 Essen, Germany; University Hospital Essen, Hufelandstr. 55, Essen, Germany; West German Cancer Center (WTZ), Hufelandstr. 55, Essen, Germany.

Proton fields delivered by the active scanning technique can be interfered with the intrafractional motion. This in-silico study seeks to mitigate the dosimetric impacts of motion artifacts, especially its interplay with the time-modulated dose delivery. Here four-dimensional (4d) robust optimization and dose repainting, which is the multiple application of the same field with reduced fluence, were combined. Two types of repainting were considered: layered and volumetric repainting. The time-resolved dose calculation, which is necessary to quantify the interplay effect, was integrated into the treatment planning system and validated. Nine clinical cases of hepatocellular carcinoma (HCC) showing motion in the range of 0.4-1.5cm were studied. It was found that the repainted delivery of 4D robustly optimized plans reduced the impact of interplay effect as quantified by the homogeneity index within the clinical target volume (CTV) to a tolerable level. Similarly, the fractional over- and underdosage was reduced sufficiently for some HCC cases to achieve the purpose of motion management. This holds true for both investigated types of repainting with small dosimetric advantages of volume repainting over layered repainting. Volume repainting, however, cannot be applied clinically in proton centers with slow energy changes. Thus, it served as a reference in the in-silico evaluation. It is recommended to perform the dynamic dose calculation for individual cases to judge if robust optimization in conjunction with repainting is sufficient to keep the interplay effect within bounds.
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http://dx.doi.org/10.1016/j.zemedi.2020.08.001DOI Listing
October 2020

Stereotactic radiotherapy combined with immunotherapy or targeted therapy for metastatic renal cell carcinoma.

BJU Int 2020 Oct 28. Epub 2020 Oct 28.

Department of Radiation Oncology, University Hospital Zürich, University of Zurich, Zurich, Switzerland.

Objectives: To evaluate the safety and efficacy of stereotactic radiotherapy (SRT) in patients with metastatic renal cell carcinoma (mRCC) concurrently receiving targeted therapy (TT) or immunotherapy.

Patients And Methods: Data on patients with mRCC were extracted from a retrospective international multicentre register study (TOaSTT), investigating SRT concurrent (≤30 days) with TT/immune checkpoint inhibitor (ICI) therapy. Overall survival (OS), progression-free survival (PFS), local metastasis control (LC) and time to systemic therapy switch were analysed using Kaplan-Meier curves and log-rank testing. Clinical and treatment factors influencing survival were analysed using multivariate Cox regression. Acute and late SRT-induced toxicity were defined according to the Common Terminology Criteria for Adverse Events v.4.03.

Results: Fifty-three patients who underwent 128 sessions of SRT were included, of whom 58% presented with oligometastatic disease (OMD). ICIs and TT were received by 32% and 68% of patients, respectively. Twenty patients (37%) paused TT for a median (range) of 14 (2-21) days. ICI therapy was not paused in any patient. A median (range) of 1 (1-5) metastatic tumour was treated per patient, with a median (range) SRT dose of 65 (40-129.4) Gy (biologically effective dose). The OS, LC and PFS rates at 1 year were 71%, 75% and 25%, respectively. The median OS and PFS were not significantly different among patients receiving TT vs those receiving ICIs (P = 0.329). New lesions were treated with a repeat radiotherapy course in 46% of patients. After 1 year, 62% of patients remained on the same systemic therapy as at the time of SRT; this was more frequent for ICI therapy compared to TT (83% vs 36%; P = 0.035). OMD was an independent prognostic factor for OS (P = 0.004, 95% confidence interval [CI] 0.035-0.528) and PFS (P = 0.004; 95% CI 0.165-0.717) in multivariate analysis. Eastern Cooperative Oncology Group performance status (ECOG-PS) was the other independent prognostic factor for OS (P = 0.001, 95% CI 0.001-0.351). Acute grade 3 toxicity was observed in two patients, and late grade 3 toxicity in one patient. No grade 4 or 5 toxicity was observed.

Conclusion: Combined treatment with TT or immunotherapy and concurrent SRT was safe, without signals of increased severe toxicity. As we observed no signal of excess toxicity, full-dose SRT should be considered to achieve optimal metastasis control in patients receiving TT or immunotherapy. Favourable PFS and OS were observed for patients with oligometastatic RCC with a good ECOG-PS, which should form the basis for prospective testing of this treatment strategy in properly designed clinical trials.
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http://dx.doi.org/10.1111/bju.15284DOI Listing
October 2020

Stereotactic Radiotherapy for the Management of Refractory Ventricular Tachycardia: Promise and Future Directions.

