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Purpose: 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). Methods and Materials: 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). Results: 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. Conclusions: 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.

Introduction: In the multidisciplinary management of oligometastatic, persistent, or recurrent (MPR) ovarian cancer, radiotherapy (RT) is becoming a more and more worthwhile treatment to potentially improve the chronicity of the disease. Particle beam RT has proved to be effective in several gynecological malignancies, but so far no data are available for ovarian cancer. Material and Methods: This is a real-world, retrospective, bi-institutional, single-arm study aimed to assess the effectiveness and the safety of carbon ion RT (CIRT) in this setting. The co-first endpoints are 1-year and 2-year actuarial local control (LC) rates and the objective response rate (ORR) defined on a “per lesion” basis. The secondary endpoint was toxicity. Actuarial outcomes were evaluated using the Kaplan-Meier method while potential predictors were explored using the Log-rank test. Bi-variable logistic regression was employed in the analysis of factors predicting the complete response on a per-lesion basis. Results: 26 patients accounting for a total of 36 lesions underwent CIRT with a total median dose of 52.8 Gy[RBE] (range: 39–64 Gy[RBE]). Five patients received CIRT for re-irradiation. No concomitant systemic therapies were administered during CIRT. Within 12 months after the treatment, 17 lesions (47 %) achieved complete response while 18 (50 %) obtained a partial response with an ORR of 97 %. The achievement of a complete response is related to the dose per fraction (>4.2 Gy[RBE], p = 0.04) and total dose (>52,8 Gy[RBE], p = 0.05). The 1-year LC was 92 % and the 2-year LC was 83 %, according to the achievement of a CR (p = 0.007) and GTV ≤ 14 cm3 (p = 0.024). No grade > 3 toxicities were recorded both in naïve and re-irradiated patients. PARP-i and anti-VEGF seemed not to exacerbate the risk of severe toxicities. Conclusions: CIRT was effective and safe in MPR ovarian cancers, even in the case of re-irradiation. Largest cohort studies and longer follow-up are needed to confirm these data.

Purpose: To generate virtual 4DCT from 4DMRI with field of view (FOV) extended to the entire involved patient anatomy, in order to evaluate its use in carbon ion radiation therapy (CIRT) of the abdominal site in a clinical scenario. Materials and methods: The virtual 4DCT was generated by deforming a reference CT in order to (1) match the anatomy depicted in the 4DMRI within its FOV, by calculating deformation fields with deformable image registration to describe inter-fractional and breathing motion, and (2) obtain physically plausible deformation outside of the 4DMRI FOV, by propagating and modulating the previously obtained deformation fields. The implemented method was validated on a digital anthropomorphic phantom, for which a ground truth (GT) 4DCT was available. A CIRT treatment plan was optimized at the end-exhale reference CT and the RBE-weighted dose distribution was recalculated on both the virtual and GT 4DCTs. The method estimation error was quantified by comparing the virtual and GT 4DCTs and the corresponding recomputed doses. The method was then evaluated on 8 patients with pancreas or liver tumors treated with CIRT using respiratory gating at end-exhale. The clinical treatment plans adopted at the National Center for Oncological Hadrontherapy (CNAO, Pavia, Italy) were considered and the dose distribution was recomputed on all respiratory phases of the planning and virtual 4DCTs. By comparing the two datasets and the corresponding dose distributions, the geometrical and dosimetric impact of organ motion was assessed. Results: For the phantom, the error outside of the 4DMRI FOV was up to 4.5 mm, but it remained sub-millimetric in correspondence to the target within the 4DMRI FOV. Although the impact of motion on the target D95% resulted in variations ranging from 22% to 90% between the planned dose and the doses recomputed on the GT 4DCT phases, the corresponding estimation error was ≤2.2%. In the patient cases, the variation of the baseline tumor position between the planning and the virtual end-exhale CTs presented a median (interquartile range) value of 6.0 (4.9) mm. For baseline variations larger than 5 mm, the tumor D95% variation between the plan and the dose recomputed on the end-exhale virtual CT resulted larger than 10%. Median variations higher than 10% in the target D95% and gastro-intestinal OARs D2% were quantified at the end-inhale, whereas close to the end-exhale phase, limited variations of relevant dose metrics were found for both tumor and OARs. Conclusions: The negligible impact of the geometrical inaccuracy in the estimated anatomy outside of the 4DMRI FOV on the overall dosimetric accuracy suggests the feasibility of virtual 4DCT with extended FOV in CIRT of the abdominal site. In the analyzed patient group, inter-fractional variations such as baseline variation and breathing variability were quantified, demonstrating the method capability to support treatment planning in gated CIRT of the abdominal site.