Safety Of Stereotactic Body Radiation Therapy Research Articles

The efficacy and safety of stereotactic body radiotherapy combined with systematic therapy for metastatic renal cell carcinoma: a systematic review and meta-analysis.

There is considerable interest in the potential of stereotactic body radiation therapy (SBRT) combined with systemic therapy such as tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs). However, its efficacy and safety remain unclear. The purpose of this study was to evaluate the efficacy and safety of conducting SBRT during ICI or TKI treatment in different disease settings for patients with metastatic renal cell carcinoma (mRCC). A total of 16 studies were ultimately included. Under the random effects model, the pooled 1-year local control rate (1-yr LCR) and objective response rate (ORR) were 90% (95% confidence interval [CI]: 80%-95%, I 2=67%) and 52% (95% CI: 37%-67%, I 2=90%), respectively. SBRT concomitant with different systemic therapy yield significant different 1-yr LCR (p<0.01) and ORR (p=0.02). Regarding survival benefits, the pooled 1-year progression-free survival (1-yr PFS) and 1-year overall survival (1-yr OS) rates were 45% (95% CI: 29%-62%, I 2=91%) and 85% (95% CI: 76%-91%, I 2=66%), respectively. 1-yr PFS and 1-yr OS in different disease settings demonstrated significant difference (p<0.01). As for toxicity, the pooled incidence of grade 3-4 adverse events was 14% (95% CI: 5%-26%, I 2=90%). This study highlights the feasibility of utilizing these strategies in mRCC patients, especially those with a low metastatic tumor burden.

Stereotactic Body Radiation Therapy and Concurrent Targeted Therapy for Lung Metastases in Pediatric Sarcoma

PurposeThe purpose of this investigation was to evaluate the efficacy and safety of stereotactic body radiotherapy (SBRT) for pulmonary metastases from pediatric sarcomas. MethodsThis study was a single institutional retrospective chart review including patients younger than 21 years of age at diagnosis who had received SBRT for pulmonary metastasis from metastatic sarcoma. Our current electronic record system was queried for all eligible patients. Primary endpoint was tumor response as defined by RECIST 1.1 criteria. Secondarily, we analyzed factors that affected tumor response as well as toxicity of treatment. Median dose was 50 Gy ranging from 45-60 Gy in 5 fractions to the planning tumor volume (PTV). ResultsThere were 7 patients, ranging from ages 6 to 21 years with a total of 14 pulmonary lesions treated with SBRT. Median and mean follow up times for the 7 patients were 10.6 months and 15.9 months respectively. The complete response rate was 50%, partial response 21%, stable disease 21%, and progressive disease 7%. Four of the seven patients were treated with concurrent systemic therapy, three of which were targeted oral therapies. Additionally, we observed that patients who were on targeted therapy such as regorafenib or pazopanib seemed to have better local control as compared to patients without. ConclusionsWith an overall response rate of 92%, SBRT provided a non-invasive effective palliative treatment option with few side effects in this small retrospective study of 7 patients. A larger prospective clinical trial is warranted to evaluate the role of SBRT in the treatment of unresectable metastatic pediatric sarcomas.

Efficacy and safety analysis of stereotactic body radiotherapy for brain multi-metastases in non-small cell lung cancer patients.

Lung cancer is prone to metastasize to the brain, which is difficult for surgery and leads to poor prognosis due to poor chemotherapy efficacy. Our aim is to evaluate the efficacy and safety of stereotactic body radiotherapy (SBRT) for brain multi-metastases. In the retrospective study, a total of 51 non-small cell lung cancer (NSCLC) patients with brain multi-metastases (3-5 metastases) receiving SBRT in the local hospital between 2016 and 2019 were enrolled for analyzing the efficacy and safety of SBRT. The primary endpoints included 1-year local control rate, radiotherapy toxicity, overall survival and progression-free survival. The median follow-up for the enrolled patients was 21 months, and the 1-year and 2-year OS rates were 82.4% and 45.1%, respectively. Demographic analysis showed no significant differences between SBRT alone and combination with whole brain radiotherapy in clinical characteristics including age, gender and Eastern Cooperative Oncology Group performance status. The 1-year local control rate was 77.3% (17/22) for SBRT alone, which was comparable to 79.3% (23/29) of combined radiotherapy. Cox proportional hazard regression demonstrated that the prognostic benefit of combining WBRT was not significantly superior to SBRT alone (HR = 0.851, P= 0.263). Their radiotherapy toxicity rate was lower in SBRT alone group (13.6%, vs. 44.8% for combination; P= 0.017). The current research suggested that SBRT alone could effectively relieve tumor burden and improve the prognosis and quality of life for NSCLC patients with brain multi-metastases, which should be validated in further prospective clinical trials.

