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The therapeutic landscape of metastatic prostate cancer has undergone a profound revolution in recent years. In addition to the introduction of novel molecules in the clinics, the field has witnessed a tremendous development of functional imaging modalities adding new biological insights which can ultimately inform tailored treatment strategies, including local therapies. The evolution and rise of Stereotactic Body Radiotherapy (SBRT) have been particularly notable in patients with oligometastatic disease, where it has been demonstrated to be a safe and effective treatment strategy yielding favorable results in terms of disease control and improved oncological outcomes. The possibility of debulking all sites of disease, matched with the ambition of potentially extending this treatment paradigm to polymetastatic patients in the not-too-distant future, makes Biology-guided Radiotherapy (BgRT) an attractive paradigm which can be used in conjunction with systemic therapy in the management of patients with metastatic prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose: Biochemical recurrence (BR) occurs in up to 40% of patients with prostate cancer (PCa) treated with primary radical prostatectomy (RP). Choline PET/CT may show, in a single-step examination, the site of tumor recurrence earlier than traditional imaging methods, particularly at low prostate-specific antigen (PSA) levels, thus influencing subsequent treatment. Methods/patients: Patients with recurrent and non-metastatic prostate cancer (nmPCa), who were assessed with choline PET/CT, were included in the analysis. Based on imaging results, the following therapeutic strategies were chosen: radiotherapy to the prostatic bed, androgen deprivation therapy (ADT), and chemotherapy or stereotactic body radiotherapy (SBRT) to either the pelvic lymph nodes or distant metastases. We assessed the impact of age, PSA levels, Gleason score (GS), and adjuvant therapy on oncological outcomes. Results: Data from 410 consecutive nmPCa patients with BR who underwent RP as primary treatment were analyzed. One hundred seventy-six (42.9%) patients had a negative choline PET/CT, and 234 (57.1%) patients resulted positive. In the multivariate analysis, only chemotherapy and PSA at recurrence were significant independent prognostic factors on overall survival (OS). In the PET-positive subgroup, the number of relapses, PSA post-prostatectomy, and chemotherapy impacted on OS. PSA (post-surgery and at recurrence) affected progression-free survival (PFS) in the univariate analysis. In the multivariate analysis, GS, the number of relapse sites, and PSA (post-surgery and at recurrence) were significant prognostic factors for disease-free survival (DFS). Conclusion: Choline PET/CT provides better accuracy than conventional imaging for the assessment of nmPCa with BR after prostatectomy, thereby enabling salvage strategies and improving quality of life. [ABSTRACT FROM AUTHOR]

Background: Metastatic soft tissue sarcoma (STS) patients may benefit from local ablative treatments due to modest efficacy of systemic chemotherapy. However, use of stereotactic body radiotherapy (SBRT) is controversial because of presumed radioresistance of STS.Methods: Patients treated with SBRT for oligometastatic and oligoprogressive metastatic STS were retrospectively reviewed to assess results in terms of local control (LC), disease-free survival (DFS), and overall survival (OS). Incidence and grade of adverse events were reported. Statistical analysis was performed to identify variables correlated with outcome and toxicity.Results: Forty patients were treated with SBRT to a median biologic effective dose (BED) of 105 (66-305) Gy5 to 77 metastases. Two-year LC, DFS, and OS were 67%, 23%, and 40%. Improved LC was shown in patients receiving a BED >150 Gy5 (hazard ratio [HR], 3.9; 95% confidence interval [CI], 1.6-9.7; P = 0.028). A delay >24 months between primary tumor diagnosis and onset of metastases was associated with improved DFS (HR, 0.46; 95% CI, 0.22-0.96; P = 0.01) and OS (HR, 0.48; 95% CI, 0.23-0.99; P = 0.03). No toxicity grade ≥3 was observed.Conclusions: Stereotactic body radiotherapy is effective in metastatic STS with a benign toxicity profile. A BED >150 Gy5 is required to maximize tumor control rates. Metastatic relapse >24 months after diagnosis is correlated to improved survival. [ABSTRACT FROM AUTHOR]

