Radio-opaque contrast agents for liver cancer targeting with KIM during radiation therapy (ROCK-RT): an observational feasibility study.

BACKGROUND: This observational study aims to establish the feasibility of using x-ray images of radio-opaque chemoembolisation deposits in patients as a method for real-time image-guided radiation therapy of hepatocellular carcinoma. METHODS: This study will recruit 50 hepatocellular carcinoma patients who have had or will have stereotactic ablative radiation therapy and have had transarterial chemoembolisation with a radio-opaque agent. X-ray and computed tomography images of the patients will be analysed retrospectively. Additionally, a deep learning method for real-time motion tracking will be developed. We hypothesise that: (i) deep learning software can be developed that will successfully track the contrast agent mass on two thirds of cone beam computed tomography (CBCT) projection and intra-treatment images (ii), the mean and standard deviation (mm) difference in the location of the mass between ground truth and deep learning detection are ≤ 2 mm and ≤ 3 mm respectively and (iii) statistical modelling of study data will predict tracking success in 85% of trial participants. DISCUSSION: Developing a real-time tracking method will enable increased targeting accuracy, without the need for additional invasive procedures to implant fiducial markers. TRIAL REGISTRATION: Registered to ClinicalTrials.gov (NCT05169177) 12th October 2021.

Stereotactic Ablative Radiation Therapy (SABR) for Adolescent and Young Adult Malignancies.

BACKGROUND: There are limited studies examining local control (LC) and overall survival (OS) following stereotactic ablative radiation therapy (SABR) for adolescent and young adult (AYA) populations/histologies with local recurrences or metastatic disease. METHODS: The RSSearch® Patient Registry, an international SABR registry, was evaluated for AYA patients treated with SABR. AYA patients with adult histologies/primaries were excluded. Kaplan-Meier analyses were employed to characterize LC and OS following SABR. Potential prognostic factors were assessed with log-rank tests for initial univariate analysis (UVA). For multivariate analyses (MVA), a Cox proportional hazards multivariate model was utilized. RESULTS: A total of 19 AYA patients with 39 lesions treated with SABR were identified and included in the analysis. Four lesions (10.3%) were treated with SABR for primary tumor recurrence and 35 lesions were treated for metastatic disease. The median patient age was 34 years (range: 16-39 years). Common lesion locations included lung (11 lesions; 28.2%), non-spinal bone (nine lesions; 23.1%), and spine (six lesions; 15.4%). The median biological effective dose (BED10) was 61.5 Gy (range: 26.4-180). One-year LC and OS following SABR were 77.7% (95% CI: 58.5-88.7) and 72.7% (95% CI: 46.3-87.6), respectively. On UVA, BED10 ≥ 60 Gy was associated with superior one-year LC (94.4% vs. 47.6%; p<0.0001) as were sarcoma primaries (two-year LC: 92.3% vs. 42.2%;p = 0.0002). Central nervous system (CNS) primaries had significantly poorer one-year LC (20% vs 87.5%; p<0.0001) as well as spinal metastases (33.3% vs. 87.0%; p<0.0001). On MVA, BED10 < 60 Gy was associated with inferior LC (hazard ratio (HR) = 5.51;p = 0.01) with sarcoma primaries associated with superior LC (HR = 0.04;p = 0.008). CONCLUSION: SABR with BED10 ≥ 60 Gy resulted in durable LC for AYA patients, particularly those with sarcoma primaries, though poor outcomes were noted in metastatic CNS malignancies.

Oligometastatic sarcoma treated with Curative intent Ablative Radiotherapy (OSCAR): A multicenter study on behalf of AIRO (Italian association of Radiotherapy and clinical Oncology).

