Predictive Factors for Long-Term Disease Control in Systemic Treatment-Naïve Oligorecurrent Renal Cell Carcinoma Treated with Up-Front Stereotactic Ablative Radiotherapy (SABR).

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.

Early and repetitive novel-tracer PET-guided stereotactic body radiotherapy for nodal oligorecurrent prostate cancer after definitive first-line therapy.

BACKGROUND: Prostate-specific membrane antigen (PSMA) positron-emission tomography (PET) imaging can detect prostate cancer (PCa) nodal oligorecurrences (NOR) at very low prostate-specific antigen (PSA) levels. Prospective studies on oligorecurrent (OR) PCa have been hampered by either dated diagnostics or inhomogeneous cohorts and/or treatment approaches. We hypothesized that early and-if necessary and feasible-repetitive PSMA-PET-based metastasis-directed therapy (MDT) using stereotactic body radiotherapy (SBRT) would improve freedom from palliative (systemic) therapy at low toxicity. METHODS: This study is a retrospective analysis of patients treated for OR PCa after definitive first-line therapy using PSMA-PET/CT-based SBRT. Endpoints were biochemical progression-free survival (bPFS), SBRT-free survival (SBRT-FS), androgen deprivation therapy (ADT)-free survival (ADT-FS), and toxicity. RESULTS: A total of 67 patients and 248 metastases (211 nodal) were treated. Patients on concurrent ADT were excluded. Median PSA at inclusion was 2.175 ng/ml. bPFS, SBRT-FS, and ADT-FS for multiple-course SBRT were 9.5, 19.5, and 35.0 months, respectively; 32 patients had ≥ 1 course of SBRT. Median PSA nadir was 0.585 ng/ml. There was no ≥ grade 2 toxicity. CONCLUSION: Modern-tracer PET/CT-based early and repetitive focal SBRT yields promising results with regard to bPFS, SBRT-FS, and ADT-FS with low toxicity. The ability of this approach to postpone initiation of palliative treatment with low toxicity should be re-evaluated prospectively.

Adrenal Insufficiency following Stereotactic Ablative Radiotherapy (SAbR) of Adrenal Gland Metastases.

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.

18F-FDG PET/CT biomarkers as predictors of long term outcomes and survival rates in patients with high risk malignant pulmonary masses/nodules treated with stereotactic ablative radiotherapy.

INTRODUCTION: Stereotactic ablative body radiotherapy (SABR) is a standard treatment option for patients with malignant pulmonary masses (including primary and metastatic lesions) who are unfit for surgery or who are medically operable but refuse surgery. Flourine-18 flurodeoxyglucose positron emission tomography (18F-FDG PET) volumetric metabolic parameters, i.e., metabolic tumour volume (MTV) and total lesion glycolysis (TLG) play an important role in assessing the biological characteristics of some tumours and its role as potential prognostic factors has also been introduced. OBJECTIVES: The aim of this retrospective study is to assess the value of baseline metabolic volumetric parameters as prognostic imaging biomarkers in patients with pulmonary masses/nodules treated with SABR. METHODS: 70 patients were included in this retrospective study (39 male and 31 female, age range 47-91 years, mean 76 years). Standardized uptake value (SUVmax), SUVmean, MTV and TLG for all the patients were calculated on baseline 18F-FDG PET/CT. Patient outcome was divided into 3 categories free of disease, stable disease and disease progression. RESULTS: There was no significant statistical difference in the SUVmax and SUVmean in all the three categories. Mean SUVmax ranges from 7.13 to 8.08 with its highest value in the stable disease and lowest value in the progressive disease categories. Similarly, the average SUVmean was 4.9 in the free of disease category and 4.68 in the progressive disease category. MTV and TLG were low in the free of disease and the highest in progressive disease. MTV increased from 2.25 cm3 in free of disease category to 3.23 cm3 and 7.29 cm3 in stable disease and progressive disease, respectively. TLG has increased from 11.7 in the disease-free survival category to 18.77 and 40.39 in the stable and progressive disease, respectively. Patients with low MTV had longer overall survival (OS) than patients with high MTV (37 months versus 27 months, p value = 0. 0018). In addition, OS was longer in patients with low TLG (36 months versus 24 months, p value = 0.016). CONCLUSIONS: TLG and MTV are more useful than SUVmax and SUVmean for predicting outcome, OS and progression-free survival (PFS) in patients receiving SABR. The TLG and MTV measurement on 18F-FDG PET imaging may be routinely recommended in baseline 18F-FDG PET/CT prior to SABR.

