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  1. Article ; Online: Increasing Incidence of Early-Onset Colorectal Cancer.

    Sinicrope, Frank A

    The New England journal of medicine

    2022  Volume 386, Issue 16, Page(s) 1547–1558

    MeSH term(s) Age of Onset ; Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/epidemiology ; Early Detection of Cancer ; Humans ; Incidence ; Risk Factors
    Language English
    Publishing date 2022-04-20
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMra2200869
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The Increasing Incidence of Early-Onset Colorectal Cancer. Reply.

    Sinicrope, Frank A

    The New England journal of medicine

    2022  Volume 387, Issue 1, Page(s) 93–94

    MeSH term(s) Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/epidemiology ; Humans ; Incidence ; SEER Program
    Language English
    Publishing date 2022-07-06
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMc2206652
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Neoadjuvant Immune Checkpoint Inhibitor Therapy for Localized Deficient Mismatch Repair Colorectal Cancer: A Review.

    Emiloju, Oluwadunni E / Sinicrope, Frank A

    JAMA oncology

    2023  Volume 9, Issue 12, Page(s) 1708–1715

    Abstract: Importance: Colorectal cancers (CRCs) with deficient DNA mismatch repair (dMMR) account for 15% of all CRCs. Deficient MMR is a predictive biomarker associated with responsiveness to immune checkpoint inhibitors (ICIs) in solid tumors, including CRC. ... ...

    Abstract Importance: Colorectal cancers (CRCs) with deficient DNA mismatch repair (dMMR) account for 15% of all CRCs. Deficient MMR is a predictive biomarker associated with responsiveness to immune checkpoint inhibitors (ICIs) in solid tumors, including CRC. The remarkable effectiveness of ICIs in metastatic CRC has led to their evaluation in the neoadjuvant and adjuvant treatment of localized disease.
    Observations: Multiple prospective phase 2 studies in limited numbers of patients with localized dMMR CRC demonstrate high complete clinical and pathological response rates (60%-100%) to neoadjuvant ICIs, with low rates of grade 3 or higher ICI-related toxic effects. Given the median follow-up of 12 to 25 months in these studies, longer-term monitoring is needed to determine the durability of response and to ensure that oncologic outcomes are not compromised in patients undergoing nonoperative management. Neoadjuvant ICI therapy is especially attractive for patients with rectal cancer given the significant morbidity that accompanies pelvic irradiation and total mesorectal excision. Ongoing and planned prospective phase 2 trials will provide further data on important issues, including optimal neoadjuvant treatment duration, ICI monotherapy vs combination, and the need for adjuvant ICI therapy.
    Conclusions and relevance: While this review found that early results of neoadjuvant immunotherapy for localized dMMR CRC show high rates of major and complete pathological response, longer-term follow-up data are needed to ensure that oncologic outcomes are not compromised and are ideally improved. Neoadjuvant ICI therapy in localized dMMR CRC represents a potential paradigm shift with implications for organ preservation.
    MeSH term(s) Humans ; Neoadjuvant Therapy ; Immune Checkpoint Inhibitors/adverse effects ; DNA Mismatch Repair ; Prospective Studies ; Rectal Neoplasms ; Pathologic Complete Response
    Chemical Substances Immune Checkpoint Inhibitors
    Language English
    Publishing date 2023-09-07
    Publishing country United States
    Document type Review ; Journal Article
    ISSN 2374-2445
    ISSN (online) 2374-2445
    DOI 10.1001/jamaoncol.2023.3323
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Mismatch Repair-Deficient Colorectal Cancer: Building on Checkpoint Blockade.

    Jin, Zhaohui / Sinicrope, Frank A

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology

    2022  Volume 40, Issue 24, Page(s) 2735–2750

    Abstract: Colorectal cancer (CRC) with deficient DNA mismatch repair (dMMR) is characterized by hypermutation leading to abundant neoantigens that activate an antitumor immune response in the tumor microenvironment. Immune checkpoint inhibitors (ICIs) have ... ...

