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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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Filippo Alongi is consultant for Elekta and received speaker honoraria. Ruggero Ruggieri is scientific consultant for Elekta and received speaker honoraria.]., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., (© 2023. Italian Society of Medical Radiology.)

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., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: We report the retrospective data of a cohort of patients who received stereotactic body radiotherapy for pulmonary oligometastases, aiming to assess the clinical factors potentially affecting clinical outcomes., Methods: The present series reports the outcomes of a cohort of 71 patients with pulmonary oligometastases with no extrapulmonary disease. All patients were treated with stereotactic body radiotherapy (SBRT) performed with volumetric modulated arc therapy-image guided radiotherapy (VMAT-IGRT) to up to five secondary lesions. Survival estimates were performed using the Kaplan-Meier method., Results: A total of 98 lesions in 71 patients were treated from February 2014 to August 2020. The most frequent histologies were colorectal in 37.7%, lung cancer in 44.8%, head and neck cancer in 8.1%, and other in 9.4%. Median age was 71 years (range 32-93 years). Concurrent systemic therapy was administered in 32.3%. SBRT was delivered to a median total dose of 60 Gy (range 55-70 Gy) in 3-10 fractions for a median BED 10  = 105 Gy (range 96-180 Gy). Median follow-up was 29.5 months (range 6-81), with no acute or late G > 2 adverse event. Our LC rates at 2 and 4 years were 92.4 and 89.8%, respectively. DPFS rates at 2 and 4 years were 45.3 and 27.2%, respectively. A second SBRT course was proposed in 21 patients (29.5%) who developed an oligoprogression, resulting in median time to second progression of 9 months (range 2-44) and 2‑year PFS2 rate of 42.4%. At univariate analysis, patients with sequential oligometastases reported better OS rates (p = 0.002), which was also confirmed at multivariate analysis, where distant progression was also related to worse OS (p = 0.022). Higher local control rates relate to better PFS (p = 0.04). The 2‑ and 4‑year OS rates were 61 and 39.7% CONCLUSION: SBRT is feasible for pulmonary oligometastases with favorable outcomes and toxicity. At multivariate analysis, patients with sequential oligometastatic progression maintain a survival advantage. Also, local control was found to be related to improved PFS rates., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Breast cancer is a heterogenous disease with a deep tailoring level. Evidence is accumulating on the role of stereotactic body radiotherapy (SBRT) in the management of oligometastatic disease, however this is limited in breast cancer. The aim of the present study is to show the effectiveness of SBRT in delaying the switch to a subsequent systemic treatment in oligoprogressive breast cancer patients. Retrospective analysis from two Institutions. Primary endpoint: time to next systemic treatment (NEST). Secondary endpoints: freedom from local progression (FLP), time to the polymetastatic conversion (tPMC) and overall survival (OS). One-hundred fifty-three (153) metastases in 79 oligoprogressive breast cancer patients were treated with SBRT. Median follow-up 24 months. Median NEST 8 months. Predictive factor of NEST at the multivariate analysis (MVA) was the number of treated oligometastases (HR 1.765, 95%CI 1.322-2.355; p = < 0.01). Systemic treatment after SBRT was changed in 29 patients for polymetastatic progression and in 10 patients for oligometastatic progression < 6 months after SBRT. The 2-year FLP in the overall population was 86.7%. A biological effective dose (BED) > 70Gy 10 was associated with improved FLP (90% versus 74.2%). The median tPMC was 10 months. At the MVA the only factors significantly associated with tPMC were the number of oligometastases (HR 1.172, 95%CI 1.000-1.368; p = 0.03), and the local control of the treated metastases (HR 2.726, CI95% 1.108-6.706; p = 0.02). SBRT can delay the switch to a subsequent systemic treatment, however patient selection is necessary. Several predictive factors for treatment tailoring have been identified., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: Aim of this study is to assess the ability of contrast-enhanced CT image-based radiomic analysis to predict local response (LR) in a retrospective cohort of patients affected by pancreatic cancer and treated with stereotactic body radiation therapy (SBRT). Secondary aim is to evaluate progression free survival (PFS) and overall survival (OS) at long-term follow-up., Methods: Contrast-enhanced-CT images of 37 patients who underwent SBRT were analyzed. Two clinical variables (BED, CTV volume), 27 radiomic features were included. LR was used as the outcome variable to build the predictive model. The Kaplan-Meier method was used to evaluate PFS and OS., Results: Three variables were statistically correlated with the LR in the univariate analysis: Intensity Histogram (StdValue feature), Gray Level Cooccurrence Matrix (GLCM25&#95;Correlation feature) and Neighbor Intensity Difference (NID25&#95;Busyness feature). Multivariate model showed GLCM25&#95;Correlation (P = 0.007) and NID25&#95;Busyness (P = 0.03) as 2 independent predictive variables for LR. The odds ratio values of GLCM25&#95;Correlation and NID25&#95;Busyness were 0.07 (95%CI 0.01-0.49) and 8.10 (95%CI 1.20-54.40), respectively. The area under the curve for the multivariate logistic regressive model was 0.851 (95%CI 0.724-0.978). At a median follow-up of 30 months, median PFS was 7 months (95%CI 6-NA); median OS was 11 months (95%CI 10-22 months)., Conclusions: This analysis identified a radiomic signature that correlates with LR. To confirm these results, prospective studies could identify patient sub-groups with different rates of radiation dose-response to define a more personalized SBRT approach., (© 2021. Italian Society of Medical Radiology.)