Front Cardiovasc Med 2020 25;7:108. Epub 2020 Jun 25.

Heart and Vessel Department, Service of Cardiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Ventricular tachycardia (VT) caused by myocardial scaring bears a significant risk of mortality and morbidity. Antiarrhythmic drug therapy (AAD) and catheter ablation remain the cornerstone of VT management, but both treatments have limited efficacy and potential adverse effects. Stereotactic body radiotherapy (SBRT) is routinely used in oncology to treat non-invasively solid tumors with high precision and efficacy. Recently, this technology has been evaluated for the treatment of VT. This review presents the basic underlying principles, proof of concept, and main results of trials and case series that used SBRT for the treatment of VT refractory to AAD and catheter ablation.
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http://dx.doi.org/10.3389/fcvm.2020.00108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329991PMC
June 2020

Predicting the Risk of Subsequent Distant Brain Metastases After Stereotactic Radiosurgery or Fractionated Stereotactic Radiotherapy in Elderly Patients.

Anticancer Res 2020 Jul;40(7):4081-4086

Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ, U.S.A.

Background/aim: Treatment for elderly patients with few brain metastases is controversial. A score was generated to predict distant brain metastases (DBMs) after stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT).

Patients And Methods: Ten characteristics were retrospectively analyzed for freedom from new DBMs in 104 elderly patients receiving SRS or FSRT alone for 1-3 brain metastases. Characteristics that were significant or showed a trend on multivariate analysis were used for the score.

Results: On multivariate analysis, favorable histology (p=0.026) and single brain metastasis (p=0.006) showed significant associations with freedom from DBMs. A trend was found for supra-tentorial location only (p=0.065). Three groups were designed, 10-14, 16-20 and 21-25 points, with 6-month rates of freedom from DBMs of 10%, 54% and 95%, respectively (p<0.0001). Positive predictive values to predict DBMs and freedom from DBMs at 6 months were 91% and 94%.

Conclusion: This new score provided high accuracy in predicting DBMs and freedom from DBMs.
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http://dx.doi.org/10.21873/anticanres.14406DOI Listing
July 2020

Survival After Stereotactic Radiosurgery (SRS) or Fractionated Stereotactic Radiotherapy (FSRT) for Cerebral Metastases in the Elderly.

In Vivo 2020 Jul-Aug;34(4):1909-1913

Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ, U.S.A.

Background/aim: Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) have gained popularity especially for treating 1-3 cerebral metastases. Elderly patients benefit from treatment personalisation. A specific survival score was created to facilitate this approach.

Patients And Methods: Ten characteristics were retrospectively analysed for survival in 104 elderly patients with 1-3 cerebral metastases receiving SRS or FSRT alone using a linear accelerator or Cyberknife®.

Results: On multivariate analysis, better survival was significantly associated with KPS of 90-100 (p=0.049), single lesion (p=0.036), maximum cumulative diameter of all lesions <16 mm (p=0.026) and supratentorial involvement only (p=0.047). Three groups were formed with 12-14 points (n=22), 15-16 points (n=33) and 17-19 points (n=49) with 12-month survival rates of 7%, 34% and 58% (p<0.0001), respectively. Positive predictive values for predicting death ≤12 months and survival ≥12 months were 95% and 54%.

Conclusion: The new score showed very high accuracy in predicting death ≤12 months, but not in predicting survival ≥12 months.
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http://dx.doi.org/10.21873/invivo.11987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439914PMC
March 2020

Tumor-dose-rate variations during robotic radiosurgery of oligo and multiple brain metastases.

Strahlenther Onkol 2020 Jun 25. Epub 2020 Jun 25.

Saphir Radiosurgery Center Frankfurt and Northern Germany, Guestrow, Germany.

Purpose: For step-and-shoot robotic stereotactic radiosurgery (SRS) the dose delivered over time, called local tumor-dose-rate (TDR), may strongly vary during treatment of multiple lesions. The authors sought to evaluate technical parameters influencing TDR and correlate TDR to clinical outcome.

Material And Methods: A total of 23 patients with 162 oligo (1-3) and multiple (>3) brain metastases (OBM/MBM) treated in 33 SRS sessions were retrospectively analyzed. Median PTV were 0.11 cc (0.01-6.36 cc) and 0.50 cc (0.12-3.68 cc) for OBM and MBM, respectively. Prescription dose ranged from 16 to 20 Gy prescribed to the median 70% isodose line. The maximum dose-rate for planning target volume (PTV) percentage p in time span s during treatment (TDR) was calculated for various p and s based on treatment log files and in-house software.