    Abstract Colorectal cancer (CRC) with deficient DNA mismatch repair (dMMR) is characterized by hypermutation leading to abundant neoantigens that activate an antitumor immune response in the tumor microenvironment. Immune checkpoint inhibitors (ICIs) have transformed the treatment of this subset of CRC and other solid tumors with dMMR, by producing frequent and durable responses that extend patient survival. Recently, the anti-programmed death-1 (PD-1) antibody pembrolizumab was shown to produce significantly longer progression-free survival with fewer adverse events compared with chemotherapy as first-line treatment of metastatic CRC (mCRC) with dMMR. Accordingly, single-agent pembrolizumab represents a new standard of care for dMMR mCRCs including patients with Lynch syndrome and the more common sporadic cases. Furthermore, data indicate that the combination of PD-1 and cytotoxic T-cell lymphocyte-4 inhibitors was more effective than single-agent PD-1 inhibition in patients with dMMR mCRCs, suggesting nonredundant mechanisms of action. Although the benefit of ICIs is currently limited to metastatic disease, studies evaluating ICIs as neoadjuvant and adjuvant therapy in earlier-stage dMMR CRC are ongoing. Despite success of ICIs in the treatment of metastatic dMMR cancers, an appreciable proportion of these tumors demonstrate intrinsic or acquired resistance, and biomarkers to identify these patients are needed. Advances in the understanding of immunotherapy resistance mechanisms hold promise for both biomarker identification and development of novel strategies to circumvent treatment resistance. In this review, we present a comprehensive overview of the evidence for the role of immunotherapy in the treatment of dMMR CRC, discuss resistance mechanisms, and outline potential strategies to circumvent primary and secondary resistance with the goal of broadening the benefit of ICIs.
    MeSH term(s) Colonic Neoplasms ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; DNA Mismatch Repair ; Humans ; Microsatellite Instability ; Programmed Cell Death 1 Receptor/genetics ; Tumor Microenvironment
    Chemical Substances Programmed Cell Death 1 Receptor
    Language English
    Publishing date 2022-06-01
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 604914-x
    ISSN 1527-7755 ; 0732-183X
    ISSN (online) 1527-7755
    ISSN 0732-183X
    DOI 10.1200/JCO.21.02691
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Evaluating Immunotherapy in Nonmetastatic Colorectal Cancer.

    Sinicrope, Frank A

    Oncology (Williston Park, N.Y.)

    2019  Volume 33, Issue 5, Page(s) 178–180

    MeSH term(s) Antibodies, Monoclonal, Humanized/administration & dosage ; Antineoplastic Agents, Immunological/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Clinical Trials as Topic ; Clinical Trials, Phase III as Topic ; Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/immunology ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/therapy ; Evaluation Studies as Topic ; Fluorouracil/administration & dosage ; Humans ; Immunotherapy/methods ; Leucovorin/administration & dosage ; Neoplasm Staging ; Organoplatinum Compounds/administration & dosage ; Randomized Controlled Trials as Topic
    Chemical Substances Antibodies, Monoclonal, Humanized ; Antineoplastic Agents, Immunological ; Organoplatinum Compounds ; atezolizumab (52CMI0WC3Y) ; Leucovorin (Q573I9DVLP) ; Fluorouracil (U3P01618RT)
    Language English
    Publishing date 2019-10-18
    Publishing country United States
    Document type Interview
    ZDB-ID 1067950-9
    ISSN 0890-9091
    ISSN 0890-9091
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Ferroptosis: Biology and Role in Gastrointestinal Disease.

    Escuder-Rodríguez, Juan-José / Liang, Deguang / Jiang, Xuejun / Sinicrope, Frank A

    Gastroenterology

    2024  

    Abstract: Ferroptosis is a form of nonapoptotic cell death that involves iron-dependent phospholipid peroxidation induced by accumulation of reactive oxygen species, and results in plasma membrane damage and the release of damage-associated molecular patterns. ... ...

