Stereotactic Radiosurgery for 1-10 Brain Metastases to avoid Whole-Brain Radiotherapy - Results of the CYBER-SPACE Randomized Phase 2 Trial.

BACKGROUND: Stereotactic Radiosurgery (SRS) is an emerging alternative to whole-brain radiotherapy (WBRT) for treating multiple brain metastases (BM), reducing toxicity and improving tumor control. The CYBER-SPACE trial compared SRS based on either SPACE or MPRAGE MRI sequence for avoiding or delaying WBRT in patients with 1-10 BM. METHODS: Patients with 1-10 untreated BM were randomized 1:1 to receive SRS of all lesions based on either SPACE or MPRAGE MRI sequences. If subsequently new BM occurred, SRS was repeated. WBRT was indicated upon occurrence of >10 new BM, leptomeningeal disease or exhausted SRS-radiotolerance. The primary outcome was freedom from WBRT indication (WBRTi). Secondary outcomes included overall survival (OS), safety, and quality of life. RESULTS: 202 patients were randomized; SPACE n=99, MPRAGE n=103. 12-month WBRTi-free survival was 77.1% (95%-CI: 69.5%-83.1%) overall, 78.5% (95%-CI: 66.7%-86.5%) for SPACE, and 76.0% (95%-CI: 65.2%-83.9%) for MPRAGE (HR=0.84, 95%-CI: 0.43-1.63, p=0.590). Patients with 5-10 BM had shorter WBRTi-free survival (HR=3.13, 95%-CI: 1.53-6.40, p=0.002). Median OS was 13.1 months overall, 10.5 months for SPACE, and 15.2 months for MPRAGE (HR=1.10, 95%-CI: 0.78-1.56, p=0.585). Neurologic death rate was 10.1%. Predictors for longer OS included Karnofsky Performance Status >80% (HR=0.51, 95%-CI: 0.33-0.77, p=0.002) and concurrent immunotherapy (HR=0.34, 95%-CI: 0.23-0.52, p<0.001). CONCLUSIONS: The more sensitive SPACE sequence did not improve outcomes over MPRAGE. SRS with thorough monitoring and immediate re-treatment for new lesions decreases the need for WBRT and achieves low neurologic death rates. SRS should be considered a favorable alternative to WBRT for patients with 1-10 BM.

Planning Benchmark Study for Stereotactic Body Radiation Therapy of Pancreas Carcinomas With Simultaneously Integrated Boost and Protection: Results of the DEGRO/DGMP Working Group on Stereotactic Radiation Therapy and Radiosurgery.

PURPOSE: The proximity or overlap of planning target volume (PTV) and organs-at-risk (OARs) poses a major challenge in stereotactic body radiation therapy (SBRT) of pancreatic cancer (PACA). This international treatment planning benchmark study investigates whether simultaneous integrated boost (SIB) and simultaneous integrated protection (SIP) concepts in PACA SBRT can lead to improved and harmonized plan quality. METHODS AND MATERIALS: A multiparametric specification of desired target doses (gross target volume [GTV]D50%, GTVD99%, PTVD95%, and PTV0.5cc) with 2 prescription doses of GTVD50% = 5 × 9.2Gy (46 Gy) and GTVD50% = 8 × 8.25 Gy (66 Gy) and OAR limits were distributed with planning computed tomography and contours from 3 PACA patients. In phase 1, plans were ranked using a scoring system for comparison of trade-offs between GTV/PTV and OAR. In phase 2, replanning was performed for the most challenging case and prescription with dedicated SIB and SIP contours provided for optimization after group discussion. RESULTS: For all 3 cases and both phases combined, 292 plans were generated from 42 institutions in 5 countries using commonly available treatment planning systems. The GTVD50% prescription was performed by only 76% and 74% of planners within 2% for 5 and 8 fractions, respectively. The GTVD99% goal was mostly reached, while the balance between OAR and target dose showed initial SIB/SIP-like optimization strategies in about 50% of plans. For plan ranking, 149 and 217 score penalties were given for 5 and 8 fractions, pointing to improvement possibilities. For phase 2, the GTVD50% prescription was performed by 95% of planners within 2%, and GTVD99% as well as OAR doses were better harmonized with notable less score penalties. Fourteen of 19 planners improved their plan rank, 9 of them by at least 2 ranks. CONCLUSIONS: Dedicated SIB/SIP concepts in combination with multiparametric prescriptions and constraints can lead to overall harmonized and high treatment plan quality for PACA SBRT. Standardized SIB/SIP treatment planning in multicenter clinical trials appears feasible after group consensus and training.

