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Treatment-related toxicity after irradiation of brain tumours has been underreported in the literature. Furthermore, there is considerable heterogeneity on how and when toxicity is evaluated. The aim of this European Particle Network (EPTN) collaborative project is to develop recommendations for uniform follow-up and toxicity scoring of adult brain tumour patients treated with radiotherapy. A Delphi method-based consensus was reached among 24 international radiation-oncology experts in the field of neuro-oncology concerning the toxicity endpoints, evaluation methods and time points. In this paper, we present a basic framework for consistent toxicity scoring and follow-up, using multiple levels of recommendation. Level I includes all recommendations that are considered minimum of care, whereas level II and III are optional evaluations in the advanced clinical or research setting, respectively. Per outcome domain, the clinical endpoints and evaluation methods per level are listed. Where relevant, the organ at risk threshold doses for recommended referral to specific organ specialists are defined. These consensus-based recommendations for follow-up will enable the collection of uniform toxicity data of brain tumour patients treated with radiotherapy. With adoptation of this standard, collaboration will be facilitated and we can further propel the research field of radiation-induced toxicities relevant for these patients. An online tool to implement this guideline in clinical practice is provided at www.cancerdata.org.

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 7 T 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 (3 T & 7 T). 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.

Background: Symptom management in conjunction with proton beam therapy (PBT) from patient's perspective has not been explored. Such knowledge is essential to optimize the care in this relatively new treatment modality. Objective: The aim of this study was to explore the process of symptom management in patients with brain tumor receiving PBT. Methods: Participants were 22 patients with primary brain tumor who received PBT, recruited in collaboration with a national center for proton therapy and 2 oncology clinics at 2 university hospitals in Sweden. Interviews using open-ended questions were conducted before, during, and/or after treatment. Verbatim interview transcripts were analyzed using classic Grounded Theory. Results: "The art of living with symptoms" emerged as the core concept. This encompassed 3 interconnected symptom management concepts: "Adapting to limited ability," "Learning about oneself," and "Creating new routines." These concepts were summarized in a substantive theoretical model of symptom management. Despite the struggle to manage symptoms, participants lived a satisfactory life. Conclusions: Symptom management in conjunction with PBT comprises a process of action, thoughts, and emotions. The concepts that emerged indicated patients' symptom management strategies were based on their own resources. Implications for Practice: It is important that PBT facilities develop an approach that facilitates the symptom management process based on patients' experiences of symptoms, as well as their actions and available resources.

For adult patients with diffuse low-grade glioma (LGG) proton therapy is an emerging radiotherapy modality. The number of proton facilities is rapidly increasing. However, there is a shortage of published data concerning the clinical effectiveness compared to photon radiotherapy and potential proton-specific toxicity. This study aimed to systematically review and summarize the relevant literature on proton therapy for adult LGG patients, including dosimetric comparisons, the type and frequency of acute and long-term toxicity and the clinical effectiveness. A systematic search was performed in several medical databases and 601 articles were screened for relevance. Nine articles were deemed eligible for in-depth analysis using a standardized data collection form by two independent researchers. Proton treatment plans compared favorably to photon-plans regarding dose to uninvolved neural tissue. Fatigue (27-100%), alopecia (37-85%), local erythema (78-85%) and headache (27-75%) were among the most common acute toxicities. One study reported no significant long-term cognitive impairments. Limited data was available on long-term survival. One study reported a 5-year overall survival of 84% and 5-year progression-free survival of 40%. We conclude that published data from clinical studies using proton therapy for adults with LGG are scarce. As the technique becomes more available, controlled clinical studies are urgently warranted to determine if the potential benefits based on comparative treatment planning translate into clinical benefits.

