Treatment Planning for Cardiac Radioablation: Multicenter Multiplatform Benchmarking for the RAdiosurgery for VENtricular TAchycardia (RAVENTA) Trial.

PURPOSE: Cardiac radioablation is a novel treatment option for patients with refractory ventricular tachycardia unsuitable for catheter ablation. The quality of treatment planning depends on dose specifications, platform capabilities, and experience of the treating staff. To harmonize the treatment planning, benchmarking of this process is necessary for multicenter clinical studies such as the RAdiosurgery for VENtricular TAchycardia trial. METHODS AND MATERIALS: Planning computed tomography data and consensus structures from 3 patients were sent to 5 academic centers for independent plan development using a variety of platforms and techniques with the RAdiosurgery for VENtricular TAchycardia study protocol serving as guideline. Three-dimensional dose distributions and treatment plan details were collected and analyzed. In addition, an objective relative plan quality ranking system for ventricular tachycardia treatments was established. RESULTS: For each case, 3 coplanar volumetric modulated arc (VMAT) plans for C-arm linear accelerators (LINAC) and 3 noncoplanar treatment plans for robotic arm LINAC were generated. All plans were suitable for clinical applications with minor deviations from study guidelines in most centers. Eleven of 18 treatment plans showed maximal one minor deviation each for target and cardiac substructures. However, dose-volume histograms showed substantial differences: in one case, the planning target volume ≥30 Gy ranged from 0.0% to 79.9% and the ramus interventricularis anterior V14Gy ranged from 4.0% to 45.4%. Overall, the VMAT plans had steeper dose gradients in the high-dose region, while the plans for the robotic arm LINAC had smaller low-dose regions. Thereby, VMAT plans required only about half as many monitor units, resulting in shorter delivery times, possibly an important factor in treatment outcome. CONCLUSIONS: Cardiac radioablation is feasible with robotic arm and C-arm LINAC systems with comparable plan quality. Although cross-center training and best practice guidelines have been provided, further recommendations, especially for cardiac substructures, and ranking of dose guidelines will be helpful to optimize cardiac radioablation outcomes.

Planning Benchmark Study for Stereotactic Body Radiation Therapy of Liver Metastases: Results of the DEGRO/DGMP Working Group on Stereotactic Radiation Therapy and Radiosurgery.

PURPOSE: Our purpose was to investigate whether liver stereotactic body radiation therapy treatment planning can be harmonized across different treatment planning systems, delivery techniques, and institutions by using a specific prescription method and to minimize the knowledge gap concerning intersystem and interuser differences. We provide best practice guidelines for all used techniques. METHODS AND MATERIALS: A multiparametric specification of target dose (gross target volume [GTV]D50%, GTVD0.1cc, GTVV90%, planning target volume [PTV]V70%) with a prescription dose of GTVD50% = 3 × 20 Gy and organ-at-risk (OAR) limits were distributed with computed tomography and structure sets from 3 patients with liver metastases. Thirty-five institutions provided 132 treatment plans using different irradiation techniques. These plans were first analyzed for target and OAR doses. Four different renormalization methods were performed (PTVDmin, PTVD98%, PTVD2%, PTVDmax). The resulting 660 treatments plans were evaluated regarding target doses to study the effect of dose renormalization to different prescription methods. A relative scoring system was used for comparisons. RESULTS: GTVD50% prescription can be performed in all systems. Treatment plan harmonization was overall successful, with standard deviations for Dmax, PTVD98%, GTVD98%, and PTVDmean of 1.6, 3.3, 1.9, and 1.5 Gy, respectively. Primary analysis showed 55 major deviations from clinical goals in 132 plans, whereas in only <20% of deviations GTV/PTV dose was traded for meeting OAR limits. GTVD50% prescription produced the smallest deviation from target planning objectives and between techniques, followed by the PTVDmax, PTVD98%, PTVD2%, and PTVDmin prescription. Deviations were significant for all combinations but for the PTVDmax prescription compared with GTVD50% and PTVD98%. Based on the various dose prescription methods, all systems significantly differed from each other, whereas GTVD50% and PTVD98% prescription showed the least difference between the systems. CONCLUSIONS: This study showed the feasibility of harmonizing liver stereotactic body radiation therapy treatment plans across different treatment planning systems and delivery techniques when a sufficient set of clinical goals is given.

