Safety Of Stereotactic Ablative Radiotherapy Research Articles

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

IntroductionTo 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 MethodsIn 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. ResultsA 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 %). ConclusionPromising 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.

Efficacy of stereotactic ablative radiotherapy in patients with oligometastatic hepatocellular carcinoma: A phase II study

Stereotactic ablative radiotherapy (SABR) can extend survival and offers the potential for cure in some patients with oligometastatic disease (OMD). However, limited evidence exists regarding its use in oligometastatic hepatocellular carcinoma (HCC). We aimed to prospectively investigate the efficacy and safety of SABR in patients with oligometastatic HCC. We enrolled patients with controlled primary HCC and one to five metastatic lesions amenable to SABR. The primary endpoint was treatment efficacy defined as overall survival (OS) and progression-free survival (PFS). The secondary endpoints included time to local progression, objective response rate, disease control rate, toxicities, and quality of life (QOL), assessed using the EORTC QLQ-C30 before, and 0, 1, and 3 months after SABR. Overall, 40 consecutive patients received SABR on 62 lesions between 2021 and 2022. The most common locations for OMD were the lungs (48.4%), lymph nodes (22.6%), and bone (17.7%). After a median follow-up of 15.5 months, the 2-year OS was 80%. Median PFS was 5.3 months, with 1- and 2-year PFS rates of 21.2% and 0%, respectively. A shorter time to OMD from the controlled primary independently correlated with PFS (p= 0.039, hazard ratio 2.127) alongside age, Child-Pugh class, and alpha-fetoprotein (p= 0.002, 0.004, 0.019, respectively). The 2-year time to local progression, objective response rate, and disease control rate were 91.1%, 75.8%, and 98.4%, respectively. Overall, 10% of patients experienced acute toxicity, and 7.5% experienced late toxicity, with no grade 3+ toxicity. All QOL scores remained stable, whereas the patients without systemic treatments had improved insomnia and social functioning scores. SABR is an effective and feasible option for oligometastatic HCC that leads to excellent local tumor control and improves survival without adversely affecting QOL. Stereotactic ablative radiotherapy (SABR) is a non-invasive treatment approach capable of efficiently ablating the target lesion; however, neither the oligometastatic disease concept nor the potential benefits of SABR have been well-defined in hepatocellular carcinoma (HCC). According to this study, SABR is an effective and safe treatment option for oligometastatic HCC, yielding excellent local tumor control and survival improvement without worsening patients' quality of life, regardless of tumor sites. We also demonstrated that patients with a later presentation of OMD from the controlled primary and lower alpha-fetoprotein levels achieved better survival outcomes. This is the first prospective study of SABR in oligometastatic HCC, providing insights for the development of novel strategies to improve oncologic outcomes. NCT05173610.

Polymetastatic Recurrence-Free Survival in Patients with Repeat Oligometastases on the SABR-5 Trial

To determine polymetastatic recurrence-free survival (PMRFS) in patients with repeat oligometastases (OM) on the SABR-5 trial. SABR-5 is a prospective, multi-center trial that evaluated the safety of stereotactic ablative radiotherapy (SABR) in patients with 1-5 OM or oligoprogressive lesions. On SABR-5, patients were followed post-SABR according to standardized protocols. Patients with repeat extra-cranial OM after metastasis-directed therapy (MDT; SABR, surgery, or thermoablation) to all initial OM (including those treated before enrolment on SABR-5) were identified. Exclusion criteria included history of multiple primary malignancies and incomplete re-staging. PMRFS was defined as time from presentation of repeat oligometastases to death or presentation of 6 or more progressing metastases, leptomeningeal metastases, lymphangitic carcinomatosis, malignant ascites, or malignant pleural effusion. PMRFS, overall survival (OS), and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Seventy-six patients with repeat OM were included, of which 44 (58%) received second MDT to all OM. The most common histology in patients who received second MDT was colorectal cancer (10/44 [23%]) and in those who did not was prostate cancer (17/32 [53%]). Patients who did vs. did not receive second MDT had fewer metastases at repeat OM (mean 1.3 vs 2.2; p<0.001) and no difference in time between initial OM and repeat OM (16 vs. 17 months; p = 0.74). For patients who received second MDT, median follow-up from presentation of repeat OM was 2.6 years. Median PFS after first and second MDT were 15 months (95% CI 11-18) and 11 months (95% CI 7-17), respectively. At last follow-up, 22/44 patients (50%) were alive without polymetastatic recurrence. 3-year PMRFS and OS from presentation of repeat OM were 51% (95% CI 33-66%) and 66% (95% CI 47-79%), respectively. Patients presenting with repeat OM after MDT may still have favorable 3-year PMRFS and OS, which may justify exploring aggressive local treatments in this subpopulation. Further randomized trials in this space are needed.

