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Objective: To evaluate the effectiveness and safety of salvage stereotactic ablative body radiotherapy (SABR) for recurrent renal cell carcinoma (RCC) after thermal ablation (TA). Materials and Methods: This study was a multi‐institutional retrospective analysis of patients with recurrent RCC following TA who received SABR between 2016 and 2020. The primary study outcome was freedom from local failure, evaluated radiographically based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. Distant failure, cancer‐specific survival (CSS), overall survival (OS), treatment‐related toxicity and renal function changes following SABR were the secondary outcomes. The Kaplan–Meier method was used to estimate freedom from local and distant failure, CSS and OS. Results: Seventeen patients with 18 biopsy‐confirmed RCCs were included, with a median (interquartile range [IQR]) age at time of SABR of 75.2 (72.6–68.7) years, a median (IQR) tumour size of 3.5 (1.9–4.1) cm and follow‐up (reverse Kaplan–Meier method) of 3.36 (95% confidence interval [CI] 1.6–4.1) years. Six of the 17 patients had a solitary kidney. Five patients had failed repeat TA prior to SABR. The median (IQR) time from TA procedure to SABR was 3.03 (1.5–5.1) years. No patient experienced local progression, with a local control rate of 100%. Four patients, two with baseline metastatic disease, experienced distant progression. The distant progression‐free survival, CSS and OS at 3 years were 72.1% (95% CI 51.9%–100%), 92.3% (95% CI 78.9%–100%) and 82.1% (95% CI 62.1%–100%), respectively. The median (IQR) glomerular filtration rate before SABR was 58 (40–71) mL/min, and at last follow‐up, it was 48 (33–57) mL/min. No patient experienced grade 3+ toxicity or went on to develop end‐stage renal disease. Conclusion: The results showed that SABR appears to be an effective and safe salvage strategy in patients with recurrent RCC following TA. [ABSTRACT FROM AUTHOR]

Background: stereotactic ablative body radiotherapy (SABR) is a disruptive radiation therapy technique which is increasingly used for the treatment of urologic cancers. The aim of this narrative review is to provide an overview on the current landscape of SABR in urologic cancers and highlight advancements on the horizon. Methods: a narrative review of the contemporary role of SABR in urologic cancers is conducted. Results: in localised prostate cancer, SABR boasts excellent tumour control and biochemical control, with acceptable GU and GI toxicity. Its comparison to laparoscopic radical prostatectomy is currently ongoing. SABR appears to be practical for metastasis-directed therapy in metastatic prostate cancer, with good local control and a low toxicity profile, either alone or in combination with ADT. In localised RCC, SABR offers adequate local control with a modest impact on renal function in patients unfit for surgical management. Its role in metastatic RCC is much more established, where it has been shown to be superior to conventional radiotherapy. Emerging evidence suggests that SABR has a role in delaying systemic therapy whilst maintaining QOL and overall survival. Intriguingly, in metastatic prostate cancer and metastatic RCC, SABR results in a cytoreductive and immunomodulatory 'abscopal effect', a focus of current investigations. Conclusions: SABR has emerged as a safe, effective, and feasible treatment for urologic cancers. Urologists should be aware of its increasing use in localised prostate cancer and metastatic RCC, with good oncological outcomes combined with acceptable toxicity. In addition, SABR holds promise for both metastatic prostate cancer and localised RCC treatment in terms of toxicity and oncological outcomes. [ABSTRACT FROM AUTHOR]

Background: Stereotactic ablative radiotherapy (SABR) is thought to activate T cell responses in patients with cancer, leading to its combination with immunotherapy and chemotherapy for treatment of non-small-cell lung cancer (NSCLC). Here, we aimed to provide a high-resolution transcriptomic profiling of the systemic T cell response following SABR, with or without preceding immunotherapy/chemotherapy. Methods: We conducted single-cell RNA and T cell receptor (TCR) sequencing of T cells from peripheral blood of seven patients with early-stage NSCLC taken pre- and post-SABR without or with prior immunotherapy and chemotherapy (icSABR). Other flow cytometry, single-cell RNA-seq data and bulk RNA-seq data were used to validate the results. Results: We uncovered distinct T cell response patterns induced by these treatments: while terminal effector CD8+ T cells showed increased cytotoxic and inhibitory scores, and upregulated immune-activated pathways post-SABR, the reverse responses occurred post-icSABR. Furthermore, the proportion of large T cell clones increased and single clone decreased post-SABR, while the opposite was seen post-icSABR. Of note, both SABR and icSABR largely changed TCR clonotypes, which were mainly large clones post-SABR but single clone post-icSABR, and predominantly from terminal effector CD8+ T cells and T helper cells, respectively. Conclusions: These findings reveal a complex interplay between SABR and immunotherapy, with potentially valuable implications for treatment strategies involving SABR and immunotherapy to induce systemic T cell responses for tumor eradication in patients with NSCLC. [ABSTRACT FROM AUTHOR]

Metastatic renal cell carcinoma (RCC) can present with oligometastatic disease and/or develop oligoprogression following systemic therapy. Cytoreductive and focal metastasis-directed therapy options include resection, stereotactic ablative radiation and thermal ablation. Aggressive focal therapy may allow delay in initiation of or modification to systemic therapy and improve clinical outcomes. In this narrative review we synthesize current practice guidelines and prospective data on focal therapy management options and highlight future research. Patient selection and the choice of focal treatment techniques are controversial due to limited and heterogeneous data and patients may benefit from multidisciplinary evaluation. Prospective comparative trials with clearly defined inclusion criteria and relevant end points are needed to clarify the risks and benefits of different approaches. Article highlights Evaluation Oligometastatic and oligoprogressive renal cell carcinoma (RCC) should be evaluated with contrast-enhanced body CT and brain MRI, with additional imaging based on symptoms or as needed for planning of future focal treatments. Guidelines stratify patients by International Metastatic RCC Database Consortium (IMDC) prognostic risk groups (section 4). Management While the quality of the data is mixed, there are myriad options for treating oligometastatic and oligoprogressive RCC, including active surveillance, systemic therapy, focal cytoreductive treatment of the primary and focal metastasis-directed therapy. Optimal patient selection, timing and choice of focal therapy in contemporary clinical practice remains unclear. Discussion of management options for metastasis-directed therapy including surgery, stereotactic ablative radiotherapy and thermal ablation should be discussed in a multidisciplinary setting (section 7). Follow-up after focal therapy After focal treatment of metastatic disease, current guidelines recommend CT body imaging every 1–6 months with annual history and physical for 5 years. There are no high-quality data on the benefits of systemic therapy after focal treatment of all sites of metastatic disease (section 8). Future directions Multiple ongoing trials are investigating the optimal choice, timing and combination of focal treatment techniques with immunotherapy for oligometastatic and oligoprogressive RCC (section 9). [ABSTRACT FROM AUTHOR]

