DEGRO guideline for personalized radiotherapy of brain metastases and leptomeningeal carcinomatosis in patients with breast cancer.

PURPOSE: The aim of this review was to evaluate the existing evidence for radiotherapy for brain metastases in breast cancer patients and provide recommendations for the use of radiotherapy for brain metastases and leptomeningeal carcinomatosis. MATERIALS AND METHODS: For the current review, a PubMed search was conducted including articles from 01/1985 to 05/2023. The search was performed using the following terms: (brain metastases OR leptomeningeal carcinomatosis) AND (breast cancer OR breast) AND (radiotherapy OR ablative radiotherapy OR radiosurgery OR stereotactic OR radiation). CONCLUSION AND RECOMMENDATIONS: Despite the fact that the biological subtype of breast cancer influences both the occurrence and relapse patterns of breast cancer brain metastases (BCBM), for most scenarios, no specific recommendations regarding radiotherapy can be made based on the existing evidence. For a limited number of BCBM (1-4), stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (SRT) is generally recommended irrespective of molecular subtype and concurrent/planned systemic therapy. In patients with 5-10 oligo-brain metastases, these techniques can also be conditionally recommended. For multiple, especially symptomatic BCBM, whole-brain radiotherapy (WBRT), if possible with hippocampal sparing, is recommended. In cases of multiple asymptomatic BCBM (≥ 5), if SRS/SRT is not feasible or in disseminated brain metastases (> 10), postponing WBRT with early reassessment and reevaluation of local treatment options (8-12 weeks) may be discussed if a HER2/Neu-targeting systemic therapy with significant response rates in the central nervous system (CNS) is being used. In symptomatic leptomeningeal carcinomatosis, local radiotherapy (WBRT or local spinal irradiation) should be performed in addition to systemic therapy. In patients with disseminated leptomeningeal carcinomatosis in good clinical condition and with only limited or stable extra-CNS disease, craniospinal irradiation (CSI) may be considered. Data regarding the toxicity of combining systemic therapies with cranial and spinal radiotherapy are sparse. Therefore, no clear recommendations can be given, and each case should be discussed individually in an interdisciplinary setting.

Moral Distress in Radiation Oncology: Insights From Residents in Germany.

Purpose: Being challenged by circumstances that force one to act in discordance with one's moral compass can lead to moral distress. The phenomenon has been widely investigated among nurses. This study was designed to shed some light on the situation of resident physicians in radiation oncology. Methods and Materials: To gain insight into moral distress among residents in radiation oncology, a web-based questionnaire was developed and distributed throughout Germany. Participants were asked to evaluate possible burdensome situations and different options for relief. To outline the main issues of moral distress, an exploratory factor analysis was conducted. Relief options were examined by frequencies. Results: The factor analysis yielded lack of time, contradiction between patient request and indication, nonmedical interests, and decisions between curative treatment and best supportive care as main issues for the 84 participants. Support from supervisors and senior physicians, as well as exchanges with resident colleagues were indicated as forms of relief. Professional support, such as ethics consultations, structured conversation groups (Balint), or psychological case supervisions, were rated as less helpful, although most participants reported a lack of experience with these. Conclusions: The results are in accordance with existing assumptions that moral distress among physicians is mainly due to uncertainty. Regarding radiation oncology residents in particular, moral distress seems to be related to uncertainty in decisions and conflicts about treatment options. Although senior physicians and supervisors present important role models in dealing with moral distress, professional services such as ethics consultations offer an opportunity for relief that can still be expanded.

Geometric accuracy in patient positioning for stereotactic radiotherapy of intracranial tumors.

