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Simple Summary: Stereotactic body radiotherapy (SBRT) is a treatment technique that delivers higher doses of conformal radiation precisely to specific targets. SBRT is utilized for the treatment of the more common cancers such as lung, liver and prostate malignancies, both in the early stage and the oligometastatic setting. The aim of this review is to highlight the current role of SBRT for renal cell carcinoma (RCC), a disease which was previously thought to be radioresistant, particularly to conventionally fractionated radiotherapy. There is now an increasing body of literature encompassing published phase II trials, reviews and meta-analyses demonstrating the effectiveness of SBRT in both early-stage RCC (as an alternative to patients who are not surgical candidates) and within the context of metastasis-directed therapy (MDT) for patients with oligometastatic and oligoprogressive RCC. Ongoing randomized trials are also exploring the role of SBRT as a cytoreductive treatment in metastatic RCC. Renal cell carcinoma (RCC) has been increasing in incidence by around 1.5% per year for several years. However, the mortality rate has been decreasing by 1.6% per year, and this can be attributed to stage migration and improvements in treatment. One treatment modality that has emerged in recent years is stereotactic body radiotherapy (SBRT), which is an advanced radiotherapy technique that allows the delivery of high-dose radiation to the tumor while minimizing doses to the organs at risk. SBRT has developed a role in the treatment of early-stage, oligometastatic and oligoprogressive RCC. In localized disease, phase II trials and meta-analyses have shown that SBRT provides a very high probability of long-term local control with a low risk of severe late toxicity. In oligometastatic (OMD) RCC, the same level of evidence has similarly shown good local control and minimal toxicity. SBRT could also delay the necessity to start or switch systemic treatments. Medical societies have started to incorporate SBRT in their guidelines in the treatment of localized disease and OMD. A possible future role of SBRT involves cytoreduction. It is theorized that SBRT can lower tumor burden and enhance immune-related response, but it cannot be recommended until the results of the phase II trials are published. [ABSTRACT FROM AUTHOR]

There is increasing interest in using stereotactic body radiation therapy (SBRT) in areas of oligoprogressive metastatic disease (OPD). Our main objective was to investigate the impact of SBRT on overall survival (OS) and the incidence of systemic therapy treatment switches in this population. A retrospective institutional review of patients treated with SBRT for OPD was performed. Patients were included if they received SBRT for 1–3 discrete progressing metastases, using a dose of at least 5 Gy per fraction. The study aimed to calculate progression-free survival (PFS), overall survival (OS), local control (LC), and incidence of treatment switch (TS). PFS and OS were calculated using the Kaplan–Meier methodology, while LC and TS were determined using cumulative incidence. Eighty-one patients with a total of 118 lesions were treated with SBRT from July 2014 to November 2020. The Median SBRT dose was 40 (18–60) Gy in 5 (2–8) fractions. Patients had primarily kidney, lung, or breast cancer. Most patients were treated with a tyrosine kinase inhibitor (TKI) (30.9%) or chemotherapy (29.6%) before OPD. The median follow-up post-SBRT was 14 months. Median OS and PFS were 25.1 (95% CI 11.2–39.1) months and 7.8 (95% CI 4.6–10.9) months, respectively. The cumulative incidence of local progression of treated lesions was 5% at 1 year and 7.3% at 2 years. Sixty patients progressed after SBRT and 17 underwent additional SBRT. Thirty-eight patients (47%) changed systemic therapy following SBRT; the cumulative incidence of TS was 28.5% at 6 months, 37.4% at 1 year, and 43.9% at 2 years. SBRT effectively controls locally progressing lesions but distant progression still occurs frequently. A sizeable number of patients can be salvaged by further SBRT or have minimally progressing diseases that may not warrant an immediate initiation/switch in systemic therapy. Further prospective studies are needed to validate this benefit. [ABSTRACT FROM AUTHOR]

While pulmonary metastases are often managed through metastasectomies, stereotactic body radiation therapy (SBRT) is a relatively novel treatment that has shown promise for this disease. This review aimed to summarize the current findings of SBRT in the treatment of pulmonary metastases. MEDLINE, EMBASE, and CENTRAL were searched for articles that examined the use of SBRT for patients with pulmonary metastases. Primary outcomes included overall survival, disease‐free survival, and progression‐free survival. Results were pooled where appropriate. Risk of bias was assessed through the Methodological Index for Non‐Randomized Studies tool. After screening, 13 studies with 545 patients conducted between 2006 and 2020 were included in this review. Primary tumor localizations included gastrointestinal, pulmonary, and bone, among others. Pooled overall survival at 1 year was 81%, 41% at 3 years, 34% at 4 years, and 26% at 5 years. Pooled progression‐free survival at 1, 2, and 3 years was 60%, 41%, and 31% respectively. Local control at 1, 2, and 3 years were 90%, 79%, and 77%, respectively. Preliminary evidence regarding SBRT for treatment of pulmonary metastases shows promising benefits for overall survival and local control. Further high‐quality prospective trials are required to investigate the effectiveness and treatment‐related adverse effects of SBRT, and should compare it with metastasectomy. [ABSTRACT FROM AUTHOR]