BACKGROUND AND PURPOSE: Stereotactic Ablative Radiotherapy (SABR) is emerging as a valid alternative to surgery in the oligometastatic setting in soft tissue sarcomas (STS), although robust data are lacking. The aim of this study is to evaluate toxicity and efficacy of SABR in oligometastatic STS. MATERIALS AND METHODS: This is a retrospective multicenter study including adult patients affected by stage IV STS, treated with SABR for a maximum of 5 cranial or extracranial metastases in up to 3 different organs. SABR was delivered with ablative purposes. Study endpoints were overall survival (OS), local control (LC), distant progression free survival (DPFS), time to polymetastatic progression (TTPP), time to new systemic therapy (TTNS) and toxicity. RESULTS: From 10 Italian RT centers, 138 patients (202 metastases) treated between 2010 and 2022 were enrolled in the study. Treatment was generally well tolerated, no acute or late toxicity ≥ G3 was recorded. Median follow up was 42.5 months. Median OS was 39.7 months. Actuarial OS at 1 and 2 years was 91.5 % and 72.7 %. Actuarial LC at 1 and 2 years was 94.8 % and 88.0 %. Median DPFS was 9.7 months. Actuarial DPFS at 1 and 2 years was 40.8 % and 19.4 %. CONCLUSION: SABR is a safe and effective approach for the treatment of oligometastatic sarcoma. One out of 5 patients is free of progression at 2-years.

Definitive Stereotactic Body Radiation Therapy in Early-Stage Solitary Hepatocellular Carcinoma: An Australian Multi-Institutional Review of Outcomes.

AIMS: 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. MATERIALS AND METHODS: 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. RESULTS: 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%). CONCLUSION: 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.

A competing risk analysis of the patterns and risk factors of recurrence in early-stage non-small cell lung cancer treated with stereotactic ablative radiotherapy.

INTRODUCTION: To assess patterns of recurrence after stereotactic ablative radiotherapy (SABR) in patient ineligible to surgery with early-stage non-small cell lung cancer (ES-NSCLC), report survival and treatment after first recurrence. METHODS: We performed a retrospective analysis on 1068 patients with ES-NSCLC and 1143 lesions. Between group differences were estimated using competing risk analysis and cause-specific hazard ratios were calculated. Overall survival (OS) after first recurrence was calculated. RESULTS: Median follow-up was 37.6 months. Univariate analysis demonstrated that ultra-central location was associated with higher risk of regional recurrence (RR) and distant metastasis (DM) (p = 0.004 and 0.01). Central lesions were associated with higher risk of local recurrence (LR) and RR (p < 0.001). Ultra-central lesions were associated with shorter OS (p = 0.002) compared to peripheral lesions. In multivariate analysis, central location was the only factor associated with increased LR and RR risks (p = 0.016 and 0.005). Median OS after first recurrence was 14.8 months. There was no difference in OS after first recurrence between ultra-central, central, and peripheral lesions (p = 0.83). Patients who received a second SABR course had an OS of 51.3 months, compared to 19.5 months with systemic therapy and 8.1 months with supportive care (p < 0.0001). DISCUSSION: The main prognostic factor for LR and RR risks was central location. Ultra-central and central tumors might benefit from treatment intensification strategies such as dose escalation and/or addition of systemic therapy to improve radiotherapy outcomes. After a first recurrence post SABR, patients with contralateral lung recurrences and those who were eligible to receive a second course of SABR had improved OS.

Progressive resolution optimizer (PRO) predominates over photon optimizer (PO) in sparing of spinal cord for spine SABR VMAT plans.

BACKGROUND: we assessed the performance of the optimization algorithms by comparing volumetric modulated arc therapy generated by a progressive resolution optimized (VMATPRO) and photon optimizer (VMATPO) in terms of plan quality, MU reduction, sparing of the spinal cord (or cauda equina), and plan complexity. METHODS: Fifty-seven patients who received spine stereotactic ablative radiotherapy (SABR) with tumors located in the cervical, thoracic, and lumbar spine were retrospectively selected. For each patient, VMATPRO and VMATPO with two full arcs were generated with using the PRO and PO algorithms. For dosimetric evaluation, the dose-volumetric (DV) parameters of the planning target volume (PTV), organs at risk (OARs), the corresponding planning organs at risk (PRV), and 1.5-cm ring structure surrounding the PTV (Ring1.5 cm) were calculated for all VMAT plans. The total number of monitor units (MUs) and the modulation complexity score for the VMAT (MCSv) were compared. To investigate the correlations of OAR sparing to plan complexity, Pearson's and Spearman's correlation tests were conducted between the two algorithms (PO - PRO, denoted as Δ) in the DV parameters for normal tissues, total MUs, and MCSv. RESULTS: For the PTVs, Target conformity and dose homogeneity in the PTVs of VMATPRO were better than those of VMATPO with statistical significance. For the spinal cords (or cauda equine) and the corresponding PRVs, all of the DV parameters for VMATPRO were markedly lower than those for VMATPO, with statistical significance (all p < 0.0001). Among them, the difference in the maximum dose to the spinal cord between VMATPRO and VMATPO was remarkable (9.04 Gy vs. 11.08 Gy with p < 0.0001). For Ring1.5 cm, no significant difference in V115% for VMATPRO and VMATPO was observed. CONCLUSIONS: The use of VMATPRO resulted in improved coverage and uniformity of dose to the PTV, as well as OARs sparing, compared with that of VMATPO for cervical, thoracic, and lumbar spine SABR. Better dosimetric plan quality generated by the PRO algorithm was observed to result in higher total MUs and plan complexity. Therefore, careful evaluation of its deliverability should be performed with caution during the routine use of the PRO algorithm.

