1. Combined low initial DNA damage and high radiation-induced apoptosis confers clinical resistance to long-term toxicity in breast cancer patients treated with high-dose radiotherapy
- Author
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Ruth Carmona-Vigo, Beatriz Pinar, María Isabel Núñez, Pedro C. Lara, Carlos Rodríguez-Gallego, Elisa Bordón, Marta Lloret, Luis Alberto Henríquez-Hernández, [Henríquez-Hernández,L.A, Carmona-Vigo,R, Pinar,B, Bordón,E, Lloret,M, Lara,PC] Radiation Oncology Department, Hospital Universitario de Gran Canaria Dr.Negrín, Spain. [Henríquez-Hernández,L.A, Rodríguez-Gallego,C, Lara,PC] Instituto Canario de Investigación del Cáncer (ICIC), Spain. [Henríquez-Hernández,L.A, Lara,PC] Clinical Sciences Department, Universidad de Las Palmas de Gran Canaria, Spain. [Núñez, M. I] Radiology Department, Hospital Universitario San Cecilio, Granada, Spain. [Rodríguez-Gallego, C.] Immunology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Spain., and This work was subsidized by a grant from the Ministerio de Educación y Ciencia (CICYT: SAF 2004-00889) and Fundación del Instituto Canario de Investigación del Cáncer (FICIC).
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Named Groups::Persons::Adult Children [Medical Subject Headings] ,medicine.medical_treatment ,ADN ,Named Groups::Persons::Age Groups::Adult::Aged::Aged, 80 and over [Medical Subject Headings] ,Apoptosis ,Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings] ,Radiation Tolerance ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Mediana Edad ,Lymphocytes ,Prospective cohort study ,Aged, 80 and over ,Adulto ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Radiotherapy [Medical Subject Headings] ,Neoplasias de la Mama ,Linfocitos ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Humanos ,Treatment Outcome ,320101 Oncología ,Daño del ADN ,Oncology ,Radiology Nuclear Medicine and imaging ,Femenina ,Toxicity ,Female ,Adult ,lcsh:Medical physics. Medical radiology. Nuclear medicine ,medicine.medical_specialty ,DNA damage ,Resultado del Tratamiento ,lcsh:R895-920 ,Anciano ,Urology ,Breast Neoplasms ,lcsh:RC254-282 ,Phenomena and Processes::Physiological Phenomena::Physiological Processes::Radiation Tolerance::Dose-Response Relationship, Radiation [Medical Subject Headings] ,Breast cancer ,Radioterapia ,medicine ,Humans ,Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes [Medical Subject Headings] ,Radiology, Nuclear Medicine and imaging ,Radiosensitivity ,Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings] ,Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings] ,Aged ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings] ,Tolerancia a Radiación ,Radiotherapy ,Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA Damage [Medical Subject Headings] ,business.industry ,Relación Dosis-Respuesta en la Radiación ,Research ,Dose fractionation ,Dose-Response Relationship, Radiation ,DNA ,medicine.disease ,Anciano de 80 o más Años ,Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::Apoptosis [Medical Subject Headings] ,Phenomena and Processes::Physiological Phenomena::Physiological Processes::Radiation Tolerance [Medical Subject Headings] ,Radiation therapy ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Radiotherapy::Radiotherapy Dosage::Dose Fractionation [Medical Subject Headings] ,Check Tags::Female [Medical Subject Headings] ,Dose Fractionation, Radiation ,Nuclear medicine ,business ,Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::DNA [Medical Subject Headings] ,DNA Damage ,Fraccionamiento de la Dosis - Abstract
Background Either higher levels of initial DNA damage or lower levels of radiation-induced apoptosis in peripheral blood lymphocytes have been associated to increased risk for develop late radiation-induced toxicity. It has been recently published that these two predictive tests are inversely related. The aim of the present study was to investigate the combined role of both tests in relation to clinical radiation-induced toxicity in a set of breast cancer patients treated with high dose hyperfractionated radical radiotherapy. Methods Peripheral blood lymphocytes were taken from 26 consecutive patients with locally advanced breast carcinoma treated with high-dose hyperfractioned radical radiotherapy. Acute and late cutaneous and subcutaneous toxicity was evaluated using the Radiation Therapy Oncology Group morbidity scoring schema. The mean follow-up of survivors (n = 13) was 197.23 months. Radiosensitivity of lymphocytes was quantified as the initial number of DNA double-strand breaks induced per Gy and per DNA unit (200 Mbp). Radiation-induced apoptosis (RIA) at 1, 2 and 8 Gy was measured by flow cytometry using annexin V/propidium iodide. Results Mean DSB/Gy/DNA unit obtained was 1.70 ± 0.83 (range 0.63-4.08; median, 1.46). Radiation-induced apoptosis increased with radiation dose (median 12.36, 17.79 and 24.83 for 1, 2, and 8 Gy respectively). We observed that those "expected resistant patients" (DSB values lower than 1.78 DSB/Gy per 200 Mbp and RIA values over 9.58, 14.40 or 24.83 for 1, 2 and 8 Gy respectively) were at low risk of suffer severe subcutaneous late toxicity (HR 0.223, 95%CI 0.073-0.678, P = 0.008; HR 0.206, 95%CI 0.063-0.677, P = 0.009; HR 0.239, 95%CI 0.062-0.929, P = 0.039, for RIA at 1, 2 and 8 Gy respectively) in multivariate analysis. Conclusions A radiation-resistant profile is proposed, where those patients who presented lower levels of initial DNA damage and higher levels of radiation induced apoptosis were at low risk of suffer severe subcutaneous late toxicity after clinical treatment at high radiation doses in our series. However, due to the small sample size, other prospective studies with higher number of patients are needed to validate these results.
- Published
- 2011