CyberKnife radiation therapy as a platform for translational mouse studies.

PURPOSE: Radiation therapy (RT) is a common nonsurgical treatment in the management of patients with cancer. While genetically engineered mouse models (GEMM) recapitulate human disease, conventional linear particle accelerator systems are not suited for state-of-the-art, imageguided targeted RT (IGRT) of these murine tumors. We employed the CyberKnife (CK; Accuray) platform for IGRT of GEMM-derived non-small cell lung cancer (NSCLC) lesions. MATERIAL AND METHODS: GEMM-derived KrasLSL-G12D/+/Trp53fl/fl -driven NSCLC flank tumors were irradiated using the CK RT platform. We applied IGRT of 2, 4, 6, and 8 Gy using field sizes of 5-12.5 mm to average gross tumor volumes (GTV) of 0.9 cm3 using Xsight Spine Tracking (Accuray). RESULTS: We found that 0 mm planning target volume (PTV) margin is sufficient for IGRT of murine tumors using the CK. We observed that higher RT doses (6-8 Gy) decreased absolute cell numbers of tumor infiltrating leukocytes (TIL) by approximately half compared to low doses (2-4 Gy) within 1 h, but even with low dose RT (2 Gy) TIL were found to be reduced after 8-24 h. CONCLUSION: We here demonstrate that the CK RT system allows for targeted IGRT of murine tumors with high precision and constitutes a novel promising platform for translational mouse RT studies.

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.

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

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 cm3, 5.9 to 79.9 cm3, and 9.4 to 34.3 cm3; surface area varied from 1087 to 3285 mm2, 1077 to 9500 mm2, and 1620 to 4179 mm2, 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.

Volumetric modulated arc therapy versus intensity-modulated proton therapy in neoadjuvant irradiation of locally advanced oesophageal cancer.

BACKGROUND: To investigate the role of intensity-modulated proton therapy (IMPT) compared to volumetric modulated arc therapy (VMAT), realised with RapidArc and RapidPlan methods (RA_RP) for neoadjuvant radiotherapy in locally advanced oesophagal cancer. METHODS: Twenty patients were retrospectively planned for IMPT (with two fields, (IMPT_2F) or with three fields (IMPT_3F)) and RA_RP and the results were compared according to dose-volume metrics. Estimates of the excess absolute risk (EAR) of secondary cancer induction were determined for the lungs. For the cardiac structures, the relative risk (RR) of coronary artery disease (CAD) and chronic heart failure (CHF) were estimated. RESULTS: Both the RA_RP and IMPT approached allowed to achieve the required coverage for the gross tumour volume, (GTV) and the clinical and the planning target volumes, CTV and PTV (V98% > 98 for CTV and GTV and V95% > 95 for the PTV)). The conformity index resulted in 0.88 ± 0.01, 0.89 ± 0.02 and 0.89 ± 0.02 for RA_RP, IMPT_2F and IMPT_3F respectively. With the same order, the homogeneity index for the PTV resulted in 5.6 ± 0.6%, 4.4 ± 0.9% and 4.5 ± 0.8%. Concerning the organs at risk, the IMPT plans showed a systematic and statistically significant incremental sparing when compared to RA_RP, especially for the heart. The mean dose to the combined lungs was 8.6 ± 2.9 Gy for RA_RP, 3.2 ± 1.5 Gy and 2.9 ± 1.2 Gy for IMPT_2F and IMPT_3F. The mean dose to the whole heart resulted to 9.9 ± 1.9 Gy for RA_RP compared to 3.7 ± 1.3 Gy or 4.0 ± 1.4 Gy for IMPT_2F or IMPT_3F; the mean dose to the left ventricle resulted to 6.5 ± 1.6 Gy, 1.9 ± 1.5 Gy, 1.9 ± 1.6 Gy respectively. Similar sparing effects were observed for the liver, the kidneys, the stomach, the spleen and the bowels. The EAR per 10,000 patients-years of secondary cancer induction resulted in 19.2 ± 5.7 for RA_RP and 6.1 ± 2.7 for IMPT_2F or 5.7 ± 2.4 for IMPT_3F. The RR for the left ventricle resulted in 1.5 ± 0.1 for RA_RP and 1.1 ± 0.1 for both IMPT sets. For the coronaries, the RR resulted in 1.6 ± 0.4 for RA_RP and 1.2 ± 0.3 for protons. CONCLUSION: With regard to cancer of the oesophagogastric junction type I and II, the use of intensity-modulated proton therapy seems to have a clear advantage over VMAT. In particular, the reduction of the heart and abdominal structures dose could result in an optimised side effect profile. Furthermore, reduced risk of secondary neoplasia in the lung can be expected in long-term survivors and would be a great gain for cured patients.

