IMPORTANCE Approximately 20% of thyroid nodules display indeterminate cytology. Molecular testing can refine the risk of malignancy and reduce the need for diagnostic hemithyroidectomy.OBJECTIVE To compare the diagnostic performance between an RNA test (Afirma genomic sequencing classifier) and DNA-RNA test (ThyroSeq v3 multigene genomic classifier). DESIGN, SETTING, AND PARTICIPANTSThis parallel randomized clinical trial of monthly block randomization included patients in the UCLA Health system who underwent thyroid biopsy from August 2017 to January 2020 with indeterminate cytology (Bethesda System for Reporting Thyroid Cytopathology category III or IV). INTERVENTIONS Molecular testing with the RNA test or DNA-RNA test. MAIN OUTCOMES AND MEASURES Diagnostic test performance of the RNA test compared with the DNA-RNA test. The secondary outcome was comparison of test performance with prior versions of the molecular tests. RESULTS Of 2368 patients, 397 were eligible for inclusion based on indeterminate cytology, and 346 (median [interquartile range] age, 55 [44-67] years; 266 [76.9%] women) were randomized to 1 of the 2 tests. In the total cohort assessed for eligibility, 3140 thyroid nodules were assessed, and 427 (13.6%) nodules were cytologically indeterminate. The prevalence of malignancy was 20% among indeterminate nodules. The benign call rate was 53% (95% CI, 47%-61%) for the RNA test and 61% (95% CI, 53%-68%) for the DNA-RNA test. The specificities of the RNA test and DNA-RNA test were 80% (95% CI, 72%-86%) and 85% (95% CI, 77%-91%), respectively (P = .33); the positive predictive values (PPV) of the RNA test and DNA-RNA test were 53% (95% CI, 40%-67%) and 63% (95% CI, 48%-77%), respectively (P = .33). The RNA test exhibited a higher PPV compared with the prior test version (Afirma gene expression classifier) (54% [95% CI, 40%-67%] vs 38% [95% CI, 27%-48%]; P = .01). The DNA-RNA test had no statistically significant difference in PPV compared with its prior version (ThyroSeq v2 next-generation sequencing) (63% [95% CI, 48%-77%] vs 58% [95% CI, 43%-73%]; P = .75). Diagnostic thyroidectomy was avoided in 87 (51%) patients tested with the RNA test and 83 (49%) patients tested with the DNA-RNA test. Surveillance ultrasonography was available for 90 nodules, of which 85 (94%) remained stable over a median of 12 months follow-up.CONCLUSIONS AND RELEVANCE Both the RNA test and DNA-RNA test displayed high specificity and allowed 49% of patients with indeterminate nodules to avoid diagnostic surgery. Although previous trials demonstrated that the prior version of the DNA-RNA test was more specific than the prior version of the RNA test, the current molecular test techniques have no statistically significant difference in performance.

The spectrum of female urethral and periurethral disorders includes both benign and malignant entities. Establishing an accurate clinical diagnosis may be challenging because symptoms and physical findings frequently overlap among the various entities. Recent technologic advances in magnetic resonance (MR) imaging and ultrasonography (US) allow more detailed evaluation of urethral and periurethral abnormalities. Advances in MR imaging hardware and pulse sequences allow high-resolution, high-contrast static and dynamic imaging of the female urethral and periurethral region in the context of the entire pelvic floor. Similarly, the introduction of high-resolution surface and intracavitary transducers in conjunction with three-dimensional acquisition have enhanced the role of US in this clinical setting. High-resolution MR imaging and real-time US have exciting potential as tools for more comprehensive analysis of the pathophysiologic features of the complex disorders that affect the female urethra and periurethral tissues.

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Purpose: The goal of this study was to test the safety and activity of a therapeutic vaccine, MKC1106-MT, in patients with metastatic melanoma. Experimental Design: MKC1106-MT comprises a plasmid (pMEL-TYR) and two peptides (E-MEL and E-TYR), corresponding to Melan A and tyrosinase, administered by intra–lymph node injection in a prime-boost sequence. All 18 patients were HLA-A*0201 positive and received a fixed priming dose of plasmid and a low or a high peptide dose. Enumeration of antigen-specific T cells was done prior to and throughout the treatment. Patients who did not exhibit disease progression remained on study and could receive up to eight cycles of treatment. Results: The MKC1106-MT regimen was well tolerated and resulted in an overall immune response rate of 50%. The treatment showed disease control, defined as stable disease that lasted for 8 weeks or more in 6 of 18 (33%) of the patients: 14% and 46% in the low and high peptide dose, respectively. Interestingly, four patients, all with tumor burden largely confined to lymph nodes and Melan A–specific T cells at baseline, showed durable disease control associated with radiologic evidence of tumor regression. There was no noticeable correlation between the expansion of antigen-specific T cells in blood and the clinical outcome; yet, there was evidence of active tumor-infiltrating lymphocytes (TIL) in two regressing lesions. Conclusions: MKC1106-MT showed immunogenicity and evidence of disease control in a defined patient population. These findings support further development of this investigational agent and the concept of therapeutic vaccination in metastatic melanoma. Clin Cancer Res; 17(9); 2987–96. ©2011 AACR.