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.

Systematic review of economic evaluations on stereotactic ablative radiotherapy (SABR) compared to other radiotherapy techniques or surgical procedures for early-stage non-small cell lung cancer.

BACKGROUND: Stereotactic ablative radiotherapy (SABR) is recommended as first-choice treatment to inoperable early-stage non-small cell lung cancer (NSCLC). However, it is not widely adopted in developing countries, and its cost-effectiveness is unclear. We aimed to perform a systematic review of full economic evaluations (EE) that compared SABR with other radiotherapy or surgical procedures to assess the results and methodological approach. METHODS: The protocol was registered on PROSPERO (CRD42021241640). We included full EE studies with early-stage NSCLC in which one group was submitted to SABR. Studies that were partial EE, included advanced NSCLC or other neoplasm were excluded. We performed the last search on June 2021 in Medline, EMBASE and other databases. The reporting quality were assessed by CHEERS checklist. The main characteristics of each study were tabulated, and the results were presented by a narrative synthesis. RESULTS: We included nine studies. Three compared radiotherapy techniques, in which SABR was found to be dominant or cost-effective. Six compared SABR with surgery, and in this group, there was not a unanimous decision. All included only direct healthcare costs but varied about categories included. The parameters used in the model-based studies were highly heterogeneous using mixed data from various sources. The items properly reported varied from 29 to 67%. CONCLUSIONS: The studies were all from developed countries and lacked in reporting quality. We recommend that developing countries produce their own studies. More strict alignment to reporting guidelines and use of robust evidence as model parameters are also advised.

Endoscopic nodal staging in oligometastatic non-small cell lung cancer (NSCLC) being treated with stereotactic ablative radiotherapy (ENDO-SABR).

BACKGROUND: Research in treatment of non-small cell lung cancer (NSCLC) has shown promising results with stereotactic ablative radiotherapy (SABR) of oligometastatic disease, wherein distant disease may be limited to one or a few distant organs by host factors. Traditionally, PET/CT has been used in detecting metastatic disease and avoiding futile surgical intervention, however, sensitivity and specificity is limited to only 81 and 79%, respectively. Mediastinal staging still identifies occult nodal disease in up to 20% of NSCLC patients initially thought to be operative candidates. Endobronchial ultrasound and transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive tool for the staging and diagnosis of thoracic malignancy. When EBUS is combined with endoscopic ultrasound using the same bronchoscope (EUS-B), the diagnostic sensitivity and negative predictive value increase to 84 and 97%, respectively. Endoscopic staging in patients with advanced disease has never been studied, but may inform treatment if a curative SABR approach is being taken. METHODS: This is a multi-centre, prospective, cohort study with two-stage design. In the first stage, 10 patients with oligometastatic NSCLC (lung tumour ± hilar/mediastinal lymphadenopathy) with up to 5 synchronous metastases will be enrolled An additional 19 patients will be enrolled in the second stage if rate of treatment change is greater than 10% in the first stage. Patients will be subject to EBUS or combined modality EBUS/EUS-B to assess bilateral lymph node stations using a N3 to N2 to N1 progression. Primary endpoint is defined as the rate of change to treatment plan including change from SABR to conventional dose radiation, change in mediastinal radiation field, and change from curative to palliative intent treatment. DISCUSSION: If a curative approach with SABR for oligometastatic disease is being explored, invasive mediastinal staging may guide treatment and prognosis. This study will provide insight into the use of endoscopic mediastinal staging in determining changes in treatment plan of NSCLC. Results will inform the design of future phase II trials. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT04852588. Date of registration: April 19, 2021. PROTOCOL VERSION: 1.1 on December 9, 2021.

Comparing stereotactic ablative radiotherapy (SABR) versus re-trans-catheter arterial chemoembolization (re-TACE) for hepatocellular carcinoma patients who had incomplete response after initial TACE (TASABR): a randomized controlled trial.

