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
| Autor: | Ruth Carmona-Vigo, Beatriz Pinar, María Isabel Núñez, Pedro C. Lara, Carlos Rodríguez-Gallego, Elisa Bordón, Marta Lloret, Luis Alberto Henríquez-Hernández |
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| Přispěvatelé: | [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., 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). |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
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 |
| Zdroj: | Radiation Oncology 2011, 6:60 Radiation Oncology, Vol 6, Iss 1, p 60 (2011) Radiation Oncology (London, England) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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