Results: TDR was 0.30 Gy/min (0.23-0.87 Gy/min) for OBM and 0.22 Gy/min (0.12-0.63 Gy/min) for MBM, respectively, and increased by 0.03 Gy/min per prescribed Gy. TDR strongly correlated with treatment time (ρ = -0.717, p < 0.001), monitor units (MU) (ρ = -0.767, p < 0.001), number of beams (ρ = -0.755, p < 0.001) and beam directions (ρ = -0.685, p < 0.001) as well as lesions treated per collimator (ρ = -0.708, P < 0.001). Median overall survival (OS) was 20 months and 1‑ and 2‑year local control (LC) was 98.8% and 90.3%, respectively. LC did not correlate with any TDR, but tumor response (partial response [PR] or complete response [CR]) correlated with all TDR in univariate analysis (e.g., TDR: hazard ration [HR] = 0.974, confidence interval [CI] = 0.952-0.996, p = 0.019). In multivariate analysis only concomitant targeted therapy or immunotherapy and breast cancer tumor histology remained a significant factor for tumor response. Local grade ≥2 radiation-induced tissue reactions were noted in 26.3% (OBM) and 5.2% (MBM), respectively, mainly influenced by tumor volume (p < 0.001).

Conclusions: Large TDR variations are noted during MBM-SRS which mainly arise from prolonged treatment times. Clinically, low TDR corresponded with decreased local tumor responses, although the main influencing factor was concomitant medication.
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http://dx.doi.org/10.1007/s00066-020-01652-6DOI Listing
June 2020

Predicting survival in melanoma patients treated with concurrent targeted- or immunotherapy and stereotactic radiotherapy : Melanoma brain metastases prognostic score.

Radiat Oncol 2020 Jun 1;15(1):135. Epub 2020 Jun 1.

Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland.

Background: Melanoma patients frequently develop brain metastases. The most widely used score to predict survival is the molGPA based on a mixed treatment of stereotactic radiotherapy (SRT) and whole brain radiotherapy (WBRT). In addition, systemic therapy was not considered. We therefore aimed to evaluate the performance of the molGPA score in patients homogeneously treated with SRT and concurrent targeted therapy or immunotherapy (TT/IT).

Methods: This retrospective analysis is based on an international multicenter database (TOaSTT) of melanoma patients treated with TT/IT and concurrent (≤30 days) SRT for brain metastases between May 2011 and May 2018. Overall survival (OS) was studied using Kaplan-Meier survival curves and log-rank testing. Uni- and multivariate analysis was performed to analyze prognostic factors for OS.

Results: One hundred ten patients were analyzed. 61, 31 and 8% were treated with IT, TT and with a simultaneous combination, respectively. A median of two brain metastases were treated per patient. After a median follow-up of 8 months, median OS was 8.4 months (0-40 months). The molGPA score was not associated with OS. Instead, cumulative brain metastases volume, timing of metastases (syn- vs. metachronous) and systemic therapy with concurrent IT vs. TT influenced OS significantly. Based on these parameters, the VTS score (volume-timing-systemic therapy) was established that stratified patients into three groups with a median OS of 5.1, 18.9 and 34.5 months, respectively (p = 0.001 and 0.03).

Conclusion: The molGPA score was not useful for this cohort of melanoma patients undergoing local therapy for brain metastases taking into account systemic TT/IT. For these patients, we propose a prognostic VTS score, which needs to be validated prospectively.
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http://dx.doi.org/10.1186/s13014-020-01558-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268472PMC
June 2020

On the pitfalls of PTV in lung SBRT using type-B dose engine: an analysis of PTV and worst case scenario concepts for treatment plan optimization.

Radiat Oncol 2020 May 29;15(1):130. Epub 2020 May 29.

Department of Radiotherapy, University Hospital Essen, Kiel Campus, 24105, Kiel, Germany.

Background: PTV concept is presumed to introduce excessive and inconsistent GTV dose in lung stereotactic body radiotherapy (SBRT). That GTV median dose prescription (D) and robust optimization are viable PTV-free solution (ICRU 91 report) to harmonize the GTV dose was investigated by comparisons with PTV-based SBRT plans.