And Yet It Moves: Clinical Outcomes and Motion Management in Stereotactic Body Radiation Therapy (SBRT) of Centrally Located Non-Small Cell Lung Cancer (NSCLC): Shedding Light on the Internal Organ at Risk Volume (IRV) Concept.

The internal organ at risk volume (IRV) concept might improve toxicity profiles in stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC). We studied (1) clinical aspects in central vs. peripheral tumors, (2) the IRV concept in central tumors, (3) organ motion, and (4) associated normal tissue complication probabilities (NTCPs). We analyzed patients who received SBRT for NSCLC (clinical aspects, n = 78; motion management, n = 35). We found lower biologically effective doses, larger planning target volume sizes, higher lung doses, and worse locoregional control for central vs. peripheral tumors. Organ motion was greater in males and tall patients (bronchial tree), whereas volume changes were lower in patients with a high body mass index (BMI) (esophagus). Applying the IRV concept (retrospectively, without new optimization), we found an absolute increase of >10% in NTCPs for the bronchial tree in three patients. This study emphasizes the need to optimize methods to balance dose escalation with toxicities in central tumors. There is evidence that organ motion/volume changes could be more pronounced in males and tall patients, and less pronounced in patients with higher BMI. Since recent studies have made efforts to further subclassify central tumors to refine treatment, the IRV concept should be considered for optimal risk assessment.

Quality requirements for MRI simulation in cranial stereotactic radiotherapy: a guideline from the German Taskforce "Imaging in Stereotactic Radiotherapy".

Accurate Magnetic Resonance Imaging (MRI) simulation is fundamental for high-precision stereotactic radiosurgery and fractionated stereotactic radiotherapy, collectively referred to as stereotactic radiotherapy (SRT), to deliver doses of high biological effectiveness to well-defined cranial targets. Multiple MRI hardware related factors as well as scanner configuration and sequence protocol parameters can affect the imaging accuracy and need to be optimized for the special purpose of radiotherapy treatment planning. MRI simulation for SRT is possible for different organizational environments including patient referral for imaging as well as dedicated MRI simulation in the radiotherapy department but require radiotherapy-optimized MRI protocols and defined quality standards to ensure geometrically accurate images that form an impeccable foundation for treatment planning. For this guideline, an interdisciplinary panel including experts from the working group for radiosurgery and stereotactic radiotherapy of the German Society for Radiation Oncology (DEGRO), the working group for physics and technology in stereotactic radiotherapy of the German Society for Medical Physics (DGMP), the German Society of Neurosurgery (DGNC), the German Society of Neuroradiology (DGNR) and the German Chapter of the International Society for Magnetic Resonance in Medicine (DS-ISMRM) have defined minimum MRI quality requirements as well as advanced MRI simulation options for cranial SRT.

Successful implementation of online educational lectures of the German Society for Radiation Oncology (DEGRO).