Stereotactic Ablative Radiotherapy Boost to Bladder Tumor for Bladder Preservation in Patients with Muscle-Invasive Bladder Cancer

Previous studies showed that selective bladder-sparing approach using TMT is an established therapy of MIBC with outcomes that are comparable to those of radical cystectomy. However, it has been shown that the 5-year local recurrence in the bladder is greater than 40% after TMT. One of the possible reasons was that the RT dose to the bladder tumor or tumor bed was insufficient. Thus, we assessed the effectiveness and safety of Stereotactic Ablative Radiotherapy (SABR) boost to bladder tumor or tumor bed for patients with muscle invasive bladder cancer (MIBC). A total of 59 consecutive patients with cT2-4 bladder cancer underwent transurethral resection of bladder tumor (TURBT). TURBT was visibly complete in 25 cases. Patients received SABR to the tumor or tumor bed in the bladder followed by conventionally fractionated RT (CFRT) to pelvis and total bladder with concomitant weekly radio-sensitizing chemotherapy. During SABR intravesical installation of isovolumetric saline through urinary catheter ensured adequate bladder filling. Response rate was assessed by cystoscopic evaluation and pelvic MRI or CT. Toxicities were reported per the RTOG acute and late Radiation Morbidity Scoring Schema. The median age of all patients was 76 years (35-90 years). All patients completed SBRT boost and 61% patients received concurrent Gemcitabine chemotherapy. After a median follow-up time of 28 months, the rate of local control (LC) at 3 years was 90.0%. The overall survival (OS) and cancer-specific survival (CSS) rates at 3 years were 61.6% and 77.5%, respectively. Of the surviving patients, 84.4% have a disease-free and functioning bladder. Acute grade 3 gastrointestinal (GI) or genitourinary (GU) toxicities occurred in only 1.7% of the patients. Late grade 3 GU toxicity occurred in 5.1% of the patients. No patients experienced grade 4 GI or GU toxicities. SABR boost followed by chemoradiation to the pelvis was found to be a well-tolerated and effective treatment for MIBC patients who are either not candidates for cystectomy or who desire bladder preservation. Randomized study is required to further evaluate this novel tri-modality treatment paradigm.

Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis

We evaluated the effectiveness and safety of stereotactic ablative radiotherapy (SABR) delivered using Cyberknife in patients with stage I non-small-cell lung cancer. The clinical results of 153 patients with 161 lung cancers treated with CyberKnife between May 2014 and August 2020 at the Osaka University Hospital were retrospectively analyzed. The median age was 80 years (range=48-99 years). Nine patients (5.6%) had interstitial pneumonia. The median radiation dose was 52 Gy (range=40-70 Gy) in 4-10 fractions, and the median follow-up extended to 21.4 months (range=0-68.9 months). The 2-year local control, progression-free, and overall survival rates were 91.9%, 61.7%, and 84.8%, respectively. Toxicities of grade ≥3 were observed in 13 (8.1%) patients; one patient with interstitial pneumonia developed grade 5 radiation pneumonitis and one patient developed grade 5 bronchopulmonary hemorrhage. In patients with stage I non-small-cell lung cancer, SABR using Cyberknife was effective with acceptable toxicity.