BACKGROUND: Hepatocellular carcinoma (HCC) accounts for 75-85% of primary liver cancers and is prevalent in the Asia-Pacific region. Till now, trans-arterial chemoembolization (TACE) is still one of common modalities in managing unresectable intermediate-stage HCC. However, post-TACE residual viable HCC is not uncommon, resulting in unsatisfied overall survival after TACE alone. Recently, stereotactic ablative radiotherapy (SABR) has been suggested to manage HCC curatively. However, evidence from phase-III trials is largely lacking. Hence, the present phase III randomized trial is designed to compare clinical outcomes between SABR and re-TACE for unresectable HCC patients who had incomplete response after initial TACE. METHODS: The present study is an open-label, parallel, randomized controlled trial. A total of 120 patients will be included into two study groups, i.e., SABR and re-TACE, with a 1:1 allocation rate. A 3-year allocating period is planned. Patients with incomplete response after initial TACE will be enrolled and randomized. The primary endpoint is 1-year freedom-form-local-progression rate. Secondary endpoints are disease-progression-free survival, overall survival, local control, response rate, toxicity, and duration of response of the treated tumor. DISCUSSION: SABR has been reported as an effective modality in managing intermediate-stage HCC patients, but evidence from phase-III randomized trials is largely lacking. As a result, conducting randomized trials to demarcate the role of SABR in these patients is warranted, especially in the Asia-Pacific region, where HBV- and HCV-related HCCs are prevalent. TRIAL REGISTRATION: Before enrolling participants, the present study was registered prospectively on ClinicalTrials.gov (trial identifier, NCT02921139 ) on Sep. 29, 2016. This study is ongoing.

Available ablation energies to treat cT1 renal cell cancer: emerging technologies.

PURPOSE: An increasing interest in percutaneous ablation of renal tumors has been caused by the increasing incidence of SRMs, the trend toward minimally invasive nephron-sparing treatments and the rapid development of local ablative technologies. In the era of shared decision making, patient preference for non-invasive treatments also leads to an increasing demand for image-guided ablation. Although some guidelines still reserve ablation for poor surgical candidates, indications may soon expand as evidence for the use of the two most validated local ablative techniques, cryoablation (CA) and radiofrequency ablation (RFA), is accumulating. Due to the collaboration between experts in the field in biomedical engineering, urologists, interventional radiologists and radiation oncologists, the improvements in ablation technologies have been evolving rapidly in the last decades, resulting in some new emerging types of ablations. METHODS: A literature search was conducted to identify original research articles investigating the clinical outcomes of new emerging technologies, percutaneous MWA, percutaneous IRE and SABR, in patients with primary cT1 localized renal cell cancer. RESULTS: Due to the collaboration between experts in the field in biomedical engineering, urologists, interventional radiologists and radiation oncologists, the improvements in ablation technologies have been evolving rapidly in the last decades. New emerging technologies such as microwave ablation (MWA), irreversible electroporation (IRE) and stereotactic ablative radiotherapy (SABR) seem to be getting ready for prime time. CONCLUSION: This topical paper describes the new emerging technologies for cT1 localized renal cell cancer and investigates how they compare to CA and RFA.

7-year follow-up after stereotactic ablative radiotherapy for patients with stage I non-small cell lung cancer: Results of a phase 2 clinical trial.