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

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.

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

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.

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

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, p = 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.

Radiomic analysis of planning computed tomograms for predicting radiation-induced lung injury and outcome in lung cancer patients treated with robotic stereotactic body radiation therapy.

OBJECTIVES: To predict radiation-induced lung injury and outcome in non-small cell lung cancer (NSCLC) patients treated with robotic stereotactic body radiation therapy (SBRT) from radiomic features of the primary tumor. METHODS: In all, 110 patients with primary stage I/IIa NSCLC were analyzed for local control (LC), disease-free survival (DFS), overall survival (OS) and development of local lung injury up to fibrosis (LF). First-order (histogram), second-order (GLCM, Gray Level Co-occurrence Matrix) and shape-related radiomic features were determined from the unprocessed or filtered planning CT images of the gross tumor volume (GTV), subjected to LASSO (Least Absolute Shrinkage and Selection Operator) regularization and used to construct continuous and dichotomous risk scores for each endpoint. RESULTS: Continuous scores comprising 1-5 histogram or GLCM features had a significant (p = 0.0001-0.032) impact on all endpoints that was preserved in a multifactorial Cox regression analysis comprising additional clinical and dosimetric factors. At 36 months, LC did not differ between the dichotomous risk groups (93% vs. 85%, HR 0.892, 95%CI 0.222-3.590), while DFS (45% vs. 17%, p < 0.05, HR 0.457, 95%CI 0.240-0.868) and OS (80% vs. 37%, p < 0.001, HR 0.190, 95%CI 0.065-0.556) were significantly lower in the high-risk groups. Also, the frequency of LF differed significantly between the two risk groups (63% vs. 20% at 24 months, p < 0.001, HR 0.158, 95%CI 0.054-0.458). CONCLUSION: Radiomic analysis of the gross tumor volume may help to predict DFS and OS and the development of local lung fibrosis in early stage NSCLC patients treated with stereotactic radiotherapy.

Stereotactic body radiotherapy dose and its impact on local control and overall survival of patients for locally advanced intrahepatic and extrahepatic cholangiocarcinoma.

PURPOSE: Non-resectable cholangiocarcinoma (CCC) is a significant therapeutic challenge because of bad prognosis. This study analyzed the outcome after SBRT for intra- and extrahepatic CCC. MATERIAL AND METHODS: Sixty-four patients with 82 CCC lesions from a retrospective multicenter database were analyzed. Available parameters were analyzed for local control (LC), overall survival (OS) and toxicity. RESULTS: Median follow-up time for patients alive was 35 months (range 7-91 months). Median overall survival (OS) time was 15 months; 2-year and 3-year OS rates were 32% and 21%. Median prescribed biological effective radiation dose (BED, α/ß = 10) was 67.2 Gy10 (range, 36-115 Gy10; SD: 20 Gy10) in median 8 fractions (range, 3-17; 95% CI: 3-12), median BEDmax was 91 Gy10. BED was the only prognostic factor for LC and OS. Patients receiving BEDmax >91 Gy10 had a median OS of 24 months vs. 13 months for those receiving lower doses (p = 0.008). LC rates at 12 and 24 months were 91% and 80% for BEDmax >91 Gy10 vs. 66% and 39% for lower doses (p = 0.009). Of note, tumor size and PTV were neither predictive nor prognostic for LC and OS. Treatment tolerance was good with 17% of grade 1 gastroduodenitis, 11% of grade 2-3 cholangitis and 4.7% of grade 3 gastrointestinal bleeding. CONCLUSION: This is the largest reported series on SBRT in cholangiocarcinoma. Overall survival and local control were significantly improved after higher doses (BED) and tolerance was excellent.

