To create a digital, online atlas for organs at risk (OAR) delineation in neuro-oncology based on high-quality computed tomography (CT) and magnetic resonance (MR) imaging. CT and 3 Tesla (3T) MR images (slice thickness 1 mm with intravenous contrast agent) were obtained from the same patient and subsequently fused. In addition, a 7T MR without intravenous contrast agent was obtained from a healthy volunteer. Based on discussion between experienced radiation oncologists, the clinically relevant organs at risk (OARs) to be included in the atlas for neuro-oncology were determined, excluding typical head and neck OARs previously published. The draft atlas was delineated by a senior radiation oncologist, 2 residents in radiation oncology, and a senior neuro-radiologist incorporating relevant available literature. The proposed atlas was then critically reviewed and discussed by European radiation oncologists until consensus was reached. The online atlas includes one CT-scan at two different window settings and one MR scan (3T) showing the OARs in axial, coronal and sagittal view. This manuscript presents the three-dimensional descriptions of the fifteen consensus OARs for neuro-oncology. Among these is a new OAR relevant for neuro-cognition, the posterior cerebellum (illustrated on 7T MR images). In order to decrease inter- and intra-observer variability in delineating OARs relevant for neuro-oncology and thus derive consistent dosimetric data, we propose this atlas to be used in photon and particle therapy. The atlas is available online at www.cancerdata.org and will be updated whenever required.

To update the digital online atlas for organs at risk (OARs) delineation in neuro-oncology based on high-quality computed tomography (CT) and magnetic resonance (MR) imaging with new OARs. In this planned update of the neurological contouring atlas published in 2018, ten new clinically relevant OARs were included, after thorough discussion between experienced neuro-radiation oncologists (RTOs) representing 30 European radiotherapy-oncology institutes. Inclusion was based on daily practice and research requirements. Consensus was reached for the delineation after critical review. Contouring was performed on registered CT with intravenous (IV) contrast (soft tissue & bone window setting) and 3 Tesla (T) MRI (T1 with gadolinium & T2 FLAIR) images of one patient (1 mm slices). For illustration purposes, delineation on a 7T MRI without IV contrast from a healthy volunteer was added. OARs were delineated by three experienced RTOs and a neuroradiologist based on the relevant literature. The presented update of the neurological contouring atlas was reviewed and approved by 28 experts in the field. The atlas is available online and includes in total 25 OARs relevant to neuro-oncology, contoured on CT and MRI T1 and FLAIR (3T & 7T). Three-dimensional (3D) rendered films are also available online. In order to further decrease inter- and intra-observer OAR delineation variability in the field of neuro-oncology, we propose the use of this contouring atlas in photon and particle therapy, in clinical practice and in the research setting. The updated atlas is freely available on www.cancerdata.org.

In this multicentric in silico trial we compared photon, proton, and carbon-ion radiotherapy plans for re-irradiation of patients with squamous cell carcinoma of the head and neck (HNSCC) regarding dose to tumour and doses to surrounding organs at risk (OARs). Twenty-five HNSCC patients with a second new or recurrent cancer after previous irradiation (70Gy) were included. Intensity-modulated proton therapy (IMPT) and ion therapy (IMIT) re-irradiation plans to a second subsequent dose of 70Gy were compared to photon therapy delivered with volumetric modulated arc therapy (VMAT). When comparing IMIT and IMPT to VMAT, the mean dose to all investigated 22 OARs was significantly reduced for IMIT and to 15 out of 22 OARs (68%) using IMPT. The maximum dose to 2% volume (D2) of the brainstem and spinal cord were significantly reduced using IMPT and IMIT compared to VMAT. The data are available on www.cancerdata.org. In this ROCOCO in silico trial, a reduction in mean dose to OARs was achieved using particle therapy compared to photons in the re-irradiation of HNSCC. There was a dosimetric benefit favouring carbon-ions above proton therapy. These dose reductions may potentially translate into lower severe complication rates related to the re-irradiation.