New metabolic tracers have improved sensitivity and specificity for the real extent of tumor burden in prostate cancer. This study aims to compare the impact of these tracers for metastasis-directed therapy. Gallium-68 prostate-specific membrane antigen-positron emission tomography-guided metastasis-directed therapy in castration-sensitive oligorecurrent prostate cancer patients resulted in higher rates of androgen deprivation therapy-free survival, when compared with 18F-fluorocholine positron emission tomography-guided treatments (P = .00). Background: The present analysis aims to compare the impact of 18F-fluorocholine (18F-choline) and gallium-68 prostatespecific membrane antigen (68Ga-PSMA) positron emission tomography (PET)-computed tomography (CT)eguided metastases-directed therapies (MDTs) in patients with castration-sensitive oligorecurrent prostate cancer (PC). Materials and Methods: Inclusion criteria were: (1) histologically proven prostate adenocarcinoma; (2) evidence of biochemical relapse after primary tumor treatment; (3) ≤ 3 hypermetabolic oligorecurrent lesions detected by 18F-choline or 68Ga-PSMA PET-CT; (4) PET-CT imaging performed in a single nuclear medicine department; (5) patients treated with upfront stereotactic body radiotherapy (SBRT) without hormone therapy; and (6) SBRT delivered with a dose per fraction ≥ 5 Gy. In the case of oligoprogression (≤ 3 lesions outside the previous RT field) after MTD, a further course of SBRT was proposed; otherwise, androgen deprivation therapy (ADT) was administered. Results: A total of 118 lesions in 88 patients were analyzed. Forty-four (50%) patients underwent 68Ga-PSMA PET-guided SBRT, and the remaining underwent choline PET-based SBRT. The median follow-up was 25 months (range, 5-87 months) for the entire cohort. Overall survival and local control were both 100%. Distant progression occurred in 48 (54.5%) patients, for a median distant progression-free survival of 22.8 months (range, 14.4-28.8 months). The median pre-SBRT prostate-specific antigen was 2.04 ng/mL in the choline PET cohort and 0.58 ng/mL in the PSMA-PET arm. Disease-free survival rates were 63.6% and 34%, respectively, in the 68Ga-PSMA and choline PET group (P = .06). The ADT administration rate was higher after choline-PETeguided SBRT (P = .00) owing to the higher incidence of polymetastatic disease after first-course SBRT compared with 68Ga-PSMA-based SBRT. Conclusion: In the setting of oligorecurrent castration-sensitive PC, PSMA-PET-guided SBRT produced a higher rate of ADT-free patients when compared with the 18F-choline-PET cohort. Randomized trials are advocated. [ABSTRACT FROM AUTHOR]

Objective: To assess the safety and effectiveness of stereotactic salvage radiotherapy (SSRT) in RT‐naïve patients affected by macroscopic prostate bed recurrence. Patients and methods: Consecutive patients treated for prostate bed macroscopic recurrence in three different Italian institutes were reviewed. Patients were treated with SSRT, with a total dose of 30–40 Gy in five fractions, the mean pre‐SSRT PSA level was 2.3 ng/mL. Two different PSA thresholds were defined and biochemical recurrence‐free survival (BCRFS) was reported, in order to better express outcome: BCRFS1 (a PSA level increase of >10% compared to the pre‐SSRT value) and BCRFS2 (a PSA level increase of >0.2 ng/mL for patients with a PSA nadir of <0.2 ng/mL or two consecutive PSA level increases of >25% compared to nadir in patients with a PSA nadir of <0.2 ng/mL). Results: In all, 90 patients were treated, with a mean (range) follow‐up of 21.2 (2–64) months, and 17 of these patients (19%) had concomitant androgen‐deprivation therapy (ADT) during SSRT. Complete biochemical response, defined as a PSA nadir of <0.2 ng/mL, was obtained in 39 of the 90 patients (43.3%). Considering BCRFS1, 25 patients (27.8%) had BCR, with an actuarial median BCRFS1 time of 36.4 months. For BCRFS2, BCR was reported in 32 patients (35.5%), with an actuarial median BCRFS2 time of 24.3 months. There was no Grade >2 toxicity. Conclusions: SSRT was found to yield significant biochemical control and allowed ADT delay despite adverse features. [ABSTRACT FROM AUTHOR]

Purpose The 11-gauge (11G) stereotactic vacuum-assisted breast biopsy (VABB) showed a better profile than 14G-VABB in terms of feasibility, safety, microcalcification sampling, and accuracy. Underestimation rates were significantly lower with 11G-VABB than with 14G-VABB. Thus, the introduction of an even larger needle at the VABB procedure could reduce this rate further. The purpose of this study was to compare the overall performance of stereotactic VABB with 8G and 11G needles. Materials and methods Four hundred and three VABBs performed between July 2012 and February 2015 at the Breast Diagnostic Unit of Careggi Hospital in Florence were retrospectively analyzed; 197 were performed with 11G-VABB and 206 with 8G-VABB. Lesions were classified according to mammographical patterns in microcalcifications, architectural distortions, or opacities, and all biopsy targets were classified according to BIRADS classification as BIRADS III, IV or V. Data were collected on radiological classification of targets, imaging presentation, procedure time, number of specimens per procedure, and microcalcification retrieval on histological findings. Surgery was always performed when high-risk or malignant lesions (B3 or B5) were detected; the final diagnosis was made on surgical pathology. Results Compared to VABB with an 11G needle, 8G-VABB allows a reduction in the time needed to complete the procedure (20.6 versus 27.4, P < 0.00001) and the number of specimens collected per lesion (21.6 versus 12.2, P < 0.00001). Moreover, 8G-VABB resulted in the same diagnostic accuracy, and the underestimation rates were comparable between the two groups for both B3 and DCIS lesions. Conclusions The 8G needle should be considered as a valid alternative option in VABB for breast lesions. [ABSTRACT FROM AUTHOR]

