Smith J Joshua, Wasserman Isaac, Milgrom Sarah A, Chow Oliver S, Chen Chin-Tung, Patil Sujata, Goodman Karyn A, Garcia-Aguilar Julio
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
Icahn School of Medicine at Mount Sinai, New York, New York.
Int J Radiat Oncol Biol Phys. 2017 Apr 1;97(5):924-930. doi: 10.1016/j.ijrobp.2016.12.015. Epub 2016 Dec 18.
To validate the finding of an association between single nucleotide polymorphisms (SNPs) and toxicity during chemoradiotherapy (CRT) in rectal cancer patients, in an independent population.
The cohort consisted of 165 patients who received CRT for rectal cancer from 2006 to 2012. Prospectively recorded toxicity information, graded according to the Common Terminology Criteria for Adverse Events version 3.0, was retrieved from the medical record. Additionally, a subset of 52 patients recorded their gastrointestinal symptoms weekly during CRT, using the 7-item Bowel Problems Scale. Deoxyribonucleic acid was extracted from normal tissue in the proctectomy specimens and screened for 3 SNPs: XRCC1 R399Q, XPD K751Q, and TGFβ1 R25P. Univariable and multivariable logistic regression models were constructed.
The median radiation dose was 50.4 Gy, and all patients received concurrent chemotherapy. Toxicities measured by the Common Terminology Criteria for Adverse Events were closely associated with patient-reported outcomes for the patients who completed the 7-item Bowel Problems Scale. Grade ≥3 toxicity occurred during CRT in 14 patients (8%). All 14 patients had either XRCC1 R399Q or TGFβ1 R25P polymorphisms. The TGFβ1 R25P polymorphism was significantly associated with grade ≥3 toxicity (odds ratio [OR] 3.47, P=.04) and, in patients who completed the Bowel Problems Scale, with grade ≥4 toxicity (OR 5.61, P=.02). The latter finding persisted in a multivariable logistic regression model controlling for ethnicity, age, and sex (adjusted OR 1.83, P=.02).
We have validated the correlation between the TGFβ1 R25P SNP and acute toxicity during CRT in an independent cohort using both clinician- and patient-reported toxicity. The information from our study could be used as a basis to formulate a prospective trial testing the utility of this SNP as a biomarker of acute toxicity during neoadjuvant treatment in locally advanced rectal cancer.
在一个独立人群中验证直肠癌患者在放化疗（CRT）期间单核苷酸多态性（SNP）与毒性之间存在关联这一发现。
该队列由2006年至2012年期间接受直肠癌CRT治疗的165例患者组成。从病历中检索前瞻性记录的毒性信息，按照不良事件通用术语标准第3.0版进行分级。此外，52例患者的一个亚组在CRT期间每周使用7项肠道问题量表记录其胃肠道症状。从直肠切除标本的正常组织中提取脱氧核糖核酸，并筛查3个SNP：XRCC1 R399Q、XPD K751Q和TGFβ1 R25P。构建单变量和多变量逻辑回归模型。
中位放射剂量为50.4 Gy，所有患者均接受同步化疗。根据不良事件通用术语标准测量的毒性与完成7项肠道问题量表的患者的患者报告结局密切相关。14例患者（8%）在CRT期间发生≥3级毒性。所有14例患者均具有XRCC1 R399Q或TGFβ1 R25P多态性。TGFβ1 R25P多态性与≥3级毒性显著相关（比值比[OR] 3.47，P = 0.04），并且在完成肠道问题量表的患者中，与≥4级毒性相关（OR 5.61，P = 0.02）。在控制种族、年龄和性别的多变量逻辑回归模型中，后一发现仍然存在（调整后的OR 1.83，P = 0.02）。
我们在一个独立队列中使用临床医生和患者报告的毒性，验证了TGFβ1 R25P SNP与CRT期间急性毒性之间的相关性。我们研究中的信息可作为制定前瞻性试验的基础，该试验测试该SNP作为局部晚期直肠癌新辅助治疗期间急性毒性生物标志物的效用。
