Feasibility and Acute Toxicity of Hypo-Fractionated Radiotherapy on 0.35T MR-LINAC: The First Prospective Study in Spain.

This observational, descriptive, longitudinal, and prospective basket-type study (Registry #5289) prospectively evaluated the feasibility and acute toxicity of hypo-fractionated radiotherapy on the first 0.35T MR-LINAC in Spain. A total of 37 patients were included between August and December 2023, primarily with prostate tumors (59.46%), followed by pancreatic tumors (32.44%). Treatment regimens typically involved extreme hypo-fractionated radiotherapy, with precise dose delivery verified through quality assurance measures. Acute toxicity assessment at treatment completion revealed manageable cystitis, with one case persisting at the three-month follow-up. Gastrointestinal toxicity was minimal. For pancreatic tumors, daily adaptation of organ-at-risk (OAR) and gross tumor volume (GTV) was practiced, with median doses to OAR within acceptable limits. Three patients experienced gastrointestinal toxicity, mainly nausea. Overall, the study demonstrates the feasibility and safety of extreme hypo-fractionated radiotherapy on a 0.35T MR-LINAC, especially for challenging anatomical sites like prostate and pancreatic tumors. These findings support the feasibility of MR-LINAC-based radiotherapy in delivering precise treatments with minimal toxicity, highlighting its potential for optimizing cancer treatment strategies.

Cancer-specific dose and fractionation schedules in stereotactic body radiotherapy for oligometastatic disease: An interim analysis of the EORTC-ESTRO E2-RADIatE OligoCare study.

BACKGROUND AND INTRODUCTION: Optimal dose and fractionation in stereotactic body radiotherapy (SBRT) for oligometastatic cancer patients remain unknown. In this interim analysis of OligoCare, we analyzed factors associated with SBRT dose and fractionation. MATERIALS AND METHODS: Analysis was based on the first 1,099 registered patients. SBRT doses were converted to biological effective doses (BED) using α/ß of 10 Gy for all primaries, and cancer-specific α/ß of 10 Gy for non-small cell lung and colorectal cancer (NSCLC, CRC), 2.5 Gy for breast cancer (BC), or 1.5 Gy for prostate cancer (PC). RESULTS: Of the interim analysis population of 1,099 patients, 999 (99.5 %) fulfilled inclusion criteria and received metastasis-directed SBRT for NSCLC (n = 195; 19.5 %), BC (n = 163; 16.3 %), CRC (n = 184; 18.4 %), or PC (n = 457; 47.5 %). Two thirds of patients were treated for single metastasis. Median number of fractions was 5 (IQR, 3-5) and median dose per fraction was 9.7 (IQR, 7.7-12.4) Gy. The most frequently treated sites were non-vertebral bone (22.8 %), lung (21.0 %), and distant lymph node metastases (19.0 %). On multivariate analysis, the dose varied significantly for primary cancer type (BC: 237.3 Gy BED, PC 300.6 Gy BED, and CRC 84.3 Gy BED), and metastatic sites, with higher doses for lung and liver lesions. CONCLUSION: This real-world analysis suggests that SBRT doses are adjusted to the primary cancers and oligometastasis location. Future analysis will address safety and efficacy of this site- and disease-adapted SBRT fractionation approach (NCT03818503).

Radiotherapy of Oligometastatic Cancers.

The enhanced multidisciplinary treatment approach and the widespread use of advanced imaging techniques have led to an improvement in survival rates, inevitably associated with an increase in the number of oligometastatic diagnoses in cancer patients [...].

ONE SHOT - single shot radiotherapy for localized prostate cancer: 18-month results of a single arm, multicenter phase I/II trial.