Background/Purpose: This study determines and compares the geometric setup errors between stereoscopic x-ray and kilo-voltage cone beam CT (CBCT) in phantom tests on a linear accelerator (linac) for image-guided (IG) stereotactic radiotherapy of intracranial tumors. Additionally, dose-volume metrics in the target volumes of the setup errors of CBCT were evaluated. Materials/Methods: A Winston-Lutz- and an anthropomorphic phantom were used. The mean deviation and root mean square error (RMSE) of CBCT and stereoscopic x-ray were compared. Dose-volume metrics of the planning target volume (PTV) and gross target volume (GTV) for CBCT were calculated. Results: The RMSEs in the tests with the Winston-Lutz-Phantom were 0.3 mm, 1.1 mm and 0.3 mm for CBCT and 0.1 mm, 0,1 mm and <0.1 mm for stereoscopic x-ray in the translational dimensions (right-left, anterior-posterior and superior-inferior). The RMSEs in the tests with the anthropomorphic phantom were 0.3 mm, 0.2 mm and 0.1 mm for CBCT and 0.1 mm, 0,1 mm and <0.1 mm for stereoscopic x-ray. The effects on dose-volume metrics of the setup errors of CBCT on the GTV were within 1 % for all considered dose values. The effects on the PTV were within 5 % for all considered dose values. Conclusion: Both IG systems provide high accuracy patient positioning within a submillimeter range. The phantom tests exposed a slightly higher accuracy of stereoscopic x-ray than CBCT. The comparison with other studies with a similar purpose emphasizes the importance of individual IG installation quality assurance.

Radiosurgery for ventricular tachycardia (RAVENTA): interim analysis of a multicenter multiplatform feasibility trial.

BACKGROUND: Single-session cardiac stereotactic radiation therapy (SBRT) has demonstrated promising results for patients with refractory ventricular tachycardia (VT). However, the full safety profile of this novel treatment remains unknown and very limited data from prospective clinical multicenter trials are available. METHODS: The prospective multicenter multiplatform RAVENTA (radiosurgery for ventricular tachycardia) study assesses high-precision image-guided cardiac SBRT with 25 Gy delivered to the VT substrate determined by high-definition endocardial and/or epicardial electrophysiological mapping in patients with refractory VT ineligible for catheter ablation and an implanted cardioverter defibrillator (ICD). Primary endpoint is the feasibility of full-dose application and procedural safety (defined as an incidence of serious [grade ≥ 3] treatment-related complications ≤ 5% within 30 days after therapy). Secondary endpoints comprise VT burden, ICD interventions, treatment-related toxicity, and quality of life. We present the results of a protocol-defined interim analysis. RESULTS: Between 10/2019 and 12/2021, a total of five patients were included at three university medical centers. In all cases, the treatment was carried out without complications. There were no serious potentially treatment-related adverse events and no deterioration of left ventricular ejection fraction upon echocardiography. Three patients had a decrease in VT episodes during follow-up. One patient underwent subsequent catheter ablation for a new VT with different morphology. One patient with local VT recurrence died 6 weeks after treatment in cardiogenic shock. CONCLUSION: The interim analysis of the RAVENTA trial demonstrates early initial feasibility of this new treatment without serious complications within 30 days after treatment in five patients. Recruitment will continue as planned and the study has been expanded to further university medical centers. TRIAL REGISTRATION NUMBER: NCT03867747 (clinicaltrials.gov). Registered March 8, 2019. Study start: October 1, 2019.

Teaching communication skills in medical education : Best practice example of an interdisciplinary seminar in radiation oncology.

BACKGROUND: Communication with patients is challenging, especially in radiation oncology. Therefore, radiation oncology is particularly suited to sensitize medical students for this topic and to train them competently. We report on experiences with an innovative teaching project for fourth- and fifth-year medical students. MATERIALS AND METHODS: The course, funded as an innovative teaching project by the medical faculty, was offered as an optional course for medical students in 2019 and again in 2022 after a pandemic-related break. The curriculum and evaluation form were developed through a two-stage Delphi process. The course consisted of, first, participation during counselling of patients prior to radiotherapy, mainly on topics with shared decision-making, and, second, a 1-week interdisciplinary block seminar with practical exercises. The topics covered a broad spectrum of the competence areas defined in the National Competence-Based Learning Objectives Catalog for Medicine (NKLM). The number of participants was limited to approximately 15 students because of the practical components. RESULTS: So far, 30 students (all at least in the seventh semester or higher) have participated in the teaching project. The most frequent reasons for participation were the desire to acquire competence in breaking bad news and confidence in talking to patients. The overall evaluation of the course was very positive, with a grade of 1.08 + 0.28 (on a scale of 1 = totally agree to 5 = totally disagree) plus German grade 1 (very good) to 6 (very bad). Notably, participants' expectations regarding specific competencies (e.g., breaking bad news) were also met. CONCLUSION: Although the evaluation results cannot be generalized to the entirety of medical students due to the limited number of voluntary participants, the very positive evaluation shows the need for such projects among students and can also be seen as an indication that radiation oncology as a patient-centered discipline is particularly well suited to teach medical communication.

