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This study investigated optimization settings that steepen the dose gradient as a function of target size for lung stereotactic body radiation therapy (SBRT). Sixty-eight lung SBRT patients with planning target volumes (PTVs) ranging from 2-203 cc were categorized into small (<20 cc), medium (20-50 cc), and large (>50 cc) groups. VMAT plans were generated using the normal tissue objective (NTO) to penalize the dose gradient at progressively steeper NTO fall-off values (0.1, 0.2, 0.3, 0.4, 0.5 mm−1). Dose was calculated using the AcurosXB algorithm and was normalized so the prescription dose covered 95% of the PTV. Mann-Whitney, Kruskal-Wallis and ANOVA tests were used to assess for statistical differences in the Conformity Index at the 50% isodose level (CI50%), global maximum dose (D max), and monitor units (MU) across the various NTO settings. All plans adhered to institutional criteria and met the guidelines of the Radiation Therapy Oncology Group 0813. Steeper NTO fall-off values significantly increased D max and MUs across all groups (p < 0.05). CI50% significantly differed with fall-off values in small (0.3 mm−1) and medium (0.2 mm−1) targets, indicating steeper NTO fall-off values improve CI50% for small and medium targets (p < 0.05). Large targets showed no significant CI50% difference across these fall-off values. As target size increases, the importance of fall-off values in achieving an acceptable CI50% diminishes. Smaller targets benefit from steeper fall-off values despite increased D max and MUs. Consideration of fall-off value relative to target size is crucial to limit dose spillage outside the target. [ABSTRACT FROM AUTHOR]

This study investigated a straightforward treatment planning technique for definitive stereotactic body radiation therapy (SBRT) for patients with early-stage lung cancer aimed at increasing dose to gross disease by strategically penalizing the normal tissue objective (NTO) in the EclipseTM treatment planning system. Twenty-five SBRT cases were replanned to 50 Gy in 5 fractions using static and dynamic NTO methods (50 plans total). The NTO had a start dose of 100% at the target border, end dose of 20%, fall-off rate of 0.4/mm, and a priority of 150. For the static NTO plans, a lower planning target volume (PTV) objective was placed at 52 Gy with a priority of 100. Maximum dose was not penalized. Optimization was performed without user interaction. In contrast, the planner incrementally increased the priority of the NTO on the dynamic NTO plans until 95% of the target volume was covered by the prescription dose. Further, the dynamic NTO plans used both PTV lower and upper objectives at 63-64 Gy with priorities of 50. Maximum dose was penalized to ensure that the hot spot was within ± 2% of the static NTO global maximum dose. Following optimization, all plans were normalized so that the prescription dose covered 95% of the PTV. Plans were scored based on RTOG 0813 criteria, and dose to the internal target volume (ITV) and PTV was evaluated. The Wilcoxon signed-rank test (threshold = 0.05) was used to evaluate differences between the static and dynamic NTO plans. All plans met RTOG 0813 planning guidelines. In comparison to the static NTO plans, the dynamic NTO plans exhibited statistically significant increases in PTV mean dose, ITV mean dose, and PTV-ITV mean dose. Notably, the dynamic NTO plans more effectively concentrated the high dose on gross disease at the center of the PTV. As compared to the static NTO plans, the mean dose was 4.6 Gy higher in the ITV while only 1.3 Gy higher in the PTV-ITV rind of the dynamic NTO plans. Global maximum doses were similar. There were some small yet statistically significant differences in dose conformity between plan types. Furthermore, the dynamic NTO plans demonstrated a significant reduction in total monitor units (MU). This study demonstrated an efficient optimization strategy for lung SBRT plans that concentrates the highest dose in the gross disease, which may improve local control. [ABSTRACT FROM AUTHOR]

Ventricular arrhythmia (VA) is the primary mechanism of sudden death in patients with structural heart disease. Cardiac stereotactic body radiation therapy (SBRT) delivered to the scar in the left ventricle significantly reduces the burden of VA. The goal of this study was to investigate the impact of SBRT on scar morphology and VA inducibility in a porcine infarct model. Myocardial infarction (MI) was created in 10 Yorkshire pigs involving the left anterior descending artery territory. Cardiac positron emission tomography and computed tomography were performed for targeted SBRT. Alternative pigs received SBRT at 25 Gy in a single fraction. The terminal experiment included endocardial mapping, programmed ventricular stimulation, and tissue harvesting. Of the 10 pigs infarcted, 2 died prematurely after MI and 8 (4 MI and 4 MI+SBRT) survived. Mean time from MI to SBRT was 48 ± 12 days, and mean time from SBRT to harvest was 32 ± 12 days. Scar was localized on intracardiac mapping in all pigs, and the scar was denser in the MI+SBRT compared with the MI-only group (33% ± 20% vs 14% ± 11%; P =.07). All 4 MI pigs had inducible VA during programmed stimulation, whereas only 1 of 4 pigs had inducible VA in the MI+SBRT arm (100% vs 25%; P =.07). No myocardial fibrosis was seen in the remote areas in either group. SBRT reduced VA inducibility in pigs with scarring after MI. Endocardial mapping revealed denser scar in pigs receiving SBRT compared with those that did not, suggesting that SBRT suppresses VA inducibility through better scar homogenization. [Display omitted] [ABSTRACT FROM AUTHOR]

The purpose was to explore the role of stereotactic body radiation therapy (SBRT) in providing local control (LC) for primary breast cancer in patients unable to undergo surgery. Between 2015 and 2019, 13 non-surgical candidates with 14 lesions were treated with SBRT for primary breast cancer. In 4 cases, SBRT was used after whole breast radiation therapy (WBRT; 40–50 Gy/20–25 fractions). SBRT dose was 30–40 ​Gy in 5 fractions for patients treated with SBRT alone and 25–32 ​Gy in 4–5 fractions for those treated with SBRT ​+ ​WBRT. LC and overall survival (OS) were estimated using Kaplan-Meier curves. Response was also assessed using RECIST guidelines. Median follow-up was 32 (range: 3.4–70.4) months. Imaging at median 2.2 (0.6–8.1) months post-SBRT showed median 43.2 ​% (range: 2–100 ​%) decrease in the largest diameter and median 68.7 ​% (range: 27.9–100 ​%) SUV reduction. There were 3 cases of local progression at 8.7–10.6 months. Estimated LC was 100 ​% at 6 months and 71.6 ​% at 12, 24 and 36 months. Estimated median OS was 100 ​% at 6 months, 76.9 ​% at 12 months, and 61.5 ​% at 24 and 36 months. Acute toxicity (n ​= ​13; 92.9 ​%) included grade (G)1 (n ​= ​8), G2 (n ​= ​4), and G4 (necrosis; n ​= ​1). Late toxicity included G2 edema (n ​= ​1) and G4 necrosis (n ​= ​2, including 1 consequential late effect). Only patients treated with SBRT ​+ ​WBRT experienced acute/late G4 toxicity, managed with resection or steroids. SBRT to primary breast cancer resulted in good LC in non-surgical/metastatic patients. Although necrosis (n ​= ​2) occurred in the SBRT ​+ ​WBRT group, it was successfully salvaged. [ABSTRACT FROM AUTHOR]

