Carbon Ion Radiotherapy (CIRT) is one of the most promising therapeutic options to reduce Local Recurrence (LR) in Sacral Chordomas (SC). The aim of this work is to compare the performances of survival models fed with dosiomics features and conventional DVH metrics extracted from relative biological effectiveness (RBE)-weighted dose (D_RBE) and dose-averaged Linear Energy Transfer (LET_d) maps, towards the identification of possible prognostic factors for LR in SC patients treated with CIRT. This retrospective study included 50 patients affected by SC with a focus on patients that presented a relapse in a high-dose region. Survival models were built to predict both LR and High-Dose Local Recurrencies (HD-LR). The models were evaluated through Harrell Concordance Index (C-index) and patients were stratified into high/low-risk groups. Local Recurrence-free Kaplan–Meier curves were estimated and evaluated through log-rank tests. The model with highest performance (median(interquartile-range) C-index of 0.86 (0.22)) was built on features extracted from LET_d maps, with D_RBE models showing promising but weaker results (C-index of 0.83 (0.21), 0.80 (0.21)). Although the study should be extended to a wider patient population, LET_d maps show potential as a prognostic factor for SC HD-LR in CIRT, and dosiomics appears to be the most promising approach against more conventional methods (e.g., DVH-based).

The clinical application of different relative biological effectiveness (RBE) models for carbon ion RBE-weighted dose calculation hinders a global consensus in defining normal tissue constraints. This work aims to update the local effect model (LEM)-based constraints for the rectum using microdosimetric kinetic model (mMKM)-defined values, relying on RBE translation and the analysis of long-term clinical outcomes. LEM-optimized plans of treated patients, having suffered from prostate adenocarcinoma (n = 22) and sacral chordoma (n = 41), were recalculated with the mMKM using an in-house developed tool. The relation between rectum dose-volume points in the two RBE systems (D_LEM|v and D_MKM|v) was fitted to translate new LEM-based constraints. Normal tissue complication probability (NTCP) values, predicting late rectal toxicity, were obtained by applying published parameters. No late rectal toxicity events were reported within the patient cohort. The rectal toxicity outcome was confirmed using dosimetric analysis: D_MKMVHs lay largely below original constraints; the translated D_LEM|v values were 4.5%, 8.3%, 18.5%, and 35.4% higher than the nominal D_MKM|v of the rectum volume, v—1%, 5%, 10% and 20%. The average NTCP value ranged from 5% for the prostate adenocarcinoma, to 0% for the sacral chordoma group. The redefined constraints, to be confirmed prospectively with clinical data, are D_LEM|5cc ≤ 61 Gy(RBE) and D_LEM|1cc ≤ 66 Gy(RBE).

Surgical treatment of pelvic sarcoma involving the bone is the standard of care but is associated with several sequelae and reduced functional quality of life (QOL). Treatment with photon and proton radiotherapy is associated with relapse. Carbon ion radiotherapy (CIRT) may reduce both relapse rates and treatment sequelae. The PROSPER study is a tricontinental, nonrandomized, prospective, three-arm, pragmatic trial evaluating treatments of pelvic sarcoma involving the bone. Patients aged at least 15 years are eligible for inclusion. Participants must have an Eastern Cooperative Oncology Group Performance Status score of two or less, newly diagnosed disease, and histopathologic confirmation of pelvic chordoma, chondrosarcoma, osteosarcoma, Ewing sarcoma with bone involvement, rhabdomyosarcoma (RMS) with bone involvement, or non-RMS soft tissue sarcoma with bone involvement. Treatment arms include (1) CIRT (n = 30) delivered in Europe and Asia, (2) surgical treatment with or without adjuvant radiotherapy (n = 30), and (3) proton therapy (n = 30). Arms two and three will be conducted at Mayo Clinic campuses in Arizona, Florida, and Minnesota. The primary end point is to compare the 1-year change in functional QOL between CIRT and surgical treatment. Additional comparisons among the three arms will be made between treatment sequelae, local control, and other QOL measures.