Ablative radiation therapy to restrain everything safely treatable (ARREST): study protocol for a phase I trial treating polymetastatic cancer with stereotactic radiotherapy

BackgroundPatients with polymetastatic cancer are most often treated with systemic therapy to improve overall survival and/or delay progression, with palliative radiotherapy reserved for sites of symptomatic disease. Stereotactic ablative radiotherapy (SABR) has shown promise in the treatment of oligometastatic disease, but the utility of SABR in treating all sites of polymetastatic disease has yet to be evaluated. This study aims to evaluate the maximally tolerated dose (MTD) of SABR in patients with polymetastatic disease.MethodsUp to 48 patients with polymetastatic cancer (> 10 sites) will be enrolled on this phase I, modified 3 + 3 design trial. Eligible patients will have exhausted (or refused) standard systemic therapy options. SABR will be delivered as an escalating number of weekly fractions of 6 Gy, starting at 6 Gy × 2 weekly fractions (dose level 1). The highest dose level (dose level 4) will be 6 Gy × 5 weekly fractions. Feasibility and safety of SABR will be evaluated 6 weeks following treatment using a composite endpoint of successfully completing treatment as well as toxicity outcomes.DiscussionThis study will be the first to explore delivering SABR in patients with polymetastatic disease. SABR will be planned using the guiding principles of: strict adherence to dose constraints, minimization of treatment burden, and minimization of toxicity. As this represents a novel use of radiotherapy, our phase I study will allow for careful selection of the MTD for exploration in future studies.Trial registrationThis trial was prospectively registered in ClinicalTrials.gov as NCT04530513 on August 28, 2020.

Synergistic Effect Of Stereotactic Ablative Radiotherapy And Immunotherapy With A Xenogeneic Fibroblast Activation Protein-Based Whole Cell Tumor Vaccine

Immunotherapies has revolutionized the treatment approach of patients with metastatic cancer, although response rates to such therapies when given alone are disappointingly limited in the majority. Stereotactic ablative radiotherapy (SABR) increases immunogenic cell death, boosts priming of APCs, activates effector T-cell responses, and serves as an ideal partner of immunotherapy. Accounting for a large proportion of cells in the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs), along with their products such as fibroblast activation protein-α (FAPα), greatly affect tumor development and treatment resistance, which make them promising targets for immunotherapy. Therefore, the application of immunotherapy targeting CAFs combined with SABR may have a synergistic effect. We previously reported a xenogeneic FAPα-based whole cell tumor vaccine (WCTV) enhance specific antitumor responses to fight cancer cells and CAFs. This study aimed to test the efficacy and safety of SABR in combination with xenogeneic FAPα-based WCTV. In the present study, we firstly compare the different radiation schemes with a same biologically effective dose, the timing and sequence of the association of irradiation and FAPα-based WCTV in mouse LLC Lewis lung cancer model to investigate the optimal protocol. Mice were monitored for tumor growth, survival and gross measures of health. With the use of mouse H22 liver and 4T1 breast cancer models, we then tested the antitumor effect, safety and anti-fibrosis effect of the optimal combination protocol. The potential immune mechanisms were investigated through adoptive immunotherapy and 51Cr release assay. The distributions of the immune cells in the TME were detected by immunohistochemical staining and flow cytometry. SABR was dramatically more effective with 3x8Gy compared to 1×16.4Gy when associated with FAPα-based WCTV, and the best anti-tumor effect was observed in the group of mice started the vaccination on the 7th day after the last irradiation. No obvious side effects were detected following treatment. Tumor-infiltrating lymphocytes (TILs) ratio increased and products of CAF, such as FAPα, α-SMA and collagen I expression decreased in the tumor tissue. further investigation showed that the anti-tumor effect involves cellular and humoral immune responses. In the combination treatment group, T cells obtained from mice showed higher cytotoxicity against cancer cells and CAFs, and autoantibodies against FAPα were detected in the sera. These findings indicate combination of SABR and xenogeneic FAPα-based WCTV can weaken CAFs-mediated immune suppression, interstitial fibrosis and treatment tolerance to effectively inhabit tumor growth and reduce side effects. This study innovatively associates radiation therapy, anti-fibrosis therapy with immunotherapy, and provide new ideas for developing new treatment strategies for patients with multiple epithelial cancers.