To present the preliminary results on the clinical utilisation of an online daily adaptive magnetic resonance-guided radiation therapy (MRgRT) for various gynaecological cancers. Twelve patients treated between September 2018 and June 2022 were included. Six patients (50%) were treated with pelvic radiation therapy followed by MRgRT boost as brachytherapy boost was ineligible or unavailable, three patients (25%) were treated with pelvic MRgRT followed by high dose rate brachytherapy, two patients (16.7%) were treated with only MRgRT, one patient (8.3%) was treated with linear accelerator-based radiation therapy followed by MRgRT boost for bulky iliac lymph nodes. The median age was 56.5 years (range 31–86 years). Eight patients (66.7%) had a complete response, three patients (25%) had a partial response and one patient (8.3%) died due to acute renal failure. The mean follow-up time was 11.2 months (range 3.1–42.6 months). The estimated 1-year overall survival was 88.9%. The median treatment time was 47 days (range 10–87 days). During external beam radiation therapy, 10 (83.3%) patients had concomitant chemoradiotherapy. Pelvic external beam radiation therapy doses for all cohorts were 45–50.4 Gy with a fraction dose of 1.8 Gy. The median magnetic resonance-guided boost dose was 32 Gy (range 20–50 Gy) and fraction doses ranged between 4 and 10 Gy. Three patients were treated with intracavitary high dose rate brachytherapy (26–28 Gy in four to five fractions). None of the patients had grade >3 late genitourinary toxicities. MRgRT is reliable and clinically feasible for treating patients with gynaecological cancers alone or in combination with brachytherapy with an acceptable toxicity and outcome. MRgRT boost could be an option when brachytherapy is not available or ineligible. • MRgRT represents a new method for delivering radiotherapy for gynaecological cancers. • MRgRT is a markerless method providing online adaptive planning and real-time tracking. • MRgRT boost could be an option when brachytherapy is not available or is ineligible. [ABSTRACT FROM AUTHOR]

Cardiac stereotactic body radiotherapy (SBRT) has emerged as a promising noninvasive treatment for refractory ventricular tachycardia (VT). The purpose of this study was to describe the safety and effectiveness of SBRT for VT in refractory to extensive ablation. After maximal medical and ablation therapy, patients were enrolled in a prospective registry. Available electrophysiological and imaging data were integrated to generate a plan target volume. All SBRTs were planned with a single 25 Gy fraction using respiratory motion mitigation strategies. Clinical outcomes at 6 weeks, 6 months, and 12 months were analyzed and compared with the 6 months prior to treatment. VT burden (implantable cardioverter-defibrillator [ICD] shocks and antitachycardia pacing sequences) as well as clinical and safety outcomes were the main outcomes. Fifteen patients were enrolled and underwent planning. Fourteen (93%) underwent treatment, with 12 (80%) surviving to the end of the 6-week period and 10 (67%) surviving to 12 months. From 6 week to 12 months, there was recurrence of VT, which resulted in either appropriate antitachycardia pacing or ICD shocks in 33% (4 of 12). There were significant reductions in treated VT at 6 weeks to 6 months (98%) and at 12 months (99%) compared to the 6 months before treatment. There was a nonsignificant trend toward lower amiodarone dose at 12 months. Four deaths occurred after treatment, with no changes in ventricular function. For a select group of high-risk patients with VT refractory to standard therapy, SBRT is associated with a reduction in VT and appropriate ICD therapies over 1 year. [ABSTRACT FROM AUTHOR]

Standard curative options for early-stage, solitary hepatocellular carcinoma (HCC) are often unsuitable due to liver dysfunction, comorbidities and/or tumour location. Stereotactic body radiation therapy (SBRT) has shown high rates of local control in HCC; however, limited data exist in the treatment-naïve, curative-intent setting. We report the outcomes of patients with solitary early-stage HCC treated with SBRT as first-line curative-intent therapy. A multi-institutional retrospective study of treatment-naïve patients with Barcelona Clinic Liver Cancer stage 0/A, solitary ≤5 cm HCC, Child-Pugh score (CPS) A liver function who underwent SBRT between 2010 and 2019 as definitive therapy. The primary end point was freedom from local progression. Secondary end points were progression-free survival, overall survival, rate of treatment-related clinical toxicities and change in CPS >1. In total, 68 patients were evaluated, with a median follow-up of 20 months (range 3–58). The median age was 68 years (range 50–86); 54 (79%) were men, 62 (91%) had cirrhosis and 50 (74%) were Eastern Cooperative Oncology Group 0. The median HCC diameter was 2.5 cm (range 1.3–5) and the median prescription biologically effective dose with a tumour a/b ratio of 10 Gy (BED10) was 93 Gy (interquartile range 72–100 Gy). Two-year freedom from local progression, progression-free survival and overall survival were 94.3% (95% confidence interval 86.6–100%), 59.5% (95% confidence interval 46.3–76.4%) and 88% (95% confidence interval 79.2–97.6%), respectively. Nine patients (13.2%) experienced grade ≥2 treatment-related clinical toxicities. A rise >1 in CPS was observed in six cirrhotic patients (9.6%). SBRT is an effective and well-tolerated option to consider in patients with solitary, early-stage HCC. Prospective, randomised comparative studies are warranted to further refine its role as a first-line curative-intent therapy. • Multi-institutional series reporting outcomes following definitive SBRT in treatment-naïve, early-stage and solitary HCC. • Two-year freedom from local progression was 94% and 2-year overall survival was 88%. • Nine patients (13.2%) experienced grade 2 treatment-related clinical toxicities. • No grade 3–5 adverse events were reported. • Six patients with cirrhosis (9.6%) had an increase in Child-Pugh score (CPS) of >1; 3 of 6 re-compensated to CPS A status. [ABSTRACT FROM AUTHOR]

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To compare the local control rate of pulmonary metastatic lesions in colorectal adenocarcinoma treated with stereotactic body radiation therapy (SBRT) using a biologically effective dose with an α/β ratio of 10 (BED 10) of 150 Gy. We analysed 231 pulmonary metastatic lesions from colorectal adenocarcinoma treated with SBRT in 135 patients. The patients were referred for the control of oligometastatic or oligoprogressive disease in the lungs. A dose of 40–60 Gy in three to eight fractions was delivered. The local control per tumour (LCpT) by BED 10 was evaluated. The local control per patient (LCpP), pulmonary progression-free survival (PPFS), any progression-free survival (APFS) and overall survival were also reported as clinical outcomes. A significant difference was observed in the LCpT between the BED 10 groups (P < 0.001). The 1-, 2- and 3-year LCpT were 38.9%, 25.9% and 25.9% in BED 10 < 100 group; 84.1%, 62.6% and 60.4% in 100 ≤ BED 10 < 150 Gy group; and 97.3%, 94.9% and 85.2% in BED 10 ≥ 150 Gy group, respectively. BED 10 ≥ 150 Gy remained significant in the multivariate analysis of LCpT. The 3-year LCpP, PPFS, APFS and overall survival rates were 62.7%, 26.5%, 24.8% and 67.7%, respectively. Oligoprogression (versus oligometastasis), multiple pulmonary nodules and extrapulmonary metastasis were associated with a poor prognosis. A BED 10 ≥ 150 Gy may be required to achieve sufficient local control. The indications for SBRT and the extent of metastatic disease should be assessed for proper estimation of the clinical outcomes. • 231 lung metastatic nodules from colorectal cancer treated with SBRT were analysed. • High local control per tumour was associated with BED 10 ≥ 150 Gy. • A good overall survival rate of 67.7% at 3 years was reported. • Oligoprogression and widespread metastatic disease were associated with a poor prognosis. [ABSTRACT FROM AUTHOR]

To describe clinical outcomes of stereotactic body radiation therapy (SBRT) applied alone or as a boost after a conventionally fractionated radiation therapy (CFRT) for the treatment of bone oligometastases. This retrospective cohort study included patients treated with SBRT from January 2007 to December 2015 in the Institut de cancérologie de Lorraine in France. The inclusion criteria involved adults treated with SBRT for one to three bone metastases from a histological proven solid tumor and a primary tumor treated, an Eastern Cooperative Oncology Group (ECOG) score inferior or equal to 2. Local control (LC), overall survival (OS), progression free survival (PFS), bone progression incidence (BPI), skeletal related events free survival (SRE-FS), toxicity and pain response were evaluated. Forty-six patients and 52 bone metastases were treated. Twenty-three metastases (44.2%) received SBRT alone mainly for non-spine metastases and 29 (55.8%) a combination of CFRT and SBRT mainly for spine metastases. The median follow-up time was 22 months (range: 4–89 months). Five local failures (9.6%) were observed and the cumulative incidences of local recurrence at 1 and 2 years respectively were 4.4% and 8% with a median time of local recurrence of 17 months (range: 4–36 months). The one- and two-years OS were 90.8% and 87.4%. Visceral metastasis (HR: 3.40, 95% confidence interval [1.10–10.50]) and a time from primary diagnosis (TPD) > 30 months (HR: 0.22 [0.06–0.82]) were independent prognostic factors of OS. The 1 and 2 years PFS were 66.8% and 30.9% with a median PFS time of 18 months [13–24]. The one- and two-years BPI were 27.7% and 55.3%. In multivariate analysis, unfavorable histology was associated with worse BPI (HR: 3.19 [1.32–7.76]). The SRE-FS was 93.3% and 78.5% % at 1 and 2 years. The overall response rate for pain was 75% in the evaluable patients (9/12). No grade ≥ 3 toxicity nor especially no radiation induced myelopathy (RIM), two patients developed asymptomatic vertebral compression fractures. The sole use of SBRT or its association with CFRT is an efficient and well-tolerated treatment that allows high LC for bone oligometastases. [ABSTRACT FROM AUTHOR]