A pilot study of stereotactic body radiotherapy combined with pelvic radiotherapy and GTVp boost based on multiparameter magnetic resonance image in patients with high-risk prostate cancer.

This pilot study aimed to explore the preliminary effects and safety of stereotactic body radiotherapy (SBRT) combined with preventive pelvic radiotherapy and primary gross tumor volumes (GTVp) boost in patients with high-risk prostate cancer based on multiparameter magnetic resonance image (mpMRI). Tumors were contoured as GTVp based on mpMRI. The prostate and proximal seminal vesicles were considered as the clinical target volume1. The pelvic lymphatic drainage area constituted clinical target volume 2. Radiation doses were 40Gy or 45Gy/5fractions to planning target volume of primary tumor, 37.5Gy/5f to prostate, seminal vesicle, and positive pelvic lymph nodes, and 25Gy/5f to pelvic synchronously. The treatment was delivered 3 times per week. Volumetric modulated arc radiotherapy and intensity-modulated radiotherapy were used to complete SBRT. The genitourinary (GU) and gastrointestinal (GI) toxicities were evaluated. Quality of life data was also captured. A total of 15 patients were enrolled in this study with a median age of 78 (56-87) from 2017 to 2020. All patients received SBRT. At 3 months after radiotherapy, the proportion of PSA < 0.006 ng/mL was 66.7% (10/15). The 2-year biochemical relapse-free survival was 93.3%. The incidence of grade 1 acute GU side effects was 80% (12/15); the incidence of acute grade 1 GI toxicity was 66.7% (10/15); and no grade 2 or higher acute GU and GI side effects was observed. Two patients presented with temporary late grade 2 GI toxicity. International Prostatic System Score increased rapidly after a transient increase at 1 week (P = .001). There were no significant differences in EORTC quality of life scores in all domains except global health status. In this pilot study, it was revealed that SBRT combined with preventive pelvic radiotherapy and GTVp boost based on mpMRI image was effective and well tolerated for patients with high-risk prostate cancer.

Real-world effectiveness and safety of stereotactic body radiotherapy for liver metastases with different respiratory motion management techniques.

Stereotactic body radiotherapy (SBRT) has been firmly established as atreatment choice for patients with oligometastases, as it has demonstrated both safety and efficacy by consistently achieving high rates of local control. Moreover, it offers potential survival benefits for carefully selected patients in real-world clinical settings. Between January 2008 and May 2020, atotal of 149 patients (with 414 liver metastases) received treatment. The Active Breathing Coordinator device was used for 68 patients, while respiratory gating was used for 65 and abdominal compression was used for 16patients. The most common histological finding was colorectal adenocarcinoma, with 37.6% of patients having three or more metastases, and 18% having two metastases. The prescribed dose ranged from 36 to 60 Gy, delivered in 3-5fractions. Local control rates at 2 and 3years were 76.1% and 61.2%, respectively, with no instances of local recurrence after 3years. Factors negatively impacting local control included colorectal histology, lower prescribed dose, and the occurrence of new liver metastases. The median overall survival from SBRT was 32months, with the presence of metastases outside the liver and the development of new liver metastases after SBRT affecting survival. The median disease-free survival was 10months. No substantial differences in both local control and survival were observed between the respiratory motion control techniques employed. Treatment tolerance was excellent, with only one patient experiencing acute gradeIV thrombocytopenia and two patients suffering from ≥ gradeII chronic toxicity. For radical management of single or multiple liver metastases, SBRT is an effective and well-tolerated treatment option. Regardless of the technology employed, experienced physicians can achieve similarly positive outcomes. However, additional studies are required to elucidate prognostic factors that can facilitate improved patient selection.

Efficacy and Safety of Stereotactic Body Radiotherapy Combined with Camrelizumab and Apatinib in Patients with Hepatocellular Carcinoma with Portal Vein Tumor Thrombus.

This study aimed to evaluate the efficacy and safety of camrelizumab plus apatinib with or without stereotactic body radiotherapy (SBRT) as first-line therapy for patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). This is a multicenter, open-label, noncomparative, randomized trial that recruited patients with HCC with type II/III/IV PVTT, who had not previously received systemic therapy. Patients were randomly assigned (2:1) to receive camrelizumab (200 mg, every 3 weeks) and apatinib (250 mg, every day) with or without SBRT [95% planning target volume (PTV), 36-40 Gy/6-8 Gy]. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response, time to progression, and safety. Sixty patients were enrolled and randomly assigned to two prospective cohorts. Median OS were 12.7 months [95% confidence interval (CI), 10.2-not available (NA)] and 8.6 months (95% CI, 5.6-NA), and median PFS were 4.6 months (95% CI, 3.3-7.0) and 2.5 months (95% CI, 2.0-7.6) for the SBRT and non-SBRT cohorts, respectively. The ORR and DCR were 47.5% and 72.5% in the SBRT cohort, and 20.0% and 40.0% in the non-SBRT cohort. The most common treatment-related adverse events of any grade were hypertension (55.0%), hand-foot syndrome (51.7%), and leukopenia (50.0%). Grade ≥ 3 was reported in 13 (21.7%) patients. First-line treatment with camrelizumab-apatinib combined with or without SBRT showed clinical benefits in patients with HCC with PVTT, with an acceptable safety profile. Thus, these combination regimens may be potential options for such patients.

