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Background The aim of this study is to evaluate results in terms of local control (LC), overall survival (OS), and toxicity profile and to better identify factors influencing clinical outcome of skull base chordoma treated with proton therapy (PT) and carbon ion radiotherapy (CIRT). Methods We prospectively collected and analyzed data of 135 patients treated between November 2011 and December 2018. Total prescription dose in the PT group (70 patients) and CIRT group (65 patients) was 74 Gy relative biological effectiveness (RBE) delivered in 37 fractions and 70.4 Gy(RBE) delivered in 16 fractions, respectively (CIRT in unfavorable patients). LC and OS were evaluated using the Kaplan–Meier method. Univariate and multivariate analyses were performed, to identify prognostic factors on clinical outcomes. Results After a median follow-up of 44 (range, 6–87) months, 14 (21%) and 8 (11%) local failures were observed in CIRT and PT group, respectively. Five-year LC rate was 71% in CIRT cohort and 84% in PT cohort. The estimated 5-year OS rate in the CIRT and PT group was 82% and 83%, respectively. On multivariate analysis, gross tumor volume (GTV), optic pathways, and/or brainstem compression and dose coverage are independent prognostic factors of local failure risk. High rate toxicity grade ≥3 was reported in 11% of patients. Conclusions Particle radiotherapy is an effective treatment for skull base chordoma with acceptable late toxicity. GTV, optic pathways, and/or brainstem compression and target coverage were independent prognostic factors for LC. Key Points • Proton and carbon ion therapy are effective and safe in skull base chordoma. • Prognostic factors are GTV, organs at risk compression, and dose coverage. • Dual particle therapy and customized strategy was adopted.

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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.

Background: Malignant melanoma of the lower genital tract is a rare disease known to have a poor prognosis. Because of the high rate of distant metastasis and unsatisfactory survival benefit, a more conservative treatment approach, instead of extensive surgery, may be warranted. Gynecological melanoma is a radioresistant tumor, an ideal disease to test the biological efficacy of carbon ion radiotherapy (CIRT). Aim: To report our preliminary experience with CIRT in the treatment of gynecological melanoma at the National Center of Oncological Hadrontherapy (CNAO). Patients and Methods: Between January 2016 and February 2017, four patients were admitted for CIRT at CNAO. A case of cervical melanoma was treated with palliative aim because of large volume macroscopic disease, while three cases of vaginal melanoma were irradiated with a total dose of 68.8 Gy (relative biological effectiveness) in 16 fractions delivered over 4 weeks (4 days a week). Results: The age of women ranged between 49 and 72 (median=60.5 years) years. Treatment was well tolerated in all patients and all women completed the scheduled treatment course. During CIRT, toxicity was mild. For patients with vaginal disease, local control was 10.23 and 12.6 months, while that for cervical malignant melanoma was 7.3 months. All patients experienced systemic progression, with median distant metastasis-free survival of 11.7 months. The median overall survival for the whole patient group was 11.41 months. Conclusion: In our first experiences, CIRT appears to be a safe non-invasive option for malignant melanoma of the lower genital tract, but more data and longer follow-up are necessary in order to evaluate the effectiveness and late effects.

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