Introduction: Surgical resection is gold standard for treatment of liver metastasis, locally ablative techniques including computer tomography (CT)-guided interstitial high-dose-rate (HDR) brachytherapy (CT-BRT) and stereotactic body radiotherapy (SBRT) have gained prominence as alternatives, offering comparable outcomes in selected patients. We aim to compare CT-BRT and SBRT - based on dosimetric analysis. Material and methods: Patients who underwent CT-BRT for oligometastatic, ≤4cm liver metastases between 2018 and 2024 were eligible. SBRT plans for Halcyon (SBRTh) and TrueBeam (SBRTtb) were prepared virtually. In the CT-BRT group CTV was equal to PTV, for SBRTh and SBRTtb planning, a 5 mm margin was applied to CTV to create PTV. Dose calculation was carried out with the TG-43 algorithm for CT-BRT and Anisotropic Analytical Algorithm for SBRTh and SBRTtb group. Descriptive statistics were used to compare the data. The Wilcoxon pairwise order test was utilized to compare dependent groups. Results: CT-BRT resulted in a more favorable dose distribution within PTVs for Dmean, D50, and D90, while SBRT showed better results for D98 and V27.5Gy. No significant differences were observed for V25Gy between CT-BRT and SBRTtb, but SBRTh favored over CT-BRT. For OARs, CT-BRT plans showed better values for V5, V10, and V11.6Gy in the uninvolved liver volume. There were no significant differences in dose distribution for the duodenum, bowel, and heart. SBRT modalities performed better in the kidney. CT-BRT had improved dose distribution in the esophagus, great vessels, ribs, skin, spinal cord, and stomach compared to SBRT. Conclusions: CT-BRT could be a viable alternative to SBRT for certain patients with liver malignancies. [ABSTRACT FROM AUTHOR]

Both spine and nonspine bone metastases are frequent sites of spread from solid organ malignancies. As bone metastases frequently cause significant morbidity for patients, it is critical to offer a treatment that can achieve rapid and durable symptomatic relief and local control, without being associated with serious risks of toxicity. Conventional palliative radiation therapy has a key treatment component in the multidisciplinary management of these patients; however, over the past decade, it has evolved to routinely deliver high biologically effective doses with precision in the form of stereotactic body radiation therapy. This change in paradigm is a result of the shifting landscape in cancer care, such that short-term pain relief is no longer the sole therapeutic aim for selected patients, and durable symptom relief and local tumor control are the goals. This review discusses the randomized prospective evidence, ongoing trials, approach to surveillance imaging, and treatment delivery for stereotactic body radiation therapy, to both spine and nonspine bone metastases, with a specific section on sacral metastases. [ABSTRACT FROM AUTHOR]

Breast cancer commonly metastasises to the skeleton, and stereotactic ablative body radiation therapy (SABR) is an emerging treatment for oligometastatic disease. Accurately imaging bone metastases and their response to treatment is challenging. [18F]NaF-PET has a higher sensitivity and specificity than conventional bone scans for detecting breast cancer bone metastases. In this pre-defined secondary analysis of a prospective trial, we evaluated the change in [18F]NaF uptake after SABR. Patients with oligometastatic breast cancer received a single fraction of 20 Gy to up to three bone metastases. [18F]NaF-PET was acquired before and 12 months after SABR. Pre- and post-treatment [18F] NaF-PET images were registered to the treatment planning CT. The relative change in tumour SUVmax and SUVmean was quantified. The intersection of each of the radiation therapy isodose contours with a non-tumour bone was created. The change in SUVmean in sub-volumes of non-tumour bone receiving doses of 0-20 Gy was quantified. In total, 14 patients, with 17 bone metastases, were available for analysis. A total of 15 metastases exhibited a reduction in SUVmax; the median reduction was 42% and the maximum reduction 82%. An increased absolute reduction in SUVmax was observed with higher pre-treatment SUVmax. One patient exhibited increased SUVmax after treatment, which was attributed to normal peri-tumoural bone regeneration in the context of a bone metastasis. There was a median reduction of 15%-34% for non-tumour bone in each dose level. [ABSTRACT FROM AUTHOR]

Purpose: Stereotactic ablative radiotherapy (SABR) for early‐stage lung cancer has shown promising results; however, regional recurrence (RR) development is not uncommon, and salvage treatment strategies have not been established. We aimed to investigate treatment patterns, prognostic factors, and survival outcomes. Materials and methods: A retrospective analysis of 391 patients who underwent SABR for primary lung cancer from 2012 to 2019 was performed. Among these patients, 90 patients showed recurrence, including local recurrence (n = 9), RR (n = 33), distant metastasis (DM) (n = 57), and RR with simultaneous DM (n = 8). The median follow‐up duration was 17.3 months. Results: The median age was 75 years, and most patients underwent primary SABR due to poor lung function (69.7%). Various salvage treatments were performed in cases of RR, including chemotherapy (n = 15), radiotherapy (n = 7), concurrent chemoradiotherapy (n = 2), and best supportive care (n = 9). The median overall survival (OS) and post‐recurrence OS (PR‐OS) were 22.9 and 11.2 months, respectively. In multivariate analysis, age ≤75 years (HR = 0.36, p = 0.040), isolated recurrence (HR = 0.34, p = 0.037), and radiotherapy without chemotherapy (HR = 0.25, p = 0.024) were significant prognostic factors for PR‐OS. Conclusions: Despite various salvage treatments, PR‐OS was less than 1 year after RR in our frail patients group who underwent primary SABR. The toxicities of salvage chemotherapy could be quite severe; thus, careful patient selection is required. Further research is needed to validate our findings. [ABSTRACT FROM AUTHOR]

Ventricular tachycardia is an irregular heartbeat conventionally treated using invasive cardiac catheter ablation and medication. However, when standard treatments have been exhausted, cardiac SABR provides a final treatment option to this high-mortality condition. Complex diagnostic mapping and planning scans enable multi-disciplinary target delineation for a 25Gy single fraction. However, organs at risk (OAR) near the target make this treatment challenging to plan and deliver. Publications from cardiologists report the efficacy of cardiac SABR, however there is limited data on the treatment delivery and image matching of this complex procedure. Four specialist therapeutic radiographers experienced in cardiac SABR reviewed 40 CBCTs from 10 patients treated in the UK. Each therapeutic radiographer conducted five image matches: a manual match (manual), an automatic match to the heart structure (auto) and the auto match followed by manual adjustment to the PTV (PTV), all using three degrees of freedom (DoF) only. The auto and PTV matches were also repeated using 6DoF. Inter-observer variability was quantified using 95% limits of agreement from a modified Bland-Altman analysis. The limits of agreement were smallest in the automatic matches suggesting the algorithm is reliable. A manual adjustment from the auto match to the PTV is clinically appropriate to optimise target coverage. The limits of agreement were smaller in the 6DoF PTV match 1.06 mm, 1.24 mm, 1.68 mm than the 3DoF PTV match 1.57 mm, 2.06 mm, 2.11 mm (lateral, vertical, longitudinal). The 6DoF CBCT image match has less variability and therefore suggest using a 6DoF couch for treatment delivery. Cardiac SABR CBCT image matching at treatment delivery is complex, optimisation of CBCT acquisition parameters and therapeutic radiographer training is essential prior to implementation. [ABSTRACT FROM AUTHOR]