Partial tumor irradiation plus pembrolizumab in treating large advanced solid tumor metastases.

2593 Background: We previously demonstrated the safety of stereotactic body radiotherapy followed by pembrolizumab (SBRT+P) in patients with advanced solid tumors. This phase 1 clinical trial was expanded to study the safety of partial tumor irradiation (partial-Rx). We assessed irradiated local failure (LF) and clinical outcomes with correlations to biomarkers including CD8-T-cell radiomics score (RS) and circulating cytokines. Methods: Patients received SBRT to 2-4 metastases and pembrolizumab ≤7 days after SBRT. Tumors &lt;65cc received the full radiation dose (complete-Rx), whereas tumors &gt; 65cc received partial-Rx. Landmark analysis was used to assess the relationship between tumor response and overall survival (OS). Multivariable analysis was performed for RS and circulating cytokines. Results: In the combined (expansion plus original) cohort, 97 patients (219 metastases) were analyzed and received SBRT+P. Forty-six (47%) patients received &gt;1 partial-Rx treatment. There were 7 (7.2%) dose-limiting toxicities (DLTs). 1-year LF was 7.6% overall, and 13.3% and 5.4% for partial-Rx and complete-Rx tumors, respectively (hazard ratio 2.32, 95% confidence interval: 0.90-5.97, p = 0.08). The overall, unirradiated, and irradiated objective response rate was 22%, 12%, and 34%, respectively. Irradiated tumor response to SBRT+P was associated with prolonged OS; 1-year OS was 71% (responders), 42% (mixed-responders), and 0% (non-responders) (p &lt; 0.01). High-RS was significantly associated with improved LF, progression-free survival (PFS), and OS. Elevated circulating IL-8 was independently associated with inferior PFS and OS. Conclusions: SBRT+P is safe in patients with large, advanced solid tumors. Additional studies are warranted to assess non-inferiority of complete versus partial irradiation of tumors in the setting of immunotherapy. Clinical trial information: NCT02608385 .

Effects of stereotactic body radiotherapy for clinical outcomes of patients with liver metastasis and hepatocellular carcinoma: A retrospective study.

This retrospective clinical study described the treatment efficacy and safety of stereotactic body radiotherapy (SBRT) for patients of hepatocellular carcinoma (HCC) and liver metastasis tumors. The therapeutic effect and prognosis of patients with liver cancer treated with stereotactic body radiation therapy (SBRT) at the Fudan University Shanghai Cancer Center (Shanghai, China) between July 2011 and December 2020 were retrospectively analyzed. Overall survival (OS), local control (LC) rates and progression-free survival (PFS) were evaluated using Kaplan-Meier analysis and the log-rank test. Local progression was defined as tumor growth after SBRT on dynamic computed tomography follow-up. Treatment-related toxicities were assessed according to the Common Terminology Criteria for Adverse Events version 4. A total of 36 patients with liver cancer were enrolled in the present study. The prescribed dosages (14 Gy in 3 fractions or 16 Gy in 3 fractions) were applied for SBRT treatments. The median follow-up time was 21.4 months. The median OS time was 20.4 [95% confidence interval (CI): 6.6-34.2] months, and the 2-year OS rates for the total population, HCC group and liver metastasis group were 47.5, 73.3 and 34.2%, respectively. The median PFS time was 17.3 (95% CI: 11.8-22.8) months and the 2-year PFS rates for the total population, HCC group and liver metastasis group were 36.3, 44.0 and 31.4%, respectively. The 2-year LC rates for the total population, HCC group and liver metastasis group were 83.4, 85.7 and 81.6%, respectively. The most common grade IV toxicity for the HCC group was liver function impairment (15.4%), followed by thrombocytopenia (7.7%). There were no grade III/IV radiation pneumonia or digestive discomfort. The present study aimed to explore a safe, effective and non-invasive treatment method for liver tumors. At the same time, the innovation of the present study is to find a safe and effective prescription dose of SBRT in the absence of consensus on guidelines.

