{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T16:26:54Z","timestamp":1771604814392,"version":"3.50.1"},"reference-count":40,"publisher":"Harborside Press, LLC","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:p>Treatment options for locally advanced rectal cancer have continued to consist largely of chemotherapy, chemoradiation, and\/or surgical resection. For patients who are unable to undergo these therapeutic modalities or who do not to experience a response to them, treatment options are limited. We report 3 cases of mismatch repair\u2013deficient (dMMR) locally advanced adenocarcinoma of the rectum that showed significant response with neoadjuvant immunotherapy\u2013based systemic treatment. The first patient was not eligible for standard therapy because of a history of radiotherapy to the prostate with concurrent comorbidities and therefore received single-agent pembrolizumab. The second patient did not respond to total neoadjuvant chemoradiation and subsequently received combined nivolumab and ipilimumab. The third patient had a known family history of Lynch syndrome and presented with locally advanced rectal cancer and a baseline carcinoembryonic antigen level of 1,566 ng\/mL. She was treated using neoadjuvant pembrolizumab and FOLFOX (folinic acid, fluorouracil, oxaliplatin). In this small series, we suggest that single-agent and combined-modality neoadjuvant immunotherapy\/chemotherapy appear to be safe and effective treatment options for patients with (dMMR) locally advanced rectal cancer. Our findings encourage further studies to investigate the role of neoadjuvant immunotherapy as a viable treatment strategy in this population.<\/jats:p>","DOI":"10.6004\/jnccn.2020.7558","type":"journal-article","created":{"date-parts":[[2020,7,7]],"date-time":"2020-07-07T19:18:01Z","timestamp":1594149481000},"page":"798-804","source":"Crossref","is-referenced-by-count":41,"title":["Neoadjuvant Immunotherapy\u2013Based Systemic Treatment in MMR-Deficient or MSI-High Rectal Cancer: Case Series"],"prefix":"10.6004","volume":"18","author":[{"given":"Rahel","family":"Demisse","sequence":"first","affiliation":[{"name":"1UC Davis Comprehensive Cancer Center, Sacramento, California;"},{"name":"2Loma Linda University Health, Loma Linda Medical Center, Loma Linda, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neha","family":"Damle","sequence":"additional","affiliation":[{"name":"1UC Davis Comprehensive Cancer Center, Sacramento, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward","family":"Kim","sequence":"additional","affiliation":[{"name":"1UC Davis Comprehensive Cancer Center, Sacramento, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Gong","sequence":"additional","affiliation":[{"name":"3Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Health System, Los Angeles, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marwan","family":"Fakih","sequence":"additional","affiliation":[{"name":"4City of Hope National Medical Center, Duarte, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cathy","family":"Eng","sequence":"additional","affiliation":[{"name":"5Vanderbilt-Ingram Cancer Center, Nashville, Tennessee;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslie","family":"Oesterich","sequence":"additional","affiliation":[{"name":"1UC Davis Comprehensive Cancer Center, Sacramento, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madison","family":"McKenny","sequence":"additional","affiliation":[{"name":"6Department of Diagnostic Radiology, UC Davis Medical Center, Sacramento, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingran","family":"Ji","sequence":"additional","affiliation":[{"name":"1UC Davis Comprehensive Cancer Center, Sacramento, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Liu","sequence":"additional","affiliation":[{"name":"1UC Davis Comprehensive Cancer Center, Sacramento, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan","family":"Louie","sequence":"additional","affiliation":[{"name":"7UC Davis Medical Center, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kit","family":"Tam","sequence":"additional","affiliation":[{"name":"1UC Davis Comprehensive Cancer