This prospective study investigated the health-related quality of life (HRQoL) of the patients with an early prostate cancer (PC) treated with radiotherapy (RT) without hormonal treatment compared to that in the agestandardized general male population. Patients have equal overall HRQoL measured with the 15D instrument compared to the general male population. Patients had more depression at the beginning of RT, and their sexual activity remained at a lower level after RT. Background: The effects of radiotherapy (RT) patients' health-related quality of life (HRQoL) are usually compared to those of other treatment modalities instead of HRQoL of the general population in oncological studies. We examined HRQoL of patients with an early prostate cancer (PC) not receiving hormonal treatment up to 3 years after RT using the 15D instrument and the FACT-P questionnaire. Methods: The 15D results were compared to those in the agestandardized general male population (N = 952) using an independent-sample t test. The study population (N = 73) received RT either with 78/2 Gy, 60/3 Gy or 36.25/7.25 Gy fractionation. Results: No significant differences in the mean total HRQoL scores were found between the RT groups and the general male population at any time point. Patients with PC had more depression (P = .015) and distress (P = .029) than the general male population before the treatment and depression up to 3 months after treatment (P = .019), which did not persist at 3 years. The sexual activity dimension had declined by the end of treatment, and this decline persisted 3 years later (P = .033). Excretion functions were worse compared to those in peers at the end of treatment (P < .001) but no longer at 3 months and later after RT. Regarding the FACT-P, HRQoL remained good at 3 years after RT in all the treatment groups and there were no significant differences between the different RT groups at this time point. Conclusion: This study demonstrated that patients treated with RT for early PC had similar HRQoL compared to the age-standardized general male population at 3 years after treatment. [ABSTRACT FROM AUTHOR]

Stereotactic body radiation therapy (SBRT) is increasingly used to treat non–small cell lung cancer. The purpose of this study is to analyze relationships between facility SBRT utilization and surgical patient selection and survival after surgery. Data on patients with TI/T2N0M0 lesions and treatment facility characteristics were abstracted from the National Cancer Database, 2008 to 2017. Facilities were stratified using an SBRT/surgery ratio previously associated with short-term survival benefit for patients treated surgically, and by a previously identified surgical volume threshold. Multiple regression analyses, Cox proportional-hazard regressions, and Kaplan–Meier log rank test were employed. In total, 182,610 patients were included. Proportion of high SBRT:surgery ratio (≥17%) facilities increased from 118 (11.5%) to 558 (48.4%) over the study period. Patients undergoing surgery at high-SBRT facilities had comparable comorbidity scores and tumor sizes to those at low-SBRT facilities, and nonclinically significant differences in age, race, and insurance status. Among low-volume surgical facilities, treatment at a high SBRT-using facility was associated with decreased 30-day mortality (1.8% vs 1.4%, P <.001) and 90-day mortality (3.3% vs 2.6%, P <.001). At high-volume surgical facilities, no difference was observed. At 5 years, a survival advantage was identified for patients undergoing resection at facilities with high surgical volumes (hazard ratio, 0.91; confidence interval, 0.90-0.93 P <.001) but not at high SBRT-utilizing facilities. Differences in short-term survival following resection at facilities with high-SBRT utilization may be attributable to low surgical volume facilities. Patients treated at high volume surgical facilities do not demonstrate differences in short-term or long-term survival based on facility SBRT utilization. [Display omitted] [Display omitted] [ABSTRACT FROM AUTHOR]

We compared the dosimetric characteristics of the target and organs at risk (OARs) as well as the preliminary clinical outcomes between two accelerated partial breast irradiation (APBI) techniques. Forty-four patients diagnosed with left-sided early breast cancer who underwent APBI using either interstitial brachytherapy (IB) or stereotactic body radiation therapy (SBRT) with CyberKnife (CK) were retrospectively reviewed. The dosimetric parameters of the target and OARs were compared. Preliminary clinical outcomes, including tumor control and acute toxicity, were analyzed. Treatment plans with CK demonstrated a better cardiac dose-sparing effect. Radiation doses to the heart at V 150cGy for the CK and IB groups were 24.4 % and 60.4 %, respectively (p < 0.001), while the mean heart doses for the CK and IB groups were 107.4 cGy and 204 cGy, respectively (p < 0.001). The heart D 1c.c. and the ipsilateral lung received a lower dose in the IB group, without any significant differences. The median follow-up time in the CK and IB groups was 28.6 and 61.3 months, respectively. No patients died from either breast cancer or cardiac events during follow-up. A locoregional recurrence event at the neck occurred in one patient within the IB group. APBI planned by CK was shown to have a better dose-sparing effect on the heart, as well as better conformity and homogeneity to the target. CK is a non-invasive treatment which showed minimal acute toxicity and promising tumor control. • APBI is time-saving, cost effectiveness and non-inferior to WBI for postoperative radiotherapy in early breast cancer. • CK is a non-invasive treatment which showed minimal acute toxicity and promising tumor control. • APBI planned by CK has a better dose-sparing effect on the heart and better conformity and homogeneity to the target. [ABSTRACT FROM AUTHOR]

• The robust data supporting dosimetric constraints for the brachial plexus following SBRT for apical lung malignancies remain elusive. • To establish dosimetric constraints for the brachial plexus at risk of developing grade ≥ 2 brachial plexopathy following SBRT. • This study establishes a dose range of 20.7 to 42.7 Gy across 1–5 fractions, aimed at mitigating the risk of grade ≥ 2 brachial plexopathy. • These findings provide valuable guidance for future ablative SBRT in patients with apical lung malignancies. The aim of this study is to establish dosimetric constraints for the brachial plexus at risk of developing grade ≥ 2 brachial plexopathy in the context of stereotactic body radiation therapy (SBRT). Individual patient data from 349 patients with 356 apical lung malignancies who underwent SBRT were extracted from 5 articles. The anatomical brachial plexus was delineated following the guidelines provided in the atlases developed by Hall, et al. and Kong, et al.. Patient characteristics, pertinent SBRT dosimetric parameters, and brachial plexopathy grades (according to CTCAE 4.0 or 5.0) were obtained. Normal tissue complication probability (NTCP) models were used to estimate the risk of developing grade ≥ 2 brachial plexopathy through maximum likelihood parameter fitting. The prescription dose/fractionation schedules for SBRT ranged from 27 to 60 Gy in 1 to 8 fractions. During a follow-up period spanning from 6 to 113 months, 22 patients (6.3 %) developed grade ≥2 brachial plexopathy (4.3 % grade 2, 2.0 % grade 3); the median time to symptoms onset after SBRT was 8 months (ranged, 3–54 months). NTCP models estimated a 10 % risk of grade ≥2 brachial plexopathy with an anatomic brachial plexus maximum dose (D max) of 20.7 Gy, 34.2 Gy, and 42.7 Gy in one, three, and five fractions, respectively. Similarly, the NTCP model estimates the risks of grade ≥2 brachial plexopathy as 10 % for BED D max at 192.3 Gy and EQD 2 D max at 115.4 Gy with an α/β ratio of 3, respectively. Symptom persisted after treatment in nearly half of patients diagnosed with grade ≥2 brachial plexopathy (11/22, 50 %). This study establishes dosimetric constraints ranging from 20.7 to 42.7 Gy across 1–5 fractions, aimed at mitigating the risk of developing grade ≥2 brachial plexopathy following SBRT. These findings provide valuable guidance for future ablative SBRT in apical lung malignancies. [ABSTRACT FROM AUTHOR]