Patterns of utilization and clinical adoption of 0.35 Tesla MR-guided radiation therapy in the United States - Understanding the transition to adaptive, ultra-hypofractionated treatments.

Purpose/Objective: Magnetic resonance-guided radiation therapy (MRgRT) utilization is rapidly expanding worldwide, driven by advanced capabilities including continuous intrafraction visualization, automatic triggered beam delivery, and on-table adaptive replanning (oART). Our objective was to describe patterns of 0.35Tesla(T)-MRgRT (MRIdian) utilization in the United States (US) among early adopters of this novel technology. Materials/Methods: Anonymized administrative data from all US MRIdian treatment systems were extracted for patients completing treatment from 2014 to 2020. Detailed treatment information was available for all MRIdian linear accelerator (linac) systems and some cobalt systems. Results: Seventeen systems at 16 centers delivered 5736 courses and 36,389 fractions (fraction details unavailable for 1223 cobalt courses), of which 21.1% were adapted. Ultra-hypofractionation (UHfx) (1-5 fractions) was used in 70.3% of all courses. At least one adaptive fraction was used for 38.5% of courses (average 1.7 adapted fractions/course), with higher oART use in UHfx dose schedules (47.7% of courses, average 1.9 adapted fractions per course). The most commonly treated organ sites were pancreas (20.7%), liver (16.5%), prostate (12.5%), breast (11.5%), and lung (9.4%). Temporal trends show a compounded annual growth rate (CAGR) of 59.6% in treatment courses delivered, with a dramatic increase in use of UHfx to 84.9% of courses in 2020 and similar increase in use of oART to 51.0% of courses. Conclusions: This is the first comprehensive study reporting patterns of utilization among early adopters of MRIdian in the US. Intrafraction MR image-guidance, advanced motion management, and increasing adoption of adaptive radiation therapy has led to a substantial transition to ultra-hypofractionated regimens. 0.35 T-MRgRT has been predominantly used to treat abdominal and pelvic tumors with increasing use of on-table adaptive replanning, which represents a paradigm shift in radiation therapy.

Radiotherapy for Pancreatic Adenocarcinoma: Recent Developments and Advances on the Horizon.

Current indications for radiotherapy in pancreatic cancer vary by surgical resectability status of the tumor. Radiation is generally not used pre-operatively for resectable tumors, but may be given adjuvantly particularly in settings of a close or positive surgical margin. For borderline resectable tumors, pre-operative radiation has been shown to improve surgical parameters including lowering nodal positivity and positive margin rates. For locally advanced unresectable tumors, radiation can improve local control, give patients an interval off of chemotherapy and provide symptomatic relief. Multidisciplinary discussion is critical for choosing the best modality and sequencing of care for patients with pancreatic cancer. Prospective trials with appropriately chosen endpoints and meticulous radiotherapy quality assurance are needed to best define populations with pancreatic cancer most likely to benefit from radiotherapy.

Clinical adoption patterns of 0.35 Tesla MR-guided radiation therapy in Europe and Asia.

