Radiation Oncology Department, Hospital Universitario de Gran Canaria Dr, Negrín, Spain.
Radiat Oncol. 2011 Jun 6;6:60. doi: 10.1186/1748-717X-6-60.
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.
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.
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.
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.
外周血淋巴细胞中初始 DNA 损伤水平较高或放射诱导细胞凋亡水平较低，均与发生晚期放射诱导毒性的风险增加有关。最近有研究报道，这两个预测性检测呈负相关。本研究的目的是探讨在一组接受高剂量超分割根治性放疗的乳腺癌患者中，这两种检测方法联合应用与临床放射诱导毒性的关系。
从 26 例局部晚期乳腺癌患者中采集外周血淋巴细胞，采用放射治疗肿瘤学组（RTOG）毒性评分方案评估急性和晚期皮肤和皮下毒性。对幸存者（n=13）进行平均 197.23 个月的随访。淋巴细胞的放射敏感性用每 Gy 和每 DNA 单位（200 Mbp）诱导的 DNA 双链断裂数来量化。用流式细胞术结合 Annexin V/碘化丙啶测量 1、2 和 8 Gy 时的放射诱导细胞凋亡（RIA）。
平均 DSB/Gy/DNA 单位为 1.70±0.83（范围 0.63-4.08；中位数，1.46）。放射诱导细胞凋亡随放射剂量增加而增加（中位数分别为 12.36、17.79 和 24.83，对应于 1、2 和 8 Gy）。我们发现，那些“预期耐药患者”（DSB 值低于 1.78 DSB/Gy/200 Mbp，且 RIA 值分别超过 1、2 和 8 Gy 时的 9.58、14.40 或 24.83）发生严重皮下晚期毒性的风险较低（多变量分析的 HR 分别为 0.223（95%CI 0.073-0.678，P=0.008）、0.206（95%CI 0.063-0.677，P=0.009）和 0.239（95%CI 0.062-0.929，P=0.039））。
提出了一种放射抵抗谱，其中那些初始 DNA 损伤水平较低、放射诱导细胞凋亡水平较高的患者，在我们的研究中，在高剂量放射治疗后，发生严重皮下晚期毒性的风险较低。然而，由于样本量较小，需要其他前瞻性研究，以增加患者数量，来验证这些结果。