PURPOSE: To assess in a prospective, multicenter, single-arm phase I/II study the early safety and efficacy profile of single fraction urethra-sparing stereotactic body radiotherapy (SBRT) for men with localized prostate cancer. MATERIAL AND METHODS: Patients with low- and intermediate-risk localized prostate cancer without significant tumor in the transitional zone were recruited. A single-fraction of 19 Gy was delivered to the prostate, with 17 Gy dose-reduction to the urethra. Intrafraction motion was monitored using intraprostatic electromagnetic transponders with intra-fraction correction of displacements exceeding 3 mm. Genitourinary (GU), gastrointestinal (GI), and sexual toxicity during the first 18 months were evaluated using the CTCAE v4.0 grading scale. Quality of life was assessed using the International Prostate Symptom Score, the Expanded Prostate Cancer Index composite 26 score, and the International Index of Erectile Function score. RESULTS: Among the 45 patients recruited in 5 centers between 2017 and 2022, 43 received the single fraction without protocol deviations, and 34 had a minimal follow-up of 18 months. The worst GU toxicity was observed at day-5 after SBRT (42.5 % and 20 % with grade 1 and 2, respectively), returning to baseline at week-12 and month-6 (<3% with grade 2), with a 12 % grade 2 flare at month 18. Gl toxicity was mild in the acute phase, with no grade ≥ 2 events (12 % grade 1 at month 6). Grade-3 proctitis was observed in one patient at month 12, with < 3 % grade 2 toxicity at month 18. Mean GU and GI bother scores showed a decline at day 5, a complete recovery at month 6, and a flare between month 12 and 18. Mean PSA dropped from 6.2 ng/ml to 1.2 ng/ml at month 18 and 0.7 ng/ml at month 24. After a median follow-up time of 26 months, 3 biochemical failures (7 %) were observed at month 17, 21 and 30. CONCLUSIONS: In this multicenter phase I/II trial, we demonstrated that a 19 Gy single-fraction urethra-sparing SBRT is feasible and associated with an acceptable toxicity rate, mostly returning to the baseline at week-12 and with a symptoms flare between months 12 and 18. Longer follow-up is needed to assess the potential long-term adverse effects and the disease control efficacy.

MR-LINAC, a New Partner in Radiation Oncology: Current Landscape.

Technological advances in radiation oncology are oriented towards improving treatment precision and tumor control. Among these advances, magnetic-resonance-image-guided radiation therapy (MRgRT) stands out, with technological advances to deliver targeted treatments adapted to a tumor's anatomy on the day while minimizing incidental exposure to organs at risk, offering an unprecedented therapeutic advantage compared to X-ray-based IGRT delivery systems. This new technology changes the traditional workflow in radiation oncology and requires an evolution in team coordination to administer more precise treatments. Once implemented, it paves the way for newer indication for radiation therapy to safely deliver higher doses than ever before, with better preservation of healthy tissues to optimize patient outcomes. In this narrative review, we assess the technical aspects of the novel linear accelerators that can deliver MRgRT and summarize the available published experience to date, focusing on oncological results and future challenges.

Health-related quality of life in men with oligometastatic prostate cancer following metastases-directed stereotactic body radiotherapy: Real-world data from the E2-RADIatE OligoCare cohort.

Objective: To evaluate the impact of metastases-directed stereotactic body radiotherapy (SBRT) on health-related quality of life (HRQoL) in men with oligometastatic prostate cancer (PCa) using real-world data from the OligoCare cohort. Materials and methods: OligoCare is a pragmatic, observational cohort designed to assess the impact of metastases-directed SBRT on patients with oligometastatic disease (OMD). We report an interim analyses of the secondary endpoint HRQoL, assessed using the EORTC QLQ-C30, within six months of metastases-directed SBRT for oligometastatic disease in men with PCa among the first 1600 registered patients. HRQoL data collection was optional within the OligoCare cohort. To compare HRQoL between baseline and first follow-up assessment, a Wilcoxon signed-rank test was used. A multiple linear regression model was used to explore the HRQoL associations with predefined factors. Results: Out of the 1600 registered patients, 658 were treated for oligometastatic PCa, of which 233 had baseline QoL data and 132 patients had both baseline and follow-up HRQoL data. At baseline, most patients had a WHO performance status of 0 or 1 (87 %), were de-novo oligometastatic (79 %), had one metastasis (90 %), and had a good overall global health status (mean 80.81, SD16.11, IQR 75-92). 51 % received hormonal therapy as concomitant systemic treatment. Patients with comorbidities as assessed by the Charlson Comorbidity index had a worse global health status at baseline (-4.88, 95 % CI:-9.35, -0.42). No clinically meaningful significant difference in global health status was observed at first assessment following SBRT (median 3.0 months) compared with baseline (mean difference 2.27, 95 % CI:-1.54, 6.08). Upon evaluating the proportions, meaningful clinically important differences (a 10-point or more difference) was observed in, 17 % and 11 % of the patients reporting deterioration and improvement of global health status, respectively. Conclusion: Metastases-directed stereotactic body radiotherapy had no negative impact on global HRQoL within the first six months after treatment.