Background: The use of stereotactic radiotherapy (SBRT) for oligometastases is supported by several literature studies, but in the setting of gynecological malignancies, this scenario remains quite unexplored. This study reports a preliminary assessment of clinical outcomes in a cohort of 40 patients with oligometastatic gynecological neoplasms., Methods: Radiotherapy was delivered in 3-10 fractions with VMAT-IGRT technique. Toxicity was retrospectively collected according to CTCAE v4.0. Data were retrospectively collected and analyzed. Univariate and multivariate analyses were performed for assessing any potential predictive factor for clinical outcomes., Results: A total of 63 oligometastases were treated from December 2014 to February 2021. Median age was 63 years (range 30-89). Most frequent primary tumors were ovarian cancer in 42.5% and endometrium cancer in 42.5%. With a median follow-up of 27 months (range 6-69), no local failures were observed, our progression-free survival rates were 43.6% and 23% at one and 2 years, respectively, while 1 and 2-year overall survival rates were both 70%. No acute or late G ≥ 2 adverse events were observed., Conclusions: In our experience, SBRT for oligometastatic gynecological malignancies resulted in promising results in terms of clinical outcomes, with excellent local control and no evidence of severe toxicity, highlighting the effectiveness of this therapeutic option. Prospective studies to further explore this approach in this setting are advocated., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Approximately one third of cancer patients will develop spinal metastases, that can be associated with back pain, neurological symptoms and deterioration in performance status. Stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT) have been offered in clinical practice mainly for the management of oligometastatic and oligoprogressive patients, allowing the prescription of high total dose delivered in one or few sessions to small target volumes, minimizing the dose exposure of normal tissues. Due to the high delivered doses and the proximity of critical organs at risk (OAR) such as the spinal cord, the correct definition of the treatment volume becomes even more important in SBRT treatment, thus making it necessary to standardize the method of target definition and contouring, through the adoption of specific guidelines and specific automatic contouring tools. An automatic target contouring system for spine SBRT is useful to reduce inter-observer differences in target definition. In this study, an automatic contouring tool was evaluated., Methods: Simulation CT scans and MRI data of 20 patients with spinal metastases were evaluated. To evaluate the advantage of the automatic target contouring tool (Elements SmartBrush Spine), which uses the identification of different densities within the target vertebra, we evaluated the agreement of the contours of 20 spinal target (2 cervical, 9 dorsal and 9 lumbar column), outlined by three independent observers using the automatic tool compared to the contours obtained manually, and measured by DICE similarity coefficient., Results: The agreement of GTV contours outlined by independent operators was superior with the use of the automatic contour tool compared to manually outlined contours (mean DICE coefficient 0.75 vs 0.57, p = 0.048)., Conclusions: The dedicated contouring tool allows greater precision and reduction of inter-observer differences in the delineation of the target in SBRT spines. Thus, the evaluated system could be useful in the setting of spinal SBRT to reduce uncertainties of contouring increasing the level of precision on target delivered doses., (© 2021. The Author(s).)

The constantly increasing life expectancy is raising the issue of treating oncological older patients, who were traditionally candidates to best supportive care or palliative treatments. Several literature data support SBRT in the treatment of the oligometastatic patient as a potentially curable therapeutic option. However, data on older patients are lacking. This study presents the outcomes of a cohort of 61 oligometastatic patients over the age of 80 years who received SBRT, that was proposed to all patients with a minimum Karnofsky Performance Status ≥ 70 and a life expectancy of at least 6 months, with up to five oligometastatic lesions. Radiotherapy was delivered in 3-10 fractions with VMAT-IGRT technique. Toxicity was retrospectively collected according to CTCAE v4.0. Data were retrospectively collected and analyzed. Univariate and multivariate analysis were performed for assessing any potential predictive factor for clinical outcomes. A total of 90 oligometastases were treated in 61 patients with median age 82 years (range, 80-90). The most frequent histology was colorectal cancer (27% of cases). Median follow-up was 20 months (range, 2-63). Local control rates at 1- and 2-years were 98.8% and 88.2%, with colorectal histology being associated with worse LC rates (p = 0.014) at univariate analysis. Progression-free survival rates at 1- and 2-years were 48.6% and 30.5%. Oligorecurrent lesions and single oligometastases were associated with better PFS rates (respectively, p = 0.04 and p = 0.011). Overall survival rates were 75% and 60.5%, polymetastatic spread being predictive of worse survival outcomes at multivariate analysis (p = 0.012). No G2 or higher adverse events were recorded. Our study supports the role of SBRT for the treatment of elderly oligometastatic patients, highlighting the possibility to further explore this therapeutic option in the management of older oncological patients., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: MR-guided daily-adaptive radiotherapy is improving the accuracy in the planning and delivery phases of the treatment. Rectal hydrogel-spacer may help in mitigating organ motion, but few data are currently available., Methods: We aimed to assess any potential impact of the device on seminal vesicles motion by measuring translational and rotational shifts between the pre- and post-treatment MRI scans of a total of 50 fractions in the first 10 patients who underwent MR-guided prostate SBRT (35 Gy/5 fx). Of them, five patients received the hydrogel-spacer. The comparative analysis was performed using the Mann-Whitney U-test., Results: Median rotational shifts were: in anteroposterior 0° (range, 0.097°/0.112°; SD = 0.05°) vs 0° (-0.162/0.04°; SD = 0.07°) in the no-spacer subgroup ( p = 0.36); lateral shifts were 0° (-0.1°/0.54°; SD = 0.28°) vs -0.85° in the no-spacer cohort (-1.56°/0.124°; SD = 0.054°; p = 0.22). Cranio-caudal shifts were 0° (-0.121°/0.029°; SD = 0.06°) in the spacer-cohort vs 0° (-0.066°/0.087°; SD = 0.69°; p = 0.53). Median translational shifts were: in anteroposterior 0.9 mm (-0.014 mm/0.031 mm; SD = 0.036 mm) in the spacer-group vs 0.030 mm (-0.14 mm/0.03 mm; SD = 0.032 mm; p = 0.8); latero-lateral shifts were -0.042 mm (-0.047 mm/0.07 mm; SD = 0.054 mm), vs -0.023 mm (-0.027 mm/-0.01 mm; SD = 0.023 mm) in the no-spacer group ( p = 0.94). In cranio-caudal, statistically significant shifts were reported: 0.082 mm (0.06 mm/0.15 mm; SD = 0.04 mm) vs 0.06 mm (-0.06/0.08 mm; SD = 0.09 mm) in the no-spacer cohort ( p = 0.031)., Conclusions: A favorable impact of the hydrogel-spacer on seminal vesicles motion was observed only in cranio-caudal translational shifts, although being not clinically significant. Further studies are required to fully investigate the potential contribution of this device on vesicles motion., Advances in Knowledge: MR-guided daily adaptive radiotherapy may represent a game changer for prostate stereotactic body radiotherapy, given the possibility to better visualize soft-tissues anatomy and to daily recalculate the treatment plan based on real-time conditions. The use of devices like rectal ballon or rectal gel spacers has gained interest in the last years for the possibility to better spare the rectum during prostate radiotherapy. This is one of the first experiences exploring the role of rectal spacer on seminal vesicles intrafraction motion during MR-guided SBRT for prostate cancer.

