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Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer
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| Zeitschriftentitel: | Journal of Clinical Oncology |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , |
| In: | Journal of Clinical Oncology, 29, 2011, 10, S. 1261-1270 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society of Clinical Oncology (ASCO)
|
| Schlagwörter: |
| author_facet |
Hutchins, Gordon Southward, Katie Handley, Kelly Magill, Laura Beaumont, Claire Stahlschmidt, Jens Richman, Susan Chambers, Philip Seymour, Matthew Kerr, David Gray, Richard Quirke, Philip Hutchins, Gordon Southward, Katie Handley, Kelly Magill, Laura Beaumont, Claire Stahlschmidt, Jens Richman, Susan Chambers, Philip Seymour, Matthew Kerr, David Gray, Richard Quirke, Philip |
|---|---|
| author |
Hutchins, Gordon Southward, Katie Handley, Kelly Magill, Laura Beaumont, Claire Stahlschmidt, Jens Richman, Susan Chambers, Philip Seymour, Matthew Kerr, David Gray, Richard Quirke, Philip |
| spellingShingle |
Hutchins, Gordon Southward, Katie Handley, Kelly Magill, Laura Beaumont, Claire Stahlschmidt, Jens Richman, Susan Chambers, Philip Seymour, Matthew Kerr, David Gray, Richard Quirke, Philip Journal of Clinical Oncology Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer Cancer Research Oncology |
| author_sort |
hutchins, gordon |
| spelling |
Hutchins, Gordon Southward, Katie Handley, Kelly Magill, Laura Beaumont, Claire Stahlschmidt, Jens Richman, Susan Chambers, Philip Seymour, Matthew Kerr, David Gray, Richard Quirke, Philip 0732-183X 1527-7755 American Society of Clinical Oncology (ASCO) Cancer Research Oncology http://dx.doi.org/10.1200/jco.2010.30.1366 <jats:sec><jats:title>Purpose</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> 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% CI, 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% CI, 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. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> MMR assays identify patients with a low risk of recurrence. KRAS mutational analysis provides useful additional risk stratification to guide use of chemotherapy. </jats:p></jats:sec> Value of Mismatch Repair, <i>KRAS</i>, and <i>BRAF</i> Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer Journal of Clinical Oncology |
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American Society of Clinical Oncology (ASCO), 2011 |
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American Society of Clinical Oncology (ASCO), 2011 |
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| title |
Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer |
| title_unstemmed |
Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer |
| title_full |
Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer |
| title_fullStr |
Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer |
| title_full_unstemmed |
Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer |
| title_short |
Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer |
| title_sort |
value of mismatch repair, <i>kras</i>, and <i>braf</i> mutations in predicting recurrence and benefits from chemotherapy in colorectal cancer |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1200/jco.2010.30.1366 |
| publishDate |
2011 |
| physical |
1261-1270 |
| description |
<jats:sec><jats:title>Purpose</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> 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% CI, 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% CI, 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. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> MMR assays identify patients with a low risk of recurrence. KRAS mutational analysis provides useful additional risk stratification to guide use of chemotherapy. </jats:p></jats:sec> |
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| author | Hutchins, Gordon, Southward, Katie, Handley, Kelly, Magill, Laura, Beaumont, Claire, Stahlschmidt, Jens, Richman, Susan, Chambers, Philip, Seymour, Matthew, Kerr, David, Gray, Richard, Quirke, Philip |
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| description | <jats:sec><jats:title>Purpose</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> 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% CI, 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% CI, 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. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> MMR assays identify patients with a low risk of recurrence. KRAS mutational analysis provides useful additional risk stratification to guide use of chemotherapy. </jats:p></jats:sec> |
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| spelling | Hutchins, Gordon Southward, Katie Handley, Kelly Magill, Laura Beaumont, Claire Stahlschmidt, Jens Richman, Susan Chambers, Philip Seymour, Matthew Kerr, David Gray, Richard Quirke, Philip 0732-183X 1527-7755 American Society of Clinical Oncology (ASCO) Cancer Research Oncology http://dx.doi.org/10.1200/jco.2010.30.1366 <jats:sec><jats:title>Purpose</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> 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% CI, 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% CI, 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. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> MMR assays identify patients with a low risk of recurrence. KRAS mutational analysis provides useful additional risk stratification to guide use of chemotherapy. </jats:p></jats:sec> Value of Mismatch Repair, <i>KRAS</i>, and <i>BRAF</i> Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer Journal of Clinical Oncology |
| spellingShingle | Hutchins, Gordon, Southward, Katie, Handley, Kelly, Magill, Laura, Beaumont, Claire, Stahlschmidt, Jens, Richman, Susan, Chambers, Philip, Seymour, Matthew, Kerr, David, Gray, Richard, Quirke, Philip, Journal of Clinical Oncology, Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer, Cancer Research, Oncology |
| title | Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer |
| title_full | Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer |
| title_fullStr | Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer |
| title_full_unstemmed | Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer |
| title_short | Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer |
| title_sort | value of mismatch repair, <i>kras</i>, and <i>braf</i> mutations in predicting recurrence and benefits from chemotherapy in colorectal cancer |
| title_unstemmed | Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1200/jco.2010.30.1366 |