Robotic Stereotactic Body Radiotherapy (SBRT) employs radiopaque fiducial markers implanted near the tumor for real-time tracking. Fiducials are usually placed before simulation under CT or ultrasound guidance. This represents a limitation to treatment availability and may result in potential treatment delay. In our Institution, an in-house percutaneous CTguided fiducial placement procedure was implemented for pelvic SBRT. The aim of our study is to evaluate the performance and side effects of in-house fiducial placement. Methods: Patients underwent percutaneous fiducial insertion with a 18 G needle under CT guidance, using a radiopaque skin marker to calculate the depth of target location from body surface (Figure 1). One week after placement, simulation CT and orthogonal X-ray imaging were acquired to verify fiducial usability for SBRT tracking. Data from a consecutive cohort of patients treated with fiducial-guided, robotic-arm pelvic SBRT were collected from January 2018 to September 2021. Success rate was defined as the implanted/tracked fiducials ratio. Kruskal Wallis-test was used to compare median success rate over time. Results: In the observed time frame, 282 patients underwent CT-guided fiducial placement, accounting for 883 implanted fiducials (median 3, range 1-4). Implantation sites were the prostate bed, extra-spinal bones and pelvic lymph nodes in 158 (56%), 37 (13%) and 87 (31%) patients, respectively. Side effects consisted of minor bleeding at the insertion site and transient pain requiring medication after 24 hours in 5 patients (2%). No grade >2 toxicity was observed. Overall success rate was 86% (719/833); median success rate per procedure was 100% (range 50-100%). Among the 114 fiducials rejected for tracking, failure was due to migration in 63 cases (55%) and misplacement in 51 cases (45%). Overall success rate increased across the observed time window from 2018 (53/73, 74%) to 2019 (245/293, 84%) to 2020 (246/272, 90%) to 2021 (175/195, 90%) (Figure 2). A consistent, statistically significant improvement in median success rate was observed over time from 2018 (75%, Interquartile Range, IQR 67-100%) to 2019 (100%, IQR 75-100%) to 2020 (100%, IQR 75-100%) to 2021 (100%, IQR 100- 100%) : p= 0.0008. Conclusions: Our in-house percutaneous CT-guided fiducial placement is a safe procedure requiring minimal standard equipment, resulting in success rates comparable with published experiences performed in a dedicated interventional radiology setting. A consistent improvement in median success rate was observed over 4 years, suggesting the need for appropriate interventions to shorten the learning curve. [ABSTRACT FROM AUTHOR]

Purpose: To assess the outcomes of a cohort of bone oligometastatic prostate cancer patients treated with PSMA-PET guided stereotactic body radiotherapy (SBRT) Methods: From April 2017 to January 2021, 40 patients with oligorecurrent prostate cancer detected by PSMAPET were treated with SBRT for bone oligometastases. Concurrent androgen deprivation therapy was an exclusion criterion. A total of 56 prostate cancer bone oligometastases were included in the present analysis. In 28 patients (70%), oligometastatic disease presented as a single lesion, two lesions in 22.5%, three lesions in 5%, four lesions in 2.5%. Results: 30.3% were spine-metastases, while 69.7% were non-spine metastases. SBRT was delivered for a median dose of 30 Gy (24-40Gy) in 3-5 fractions, with a median EQD2=85 Gy2 (64.3 - 138.9Gy2). With a median followup of 22 months (range, 2-48 months), local control (LC) 1- and 2-years rates were 96.3% and 93.9%, while distant progression-free survival (DPFS) rates were 45.3% and 27%. At multivariate analysis, the lower PSA nadir value after SBRT remained significantly related to better DPFS rates (p=0.03). In 7 patients, a second SBRT course was proposed with concurrent ADT, while 11 patients, due to polymetastatic spread, received ADT alone, resulting in 1- and 2-years ADT-free survival rates of 67.5% and 61.8%. At multivariate analysis, a lower number of treated oligometastases maintained a correlation with higher ADT-free survival rates (p=0.04). Conclusions: In our experience, PSMA-PET guided SBRT resulted in excellent results in terms of clinical outcomes, representing a helpful tool with the aim to delay the start of ADT. [ABSTRACT FROM AUTHOR]