ICRU report 91 on prescribing, recording, and reporting of stereotactic treatments with small photon beams : Statement from the DEGRO/DGMP working group stereotactic radiotherapy and radiosurgery.

The International Commission on Radiation Units and Measurements (ICRU) report 91 with the title "prescribing, recording, and reporting of stereotactic treatments with small photon beams" was published in 2017. This extensive publication covers different relevant aspects of stereotactic radiotherapy such as small field dosimetry, accuracy requirements for volume definition and planning algorithms, and the precise application of treatment by means of image guidance. Finally, recommendations for prescribing, recording and reporting are given.

Proton versus photon deep inspiration breath hold technique in patients with hodgkin lymphoma and mediastinal radiation : A PLANNING COMPARISON OF DEEP INSPIRATION BREATH HOLD INTENSITY MODULATION RADIOTHERAPY AND INTENSITY MODULATED PROTON THERAPY.

BACKGROUND: The benefits of proton therapy in the treatment of patients with Hodgkin lymphoma (HL) are controversially discussed. Therefore we compared intensitiy modulated proton therapy (IMPT) with intensity modulated radiotherapy (IMRT), in the form of volumetric modulated arc therapy (VMAT) in patients with Hodgkin lymphoma (HL), through a comparative treatment planning study. METHODS: Radiation plans for 21 patients with Hodgkin Lymphoma (HL) were computed for IMPT and deep inspiration breath hold (DIBH) VMAT. Plans were optimized and computed assuming deep inspiration breath holding conditions. Dosimetric comparison on standard metrics from dose volume histograms was performed to appraise the relative merits of the two techniques, while proton plan robustness was assessed by re-computing the dose distribution of each plan by varying the Hounsfield Units to stopping power calibration by applying a ± 3 and 4% error. RESULTS: DIBH-VMAT and IMPT both provided excellent coverage, conformity and heterogeneity of the clinical target volume (CTV) and planning target volume (PTV). IMPT reduced mean doses to the breasts, lungs, heart and normal tissue by 38-83%. IMPT significantly reduced mean doses to the heart to < 5 Gy despite bulky mediastinal disease and decreased breast doses in female patients to < 1 Gy. Despite the simulated 3 and 4% miscalibration errors, no remarkable or measurable impact was observed on the organs at risk (OARs). CONCLUSIONS: This is the first comparison between DIBH-VMAT and IMPT in HL treatment. We could demonstrate statistically significant decreases in all dose/volume metrics of the OARs. Regardless of the planning paradigm used, range uncertainties can substantially under dose the PTV, while perhaps not leading to clinically significant deterioration of CTV coverage. With the geometry applied no impact was observed for OARs, suggesting IMPT as a superior technique for potentially reducing future health risks for HL patients.

Risk-adapted robotic stereotactic body radiation therapy for inoperable early-stage non-small-cell lung cancer.