PURPOSE: Modern digital teaching formats have become increasingly important in recent years, in part due to the COVID-19 pandemic. In January 2021, an online-based webinar series was established by the German Society for Radiation Oncology (DEGRO) and the young DEGRO (yDEGRO) working group. In the monthly 120-minute courses, selected lecturers teach curricular content as preparation for the board certification exam for radiation oncology. METHODS: The evaluation of the 24 courses between 01.2021 and 12.2022 was performed using a standardized questionnaire with 21 items (recording epidemiological characteristics of the participants, didactic quality, content quality). A Likert scale (1-4) was used in combination with binary and open-ended questions. RESULTS: A combined total of 4200 individuals (1952 in 2021 and 2248 in 2022) registered for the courses, and out of those, 934 participants (455 in 2021 and 479 in 2022) later provided evaluations for the respective courses (36% residents, 35% specialists, 21% medical technicians for radiology [MTR], 8% medical physics experts [MPE]). After 2 years, 74% of the DEGRO Academy curriculum topics were covered by the monthly webinars. The overall rating by participants was positive (mean 2021: 1.33 and 2022: 1.25) and exceeded the curriculum offered at each site for 70% of participants. Case-based learning was identified as a particularly well-rated method. CONCLUSION: The DEGRO webinar expands the digital teaching opportunities in radiation oncology. The consistently high number of participants confirms the need for high-quality teaching and underlines the advantages of e­learning methods. Optimization opportunities were identified through reevaluation of feedback from course participants. In its design as a teaching format for a multiprofessional audience, the webinar series could be used as a practice model of online teaching for other disciplines.

Dermal Real-Time Quaking-Induced Conversion Is a Sensitive Marker to Confirm Isolated Rapid Eye Movement Sleep Behavior Disorder as an Early α-Synucleinopathy.

BACKGROUND: Skin biopsy is a potential tool for the premortem confirmation of an α-synucleinopathy. OBJECTIVE: The aim was to assess the aggregation assay real-time quaking-induced conversion (RT-QuIC) of skin biopsy lysates to confirm isolated rapid eye movement sleep behavior disorder (iRBD) as an α-synucleinopathy. METHODS: Skin biopsies of patients with iRBD, Parkinson's disease (PD), and controls were analyzed using RT-QuIC and immunohistochemical detection of phospho-α-synuclein. RESULTS: α-Synuclein aggregation was detected in 97.4% of iRBD patients (78.4% of iRBD biopsies), 87.2% of PD patients (70% of PD biopsies), and 13% of controls (7.9% of control biopsies), with a higher seeding activity in iRBD compared to PD. RT-QuIC was more sensitive but less specific than immunohistochemistry. CONCLUSIONS: Dermal RT-QuIC is a sensitive method to detect α-synuclein aggregation in iRBD, and high seeding activity may indicate a strong involvement of dermal nerve fibers in these patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Rhabdomyosarcoma xenotransplants in zebrafish embryos.

Rhabdomyosarcomas (RMS) are the most common pediatric soft tissue sarcomas. High-risk and metastatic disease continues to be associated with very poor prognosis. RMS model systems that faithfully recapitulate the human disease and provide rapid, cost-efficient estimates of antitumor efficacy of candidate drugs are needed to facilitate drug development and personalized medicine approaches. Here, we present a new zebrafish-based xenotransplant model allowing for rapid and easily accessible drug screening using low numbers of viable tumor cells and relatively small amounts of water-soluble chemicals. Under optimized temperature conditions, embryonal RMS xenografts were established in zebrafish embryos at 3 h postfertilization (hpf). In proof-of-principle experiments, chemotherapy drugs with established clinical anti-RMS efficacy (vincristine, dactinomycin) and the mitogen-activated protein kinase kinase inhibitor trametinib were shown to significantly reduce the cross-sectional area of the tumors by 120 hpf. RMS xenograft models in zebrafish embryos henceforth could serve as a valuable addition to cell culture and mammalian models of RMS and represent a rapid and cost-effective solution for preclinical candidate drug testing.

Patterns of Pretreatment Diagnostic Assessment in Patients Treated with Stereotactic Body Radiation Therapy (SBRT) for Non-Small Cell Lung Cancer (NSCLC): Special Characteristics in the COVID Pandemic and Influence on Outcomes.

