Validation of echo planar imaging based diffusion-weighted magnetic resonance imaging on a 0.35 T MR-Linac.

Background and Purpose: The feasibility of acquiring diffusion-weighted imaging (DWI) images on an MR-Linac for quantitative response assessment during radiotherapy was explored. DWI data obtained with a Spin Echo Echo Planar Imaging sequence adapted for a 0.35 T MR-Linac were examined and compared with DWI data from a conventional 3 T scanner. Materials and Methods: Apparent diffusion coefficient (ADC) measurements and a distortion correction technique were investigated using DWI-calibrated phantoms and in the brains of seven volunteers. All DWI utilized two phase-encoding directions for distortion correction and off-resonance field estimation. ADC maps in the brain were analyzed for automatically segmented normal tissues. Results: Phantom ADC measurements on the MR-Linac were within a 3 % margin of those recorded by the 3 T scanner. The maximum distortion observed in the phantom was 2.0 mm prior to correction and 1.1 mm post-correction on the MR-Linac, compared to 6.0 mm before correction and 3.6 mm after correction at 3 T. In vivo, the average ADC values for gray and white matter exhibited variations of 14 % and 4 %, respectively, for different selections of b-values on the MR-Linac. Distortions in brain images before correction, estimated through the off-resonance field, reached 2.7 mm on the MR-Linac and 12 mm at 3 T. Conclusion: Accurate ADC measurements are achievable on a 0.35 T MR-Linac, both in phantom and in vivo. The selection of b-values significantly influences ADC values in vivo. DWI on the MR-Linac demonstrated lower distortion levels, with a maximum distortion reduced to 1.1 mm after correction.

Stereotactic body radiotherapy for oligoprogression with or without switch of systemic therapy.

Background: Oligoprogression is defined as cancer progression of a limited number of metastases under active systemic therapy. The role of metastasis-directed therapy, using stereotactic body radiotherapy (SBRT), is controversial as is the continuation versus switch of systemic therapy. We report outcomes of oligoprogressive patients after SBRT, and compare those patients that continued or switched their current line of systemic therapy. Material/Methods: We included patients who developed up to 5 progressive extracranial metastases under systemic therapy for any solid organ malignancy and were treated with SBRT to all lesions at our institution between 01/2014 and 12/2019. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method, and the interval to the next systemic therapy line determined using cumulative incidence functions. Multivariable Cox regression models were used to analyze the influence of baseline and post-progression variables on OS, PFS and survival with the next systemic therapy after SBRT. Results: Among 135 patients with oligoprogressive disease of which the most common primary tumor was lung cancer (n = 46, 34.1 %), 96 continued their current line of systemic therapy after oligoprogression. Among 39 who switched systemic therapy, 28 (71.8 %) paused or discontinued, while 11 (28.2 %) immediately started another systemic treatment. After a median follow-up of 27.2 months, patients that switched and those who continued systemic therapy after oligoprogression had comparable median OS (32.1 vs. 38.2 months, p = 0.47) and PFS (4.3 vs. 3.4 months, p = 0.6). The intervals to the next systemic therapy line were comparable between both cohorts (p = 0.6). An ECOG performance status of 2 and immediately starting a new systemic therapy after oligoprogression were associated with a poorer survival without next systemic therapy, while the de-novo OMD state was associated with better survival without next systemic therapy compared to the induced state. Conclusion: Oncological outcomes of patients that continued or switched systemic therapy after SBRT for oligoprogression were comparable, potentially indicating that further lines of treatment may be safely delayed in selected cases.

Association of Skin Microbiome Dynamics With Radiodermatitis in Patients With Breast Cancer.