Simple Summary: Stereotactic ablative radiation (SAbR) is a focused, high-dose radiation technique used to treat cancers that have spread to the adrenal glands. One of the feared consequences of this therapy is causing adrenal insufficiency in patients, which is a lack of adrenal function; however, the rates and severity at which this occurs in patients are still poorly studied. We studied patients with 66 treated adrenal glands using SAbR, which demonstrated that this technique was effective at controlling cancer sites with a control rate of 75% at 1 year. The risk of patients developing adrenal insufficiency in the entire cohort was significant at 14%, with a median time of 4.3 months. There was a higher risk in patients who had both adrenal glands treated with SAbR, or who had received a prior surgical removal of their other adrenal gland prior to SAbR therapy, with 44% of these patients developing adrenal insufficiency. Background: Adrenal metastases are often treated with stereotactic ablative radiation (SAbR). We aimed to assess the incidence, timing, and factors associated with the development of primary adrenal insufficiency (PAI) following SAbR. Methods: A retrospective cohort study comprised 66 consecutive patients (73% men, median age 61 years) who underwent SAbR for adrenal metastasis. Results: The series encompassed metastases from renal cell carcinoma (41%), lung tumors (38%), colorectal adenocarcinoma (9%), melanoma (5%), and others (7%). Median follow-up was 17 months from SAbR. Nine (14%) patients developed PAI at a median of 4.3 months (range, 0.7–20.2). The incidence of PAI was 44% in patients with prior adrenalectomy receiving unilateral SAbR, 44% with bilateral SAbR, 2% with unaffected contralateral gland, and 0% with bilateral metastases treated with unilateral SAbR. PAI was associated with prior adrenalectomy (odds ratio [OR] 32) and bilateral SAbR (OR 8.2), but not age, sex, metastasis size, or biological effective dose. Post-SAbR 6-month and 1-year local control rates were 82% and 75%, respectively. Conclusions: Patients undergoing SAbR for adrenal metastasis are at high risk of developing PAI. PAI is associated with bilateral SAbR and contralateral adrenalectomy. PAI is unlikely with a remaining unaffected adrenal gland or in the setting of bilateral adrenal metastases with unilateral SAbR. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastatic renal cell carcinoma (RCC) represents a significant challenge in oncology, and systemic therapy remains the primary treatment modality. Radiation therapy (RT) offers a non-invasive ablative approach to the management of oligometastatic disease, and the use of Stereotactic Ablative Radiotherapy (SABR) has demonstrated remarkably high disease control. Within the broad spectrum of oligometastatic disease, we evaluated the efficacy of SABR on oligorecurrent RCC systemic treatment-naïve, and we aimed to identify predictive factors for long-term disease control. We demonstrated the potential of SABR to delay the need for systemic therapy and confirmed the long-term efficacy of SABR for oligometastatic RCC patients, with a superior benefit for patients with single lung metastasis, potentially refining patient selection processes to tailor treatments. Background: Stereotactic ablative radiotherapy (SABR) is emerging as a potential local treatment option for oligometastatic RCC. This study aims to evaluate the efficacy of SABR in patients with oligorecurrent RCC. Methods: A total of 50 patients with histologically confirmed RCC underwent SABR for oligorecurrence between 2006 and 2022. Eligible patients had up to five extracranial metastases and were systemic treatment-naïve at the time of irradiation. The primary endpoints of the analysis were overall survival (OS), local control (LC), distant metastasis–free survival (DMFS), and time to systemic therapy initiation. Results: The median OS was not reached, with 1- and 3-year OS rates of 93.8% and 77.5%, respectively. LC rates at one and three years were 95.8% and 86.5%, respectively. The median time to systemic therapy initiation was 63.8 months, and the median DMFS was 17.9 months, with one- and three-year rates of 63.4% and 36.6%, respectively. Multiple metastases were a negative predictive factor for DMFS (HR 2.39, p = 0.023), whereas lung metastases were associated with a more favorable outcome (HR 0.38, p = 0.011). Conclusions: SABR offers a valuable treatment option for oligometastatic RCC, demonstrating significant potential for achieving long-term disease control and delaying the need for systemic therapy. [ABSTRACT FROM AUTHOR]

Prognosis of locally advanced pancreatic cancer (LAPC) remains poor with limited therapeutic options. Radiation therapy in pancreatic cancer has been restricted by the disease's proximity to radiosensitive organs at risk (OAR). However, stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) has demonstrated promise in delivering ablative doses safely. We sought to report clinical outcomes from a UK-based Compassionate Access Programme that provided access to SMART to patients with LAPC. This was a registry retrospective study conducted at a single centre with access to SMART. Patients with LAPC were treated with prescription dose of 40 Gy in 5 fractions. The planning objective was that 98% of PTV received ≥95% of the prescribed dose, prioritising duodenal, stomach and bowel UK SABR consortium constraints. Daily online adaptation was performed using magnetic resonance guidance and on-table re-optimisation. 0–3 months and > 3-month post-treatment-related toxicities, local progression-free survival, metastatic-free survival and overall survival were evaluated. 55 patients were treated with SMART at our institution from 2020 to 2022. Median follow-up from date of diagnosis was 17 months (range 5–37 months). Median age was 69.87% of patients underwent induction chemotherapy. 71% of patients reported 0–1 grade acute toxicity only. No grade >3 acute toxicity was reported. 5 patients (9%) reported a grade 3 toxicity (fatigue, nausea, abdominal pain, duodenal stricture). No grade >3 toxicity after 3 months was reported. 6 (10%) of patients had grade 3 toxicity (fatigue, nausea, abdominal pain, duodenal haemorrhage). Median local PFS post diagnosis was 17 months (95% CI 15.3–18.7). Median OS post diagnosis was 19 months (95% CI 15.9–22.1). One-year local control post SMART was 65%. This is the first UK-reported experience of MR-guided daily adaptive pancreatic SABR. SMART shows promise in delivering ablative doses with acceptable toxicity rates and good clinical outcomes. • No acute or late grade >3 toxicity reported. • Majority of patients (71%) experienced no or grade 1 only acute toxicity. • Acute and late G3 toxicity incidence was 9% and 10% respectively. • 65% of all patients maintained local control at 1 year post SMART. • Median OS was 21 months with chemotherapy followed by consolidatory pancreas SMART. [ABSTRACT FROM AUTHOR]

