[en] In addition to local tumor control, the aim of any curative radio-oncological treatment is to maintain quality of life. In the treatment of patients with meningioma with a close relationship to optical structures, the preservation of visual performance is a particular challenge. Use of proton therapy can reduce the dose burden to organs at risk immediately adjacent to the tumor. The aim of this study was to score the subjective assessment of visual performance in patients with meningioma involving the optical structures before and after proton therapy. All proton-treated patients with meningioma WHO I whose planning target volumes (PTV) included parts of the optic nerve and/or chiasm were included in this study. Subjective assessment of visual performance was evaluated using the Visual Disorder Scale (VDS) of the EORTC QLQ-BN20 questionnaire. This scale includes values from 0 to 100, whereby high values reflect a high degree of subjective symptom burden and thus subjective visual impairment. The visual acuity in externally performed eye tests at baseline and follow-ups (FU) was also evaluated. The timepoints for testing were before the start of radiotherapy, at the end of treatment, and 3, 6, 12, and 24 months in FU (times t1-t6). All patients with at least the first annual postradiation FU at the time of the evaluation were included. The correlation between VDS changes and potential influencing factors such as previous therapies, dosimetric data, initial tumor volume, and tumor shrinkage 1 year after treatment was assessed. A total of 56 patients (45 female/11 male) aged 24-82 years (mean ± SD = 53.9 ± 13.3) treated between March 2017 and September 2019 were included in the analysis. The prescription dose was 54.0 Gy (RBE) with active scanned proton therapy. The mean/D2% dose ± SD for the optic chiasm and ipsilateral optic nerve was 43.4 ± 8.9 Gy (RBE)/49.9 ± 7.1 Gy (RBE) and 35.6 ± 11.7 Gy (RBE)/51.7 ± 4.8 Gy (RBE); the mean/D2% dose ± SD of the contralateral optic nerve was 18.8 ± 12.1 Gy (RBE)/42.4 ± 14.6 Gy (RBE), respectively. A total of 302 data collections were available (t1/t2/t3/t4/t5/t6: n = 56/56/48/56/52/34). Median observation time was 23.6 months. Mean symptom burden decreased over time (mean VDS: t1 29.8 ± 27.9; t2 25.0 ± 27.9; t3 21.8 ± 26.0; t4 22.2 ± 26.0; t5 21.4 ± 26.2; t6 17.3 ± 23.6) with statistically significant improvement at 3- and 6-month FU as well as 1 year after proton therapy (p = 0.0205; p = 0.0187; p = 0.0054). Objective eye tests available in 41/52 patients confirm the trend towards improved visual acuity (97.5% stable/improved until 24-month FU). However, no potential predictor for VDS changes was revealed. Proton treatment of patients with meningioma WHO I with involvement of optical structures does not impair subjective visual performance. After treatment, there is a significant improvement in perceived visual performance.

[en] New high-precision radiotherapy (RT) techniques, such as intensity-modulated radiation therapy (IMRT) or hadrontherapy, allow better dose distribution within the target and spare a larger portion of normal tissue than conventional RT. These techniques require accurate tumour volume delineation and intrinsic characterization, as well as verification of target localisation and monitoring of organ motion and response assessment during treatment. These tasks are strongly dependent on imaging technologies. Among these, computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography (US) and positron emission tomography (PET) have been applied in high-precision RT. For tumour volume delineation and characterization, PET has brought an additional dimension to the management of cancer patients by allowing the incorporation of crucial functional and molecular images in RT treatment planning, i.e. direct evaluation of tumour metabolism, cell proliferation, apoptosis, hypoxia and angiogenesis. The combination of PET and CT in a single imaging system (PET/CT) to obtain a fused anatomical and functional dataset is now emerging as a promising tool in radiotherapy departments for delineation of tumour volumes and optimization of treatment plans. Another exciting new area is image-guided radiotherapy (IGRT), which focuses on the potential benefit of advanced imaging and image registration to improve precision, daily target localization and monitoring during treatment, thus reducing morbidity and potentially allowing the safe delivery of higher doses. The variety of IGRT systems is rapidly expanding, including cone beam CT and US. This article examines the increasing role of imaging techniques in the entire process of high-precision radiotherapy. (orig.)

