Stereotactic Body Radiotherapy for Oligometastases From Colorectal Cancer
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ABSTRACT:
DISEASE(S): Colorectal Cancer,Colorectal Neoplasms
PROVIDER: 2225646 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Purpose: Stereotactic body radiotherapy (SBRT) is an emerging treatment modality for pancreatic ductal adenocarcinoma (PDAC) that can effectively prime cytotoxic T cells by inducing immunogenic tumor cell death in preclinical models. SBRT effects on human PDAC have yet to be thoroughly investigated, therefore, this study aimed to characterize immunomodulation in the human PDAC tumor microenvironment following therapy. Experimental Design: Tumor samples were obtained from patients with resectable PDAC. Radiotherapy was delivered a median of seven days prior to surgical resection, and sections were analyzed by multiplex IHC (mIHC), RNA-Seq, and T cell receptor sequencing (TCR-Seq). Results: Analysis of SBRT-treated tumor tissue indicated reduced tumor cell density and increased immunogenic cell death relative to untreated controls. Radiotherapy promoted collagen deposition, however, vasculature was unaffected and spatial analyses lacked evidence of T cell sequestration. Conversely, SBRT resulted in fewer tertiary lymphoid structures and failed to lessen or reprogram abundant immune suppressor populations. Higher percentages of PD-1+ T cells were observed following SBRT, and a subset of tumors displayed more clonal T cell repertoires. Conclusions: These findings suggest that SBRT augmentation of antitumor immunogenicity may be dampened by an overabundance of refractory immunosuppressive populations, and support the continued development of SBRT/immunotherapy combination for human PDAC.
2021-10-08 | GSE185311 | GEO
Project description:Immune checkpoint inhibitor (ICI) resistance in advanced hepatocellular carcinoma (HCC)poses a major therapeutic challenge. Here, we report a phase 2 trial evaluating stereotactic bodyradiotherapy (SBRT) combined with the anti-PD-1 antibody sintilimab and bevacizumabbiosimilar (lBI305) to re-sensitize ICI-refractory HCC. Twenty-one patients with progressiveHCC after prior ICI therapy received SBRT (25-50 Gy in 5 fractions) followed by sintilimab(200 mg) and IBl305 (15 mgkg) every 3 weeks. The primary endpoint, objective response rate(ORR) in non-irradiated lesions, was 33.3% (7/21), with a disease control rate of66.7%(14/21)Median progression-free survival (PFS) was 6.2 months (95% CI 3.7-15.1), and estimatedmedian overall survival (OS) was 24.4 months (95% CI 9.2-NA). SBRT achieved 100% localcontrol, while grade >3 treatment-related adverse events occurred in 33.3% of patientsLongitudinal proteomic profiling revealed that responders exhibited lower baseline IFN-y (p0.025) and elevated IL-6 (p=0.002), with post-SBRT increases in IFN-y, IL-2, and IL-6correlating with improved outcomes. These findings demonstrate that SBRT synergizes withdual PD-1/VEGF blockade to overcome ICI resistance, potentially through radiation-inducedimmune remodeling. Biomarker dynamics highlight actionable targets for optimizingcombination therapies in anti-PD-1-refractory HCC.
2025-10-15 | PAD000004 | Pride
Project description:AimsTo evaluate the efficacy and toxicity of extracranial stereotactic body radiotherapy (SBRT) in the treatment of oligometastatic lymph node involvement in the mediastinum, retroperitoneum, or pelvis, in a consecutive group of patients from real clinical practice outside clinical trials.MethodsA retrospective analysis of 90 patients with a maximum of four oligometastases and various primary tumors (the most common being colorectal cancers). The endpoints were local control of treated metastases (LC), freedom from widespread dissemination (FFWD), progression-free survival (PFS), overall survival (OS), and freedom from systemic treatment (FFST). Acute and delayed toxicities were also evaluated.ResultsThe median follow-up after SBRT was 34.9 months. The LC rate at three and five years was 68.4 and 56.3%, respectively. The observed median FFWD was 14.6 months, with a five-year FFWD rate of 33.7%. The median PFS was 9.4 months; the three-year PFS rate was 19.8%. The median FFST was 14.0 months; the five-year FFST rate was 23.5%. The OS rate at three and five years was 61.8 and 39.3%, respectively. Median OS was 53.1 months. The initial dissemination significantly shortened the time to relapse, death, or activation of systemic treatment-LC (HR 4.8, p < 0.001), FFWD (HR 2.8, p = 0.001), PFS (HR 2.1, p = 0.011), FFST (HR 2.4, p = 0.005), OS (HR 2.2, p = 0.034). Patients classified as having radioresistant tumors noticed significantly higher risk in terms of LC (HR 13.8, p = 0.010), FFWD (HR 3.1, p = 0.006), PFS (HR 3.5, p < 0.001), FFST (HR 3.2, p = 0.003). The multivariable analysis detected statistically significantly worse survival outcomes for initially disseminated patients as well as separately in groups divided according to radiosensitivity. No grade III or IV toxicity was reported.ConclusionOur study shows that targeted SBRT is a very effective and low toxic treatment for oligometastatic lymph node involvement. It can delay the indication of cytotoxic chemotherapy and thus improve and maintain patient quality of life. The aim of further studies should focus on identifying patients who benefit most from SBRT, as well as the correct timing and dosage of SBRT in treatment strategy.
