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The application and exploration of Fruquintnib combined with TAS-102 and Stereotactic Body Radiotherapy(SBRT)for Third-line and Beyond Treatment of Metastatic Colorectal Cancer

ABSTRACT: Interventions: Cohort 1:Fruquintnib combined with TAS-102 and SBRT;Cohort 2:Fruquintnib combined with TAS-102 Primary outcome(s): Progression-free survival assessed by the investigator Study Design: Factorial

DISEASE(S): Colorectal Cancer

PROVIDER: 87000 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Immune System Modulation with Oral Vancomycin in combination with Stereotactic Body Radiotherapy (SBRT) for medically inoperable Early-Stage Non-small Cell Lung Cancer

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

Application and exploration of Fuquinitinib combined immunotherapy and SBRT in third-line and beyond treatment of metastatic colorectal cancer

Project description:Interventions: cohort 1:Fuquinitinib combined sintilimab and SBRT Primary outcome(s): Progression-free survival assessed by the investigator Study Design: Single arm

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Changes in peripheral blood mononuclear cells (PBMCs) of 10 patients who underwent continued ADT and stereotactic body radiation therapy (SBRT).

Project description:Immunotherapy has been effective in many cancer types, but failed in multiple clinical trials in cancers of the prostate, an organ largely influenced by androgen action. However, the prostate propensity cannot be explained by the immune suppressive activity of androgen receptor (AR) in T cells as reported recently. We use single-cell sequencing to analyze the changes in blood PBMCs of patients who respond good or poorly with ADT and SBRT.

2025-10-29 | GSE277590 | GEO

Modulation of the human pancreatic ductal adenocarcinoma immune microenvironment by stereotactic body radiotherapy

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

Clinical efficacy and biomarker analysis of stereotactic body radiotherapy combined with sintilimab and a bevacizumab biosimilar in anti-PD-1 refractory hepatocellular carcinoma

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

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Stereotactic Body Radiation Therapy (SBRT) for Unresectable Liver Metastases

Project description:This is a Phase II study to determine the efficacy of SBRT to treat liver metastases in patients with Colorectal Adenocarcinoma, Carcinoma of the Anal Canal and Gastrointestinal Neuroendocrine Tumors that are not amenable to surgery. Patients should have no evidence of extra-hepatic disease or have disease that is planned to be treated with curative intent. Therefore, SBRT is being considered as a potentially curative procedure.

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A phase II study of guadecitabien combined with irinotecan vs regorafenib or TAS-102 in previously treated metastatic colorectal cancer patients

Project description:A phase II study of guadecitabien combined with irinotecan vs regorafenib or TAS-102 in previously treated metastatic colorectal cancer patients

2023-03-31 | GSE226221 | GEO

Stereotactic Body Radiation Therapy (SBRT) in Liver Metastasis (COLD 3)

Project description:This study is designed to see whether stereotactic body radiation therapy (SBRT) can reduce tumour size, slow progression of the disease, prolong life and improve quality of life. SBRT is concentrated focused radiation therapy delivered very precisely to the liver tumour. Presently, the treatment for unresectable liver metastases from colorectal cancer is most often chemotherapy or novel targeted therapy. These treatments may improve survival, but not control the metastases permanently; so new treatments are needed to control metastases. It is hoped that knowledge obtained from this study will improve our ability to treat patients with liver tumours that cannot be treated with surgery and other methods, and that SBRT may prove to be a treatment that can lead to long-term and permanent control of liver tumours for some patients.

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Towards a mechanistic understanding of response to SBRT by patients with borderline resectable pancreatic cancer

Project description:Five year survival rates for pancreatic cancer remain low, around 11%. We assessed differential gene expression between SBRT responders and non-responders as well as expression pre and post SBRT. Samples were obtained from the University of Colorado biorepository. All patients had borderline resectable pancreatic cancer, treated with neoadjuvant chemotherapy followed by restaging, and treatment with 30–33.6 Gy SBRT to pancreatic tumors, followed by pancreaticoduodenectomy and adjuvant chemotherapy. We observed increases in PDL1, PD1, CD25, and a decrease in CD122 expression following RT. Furthermore, we found that responders to SBRT exhibit decrased CD25 expression with increased CD122 and CD132 expression compared to non-responders. Using GSEA of responders vs. non-responders, we found responders to SBRT exhibit enrichment of inflammatory response, IFN signaling, and IL2/STAT5 signaling.

2023-04-20 | GSE225767 | GEO

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