[en] CNAO will be a dual center capable of providing therapeutic beams of protons and carbon ions with maximum energy of 400 MeV/u. At the beginning, it will be equipped with three treatment rooms with fixed horizontal and vertical beam lines. In a subsequent phase, two more rooms with a rotating gantry are foreseen. An active spot scanning dose delivery system will be employed. Initially, 80% of the treatments will be carried out with carbon ions. All patients will be treated within clinical trials to assess carbon ion indications with an evidence-based methodology. Seven disease-specific working groups have been developed: lung tumors, liver tumors, sarcomas, head and neck tumors, central nervous system lesions, eye tumors and pediatric tumors. The last two groups will be treated mainly with protons. In the first phase, CNAO will focus on head and neck cancers, treating inoperable, residual or recurrent malignant salivary gland tumors, mucosal melanoma, adenocarcinoma and unfavorably located SCC (nasal and paranasal sinuses). Carbon ions will be employed as a boost in the treatment of locally advanced, poor prognosis, SCC of the hypopharynx and tongue base. Bone and soft tissue sarcomas of the extremity will be treated with a limb-sparing approach, and trunk sarcomas will be treated with exclusive or post-operative irradiation. Skull base tumors (chordoma and chondrosarcoma), recurrent or malignant meningioma and glial tumors will be treated with carbon ions. After sufficient expertise has been gained in coping with organ motion, CNAO will start treating thoracic and abdominal targets. HCC will be treated in inoperable patients with one or more lesions that can be included in a single CTV. Early stage NSCLC will be treated. In the second phase, two more groups on gynecological malignancies and digestive tumors (esophageal cancer, rectal cancer, pancreatic cancer) will be created.

[en] Overexpression of the somatostatin receptor (SSTR) has led to adoption of SSTR PET/CT for diagnosis and radiotherapy planning in meningioma, but data on SSTR expression during follow-up remain scarce. We investigated PET/CT quantifiers of SSTR tracers in WHO grade I meningioma following fractionated proton beam therapy (PBT) compared to standard response assessment with MRI. Twenty-two patients diagnosed with low-grade meningioma treated by PBT were included. Follow-up included clinical visits, MRI, and [${}^{68}$Ga]Ga-DOTATOC PET/CT scans. Radiologic tumor response, MRI and PET volume (V${}_{MRI}$ and V${}_{PET}$), maximum and mean standardied uptake value (SUVmax/SUVmean), total lesion activity (TLA), and heterogeneity index (HI) were evaluated. Median follow-up was 35.3 months (range: 6.4-47.9). Nineteen patients (86.4%, p = 0.0009) showed a decrease of SUVmax between baseline and first follow-up PET/CT (median: -24%, range: -53% to +89%) and in 81.8% of all cases, the SUVmax, SUVmean, and TLA at last follow-up were eventually lower than at baseline (p = 0.0043). Ambiguous trends without significance between the timepoints analyzed were observed for V${}_{PET}$. HI increased between baseline and last follow-up in 75% of cases (p = 0.024). All patients remained radiologically and clinically stable. Median V${}_{MRI}$ decreased by -9.3% (range 0-32.5%, p < 0.0001) between baseline and last follow-up. PET/CT in follow-up of irradiated meningioma showed an early trend towards decreased binding of SSTR-specific tracers following radiation and MRI demonstrated consistently stable or decreasing tumor volume. Translational research is needed to clarify the underlying biology of the subsequent increase in SSTR PET quantifiers.

[en] Purpose: Fatigue is an underevaluated cancer-related and treatment-related symptom. We analyzed fatigue in head and neck cancer patients undergoing radiotherapy (RT). Methods and Materials: A total of 117 patients were enrolled (mean age, 58 years). Radiation therapy (median dose, 66 Gy) was given with either exclusive or postoperative intent in 52 and 65 patients, respectively. Chemotherapy (CT) was added before and/or during RT in 61 patients. The patients completed a 20-item questionnaire (Multidimensional Fatigue Inventory [MFI-20]) before, during (weekly), and after RT. The impact of patient-, tumor-, and treatment-related factors on fatigue was evaluated with unifactorial and multifactorial tests. Results: Fatigue level increased during RT reaching a maximum at Week 6 and then slowly decreased. In multivariate stepwise regression analysis age (inversely related, p < 0.05), psychologic disorders (p < 0.005), and previous head-and-neck surgery (inversely related, p < 0.005) were correlated with higher pre-RT fatigue level. Pre-RT fatigue score (p < 0.0001), induction and/or concomitant CT (p = 0.035), need of cortisone during RT (p = 0.005), and thyroid disorders (p = 0.032) were correlated with higher during-RT fatigue level. Pre-RT fatigue score (p < 0.0001), induction and/or concomitant CT (p < 0.001), and need of cortisone during RT (p < 0.005) were correlated with higher post-RT fatigue level. No impact of gender, performance status, comorbidities other than psychologic and thyroid, tumor stage/site, RT intent, dose, volume, duration, or toxicity was observed. Conclusion: Fatigue affects all patients undergoing RT for head-and-neck cancer, reaches maximum score at the 6th week of RT, and slowly decreases thereafter. Age, thyroid dysfunction, psychologic disorders, pre-RT fatigue score, CT, and cortisone use are correlated with RT-related fatigue levels

