Concurrent or sequential letrozole with adjuvant breast radiotherapy: final results of the CO-HO-RT phase II randomized trial
Concurrent or sequential letrozole with adjuvant breast radiotherapy: final results of the CO-HO-RT phase II randomized trial
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DOI：
10.1093/annonc/mdv602
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发表时间：
2016-03-01
影响因子：
50.5
通讯作者：
Azria, D.
中科院分区：
文献类型：
--
作者：
Bourgier, C.;Kerns, S.;Azria, D.
在此，我们介绍了队列试验和两项转化亚研究的最终临床结果，旨在确定有辐射诱导的皮下纤维化（RISF）风险的患者：(i)辐射诱导的淋巴细胞凋亡（RILA）和（ii）某些单核苷酸多态性（snp）的候选物。绝经后I-II期乳腺癌患者（n = 150）被纳入研究，并被分配到同步放疗（A组）或序贯放疗(RT)-来曲唑（B组）。其中121例符合RILA和SNP检测的条件。a级每千日元2 RISF是主要终点。次要终点是肺和心脏事件以及癌变结果。RILA用于预测个体间RISF的差异。进行了一项全基因组关联研究，以确定与RILA和RISF相关的snp。分析是按照意向进行的。在中位随访74个月后，5名患者发展为a级千分之一日元RISF。在A组和b组之间没有观察到显著差异。没有观察到A级千元肺毒性和症状性心脏毒性。5例千分之一日元2级RISF患者的中位RILA值显著低于千分之一日元1级RISF患者（6.9%对13%，P = 0.02）。两个snp被鉴定为与RILA显著相关：rs1182531 （P = 4.2 × 10(-9)）和rs1182532 (P = 3.6 × 10(-8))；都位于染色体20q13.33上的PHACTR3基因内。通过长期随访，来曲唑可以安全地与乳腺辅助放疗一起使用。转化亚研究显示，高RILA值与未发生RISF.NCT00208273的患者相关。
We present here final clinical results of the COHORT trial and both translational sub-studies aiming at identifying patients at risk of radiation-induced subcutaneous fibrosis (RISF): (i) radiation-induced lymphocyte apoptosis (RILA) and (ii) candidates of certain single-nucleotide polymorphisms (SNPs).Post-menopausal patients with stage I-II breast cancer (n = 150) were enrolled and assigned to either concurrent (arm A) or sequential radiotherapy (RT)-letrozole (arm B). Among them, 121 were eligible for RILA and SNP assays. Grade a parts per thousand yen2 RISF were the primary end point. Secondary end points were lung and heart events and carcinologic outcome. RILA was performed to predict differences in RISF between individuals. A genome-wide association study was performed to identify SNPs associated with RILA and RISF. Analyses were done by intention to treat.After a median follow-up of 74 months, 5 patients developed a grade a parts per thousand yen2 RISF. No significant difference was observed between arms A and B. Neither grade a parts per thousand yen2 lung nor symptomatic cardiac toxicity was observed. Median RILA value of the five patients who had grade a parts per thousand yen2 RISF was significantly lower compared with those who developed grade a parts per thousand currency sign1 RISF (6.9% versus 13%, P = 0.02). Two SNPs were identified as being significantly associated with RILA: rs1182531 (P = 4.2 x 10(-9)) and rs1182532 (P = 3.6 x 10(-8)); both located within the PHACTR3 gene on chromosome 20q13.33.With long-term follow-up, letrozole can safely be delivered concomitantly with adjuvant breast RT. Translational sub-studies showed that high RILA values were correlated with patients who did not develop RISF.NCT00208273.