Purpose: Radiosurgery (SRS) is an effective treatment option for brain metastases (BMs). Long-term results of the first worldwide experience with a mono-isocentric, non-coplanar, linac-based stereotactic technique in the treatment of multiple BMs are reported., Methods: patients with multiple BMs, life expectancy > 3 months, and good performance status (≤ 2) were treated with simultaneous SRS with volumetric modulated arc technique. Data were retrospectively evaluated., Results: 172 patients accounting for 1079 BMs were treated at our institution from 2017 to 2020. The median number of treated metastases was 4 (range 2-22). Primary tumor histology was: lung (44.8%), breast (32%), and melanoma (9.4%). The 2-year LPFS was 71.6%, respectively. A biological effective dose (BED) ≥ 51.3 Gy 10 correlated with higher local control. Uncontrolled systemic disease and melanoma histology were independent prognostic factors correlated with decreased iPFS. Patients with > 10 BMs had a trend towards shorter iPFS (p = 0.055). 31 patients received multiple SRS courses (2-7) in case of intracranial progression. The median iOS was 22.4 months. Brainstem metastases and total PTV > 7.1 cc correlated with shorter iOS. The 1- and 2-year WBRT-free survival was 83.2% and 61.1%, respectively., Conclusion: Long-term results in a large patient population treated with a mono-isocentric, dedicated technique demonstrated its effectiveness and safety also in the case of multiple courses. The shortened treatment time and the possibility to safely spare healthy brain tissue allows the safe treatment of patients with a large number of metastases and to deliver multiple courses of SRS. In selected cases, the administration of WBRT can be delayed.

Objectives: To report preliminary data on feasibility and patient-reported outcomes following PSMA-PET/CT guided SBRT by means of 1.5 T MRI-Linac., Methods and Materials: Between October 2019 and April 2020, twenty consecutive castration sensitive oligorecurrent prostate cancer patients were enrolled in an ethical committee approved prospective observational study (Protocol n. XXXX) and treated with PSMA-PET/CT guided SBRT by means of 1.5 T MRI-Linac (Unity, Elekta AB, Stockholm, Sweden). The mean delivered dose was 35 Gy in 5 fractions. Clinicians reported toxicity was prospectively collected according to Common Terminology Criteria for Adverse Events v5.0. Quality of life (QoL) assessment was performed using EORTC-QLQ C30 questionnaires administered at baseline, end of treatment and at first follow-up., Results: Twenty-five lesions in 20 castration sensitive oligorecurrent patients were treated: the most commonly treated anatomic sites were nodal (n = 16) and pelvic bone (n = 9). Median PSA-value preMRI guided SBRT was 1.16 ng/mL (range, 0.27-8.9), whereas median PSA value at first follow-up after SBRT was 0.44 ng/mL (range, 0.06-8.15). At first follow-up, for 16 patients showing detectable PSA, PSMA-PET/CT was performed detecting, respectively, in 6 cases partial response and in 10 cases complete response. In the remaining cases, PSA-value was undetectable after SBRT. Radiotherapy treatment was safe and well tolerated according to the PROMs. No acute G2 or higher toxicities were recorded., Conclusions: The current series represent the largest one exploring the feasibility and patient-reported outcomes following PSMA-PET/CT guided SBRT by means of 1.5 T MRI-Linac. The preliminary findings here reported are encouraging in terms of effectiveness and tolerability.

Aim: To evaluate differences between MR-guided daily-adaptive RT (MRgRT) and image-guided RT (IGRT) with or without fiducial markers in prostate cancer (PCa) stereotactic body radiotherapy (SBRT) in terms of dose distribution on critical structures., Material and Methods: Two hundred treatment sessions in 40 patients affected by low and intermediate PCa were evaluated. The prescribed dose was 35 Gy in 5 fractions delivered on alternate days. MRgRT patients (10) were daily recontoured, re-planned, and treated with IMRT technique. IGRT patients without (20) and with (10) fiducials were matched on soft tissues or fiducials and treated with VMAT technique. Respective CBCTs were retrospectively delineated and the prescribed plan was overlaid for dosimetric analysis. The daily dose for rectum, bladder, and prostate was registered., Results: MRgRT resulted in a significantly lower rate of constraints violation as compared to IGRT without fiducials, especially for rectum V28Gy, rectum V32Gy, rectum V35Gy, rectum Dmax, and bladder Dmax. IGRT with fiducials reported high accuracy levels, comparable to MRgRT. MRgRT and IGRT with fiducials reported no significant prostate CTV underdosage, while IGRT without fiducials was associated with occasional cases of prostate CTV under dosage., Conclusion: MR-guided daily-adaptive SBRT seems a feasible and accurate strategy for treating prostate cancer with ablative doses. IGRT with the use of fiducials provides a comparable level of accuracy and acceptable real-dose distribution over treatment fractions. Future study will provide additional data regarding the tolerability and the clinical outcome of this new technological approach.

Objective: The main aim of the current analysis was to explore the hypothetical advantages using rectal spacer during 1.5T MR-guided and daily adapted prostate cancer stereotactic body radiotherapy (SBRT) compared to a no-rectal spacer hydrogel cohort of patients., Methods: The SBRT-protocol consisted of a 35 Gy schedule delivered in 5 fractions. Herein, we present a dosimetric analysis between spacer and no-spacer patients. Furthermore, treatment tolerability and feasibility were preliminarily assessed according to clinicians-reported outcomes at the end of treatment and patient-reported outcomes measures (PROMs) in both arms. Toxicity and quality of life were assessed at baseline and after treatment using the Common Terminology Criteria for Adverse Events v. 5.0, International Prostatic Symptoms Score, ICIQ-SF, IIEF-5, and EORTC-QLQ-C30 and PR-25 questionnaires., Results: 120 plans (pre- and daily adaptive SBRT planning) were analyzed in 20 patients (10 patients in spacer group and 10 patients in no-spacer group) treated using 1.5T MR-guided adaptive SBRT. Statistically significant dosimetric advantages were observed in favor of the spacer insertion, improving the planning target volume coverage in terms of V33.2Gy >95% and planning target volume 37.5 Gy <2% mainly during daily-adapted SBRT. Also, rectum V32, V28 and V18Gy and bladder V35Gy <1 cc were significantly reduced in the spacer cohort. Concerning the PROMS, all questionnaires showed no difference between the pre- and post-SBRT evaluation in both arms, excepting the physical functioning item of EORTC QLQ-C30 questionnaire that was declined in the no-spacer group., Conclusion: These preliminary results strongly suggest the adoption of perirectal spacer due to dosimetric advantages not only for rectal sparing but also for target coverage. Longer follow-up is required to validate the clinical impact in terms of clinicians-reported toxicity and PROMs., Advances in Knowledge: This the first experience reporting preliminary data concerning the potential dosimetric impact of rectal hydrogel spacer on MR-guided SBRT for prostate cancer.