Center, Sacramento, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sepideh","family":"Gholami","sequence":"additional","affiliation":[{"name":"8Department of Surgical Oncology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wissam","family":"Halabi","sequence":"additional","affiliation":[{"name":"9Department of Colorectal Surgery, UC Davis Medical Center, Sacramento, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arta","family":"Monjazeb","sequence":"additional","affiliation":[{"name":"10Department of Radiation Oncology, UC Davis Comprehensive Cancer Center, Sacramento, California; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farshid","family":"Dayyani","sequence":"additional","affiliation":[{"name":"11Division of Hematology\/Oncology, Department of Medicine, University of California Irvine, Orange, California."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"May","family":"Cho","sequence":"additional","affiliation":[{"name":"1UC Davis Comprehensive Cancer Center, Sacramento, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4047","reference":[{"key":"ref321","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1053\/j.gastro.2003.12.023","article-title":"Use of 5-fluorouracil and survival in patients with microsatellite-unstable colorectal cancer","volume":"126","author":"Carethers","year":"2004","journal-title":"Gastroenterology"},{"key":"ref231","article-title":"Microsatellite instability (MSI) as an independent predictor of pathologic complete response (PCR) in locally advanced rectal cancer: a National Cancer Database (NCDB) analysis [published online September 13, 2018]","author":"Hasan","journal-title":"Ann Surg"},{"key":"ref361","doi-asserted-by":"crossref","first-page":"e180071","DOI":"10.1001\/jamaoncol.2018.0071","article-title":"Adoption of total neoadjuvant therapy for locally advanced rectal cancer","volume":"4","author":"Cercek","year":"2018","journal-title":"JAMA Oncol"},{"key":"ref141","doi-asserted-by":"crossref","first-page":"e180071","DOI":"10.1001\/jamaoncol.2018.0071","article-title":"Adoption of total neoadjuvant therapy for locally advanced rectal cancer","volume":"4","author":"Cercek","year":"2018","journal-title":"JAMA Oncol"},{"key":"ref181","doi-asserted-by":"crossref","first-page":"e1663108","DOI":"10.1080\/2162402X.2019.1663108","article-title":"Complete response in patients with locally advanced rectal cancer after neoadjuvant treatment with nivolumab","volume":"8","author":"Zhang","year":"2019","journal-title":"OncoImmunology"},{"key":"ref271","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1016\/S1470-2045(17)30422-9","article-title":"Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study","volume":"18","author":"Overman","year":"2017","journal-title":"Lancet Oncol"},{"key":"ref311","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3233\/CBM-2006-21-206","article-title":"Chemotherapeutic implications in microsatellite unstable colorectal cancer","volume":"2","author":"Jo","year":"2006","journal-title":"Cancer Biomark"},{"key":"ref391","doi-asserted-by":"crossref","DOI":"10.1093\/annonc\/mdy424.047","article-title":"Neoadjuvant ipilimumab plus nivolumab in early stage colon cancer","volume":"29","author":"Chalabi","year":"2018","journal-title":"Ann Oncol"},{"key":"ref191","doi-asserted-by":"crossref","DOI":"10.1200\/JCO.2017.35.15_suppl.TPS3630","article-title":"Randomized trial of FOLFOX alone or combined with atezolizumab in adjuvant therapy for patients with stage III colon cancer and deficient DNA mismatch repair or microsatellite instability (ATOMIC, Alliance A021502) [abstract]","volume":"35","author":"Sinicrope","year":"2017","journal-title":"J Clin Oncol"},{"key":"ref131","author":"Bosset JF","year":"2005","journal-title":"J Clin Oncol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/sj.bjc.6604867","article-title":"Deficient mismatch repair system in patients with sporadic advanced colorectal cancer","volume":"100","author":"Koopman","year":"2009","journal-title":"Br J Cancer"},{"key":"ref31","first-page":"35414","article-title":"Pembrolizumab for patients with advanced microsatellite instability high (MSI-H) colorectal cancer [abstract]","volume":"36(Suppl)","author":"Le","year":"2018","journal-title":"J