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.

Development, implementation, and results of a simulation-based hands-on brachytherapy workshop for medical students.

PURPOSE: The new Medical Licensing Regulations 2025 (Ärztliche Approbationsordnung, ÄApprO) require the development of competence-oriented teaching formats. In addition, there is a great need for high-quality teaching in the field of radiation oncology, which manifests itself already during medical school. For this reason, we developed a simulation-based, hands-on medical education format to teach competency in performing accelerated partial breast irradiation (APBI) with interstitial multicatheter brachytherapy for early breast cancer. In addition, we designed realistic breast models suitable for teaching both palpation of the female breast and implantation of brachytherapy catheters. METHODS: From June 2021 to July 2022, 70 medical students took part in the hands-on brachytherapy workshop. After a propaedeutic introduction, the participants simulated the implantation of single-lead catheters under supervision using the silicone-based breast models. Correct catheter placement was subsequently assessed by CT scans. Participants rated their skills before and after the workshop on a six-point Likert scale in a standardized questionnaire. RESULTS: Participants significantly improved their knowledge-based and practical skills on APBI in all items as assessed by a standardized questionnaire (mean sum score 42.4 before and 16.0 after the course, p < 0.001). The majority of respondents fully agreed that the workshop increased their interest in brachytherapy (mean 1.15, standard deviation [SD] 0.40 on the six-point Likert scale). The silicone-based breast model was found to be suitable for achieving the previously defined learning objectives (1.19, SD 0.47). The learning atmosphere and didactic quality were rated particularly well (mean 1.07, SD 0.26 and 1.13, SD 0.3 on the six-point Likert scale). CONCLUSION: The simulation-based medical education course for multicatheter brachytherapy can improve self-assessed technical competence. Residency programs should provide resources for this essential component of radiation oncology. This course is exemplary for the development of innovative practical and competence-based teaching formats to meet the current reforms in medical education.

Stereotactic body radiotherapy of adrenal metastases-A dose-finding study.

Optimal doses for the treatment of adrenal metastases with stereotactic radiotherapy (SBRT) are unknown. We aimed to identify dose-volume cut-points associated with decreased local recurrence rates (LRR). A multicenter database of patients with adrenal metastases of any histology treated with SBRT (biologically effective dose, BED10 ≥50 Gy, ≤12 fractions) was analyzed. Details on dose-volume parameters were required (planning target volume: PTV-D98%, PTV-D50%, PTV-D2%; gross tumor volume: GTV-D50%, GTV-mean). Cut-points for LRR were optimized using the R maxstat package. One hundred and ninety-six patients with 218 lesions were included, the largest histopathological subgroup was adenocarcinoma (n = 101). Cut-point optimization resulted in significant cut-points for PTV-D50% (BED10: 73.2 Gy; P = .003), GTV-D50% (BED10: 74.2 Gy; P = .006), GTV-mean (BED10: 73.0 Gy; P = .007), and PTV-D2% (BED10: 78.0 Gy; P = .02) but not for the PTV-D98% (P = .06). Differences in LRR were clinically relevant (LRR ≥ doubled for cut-points that were not achieved). Further dose-escalation was not associated with further improved LRR. PTV-D50%, GTV-D50%, and GTV-mean cut-points were also associated with significantly improved LRR in the adenocarcinoma subgroup. Separate dose optimizations indicated a lower cut-point for the PTV-D50% (BED10: 69.1 Gy) in adenocarcinoma lesions, other values were similar (<2% difference). Associations of cut-points with overall survival (OS) and progression-free survival were not significant but durable freedom from local recurrence was associated with OS in a landmark model (P < .001). To achieve a significant improvement of LRR for adrenal SBRT, a moderate escalation of PTV-D50% BED10 >73.2 Gy (adenocarcinoma: 69.1 Gy) should be considered.

Breast clinical target volume: HU-based glandular CTVs and ESTRO CTVs in modern and historical radiotherapy treatment planning.