Methods: Thirteen SBRT plans were optimized for 54 Gy / 3 fractions and prescribed (i) to 95% of the PTV (D) expanded 5 mm from the ITV on the averaged intensity project (AIP) CT, i.e., PTV, (ii) to D of PTV derived from the van Herk (VH)'s margin recipe on the mid-ventilation (MidV)-CT, i.e., PTV, (iii) to ITV D by worst case scenario (WCS) optimization on AIP,i.e., WCS and (iv) to GTV D by WCS using all 4DCT images, i.e., WCS. These plans were subsequently recalculated on all 4DCT images and deformably summed on the MidV-CT. The dose differences between these plans were compared for the GTV and selected normal organs by the Friedman tests while the variability was compared by the Levene's tests. The phase-to-phase changes of GTV dose through the respiration were assessed as an indirect measure of the possible increase of photon fluence owing to the type-B dose engine. Finally, all plans were renormalized to GTV D and all the dosimetric analyses were repeated to assess the relative influences of the SBRT planning concept and prescription method on the variability of target dose.

Results: By coverage prescriptions (i) to (iv), significantly smaller chest wall volume receiving ≥30 Gy (CW) and normal lung ≥20 Gy (NL) were achieved by WCS and WCS compared to PTV and PTV (p > 0.05). These plans differed significantly in the recalculated and summed GTV D, D and D (p <  0.05). The inter-patient variability of all GTV dose parameters is however equal between these plans (Levene's tests; p > 0.05). Renormalizing these plans to GTV D reduces their differences in GTV D, and D to insignificant level (p > 0.05) and their inter-patient variability of all GTV dose parameters. None of these plans showed significant differences in GTV D, D and D between respiratory phases, nor their inter-phase variability is significant.

Conclusion: Inconsistent GTV dose is not unique to PTV concept but occurs to other PTV-free concept in lung SBRT. GTV D renormalization effectively harmonizes the target dose among patients and SBRT concepts of geometric uncertainty management.
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http://dx.doi.org/10.1186/s13014-020-01573-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260838PMC
May 2020

Radiosurgery for ventricular tachycardia: preclinical and clinical evidence and study design for a German multi-center multi-platform feasibility trial (RAVENTA).

Clin Res Cardiol 2020 Nov 18;109(11):1319-1332. Epub 2020 Apr 18.

Klinik für Innere Medizin III, Abteilung für Elektrophysiologie und Rhythmologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany.

Background: Single-session high-dose stereotactic radiotherapy (radiosurgery) is a new treatment option for otherwise untreatable patients suffering from refractory ventricular tachycardia (VT). In the initial single-center case studies and feasibility trials, cardiac radiosurgery has led to significant reductions of VT burden with limited toxicities. However, the full safety profile remains largely unknown.

Methods/design: In this multi-center, multi-platform clinical feasibility trial which we plan is to assess the initial safety profile of radiosurgery for ventricular tachycardia (RAVENTA). High-precision image-guided single-session radiosurgery with 25 Gy will be delivered to the VT substrate determined by high-definition endocardial electrophysiological mapping. The primary endpoint is safety in terms of successful dose delivery without severe treatment-related side effects in the first 30 days after radiosurgery. Secondary endpoints are the assessment of VT burden, reduction of implantable cardioverter defibrillator (ICD) interventions [shock, anti-tachycardia pacing (ATP)], mid-term side effects and quality-of-life (QoL) in the first year after radiosurgery. The planned sample size is 20 patients with the goal of demonstrating safety and feasibility of cardiac radiosurgery in ≥ 70% of the patients. Quality assurance is provided by initial contouring and planning benchmark studies, joint multi-center treatment decisions, sequential patient safety evaluations, interim analyses, independent monitoring, and a dedicated data and safety monitoring board.

Discussion: RAVENTA will be the first study to provide the initial robust multi-center multi-platform prospective data on the therapeutic value of cardiac radiosurgery for ventricular tachycardia.

Trial Registration Number: NCT03867747 (clinicaltrials.gov). Registered March 8, 2019. The study was initiated on November 18th, 2019, and is currently recruiting patients.
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http://dx.doi.org/10.1007/s00392-020-01650-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588361PMC
November 2020

Definition and quality requirements for stereotactic radiotherapy: consensus statement from the DEGRO/DGMP Working Group Stereotactic Radiotherapy and Radiosurgery.

Strahlenther Onkol 2020 May;196(5):417-420

Klinik für Strahlentherapie, Universitätsklinikum Münster, Munster, Germany.