Despite recent advances, the prognosis of pancreatic adenocarcinomas remains poor, even for patients with resectable tumors. For these latter, new approaches based on neoadjuvant treatment have been developed. Two components are used: chemotherapy and radiation therapy (RT). Indeed, pre-operative RT has many advantages in terms of efficacy and tolerance. It increases notably the chances of subsequent complete tumor resection. Several prospective trials are currently ongoing to clarify its place in the therapeutic arsenal. Another crucial question is to know which is the best RT technique: conventional normofractionated chemoradiotherapy or hypofrationated stereotactic body RT? [ABSTRACT FROM AUTHOR]

• One of few prospective phase II studies evaluating SBRT with ablative doses. • MRI-guided SBRT is safe and well tolerated. • SBRT can benefit certain patients with LAPC. Stereotactic body radiotherapy (SBRT) has emerged as a promising new modality for locally advanced pancreatic cancer (LAPC). The current study evaluated the efficacy and toxicity of SBRT in patients with LAPC (NCT03648632). This prospective single institution phase II study recruited patients with histologically or cytologically proven adenocarcinoma of the pancreas after more than two months of combination chemotherapy with no sign of progressive disease. Patients were prescribed 50–60 Gy in 5–8 fractions. Patients were initially treated on a standard linac (n = 4). Since 2019, patients were treated using online magnetic resonance (MR) image-guidance on a 1.5 T MRI-linac, where the treatment plan was adapted to the anatomy of the day. The primary endpoint was resection rate. Twenty-eight patients were enrolled between August 2018 and March 2022. All patients had non-resectable disease at time of diagnosis. Median follow-up from inclusion was 28.3 months (95 % CI 24.0-NR). Median progression-free and overall survival from inclusion were 7.8 months (95 % CI 5.0–14.8) and 16.5 months (95 % CI 10.7–22.6), respectively. Six patients experienced grade III treatment-related adverse events (jaundice, nausea, vomiting and/or constipation). One of the initial four patients receiving treatment on a standard linac experienced a grade IV perforation of the duodenum. Six patients (21 %) underwent resection. A further one patient was offered resection but declined. This study demonstrates that SBRT in patients with LAPC was associated with promising overall survival and resection rates. Furthermore, SBRT was safe and well tolerated, with limited severe toxicities. [ABSTRACT FROM AUTHOR]

The purpose of this study was to report on outcomes of a cohort of patients who were treated with reirradiation with stereotactic body radiation therapy (SBRT) for locally recurrent pancreatic adenocarcinoma. Patients treated with SBRT reirradiation for locally recurrent pancreatic adenocarcinoma from December 2009 to April 2020 were included in the study. Descriptive statistics were used to record patient demographics, tumour and treatment characteristics. Kaplan–Meier analysis was used to evaluate overall survival, local progression-free survival (LPFS), distant metastasis-free survival and progression-free survival (PFS). In total, 27 patients were included in the study. The median follow-up time from local recurrence was 19.7 months (range 4.2–43.1 months). Most patients received five-fraction SBRT (26/27, 96%). The median overall survival after local recurrence treatment was 18.3 months (range 3.0–42.6 months), with 6-month, 1-year and 2-year overall survival rates of 88.5%, 73.1% and 33.6%. The median LPFS after local recurrence treatment was 16.2 months (range 2.3–33.6 months), with 6-month, 1-year and 2-year LPFS rates of 95.8%, 62.9% and 27.2%. Peri-SBRT chemotherapy improved LPFS (median 17.5 versus 8.5 months; P = 0.010) and overall survival (median 19.3 versus 5.5 months; P = 0.049). Tumours ≤ 3 cm in the greatest dimension showed better local control (median LPFS 19.2 versus 10.2 months; P = 0.130). There was one case (4%) of acute grade 3 pain and one case (4%) of late grade 3 gastrointestinal toxicity. Reirradiation with five-fraction SBRT is safe, but local control remains suboptimal. Patients with smaller tumours experienced improved outcomes, as did patients whose treatment plan included the administration of peri-SBRT chemotherapy. • Locoregional failure alone is common after treatment of localised pancreatic cancer. • Reirradiation with SBRT is safe and feasible but local control can be suboptimal. • Peri-SBRT chemotherapy improved both survival and local control. • Smaller recurrences (≤3 cm) were associated with improved local control. [ABSTRACT FROM AUTHOR]

Background Context: With improvements in adjuvant radiotherapy and minimally invasive surgical techniques, separation surgery has become the default surgical intervention for spine metastases at many centers. However, it is unclear if there is clinical benefit from anterior column resection in addition to simple epidural debulking prior to stereotactic body radiotherapy (SBRT).Purpose: To examine the effect of anterior column debulking versus epidural disease resection alone in the local control of metastases to the bony spine.Study Design: Retrospective cohort study.Patient Sample: Ninety-seven patients who underwent open surgery followed by SBRT for spinal metastases at a single comprehensive cancer center.Outcome Measures: Local tumor recurrence following surgery and SBRT.Methods: Data were collected regarding radiation dose, cancer histology, extent of anterior column resection, and recurrence. Tumor involvement was categorized using the International Spine Radiosurgery Consortium guidelines. Univariable analyses were conducted to determine predictors of local recurrence and time to local recurrence.Results: Among the 97 included patients, mean age was 60.5±11.4 years and 51% of patients were male. The most common primary tumor types were lung (20.6%), breast (17.5%), kidney (13.4%) and prostate (12.4%). Recurrence was seen in 17 patients (17.5%) and local control rates were: 85.5% (1-year), 81.1% (2-year), and 54.9% (5-year). Overall predictors of local recurrence were tumor pathology (p<.01; renal cell carcinoma and colorectal adenocarcinoma associated with poorest PFS) and undergoing anterior column debulking versus epidural decompression-alone (p=.03). Only tumor pathology predicted time to local recurrence (p<.01), though inspection of Kaplan-Meier functions showed superior long-term local control in patients with radiosensitive tumor pathologies, no previous irradiation of the metastasis, and who underwent anterior column resection versus epidural removal alone. Median time to recurrence was 288 days with 100% of lesions showing anterior column recurrence and recurrence in the epidural space.Conclusions: With the increasing shift towards surgery as a neoadjuvant to radiotherapy for patients with spinal column metastases, the role for surgical debulking has become less clear. In the present study, we find that anterior column debulking as opposed to epidural debulking-alone decreases the odds of local recurrence and improves long-term local control. [ABSTRACT FROM AUTHOR]

Radiotherapy is an alternative local therapy to metastasectomy in the treatment of thoracic metastases from renal cell carcinoma. We retrospectively reviewed 71 patients who were treated with radiation for 89 lung (n = 58) or mediastinal (n = 31) metastases and reported overall survival and metastasis control. Local control was safely achieved, including lesions at high risk for causing a life-threatening event. Introduction/Background: Radiotherapy (RT) is an alternative local therapy to metastasectomy in the treatment of thoracic metastases from renal cell carcinoma (RCC), including the management of life-threatening disease. Patients and Methods: We reviewed patients with lung and mediastinal RCC metastases treated with RT at our institution. Overall survival (OS) and metastasis control (MC) was measured from the start of RT using the Kaplan-Meier (KM) method. Results: Seventy-one patients were treated with RT for 89 lung (n = 58) or mediastinal (n = 31) metastases. Of 89 treated lesions, 11 (12%) had local tumor recurrence, at a median of 1.6 years (range 0.4-2.9). MC at 1, 3, and 5-years was 96.6%, 83.5%, and 67.9%, respectively. For the 58-lung metastasis-directed RT courses, MC rates at 1, 3, and 5-years were 95.0%, 84.5%, and 84.5%, respectively (median MC not reached). For the 31-mediastinum metastasisdirected RT courses, MC rates at 1, 3, and 5-years were 100%, 43.4%, and 43.4%, respectively (median MC 2.9 years). MC was significantly improved for lung lesions compared to mediastinal lesions (P = .046). OS for the entire cohort at 1, 3, and 5 years was 65.2%, 48.5%, and 38.0%. There was no difference in OS based on metastatic sites in the 71 patients. Nineteen patients received RT to 19 lesions with the intention of preventing an event such as airway compromise or vascular invasion. One and two-year MC for these 19 lesions were 88.9% and 71.1%, respectively (median local control 2.4 years). OS in these 19 patients at 1, 2, and 5 years were 62.1%, 48.3%, and 32.2% respectively, with median survival 1.2 years. No patients developed grade 4 or 5 acute or late toxicities. Conclusion: Radiation therapy can safely achieve high metastasis control rates for lung and mediastinal metastases from RCC, including lesions at high risk for causing a life-threatening event. [ABSTRACT FROM AUTHOR]