Purpose: Adaptive Stereotactic Body Radiotherapy (SBRT) of prostate cancer (PC) by online 1.5 T MRi-guidance prolongs session-time, due to contouring and planning tasks, thus increasing the risk of prostate motion. Hence, the interest to verify the adequacy of the delivered dose., Material and Methods: For twenty PC patients treated by 35 Gy (D p ) in five fractions, daily pre- and post- delivery MRi scans were respectively used for adapt-to-shape (ATS) optimization, and re-computation of the delivered irradiation (D rec ). Two expansion recipes, from Clinical (CTV) to Planning target volume (PTV), which slightly differed in the posterior margin were used for groups I and II, of ten patients each. Plans had to assure D 95%  ≥ 95%D p to PTV, and D 1cc  ≤ D p to rectum, bladder, penile bulb, and urethral planning-risk-volume (urethral-PRV). The adequacy of the delivered dose was estimated by inter-fraction average (ifa) of dose-volume metrics computed from D rec . A cumulative dose (D sum ) was calculated from the five daily D rec deformed onto the simulation MRi., Results: For each patient, CTV coverage resulted in D 95%  > 95%D p when estimated as ifa by D rec . No significant difference for D 95% and D 99% metrics to CTV resulted between groups I and II. D 1cc was < D p for rectum, urethral-PRV, and penile bulb, whereas < 103.5%D p for the bladder. Significant correlations resulted between metrics computed by D sum and as ifa by D rec , by both linear-correlation analysis, and Receiver-Operating-Characteristic curve analysis., Conclusions: Our results for PC-SBRT confirm the adequacy of the delivered dose by ATS with 1.5 T MR-linac, and the consistency between dose-volume metrics computed by D rec and D sum ., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Introduction: To date, the optimal management of locally relapsed prostate cancer patients after an initial course of radiotherapy remains a matter of debate. In recent years, local approaches have been proposed as a therapeutic option, which may potentially delay the initiation of hormone therapy. In the case of external beam radiotherapy (EBRT), re-irradiation has been supported by growing evidence in the literature, mostly represented by extreme hypofractionated schedules delivered with stereotactic body radiotherapy (SBRT)., Areas Covered: We performed a systematic review of the literature using the PICO methodology to explore the available evidence regarding the use of EBRT in the setting of locally relapsed prostate cancer, both in terms of safety, tolerability and preliminary clinical outcomes., Expert Opinion: Current literature data report the use of EBRT and particularly of SBRT for the safe and feasible re-treatment of locally recurrent prostate cancer after an initial treatment course of radiotherapy. When extreme hypofractionation is adopted, only occasional grade ≥3 late adverse events are reported. Despite the current lack of high-level evidence and the short follow-up, preliminary clinical outcomes are promising and allow clinicians to hypothesize further prospective studies to evaluate SBRT as an alternative to the early initiation of androgen-deprivation therapy.

Purpose: Stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy (SABR) has been shown to increase survival rates in oligometastatic disease (OMD), but local control of colorectal metastases remains poor. We aimed to explore the natural course of oligometastatic colorectal cancer and to investigate how SBRT of lung metastases can delay the progression to polymetastatic disease (PMD)., Methods: 107 lung oligometastases in 38 patients were treated with SBRT at a single institution. The median number of treated lesions was 2 (range 1-5). Time to PMD (ttPMD) was defined as the time from SBRT to the occurrence of >5 new metastases. Genetic biomarkers such as EGFR, KRAS, NRAS, BRAF, and microsatellite instability were investigated as predictive factors for response rates., Results: Median follow-up was 28 months. At median follow-up, 7 patients were free from disease and 31 had progression: 18 patients had sequential oligometastatic disease (SOMD) and 13 polymetastatic progression. All SOMD cases received a second SBRT course. Median progression-free survival (PFS) was 7 months (range 4-9 months); median ttPMD was 25.8 months (range 12-39 months) with 1‑ and 2‑year PFS rates of 62.5% and 53.4%, respectively. 1‑ and 2‑year local PFS (LPFS) rates were 91.5% and 80%, respectively. At univariate analysis, BRAF wildtype correlated with better LPFS (p = 0.003), SOMD after primary SBRT was associated with longer cancer-specific survival (p = 0.031). Median overall survival (OS) was 39.5 months (range 26-64 months) and 2‑year OS was 71.1%., Conclusion: The present results support local ablative treatment of lung metastases using SBRT in oligometastatic colorectal cancer patients, as it can delay the transition to PMD. Patients who progressed as SOMD maintained a survival advantage compared to those who developed PMD.