The impact of palliative radiotherapy on health-related quality of life in patients with head and neck cancer - Results of a multicenter prospective cohort study.

Purpose: Palliative radiotherapy for patients with head and neck cancer can be used to alleviate symptoms. Only a few studies have investigated its impact on patient-reported outcomes (PRO). Therefore, we conducted a prospective multicenter observational study. The primary objective was to assess changes in health-related quality of life (HrQoL) per PRO. Methods: Eligibility criteria included i.) head and neck cancer and ii.) palliative radiotherapy indicated (EQD2Gy < 60 Gy). The primary follow-up date was eight weeks after radiotherapy (t8w). PRO measures included the EORTC QLQ-C30 and EORTC QLQ-H&N43 and pain per Numeric Rating Scale (NRS). Per protocol, five PRO domains were to be reported in detail as well as PRO domains corresponding to a primary and secondary symptom as determined by the individual patient. We defined a minimal important difference (MID) of 10 points. Results: From 06/2020 to 06/2022, 61 patients were screened and 21 patients were included. Due to death or decline in health-status, HrQoL data was available for 18 patients at the first fraction and for eight patients at t8w. The MID was not met for the predefined domains in terms of mean values as compared from first fraction to t8w. Individually in those patients with available HrQoL data at t8w, 71% (5/7) improved in their primary and 40% (2/5) in their secondary symptom domain reaching the MID from first fraction to t8w, respectively. There was a significant improvement in pain per NRS in those patients with available data at t8w per Wilcoxon signed rank test (p = 0.041). Acute mucositis of grade ≥3 per CTCAE v5.0 occurred in 44% (8/18) of the patients. The median overall survival was 11 months. Conclusion: Despite low patient numbers and risk of selection bias, our study shows some evidence of a benefit from palliative radiotherapy for head and neck cancer as measured by PRO.German Clinical Trial Registry identifier: DRKS00021197.

Long-term characterization of MRI-morphologic alterations after active motion-compensated liver SBRT: a multi-institutional pooled analysis.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is an effective therapeutic approach in patients with liver metastases. However, long-term changes in hepatic normal tissue have to be taken into account in multimodal treatment regimes. Magnetic-resonance-imaging (MRI) based morphologic liver alterations (MMA) after liver SBRT have been analyzed longitudinally. MATERIAL AND METHODS: 57 patients treated with gantry-based or robotic-based SBRT of 69 treatment volumes of liver metastases, who had long-term follow-up (FU) ≥6 months were included in this retrospective analysis. Post-SBRT MMAs were contoured on each contrast-enhanced-T1-weighted (T1w) MRI-sequence. Morphologic/volumetric data of the liver and MMAs were evaluated longitudinally, including the dependency on treatment-related factors of the planning target volume (PTV) and liver. RESULTS: The median FU time was 1 year [6-48 months]. 66 of 69 treatment volumes developed MMAs (mean 143.8 ± 135.1 ccm at first appearance). 31.8% of MMAs resolved completely during FU. Of the persisting MMAs 82.2%/13.3% decreased/increased in size until last available FU. Morphological characterization of the MMAs at first appearance included 75% hypointense and 25% hyperintense T1w-MRI-based appearances. Hypointense as compared to hyperintense appearance was significantly associated with a higher mean liver dose EQD2α/ß=3 Gy (p = 0.0212) and non-significantly greater MMA size. Variance analysis demonstrated a significant reduction of MMA and total liver volume after SBRT (p < 0.0001). The volume reduction decelerated longitudinally for both MMA (p < 0.0001) and liver size (p = 0.0033). Radiation doses (PTV-BEDα/ß=3 Gy and 10 Gy) were not significantly associated with MMA volume reduction. SBRT of liver metastases with mean liver dose EQD2α/ß=3 Gy > 18 Gy were characterized by greater MMA volumes (p = 0.0826) and steeper MMA reduction gradients during FU than those with EQD2α/ß=3 Gy ≤ 18 Gy (p < 0.0001). CONCLUSION: Radiogenic MMAs either completely resolve or usually decrease in volume with pronounced reduction during short-term FU. This course was independent of the MMA's morphological appearance. Further, increased mean liver dose was associated with greater MMA size and a greater gradient of MMA size reduction during FU.