| S-EPMC7892582 | biostudies-literature
Project description:We report the results of a randomized, open-label pilot study evaluating oral vancomycin combined with SBRT in early-stage non-small cell lung cancer. Building on prior research, vancomycin was found to enhance antitumor effects by modulating gut microbiota and boosting immune responses notably improving progression-free and overall survival (P.F.S. and O.S.). Patients treated with vancomycin (125 mg QID for 5 weeks starting one week before SBRT) showed increased expression of antigen presenation machinary in PBMCs and councurrent T-cell activation, and significant changes in gut microbiome composition and metabolite profiles, including reduced Short Chain Fatty Acids and elevated TNF-beta levels. With minimal adverse events, vancomycin appears to synergistically enhance RT-induced antitumor immunity, positioning it as a viable strategy for improving oncological outcomes. Further studies with larger cohorts are needed to confirm these results.
2025-07-23 | GSE277984 | GEO
Project description:Background and purpose: To directly reveal the change in genome mutation, RNA transcript of tumor cells, and tumor microenvironment (TME) after stereotactic body radiotherapy (SBRT) in paired human lung tumor specimens.
2020-12-10 | GSE162945 | GEO
Project description:Background and purpose: To directly reveal the change in genome mutation, RNA transcript of tumor cells, and tumor microenvironment (TME) after stereotactic body radiotherapy (SBRT) in paired human lung tumor specimens.
2020-12-10 | GSE162944 | GEO
Project description:BackgroundStereotactic body radiotherapy (SBRT) is a precise and effective treatment for pulmonary oligometastases, offering high local control (LC) rates. However, the optimal SBRT dose when combined with immunotherapy remains unclear, and there is a lack of comprehensive studies focusing on dose optimization in this setting. This study addresses this knowledge gap by exploring different SBRT dose regimens and their impact on progression-free survival (PFS), overall survival (OS), and LC in patients receiving concurrent immunotherapy, offering novel insights into the synergistic effects of these treatments.MethodsA retrospective cohort study was conducted of 101 patients with 141 pulmonary oligometastases treated from April 2018 to April 2022. Inclusion criteria included patients with a maximum of five lung metastases and an Eastern Cooperative Oncology Group performance status of ≤2. Patients received SBRT with doses ranging from 50-70 Gy in 5-10 fractions. Follow-up was performed quarterly, and the best dose was determined by comparing survival outcomes across different dose groups. The patients received SBRT with doses ranging from 50-70 Gy in 5-10 fractions. Patient demographics, tumor characteristics, treatment details, and outcomes were collected. The Kaplan-Meier method was used for the survival analysis, and Cox regression models were used to identify prognostic factors for LC, PFS, and OS.ResultsThe median follow-up for the 101 patients was 22.4 months (range, 1-58 months). The cohort comprised 82.2% male patients with a median age of 64 years (range, 36-81 years). The majority of the patients (64.4%) had primary tumors originating from non-lung sites, with adenocarcinoma being the predominant histological subtype (47.5%). The median tumor size was 13.5 mm. Across the entire cohort, the median OS was 39 months, and the median PFS was 11 months. Pre-treatment with immunotherapy significantly improved outcomes: the PFS increased to 13 months compared to 7 months for those who did not receive immunotherapy [P=0.02, hazard ratio (HR) = 0.523, 95% confidence interval (CI): 0.302-0.906], and the OS was also significantly improved (P=0.008, HR =0.411, 95% CI: 0.214-0.792). The SBRT regimen of 60 Gy in 10 fractions provided the best outcomes, with a median OS of 39 months, a median PFS of 10 months, and a LC rate of 92.4%, with relatively low toxicity compared to other regimens.ConclusionsSBRT is a potent, minimally invasive option for managing pulmonary oligometastases, especially when preceded by immunotherapy. The 60 Gy in 10 fractions regimen demonstrated significant efficacy in terms of OS and LC, while maintaining manageable toxicity. Although the retrospective nature of the study introduces some selection bias, this dose regimen appears to offer a promising therapeutic option for pulmonary oligometastases. Further validation through well-designed prospective studies would help confirm the optimal SBRT dose and clarify the role of immunotherapy in this setting.