Background: The assessment of organ motion is a crucial feature for prostate stereotactic body radiotherapy (SBRT). Rectal spacer may represent a helpful device in order to outdistance rectal wall from clinical target, but its impact on organ motion is still a matter of debate. MRI-Linac is a new frontier in radiation oncology as it allows a superior visualization of the real-time anatomy of the patient and the current highest level of adaptive radiotherapy., Methods: We present data regarding a total of 100 fractions in 20 patients who underwent MRI-guided prostate SBRT for low-to-intermediate risk prostate cancer with or without spacer. Translational and rotational shifts were computed on the pre- and post-treatment MRI acquisitions referring to the delivery position for antero-posterior, latero-lateral and cranio-caudal direction, and assessed using the Mann-Whitney U-Test., Results: All patients were treated with a five sessions schedule (35 Gy/5fx) using MRI-Linac for a median fraction treatment time of 50 min (range, 46-65). In the entire study sample, median rotational displacement was 0.1° in cranio-caudal, - 0.002° in latero-lateral and 0.01° in antero-posterior direction; median translational shift was 0.11 mm in cranio-caudal, - 0.24 mm in latero-lateral and - 0.22 mm in antero-posterior. A significant difference between spacer and no-spacer patients in terms of rotational shifts in the antero-posterior direction (p = 0.033) was observed; also for translational shifts a positive trend was detected in antero-posterior direction (p = 0.07), although with no statistical significance. We observed statistically significant differences in the pre-treatment planning phase in favor of the spacer cohort for several rectum dose constraints: rectum V32Gy < 5% (p = 0.001), V28 Gy < 10% (p = 0.001) and V18Gy < 35% (p = 0.039). Also for bladder V35 Gy < 1 cc, the use of spacer provided a dosimetric advantage compared to the no-spacer subpopulation (p = 0.04). Furthermore, PTV V33.2Gy > 95% was higher in the spacer cohort compared to the no-spacer one (p = 0.036)., Conclusion: In our experience, the application of rectal hydrogel spacer for prostate SBRT resulted in a significant impact on rotational antero-posterior shifts contributing to limit prostate intra-fraction motion. Further studies with larger sample size and longer follow-up are required to confirm this ideally favorable effect and to assess any potential impact on clinical outcomes.

Background and Objective: The optimal management of prostate cancer (PC) recurrences after definitive or postoperative radiotherapy (RT) is still controversial. The aim of the present retrospective study was to report the preliminary clinical results and toxicity of a mono-institutional series of patients re-irradiated with linac-based SBRT in recurrent prostate cancer., Methods: Inclusion criteria were previous definitive or adjuvant/salvage RT, evidence of biochemical recurrence and radiological detection of local relapse (Magnetic Resonance Imaging or PSMA/choline-Positron Emission Tomography), and IPSS <10. Toxicity was assessed according to Common Terminology Criteria for Adverse Events v4.0., Results: Between 12/2014 and 12/2019, 24 patients with median age 75 years (65-89) underwent re-RT for PC recurrence. Median follow-up was 21 months (2-68). The recurrences occurred in 13 cases within the prostate and in 11 cases within the prostate bed. All patients were treated with SBRT to a median total dose of 30 Gy (25-36 Gy) in 5-6 fractions, and simultaneous androgen deprivation therapy was administered in 4 patients. Acute toxicity was G1 in 8.3% and G2 in 12.5% for genitourinary (GU), no acute gastrointestinal (GI) toxicity occurred. Concerning late side effects, 19.7% of patients were found to have ≥G2 GU toxicity, including one G3 urethral stenosis. Only one case of G1 late GI toxicity occurred and no ≥G2. The 2‑year overall survival was 95%. The 1‑ and 2‑year biochemical relapse-free survival (BRFS) and progression-free survival (PFS) rates were 80 and 54.9%, respectively., Conclusion: Despite of the heterogeneity of the sample, linac-based SBRT as a salvage treatment in previously irradiated locally recurrent PC patients seems to be a safe and feasible treatment option. Long-term data are pending.

Background: Unity Elekta is a unique magnetic resonance (MR)-linac that conjugates a 1.5 Tesla MR unit with a 7 MV flattening filter free accelerator.A prospective observational study for the clinical use of Elekta Unity is currently ongoing in our department. Herein, we present our preliminary report on the feasibility, quality of life, and patient-reported outcomes measures (PROMs) for localized prostate cancer (PC) treated with stereotactic body radiotherapy (SBRT)., Methods: The SBRT protocol consisted of a 35 Gy schedule delivered in 5 fractions within 2 weeks. Toxicity and quality of life (QoL) were assessed at baseline and after treatment using the Common Terminology Criteria for Adverse Events v5.0, International Prostatic Symptoms Score (IPSS), ICIQ-SF, IIEF-5, and EORTC-QLQ-C30 and PR-25 questionnaires., Results: Between October 2019 and January 2020, 25 patients with localized PC were recruited. The median age was 68 years (range, 54-82); 4 were low risk, 11 favorable intermediate risk (IR) and 10 unfavorable IR. Median iPSA was 6.8 ng/ml (range, 1-19), and 9 of these patients (36%) received concurrent androgen deprivation therapy. Median prostate volume was 36 cc (range, 20-61); median baseline IPSS was 5 (range, 0-10). Median time for fraction was 53 min (range, 34-86); adaptive strategy with daily critical structure and target re-contouring and daily replanning (adapt to shape) was performed in all cases. No grade ≥ 3 adverse event was observed, three patients (12%) reported grade 2 acute genitourinary toxicity (urinary frequency, urinary tract pain and urinary retention), while only one patient reported mild rectal pain. No relevant deteriorations were reported in PROMs., Conclusion: To the best of our knowledge, this is the first experience reporting feasibility, clinician-reported outcome measurements, and PROMs for 1.5 T MR-guided adaptive SBRT for localized prostate cancer. The preliminary data collected here report optimal safety and excellent tolerability, as also confirmed by PROMs questionnaires. Moreover, the data on technical feasibility and timing of online daily adapted planning and delivery are promising. More mature data are warranted., Trial Registration: Date of approval April 2019 and numbered MRI/LINAC n°23,748.

Stereotactic radiosurgery (SRS) is an effective treatment option for multiple brain metastases (BMs). Modern mono-isocentric techniques allow the delivery of multiple stereotactic courses, in the event of intracranial failure. Nevertheless, limited data on effectiveness and toxicity have been reported in comparison to WBRT. Aim of this retrospective matched-pair analysis was to compare patients affected by limited BMs treated with multiple SRS courses using a mono-isocentric, non-coplanar technique (HyperArc™, Varian Medical System) to upfront WBRT. One hundred and two patients accounting for 677 BMs were treated with HyperArc™. In case of further intracranial progression, 44 treatment courses of 201 metastases in 19 patients, were treated by subsequent HyperArc™ courses. This population was matched with 38 patients treated with WBRT. The median BMs number was 4 (range 2-10) for HyperArc™ and 5 (range 2-10) for WBRT. Overall survival (OS) and toxicity were evaluated. The median follow-up was 9 months (range 3-40 months). The median OS was not reached (range 5-22 months) for HyperArc™ patients and 8 months (range 3-40 months) for WBRT patients, while the 1-year OS was 77% and 34.6% for HyperArc™ and WBRT, respectively (p = 0.001; HR 4.77, 95% CI 1.62-14.00). There was one case of radionecrosis. HyperArc™ is an effective and safe technique for the treatment of multiple BMs. In selected cases of intracranial oligorecurrence, further subsequent courses can be safely delivered with the same technical approach. Moreover, in patients with a limited number of BMs, SRS showed an improved survival outcome when compared to WBRT.