BACKGROUND: The authors evaluated the efficacy, patterns of failure, and toxicity of stereotactic ablative radiotherapy (SABR) for patients with medically inoperable, clinical stage I non-small cell lung cancer (NSCLC) in a prospective clinical trial with 7 years of follow-up. Clinical staging was performed according to the seventh edition of the American Joint Committee on Cancer TNM staging system. METHODS: Eligible patients with histologically confirmed NSCLC of clinical stage I as determined using positron emission tomography staging were treated with SABR (50 grays in 4 fractions). The primary endpoint was progression-free survival. Patients were followed with computed tomography and/or positron emission tomography/computed tomography every 3 months for the first 2 years, every 6 months for the next 3 years, and then annually thereafter. RESULTS: A total of 65 patients were eligible for analysis. The median age of the patients was 71 years, and the median follow-up was 7.2 years. A total of 18 patients (27.7%) developed disease recurrence at a median of 14.5 months (range, 4.3-71.5 months) after SABR. Estimated incidences of local, regional, and distant disease recurrence using competing risk analysis were 8.1%, 10.9%, and 11.0%, respectively, at 5 years and 8.1%, 13.6%, and 13.8%, respectively, at 7 years. A second primary lung carcinoma developed in 12 patients (18.5%) at a median of 35 months (range, 5-67 months) after SABR. Estimated 5-year and 7-year progression-free survival rates were 49.5% and 38.2%, respectively; the corresponding overall survival rates were 55.7% and 47.5%, respectively. Three patients (4.6%) experienced grade 3 treatment-related adverse events. No patients developed grade 4 or 5 adverse events (toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]). CONCLUSIONS: With long-term follow-up, the results of the current prospective study demonstrated outstanding local control and low toxicity after SABR in patients with clinical stage I NSCLC. Regional disease recurrence and distant metastases were the dominant manifestations of failure. Surveillance for second primary lung carcinoma is recommended. Cancer 2017;123:3031-39. © 2017 American Cancer Society.

Reconciling the discrepancies in randomized data of combining immunotherapy and radiation therapy: Not all radiotherapy is created equal.

It remains highly unclear and debatable whether combining radiotherapy (RT) and immune checkpoint blocker (ICB) therapy yields improved outcomes compared to either modality alone. Whereas some randomized data have shown improved outcomes, others have not. As a result of these conflicting data, it is essential to reconcile differences in the data and postulate reasons thereof. This work seeks to address these discrepancies, and uses the lessons learned from both positive and negative trials, including the most cutting-edge data available, in order to guide future clinical trial design and clarify the ideal/expected role of combinatorial therapy going forward. Because RT offers two distinct contributions (cytoreductive (local) effects & immune-stimulating (systemic) effects), RT should complement immunotherapy by addressing immunotherapy-resistant clones, and immunotherapy should complement RT by addressing RT-resistant or out-of-field clones. RT is not merely a single "drug", but rather a constellation of diverse "drugs" that can be varied based on dose regimens, previous systemic therapy regimens, number of irradiated sites, treatment intent/location/timing, tumor biology, and individual patient immunological circumstances. These factors are discussed as an important explanation for the discrepancies in results of various randomized trials in heterogeneous populations and clinical settings, and these discrepancies may continue until trials of more uniform circumstances are designed to use particular RT paradigms that meaningfully add value to systemic therapy.

Intrafraction organ movement in adaptive MR-guided radiotherapy of abdominal lesions - dosimetric impact and how to detect its extent in advance.

INTRODUCTION: Magnetic resonance guided radiotherapy (MRgRT) allows daily adaptation of treatment plans to compensate for positional changes of target volumes and organs at risk (OARs). However, current adaptation times are relatively long and organ movement occurring during the adaptation process might offset the benefit gained by adaptation. The aim of this study was to evaluate the dosimetric impact of these intrafractional changes. Additionally, a method to predict the extent of organ movement before the first treatment was evaluated in order to have the possibility to compensate for them, for example by adding additional margins to OARs. MATERIALS & METHODS: Twenty patients receiving adaptive MRgRT for treatment of abdominal lesions were retrospectively analyzed. Magnetic resonance (MR) images acquired at the start of adaptation and immediately before irradiation were used to calculate adapted and pre-irradiation dose in OARs directly next to the planning target volume. The extent of organ movement was determined on MR images acquired during simulation sessions and adaptive treatments, and their agreement was evaluated. Correlation between the magnitude of organ movement during simulation and the duration of simulation session was analyzed in order to assess whether organ movement might be relevant even if the adaptation process could be accelerated in the future. RESULTS: A significant increase in dose constraint violations was observed from adapted (6.9%) to pre-irradiation (30.2%) dose distributions. Overall, OAR dose increased significantly by 4.3% due to intrafractional organ movement. Median changes in organ position of 7.5 mm (range 1.5-10.5 mm) were detected within a median time of 17.1 min (range 1.6-28.7 min). Good agreement was found between the range of organ movement during simulation and adaptation (66.8%), especially if simulation sessions were longer and multiple MR images were acquired. No correlation was determined between duration of simulation sessions and magnitude of organ movement. CONCLUSION: Intrafractional organ movement can impact dose distributions and lead to violations of OAR tolerance doses, which impairs the benefit of daily on-table plan adaptation. By application of simulation images, the extent of intrafractional organ movement can be predicted, which possibly allows to compensate for them.