Dose-perturbation characteristics are important to consider during the calculation of radiation therapy protocols for patients who are going to receive high doses that would reach the tolerance limits of the spinal cord [1]. Several studies have investigated dose perturbations introduced by metal implants in close proximity to spine SABR treatments [2–7]. However, there is a lack of work assessing this effect using the RayStation TPS [8]. We present an initial design for a low-cost phantom to evaluate spine stereotactic ablative radiotherapy (SABR) in the presence of prosthetic vertebral stabilization. The phantom is modular, allowing the prosthetic at the centre of the phantom to be removed by exchanging the central block. It also includes space to insert ion chamber and film. The agreement of the RayStation TPS (v8.0B) collapsed cone convolution (CCC) calculation and measurement was determined for phantom versions with and without prosthetic. There was little to no change in the agreement between the measured and calculated dose when introducing metallic hardware. This suggests that our Raystation-based SABR planning approach for patients with spinal hardware meets clinical expectations. Departments without access to anthropomorphic phantoms may find this design useful but should test their phantom design in typical clinical settings to ensure it is robust to real world situations. [ABSTRACT FROM AUTHOR]

Abstract Background Limited literature exists on the feasibility and effectiveness of integrating stereotactic ablative radiotherapy (SABR) techniques with hyperfractionated regimens for patients with lung cancer. This study aims to assess whether the SABR technique with hyperfractionation can potentially reduce lung toxicity. Methods We utilized the linear‐quadratic model to find the optimal fraction to maximize the tumor biological equivalent dose (BED) to normal‐tissue BED ratio. Validation was performed by comparing the SABR plans with 50 Gy/5 fractions and hyperfractionationed plans with 88.8 Gy/74 fractions with the same tumor BED and planning criteria for 10 patients with early‐stage lung cancer. Mean lung BED, Lyman–Kutcher–Burman (LKB) normal tissue complication probability (NTCP), critical volume (CV) criteria (volume below BED of 22.92 and 25.65 Gy, and mean BED for lowest 1000 and 1500 cc) and the percentage of the lung receiving 20Gy or more (V20) were compared using the Wilcoxon signed‐rank test. Results The transition point occurs when the tumor‐to‐normal tissue ratio (TNR) of the physical dose equals the TNR of α/β in the BED dose‐volume histogram of the lung. Compared with the hypofractionated regimen, the hyperfractionated regimen is superior in the dose range above but inferior below the transition point. The hyperfractionated regimen showed a lower mean lung BED (6.40 Gy vs. 7.73 Gy) and NTCP (3.50% vs. 4.21%), with inferior results concerning CV criteria and higher V20 (7.37% vs. 7.03%) in comparison with the hypofractionated regimen (p

Abstract Background Therapeutic options for early-stage hepatocellular carcinoma (HCC) in individual patients can be limited by tumor and location, liver dysfunction and comorbidities. Many patients with early-stage HCC do not receive curative-intent therapies. Stereotactic ablative body radiotherapy (SABR) has emerged as an effective, non-invasive HCC treatment option, however, randomized evidence for SABR in the first line setting is lacking. Methods Trans-Tasman Radiation Oncology Group (TROG) 21.07 SOCRATES-HCC is a phase II, prospective, randomised trial comparing SABR to other current standard of care therapies for patients with a solitary HCC ≤ 8 cm, ineligible for surgical resection or transplantation. The study is divided into 2 cohorts. Cohort 1 will compromise 118 patients with tumors ≤ 3 cm eligible for thermal ablation randomly assigned (1:1 ratio) to thermal ablation or SABR. Cohort 2 will comprise 100 patients with tumors > 3 cm up to 8 cm in size, or tumors ≤ 3 cm ineligible for thermal ablation, randomly assigned (1:1 ratio) to SABR or best other standard of care therapy including transarterial therapies. The primary objective is to determine whether SABR results in superior freedom from local progression (FFLP) at 2 years compared to thermal ablation in cohort 1 and compared to best standard of care therapy in cohort 2. Secondary endpoints include progression free survival, overall survival, adverse events, patient reported outcomes and health economic analyses. Discussion The SOCRATES-HCC study will provide the first randomized, multicentre evaluation of the efficacy, safety and cost effectiveness of SABR versus other standard of care therapies in the first line treatment of unresectable, early-stage HCC. It is a broad, multicentre collaboration between hepatology, interventional radiology and radiation oncology groups around Australia, coordinated by TROG Cancer Research. Trial registration anzctr.org.au, ACTRN12621001444875, registered 21 October 2021.

Simple Summary: RCC has traditionally been considered radioresistant, with surgery being the gold standard for primary localized RCC. However, not all patients are suitable for surgery and percutaneous, non-surgical options are invasive, with significant limitations. SABR is a non-invasive advanced RT technique that delivers high doses accurately. Growing evidence supports SABR as a definitive alternative therapy for medically inoperable patients, those who decline surgery, are unfit for invasive ablation, or are at high-risk of requiring postoperative dialysis. SABR has shifted the renal radioresistance paradigm, widening the therapeutic window. Additionally, SABR is increasingly used for locally recurrent, oligoprogressive, and oligometastatic disease. This review aims to support the use of SABR across various stages of RCC disease and explore future directions. The overall landscape of RCC is promising, and we are confident that our update will stimulate further research in this field and contribute to the advancement of patient care. Renal cell cancer (RCC) has traditionally been considered radioresistant. Because of this, conventional radiotherapy (RT) has been predominantly relegated to the palliation of symptomatic metastatic disease. The implementation of stereotactic ablative radiotherapy (SABR) has made it possible to deliver higher ablative doses safely, shifting the renal radioresistance paradigm. SABR has increasingly been adopted into the multidisciplinary framework for the treatment of locally recurrent, oligoprogressive, and oligometastatic disease. Furthermore, there is growing evidence of SABR as a non-invasive definitive therapy in patients with primary RCC who are medically inoperable or who decline surgery, unsuited to invasive ablation (surgery or percutaneous techniques), or at high-risk of requiring post-operative dialysis. Encouraging outcomes have even been reported in cases of solitary kidney or pre-existing chronic disease (poor eGFR), with a high likelihood of preserving renal function. A review of clinical evidence supporting the use of ablative radiotherapy (SABR) in primary, recurrent, and metastatic RCC has been conducted. Given the potential immunogenic effect of the high RT doses, we also explore emerging opportunities to combine SABR with systemic treatments. In addition, we explore future directions and ongoing clinical trials in the evolving landscape of this disease. [ABSTRACT FROM AUTHOR]

Introduction: Stereotactic ablative body radiotherapy (SABR) is a highly conformal technique utilising a high dose per fraction commonly employed in the re‐treatment of spinal metastases. This study sought to determine the safety and efficacy of re‐irradiation with SABR to previously treated spinal metastases. Methods: This was a retrospective analysis of patients at three Australian centres who have undergone spinal SABR after previous spinal radiotherapy to the same or immediately adjacent vertebral level. Efficacy was determined in terms of rates of local control, while safety was characterised by rates of serious complications. Results: Thirty‐three spinal segments were evaluated from 32 patients. Median follow‐up for all patients was 2.6 years, and median overall survival was 4.3 years. Eleven of 33 (33.3%) treated spinal segments had local progression, with a local control rate at 12 months of 71.4% (95% C.I. 55.2%–92.4%). Four patients (16.7%) went on to develop cauda equina or spinal cord compression. Thirteen out of 32 patients (40.6%) experienced acute toxicity, of which 12 were grade 2 or less. Five out of 30 spinal (16.7%) segments with follow‐up imaging had a radiation‐induced vertebral compression fracture. There was one case of radiation myelitis which occurred in a patient who had mediastinal radiotherapy with a treatment field which overlapped their prior spinal radiation. Conclusion: The patients in this study experienced long median survival, durable tumour control and high rates of freedom from long‐term sequelae of treatment. These results support the use of SABR in patients who progress in the spine despite previous radiotherapy. [ABSTRACT FROM AUTHOR]