The pandemic raised a discussion about the postponement of medical interventions for non-small cell lung cancer (NSCLC). We analyzed the characteristics of pretreatment diagnostic assessment in the pandemic and the influence of diagnostic assessment on outcomes. A total of 96 patients with stereotactic body radiation therapy (SBRT) for NSCLC were included. The number of patients increased from mean 0.9 (2012-2019) to 1.45 per month in the COVID era (p < 0.05). Pandemic-related factors (contact reduction, limited intensive care unit resources) might have influenced clinical decision making towards SBRT. The time from pretreatment assessment (multidisciplinary tumor board decision, bronchoscopy, planning CT) to SBRT was longer during the COVID period (p < 0.05). Reduced services, staff shortage, or appointment management to mitigate infection risks might explain this finding. Overall survival, progression-free survival, locoregional progression-free survival, and distant progression-free survival were superior in patients who received a PET/CT scan prior to SBRT (p < 0.05). This supports that SBRT guidelines advocate the acquisition of a PET/CT scan. A longer time from PET/CT scan/conventional staging to SBRT (<10 vs. ≥10 weeks) was associated with worse locoregional control (p < 0.05). The postponement of diagnostic or therapeutic measures in the pandemic should be discussed cautiously. Patient- and tumor-related features should be evaluated in detail.

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.

Diagnostic value of skin RT-QuIC in Parkinson's disease: a two-laboratory study.

Skin α-synuclein deposition is considered a potential biomarker for Parkinson's disease (PD). Real-time quaking-induced conversion (RT-QuIC) is a novel, ultrasensitive, and efficient seeding assay that enables the detection of minute amounts of α-synuclein aggregates. We aimed to determine the diagnostic accuracy, reliability, and reproducibility of α-synuclein RT-QuIC assay of skin biopsy for diagnosing PD and to explore its correlation with clinical markers of PD in a two-center inter-laboratory comparison study. Patients with clinically diagnosed PD (n = 34), as well as control subjects (n = 30), underwent skin punch biopsy at multiple sites (neck, lower back, thigh, and lower leg). The skin biopsy samples (198 in total) were divided in half to be analyzed by RT-QuIC assay in two independent laboratories. The α-synuclein RT-QuIC assay of multiple skin biopsies supported the clinical diagnosis of PD with a diagnostic accuracy of 88.9% and showed a high degree of inter-rater agreement between the two laboratories (92.2%). Higher α-synuclein seeding activity in RT-QuIC was shown in patients with longer disease duration and more advanced disease stage and correlated with the presence of REM sleep behavior disorder, cognitive impairment, and constipation. The α-synuclein RT-QuIC assay of minimally invasive skin punch biopsy is a reliable and reproducible biomarker for Parkinson's disease. Moreover, α-synuclein RT-QuIC seeding activity in the skin may serve as a potential indicator of progression as it correlates with the disease stage and certain non-motor symptoms.

Innovative radiation oncology Together - Precise, Personalized, Human : Vision 2030 for radiotherapy & radiation oncology in Germany.

PURPOSE: Scientific and clinical achievements in radiation, medical, and surgical oncology are changing the landscape of interdisciplinary oncology. The German Society for Radiation Oncology (DEGRO) working group of young clinicians and scientists (yDEGRO) and the DEGRO representation of associate and full professors (AKRO) are aware of the essential role of radiation oncology in multidisciplinary treatment approaches. Together, yDEGRO and AKRO endorsed developing a German radiotherapy & radiation oncology vision 2030 to address future challenges in patient care, research, and education. The vision 2030 aims to identify priorities and goals for the next decade in the field of radiation oncology. METHODS: The vision development comprised three phases. During the first phase, areas of interest, objectives, and the process of vision development were defined jointly by the yDEGRO, AKRO, and the DEGRO board. In the second phase, a one-day strategy retreat was held to develop AKRO and yDEGRO representatives' final vision from medicine, biology, and physics. The third phase was dedicated to vision interpretation and program development by yDEGRO representatives. RESULTS: The strategy retreat's development process resulted in conception of the final vision "Innovative radiation oncology Together - Precise, Personalized, Human." The first term "Innovative radiation oncology" comprises the promotion of preclinical research and clinical trials and highlights the development of a national committee for strategic development in radiation oncology research. The term "together" underpins collaborations within radiation oncology departments as well as with other partners in the clinical and scientific setting. "Precise" mainly covers technological precision in radiotherapy as well as targeted oncologic therapeutics. "Personalized" emphasizes biology-directed individualization of radiation treatment. Finally, "Human" underlines the patient-centered approach and points towards the need for individual longer-term career curricula for clinicians and researchers in the field. CONCLUSION: The vision 2030 balances the ambition of physical, technological, and biological innovation as well as a comprehensive, patient-centered, and collaborative approach towards radiotherapy & radiation oncology in Germany.

