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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Radiation Toxicity, Advanced Cancer, Radiosensitivity

Intervention / Treatment
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* Genetic: next generation sequence


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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; Patients need conventional fractionation and adequate radiotherapy; Age ≥ 18 years old, male and female; Expected survival time ≥ 12 weeks; PS score 0-2 within 2 weeks before admission to the group; There are tumor tissue samples and blood samples can be used for NGS inspection; 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: The patient's previous radiation therapy leads to overlapping potential fields; Stage IV patients and stage I patients to be treated with SBRT The patient cannot receive regular imaging examinations; 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; The researcher believes that it is not suitable for the group.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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radiotherapy, radiosensitivity, radiation toxity, NGS