Prostate volume variation during 1.5T MR-guided adaptive stereotactic body radiotherapy (SBRT) and correlation with treatment toxicity.

INTRODUCTION: To evaluate prostate volume change during daily-adaptive prostate SBRT on 1.5 T MR-linac and to correlate it with treatment toxicity. METHODS: a series of patients affected by low-to-intermediate risk prostate cancer was treated by 5-fraction SBRT within a prospective study (Prot. n° 23748). Total dose was 35 Gy and 36.25 Gy delivered every day or on alternate days. Treatment toxicity was recorded with the following patient reported outcomes (PROMs): IPSS, ICIQ-SF, and EPIC-26. RESULTS: 254 patients were included in the analysis. Baseline median CTV volume was 55 cc (range 15.3-163.3). Mean prostate volume were 58.9 cc, and 62.7 cc at first and last fraction respectively (mean volume increase 6.4 %; p = <0.0001). We observed prostate swelling (mean 15.4 % increase) in 50 % of cases, stable volume (≤5% volume change) in 39 % of patients, and prostate shrinkage in 11 % of cases (mean 12.2 % reduction). Baseline CTV > 55 cc showed a trend towards higher CTV shrinkage (-10.5 % versus -14.5 %; p = 0.052). We found no correlation between CTV change and PROMs. Prostate swelling was generally compensated by the planned PTV expansion, even though the mean setup volume dropped from 47.4 cc to 38.9 cc at last fraction, with few cases not covered by initial setup margins. CONCLUSION: The present study reported a significant prostate volume change during prostate SBRT on 1.5T MR-linac. We observed both prostate swelling in half of cases and few cases of prostate shrinkage. No correlations were found with PROMs in this population treatment with daily-adaptive strategy.

The state-of-the-art technic of stereotactic radioablation for the treatment of cardiac arrhythmias: An overview.

Introduction: Cardiac arrhythmias, including ventricular tachycardia (VT), stand as a significant threat to health, often leading to mortality and sudden cardiac death. While conventional treatments for VT exhibit efficacy, cases of refractory VT pose challenges. Stereotactic Arrhythmia Radioablation (STAR) offers a novel approach, delivering precise high-dose radiation to well-defined targets with minimal collateral damage. This study explores the potential of STAR as an alternative therapy, especially for high-risk patients or those with refractory VT. Methods: This research reviews ongoing studies and preliminary investigations into the evaluation of the efficacy and safety of STAR. The method involves targeted radiation delivery, assessing reductions in VT recurrence and the early safety profile in refractory VT patients. However, given STAR's early stage and limited clinical evidence, cautious interpretation is advised. Results: Preliminary findings indicate a reduction in VT recurrence with STAR, suggesting promise as a therapeutic option. Early safety profiles are encouraging, but definitive statements on efficacy and safety require further investigation. Positive initial outcomes underscore the need for additional data and long-term studies. Conclusion: Stereotactic Arrhythmia Radioablation is recently emerging as a promising treatment for refractory VT. While early results are encouraging, careful interpretation is needed, due to STAR's early stages. Ongoing investigations are critical for a comprehensive understanding of its long-term efficacy and tolerability. This review provides fundamental insights into STAR's background, principles, pre-treatment procedures, clinical implications, and toxicity, setting the stage for future research in this evolving therapeutic field.

"Things Have Changed"-Laparoscopic Cytoreduction for Advanced and Recurrent Ovarian Cancer: The Experience of a Referral Center on 108 Patients.