Background: Soft tissue sarcomas (STS) are a group of rare, heterogeneous tumors. Scarce terapeuthic options are currently available, given the limited efficacy of systemic chemotherapy. Patients with low-burden metastatic disease may benefit from adjunction of local ablative treatments. However, because of the presumed radioresistance of STS, stereotactic body radiotherapy (SBRT) has not been steadily considered as a viable treatment option. Methods: We retrospectively reviewed STS patients treated with SBRT in a single institution,, for oligometastatic and oligoprogressive metastatic disease. Local control (LC), disease-free survival (DFS), and overall survival (OS) were assessed. We also reported the incidence of early and late adverse events and their grade according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0. Univariate and multivariate statistical analysis were carried out to investigate variables correlated with outcome and toxicity. Results: Forty patients were treated between 2012 and 2019 to 77 metastases with SBRT to a median biologic effective dose (BED5, assuming an α/β=5) of 105 Gy (range 66 to 305 Gy). 63% of patients had received 2 or more chemotherapy lines at the time of SBRT. LC, DFS and OS at two years were 67%, 23% and 40% respectively. At multivariate analysis, LC only significantly improved in patients receving a BED5>150 Gy (hazard ratio [HR] 3.9. 95% confidence interval [CI], 1.6-9.7; p=0.028), while an interval>24 months between primary tumor diagnosis and metastatic disease relapse was correlated with improved DFS and OS (HR, 0.46; 95% CI, 0.22-0.96; P = 0.01 and HR, 0.48; 95% CI, 0.23- 0.99; P = 0.03, respectively). Early toxicity was observed in 4 patients, late toxicity in 1 patient. No toxicity grade>2 was observed. Conclusions: SBRT is an effective therapeutic option in metastatic STS. A BED5>150 Gy5 is required to obtain better tumor control rates. Metastatic relapse>24 months after diagnosis is correlated with improved overall survival. Adverse events are scarce and mostly transient, meaning SBRT is safe and could be an option even in heavily pretreated patients. [ABSTRACT FROM AUTHOR]

Purpose or objective: Stereotactic Body Radiotherapy (SBRT) is widely used for treatment of uncomplicated spine metastases to palliate symptoms and prolong disease control. However, criteria for patient selection are not available. The aim of this study is to identify determinants of local failure and progression-free interval in patients treated with SBRT to spinal metastases. Materials and methods: Data from consecutive patients treated with Cyberknife-based spine SBRT between January 2019 and March 2020 were retrospectively collected. Dose was expressed as Biological Effective Dose for α/β=10 (BED10). Kaplan-Meyer method was used to calculate Local Control (LC) and Disease Free Survival (DFS) from date of SBRT to event. Univariate (UVA) and Multivariate analysis (MVA) were performed using log-rank and Cox model, respectively. Results: Sixty-two patients accounting for 70 spinal metastases were included. Median age was 66 (range 32- 87) years. Disease was metastatic at diagnosis in 21 patients (34%) : an active primary tumor was present in 17 patients (27%). Among treated sites, most represented primary malignancies were prostate (n=28, 40%) and breast (n=21, 30%). Dose regimens consisted of 25-30 Gy in 5 fractions and 21-30 Gy in 3 fractions in respectively 61 (87%) and 9 (13%) cases, resulting in a median BED of 43.2 (range 37.5-60) Gy10. Concurrent chemotherapy (including cytotoxic or targeted agents) was administered in 43% of cases (n=30). After a median follow up of 10 months (range 1-24 months), 9 local relapses and 40 distant progressions were observed. One year LC was 87% (Fig.1): nonprostate primary tumor (p=0.003, Fig.2) and concurrent chemotherapy (p=0.006, Fig.3) were associated to poorer LC at UVA, and an independent correlation was confirmed at MVA (respectively p=0.017 and p=0.024). One-year DFS was 43% (Fig.4). UVA showed a correlation between impaired DFS and active primary tumor (p=0.003), metastatic dissemination at diagnosis (p=0.02) and nonprostate primary tumor (p=0.009), although only an active primary tumor site was independently associated to DFS at MVA (p=0.007, Fig.5). Only G2 acute pain or nausea were observed. No late toxicity, in particular vertebral fracture, was reported. Conclusion: Spine SBRT results in high LC rates and durable progression-free survival with low incidence of mild toxicity. Clinical nomograms based on patient-related characteristics may help to select candidates for this approach. [ABSTRACT FROM AUTHOR]

