title: DNA Mismatch Repair Deficiency in Rectal Cancer: Benchmarking Its Impact on Prognosis, Neoadjuvant Response Prediction, and Clinical Cancer Genetics.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Nicole
authors.initials: N
authors.lastname: de Rosa
authors.affiliation: 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.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Rodriguez-Bigas
authors.affiliation: 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.
authors.forename: George J
authors.initials: GJ
authors.lastname: Chang
authors.affiliation: 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.
authors.forename: Jula
authors.initials: J
authors.lastname: Veerapong
authors.affiliation: 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.
authors.forename: Ester
authors.initials: E
authors.lastname: Borras
authors.affiliation: 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.
authors.forename: Sunil
authors.initials: S
authors.lastname: Krishnan
authors.affiliation: 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.
authors.forename: Brian
authors.initials: B
authors.lastname: Bednarski
authors.affiliation: 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.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Messick
authors.affiliation: 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.
authors.forename: John M
authors.initials: JM
authors.lastname: Skibber
authors.affiliation: 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.
authors.forename: Barry W
authors.initials: BW
authors.lastname: Feig
authors.affiliation: 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.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Lynch
authors.affiliation: 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.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Vilar
authors.affiliation: 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.
authors.forename: Y Nancy
authors.initials: YN
authors.lastname: You
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019985:Benchmarking; D014408:Biomarkers, Tumor; D059186:Chemoradiotherapy, Adjuvant; D053843:DNA Mismatch Repair; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy / Q000628:therapy*; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D005472:Fluorouracil