OBJECTIVE: To report the feasibility of laparoscopic cytoreduction surgery for primary and recurrent ovarian cancer in a select group of patients. METHODS: A retrospective analysis was conducted on a cohort of patients with FIGO stage IIIA-IV advanced ovarian cancer who underwent laparoscopic primary debulking surgery (PDS), interval debulking surgery (IDS), or secondary debulking surgery (SDS) between June 2008 and January 2020. The primary endpoint was achieving optimal cytoreduction, defined as residual tumor less than 1 cm. Secondary endpoints included evaluating surgical complications and long-term survival, assessed at three-month intervals during the initial two years and then every six months. RESULTS: This study included a total of 108 patients, among whom, 40 underwent PDS, 44 underwent IDS, and 24 underwent SDS. Optimal cytoreduction rates were found to be 95.0%, 97.7%, and 95.8% for the PDS, ISD, and SDS groups, respectively. Early postoperative complications (<30 days from surgery) occurred in 19.2% of cases, with 7.4% of these cases requiring reintervention. One patient died following postoperative respiratory failure. Late postoperative complications (<30 days from surgery) occurred in 9.3% of cases, and they required surgical reintervention only in one case. After laparoscopic optimal cytoreduction with a median follow-up time of 25 months, the overall recurrence rates were 45.7%, 38.5%, and 39.3% for PDS, ISD, and SDS, respectively. The three-year overall survival rates were 84%, 66%, and 63%, respectively, while the three-year disease-free survival rates were 48%, 51%, and 71%, respectively. CONCLUSIONS: Laparoscopic cytoreduction surgery is feasible for advanced ovarian cancer in carefully selected patients, resulting in high rates of optimal cytoreduction, satisfactory peri-operative morbidity, and encouraging survival outcomes. Future studies should focus on establishing standardized selection criteria and conducting well-designed investigations to further refine patient selection and evaluate long-term outcomes.

Development of a comprehensive cardiac atlas on a 1.5 Tesla Magnetic Resonance Linear Accelerator.

Background and purpose: The 1.5 Tesla (T) Magnetic Resonance Linear Accelerator (MRL) provides an innovative modality for improved cardiac imaging when planning radiation treatment. No MRL based cardiac atlases currently exist, thus, we sought to comprehensively characterize cardiac substructures, including the conduction system, from cardiac images acquired using a 1.5 T MRL and provide contouring guidelines. Materials and methods: Five volunteers were enrolled in a prospective protocol (NCT03500081) and were imaged on the 1.5 T MRL with Half Fourier Single-Shot Turbo Spin-Echo (HASTE) and 3D Balanced Steady-State Free Precession (bSSFP) sequences in axial, short axis, and vertical long axis. Cardiac anatomy was contoured by (AS) and confirmed by a board certified cardiologist (JR) with expertise in cardiac MR imaging. Results: A total of five volunteers had images acquired with the HASTE sequence, with 21 contours created on each image. One of these volunteers had additional images obtained with 3D bSSFP sequences in the axial plane and additional images obtained with HASTE sequences in the key cardiac planes. Contouring guidelines were created and outlined. 15-16 contours were made for the short axis and vertical long axis. The cardiac conduction system was demonstrated with eleven representative contours. There was reasonable variation of contour volume across volunteers, with structures more clearly delineated on the 3D bSSFP sequence. Conclusions: We present a comprehensive cardiac atlas using novel images acquired prospectively on a 1.5 T MRL. This cardiac atlas provides a novel resource for radiation oncologists in delineating cardiac structures for treatment with radiotherapy, with special focus on the cardiac conduction system.

Activity of sotorasib against brain metastases from NSCLC harboring KRAS p.G12C mutation: a case report.

In the CodeBreaK 100 phase 2 study, sotorasib was active for patients with metastatic non-small cell lung cancer (NSCLC) harboring Kirsten rat sarcoma viral oncogene homologue (KRAS) p.G12C mutation. However, patients with untreated and/or active brain metastases were excluded from the trial, and the activity of sotorasib in the setting of brain metastases should be further investigated. Here we report the case of a KRAS p.G12C mutant NSCLC patient with three brain metastases, of whom one was untreated and the other two had progressed after radiotherapy with symptoms requiring steroids, that responded to sotorasib. Our report suggests that sotorasib may be active against untreated or progressive brain metastases, supporting further evaluation of sotorasib in this setting.

