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

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

DISEASE(S): Colorectal Cancer

PROVIDER: 87133 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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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

Project description: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

| 87000 | ecrin-mdr-crc

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

Cellular Damage in the Target and Out-of-Field Peripheral Organs during VMAT SBRT Prostate Radiotherapy: An In Vitro Phantom-Based Study

Project description:New developments show that patients with prostate cancer can benefit from radiotherapy deliv-ered with a hypo-fractionated regimen. The aim of our study was to investigate the effect of hy-po-fractionated stereotactic body radiation therapy (SBRT) of prostate cancer on out-of-field organs. We used a humanoid phantom to irradiate prostate cells in conditions similar to patient therapy, using SBRT planning. Our results show that radiation doses in the location of the intes-tine and lung resulted in significantly higher radiation doses than the further locations. We observed a high radiotoxic effect in the cells irradiated in the prostate, and a small increase in DNA damage and cell killing in the intestine location. Gene expression analysis revealed significant enrichment of the biological processes related to the radiation response in the prostate. In the lung and thyroid, the enrichment of several gene groups was revealed, however the processes were not clearly related to the response to radiation. Our study provides extensive data on out-of-field safety of prostate SBRT.

2022-05-30 | GSE205026 | GEO

SBRT Sequential CapeOX Regimen Combined With Bevacizumab and Sintilimab in First-line Treatment of mCRC

Project description:Immune checkpoint inhibitors have a poor effect on MSS colorectal cancer. Studies have shown that SBRT, chemotherapy and anti-vascular therapy can enhance the anti-tumor effect of PD-1 antibody. This is a prospective, single-arm study to explore the efficacy and safety of SBRT Sequential CapeOX Regimen Chemotherapy Combined With Bevacizumab and Sintilimab in treatment with patients with initially unresectable advanced colorectal cancer.

| 2737317 | ecrin-mdr-crc

Immunotherapy Combined With Y-90 and SBRT for Colorectal Liver Metastases

Project description:This study is evaluating the combination of Y-90 radioembolization followed by SBRT with the immunotherapy drugs, durvalumab and tremelimumab, to improve disease control of liver metastases for patients with microsatellite stable colorectal cancer.

| 2294253 | ecrin-mdr-crc

SBRT Combined With Fruquintinib Plus PD-1/CTLA-4 Antibody for Third-line Treatment in mCRC

Project description:The study is a phase II clinical study. The purpose of the study is to evaluate the efficacy and safety of SBRT combined with Fruquintinib Plus PD-1/CTLA-4 Antibody for Third-line Treatment in mCRC.

| 9849 | ecrin-mdr-crc

The Yin and Yang of Cytoreductive SBRT in Oligometastases and Beyond.

Project description:Background: Oligometastatic disease has emerged as a possibly distinct metastatic phenotype in numerous cancer histologies. With the advancement in treatment modalities including stereotactic body radiation therapy (SBRT), certain patients may derive benefits from local ablative therapy. SBRT alone has already shown to have potential benefits in certain oligometastatic disease types. However, more understanding of the immunologic modulation and microenvironment is needed to guide which patients may benefit from SBRT alone or with combination therapy, if at all. Purpose: The purpose of this review is to offer an update on the emerging data testing SBRT combined with immunotherapy, review the pro-inflammatory and immunosuppressive effects of the tumor microenvironment, discuss novel molecular targets used to augment the immune response, and review potential methods used to decrease toxicity in order to improve the therapeutic ratio.

| S-EPMC6688093 | biostudies-literature

Phase II Study to Evaluate the Efficacy and Safety of Fruquintinib Plus Sintilimab as Third-line Therapy for Colorectal Cancer

Project description:This study is a single center, investigator initiated phase II clinical study to evaluate the efficacy and safety of fruquintinib plus Sintilimab as third-line therapy for colorectal cancer

| 2323156 | ecrin-mdr-crc

Survival Outcome Analysis of Stereotactic Body Radiotherapy and Immunotherapy (SBRT-IO) versus SBRT-Alone in Unresectable Hepatocellular Carcinoma.

Project description:IntroductionWhile combination of stereotactic body radiotherapy (SBRT) and immunotherapy are promising, their efficacy and safety have not been compared with SBRT-alone in patients with unresectable hepatocellular carcinoma (HCC).MethodsThis retrospective study included 100 patients with nonmetastatic, unresectable HCC in two hospitals. Eligible patients had tumor nodules ≤3 and Child-Pugh liver function score of A5 to B7. Seventy patients received SBRT-alone, and 30 patients underwent combined SBRT and immunotherapy (SBRT-IO). Overall survival (OS), time to progression (TTP), overall response rate (ORR), and toxicity were analyzed. We adjusted for the potential confounding factors using propensity score matching.ResultsThe median tumor size was 7.3 cm (range, 2.6-18 cm). Twenty-five (25%) of patients had vascular invasion. Before propensity score matching, the 1-year and 3-year OS rate was 89.9% and 59.8% in the SBRT-IO group and 75.7% and 42.3% in SBRT-alone group (p = 0.039). After propensity score matching (1:2), 25 and 50 patients were selected from the SBRT-IO and SBRT-alone group. The 1-year and 3-year OS was 92.0% and 63.9% in the SBRT-IO group versus 74.0% and 43.3% in the SBRT-alone group (p = 0.034). The 1-year and 3-year TTP was better in SBRT-IO group (1-year: 68.9% vs. 58.9% and 3-year: 61.3% vs. 32.5%, p = 0.057). The ORR of 88% (complete response [CR]: 56%, partial response [PR]: 22%) in SBRT-IO arm was significantly better than 50% (CR: 20%, PR: 30%) in the SBRT-alone arm (p = 0.006). Three patients (12%) developed ≥grade 3 immune-related treatment adverse events (n = 2 hepatitis, n = 1 dermatitis) leading to permanent treatment discontinuation.ConclusionAdding immunotherapy to SBRT resulted in better survival with manageable toxicities. Prospective randomized trial is warranted.

| S-EPMC11095610 | biostudies-literature

PARP Inhibitor CVL218 in Combination Therapy for Patients With Advanced Solid Tumors

Project description:This study aims to evaluate the efficacy of CVL218 in combination with Toripalimab injection/Sintilimab injection (Darbersol, Sintilimab) in the treatment of advanced solid tumors. It focuses on assessing the safety, tolerability, and pharmacokinetic profile of a three-drug combination regimen comprising albumin-bound paclitaxel injection (Kealil), paclitaxel injection (Taxol), and Fuquinitinib capsule (Aiutec, Fruquintinib).

| 108884 | ecrin-mdr-crc

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