Efficacy and Safety of Stereotactic Body Radiation Therapy in Oligometastatic Uterine Cancer (MITO-RT2/RAD): A Large, Real-World Study in Collaboration With Italian Association of Radiation Oncology, Multicenter Italian Trials in Ovarian Cancer, and Mario Negri Gynecologic Oncology Group Groups

This retrospective, multicenter study analyzes the efficacy and safety of stereotactic body radiotherapy in a large cohort of oligometastatic/persistent/recurrent uterine cancer patients. Clinical and radiotherapy data from several radiotherapy centers treating patients by stereotactic body radiotherapy between March 2006 and October 2021 were collected. Objective response rate was defined as complete and partial response, while clinical benefit included objective response rate plus stable disease. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer and Common Terminology Criteria for Adverse Events scales were used to grade toxicities. Primary endpoints were the rate of complete response to stereotactic body radiotherapy, and the 2-year actuarial local control rate 'per-lesion' basis. Secondary endpoints were progression-free survival and overall survival, as well as toxicity. 157 oligometastatic/persistent/recurrent uterine cancer patients bearing 272 lesions treated by stereotactic body radiotherapy at 14 centers were analyzed. Lymph node metastases (137, 50.4%) were prevalent, followed by parenchyma lesions (135, 49.6%). Median total dose was 35 Gy (10-75.2), in five fractions (range 1-10). Complete and partial responses were 174 (64.0%), and 54 (19.9%), respectively. Stable disease was registered in 29 (10.6%), while 15 (5.5%) lesions progressed. Type of lesion (lymph node), volume (≤ 13.7 cc) and total dose (BED10 >59.5 Gy) were significantly associated with a higher probability of achieving complete response. Patients achieving complete response (CR) 'per-lesion' basis experienced a 2-year actuarial local control rate of 92.4% versus 33.5% in lesions not achieving complete response (NCR) (p<0.001). Moreover, the 2-year actuarial progression-free survival rate in patients with CR was 45.4%, while patients with NCR had a 2-year rate of 17.6% (p value: <0.001). Finally, patients who had a CR had a 2-year overall survival rate of 82.7%, compared to 56.5% for NCR ONES (P VALUE: <0.001) . Severe acute toxicity was around 2%, including one toxic death due to gastric perforation, and severe late toxicity around 4%. The efficacy of stereotactic body radiotherapy in this setting was confirmed. The low toxicity profile and the high local control rate in complete responder patients encourage the wider use of this approach.

EGFR-TKIs plus stereotactic body radiation therapy (SBRT) for stage IV Non-small cell lung cancer (NSCLC): A prospective, multicenter, randomized, controlled phase II study

BackgroundEpidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have a significant therapeutic effect in the treatment of advanced non-small-cell lung cancer (NSCLC) with EGFR mutations. However, the acquired resistance greatly limits the survival benefit of EGFR-TKIs for EGFR-mutant NSCLC patients. We aimed to assess the efficacy and safety of stereotactic body radiotherapy (SBRT) plus EGFR-TKIs in these patients. MethodsIn this prospective, randomized, controlled, phase 2 study, participants were recruited from 4 different hospitals in Wuhan, China. Eligible patients were histologically confirmed to have NSCLC with an EGFR-sensitive mutation (19DEL or 21L858R) and diagnosed at stage IV. Patients who had received first-line EGFR-TKIs treatment including gefitinib, erlotinib, and icotinib and achieved stable disease or partial response were enrolled after three months. Eligible participants were randomly assigned (1:1) to receive SBRT plus EGFR-TKIs or EGFR-TKIs treatment alone. In the combination-group, different tumor sites were irradiated at doses ranging from 30–50 Gy in five fractions. Considering the short duration of SBRT, the TKIs were continued during the radiotherapy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS) and safety. This study was registered at ClinicalTrials.gov, with the registration number of NCT03595644. ResultsBetween May 4, 2018 and Dec 20, 2019, 74 patients were screened, of whom 62 patients were enrolled and randomized. The study was closed early with 62/72 patients due to slow accrual. The enrolled patients were randomly assigned to receive SBRT plus EGFR-TKI(n = 31) or EGFR-TKI alone (n = 31). One patient who was randomized to the SBRT plus EGFR-TKI group refused to receive SBRT during the treatment, and, 61 patients were included the modified intention-to-treat (mITT) analysis, with 30 in the SBRT plus EGFR-TKI and 31 in the EGFR-TKI group. As of the clinical cutoff date (Feb 14, 2022), the median follow-up was 29.4 months (IQR 6.9–38.9). The median PFS of the EGFR-TKI group and SBRT combination group was 9.0 vs 17.6 months (hazard ratio [HR] = 0.52, 95% confidence interval [95%CI], 0.31–0.89, P = 0.016). Meanwhile, the median OS was 23.2 vs 33.6 months (HR [95%CI], 0.53(0.30–0.95); P = 0.026). There was no grade 3 or greater toxicity observed in either group, the grade 2 adverse events were 50% in the EGFR-TKIs + SBRT group while the percentage was 45.2% in the EGFR-TKIs group. ConclusionsThe addition of SBRT significantly delayed the onset of acquired resistance to EGFR-TKIs and prolonged the PFS and OS of patients. Radiotherapy of the primary lesion alone might be superior to metastatic sites. Further confirmatory studies are needed to confirm our findings.