In the era of COVID-19, there has been a large shift toward delivering larger doses of radiation over fewer treatments using stereotactic body radiation therapy (SBRT). There is a radiobiologic basis for using SBRT, as prostate cancer cells are more sensitive to higher doses of radiation delivered over fewer treatments. Here we show that men with unfavorable intermediate-risk prostate cancer treated with SBRT lived significantly longer when treated with SBRT relative to longer courses of radiotherapy. While we await results from several ongoing clinical trials, this study lends support to the use of SBRT in men with unfavorable intermediate-risk prostate cancer. Background: Prostate stereotactic body radiotherapy (SBRT), which delivers high-dose precision treatment in =5 fractions, is a shorter, more convenient, and less expensive alternative to conventionally fractionated radiotherapy (CRFT; ~44 fractions) or moderately hypofractionated radiotherapy (MFRT; 20-28 fractions). SBRT has not been widely adopted but may have radiobiologic advantages over CFRT/MFRT. We hypothesized that SBRT would be associated with improved overall survival (OS) versus CFRT or MFRT ± androgen deprivation therapy (ADT) for unfavorable-intermediate-risk prostate cancer (UIR-PCa). Methods: Men with UIR-PCa treated with SBRT (35-40Gy in =5 fractions) or biologically equivalent doses of CFRT (72-86.4Gy in 1.8-2.0Gy/fraction) or MRFT (=60Gy in 2.4-3.2Gy/fraction; biologically effective doses =120) were identified in the National Cancer Database (NCDB). Unweighted and propensityweighted multivariable Cox analysis (MVA) was used to compare OS hazard ratios. Results: Of 28,028 men with UIRPCa who received CFRT with (n = 12,872) or without ADT (n = 12,984); MFRT with (n = 251) or without ADT (n = 281); and SBRT with (n = 212) or without ADT (n = 1,428) were identified. Relative to CFRT without ADT, CFRT + ADT (HR 0.92, 95% CI 0.87-0.97, P = .002) and SBRT without ADT (HR 0.74, 95% CI 0.61-0.89, P = .002) were both associated with improved OS on MVA. Relative to CFRT + ADT, SBRT without ADT correlated with improved OS on MVA (HR:0.81, 95% CI 0.67-0.99, P = .04). Propensity-weighted MVA demonstrated that SBRT (HR:0.80, 95% CI 0.65-0.98, P = .036) and ADT (HR:0.91, 95% CI 0.86-0.97, P = .002) correlated with improved OS. SBRT was not associated with improved OS versus MFRT. Conclusion: SBRT, which offers a cheaper and shorter treatment course that mitigates COVID-19 exposure, was associated with improved OS versus CFRT for UIR-PCa. These results confirm guideline-based recommendations that SBRT is a viable option for UIR prostate cancer. The results from this large retrospective study require further validation in clinical trials. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitor monotherapy in metastatic castration-resistant prostate cancer (mCRPC) has produced modest results. High-dose radiotherapy may be synergistic with checkpoint inhibitors. To evaluate the efficacy and safety of the PD-L1 inhibitor avelumab with stereotactic ablative body radiotherapy (SABR) in mCRPC. From November 2017 to July 2019, this prospective phase 2 study enrolled 31 men with progressive mCRPC after at least one prior androgen receptor–directed therapy. Median follow-up was 18.0 mo. Avelumab 10 mg/kg intravenously every 2 wk for 24 wk (12 cycles). A single fraction of SABR (20 Gy) was administered to one or two disease sites within 5 d before the first and second avelumab treatments. The primary endpoint was the disease control rate (DCR), defined as a confirmed complete or partial response of any duration, or stable disease/non–complete response/non–progressive disease for ≥6 mo (Prostate Cancer Clinical Trials Working Group 3–modified Response Evaluation Criteria in Solid Tumours version 1.1). Secondary endpoints were the objective response rate (ORR), radiographic progression-free survival (rPFS), overall survival (OS), and safety. DCR and ORR were calculated using the Clopper-Pearson exact binomial method. Thirty-one evaluable men were enrolled (median age 71 yr, 71% with ≥2 prior mCRPC therapy lines, 81% with >5 total metastases). The DCR was 48% (15/31; 95% confidence interval [CI] 30–67%) and ORR was 31% (five of 16; 95% CI 11–59%). The ORR in nonirradiated lesions was 33% (four of 12; 95% CI 10–65%). Median rPFS was 8.4 mo (95% CI 4.5–not reached [NR]) and median OS was 14.1 mo (95% CI 8.9–NR). Grade 3–4 treatment-related adverse events occurred in six patients (16%), with three (10%) requiring high-dose corticosteroid therapy. Plasma androgen receptor alterations were associated with lower DCR (22% vs 71%, p = 0.13; Fisher's exact test). Limitations include the small sample size and the absence of a control arm. Avelumab with SABR demonstrated encouraging activity and acceptable toxicity in treatment-refractory mCRPC. This combination warrants further investigation. In this study of men with advanced and heavily pretreated prostate cancer, combining stereotactic radiotherapy with avelumab immunotherapy was safe and resulted in nearly half of patients experiencing cancer control for 6 months or longer. Stereotactic radiotherapy may potentially improve the effectiveness of immunotherapy in prostate cancer. In this phase 2 trial, avelumab with stereotactic ablative body radiotherapy achieved disease control in approximately half of patients with advanced treatment-refractory metastatic castration-resistant prostate cancer and radiographic responses in nearly one-third of patients, with an acceptable toxicity profile. This combination has promising activity and warrants further investigation in randomised trials. [ABSTRACT FROM AUTHOR]