[en] To establish a common database on particle therapy for the evaluation of clinical studies integrating a large variety of voluminous datasets, different documentation styles, and various information systems, especially in the field of radiation oncology. We developed a web-based documentation system for transnational and multicenter clinical studies in particle therapy. 560 patients have been treated from November 2009 to September 2011. Protons, carbon ions or a combination of both, as well as a combination with photons were applied. To date, 12 studies have been initiated and more are in preparation. It is possible to immediately access all patient information and exchange, store, process, and visualize text data, any DICOM images and multimedia data. Accessing the system and submitting clinical data is possible for internal and external users. Integrated into the hospital environment, data is imported both manually and automatically. Security and privacy protection as well as data validation and verification are ensured. Studies can be designed to fit individual needs. The described database provides a basis for documentation of large patient groups with specific and specialized questions to be answered. Having recently begun electronic documentation, it has become apparent that the benefits lie in the user-friendly and timely workflow for documentation. The ultimate goal is a simplification of research work, better study analyses quality and eventually, the improvement of treatment concepts by evaluating the effectiveness of particle therapy

[en] A multidisciplinary and multi-institutional working group applied the Failure Mode and Effects Analysis (FMEA) approach to the actively scanned proton beam radiotherapy process implemented at CNAO (Centro Nazionale di Adroterapia Oncologica), aiming at preventing accidental exposures to the patient. FMEA was applied to the treatment planning stage and consisted of three steps: i) identification of the involved sub-processes; ii) identification and ranking of the potential failure modes, together with their causes and effects, using the risk probability number (RPN) scoring system, iii) identification of additional safety measures to be proposed for process quality and safety improvement. RPN upper threshold for little concern of risk was set at 125. Thirty-four sub-processes were identified, twenty-two of them were judged to be potentially prone to one or more failure modes. A total of forty-four failure modes were recognized, 52% of them characterized by an RPN score equal to 80 or higher. The threshold of 125 for RPN was exceeded in five cases only. The most critical sub-process appeared related to the delineation and correction of artefacts in planning CT data. Failures associated to that sub-process were inaccurate delineation of the artefacts and incorrect proton stopping power assignment to body regions. Other significant failure modes consisted of an outdated representation of the patient anatomy, an improper selection of beam direction and of the physical beam model or dose calculation grid. The main effects of these failures were represented by wrong dose distribution (i.e. deviating from the planned one) delivered to the patient. Additional strategies for risk mitigation, easily and immediately applicable, consisted of a systematic information collection about any known implanted prosthesis directly from each patient and enforcing a short interval time between CT scan and treatment start. Moreover, (i) the investigation of dedicated CT image reconstruction algorithms, (ii) further evaluation of treatment plan robustness and (iii) implementation of independent methods for dose calculation (such as Monte Carlo simulations) may represent novel solutions to increase patient safety. FMEA is a useful tool for prospective evaluation of patient safety in proton beam radiotherapy. The application of this method to the treatment planning stage lead to identify strategies for risk mitigation in addition to the safety measures already adopted in clinical practice

[en] Treatment standard for patients with rectal cancer depends on the initial staging and includes surgical resection, radiotherapy as well as chemotherapy. For stage II and III tumors, radiochemotherapy should be performed in addition to surgery, preferentially as preoperative radiochemotherapy or as short-course hypofractionated radiation. Advances in surgical approaches, especially the establishment of the total mesorectal excision (TME) in combination with sophisticated radiation and chemotherapy have reduced local recurrence rates to only few percent. However, due to the high incidence of rectal cancer, still a high absolute number of patients present with recurrent rectal carcinomas, and effective treatment is therefore needed. Carbon ions offer physical and biological advantages. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increase relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the cell line as well as the endpoint analyzed. Japanese data on the treatment of patients with recurrent rectal cancer previously not treated with radiation therapy have shown local control rates of carbon ion treatment superior to those of surgery. Therefore, this treatment concept should also be evaluated for recurrences after radiotherapy, when dose application using conventional photons is limited. Moreover, these patients are likely to benefit from the enhanced biological efficacy of carbon ions. In the current Phase I/II-PANDORA-01-Study the recommended dose of carbon ion radiotherapy for recurrent rectal cancer will be determined in the Phase I part, and feasibilty and progression-free survival will be assessed in the Phase II part of the study. Within the Phase I part, increasing doses from 12 × 3 Gy E to 18 × 3 Gy E will be applied. The primary endpoint in the Phase I part is toxicity, the primary endpoint in the Phase II part is progression-free survival. With conventional photon irradiation treatment of recurrent rectal cancer is limited, and the clinical effect is only moderate. With carbon ions, an improved outcome can be expected due to the physical and biological characteristics of the carbon ion beam. However, the optimal dose applicable in this clincial situation as re-irradiation still has to be determined. This, as well as efficacy, is to be evaluated in the present Phase I/II trial. http://www.clinicaltrials.gov/ct2/show/NCT01528683

[en] PurposeFor unbiased comparison of different radiation modalities and techniques, consensus on delineation of radiation sensitive organs at risk (OARs) and on their dose constraints is warranted. Following the publication of a digital, online atlas for OAR delineation in neuro-oncology by the same group, we assessed the brain OAR-dose constraints in a follow-up study.