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Simple Summary: Cancers of the pancreas, gallbladder and bile duct (pancreaticobiliary tract) are often aggressive with poor survival. However, these cancers are not easily identifiable or detected because of vague (non-specific) symptoms and the absence of accurate blood tests. The diagnosis of these cancers involves imaging or endoscopy followed by sampling (biopsy) of suspected tissue for histopathological examination (HPE). Where the tissue sample is not of acceptable quality or is insufficient, the diagnosis (and treatment) can be hindered or delayed. In this manuscript, we describe a blood test that can detect pancreaticobiliary tract cancers with high accuracy. The test may be able to facilitate timely diagnosis of these cancers in suspected patients, especially where tissue-sampling-based diagnosis has been inconclusive or is not possible. Circulating tumor cells (CTCs) have historically been used for prognostication in oncology. We evaluate the performance of liquid biopsy CTC assay as a diagnostic tool in suspected pancreaticobiliary cancers (PBC). The assay utilizes functional enrichment of CTCs followed by immunofluorescent profiling of organ-specific markers. The performance of the assay was first evaluated in a multicentric case-control study of blood samples from 360 participants, including 188 PBC cases (pre-biopsy samples) and 172 healthy individuals. A subsequent prospective observational study included pre-biopsy blood samples from 88 individuals with suspicion of PBC and no prior diagnosis of cancer. CTCs were harvested using a unique functional enrichment method and used for immunofluorescent profiling for CA19.9, Maspin, EpCAM, CK, and CD45, blinded to the tissue histopathological diagnosis. TruBlood® malignant or non-malignant predictions were compared with tissue diagnoses to establish sensitivity and specificity. The test had 95.9% overall sensitivity (95% CI: 86.0–99.5%) and 92.3% specificity (95% CI: 79.13% to 98.38%) to differentiate PBC (n = 49) from benign conditions (n = 39). The high accuracy of the CTC-based TruBlood test demonstrates its potential clinical application as a diagnostic tool to assist the effective detection of PBC when tissue sampling is unviable or inconclusive. [ABSTRACT FROM AUTHOR]

Simple Summary: Detection of breast cancer in the early stages is associated with higher cure rates and better survival, and also requires fewer intensive treatments. Current breast cancer screening via mammography is unsuitable for use among (younger) women with more dense breasts, and also has limitations in its ability to detect aggressive breast cancers. In this research article, we describe a breast cancer detection test that is based on the detection of 'circulating tumor cells' in blood samples. This test can detect breast cancer CTCs with high accuracy across all age groups, hormone receptor subtypes, histological subtypes, and disease grade. In our study, this test detected breast cancer cases and differentiated them from healthy (cancer-free) females as well as those with non-cancerous conditions with high accuracy. This test has negligible risk of false positive findings, as well as high detection rate for early-stage (localized) breast cancer. Clinical adoption of this test can be beneficial in cancer screening as well as in detection of breast cancers in suspected cases. Background: The early detection of breast cancer (BrC) is associated with improved survival. We describe a blood-based breast cancer detection test based on functional enrichment of breast-adenocarcinoma-associated circulating tumor cells (BrAD-CTCs) and their identification via multiplexed fluorescence immunocytochemistry (ICC) profiling for GCDFP15, GATA3, EpCAM, PanCK, and CD45 status. Methods: The ability of the test to differentiate BrC cases (N = 548) from healthy women (N = 9632) was evaluated in a case–control clinical study. The ability of the test to differentiate BrC cases from those with benign breast conditions was evaluated in a prospective clinical study of women (N = 141) suspected of BrC. Results: The test accurately detects BrAD-CTCs in breast cancers, irrespective of age, ethnicity, disease stage, grade, or hormone receptor status. Analytical validation established the high accuracy and reliability of the test under intended use conditions. The test detects and differentiates BrC cases from healthy women with 100% specificity and 92.07% overall sensitivity in a case–control study. In a prospective clinical study, the test shows 93.1% specificity and 94.64% overall sensitivity in differentiating breast cancer cases (N = 112) from benign breast conditions (N = 29). Conclusion: The findings reported in this manuscript support the clinical potential of this test for blood-based BrC detection. [ABSTRACT FROM AUTHOR]

In this paper we report long-term therapy management based on iterative de novo molecular and cellular analysis in a case of metastatic non-small cell lung cancer (NSCLC), with prior history of treated colorectal cancer. In the described case temporal tumor evolution, emergent therapy resistance and disease recurrences were addressed via the administration of personalized label- and organ-agnostic treatments based on de novo tumor profiling. This adaptive and iterative treatment strategy countered disease progression at each instance and led to the durable regression of primary as well as metastatic lesions. Concurrently, serial evaluation of mutations in cell-free circulating tumor DNA (ctDNA) via liquid biopsy (LBx) was performed to monitor disease status, ascertain treatment response, identify emergent drug resistance and detect recurrence at sub-radiological levels. The treatment management strategy described herein effectively addressed multiple, sequential clinical conundrums for which viable options were unavailable under the current Standard of Care (SoC). [ABSTRACT FROM AUTHOR]