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.

Effectiveness of Stereotactic Ablative Radiotherapy for Systemic Therapy Respondents with Inoperable Pulmonary Oligometastases and Oligoprogression.

Stereotactic ablative radiotherapy (SABR) may improve survival in patients with inoperable pulmonary oligometastases. However, the impact of pulmonary oligometastatic status after systemic therapy on SABR outcomes remains unclear. Hence, we investigated the outcomes of SABR in 45 patients with 77 lung tumors and the prognostic value of pulmonary oligoprogression. Eligibility criteria were pulmonary oligometastases (defined as ≤5 metastatic lung tumors), controlled extrapulmonary disease (EPD) after front-line systemic therapy, SABR as primary local treatment for inoperable pulmonary metastases, and consecutive imaging follow-up. Oligometastatic lung tumor was classified into controlled or oligoprogressive status. Overall survival (OS), in-field progression-free survival (IFPFS), out-field progression-free survival (OFPFS), and prognostic variables were evaluated. With 21.8 months median follow-up, the median OS, IFPFS, and OFPFS were 28.3, not reached, and 6.5 months, respectively. Two-year OS, IFPFS, and OFPFS rates were 56.0%, 74.2%, and 17.3%, respectively. Oligoprogressive status (p = 0.003), disease-free interval < 24 months (p = 0.041), and biologically effective dose (BED10) < 100 Gy (p = 0.006) were independently associated with inferior OS. BED10 ≥ 100 Gy (p = 0.029) was independently correlated with longer IFPFS. Oligoprogressive status (p = 0.017) and EPD (p = 0.019) were significantly associated with inferior OFPFS. Grade ≥ 2 radiation pneumonitis occurred in four (8.9%) patients. Conclusively, SABR with BED10 ≥ 100 Gy could provide substantial in-field tumor control and longer OS for systemic therapy respondents with inoperable pulmonary oligometastases. Oligoprogressive lung tumors exhibited a higher risk of out-field treatment failure and shorter OS. Hence, systemic therapy should be tailored for patients with oligoprogression to reduce the risk of out-field treatment failure. However, in the absence of effective systemic therapy, SABR is a reasonable alternative to reduce resistant tumor burden.

Five-year overall survival with ipilimumab and stereotactic ablative radiotherapy for metastatic disease.