BACKGROUND: Magnetic resonance-guided radiotherapy (MRgRT) utilization is rapidly expanding, driven by advanced capabilities including better soft tissue imaging, continuous intrafraction target visualization, automatic triggered beam delivery, and the availability of on-table adaptive replanning. Our objective was to describe patterns of 0.35 Tesla (T)-MRgRT utilization in Europe and Asia among early adopters of this novel technology. METHODS: Anonymized administrative data from all 0.35T-MRgRT treatment systems in Europe and Asia were extracted for patients who completed treatment from 2015 to 2020. Detailed treatment information was analyzed for all MR-linear accelerators (linac) and -cobalt systems. RESULTS: From 2015 through the end of 2020, there were 5796 completed treatment courses delivered in 46,389 individual fractions. 23.5% of fractions were adapted. Ultra-hypofractionated (UHfx) dose schedules (1-5 fractions) were delivered for 63.5% of courses, with 57.8% of UHfx fractions adapted on-table. The most commonly treated tumor types were prostate (23.5%), liver (14.5%), lung (12.3%), pancreas (11.2%), and breast (8.0%), with increasing compound annual growth rates (CAGRs) in numbers of courses from 2015 through 2020 (pancreas: 157.1%; prostate: 120.9%; lung: 136.0%; liver: 134.2%). CONCLUSIONS: This is the first comprehensive study reporting patterns of utilization among early adopters of a 0.35T-MRgRT system in Europe and Asia. Intrafraction MR image-guidance, advanced motion management, and increasing adoption of on-table adaptive RT have accelerated a transition to UHfx regimens. MRgRT has been predominantly used to treat tumors in the upper abdomen, pelvis and lungs, and increasingly with adaptive replanning, which is a radical departure from legacy radiotherapy practices.

Limits for the therapeutic application of the analytical anisotropic algorithm in the context of ablative lung radiotherapy near the minima of lung density and tumor size.

PURPOSE: To systematically investigate the performance of the analytical anisotropic algorithm (AAA) within the extremes of small tumor volumes and near-minimum lung and tumor tissue densities in order to identify combinations of these parameters where the use of AAA could result in a therapeutically unacceptable loss of tumor coverage on an energy and fractionation-specific basis. METHODS: Clinically appropriate volumetric modulated arc therapy (VMAT) treatment plans were generated with AAA for 180 unique combinations of lung density (0.05-0.30 g/cm3 ), tumor density (0.30-1.00 g/cm3 ), tumor diameter (0.5-2.5 cm), and beam energy (6 and 10 MV) and recomputed using the AcurosXB algorithm. Regression analysis was used to identify the strongest predictors of a reduction in biologically effective dose at a clinically relevant level (100 Gy BED10) for commonly utilized 1-5 fraction treatment regimens. Measurements were performed within a phantom mimicking the lower extremes of lung and tumor densities to validate AcurosXB as the approximate ground truth within these scenarios. RESULTS: The strongest predictors of a statistically significant reduction in tumor coverage were lung density ≤0.15 g/cm3 , tumor diameter ≤10 mm, tumor density equal to 0.30 g/cm3 , and a beam energy of 10 MV. Overestimation of clinical target volume (CTV) D95% and CTV V100Gy (BED10) by AAA can exceed 30%-40% in some scenarios. Measurements supported AcurosXB as highly accurate even for these challenging scenarios. CONCLUSIONS: The accuracy of AAA rapidly diminishes near the minima of clinical lung density, particularly in combination with small tumors and when using a photon energy of 10 MV. The magnitude of the effect can be more dramatic than previously reported data suggests and could potentially compromise the ablative qualities of treatments performed within these environments, particularly with less aggressive fractionation approaches.

Propensity Score-Matched Analysis of Single Fraction Robotic Radiosurgery Versus Open Partial Nephrectomy in Renal Cell Carcinoma: Oncological Outcomes.

Introduction High-dose local stereotactic robotic radiosurgery (RRS) is a non-invasive alternative to surgery in renal masses and selected patients. We have, so far, limited its use to the elderly and patients at high risk from surgery. In this study, we matched patients with renal tumors who were treated with single fraction RRS to patients who underwent open partial nephrectomy (OPN). Methods Between January 2009 and December 2017, we included 571 consecutive patients undergoing OPN and 99 patients who underwent RRS in this retrospective analysis. Patients had to have a follow-up of at least six months and we were able to match 35 with a propensity score. Matching criteria were Eastern Cooperative Oncology Group (ECOG) status, age, clinical tumor, nodes, and metastases (TNM), and tumor diameter. Tumor response, renal function, survival, and adverse events were evaluated every three months until progression or death. Results Median age was 65 years for RRS (range 58-75) and 71 (range 56-76) for OPN (p=0.131). Median diameter of renal tumors was 2.8 cm (range 2.4-3.9) for RRS and 3.5 cm (2.8-4.5) for OPN, p=0.104. Median follow-up was 28.1 months (range 6.0-78.3 months). Local tumor control nine months after RRS and OPN was 98% (95% CI: 89-99%). Renal function remained stable with a median creatinine clearance (Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)) at baseline of 76.8mlmin/1.73m2 (range 25.3-126.3) and 70.3ml/min/1.73m2 (range 18.6-127.3) at follow-up (p=0.89). Median overall survival was not reached. No difference in overall survival (OS) was seen in RRS compared to OPN (p=0.459). Conclusions Single fraction RRS is an alternative to OPN in patients unfit for surgery. Oncological and functional results are comparable to those of OPN. Further studies are needed to determine long-term results and limits of RRS in this setting and in younger patients.