Background: Breast-conserving surgery (BCS) followed by postoperative radiation therapy (RT) to the residual breast represents the current standard of care for most women affected by early breast cancer. However, standard postoperative regimens are characterized by postsurgical waiting time and potential acute and late locoregional adverse events. Several studies suggested that breast cancer cells can be more sensitive to high doses administered in short intervals. Preoperative robotic stereotactic radiotherapy (SBRT) followed by BCS may yield potential advantages in selected patients. An exploratory phase II study (ROCK trial – NCT03520894) was conducted in our institution. Materials: Women with histologically proven unifocal invasive hormonal receptors positive, HER2 negative breast cancer, sized less than 25 mm, with negative clinical nodal status, aged 50+ and eligible for BCS were enrolled. Fiducial markers were introduced in peri/ intralesional position. Magnetic resonance imaging (MRI) was used in addition to standard CT-based planning. Patients received 21 Gy in single fraction with CyberKnife® followed by BCS two weeks after preoperative SBRT. The primary endpoint was the acute skin toxic effect rate. Secondary objectives were the pathological response rate and the late adverse events rate. Echocardiography and spirometry were performed before preoperative SBRT and yearly thereafter. Translational research was conducted to identify correlations between radiogenomic, immunological and biochemical biomarkers with treatment-related response and toxicity. Results: From August 2018 to September 2021, a total of 70 patients were screened on mammography; 29 of them were eligible following inclusion criteria. Seven were excluded due to multiple foci disease at basal MRI, and 22 patients were successfully treated. All required dosimetric parameters and normal tissue constraints were met in all cases. Median age at diagnosis was 68 years (range 50-86) and median tumor size was 13 mm (range 7.5-25). All treated patients received surgery within 14 days from preoperative SBRT without any delay or complication. No patients experienced acute skin toxicity of grade (G) 2 or higher; only one patient had a G1 erythema one month after BCS. Two patients reported a pathological complete response, according to Chevallier’s classification. At a median follow up of 18 months, no patients experienced locoregional recurrence or distant metastases. No clinically meaningful changes were observed regarding left-ventricular ejection fraction and spirometric parameters. Conclusion: Results from the ROCK trial showed that single fraction preoperative robotic SBRT is a feasible technique in selected breast cancer patients with a good safety profile and encouraging activity. This new approach warrants further investigations. [ABSTRACT FROM AUTHOR]

Differentiated thyroid cancer is usually associated with a good prognosis. The development of metastases in Iodine-refractory thyroid cancer adversely affect patients’ quality of life and survival. The advent of tyrosine-kinase inhibitors drugs (TKI) allowed a great improvement of patients’ outcome but, in case of oligometastatic disease, a locoregional ablative approach such as Stereotactic Radiation Therapy (SRT) could effectively control tumour progression and possibly defer the need of systemic therapies. In our study, we analysed the effectiveness of SRT in oligometastatic Iodine-refractory thyroid cancer patients. Methods: We retrospectively analysed patients with differentiated oligometastatic thyroid cancer treated with SRT in our Radiation Oncology Unit from 2011 to 2020. We collected demographics and treatment-related characteristics. Local Control (LC), Progression Free Survival (PFS) and Overall Survival (OS) rates were evaluated. Patients with anaplastic histology, incomplete treatment or without follow-up information were excluded. Results: We retrospective analysed a cohort of 15 patients, aged between 47 and 72 years old (median 63,3). 8 (53,3%) patients were males and 7 (46,7%) were females. A total of 42 lesions were treated: 19 were located in bones (45,2%), 11 in lymph nodes (26,2%), 3 visceral (7.1%), 7 in the brain (16,7%) and 2 in the lungs (4,8%). SBRT was delivered in 1-8 fractions, with a median dose of 30Gy (range 14-60Gy). Median followup from the date of the first SRT was 47,7 months (range 14,4–105 months). After SRT we observed a complete response in 21 lesions (50%), partial response in 13 (31%), stable disease in 7 (16,7%) and only 1 progressive lesion (2,4%). We observed 9 local recurrences (21,4%) with an actuarial LC of 95% and 89,9% at 12 and 24 months respectively, while PFS was 45.6% and 32,9% at 12 and 24 months respectively. The OS at 12, 24, 48 months was 93,3%, 86,2% and 79%, respectively. A total number of 10 patients (66,7%) underwent TKI treatment (4 Sunitinib and 5 Lenvatinib) for progressive disease: median time to first systemic treatment from the SBRT was 17,7 months (range 1-47,7 months). At the end of this analysis, 5 patients (33.3%) were still without systemic therapy, showing a good disease control after a median follow-up of 50,6 months (range 35.3-57). Conclusions: In our experience, SRT yields satisfying local control rates in oligometastatic Iodine-refractory thyroid cancer, allowing for a deferral of systemic therapies. [ABSTRACT FROM AUTHOR]