    Abstract Ferroptosis is a form of nonapoptotic cell death that involves iron-dependent phospholipid peroxidation induced by accumulation of reactive oxygen species, and results in plasma membrane damage and the release of damage-associated molecular patterns. Ferroptosis has been implicated in aging and immunity, as well as disease states including intestinal and liver conditions and cancer. To date, several ferroptosis-associated genes and pathways have been implicated in liver disease. Although ferroptotic cell death is associated with dysfunction of the intestinal epithelium, the underlying molecular basis is poorly understood. As the mechanisms regulating ferroptosis become further elucidated, there is clear potential to use ferroptosis to achieve therapeutic benefit.
    Language English
    Publishing date 2024-03-01
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 80112-4
    ISSN 1528-0012 ; 0016-5085
    ISSN (online) 1528-0012
    ISSN 0016-5085
    DOI 10.1053/j.gastro.2024.01.051
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Synchronous Neoplasia Rates at Colonoscopic Diagnosis of Early-Onset vs Average-Onset Colorectal Cancer.

    Emiloju, Oluwadunni E / Saberzadeh-Ardestani, Bahar / Sinicrope, Frank A

    JAMA network open

    2023  Volume 6, Issue 7, Page(s) e2324038

    Abstract: Importance: The incidence of early-onset colorectal cancer (CRC) (age, <50 years) continues to increase globally within high-income countries.: Objective: To examine and compare rates of synchronous neoplasia found in patients at colonoscopic ... ...

    Abstract Importance: The incidence of early-onset colorectal cancer (CRC) (age, <50 years) continues to increase globally within high-income countries.
    Objective: To examine and compare rates of synchronous neoplasia found in patients at colonoscopic diagnosis of early-onset CRC with rates found at diagnosis of average-onset CRC.
    Design, setting, and participants: In this multisite retrospective and cross-sectional study conducted at Mayo Clinic sites and in the Mayo Clinic Health System from January 1, 2012, to December 31, 2022, 150 randomly selected patients with early-onset CRC were identified from the electronic health record and matched with 150 patients with average-onset CRC based on sex and colonoscopic indication. Patients with known hereditary syndromes, past history of CRC, or inflammatory bowel disease were excluded.
    Main outcomes and measures: Colonoscopic findings (polyp size, number, site) and related histopathologic findings (adenoma, advanced adenoma, sessile serrated polyp) were analyzed in association with cancer clinicopathologic features and molecular data (mismatch repair status, KRAS, and BRAFV600E).
    Results: Among 300 patients (156 men [52%]), the median age at diagnosis was 43 years (IQR, 39-47 years) for those with early-onset CRC and 67 years (IQR, 57-76) for those with average-onset CRC. Overall, 85% of patients were symptomatic at CRC diagnosis. Cancer stage, grade, molecular features, body mass index, and family history did not differ significantly between these groups. Among patients with colon cancer, the overall prevalence of synchronous neoplasia was similar, yet advanced adenomas were 3 times more frequent in those with early-onset vs average-onset cancers (31 of 75 [41%] vs 10 of 75 [13%]; P < .001). This difference was not associated with cancer stage or primary location. Among patients with rectal cancer, nonadvanced adenomas were less frequent among the early-onset group than the average-onset group (21 of 75 [28%] vs 36 of 75 [48%]), and although the prevalence of advanced adenomas was similar (11 of 75 [15%] vs 14 of 75 [19%]), they were more commonly located in the rectum (early onset, 5 of 11 [45%] vs average onset, 1 of 14 [7%]). Patients with early-onset cancer of the colon were significantly more likely than those with early-onset cancer of the rectum to have a synchronous advanced adenoma (31 of 75 [41%] vs 11 of 75 [15%]; P < .001).
    Conclusions and relevance: In this cross-sectional study, synchronous advanced adenomas were more commonly found in patients with early-onset colon cancer compared with average-onset colon cancer, and they were distributed throughout the colon. In contrast, advanced adenomas were not increased in patients with rectal cancer and, when detected, were predominantly located in the rectum.
    MeSH term(s) Male ; Humans ; Middle Aged ; Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/epidemiology ; Colorectal Neoplasms/pathology ; Retrospective Studies ; Cross-Sectional Studies ; Colonic Neoplasms/pathology ; Adenoma/diagnosis ; Adenoma/epidemiology ; Adenoma/pathology ; Neoplasms, Multiple Primary/diagnosis ; Neoplasms, Multiple Primary/epidemiology ; Rectal Neoplasms
    Language English
    Publishing date 2023-07-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2574-3805
    ISSN (online) 2574-3805
    DOI 10.1001/jamanetworkopen.2023.24038
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Lynch Syndrome-Associated Colorectal Cancer.

