RT Journal Article
T1 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
A1 Henríquez-Hernández, Luis Alberto
A1 Carmona-Vigo, Ruth
A1 Pinar, Beatriz
A1 Bordón, Elisa
A1 Lloret, Marta
A1 Núñez, María Isabel
A1 Rodríguez-Gallego, Carlos
A1 Lara, Pedro C
K1 Adulto
K1 ADN
K1 Anciano
K1 Anciano de 80 o más Años
K1 Apoptosis
K1 Neoplasias de la Mama
K1 Daño del ADN
K1 Fraccionamiento de la Dosis
K1 Relación Dosis-Respuesta en la Radiación
K1 Femenina
K1 Humanos
K1 Linfocitos
K1 Mediana Edad
K1 Tolerancia a Radiación
K1 Radioterapia
K1 Resultado del Tratamiento
AB 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.
PB BIOMED CENTRAL LTD
YR 2011
FD 2011
LK http://hdl.handle.net/10668/543
UL http://hdl.handle.net/10668/543
LA en
NO Henríquez-Hernández LA, Carmona-Vigo R, Pinar B, Bordón E, Lloret M, Núñez MI, et al. 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. Radiat Oncol; 6:60
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 10, 2025