Purpose: External beam radiotherapy (EBRT) is an effective treatment option for low- and favorable intermediate-risk prostate cancer (PCa) and it is usually delivered in conventional fractionation or with moderate hypofractionation (hRT), with comparable results. In the last years, a new treatment approach with stereotactic body radiotherapy (SBRT) has shown promising results. The aim of the present study was to directly compare the toxicity and outcome between hRT and SBRT in low and favorable intermediate PCa patients., Materials and Methods: The hRT schedules were: 71.4 Gy or 74.2 Gy in 28 fractions for low- or favorable intermediate-risk PCa, respectively, while the SBRT schedules were: 35 Gy or 37.5 Gy in five fractions, for low or favorable intermediate risk, respectively. Toxicity assessment was performed according to CTCAE v5.0 grading. The International Prostatic Symptoms Score (IPSS) was also recorded., Results: One hundred forty-nine patients were analyzed, overall 81 (54.36%) patients were low risk and 68 (45.64%) were favorable intermediate risk. Sixty-nine (46.3%) patients were treated with hypo-RT and 80 (53.7%) with SBRT. Median follow-up was 33 months (range 11-58 months). The actuarial survival rate was 98.66%. The 3-years BFS rates were 95.5% and 100% for hRT and SBRT, respectively (p = 0.051). One case (0.6%) of acute grade 3 urinary toxicity occurred in a patient with favorable intermediate risk treated with hRT. He initially suffered gross hematuria and acute urinary retention not treatable with urinary catheter, therefore a suprapubic catheter was placed and steroids were administered. No differences in acute, late or severe toxicity were detected., Conclusion: Stereotactic body radiotherapy reported a good clinical outcome and safe toxicity profile. Results are comparable to hRT, but a longer follow-up is needed to assess the late effectiveness and toxicity.

Aim: It is recognized that stereotactic body radiotherapy (SBRT) for centrally located lung metastases is affected by higher rates of severe toxicity. In the present study, we report the clinical outcomes following a novel intensity-modulated radiotherapy prescription dose, termed simultaneous integrated protection (SIP), for nearby organs at risk (OARs)., Materials and Methods: The prescribed total doses of SBRT were 70 Gy in 10 fractions and 60 Gy in 8 fractions. For ultra-centrally located lesions, a dose of 60 Gy in 10 fractions was delivered. The main planning instructions were: (1) to remain within the limits of the given dose constraints for an OAR; (2) to make use of the maximum possible dose to the OARs to minimize dose inhomogeneity for the Planning Target Volume (PTV). SBRT-related toxicity was prospectively assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. The primary clinical endpoint was the SBRT-related toxicity. Secondary endpoint was local control., Results: Forty patients affected by a single central malignancy were analyzed. The median follow-up was 20 months (range, 6-58 months). Acute and late clinical pulmonary toxicity ≥grade 2 was recorded in 2 out of 40 patients (5%) and 3 out of 40 patients (7%), respectively. No patient experienced cardiac toxicity. No narrowing or stenosis of any airway or vessel was registered. One-year local control rate was 91%. The median time to local progression was 13 months (range, 6-46 months)., Conclusion: SBRT using a PTV-SIP approach for single central lung metastases achieved low SBRT-related toxicity with acceptable local control.

Aim: The aim of this study was to analyze the feasibility and clinical results of linear accelerator (linac-)based stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (SFRT) with flattening filter-free (FFF) volumetric modulated arc therapy (VMAT) in elderly patients affected by brain metastases (BMs)., Patients and Methods: Patients selected for the present analysis were ≥65 years old with a life expectancy of >3 months, a controlled or synchronous primary tumor, and <10 BMs with a diameter <3 cm. All patients were treated with FFF linac-based SRS/SFRT. The prescribed total dose (15-30 Gy/1-5 fractions) was based on BM size and proximity to organs at risk (OAR). Toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. MedCalc v18.2 (MedCalc Software, Ostend, Belgium) was used for statistical analysis., Results: From April 2014 to December 2017, 40 elderly patients with 110 BMs were treated by FFF linac-based SRS/SFRT. With a median follow-up of 28 months (range 6-50 months), median and 1‑year overall survival were 9 months and 39%, respectively; median intracranial progression-free survival was 6 months. At the time of the analysis, local control was reported in 109/110 BMs (99.1%): 12 BMs had a complete response; 51 a partial response; 46 showed stable disease. One BM (0.9%) progressed after 2 months. BM volume (<1 cc) and higher SRS/SFRT dose correlated to treatment response (p = 0.01 and p = 0.0017, respectively). No adverse events higher than grade 2 were observed., Conclusion: The present findings highlight the feasibility, safety, and effectiveness of FFF linac-based SRS/SFRT in elderly patients with BMs.

