Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Using Preclinical Data to Design Combination Clinical Trials of Radiation Therapy and Immunotherapy.

ABSTRACT: Immunotherapies are rapidly entering the clinic as approved treatments for diverse cancer pathologies. Radiation therapy is an integral partner in cancer therapy, commonly as part of complicated multimodality approaches that optimize patient outcomes. Preclinical studies have demonstrated that the success of radiation therapy in tumor control is due in part to immune mechanisms, and that outcomes following radiation therapy can be improved through combination with a range of immunotherapies. However, preclinical models of cancer are very different from patient tumors, and the way these preclinical tumors are treated is often very different from standard of care treatment of patients. This review examines the preclinical and clinical data for the role of the immune system in radiation therapy outcomes, and how to integrate preclinical findings into clinical trials, using ongoing studies as examples.

SUBMITTER: Gough MJ

PROVIDER: S-EPMC7213059 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Radiation nanosensitizers in cancer therapy-From preclinical discoveries to the outcomes of early clinical trials.

Project description:Improving the efficacy and spatial targeting of radiation therapy while sparing surrounding normal tissues has been a guiding principle for its use in cancer therapy. Nanotechnologies have shown considerable growth in terms of innovation and the development of new therapeutic approaches, particularly as radiosensitizers. The aim of this study was to systematically review how nanoparticles (NPs) are used to enhance the radiotherapeutic effect, including preclinical and clinical studies. Clinicaltrials.gov was used to perform the search using the following terms: radiation, cancer, and NPs. In this review, we describe the various designs of nano-radioenhancers, the rationale for using such technology, as well as their chemical and biological effects. Human trials are then discussed with an emphasis on their design and detailed clinical outcomes.

| S-EPMC8780058 | biostudies-literature

Data-Based Radiation Oncology: Design of Clinical Trials in the Toxicity Biomarkers Era.

Project description:The ability to stratify patients using a set of biomarkers, which predict that toxicity risk would allow for radiotherapy (RT) modulation and serve as a valuable tool for precision medicine and personalized RT. For patients presenting with tumors with a low risk of recurrence, modifying RT schedules to avoid toxicity would be clinically advantageous. Indeed, for the patient at low risk of developing radiation-associated toxicity, use of a hypofractionated protocol could be proposed leading to treatment time reduction and a cost-utility advantage. Conversely, for patients predicted to be at high risk for toxicity, either a more conformal form or a new technique of RT, or a multidisciplinary approach employing surgery could be included in the trial design to avoid or mitigate RT when the potential toxicity risk may be higher than the risk of disease recurrence. In addition, for patients at high risk of recurrence and low risk of toxicity, dose escalation, such as a greater boost dose, or irradiation field extensions could be considered to improve local control without severe toxicities, providing enhanced clinical benefit. In cases of high risk of toxicity, tumor control should be prioritized. In this review, toxicity biomarkers with sufficient evidence for clinical testing are presented. In addition, clinical trial designs and predictive models are described for different clinical situations.

| S-EPMC5406456 | biostudies-literature

A Syngeneic ErbB2 Mammary Cancer Model for Preclinical Immunotherapy Trials

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-03-03 | GSE113380 | GEO

Adaptive Phase 1 Design in Radiation Therapy Trials.

Project description: Not available

| S-EPMC9260906 | biostudies-literature

Current clinical trials testing combinations of immunotherapy and radiation.

Project description:Preclinical evidence of successful combinations of ionizing radiation with immunotherapy has inspired testing the translation of these results to the clinic. Interestingly, the preclinical work has consistently predicted the responses encountered in clinical trials. The first example came from a proof-of-principle trial started in 2001 that tested the concept that growth factors acting on antigen-presenting cells improve presentation of tumor antigens released by radiation and induce an abscopal effect. Granulocyte-macrophage colony-stimulating factor was administered during radiotherapy to a metastatic site in patients with metastatic solid tumors to translate evidence obtained in a murine model of syngeneic mammary carcinoma treated with cytokine FLT-3L and radiation. Subsequent clinical availability of vaccines and immune checkpoint inhibitors has triggered a wave of enthusiasm for testing them in combination with radiotherapy. Examples of ongoing clinical trials are described in this report. Importantly, most of these trials include careful immune monitoring of the patients enrolled and will generate important data about the proimmunogenic effects of radiation in combination with a variety of immune modulators, in different disease settings. Results of these studies are building a platform of evidence for radiotherapy as an adjuvant to immunotherapy and encourage the growth of this novel field of radiation oncology.

| S-EPMC4640687 | biostudies-literature

Radiation therapy and immunotherapy-a potential combination in cancer treatment.