Glioblastoma (GBM) is the most malignant primary brain tumor for which no curative treatment options exist. Non-invasive qualitative (Visually Accessible Rembrandt Images (VASARI)) and quantitative (radiomics) imaging features to predict prognosis and clinically relevant markers for GBM patients are needed to guide clinicians. A retrospective analysis of GBM patients in two neuro-oncology centers was conducted. The multimodal Cox-regression model to predict overall survival (OS) was developed using clinical features with VASARI and radiomics features in isocitrate dehydrogenase (IDH)-wild type GBM. Predictive models for IDH-mutation, 06-methylguanine-DNA-methyltransferase (MGMT)-methylation and epidermal growth factor receptor (EGFR) amplification using imaging features were developed using machine learning. The performance of the prognostic model improved upon addition of clinical, VASARI and radiomics features, for which the combined model performed best. This could be reproduced after external validation (C-index 0.711 95% CI 0.64–0.78) and used to stratify Kaplan–Meijer curves in two survival groups (p-value < 0.001). The predictive models performed significantly in the external validation for EGFR amplification (area-under-the-curve (AUC) 0.707, 95% CI 0.582–8.25) and MGMT-methylation (AUC 0.667, 95% CI 0.522–0.82) but not for IDH-mutation (AUC 0.695, 95% CI 0.436–0.927). The integrated clinical and imaging prognostic model was shown to be robust and of potential clinical relevance. The prediction of molecular markers showed promising results in the training set but could not be validated after external validation in a clinically relevant manner. Overall, these results show the potential of combining clinical features with imaging features for prognostic and predictive models in GBM, but further optimization and larger prospective studies are warranted.

Maintenance of quality of life is the primary goal during treatment of brain metastases (BM). This is a protocol of an ongoing phase III randomised multicentre study. This study aims to determine the exact additional palliative value of stereotactic radiosurgery (SRS) over whole brain radiotherapy (WBRT) in patients with 4–10 BM. The study will include patients with 4–10 BM from solid primary tumours diagnosed on a high-resolution contrast-enhanced MRI scan with a maximum lesional diameter of 2.5 cm in any direction and a maximum cumulative lesional volume of 30 cm3. Patients will be randomised between WBRT in five fractions of 4 Gy to a total dose of 20 Gy (standard arm) and single dose SRS to the BMs (study arm) in the range of 15–24 Gy. The largest BM or a localisation in the brainstem will determine the prescribed SRS dose. The primary endpoint is difference in quality of life (EQ5D EUROQOL score) at 3 months after radiotherapy with regard to baseline. Secondary endpoints are difference in quality of life (EQ5D EUROQOL questionnaire) at 6, 9 and 12 months after radiotherapy with regard to baseline. Other secondary endpoints are at 3, 6, 9 and 12 months after radiotherapy survival, Karnofsky ≥ 70, WHO performance status, steroid use (mg), toxicity according to CTCAE V4.0 including hair loss, fatigue, brain salvage during follow-up, type of salvage, time to salvage after randomisation and Barthel index. Facultative secondary endpoints are neurocognition with the Hopkins verbal learning test revised, quality of life EORTC QLQ-C30, quality of life EORTC BN20 brain module and fatigue scale EORTC QLQ-FA13. Worldwide, most patients with more than 4 BM will be treated with WBRT. Considering the potential advantages of SRS over WBRT, i.e. limiting radiation doses to uninvolved brain and a high rate of local tumour control by just a single treatment with fewer side effects, such as hair loss and fatigue, compared to WBRT, SRS might be a suitable alternative for patients with 4–10 BM. Trial registration number: NCT02353000 , trial registration date 15th January 2015, open for accrual 1st July 2016, nine patients were enrolled in this trial on 14th April 2017.

Purpose. To discuss several pertinent issues related to shoot-through FLASH proton therapy based on an illustrative case. Methods. We argue that with the advent of FLASH proton radiotherapy and due to the issues associated with conventional proton radiotherapy regarding the uncertainties of positioning of the Bragg peaks, the difficulties of in vivo verification of the dose distribution, the use of treatment margins and the uncertainties surrounding linear energy transfer (LET) and relative biological effectiveness (RBE), a special mode of shoot-through FLASH proton radiotherapy should be investigated. In shoot-through FLASH, the proton beams have sufficient energy to reach the distal exit side of the patient. Due to the FLASH sparing effect of normal tissues at both the proximal and distal side of tumors, radiotherapy plans can be developed that meet current planning constraints and issues regarding RBE can be avoided. Results. A preliminary proton plan for a neurological tumor in close proximity to various organs at risk (OAR) with strict dose constraints was studied. A plan with four beams mostly met the constraints for the OAR, using a treatment planning system that was not optimized for this novel treatment modality. When new treatment planning algorithms would be developed for shoot-through FLASH, constraints would be easier to meet. The shoot-through FLASH plan led to a significant effective dose reduction in large parts of the healthy tissue. The plan had no uncertainties associated to Bragg peak positioning, needed in principle no large proximal or distal margins and LET increases near the Bragg peak became irrelevant. Conclusion. Shoot-through FLASH proton radiotherapy may be an interesting treatment modality to explore further. It would remove some of the current sources of uncertainty in proton radiotherapy. An additional advantage could be that portal dosimetry may be possible with beams penetrating the patient and impinging on a distally placed imaging detector, potentially leading to a practical treatment verification method. With current proton accelerator technology, trials could be conducted for neurological, head&neck and thoracic cancers. For abdominal and pelvic cancer a higher proton energy would be required.