PURPOSE: Ipilimumab plus stereotactic ablative radiotherapy (SABR) demonstrate satisfactory short-term clinical benefit and low toxicities in metastatic cancers. Here, we report the 5-year overall survival (OS) rates for patients with metastatic disease treated with this combined-modality therapy in a phase II trial (NCT02239900). METHODS AND MATERIALS: SABR was delivered to patients with metastatic lesions in the liver and lung either during the first dose (concurrent) or 1 week after the second dose (sequential) of ipilimumab (every 3 weeks for 4 cycles). SABR was administered to liver or lung metastases as 50 Gy in 4 fractions or 60 Gy in 10 fractions, considering the tumor location. The OS rates at 12, 36, and 60 months were estimated by the Kaplan-Meier method; subgroup analyses of progression-free survival (PFS) and OS by SABR-targeted lesions (liver/lung) were performed by log-rank tests. RESULTS: A total of 106 patients were enrolled in this long-term follow-up analysis. At the median follow-up time of 15.32 months (range, 0.97-82.13 months), the median PFS was 6.52 months (95% CI, 5.86-7.14) and the median OS was 15.32 months (95% CI,13.03-17.23). The 12-, 36-, and 60-month OS rates were 61%, 23%, and 15%, respectively. There was a significant difference in OS between cohorts (P = 0.039), with a stronger response observed in lung-treated subgroups. Patients who had received sequential fractions (50 Gy/4f) to the lung had improved OS compared to those who had received sequential fractions (18.29 vs 8.9 months, P = 0.043) to the liver. Subgroup analysis of SABR-targeted lesions showed that lung-targeted groups had significantly longer PFS (6.87 months vs. 5.63 months, P = 0.034) and OS (18.67 months vs. 13.63 months, P = 0.013) compared to liver-targeted groups. The sequence did not affect the outcomes of PFS and OS. Exploratory analyses showed that SABR-targeted lesions and smoking history comprised an independent risk factor for OS. CONCLUSIONS: Updated 5-year OS data from the phase II trial demonstrate the long-term clinical benefit of ipilimumab and SABR, which warrants further research and cumulative data.

Treatment-related neuroendocrine prostate cancer managed with partial stereotactic ablative radiotherapy (P-SABR) for long-term survival: a case series.

Background: The amount of treatment-related neuroendocrine prostate cancer (t-NEPC) increases after hormonal therapy, especially novel androgen receptor pathway inhibitors (ARPIs). T-NEPC is considered a hormone refractory [androgen receptor (AR)-negative] subtype of prostate cancer. Although tumors are initially responsive to platinum-based chemotherapy, the drugs are only effective for a short time. Therefore, whether or not local treatment can prolong survival is of great concern. Case Description: In this case series, we discuss 4 t-NEPC cases who were treated with partial stereotactic ablative radiotherapy (P-SABR) for bulky tumors. P-SABR is a radiotherapy regimen that is used in a SABR boost [such as 6 Gy × 4 fractions (f), 8 Gy × 3 f] prior to conventional radiotherapy to enhance the tumor biological effective dose (BED) without increasing the dose to organs at risk. All patients achieved good local control after P-SABR. For patient 1, P-SABR was used for the prostate tumor. After radiotherapy, pathological complete remission (pCR) was achieved, and the prostate lesion remained stable thus far. As of this writing, the patient has been in remission for 3 years after initial t-NEPC diagnosis. Conclusions: We describe 4 cases and indicate that P-SABR is safe and effective in the treatment of a large prostate mass and may prolong the survival of these patients.

Case report: L5 tomita En bloc spondylectomy for oligometastatic liposarcoma with post adjuvant stereotactic ablative radiotherapy.

Introduction: Tomita En-bloc spondylectomy of L5 is one of the most challenging techniques in radical oncological spine surgery. A 42-year-old female was referred with lower back pain and L5 radiculopathy with a background of right shoulder liposarcoma excision. CT-PET confirmed a solitary L5 oligometastasis. MRI showed thecal sac indentation hence wasn't suitable for Stereotactic Ablative Radiotherapy (SABR) alone. The seeding nature of sarcoma prevents the indication of separation surgery hence excisional surgery is considered for radical curative treatment. This case report demonstrates dual-staged modified TES including the utilisation of novel techniques to allow for maximum radical oncological control in the era of SABR and lesser invasive surgery. Methods: First-stage: Carbonfibre pedicle screws planned from L2 to S2AI-Pelvis, aligned, to her patient-specific rods. Radiofrequency ablation of L5 pedicles prior to osteotomy was performed to prevent sarcoma cell seeding. Microscope-assisted thecal sac tumour separation and L5 nerve root dissection was performed. Novel surgical navigation of the ultrasonic bone-cutter assisted inferior L4 and superior S1 endplate osteotomies. Second-stage: Vascular-assisted retroperitoneal approach at L4-S1 was undertaken protecting the great vessels. Completion of osteotomies at L4 and S1 to En-bloc L5: (L4 inferior endplate, L4/5 disc, L5 body, L5/S1 disc and S1 superior endplate). Anterior reconstruction used an expandable PEEK cage obviating the need for a third posterior stage. Reinforced with a patient-specific carbon plate L4-S1 promontory. Results: Patient rehabilitated well and was discharged after 42 days. Cyberknife of 30Gy in 5 fractions was delivered two months post-op. Despite left foot drop, she's walking independently 9 months post-op. Conclusion: These are challenging cases require a truly multi-disciplinary team approach. We share this technique for a dual stage TES and metal-free construct with post adjuvant SABR to achieve maximum local control in spinal oligometastatic disease. This case promotes our modified TES technique in the era of SABR and separation surgery in carefully selected cases.