Evaluation of Uterine Brachytherapy as Primary Treatment Option for Elderly Patients with Medically Inoperable Endometrial Cancer-A Single-Center Experience and Review of the Literature.

We aimed to gain more evidence regarding the feasibility, toxicity, and oncological outcome of primary brachytherapy in patients with medically inoperable endometrial cancer. Thirteen patients receiving primary brachytherapy ± external beam radiotherapy (EBRT) for endometrial cancer due to medical inoperability were identified. The Kaplan-Meier method was used to estimate overall survival (OS), progression-free survival (PFS), and local failure-free survival (LFFS). Univariate outcome analyses were performed using the log-rank test. Peri-interventional complications, acute and chronic toxicities were evaluated. Additionally, we performed a Pubmed search and review of the literature of the last 10 years. Mean age at time of diagnosis was 73.9 years (60.4-87.1 years). Eleven patients were staged FIGO IA/B and one patient each with FIGO IIIA and IIIC. Kaplan-Meier-estimated 2-/5-year LFFS were 76.2%/56.4%, respectively. High grading correlated with a worse LFFS (p = 0.069). Kaplan-Meier-estimated 2-/5-year PFS were 76.9%/53.8% and 2-/5-year-OS were 76.9%/69.2%, respectively. No acute toxicities > grade II and only two late toxicities grade II/III occurred. We observed three peri-interventional complications. The available evidence suggests high rates of local control after definitive brachytherapy for inoperable endometrial cancer with a favorable toxicity profile. Definitive brachytherapy +/- EBRT should be considered as the preferred approach for this patient group.

Stereotactic Cavity Irradiation or Whole-Brain Radiotherapy Following Brain Metastases Resection-Outcome, Prognostic Factors, and Recurrence Patterns.

Introduction: Following the resection of brain metastases (BM), whole-brain radiotherapy (WBRT) is a long-established standard of care. Its position was recently challenged by the less toxic single-session radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) of the resection cavity, reducing dose exposure of the healthy brain. Patients and Methods: We analyzed 101 patients treated with either SRS/FSRT (n = 50) or WBRT (n = 51) following BM resection over a 5-year period. Propensity score adjustment was done for age, total number of BM, timepoint of BM diagnosis, controlled primary and extracranial metastases. A Cox Proportional Hazards model with univariate and multivariate analysis was fitted for overall survival (OS), local control (LC) and distant brain control (DBC). Results: Median patient age was 61 (interquartile range, IQR: 56-67) years and the most common histology was non-small cell lung cancer, followed by breast cancer. 38% of the patients had additional unresected BM. Twenty-four patients received SRS, 26 patients received FSRT and 51 patients received WBRT. Median OS in the SRS/FSRT subgroup was not reached (IQR NA-16.7 months) vs. 12.6 months (IQR 21.3-4.4) in the WBRT subgroup (hazard ratio, HR 3.3, 95%-CI: [1.5; 7.2] p < 0.002). Twelve-months LC-probability was 94.9% (95%-CI: [88.3; 100.0]) in the SRS subgroup vs. 81.7% (95%-CI: [66.6; 100.0]) in the WBRT subgroup (HR 0.2, 95%-CI: [0.01; 0.9] p = 0.037). Twelve-months DBC-probabilities were 65.0% (95%-CI: [50.8; 83.0]) and 58.8% (95%-CI: [42.9; 80.7]), respectively (HR 1.4, 95%-CI: [0.7; 2.7] p = 0.401). In propensity score-adjusted multivariate analysis, incomplete resection negatively impacted OS (HR 3.9, 95%-CI: [2.0;7.4], p < 0.001) and LC (HR 5.4, 95%-CI: [1.3; 21.9], p = 0.018). Excellent clinical performance (HR 0.4, 95%-CI: [0.2; 0.9], p = 0.030) and better graded prognostic assessment (GPA) score (HR 0.4, 95%-CI: [0.2; 1.0], p = 0.040) were prognostic of superior OS. A higher number of BM was associated with a greater risk of developing new distant BM (HR 5.6, 95%-CI: [1.0; 30.4], p = 0.048). In subgroup analysis, larger cavity volume (HR 1.1, 95%-CI: [1.0; 1.3], p = 0.033) and incomplete resection (HR 12.0, 95%-CI: [1.2; 118.3], p = 0.033) were associated with inferior LC following SRS/FSRT. Conclusion: This is the first propensity score-adjusted direct comparison of SRS/FSRT and WBRT following the resection of BM. Patients receiving SRS/FSRT showed longer OS and LC compared to WBRT. Future analyses will address the optimal choice of safety margin, dose and fractionation for postoperative stereotactic RT of the resection cavity.