PSMA-PET/CT-Based Stereotactic Body Radiotherapy (SBRT) in the Treatment of Uncomplicated Non-Spinal Bone Oligometastases from Prostate Cancer.

BACKGROUND AND PURPOSE: Stereotactic body radiotherapy (SBRT) has a consolidated role in the treatment of bone oligometastases from prostate cancer (PCa). While the evidence for spinal oligometastases SBRT was robust, its role in non-spinal-bone metastases (NSBM) is not standardized. In fact, there was no clear consensus about dose and target definition in this setting. The aim of our study was to evaluate efficacy, toxicity, and the pattern of relapse in SBRT delivered to NSBM from PCa. MATERIALS AND METHODS: From 2016 to 2021, we treated a series of oligo-NSBM from PCa with 68Ga-PSMA PET/CT-guided SBRT. The primary endpoint was local progression-free survival (LPFS). The secondary endpoints were toxicity, the pattern of intraosseous relapse, distant progression-free survival (DPFS), polimetastases-free survival (PMFS), and overall survival (OS). RESULTS: a total of 150 NSBM in 95 patients were treated with 30-35 Gy in five fractions. With a median follow-up of 26 months, 1- and 3 years LPFS was 96.3% and 89%, respectively. A biologically effective dose (BED) ≥ 198 Gy was correlated with improved LPFS (p = 0.007). Intraosseous relapse occurred in eight (5.3%) cases. Oligorecurrent disease was associated with a better PMFS compared to de novo oligometastatic disease (p = 0.001) and oligoprogressive patients (p = 0.007). No grade ≥ 3 toxicity occurred. CONCLUSION: SBRT is a safe and effective tool for NSBM from PCa in the oligometastatic setting. Intraosseous relapse was a relatively rare event. Predictive factors of the improved outcomes were defined.

Proton Beam Therapy in the Oligometastatic/Oligorecurrent Setting: Is There a Role? A Literature Review.

BACKGROUND: Stereotactic ablative radiotherapy (SABR) and stereotactic radiosurgery (SRS) with conventional photon radiotherapy (XRT) are well-established treatment options for selected patients with oligometastatic/oligorecurrent disease. The use of PBT for SABR-SRS is attractive given the property of a lack of exit dose. The aim of this review is to evaluate the role and current utilisation of PBT in the oligometastatic/oligorecurrent setting. METHODS: Using Medline and Embase, a comprehensive literature review was conducted following the PICO (Patients, Intervention, Comparison, and Outcomes) criteria, which returned 83 records. After screening, 16 records were deemed to be relevant and included in the review. RESULTS: Six of the sixteen records analysed originated in Japan, six in the USA, and four in Europe. The focus was oligometastatic disease in 12, oligorecurrence in 3, and both in 1. Most of the studies analysed (12/16) were retrospective cohorts or case reports, two were phase II clinical trials, one was a literature review, and one study discussed the pros and cons of PBT in these settings. The studies presented in this review included a total of 925 patients. The metastatic sites analysed in these articles were the liver (4/16), lungs (3/16), thoracic lymph nodes (2/16), bone (2/16), brain (1/16), pelvis (1/16), and various sites in 2/16. CONCLUSIONS: PBT could represent an option for the treatment of oligometastatic/oligorecurrent disease in patients with a low metastatic burden. Nevertheless, due to its limited availability, PBT has traditionally been funded for selected tumour indications that are defined as curable. The availability of new systemic therapies has widened this definition. This, together with the exponential growth of PBT capacity worldwide, will potentially redefine its commissioning to include selected patients with oligometastatic/oligorecurrent disease. To date, PBT has been used with encouraging results for the treatment of liver metastases. However, PBT could be an option in those cases in which the reduced radiation exposure to normal tissues leads to a clinically significant reduction in treatment-related toxicities.

Linac-based versus MR-guided SBRT for localized prostate cancer: a comparative evaluation of acute tolerability.