| S-EPMC11565358 | biostudies-literature
Project description:This is a single-centre, single-arm open-label proof-of-concept study to analyze the imaging (DCE-CT,CEUS and Quantitative US) effects of neoadjuvant bevacizumab and SBRT on colorectal metastases to the liver. Patients will receive 2 doses of bevacizumab 5mg/kg IV prior to SBRT. The second dose of bevacizumab will be given 2 weeks after the first dose of bevacizumab and within 48 hours of starting the first dose of SBRT. The SBRT prescription dose will be up to 60 Gy in 6 fractions, delivered on alternating weekdays for 2 weeks. Total SBRT dose will be determined by size of target lesion, liver sparing and organs-at-risk dose constraints. DCE-CT, CEUS and Quantitative US will be performed within 7 days prior to the first dose of bevacizumab, after the second dose of bevacizumab and within 7 days of completing SBRT.
| 2123176 | ecrin-mdr-crc
Project description:This is a randomized open-label multicentre Phase III superiority study of the effect of adding SBRT to the standard of care treatment on overall survival in patients with rare oligometastatic cancers.
Patients will be randomized in a 1:1 ratio between current standard of care treatment vs. standard of care treatment + SBRT to all sites of known metastatic disease.
The primary objective of this trial is to assess if the addition of stereotactic body radiotherapy (SBRT) to standard of care treatment improves overall survival (OS) as compared to standard of care treatment alone in patients with rare oligometastatic cancers.
| 2347710 | ecrin-mdr-crc
Project description:IntroductionStereotactic radiotherapy (SBRT) potentially has a role in the management of oligometastatic melanoma. However, literature with data specific to this management is very limited. The objectives of this study were to evaluate the time to local control (LC) of extra-cranial melanoma metastases after SBRT treatment and to help establish if SBRT is a useful therapy for oligometastatic melanoma.MethodsA retrospective study was conducted with data collected from two referral centers in France between 2007 and 2020. The oligometastatic status of patients was reported based on the latest recommendations with a maximum of three lesions prior to treatment.ResultsA total of 69 patients receiving SBRT for 88 oligometastatic melanoma metastases were included. The median follow-up time was 42.6 months. Most patients were treated for metachronous oligometastatic lesions. Occurrence of oligoprogression, oligorecurrence, and oligopersistence was reported in 42.0%, 39.1%, and 17.4% of cases, respectively. Treated lesions were mostly pulmonary (40.6%), followed by lymph node (34.8%) and hepatic sites (24.6%). Progression-free survival at 1, 2, and 3 years were 47.0% (35-59), 27.0% (16-39), and 25.0% (15.0-37.0), respectively. Time to LC rates at 1, 2, and 3 years were 94.2% (87.0-98.1), 90.3% (81.3-96.1), and 90.3% (81.3-96.1), respectively. Overall survival at 1, 2, and 3 years were 87% (76.0-93.0), 74.0% (76.0-93.0), and 61.0% (47.0-73.0), respectively. Only 17.4% of patients experienced acute, grade 1 or grade 2 toxicities with no reports of grade 3 or higher toxicities.ConclusionSBRT demonstrated efficacy in managing melanoma patients with extracranial oligometastases and showed an overall low toxicity profile. Future randomized studies are needed to establish the role of SBRT in therapeutic approaches for patients with oligometastatic melanoma.
| S-EPMC10949887 | biostudies-literature