Stereotactic ablative radiotherapy for early-stage lung cancer following double lung transplantation

BackgroundDevelopment of primary lung cancer in donor lung post-lung transplantation is very rare, with few described cases. The safety of stereotactic ablative radiotherapy (SABR) for early-stage lung cancer arising from donor lung is unclear.Case presentationHerein, we present a case of a patient with a Stage IB adenocarcinoma arising from donor lung 8 years post-double lung transplantation, which was performed due to advanced emphysema. The patient was ineligible for surgical management due to chronic lung allograft dysfunction, which significantly compromised pulmonary function. Full dose SABR was delivered with curative intent after a discussion with the patient. The patient tolerated the treatment well, with one episode of subacute toxicity that resolved with treatment. There was no evidence of recurrence at 15 months post-treatment and the patient’s pulmonary function did not deviate from the pre-SABR baseline.ConclusionsSABR appears feasible for medically-inoperable early-stage primary lung adenocarcinoma in the setting of previous double-lung transplantation.

Safety and feasibility of prostate stereotactic ablative radiotherapy using multimodality imaging and flattening filter free.

To investigate feasibility and safety of stereotactic ablative radiotherapy in the management of prostate cancer while employing MR/CT fusion for delineation, fiducial marker seeds for positioning and Varian RapidArc with flattening filter free (FFF) delivery. 41 patients were treated for low-intermediate risk prostate cancer with initial prostate-specific antigen of ≤20 ng ml-1, Gleason score 6-7. Patients had MR/CT fusion for delineation of prostate ±seminal vesicles. CT/MR fusion images were used for delineation and planned using flattening filter free modality. Verification on treatment was cone beam CT imaging with fiducial markers for matching. Patients had Radiation Therapy Oncology Group scoring for genitourinary and gastointestinal symptoms at baseline, week 4, 10 and 18. Clinically acceptable plans were achieved for all patients, all plans achieved the objective clinical target volume D99% ≥ 95%, and for planning target volume D95% ≥ 95%. Rectum dose constraints were met for 95.1% for V18 Gy ≤ 35%, 80% V28 Gy ≤ 10%. A total of 32 (78.0%) plans achieved all rectum dose constraints. Grade 1 acute genitourinary symptoms were 53.7% of patients at baseline, 90.2% [95% CI (76.8-97.3%)] (p = 0.0005) at treatment 5, falling to 78.0% (62.4-89.4%) at week 4, and 75.0% (58.8-87.3%) by week 10 and 52.5% (36.1-68.5%) (p = 1.00) at week 18. Acute gastrointestinal symptoms were 5% at baseline, 46.3% [95% CI (30.7-62.6%)] at treatment 5, week 4 43.9% [95% CI (28.5-60.3%)], week 10 25.0% (11.1-42.3%), and declined slightly by week 18 [-20.095% CI (12.7-41.2)] p = 0.039. Overall 75.6% (31/41) of patients experienced Grade 1-2 toxicity during or after treatment. This planning and delivery technique is feasible, safe and efficient. A homogeneous dose can be delivered to prostate with confidence, whilst limiting high dose to nearby structures. The use of this technology can be applied safely within further randomized study protocols. Advances in knowledge: Multimodality imaging for delineation and linac-based image-guided RT with FFF for the treatment of prostate stereotactic ablative radiotherapy.

Stereotactic ablative radiotherapy for patients with unresectable or medically inoperable cholangiocarcinoma.