Breast conserving treatment typically involves surgical excision of tumor and adjuvant radiotherapy targeting the breast area or tumor bed. Accurately defining the tumor bed is challenging and lead to irradiation of greater volume of healthy tissues. Preoperative stereotactic body radiotherapy (SBRT) which target tumor may solves that issues. We conducted a systematic literature review to evaluates the early toxicity and cosmetic outcomes of this promising treatment approach. Secondary we reviewed pathological complete response (pCR) rates, late toxicity, patient selection criteria and radiotherapy protocols. We retrieved literature from PubMed, Scopus, Web of Science, Cochrane, ScienceDirect, and ClinicalTrials.gov. The study adhered to the PRISMA 2020 guidelines. Ten prospective clinical trials (7 phase II, 3 phase I), encompassing 188 patients (aged 18–75 years, cT1-T3 cN0-N3 cM0, primarily with ER/PgR-positive, HER2-negative status,), were analyzed. Median follow-up was 15 months (range 3–30). Treatment involved single-fraction SBRT (15-21Gy) in five studies and fractionated (19.5–31.5Gy in 3 fractions) in the rest. Time interval from SBRT to surgery was 9.5 weeks (range 1–28). Acute and late G2 toxicity occurred in 0–17% and 0–19% of patients, respectively, G3 toxicity was rarely observed. The cosmetic outcome was excellent in 85–100%, fair in 0–10% and poor in only 1 patient. pCR varied, showing higher rates (up to 42%) with longer intervals between SBRT and surgery and when combined with neoadjuvant systemic therapy (up to 90%). Preoperative SBRT significantly reduce overall treatment time, enabling to minimalize volumes. Early results indicate excellent cosmetic effects and low toxicity. [ABSTRACT FROM AUTHOR]

Background: Limited literature exists on the feasibility and effectiveness of integrating stereotactic ablative radiotherapy (SABR) techniques with hyperfractionated regimens for patients with lung cancer. This study aims to assess whether the SABR technique with hyperfractionation can potentially reduce lung toxicity. Methods: We utilized the linear‐quadratic model to find the optimal fraction to maximize the tumor biological equivalent dose (BED) to normal‐tissue BED ratio. Validation was performed by comparing the SABR plans with 50 Gy/5 fractions and hyperfractionationed plans with 88.8 Gy/74 fractions with the same tumor BED and planning criteria for 10 patients with early‐stage lung cancer. Mean lung BED, Lyman–Kutcher–Burman (LKB) normal tissue complication probability (NTCP), critical volume (CV) criteria (volume below BED of 22.92 and 25.65 Gy, and mean BED for lowest 1000 and 1500 cc) and the percentage of the lung receiving 20Gy or more (V20) were compared using the Wilcoxon signed‐rank test. Results: The transition point occurs when the tumor‐to‐normal tissue ratio (TNR) of the physical dose equals the TNR of α/β in the BED dose‐volume histogram of the lung. Compared with the hypofractionated regimen, the hyperfractionated regimen is superior in the dose range above but inferior below the transition point. The hyperfractionated regimen showed a lower mean lung BED (6.40 Gy vs. 7.73 Gy) and NTCP (3.50% vs. 4.21%), with inferior results concerning CV criteria and higher V20 (7.37% vs. 7.03%) in comparison with the hypofractionated regimen (p < 0.01 for all). Conclusions: The hyperfractionated regimen has an advantage in the high‐dose region of the lung but a disadvantage in the low‐dose region. Further research is needed to determine the superiority between hypo‐ and hyperfractionation. [ABSTRACT FROM AUTHOR]

Background: Therapeutic options for early-stage hepatocellular carcinoma (HCC) in individual patients can be limited by tumor and location, liver dysfunction and comorbidities. Many patients with early-stage HCC do not receive curative-intent therapies. Stereotactic ablative body radiotherapy (SABR) has emerged as an effective, non-invasive HCC treatment option, however, randomized evidence for SABR in the first line setting is lacking. Methods: Trans-Tasman Radiation Oncology Group (TROG) 21.07 SOCRATES-HCC is a phase II, prospective, randomised trial comparing SABR to other current standard of care therapies for patients with a solitary HCC ≤ 8 cm, ineligible for surgical resection or transplantation. The study is divided into 2 cohorts. Cohort 1 will compromise 118 patients with tumors ≤ 3 cm eligible for thermal ablation randomly assigned (1:1 ratio) to thermal ablation or SABR. Cohort 2 will comprise 100 patients with tumors > 3 cm up to 8 cm in size, or tumors ≤ 3 cm ineligible for thermal ablation, randomly assigned (1:1 ratio) to SABR or best other standard of care therapy including transarterial therapies. The primary objective is to determine whether SABR results in superior freedom from local progression (FFLP) at 2 years compared to thermal ablation in cohort 1 and compared to best standard of care therapy in cohort 2. Secondary endpoints include progression free survival, overall survival, adverse events, patient reported outcomes and health economic analyses. Discussion: The SOCRATES-HCC study will provide the first randomized, multicentre evaluation of the efficacy, safety and cost effectiveness of SABR versus other standard of care therapies in the first line treatment of unresectable, early-stage HCC. It is a broad, multicentre collaboration between hepatology, interventional radiology and radiation oncology groups around Australia, coordinated by TROG Cancer Research. Trial registration: anzctr.org.au, ACTRN12621001444875, registered 21 October 2021. [ABSTRACT FROM AUTHOR]

Simple Summary: Adrenal metastases are frequent in solid malignancies such as lung cancer and melanoma. Recent studies support the use of ablative local therapies in oligometastatic or oligoprogressive patients. Online adaptive MR-guided radiotherapy improves tumor coverage and organ-at-risk sparing compared to non-adaptive radiotherapy. However, clinical data, especially the long-term results of this promising technique, are still limited. We here report the long-term outcomes of a large single-center cohort. (1) Background: Recent publications foster stereotactic body radiotherapy (SBRT) in patients with adrenal oligometastases or oligoprogression. However, local control (LC) after non-adaptive SBRT shows the potential for improvement. Online adaptive MR-guided SBRT (MRgSBRT) improves tumor coverage and organ-at-risk (OAR) sparing. Long-term results of adaptive MRgSBRT are still sparse. (2) Methods: Adaptive MRgSBRT was performed on a 0.35 T MR-Linac. LC, overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and toxicity were assessed. (3) Results: 35 patients with 40 adrenal metastases were analyzed. The median gross tumor volume was 30.6 cc. The most common regimen was 10 fractions at 5 Gy. The median biologically effective dose (BED10) was 75.0 Gy. Plan adaptation was performed in 98% of all fractions. The median follow-up was 7.9 months. One local failure occurred after 16.6 months, resulting in estimated LC rates of 100% at one year and 90% at two years. ORR was 67.5%. The median OS was 22.4 months, and the median PFS was 5.1 months. No toxicity > CTCAE grade 2 occurred. (4) Conclusions: LC and ORR after adrenal adaptive MRgSBRT were excellent, even in a cohort with comparably large metastases. A BED10 of 75 Gy seems sufficient for improved LC in comparison to non-adaptive SBRT. [ABSTRACT FROM AUTHOR]