Radiotherapy-related toxicity for localized prostate cancer: meta-analysis comparing conventional or moderately hypofractionated vs. ultrahypofractionated protocols.

BACKGROUND: To compare toxicities in relation to standard radiation treatments [conventional fractionation RT (CRT) and moderate hypofractionated RT (MRT)] with ultrahypofractionated RT (URT) in the treatment of patients with localized PCa. METHODS: A searched was performed in Medline, Embase, Cochrane CENTRAL, and LILACS to January 2020 for studies comparing URT to CRT and/or MRT in relation to genitourinary (GU) and gastrointestinal (GI) toxicity in the treatment of patients with localized PCa. URT, MRT and CRT were defined as protocols delivering a daily dose of ≥5 Gy, 2.4-4.9 Gy, and <2.4 Gy per fractions regardless total dose, respectively. RESULTS: Eight studies with 2929 patients with localized PCa were included in the analysis. These eight studies did not find any difference between URT and MRT/CRT groups in relation to acute GU toxicity (21.0% × 23.8%, RD -0.04; 95% CI -0.13, 0.06; p = 0.46; I2 = 89%) and acute GI toxicity (4.9% × 6.9%, RD -0.03; 95% CI -0.07, 0.01; p = 0.21; I2 = 79%). Six studies did not find any difference between URT and MRT/CRT groups in relation to late GU toxicity (3.9% × 4.7%, RD -0.01; 95% CI -0.03, 0.00; p = 0.16; I2 = 19%) and late GI toxicity (2.1% × 3.5%, RD -0.01; 95% CI -0.03, 0.00; p = 0.05; I2 = 22%). CONCLUSION: The present study suggests that acute GU/GI and late GU/GI toxicity are similar between URT and standard protocols. More studies with longer follow-ups directed to oncology outcomes are warranted before any recommendation on this topic.

A Systematic Review of Patients' Values, Preferences, and Expectations for the Treatment of Metastatic Prostate Cancer.

CONTEXT: Advances in systemic agents have increased overall survival for men diagnosed with metastatic prostate cancer. Additional cytoreductive prostate treatments and metastasis-directed therapies are under evaluation. These confer toxicity but may offer incremental survival benefits. Thus, an understanding of patients' values and treatment preferences is important for counselling, decision-making, and guideline development. OBJECTIVE: To perform a systematic review of patients' values, preferences, and expectations regarding treatment of metastatic prostate cancer. EVIDENCE ACQUISITION: The MEDLINE, Embase, and CINAHL databases were systematically searched for qualitative and preference elucidation studies reporting on patients' preferences for treatment of metastatic prostate cancer. Certainty of evidence was assessed using Grading of Recommendation, Assessment, Development and Evaluation (GRADE) or GRADE Confidence in the Evidence from Reviews of Qualitative Research (CERQual). The protocol was registered on PROSPERO as CRD42020201420. EVIDENCE SYNTHESIS: A total of 1491 participants from 15 studies met the prespecified eligibility for inclusion. The study designs included were discrete choice experiments (n = 5), mixed methods (n = 3), and qualitative methods (n = 7). Disease states reported per study were: metastatic castration-resistant prostate cancer in nine studies (60.0%), metastatic hormone-sensitive prostate cancer in two studies (13.3%), and a mixed cohort in four studies (26.6%). In quantitative preference elicitation studies, patients consistently valued treatment effectiveness and delay in time to symptoms as the two top-ranked treatment attributes (low or very low certainty). Patients were willing to trade off treatment-related toxicity for potential oncological benefits (low certainty). In qualitative studies, thematic analysis revealed cancer progression and/or survival, pain, and fatigue as key components in treatment decisions (low or very low certainty). Patients continue to value oncological benefits in making decisions on treatments under qualitative assessment. CONCLUSIONS: There is limited understanding of how patients make treatment and trade-off decisions following a diagnosis of metastatic prostate cancer. For appropriate investment in emerging cytoreductive local tumour and metastasis-directed therapies, we should seek to better understand how this cohort weighs the oncological benefits against the risks. PATIENT SUMMARY: We looked at how men with advanced (metastatic) prostate cancer make treatment decisions. We found that little is known about patients' preferences for current and proposed new treatments. Further studies are required to understand how patients make decisions to help guide the integration of new treatments into the standard of care.

