DNA Mismatch Repair Deficiency in Rectal Cancer: Benchmarking Its Impact on Prognosis, Neoadjuvant Response Prediction, and Clinical Cancer Genetics.

Autor:	de Rosa N; Nicole de Rosa, Miguel A. Rodriguez-Bigas, George J. Chang, Jula Veerapong, Ester Borras, Sunil Krishnan, Brian Bednarski, Craig A. Messick, John M. Skibber, Barry W. Feig, Patrick M. Lynch, Eduardo Vilar, and Y. Nancy You, University of Texas MD Anderson Cancer Center, Houston, TX; Nicole de Rosa, University of Nebraska Medical Center, Omaha, NE; and Jula Veerapong, St Louis University, St Louis, MO., Rodriguez-Bigas MA; Nicole de Rosa, Miguel A. Rodriguez-Bigas, George J. Chang, Jula Veerapong, Ester Borras, Sunil Krishnan, Brian Bednarski, Craig A. Messick, John M. Skibber, Barry W. Feig, Patrick M. Lynch, Eduardo Vilar, and Y. Nancy You, University of Texas MD Anderson Cancer Center, Houston, TX; Nicole de Rosa, University of Nebraska Medical Center, Omaha, NE; and Jula Veerapong, St Louis University, St Louis, MO., Chang GJ; Nicole de Rosa, Miguel A. Rodriguez-Bigas, George J. Chang, Jula Veerapong, Ester Borras, Sunil Krishnan, Brian Bednarski, Craig A. Messick, John M. Skibber, Barry W. Feig, Patrick M. Lynch, Eduardo Vilar, and Y. Nancy You, University of Texas MD Anderson Cancer Center, Houston, TX; Nicole de Rosa, University of Nebraska Medical Center, Omaha, NE; and Jula Veerapong, St Louis University, St Louis, MO., Veerapong J; Nicole de Rosa, Miguel A. Rodriguez-Bigas, George J. Chang, Jula Veerapong, Ester Borras, Sunil Krishnan, Brian Bednarski, Craig A. Messick, John M. Skibber, Barry W. Feig, Patrick M. Lynch, Eduardo Vilar, and Y. Nancy You, University of Texas MD Anderson Cancer Center, Houston, TX; Nicole de Rosa, University of Nebraska Medical Center, Omaha, NE; and Jula Veerapong, St Louis University, St Louis, MO., Borras E; Nicole de Rosa, Miguel A. Rodriguez-Bigas, George J. Chang, Jula Veerapong, Ester Borras, Sunil Krishnan, Brian Bednarski, Craig A. Messick, John M. Skibber, Barry W. Feig, Patrick M. Lynch, Eduardo Vilar, and Y. Nancy You, University of Texas MD Anderson Cancer Center, Houston, TX; Nicole de Rosa, University of Nebraska Medical Center, Omaha, NE; and Jula Veerapong, St Louis University, St Louis, MO., Krishnan S; Nicole de Rosa, Miguel A. Rodriguez-Bigas, George J. Chang, Jula Veerapong, Ester Borras, Sunil Krishnan, Brian Bednarski, Craig A. Messick, John M. Skibber, Barry W. Feig, Patrick M. Lynch, Eduardo Vilar, and Y. Nancy You, University of Texas MD Anderson Cancer Center, Houston, TX; Nicole de Rosa, University of Nebraska Medical Center, Omaha, NE; and Jula Veerapong, St Louis University, St Louis, MO., Bednarski B; Nicole de Rosa, Miguel A. Rodriguez-Bigas, George J. Chang, Jula Veerapong, Ester Borras, Sunil Krishnan, Brian Bednarski, Craig A. Messick, John M. Skibber, Barry W. Feig, Patrick M. Lynch, Eduardo Vilar, and Y. Nancy You, University of Texas MD Anderson Cancer Center, Houston, TX; Nicole de Rosa, University of Nebraska Medical Center, Omaha, NE; and Jula Veerapong, St Louis University, St Louis, MO., Messick CA; Nicole de Rosa, Miguel A. Rodriguez-Bigas, George J. Chang, Jula Veerapong, Ester Borras, Sunil Krishnan, Brian Bednarski, Craig A. Messick, John M. Skibber, Barry W. Feig, Patrick M. Lynch, Eduardo Vilar, and Y. Nancy You, University of Texas MD Anderson Cancer Center, Houston, TX; Nicole de Rosa, University of Nebraska Medical Center, Omaha, NE; and Jula Veerapong, St Louis University, St Louis, MO., Skibber JM; Nicole de Rosa, Miguel A. Rodriguez-Bigas, George J. Chang, Jula Veerapong, Ester Borras, Sunil Krishnan, Brian Bednarski, Craig A. Messick, John M. Skibber, Barry W. Feig, Patrick M. Lynch, Eduardo Vilar, and Y. Nancy You, University of Texas MD Anderson Cancer Center, Houston, TX; Nicole de Rosa, University of Nebraska Medical Center, Omaha, NE; and Jula Veerapong, St Louis University, St Louis, MO., Feig BW; Nicole de Rosa, Miguel A. Rodriguez-Bigas, George