Robotic stereotactic body radiotherapy for localized prostate cancer: final analysis of the German HYPOSTAT trial.

PURPOSE: We report results of the first German prospective multicenter single-arm phase II trial (ARO 2013-06; NCT02635256) of hypofractionated robotic stereotactic body radiotherapy (SBRT) for patients with localized prostate cancer (HYPOSTAT). METHODS: Patients eligible for the HYPOSTAT study had localized prostate cancer (cT1­3 cN0 cM0), Gleason score ≤ 7, prostate-specific antigen (PSA) ≤ 15 ng/ml, prostate volume ≤ 80 cm3, and an International Prostate Symptom Score (IPSS) ≤ 12. Initially, inclusion was limited to patients ≥ 75 years or patients 70-74 years with additional risk factors. The trial protocol was later amended to allow for enrolment of patients aged ≥ 60 years. The treatment consisted of 35 Gy delivered in 5 fractions to the prostate and for intermediate- or high-risk patients, also to the proximal seminal vesicles using the CyberKnife system (Accuray Inc., Sunnyvale, CA, USA). Primary endpoint was the rate of treatment-related gastrointestinal or genitourinary grade ≥ 2 toxicity based on the RTOG scale 12-15 months after treatment. Secondary endpoints were acute toxicity, late toxicity, urinary function, quality of life, and PSA response. RESULTS: From July 2016 through December 2018, 85 eligible patients were enrolled and received treatment, of whom 83 could be evaluated regarding the primary endpoint. Patients mostly had intermediate-risk disease with a median PSA value of 7.97 ng/ml and Gleason score of 7a and 7b in 43.5% and 25.9% of patients, respectively. At the final follow-up 12-15 months after treatment, no patient suffered from treatment-related gastrointestinal or genitourinary grade ≥ 2 toxicity. Acute toxicity was mostly mild, with three grade 3 events, and the cumulative rate of grade ≥ 2 genitourinary toxicity was 8.4% (95% CI 4.1-16.4%). There were no major changes in urinary function or quality of life. The median PSA value dropped to 1.18 ng/ml 12-15 months after treatment. There was one patient who developed distant metastases. CONCLUSION: Robotic SBRT with 35 Gy in 5 fractions was associated with a favorable short-term toxicity profile. Recruitment for the HYPOSTAT­2 trial (ARO-2018­4; NCT03795337), which further analyses the late toxicity of this regimen with a planned sample size of 500 patients, is ongoing.

Accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy compared with whole-breast irradiation with boost for early breast cancer: 10-year results of a GEC-ESTRO randomised, phase 3, non-inferiority trial.

BACKGROUND: Several randomised, phase 3 trials have investigated the value of different techniques of accelerated partial breast irradiation (APBI) for patients with early breast cancer after breast-conserving surgery compared with whole-breast irradiation. In a phase 3 randomised trial, we evaluated whether APBI using multicatheter brachytherapy is non-inferior compared with whole-breast irradiation. Here, we present the 10-year follow-up results. METHODS: We did a randomised, phase 3, non-inferiority trial at 16 hospitals and medical centres in Austria, Czech Republic, Germany, Hungary, Poland, Spain, and Switzerland. Patients aged 40 years or older with early invasive breast cancer or ductal carcinoma in situ treated with breast-conserving surgery were centrally randomly assigned (1:1) to receive either whole-breast irradiation or APBI using multicatheter brachytherapy. Whole-breast irradiation was delivered in 25 daily fractions of 50 Gy over 5 weeks, with a supplemental boost of 10 Gy to the tumour bed, and APBI was delivered as 30·1 Gy (seven fractions) and 32·0 Gy (eight fractions) of high-dose-rate brachytherapy in 5 days or as 50 Gy of pulsed-dose-rate brachytherapy over 5 treatment days. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was ipsilateral local recurrence, analysed in the as-treated population; the non-inferiority margin for the recurrence rate difference (defined for 5-year results) was 3 percentage points. The trial is registered with ClinicalTrials.gov, NCT00402519; the trial is complete. FINDINGS: Between April 20, 2004, and July 30, 2009, 1328 female patients were randomly assigned to whole breast irradiation (n=673) or APBI (n=655), of whom 551 in the whole-breast irradiation group and 633 in the APBI group were eligible for analysis. At a median follow-up of 10·36 years (IQR 9·12-11·28), the 10-year local recurrence rates were 1·58% (95% CI 0·37 to 2·8) in the whole-breast irradiation group and 3·51% (1·99 to 5·03) in the APBI group. The difference in 10-year rates between the groups was 1·93% (95% CI -0·018 to 3·87; p=0·074). Adverse events were mostly grade 1 and 2, in 234 (60%) of 393 participants in the whole-breast irradiation group and 314 (67%) of 470 participants in the APBI group, at 7·5-year or 10-year follow-up, or both. Patients in the APBI group had a significantly lower incidence of treatment-related grade 3 late side-effects than those in the whole-breast irradiation group (17 [4%] of 393 for whole-breast irradiation vs seven [1%] of 470 for APBI; p=0·021; at 7·5-year or 10-year follow-up, or both). At 10 years, the most common type of grade 3 adverse event in both treatment groups was fibrosis (six [2%] of 313 patients for whole-breast irradiation and three [1%] of 375 patients for APBI, p=0·56). No grade 4 adverse events or treatment-related deaths have been observed. INTERPRETATION: Postoperative APBI using multicatheter brachytherapy after breast-conserving surgery in patients with early breast cancer is a valuable alternative to whole-breast irradiation in terms of treatment efficacy and is associated with fewer late side-effects. FUNDING: German Cancer Aid, Germany.