Background and Purpose: Three mono-isocenter techniques with multiple non-coplanar arcs are nowadays clinically available for linac-based stereotactic radiosurgery (SRS) of multiple brain metastases (BM): HyperArc (HA), Multiple Brain Mets (MBM), and Monaco-HDRS. Two of them, HA and MBM, are here compared in terms of plan-quality, and dosimetric consistency between planning and delivering., Materials and Methods: For 20 patients with multiple BM (2-10), treated by mono-isocenter volumetric modulated arc therapy (VMAT) HA plans, mono-isocenter MBM dynamic conformal arc plans were generated. Prescription dose (Dp) was 18-25 Gy, for single-fraction, and 21-27 Gy, for three-fractions. Mean overall Planning Target Volume (PTV), expanded by 2 mm from each lesion, was 9.6 cm 3 (0.5-27.9 cm 3 ). Dose normalization of 100%Dp at 98%PTV was adopted. Plan-quality was compared by the Paddick conformity (CI) and gradient (GI) index, for the target, mean dose and V 12 volume, for the healthy brain, and number of monitor units (MU). Further, verification dosimetry by radiochromic films was performed for each plan, thus comparing also, by γ-analysis, the consistency between in-phantom computed and measured dose distributions., Results: CI significantly improved for HA plans, changing on average from 0.75 (MBM) to 0.94 (HA) (p < .001). No significant differences between HA and MBM plans were computed for GI (p = .216), and for mean dose (p = .436) and V 12 (p = .062) to the healthy brain; although V 12 increased on average from 23.7 cm 3 (HA) to 37.3 cm 3 (MBM). No significant difference resulted for MU (p = .107), whereas γ (1 mm, 3%) and γ (2 mm, 2%) passing-rates significantly improved for HA plans (p = .006; p = .023)., Conclusions: HA plans assured a higher CI, while no significant difference resulted for any of the other planning metrics. Although on average slightly higher for HA plans, the dosimetric consistency between planned and delivered was satisfactory from both techniques. Hence, our judgement of near equal plan-quality from HA and MBM SRS-techniques., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Radiosurgery (SRS) or stereotactic fractionated radiotherapy (SFRT) is increasing in the treatment of brain metastases (BMs). Aim of the present study was to evaluate the safety and effectiveness of SRS/SFRT for BMs, using a new mono-isocenter non-coplanar solution (HyperArc™ Varian Medical System)., Methods: BMs patients with a diameter inferior to 3 cm, a life expectancy of more than 3 months and a good performance status, were eligible for Linac-based volumetric modulated arc therapy (VMAT) SFRT/SRS with HyperArc™. A retrospective analysis of patients and BMs was performed., Results: From August 2017 to May 2018, 381 BMs in 64 patients were treated and 246 BMs (43 patients, median number of BMs: 5) of them were suitable for analysis. With a median FU time of 6 months, 244 out 246 (99%) BMs were controlled (18% complete response; 41% partial response, 40% stable disease), 2 BMs showed a progression, at the first control. No acute or late toxicities were reported. Median overall survival (OS) has not yet been achieved, while median time to progression was 5 months. In univariate analysis, statistically negative prognostic factors for OS were histology of primary tumor (p = 0.009): lung/breast cancer had better survival rates as compared to others. Cumulative intracranial volume disease ≥ 15 cc and systemic progression disease were independent prognostic factors for OS at univariate (p = 0.04; p = 0.005) and multivariate (p = 0.04; p = 0.009) analysis, respectively., Conclusion: The present first clinical data show that SFRT/SRS with HyperArc™ is safe and effective for BMs patients. The utilization of SFRT/SRS for BMs is promising and should be further explored in randomized trials.

Aim: Metastases from colorectal cancer are poorly responsive to stereotactic ablative radiation therapy (SABR) due to intratumoral hypoxia. Intratumoral oxygenation is improved by administration of angiogenesis inhibitors. Thus, there could be a clinical synergistic effect of SABR with bevacizumab on metastases from colorectal cancer. The aim of this study was to evaluate the feasibility and efficacy of SABR after bevacizumab in lung oligometastases from colon cancer., Methods: The data of patients with lung metastases from colon cancer who underwent SABR were retrospectively evaluated according to the following inclusion criteria: number of metastases ≤3; lung oligometastases from colon cancer in patients who underwent SABR; patients receiving previous chemotherapy alone or in combination with bevacizumab; Karnofsky performance status >80; life expectancy >6 months; at least 6 months' follow-up after SABR; presence of KRAS mutation. The results were compared with those of a similar cohort of patients with irradiated lung lesions from colorectal cancer in whom bevacizumab was not previously administered., Results: A total of 40 lung metastases were analyzed. The complete response rate after SABR was higher in patients who had received bevacizumab than in those who had not (p = 0.04). Additionally, in the bevacizumab group, a higher rate of post-SABR complete response was observed in case of oligopersistent versus oligorecurrent metastases (p = 0.001)., Conclusions: In the setting of lung oligometastases from colon cancer the present study attested the higher efficacy of SABR after bevacizumab administration. Further studies in this field of research are strongly advocated.