Knowing When to Use Stereotactic Ablative Radiation Therapy in Oligometastatic Cancer.

Oligometastatic patients are a heterogeneous and yet not well-defined population. The actual definition identifies as oligometastatic, patients with 1-5 metastases in 1-3 different organs. However, only a proportion of these patients are "true" oligometastatic and therefore derive some kinds of benefit from local ablative approaches like stereotactic ablative radiation therapy (SABR). Since SABR is an easily accessible, effective and well-tolerated treatment, it is widely employed in the oligometastatic scenarios, without a particular focus on selection criteria. However, it should be crucial to identify predictive and prognostic features that could be clinically implemented. Therefore, we conducted this narrative review of the available literature to summarize all clinical, radiomic, genetic and epigenetic features found to be predictive of overall survival, progression-free survival or local control of oligometastatic patients treated with SABR.

Stereotactic radioablation of ventricular arrhythmias in patients with structural heart disease - A systematic review.

BACKGROUND AND PURPOSE: Several studies have suggested stereotactic arrhythmia radioablation (STAR) as a treatment option for patients suffering from therapy-refractory ventricular tachycardia or fibrillation (VT/VF). MATERIAL AND METHODS: We performed a systematic review of human reports of STAR for structural VT/VF to assess its effectivity and safety. All identified publications were assessed for inclusion. This study adheres to the PRISMA guidelines and was registered on PROSPERO (CRD42020183044). RESULTS: Thirteen studies were included resulting in a population of 57 patients. Median age was 64 (range 34-83), 31 patients (54%) had ischemic cardiomyopathy and 50 patients (88%) had prior catheter ablation (CA) for VT/VF. A mean planned target volume of 64.4 cc (range 3.5-238) with a mean safety margin of 3.3 mm (0-5) was treated with 25 Gy. Immediately following STAR, four patients (7%) experienced an electrical storm. During a mean follow-up duration of 410 days, all patients suffering from sustained VT/VF prior to STAR (n = 55) had a reduction of their sustained VT/VF-burden after STAR, but recurrence occurred in 41 patients (75%) during follow-up. Forty-six patients (81%) had an adverse effect from therapy, but no treatment-related death occurred. Evidence of scar-formation after STAR either by imaging, invasive mapping or histopathology was found in six of nine examined patients (67%). CONCLUSION: From the still very limited experience, STAR appears effective and safe in patients with structural heart disease and therapy-refractory sustained VT/VF. It is associated with a significant short-term reduction of sustained VT/VF-burden, but recurrences are common.

Magnetic Resonance Imaging-Guided Adaptive Radiotherapy for Colorectal Liver Metastases.

Technological advances have enabled well tolerated and effective radiation treatment for small liver metastases. Stereotactic ablative radiation therapy (SABR) refers to ablative dose delivery (>100 Gy BED) in five fractions or fewer. For larger tumors, the safe delivery of SABR can be challenging due to a more limited volume of healthy normal liver parenchyma and the proximity of the tumor to radiosensitive organs such as the stomach, duodenum, and large intestine. In addition to stereotactic treatment delivery, controlling respiratory motion, the use of image guidance, adaptive planning and increasing the number of radiation fractions are sometimes necessary for the safe delivery of SABR in these situations. Magnetic Resonance (MR) image-guided adaptive radiation therapy (MRgART) is a new and rapidly evolving treatment paradigm. MR imaging before, during and after treatment delivery facilitates direct visualization of both the tumor target and the adjacent normal healthy organs as well as potential intrafraction motion. Real time MR imaging facilitates non-invasive tumor tracking and treatment gating. While daily adaptive re-planning permits treatment plans to be adjusted based on the anatomy of the day. MRgART therapy is a promising radiation technology advance that can overcome many of the challenges of liver SABR and may facilitate the safe tumor dose escalation of colorectal liver metastases.