The role of stereotactic ablative radiotherapy (SABR) in patients with unresectable or medically inoperable cholangiocarcinoma remains unclear. We examined the efficacy and safety of SABR in this group of patients. From January 2008 to December 2014, 15 patients with 17 lesions were included in this study. The lesions included 14 intrahepatic, 1 hilar, and 2 distal bile duct tumors. Three patients were classified as medically inoperable because of old age or multiple comorbidities. Tumors measured 0.8-13 cm (median, 3.6 cm). The median prescribed dose was 45 Gy delivered in 5 fractions over 5 consecutive days. The median follow-up period for surviving patients was 29.9 months. Objective responses were observed for 10 of 17 tumors (58.8%), including 3 complete responses (17.6%). The median survival duration was 12.6 months, and the 1- and 2-year overall survival rates were 50.3% and 14.4%, respectively. The 1- and 2-year in-field failure-free rates were 61.5% and 30.8%, respectively. For patients with biologically effective doses (BEDs) exceeding 75 Gy10, the 1- and 2-year overall survival rates were 58.3% and 33.3%, respectively, compared to 20.0% and 0%, respectively for those with BEDs lower than 75 Gy10. Radiation-induced liver disease did not develop in any patient. Acute toxicities were generally mild and tolerable. Stereotactic ablative radiotherapy could be an alternative treatment for unresectable or medically inoperable cholangiocarcinoma. Further dose escalation may be considered to optimize local control.

Stereotactic ablative radiotherapy with CyberKnife in the treatment of locally advanced prostate cancer: preliminary results.

Recent clinical reports of stereotactic ablative radiotherapy (SABR) in the treatment of low-risk prostate cancer have been encouraging. Our study evaluates the efficacy and safety of SABR using the CyberKnife system for treating intermediate- to very-high-risk prostate cancer. Between May 2010 and June 2013, 31 patients (15 intermediate risk, 14 high risk, and 2 very high risk) without pelvic lymph node metastasis were enrolled retrospectively. The treatment consisted of 37.5 Gy in 5 fractions over 1-2 weeks using CyberKnife SABR. Twenty-five patients (81%) received androgen deprivation therapy (ADT). Biochemical failure was defined using the nadir + 2 criterion. Toxicity was assessed with the Common Terminology Criteria of Adverse Events (version 4). The median follow-up was 36 months (range 7-58 months). The median pretreatment prostate--pecific antigen (PSA) was 13.5 ng/mL (range 4.5-124.0 ng/mL). The median PSA decreased to 0.09 ng/mL (range &lt;0.04-5.38 ng/mL) and 0.12 ng/mL (range &lt;0.04-2.63 ng/mL) at 6 months and 12 months after SABR, respectively. The 3-year biochemical relapse-free survival was 90.2% for all patients, 100% for the intermediate-risk patients, and 82% for the high- and very-high-risk patients (p = 0.186). No patient experienced ≥ grade 3 toxicity. There were 7 acute and 5 late grade 2 genitourinary toxicities and 1 acute and no late grade 2 gastrointestinal toxicity. Our preliminary results support that CyberKnife SABR with ADT is safe and feasible in patients with intermediate- to high-risk prostate cancer. A further large-scale clinical trial with longer follow-up is warranted.

Efficacy and safety of stereotactic ablative radiotherapy in patients with previous pneumonectomy.

Thoracic surgery for a newly diagnosed primary lung tumor following a previous pneumonectomy is rarely indicated. Stereotactic ablative radiotherapy (SABR) might represent a curative option. This report focuses on outcomes, toxicity and quality of life (QoL) after SABR. Nine patients were treated with SABR between 2004 and 2011; median time since surgery was 8.4 years. In 4 cases, a histological confirmation was possible with bronchoscopy. In 5 cases, the clinical proof of malignancy was based on radiological criteria. Forced expiratory volume in 1 second (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO) were tested in all patients. A SABR biologically equivalent dose of &gt;100 Gy was prescribed in all cases. QoL questionnaire forms were administered before SABR and during follow-up. Median follow-up was 41.8 months. We did not observe grade ≥3 acute toxicity, and concerning late toxicity, we registered 2 cases. QoL was decreased during the first 12 months of follow-up, followed by a progressive improvement after this time. One patient had a local relapse at 7.4 years; 1 developed a new nodule at 5.5 years, associated with metastases; and 1 developed a new nodule without any systemic disease at 3 years. There were 2 cancer-related deaths (18.2%) at 3 and 12 months after progression. Data support efficacy and safety of SABR in patients with a new primary lung cancer following previous pneumonectomy, with acceptable acute, late toxicity profile and without significant impairment of QoL. Our results were comparable to those in the literature.