Mutation detection using plasma circulating tumor DNA (ctDNA) in a cohort of asymptomatic adults at increased risk for cancer.

PURPOSE: The primary purpose of this study was to clinically evaluate circulating tumor DNA (ctDNA) with a nine gene, 96 mutation panel among subjects at increased risk for cancer with no previous cancer diagnosis. SUBJECTS AND METHODS: DNA from 1059 asymptomatic subjects was analyzed for detection of low levels ctDNA using a blood plasma liquid biopsy assay. Subjects with detectable copies of ctDNA were asked to provide additional blood samples and relevant medical records throughout their one-year of participation. Subjects with a negative result were followed-up at one-year with a questionnaire. RESULTS: Mutations were detected in 58 subjects and not detected in 1001 subjects. Among the subjects who tested positive for one or more mutations, four were diagnosed with cancer, two of which through study-triggered clinical follow-up. Two subjects who tested negative on the screen received an early cancer diagnosis over the course of the year. The sensitivity of the assay at a threshold of ≥2 copies in this population was 66.67% and specificity was 94.87%. While the negative predictive value was 99.8%, the positive predictive value was only 6.9% in this cohort. Analysis of buffy coat DNA from eight positive subjects, including one who was diagnosed with cancer, revealed matching mutations suggesting that the ctDNA could have been derived from clonal hematopoiesis. CONCLUSION: The observed false positive rate of ctDNA on a 96-mutation assay in an asymptomatic high-risk population is much greater than the true positive rate, limiting its usefulness as a cancer screening tool in its current form.

Alopecia areata as a paraneoplastic syndrome of Hodgkin's lymphoma: A case report.

Alopecia areata (AA) has been classically associated with several autoimmune disorders. However, AA as a paraneoplastic syndrome of Hodgkin's lymphoma (HL) remains a rare entity and our understanding of this phenomenon is limited to a few case reports. This is the case report of a 46-year-old male patient who was diagnosed with AA several months prior to the onset of B symptoms and the diagnosis of stage IVB classical HL. The patient was subsequently treated with 6 cycles of adriamycin, bleomycin, vinblastine and dacarbazine and experienced a complete response and resolution of his AA. In our case, the onset of AA preceded the onset of systemic manifestations and diagnosis of HL, whereas in other cases AA was shown to occur concurrently with the clinical manifestations of HL. In all the cases, however, treatment of the HL subsequently led to resolution of the AA. The present case report highlights the significance of AA as a herald of underlying malignancy, although AA in classical HL remains poorly characterized in the literature.

Personalized medicine and pharmacogenetic biomarkers: progress in molecular oncology testing.

In the field of oncology, clinical molecular diagnostics and biomarker discoveries are constantly advancing as the intricate molecular mechanisms that transform a normal cell into an aberrant state in concert with the dysregulation of alternative complementary pathways are increasingly understood. Progress in biomarker technology, coupled with the companion clinical diagnostic laboratory tests, continue to advance this field, where individualized and customized treatment appropriate for each individual patient define the standard of care. Here, we discuss the current commonly used predictive pharmacogenetic biomarkers in clinical oncology molecular testing: BRAF V600E for vemurafenib in melanoma; EML4-ALK for crizotinib and EGFR for erlotinib and gefitinib in non-small-cell lung cancer; KRAS against the use of cetuximab and panitumumab in colorectal cancer; ERBB2 (HER2/neu) for trastuzumab in breast cancer; BCR-ABL for tyrosine kinase inhibitors in chronic myeloid leukemia; and PML/RARα for all-trans-retinoic acid and arsenic trioxide treatment for acute promyelocytic leukemia.