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Introduction/purpose: This study assessed long‐term clinical and radiological outcomes following treatment with combination stereotactic radiosurgery (SRS) and immunotherapy (IT) for melanoma brain metastases (BM). Methods: A retrospective review was performed in a contemporary cohort of patients with melanoma BM at a single tertiary institution receiving Gamma Knife® SRS for melanoma BM. Multivariate Cox proportional‐hazards modelling was performed with a P <0.05 for significance. Results: 101 patients (435 melanoma BM) were treated with SRS between January‐2015 and June‐2019. 68.3% of patients received IT within 4 weeks of SRS (concurrent) and 31.7% received SRS alone or non‐concurrently with IT. Overall, BM local control rate was 87.1% after SRS. Median progression free survival was 8.7 months. Median follow‐up was 29.2 months. On multivariate analysis (MVA), patients receiving concurrent SRS‐IT maintained a higher chance of achieving a complete (CR) or partial response (PR) [HR 2.6 (95% CI: 1.2–5.5, P = 0.012)] and a reduced likelihood of progression of disease (PD) [HR 0.52 (95% CI: 0.16–0.60), P = 0.048]. Any increase in BM volume on the initial MRI 3 months after SRS predicted a lower likelihood of achieving long‐term CR or PR on MVA accounting for concurrent IT, BRAF status and dexamethasone use [HR = 0.048 (95% CI: 0.007–0.345, P = 0.0026)]. Stratified volumetric change demonstrated a sequential relationship with outcomes on Kaplan–Meier analysis. Conclusion: Concurrent SRS‐IT has favourable clinical and radiological outcomes with respect to CR, PR and a reduced likelihood of PD. Changes in BM volume on the initial MRI 3 months after SRS were predictive of long‐term outcomes for treatment response. [ABSTRACT FROM AUTHOR]

Summary: There is a growing body of literature supporting the use of stereotactic ablative body radiotherapy (SABR) in the management of primary hepatocellular carcinoma (HCC). This systematic review and meta‐analysis of the current published evidence for SABR for HCC assessed the impact of treatment dose, fractionation and tumour size on the outcomes of local control (LC), overall survival (OS) and toxicity. A systematic search was independently performed by two authors for articles published in peer‐reviewed journals between January 2005 and December 2019. A DerSimonian and Laird random effects model was used to assess pooled results. A multivariate meta‐regression analysis incorporated the effect of explanatory variables (radiation dose in EQD2[10], fractionation and tumour size) on outcomes of OS, LC and toxicity. Forty‐nine cohorts involving 2846 HCC patients with 3088 lesions treated with SABR were included. Pooled 1‐, 2‐ and 3‐year LC rates were 91.1% (95% confidence interval [CI] 88.3–93.2), 86.7% (95% CI 82.7–89.8) and 84.2% (95% CI 77.9–88.9) respectively. Pooled 1‐, 2‐ and 3‐year OS rates were 78.4% (95% CI 73.4–82.6), 61.3% (55.2–66.9) and 48.3% (95% CI 39.0–57). Population‐weighted median grade 3 toxicity rates were 6.5% (IQR 3.2–16) and mean grade 4/5 rates were 1.4% (IQR 0–2.1). Within EQD2[10] ranges of 40 to 83.33 Gy corresponding to common dose‐fractionation regimens of 30–50 Gy in 5 fractions, there was a multivariate association between superior LC and OS with increasing EQD2[10], with a proportionately smaller increase in grade 3 toxicity and no association with grade 4/5 toxicity. Stereotactic ablative body radiotherapy is a viable treatment option for HCC with high LC rates and low rates of reported grade 3/4 toxicity. Increasing EQD2[10] was associated with improvements in LC and OS with a comparatively smaller increase in toxicity. Prospective randomised trials are warranted to define optimal patient selection and dose‐fractionation regimens. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the third most common cause of cancer‐related death. Long‐term prognosis remains poor with treatment options frequently limited by advanced tumor stage, tumor location, or underlying liver dysfunction. Stereotactic ablative body radiotherapy (SABR) utilizes technological advances to deliver highly precise, tumoricidal doses of radiation. There is an emerging body of literature on SABR in HCC demonstrating high rates of local control in the order of 80–90% at 3 years. SABR is associated with a low risk of radiation‐induced liver disease or decompensation in appropriately selected HCC patients with compensated liver function and is now being incorporated into guidelines as an additional treatment option. This review outlines the emerging role of SABR in the multidisciplinary management of HCC and summarizes the current evidence for its use as an alternative ablative option for early‐stage disease, as a bridge to transplant, and as palliation for advanced‐stage disease. We outline specific considerations regarding patient selection, toxicities, and response assessment. Finally, we compare current international guidelines and recommendations for the use of SABR and summarize ongoing studies. [ABSTRACT FROM AUTHOR]