Stereotactic radiotherapy with its forms of intracranial stereotactic radiosurgery (SRS), intracranial fractionated stereotactic radiotherapy (FSRT) and stereotactic body radiotherapy (SBRT) is today a guideline-recommended treatment for malignant or benign tumors as well as neurological or vascular functional disorders. The working groups for radiosurgery and stereotactic radiotherapy of the German Society for Radiation Oncology (DEGRO) and for physics and technology in stereotactic radiotherapy of the German Society for Medical Physics (DGMP) have established a consensus statement about the definition and minimal quality requirements for stereotactic radiotherapy to achieve best clinical outcome and treatment quality in the implementation into routine clinical practice.
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http://dx.doi.org/10.1007/s00066-020-01603-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182610PMC
May 2020

Technological quality requirements for stereotactic radiotherapy : Expert review group consensus from the DGMP Working Group for Physics and Technology in Stereotactic Radiotherapy.

Strahlenther Onkol 2020 May 24;196(5):421-443. Epub 2020 Mar 24.

Klinik für Strahlentherapie-Radioonkologie, Universitätsklinikum Münster, Münster, Germany.

This review details and discusses the technological quality requirements to ensure the desired quality for stereotactic radiotherapy using photon external beam radiotherapy as defined by the DEGRO Working Group Radiosurgery and Stereotactic Radiotherapy and the DGMP Working Group for Physics and Technology in Stereotactic Radiotherapy. The covered aspects of this review are 1) imaging for target volume definition, 2) patient positioning and target volume localization, 3) motion management, 4) collimation of the irradiation and beam directions, 5) dose calculation, 6) treatment unit accuracy, and 7) dedicated quality assurance measures. For each part, an expert review for current state-of-the-art techniques and their particular technological quality requirement to reach the necessary accuracy for stereotactic radiotherapy divided into intracranial stereotactic radiosurgery in one single fraction (SRS), intracranial fractionated stereotactic radiotherapy (FSRT), and extracranial stereotactic body radiotherapy (SBRT) is presented. All recommendations and suggestions for all mentioned aspects of stereotactic radiotherapy are formulated and related uncertainties and potential sources of error discussed. Additionally, further research and development needs in terms of insufficient data and unsolved problems for stereotactic radiotherapy are identified, which will serve as a basis for the future assignments of the DGMP Working Group for Physics and Technology in Stereotactic Radiotherapy. The review was group peer-reviewed, and consensus was obtained through multiple working group meetings.
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http://dx.doi.org/10.1007/s00066-020-01583-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182540PMC
May 2020

Cardiac radioablation-A systematic review.

Heart Rhythm 2020 08 20;17(8):1381-1392. Epub 2020 Mar 20.

Heart Center, Department of Clinical and Experimental Cardiology, Amsterdam UMC, University of Amsterdam, Cardiovascular Sciences, Amsterdam, The Netherlands. Electronic address:

Failure of drugs and catheter ablation procedures for the treatment of ventricular arrhythmias is still extremely relevant. Recently, stereotactic body radiotherapy has been introduced to treat therapy refractory patients. In this systematic review (International Prospective Register of Systematic Reviews, CRD42019133212), we aimed to summarize electrophysiological and histopathological effects of radioablation in animals, patients, and extracted and perfused hearts. A systematic search was performed in OVID MEDLINE, OVID Embase, the Cochrane Central Register of Controlled Trials, Web of Science, Google Scholar, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) from inception to September 2019. Identified records were independently screened for eligibility by 2 reviewers. Risk of bias and methodological quality were assessed using the SYRCLE, ROBINS-I, or Murad tool and tailored to the different study designs. We included 13 preclinical and 10 clinical publications. Large heterogeneity in study designs prompted a narrative synthesis approach. Baseline, (pre-)procedural details, outcome, target tissue analyses, and safety data were extracted and summarized. In animal studies evaluating electrophysiological parameters, radioablation induced a reduction in voltage/potential amplitude or bidirectional block in target areas in 93.2% of animals. Atrioventricular block (first to third degree) was induced in 78.3% of animals, and in studies evaluating ventricular arrhythmia inducibility, 75% reduction was achieved. In patients, predominantly ventricular tachycardias were targeted with >85% reduction in arrhythmia episodes during follow-up with an encouraging short-term safety profile. Preclinical and clinical evidence on the efficacy and safety of radioablation is limited in both quantity and quality. The results of radioablation for therapy refractory patients with ventricular tachycardia are promising, but further research is needed.
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http://dx.doi.org/10.1016/j.hrthm.2020.03.013DOI Listing
August 2020

Correlating Dose Variables with Local Tumor Control in Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer: A Modeling Study on 1500 Individual Treatments.