J. Chang, Jula Veerapong, Ester Borras, Sunil Krishnan, Brian Bednarski, Craig A. Messick, John M. Skibber, Barry W. Feig, Patrick M. Lynch, Eduardo Vilar, and Y. Nancy You, University of Texas MD Anderson Cancer Center, Houston, TX; Nicole de Rosa, University of Nebraska Medical Center, Omaha, NE; and Jula Veerapong, St Louis University, St Louis, MO., Lynch PM; Nicole de Rosa, Miguel A. Rodriguez-Bigas, George J. Chang, Jula Veerapong, Ester Borras, Sunil Krishnan, Brian Bednarski, Craig A. Messick, John M. Skibber, Barry W. Feig, Patrick M. Lynch, Eduardo Vilar, and Y. Nancy You, University of Texas MD Anderson Cancer Center, Houston, TX; Nicole de Rosa, University of Nebraska Medical Center, Omaha, NE; and Jula Veerapong, St Louis University, St Louis, MO., Vilar E; Nicole de Rosa, Miguel A. Rodriguez-Bigas, George J. Chang, Jula Veerapong, Ester Borras, Sunil Krishnan, Brian Bednarski, Craig A. Messick, John M. Skibber, Barry W. Feig, Patrick M. Lynch, Eduardo Vilar, and Y. Nancy You, University of Texas MD Anderson Cancer Center, Houston, TX; Nicole de Rosa, University of Nebraska Medical Center, Omaha, NE; and Jula Veerapong, St Louis University, St Louis, MO., You YN; Nicole de Rosa, Miguel A. Rodriguez-Bigas, George J. Chang, Jula Veerapong, Ester Borras, Sunil Krishnan, Brian Bednarski, Craig A. Messick, John M. Skibber, Barry W. Feig, Patrick M. Lynch, Eduardo Vilar, and Y. Nancy You, University of Texas MD Anderson Cancer Center, Houston, TX; Nicole de Rosa, University of Nebraska Medical Center, Omaha, NE; and Jula Veerapong, St Louis University, St Louis, MO. ynyou@mdanderson.org.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2016 Sep 01; Vol. 34 (25), pp. 3039-46. Date of Electronic Publication: 2016 Jul 18.
DOI:	10.1200/JCO.2016.66.6826
Abstrakt:	Purpose: DNA mismatch repair deficiency (dMMR) hallmarks consensus molecular subtype 1 of colorectal cancer. It is being routinely tested, but little is known about dMMR rectal cancers. The efficacy of novel treatment strategies cannot be established without benchmarking the outcomes of dMMR rectal cancer with current therapy. We aimed to delineate the impact of dMMR on prognosis, the predicted response to fluoropyrimidine-based neoadjuvant therapy, and implications of germline alterations in the MMR genes in rectal cancer. Methods: Between 1992 and 2012, 62 patients with dMMR rectal cancers underwent multimodality therapy. Oncologic treatment and outcomes as well as clinical genetics work-up were examined. Overall and rectal cancer-specific survival were calculated by the Kaplan-Meier method. Results: The median age at diagnosis was 41 years. MMR deficiency was most commonly due to alterations in MSH2 (53%) or MSH6 (23%). After a median follow-up of 6.8 years, the 5-year rectal cancer-specific survival was 100% for stage I and II, 85.1% for stage III, and 60.0% for stage IV disease. Fluoropyrimidine-based neoadjuvant chemoradiation was associated with a complete pathologic response rate of 27.6%. The extent of surgical resection was influenced by synchronous colonic disease at presentation, tumor height, clinical stage, and pelvic radiation. An informed decision for a limited resection focusing on proctectomy did not compromise overall survival. Five of the 11 (45.5%) deaths during follow-up were due to extracolorectal malignancies. Conclusion: dMMR rectal cancer had excellent prognosis and pathologic response with current multimodality therapy including an individualized surgical treatment plan. Identification of a dMMR rectal cancer should trigger germline testing, followed by lifelong surveillance for both colorectal and extracolorectal malignancies. We herein provide genotype-specific outcome benchmarks for comparison with novel interventions. Competing Interests: Authors’ disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article. (© 2016 by American Society of Clinical Oncology.)
Databáze:	MEDLINE
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