Author:
Michuda Jackson,Breschi Alessandra,Kapilivsky Joshuah,Manghnani Kabir,McCarter Calvin,Hockenberry Adam J,Mineo Brittany,Igartua Catherine,Dudley Joel T,Stumpe Martin C,Beaubier Nike,Shirazi Maryam,Jones Ryan,Morency Elizabeth,Blackwell Kim,Guinney Justin,Beauchamp Kyle A,Taxter Timothy
Abstract
AbstractCancers assume a variety of distinct histologies and may originate from a myriad of sites including solid organs, hematopoietic cells, and connective tissue. Clinical decision making based on consensus guidelines such as NCCN is often predicated on a specific histologic and anatomic diagnosis, supported by clinical features and pathologist interpretation of morphology and immunohistochemical (IHC) staining patterns. However, in patients with nonspecific morphologic and IHC findings—in addition to ambiguous clinical presentations such as recurrence versus new primary—a definitive diagnosis may not be possible, resulting in the patient being categorized as having a cancer of unknown primary (CUP). Therapeutic options and clinical outcomes are poor for CUP patients, with a median survival of 8-11 months. Here we describe and validate the Tempus Tumor Origin (Tempus TO) assay, an RNA-seq-based machine learning classifier capable of discriminating between 68 clinically relevant cancer subtypes. We show that the Tempus TO model is 91% accurate when assessed on retrospectively and prospectively held out cohorts of containing 9,210 samples with known diagnoses. When evaluated on a cohort of CUPs, the model recapitulated established associations between genomic alterations and cancer subtype. Combining diagnostic prediction tests (e.g., Tempus TO) with sequencing-based variant reporting (e.g., Tempus xT) may expand therapeutic options for patients with cancers of unknown primary or uncertain histology.
Publisher
Cold Spring Harbor Laboratory
Reference48 articles.
1. Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology
2. Cancer of Unknown Primary Site
3. Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
4. National Comprehensive Cancer Network. Occult Primary, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw, n.d.
5. Key statistics for cancers of unknown primary, n.d. https://www.cancer.org/cancer/cancer-unknown-primary/about/key-statistics.html. (Accessed April 13, 2021)
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献