AIM: This study aims to compare acute toxicity of prostate cancer (PCa) stereotactic body radiotherapy (SBRT) delivered by MR-guided radiotherapy (MRgRT) with 1.5-T MR-linac or by volumetric modulated arc (VMAT) with conventional linac. METHODS: Patients with low-to-favorable intermediate risk class PCa were treated with exclusive SBRT (35 Gy in five fractions). Patients treated with MRgRT were enrolled in an Ethical Committee (EC) approved trial (Prot. n° 23,748), while patients treated with conventional linac were enrolled in an EC approved phase II trial (n° SBRT PROG112CESC). The primary end-point was the acute toxicity. Patients were included in the analysis if they had at least 6 months of follow-up for the primary end-point evaluation. Toxicity assessment was performed according to CTCAE v5.0 scale. International Prostatic Symptoms Score (IPSS) was also performed. RESULTS: A total of 135 patients were included in the analysis. Seventy-two (53.3%) were treated with MR-linac and 63 (46.7%) with conventional linac. The median initial PSA before RT was 6.1 ng/ml (range 0.49-19). Globally, acute G1, G2, and G3 toxicity occurred in 39 (28.8%), 20 (14.5%), and 5 (3.7%) patients. At the univariate analysis, acute G1 toxicity did not differ between MR-linac and conventional linac (26.4% versus 31.8%), as well as G2 toxicity (12.5% versus 17.5%; p = 0.52). Acute G2 gastrointestinal (GI) toxicity occurred in 7% and 12.5% of cases in MR-linac and conventional linac group, respectively (p = 0.06), while acute G2 genitourinary toxicity occurred in 11% and 12.8% in MR-linac and conventional linac, respectively (p = 0.82). The median IPSS before and after SBRT was 3 (1-16) and 5 (1-18). Acute G3 toxicity occurred in two cases in the MR-linac and three cases in the conventional linac group (p = n.s.). CONCLUSION: Prostate SBRT with 1.5-T MR-linac is feasible and safe. Compared to conventional linac, MRgRT might to potentially reduce the overall G1 acute toxicity at 6 months, and seems to show a trend toward a lower incidence of grade 2 GI toxicity. A longer follow-up is necessary to assess the late efficacy and toxicity.

Salvage Stereotactic Reirradiation for Local Recurrence in the Prostatic Bed After Prostatectomy: A Retrospective Multicenter Study.

BACKGROUND: Management of local recurrence of prostate cancer (PCa) in the prostatic bed after radical prostatectomy (RP) and radiotherapy remains challenging. OBJECTIVE: To assess the efficacy and safety of salvage stereotactic body radiotherapy (SBRT) reirradiation in this setting and evaluate prognostic factors. DESIGN, SETTING, AND PARTICIPANTS: We conducted a large multicenter retrospective series that included 117 patients who were treated with salvage SBRT for local recurrence in the prostatic bed after RP and radiotherapy in 11 centers across three countries. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Progression-free survival (PFS; biochemical, clinical, or both) was estimated using the Kaplan-Meier method. Biochemical recurrence was defined as prostate-specific antigen nadir +0.2 ng/ml, confirmed by a second increasing measure. The cumulative incidence of late toxicities was estimated using the Kalbfleisch-Prentice method by considering recurrence or death as a competing event. RESULTS AND LIMITATIONS: The median follow-up was 19.5 mo. The median SBRT dose was 35 Gy. The median PFS was 23.5 mo (95% confidence interval [95% CI], 17.6-33.2). In the multivariable models, the volume of the recurrence and its contact with the urethrovesical anastomosis were significantly associated with PFS (hazard ratio [HR]/10 cm3 = 1.46; 95% CI, 1.08-1.96; p = 0.01 and HR = 3.35; 95% CI, 1.38-8.16; p = 0.008, respectively). The 3-yr cumulative incidence of grade ≥2 late GU or GI toxicity was 18% (95% CI, 10-26). In the multivariable analysis, a recurrence in contact with the urethrovesical anastomosis and D2% of the bladder were significantly associated with late toxicities of any grade (HR = 3.65; 95% CI, 1.61-8.24; p = 0.002 and HR/10 Gy = 1.88; 95% CI, 1.12-3.16; p = 0.02, respectively). CONCLUSIONS: Salvage SBRT for local recurrence in the prostate bed may offer encouraging control and acceptable toxicity. Therefore, further prospective studies are warranted. PATIENT SUMMARY: We found that salvage stereotactic body radiotherapy after surgery and radiotherapy allows for encouraging control and acceptable toxicity in locally relapsed prostate cancer.

