Browse
Submit Data
Databases
API
Help

Dataset Information

0 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 | 2020 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

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

Gough Michael J MJ Sharon Shay S Crittenden Marka R MR Young Kristina H KH

Seminars in radiation oncology 20200401 2

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. How ...[more]

PMID: 32381295

Similar Datasets

Radiation therapy digital data submission process for national clinical trials network.

Project description: Not available

| S-EPMC4292925 | biostudies-literature

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

Adaptive Phase 1 Design in Radiation Therapy Trials.

Project description: Not available

| S-EPMC9260906 | 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

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:BackgroundRadiation 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.MethodsThe 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.ResultsUp-to-date literature concerning the mechanisms, interactions, and latest knowledge about rt and immunotherapy was reviewed and summarized, and is presented here.ConclusionsThe 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

Computational design of clinical trials using a combination of simulation and the genetic algorithm.

Project description:Artificial intelligence (AI) has come to be used in various technological fields in recent years. However, there have been no reports of AI-designed clinical trials. In this study, we tried to develop study designs by a genetic algorithm (GA), which is an AI solution for combination optimization problems. Specifically, the computational design approach was applied to optimize the blood sampling schedule for a bioequivalence (BE) study in pediatrics and optimize the allocation of dose groups for a dose-finding study. The GA could reduce the number of blood collection points from 15 (typical standard) to seven points without meaningful impact on the accuracy and precision of the pharmacokinetic estimation for the pediatric BE study. For the dose-finding study, up to 10% reduction of the total number of required subjects from the standard design could be achieved. The GA also created a design that would lead to a drastic reduction of the required number of subjects in the placebo arm while keeping the total number of subjects at a minimum level. These results indicated the potential usefulness of the computational clinical study design approach for innovative drug development.

| S-EPMC10088085 | biostudies-literature

Designing Clinical Trials for Combination Immunotherapy: A Framework for Glioblastoma.

Project description:Immunotherapy has revolutionized treatment for many hard-to-treat cancers but has yet to produce significant improvement in outcomes for patients with glioblastoma. This reflects the multiple and unique mechanisms of immune evasion and escape in this highly heterogeneous tumor. Glioblastoma engenders profound local and systemic immunosuppression and is remarkably effective at inducing T-cell dysfunction, posing a challenge to any immunotherapy-based approach. To overcome these mechanisms, multiple disparate modes of immune-oriented therapy will be required. However, designing trials that can evaluate these combinatorial approaches requires careful consideration. In this review, we explore the immunotherapy resistance mechanisms that have been encountered to date and how combinatorial approaches may address these. We also describe the unique aspects of trial design in both preclinical and clinical settings and consider endpoints and markers of response best suited for an intervention involving multiple agents.

| S-EPMC9306329 | 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