La radiothérapie stéréotaxique est réalisée régulièrement pour l'irradiation des métastases osseuses des os périphériques mais sa place reste mal connue. Cette mise au point en radiothérapie stéréotaxique des oligométastases osseuses des os périphériques présente la synthèse des données actuelles de la science relatives aux indications, à la simulation virtuelle, à la délinéation des volumes cibles, à la dose totale et le fractionnement, à l'efficacité et la tolérance. Les cancers oligométastatiques sont classés ont 4 catégories : oligorécidive, oligométastase, oligopersistance, oligoprogression. Le pronostic sera évalué selon les caractéristiques suivantes : tumeur primitive, caractéristiques quantitatives, cinétique, caractéristiques qualitatives. La délinéation du volume tumoral macroscopique (GTV) comprend les extensions aux parties molles et à la moelle osseuse en s'aidant de l'IRM et de le TEP. Le volume cible anatomoclinique (CTV) correspond à une marge de 2 à 5 mm et le volume cible prévisionnel (PTV) à une marge de 2 mm (à définir en fonction des contraintes de chaque service et contention). Les schémas d'irradiation les plus utilisés sont : une séance unique de 18 à 24 Gy ; 24 Gy en deux fractions ; 27 à 30 Gy en trois fractions ; 30 à 35 Gy en cinq fractions. La radiothérapie stéréotaxique permet un taux de contrôle local de 90 % à 1 an et un bon contrôle de la douleur. Les effets secondaires sont peu marqués. La radiothérapie stéréotaxique est faisable, non-invasive, peu toxique et efficace avec un bon taux de contrôle local et un bon soulagement des douleurs. La principale problématique reste celle de la sélection des patients les plus à même d'en bénéficier. Stereotaxic radiotherapy is performed regularly for the irradiation of non-spine bone metastases, but its place is not well understood. This article in stereotaxic radiotherapy of non-spine bones oligometastases presents the current scientific data relating to the indications, to virtual simulation, to the delineation of target volumes, to the total dose and fractionation, to the efficacy and tolerance. Oligometastatic patients are classified into 4 categories: oligorecurrences, oligometastasis, oligopersistence, oligoprogression. The prognosis will be evaluated according to the following characteristics: primary tumor, quantitative characteristics, kinetics, qualitative characteristics. The delineation of GTV includes extensions to the soft tissue and bone marrow with the aid of MRI and PET. The CTV corresponds to a margin of 2 to 5 mm and the PTV to a margin of 2 mm. The most widely used irradiation schemes are: 1 single fraction of 18 to 24 Gy/1 fr; 24 Gy/2 fr; 27 to 30 Gy/3 fr; 30 to 35 Gy/5 fr. Stereotaxis provides 90% local control at 1 year and good pain control. The side effects are not very marked. Stereotaxic radiotherapy is feasible, non-invasive, minimally toxic and effective with good local control and good pain relief. The main issue remains selecting the patients most likely to benefit from it. [ABSTRACT FROM AUTHOR]

• Retrospective review of head and neck skin cancer (HNSC) patients treated with stereotactic body radiation therapy (SBRT). Largest North American experience published in the modern era. • SBRT for HNSC provides durable local control rates with acceptable late toxicity rates. To report outcomes of Stereotactic Body Radiotherapy (SBRT) for head and neck skin cancer (HNSC) patients treated at a high-volume center. A retrospective review of HNSC SBRT patients from 2012 to 2019 was conducted. Kaplan–Meier method was used to estimate local control (LC), locoregional control (LRC) outside of SBRT field, overall survival (OS), progression-free survival (PFS) and late toxicity (LT). Univariate and multivariate analyses were performed. Grade 3-4 acute and late toxicities were reported by the Common Terminology Criteria for Adverse Events v5.0. One hundred and six medically unfit HNSC patients (112 lesions) were included. Median follow-up was 8 months. Median patient age at diagnosis was 86 years (range: 56–102 years). The majority of patients had advanced disease (overall stage III-IV [ n = 90, 85%]) with median gross tumor volumes (GTV) of 31 cm3 (range: 17–56 cm3). Treated sites were: primary (n = 51), nodal (n = 47) or primary plus nodal (n = 8). SBRT doses ranged from 32-50 Gy delivered twice weekly in 4–6 fractions to the gross tumor volume (GTV). One and 2-year LC rates were 78% (69–88) and 67% (53–82), respectively. One-year LRC outside of SBRT field, OS, PFS and LT rates were 72% (62–84), 53% (43–65), 52% (40–62), and 7% (2–17), respectively. Thirty-three patients (31%) developed acute grade ≥ 3 treatment-related toxicity, most commonly dermatitis (n = 31). Nine patients (8%) experienced late grade ≥ 3 toxicity, including 7 grade 3 fibrosis, 1 grade 3 bone radionecrosis and 1 grade 4 skin ulceration. No treatment-related deaths (grade 5) were observed. SBRT provides durable disease control with acceptable toxicity for medically unfit high-risk HNSC patients unable to undergo standard of care curative treatment approaches. [ABSTRACT FROM AUTHOR]

We investigated the interfractional variation in the tumor position during lung stereotactic body radiotherapy (SBRT) under expiratory-phase breath hold (BH) using cone-beam computed tomography (CBCT). A total of 79 patients with lung cancer were treated with lung SBRT, wherein the Abches system under expiratory-phase BH was used to study interfractional variation. The tumors were located in the upper lobe in 31 cases, in the middle lobe in 11 cases, and in the lower lobe in 37 cases. Planning CTs were scanned under expiratory-phase BH with the Abches system. The 3-degrees-of-freedom (DOF) tumor-based setup using CBCT images under expiratory-phase BH was performed after a 6-DOF bony vertebrae-based setup using an ExacTrac X-ray system. Interfractional variation in the lung tumor position was defined as the difference in the position of the lung tumor relative to the bone anatomy in the left-right (LR), antero-posterior (AP), and craniocaudal (CC) directions represented as absolute values. The interfractional variation in the lung tumor position was very similar in all the lung regions, and its mean ± standard deviation values in all patients were 1.0 ± 1.1, 1.6 ± 1.9, and 1.6 ± 1.9 mm in the LR, AP, and CC directions, respectively. Further, 99.1%, 92.4%, and 92.7% of all the fractions for the interfractional tumor positional variation in the LR, AP, and CC directions were less than 5 mm, respectively. The interfractional variation in the tumor position was small for lung cancer patients treated with the Abches system under expiratory-phase BH. [ABSTRACT FROM AUTHOR]

The purpose of this work was to develop a treatment plan verification routine for a linear accelerator dedicated to SBRT treatments with gimbal based dynamic tumor tracking using three commercially available phantoms. The accelerator system has two special features: It operates with a rotation of the ring shaped gantry instead of a couch rotation and target motion can be compensated for via a gimbal system (dynamic tumor tracking, DTT). DTT plans were each measured with the three different phantoms. Afterwards the measured dose distribution was compared with the calculated dose distribution via global Gamma Index analysis (3 mm / 3%, threshold: 10%). The global gamma pass rates were on average (93.5 ± 7.2) % for ArcCHECK, (98.0 ± 2.6) % for OCTAVIUS® 4D and (98.4 ± 4.2) % for MatriXX Evolution. All three systems could be used for quality assurance with ring rotations and DTT, however, each with limitations. [ABSTRACT FROM AUTHOR]

L'immunothérapie occupe une place grandissante en cancérologie urologique, principalement pour les cancers du rein et de la vessie. Sur la base de travaux précliniques encourageants, la combinaison de l'immunothérapie avec la radiothérapie ambitionne de majorer la réponse tumorale, y compris des tumeurs métastatiques ce qui suscite de nombreux espoirs dont cet article fait le bilan. Immunotherapy occupies a growing place in urologic oncology, mainly for kidney and bladder cancers. On the basis of encouraging preclinical work, the combination of immunotherapy with radiotherapy aims to increase the tumor response, including in metastatic tumors, which raises many hopes, which this article reviews. [ABSTRACT FROM AUTHOR]

Microwave (MW) ablation and stereotactic body radiation therapy (SBRT) are both used in treating inoperable renal cell carcinoma (RCC). MW ablation and SBRT have potentially complementary advantages and limitations. Combining SBRT and MW ablation may optimize tumor control and toxicity for patients with larger (> 5 cm) RCCs or those with vascular involvement. Seven patients with RCC were treated at our institution with combination of SBRT and MW ablation, median tumor size of 6.4 cm. Local control was 100% with a median follow-up of 15 months. Four patients experienced grade 2 nausea during SBRT. Three patients experienced toxicities after MW ablation, 2 with grade 1 hematuria and 1 with grade 3 retroperitoneal bleed/collecting system injury. Median eGFR (estimated glomerular filtration rate) preceding and following SBRT and MW ablation was 69 mL/min/1.73 m² and 68 mL/min/1.73 m² (P = .19), respectively. In patients who are not surgical candidates, larger RCCs or those with vascular invasion are challenging to treat. Combination treatment with SBRT and MW ablation may balance the risks and benefits of both therapies and demonstrates high local control in our series. MW ablation and SBRT have potentially complementary advantages and limitations. [ABSTRACT FROM AUTHOR]