Volumetric and dosimetric impact of MRI in delineation of gross tumor volume of non-spinal vertebral metastases treated with stereotactic ablative radiation therapy.

PURPOSE: To investigate the Gross Tumor Volumes (GTV) and its dosimetric impact of magnetic resonance imaging (MRI) assisted contouring for non-spinal metastasis treated with stereotactic ablative body radiotherapy (SABR). MATERIAL AND METHODS: Five observer contours on CT (GTVCT) and CT+MR (GTVCT+MR) were evaluated against expert team contours (GTVEC) for 14 selected cases. Dice Similarity Index (DSC) and Geographical Miss Index (GMI) quantify observer variation. We also analyze the maximum dose (Dmax) and dose received by 0.35cc (D0.35cc) of the spinal cord (SC) for GTVCT and GTVCT+MR, where optimization parameters and priorities were unchanged. Percent rank function is also evaluated for SC doses. RESULTS: The mean DSC and GMI scores for the CT-only dataset are 0.6974 and 0.2851 and for CT+MR dataset is 0.7764 and 0.1907 respectively. Statistically, significant results were found for mean GTV volumes between GTVEC versus GTVCT and GTVCT versus GTVCT+MR (P<0.001). Dosimetric analysis of Dmax and D0.35cc exceeded 84.2% and 88.5% of times its respective threshold doses for CT-only dataset, whereas for the CT+MR dataset, it exceeded only by 18% and 15.7% times. 'Percent rank' function analysis for SC doses also indicates the same. CONCLUSION: This study supports MRI fusion for GTV and OAR delineation for non-spinal metastasis. Our study showed that the dosimetric analysis is vital for observer variation studies and the addition of the MR data set is significant to improve the confidence of Stereotactic treatments.

The role of immunotherapy in combination with oligometastasis-directed therapy: a narrative review.

Metastatic disease is a significant cause of morbidity and mortality among patients with cancer. Patients with oligometastatic cancer represent a subset of the metastatic population with a limited amount of disease that has metastasized distantly and progresses at a slow pace and thus has the potential to be cured with metastasis-directed local therapy. Recent studies examining the role of metastasis-directed therapy in patients with oligometastatic disease have primarily focused upon treatment with ablative doses of radiation, commonly referred to as stereotactic body radiation therapy (SBRT). While the use of SBRT to treat oligometastases has increased considerably in recent years, the benefit of this approach has yet to be confirmed in phase III randomized controlled trials; moreover, distant failure remains a significant problem in patients with oligometastatic disease treated with SBRT. Given the propensity for distant failure in patients with oligometastatic disease treated with SBRT, there is growing interest in the utility of combining SBRT with systemic agents such as immunotherapy. Immunotherapy, and specifically immune checkpoint blockade (ICB), represents a rapidly evolving systemic therapy option with a growing number of indications among patients with metastatic disease; however, despite its promise, only a minority of patients respond to ICB and among those who do, the majority eventually progress. SBRT and ICB are both dependent upon, and have the ability to shift, the balance between antitumor immune surveillance and immunosuppressive states in the tumor and tumor microenvironment. As a result, it has been speculated that SBRT and ICB have the potential to act synergistically when used in combination. SBRT has been demonstrated to be safe in combination with ICB in studies with short-term follow-up and although additional research is needed, preliminary prospective data support the potential efficacy of this approach. In addition to confirming the safety and efficacy of SBRT in combination with immunotherapy, further studies are needed to determine how to maximize the therapeutic ratio of this treatment paradigm for the full potential of immunotherapy in the oligometastatic population to be realized.

Predicting pathological complete response (pCR) after stereotactic ablative radiation therapy (SABR) of lung cancer using quantitative dynamic [18F]FDG PET and CT perfusion: a prospective exploratory clinical study.