Single-Isocenter Volumetric Modulated Arc Therapy vs. CyberKnife M6 for the Stereotactic Radiosurgery of Multiple Brain Metastases.

Introduction: Stereotactic radiosurgery (SRS) is becoming more frequently used for patients with multiple brain metastases (BMs). Single-isocenter volumetric modulated arc therapy (SI-VMAT) is an emerging alternative to dedicated systems such as CyberKnife (CK). We present a dosimetric comparison between CyberKnife M6 and SI-VMAT, planned at RayStation V8B, for the simultaneous SRS of five or more BM. Patients and Methods: Twenty treatment plans of CK-based single-session SRS to ≥5 brain metastases were replanned using SI-VMAT for delivery at an Elekta VersaHD linear accelerator. Prescription dose was 20 or 18 Gy, conformally enclosing at least 98% of the total planning target volume (PTV), with PTV margin-width adapted to the respective SRS technique. Comparatively analyzed quality metrics included dose distribution to the healthy brain (HB), including different isodose volumes, conformity, and gradient indices. Estimated treatment time was also compared. Results: Median HB isodose volumes for 3, 5, 8, 10, and 12 Gy were consistently smaller for CK-SRS compared to SI-VMAT (p < 0.001). Dose falloff outside the target volume, as expressed by the gradient indices GI_high and GI_low, was consistently steeper for CK-SRS compared to SI-VMAT (p < 0.001). CK-SRS achieved a median GI_high of 3.1 [interquartile range (IQR), 2.9-1.3] vs. 5.0 (IQR 4.3-5.5) for SI-VMAT (p < 0.001). For GI_low, the results were 3.0 (IQR, 2.9-3.1) for CK-SRS vs. 5.6 (IQR, 4.3-5.5) for SI-VMAT (p < 0.001). The median conformity index (CI) was 1.2 (IQR, 1.1-1.2) for CK-SRS vs. 1.5 (IQR, 1.4-1.7) for SI-VMAT (p < 0.001). Estimated treatment time was shorter for SI-VMAT, yielding a median of 13.7 min (IQR, 13.5-14.0) compared to 130 min (IQR, 114.5-154.5) for CK-SRS (p < 0.001). Conclusion: SI-VMAT offers enhanced treatment efficiency in cases with multiple BM, as compared to CyberKnife, but requires compromise regarding conformity and integral dose to the healthy brain. Additionally, delivery at a conventional linear accelerator (linac) may require a larger PTV margin to account for delivery and setup errors. Further evaluations are warranted to determine whether the detected dosimetric differences are clinically relevant. SI-VMAT could be a reasonable alternative to a dedicated radiosurgery system for selected patients with multiple BM.

A matched-pair analysis comparing stereotactic radiosurgery with whole-brain radiotherapy for patients with multiple brain metastases.

