Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Infections

Wounds and Injuries

Symptoms and General Pathology

Lung Neoplasms

Pneumonia

Radiation Pneumonitis

Communicable Diseases

Respiratory Tract Infections

Lung Diseases

Respiratory Tract Diseases

Lung Diseases, Interstitial

Lung Injury

Radiation Injuries

Lung cancer patients treated with thoracic radiation therapy

Xianglin Yuan, MD, PhD

Yang Tang, MD, PhD

Radiation pneumonitis is the most common complication and the major dose-limiting toxicity associated with radiotherapy, which can cause poor quality of life or life-threatening symptoms and might hinder the tumor-controlling effects of radiotherapy. Consequently, establishing reliable predictors for the occurrence of RP is of great significance such that the therapeutic effects of RT can be maximized while minimizing its adverse effects. The aim of this study is to figure out the biological prediction models of radiation pneumonitis.

1. Establish a clinical data base for the lung cancer patients treated with radiotherapy in Tongji Hospital.

   Data including age, gender, smoking state, KPS, pulmonary function, disease history, histology, stage, surgery, chemotherapy, dosimetric parameters of radiotherapy were collected.

   Peripheral blood was collected from all patients enrolled. All patients enrolled in this study are examined during and one month after radiotherapy. Then, the patients are followed every three months for the first year and every six months thereafter. At each follow-up visits, all patients are asked to undergo a chest X-ray or CT and clinical information, including symptoms, is collected. RP is graded by two radiation oncologists according to the Common Terminology Criteria for Adverse Events 4.0.
2. Select candidate genes and pathways which may be associated with radiation pneumonitis and identify their tagSNPs by Haploview.
3. Use Kaplan-Meier and Cox model to analyze the association of all the factors collected with radiation pneumonitis.
4. Establish a biological prediction models for radiation pneumonitis based on the statistics analysis

Study on the Biological Prediction Models of Radiation Pneumonitis

Huazhong University of Science and Technology

Professor, Chief Physician

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Lymphoma

Leukemia

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Vincristine

Adult survivors who developed persistent treatment-related neuropathy.

Adult survivors who did not develop persistent treatment-related neuropathy.

William E. Evans, PharmD

This observational study is designed to establish induced pluripotent stem cells (iPSCs) from childhood cancer survivors who did or did not develop persistent treatment-induced peripheral neuropathy, from which to make human neurons for comparing their sensitivity to vincristine and other potentially neurotoxic drugs.

Investigators will assess the effects of inherited genome variations on treatment-induced peripheral neuropathy that persists in adults who were cured of childhood cancer. Cells from childhood cancer survivors who did or did not develop drug-induced neuropathy will be isolated and induced to become neurons. Cell sensitivity to anticancer agents will be tested in both groups and compared to determine if the survivors have genetic variants that correspond to those identified in companion genomic studies. This will assist in determining if gene variants increase the risk of treatment-induced neurotoxicity.

The investigators are interested in detecting changes of phenotype pre-post treatment in each group (cases, controls) respectively, as well in comparing the pre-post treatment phenotypic changes between the two groups (cases vs. controls).

Participants will be recruited from an existing protocol at St. Jude (SJLIFE, NCT00760656). Complete neuropathic evaluations are obtained as part of SJLIFE, and the information will be shared for use in the SJLPSC study. A one-time blood draw will be obtained, and peripheral blood mononuclear cells (PBMC's) will be isolated for eventual creation of induced pluripotent stem cells (iPSC) that will be differentiated into human neurons. These human neurons will allow the investigators to functionally validate and further interrogate CEP72 genetic variants or variants in other genes that are associated with persistent (or acute) vincristine neuropathy using a "state of the art" cellular model of human neurons. Furthermore, creating neurons from patients at the extremes (highly sensitive to vincristine-induced neuropathy and matched controls) allows the study of differences at baseline and after treatment with vincristine.

PRIMARY OBJECTIVE:

* To establish induced pluripotent stem cells (iPSCs) from childhood cancer survivors who did or did not develop persistent treatment-induced peripheral neuropathy, from which to make human neurons to assess their sensitivity to vincristine and determine whether neurons from patients who developed neuropathy are more sensitive to vincristine or other neurotoxic chemotherapy.

SECONDARY OBJECTIVE:

* To evaluate the iPSC neurons made from patients with persistent treatment-related neuropathy and iPSC neurons from patients who did not develop neuropathy from the same treatment, for phenotypic difference prior to and after exposure to vincristine or other potentially neurotoxic medications.

Blood samples will be obtained from each cohort.

iPSC Neurons From Adult Survivors of Childhood Cancer Who Have Persistent Vincristine-Induced Neuropathy

Collection of PBMC's From Patients With Unusually Severe Vincristine-Induced Neuropathy for the Creation of Neuronal-Like Cells

Blood will be drawn on Day 1, processed and sent to the University of Chicago for infectious diseases testing and creation of PBMCs for eventual development of iPS cells.

Cell phenotypes of the iPSC neurons made from each patient (case or control) will be observed before and after treatment of neurotoxic drugs, giving for each drug a pair of observations from a patient.

Study title	NCT ID	Conditions	Eligibility	Organization
Study on the Biological Prediction Models of Radiation Pneumonitis	NCT02490319	Radiation Pneum...	18 Years - 80 Years	Huazhong University of Science and Technology
Study on the Biological Prediction Models of Radiation Pneumonitis	NCT02490319	Radiation Pneum...	18 Years - 80 Years	Huazhong University of Science and Technology
iPSC Neurons From Adult Survivors of Childhood Cancer Who Have Persistent Vincristine-Induced Neuropathy	NCT02564484	Leukemia Lymphoma	18 Years -	St. Jude Children's Research Hospital

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