{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T19:24:33Z","timestamp":1793733873820,"version":"4.6.1"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T00:00:00Z","timestamp":1669593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T00:00:00Z","timestamp":1669593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Medical Research Future Fund","award":["MRF1200535"],"award-info":[{"award-number":["MRF1200535"]}],"id":[{"id":"https:\/\/ror.org\/0513v5k17","id-type":"ROR","asserted-by":"crossref"}]},{"name":"PRIMCAT","award":["MRF 1199701"],"award-info":[{"award-number":["MRF 1199701"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Immune checkpoint inhibitors have been approved in the USA for tumours exhibiting mismatch repair deficiency (dMMR), microsatellite instability (MSI), or high tumour mutational burden (TMB), with regulatory and reimbursement applications in multiple other countries underway. As the estimated budget impacts of future reimbursements depend on the size of the potential target population, we performed a scoping review and meta-analysis of the prevalence of these pan-tumour biomarkers in different cancers. We systematically searched Medline\/Embase and included studies reporting the prevalence of dMMR\/MSI\/high TMB in solid tumours published 01\/01\/2018\u201331\/01\/2021. Meta-analyses were performed separately for the pan-cancer prevalence of each biomarker, and by cancer type and stage where possible. The searches identified 3890 papers, with 433 prevalence estimates for 32 different cancer types from 201 studies included in meta-analyses. The pooled overall prevalence of dMMR, MSI and high TMB (\u2265\u200910 mutations\/Mb) in pan-cancer studies was 2.9%, 2.7% and 14.0%, respectively. The prevalence profiles of dMMR\/MSI and high TMB differed across cancer types. For example, endometrial, colorectal, small bowel and gastric cancers showed high prevalence of both dMMR and MSI (range: 8.7\u201326.8% and 8.5\u201321.9%, respectively) and high TMB (range: 8.5\u201343.0%), while cervical, esophageal, bladder\/urothelial, lung and skin cancers showed low prevalence of dMMR and MSI (&lt;\u20095%), but high prevalence of high TMB (range: 23.7\u201352.6%). For other cancer types, prevalence of all three biomarkers was generally low (&lt;\u20095%). This structured review of dMMR\/MSI\/high TMB prevalence across cancers and for specific cancer types and stages provide timely evidence to inform budget impact forecasts in health technology assessments for drug approvals based on these pan-tumour biomarkers.<\/jats:p>","DOI":"10.1038\/s41598-022-23319-1","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T08:03:52Z","timestamp":1669622632000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":86,"title":["A scoping review and meta-analysis on the prevalence of pan-tumour biomarkers (dMMR, MSI, high TMB) in different solid tumours"],"prefix":"10.1038","volume":"12","author":[{"given":"Yoon-Jung","family":"Kang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"O\u2019Haire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Franchini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten","family":"IJzerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Zalcberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Finlay","family":"Macrae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Canfell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Steinberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,28]]},"reference":[{"issue":"9","key":"23319_CR1","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1038\/s41571-020-0384-0","volume":"17","author":"RC Pestana","year":"2020","unstructured":"Pestana, R. C., Sen, S., Hobbs, B. P. & Hong, D. S. Histology-agnostic drug development\u2014Considering issues beyond the tissue. Nat. Rev. Clin. Oncol. 17(9), 555\u2013568 (2020).","journal-title":"Nat. Rev. Clin. Oncol."},{"issue":"15","key":"23319_CR2","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1056\/NEJMp1709968","volume":"377","author":"S Lemery","year":"2017","unstructured":"Lemery, S., Keegan, P. & Pazdur, R. First FDA approval agnostic of cancer site\u2014When a biomarker defines the indication. N. Engl. J. Med. 377(15), 1409\u20131412 (2017).","journal-title":"N. Engl. J. Med."},{"key":"23319_CR3","unstructured":"U.S. Food & Drug Administration. FDA News release: FDA approves first cancer treatment for any solid tumor with a specific genetic feature. https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-first-cancer-treatment-any-solid-tumor-specific-genetic-feature. Accessed 21 October 2020."},{"key":"23319_CR4","unstructured":"Therapeutic Goods Administration. Prescription medicines: new or extended uses, or new combinations of registered medicines, 2019. https:\/\/www.tga.gov.au\/prescription-medicines-new-or-extended-uses-or-new-combinations-registered-medicines-2019. Accessed 21 October 2020."},{"key":"23319_CR5","unstructured":"Merck Receives Positive EU CHMP Opinion for KEYTRUDA\u00ae (pembrolizumab) as First-Line Treatment in Adult Patients With Metastatic Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Colorectal Cancer. https:\/\/www.merck.com\/news\/merck-receives-positive-eu-chmp-opinion-for-keytruda-pembrolizumab-as-first-line-treatment-in-adult-patients-with-metastatic-microsatellite-instability-high-msi-h-or-mismatch-repair-deficien\/. 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Cancer Sci. 111(2), 687\u2013699 (2020).","journal-title":"Cancer Sci."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-23319-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-23319-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-23319-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T21:22:05Z","timestamp":1669670525000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-23319-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,28]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["23319"],"URL":"https:\/\/doi.org\/10.1038\/s41598-022-23319-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,28]]},"assertion":[{"value":"2 February 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 October 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 November 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Professor Karen Canfell is co\u2013principle investigator of an investigator-initiated trial of cervical screening, \u201cCompass\u201d, run by The Australian Centre for the Prevention of Cervical Cancer (ACPCC), which is a government-funded not-for-profit charity; \u201cCompass\u201d receives infrastructure support from the Australian government and the ACPCC has received equipment and a funding contribution from Roche Molecular Diagnostics, USA. She is also co\u2013principle investigator on a major implementation program Elimination of Cervical Cancer in the Western Pacific which has received support from the Minderoo Foundation and the Frazer Family Foundation, and equipment donations from Cepheid Inc. She also receives support for a range of other Australian and international government projects including support from philanthropic organizations, WHO, and government agencies related to cervical cancer control. K.C. is a Chair or member of a number of government or meetings convened by the World Health Organization (WHO), or philanthropic organizations such as Bill and Melinda Gates Foundation (BMGF). \nProfessor John Zalcberg has stock and other ownership interests in Biomarin, Ophthea, Amarin, Concert Pharmaceuticals, Frequency Therapeutics, Gilead, Madrigal Pharmaceuticals, UniQure, Zogenix, rphazyme, Moderna Therapeutics, TWST and Novavax. JZ holds a consulting or advisory role in Merck Serono, Targovax, Merck Sharp & Dohme, Halozyme, Lipotek, Specialized Therapeutics, CEND, Deciphera, REVOLUTION MEDICINE, FivePHusion, Genorbio, 1Global and Novotech. JZ\u2019s institution received funding from Merck Serono, Bristol-Hyers Squibb, AstraZeneca, Pfizer, IQvia, Mylan, Ipsen, Elsai, Medtronic and MSD Oncology. JZ received travel, accommodations and expenses from Merck Serono, AstraZeneca, Merck Sharp & Dohme, Deciphera and Sanofi. \nProfessor Finlay Macrae is a member of the Clinical Advisory Group of the National Bowel Cancer Screening Program. His group receives support from Cancer Australia and the Victorian Cancer Agency for Australian leadership of the CAPP trials for cancer prevention in Lynch Syndrome. He chairs the Australian and New Zealand Gastrointestinal International Training Association which receives support from industry, philanthropic organizations and Australian Government for its activities in the Indo-Pacific region. He is the principal investigator of several clinical trials funded by the pharmaceutical industry. \nOther authors do not have competing interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"20495"}}