Focal therapy for oligometastatic and oligoprogressive renal cell carcinoma: a narrative review.

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.

[Box: see text].

Stereotactic radiotherapy for localized prostate cancer: 10-year outcomes from three prospective trials.

BACKGROUND AND PURPOSE: Stereotactic ablative radiotherapy (SABR) is growingly accepted for the treatment of localized prostate cancer with recent randomized trials showing non-inferiority compared to conventional or moderately hypofractionated radiotherapy. The natural history of prostate cancer necessitates extended surveillance for recurrence; however, there are few prospective studies reporting long-term outcomes. MATERIALS AND METHODS: This study included patients with low and intermediate risk localized prostate cancer from three Canadian clinical trials enrolled from 2006-2013. All patients received SABR to the prostate consisting of 35-40 Gy in 5 fractions over 11-29 days. PSA, distant metastasis, and vital status were prospectively recorded. Occurrence of second malignancy after treatment was assessed by chart review and classified using modified Cahan's criteria. RESULTS: 267 patients were included. Median follow up was 10.3 years (IQR 7.8 - 12.7). 10-year BF (95% CI) was 7.7% (3.9-11.5). 10-year OS, PCSS, and FFM were 84.1% (79.3 - 89.1%), 99.2% (98.1 - 100), and 98.8% (97.5-100), respectively. 27/267 (10.1%) patients experienced a SM, with 6/27 patients (22.2%) classified as having a SM likely (n=3) or possibly (n=3) related to prior radiotherapy. 10-year freedom from SM was 89.2%. CONCLUSION: SABR shows excellent long-term disease control for low and intermediate risk localized prostate cancer. Patients treated for prostate cancer have a moderate risk of second malignancy, consistent with background rates for the population.

Cumulative rib fracture risk after stereotactic body radiotherapy in patients with localized non-small cell lung cancer.

INTRODUCTION: Rib fracture is a known complication after stereotactic body radiotherapy (SBRT). Patient-related parameters are essential to provide patient-tailored risk estimation, however, their impact on rib fracture is less documented compared to dosimetric parameters. This study aimed to predict the risk of rib fractures in patients with localized non-small cell lung cancer (NSCLC) post-SBRT based on both patient-related and dosimetric parameters with death as a competing risk. MATERIALS AND METHODS: In total, 602 patients with localized NSCLC treated with SBRT between 2010-2020 at Odense University Hospital, Denmark were included. All patients received SBRT with 45-66 Gray (Gy)/3 fractions. Rib fractures were identified in CT-scans using a word embedding model. The cumulative incidence function was based on cause-specific Cox hazard models with variable selection based on cross-validation model likelihood performed using 50 bootstraps. RESULTS: In total, 19 % of patients experienced a rib fracture. The cumulative risk of rib fracture increased rapidly from 6-54 months post-SBRT. Female gender, bone density, near max dose to the rib, V30 and V40 to the rib, gross tumor volume, and mean lung dose were significantly associated with rib fracture risk in univariable analysis. The final multi-variable model consisted of V20 and V30 to the rib and mean lung dose. CONCLUSION: Female gender and low bone density in male patients are significant predictors of rib fracture risk. The final model predicting cumulative rib fracture risk of 19 % in patients with localized NSCLC treated with SBRT contained no patient-related parameters, suggesting that dosimetric parameters are the primary drivers.