STereotactic Arrhythmia Radioablation (STAR): the Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary consortium (STOPSTORM.eu) and review of current patterns of STAR practice in Europe.

The EU Horizon 2020 Framework-funded Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary (STOPSTORM) consortium has been established as a large research network for investigating STereotactic Arrhythmia Radioablation (STAR) for ventricular tachycardia (VT). The aim is to provide a pooled treatment database to evaluate patterns of practice and outcomes of STAR and finally to harmonize STAR within Europe. The consortium comprises 31 clinical and research institutions. The project is divided into nine work packages (WPs): (i) observational cohort; (ii) standardization and harmonization of target delineation; (iii) harmonized prospective cohort; (iv) quality assurance (QA); (v) analysis and evaluation; (vi, ix) ethics and regulations; and (vii, viii) project coordination and dissemination. To provide a review of current clinical STAR practice in Europe, a comprehensive questionnaire was performed at project start. The STOPSTORM Institutions' experience in VT catheter ablation (83% ≥ 20 ann.) and stereotactic body radiotherapy (59% > 200 ann.) was adequate, and 84 STAR treatments were performed until project launch, while 8/22 centres already recruited VT patients in national clinical trials. The majority currently base their target definition on mapping during VT (96%) and/or pace mapping (75%), reduced voltage areas (63%), or late ventricular potentials (75%) during sinus rhythm. The majority currently apply a single-fraction dose of 25 Gy while planning techniques and dose prescription methods vary greatly. The current clinical STAR practice in the STOPSTORM consortium highlights potential areas of optimization and harmonization for substrate mapping, target delineation, motion management, dosimetry, and QA, which will be addressed in the various WPs.

Metastases-directed stereotactic body radiotherapy in combination with targeted therapy or immunotherapy: systematic review and consensus recommendations by the EORTC-ESTRO OligoCare consortium.

Stereotactic body radiotherapy (SBRT) for patients with metastatic cancer, especially when characterised by a low tumour burden (ie, oligometastatic disease), receiving targeted therapy or immunotherapy has become a frequently practised and guideline-supported treatment strategy. Despite the increasing use in routine clinical practice, there is little information on the safety of combining SBRT with modern targeted therapy or immunotherapy and a paucity of high-level evidence to guide clinical management. A systematic literature review was performed to identify the toxicity profiles of combined metastases-directed SBRT and targeted therapy or immunotherapy. These results served as the basis for an international Delphi consensus process among 28 interdisciplinary experts who are members of the European Society for Radiotherapy and Oncology (ESTRO) and European Organisation for Research and Treatment of Cancer (EORTC) OligoCare consortium. Consensus was sought about risk mitigation strategies of metastases-directed SBRT combined with targeted therapy or immunotherapy; a potential need for and length of interruption to targeted therapy or immunotherapy around SBRT delivery; and potential adaptations of radiation dose and fractionation. Results of this systematic review and consensus process compile the best available evidence for safe combination of metastases-directed SBRT and targeted therapy or immunotherapy for patients with metastatic or oligometastatic cancer and aim to guide today's clinical practice and the design of future clinical trials.

Current practices and perspectives on the integration of contrast agents in MRI-guided radiation therapy clinical practice: A worldwide survey.