PURPOSE: The current study aimed to compare contouring of glandular tissue only (gCTV) with the clinical target volume (CTV) as defined according to European Society for Radiotherapy and Oncology (ESTRO) guidelines (eCTV) and historically treated volumes (marked by wire and determined by palpation and anatomic landmarks) in breast cancer radiotherapy. METHODS: A total of 56 consecutive breast cancer patients underwent treatment planning based solely on anatomic landmarks/wire markings ("wire based"). From these treatment plans, the 50% and 95% isodoses were transferred as structures and compared to the following CT-based volumes: eCTV; a Hounsfield unit (HU)-based automatic contouring of the gCTV; and standardized planning target volumes (PTVs) generated with 1­cm safety margins (resulting in the ePTVs and gPTVs, respectively). RESULTS: The 95% isodose volume of the wire-based plan was larger than the eCTV by 352.39 ± 176.06 cm3 but smaller than the ePTV by 157.58 ± 189.32 cm3. The 95% isodose was larger than the gCTV by 921.20 ± 419.78 cm3 and larger than the gPTV by 190.91 ± 233.49 cm3. Patients with larger breasts had significantly less glandular tissue than those with small breasts. There was a trend toward a lower percentage of glandular tissue in older patients. CONCLUSION: Historical wire and anatomic landmarks-based treatment planning sufficiently covers the glandular tissue and the theoretical gPTV generated for the glandular tissue. Modern CT-based CTV and PTV definition according to ESTRO results in a larger treated volume than the historical wire-based techniques. HU-standardized glandular tissue contouring results in a significantly smaller CTV and might be an option for reducing the treatment volume and improving reproducibility of contouring between institutions.

No impact of time to treatment initiation for head and neck cancer in a tertiary university center in 2003, 2008 and 2013.

BACKGROUND: This retrospective study investigated factors influencing time to treatment initiation (TTI) and the influence of TTI on overall survival (OS) of primary head and neck cancer (HNC) patients in cohorts from 2003, 2008 and 2013. METHODS: Two hundred and ninenty seven patients (78.8% men; median age: 62 years) were included. Kaplan-Meier analyses and multivariate Cox regression were performed to investigate OS. RESULTS: Mean times to treatment initiation (TTI) of 2003, 2008 and 2013 were 17.11 ± 18.00, 30.26 ± 30.08 and 17.30 ± 37.04 days, respectively. TTI for patients with T3/T4 tumors was higher than for T1/T2 (p = 0.010). In univariable analysis on OS, TTI > 5 days showed lower OS (p = 0.047). In multivariate analysis, longer TTI had no influence on lower OS [hazard ratio (HR) 1.236; 95% CI 0.852-1.791; p = 0.264], but male gender [HR 2.342; 95% CI 1.229-4.466; p = 0.010], increased age [HR 1.026; 95% CI 1.008-1.045; p = 0.005], M1 [HR 5.823; 95% CI 2.252-15.058; p = 0.003], hypopharynx tumor [HR 2.508; 95% CI 1.571-4.003; p < 0.001] and oral cavity tumor [HR 1.712; CI 1.101-2.661; p = 0.017]. The year of treatment showed no significant effect on OS. CONCLUSION: Median TTI seemed to be very short compared to other studies. There was no clear trend in the impact of TTI on OS from 2003 to 2013.

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

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

Peripherally inserted central venous catheter (PICC) in outpatient and inpatient oncological treatment.

PURPOSE: So far there is little evidence on peripherally inserted central venous catheter (PICC) in radiation oncology patients maintaining the access during the periods of ambulatory and hospital treatment. METHODS: A total of 522 PICC placements in 484 patients were performed between 11/2011 and 07/2016 at the Department of Radiation Oncology and analysed retrospectively for complications and treatment- and patient-related factors during ambulatory and hospital inpatient use. On initial hospitalization, all patients received a multimodal radio-oncological treatment consisting of radiation and intravenous therapy administered via the PICC. RESULTS: A total of 18,292 catheter days were documented. Median follow-up from catheter insertion to their removal was 37 days (1-97). The overall complication rate was 4.1 per 1000 catheter days (n = 75, 14.4%). Complications were similar between the cohort of outpatient 3.6 per 1000 catheter days and the cohort of inpatient 4.8 per 1000 catheter days (OR 0.976; 95% CI [0.598; 1.619]; p = 0.924). Severe bloodstream infections occurred at a rate of 0.60 per 1000 catheter days (n = 11, 2.1%), deep vein thrombosis at a rate of 0.82 per 1.000 catheter days (n = 15, 2.9%) and local inflammation at a rate of 1.26 per 1.000 catheter days (n = 23, 4.4%). Only immunotherapy could be identified as an independent risk factor for complications (OR 5.6; 95% CI [2.4; 13.1]; p < 0.001). CONCLUSION: Using PICC in outpatients is not associated with an elevated risk of complications. Particular attention should be payed to early identification of PICC associated bloodstream infections. Immunotherapy is an independent risk factor for local skin complication.

