A Phase 2 Trial of Enhancing Immune Checkpoint Blockade by Stereotactic Radiation and In Situ Virus Gene Therapy in Metastatic Triple-Negative Breast Cancer.

PURPOSE: A Phase 2 trial of stereotactic radiotherapy and in situ cytotoxic virus therapy in patients with metastatic triple-negative breast cancer (mTNBC) followed by pembrolizumab (STOMP) was designed to evaluate dual approach of enhancing single-agent immune checkpoint blockade with adenovirus-mediated expression of herpes-simplex-virus thymidine-kinase (ADV/HSV-tk) plus valacyclovir gene therapy and stereotactic body radiotherapy (SBRT) in patients with mTNBC. PATIENTS AND METHODS: In this single-arm, open-label Phase 2 trial, patients with mTNBC were treated with ADV/HSV-tk [5 × 1011 virus particles (vp)] intratumoral injection, followed by SBRT to the injected tumor site, then pembrolizumab (200 mg, every 3 weeks). The primary endpoint was clinical benefit rate [CBR; complete response (CR), partial response (PR), or stable disease (SD) ≥ 24 weeks per RECIST version1.1 at non-irradiated site]. Secondary endpoints included duration on treatment (DoT), overall survival (OS), and safety. Exploratory endpoints included immune response to treatment assessed by correlative tissue and blood-based biomarkers. RESULTS: Twenty-eight patients were enrolled and treated. CBR was seen in 6 patients (21.4%), including 2 CR (7.1%), 1 PR (3.6%), and 3 SD (10.7%). Patients with clinical benefit had durable responses, with median DoT of 9.6 months and OS of 14.7 months. The median OS was 6.6 months in the total population. The combination was well tolerated. Correlative studies with Cytometry by Time of Flight (CyTOF) and imaging mass cytometry (IMC) revealed a significant increase of CD8 T cells in responders and of myeloid cells in non-responders. CONCLUSIONS: The median OS increased by more than 2-fold in patients with clinical benefit. The therapy is a well-tolerated treatment in heavily pretreated patients with mTNBC. Early detection of increased effector and effector memory CD8 T cells and myeloids correlate with response and non-response, respectively.

Thyroid Fine Needle Aspiration: Successful Prospective Implementation of Strategies to Eliminate Unnecessary Biopsy in the Veteran Population.

OBJECTIVE: Thyroid nodules are prevalent in over half the general population. Several multidisciplinary societies have management recommendations. However, the majority of data to support these guidelines are derived from studies of predominantly younger and female populations. This study's aim was to evaluate characteristics of thyroid nodules in a largely older and male Veteran population and apply these findings prospectively to reduce unnecessary thyroid fine needle aspiration (FNA). MATERIALS AND METHODS: Over a 4-year period, all ultrasound-guided FNA of thyroid nodules performed in our department were reviewed. Sonographic features, patterns, and histopathology were evaluated. A prospective strategy of avoiding FNA in all lesions matching imaging patterns of benignity was implemented and positive predictive value (PPV) of malignancy was calculated and compared to the retrospective data. RESULTS: Retrospectively, FNA was performed on 351 successive thyroid nodules, 9 of which were malignant. Statistically significant malignant features include presence of microcalcifications, irregular or amorphous morphology, taller-than-wide shape, spiculated margins, vascularity, and lymphadenopathy. PPV of thyroid FNA was 2.6% in this period. Four sonographic patterns were 100% specific for benignity, including: "spongiform," "cyst with a colloid clot," "giraffe," and "white knight" patterns. Over 23 months, prospective avoidance of FNA of lesions characterized as a benign pattern (159 nodules) was implemented and PPV was calculated as 7.2% resulting in a cost savings of $477,000. CONCLUSION: Four sonographic patterns were 100% specific for benignity in the older and predominantly male Veteran population. Strict prospective application of avoiding biopsy in these benign patterns resulted in a decrease of unnecessary biopsies, decrease in patient morbidity, and improved allocation of health care resources.

Post-embolization syndrome as an early predictor of overall survival after transarterial chemoembolization for hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolization (TACE) is the most common treatment for patients with unresectable hepatocellular carcinoma (HCC). Post-embolization syndrome (PES) is a common post-TACE complication. The goal of this study was to evaluate PES as an early predictor of the long-term outcome. METHODS: A retrospective cohort study of HCC patients treated with TACE at a tertiary referral centre was performed (2008-2014). Patients were categorized on the basis of PES, defined as fever with or without abdominal pain within 14 days of TACE. The primary outcome was overall survival (OS). Multivariate Cox regression was done to examine the association between PES and OS. RESULTS: Among 144 patients, 52 (36.1%) experienced PES. The median follow-up for the cohort was 11.4 months. The median and 3-year OS rates were 16 months and 18% in the PES group versus 25 months and 41% in the non-PES group (log rank, P = 0.027). After multivariate analysis, patients with PES had a significantly increased risk of death [hazard ratio 2.0 (95%CI 1.2-3.3), P = 0.011]. CONCLUSIONS: PES is a common complication after TACE and is associated with a two-fold increased risk of death. Future studies should incorporate PES as a relevant early predictor of OS and examine the biological basis of this association.