Acute toxicity in patients with oligometastatic cancer following metastasis-directed stereotactic body radiotherapy: An interim analysis of the E2-RADIatE OligoCare cohort.

AIM: To evaluate acute toxicity at 6 months after stereotactic body radiotherapy (SBRT) in patients with oligometastatic cancer within the OligoCare cohort. MATERIAL AND 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. CONCLUSION: 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.

Stereotactic Ablative Radiotherapy for Early-stage Lung Cancer in Patients With Left Ventricular Assist Device: A Case Series.

BACKGROUND/AIM: Radiotherapy-induced malfunction of pacemakers and cardiac defibrillators has been reported, and corresponding guidelines have been developed in various countries. Although several studies have reported the effects of radiotherapy in patients with implantable left ventricular assist device (LVAD), its safety remains unclear. Herein, we report three cases of stereotactic ablative radiotherapy (SABR) using CyberKnife for early-stage lung cancer in patients with implantable LVAD. CASE REPORT: Three patients in their 50s or 60s, including two women and one man, who had LVADs due to dilated or ischemic cardiomyopathy and performance status of 0 or 1, were diagnosed with stage IA2 lung cancer (cT1bN0M0) by imaging only. All three patients were deemed inoperable due to cardiac comorbidity and underwent SABR at the Osaka University Hospital. The total radiation dose was 42-52 Gy, administered in four fractions. All treatment plans were designed to keep the LVAD dose below 2 Gy. In all patients, SABR was completed without acute adverse events or LVAD malfunction. During the follow-up period of 3-29 months, no disease progression or chronic adverse events were observed in any of the patients. CONCLUSION: This case series indicated that SABR using CyberKnife is a safe treatment option for early-stage lung cancer in patients with LVAD by reducing the dose to the LVAD.

Cardiac SABR: Image matching techniques for accurate treatment delivery.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: The 6DoF CBCT image match has less variability and therefore suggest using a 6DoF couch for treatment delivery. IMPLICATIONS FOR PRACTICE: Cardiac SABR CBCT image matching at treatment delivery is complex, optimisation of CBCT acquisition parameters and therapeutic radiographer training is essential prior to implementation.

Salvage stereotactic ablative body radiotherapy after thermal ablation of primary kidney cancer.

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.

Advances in breast cancer treatment: a systematic review of preoperative stereotactic body radiotherapy (SBRT) for breast cancer.

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.

Comparative analysis of delivered and planned doses in target volumes for lung stereotactic ablative radiotherapy.

BACKGROUND: Adaptive therapy has been enormously improved based on the art of generating adaptive computed tomography (ACT) from planning CT (PCT) and the on-board image used for the patient setup. Exploiting the ACT, this study evaluated the dose delivered to patients with non-small-cell lung cancer (NSCLC) patients treated with stereotactic ablative radiotherapy (SABR) and derived relationship between the delivered dose and the parameters obtained through the evaluation procedure. METHODS: SABR treatment records of 72 patients with NSCLC who were prescribed a dose of 60 Gy (Dprescribed) to the 95% volume of the planning target volume (PTV) in four fractions were analysed in this retrospective study; 288 ACTs were generated by rigid and deformable registration of a PCT to a cone-beam computed tomography (CBCT) per fraction. Each ACT was sent to the treatment planning system (TPS) and treated as an individual PCT to calculate the dose. Delivered dose to a patient was estimated by averaging four doses calculated from four ACTs per treatment. Through the process, each ACT provided the geometric parameters, such as mean displacement of the deformed PTV voxels (Warpmean) and Dice similarity coefficient (DSC) from deformation vector field, and dosimetric parameters, e.g. difference of homogeneity index (ΔHI, HI defined as (D2%-D98%)/Dprescribed*100) and mean delivered dose to the PTV (Dmean), obtained from the dose statistics in the TPS. Those parameters were analyzed using multiple linear regression and one-way-ANOVA of SPSS® (version 27). RESULTS: The prescribed dose was confirmed to be fully delivered to internal target volume (ITV) within maximum difference of 1%, and the difference between the planned and delivered doses to the PTV was agreed within 6% for more than 95% of the ACT cases. Volume changes of the ITV during the treatment course were observed to be minor in comparison of their standard deviations. Multiple linear regression analysis between the obtained parameters and the dose delivered to 95% volume of the PTV (D95%) revealed four PTV parameters [Warpmean, DSC, ΔHI between the PCT and ACT, Dmean] and the PTV D95% to be significantly related with P-values < 0.05. The ACT cases of high ΔHI were caused by higher values of the Warpmean and DSC from the deformable image registration, resulting in lower PTV D95% delivered. The mean values of PTV D95% and Warpmean showed significant differences depending on the lung lobe where the tumour was located. CONCLUSIONS: Evaluation of the dose delivered to patients with NSCLC treated with SABR using ACTs confirmed that the prescribed dose was accurately delivered to the ITV. However, for the PTV, certain ACT cases characterised by high HI deviations from the original plan demonstrated variations in the delivered dose. These variations may potentially arise from factors such as patient setup during treatment, as suggested by the statistical analyses of the parameters obtained from the dose evaluation process.