Introduction: Aim of the present study is to evaluate homolateral and contralateral hippocampus (H-H, C-H, respectively) dose during Fractionated Stereotactic Radiotherapy (FSRT) or Radiosurgery (SRS) for brain metastases (BM)., Materials & Methods: Patients with BM<5, size≤30mm, KPS≥80 and a life expectancy>3months, were considered for SRS/FSRT (total dose 15-30Gy, 1-5 fractions). For each BM, a Flattening Filter Free (FFF) Volumetric Modulated Arc Therapy (VMAT) plan was generated with one or two arcs. Hippocampi were not considered during optimizations phase and were contoured and evaluated retrospectively in terms of dose: the Dmedian, Dmean, D0.1cc and the V1Gy, V2Gy, V5Gy and V10Gy were analyzed., Results: From April 2014 to December 2015, 81 BM were treated with FFF-FSRT/SRS. For the H-H, the average values of Dmedian, Dmean and D0.1cc were 1.5Gy, 1.54Gy and 2.2Gy, respectively, while the V1Gy, V2Gy, V5Gy and V10Gy values were 25%, 8.9%, 8.9% and 2.1%, respectively. For the C-H, the average Dmedian, Dmean and D0.1cc were 0.7Gy, 0.7Gy, 0.9Gy, respectively, while the average values of V1Gy, V2Gy, V5Gy and V10Gy were 18%, 10.2%, 2.8% and 1.4%, respectively. Tumor dimension, tumor cranial-caudal length and the distance between BM and H-H were correlated to Dmedian, Dmean and D0.1cc. For C-H, only the distance from PTV was correlated with a dose reduction., Conclusion: During FFF-FSRT/SRS, hippocampus received a negligible dose. Despite its clinical significance is still under evaluation, in patients with a long life expectancy, H-H should be considered during Linac-based FSRT/SRS., (Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Background: Linac-based stereotactic radiosurgery or fractionated stereotactic radiotherapy (SRS/FSRT) of multiple brain lesions using volumetric modulated arc therapy (VMAT) is typically performed by a multiple-isocenter approach, i.e. one isocenter per lesion, which is time-demanding for the need of independent setup verifications of each isocenter. Here, we present our initial experience with a new dedicated mono-isocenter technique with multiple non-coplanar arcs (HyperArc™, Varian Inc.) in terms of a plan comparison with a multiple-isocenter VMAT approach., Methods: From August 2017 to October 2017, 20 patients with multiple brain metastases (mean 5, range 2-10) have been treated by HyperArc in 1-3 fractions. The prescribed doses (Dp) were 18-25 Gy in single-fraction, and 21-27 Gy in three-fractions. Planning Target Volume (PTV), defined by a 2 mm isotropic margin from each lesion, had mean dimension of 9.6 cm 3 (range 0.5-27.9 cm 3 ). Mono-isocenter HyperArc VMAT plans (HA) with 5 non-coplanar 180°-arcs (couch at 0°, ±45°, ±90°) were generated and compared to multiple-isocenter VMAT plans (RA) with 2 coplanar 360°-arcs per isocenter. A dose normalization of 100%Dp at 98%PTV was adopted, while D 2% (PTV) < 150%D p was accepted. All plans had to respect the constraints on maximum dose to the brainstem (D 0.5cm3  < 18 Gy) as well as to the optical nerves/chiasm, eyes and lenses (D 0.5cm3  < 15 Gy). HA and RA plans were compared in terms of dose-volume metrics, by Paddick conformity (CI) and gradient (GI) index and by V 12 and mean dose to the brain-minus-PTV, and in terms of MU and overall treatment time (OTT) per fraction. OTT was measured for HA treatments, whereas for RA plans OTT was estimated by assuming 3 min. For initial patient setup plus 5 min. For each CBCT-guided setup correction per isocenter., Results: Significant variations in favour of HA plans were computed for both target dose indexes, CI (p < .01) and GI (p < .01). The lower GI in HA plans was the likely cause of the significant reduction in V 12 to the brain-minus-PTV (p = .023). Although at low doses, below 2-5 Gy, the sparing of the brain-minus-PTV was in favour of RA plans, no significant difference in terms of mean doses to the brain-minus-PTV was observed between the two groups (p = .31). Finally, both MU (p < .01) and OTT (p < .01) were significantly reduced by HyperArc plans., Conclusions: For linac-based SRS/FSRT of multiple brain lesions, HyperArc plans assured a higher CI and a lower GI than standard multiple-isocenter VMAT plans. This is consistent with the computed reduction in V 12 to the brain-minus-PTV. Finally, HyperArc treatments were completed within a typical 20 min. time slot, with a significant time reduction with respect to the expected duration of multiple-isocenters VMAT.

Aim: For selected patients with brain metastases (BMs), the role of stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (SFRT) is well recognized. The recent introduction of flattening filter free (FFF) delivery during linac-based SRS or SFRT allows shorter beam-on-time, improving patients' comfort and facility workflow. Nevertheless, limited experiences evaluated the impact of FFF linac-based SRS and SFRT in BMs treatment. Aim of the current study was to analyze SRS/SFRT linac-based FFF delivery for BMs in terms of dosimetric and early clinical results., Materials and Methods: Patients with life expectancy >3 months, number of BMs <5, diameter <3 cm, and controlled or synchronous primary tumor received SRS/SFRT. The prescribed total dose and fractionation, based on BMs size and proximity to organs at risk, ranged from 15 Gy in 1 fraction to 30 Gy in 5 fractions. A FFF volumetric modulated arc therapy (VMAT) plan was generated with one or two coplanar partial arcs. Toxicity was assessed according to CTCAE v4.0., Results: From April 2014 to February 2016, 45 patients (89 BMs) were treated with SRS/SFRT linac-based FFF delivery. The mean beam-on-time was 140 s for each lesion (range 90-290 s) and the average brain Dmean was 1 Gy (range 0.1-4.8 Gy). At the time of analysis, local control was reported in 93.2% (83/89 BMs). With a median follow-up time of 12 months (range 1-27 months), the median overall survival was 14 months and the 6-month overall survival was 77%. Finally, the median intracranial disease control was 11 months. Acute and late toxicities were acceptable without severe events (no adverse events ≥G2 were recorded)., Conclusions: These preliminary results highlighted the feasibility and safety of linac-based SRS/SFRT with FFF mode for BMs patients. A longer follow-up is necessary to confirm the efficacy of this treatment modality in BM patients.

Objectives: The objective of this study was to investigate fludeoxyglucose F 18 positron emission tomography/computed tomography ( 18 FDG-PET/CT) parameters as predictive of response after stereotactic ablative radiotherapy (SABR) for lung oligometastases., Methods: The inclusion criteria of the current retrospective study were as follows: (1) lung oligometastases treated by SABR, (2) presence of 18 FDG-PET/CT before and after SABR for at least two subsequent evaluations, (3) Karnofsky performance status higher than 80, and (4) life expectancy longer than 6 months. All patients were treated with a biologically equivalent dose of at least 100 Gy with an alpha/beta ratio of 10. The following metabolic parameters were semiquantitatively defined: maximum standardized uptake value (SUV max ), mean standardized uptake value (SUV mean ), metabolic tumor volume, and total lesion glycolysis., Results: A total of 50 patients met the inclusion criteria, for a total of 70 lung metastases. The pre-SABR median SUV max was 6.5 (range 4-17), the median SUV mean was 3.7 (range 2.5-6.5), and the median metabolic tumor volume was 2.3 cm 3 (0.2-31 cm 3 ). The following metabolic parameters were significantly related to complete response at 6 months: SUV max less than 5 (p < 0.001) and SUV mean less than 3.5 (p = 0.03). ΔSUV max at 3 to 6 months was +126% for lesions with in-field progression versus -26% for the remaining lesions (p = 0.002). ΔSUV mean at 3 to 6 months was +15% for lesions with in-field progression versus -26% for the remaining metastases (p = 0.008)., Conclusions: In the current analysis, complete response from lung metastasis at 6 months after stereotactic body radiation therapy was significantly associated with both the maximum and mean values of pre-SABR 18 FDG-PET/CT SUV. Longer-term trials are strongly advocated to improve the personalization of the monitoring of tumor response in patients with lung oligometastases and, consequently, monitoring of the cost-effectiveness of the health care., (Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)