Introduction: Inaccuracies in prostate apex contour delineation based on simulation computed tomography (CT) imaging can impact treatment outcomes and toxicity profiles for prostate cancer radiotherapy. Transperineal ultrasound (TPUS) is a non-invasive imaging modality that can improve delineation of prostate volumes. We performed a pilot analysis to assess for differences in anatomical position between conventional CT and a TPUS delineated prostate apex and determined whether these translated into a clinically significant difference in apical point dose.Methods: A 2D 5 MHz TPUS autoscan image guidance system was utilised during definitive intensity-modulated radiotherapy (IMRT) for prostate cancer. Distances were measured from a fixed reference point to prostate apex on both US and CT in the mid-sagittal plane. Differences between groups were assessed using the Wilcoxon sign rank test with a two-tailed significance of α = 0.05.Results: Fifty-nine consecutive patients were independently assessed. There was strong evidence of a difference between CT and TPUS delineated apex position (P = 0.0075). Median apex position was 3.6 mm caudal on TPUS vs. CT imaging (95% CI: 2.5-4.8 mm). There was strong evidence of a difference in point dose between CT and TPUS delineated apex (P = 0.0029). Median point dose at the TPUS contoured apex was 1.9 Gy lower than CT (95% CI: 0.7-3.1 Gy) corresponding to 98% of prescribed dose.Conclusions: This study demonstrates a difference in anatomical delineation of prostate apex position between CT imaging compared to TPUS, corresponding to a statistically significant difference in apex point dose. Further analysis will determine whether this translates to a clinically significant difference in outcomes. [ABSTRACT FROM AUTHOR]

Background: Studies suggest that combining radiotherapy (RT) with programmed cell death protein 1 (PD‐1) blockade may elicit a synergistic antitumor response. We aimed to assess whether prior or concurrent RT was associated with improved disease control in patients with metastatic non–small cell lung cancer (NSCLC) treated with nivolumab. Methods: We conducted a retrospective study of patients receiving nivolumab as second or subsequent line therapy for metastatic NSCLC. Patients were categorized into those who received any RT for NSCLC prior to or during nivolumab therapy, and those with no history of RT for NSCLC. Results: A total of 85 patients received nivolumab between July 2015 and December 2016 and were followed up for a median of 15 months. Sixty‐five patients (76.4%) received RT prior to or during nivolumab and 20 patients (23.6%) received nivolumab alone. Baseline characteristics of age, performance status, histology, smoking status and previous therapy were similar between the two groups. Prior or concurrent RT was associated with a superior PFS, median 2.8 months with RT versus 1.3 months without RT (Hazard Ratio (HR) = 0.494; 95% Confidence Interval (CI), 0.279–0.873; P = 0.02). The median OS of the group receiving RT was 6.4 months versus 4.2 months for the no RT group (P = 0.20). RT was not associated with an increase in toxicity. Conclusion: RT prior to or concurrent with nivolumab for metastatic NSCLC was associated with a modest improvement in PFS over nivolumab alone with no evidence of increase in adverse effects. RT may potentiate the effect of anti–PD‐1 immunotherapy in NSCLC. [ABSTRACT FROM AUTHOR]

