Background: 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. Methods: 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. Results: 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 Other significant failure modes consisted of an outdated representation of the patient anatomy, an improper selection of beam direction and of the physical beam model or dose calculation grid.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. Conclusions: 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.

Skull-base chordoma (SBC) can be treated with carbon ion radiotherapy (CIRT) to improve local control (LC). The study aimed to explore the role of multi-parametric radiomic, dosiomic and clinical features as prognostic factors for LC in SBC patients undergoing CIRT. Before CIRT, 57 patients underwent MR and CT imaging, from which tumour contours and dose maps were obtained. MRI and CT-based radiomic, and dosiomic features were selected and fed to two survival models, singularly or by combining them with clinical factors. Adverse LC was given by in-field recurrence or tumour progression. The dataset was split in development and test sets and the models’ performance evaluated using the concordance index (C-index). Patients were then assigned a low- or high-risk score. Survival curves were estimated, and risk groups compared through log-rank tests (after Bonferroni correction α = 0.0083). The best performing models were built on features describing tumour shape and dosiomic heterogeneity (median/interquartile range validation C-index: 0.80/024 and 0.79/0.26), followed by combined (0.73/0.30 and 0.75/0.27) and CT-based models (0.77/0.24 and 0.64/0.28). Dosiomic and combined models could consistently stratify patients in two significantly different groups. Dosiomic and multi-parametric radiomic features showed to be promising prognostic factors for LC in SBC treated with CIRT.

Experimental assessment of inter-centre variation and absolute accuracy of stopping-power-ratio (SPR) prediction within 17 particle therapy centres of the European Particle Therapy Network. A head and body phantom with seventeen tissue-equivalent materials were scanned consecutively at the participating centres using their individual clinical CT scan protocol and translated into SPR with their in-house CT-number-to-SPR conversion. Inter-centre variation and absolute accuracy in SPR prediction were quantified for three tissue groups: lung, soft tissues and bones. The integral effect on range prediction for typical clinical beams traversing different tissues was determined for representative beam paths for the treatment of primary brain tumours as well as lung and prostate cancer. An inter-centre variation in SPR prediction (2σ) of 8.7%, 6.3% and 1.5% relative to water was determined for bone, lung and soft-tissue surrogates in the head setup, respectively. Slightly smaller variations were observed in the body phantom (6.2%, 3.1%, 1.3%). This translated into inter-centre variation of integral range prediction (2σ) of 2.9%, 2.6% and 1.3% for typical beam paths of prostate-, lung- and primary brain-tumour treatments, respectively. The absolute error in range exceeded 2% in every fourth participating centre. The consideration of beam hardening and the execution of an independent HLUT validation had a positive effect, on average. The large inter-centre variations in SPR and range prediction justify the currently clinically used margins accounting for range uncertainty, which are of the same magnitude as the inter-centre variation. This study underlines the necessity of higher standardisation in CT-number-to-SPR conversion.

Background: Purpose of this study is to explore the trade-offs between radio-induced toxicities and second malignant neoplasm (SMN) induction risk of different emerging radiotherapy techniques for Hodgkin’s lymphoma (HL) through a comprehensive dosimetric analysis on a representative clinical model. Methods: Three different planning target volume (PTV_i) scenarios of a female patient with supradiaphragmatic HL were used as models for the purpose of this study. Five treatment radiation techniques were simulated: an anterior-posterior parallel-opposed (AP-PA), a forward intensity modulated (FIMRT), an inverse intensity modulated (IMRT), a Tomotherapy (TOMO), a proton (PRO) technique. A radiation dose of 30 Gy or CGE was prescribed. Dose-volume histograms of PTVs and organs-at-risk (OARs) were calculated and related to available dose-volume constraints. SMN risk for breasts, thyroid, and lungs was estimated through the Organ Equivalent Dose model considering cell repopulation and inhomogeneous organ doses. Results: With similar level of PTV_i coverage, IMRT, TOMO and PRO plans generally reduced the OARs’ dose and accordingly the related radio-induced toxicities. However, only TOMO and PRO plans were compliant with all constraints in all scenarios. For the IMRT and TOMO plans an increased risk of development of breast, and lung SMN compared with AP-PA and FIMRT techniques was estimated. Only PRO plans seemed to reduce the risk of predicted SMN compared with AP-PA technique. Conclusions: Our model–based study supports the use of advanced RT techniques to successfully spare OARs and to reduce the risk of radio-induced toxicities in HL patients. However, the estimated increase of SMNs’ risk inherent to TOMO and IMRT techniques should be carefully considered in the evaluation of a risk-adapted therapeutic strategy.

A fast and accurate dose calculation engine for hadrontherapy is critical for both routine clinical and advanced research applications. FRoG is a graphics processing unit (GPU)-based forward calculation tool developed at CNAO (Centro Nazionale di Adroterapia Oncologica) and at HIT (Heidelberg Ion Beam Therapy Center) for fast and accurate calculation of both physical and biological dose. FRoG calculation engine adopts a triple Gaussian parameterization for the description of the lateral dose distribution. FRoG provides dose, dose-averaged linear energy transfer, and biological dose-maps, -profiles, and -volume-histograms. For the benchmark of the FRoG calculation engine, using the clinical settings available at CNAO, spread-out Bragg peaks (SOBPs) and patient cases for both proton and carbon ion beams have been calculated and compared against FLUKA Monte Carlo (MC) predictions. In addition, FRoG patient-specific quality assurance (QA) has been performed for twenty-five proton and carbon ion fields. As a result, for protons, biological dose values, using a relative biological effectiveness (RBE) of 1.1, agree on average with MC within ~1% for both SOBPs and patient plans. For carbon ions, RBE-weighted dose (D_RBE) agreement against FLUKA is within ~2.5% for the studied SOBPs and patient plans. Both MKM (Microdosimetric Kinetic Model) and LEM (Local Effect Model) D_RBE are implemented and tested in FRoG to support the NIRS (National Institute of Radiological Sciences)-based to LEM-based biological dose conversion. FRoG matched the measured QA dosimetric data within ~2.0% for both particle species. The typical calculation times for patients ranged from roughly 1 to 4 min for proton beams and 3 to 6 min for carbon ions on a NVIDIA^® GeForce^® GTX 1080 Ti. This works demonstrates FRoG’s potential to bolster clinical activity with proton and carbon ion beams at CNAO.