Background: Lymph-nodal prostate cancer oligometastases are differently treated according to their site: pelvic are locoregional lymph nodes; instead, para-aortic lymph nodes are considered as distant metastases. The aim of the study was a comparison between para-aortic and pelvic oligometastases treated with stereotactic body radiation therapy (SBRT). Methods: This is a retrospective analysis. De novo metastatic or extra-nodal disease were excluded. Univariate and multivariate analyses were performed; the pattern of recurrence was also evaluated. A propensity score matching (PSM) was applied to create comparable cohorts. The primary end-point was the progression-free survival (PFS). The secondary end-points were biochemical relapse-free survival (BRFS), ADT-free survival (ADTFS), polymetastases-free survival (PMFS), local progression-free survival (LPFS), and pattern of relapse. Results: In total, 240 lymph-nodal oligometastases in 164 patients (127 pelvic and 37 para-aortic) were treated. The median PFS was 20 and 11 months in pelvic and para-aortic patients, respectively (p = 0.042). The difference was not confirmed in the multivariate analysis (p = 0.06). The median BRFS was 16 and 9 months, respectively, in the pelvic and para-aortic group (p = 0.07). No statistically significant differences for ADTFS or PMFS were detected. The cumulative 5-year LPFS was 90.5%. In PSM, no statistically significant differences for all the study end-points were detected. Conclusions: Patients affected by para-aortic disease might have a PFS comparable to pelvic disease; local control is high in both cohorts. Our results also support the use of SBRT for para-aortic metastases. [ABSTRACT FROM AUTHOR]

Simple Summary: Pediatric patients with recurrent and metastatic cancers often present with substantial tumor and symptom burden. Local control is an important factor to consider in this setting. Stereotactic ablative radiation therapy (SABR) offers a therapeutic advantage with higher, ablative doses potentially providing durable local control and a shorter fractionation schedule allowing minimum interruptions in systemic therapy and disruption in quality of life. In this study, we evaluate the outcomes of pediatric patients treated with SABR. We observed that SABR is well tolerated with local failure rates of <10% at 1 year and a median survival of 16.9 months. Patients with oligometastatic disease had a better survival rate than patients with widely metastatic disease, suggesting that the total consolidation of all metastatic sites in patients with a limited metastatic burden may be associated with better survival outcomes. Higher local control was associated with a higher radiation dose and sarcoma histology. Future studies evaluating SABR in combination with systemic therapy are warranted. Background: Pediatric patients with metastatic and/or recurrent solid tumors have poor survival outcomes despite standard-of-care systemic therapy. Stereotactic ablative radiation therapy (SABR) may improve tumor control. We report the outcomes with the use of SABR in our pediatric solid tumor population. Methods: This was a single-institutional study in patients < 30 years treated with SABR. The primary endpoint was local control (LC), while the secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. The survival analysis was performed using Kaplan–Meier estimates in R v4.2.3. Results: In total, 48 patients receiving 135 SABR courses were included. The median age was 15.6 years (interquartile range, IQR 14–23 y) and the median follow-up was 18.1 months (IQR: 7.7–29.1). The median SABR dose was 30 Gy (IQR 25–35 Gy). The most common primary histologies were Ewing sarcoma (25%), rhabdomyosarcoma (17%), osteosarcoma (13%), and central nervous system (CNS) gliomas (13%). Furthermore, 57% of patients had oligometastatic disease (≤5 lesions) at the time of SABR. The one-year LC, PFS, and OS rates were 94%, 22%, and 70%, respectively. No grade 4 or higher toxicities were observed, while the rates of any grade 1, 2, and 3 toxicities were 11.8%, 3.7%, and 4.4%, respectively. Patients with oligometastatic disease, lung, or brain metastases and those who underwent surgery for a metastatic site had a significantly longer PFS. LC at 1-year was significantly higher for patients with a sarcoma histology (95.7% vs. 86.5%, p = 0.01) and for those who received a biological equivalent dose (BED10) > 48 Gy (100% vs. 91.2%, p = 0.001). Conclusions: SABR is well tolerated in pediatric patients with 1-year local failure and OS rates of <10% and 70%, respectively. Future studies evaluating SABR in combination with systemic therapy are needed to address progression outside of the irradiated field. [ABSTRACT FROM AUTHOR]

Background and purpose: Tumours in the liver often develop on a background of liver cirrhosis and impaired liver function. As a result, radiotherapy treatments are limited by radiation-induced liver disease, parameterised by the liver mean dose (LMD). Liver function is highly heterogeneous, especially in liver cancer, but the use of LMD does not take this into account. One possible way to improve liver treatments is to use quantitative imaging techniques to assess liver health and prioritise the sparing of healthy liver tissue. Materials and methods: Anatomical T2 and quantitative iron-corrected T1 (cT1) images were made available for 10 patients with liver metastases. Functional liver volumes were automatically segmented on the quantitative images using a threshold. Liver stereotactic ablative body radiotherapy (SABR) plans were made using a departmental protocol. Liver-sparing plans were then made by reducing the dose to the functional sub-volume. Results: The sparing plans achieved a statistically significant (p=0.002) reduction in the functional liver mean dose, with a mean reduction of 1.4 Gy. The LMD was also significantly different (p=0.002) but had a smaller magnitude with a mean reduction of 0.7 Gy. There were some differences in the planning target volume D99% (p=0.04) but the sparing plans remained within the optimal tolerance and the D95% was not significantly different (p=0.2). Conclusions: This study has, for the first time, demonstrated the use of cT1 maps in radiotherapy showing significant reductions in dose to the healthy liver. Further work is needed to validate this in liver cancer patients, who would likely benefit most.

