Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer

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Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer. / Hutchins, G; Southward, K; Handley, Kelly; Magill, Elizabeth; Beaumont, C; Stahlschmidt, J; Richman, S; Chambers, P; Seymour, M; Kerr, D; Gray, Richard; Quirke, P.

In: Journal of Clinical Oncology, Vol. 29, No. 10, 01.04.2011, p. 1261-1270.

Research output: Contribution to journalArticle

Harvard

Hutchins, G, Southward, K, Handley, K, Magill, E, Beaumont, C, Stahlschmidt, J, Richman, S, Chambers, P, Seymour, M, Kerr, D, Gray, R & Quirke, P 2011, 'Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer', Journal of Clinical Oncology, vol. 29, no. 10, pp. 1261-1270. https://doi.org/10.1200/JCO.2010.30.1366

APA

Hutchins, G., Southward, K., Handley, K., Magill, E., Beaumont, C., Stahlschmidt, J., Richman, S., Chambers, P., Seymour, M., Kerr, D., Gray, R., & Quirke, P. (2011). Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer. Journal of Clinical Oncology, 29(10), 1261-1270. https://doi.org/10.1200/JCO.2010.30.1366

Vancouver

Author

Hutchins, G ; Southward, K ; Handley, Kelly ; Magill, Elizabeth ; Beaumont, C ; Stahlschmidt, J ; Richman, S ; Chambers, P ; Seymour, M ; Kerr, D ; Gray, Richard ; Quirke, P. / Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 10. pp. 1261-1270.

Bibtex

@article{e71d7f6ee7614054824b12bbb1584689,
title = "Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer",
abstract = "Purpose It is uncertain whether modest benefits from adjuvant chemotherapy in stage II colorectal cancer justify the toxicity, cost, and inconvenience. We investigated the usefulness of defective mismatch repair (dMMR), BRAF, and KRAS mutations in predicting tumor recurrence and sensitivity to chemotherapy. Patients and Methods Immunohistochemistry for dMMR and pyrosequencing for KRAS/BRAF were performed for 1,913 patients randomly assigned between fluorouracil and folinic acid chemotherapy and no chemotherapy in the Quick and Simple and Reliable (QUASAR) trial. Results Twenty-six percent of 695 right-sided colon, 3% of 685 left-sided colon, and 1% of 407 rectal tumors were dMMR. Similarly, 17% of right colon, 2% of left colon, and 2% of rectal tumors were BRAF mutant. KRAS mutant tumors were more evenly distributed: 40% right colon, 28% left colon, and 36% rectal tumors. Recurrence rate for dMMR tumors was half that for MMR-proficient tumors (11% [25 of 218] v 26% [438 of 1,695] recurred; risk ratio [RR], 0.53; 95% Cl, 0.40 to 0.70; P <.001). Risk of recurrence was also significantly higher for KRAS mutant than KRAS wild-type tumors (28% [150 of 542] v 21% [219 of 1,041]; RR, 1.40; 95% Cl, 1.12 to 1.74; P = .002) but did not differ significantly between BRAF mutant and wild-type tumors (P = .36). No marker predicted benefit from chemotherapy with efficacy not differing significantly by MMR, KRAS, or BRAF status. The prognostic value of MMR and KRAS was similar in the presence and absence of chemotherapy. Conclusion MMR assays identify patients with a low risk of recurrence. KRAS mutational analysis provides useful additional risk stratification to guide use of chemotherapy.",
author = "G Hutchins and K Southward and Kelly Handley and Elizabeth Magill and C Beaumont and J Stahlschmidt and S Richman and P Chambers and M Seymour and D Kerr and Richard Gray and P Quirke",
year = "2011",
month = apr,
day = "1",
doi = "10.1200/JCO.2010.30.1366",
language = "English",
volume = "29",
pages = "1261--1270",
journal = "Journal of Clinical Oncology ",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "10",

