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Introduction/BackgroundRe-irradiation of local recurrences of gynaecological cancer pose a difficult challenge to Oncologist. For their biological and physical characteristics particle therapy (PT) could be an interesting treatment.MethodologyThe aim of the study was to evaluate the feasibility and early clinical outcome in patients (pts) with gynaecological pelvic sidewall recurrence (PSWr). Between May 2014 to December 2018, 10 patients (median age 56) with PSWr within or at the edge of the previously irradiated field were treated using PT. They had recurrence of: cervical (5), endometrial (3), uterine (1) and ovarian (1) cancer. Previous radiotherapy prescription dose ranged from 46 to 59.4 Gy and 5 patients underwent brachytherapy (range: 7–28 Gy).Two patients, with marginal lymph node recurrence, were irradiated with protons with up to a total dose of 25 GyRBE and 51 GyRBE, respectively. The remaining women underwent carbon-ion radiotherapy (median total dose 50.4 GyRBE; range: 36–57) administered in a median number of 12 fractions. Six patients with PSWr received surgical spacer placement by open surgery to keep intestinal tracts apart from the tumour as the distance between tumour and nearest intestinal tracts was not sufficient. No pts received concurrent chemotherapy. Preliminary local control (LC) and toxicity profile (according to CTCAE V4.03 scale) were evaluated.ResultsAll patients completed the planned treatment and no acute toxicities G>2 were observed. For the evaluable patients, 1 case of intermediate G≥3 toxicity was reported in women received sequential Bevacizumab (BV). For pts with a follow-up ≥3 months, median LC was 7 months (range: 3–14), median MFS was 4.5 months (range: 3–14,5) and median OS was 7 months (range: 3–14,5). 1 pt experienced local progression and 4 pts died for systemic progression. Data are still ongoing.ConclusionFor pts with PSWr a PT approach seems to be feasible and our results showed a promising short-term outcome and limited radiation-related side effects. Longer follow-up and large patient accrual are required.DisclosureNothing to disclose.

We report the initial toxicity data with scanned proton beams at the Italian National Center for Hadrontherapy (CNAO). In September 2011, CNAO commenced patient treatment with scanned proton beams within two prospective Phase II protocols approved by the Italian Health Ministry. Patients with chondrosarcoma or chordoma of the skull base or spine were eligible. By October 2012, 21 patients had completed treatment. Immobilization was performed using rigid non-perforated thermoplastic-masks and customized headrests or body-pillows as indicated. Non-contrast CT scans with immobilization devices in place and MRI scans in supine position were performed for treatment-planning. For chordoma, the prescribed doses were 74 cobalt grey equivalent (CGE) and 54 CGE to planning target volume 1 (PTV1) and PTV2, respectively. For chondrosarcoma, the prescribed doses were 70 CGE and 54 CGE to PTV1 and PTV2, respectively. Treatment was delivered five days a week in 35–37 fractions. Prior to treatment, the patients' positions were verified using an optical tracking system and orthogonal X-ray images. Proton beams were delivered using fixed-horizontal portals on a robotic couch. Weekly MRI incorporating diffusion-weighted-imaging was performed during the course of proton therapy. Patients were reviewed once weekly and acute toxicities were graded with the Common Terminology Criteria for Adverse Events (CTCAE). Median age of patients = 50 years (range, 21–74). All 21 patients completed the proton therapy without major toxicities and without treatment interruption. Median dose delivered was 74 CGE (range, 70–74). The maximum toxicity recorded was CTCAE Grade 2 in four patients. Our preliminary data demonstrates the clinical feasibility of scanned proton beams in Italy.

This review aims to summarize what is currently known about neurocognitive outcome and quality of life in patients with brain tumors treated with radiotherapy. Whether potential tumor-controlling benefits of radiotherapy outweigh its potential toxicity in the natural history of brain tumors is a matter of debate. This review focuses on some of the adult main brain tumors, for which the issue of neurocognitive decline has been thoroughly studied: low-grade gliomas, brain metastases, and primary central nervous system lymphomas. The aims of this review are: (1) the analysis of existing data regarding the relationship between radiotherapy and neurocognitive outcome; (2) the identification of strategies to minimize radiotherapy-related neurotoxicity by reducing the dose or the volume; (3) the evidence-based data concerning radiotherapy withdrawal; and (4) the definition of patients subgroups that could benefit from immediate radiotherapy. For high grade gliomas, the main findings from literature are summarized and some strategies to reduce the neurotoxicity of the treatment are presented. Although further prospective studies with adequate neuropsychological follow-up are needed, this article suggests that cognitive deficits in patients with brain tumor have a multifactorial genesis: radiotherapy may contribute to the neurocognitive deterioration, but the causes of this decline include the tumor itself, disease progression, other treatment modalities and comorbidities. Treatment variables, such as total and fractional dose, target volume, and irradiation technique can dramatically affect the safety of radiotherapy: optimizing radiation parameters could be an excellent approach to improve outcome and to reduce neurotoxicity. At the same time, delayed radiotherapy could be a valid option for highly selected patients.