Background: Stereotactic ablative radiotherapy (SABR) is a safe and effective modality in patients with liver cancer who are ineligible for other local therapies. However SABR is not current standard of practice and requires further validation. Patient reported quality of life (QOL) is key to this validation, yet no systematic reviews to date have been performed to analyse QOL following liver SABR. QOL is a critical part of therapy evaluation, particularly in disease states with short life expectancy. The purpose of this study was to conduct a systematic review of QOL outcomes for liver SABR.Materials and Methods: MEDLINE and EMBASE databases from 1996 to October 2015 were queried to obtain English language studies analysing QOL following liver SABR. Included studies described patient-reported QOL as either a primary or secondary endpoint, and analysed QOL change over time. Studies were screened, and relevant data were abstracted and analysed.Results: Of 2181 initially screened studies, 5 met all inclusion criteria. Extracted studies included a total of 392 eligible patients with hepatocellular carcinoma, liver metastases and intrahepatic cholangiocarcinoma. Four studies were prospective in design, and only one study was a conference abstract. Extracted studies were heterogeneous in dose prescription used (11-70 Gy in 3-30 fractions), in addition to reported QOL metrics (EORTC QLQ C-15 PAL,/C-30/LM-21, EuroQol 5D, FACT-Hep, FLIC) and final endpoints (range 6 weeks to 12 months). Despite this there were few statistically significant declines in QOL scores following SABR. Four studies demonstrated transient fatigue in the first 1-4 weeks, while 2 studies showed transient worsening of appetite at 1 month. In all but one instance (loss of appetite at 6 weeks), levels returned to insignificant difference baseline by the final endpoints. All studies showed no significant QOL decline in any domain at their respective endpoints. In studies with overlapping QOL tools, estimates of 3-month post SABR global QOL were similar.Conclusion: Results of this systematic review demonstrate well-preserved post liver SABR QOL. These findings strengthen the argument for liver SABR, and should aim to support future comparative effectiveness trials with other local modalities including surgery, chemoembolization and radiofrequency ablation, with a focus on QOL outcomes as an important endpoint. [ABSTRACT FROM AUTHOR]

Stereotactic body radiotherapy (SBRT) is a highly ablative local therapy which has emerged as part of the treatment paradigm for patients with oligometastatic (OM) breast cancer (defined by 5 or fewer sites). This patient group has demonstrated improved prognosis in some cases and may therefore, benefit from aggressive local treatment. The role of upfront SBRT in newly diagnosed OM breast cancer in addition to systemic therapy is not clear, yet it is being increasingly utilized within the oncology community. The Canadian medical system is an ideal platform in which to investigate SBRT into the OM breast cancer setting, as it is not routinely implemented across centers at this time, as there is potential for robust collaboration between oncologists in the small community to investigate SBRT, and there is limited financial or industry motivation for early SBRT uptake compared with other countries. It is critical therefore to define the optimal patient population and scenarios for which SBRT should be investigated, as well as offered in the interim to Canadian patients. We therefore conducted a survey of Canadian Medical Oncologists, the primary physicians and gatekeepers of patients with OM breast cancer, to characterize their beliefs, opinions, and areas of controversy in the use of SBRT for OM breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether the accumulated dose using image guided radiation therapy is a stronger predictor of clinical outcomes than the planned dose in stereotactic body radiation therapy (SBRT) for liver metastases.Methods and Materials: From 2003 to 2009, 81 patients with 142 metastases were treated in institutional review board-approved SBRT studies (5-10 fractions). Patients were treated during free breathing (with or without abdominal compression) or with controlled exhale breath-holding. SBRT was planned on a static exhale computed tomography (CT) scan, and the minimum planning target volume dose to 0.5 cm(3) (minPTV) was recorded. The accumulated minimum dose to the 0.5 cm(3) gross tumor volume (accGTV) was calculated after performing dose accumulation from exported image guided radiation therapy data sets registered to the planning CT using rigid (2-dimensional MV/kV orthogonal) or deformable (3-dimensional/4-dimensional cone beam CT) image registration. Univariate and multivariate Cox regression models assessed the factors influencing the time to local progression (TTLP). Hazard ratios for accGTV and minPTV were compared using model goodness-of-fit and bootstrapping.Results: Overall, the accGTV dose exceeded the minPTV dose in 98% of the lesions. For 5 to 6 fractions, accGTV doses of >45 Gy were associated with 1-year local control of 86%. On univariate analysis, the cancer subtype (breast), smaller tumor volume, and increased dose were significant predictors for improved TTLP. The dose and volume were uncorrelated; the accGTV dose and minPTV dose were correlated and were tested separately on multivariate models. Breast cancer subtype, accGTV dose (P<.001), and minPTV dose (P=.02) retained significance in the multivariate models. The univariate hazard ratio for TTLP for 5-Gy increases in accGTV versus minPTV was 0.67 versus 0.74 (all patients; 95% confidence interval of difference 0.03-0.14). Goodness-of-fit testing confirmed the accGTV dose as a stronger dose-response predictor than the minPTV dose.Conclusions: The accGTV dose is a better predictor of TTLP than the minPTV dose for liver metastasis SBRT. The use of modern image guided radiation therapy in future analyses of dose-response outcomes should increase the concordance between the planned and delivered doses. [ABSTRACT FROM AUTHOR]