}

RIS

TY - JOUR

T1 - Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer

AU - Hutchins, G

AU - Southward, K

AU - Handley, Kelly

AU - Magill, Elizabeth

AU - Beaumont, C

AU - Stahlschmidt, J

AU - Richman, S

AU - Chambers, P

AU - Seymour, M

AU - Kerr, D

AU - Gray, Richard

AU - Quirke, P

PY - 2011/4/1

Y1 - 2011/4/1

N2 - Purpose It is uncertain whether modest benefits from adjuvant chemotherapy in stage II colorectal cancer justify the toxicity, cost, and inconvenience. We investigated the usefulness of defective mismatch repair (dMMR), BRAF, and KRAS mutations in predicting tumor recurrence and sensitivity to chemotherapy. Patients and Methods Immunohistochemistry for dMMR and pyrosequencing for KRAS/BRAF were performed for 1,913 patients randomly assigned between fluorouracil and folinic acid chemotherapy and no chemotherapy in the Quick and Simple and Reliable (QUASAR) trial. Results Twenty-six percent of 695 right-sided colon, 3% of 685 left-sided colon, and 1% of 407 rectal tumors were dMMR. Similarly, 17% of right colon, 2% of left colon, and 2% of rectal tumors were BRAF mutant. KRAS mutant tumors were more evenly distributed: 40% right colon, 28% left colon, and 36% rectal tumors. Recurrence rate for dMMR tumors was half that for MMR-proficient tumors (11% [25 of 218] v 26% [438 of 1,695] recurred; risk ratio [RR], 0.53; 95% Cl, 0.40 to 0.70; P <.001). Risk of recurrence was also significantly higher for KRAS mutant than KRAS wild-type tumors (28% [150 of 542] v 21% [219 of 1,041]; RR, 1.40; 95% Cl, 1.12 to 1.74; P = .002) but did not differ significantly between BRAF mutant and wild-type tumors (P = .36). No marker predicted benefit from chemotherapy with efficacy not differing significantly by MMR, KRAS, or BRAF status. The prognostic value of MMR and KRAS was similar in the presence and absence of chemotherapy. Conclusion MMR assays identify patients with a low risk of recurrence. KRAS mutational analysis provides useful additional risk stratification to guide use of chemotherapy.

AB - Purpose It is uncertain whether modest benefits from adjuvant chemotherapy in stage II colorectal cancer justify the toxicity, cost, and inconvenience. We investigated the usefulness of defective mismatch repair (dMMR), BRAF, and KRAS mutations in predicting tumor recurrence and sensitivity to chemotherapy. Patients and Methods Immunohistochemistry for dMMR and pyrosequencing for KRAS/BRAF were performed for 1,913 patients randomly assigned between fluorouracil and folinic acid chemotherapy and no chemotherapy in the Quick and Simple and Reliable (QUASAR) trial. Results Twenty-six percent of 695 right-sided colon, 3% of 685 left-sided colon, and 1% of 407 rectal tumors were dMMR. Similarly, 17% of right colon, 2% of left colon, and 2% of rectal tumors were BRAF mutant. KRAS mutant tumors were more evenly distributed: 40% right colon, 28% left colon, and 36% rectal tumors. Recurrence rate for dMMR tumors was half that for MMR-proficient tumors (11% [25 of 218] v 26% [438 of 1,695] recurred; risk ratio [RR], 0.53; 95% Cl, 0.40 to 0.70; P <.001). Risk of recurrence was also significantly higher for KRAS mutant than KRAS wild-type tumors (28% [150 of 542] v 21% [219 of 1,041]; RR, 1.40; 95% Cl, 1.12 to 1.74; P = .002) but did not differ significantly between BRAF mutant and wild-type tumors (P = .36). No marker predicted benefit from chemotherapy with efficacy not differing significantly by MMR, KRAS, or BRAF status. The prognostic value of MMR and KRAS was similar in the presence and absence of chemotherapy. Conclusion MMR assays identify patients with a low risk of recurrence. KRAS mutational analysis provides useful additional risk stratification to guide use of chemotherapy.

U2 - 10.1200/JCO.2010.30.1366

DO - 10.1200/JCO.2010.30.1366

M3 - Article

C2 - 21383284

VL - 29

SP - 1261

EP - 1270

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 10

ER -