PURPOSE: To evaluate efficacy and toxicity of stereotactic body radiation therapy (SBRT) with CyberKnife® (Accuray, Sunnyvale, CA, USA) in a selected cohort of primary, medically inoperable early-stage non-small cell lung cancer (NSCLC) patients. METHODS: From 2012 to 2016, 106 patients (median age 74 years, range 50-94 years) with primary NSCLC were treated with SBRT using CyberKnife®. Histologic confirmation was available in 87 patients (82%). For mediastinal staging, 92 patients (87%) underwent 18F-fluorodeoxyglucose positron-emission tomography (18-FDG-PET) and/or endobronchial ultrasound (EBUS)-guided lymph node biopsy or mediastinoscopy. Tumor stage (UICC8, 2017) was IA/B (T1a-c, 1-3 cm) in 86 patients (81%) and IIA (T2a/b, 3-5 cm) in 20 patients (19%). Depending on tumor localization, three different fractionation schedules were used: 3 fractions of 17Gy, 5 fractions of 11Gy, or 8 fractions of 7.5 Gy. Tracking was based on fiducial implants in 13 patients (12%) and on image guidance without markers in 88%. RESULTS: Median follow-up was 15 months (range 0.5-46 months). Acute side effects were mild (fatigue grade 1-2 in 20% and dyspnea grade 1-2 in 17%). Late effects were observed in 4 patients (4%): 3 patients developed pneumonitis requiring therapy (grade 2) and 1 patient suffered a rib fracture (grade 3). In total, 9/106 patients (8%) experienced a local recurrence, actuarial local control rates were 88% (95% confidence interval, CI, 80-96%) at 2 years and 77% (95%CI 56-98%) at 3 years. The median disease-free survival time was 27 months (95%CI 23-31 months). Overall survival was 77% (95%CI 65-85%) at 2 years and 56% (95%CI 39-73%) at 3 years. CONCLUSION: CyberKnife® lung SBRT which allows for real-time tumor tracking and risk-adapted fractionation achieves satisfactory local control and low toxicity rates in inoperable early-stage primary lung cancer patients.

Robot-assisted Extracranial Stereotactic Radiotherapy of Adrenal Metastases in Oligometastatic Non-small Cell Lung Cancer.

AIM: The aim of this study was to evaluate the efficacy and toxicity of stereotactic body radiation therapy (SBRT) in the treatment of patients with adrenal metastases in oligometastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between November 2012 and May 2015, fifteen patients with oligometastatic non-small cell lung cancer and adrenal metastases were treated with the Cyberknife® system. The primary endpoint was local control. RESULTS: The 1-year and 2-year local control rates were 60% and 46.6%, respectively. The differences in local control for patients with metachronous and synchronous metastases reached statistical significance (p=0.00028). Two-year overall survival of 91.2% for patients with metachronous metastases was also more favourable compared to patients with synchronous adrenal metastases with 42.8%. CONCLUSION: Extracranial stereotactic radiotherapy with the Cyberknife® is a safe and non-invasive technique that extends the therapeutic spectrum in the treatment of patients with adrenal metastases in oligometastatic NSCLC.

Radiotoxicity in robotic radiosurgery: proposing a new quality index for optimizing the treatment planning of brain metastases.

BACKGROUND: As irradiated brain volume at 12 Gy (V12) is a predictor for radionecrosis, the purpose of the study was to develop a model for Cyberknife (CK) plans that is able to predict the lowest achievable V12 at a given tumor size and prescription dose (PD), and to suggest a new quality index regarding V12 for optimizing the treatment planning of brain metastases. METHOD: In our model V12 was approximated as a spherical shell around the tumor volume. The radial distance between tumor surface and the 12 Gy isodose line was calculated using an approximation of the mean dose gradient in that area. Assuming a radially symmetrical irradiation from the upper half space, the dose distribution is given by the superposition of single fields. The dose profiles of a single field were derived by the measured off-center ratios (OCR) of the CK system. Using the calculated gradients of the sum dose profiles, minimal-V12 was estimated for different tumor sizes. The model calculation was tested using a phantom dataset and retrospectively applied on clinical cases. RESULTS: Our model allows the prediction of a best-case scenario for V12 at a given tumor size and PD which was confirmed by the results of the isocentric phantom plans. The results of the non-isocentric phantom plans showed that an optimization of coverage caused an increase in V12. This was in accordance with the results of the retrospective analysis. V12 s of the clinical cases were on average twice that of the predicted model calculation. A good agreement was achieved for plans with an optimal conformity index (nCI). Re-planning of cases with high V12 showed that lower values could be reached by selecting smaller collimators and by allowing a larger number of total MU and more MU per beam. CONCLUSIONS: V12 is a main parameter for assessing plan quality in terms of radiotoxicity. The index f12 defined as the ratio of V12 from the actual plan with the evaluated V12 from our model describes the conformity of an optimally possible V12 and thus can be used as a new quality index for optimizing treatment plans.