Importance: The interindividual differences in severity of acute radiation dermatitis are not well understood. To date, the pathomechanism and interplay of microbiome and radiodermatitis before and during treatment remain largely unknown. Objective: To assess the association of skin microbiome baseline composition and dynamics with severity of radiodermatitis in patients undergoing adjuvant radiotherapy for breast cancer. Design, Setting, and Participants: A longitudinal prospective pilot observational study was conducted between January 2017 and January 2019. Sequencing results were received in March 2021, and the data were analyzed from August 2021 to March 2023. This study was performed at an urban academic university cancer center. A total of 21 female patients with breast cancer after surgery were consecutively approached, of which 1 patient withdrew consent before the study started. Exposure: Adjuvant radiotherapy for breast cancer for 7 weeks. Main Outcomes and Measures: The main outcome was the association of baseline skin microbiome composition and its dynamics with the severity of radiodermatitis. A total of 360 skin microbiome samples from patients were analyzed, taken before, during, and after radiotherapy, from both the treated and contralateral healthy sides. The skin microbiome samples were analyzed using 16S (V1-V3) amplicon sequencing and quantitative polymerase chain reaction bacterial enumeration. Results: Twenty female patients with breast cancer after surgery who underwent radiotherapy enrolled in the study had a median (range) age of 61 (37-81) years. The median (range) body mass index of the patients was 24.2 (17.6-38.4). The 16S sequencing revealed that low (<5%) relative abundance of commensal skin bacteria (Staphylococcus epidermidis, Staphylococcus hominis, Cutibacterium acnes) at baseline composition was associated with the development of severe radiodermatitis with an accuracy of 100% (sensitivity and specificity of 100%, P < .001). Furthermore, in patients with severe radiodermatitis, quantitative polymerase chain reaction bacterial enumeration revealed a general non-species-specific overgrowth of skin bacterial load before the onset of severe symptoms. Subsequently, the abundance of commensal bacteria increased in severe radiodermatitis, coinciding with a decline in total bacterial load. Conclusions and Relevance: The findings of this observational study indicated a potential mechanism associated with the skin microbiome for the pathogenesis of severe radiodermatitis, which may be a useful biomarker for personalized prevention of radiodermatitis in patients undergoing adjuvant radiotherapy for breast cancer.

Health-related quality of life in men with oligometastatic prostate cancer following metastases-directed stereotactic body radiotherapy: Real-world data from the E2-RADIatE OligoCare cohort.

Objective: To evaluate the impact of metastases-directed stereotactic body radiotherapy (SBRT) on health-related quality of life (HRQoL) in men with oligometastatic prostate cancer (PCa) using real-world data from the OligoCare cohort. Materials and methods: OligoCare is a pragmatic, observational cohort designed to assess the impact of metastases-directed SBRT on patients with oligometastatic disease (OMD). We report an interim analyses of the secondary endpoint HRQoL, assessed using the EORTC QLQ-C30, within six months of metastases-directed SBRT for oligometastatic disease in men with PCa among the first 1600 registered patients. HRQoL data collection was optional within the OligoCare cohort. To compare HRQoL between baseline and first follow-up assessment, a Wilcoxon signed-rank test was used. A multiple linear regression model was used to explore the HRQoL associations with predefined factors. Results: Out of the 1600 registered patients, 658 were treated for oligometastatic PCa, of which 233 had baseline QoL data and 132 patients had both baseline and follow-up HRQoL data. At baseline, most patients had a WHO performance status of 0 or 1 (87 %), were de-novo oligometastatic (79 %), had one metastasis (90 %), and had a good overall global health status (mean 80.81, SD16.11, IQR 75-92). 51 % received hormonal therapy as concomitant systemic treatment. Patients with comorbidities as assessed by the Charlson Comorbidity index had a worse global health status at baseline (-4.88, 95 % CI:-9.35, -0.42). No clinically meaningful significant difference in global health status was observed at first assessment following SBRT (median 3.0 months) compared with baseline (mean difference 2.27, 95 % CI:-1.54, 6.08). Upon evaluating the proportions, meaningful clinically important differences (a 10-point or more difference) was observed in, 17 % and 11 % of the patients reporting deterioration and improvement of global health status, respectively. Conclusion: Metastases-directed stereotactic body radiotherapy had no negative impact on global HRQoL within the first six months after treatment.

Patterns of metastatic spread and tumor burden in unselected cancer patients using PET imaging: Implications for the oligometastatic spectrum theory.