Eye tracking techniques based on deep learning are rapidly spreading in a wide variety of application fields. With this study, we want to exploit the potentiality of eye tracking techniques in ocular proton therapy (OPT) applications. We implemented a fully automatic approach based on two-stage convolutional neural networks (CNNs): the first stage roughly identifies the eye position and the second one performs a fine iris and pupil detection. We selected 707 video frames recorded during clinical operations during OPT treatments performed at our institute. 650 frames were used for training and 57 for a blind test. The estimations of iris and pupil were evaluated against the manual labelled contours delineated by a clinical operator. For iris and pupil predictions, Dice coefficient (median = 0.94 and 0.97), Szymkiewicz–Simpson coefficient (median = 0.97 and 0.98), Intersection over Union coefficient (median = 0.88 and 0.94) and Hausdorff distance (median = 11.6 and 5.0 (pixels)) were quantified. Iris and pupil regions were found to be comparable to the manually labelled ground truths. Our proposed framework could provide an automatic approach to quantitatively evaluating pupil and iris misalignments, and it could be used as an additional support tool for clinical activity, without impacting in any way with the consolidated routine.

The use of three-dimensional (3D)-printed custom-made implants is spreading in the orthopedics field for the reconstruction of bone losses or for joint replacement, thanks to their unparalleled versatility. In particular, this novel technology opens new perspectives to formulate custom-made fixation strategies for the upper cervical region, sacrum and pelvis, where reconstruction is challenging. We report and analyze the literature concerning upper cervical reconstruction with 3D-printed personalized implants after tumor surgery, and discuss two cases of patients where this technology was used to reconstruct the anterior column after extracapsular debulking of C2 recurrent chordoma at our institution.

To investigate the outcome and toxicity of patients affected by malignant peripheral nerve sheath tumors (MPNSTs) treated with high-dose carbon ion radiation therapy (CIRT). We retrospectively analyzed the outcome of 23 patients with MPNSTs treated between July 2013 and December 2020. Out of these, 13 patients (56.5%) had incompletely resected tumors, 8 patients (34.7%) experienced recurrence after surgery, and 2 patients (8.7%) had unresectable tumors. Before CIRT treatment, 4 patients underwent a second surgery after the first local recurrence (LR), and 1 patient underwent a third surgery for the second local relapse of the disease. Six (26%) patients received neoadjuvant chemotherapy. The most frequent tumor site was the brachial plexus (n = 9; 39.1%). In 5 patients (21.7%), neurofibromatosis type 1 disorder was found, while 4 patients (17, 4%) had radiation-induced MPNSTs. The median CIRT prescribed total dose was 69.8 Gy (relative biological effectiveness; range, 54-76.8) delivered in a median of 16 fractions (range, 15-22). Eleven patients (47.82%) were treated according to a sequential boost protocol with a median prescribed dose to clinical target volume LR of 45 Gy (relative biological effectiveness; range, 41.4-54). After a median follow-up time of 23 months (range, 3-100 months), the overall survival rates at 1 and 2 years were 82.38% and 61.51%, respectively. The 1-year and 2-year local relapse-free survival rates were 65.07% and 48.80%, respectively, and the 1-year and 2-year progression-free survival rates were 56.37% and 40.99%, respectively. No patients showed acute or late grade 4 toxicity or any treatment-related deaths. Ten patients (43.48%) reported acute toxicities of grade ≥ 2, which included dermatitis in 6 patients, mucositis in 2 patients, and peripheral neuropathy in 4 patients. Eight patients (34.78%) reported late toxicities of grade ≥ 2, mainly due to loco-regional neuropathy. High-dose CIRT shows favorable local effects with acceptable toxicities in patients with gross residual and LR after surgery or unresectable malignant peripheral nerve sheath tumors. Advanced treatment modalities such as particle therapy should be considered for MPNSTs.