Optimization of Radiation Protection Through Genomic Analyses (ORtogether)

Optimization of Radiation Protection Through Genomic Analyses in the Analysis of Changes in Cells of the Hematopoietic System Before and During High Dose External Beam Radiotherapy

The long-term goal is to define "signatures" in the form of genomic changes through sequence analyses of genomic DNA using modern Next Generation Sequencing (NGS) methods, which

1. determine the radiation exposure of humans.
2. provide information about the exposure (dose).
3. determine the radiation quality.
4. predict the repair capacity and radiation resistance of an individual.

Study Overview

• Status: Recruiting
• Conditions: Cancer; Radiation; DNA
• Intervention / Treatment: Radiation: genomic alterations

Detailed Description

The planned research work will investigate structural changes in DNA caused by loosely ionizing and high-LET (Linear Energy Transfer) radiation as well as their attribution to double-strand break repair pathways, which will be analysed in parallel using modern microscopy methods. Our aim is to incorporate sequencing technologies into the spectrum of methods used in radiation research and radiation protection. It is important for us to consider the practical requirements of radiation protection and to extend our experimental approaches to cell types relevant to radiation protection. For this reason, we have now created a separate work program that will focus specifically on sequence analyses in irradiated human lymphocytes. The aim is to successfully transfer the experimental approaches and bioinformatic analyses established in previous experiments in human skin fibroblasts to lymphocytes. Subjects can donate blood samples on a voluntary basis at predetermined times. Only subjects without previous radiotherapy, chemotherapy, immunotherapy, targeted therapy, etc. and without a previous tumor diagnosis in the medical history and in good performance status (ECOG 0-1) will be included.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Germany / NRW
    • Essen, Germany / NRW, Germany, 45147
      • Recruiting
      • Department for Radiotherapy, University Hospital Essen, National Center for Tumor Diseases (NCT) West
      • Contact: Maja Guberina, PD Dr. med. (MD), specialist; Phone Number: +492017232321; Email: maja.guberina@uk-essen.de
      • Contact: Ina Grübel
      • Principal Investigator: Maja Guberina, PD Dr. med. (MD)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

ECOG 0/1 no prior treatment no prior cancer diagnosis thoracic or head and neck cancer

Exclusion Criteria:

prior treatment (chemotherapy, radiotherapy, etc.) prior cancer diagnosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Interventional Arm	Radiation: genomic alterations; Alteration of the genome under radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alteration of the genome under radiotherapy	Radiotherapy of patients, quantitative tissue sampling, cell culture survival rate and mitotic index after predifined radiation treatment, Incidence of the sample and percentage	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Progression Free Survival	5 years
Overall Survival	Overall Survival	5 years
Radiation induced changes in the genome	Radiation induced changes in the genome analyzing human skin fibroblasts and lymphocytes: translocations that permitted cell division andm mismatch repair of radiation-induced DNA damage (PCR and M-FISH), Incidence of the sample and percentage	2 months to 5 years

Collaborators and Investigators

• Sponsor: University Hospital, Essen

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2024
• Primary Completion (Estimated): December 15, 2025
• Study Completion (Estimated): January 15, 2030

Study Registration Dates

• First Submitted: December 30, 2023
• First Submitted That Met QC Criteria: February 7, 2024
• First Posted (Actual): February 12, 2024

Study Record Updates

• Last Update Posted (Actual): September 27, 2024
• Last Update Submitted That Met QC Criteria: September 25, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: DNA; cancer; outcome; genomic; lymphocyte; thoracic radiotherapy; sequencing technologies; loosely ionizing radiation; Linear Energy Transfer
• Other Study ID Numbers: 23-11672-BO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No