The optimal treatment strategy for low-grade glioma (LGG) is still a matter of controversy. Considering that the prognosis is typically favorable, the prevention of late sequelae is of particular importance. Proton beam therapy (PRT) has the potential to further reduce the burden of treatment related side effects. We set out to evaluate the clinical outcome of proton irradiation with a particular focus on morphologic features on magnetic resonance imaging (MRI). We assessed prospectively 110 patients who received radiotherapy with protons for histologically proven LGG. Clinical and radiological information were analyzed resulting in more than 1200 available MRI examinations with a median follow-up of 39 months. Newly diagnosed contrast-enhancing lesions on MRI were delineated and correlated with parameters of the corresponding treatment plan. A voxel-based dose-matched paired analysis of the linear energy transfer (LET) inside vs outside lesions was performed. Proton beam irradiation of patients with low-grade glioma results in overall survival (OS) of 90% after seven years. Median progression free survival had not yet been reached with surviving fraction of 54% after seven years. The incidence of temporary or clinically silent radiation induced contrast enhancement was significantly higher than previously assumed, however, symptomatic radiation necrosis was only detected in one patient. These radiation-induced contrast-enhancing lesions were almost exclusively seen at the distal beam end of the proton beam. In 22 out of 23 patients, the average LET of voxels inside contrast-enhancing lesions was significantly increased, compared to dose-matched voxels outside the lesions. Symptomatic radiation necrosis following PRT was as rare as conventional photon-based treatment series suggest. However, the increased incidence of asymptomatic radiation-induced brain injuries with an increased average LET observed in this cohort provides strong clinical evidence to support the hypothesis that the relative biological effectiveness of protons is variable and different to the fixed factor of 1.1 currently used worldwide.

There are already numerous reports about high local control rates in patients with craniopharyngioma but there are only few studies with follow up times of more than 10 years. This study is an analysis of long term control, tumor response and side effects after fractionated stereotactic radiotherapy (FSRT) for patients with craniopharyngioma. 55 patients who were treated with FSRT for craniopharyngioma were analyzed. Median age was 37 years (range 6–70 years), among them eight children < 18 years. Radiotherapy (RT) was indicated for progressive disease after neurosurgical resection or postoperatively after repeated resection or partial resection. A median dose of 52.2 Gy (50 – 57.6 Gy) was applied with typical dose per fraction of 1.8 Gy five times per week. The regular follow up examinations comprised in addition to contrast enhanced MRI scans thorough physical examinations and clinical evaluation. During median follow up of 128 months (2 – 276 months) local control rate was 95.3% after 5 years, 92.1% after 10 years and 88.1% after 20 years. Overall survival after 10 years was 83.3% and after 20 years 67.8% whereby none of the deaths were directly attributed to craniopharyngioma. Overall treatment was tolerated well with almost no severe acute or chronic side effects. One patient developed complete anosmia, another one’s initially impaired vision deteriorated further. In 83.6% of the cases with radiological follow up a regression of irradiated tumor residues was monitored, in 7 cases complete response was achieved. 44 patients presented themselves initially with endocrinologic dysfunction none of them showed signs of further deterioration during follow up. No secondary malignancies were observed. Long term results for patients with craniopharyngioma after stereotactic radiotherapy are with respect to low treatment related side effects as well as to local control and overall survival excellent.

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.

(1) Background: Selecting patients that will benefit the most from proton radiotherapy (PRT) is of major importance. This study sought to assess dose reductions to numerous organs-at-risk (OARs) with PRT, as compared to three-dimensional conformal radiotherapy (3DCRT) and volumetric-modulated arc therapy (VMAT), as a function of tumor location. (2) Materials/Methods: Patients with intracranial neoplasms (all treated with PRT) were stratified into five location-based groups (frontal, suprasellar, temporal, parietal, posterior cranial fossa; n = 10 per group). Each patient was re-planned for 3DCRT and intensity-modulated radiotherapy (IMRT) using similar methodology, including the originally planned target and organ-at-risk (OAR) dose constraints. (3) Results: In parietal tumors, PRT showed the most pronounced dose reductions. PRT lowered doses to nearly every OAR, most notably the optical system and several contralateral structures (subventricular zone, thalamus, hippocampus). For frontal lobe cases, the greatest relative dose reductions in mean dose (D_mean) with PRT were to the infratentorial normal brain, contralateral hippocampus, brainstem, pituitary gland and contralateral optic nerve. For suprasellar lesions, PRT afforded the greatest relative D_mean reductions to the infratentorial brain, supratentorial brain, and the whole brain. Similar results could be observed in temporal and posterior cranial fossa disease. (4) Conclusions: The effectiveness and degree of PRT dose-sparing to various OARs depends on intracranial tumor location. These data will help to refine selection of patients receiving PRT, cost-effectiveness, and future clinical toxicity assessment.

The first hospital-based treatment facilities for particle therapy started operation about thirty years ago. Since then, the clinical experience with protons and carbon ions has grown continuously and more than 200,000 patients have been treated to date. The promising clinical results led to a rapidly increasing number of treatment facilities and many new facilities are planned or under construction all over the world. An inverted depth–dose profile combined with potential radiobiological advantages make charged particles a precious tool for the treatment of tumours that are particularly radioresistant or located nearby sensitive structures. A rising number of trials have already confirmed the benefits of particle therapy in selected clinical situations and further improvements in beam delivery, image guidance and treatment planning are expected. This review summarises some physical and biological characteristics of accelerated charged particles and gives some examples of their clinical application. Furthermore, challenges and future perspectives of particle therapy will be discussed.

The rapid rise of particle therapy across the world necessitates evidence to justify its ever-increasing utilization. This narrative review summarizes the current status of these technologies on treatment of both meningiomas and gliomas, the most common benign and malignant primary brain tumors, respectively. Proton beam therapy (PBT) for meningiomas displays high rates of long-term local control, low rates of symptomatic deterioration, along with the potential for safe dose-escalation in select (but not necessarily routine) cases. PBT is also associated with low adverse events and maintenance of functional outcomes, which have implications for quality of life and cost-effectiveness measures going forward. Data on carbon ion radiation therapy (CIRT) are limited; existing series describe virtually no high-grade toxicities and high local control. Regarding the few available data on low-grade gliomas, PBT provides opportunities to dose-escalate while affording no increase of severe toxicities, along with maintaining appropriate quality of life. Although dose-escalation for low-grade disease has been less frequently performed than for glioblastoma, PBT and CIRT continue to be utilized for the latter, and also have potential for safer re-irradiation of high-grade gliomas. For both neoplasms, the impact of superior dosimetric profiles with endpoints such as neurocognitive decline and neurologic funcionality, are also discussed to the extent of requiring more data to support the utility of particle therapy. Caveats to these data are also described, such as the largely retrospective nature of the available studies, patient selection, and heterogeneity in patient population as well as treatment (including mixed photon/particle treatment). Nevertheless, multiple prospective trials (which may partially attenuate those concerns) are also discussed. In light of the low quantity and quality of available data, major questions remain regarding economic concerns as well.