Incorporating Stereotactic Ablative Radiotherapy into the Multidisciplinary Management of Renal Cell Carcinoma.

Stereotactic ablative radiotherapy (SABR) has challenged the conventional wisdom surrounding the radioresistance of renal cell carcinoma (RCC). In the past decade, there has been a significant accumulation of clinical data to support the safety and efficacy of SABR in RCC. Herein, we review the use of SABR across the spectrum of RCC. We performed an online search of the Pubmed database from January 1990 through April 2023. Studies of SABR/stereotactic radiosurgery targeting primary, extracranial, and intracranial metastatic RCC were included. For SABR in non-metastatic RCC, this includes its use in small renal masses, larger renal masses, and inferior vena cava tumor thrombi. In the metastatic setting, SABR can be used at diagnosis, for oligometastatic and oligoprogressive disease, and for symptomatic reasons. Notably, SABR can be used for both the primary renal tumor and metastasis-directed therapy. Management of RCC is evolving rapidly, and the role that SABR will have in this landscape is being assessed in a number of ongoing prospective clinical trials. The objective of this narrative review is to summarize the evidence corroborating the use of SABR in RCC.

Applications of artificial intelligence in stereotactic body radiation therapy.

This topical review focuses on the applications of artificial intelligence (AI) tools to stereotactic body radiation therapy (SBRT). The high dose per fraction and the limited number of fractions in SBRT require stricter accuracy than standard radiation therapy. The intent of this review is to describe the development and evaluate the possible benefit of AI tools integration into the radiation oncology workflow for SBRT automation. The selected papers were subdivided into four sections, representative of the whole radiotherapy process: 'AI in SBRT target and organs at risk contouring', 'AI in SBRT planning', 'AI during the SBRT delivery', and 'AI for outcome prediction after SBRT'. Each section summarises the challenges, as well as limits and needs for improvement to achieve better integration of AI tools in the clinical workflow.