    Sinicrope, Frank A

    The New England journal of medicine

    2018  Volume 379, Issue 8, Page(s) 764–773

    MeSH term(s) Abdominal Pain/etiology ; Adenocarcinoma/diagnosis ; Adenocarcinoma/surgery ; Cecum/pathology ; Colonic Neoplasms/diagnosis ; Colonic Neoplasms/surgery ; Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis ; Colorectal Neoplasms, Hereditary Nonpolyposis/genetics ; Colorectal Neoplasms, Hereditary Nonpolyposis/therapy ; Combined Modality Therapy ; DNA Mismatch Repair ; Genetic Counseling ; Humans ; Male ; Middle Aged ; Practice Guidelines as Topic
    Language English
    Publishing date 2018-08-31
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMcp1714533
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Evaluating the Combination of Microsatellite Instability and Mutation in BRAF as Prognostic Factors for Patients With Colorectal Cancer.

    Sinicrope, Frank A

    Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association

    2018  Volume 17, Issue 3, Page(s) 391–394

    MeSH term(s) Colorectal Neoplasms/genetics ; Humans ; Microsatellite Instability ; Microsatellite Repeats ; Mutation ; Prognosis ; Proto-Oncogene Proteins B-raf/genetics
    Chemical Substances BRAF protein, human (EC 2.7.11.1) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1)
    Language English
    Publishing date 2018-06-30
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 2119789-1
    ISSN 1542-7714 ; 1542-3565
    ISSN (online) 1542-7714
    ISSN 1542-3565
    DOI 10.1016/j.cgh.2018.06.038
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Prognostic and Predictive Values of Mismatch Repair Deficiency in Non-Metastatic Colorectal Cancer.

    Jin, Zhaohui / Sinicrope, Frank A

    Cancers

    2021  Volume 13, Issue 2

    Abstract: Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Universal MMR/MSI testing is standard of care for all patients with newly diagnosed CRC based on multi-society guidelines in the United States. Such testing is intended to ... ...

    Abstract Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Universal MMR/MSI testing is standard of care for all patients with newly diagnosed CRC based on multi-society guidelines in the United States. Such testing is intended to identify patients with Lynch Syndrome due to a germline mutation in an MMR gene, but also detects those with sporadic dMMR/MSI-high CRCs. The prognostic utility of MMR/MSI status in non-metastatic colorectal cancer has been studied extensively, yet more limited data are available for its predictive utility. Results have not been entirely consistent due to potential stage-related differences and limited numbers of dMMR/MSI-H patients included in the studies. In this review, we summarize the current evidence for the prognostic and predictive value of dMMR/MSI-H in non-metastatic CRC, and discuss the use of this biomarker for patient management and treatment decisions in clinical practice.
    Language English
    Publishing date 2021-01-15
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13020300
    Database MEDical Literature Analysis and Retrieval System OnLINE

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