Urinary Proteomics Profiles Are Useful for Detection of Cancer Biomarkers and Changes Induced by Therapeutic Procedures.

Boron neutron capture therapy (BNCT) is a binary cancer treatment modality where two different agents (10B and thermal neutrons) have to be present to produce an effect. A dedicated trial design is necessary for early clinical trials. The concentration of 10B in tissues is an accepted surrogate to predict BNCT effects on tissues. Tissue, blood, and urines were sampled after infusion of two different boron carriers, namely BSH and BPA in the frame of the European Organisation for Research and Treatment of Cancer (EORTC) trial 11001. In this study, urine samples were used to identify protein profiles prior and after drug infusion during surgery. Here, an approach that is based on the mass spectrometry (MS)-based proteomic analysis of urine samples from head and neck squamous cell carcinoma (HNSCC) and thyroid cancer patients is presented. This method allowed the identification of several inflammation- and cancer-related proteins, which could serve as tumor biomarkers. In addition, changes in the urinary proteome during and after therapeutic interventions were detected. In particular, a reduction of three proteins that were involved in inflammation has been observed: Galectin-3 Binding Protein, CD44, and osteopontin. The present work represents a proof of principle to follow proteasome changes during complex treatments based on urine samples.

Stereotactic body radiotherapy for centrally located stage I NSCLC: a multicenter analysis.

PURPOSE: The purpose of this work is to analyze patterns of care and outcome after stereotactic body radiotherapy (SBRT) for centrally located, early-stage, non-small cell lung cancer (NSCLC) and to address the question of potential risk for increased toxicity in this entity. METHODS AND MATERIALS: A total of 90 patients with centrally located NSCLC were identified among 613 cases in a database of 13 German and Austrian academic radiotherapy centers. The outcome of centrally located NSCLC was compared to that of cases with peripheral tumor location from the same database. RESULTS: Patients with central tumors most commonly presented with UICC stage IB (50 %), while the majority of peripheral lesions were stage IA (56 %). Average tumor diameters were 3.3 cm (central) and 2.8 cm (peripheral). Staging PET/CT was available for 73 and 74 % of peripheral and central tumors, respectively. Biopsy was performed in 84 % (peripheral) and 88 % (central) of cases. Doses varied significantly between central and peripheral lesions with a median BED10 of 72 Gy and 84 Gy, respectively (p < 0.001). Fractionation differed as well with medians of 5 (central) and 3 (peripheral) fractions (p < 0.001). In the Kaplan-Meier analysis, 3-year actuarial overall survival was 29 % (central) and 51 % (peripheral; p = 0.004) and freedom from local progression was 52 % (central) and 84 % (peripheral; p < 0.001). Toxicity after treatment of central tumors was low with no grade III/IV and one grade V event. Mortality rates were 0 and 1 % after 30 and 60 days, respectively. CONCLUSION: Local tumor control in patients treated with SBRT for centrally located, early-stage NSCLC was favorable, provided ablative radiation doses were prescribed. This was, however, not the case in the majority of patients, possibly due to concerns about treatment-related toxicity. Reported toxicity was low, but prospective trials are needed to resolve the existing uncertainties and to establish safe high-dose regimens for this cohort of patients.

Changes in the radiological depth correlate with dosimetric deterioration in particle therapy for stage I NSCLC patients under high frequency jet ventilation.

