title: Role of KRAS mutation as predictor of pathologic response after neoadjuvant chemoradiation therapy for rectal cancer.
abstract: Individual patient response to neoadjuvant treatment is variable and reproducible biomarkers of response are needed. The role of the V-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS) in rectal cancer remains equivocal. The aim of the current study was to evaluate the effect of KRAS mutation on outcomes following neoadjuvant chemoradiation therapy (CRT) for rectal cancer. A total of 76 stage II-III rectal cancer patients underwent preoperative CRT followed by surgery. In every patient tumor-related features and outcome results were considered for analysis and correlation with KRAS mutations. Forty-four patients (58%) obtained a downstaging after CRT, and in 7 patients (9%) a complete pathological response was found. Twenty-six (33%) mutations of KRAS were found in 26 patients. Nineteen mutations (73%) were located in codon 12, 6 in codon 13(23%) and 1 in codon 61. T-level downsizing and tumor downstaging showed no significant association with KRAS mutation status, except for mutation of codon 13(G13D). No correlation between cancer-associated mortality following CRT and surgery and KRAS mutation was observed. No correlation between pelvic recurrence and KRAS mutation was observed. KRAS mutation also failed to correlate with disease-free survival. No patients with a pCR had a local or distant failure. There appears to be no significant difference in pCR, tumor down-staging, T-downsizing or effects on cancer-associated mortality, overall survival and disease-free survival in patients with KRAS mutations except for patients with KRAS codon 13 mutations that seem to be resistant to neoadjuvant CRT and less likely to achieve a pCR.
authors.affiliation: General, Emergency and Mininvasive Surgery I, Careggi University Hospital, Largo Brambilla 3, 50134, Florence, Italy, jamjac64@hotmail.com.
authors.forename: Jacopo
authors.initials: J
authors.lastname: Martellucci
authors.forename: Giovanni
authors.initials: G
authors.lastname: Alemanno
authors.forename: Francesca
authors.initials: F
authors.lastname: Castiglione
authors.forename: Carlo
authors.initials: C
authors.lastname: Bergamini
authors.forename: Andrea
authors.initials: A
authors.lastname: Valeri
mesh_terms: D059186:Chemoradiotherapy, Adjuvant; D003113:Colonoscopy; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D019160:Endosonography; D005500:Follow-Up Studies; D008279:Magnetic Resonance Imaging; D009154:Mutation; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging / Q000379:methods*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011446:Prospective Studies; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics* / Q000378:metabolism; D012004:Rectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D014057:Tomography, X-Ray Computed
chemical_list: D004273:DNA, Neoplasm; C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)