Multicenter retrospective study of stereotactic body radiotherapy for patients with previously untreated initial small hepatocellular carcinoma.

We aimed to verify the therapeutic efficacy and safety of stereotactic body radiotherapy (SBRT) for previously untreated initial small hepatocellular carcinoma (HCC) in a multicenter, retrospective study. Patients who underwent SBRT for HCC at the Japanese Society of Clinical Oncology (JCOG) member hospitals in Japan between July 2013 and December 2017 and met the following eligibility criteria were included: (1) initial HCC; (2) ≤3 nodules, ≤5cm in diameter; (3) Child-Pugh score of A or B; and (4) unsuitability for or refusal of standard treatment. We analyzed the overall survival, recurrence-free survival, and cumulative incidence of local recurrence rate, and adverse events directly related to SBRT. Seventy-three patients with 79 lesions from 14 hospitals were analyzed. The median age was 77years (range: 50-89years), and the median tumor size was 23mm (range: 6-50mm). The median radiation dose was 40Gy (range: 35-60Gy) in five fractions (range: 4-8). The median follow-up period was 45months (range: 0-103months). The 3-year overall survival, recurrence-free survival, and cumulative incidence of local recurrence rates were 69.9% (95% CI: 58.7%-81%), 57.9% (95% CI: 45.2%-70.5%), and 20.0% (95% CI: 11.2%-30.5%), respectively. Four cases (5.5%) of adverse events of grade 3 or higher were reported: three cases of grade 3 and one case of grade 4 (duodenal ulcer). No grade 5 toxicities were observed. SBRT is a promising treatment modality, particularly for small HCCs, as they are not suitable for standard treatment.

Comparison of stereotactic body radiotherapy with and without lenvatinib for advanced hepatocellular carcinoma: a propensity score analysis.

Lack of evidence on the benefit of stereotactic body radiotherapy (SBRT) in combination with lenvatinib for advanced hepatocellular carcinoma (HCC). Our research compared the efficacy and safety of SBRT plus lenvatinib versus SBRT alone in clinical practice for the treatment of advanced HCC. Propensity score matching (PSM) analysis was used to reduce selection bias. Overall survival (OS), progression-free survival (PFS), intrahepatic PFS (IHPFS), and objective response rate (ORR) were compared between the two groups. Additionally, safety profiles were also evaluated in the two groups. After PSM, 35 patients from each group were selected and the date was compared. Compared with the SBRT alone group, the median OS, PFS, and IHPFS were significantly prolonged in SBRT plus lenvatinib group (median OS 16.8 vs. 11.0months, pOS = 0.043; median PFS 9.1 vs. 3.7months, pPFS < 0.001; median IHPFS 9.5 vs. 4.2months, pIHPFS = 0.004). The 6- and 12-month OS rates were 91.4% and 68.6% in the combined therapy group and 82.9% and 48.6% in the monotherapy group, respectively. The 6- and 12-month PFS rates were 68.6% and 34.3% in the combined therapy group and 31.4% and 8.6% in the monotherapy group, respectively. Furthermore, a higher ORR was observed in SBRT plus lenvatinib group (54.29% vs. 22.86%, p = 0.007). Subgroup analysis of patients with macroscopic vascular invasion (MVI) also had similar results. Moreover, most adverse events (AEs) were mild-to-moderate and manageable in the SBRT plus lenvatinib group. SBRT plus lenvatinib is expected to significantly improve OS, PFS, IHPFS, and ORR for patients with advanced HCC when compared to SBRT alone, with manageable adverse effects.

The analysis of the efficacy and safety of stereotactic body radiotherapy with sequential immune checkpoint inhibitors in the management of oligoprogressive advanced non-small cell lung cancer

The analysis of the efficacy and safety of stereotactic body radiotherapy with sequential immune checkpoint inhibitors in the management of oligoprogressive advanced non-small cell lung cancer

Observation on the Clinical Effect of Stereotactic Body Radiotherapy in Patients with Oligometastatic Tumors