BACKGROUND: Particle dose distributions are highly sensitive to anatomy changes in the beam path, which may lead to substantial dosimetric deviations. Robust planning and dedicated image guidance together with strategies for online decision making to counteract dosimetric deterioration are thus mandatory. We aimed to develop methods to quantify anatomical discrepancies as depicted by repeated computed tomography (CT) imaging and to test whether they can predict deviations in target coverage. MATERIAL AND METHODS: Dedicated software tools allowed for voxel-based calculations of changes in the water equivalent path length (WEPL) in beam directions. We prepared proton and carbon ion plans with different coplanar beam angle settings on a series of lung cancer patients, for which planning and localization CT scans under high frequency jet ventilation (HFJV) for tumor fixation were performed. We investigated the reproducibility of target coverage between the optimized and recalculated treatment plans. We then studied how different raster scan and planning settings influence the robustness. Finally, we carried out a systematic analysis of the variations in the WEPL along different coplanar beam angles to find beam directions, which could minimize such variations. RESULTS: The Spearman's correlations for the GTV ΔV95 and ΔV98 with the ΔWEPL for the proton plans with a 0° and -45° two-field configuration were 0.701 (p = 0.02) and 0.719 (p = 0.08), respectively. For beam configurations 0° and -90°, or 0° and + 45°, with lower ΔWEPL, the correlations were no significant. The same trends were observed for the carbon ion plans. Increased beam spot overlap reduced dosimetric deterioration in case of large ΔWEPL. CONCLUSION: Software tools for fast online analysis of WEPL changes might help supporting clinical decision making of image guidance. Raster scan and treatment planning settings can help to compensate for anatomical deviations.

Increased radiosensitivity of HPV-positive head and neck cancer cell lines due to cell cycle dysregulation and induction of apoptosis.

BACKGROUND AND PURPOSE: Human Papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) respond favourably to radiotherapy as compared to HPV-unrelated HNSCC. We investigated DNA damage response in HPV-positive and HPV-negative HNSCC cell lines aiming to identify mechanisms, which illustrate reasons for the increased sensitivity of HPV-positive cancers of the oropharynx. METHODS: Radiation response including clonogenic survival, apoptosis, DNA double-strand break (DSB) repair, and cell cycle redistribution in four HPV-positive (UM-SCC-47, UM-SCC-104, 93-VU-147T, UPCI:SCC152) and four HPV-negative (UD-SCC-1, UM-SCC-6, UM-SCC-11b, UT-SCC-33) cell lines was evaluated. RESULTS: HPV-positive cells were more radiosensitive (mean SF2: 0.198 range: 0.22-0.18) than HPV-negative cells (mean SF2: 0.34, range: 0.45-0.27; p = 0.010). Irradiated HPV-positive cell lines progressed faster through S-phase showing a more distinct accumulation in G2/M. The abnormal cell cycle checkpoint activation was accompanied by a more pronounced increase of cell death after x-irradiation and a higher number of residual and unreleased DSBs. CONCLUSIONS: The enhanced responsiveness of HPV-related HNSCC to radiotherapy might be caused by a higher cellular radiosensitivity due to cell cycle dysregulation and impaired DNA DSB repair.

Stereotactic radiosurgery for treatment of brain metastases. A report of the DEGRO Working Group on Stereotactic Radiotherapy.

BACKGROUND: This report from the Working Group on Stereotaktische Radiotherapie of the German Society of Radiation Oncology (Deutsche Gesellschaft für Radioonkologie, DEGRO) provides recommendations for the use of stereotactic radiosurgery (SRS) on patients with brain metastases. It considers existing international guidelines and details them where appropriate. RESULTS AND DISCUSSION: The main recommendations are: Patients with solid tumors except germ cell tumors and small-cell lung cancer with a life expectancy of more than 3 months suffering from a single brain metastasis of less than 3 cm in diameter should be considered for SRS. Especially when metastases are not amenable to surgery, are located in the brain stem, and have no mass effect, SRS should be offered to the patient. For multiple (two to four) metastases--all less than 2.5 cm in diameter--in patients with a life expectancy of more than 3 months, SRS should be used rather than whole-brain radiotherapy (WBRT). Adjuvant WBRT after SRS for both single and multiple (two to four) metastases increases local control and reduces the frequency of distant brain metastases, but does not prolong survival when compared with SRS and salvage treatment. As WBRT carries the risk of inducing neurocognitive damage, it seems reasonable to withhold WBRT for as long as possible. CONCLUSION: A single (marginal) dose of 20 Gy is a reasonable choice that balances the effect on the treated lesion (local control, partial remission) against the risk of late side effects (radionecrosis). Higher doses (22-25 Gy) may be used for smaller (< 1 cm) lesions, while a dose reduction to 18 Gy may be necessary for lesions greater than 2.5-3 cm. As the infiltration zone of the brain metastases is usually small, the GTV-CTV (gross tumor volume-clinical target volume) margin should be in the range of 0-1 mm. The CTV-PTV (planning target volume) margin depends on the treatment technique and should lie in the range of 0-2 mm. Distant brain recurrences fulfilling the aforementioned criteria can be treated with SRS irrespective of previous WBRT.

