Background: The standard treatment for skull base chondrosarcoma (SB-CHS) consists of surgery and high-dose radiation therapy. Our aim was to evaluate outcome in terms of local control (LC) and toxicity of proton therapy (PT) and carbon ion (CIRT) after surgery. Materials and methods: From September 2011 to July 2020, 48 patients underwent particle therapy (67% PT, 33% CIRT) for SB-CHS. PT and CIRT total dose was 70 GyRBE (relative biological effectiveness) in 35 fractions and 70.4 GyRBE in 16 fractions, respectively. Toxicity was assessed using the Common Terminology Criteria for Adverse Events (CTCAE v5). Results: After a median follow-up time of 38 months, one local failure (2%) was documented and the patient died for progressive disease. Overall, 3-year LC was 98%. One (2%) and 4 (8%) patients experienced G3 acute and late toxicity, respectively. White-matter brain changes were documented in 22 (46%) patients, but only 7 needed steroids (G2). No patients had G3 brain toxicity. No G4–5 complications were reported. We did not find any correlation between high-grade toxicity or white-matter changes and characteristics of patients, disease and surgery. Conclusions: PT and CIRT appeared to be effective and safe treatments for patients with SB-CHS, resulting in high LC rates and an acceptable toxicity profile.

(1) Background: we proposed an integrated strategy to support clinical allocation of nasopharyngeal patients between proton and photon radiotherapy. (2) Methods: intensity-modulated proton therapy (IMPT) plans were optimized for 50 consecutive nasopharyngeal carcinoma (NPC) patients treated with volumetric modulated arc therapy (VMAT), and differences in dose and normal tissue complication probability (ΔNTCPx-p) for 16 models were calculated. Patient eligibility for IMPT was assessed using a model-based selection (MBS) strategy following the results for 7/16 models describing the most clinically relevant endpoints, applying a model-specific ΔNTCPx-p threshold (15% to 5% depending on the severity of the complication) and a composite threshold (35%). In addition, a comprehensive toxicity score (CTS) was defined as the weighted sum of all 16 ΔNTCPx-p, where weights follow a clinical rationale. (3) Results: Dose deviations were in favor of IMPT (ΔD_mean ≥ 14% for cord, esophagus, brainstem, and glottic larynx). The risk of toxicity significantly decreased for xerostomia (−12.5%), brain necrosis (−2.3%), mucositis (−3.2%), tinnitus (−8.6%), hypothyroidism (−9.3%), and trismus (−5.4%). There were 40% of the patients that resulted as eligible for IMPT, with a greater advantage for T3–T4 staging. Significantly different CTS were observed in patients qualifying for IMPT. (4) Conclusions: The MBS strategy successfully drives the clinical identification of NPC patients, who are most likely to benefit from IMPT. CTS summarizes well the expected global gain.

(1) Background: In this work, we aim to provide selection criteria based on normal tissue complication probability (NTCP) models and additional explanatory dose-volume histogram parameters suitable for identifying locally advanced sinonasal cancer patients with orbital invasion benefitting from proton therapy. (2) Methods: Twenty-two patients were enrolled, and two advanced radiation techniques were compared: intensity modulated proton therapy (IMPT) and photon volumetric modulated arc therapy (VMAT). Plans were optimized with a simultaneous integrated boost modality: 70 and 56 Gy(RBE) in 35 fractions were prescribed to the high risk/low risk CTV. Several endpoints were investigated, classified for their severity and used as discriminating paradigms. In particular, when NTCP models were already available, a first selection criterion based on the delta-NTCP was adopted. Additionally, an overall analysis in terms of DVH parameters was performed. Furthermore, a second selection criterion based on a weighted sum of the $\Delta$NTCP and $\Delta$DVH was adopted. (3) Results: Four patients out of 22 (18.2%) were suitable for IMPT due to $\Delta$NTCP > 3% for at least one severe toxicity, 4 (18.2%) due to $\Delta$NTCP > 20% for at least three concurrent intermediate toxicities and 16 (72.7%) due to the mixed sum of $\Delta$NTCP and $\Delta$DVH criterion. Since, for some cases, both criteria were contemporary fulfilled, globally 17/22 patients (77.3%) would benefit from IMPT. (4) Conclusions: For this rare clinical scenario, the use of a strategy including DVH parameters and NTCPs when comparing VMAT and IMPT is feasible. We showed that patients affected by sinonasal cancer could profit from IMPT compared to VMAT in terms of optical and central nervous system organs at risk sparing.

Background: Stereotactic arrhythmia radioablation (STAR) is an emerging, non‐invasive treatment for refractory ventricular arrhythmias. The technology requires target motion management. Purpose: We studied the integration of a novel ultrasound probe and holder for heart motion management into proton‐beam STAR treatment plans. Methods: Data were collected in eight of the 23 patients enrolled to‐date, in an ongoing prospective, multicenter, observational in silico study comparing treatment planning with photons versus proton radiotherapy in patients affected by Ventricular Tachycardia with indication for catheter ablation procedure. In such subgroup of patients hands‐free transthoracic echocardiography was performed in apical and parasternal positions, followed by planning Computed Tomography with ultrasound probe positions marked on the chest. A total of eleven targets were contoured and, for the proton therapy part, pencil beam scanning intensity‐modulated proton therapy plans were optimized, assuming cardio‐respiratory (dual) gated delivery. Results: In all eleven cases, it was possible to avoid beams intercepting the probe and the dosimetric constraints were fulfilled. In four cases, the position of the probe did not interfere with the beam angles defined a‐priori. In four cases, beam angles had to be modified to avoid intercepting the probe but the modified plan was equivalent to the a‐priori plan. In three cases, the modified plans included beams with longer penetration depth compared to the a‐priori plan, but all planning constraints were fulfilled. Conclusions: These results support the feasibility of using the novel ultrasound probe and holder for heart motion management. The technology would facilitate dedicated patient setup, monitoring and cardiorespiratory gating for STAR using proton beams.