Purpose: To create a digital, online atlas for organs at risk (OAR) delineation in neuro-oncology based on high-quality computed tomography (Cr) and magnetic resonance (MR) imaging. Methods: 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. Results: 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). Conclusion: 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 w.cancerdata.c and will be updated whenever required.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Craniopharyngiomas are histologically benign but locally aggressive tumors in the sellar region that may cause devastating neurological and endocrine deficits. They tend to recur following surgery with high morbidity; hence, postoperative radiotherapy is recommended following sub-total resection. BRAFV600E mutation is the principal oncogenic driver in the papillary variant of craniopharyngiomas. Recently, a dramatic tumor reduction has been reported in a patient with BRAFV600E mutated, multiply recurrent papillary craniopharyngioma using a combination therapy of BRAF inhibitor dabrafenib and MEK inhibitor trametinib. Here, we report on near-radical reduction of a growing residual BRAFV600E craniopharyngioma using the same neoadjuvant therapy.

Purpose: To determine the inter-observer variation in delineating the coronary arteries as organs at risk (OAR) in breast cancer (BC) radiotherapy (RT) and how this variation affects the estimated coronary artery radiation dose. Method: Delineation of the left main and the left anterior descending coronary artery (LMCA and LAD), and the right coronary artery (RCA), by using the heart atlas by Feng et al., was performed by three radiation oncologists in 32 women who had received adjuvant RT for BC. Centres of the arteries were calculated and distances between artery centres were measured and the artery radiation doses were estimated. The intraclass correlation coefficient (ICC) was used to quantify the variability in doses. Results: Along the extent of RCA, the median distance between centres of arteries varied from 2 to 9 mm with similar patterns over pairs of oncologists. For the LMCA-LAD the median distance varied from 1 to 4 mm. The estimated maximum radiation doses showed an ICC variation from 0.82 to 0.97. Conclusion: The coronary arteries can be reliably identified and delineated as OARs in BC RT. The spatial variance is limited and the total variation in radiation dose is almost completely determined by the between patient variation.

Background: Women irradiated for left-sided breast cancer (BC) have an increased risk of coronary artery disease compared to women with right-sided BC. We describe the distribution of radiation dose in segments of coronary arteries in women receiving adjuvant radiotherapy (RT) for left- or right-sided BC.Material and methods: Fifteen women with BC, seven left-sided and eight right-sided, who had received three-dimensional conformal radiotherapy (3DCRT), constituted the study base. The heart and the segments of the coronary arteries were defined as separate organs at risk (OAR), and the mean and maximum radiation doses were calculated for each OAR.Results: In women with left-sided BC, irrespective of if regional lymph node RT was given or not, maximum dose in mid and distal left anterior descending artery (mdLAD) was approximately 50Gy in 6/7 patients, whereas women with right-sided BC mainly received low doses of radiation. In women with left-sided BC, 6/7 patients had substantially higher mean dose to the distal LAD than to the heart, ranging from 30 to 55Gy and 3 to13Gy, respectively.Conclusion: We found a pronounced difference of radiation dose distribution in the coronary arteries between women with left- and right-sided BC. Women with left-sided BC had almost full treatment dose in parts of mdLAD, regardless of if regional lymph node irradiation was given or not, while women with right-sided BC mainly received low doses to the coronary arteries.

Objectives: To assess the interaction between comorbidity and breast cancer (BC) on the rate of venous thromboembolism (VTE) beyond what can be explained by the independent effects of BC and comorbidity. Design: Population-based matched cohort study. Setting: Denmark. Participants: Danish patients with BC (n=62 376) diagnosed in 1995-2010 and a comparison cohort of women without BC (n=304 803) from the general population were matched to the patients with BC on year of birth in 5-year intervals and on the specific diseases included in the Charlson Comorbidity Index (CCI) and atrial fibrillation and obesity. Measures: The rate ratios of VTE per 1000 person-years (PY) were computed by comorbidity levels using the CCI, and interaction contrasts (IC) were calculated as a measure of the excess or deficit VTE rate not explained by the independent effects of BC and comorbidity. Results: Among patients with BC with a CCI score of 1, the 0-1 year VTE rate was 12/1000 PY, and interaction accounted for 10% of the rate (IC=3.2, 95% CI 0.5 to 5.9). Among patients with BC with CCI >= 4, the VTE rate was 17, and interaction accounted for 8% of the rate (IC=1.2, 95% CI -1.8 to 4.2). There was no interaction during 2-5 years of follow-up. Conclusions: There was only little interaction between BC and the CCI score on the rate of VTE.