Effective bridging strategies prior to infusion with tisagenlecleucel results in high response rates and long-term remission in relapsed/refractory large B-cell lymphoma: findings from a German monocentric study.

BACKGROUND: Incorporating chimeric antigen receptor (CAR)-T cell therapy into relapsed or refractory large B-cell lymphoma (rr LBCL) treatment algorithms has yielded remarkable response rates and durable remissions, yet a substantial portion of patients experience progression or relapse. Variations in outcomes across treatment centers may be attributed to different bridging strategies and remission statuses preceding CAR-T cell therapy. PATIENTS: Twenty-nine consecutive adult patients receiving tisagenlecleucel (tisa-cel) for rr LBCL from December 2019 to February 2023 at Jena University Hospital were analyzed. RESULTS: The median age was 63, with a median of 3 prior treatments. Twenty patients (69%) were refractory to any systemic therapy before CAR-T cell treatment. Following leukapheresis, 25 patients (86%) received bridging therapy with the majority undergoing chemotherapy (52%) or combined modality therapy (32%). Radiotherapy (RT) was part of the bridging strategy in 44%, with moderately hypofractionated involved site RT (30.0 Gy/2.5 Gy) being applied most frequently (64%). Post-CAR-T infusion, the objective response rate at 30 days was 83%, with 55% achieving complete response. Twelve-month progression-free (PFS) and overall survival (OS) were 60% and 74%, respectively, with a median follow up of 11.1 months for PFS and 17.9 months for OS. Factors significantly associated with PFS were chemotherapy sensitivity pre-leukapheresis and response to bridging. CONCLUSION: The study underscores the importance of minimal tumor burden at CAR-T initiation, emphasizing the need for suitable bridging regimens. The findings advocate for clinical trials and further real-world analyses to optimize CAR-T cell therapy outcomes by identifying the most effective bridging strategies.

The Safety and Efficacy of the Combination of Sacituzumab Govitecan and Palliative Radiotherapy-A Retrospective Multi-Center Cohort Study.

Sacituzumab govitecan (SG) is a new treatment option for patients with metastatic triple-negative and hormone receptor-positive, HER2-negative breast cancer. This antibody-drug conjugate is currently approved as monotherapy. Palliative radiotherapy is frequently used to treat symptomatic metastases locally. Concurrent use of SG and irradiation was excluded in clinical trials of SG, and there are currently limited published data. We report here a systematic review, as well as a retrospective multi-center study of 17 patients with triple-negative breast cancer who received concurrent SG and radiotherapy. In these patients, concurrent use was found to be efficient, safe and well tolerated. There were no apparent differences in moderate or severe acute toxicity according to the timing of SG administration.

Re-evaluation of the prospective risk analysis for artificial-intelligence driven cone beam computed tomography-based online adaptive radiotherapy after one year of clinical experience.