Introduction and background: Metastatic disease has been proposed as a continuum, with no clear cut-off between oligometastatic and polymetastatic disease. This study aims to quantify tumor burden and patterns of spread in unselected metastatic cancer patients referred for PET-based staging, response assessment of restaging. Materials and methods: All oncological fluorodeoxyglucose (FDG-) and prostate-specific membrane antigen (PSMA-) positron emission tomography (PET) scans conducted at a single academic center in 2020 were analyzed. Imaging reports of all patients with metastatic disease were reviewed and assessed. Results: For this study, 7,000 PET scans were screened. One third of PET scans (n = 1,754; 33 %) from 1,155 unique patients showed presence of metastatic disease from solid malignancies, of which 601 (52 %) and 554 (48 %) were classified as oligometastatic (maximum 5 metastases) and polymetastatic (>5 metastases), respectively. Lung and pleural cancer, skin cancer, and breast cancer were the most common primary tumor histologies with 132 (23.8 %), 88 (15.9 %), and 72 (13.0 %) cases, respectively. Analysis of the number of distant metastases showed a strong bimodal distribution of the metastatic burden with 26 % of patients having one solitary metastasis and 43 % of patients harboring >10 metastases. Yet, despite 43 % of polymetastatic patients having >10 distant metastases, their pattern of distribution was restricted to one or two organs in about two thirds of patients, and there was no association between the number of distant metastases and the number of involved organs. Conclusion: The majority of metastatic cancer patients are characterized by either a solitary metastasis or a high tumor burden with >10 metastases, the latter was often associated with affecting a limited number of organs. These findings support both the spectrum theory of metastasis and the seed and soil hypothesis and can support in designing the next generation of clinical trials in the field of oligometastatic disease.

Dosimetric Analysis of Proximal Bronchial Tree Subsegments to Assess The Risk of Severe Toxicity After Stereotactic Body Radiation Therapy of Ultra-central Lung Tumors.

•Stereotactic body radiation therapy (SBRT) for ultra-central lung tumors is associated with high toxicity rates.•To evaluate differences in radiosensitivity within the proximal bronchial tree (PBT), the PBT was sub-segmented into seven anatomical sections.•A risk-adapted SBRT regimen of EQD2_10 = 54.4 Gy in 8 or 10 fractions results in excellent local control and low rates of severe toxicity.•Data from a recent meta-analysis, the NORDIC Hilus trial and dosimetric data from this study were combined to create a NTCP model.•A dose threshold of EQD2_3 = 100 Gy to the PBT or any of its subsegments is expected to result in low rates of severe bronchial toxicity.

Dose escalation for stereotactic arrhythmia radioablation of recurrent ventricular tachyarrhythmia - a phase II clinical trial.

BACKGROUND: Stereotactic arrhythmia radioablation (STAR) is delivered with a planning target volume (PTV) prescription dose of 25 Gy, mostly to the surrounding 75-85% isodose line. This means that the average and maximum dose received by the target is less than 35 Gy, which is the minimum threshold required to create a homogenous transmural fibrosis. Similar to catheter ablation, the primary objective of STAR should be transmural fibrosis to prevent heterogenous intracardiac conduction velocities and the occurrence of sustained ventricular arrhythmias (sVA) caused by reentry. We hypothesize that the current dose prescription used in STAR is inadequate for the long-term prevention of sVA and that a significant increase in dose is necessary to induce transmural scar formation. OBJECTIVE: A single arm, multi-center, phase II, dose escalation prospective clinical trial employing the i3 + 3 design is being conducted to examine the safety of a radiation dose-escalation strategy aimed at inducing transmural scar formation. The ultimate objective of this trial is to decrease the likelihood of sVA recurrence in patients at risk. METHODS: Patients with ischemic or non-ischemic cardiomyopathy and recurrent sVA, with an ICD and history of ≥ 1 catheter ablation for sVA will be included. This is a prospective, multicenter, one-arm, dose-escalation trial utilizing the i3 + 3 design, a modified 3 + 3 specifically created to overcome limitations in traditional dose-finding studies. A total of 15 patients will be recruited. The trial aims to escalate the ITV dose from 27.0 Gy to an ITV prescription dose-equivalent level of maximum 35.1 Gy by keeping the PTV prescription dose constant at 25 Gy while increasing the dose to the target (i.e. the VT substrate without PTV margin) by step-wise reduction of the prescribing isodose line (85% down to 65%). The primary outcome of this trial is safety measured by registered radiation associated adverse events (AE) up to 90 days after study intervention including radiation associated serious adverse events graded as at least 4 or 5 according to CTCAE v5, radiation pneumonitis or pericarditis requiring hospitalization and decrease in LVEF ≥ 10% as assessed by echocardiography or cardiac MRI at 90 days after STAR. The sample size was determined assuming an acceptable primary outcome event rate of 20%. Secondary outcomes include sVA burden at 6 months after STAR, time to first sVA recurrence, reduction in appropriate ICD therapies, the need for escalation of antiarrhythmic drugs, non-radiation associated safety and patient reported outcome measures such as SF-36 and EQ5D. DISCUSSION: DEFT-STAR is an innovative prospective phase II trial that aims to evaluate the optimal radiation dose for STAR in patients with therapy-refractory sVA. The trial has obtained IRB approval and focuses on determining the safe and effective radiation dose to be employed in the STAR procedure. TRIAL REGISTRATION: NCT05594368.