IntroductionSurgical resection is gold standard for treatment of liver metastasis, locally ablative techniques including computer tomography (CT)-guided interstitial high-dose-rate (HDR) brachytherapy (CT-BRT) and stereotactic body radiotherapy (SBRT) have gained prominence as alternatives, offering comparable outcomes in selected patients. We aim to compare CT-BRT and SBRT - based on dosimetric analysis.Material and methodsPatients who underwent CT-BRT for oligometastatic, ≤4cm liver metastases between 2018 and 2024 were eligible. SBRT plans for Halcyon (SBRTh) and TrueBeam (SBRTtb) were prepared virtually. In the CT-BRT group CTV was equal to PTV, for SBRTh and SBRTtb planning, a 5 mm margin was applied to CTV to create PTV. Dose calculation was carried out with the TG-43 algorithm for CT-BRT and Anisotropic Analytical Algorithm for SBRTh and SBRTtb group. Descriptive statistics were used to compare the data. The Wilcoxon pairwise order test was utilized to compare dependent groups.ResultsCT-BRT resulted in a more favorable dose distribution within PTVs for Dmean, D50, and D90, while SBRT showed better results for D98 and V27.5Gy. No significant differences were observed for V25Gy between CT-BRT and SBRTtb, but SBRTh favored over CT-BRT. For OARs, CT-BRT plans showed better values for V5, V10, and V11.6Gy in the uninvolved liver volume. There were no significant differences in dose distribution for the duodenum, bowel, and heart. SBRT modalities performed better in the kidney. CT-BRT had improved dose distribution in the esophagus, great vessels, ribs, skin, spinal cord, and stomach compared to SBRT.ConclusionsCT-BRT could be a viable alternative to SBRT for certain patients with liver malignancies.

Background and purpose: The impact of respiratory motion management strategies for abdominal radiotherapy, such as abdominal compression (AC) and breath hold (BH), on abdominal organ at risk (OAR) delineation on magnetic resonance imaging (MRI) is unknown. This feasibility study compared the inter- and intra- observer delineation variation on MRI acquired with AC, BH for three critical abdominal OAR. Materials and methods: T2-weighted (W) 3D MRI in free-breathing (FB) and with AC, and T1W 3D mDixon exhale BH were acquired. Four observers blinded to motion management strategy used, delineated stomach, liver, and duodenum on all MRI. One case per strategy was repeated over 6 weeks later to quantify intra-observer variation. Simultaneous truth and performance level estimation (STAPLE) contours for each OAR were generated, median and IQR mean distance to agreement (mDTA) and maximum Hausdorff distance (HD) between observer and STAPLE contours were calculated. Observers scored organ visibility on each MRI using a four-point Likert scale. Results: A total of 27 scans including repeats were delineated. Pooled mDTA for all OARs was 1.3 mm (0.5 mm) with AC, 1.4 mm (1.0 mm) with BH, and 1.3 mm (0.5 mm) in FB. Intra-observer mDTA was highest for all organs in FB with 10.8 mm for duodenum, 1.8 mm for liver, and 2.7 mm for stomach. The pooled mean perceptual quality score value was highest for AC across organs. Conclusions: No motion management strategy demonstrated superior similarity across OAR, emphasizing the need for personalised approaches based on individual clinical and patient factors.

Abstract Background Stereotactic ablative body radiotherapy (SABR) is an emerging treatment alternative for patients with localized low and intermediate risk prostate cancer patients. As already explored by some authors in the context of conventional moderate hypofractionated radiotherapy, focal boost of the index lesion defined by magnetic resonance imaging (MRI) is associated with an improved biochemical outcome. The objective of this phase II trial is to determine the effectiveness (in terms of biochemical, morphological and functional control), the safety and impact on quality of life, of prostate SABR with MRI guided focal dose intensification in males with intermediate and high-risk localized prostate cancer. Methods Patients with intermediate and high-risk prostate cancer according to NCCN definition will be treated with SABR 36.25 Gy in 5 fractions to the whole prostate gland with MRI guided simultaneous integrated focal boost (SIB) to the index lesion (IL) up to 50 Gy in 5 fractions, using a protocol of bladder trigone and urethra sparing. Intra-fractional motion will be monitored with daily cone beam computed tomography (CBCT) and intra-fractional tracking with intraprostatic gold fiducials. Androgen deprivation therapy (ADT) will be allowed. The primary endpoint will be efficacy in terms of biochemical and local control assessed by Phoenix criteria and post-treatment MRI respectively. The secondary endpoints will encompass acute and late toxicity, quality of life (QoL) and progression-free survival. Finally, the subgroup of high-risk patients will be involved in a prospective study focused on immuno-phenotyping. Discussion To the best of our knowledge, this is the first trial to evaluate the impact of post-treatment MRI on local control among patients with intermediate and high-risk prostate cancer undergoing SABR and MRI guided focal intensification. The results of this trial will enhance our understanding of treatment focal intensification through the employment of the SABR technique within this specific patient subgroup, particularly among those with high-risk disease, and will help to clarify the significance of MRI in monitoring local responses. Hopefully will also help to design more personalized biomarker-based phase III trials in this specific context. Additionally, this trial is expected to be incorporated into a prospective radiomics study focused on localized prostate cancer treated with radiotherapy. Trial registration Clinicaltrials.gov identifier: NCT05919524; Registered 17 July 2023. Trial Sponsor IRAD/SEOR (Instituto de Investigación de Oncología Radioterápica / Sociedad Española de Oncología Radioterápica). Study setting Clinicaltrials.gov identifier: NCT05919524; Registered 17 July 2023. Trial status Protocol version number and date: v. 5/ 17 May-2023. Date of recruitment start: August 8, 2023. Date of recruitment completion: July 1, 2024.

Abstract Background Dose-escalated radiotherapy is known to improve progression free survival in patients with localized prostate cancer, and recent advances have led to the standardization of ultrahypofractionated stereotactic ablative radiotherapy (SABR) delivered in just 5-fractions. Based on the known effectiveness of the accepted though invasive 2-fraction treatment method of high-dose-rate brachytherapy and given the ubiquity of prostate cancer, a further reduction in the number of treatments of external-beam SABR is possible. This study aims to evaluate the safety, efficacy, and non-inferiority of generalizable 2-fraction SABR compared to the current 5-fraction regimen. Methods 502 patients will be enrolled on this phase II/III randomized control trial. Eligible patients will have previously untreated low- or favorable intermediate-risk adenocarcinoma of the prostate. Patients will be randomized between standard SABR of 40 Gy in 5 fractions given every-other-day and 27 Gy in 2 fractions at least two days apart but completing within seven days. MRI-based planning, radiopaque hydrogel spacer insertion, and fiducial marker placement are required, and SABR will be delivered on either a standard CT-guided linear accelerator or MR-LINAC. The primary endpoint will be freedom from disease progression, with additional secondary clinical, toxicity, and quality of life endpoints. Discussion This study will be the largest prospective randomized trial, adequately powered to demonstrate non-inferiority, comparing 2-fraction SABR to standard 5-fraction SABR for localized prostate cancer. As the protocol does not obligate use of an MRI-LINAC or other adaptive technologies, results will be broadly generalizable to the wider community. Trial registration This trial is registered on Clinicaltrials.gov: ClinicalTrials.gov Identifier: NCT06027892.