Project description:Background:Radiation therapy (rt) is a longstanding treatment modality for cancer. In addition, immune checkpoint blockade has been a significant development in the field of immunotherapy, modifying key immunosuppressive pathways of cancer cells. Methods:The aim of the present work was to review current concepts of rt and immunotherapy synergism, the abscopal effect, and the molecular effects of rt in the tumour microenvironment, its influence on immune stimulation, and potential clinical outcomes that might evolve from ongoing studies. We also discuss potential predictors of clinical response. Results:Up-to-date literature concerning the mechanisms, interactions, and latest knowledge about rt and immunotherapy was reviewed and summarized, and is presented here. Conclusions:The possibility of using hyperfractionated rt to combine an abscopal effect with the enhanced effect of immune treatment using checkpoint blockade is a very promising method for future tumour treatments.

| S-EPMC6209565 | biostudies-literature

A Syngeneic ErbB2 Mammary Cancer Model for Preclinical Immunotherapy Trials [microarray]

Project description:A cell line was derived from a mammary carcinoma in the transgenic FVB/N-Tg(MMTV-ErbB2)NDL2-5Mul mouse. The line, referred to as “NDL(UCD)” is adapted to standard cell culture and can be transplanted into syngeneic FVB/N mouse. The line maintains stable phenotype over multiple in vitro passages and rounds of in vivo transplantation. The cell line exhibits high expression of ErbB2 and ErbB3 and signaling molecules downstream ErbB2. The line was previously shown to be reactive to anti-immune checkpoint therapy with responses conducive to immunotherapy studies. Here, using both histology/immunophenotyping and gene expression/microarray analysis, we show that the syngeneic transplant tumors elicit an immune reaction in the adjacent stroma, with additional tumor infiltrating lymphocytes. We also show that this immune activating effect is greater in the syngeneic transplants than in the tumors arising in the transgenic mouse. We further analyzed the PD-1 and PD-L-1 expression in the model and found strong PD-L1 expression in the tumors and in vitro. Three distinct transplantable syngenic mouse models of mammary carcinoma were compared to identify differentially expressed genes.

2019-03-06 | GSE112723 | GEO

Current clinical trials testing the combination of immunotherapy with radiotherapy.

Project description:Increasing evidence demonstrates that radiation acts as an immune stimulus, recruiting immune mediators that enable anti-tumor responses within and outside the radiation field. There has been a rapid expansion in the number of clinical trials harnessing radiation to enhance antitumor immunity. If positive, results of these trials will lead to a paradigm shift in the use of radiotherapy. In this review, we discuss the rationale for trials combining radiation with various immunotherapies, provide an update of recent clinical trial results and highlight trials currently in progress. We also address issues pertaining to the optimal incorporation of immunotherapy with radiation, including sequencing of treatment, radiation dosing and evaluation of clinical trial endpoints.

| S-EPMC5028964 | biostudies-literature

Preclinical rationale for combining radiation therapy and immunotherapy beyond checkpoint inhibitors (i.e., CART).

Project description:An increasing appreciation for the role of the immune system in targeting cancer cells over the last decade has led to the development of several immunomodulatory agents aimed at enhancing the systemic antitumor immune response. One such method is the use of T cells that are genetically engineered to express chimeric antigen receptors (CARs). The remarkable success of this approach in advanced hematologic malignancies has garnered much enthusiasm for using this novel tool in treating other cancers. However, multiple challenges have hampered the application of this therapy to a broader set of solid tumors, most notably lung cancer. Immunotherapy has already shown great success in lung cancer, and is now the first-line treatment in PD-L1 expressing metastatic disease. Given the mounting evidence that radiation therapy plays a crucial role in amplifying the immune response elicited by immunomodulatory agents, there is potential for radiation to help in overcoming some of these challenges. In this review, we describe the basic principles of CAR T cell therapy and examine its successes and challenges to date. We then discuss the preclinical and clinical data supporting the use of radiation with immunomodulatory agents with a focus on preclinical rationale for combining CAR T cells and radiation therapy in future experiments with a focus on lung cancer.

| S-EPMC5420544 | biostudies-literature

Evaluating the utility of knowledge-based planning for clinical trials using the TROG 08.03 post prostatectomy radiation therapy planning data.

Project description:Background and purposePoor quality radiotherapy can detrimentally affect outcomes in clinical trials. Our purpose was to explore the potential of knowledge-based planning (KBP) for quality assurance (QA) in clinical trials.Materials and methodsUsing 30 in-house post-prostatectomy radiation treatment (PPRT) plans, an iterative KBP model was created according to the multicentre clinical trial protocol, delivering 64 Gy in 32 fractions. KBP was used to replan 137 plans. The KB (knowledge based) plans were evaluated for their ability to fulfil the trial constraints and were compared against their corresponding original treatment plans (OTP). A second analysis between only the 72 inversely planned OTPs (IP-OTPs) and their corresponding KB plans was performed.ResultsAll dose constraints were met in 100% of KB plans versus 69% of OTPs. KB plans demonstrated significantly less variation in PTV coverage (Mean dose range: KB plans 64.1 Gy-65.1 Gy vs OTP 63.1 Gy-67.3 Gy, p < 0.01). KBP resulted in significantly lower doses to OARs. Rectal V60Gy and V40Gy were 17.7% vs 27.7% (p < 0.01) and 40.5% vs 53.9% (p < 0.01) for KB plans and OTP respectively. Left femoral head (FH) V45Gy and V35Gy were 0.4% vs 7.4% (p < 0.01) and 7.9% vs 34.9% (p < 0.01) respectively. In the second analysis plan improvements were maintained.ConclusionsKBP created high quality PPRT plans using the data from a multicentre clinical trial in a single optimisation. It is a powerful tool for utilisation in clinical trials for patient specific QA, to reduce dose to surrounding OARs and variations in plan quality which could impact on clinical trial outcomes.

| S-EPMC9117914 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data