Initial experience and patient tolerance of proton stereotactic body radiotherapy.

Purpose: To review our initial experience with proton-based SBRT to evaluate the planning outcomes and initial patient tolerance of treatment. Patients and methods: From Sep. 2019 to Dec. 2020, 52 patients were treated with proton SBRT to 62 lesions. Fractionation varied by indication and site with a median of 5 fractions and median fractional dose of 8 Gy. Planning outcomes, including plan heterogeneity, conformity, and PTV volume receiving 100% of the prescription dose (PTV V100%) were evaluated. Acute toxicities were prospectively recorded, and patient reported outcomes were assessed prior to and at completion of treatment using the MD Anderson Symptom Inventory (MDASI) and EQ-5D5L visual analogue score (VAS). Results: All treated patients completed their course of proton-based SBRT. The mean conformity index was 1.05 (range 0.51-1.48). R50% values were comparable to ideal photon parameters. PTV V100% was 89.9% on average (40.44% - 99.76%). 5 patients (10%) required plan modification due to setup or tumor changes. No patients developed a new grade 3 or greater toxicity during treatment. Comparing pretreatment to end of treatment timepoints, there was a significant improvement in the mean VAS (65 to 75, p = 0.014), with no significant change in the mean MDASI symptom (1.7, 1.8; p = 0.79) or interference (2.3, 2.4; p = 0.452) scores. Conclusion: Proton-based SBRT can achieve dosimetric goals required by major clinical photon trials. It was well-tolerated with no decrement in patient reported outcomes and a mean 10-point improvement in VAS at the conclusion of SBRT. Further follow-up is necessary for tumor control and late effects analysis.

The Landscape of Stereotactic Ablative Radiotherapy (SABR) for Renal Cell Cancer (RCC).

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.

Harnessing the Power of Radiotherapy for Lung Cancer: A Narrative Review of the Evolving Role of Magnetic Resonance Imaging Guidance.

Compared with computed tomography (CT), magnetic resonance imaging (MRI) traditionally plays a very limited role in lung cancer management, although there is plenty of room for improvement in the current CT-based workflow, for example, in structures such as the brachial plexus and chest wall invasion, which are difficult to visualize with CT alone. Furthermore, in the treatment of high-risk tumors such as ultracentral lung cancer, treatment-associated toxicity currently still outweighs its benefits. The advent of MR-Linac, an MRI-guided radiotherapy (RT) that combines MRI with a linear accelerator, could potentially address these limitations. Compared with CT-based technologies, MR-Linac could offer superior soft tissue visualization, daily adaptive capability, real-time target tracking, and an early assessment of treatment response. Clinically, it could be especially advantageous in the treatment of central/ultracentral lung cancer, early-stage lung cancer, and locally advanced lung cancer. Increasing demands for stereotactic body radiotherapy (SBRT) for lung cancer have led to MR-Linac adoption in some cancer centers. In this review, a broad overview of the latest research on imaging-guided radiotherapy (IGRT) with MR-Linac for lung cancer management is provided, and development pertaining to artificial intelligence is also highlighted. New avenues of research are also discussed.

