The median overall survival (OS) and local control (LC) of patients with melanoma brain metastases (MBMs) are poor even with immune checkpoint inhibitors and/or radiotherapy (RT). The aims of the study were to evaluate the association and timing of stereotactic radiotherapy (SRT)/radiosurgery (SRS) performed with the CyberKnife^® System and ipilimumab (IPI). A total of 63 MBMs patients were analyzed: 53 received RT+IPI and 10 RT alone. Therefore, the patients were divided into four groups: RT PRE-PI (>4 weeks before IPI) (18), RT CONC-IPI (4 weeks before/between first and last cycle/within 3 months of last cycle of IPI) (20), RT POST-IPI (>3 months after IPI) (15), and NO-IPI (10). A total of 127 lesions were treated: 75 with SRS (one fraction) and 24 with SRT (three to five fractions). The median follow-up was 10.6 months. The median OS was 10.6 months for all patients, 10.7 months for RT+IPI, and 3.3 months for NO-IPI (p = 0.96). One-year LC was 50% for all patients, 56% for RT+IPI, and 18% for NO-IPI (p = 0.08). The 1-year intracranial control was 45% for all patients, 44% for RT+IPI, and 51% for NO-IPI (p = 0.73). IPI with SRS/SRT in MBMs treatment could improve LC. However, the impact and timing of the two modalities on patients’ outcomes are still unclear.

The management of prostate cancer recurrence following external beam radiotherapy is not defined yet. Stereotaxic body reirradiation therapy showed encouraging results for local and biochemical control. From April 2017 to December 2020, 29 patients with prostate cancer recurrence were collected, joining the retrospective studies CyPro (prot. 46/19 OSS) and CLARO (Prot. 19/20 OSS) trials. Patients received Cyberknife^® treatment (17 pts) or alternatively VMAT (Volumetric Modulated Arc Technique) therapy by IGRT (Image-Guided Radiation Therapy)/Clarity^® (12 pts). By comparing the reirradiation of two groups, urinary (GU), rectal (GI) toxicities, and biochemical control were investigated. Further, the two techniques were dosimetrically compared by rival plans. The VMAT-IGRT Clarity^® treatments were replanned with an optimized template developed for prostate VMAT-SBRT in FFF mode keeping the same dose and fractionation scheduled for Cyberknife Group (30 Gy in 5 fx, at 80% isodose). In the CK group, 23% of patients experienced grade 2 acute GU, while 6% grade 2 acute GI. In the VMAT-Clarity^® group, acute GU toxicity was recorded in 17%, while for 8% grade 2 late toxicity was recorded. The dosimetric analysis shows that the VMAT-FFF allows to deliver a biological equivalent dose to CK, with the advantage of reducing the likelihood of toxicities arising.

Background: in recent years, the management of advanced colorectal cancer (CRC) has been greatly improved with integrated strategies including stereotactic radiation therapy (SRT). The administration of SRT has been demonstrated, particularly in oligo-metastatic (om) CRC, to be a safe and effective option. Interestingly, it has been demonstrated that SRT can induce regression of tumors in non-irradiated regions (“abscopal effect”) through stimulation of anti-tumor immune effects (“radiation-induced immunity”). We have recently shown that lung-limited omCRC is characterized by regression of tumor clones bearing specific key driver gene mutations. Aims: to assess the genetic evolution on tumor cancer cells induced by SRT in lung-limited omCRC. Secondary objectives included descriptions of the abscopal effect, responses’ duration, toxicity, and progression-free survival. A translational research will be performed to evaluate tumor genetic evolution (through liquid biopsies and Next Generation Sequencing), HLA class I repertoire, peripheral immune cells, and cytokine dynamics. Methods: PRELUDE-1 is a prospective translational study. SRT will be administered only to the largest nodule (with a maximum diameter ≤ 25 mm) in omCRC with two or three radiologically evident lesions. The sample size is based on the innovative hypothesis that radiation-induced immunity could induce regression of tumor clones bearing KRAS oncogene mutations. According to the binomial test, considering the frequency of KRAS mutations and assuming a probability of mutant KRAS→wild type KRAS of p₀ = 0.0077, with α = 0.05 and 1-β = 0.60, the final sample size is 25 patients.

Brain metastases (BMs) represent the most common intracranial tumours in adults with advanced solid cancers, significantly impacting morbidity and mortality. While the emergence of systemic therapies such as immunotherapy (IT) and targeted therapy (TT) has improved survival outcomes, the interaction of these modalities with stereotactic radiotherapy/radiosurgery (SRS/SRT) remains poorly explored. This study aims to evaluate the safety, local control (LC), and efficacy of combining SRS/SRT with IT or TT in patients with BM. This prospective, monocentric study ("RaBITT Trial") analysed patients with BM treated with SRS/SRT using the CyberKnife system (Accuray) between May 2020 and May 2023. Patients received IT or TT in conjunction with SRS/SRT. Outcomes assessed included LC, overall survival (OS), disease-free survival (DFS), and next-line systemic treatment-free survival (NEST-FS). Toxicity, including radionecrosis and haemorrhage, was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria. Statistical analysis employed Kaplan-Meier curves and univariate (UVA) and multivariate (MVA) regression models. We analysed 45 patients with a total of 225 BMs. The LC rate at 1 and 2 years was 85.7% and 79.8%, respectively. The overall response rate was 85.3%, with 56 complete responses (CRs). Multivariate analysis identified a higher biological effective dose with an α/β ratio of 10 and prescription isodose as predictors of CR. DFS rates at 1 and 2 years were 37.1% and 27.5%, respectively, while OS rates were 52.5% and 44.7%, respectively. NEST-FS rates at 1 and 2 years were 35.9% and 25.5%, respectively. Toxicity analysis revealed a radionecrosis rate of 20% for patients (6.7% of total lesions), with most cases being asymptomatic. Intralesional haemorrhage occurred in 1.7% of lesions, predominantly in melanoma and lung cancer patients. The combination of SRS/SRT with IT or TT yields high rates of LC and overall response with a manageable safety profile, emphasising the importance of personalised dosimetric planning and careful toxicity monitoring. Despite promising outcomes, the study's monocentric nature and limited sample size highlight the need for multicenter trials with extended follow-up to optimise treatment strategies and better understand long-term risks and benefits.

Prostate cancer (PCa) is one of the most common malignancies in men and remains a major cause of cancer-related death worldwide. Radiotherapy is a well-established treatment modality for PCa, offering clinical outcomes comparable to surgical approaches. In recent years, stereotactic body radiotherapy (SBRT), characterized by the delivery of high radiation doses in a limited number of fractions, has been increasingly adopted as a standard approach in the treatment of prostate cancer, due to its favorable efficacy and toxicity profile. CyberKnife (CK) is one of the most commonly used hypofractionated radiotherapy techniques. This preliminary study aimed to evaluate and compare the radiation dose delivery and treatment time of CK-based SBRT using two different collimation systems: the multileaf collimator (MLC) and the IRIS variable aperture collimator, a dynamic device that adjusts its opening to simulate different circular field sizes. A total of 19 patients with low-to-intermediate-risk PCa were selected and treated at the Radiation Oncology Department of the National Cancer Institute IRCCS Fondazione G. Pascale in Naples between January 2024 and January 2025. For each patient, two treatment plans were generated—one with the IRIS collimator and one with the MLC. The results demonstrated that the use of the MLC significantly reduced treatment time while maintaining dosimetric quality comparable to IRIS-based plans. These findings support the clinical benefit of MLC implementation in prostate SBRT with the CK system.