Sarcoma spinal metastases (SSM) are particularly difficult to manage given their poor response rates to chemotherapy and inherent radioresistance. We evaluated outcomes in a cohort of patients with SSM uniformly treated using single-fraction simultaneous-integrated-boost (SIB) spine stereotactic radiosurgery (SSRS). A retrospective review was conducted at a single tertiary institution treated with SSRS for SSM between April 2007-April 2023. 16–24 Gy was delivered to the GTV and 16 Gy uniformly to the CTV. Kaplan-Meier analysis was conducted to assess time to progression of disease (PD) with proportionate hazards modelling used to determine hazard ratios (HR) and respective 95 % confidence intervals (CI). 70 patients with 100 lesions underwent SSRS for SSM. Median follow-up was 19.3 months (IQR 7.7–27.8). Median age was 55 years (IQR42-63). Median GTV and CTVs were 14.5 cm3 (IQR 5–32) and 52.7 cm3 (IQR 29.5–87.5) respectively. Median GTV prescription dose and biologically equivalent dose (BED) [α/β = 10] was 24 Gy and 81.6 Gy respectively. 85 lesions received 24 Gy to the GTV. 27 % of patients had Bilsky 1b or greater disease. 16 of 100 lesions recurred representing a crude local failure rate of 16 % with a median time to failure of 10.4 months (IQR 5.7–18) in cases which failed locally. 1-year actuarial local control (LC) was 89 %. Median overall survival (OS) was 15.3 months (IQR 7.7–25) from SSRS. Every 1 Gy increase in GTV absolute minimum dose (DMin) across the range (5.8–25 Gy) was associated with a reduced risk of local failure (HR = 0.871 [95 % CI 0.782–0.97], p = 0.009). 9 % of patients developed vertebral compression fractures at a median of 13 months post SSRS (IQR 7–25). This study represents one of the most homogenously treated and the largest cohorts of patients with SSM treated with single-fraction SSRS. Despite inherent radioresistance, SSRS confers durable and high rates of local control in SSM without unexpected long-term toxicity rates. [ABSTRACT FROM AUTHOR]

Background Re-irradiation may be considered for select patients with recurrent high-grade glioma. Treatment techniques include conformal radiotherapy employing conventional fractionation, hypofractionated stereotactic radiotherapy (FSRT), and single-fraction stereotactic radiosurgery (SRS). Methods A pooled, population-weighted, multiple linear regression analysis of publications from 1992 to 2016 was performed to evaluate the relationships between re-irradiation technique and median overall survival (OS) and radionecrosis outcomes. Results Seventy published articles were analyzed, yielding a total of 3302 patients. Across all studies, initial treatment was external beam radiotherapy to a median dose of 60 Gy in 30 fractions, with or without concurrent chemotherapy. On multivariate analysis, there was a significant correlation between OS and radiotherapy technique after adjusting for age, re-irradiation biologically equivalent dose (EQD2), interval between initial and repeat radiotherapy, and treatment volume (P <.0001). Adjusted mean OS was 12.2 months (95% CI, 11.8–12.5) after SRS, 10.1 months (95% CI, 9.7–10.5) after FSRT, and 8.9 months (95% CI, 8.4–9.4) after conventional fractionation. There was also a significant association between radionecrosis and treatment technique after adjusting for age, re-irradiation EQD2, interval, and volume (P <.0001). Radionecrosis rate was 7.1% (95% CI, 6.6–7.7) after FSRT, 6.1% (95% CI, 5.6–6.6) after SRS, and 1.1% (95% CI, 0.5–1.7) after conventional fractionation. Conclusions The published literature suggests that OS is highest after re-irradiation using SRS, followed by FSRT and conventionally fractionated radiotherapy. Whether this represents superiority of the treatment technique or an uncontrolled selection bias is uncertain. The risk of radionecrosis was low for all modalities overall. Re-irradiation is a feasible option in appropriately selected patients. [ABSTRACT FROM AUTHOR]

Purpose: This cross-sectional study used transmission-mode ultrasound to evaluate dynamic tendon properties during walking in surgically repaired and contralateral Achilles tendon (AT), with a median (range) post-operative period of 22 (4-58) months. It was hypothesised that the axial transmission speed of ultrasound (TSOU) during walking would be slower, indicating lower material stiffness in repaired compared with contralateral AT.Methods: Ten patients [median (range) age 47 (37-69) years; height 180 (170-189) cm; weight 93 (62-119) kg], who had undergone open surgical repair of the AT and were clinically recovered according to their treating clinicians, walked barefoot on a treadmill at self-selected speed (1.0 ± 0.2 m/s). Synchronous measures of TSOU, sagittal ankle motion, vertical ground reaction force (GRF), and spatiotemporal gait parameters were recorded during 20 s of steady-state walking. Paired t tests were used to evaluate potential between-limb differences in TSOU, GRF, ankle motion, and spatiotemporal gait parameters.Results: TSOU was significantly lower (≈175 m/s) in the repaired than in the contralateral AT over the entire gait cycle (P < 0.05). Sagittal ankle motion was significantly greater (≈3°) in the repaired than in the contralateral limb (P = 0.036). There were no significant differences in GRF or spatiotemporal parameters between limbs.Conclusions: Repaired AT was characterised by a lower TSOU, reflecting a lower material stiffness in the repaired tendon than in the contralateral tendon. A lower material stiffness may underpin greater ankle joint motion of the repaired limb during walking and long-term deficits in the muscle-tendon unit reported with AT repair. Treatment and rehabilitation approaches that focus on increasing the material stiffness of the repaired AT may be clinically beneficial. Transmission-mode ultrasound would seem useful for quantifying tendon properties post AT rupture repair and may have the potential to individually guide rehabilitation programmes, thereby aiding safer return to physical activity.Level Of Evidence: II. [ABSTRACT FROM AUTHOR]