BACKGROUND: Stereotactic ablative radiation therapy (SABR) is effective in treating inoperable stage I non-small cell lung cancer (NSCLC), but imaging assessment of response after SABR is difficult. This prospective study aimed to develop a predictive model for true pathologic complete response (pCR) to SABR using imaging-based biomarkers from dynamic [18F]FDG-PET and CT Perfusion (CTP). METHODS: Twenty-six patients with early-stage NSCLC treated with SABR followed by surgical resection were included, as a pre-specified secondary analysis of a larger study. Dynamic [18F]FDG-PET and CTP were performed pre-SABR and 8-week post. Dynamic [18F]FDG-PET provided maximum and mean standardized uptake value (SUV) and kinetic parameters estimated using a previously developed flow-modified two-tissue compartment model while CTP measured blood flow, blood volume and vessel permeability surface product. Recursive partitioning analysis (RPA) was used to establish a predictive model with the measured PET and CTP imaging biomarkers for predicting pCR. The model was compared to current RECIST (Response Evaluation Criteria in Solid Tumours version 1.1) and PERCIST (PET Response Criteria in Solid Tumours version 1.0) criteria. RESULTS: RPA identified three response groups based on tumour blood volume before SABR (BVpre-SABR) and change in SUVmax (ΔSUVmax), the thresholds being BVpre-SABR = 9.3 mL/100 g and ΔSUVmax = - 48.9%. The highest true pCR rate of 92% was observed in the group with BVpre-SABR < 9.3 mL/100 g and ΔSUVmax < - 48.9% after SABR while the worst was observed in the group with BVpre-SABR ≥ 9.3 mL/100 g (0%). RPA model achieved excellent pCR prediction (Concordance: 0.92; P = 0.03). RECIST and PERCIST showed poor pCR prediction (Concordance: 0.54 and 0.58, respectively). CONCLUSIONS: In this study, we developed a predictive model based on dynamic [18F]FDG-PET and CT Perfusion imaging that was significantly better than RECIST and PERCIST criteria to predict pCR of NSCLC to SABR. The model used BVpre-SABR and ΔSUVmax which correlates to tumour microvessel density and cell proliferation, respectively and warrants validation with larger sample size studies. TRIAL REGISTRATION: MISSILE-NSCLC, NCT02136355 (ClinicalTrials.gov). Registered May 8, 2014, https://clinicaltrials.gov/ct2/show/NCT02136355.

The Potential Role of Intensity-Modulated Proton Therapy in Hepatic Carcinoma in Mitigating the Risk of Dose De-Escalation.

PURPOSE: To investigate the role of intensity-modulated proton therapy (IMPT) for hepatocellular carcinoma (HCC) patients to be treated with stereotactic body radiation therapy (SBRT) in a risk-adapted dose prescription regimen. METHODS: A cohort of 30 patients was retrospectively selected as "at-risk" of dose de-escalation due to the proximity of the target volumes to dose-limiting healthy structures. IMPT plans were compared to volumetric modulated arc therapy (VMAT) RapidArc (RA) plans. The maximum dose prescription foreseen was 75 Gy in 3 fractions. The dosimetric analysis was performed on several quantitative metrics on the target volumes and organs at risk to identify the relative improvement of IMPT over VMAT and to determine if IMPT could mitigate the need of dose reduction and quantify the consequent potential patient accrual rate for protons. RESULTS: IMPT and VMAT plans resulted in equivalent target dose distributions: both could ensure the required coverage for CTV and PTV. Systematic and significant improvements were observed with IMPT for all organs at risk and metrics. An average gain of 9.0 ± 11.6, 8.5 ± 7.7, 5.9 ± 7.1, 4.2 ± 6.4, 8.9 ± 7.1, 6.7 ± 7.5 Gy was found in the near-to-maximum doses for the ribs, chest wall, heart, duodenum, stomach and bowel bag respectively. Twenty patients violated one or more binding constraints with RA, while only 2 with IMPT. For all these patients, some dose de-intensification would have been required to respect the constraints. For photons, the maximum allowed dose ranged from 15.0 to 20.63 Gy per fraction while for the 2 proton cases it would have been 18.75 or 20.63 Gy. CONCLUSION: The results of this in-silico planning study suggests that IMPT might result in advantages compared to photon-based VMAT for HCC patients to be treated with ablative SBRT. In particular, the dosimetric characteristics of protons may avoid the need for dose de-escalation in a risk-adapted prescription regimen for those patients with lesions located in proximity of dose-limiting healthy structures. Depending on the selection thresholds, the number of patients eligible for treatment at the full dose can be significantly increased with protons.