KRAS and Combined KRAS/TP53 Mutations in Locally Advanced Rectal Cancer are Independently Associated with Decreased Response to Neoadjuvant Therapy.
KRAS and Combined KRAS/TP53 Mutations in Locally Advanced Rectal Cancer are Independently Associated with Decreased Response to Neoadjuvant Therapy.
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DOI：
10.1245/s10434-016-5205-4
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发表时间：
2016-08
影响因子：
3.7
通讯作者：
Garcia-Aguilar J
中科院分区：
文献类型：
--
作者：
Chow OS;Kuk D;Keskin M;Smith JJ;Camacho N;Pelossof R;Chen CT;Chen Z;Avila K;Weiser MR;Berger MF;Patil S;Bergsland E;Garcia-Aguilar J
直肠癌对新辅助放化疗（CRT）的反应是可变的，但仍然缺乏预测反应的工具。我们评估了KRAS和TP 53突变是否与调整新辅助治疗方案后的病理完全缓解（pCR）和淋巴结转移相关。对229例II/III期直肠癌患者的预处理活检进行了回顾性分析。所有患者均接受CRT。患者在CRT之前或之后接受0至8个周期的FOLFOX，但在手术切除之前。分析了一个子集，以评估通过桑格测序和下一代测定法进行的突变调用之间的一致性。96例（42%）肿瘤有KRAS突变，150例有TP 53突变（66%），59例（26%）两者都有。59例患者（26%）在新辅助治疗后达到pCR。133例KRAS野生型肿瘤中有45例（34%）具有pCR，而96例KRAS突变型肿瘤中有14例（15%）具有pCR（p=0.001）。在调整临床分期、CRT至手术间隔和FOLFOX周期后，多变量分析中KRAS突变仍与较低的pCR率独立相关（OR 0. 34，95% CI：0. 17 - 0. 66，p <0. 01）。在29例KRAS G12 V或G13 D患者中，仅2例（7%）达到pCR。KRAS和TP 53突变均与淋巴结转移有关。KRAS平台之间的一致性较高（40/43，93%）。在调整新辅助治疗方案的变化后，KRAS突变与局部晚期直肠癌较低的pCR率独立相关基因组数据可能用于选择患者进行“观察和等待”策略。
The response of rectal cancers to neoadjuvant chemoradiation (CRT) is variable, but tools to predict response remain lacking. We evaluated whether KRAS and TP53 mutations are associated with pathologic complete response (pCR) and lymph node metastasis after adjusting for neoadjuvant regimen. Retrospective analysis of 229 pretreatment biopsies from patients with stage II/III rectal cancer was performed. All patients received CRT. Patients received zero to eight cycles of FOLFOX either before or after CRT, but prior to surgical excision. A subset was analyzed to assess concordance between mutation calls by Sanger sequencing and a next-generation assay. 96 (42%) tumors had KRAS mutation, 150 had TP53 mutation (66%), and 59 (26%) had both. 59 patients (26%) achieved pCR following neoadjuvant therapy. 45 of 133 (34%) KRAS wild-type tumors had pCR, compared with 14 of 96 (15%) KRAS mutant tumors (p=0.001). KRAS mutation remained independently associated with a lower pCR rate on multivariable analysis after adjusting for clinical stage, CRT-to-surgery interval, and cycles of FOLFOX (OR 0.34, 95% CI: 0.17-0.66, p < 0.01). Of 29 patients with KRAS G12V or G13D, only 2 (7%) achieved pCR. Tumors with both KRAS and TP53 mutation were associated with lymph node metastasis. The concordance between platforms was high for KRAS (40 of 43, 93%). KRAS mutation is independently associated with a lower pCR rate in locally advanced rectal cancer after adjusting for variations in neoadjuvant regimen. Genomic data can potentially be used to select patients for “watch and wait” strategies.
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DOI：
10.1007/s00432-014-1718-z
发表时间：
2014-10-01
影响因子：
3.6
作者：
Calvo, Felipe A.;Morillo, Virginia;Sole, Claudio
通讯作者：
Sole, Claudio
影响因子：
3.7
作者：
Wolthuis, Albert M.;Penninckx, Freddy;D'Hoore, Andre
通讯作者：
D'Hoore, Andre
影响因子：
3.7
作者：
Duldulao MP;Lee W;Nelson RA;Li W;Chen Z;Kim J;Garcia-Aguilar J
通讯作者：
Garcia-Aguilar J
纪念斯隆·克特林癌症中心的精密医学：临床下一代测序实现下一代目标治疗试验。
影响因子：
7.4
作者：
Hyman DM;Solit DB;Arcila ME;Cheng DT;Sabbatini P;Baselga J;Berger MF;Ladanyi M
通讯作者：
Ladanyi M
影响因子：
3.7
作者：
Lee, Dae-Won;Kim, Kyung Ju;Kim, Tae-You
通讯作者：
Kim, Tae-You