Purpose: Stereotactic body radiotherapy (SBRT) has emerged as a novel therapeutic option to improve outcome of patients with locally advanced pancreatic cancer (LAPC). More intensive schedules are often challenging due to proximity of organs at risks (OARs). Local control is closely related to a biologically effective dose (BED) of 100 Gy10, corresponding to a dose of 50 Gy in 5 fractions. An in-silico study was performed to evaluate the feasibility of dose escalation in SBRT treatments of LAPC through inhomogeneous dose prescription, and to identify patients suitable for this strategy, based on anatomical proximity between target volumes and OARs. Materials and methods: We collected dosimetric data from 14 patients treated at our center for LAPC. For each patient, a CyberKnife (CK) Synchrony re-planning for fiducial-guided pancreatic SBRT treatment was developed for a planned dose of 50 Gy and 40 Gy in 5 fractions to gross tumor volume (GTV) and target volume planning (PTV), respectively. Priority was given to OAR constraints. Criteria for acceptable coverage of the target were: a) 50 Gy and 47.5 Gy to ≥90% and ≥95% of the GTV, respectively, and b) 40 Gy to ≥95% of the PTV. For each plan, a Expansion-Intersection Volume (EIV), corresponding to the intersection volume between PTV and OARs expanded by 5 mm, was calculated. The planned doses to the target volumes and the OARs were evaluated and statistically analyzed. Results: Median GTV and PTV sizes were 40.8 (range 22.3-205.3) cc and 73.7 (range 36.1-266.7) cc, respectively. Treatment plans have been optimized to keep a V35 in the duodenum, stomach and intestines below 0.5cc in all cases. Median V50 and V47.5 for GTV was 91.0% (range 82.4% -97.8%) and 96.8% (range 92.5% -99.9%), respectively: GTV coverage was acceptable in 10 out of 14 cases. Median V40Gy for PTV was 96.8% (range 90.0% -99.8%): PTV coverage was acceptable in 11 of 14 cases. Median EIV was 12.9 (3.9- 25.1) cc. Spearman correlation showed a significant association between EIV and V47.5Gy for GTV (rho -0.77228, p<0.001) and V40Gyfor PTV (rho -0.68352, p <0.001), respectively (Figure 1). Conclusions: Inhomogenous dose escalated prescription to a BED≥100Gy10 is a feasible treatment strategy in selected patients with LAPC (Figure 2). EIV represents a simple tool to identify suitable patients for this approach [ABSTRACT FROM AUTHOR]

Purpose: Brain metastases (BMs) accounts for more than one-half of all intracranial tumors. Survival of patients (pts) with BMs has increased in recent years with the entry of stereotactic radiosurgery (SRS), providing excellent rates of local disease control. Silibinin or silybin, a natural polyphenolic flavonoid isolated from milk thistle seed extracts, showed promising antitumor activity in preclinical studies. Furthermore, the use of a silibinin-based nutraceutical has resulted in significant clinical and radiological improvement of BMs in pts with progressive non-small cell lung cancer (NSCLC) after whole brain radiotherapy and chemotherapy. The aim of our exploratory study is to evaluate whether the use of a silibinin-based nutraceutical significantly reduces distant-brain failure (DBF) at 6 months in pts with first-diagnosed BMs treated with SRS with or without surgery. Here a preliminary analysis on the first 18 pts enrolled is reported. Methods: SUSTAIN is a prospective, single arm, phase II study. A total of 80 pts with newly diagnosed BMs treated in our center and complying with the entry criteria are planned to be enrolled. Pts receive 2 capsules (cps) of SILLBRAIN® per day for the first month after SRS and 1 cp per day thereafter. The 6-month DBF rate is assessed according to RANO criteria for brain metastases (RANO-BM). Contrast-enhanced magnetic resonance (MRI) of the brain is performed at baseline and every 12 weeks after SRS. Validated health-related quality of life questionnaires (EORTC QLQ-C30 and BN20) are administered at baseline and every 12 weeks after SRS. Results: Eighteen pts had been enrolled at the time of this primary analysis. NSCLC and breast cancer were the prevalent histologies, with 9 and 4 cases respectively. Ten pts had metachronous BMs onset, and 8 pts synchronous. Nine pts received at least 1 line of systemic therapy and 17 pts reported a controlled extracranial disease at BMs diagnosis. The overall number of BMs was 55. All BMs were treated with SRS, with a median prescription dose and median prescription isodose of 24Gy and 80%, respectively. According to RANOBM criteria, 2 pts reported distant intracranial failure with 3 and 19 months of DBF. One pts discontinued SILLBRAIN® assumption due to grade 1 nausea (CTCAE v5.0). No other adverse events were reported. Conclusion: The use of silibinin-based nutraceuticals after SRS might prolong distant brain failure-free survival in BMs pts, with a favorable safety profile. Final results from SUSTAIN trial are awaited to confirm these encouraging findings. [ABSTRACT FROM AUTHOR]