Objective: To observe the efficacy and safety of stereotactic body radiotherapy (SBRT) in the treatment of extracranial oligometastases. Method: A retrospective analysis of 70 patients with extracranial oligometastasis of malignant tumors who underwent SBRT in our hospital (Shaanxi Provincial People’s Hospital) from January 2019 to December 2021 with ? 5 metastases, ?3 metastatic organs, and metastases with diameters of ? 5 cm. According to the clinical data of patients, the dose-fractionation mode of SBRT is mainly determined according to the pathology of the primary tumor, the location of the metastatic tumor, and the important structures around the tumor. The local control, survival and adverse reactions were observed. Results: A total of 219 oligometastatic lesions in 70 patients were treated with SBRT. The median follow-up time was 24 months (12–40 months). The local control rate (LCR) of all target lesions assessed 3 months after radiotherapy was 94.1%; the 1-, 2-, and 3-year LCRs were 88.6%, 74.6%, and 64.9%, respectively. The median progression-free survival (PFS) was 11.8 months (95% CI, 8.9–14.7 months), and the 1- and 2-year PFS rates were 48.6% and 32.6%, respectively; the median overall survival (OS) was 31.9 month (95% CI 26.0-37.8 months), the 1-year OS rate was 84.3%. The local control time, PFS, and OS of patients with metastases ? 3 cm were significantly better than those with metastases &gt; 3 cm, and the differences were statistically significant (P &lt; 0.05). Acute adverse reactions after SBRT treatment in oligometastatic patients were mainly bone marrow suppression and gastrointestinal reactions, with incidence rates of 48.98% and 30.61%, respectively; chronic adverse reactions were mainly pain (bone, muscle), radiation enteritis, and radiation pneumonitis, with incidence rates of 38.57%, 30.00%, and 24.29%, respectively. The treatment-related adverse reactions were mainly grade 1, which were all improved after symptomatic treatment, except for one patient with bone metastases from lung cancer who had grade 4 myelosuppression. No grade 4 or 5 adverse events occurred in the other patients. Conclusion: The application of SBRT in the treatment of extracranial oligometastases is safe, effective, and has high tolerability.

Stereotactic Body Radiation Therapy vs. Conventional External Beam Radiation Therapy for Painful Bone Metastases: A Systematic Review and Meta-Analysis of Randomized Trials

<h3>Purpose/Objective(s)</h3> The magnitude of benefit and toxicity of stereotactic body radiation therapy (SBRT) compared with conventional external beam radiation therapy (cEBRT) in treating symptomatic bone metastases is unclear due to the conflicting results from randomized controlled trials (RCTs). We performed a systematic review and meta-analysis to compare the efficacy and safety of SBRT and cEBRT in patients with previously unirradiated painful bone metastases. <h3>Materials/Methods</h3> We searched various databases and major oncologic conference proceedings from inception to Oct 2021 for RCTs comparing SBRT with cEBRT for previously unirradiated painful bone metastases. The outcomes of interest were efficacy (overall and complete pain response rates, local progression, overall survival (OS) and quality of life (QoL)) and safety (post-irradiation fractures, pain flares and radiation myelopathy). We assessed the methodologic quality of individual trials using the revised Cochrane risk-of-bias (RoB2) tool. We performed one-stage individual patient data meta-analysis using multilevel logistic regression model. Sensitivity analyses were conducted using two-stage frequentist and Bayesian meta-analyses. We adopted Synthesis Without Meta-analysis (SWiM) approach to summarize adverse events and quality of life outcomes. We assessed the certainty of the evidence for the efficacy outcomes using GRADE approach. <h3>Results</h3> Six RCTs including 894 patients were identified. Five of the included trials had low risk of bias. There was no significant difference in overall pain response rates at 3 months between SBRT and cEBRT (odd ratio (OR), 1.10; 95% confidence interval (CI), 0.84-1.44; P, 0.48; GRADE, moderate certainty). SBRT significantly improved complete pain response rates at 3 months (OR, 3.38; 95% CI, 1.88-6.07; P< 0.01; GRADE, high certainty) and reduced local progression rates (OR, 0.15; 95% CI, 0.04-0.53; P< 0.01; GRADE, high certainty), compared to cEBRT. Sensitivity analyses showed consistent findings. SBRT was associated with a modest increase in pain flare rates, compared to cEBRT. There were no significant differences between the two groups in OS, post-irradiation fracture and radiation myelopathy. The QoL was similar, except for improved perception of financial burden with SBRT at 4 weeks. <h3>Conclusion</h3> Among the patients with previously unirradiated symptomatic bone metastases, SBRT significantly improved complete but not overall pain response rates at 3 months and delayed local progression without adversely impacting on the quality of life and overall survival, compared to cEBRT. SBRT was associated with a modest increase in the pain flare rates, compared to cEBRT.