Background and Aims Current tools for risk stratification of chronic liver disease subjects are limited. We aimed to determine whether the serum-based ELF (Enhanced Liver Fibrosis) test predicted liver-related clinical outcomes, or progression to advanced liver disease, and to compare the performance of ELF to liver biopsy and non-invasive algorithms. Methods Three hundred patients with ELF scores assayed at the time of liver biopsy were followed up (median 6.1 years) for liver-related clinical outcomes ( n = 16) and clear evidence of progression to advanced fibrosis ( n = 18), by review of medical records and clinical data. Results Fourteen of 73 (19.2%) patients with ELF score indicative of advanced fibrosis (≥9.8, the manufacturer's cut-off) had a liver-related clinical outcome, compared to only two of 227 (<1%) patients with ELF score <9.8. In contrast, the simple scores APRI and FIB-4 would only have predicted subsequent decompensation in six and four patients respectively. A unit increase in ELF score was associated with a 2.53-fold increased risk of a liver-related event (adjusted for age and stage of fibrosis). In patients without advanced fibrosis on biopsy at recruitment, 55% (10/18) with an ELF score ≥9.8 showed clear evidence of progression to advanced fibrosis (after an average 6 years), whereas only 3.5% of those with an ELF score <9.8 (8/207) progressed (average 14 years). In these subjects, a unit increase in ELF score was associated with a 4.34-fold increased risk of progression. Conclusions The ELF score is a valuable tool for risk stratification of patients with chronic liver disease. [ABSTRACT FROM AUTHOR]

Hypofractionated stereotactic radiotherapy is a treatment option for large vestibular schwannomas supported by an increasing evidence. A single institution retrospective review of large (>3.5cc) vestibular schwannomas treated with hypofractionated stereotactic radiotherapy and singlesession radiosurgery was conducted. Using serial follow up scans, a volumetric analysis of tumor volume change over time was performed. Vestibular schwannomas treated with hypofractionated stereotactic radiotherapy appeared to reduce in volume significantly faster than those treated with single-session radiosurgery. Cystic lesions reduced in volume faster than solid lesions. There was no significant difference in the rates of radiological and symptomatic oedema, nor subsequent dexamethasone requirement between the two treatment modalities. [ABSTRACT FROM AUTHOR]

ABSTRACT: Bone fracture healing is sensitive to the fixation stability. However, it is unclear which phases of healing are mechano‐sensitive and if mechanical stimulation is required throughout repair. In this study, a novel bone defect model, which isolates an experimental fracture from functional loading, was applied in sheep to investigate if stimulation limited to the early proliferative phase is sufficient for bone healing. An active fixator controlled motion in the fracture. Animals of the control group were unstimulated. In the physiological‐like group, 1 mm axial compressive movements were applied between day 5 and 21, thereafter the movements were decreased in weekly increments and stopped after 6 weeks. In the early stimulatory group, the movements were stopped after 3 weeks. The experimental fractures were evaluated with mechanical and micro‐computed tomography methods after 9 weeks healing. The callus strength of the stimulated fractures (physiological‐like and early stimulatory) was greater than the unstimulated control group. The control group was characterized by minimal external callus formation and a lack of bone bridging at 9 weeks. In contrast, the stimulated groups exhibited advanced healing with solid bone formation across the defect. This was confirmed quantitatively by a lower bone volume in the control group compared to the stimulated groups.The novel experimental model permits the application of a well‐defined load history to an experimental bone fracture. The poor healing observed in the control group is consistent with under‐stimulation. This study has shown early mechanical stimulation only is sufficient for a timely healing outcome. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1790–1796, 2018. [ABSTRACT FROM AUTHOR]