Refining critical structure contouring in STereotactic Arrhythmia Radioablation (STAR): Benchmark results and consensus guidelines from the STOPSTORM.eu consortium.

BACKGROUND AND PURPOSE: In patients with recurrent ventricular tachycardia (VT), STereotactic Arrhythmia Radioablation (STAR) shows promising results. The STOPSTORM.eu consortium was established to investigate and harmonise STAR treatment in Europe. The primary goals of this benchmark study were to standardise contouring of organs at risk (OAR) for STAR, including detailed substructures of the heart, and accredit each participating centre. MATERIALS AND METHODS: Centres within the STOPSTORM.eu consortium were asked to delineate 31 OAR in three STAR cases. Delineation was reviewed by the consortium expert panel and after a dedicated workshop feedback and accreditation was provided to all participants. Further quantitative analysis was performed by calculating DICE similarity coefficients (DSC), median distance to agreement (MDA), and 95th percentile distance to agreement (HD95). RESULTS: Twenty centres participated in this study. Based on DSC, MDA and HD95, the delineations of well-known OAR in radiotherapy were similar, such as lungs (median DSC = 0.96, median MDA = 0.1 mm and median HD95 = 1.1 mm) and aorta (median DSC = 0.90, median MDA = 0.1 mm and median HD95 = 1.5 mm). Some centres did not include the gastro-oesophageal junction, leading to differences in stomach and oesophagus delineations. For cardiac substructures, such as chambers (median DSC = 0.83, median MDA = 0.2 mm and median HD95 = 0.5 mm), valves (median DSC = 0.16, median MDA = 4.6 mm and median HD95 = 16.0 mm), coronary arteries (median DSC = 0.4, median MDA = 0.7 mm and median HD95 = 8.3 mm) and the sinoatrial and atrioventricular nodes (median DSC = 0.29, median MDA = 4.4 mm and median HD95 = 11.4 mm), deviations between centres occurred more frequently. After the dedicated workshop all centres were accredited and contouring consensus guidelines for STAR were established. CONCLUSION: This STOPSTORM multi-centre critical structure contouring benchmark study showed high agreement for standard radiotherapy OAR. However, for cardiac substructures larger disagreement in contouring occurred, which may have significant impact on STAR treatment planning and dosimetry evaluation. To standardize OAR contouring, consensus guidelines for critical structure contouring in STAR were established.

Dosimetric analysis of 17 cardiac Sub-structures, Toxicity, and survival in ultra central lung tumor patients treated with SBRT.

•Data on cardiac toxicity after SBRT for ultra-central lung tumors remains limited.•We analyzed the dose to 18 cardiac sub-structures and cardiovascular toxicity.•A SBRT regimen of 45 Gy in 8-10 fractions yields good local control and low toxicity.•The highest cardiac doses were observed in the pulmonary artery and left atrium.•Higher doses to the base of the heart seem to be associated with non-cancer deaths.