Int J Radiat Oncol Biol Phys 2020 07 15;107(3):579-586. Epub 2020 Mar 15.

Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland.

Background: Large variation regarding prescription and dose inhomogeneity exists in stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer. The aim of this modeling study was to identify which dose metric correlates best with local tumor control probability to make recommendations regarding SBRT prescription.

Methods And Materials: We combined 2 retrospective databases of patients with non-small cell lung cancer, yielding 1500 SBRT treatments for analysis. Three dose parameters were converted to biologically effective doses (BEDs): (1) the (near-minimum) dose prescribed to the planning target volume (PTV) periphery (yielding BED); (2) the (near-maximum) dose absorbed by 1% of the PTV (yielding BED); and (3) the average between near-minimum and near-maximum doses (yielding BED). These BED parameters were then correlated to the risk of local recurrence through Cox regression. Furthermore, BED-based prediction of local recurrence was attempted by logistic regression and fast and frugal trees. Models were compared using the Akaike information criterion.

Results: There were 1500 treatments in 1434 patients; 117 tumors recurred locally. Actuarial local control rates at 12 and 36 months were 96.8% (95% confidence interval, 95.8%-97.8%) and 89.0% (87.0%-91.1%), respectively. In univariable Cox regression, BED was the best predictor of risk of local recurrence, and a model based on BED had substantially less evidential support. In univariable logistic regression, the model based on BED also performed best. Multivariable classification using fast and frugal trees revealed BED to be the most important predictor, followed by BED.

Conclusions: BED was generally better correlated with tumor control probability than either BED or BED. Because the average between near-minimum and near-maximum doses was highly correlated to the mean gross tumor volume dose, the latter may be used as a prescription target. More emphasis could be placed on achieving sufficiently high mean doses within the gross tumor volume rather than the PTV covering dose, a concept needing further validation.
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http://dx.doi.org/10.1016/j.ijrobp.2020.03.005DOI Listing
July 2020

Postoperative stereotactic radiosurgery and hypofractionated radiotherapy for brain metastases using Gamma Knife and CyberKnife: a dual-center analysis.

J Neurosurg Sci 2020 Feb 4. Epub 2020 Feb 4.

Department of Radiation Oncology, University Hospital Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany -

Background: Postoperative stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (hFSRT) to tumor cavities is emerging as a new standard of care after resection of brain metastases. Both Gamma Knife (GK) and CyberKnife (CK) are modalities commonly used for stereotactic radiotherapy, but fractional schemes are not consistent. The objective of this study was to evaluate outcomes in patients receiving postoperative stereotactic radiotherapy of resected brain metastases (BM) using different fractionation schedules and modalities in two large centers.

Methods: Patients with newly diagnosed BM who underwent postoperative SRS or hFSRT with either GK or CK at two large cancer centers were retrospectively evaluated. We analyzed local control (LC), regional control (RC) and overall survival (OS).

Results: From 04/14 to 05/18 79 patients with 81 resection cavities were treated. Forty-seven patients (59.5%) received GK and 32 patients (40.5%) received CK treatment. Fifty-four cavities (66.7%) were treated with hFSRT and 27 (33.3%) with SRS. The most common hFSRT and SRS scheme was 3x10 Gy and 1x16 Gy, respectively. Median OS was 11.7 months with survival rates of 44.7% at 1 year and 18.5% at 2 years. LC was 83.3% after 1 year. Median time to regional progression was 12.0 months with RC rates of 61.1% at 6 months and 41.0% at 12 months. There was no difference in OS, LC or RC between GK and CK treatments or SRS and hFSRT.

Conclusions: Both SRS and hFSRT provide high local control rates in resected BM regardless of the applied modality.
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http://dx.doi.org/10.23736/S0390-5616.20.04830-4DOI Listing
February 2020

Dosimetric Multicenter Planning Comparison Studies for Stereotactic Body Radiation Therapy: Methodology and Future Perspectives.

Int J Radiat Oncol Biol Phys 2020 02 7;106(2):403-412. Epub 2019 Nov 7.

Medical Physics unit, Radiotherapy Department, Humanitas Clinical and Research Hospital, Milano, Italy.

