Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, QC H2X 3E4, Canada.
Curr Oncol. 2022 Jan 26;29(2):497-509. doi: 10.3390/curroncol29020045.
: 5-FU-based chemoradiotherapy (CRT) could be associated with severe treatment-related toxicities in patients harboring at-risk polymorphisms. : The studied population included consecutive patients with locoregionally advanced oropharyngeal carcinoma treated with carboplatin and 5-FU-based CRT one year before and after the implementation of upfront genotyping. We aimed to determine the effect of genotyping on grade ≥3 toxicities. : 181 patients were analyzed (87 patients before and 94 patients following screening). Of the patients, 91% ( = 86) were prospectively genotyped for the allele. Of those screened, 2% ( = 2/87) demonstrated a heterozygous mutation. Extended genotyping of -negative patients later allowed for the retrospective identification of six additional patients with alternative variants (two c.2846A>T and four c.1236G>A mutations). Grade ≥3 toxicities occurred in 71% of the patients before screening versus 62% following upfront genotyping ( = 0.18). When retrospectively analyzing additional non- variants, the relative risks for mucositis (RR 2.36 [1.39-2.13], = 0.0063), dysphagia (RR 2.89 [1.20-5.11], = 0.019), and aspiration pneumonia (RR 13 [2.42-61.5)], = 0.00065) were all significantly increased. : The , c.2846A>T, and c.1236G>A polymorphisms are associated with an increased risk of grade ≥3 toxicity to 5-FU. Upfront genotyping can identify patients in whom 5-FU-related toxicity should be avoided.
基于 5-FU 的放化疗（CRT）可能与携带高危多态性的患者的严重治疗相关毒性有关。
研究人群包括在实施基因分型前一年和后一年接受卡铂和基于 5-FU 的 CRT 治疗的局部晚期或口咽癌连续患者。我们旨在确定基因分型对≥3 级毒性的影响。
分析了 181 例患者（87 例在前，94 例在后）。86%（=86）的患者前瞻性地对 等位基因进行了基因分型。在筛选的患者中，有 2%（=2/87）表现出杂合性 突变。对-阴性患者的进一步扩展基因分型后来允许回顾性识别另外 6 例具有替代 变体的患者（2 例 c.2846A>T 和 4 例 c.1236G>A 突变）。筛选前，71%的患者发生≥3 级毒性，筛选后，62%的患者发生≥3 级毒性（=0.18）。当回顾性分析额外的非变体时，粘膜炎的相对风险（RR 2.36 [1.39-2.13]，=0.0063）、吞咽困难（RR 2.89 [1.20-5.11]，=0.019）和吸入性肺炎（RR 13 [2.42-61.5]，=0.00065）的相对风险均显著增加。
、c.2846A>T 和 c.1236G>A 多态性与 5-FU 相关的≥3 级毒性风险增加相关。 upfront 基因分型可以识别应避免 5-FU 相关毒性的患者。