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.

Errors detected during physics plan review for external beam radiotherapy.

Background and purpose: Risk management in radiotherapy is of high importance. There is not much data published on errors occurring in the treatment planning process of external beam techniques. The aim of this study was to investigate errors occurring during physics plan review in external beam radiotherapy. Materials and methods: Over a period of 14 months errors observed during the physical review process are reported. The errors were grouped and evaluated regarding treatment machine, technique, and treatment site. In addition, a correlation between frequency of errors and staff shortage was analyzed. Results: Subgroups of grave errors (g-errors) and slight errors (s-errors) were defined to consider the different impact on the patient and clinical workflow of the errors. In 1056 plans reviewed, 110 errors (41 g-errors, 69 s-errors) were detected. The most common g-errors and s-errors were "Wrong gantry angle at setup field" (n = 19) and "Wrong field label" (n = 24), respectively. A correlation of number of errors and treatment machine, technique, or anatomical site could not be found. No correlation between staff shortage and number of errors was observed. Conclusions: The process of reviewing treatment plans is a relevant topic to consider in risk analysis of the radiotherapy workflow. The review process could be improved by enhancements in the treatment planning systems, use of digital dose prescription, and treatment planning templates.

Clinical endpoints in trials of palliative radiotherapy: A systematic meta-research analysis.

PURPOSE: Up to 50% of radiotherapy courses are delivered in palliative intent for various indications. Despite the large number of treated patients, we know little about the choice of endpoints in trials of palliative radiotherapy. Our primary aim was, therefore, to analyze primary endpoints in trials of palliative radiotherapy. METHODS: We conducted a pre-registered (https://doi.org/10.17605/OSF.IO/GMCAF) meta-research analysis searching Pubmed/MEDLINE, EMBASE, CENTRAL, and "ClinicalTrials.gov" for clinical trials of palliative radiotherapy published 1990-2020. Endpoints were categorized in "patient-centered endpoints", including overall survival and patient-reported outcomes, and "tumor-centered endpoints" such as local control. The remainder were "other endpoints" including toxicity or observer-rated symptoms. We applied descriptive statistics to summarize data and logistic regression to assess if year of publication predicted the choice of primary endpoints. RESULTS: Of 7379 records screened, 292 were eligible. Trials were characterized by small sample sizes and use of external beam radiotherapy for metastases or thoracic primaries. Median patient age was 64 and median ECOG was 1. Only 64.4%(145/225) of published trials clearly stated their primary endpoint. Published trials employed a "patient-centered primary endpoint" in 45.5%(66/145) and a "tumor-centered primary endpoint" in 17.3%(25/145) of the cases. There was no statistically significant trend in time for the use of "patient-centered primary endpoints". Registered ongoing trials used a "patient-centered primary endpoint" in 32.8%(22/67) and a "tumor-centered primary endpoint" in 26.9%(18/67) of the cases. CONCLUSION: Although "patient-centered primary endpoints" appear relatively prevalent in published trials of palliative radiotherapy, their use is still suboptimal and appears to be lower in currently ongoing trials.