Introduction: Only 30% of patients with liver metastases (LM) may be suitable for surgery due to unfavourable location, comorbidities or extrahepatic disease burden. Patients treated with stereotactic radiotherapy (SBRT) reported excellent local control (LC) and low toxicity rate although data on global disease control are missing. The aim of this preliminary analysis was to assess patterns of failure in a cohort of patients treated with SBRT for LM. Method: Data from patients treated between 2018 and 2020 at our Institution with SBRT to LM receiving at least an EQD2 of 50 Gy (α/β=10) as per ESTRO consensus were collected. Failure patterns following SBRT and rates of local control (LC), intrahepatic relapse (excluding treated site, IHR), extrahepatic relapse (EHR), and overall survival (OS) were evaluated. Results: Forty-three patients received liver SBRT due to oligometastatic (20,46%) and oligoprogressive (23,54%) disease. Most common primary tumors were breast (n=18,42%) and colon (n=10,23%) cancer. SBRT was performed using Cyberknife real-time tumor tracking(n=30,70%) or abdominal compression-assisted VMAT (n=13,30%) delivering 35-60 Gy in 3-5 fractions, corresponding to median EQD2 of 94 (50-150) Gy. Twelve (28%) patients were chemotherapy-naïve, while the remaining patients received 1(20,46%), 2(5,12%) or ≥3(6,14%) chemotherapy lines. Median follow-up was 12 months. Patterns of failure are reported in Table 1. One-year LC, IHR, EHR and OS were 80%,51%,49% and 87% respectively. At multivariate analysis LC was significantly correlated with EQD2≥94Gy(p=0.009) and ≥3 chemotherapy lines(p=0.04). IHR and EHR were significantly associated with local failure (p=0.0013) and intrahepatic progression (p=0.03), respectively. A significant correlation between OS and local relapse was shown (p=0.026). Conclusion: In our experience, improved LC using high BED in non-heavily pretreated patients was correlated to reduced risk of IHR and to improved OS. IHR was the dominant mode of failure in patients treated with SBRT for LM,and was correlated to further progression at extrahepatic sites. Our findings suggest that IHR may result from uncontrolled macroscopic LM rather than ubiquitous micrometastatic dissemination, and preceed further systemic spread at distant sites. Our findings support the use of SBRT as an efficient tool to block stepwise metastatic spread from uncontrolled isolated LM to liver, and from liver to distant site, thus extending global disease control. [ABSTRACT FROM AUTHOR]

Purpose or objective: Oligoprogression (OPD) is defined as a condition where limited progression (1-3 metastases) is observed in patients undergoing systemic cancer treatment. Local treatment of OPD might delay systemic therapy line switch, which could be beneficial in patients experiencing prolonged global disease control with novel targeted or immune therapies. In this study we investigated the impact on outcome of stereotactic body radiotherapy (SBRT) in patients with OPD from metastatic lung cancer. Materials and methods: Data from a cohort of consecutive patients treated with Cyberknife and Linacbased SBRT between June 2015 and August 2021 were collected. All extracranial metastatic sites of OPD from lung cancer were included. Dose regimens consisted of 24 in 2 fractions, 30-51 Gy in 3 fractions, 30-55 Gy in 5 fractions, 52.5 Gy in 7 fractions and 44-56 Gy in 8 fractions. Dose was expressed as Biological Effective Dose for α/β=10 (BED10). Kaplan-Meyer method was used to calculate Overall Survival (OS), Local Control (LC) and Disease Progression-free Survival (DPFS) from the start date of SBRT to event. Results: Sixty-three patients, 34 female and 29 male were included. Median age was 75 years (range 25–83). All patients received concurrent systemic treatment before the start of the SBRT: 19 chemotherapy (CT) alone (30%), 26 CT plus immunotherapy (IT) or plus Tyrosin kinase inhibitors (TKI) (41%) and 18 IT/TKI alone (29%). SBRT was delivered to lung (n=29), mediastinal node (n=9), bone (n=7), adrenal gland (n=19), other visceral metastases (1) and other node metastases (n=4). A median BED10 of 104 (range 39-151) Gy10 was delivered. After a median follow up of 20 months (range 1-48), median overall survival was median OS was 23 months (figure 1). LC was 93% at 1 year and 87% at 2 years. DPFS was 7 months. At univariate analysis, age, type of systemic treatment, metastatic site receiving SBRT and BED were not significant prognostic factors for overall survival. Conclusion: SBRT in lung cancer patients for oligoprogression resulted in a long median OS of 23 months. One-year LC was 93%. Median DPFS was 7 months, translating into continuation of effective systemic treatment as other metastases grow slowly. SBRT could be useful to postpone the change of chemotherapy and/or immunotherapy. More research is needed to select OPD patients eligible for SBRT. [ABSTRACT FROM AUTHOR]