Purpose: Vertebral compression fracture is a common complication of spinal stereotactic body radiation therapy. Development of an in vivo model is crucial to fully understand how focal radiation treatment affects vertebral integrity and biology at various dose fractionation regimens. We present a clinically relevant animal model to analyze the effects of localized, high-dose radiation on vertebral microstructure and mechanical integrity. Using this model, we test the hypothesis that fractionation of radiation dosing can reduce focused radiation therapy's harmful effects on the spine.Methods and Materials: The L5 vertebra of New Zealand white rabbits was treated with either a 24-Gy single dose of focused radiation or 3 fractionated 8-Gy doses over 3 consecutive days via the Small Animal Radiation Research Platform. Nonirradiated rabbits were used as controls. Rabbits were euthanized 6 months after irradiation, and their lumbar vertebrae were harvested for radiologic, histologic, and biomechanical testing.Results: Localized single-dose radiation led to decreased vertebral bone volume and trabecular number and a subsequent increase in trabecular spacing and thickness at L5. Hypofractionation of the radiation dose similarly led to reduced trabecular number and increased trabecular spacing and thickness, yet it preserved normalized bone volume. Single-dose irradiated vertebrae displayed lower fracture loads and stiffness compared with those receiving hypofractionated irradiation and with controls. The hypofractionated and control groups exhibited similar fracture load and stiffness. For all vertebral samples, bone volume, trabecular number, and trabecular spacing were correlated with fracture loads and Young's modulus (P < .05). Hypocellularity was observed in the bone marrow of both irradiated groups, but osteogenic features were conserved in only the hypofractionated group.Conclusions: Single-dose focal irradiation showed greater detrimental effects than hypofractionation on the microarchitectural, cellular, and biomechanical characteristics of irradiated vertebral bodies. Correlation between radiologic measurements and biomechanical properties supported the reliability of this animal model of radiation-induced vertebral compression fracture, a finding that can be applied to future studies of preventative measures. [ABSTRACT FROM AUTHOR]

• MR-guided adaptive adrenal SABR reduces the chance of stomach toxicity. • Reduction in predicted stomach toxicity was mainly for left adrenal lesions. • Consider dose escalation for right adrenal lesions due to low predicted toxicity. Stereotactic ablative radiotherapy (SABR) can achieve good local control for metastatic adrenal lesions. Magnetic resonance (MR)-guidance with daily on-table plan adaptation can augment the delivery of SABR with greater dose certainty. The goal of this study was to quantify the potential clinical benefit MR-guided daily-adaptive adrenal SABR using the normal tissue complication probability (NTCP) framework. Patients treated with adrenal MR-guided SABR at a single institution were retrospectively reviewed. Lyman-Kutcher-Burman NTCP models were used to calculate the NTCP of upper abdominal organs-at-risk (OARs) at simulation and both before and after daily on-table plan adaptation. Differences in OAR NTCPs were assessed using signed-rank tests. Potential predictors of the benefits of adaptation were assessed by linear regression. Fifty-two adrenal MR-guided SABR courses were analyzed. The baseline simulation plan underestimated the absolute stomach NTCP by 10.0% on average (95% confidence interval: 4.7–15.2%, p < 0.001). Daily on-table adaptation lowered absolute NTCP by 8.7% (4.2–13.2%, p < 0.001). The most significant predictor of the benefits of adaptation was lesion laterality (p = 0.018), with left-sided lesions benefitting more (13.3% [6.3–20.4%], p < 0.001) than right-sided lesions (2.1% [−1.6–5.7%], p = 0.25). Sensitivity analyses did not change the statistical significance of the findings. NTCP analysis revealed that patients with left adrenal tumors were more likely to benefit from MR-guided daily on-table adaptive SABR using current dose/fractionation regimens due to reductions in predicted gastric toxicity. Right-sided adrenal lesions may be considered for dose escalation due to low predicted NTCP. [ABSTRACT FROM AUTHOR]

Purpose: Our individualized functional response adaptive approach to liver stereotactic body radiation therapy (SBRT) with assessment of indocyanine green (ICG) retention at baseline and midtreatment to detect subclinical changes in liver function, permitting dose adjustment, has decreased toxicity while preserving efficacy. We hypothesized that assessment of the albumin-bilirubin (ALBI) score at baseline and midtreatment would allow for more practical identification of patients at risk for treatment-related toxicity (TRT).Methods and Materials: Patients with hepatocellular carcinoma were treated on 3 prospective institutional review board-approved trials using baseline and midtreatment ICG to deliver individualized functional response adaptive liver SBRT. Patients received 3 or 5 fractions, with fraction 3 followed by a 1-month treatment break. TRT was a ≥2-point rise in Child-Pugh score within 6 months of SBRT. Logistic regression was used to estimate odds ratios (ORs) and confidence intervals (CIs) for assessment of TRT. Area under the receiver operating curve was used to compare predictive ability across models.Results: In total, 151 patients underwent 166 treatments. Baseline Child-Pugh class and ALBI grade were A (66.9%), B (31.3%), or C (1.8%) and 1 (25.9%), 2 (65.7%), or 3 (8.4%), respectively. Thirty-five patients (20.3%) experienced TRT. On univariate analysis, baseline ALBI (OR, 1.8; 95% CI, 1.24-2.62; P = .02), baseline ICG (OR, 1.66; 95% CI, 1.17-2.35; P = .04), and change in ALBI (OR, 3.07; 95% CI, 1.29-7.32; P = .003) were associated with increased odds of TRT. ALBI-centric models performed similarly to ICG-centric models on multivariate analyses predicting toxicity (area under the receiver operating curve of 0.79 for both). In a model incorporating baseline and midtreatment change in ALBI and ICG, both ALBI values were statistically significantly associated with toxicity, whereas ICG values were not.Conclusions: Incorporation of midtreatment change in ALBI in addition to baseline ALBI improves the ability to predict TRT in patients with hepatocellular carcinoma receiving SBRT. Our findings suggest that functional response adaptive treatment could be implemented in a practical manner because the ALBI score is easily obtained from standard laboratory values. [ABSTRACT FROM AUTHOR]

• Estimation of delivered dose to lung tumours in SBRT considering geometrical errors. • Quantitative estimates, on statistical basis, of delivered tumour dose. • Estimation of difference between two IGRT methods extensively used in SBRT. • Illustration of a framework for carrying out estimates of delivered dose. • Online cone-beam CT image-guidance typically leads to higher tumour dose. Dose-response relationships for local control of lung tumours treated with stereotactic body radiotherapy (SBRT) have proved ambiguous, however, these have been based on the prescribed or planned dose. Delivered dose to the target may be a better predictor for local control. In this study, the probability of the delivered minimum dose to the clinical target volume (CTV) in relation to the prescribed dose was estimated for a cohort of patients, considering geometrical uncertainties. Delivered doses were retrospectively simulated for 50 patients treated with SBRT for lung tumours, comparing two image-guidance techniques: pre-treatment verification computed tomography (IG1) and online cone-beam computed tomography (IG2). The prescribed dose was typically to the 67% isodose line of the treatment plan. Simulations used in-house software that shifted the static planned dose according to a breathing motion and sampled setup/matching errors. Each treatment was repeatedly simulated, generating a multiplicity of dose-volume histograms (DVH). From these, tumour-specific and population-averaged statistics were derived. For IG1, the probability that the minimum CTV dose (D 98%) exceeded 100% of the prescribed dose was 90%. With IG2, this probability increased to 99%. Doses below the prescribed dose were delivered to a considerably larger part of the population prior to the introduction of online soft-tissue image-guidance. However, there is no clear evidence that this impacts local control, when compared to previous published data. [ABSTRACT FROM AUTHOR]

