KRAS and combined KRAS/TP53 mutations in locally advanced rectal cancer are independently associated with decreased response to neoadjuvant therapy Journal Article


Authors: Chow, O. S.; Kuk, D.; Keskin, M.; Smith, J. J.; Camacho, N.; Pelossof, R.; Chen, C. T.; Chen, Z.; Avila, K.; Weiser, M. R.; Berger, M. F.; Patil, S.; Bergsland, E.; Garcia-Aguilar, J.
Article Title: KRAS and combined KRAS/TP53 mutations in locally advanced rectal cancer are independently associated with decreased response to neoadjuvant therapy
Abstract: 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 0-8 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. A total of 96 tumors (42 %) had KRAS mutation, 150 had TP53 mutation (66 %), and 59 (26 %) had both. Following neoadjuvant therapy, 59 patients (26 %) achieved pCR. Of 133 KRAS wild-type tumors, 45 (34 %) had pCR, compared with 14 of 96 (15 %) KRAS mutant tumors (p = .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 < .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.
Keywords: accuracy; ultrasonography; chemoradiotherapy; impact; colorectal-cancer; endorectal; stage-iii; metaanalysis; chemoradiation therapy; preoperative chemoradiation; nonoperative treatment
Journal Title: Annals of Surgical Oncology
Volume: 23
Issue: 8
ISSN: 1068-9265
Publisher: Springer  
Date Published: 2016-08-01
Start Page: 2548
End Page: 2555
Language: English
ACCESSION: WOS:000379189900027
DOI: 10.1245/s10434-016-5205-4
PROVIDER: wos
PUBMED: 27020587
PMCID: PMC5047012
Notes: Article -- Source: Wos
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MSK Authors
  1. Sujata Patil
    383 Patil
  2. Martin R Weiser
    338 Weiser
  3. Michael Forman Berger
    380 Berger
  4. Deborah Kuk
    81 Kuk
  5. Chin-Tung Chen
    33 Chen
  6. Karin Avila
    9 Avila
  7. Jesse Joshua Smith
    40 Smith
  8. Metin   Keskin
    5 Keskin