MR-guided adaptive versus ITV-based stereotactic body radiotherapy for hepatic metastases (MAESTRO): a randomized controlled phase II trial.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is an established local treatment method for patients with hepatic oligometastasis or oligoprogression. Liver metastases often occur in close proximity to radiosensitive organs at risk (OARs). This limits the possibility to apply sufficiently high doses needed for optimal local control. Online MR-guided radiotherapy (oMRgRT) is expected to hold potential to improve hepatic SBRT by offering superior soft-tissue contrast for enhanced target identification as well as the benefit of gating and daily real-time adaptive treatment. The MAESTRO trial therefore aims to assess the potential advantages of adaptive, gated MR-guided SBRT compared to conventional SBRT at a standard linac using an ITV (internal target volume) approach. METHODS: This trial is conducted as a prospective, randomized, three-armed phase II study in 82 patients with hepatic metastases (solid malignant tumor, 1-3 hepatic metastases confirmed by magnetic resonance imaging (MRI), maximum diameter of each metastasis ≤ 5 cm (in case of 3 metastases: sum of diameters ≤ 12 cm), age ≥ 18 years, Karnofsky Performance Score ≥ 60%). If a biologically effective dose (BED) ≥ 100 Gy (α/ß = 10 Gy) is feasible based on ITV-based planning, patients will be randomized to either MRgRT or ITV-based SBRT. If a lesion cannot be treated with a BED ≥ 100 Gy, the patient will be treated with MRgRT at the highest possible dose. Primary endpoint is the non-inferiority of MRgRT at the MRIdian Linac® system compared to ITV-based SBRT regarding hepatobiliary and gastrointestinal toxicity CTCAE III or higher. Secondary outcomes investigated are local, locoregional (intrahepatic) and distant tumor control, progression-free survival, overall survival, possible increase of BED using MRgRT if the BED is limited with ITV-based SBRT, treatment-related toxicity, quality of life, dosimetric parameters of radiotherapy plans as well as morphological and functional changes in MRI. Potential prognostic biomarkers will also be evaluated. DISCUSSION: MRgRT is known to be both highly cost- and labor-intensive. The MAESTRO trial aims to provide randomized, higher-level evidence for the dosimetric and possible consecutive clinical benefit of MR-guided, on-table adaptive and gated SBRT for dose escalation in critically located hepatic metastases adjacent to radiosensitive OARs. TRIAL REGISTRATION: The study has been prospectively registered on August 30th, 2021: Clinicaltrials.gov, "Magnetic Resonance-guided Adaptive Stereotactic Body Radiotherapy for Hepatic Metastases (MAESTRO)", NCT05027711.

Bibliometric Analysis of the Top-Cited Publications and Research Trends for Stereotactic Body Radiotherapy.

OBJECTIVE: This study aims to analyze the 100 most cited papers and research trends on stereotactic body radiotherapy (SBRT). METHODS: We used Web of Science to identify the 100 most frequently cited papers on SBRT on September 29, 2021 and extracted the following data: publication year, source title, country/region, organization, total citations, and average number of citations per year. The research type and research domain were classified independently by the authors. Then we carried out a bibliometric analysis to determine the trends in research on SBRT. RESULTS: These 100 papers were cited a total of 26,540 times, and the median number of citations was 190 (range, 138-1688). "Stereotactic body radiation therapy for inoperable early stage lung cancer" by Timmerman et al. had the highest number of total citations (1688 times). International Journal of Radiation Oncology, Biology, Physics published the largest number of papers (37 papers), followed by Journal of Clinical Oncology (13 papers). The USA contributed the most papers (67 papers), followed by Canada (18 papers). Primary lung cancer (33 papers, 10,683 citations) and oligometastases (30 papers, 7,147 citations) were the most cited research areas. CONCLUSIONS: To the best of our knowledge, this is the first bibliometric analysis of the most frequently cited papers on SBRT. Our results provide insight into the historical development of SBRT and important advances in its application to cancer treatment. Early-stage non-small-cell lung cancer and oligometastases were the most cited research areas in the top 100 publications on SBRT, and SBRT combined with immunotherapy was a hot topic in the past few years. This study is helpful for researchers to identify the most influential papers and current research hotspots on SBRT.

Stereotactic body radiotherapy to treat breast cancer oligometastases: A systematic review with meta-analysis.

OBJECTIVES: Stereotactic ablative radiotherapy (SABR) has been reported to be an effective treatment for oligometastatic disease from different primary cancer sites. Here we assess the effectiveness and safety of SABR for oligometastatic breast cancer patients by performing a meta-analysis. METHODS: Following PRISMA and MOOSE guidelines, a systematic review and meta-analysis was performed. Eligible studies were identified on Medline, Embase, Cochrane Library, and annual meetings proceedings from 1990 to June 2021. A meta-regression analysis was performed to assess if there was a correlation between moderator variables and outcomes, and a p-value <0.05 was considered significant. RESULTS: Ten studies met criteria for inclusion, comprising 467 patients and 653 treated metastases. The 1- and 2-year local control rates were 97% (95% CI 95-99%), and 90% (95% CI 84-94%), respectively. Overall survival (OS) was 93% (95% CI 89-96%) at 1 year, 81% (95% CI 72-88%) at 2 years. The rate of any grade 2 or 3 toxicity was 4.1 % (95% CI 0.1-5%), and 0.7% (0-1%), respectively. In the meta-regression analysis, only prospective design (p = 0.001) and bone-only metastases (p = 0.01) were significantly associated with better OS. In the subgroup analysis, the OS at 2y were significantly different comparing HER2+, HR+/HER2(-) and triple negative breast cancer 100%, 86% and 32%, p = 0.001. For local control outcomes, hormone receptor status (p = 0.01) was significantly associated on meta-regression analysis. CONCLUSION: SABR for oligometastatic breast cancer is safe and associated with high rates of local control. Longer follow-up of existing data and ongoing prospective trials will help further define the role of this management strategy.