KEYNOTE-867: Phase 3, Randomized, Placebo-Controlled Study of Stereotactic Body Radiotherapy (SBRT) with or without Pembrolizumab in Patients with Unresected Stage I or II Non–Small-Cell Lung Cancer (NSCLC)

<h3>Purpose/Objective(s)</h3> Anti–PD-(L)1-directed therapy following radiotherapy or following concurrent chemoradiation is associated with significantly longer PFS and OS in patients with advanced or metastatic NSCLC, including those with locally advanced inoperable tumors. KEYNOTE-867 (NCT03924869) evaluates the efficacy and safety of SBRT with or without pembrolizumab in patients with unresected stage I or II NSCLC. <h3>Materials/Methods</h3> In this phase 3, randomized, placebo-controlled study, approximately 530 adult patients with previously untreated, unresected, histologically/cytologically confirmed stage I or II (T1 to limited T3, N0, M0) NSCLC are randomized 1:1 to receive thoracic SBRT to primary tumors for ≤2 wk (Table) and either pembrolizumab 200 mg or placebo every 3 wk for 17 cycles (approximately 1 year) or until disease recurrence, development of unacceptable AEs, SBRT not started for any reason, or study withdrawal. Randomization is stratified by disease stage (I vs II), ECOG PS (0 or 1 vs 2), geographic region (East Asia vs non-East Asia), and reason for not receiving surgery (medically inoperable vs refused surgery). Imaging assessment by blinded independent central review (BICR) occurs at 12 wk (≥10 wk after SBRT completion), followed by every 16 wk for 3 y, and then every 6 mo. Primary endpoints are event-free survival (EFS) by BICR and OS. Secondary endpoints include time to death or distant metastases and safety; exploratory endpoints are time to subsequent treatment, disease-specific survival, and time to recurrence/progression on subsequent line of therapy. AEs are monitored throughout the trial until 30 d after last dose (90 for serious AEs) and graded according to NCI CTCAE version 4.0. EFS and OS are analyzed by the nonparametric Kaplan-Meier method, treatment differences by stratified log-rank test, and hazard ratios by stratified Cox proportional hazard model with Efron's method of tie handling. Enrollment started on June 17, 2019, and is ongoing at 169 sites in North America, South America, Europe, Asia and Australasia. <h3>Results</h3> TBD <h3>Conclusion</h3> TBD

SBRT for Nodal Metastasis

<h3>Purpose/Objective(s)</h3> Lymph node metastases (NMs) are a common site of tumor spread that can occur at the time of diagnosis or during systemic therapy or during follow-up with variable incidence based on the primary tumor site, stage, histology, and grading. Stereotactic body Radiation Therapy (SBRT) can be a therapeutic option for NMs in the setting of oligometastatic disease (OMD). The oligometastatic disease is an area of research rapidly evolving in the definition, characterization and treatment. The first end point of this study is to evaluate the outcomes of lymph node metastases treated with SBRT in terms of Local Control (LC), Loco Regional Nodal Control (LRNC), Distant Nodal Control (DNC), Distant Metastasis Free Survival (DMFS), Progression Free Survival (PFS) and Overall Survival (OS). The secondary end point is to identify predictive factors of response and to assess the toxicities. <h3>Materials/Methods</h3> In this study we included patients with a maximum of 5 metastasis and various primary tumors (31% lung, 22% prostate, 13% colon rectal, 10% gynecological, 7% breast, 6% upper GI, 5% genito urinary, 2% H&N, 4% others). Concomitant treatments were allowed. From November 2007 to September 2021, 228 NMs were treated in 174 patients with SBRT (<8 fractions). At time of treatment 49% of patients were classified as oligorecurrent, 41% oligoprogressive, 3% oligometastatic and 7% oligopersistent. The single fraction and multiple fractions were administered respectively in the 22% and 78% of cases. Most represented schedule was 30 Gy in 5 fractions, the medium BED (10) of SBRT was 74,7 Gy (range: 33,6- 120 Gy). <h3>Results</h3> The median follow-up was 22 months (range 0-148 months). Rates of LC at 1, 2 and 3 years were 93%, 89% and 86%. Rates of LRNC at 1, 2 and 3 years were 88%, 81% and 82%. Rates of DNC were at 1, 2 and 3 years 90%, 86%, and 83%. Rates of DMFS were at 1, 2 and 3 years 58%, 49%, and 42%. Rates of PFS were at 1, 2 and 3 years 41%, 28% and 22%. Rates of OS were at 1, 2 and 3 years 73%, 56% and 43%. At univariate analysis, the total number of metastases were associated with worse DMFS (P< 0,0001) and PFS (P = 0,0004). The genitor-urinary and gynecological tumors showed a statistically significant correlation with worse results in terms of DMFS (P = 0,0003), PFS (P = 0,0460) and OS (P = 0,0023). Treatment was well tolerated. The acute toxicities were 9 (4%) cases Grade 1, in the form of pain, fatigue, nausea, vomiting and cough, one case (0.44%) of anemia G2 and one case (0.44%) of death caused by esophageal bleeding, G5. The late toxicity was a case G2 (0.44%) in the form of dyspnea. <h3>Conclusion</h3> In conclusion, our analysis confirmed the efficacy and safety of SBRT in the treatment of NMs. Despite the marked heterogeneity of the included cases and the retrospective nature of the analysis, the results of this study are encouraging. Prospective studies are required to further confirm the benefit of this treatment.