Abstract Stereotactic radiotherapy is a term collectively used to describe the radiation treatment techniques that allow for the delivery of highly precise ionizing radiation. It is usually a high dose per session in single or few fractions. This treatment approach has been in medical use for over six decades and has primarily evolved in the last two decades. Many patients benefit from this unique non‐conventional radiotherapy approach. Its indications include various malignant, benign and functional problems in cranial and body sites. This technique is not widespread in developing countries compared to developed countries. This work is an educational narrative review for learners in radiation oncology. We aim to share the knowledge of this practice to improve precision radiation oncology globally. This review summarizes the basics of stereotactic radiotherapy, the technical prerequisites, the clinical considerations, the practical recommendations and the learning points from each site‐specific region.

Background: Stereotactic ablative body radiotherapy (SABR) is an emerging treatment alternative for patients with localized low and intermediate risk prostate cancer patients. As already explored by some authors in the context of conventional moderate hypofractionated radiotherapy, focal boost of the index lesion defined by magnetic resonance imaging (MRI) is associated with an improved biochemical outcome. The objective of this phase II trial is to determine the effectiveness (in terms of biochemical, morphological and functional control), the safety and impact on quality of life, of prostate SABR with MRI guided focal dose intensification in males with intermediate and high-risk localized prostate cancer. Methods: Patients with intermediate and high-risk prostate cancer according to NCCN definition will be treated with SABR 36.25 Gy in 5 fractions to the whole prostate gland with MRI guided simultaneous integrated focal boost (SIB) to the index lesion (IL) up to 50 Gy in 5 fractions, using a protocol of bladder trigone and urethra sparing. Intra-fractional motion will be monitored with daily cone beam computed tomography (CBCT) and intra-fractional tracking with intraprostatic gold fiducials. Androgen deprivation therapy (ADT) will be allowed. The primary endpoint will be efficacy in terms of biochemical and local control assessed by Phoenix criteria and post-treatment MRI respectively. The secondary endpoints will encompass acute and late toxicity, quality of life (QoL) and progression-free survival. Finally, the subgroup of high-risk patients will be involved in a prospective study focused on immuno-phenotyping. Discussion: To the best of our knowledge, this is the first trial to evaluate the impact of post-treatment MRI on local control among patients with intermediate and high-risk prostate cancer undergoing SABR and MRI guided focal intensification. The results of this trial will enhance our understanding of treatment focal intensification through the employment of the SABR technique within this specific patient subgroup, particularly among those with high-risk disease, and will help to clarify the significance of MRI in monitoring local responses. Hopefully will also help to design more personalized biomarker-based phase III trials in this specific context. Additionally, this trial is expected to be incorporated into a prospective radiomics study focused on localized prostate cancer treated with radiotherapy. Trial registration: Clinicaltrials.gov identifier: NCT05919524; Registered 17 July 2023. Trial Sponsor: IRAD/SEOR (Instituto de Investigación de Oncología Radioterápica / Sociedad Española de Oncología Radioterápica). Study setting: Clinicaltrials.gov identifier: NCT05919524; Registered 17 July 2023. Trial status: Protocol version number and date: v. 5/ 17 May-2023. Date of recruitment start: August 8, 2023. Date of recruitment completion: July 1, 2024. [ABSTRACT FROM AUTHOR]

Introduction: The rate of isolated locoregional recurrence after surgery for pancreatic adenocarcinoma (PDAC) approaches 25%. Ablative radiation therapy (A-RT) has improved outcomes for locally advanced disease in the primary setting. We sought to evaluate the outcomes of salvage A-RT for isolated locoregional recurrence and examine the relationship between subsequent patterns of failure, radiation dose, and treatment volume. Methods: We conducted a retrospective analysis of all consecutive participants who underwent A-RT for an isolated locoregional recurrence of PDAC after prior surgery at our institution between 2016 and 2021. Treatment consisted of ablative dose (BED10 98–100 Gy) to the gross disease with an additional prophylactic low dose (BED10 < 50 Gy), with the elective volume covering a 1.5 cm isotropic expansion around the gross disease and the circumference of the involved vessels. Local and locoregional failure (LF and LRF, respectively) estimated by the cumulative incidence function with competing risks, distant metastasis-free and overall survival (DMFS and OS, respectively) estimated by the Kaplan–Meier method, and toxicities scored by CTCAE v5.0 are reported. Location of recurrence was mapped to the dose region on the initial radiation plan. Results: Among 65 participants (of whom two had two A-RT courses), the median age was 67 (range 37–87) years, 36 (55%) were male, and 53 (82%) had undergone pancreaticoduodenectomy with a median disease-free interval to locoregional recurrence of 16 (range, 6–71) months. Twenty-seven participants (42%) received chemotherapy prior to A-RT. With a median follow-up of 35 months (95%CI, 26–56 months) from diagnosis of recurrence, 24-month OS and DMFS were 57% (95%CI, 46–72%) and 22% (95%CI, 14–37%), respectively, while 24-month cumulative incidence of in-field LF and total LRF were 28% (95%CI, 17–40%) and 36% (95%CI 24–48%), respectively. First failure after A-RT was distant in 35 patients (53.8%), locoregional in 12 patients (18.5%), and synchronous distant and locoregional in 10 patients (15.4%). Most locoregional failures occurred in elective low-dose volumes. Acute and chronic grade 3–4 toxicities were noted in 1 (1.5%) and 5 patients (7.5%), respectively. Conclusions: Salvage A-RT achieves favorable OS and local control outcomes in participants with an isolated locoregional recurrence of PDAC after surgical resection. Consideration should be given to extending high-dose fields to include adjacent segments of at-risk vessels beyond direct contact with the gross disease. [ABSTRACT FROM AUTHOR]

To investigate the predictive value of the pre-treatment diffusion parameters of diffusion-weighted magnetic resonance imaging (DW-MRI) using artificial intelligence (AI) for prostate-specific antigen (PSA) response in patients with low- and intermediate-risk prostate cancer (PCa) treated with stereotactic ablative radiotherapy (SABR). Retrospective evaluation was performed for 30 patients using pre-treatment multi-parametric MR image datasets between 2017 and 2021. MR-based mean- and minimum apparent diffusion coefficients (ADC mean , ADC min) were calculated for the intraprostatic dominant lesion. Therapeutic response was assessed using PSA levels. Predictive performance was assessed by the receiver operating characteristic (ROC) analysis. Statistics performed with a significance level of p ≤ 0.05. No biochemical relapse was detected after a median follow-up of twenty-three months (range: 3–50), with a median PSA of 0.01 ng/ml (range: 0.006–2.8) at the last examination. Significant differences were observed between the pre-treatment ADC mean , ADC min parameters, and the group averages of patients with low and high 1-year-PSA measurements (p < 0.0001, p < 0.0001). In prediction, the random forest (RF) model outperformed the decision tree (DT) and support vector machine (SVM) models by yielding area under the curves (AUC), with 0.722, 0.685, and 0.5, respectively. Our findings suggest that pre-treatment MR diffusion data may predict therapeutic response using the novel approach of machine learning in PCa patients treated with SABR. Clinicians shall measure and implement the evaluation of the suggested parameters (ADC min , ADC mean) to provide the most accurate therapy for the patient. [ABSTRACT FROM AUTHOR]