• Stereotactic body radiation therapy (SBRT) has been safe and efficacious for management of early-stage hepatocellular carcinoma (HCC), but optimal fractionation schemes are unknown. • We collected 1- to 5-year clinical local tumor control probability (TCP) of 4313 patients for SBRT of early-stage HCC and studied TCP as a function of biologically effective dose (BED) using three representative radiobiological models developed per the Hypofractionated Treatment Effects in the Clinic (HyTEC) initiative. • The fits to the clinical TCP data show that TCP increases steeply with BED and reaches an asymptotic maximal plateau. We presented the first determination of radiobiological parameters and model-independent optimal SBRT and hypofractionated radiotherapy schemes of least doses to achieve maximal tumor control for early-stage HCC. • The proposed optimal fractionation schemes are in good agreement with clinical practice for SBRT of early-stage HCC. Most existing hypofractionated schemes of 3–5 Gy/fraction are not optimal to maximize tumor control, higher radiation doses are required. Stereotactic body radiation therapy (SBRT) has been emerging as an efficacious and safe treatment modality for early-stage hepatocellular carcinoma (HCC), but optimal fractionation regimens are unknown. This study aims to analyze published clinical tumor control probability (TCP) data as a function of biologically effective dose (BED) and to determine radiobiological parameters and optimal fractionation schemes for SBRT and hypofractionated radiation therapy of early-stage HCC. Clinical 1- to 5-year TCP data of 4313 patients from 41 published papers were collected for hypofractionated radiation therapy at 2.5–4.5 Gy/fraction and SBRT of early-stage HCC. BED was calculated at isocenter using three representative radiobiological models developed per the Hypofractionated Treatment Effects in the Clinic (HyTEC) initiative. Radiobiological parameters were determined from a fit to the TCP data using the least χ2 method with one set of model parameters regardless of tumor stages or Child-Pugh scores A and B. The fits to the clinical TCP data for SBRT of early-stage HCC found consistent α/β ratios of about 14 Gy for all three radiobiological models. TCP increases sharply with BED and reaches an asymptotic maximal plateau, which results in optimal fractionation schemes of least doses to achieve asymptotic maximal tumor control for SBRT and hypofractionated radiation therapy of early-stage HCC that are found to be model-independent. From the fits to the clinical TCP data, we presented the first determination of radiobiological parameters and model-independent optimal fractionation regimens in 1–20 fractions to achieve maximal tumor control whenever safe for SBRT and hypofractionated radiation therapy of early-stage HCC. The determined optimal fractionation schemes agree well with clinical practice for SBRT of early-stage HCC. However, most existing hypofractionated radiation therapy schemes of 3–5 Gy/fraction are not optimal, higher doses are required to maximize tumor control, further validation of these findings is essential with clinical TCP data. [ABSTRACT FROM AUTHOR]

• This comprehensive meta-analysis of 724 patients across 22 studies evaludated the impact of BED escalation in SBRT on outcomes in primary RCC. • Excellent local control rates were observed across a wide range of BEDs, with 1, 2, and 5-year estimates of 99%, 98%, and 94%, respectively. • No significant dose-response relationship was seen between increasing BED and local control, progression-free survival, or overall survival. • We recommend SBRT dose escalation in RCC only in the context of safe organ-at-risk doses. Stereotactic ablative radiation therapy (SBRT) is an emerging treatment option for primary renal cell carcinoma (RCC), particularly in patients who are unsuitable for surgery. The aim of this review is to assess the effect of increasing the biologically equivalent dose (BED) via various radiation fractionation regimens on clinical outcomes. A literature search was conducted in PubMed (Medline), EMBASE, and the Cochrane Library for studies published up to October 2023. Studies reporting on patients with localized RCC receiving SBRT were included to determine its effectiveness on local control, progression-free survival, and overall survival. A random effects model was used to meta-regress clinical outcomes relative to the BED for each study and heterogeneity was assessed by I2. A total of 724 patients with RCC from 22 studies were included, with a mean age of 72.7 years (range: 44.0–81.0). Local control was excellent with an estimate of 99 % (95 %CI: 97–100 %, I2 = 19 %), 98 % (95 %CI: 96–99 %, I2 = 8 %), and 94 % (95 %CI: 90–97 %, I2 = 11 %) at one year, two years, and five years respectively. No definitive association between increasing BED and local control, progression-free survival and overall survival was observed. No publication bias was observed. A significant dose response relationship between oncological outcomes and was not identified, and excellent local control outcomes were observed at the full range of doses. Until new evidence points otherwise, we support current recommendations against routine dose escalation beyond 25–26 Gy in one fraction or 42–48 Gy in three fractions, and to consider de-escalation or compromising target coverage if required to achieve safe organ at risk doses. [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]

The purpose of this study was to evaluate the feasibility and efficacy of HyperArc (HA) for recurrent nasopharyngeal cancer (NPC) by comparing it with the CyberKnife system (CK). Fifteen patients with recurrent nasopharyngeal cancer who were treated using the noncoplanar cone-based robotic CK system were enrolled. CK was delivered with a median dose of 37.5 Gy in 5 fractions. The delivered CK treatment plans were the sources for the corresponding homogeneous HA (HA-H) and inhomogeneous HA (HA-IH) plans. The HA-H plans were generated to meet the corresponding treatment plan criteria for the CK plans. The HA-IH plans were designed to emulate the corresponding inhomogeneous CK isodose distributions. These three SBRT treatment plans were compared with target coverage, sparing of organs at risk (OARs), and dose distribution metrics. The HA-H and HA-IH plans consistently exhibited CTV and PTV coverage levels similar or better to those of the CK plans but significantly reduced the dose to OARs. Using the HA techniques (both HA-H and HA-IH plans), the mean maximal doses to the spinal cord, brainstem, optic nerves, and optic chiasm were reduced by approximately 60%, compared to the CK plans. The high dose spillage, conformity, and homogeneity indices of the HA-H plans were significantly better than those of the CK plans. The HA-IH plans showed faster dose falloff and similar conformity of the HA-H plans and dose heterogeneity of the CK plans. Here we demonstrated the HA treatment plan system for recurrent NPC is feasible, either homogeneous or inhomogeneous delivery. Excellent sparing of OARs and dosimetric distribution and very efficient delivery make HA an attractive SBRT technique for recurrent NPC treatment. [ABSTRACT FROM AUTHOR]

• Clinical and dosimetric risk factors for symptomatic RP after SBRT were analyzed in a large series of patients. • Respiratory comorbidity, previous lung radiation, right lung location, BED10 of the prescription dose, MLD and V20 of total lungs, and MLD of ipsilateral lung were significant factors for higher risk of symptomatic RP. • Should the risk of RP2 be limited less than 10%, the mean doses of total lung and ipsilateral lung be constrained to less than 6 Gy and 20 Gy, respectively. Radiation pneumonitis (RP) can be a potential fatal toxicity of stereotactic body radiation therapy (SBRT) for medically inoperable non-small cell lung cancer (NSCLC). This study aimed to examine the risk factors that predict RP and explore dosimetric tolerance for safe practice in a large institutional series of NSCLC patients. Patients with early-stage and locally recurrent NSCLC who received lung SBRT between 2002 and 2015 formed the study population. The primary endpoint was grade 2 or above radiation pneumonitis (RP2). Lungs were re-contoured consistently by one radiation oncologist according to the RTOG atlas for organs at risk. Dosimetric factors were computed consistently with exclusion of gross tumor volume of either ipsilateral, contralateral, or total lungs. A total of 339 patients were eligible. With a median follow-up of 47 months, RP2 was recorded in 10% patients. History of respiratory comorbidity, previous thoracic radiation, right lung location, mean lung doses of total or ipsilateral lung, and total lung volume receiving 20 Gy were all significantly associated with the risk of RP2. The dosimetric parameters of contralateral lung, including mean dose and volume receiving more than 5, 10, and 20 Gy, were not significantly associated with RP2 (ps > 0.05). A model of combining significant clinical and dosimetric factors had a predictive accuracy AUC of 0.76. According to this model, RP2 can be limited to <10% should the patient have no previous lung radiation and the mean dose of total and ipsilateral lungs be kept less than 6 Gy and 20 Gy, respectively. Dosimetric factors of total or ipsilateral lung together with important clinical factors were significant risk factors for symptomatic radiation pneumonitis after SBRT. Constraining mean lung dose can limit clinically significant lung toxicity. [ABSTRACT FROM AUTHOR]