Aims: The introduction of on-line magnetic resonance image-guided radiotherapy (MRIgRT) has led to an improvement in the therapeutic workflow of radiotherapy treatments thanks to the better visualization of therapy volumes assured by the higher soft tissue contrast. Magnetic Resonance contrast agents (MRCA) could improve the target delineation in on-line MRIgRT planning as well as reduce inter-observer variability and enable innovative treatment optimization protocols. The aim of this survey is to investigate the utilization of MRCA among centres that clinically implemented on-line MRIgRT technology. Methods: In September 2021, we conducted an online survey consisting of a sixteen-question questionnaire that was distributed to the all the hospitals around the world equipped with MR Linacs. The questionnaire was developed by two Italian 0.35 T and 1.5 T MR-Linac centres and was validated by four other collaborating centres, using a Delphi consensus methodology. Results: The survey was distributed to 52 centres and 43 centres completed it (82.7%). Among these centres, 23 institutions (53.5%) used the 0.35T MR-Linac system, while the remaining 20 (46.5%) used the 1.5T MR-Linac system.According to results obtained, 25 (58%) of the centres implemented the use of MRCA for on-line MRIgRT. Gadoxetate (Eovist®; Primovist®) was reported to be the most used MRCA (80%) and liver the most common site of application (58%). Over 70% of responders agreed/strongly agreed to the need for international guidelines. Conclusions: The use of MRCA in clinical practice presents several pitfalls and future research will be necessary to understand the actual advantage derived from the use of MRCA in clinical practice, their toxicity profiles and better define the need of formulating guidelines for standardising the use of MRCA in MRIgRT workflow.

A predictive model of polymetastatic disease from a multicenter large retrospectIve database on colorectal lung metastases treated with stereotactic ablative radiotherapy: The RED LaIT-SABR study.

Aim: Stereotactic ablative radiotherapy (SABR) showed increasing survival in oligometastatic patients. Few studies actually depicted oligometastatic disease (OMD) evolution and which patient will remain disease-free and which will rapidly develop a polymetastatic disease (PMD) after SABR. Therefore, apart from the number of active metastases, there are no clues on which proven factor should be considered for prescribing local treatment in OMD. The study aims to identify predictive factors of polymetastatic evolution in lung oligometastatic colorectal cancer patients. Methods: This international Ethical Committee approved trial (Prot. Negrar 2019-ZT) involved 23 Centers and 450 lung oligometastatic patients. Primary end-point was time to the polymetastatic conversion (tPMC). Additionally, oligometastases number and cumulative gross tumor volume (cumGTV) were used as combined predictive factors of tPMC. Oligometastases number was stratified as 1, 2-3, and 4-5; cumGTV was dichotomized to the value of 10 cc. Results: The median tPMC in the overall population was 26 months. Population was classified in the following tPMC risk classes: low-risk (1-3 oligometastases and cumGTV ≤ 10 cc) with median tPMC of 35.1 months; intermediate-risk (1-3 oligometastases and cumGTV > 10 cc), with median tPMC of 13.9 months, and high-risk (4-5 oligometastases, any cumGTV) with median tPMC of 9.4 months (p = 0.000). Conclusion: The present study identified predictive factors of polymetastatic evolution after SABR in lung oligometastatic colorectal cancer. The results demonstrated that the sole metastases number is not sufficient to define the OMD since patients defined oligometastatic from a numerical point of view might rapidly progress to PMD when the cumulative tumor volume is high. A tailored approach in SABR prescription should be pursued considering the expected disease evolution after SABR, with the aim to avoid unnecessary treatment and toxicity in those at high risk of polymetastatic spread, and maximize local treatment in those with a favorable disease evolution.

Stereotactic Body Radiotherapy for a Rare Case of Sinonasal Metastasis Arising from Renal Cell Cancer.

BACKGROUND/AIM: Sinonasal metastases arising from renal cell cancer are rare and usually managed with surgery. Few studies describe the use of radiotherapy in this specific setting, while the use of stereotactic body radiotherapy (SBRT) has been rarely reported as well. CASE REPORT: We present the case of a solitary left sinonasal metastasis in a 65-year-old man with clear cell renal cancer who also received bilateral nephrectomy and subsequent kidney transplantation. The patient received subtotal surgery and subsequently he was candidate to SBRT to avoid systemic treatment, due to renal comorbidities. CONCLUSION: The patient was treated with SBRT for a total dose of 35 Gy in 5 fractions and after 24 months of follow-up there is no evidence of local relapse. No major side-effects were reported. Our experience supports SBRT as a safe and feasible treatment option in the case of sinonasal metastases from RCC.