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.

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.

OBJECTIVE: To evaluate acute toxicity at 6 months after stereotactic body radiotherapy (SBRT) in patients with oligometastatic cancer within the OligoCare cohort.
METHODS: OligoCare is a prospective, registry-based, single-arm, observational study that aims to report prospective real-world data of patients with oligometastases from solid cancer treated with SBRT (NCT03818503). Primary tumor included non-small cell lung cancer (NSCLC), breast cancer (BC), colorectal cancer (CRC), and prostate cancer (PC). This analysis addresses a secondary endpoint of the trial, acute toxicity within 6 months after SBRT.
RESULTS: Out of 1,597registered patients, 1\'468 patients were evaluated for acute toxicity. Globally, 290 (20 %) had NSCLC primary disease, 227 (16 %) had BC, 293 (20 %) had CRC, and 658 (45 %) had PC. Concomitant systemic treatment was administered in 527 (35.9 %) patients. According to the EORTC/ESTRO oligometastatic disease (OMD) classification, 828 (56 %) patients had de novo OMD, 464 (32 %) repeat OMD, and 176 (12 %) induced OMD. Acute grade ≥ 3 SBRT related adverse events were reported in 8 (0.5 %) patients, including 2 (0.1 %) fatal AEs. In particular, 6 (0.4 %) grade 3 events were: 1 empyema, 1 pneumonia, 1 radiation pneumonitis, 1 radiation skin injury, 1 decreased appetite, and 1 bone pain. Among those 2 occurred in NSCLC patients, 2 in BC patients, and 1 in CRC and PC patients each. The two (0.1 %) grade 5 toxicity were represented by: pneumonitis and cerebral hemorrhage.
CONCLUSIONS: OligoCare is the largest prospective registry cohort on oligometastatic disease. Acute toxicity within 6 months was low, confirming the safety of SBRT in the treatment of oligometastases.

OBJECTIVE: SABR-Dual is a phase-III trial with an initial phase-I safety cohort, of 2-fraction stereotactic radiotherapy (SABR) with optional magnetic resonance imaging (MRI)-based focal boost, using peri-rectal spacing, for localized prostate cancer. This represents the initial report from the phase-I non-randomized cohort.
METHODS: Subjects had favorable intermediate risk (FIR) or low risk prostate adenocarcinoma, and gland volume <80 cc. All underwent radiopaque hydrogel spacer and fiducial marker placement before simulation (computed tomography and 3-tesla T2 MRI). The clinical target volume included the entire prostate, and in FIR patients, 1-2 cm of seminal vesicle. A 2-mm expansion was applied for planning target volume (PTV), and a dose of 27 Gy was prescribed to the PTV-prostate, 23 Gy to the PTV-seminal vesicle, with an optional 30 Gy simultaneous boost to an MRI-defined dominant lesion. Primary endpoint was 3-month patient-reported changes in quality of life based on the Expanded Prostate Cancer Index Composite-26, International Prostate Symptom Score, and Sexual Health Inventory for Men questionnaires. Secondary endpoints were 6-month quality of life, acute toxicity (using Common Terminology Criteria for Adverse Events version 5.0) and early Prostate specific antigen (PSA) response.
RESULTS: Among the 20 patients in the phase-I cohort, 95% had FIR disease, and 50% received a simultaneous boost. At median follow-up of 8 months, a 3-month minimally clinically important change occurred in 1/20 (5%), 6/20 (30%), 2/20 (10%), 4/20 (20%), and 5/20 (25%) in urinary incontinence, urinary obstructive, bowel, sexual, and hormonal domains. There was a mean increase of 1 ± 5.4 in International Prostate Symptom Score and decrease of 1.8 ± 6.5 in Sexual Health Inventory for Men scores. Rates of grade 2 urinary and bowel toxicity were 10% and 0%, respectively, with no grade ≥3 toxicities. Mean PSA decrease at last follow-up was 70.4% ± 17.7%.
CONCLUSIONS: This generalizable protocol of 2-fraction prostate SABR using peri-rectal spacing is a safe approach for ultra-hypofractionated dose-escalation, with minimal acute toxicity. Longer-term outcomes and direct comparison with standard 5-fraction SABR are being studied in the phase-III randomized portion of SABR-Dual.

BACKGROUND: 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.
CONCLUSIONS: 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.

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.
CONCLUSIONS: 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.
BACKGROUND: anzctr.org.au, ACTRN12621001444875, registered 21 October 2021.

(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.

Stereotactic ablative radiotherapy (SABR) is increasingly used for the treatment of early-stage non-small cell lung cancer (ES-NSCLC) and for pulmonary metastases. In patients with ES-NSCLC, SABR is highly successful with reported 5-year local control rates of approximately 90%. However, the assessment of local control following lung SABR can be challenging as radiological changes arising from radiation-induced lung injury (RILI) can be observed in up to 90% of patients. These so-called \'benign\' radiological changes evolve with time and are often asymptomatic. Several radiological and metabolic features have been explored to help distinguish RILI from local recurrences (LR). These include the Response Evaluation Criteria for Solid Tumors (RECIST), high-risk features (HRF\'s) and maximum standardized uptake value (SUVmax) on FDG-PET-CT. However, use of some of these approaches have poor predictive values and low specificity for recurrence. A proposed new workflow for the evaluation of post-lung SABR radiological changes will be reviewed which uses the presence of so-called \'actionable radiological features\' to trigger changes to imaging schedules and identifies the need for a multidisciplinary board review. Furthermore, this critical review of post-lung SABR imaging will highlight current challenges, new insights, and unknowns in this field.

OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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%.
CONCLUSIONS: 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.

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.