Planning benchmark study for SBRT of early stage NSCLC : Results of the DEGRO Working Group Stereotactic Radiotherapy.

PURPOSE: The aim was to evaluate stereotactic body radiation therapy (SBRT) treatment planning variability for early stage nonsmall cell lung cancer (NSCLC) with respect to the published guidelines of the Stereotactic Radiotherapy Working Group of the German Society for Radiation Oncology (DEGRO). MATERIALS AND METHODS: Planning computed tomography (CT) scan and the structure sets (planning target volume, PTV; organs at risk, OARs) of 3 patients with early stage NSCLC were sent to 22 radiotherapy departments with SBRT experience: each department was asked to prepare a treatment plan according to the DEGRO guidelines. The prescription dose was 3 fractions of 15 Gy to the 65% isodose. RESULTS: In all, 87 plans were generated: 36 used intensity-modulated arc therapy (IMAT), 21 used three-dimensional conformal radiation therapy (3DCRT), 6 used static field intensity-modulated radiation therapy (SF-IMRT), 9 used helical radiotherapy and 15 used robotic radiosurgery. PTV dose coverage and simultaneously kept OARs doses were within the clinical limits published in the DEGRO guidelines. However, mean PTV dose (mean 58.0 Gy, range 52.8-66.4 Gy) and dose conformity indices (mean 0.75, range 0.60-1.00) varied between institutions and techniques (p ≤ 0.02). OARs doses varied substantially between institutions, but appeared to be technique independent (p = 0.21). CONCLUSION: All studied treatment techniques are well suited for SBRT of early stage NSCLC according to the DEGRO guidelines. Homogenization of SBRT practice in Germany is possible through the guidelines; however, detailed treatment plan characteristics varied between techniques and institutions and further homogenization is warranted in future studies and recommendations. Optimized treatment planning should always follow the ALARA (as low as reasonably achievable) principle.

Inverse treatment planning for spinal robotic radiosurgery: an international multi-institutional benchmark trial.

Stereotactic radiosurgery (SRS) is the accurate, conformal delivery of high-dose radiation to well-defined targets while minimizing normal structure doses via steep dose gradients. While inverse treatment planning (ITP) with computerized optimization algorithms are routine, many aspects of the planning process remain user-dependent. We performed an international, multi-institutional benchmark trial to study planning variability and to analyze preferable ITP practice for spinal robotic radiosurgery. 10 SRS treatment plans were generated for a complex-shaped spinal metastasis with 21 Gy in 3 fractions and tight constraints for spinal cord (V14Gy < 2 cc, V18Gy < 0.1 cc) and target (coverage > 95%). The resulting plans were rated on a scale from 1 to 4 (excellent-poor) in five categories (constraint compliance, optimization goals, low-dose regions, ITP complexity, and clinical acceptability) by a blinded review panel. Additionally, the plans were mathemati-cally rated based on plan indices (critical structure and target doses, conformity, monitor units, normal tissue complication probability, and treatment time) and compared to the human rankings. The treatment plans and the reviewers' rankings varied substantially among the participating centers. The average mean overall rank was 2.4 (1.2-4.0) and 8/10 plans were rated excellent in at least one category by at least one reviewer. The mathematical rankings agreed with the mean overall human rankings in 9/10 cases pointing toward the possibility for sole mathematical plan quality comparison. The final rankings revealed that a plan with a well-balanced trade-off among all planning objectives was preferred for treatment by most par-ticipants, reviewers, and the mathematical ranking system. Furthermore, this plan was generated with simple planning techniques. Our multi-institutional planning study found wide variability in ITP approaches for spinal robotic radiosurgery. The participants', reviewers', and mathematical match on preferable treatment plans and ITP techniques indicate that agreement on treatment planning and plan quality can be reached for spinal robotic radiosurgery.