External validation of three prognostic scores for brain metastasis velocity in patients treated with intracranial stereotactic radiotherapy.

BACKGROUND AND INTRODUCTION: Brain metastasis velocity (BMV) has been proposed as a prognostic factor for overall survival (OS) in patients with brain metastases (BMs). In this study, we conducted an external validation and comparative assessment of the performance of all three BMV scores. MATERIALS AND METHODS: Patients treated with intracranial stereotactic radiotherapy (SRT) for BM at a single center between 2014 and 2018 were identified. Where possible, all three BMV scores were calculated. Log-rank tests and linear, logistic and Cox regression analysis were used for validation and predictor identification of OS. RESULTS: For 333 of 384 brain metastasis patients, at least one BMV score could be calculated. In a sub-group of 187 patients, "classic" BMV was validated as categorical (p < 0.0001) and continuous variable (HR 1.02; 95% CI 1.02-1.03; p < 0.0001). In a sub-group of 284 patients, "initial" BMV was validated as categorical variable (high-risk vs. low-risk; p < 0.01), but not as continuous variable (HR 1.02; 95% CI 0.99-1.04; p = 0.224). "Volume-based" BMV could not be validated in a sub-group of 104 patients. On multivariable Cox regression analysis, iBMV (HR 1.85; 95% CI 1.01-3.38; p < 0.05) and cBMV (HR 2.32; 95% CI 1.15 4.68; p < 0.05) were predictors for OS for intermediate-risk patients after first SRT and first DBFs, respectively. cBMV proved to be the dominant predictor for OS for high-risk patients (HR 2.99; 95% CI 1.30-6.91; p < 0.05). CONCLUSION: This study externally validated cBMV and iBMV as prognostic scores for OS in patients treated with SRT for BMs whereas validation of vBMV was not achieved.

Recurrences of ventricular tachycardia after stereotactic arrhythmia radioablation arise outside the treated volume: analysis of the Swiss cohort.

AIMS: Stereotactic arrhythmia radioablation (STAR) has been recently introduced for the management of therapy-refractory ventricular tachycardia (VT). VT recurrences have been reported after STAR but the mechanisms remain largely unknown. We analysed recurrences in our patients after STAR. METHODS AND RESULTS: From 09.2017 to 01.2020, 20 patients (68 ± 8 y, LVEF 37 ± 15%) suffering from refractory VT were enrolled, 16/20 with a history of at least one electrical storm. Before STAR, an invasive electroanatomical mapping (Carto3) of the VT substrate was performed. A mean dose of 23 ± 2 Gy was delivered to the planning target volume (PTV). The median ablation volume was 26 mL (range 14-115) and involved the interventricular septum in 75% of patients. During the first 6 months after STAR, VT burden decreased by 92% (median value, from 108 to 10 VT/semester). After a median follow-up of 25 months, 12/20 (60%) developed a recurrence and underwent a redo ablation. VT recurrence was located in the proximity of the treated substrate in nine cases, remote from the PTV in three cases and involved a larger substrate over ≥3 LV segments in two cases. No recurrences occurred inside the PTV. Voltage measurements showed a significant decrease in both bipolar and unipolar signal amplitude after STAR. CONCLUSION: STAR is a new tool available for the treatment of VT, allowing for a significant reduction of VT burden. VT recurrences are common during follow-up, but no recurrences were observed inside the PTV. Local efficacy was supported by a significant decrease in both bipolar and unipolar signal amplitude.

Identifying core MRI sequences for reliable automatic brain metastasis segmentation.