Clin Oncol"},{"key":"ref01","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J Clin"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"3753","DOI":"10.1158\/1078-0432.CCR-18-4070","article-title":"FDA approval summary: pembrolizumab for the treatment of microsatellite instability-high solid tumors","volume":"25","author":"Marcus","year":"2019","journal-title":"Clin Cancer Res"},{"key":"ref121","first-page":"546","article-title":"Neoadjuvant combined-modality therapy for locally advanced rectal cancer and its future direction","volume":"30","author":"Salem","year":"2016","journal-title":"Oncology (Williston Park)"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1200\/JCO.2017.76.9901","article-title":"Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-deficient\/microsatellite instability-high metastatic colorectal cancer","volume":"36","author":"Overman","year":"2018","journal-title":"J Clin Oncol"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1200\/JCO.2009.27.1825","article-title":"Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer","volume":"28","author":"Sargent","year":"2010","journal-title":"J Clin Oncol"},{"key":"ref151","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1056\/NEJMoa1500596","article-title":"PD-1 blockade in tumors with mismatch-repair deficiency","volume":"372","author":"Le","year":"2015","journal-title":"N Engl J Med"},{"key":"ref401","doi-asserted-by":"crossref","first-page":"e1663108","DOI":"10.1080\/2162402X.2019.1663108","article-title":"Complete response in patients with locally advanced rectal cancer after neoadjuvant treatment with nivolumab","volume":"8","author":"Zhang","year":"2019","journal-title":"OncoImmunology"},{"key":"ref261","doi-asserted-by":"crossref","first-page":"3753","DOI":"10.1158\/1078-0432.CCR-18-4070","article-title":"FDA approval summary: pembrolizumab for the treatment of microsatellite instability-high solid tumors","volume":"25","author":"Marcus","year":"2019","journal-title":"Clin Cancer Res"},{"key":"ref381","doi-asserted-by":"crossref","DOI":"10.1200\/JCO.2019.37.4_suppl.635","article-title":"Nivolumab (NIVO) + low-dose ipilimumab (IPI) in previously treated patients (pts) with microsatellite instability-high\/mismatch repair-deficient (MSI-H\/dMMR) metastatic colorectal cancer (mCRC): long-term follow-up [abstract]","volume":"37","author":"Overman","year":"2019","journal-title":"J Clin Oncol"},{"key":"ref171","doi-asserted-by":"crossref","DOI":"10.1093\/annonc\/mdy424.047","article-title":"Neoadjuvant ipilimumab plus nivolumab in early stage colon cancer","volume":"29","author":"Chalabi","year":"2018","journal-title":"Ann Oncol"},{"key":"ref241","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/sj.bjc.6604867","article-title":"Deficient mismatch repair system in patients with sporadic advanced colorectal cancer","volume":"100","author":"Koopman","year":"2009","journal-title":"Br J Cancer"},{"key":"ref351","author":"Bosset JF","year":"2005","journal-title":"J Clin Oncol"},{"key":"ref331","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1200\/JCO.2009.27.1825","article-title":"Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer","volume":"28","author":"Sargent","year":"2010","journal-title":"J Clin Oncol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1016\/S1470-2045(17)30422-9","article-title":"Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study","volume":"18","author":"Overman","year":"2017","journal-title":"Lancet Oncol"},{"key":"ref301","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1007\/s10552-009-9410-3","article-title":"Microsatellite instability and survival in rectal cancer","volume":"20","author":"Samowitz","year":"2009","journal-title":"Cancer Causes Control"},{"key":"ref291","doi-asserted-by":"crossref","first-page":"Abstract VIII714","DOI":"10.1093\/annonc\/mdy424.019","article-title":"Durable clinical benefit with nivolumab (NIVO) plus low-dose ipilimumab (IPI) as first-line therapy in microsatellite instability-high\/mismatch repair deficient (MSI-H\/dMMR) metastatic colorectal cancer (mCRC) [abstract]","volume":"29","author":"Lenz","year":"2018","journal-title":"Ann