Management of oligometastatic ovarian cancer recurrence during PARP inhibitor maintenance

ObjectiveThe benefit of surgery and maintenance treatment with PARP inhibitors (PARPi) has been clearly demonstrated in ovarian cancer. Also, the efficacy and safety of stereotactic body radiotherapy has been shown...

Stereotactic Body Radiotherapy for Locally Advanced Pancreatic Cancer Using Optical Surface Management System - AlignRT as an Optical Body Surface Motion Management in Deep Breath Hold Patients: Results from a Single-Arm Retrospective Study.

PurposeTo assess the efficacy and safety of stereotactic body radiotherapy for patients with unresectable, locally advanced pancreatic cancer using Optical Surface Management System – AlignRT (OSMS-AlignRT) as an optical body surface motion management in deep breath hold.Patients and MethodsForty-five patients diagnosed with locally advanced pancreatic cancer were treated with stereotactic body radiotherapy in 3 or 5 fractions, and received varying BED10 (median 79.5 Gy) from April 2017 to December 2020. All patients were treated in deep breath hold with OSMS-AlignRT used as optical body surface motion management. Thirty-three patients received systemic treatment before and/or after stereotactic body radiotherapy, and twelve patients received no systemic treatment. In this retrospective, observational, single-arm study, primary endpoints were overall survival and freedom from local progression (ie, local control). Secondary endpoints were progression-free survival and toxicity. Actuarial survival analysis and univariate analysis were investigated.ResultsData from forty-five patients were analyzed. Median follow-up was 15 months. One-year freedom from local progression and survival were 95.5% and 71.1%, respectively. Median progression-free survival was 14 months. Median overall survival from diagnosis for all patients was 17 months, and 19 months for patients alive at the time of analysis. No patient had >G2 toxicity.ConclusionStereotactic body radiotherapy for locally advanced pancreatic cancer using OSMS-AlignRT as optical body surface motion management in deep breath hold patients is an effective and safe local treatment option, with no >G2 toxicity, and could be a promising therapeutic option with acceptable toxicity, either as a single treatment or in a multimodal regimen. OSMS-AlignRT provided accurate and reliable body surface motion management during stereotactic body radiotherapy.

Phase 3, randomized, placebo-controlled study of stereotactic body radiotherapy (SBRT) with or without pembrolizumab in patients with unresected stage I or II non–small cell lung cancer (NSCLC): KEYNOTE-867.

TPS8597 Background: Anti–PD-(L)1-directed therapy following radiotherapy or following concurrent chemoradiation is associated with significantly longer PFS and OS in patients with advanced or metastatic NSCLC, including those with locally advanced inoperable tumors. KEYNOTE-867 (NCT03924869) evaluates the efficacy and safety of SBRT with or without pembrolizumab in patients with unresected stage I or II NSCLC. Methods: In this phase 3, randomized, placebo-controlled study, approximately 530 adult patients with previously untreated, unresected, histologically/cytologically confirmed stage I or II (T1 to limited T3, N0, M0) NSCLC are randomized 1:1 to receive thoracic SBRT to primary tumors for ≤2 wk (Table) and either pembrolizumab 200 mg or placebo every 3 wk for 17 cycles (approximately 1 year) or until disease recurrence, development of unacceptable AEs, SBRT not started for any reason, or study withdrawal. Randomization is stratified by disease stage (I vs II), ECOG PS (0 or 1 vs 2), geographic region (East Asia vs non-East Asia), and reason for not receiving surgery (medically inoperable vs refused surgery). Imaging assessment by blinded independent central review (BICR) occurs at 12 wk (≥10 wk after SBRT completion), followed by every 16 wk for 3 y, and then every 6 mo. Primary endpoints are event-free survival (EFS) by BICR and OS. Secondary endpoints include time to death or distant metastases and safety; exploratory endpoints are time to subsequent treatment, disease-specific survival, and time to recurrence/progression on subsequent line of therapy. AEs are monitored throughout the trial until 30 d after last dose (90 for serious AEs) and graded according to NCI CTCAE version 4.0. EFS and OS are analyzed by the nonparametric Kaplan-Meier method, treatment differences by stratified log-rank test, and hazard ratios by stratified Cox proportional hazard model with Efron's method of tie handling. Enrollment started on June 17, 2019, and is ongoing at 168 sites around the world. Clinical trial information: NCT03924869. [Table: see text]