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.

Purpose To report the outcomes of a large series of intracranial meningiomas (IMs) submitted to proton therapy (PT) with curative intent. Methods We conducted a retrospective analysis on all consecutive IM patients treated between 2014 and 2021. The median PT prescription dose was 55.8 Gy relative biological effectiveness (RBE) and 66 GyRBE for benign/radiologically diagnosed and atypical/anaplastic IMs, respectively. Local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), overall survival (OS), and radionecrosis-free survival (RNFS) were evaluated with the Kaplan-Meier method. Univariable analysis was performed to identify potential prognostic factors for clinical outcomes. Toxicity was reported according to the latest Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results Overall, 167 patients were included. With a median follow-up of 41 months (range, 6–99), twelve patients (7%) developed tumor local recurrence after a median time of 39 months. The 5-year LRFS was 88% for the entire cohort, with a significant difference between benign/radiologically diagnosed and atypical/anaplastic IMs (98% vs. 47%, p  < 0.001); this significant difference was maintained also for the 5-year OS and the 5-year DRFS rates. Patients aged ≤ 56 years reported significantly better outcomes, whereas lower prescription doses and skull base location were associated with better RNFS rates. Two patients experienced G3 acute toxicities (1.2%), and three patients G3 late toxicities (1.8%). There were no G4-G5 adverse events. Conclusion PT proved to be effective with an acceptable toxicity profile. To the best of our knowledge this is one of the largest series including IM patients submitted to PT.

Purpose To assess early microstructural changes of meningiomas treated with proton therapy through quantitative analysis of intravoxel incoherent motion (IVIM) and diffusion-weighted imaging (DWI) parameters. Methods Seventeen subjects with meningiomas that were eligible for proton therapy treatment were retrospectively enrolled. Each subject underwent a magnetic resonance imaging (MRI) including DWI sequences and IVIM assessments at baseline, immediately before the 1st (t0), 10th (t10), 20th (t20), and 30th (t30) treatment fraction and at follow-up. Manual tumor contours were drawn on T2-weighted images by two expert neuroradiologists and then rigidly registered to DWI images. Median values of the apparent diffusion coefficient (ADC), true diffusion (D), pseudo-diffusion (D*), and perfusion fraction (f) were extracted at all timepoints. Statistical analysis was performed using the pairwise Wilcoxon test. Results Statistically significant differences from baseline to follow-up were found for ADC, D, and D* values, with a progressive increase in ADC and D in conjunction with a progressive decrease in D*. MRI during treatment showed statistically significant differences in D values between t0 and t20 ( p  = 0.03) and t0 and t30 ( p  = 0.02), and for ADC values between t0 and t20 ( p  = 0.04), t10 and t20 ( p  = 0.02), and t10 and t30 ( p  = 0.035). Subjects that showed a volume reduction greater than 15% of the baseline tumor size at follow-up showed early D changes, whereas ADC changes were not statistically significant. Conclusion IVIM appears to be a useful tool for detecting early microstructural changes within meningiomas treated with proton therapy and may potentially be able to predict tumor response.

Skull-base chordoma and chondrosarcoma are rare radioresistant tumors treated with surgical resection and/or radiotherapy. Because of the established dosimetric and biological benefits of heavy particle therapy, we performed a systematic and evidence-based review of the clinical outcomes of patients with skull-base chordoma and chondrosarcoma treated with carbon ion radiotherapy (CIRT). A literature review was performed using a MEDLINE search of all articles to date. We identified 227 studies as appropriate for review, and 24 were ultimately included. The published data illustrate that CIRT provides benchmark disease control outcomes for skull-base chordoma and chondrosarcoma, respectively, with acceptable toxicity. CIRT is an advanced treatment technique that may provide not only dosimetric benefits over conventional photon therapy but also biologic intensification to overcome mechanisms of radioresistance. Ongoing research is needed to define the magnitude of benefit, patient selection, and cost-effectiveness of CIRT compared to other forms of radiotherapy.