Oncol"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1053\/j.gastro.2003.12.023","article-title":"Use of 5-fluorouracil and survival in patients with microsatellite-unstable colorectal cancer","volume":"126","author":"Carethers","year":"2004","journal-title":"Gastroenterology"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1007\/s10552-009-9410-3","article-title":"Microsatellite instability and survival in rectal cancer","volume":"20","author":"Samowitz","year":"2009","journal-title":"Cancer Causes Control"},{"key":"ref161","doi-asserted-by":"crossref","DOI":"10.1200\/JCO.2019.37.4_suppl.635","article-title":"Nivolumab (NIVO) + low-dose ipilimumab (IPI) in previously treated patients (pts) with microsatellite instability-high\/mismatch repair-deficient (MSI-H\/dMMR) metastatic colorectal cancer (mCRC): long-term follow-up [abstract]","volume":"37","author":"Overman","year":"2019","journal-title":"J Clin Oncol"},{"key":"ref251","first-page":"35414","article-title":"Pembrolizumab for patients with advanced microsatellite instability high (MSI-H) colorectal cancer [abstract]","volume":"36(Suppl)","author":"Le","year":"2018","journal-title":"J Clin Oncol"},{"key":"ref281","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1200\/JCO.2017.76.9901","article-title":"Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-deficient\/microsatellite instability-high metastatic colorectal cancer","volume":"36","author":"Overman","year":"2018","journal-title":"J Clin Oncol"},{"key":"ref411","doi-asserted-by":"crossref","DOI":"10.1200\/JCO.2017.35.15_suppl.TPS3630","article-title":"Randomized trial of FOLFOX alone or combined with atezolizumab in adjuvant therapy for patients with stage III colon cancer and deficient DNA mismatch repair or microsatellite instability (ATOMIC, Alliance A021502) [abstract]","volume":"35","author":"Sinicrope","year":"2017","journal-title":"J Clin Oncol"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"Abstract VIII714","DOI":"10.1093\/annonc\/mdy424.019","article-title":"Durable clinical benefit with nivolumab (NIVO) plus low-dose ipilimumab (IPI) as first-line therapy in microsatellite instability-high\/mismatch repair deficient (MSI-H\/dMMR) metastatic colorectal cancer (mCRC) [abstract]","volume":"29","author":"Lenz","year":"2018","journal-title":"Ann Oncol"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3233\/CBM-2006-21-206","article-title":"Chemotherapeutic implications in microsatellite unstable colorectal cancer","volume":"2","author":"Jo","year":"2006","journal-title":"Cancer Biomark"},{"key":"ref221","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J Clin"},{"key":"ref371","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1056\/NEJMoa1500596","article-title":"PD-1 blockade in tumors with mismatch-repair deficiency","volume":"372","author":"Le","year":"2015","journal-title":"N Engl J Med"},{"key":"ref11","article-title":"Microsatellite instability (MSI) as an independent predictor of pathologic complete response (PCR) in locally advanced rectal cancer: a National Cancer Database (NCDB) analysis [published online September 13, 2018]","author":"Hasan","journal-title":"Ann Surg"},{"key":"ref341","first-page":"546","article-title":"Neoadjuvant combined-modality therapy for locally advanced rectal cancer and its future direction","volume":"30","author":"Salem","year":"2016","journal-title":"Oncology (Williston Park)"}],"container-title":["Journal of the National Comprehensive Cancer Network"],"original-title":[],"link":[{"URL":"https:\/\/jnccn.org\/view\/journals\/jnccn\/18\/7\/article-p798.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/jnccn.org\/downloadpdf\/journals\/jnccn\/18\/7\/article-p798.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T20:17:53Z","timestamp":1596831473000},"score":1,"resource":{"primary":{"URL":"https:\/\/jnccn.org\/view\/journals\/jnccn\/18\/7\/article-p798.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7]]},"references-count":40,"journal-issue":{"issue":"7"},"URL":"https:\/\/doi.org\/10.6004\/jnccn.2020.7558","relation":{},"ISSN":["1540-1405","1540-1413"],"issn-type":[{"value":"1540-1405","type":"print"},{"value":"1540-1413","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7]]}}}