• Optimal dose and fractionation in SBRT for oligometastatic cancer patients remain unknown. • In the first 1,099 OligoCare patients, median number of fractions was 5 and fraction dose 9.7 Gy. • On multivariate analysis, dose varied significantly for primary cancer type and metastatic sites. • Future analysis will address safety and efficacy of this site- and disease-adapted SBRT practice. 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. Analysis was based on the first 1,099 registered patients. SBRT doses were converted to biological effective doses (BED) using α/β of 10 Gy for all primaries, and cancer-specific α/β 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). 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. 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). [ABSTRACT FROM AUTHOR]

Objectives: Oligometastatic head and neck squamous cell carcinoma (HNSCC) is a rare entity with no evidence-based treatment recommendations available to support the use of local ablative therapies. The aim of our study was to report on the clinical benefit of stereotactic body radiotherapy (SBRT) for patients with lung-only oligometastases, defined by the presence of 1 to 5 pulmonary lesions.Material and Methods: SBRT was applied in case of single lesions deemed amenable to local treatment only ("de novo" pattern) or after first line chemotherapy at time of disease oligoprogression ("induced" pattern). To assess the potential deferral of systemic therapy in both time points, we analyzed time to progression (TTP) defined as the time from the last day of SBRT to disease progression or death from any cause. Cox regression analysis was performed to identify predictive factors of better outcome.Results: Twenty-seven patients were retrospectively evaluated. The majority (81.5%) had HPV negative disease and a "de novo" oligometastatic pattern (78.6%). The median maximum lesion diameter and target size were 1.5 cm and 22.7 cc, respectively. At a median follow-up of 22 months (range 6-73), the median TTP was 10 months (95% CI: 9.5-21.1), with 1- and 2-year rates of 56.2% and 35%, respectively. The objective response rate at 3 months after SBRT was 75%. At multivariate analysis baseline T3/T4 stage had a HR for worse outcome of 5.38 (p = 0.033). Acute toxicity was minimal (G1/G2 of 14.8%).Conclusion: In properly selected oligometastatic patients, SBRT has potential for sustained deferral of systemic treatment. [ABSTRACT FROM AUTHOR]

The primary aim of this review is to provide practical recommendations in terms of fractionation, dose, constraints and selection criteria to be used in the daily clinical routine. Based on the analysis of the literature reviewed, in order to keep the risk of severe side effects ≤3,5%, patients should be stratified according to the target volume. Thus, patients should be treated with different fractionation and total EQD2 (<12.5 ml: EQD2 < 65 Gy with radiosurgery; >12.5 ml and <35 ml: EQD2 < 50 Gy with hypofractionated stereotactic radiotherapy; >35 ml and <50 ml: EQD2 < 36 Gy with conventionally fractionated radiotherapy). Concurrent approaches with temozolomide or bevacizumab do not seem to improve the outcomes of reirradiation and may lead to a higher risk of toxicity but these findings need to be confirmed in prospective series. [ABSTRACT FROM AUTHOR]

• Tyrosine Kinases Inhibitors were used in combination with SBRT in 93% of cases. • Radiotherapy schedules of single fraction doses were 10–20 Gy. • Radiotherapy schedules of hypofractionated doses were 35–60 Gy in 3–5 fractions. • Local control of irradiated lesions was achieved in 76–100% of the patients. • The 2-year overall survival was 71% after combined approach. To conduct a systematic review and meta-analysis of the role of SBRTdrug combination in patients affected by mRCC and associated oncologic outcomes and toxicity profiles. We performed a critical review of the Pubmed, Medline, and Embase databases from January 1, 2000 through April 30, 2020 according to the Preferred Reporting Items and Meta-Analyses statement. To assess the overall quality of the literature reviewed, we used a modified Delphi tool. A total of 6 studies were included, corresponding to a cohort of 216 patients. Tyrosine Kinases Inhibitors were the most widely used drugs in combination with SBRT, being administered in 93% patients. No study reported an increase of radiation-induced toxicity. SBRT resulted to be safe, without increase in terms of drugs-related adverse events in this setting. Moreover, this approach showed promising clinical outcomes in terms of LC and OS [ABSTRACT FROM AUTHOR]