BACKGROUND: Many automatic approaches to brain tumor segmentation employ multiple magnetic resonance imaging (MRI) sequences. The goal of this project was to compare different combinations of input sequences to determine which MRI sequences are needed for effective automated brain metastasis (BM) segmentation. METHODS: We analyzed preoperative imaging (T1-weighted sequence ± contrast-enhancement (T1/T1-CE), T2-weighted sequence (T2), and T2 fluid-attenuated inversion recovery (T2-FLAIR) sequence) from 339 patients with BMs from seven centers. A baseline 3D U-Net with all four sequences and six U-Nets with plausible sequence combinations (T1-CE, T1, T2-FLAIR, T1-CE + T2-FLAIR, T1-CE + T1 + T2-FLAIR, T1-CE + T1) were trained on 239 patients from two centers and subsequently tested on an external cohort of 100 patients from five centers. RESULTS: The model based on T1-CE alone achieved the best segmentation performance for BM segmentation with a median Dice similarity coefficient (DSC) of 0.96. Models trained without T1-CE performed worse (T1-only: DSC = 0.70 and T2-FLAIR-only: DSC = 0.73). For edema segmentation, models that included both T1-CE and T2-FLAIR performed best (DSC = 0.93), while the remaining four models without simultaneous inclusion of these both sequences reached a median DSC of 0.81-0.89. CONCLUSIONS: A T1-CE-only protocol suffices for the segmentation of BMs. The combination of T1-CE and T2-FLAIR is important for edema segmentation. Missing either T1-CE or T2-FLAIR decreases performance. These findings may improve imaging routines by omitting unnecessary sequences, thus allowing for faster procedures in daily clinical practice while enabling optimal neural network-based target definitions.

Potential of ChatGPT in facilitating research in radiation oncology?

PURPOSE: To evaluate the potential of the artificial intelligence (AI) chatbot ChatGPT in supporting young clinical scientists with scientific tasks in radio oncological research. MATERIALS AND METHODS: Seven scientific tasks were to be completed in 3 h by 8 radiation oncologists with different scientific experience working at a university hospital: creation of a scientific synopsis, creation of a research question and corresponding clinical trial hypotheses, writing of the first paragraph of a manuscript introduction, clinical trial sample size calculation, and clinical data analyses (multivariate analysis, boxplot and survival curve). No participant had prior experience with an AI chatbot. All participants were instructed in ChatGPT v3.5 and its use was provided for all tasks. Answers were scored independently by two blinded experts. The subjective value of ChatGPT was rated by each participant. Data were analyzed with regression-, t-test and Spearman correlation (p < 0.05). RESULTS: Participants completed tasks 1-3 with an average score of 50% and 4-7 with 56%. Scientific experience, number of original publications and of first/last authorships showed a positive correlation with overall scoring (p = 0.01-0.04). Participants with little to moderate scientific experience scored ChatGPT to be more helpful in solving tasks 4-7 compared to more experienced participants (p = 0.04), with simultaneously presenting lower scorings (p = 0.03). CONCLUSIONS: ChatGPT did not compensate for differences in scientific experience of young clinical scientists, with less experienced researchers believing false AI-generated scientific results.

Stereotactic Body Radiotherapy for Lung Oligo-metastases: Systematic Review and International Stereotactic Radiosurgery Society Practice Guidelines.

PURPOSE: A systematic review of treatment characteristics, outcomes, and treatment-related toxicities of stereotactic body radiation therapy (SBRT) for pulmonary oligometastases served as the basis for development of this International Stereotactic Radiosurgery Society (ISRS) practice guideline. METHODS: In accordance with PRISMA guidelines, a systematic review was performed of retrospective series with ≥50 patients/lung metastases, prospective trials with ≥25 patients/lung metastases, analyses of specific high-risk situations, and all randomized trials published between 2012 and July 2022 in the MEDLINE or Embase database using the key words "lung oligometastases", "lung metastases", "pulmonary metastases", "pulmonary oligometastases", "stereotactic body radiation therapy (SBRT)" and "stereotactic ablative body radiotherapy (SBRT)". Weighted random effects models were used to calculate pooled outcomes estimates. RESULTS: Of the 1884 articles screened, 35 analyses (27 retrospective-, 5 prospective, and 3 randomized trials) reporting on treatment of >3600 patients and >4650 metastases were included. The median local control was 90 % (Range: 57-100 %) at 1 year and 79 % (R: 70-96 %) at 5 years. Acute toxicity ≥3 was reported for 0.5 % and late toxicity ≥3 for 1.8 % of patients. A total of 21 practice recommendations covering the areas of staging & patient selection (n = 10), SBRT treatment (n = 10), and follow-up (n = 1) were developed, with agreements rates of 100 %, except for recommendation 13 (83 %). CONCLUSION: SBRT represents an effective definitive local treatment modality combining high local control rates with low risk of radiation-induced toxicities.

