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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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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

| 87133 | ecrin-mdr-crc

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

Stereotactic body radiation therapy (SBRT) combined with PD1 inhibitor for the treatment of colorectal cancer liver metastasis: a prospective, multicenter, phase II clinical study

Project description:Interventions: SBRT combined with placebo treatment group:SBRT combined with placebo treatment;SBRT combined with immune checkpoint inhibitor treatment group:SBRT combined with immune checkpoint inhibitor treatment Primary outcome(s): Local control and survival rates Study Design: Parallel

| 113557 | ecrin-mdr-crc

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.

| 2170197 | ecrin-mdr-crc

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.

| 2073283 | 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

Repeat stereotactic body radiation therapy (SBRT) for salvage of isolated local recurrence after definitive lung SBRT.

Project description:PurposeOptimal management of isolated local recurrences after stereotactic body radiation therapy (SBRT) for early non-small cell lung cancer (NSCLC) is unknown and literature describing repeat SBRT for in-field recurrences after initial SBRT are sparse. We investigate the safety and efficacy of salvage SBRT for isolated local failures after initial SBRT for NSCLC.Methods/materialsPatients receiving SBRT for isolated local recurrence after initial SBRT for early NSCLC were identified using a prospective registry. Both courses were 3-5 fractions with a biologically effective dose (BED10) of ≥100 Gy. Local failure was defined as within 1 cm of the initial planning target volume (PTV) or an overlap of the ≥25% isodose lines of the first and second treatments. Failures >1 cm beyond the PTV and without ≥25% overlap, or with additional recurrence sites were excluded. Kaplan-Meier analysis was used to estimate survival.ResultsA total 21 patients receiving salvage SBRT from 2008 to 2017 were identified. Median interval from initial SBRT to salvage SBRT was 23 months (7-52). Six patients (29%) had central tumors. Median follow-up time from salvage SBRT was 24 months (3-60). Median overall survival after salvage was 39 months. After reirradiation, two-year primary tumor control was 81%, regional nodal control was 89%, distant control was 75% and overall survival was 68%. Grade 2 pneumonitis occurred in 2 patients (10%) and grade 2 chest wall toxicity in 4 patients (19%). No grade 3+ toxicity was observed.ConclusionsSalvage SBRT for isolated local failures after initial SBRT appears safe, with low treatment-related toxicity and encouraging rates of tumor control.

| S-EPMC7655115 | biostudies-literature

Multiple Primary Lung Cancers: Treatment Outcomes After Stereotactic Body Radiotherapy (SBRT).

Project description:Purpose/objectivesPatients with lung cancer sometimes present with multiple primary lung cancers (MPLCs), either simultaneously (synchronous) or after treatment of an initial lesion (metachronous). Although open surgery remains a treatment mainstay for patients with stage I-II non-small-cell lung cancer (NSCLC), stereotactic body radiation therapy (SBRT) is an acceptable alternative for patients who are medically unfit for or who refuse surgery. In this study, we retrospectively examine the outcome among patients with early-stage MPLCs treated at our institution with SBRT.Materials/methodsPatients at our institution receiving SBRT for MPLC between June 2011 and March 2020 were reviewed retrospectively. Prior to undergoing definitive SBRT, the imaging, and pathology for every patient were reviewed in a multi-disciplinary thoracic/pulmonary tumor board. Dose and fractionation varied with the most common prescriptions being 50 Gy/5 fractions, 56 Gy/4 fractions, and 55 Gy/5 fractions.ResultsA total of 38 patients with a total of 80 MPLCs were treated, among which 68 were T1 lesions and 12 were T2 lesions. Median follow-up was 25.9 months, with local control (LC) rates calculated per lesion to be 98.6%, 93.3%, and 88.2% at one, two, and three years. Median overall survival (OS) was 43.5 months; 83.6%, 67.8%, and 52.3% at one, two, and three years, respectively. Sixty-two of the 80 (77.5%) treated lesions were not associated with any subsequent acute or late toxicity. The 18 (22.5%) lesions associated with toxicity included nine acute and nine late events. All toxicity was either grade 1 (13 of 18) or grade 2 (five of 18).ConclusionsSBRT for early-stage MPLC achieves high control rates with limited toxicity. MPLC patients deemed unfit for open surgical management should be considered for definitive SBRT.

| S-EPMC10395656 | biostudies-literature

Stereotactic body radiotherapy is effective in modifying the tumor genome and tumor immune microenvironment in non-small cell lung cancer or lung metastatic carcinoma [RNA-seq]

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

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