In this review a summary of the published literature pertaining to the stereotactic body radiation therapy multiplanning comparison, data sharing strategies, and implementation of benchmark planning cases to improve the skills and knowledge of the participating centers was investigated. A total of 30 full-text articles were included. The studies were subdivided in 3 categories: multiplanning studies on dosimetric variability, planning harmonization before clinical trials, and technical and methodologic studies. The methodology used in the studies were critically analyzed to find common and original elements with the pros and cons. Multicenter planning studies have played a key role in improving treatment plan harmonization, treatment plan compliance, and even clinical practices. This review has highlighted that some fundamental steps should be taken to transform a simple treatment planning comparison study into a potential credentialing method for stereotactic body radiation therapy accreditation. In particular, prescription and general requirements should always be well defined; data analysis should be performed with independent dose volume histogram or dose calculations; quality score indices should be constructed; feedback and correction strategies should be provided; and a simple web-based collaboration platform should be used. The results reported clearly showed that a crowd-based replanning approach is a viable method for achieving harmonization and standardization of treatment planning among centers using different technologies.
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http://dx.doi.org/10.1016/j.ijrobp.2019.10.041DOI Listing
February 2020

Stereotactic body radiotherapy for ventricular tachycardia (cardiac radiosurgery) : First-in-patient treatment in Germany.

Strahlenther Onkol 2020 Jan 31;196(1):23-30. Epub 2019 Oct 31.

Klinik für Innere Medizin III, Kardiologie, Abteilung für Elektrophysiologie und Rhythmologie, Universitätsklinikum Schleswig-Holstein, Kiel, Germany.

Purpose: Single-session cardiac stereotactic body radiotherapy, called cardiac radiosurgery (CRS) or radioablation (RA), may offer a potential treatment option for patients with refractory ventricular tachycardia (VT) and electrical storm who are otherwise ineligible for catheter ablation. However, there is only limited clinical experience. We now present the first-in-patient treatment using (CRS/RA) for VT in Germany.

Methods: A 78-year-old male patient with dilated cardiomyopathy and significantly reduced ejection fraction (15%) presented with monomorphic VT refractory to poly-anti-arrhythmic medication and causing multiple implantable cardioverter-defibrillator (ICD) interventions over the course of several weeks, necessitating prolonged treatment on an intensive care unit. Ultra-high-resolution electroanatomical voltage mapping (EVM) revealed a re-entry circuit in the cardiac septum inaccessible for catheter ablation. Based on the EVM, CRS/RA with a single session dose of 25 Gy (83% isodose) was delivered to the VT substrate (8.1 cc) using a c-arm-based high-precision linear accelerator on November 30, 2018.

Results: CRS/RA was performed without incident and dysfunction of the ICD was not observed. Following the procedure, a significant reduction in monomorphic VT from 5.0 to 1.6 episodes per week and of ICD shock interventions by 81.2% was observed. Besides periprocedural nausea with a single episode of vomiting, no treatment-associated side effects were noted. Unfortunately, the patient died 57 days after CRS/RA due to sepsis-associated cardiac circulatory failure after Clostridium difficile-associated colitis developed during rehabilitation. Histopathologic examination of the heart as part of a clinical autopsy revealed diffuse fibrosis on most sections of the heart without apparent differences between the target area and the posterior cardiac wall serving as a control.

Conclusion: CRS/RA appears to be a possible treatment option for otherwise untreatable patients suffering from refractory VT and electrical storm. A relevant reduction in VT incidence and ICD interventions was observed, although long-term outcome and consequences of CRS/RA remain unclear. Clinical trials are strongly warranted and have been initiated.
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http://dx.doi.org/10.1007/s00066-019-01530-wDOI Listing
January 2020

[Ultra-hypofractionation in localized prostate cancer. 5-year results of the HYPO-RT-PC trial: Commentary I].

Strahlenther Onkol 2019 12;195(12):1116-1118

Klinik für Strahlentherapie, Christian-Albrechts-Universität zu Kiel & Universitätsklinikum Schleswig-Holstein, Kiel, Deutschland.

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http://dx.doi.org/10.1007/s00066-019-01535-5DOI Listing
December 2019

Stereotactic Body Radiation Therapy as an Alternative Treatment for Patients with Hepatocellular Carcinoma Compared to Sorafenib: A Propensity Score Analysis.

Liver Cancer 2019 Jul 12;8(4):281-294. Epub 2018 Jul 12.

Department of Radiation Oncology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Background And Aims: Stereotactic body radiation therapy (SBRT) has emerged as a safe and effective treatment for patients with hepatocellular carcinoma (HCC), but its role in patients with advanced HCC is not yet defined. In this study, we aim to assess the efficacy and safety of SBRT in comparison to sorafenib treatment in patients with advanced HCC.