INTRODUCTION: Stereotactic radiosurgery (SRS) is an emerging treatment for patients with multiple brain metastases (BM). The present work compares the SRS of multiple brain metastases with whole-brain radiotherapy (WBRT). METHODS: We performed a matched-pair analysis for 128 patients with multiple BM treated with either SRS or WBRT over a 5-year period. Patients were matched pairwise for seven potential prognostic factors. A mixed Cox Proportional Hazards model with univariate and multivariate analysis was fitted for overall survival (OS). Distant intracranial progression-free survival (icPFS) and local control were assessed using a Fine and Gray subdistribution hazard model and considering death as competing event. RESULTS: Patients undergoing SRS had a median of 4 BM (range 3-16). 1-year local control of individual BM following SRS was 91.7%. Median OS in the SRS subgroup was 15.7 months (IQR 9.7-36.4) versus 8.0 months (interquartile range, IQR 3.8-18.0) in the WBRT subgroup (HR 2.25, 95% CI [1.5; 3.5], p < 0.001). Median icPFS was 8.6 (IQR 3.4-18.0) versus 22.4 (IQR 5.6-28.6) months, respectively (HR for WBRT 0.41, 95% CI [0.24; 0.71], p = 0.001). Following SRS, synchronous BM diagnosis (HR 2.51, 95% CI [1.30; 4.70], p = 0.004), higher initial number of BM (HR 1.21, 95% CI [1.10; 1.40], p = 0.002) and lung cancer histology (HR 2.05, 95% CI [1.10; 3.80], p = 0.024) negatively impacted survival. Excellent clinical performance (KPI 90%) was a positive prognosticator (HR 0.38, 95% CI [0.20; 0.72], p = 0.003), as was extracerebral tumor control (HR 0.48, 95% CI [0.24; 0.97], p = 0.040). Higher initial (HR 1.19, 95% CI [1.00; 1.40], p < 0.013) and total number of BM (HR 1.23, 95% CI [1.10; 1.40], p < 0.001) were prognostic for shorter icPFS. CONCLUSION: This is the first matched-pair analysis to compare SRS alone versus WBRT alone for multiple BM. OS was prolonged in the SRS subgroup and generally favorable in the entire cohort. Our results suggest SRS as a feasible and effective treatment for patients with multiple BM.

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.

Second breast conserving therapy after ipsilateral breast tumor recurrence - a 10-year experience of re-irradiation.

PURPOSE: The aim of this study is to evaluate the efficacy and toxicity of post-operative partial breast re-irradiation with multi-catheter brachytherapy after second breast conserving therapy (BCT) in patients with small, low-risk ipsilateral breast tumor recurrence (IBTR). MATERIAL AND METHODS: Between 2008 and 2018, 19 consecutive patients with low-risk IBTR (max. rpT1 cN0 cM0, Her2 negative, preferably positive hormone receptor status) who refused mastectomy were treated with salvage lumpectomy, followed by post-operative partial breast re-irradiation with multi-catheter brachytherapy. Eight patients were irradiated using PDR brachytherapy (49.8-50.4 Gy in pulses of 0.5-0.7 Gy) and 11 patients using HDR brachytherapy (34.2 Gy in fractions of 3.8 Gy or 32 Gy in fractions of 4 Gy). All patients had undergone prior BCT for their primary tumor, followed by adjuvant whole breast radiotherapy. Local control (LC), locoregional control (LRC), overall survival (OS), disease-free survival (DFS) as well as toxicity were evaluated in the present study. RESULTS: After a median follow-up of 65 months following IBTR (18-120 months), only one second IBTR in 19 patients was diagnosed 77 months after re-irradiation, resulting in a LC rate of 100% at 5 years. DFS and OS rates were both 100% at 5 years following re-irradiation. Except for the above mentioned second IBTR, no regional or distant relapse was recorded. Regarding toxicity, 63% of patients developed adverse events (CTCAE grade ≤ 2), with fibrosis detected in 37% (7/19) of patients, necrosis in 11% (2/19), hyperpigmentation in 47% (9/19), and telangiectasia in 11% (2/19), respectively. No patient showed a high-grade (CTCAE grade ≥ 3) adverse event. CONCLUSIONS: In case of small, low-risk IBTR, adjuvant re-irradiation using multi-catheter brachytherapy is a feasible, safe, and effective treatment method after repeated lumpectomy, and an alternative to mastectomy.