Stereotactic ablative radiotherapy for locally advanced non-small cell lung cancer: A systematic review and meta-analysis.

INTRODUCTION: To evaluate the feasibility, efficacy and safety of stereotactic ablative radiotherapy (SABR) to the primary tumor and lymph nodes in patients with locally advanced non-small cell lung cancer (LA-NSCLC) who are ineligible for or refused concomitant chemoradiation. MATERIALS AND METHODS: In accordance with the PRISMA and MOOSE guidelines, a systematic review with meta-analysis was conducted. The study included reports that assessed the outcomes of SABR treatment in patients with LA-NSCLC. Studies evaluating SBRT as a boost following primary radiotherapy were excluded. The primary outcomes measured were local control (LC) and overall survival (OS). The secondary endpoint was the incidence of severe toxicity (grades 3-5). A meta-regression analysis was performed to explore the relationship between LC, OS, and severe toxicity. The Biologically Effective Dose (BED) was analyzed as a continuous variable. Statistical significance was defined as a p-value < 0.05. RESULTS: A total of seven studies (3 prospective and 4 retrospective studies) involving 268 patients (SBRT to primary and lymph nodes) were included in the analysis. The pooled 1-year LC rate was 80 % (95 % CI: 63-94 %), and the factors significantly associated with LC were BEDGy10 (p = 0.005) and neoadjuvant chemotherapy (p = 0.005). The 1-year and 2-year OS rates were 74 % (95 % CI: 58-90 %) and 55 % (95 % CI: 34-76 %), respectively. Meta-regression analysis indicated a linear relationship between OS and LC, with a 0.7 % increase in OS for each 1 % improvement in LC (p = 0.005). The pooled rate of grade 3 acute toxicity was 5 % (95 % CI: 1-10 %), and the rate of grade 5 toxicity was 1.7 % (95 % CI: 0-3 %). CONCLUSION: Promising results (LC and OS) with limited toxicity (feasibility) using SABR in LA-NSCLC warrant further research, emphasizing the need for larger, well-designed trials for further validation of the approach.

A multi-centre retrospective study of long-term outcomes of spinal re-irradiation with SABR.

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.

A randomised controlled trial of Standard Of Care versus RadioAblaTion in Early Stage HepatoCellular Carcinoma (SOCRATES HCC).

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.

Stereotactic Body Radiotherapy: is less fractionation more effective in adrenal and renal malignant lesions?

PURPOSE: Stereotactic body radiotherapy (SBRT) has become an excellent non-invasive alternative for many patients with primary renal cell carcinoma (RCC) and adrenal malignancies (AM). The aims of this study were to analyse how tumor-, patient- and treatment-related factors may influence the outcomes and side effects of SBRT and to assess its benefits as an alternative to surgery. METHODS: This retrospective, multicenter study included 25 lesions in 23 patients treated with SBRT using different devices (LINAC, CyberKnife® and Tomotherapy®). A multivariate linear regression was used for the statistical study. RESULTS: Local control time was higher than six months in more than 87% of patients and treatment response was complete for 73.68%. There was an overall 2-year survival of 40% and none of the deaths were secondary to renal or adrenal local progression. Patients treated with lower total radiation dose (mean [m] = 55 Gy) but less fractions with more dose per fraction (> 8.5 Gy) showed better outcome. Patients with previous chemotherapy and surgery treatments also showed higher complete response and disease-free survival (> 6 months). CONCLUSIONS: This study highlights the importance of ultra-hypofractionated regimens with higher doses per session. Thus, the referral of patients with RCC and AM to Radiotherapy and Oncology departments should be encouraged supporting the role of SBRT as a minimally invasive and outpatient treatment.