Standardization of thyroid ultrasound reporting in the community setting decreases biopsy rates.

OBJECTIVE: With the rising incidence of thyroid cancer, a standardized approach to the evaluation of thyroid nodules is essential. Despite the presence of multiple national guidelines detailing evaluation and management of these nodules, significant variability exists in the information that is collected and reported to clinicians from diagnostic imaging. The aim of this study was to evaluate the impact of thyroid ultrasound standardization on thyroid cancer detection in a community practice setting. DESIGN: As part of a physician-driven quality improvement project, a multidisciplinary team created an electronic worksheet to be utilized by sonographers to capture suspicious findings based on societal guidelines and agreed on institutional criteria for recommending fine needle aspiration (FNA) of thyroid nodules. PATIENTS: For a one-year period prior to and after the intervention, all ultrasounds performed for suspected thyroid pathology, excluding patients undergoing follow-up imaging, were reviewed at two affiliated community hospitals served by a single radiology and pathology group. MEASUREMENTS: The number of fine needle biopsies recommended and performed, as well as the percentage of FNAs positive for malignancy were evaluated. RESULTS: A total of 608 and 675 ultrasounds were reviewed in pre- and post-standardization periods, respectively. Following standardization, there was a similar percentage of FNAs recommended (35% vs. 37%, p = .68), fewer FNAs per total ultrasounds performed (36% vs. 31%, p = .03), fewer FNAs performed when FNA was not explicitly recommended (9.9% vs. 2.8%, p = .000046) and an increased detection of cytology consistent with, or suspicious for, malignancy (5% vs. 11.5%, p = .0028). CONCLUSIONS: Standardization of thyroid imaging protocol and management recommendations can reduce the number of FNAs performed and increase the percentage of positive tests in a community setting.

HDAC inhibition prevents transgene expression downregulation and loss-of-function in T-cell-receptor-transduced T cells.

T cells that are gene-modified with tumor-specific T cell receptors are a promising treatment for metastatic melanoma patients. In a clinical trial, we treated seven metastatic melanoma patients with autologous T cells transduced to express a tyrosinase-reactive T cell receptor (TCR) (TIL 1383I) and a truncated CD34 molecule as a selection marker. We followed transgene expression in the TCR-transduced T cells after infusion and observed that both lentiviral- and retroviral-transduced T cells lost transgene expression over time, so that by 4 weeks post-transfer, few T cells expressed either lentiviral or retroviral transgenes. Transgene expression was reactivated by stimulation with anti-CD3/anti-CD28 beads and cytokines. TCR-transduced T cell lentiviral and retroviral transgene expression was also downregulated in vitro when T cells were cultured without cytokines. Transduced T cells cultured with interleukin (IL)-15 maintained transgene expression. Culturing gene-modified T cells in the presence of histone deacetylase (HDAC) inhibitors maintained transgene expression and functional TCR-transduced T cell responses to tumor. These results implicate epigenetic processes in the loss of transgene expression in lentiviral- and retroviral-transduced T cells.

Randomized phase II study of stereotactic body radiotherapy and interleukin-2 versus interleukin-2 in patients with metastatic melanoma.

BACKGROUND: A pilot study of stereotactic body radiation therapy (SBRT) followed by high-dose interleukin-2 (IL-2) showed a higher than anticipated objective response rate (ORR) among patients with metastatic melanoma (MM). We performed a prospective randomized study to determine if the ORR of SBRT + IL-2 was greater than IL-2 monotherapy in patients with advanced melanoma. METHODS: Patients with MM who had adequate physiological reserve for IL-2 and at least one site suitable for SBRT were eligible. There was a 1:1 randomization to SBRT + IL-2 or IL-2 monotherapy. Patients received one or two doses of SBRT (20 Gy per fraction) with the last dose administered 3 days before starting the first cycle of IL-2. IL-2 (600,000 IU per kg via intravenous bolus infusion) was given every 8 hours for a maximum of 14 doses with a second cycle after a 2-week rest. Responding patients received up to six IL-2 cycles. Patients assigned to IL-2 monotherapy who exhibited progression of melanoma after cycle 2 were allowed to crossover and receive SBRT and additional IL-2. Response Evaluation Criteria in Solid Tumors 1.1 criteria were applied to non-irradiated lesions for response assessment. RESULTS: 44 patients were included in the analysis. The ORR in the SBRT + IL-2 group was 54%: 21% complete response (CR), 33% partial response (PR), 21% stable disease (SD) and 25% progressive disease (PD). The ORR in patients receiving IL-2 monotherapy was 35%: 15% CR, 20% PR, 25% SD and 40% PD. Seven patients assigned to IL-2 subsequently received SBRT + IL-2. One CR and two PRs were observed in the crossover group. There was no difference in progression-free or overall survival (OS). At 5 years the OS was 26% in the SBRT + IL-2 group and 25% in the IL-2 monotherapy group. The disease control rate (DCR) was higher in the SBRT + IL-2 group (75% vs 60%, p=0.34). CONCLUSIONS: SBRT + IL-2 induced more objective responses with a higher DCR compared to IL-2 monotherapy in MM. IL-2 monotherapy resulted in a significantly higher ORR than anticipated. Some patients in the crossover group also achieved objective responses. TRIAL REGISTRATION NUMBER: NCT01416831.