BACKGROUND: This study was undertaken to determine outcomes of stereotactic body radiotherapy for colorectal liver metastases in a pooled patient cohort. METHODS: Patients with colorectal liver metastases from 3 institutions were included if they had 1 to 4 lesions, received 1 to 6 fractions of stereotactic body radiotherapy, and had radiologic imaging ≥3 months post-treatment. Sixty-five patients with 102 lesions treated from August 2003 to May 2009 were retrospectively analyzed. A tumor control probability (TCP) model was used to estimate the 3-fraction dose required for >90% local control after converting the schedule into biologically equivalent dose (BED), single-fraction equivalent dose, or linear quadratic model-based single-fraction dose. RESULTS: Forty-seven (72%) patients had ≥1 chemotherapy regimen before stereotactic body radiotherapy, and 27 (42%) patients had ≥2 regimens. The median follow-up was 1.2 years (range, 0.3-5.2 years). The median dose was 42 gray (Gy; range, 22-60 Gy). When evaluated separately by multivariate analysis, total dose ( P = .0015), dose/fraction ( P = .003), and BED ( P = .004) all correlated with local control by lesion. On multivariate analysis, nonactive extrahepatic disease was associated with overall survival (OS; P = .046), and sustained local control was closely correlated ( P = .06). By using single-fraction equivalent dose, BED, or linear quadratic model-based single-fraction dose in the TCP model, the estimated dose range needed for 1-year local control >90% is 46 to 52 Gy in 3 fractions. CONCLUSIONS: Liver stereotactic body radiotherapy is well tolerated and effective for colorectal liver metastases. The strong correlation between local control and OS supports controlling hepatic disease even for heavily pretreated patients. For a 3-fraction regimen of stereotactic body radiotherapy, a prescription dose of ≥48 Gy should be considered, if normal tissue constraints allow. Cancer 2011. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Stereotactic ablative radiotherapy (SABR) has emerged as a new treatment option for patients with oligometastatic disease. SABR delivers precise, high-dose, hypofractionated radiotherapy, and achieves excellent rates of local control for primary tumors or metastases. A recent randomized phase II trial evaluated SABR in a group of patients with a small burden of oligometastatic disease (mostly with 1-3 metastatic lesions), and found that SABR was associated with benefits in progression-free survival and overall survival. The goal of this phase III trial is to assess the impact of SABR in patients with 4-10 metastatic cancer lesions.Methods: One hundred and fifty-nine patients will be randomized in a 1:2 ratio between the control arm (consisting of standard of care palliative-intent treatments), and the SABR arm (consisting of standard of care treatment + SABR to all sites of known disease). Randomization will be stratified by two factors: histology (Group 1: prostate, breast, or renal; Group 2: all others), and type of pre-specified systemic therapy (Group 1: immunotherapy/targeted; Group 2: cytotoxic; Group 3: observation). SABR is to be completed within 2 weeks, allowing for rapid initiation of systemic therapy. Recommended SABR doses are 20 Gy in 1 fraction, 30 Gy in 3 fractions, or 35 Gy in 5 fractions, chosen to minimize risks of toxicity. The primary endpoint is overall survival, and secondary endpoints include progression-free survival, time to development of new metastatic lesions, quality of life, and toxicity. Translational endpoints include assessment of circulating tumor cells, cell-free DNA, and tumor tissue as prognostic and predictive markers, including assessment of immunological predictors of response and long-term survival.Discussion: This study will provide an assessment of the impact of SABR on clinical outcomes and quality of life, to determine if long-term survival can be achieved for selected patients with 4-10 oligometastatic lesions.Trial Registration: Clinicaltrials.gov identifier: NCT03721341 . Date of registration: October 26, 2018. [ABSTRACT FROM AUTHOR]