A review of ongoing trials of stereotactic ablative radiotherapy for oligometastatic disease in the context of new consensus definitions.

The characterization and treatment of oligometastatic disease (OMD) are rapidly growing areas of research. Consensus statements have recently been developed by European Society for Radiotherapy and Oncology (ESTRO)/American Society for Radiation Oncology (ASTRO) and ESTRO/European Organization for Research and Treatment of Cancer (EORTC) in an effort to harmonize terminology describing OMD. The purpose of this study was to assess patient populations eligible for ongoing clinical trials evaluating stereotactic ablative radiotherapy (SABR) in OMD in the context of key definitions from both statements. Using the clinicaltrials.gov database, a search of ongoing OMD clinical trials evaluating the use of SABR was performed from inception to January 2020, using the keywords "oligometastasis", "stereotactic radiotherapy", and related terms. Results were independently reviewed by two investigators, with discrepancies settled by a third. Information from these trials including study design, population criteria, and primary endpoints were extracted. OMD was defined in general as a limited number of metastases that could be safely treated with metastasis-directed therapy. States of OMD were broadly categorized into de novo, repeat, and induced, with synchronous and metachronous being subsets of de novo. The initial search strategy identified 293 trials, of which 85 met our eligibility criteria. Phase II trials were by far the most common (n=46, 52%). Most trials had a single treatment arm (n=43, 51%), and 31 (36%) were randomized. The majority of trials (n=65, 76%) had populations that included all three subsets of OMD. Notably, 70 trials (82%) also included oligoprogressive disease, which is debatably a distinct entity from OMD. Progression-free survival was the most common primary endpoint (n=31, 36%), followed by local control (n=17, 20%), toxicity (n=14, 16%) and overall survival (n=7, 8%). Although the use of SABR for OMD is an active area of prospective clinical trial research, ongoing studies include mixed populations as defined by new consensus statements. Therefore, the applicability of results from these trials should be considered within relevant OMD scenarios.

Systematic review of stereotactic body radiotherapy in stage III non-small cell lung cancer.

Despite adequate treatment, 50% of stage III locally advanced inoperable non-small cell lung cancer (NSCLC) patients have a locoregional relapse. Local control on early stages on the contrary, is as high as 85-90% with stereotactic body radiotherapy (SBRT). The addition of SBRT to conventional chemoradiation or its use in monotherapy in stage III NSCLC is a novel strategy to decrease local failure that has been explored by various authors. This is a systematic review of studies using SBRT in inoperable stage III NSCLC. Search results obtained 141 articles of which only 6 original studies were pointed as relevant. Three of these studies were prospective, of which 2 were phase I dose-scalation studies and remaining 3 were retrospective. In summary, SBRT outcomes on 134 patients were included. Median dose in the SBRT treatment was 22.5 Gy in 2 to 7 fractions. Obtained global toxicity was 3.7% grade 5 and 14.17% grade 3. Dose-escalation studies proposed a 2 fraction SBRT schedule of 20-24 Gy, obtaining a 78% local control rate at 1 year and an OS of 67%. Initial improvement in local control with this innovative therapeutic strategy has led to ongoing phase II and III clinical trials that will evaluate the efficiency of SBRT in stage III NSCLC clinical scenario.