Methods: We included 901 patients treated with sorafenib at six tertiary centers in Europe and Asia and 122 patients treated with SBRT from 13 centers in Germany and Switzerland. Medical records were reviewed including laboratory parameters, treatment characteristics and development of adverse events. Propensity score matching was performed to adjust for differences in baseline characteristics. The primary endpoint was overall survival (OS) and progression-free survival.

Results: Median OS of SBRT patients was 18.1 (10.3-25.9) months compared to 8.8 (8.2-9.5) in sorafenib patients. After adjusting for different baseline characteristics, the survival benefit for patients treated with SBRT was still preserved with a median OS of 17.0 (10.8-23.2) months compared to 9.6 (8.6-10.7) months in sorafenib patients. SBRT treatment of intrahepatic lesions in patients with extrahepatic metastases was also associated with improved OS compared to patients treated with sorafenib in the same setting (17.0 vs. 10.0 months, = 0.012), whereas in patients with portal vein thrombosis there was no survival benefit in patients with SBRT.

Conclusions: In this retrospective comparative study, SBRT showed superior efficacy in HCC patients compared to patients treated with sorafenib.
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http://dx.doi.org/10.1159/000490260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738268PMC
July 2019

Long-term Follow-up and Patterns of Recurrence of Patients With Oligometastatic NSCLC Treated With Pulmonary SBRT.

Clin Lung Cancer 2019 11 27;20(6):e667-e677. Epub 2019 Jun 27.

Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

Introduction: This multicenter study aims to analyze outcome as well as early versus late patterns of recurrence following pulmonary stereotactic body radiotherapy (SBRT) for patients with oligometastatic non-small-cell lung cancer (NSCLC).

Materials And Methods: This analysis included 301 patients with oligometastatic NSCLC treated with SBRT for 336 lung metastases. Although treatment of the primary tumor consisted of surgical resection, radiochemotherapy, and/or systemic therapy, pulmonary oligometastases were treated with SBRT.

Results: The median follow-up time was 16.1 months, resulting in 2-year overall survival (OS), local control (LC), and distant control (DC) of 62.2%, 82.0%, and 45.2%, respectively. Multivariate analysis identified age (P = .019) and histologic subtype (P = .028), as well as number of metastatic organs (P < .001) as independent prognostic factors for OS. LC was superior for patients with favorable histologic subtype (P = .046) and SBRT with a higher biological effective dose at isocenter (P = .037), whereas DC was inferior for patients with metastases in multiple organs (P < .001) and female gender (P = .027). Early (within 24 months) local or distant progression was observed in 15.3% and 36.5% of the patients. After 24 months, the risk of late local failure was low, with 3- and 4-year local failure rates of only 4.0%, and 7.6%. In contrast, patients remained at a high risk of distant progression with 3- and 4-year failure rates of 13.3% and 24.1%, respectively, with no plateau observed.

Conclusion: SBRT for pulmonary oligometastatic NSCLC resulted in favorable LC and promising OS. The dominant failure pattern is distant with a continuously high risk of disease progression for many years.
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http://dx.doi.org/10.1016/j.cllc.2019.06.024DOI Listing
November 2019

[Stereotactic Body Radiation Therapy for Liver Metastases].

Zentralbl Chir 2019 Jun 5;144(3):242-251. Epub 2019 Jun 5.

Klinik für Strahlentherapie, Universitätsklinikum Schleswig-Holstein, Kiel, Deutschland.

In this review, the current state of stereotactic body radiation therapy (SBRT) is presented as a local therapy for patients with oligometastatic, oligoprogressive and oligorecurrent liver metastases - focusing on recent publications from German-speaking countries. In addition to precise imaging, modern SBRT techniques also use gating and tracking techniques that have made local therapy of liver metastases more effective. In combination with optimisation of central tumour dose, local control rates of up to 90% have been achieved with minimal side effects in less than 1% of patients and 5-year survival rates of more than 30% in selected (inoperable) patient populations. In future, hybrid ultrasound or MRI irradiation systems can overcome fiducial marker implantation. Due to the current outcome data, SBRT is a valuable addition to the therapeutic armamentarium for patients with liver metastases and is a true alternative to minimally invasive ablative procedures or can be used in combination with other local or systemic treatments in an interdisciplinary context.
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http://dx.doi.org/10.1055/a-0883-6583DOI Listing
June 2019