Repeat stereotactic body radiotherapy for oligometastatic disease.

BACKGROUND: Patients with oligometastatic disease (OMD) treated with metastasis-directed definitive local therapy such as stereotactic body radiotherapy (SBRT) are at risk of developing new metastases. Here, we compare characteristics and outcomes of patients treated with a single course and repeat SBRT. MATERIALS/METHODS: OMD patients treated with SBRT to 1-5 metastases were included in this retrospective study, and classified as single course or repeat SBRT. Progression-free survival (PFS), widespread failure-free survival (WFFS), overall survival (OS), systemic therapy-free survival (STFS) and cumulative incidence of different first failures were analyzed. Patient and treatment characteristics predicting the use of repeat SBRT were investigated using univariable and multivariable logistic regression. RESULTS: Among the 385 patients included, 129 and 256 received repeat or single course SBRT, respectively. The most common primary tumor and OMD state in both groups were lung cancer and metachronous oligorecurrence. Patients treated with repeat SBRT had shorter PFS (p < 0.0001), while WFFS (p = 0.47) and STFS (p = 0.22) were comparable. Distant failure, particularly with a single metastasis, was more frequently observed in repeat SBRT patients. Repeat SBRT patients had longer median OS (p = 0.01). On multivariable logistic regression, low distant metastases velocity and more previous lines of systemic therapy significantly predicted the use of repeat SBRT. CONCLUSION: Despite shorter PFS and comparable WFFS and STFS, repeat SBRT patients had longer OS. The role of repeat SBRT for OMD patients warrants further prospective investigation, focussing on predictive factors to select patients that might derive a benefit.

Quality assurance process within the RAdiosurgery for VENtricular TAchycardia (RAVENTA) trial for the fusion of electroanatomical mapping and radiotherapy planning imaging data in cardiac radioablation.

A novel quality assurance process for electroanatomical mapping (EAM)-to-radiotherapy planning imaging (RTPI) target transport was assessed within the multi-center multi-platform framework of the RAdiosurgery for VENtricular TAchycardia (RAVENTA) trial. A stand-alone software (CARDIO-RT) was developed to enable platform independent registration of EAM and RTPI of the left ventricle (LV), based on pre-generated radiotherapy contours (RTC). LV-RTC were automatically segmented into the American-Heart-Association 17-segment-model and a manual 3D-3D method based on EAM 3D-geometry data and a semi-automated 2D-3D method based on EAM screenshot projections were developed. The quality of substrate transfer was evaluated in five clinical cases and the structural analyses showed substantial differences between manual target transfer and target transport using CARDIO-RT.

Recognition of and treatment recommendations for oligometastatic disease in multidisciplinary tumor boards.

Background and introduction: Growing evidence supports a combined modality treatment strategy for patients with oligometastatic disease. However, lack of phase III trial data and uncertainties around patient selection highlight the importance of multidisciplinary tumor boards (MDT) in therapeutic decision-making. This study aimed to analyze the recognition of and treatment recommendations for oligometastatic patients by MDTs at a large comprehensive cancer center in order to better understand current treatment patterns of oligometastasis. Materials and methods: For this retrospective single-center cross-sectional study, oligometastatic patients were identified by screening oncological PET and concurrent brain MRI scans conducted at our center in 2020. MDT discussions and recommendations within four weeks of the imaging diagnosis of oligometastasis were analyzed. Logistic regression analysis was used to identify predictors for the addition of local therapy to standard-of-care. Results: A total of 787 oligometastatic cases were identified. Lung cancer and mesothelioma, skin cancer, and prostate cancer were the most common histologies with 231 (29 %), 160 (20 %), and 84 (11 %) cases, respectively. Almost half of the cases (46 %) had one distant metastasis on imaging only. More than half (56 %) of all oligometastatic cases were discussed at an MDT. In 47 % of cases, for which a therapeutic recommendation was reached in an MDT, local therapy was part of the therapeutic strategy. On logistic regression analysis, oligometastatic skin cancer was significantly associated with a recommendation for local therapy (p < 0.05), whereas the number of oligometastases was not (p = 0.202). Conclusion: More than half of oligometastatic cases were discussed in MDTs, of which more than every second received a recommendation including the addition of local therapy. This frequency of MDT use underscores the importance of multidisciplinary decision-making, yet efforts should be increased to standardize reporting and use standard nomenclature on oligometastasis in MDTs to better frame multidisciplinary discussion.

