Validation Studies of Biomarkers for Precision Radiation Oncology in Locally Advanced Solid Tumors

Despite the common application of radiotherapy in cancer treatment, the prediction of radiosensitivity and treatment response has not yet entered the era of precision medicine. Therefore, development of genome-based methods for predicting radiosensitivity and treatment response is a central goal of radiation oncology. In the previous study, the investigators have identified a set of novel potential biomarkers associated with radiosensitivity and recurrence，through correlating patients' genomic profiles with toxicity, disease progression and overall survival after RT.

Study Overview

• Status: Unknown
• Conditions: Advanced Cancer; Radiation Toxicity; Radiosensitivity
• Intervention / Treatment: Genetic: next generation sequence

Detailed Description

Researchers have long recognized that individual differences in sensitivity to radiation are caused by genetic variations and implicated multiple key pathways that might explain radiation toxicity. Normal tissue toxicity is a complex trait that involves the combined effect of a multitude of genes and pathways, and also dynamic interactions with the evolving cancer genome. The effect size of any individual factor is likely small. As a consequence, candidate gene approach and genome-wide association studies rarely lead to the identification of genetic determinants of radiation toxicity. Targeted next-generation sequencing (NGS), on the other hand, has become increasingly routine in the clinic and would allow simultaneous assessment of multiple genetic alterations.

• Study Type: Observational
• Enrollment (Anticipated): 600

Contacts and Locations

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250117
      • Recruiting
      • Shandong Cancer Hospital and Institute
      • Contact: Jinming Yu; Phone Number: 8653167626891

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients in the study with locally advanced solid tumors undergoing conventional fractionation or preoperative neoadjuvant radiotherapy (except stage IV patients and stage I patients to be treated with SBRT), including lung cancer, esophageal cancer, rectal cancer (neoadjuvant), cervical cancer, nasopharyngeal carcinoma and liver cancer

Description

Inclusion Criteria:

1. Patients with locally advanced solid tumors (lung cancer, esophageal cancer, rectal cancer (neoadjuvant), cervical cancer, nasopharyngeal carcinoma cancer and liver cancer) identified by cytology and pathology;
2. Patients need conventional fractionation and adequate radiotherapy;
3. Age ≥ 18 years old, male and female;
4. Expected survival time ≥ 12 weeks;
5. PS score 0-2 within 2 weeks before admission to the group;
6. There are tumor tissue samples and blood samples can be used for NGS inspection;
7. Patients volunteered to join this study, sign informed consent, provide all diagnosis and treatment data after cancer diagnosis before entering the group, good compliance, cooperate with follow-up.

Exclusion Criteria:

1. The patient's previous radiation therapy leads to overlapping potential fields;
2. Stage IV patients and stage I patients to be treated with SBRT
3. The patient cannot receive regular imaging examinations;
4. Any serious or uncontrolled signs of systemic disease that the investigator believes may significantly affect the patient's risk/benefit balance, including hepatitis B, hepatitis C, and human immunodeficiency virus;
5. The researcher believes that it is not suitable for the group.

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
non-smell cell lung cancer (NSCLC); Advanced NSCLC patients receiving radiotherapy or chemo-radiotherapy	Genetic: next generation sequence; targeted NGS of patients' pretreatment tumor biopsy samples using a 474-gene panel, which covers cancer- and radio-sensitivity-related mutations and SNPs.
Rectal cancer; Rectal cancer patients receiving neoadjuvant radiotherapy or chemo-radiotherapy	Genetic: next generation sequence; targeted NGS of patients' pretreatment tumor biopsy samples using a 474-gene panel, which covers cancer- and radio-sensitivity-related mutations and SNPs.
Smell cell lung cancer (SCLC); SCLC patients receiving radiotherapy or chemo-radiotherapy	Genetic: next generation sequence; targeted NGS of patients' pretreatment tumor biopsy samples using a 474-gene panel, which covers cancer- and radio-sensitivity-related mutations and SNPs.
Esophageal cancer; Esophageal cancer patients receiving radiotherapy or chemo-radiotherapy	Genetic: next generation sequence; targeted NGS of patients' pretreatment tumor biopsy samples using a 474-gene panel, which covers cancer- and radio-sensitivity-related mutations and SNPs.
Cervical cancer; Cervical cancer patients receiving radiotherapy or chemo-radiotherapy	Genetic: next generation sequence; targeted NGS of patients' pretreatment tumor biopsy samples using a 474-gene panel, which covers cancer- and radio-sensitivity-related mutations and SNPs.
Liver cancer; Liver cancer atients receiving radiotherapy or chemo-radiotherapy	Genetic: next generation sequence; targeted NGS of patients' pretreatment tumor biopsy samples using a 474-gene panel, which covers cancer- and radio-sensitivity-related mutations and SNPs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TTP	Time to progression	2 years
OS	Time to death	2 years

Collaborators and Investigators

• Sponsor: Shandong Cancer Hospital and Institute
• Investigators: Principal Investigator: Jinming Yu, Ph.D, Shandong Cancer Hospital and Institute

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 8, 2018
• Primary Completion (ANTICIPATED): October 8, 2021
• Study Completion (ANTICIPATED): October 8, 2021

Study Registration Dates

• First Submitted: June 12, 2019
• First Submitted That Met QC Criteria: September 29, 2019
• First Posted (ACTUAL): October 1, 2019

Study Record Updates

• Last Update Posted (ACTUAL): October 1, 2019
• Last Update Submitted That Met QC Criteria: September 29, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: radiotherapy; radiosensitivity; NGS; radiation toxity
• Other Study ID Numbers: GBRT-043

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