Cone-beam computed tomography (CBCT)-based online adaptation is increasingly being introduced into many clinics. Upon implementation of a new treatment technique, a prospective risk analysis is required and enhances workflow safety. We conducted a risk analysis using Failure Mode and Effects Analysis (FMEA) upon the introduction of an online adaptive treatment programme (Wegener et al., Z Med Phys. 2022). A prospective risk analysis, lacking in-depth clinical experience with a treatment modality or treatment machine, relies on imagination and estimates of the occurrence of different failure modes. Therefore, we systematically documented all irregularities during the first year of online adaptation, namely all cases in which quality assurance detected undesired states potentially leading to negative consequences. Additionally, the quality of automatic contouring was evaluated. Based on those quantitative data, the risk analysis was updated by an interprofessional team. Furthermore, a hypothetical radiation therapist-only workflow during adaptive sessions was included in the prospective analysis, as opposed to the involvement of an interprofessional team performing each adaptive treatment. A total of 126 irregularities were recorded during the first year. During that time period, many of the previously anticipated failure modes (almost) occurred, indicating that the initial prospective risk analysis captured relevant failure modes. However, some scenarios were not anticipated, emphasizing the limits of a prospective risk analysis. This underscores the need for regular updates to the risk analysis. The most critical failure modes are presented together with possible mitigation strategies. It was further noted that almost half of the reported irregularities applied to the non-adaptive treatments on this treatment machine, primarily due to a manual plan import step implemented in the institution's workflow.

Radiomics-based prediction of local control in patients with brain metastases following postoperative stereotactic radiotherapy.

BACKGROUND: Surgical resection is the standard of care for patients with large or symptomatic brain metastases (BMs). Despite improved local control after adjuvant stereotactic radiotherapy, the risk of local failure (LF) persists. Therefore, we aimed to develop and externally validate a pre-therapeutic radiomics-based prediction tool to identify patients at high LF risk. METHODS: Data were collected from A Multicenter Analysis of Stereotactic Radiotherapy to the Resection Cavity of Brain Metastases (AURORA) retrospective study (training cohort: 253 patients from two centers; external test cohort: 99 patients from five centers). Radiomic features were extracted from the contrast-enhancing BM (T1-CE MRI sequence) and the surrounding edema (FLAIR sequence). Different combinations of radiomic and clinical features were compared. The final models were trained on the entire training cohort with the best parameter set previously determined by internal 5-fold cross-validation and tested on the external test set. RESULTS: The best performance in the external test was achieved by an elastic net regression model trained with a combination of radiomic and clinical features with a concordance index (CI) of 0.77, outperforming any clinical model (best CI: 0.70). The model effectively stratified patients by LF risk in a Kaplan-Meier analysis (p < 0.001) and demonstrated an incremental net clinical benefit. At 24 months, we found LF in 9% and 74% of the low and high-risk groups, respectively. CONCLUSIONS: A combination of clinical and radiomic features predicted freedom from LF better than any clinical feature set alone. Patients at high risk for LF may benefit from stricter follow-up routines or intensified therapy.

Quality of life after stereotactic radiotherapy for meningioma: a prospective non-randomized study.

Stereotactic radiotherapy (SRT) is well-established in the treatment of meningiomas offering high local control with low toxicity. However, the impact of SRT on quality of life (QoL) of patients remains largely unknown. This work aimed to prospectively evaluate QoL (longitudinal analysis) during and after SRT of meningiomas. We performed a single center, one-armed, prospective non-randomized study to assess QoL before and at the end of SRT (median fraction dose: 1.8 Gy; median cumulative dose: 54.0 Gy) and furthermore biannually until 24 months after SRT with the "medical outcome study short form 36". This questionnaire evaluates 8 health parameters summarized in "physical component scale" (PCS) and "mental component scale" (MCS). Between 2005 and 2007, 67 patients were enrolled and treated with SRT. 42/52 patients underwent previous operations and 10/52 primary SRT. Complete follow-up data were available from 44 patients. Compared to the german normal population (GNP) a general decrease in the mean values of all parameters was observed. After SRT mean values still declined and 12 months after SRT all parameters normalized towards their initial values. The cohort (previous operations) had better values for MCS (p = 0.004). The cohort (primary SRT) had worse values for PCS that increased asymptotically 6 months after SRT to values of cohort (previous operations) (p = 0.054). Gender, age and tumor related symptoms did not affect QoL according to MCS and PCS (p > 0.05). Local control was 98 %. Treatment was well tolerated and no severe side effects were observed. Patients with meningiomas have an impaired QoL compared to GNP. The QoL assessment after SRT revealed three phases: "depressive phase", "recovery phase" and "normalization phase". Patients treated with primary SRT developed a stable increase of the mean values for PCS. Gender, age, applied dose, symptomatology did not affect QoL.