Development and external validation of an MRI-based neural network for brain metastasis segmentation in the AURORA multicenter study.

BACKGROUND: Stereotactic radiotherapy is a standard treatment option for patients with brain metastases. The planning target volume is based on gross tumor volume (GTV) segmentation. The aim of this work is to develop and validate a neural network for automatic GTV segmentation to accelerate clinical daily routine practice and minimize interobserver variability. METHODS: We analyzed MRIs (T1-weighted sequence ± contrast-enhancement, T2-weighted sequence, and FLAIR sequence) from 348 patients with at least one brain metastasis from different cancer primaries treated in six centers. To generate reference segmentations, all GTVs and the FLAIR hyperintense edematous regions were segmented manually. A 3D-U-Net was trained on a cohort of 260 patients from two centers to segment the GTV and the surrounding FLAIR hyperintense region. During training varying degrees of data augmentation were applied. Model validation was performed using an independent international multicenter test cohort (n = 88) including four centers. RESULTS: Our proposed U-Net reached a mean overall Dice similarity coefficient (DSC) of 0.92 ± 0.08 and a mean individual metastasis-wise DSC of 0.89 ± 0.11 in the external test cohort for GTV segmentation. Data augmentation improved the segmentation performance significantly. Detection of brain metastases was effective with a mean F1-Score of 0.93 ± 0.16. The model performance was stable independent of the center (p = 0.3). There was no correlation between metastasis volume and DSC (Pearson correlation coefficient 0.07). CONCLUSION: Reliable automated segmentation of brain metastases with neural networks is possible and may support radiotherapy planning by providing more objective GTV definitions.

Stereotactic body radiotherapy to defer systemic therapy in patients with oligorecurrent disease.

Background: Patients who develop oligorecurrent disease may be treated with metastasis-directed stereotactic body radiotherapy (SBRT) to defer the start of systemic therapy and delay its potential side effects. We report oncological outcomes and patterns of failure in patients with oligorecurrent disease treated with SBRT and determine which factors impact the interval to initiation of systemic therapy. Material/Methods: This retrospective study included patients with oligorecurrent disease (≤5 lesions) from any solid organ malignancy, treated with SBRT to all metastases and no systemic therapy for a minimum one month after SBRT between 01/2014 and 12/2019. The Kaplan-Meier method was used to analyze overall survival (OS) and progression-free survival (PFS), and the cumulative incidence of initiation of systemic therapy was analyzed assuming death without systemic therapy as a competing risk. Univariable and multivariable analyses are used to assess predictors of the systemic therapy-free interval. Results: Among 545 patients treated with SBRT for oligometastatic disease, 142 patients were treated with SBRT only for oligorecurrent disease. The most common primary tumors were lung and gastrointestinal cancer in 47 (33.1 %) and 28 (19.7 %) patients, respectively. After a median follow-up of 25 months, the median PFS and OS was 6.1 months and 48.9 months, respectively. Distant metastases were the most common first failure, and oligometastatic distant failure occured in 86 patients (60.6 %). New metastases were treated with repeat SBRT in 48 patients (33.8 %). The 1- and 2-year cumulative incidence of initiation of systemic therapy was 24.6 % and 36.8 %, respectively. In multivariable analysis, the number of previous lines of systemic therapy and the cumulative volume of metastases were significantly associated with the interval to initiation of systemic therapy. Conclusion: Selected patients with oligorecurrence achieved favorable OS and low cumulative incidence of initiation of systemic therapy. Prospective studies are warranted to determine how the deferral of systemic therapy impacts OS compared with immediate systemic therapy in combination with SBRT.