Intratumoral OH2, an oncolytic herpes simplex virus 2, in patients with advanced solid tumors: a multicenter, phase I/II clinical trial.

BACKGROUND: OH2 is a genetically engineered oncolytic herpes simplex virus type 2 designed to selectively amplify in tumor cells and express granulocyte-macrophage colony-stimulating factor to enhance antitumor immune responses. We investigated the safety, tolerability and antitumor activity of OH2 as single agent or in combination with HX008, an anti-programmed cell death protein 1 antibody, in patients with advanced solid tumors. METHODS: In this multicenter, phase I/II trial, we enrolled patients with standard treatment-refractory advanced solid tumors who have injectable lesions. In phase I, patients received intratumoral injection of OH2 at escalating doses (106, 107 and 108CCID50/mL) as single agent or with fixed-dose HX008. The recommended doses were then expanded in phase II. Primary endpoints were safety and tolerability defined by the maximum-tolerated dose and dose-limiting toxicities (DLTs) in phase I, and antitumor activity assessed per Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) and immune-RECIST in phase II. RESULTS: Between April 17, 2019 and September 22, 2020, 54 patients with metastatic cancers were enrolled. Forty patients were treated with single agent OH2, and 14 with OH2 plus HX008. No DLTs were reported with single agent OH2 in phase I. Four patients, having metastatic mismatch repair-proficient rectal cancer or metastatic esophageal cancer, achieved immune-partial response, with two from the single agent cohort and two from the combination cohort. The duration of response were 11.25+ and 14.03+ months for the two responders treated with single agent OH2, and 1.38+ and 2.56+ months for the two responders in the combination cohort. The most common treatment-related adverse event (TRAE) with single agent OH2 was fever (n=18, 45.0%). All TRAEs were of grade 1-2, except one case of grade 3 fever in the 108CCID50/mL group. No treatment-related serious AEs occurred. Single agent OH2 induced alterations in the tumor microenvironment, with clear increases in CD3+ and CD8+ cell density and programmed death-ligand 1 expression in the patients' post-treatment biopsies relative to baseline. CONCLUSIONS: Intratumoral injection of OH2 was well-tolerated, and demonstrated durable antitumor activity in patients with metastatic esophageal and rectal cancer. Further clinical development of OH2 as single agent or with immune checkpoint inhibitors in selected tumor types is warranted.

Usefulness of real-time contrast-enhanced ultrasound guided coaxial needle biopsy for focal liver lesions.

PURPOSE: To evaluate the utility of real-time contrast-enhanced ultrasound (CEUS)-guided coaxial needle biopsies for focal liver lesions (FLL) that were inconspicuous or could not be accurately identified the active site on B-mode ultrasound (US). MATERIALS AND METHODS: This prospective study included 76 patients who had CEUS-guided coaxial needle biopsies for FLL between December 2015 and June 2017. We recorded characteristics of target lesions. We evaluated conspicuity of target lesions and accuracy of identifying the active site of target lesions on B-mode US and CEUS using a 5-point scale. Patients were divided into three groups, and analyzed according to body mass index (BMI). Based on the final diagnosis, the diagnostic performance was evaluated. RESULTS: The mean size and depth of target lesions were 41.5 ± 28.5 and 47.9 ± 18.9 mm on CEUS, respectively. In arterial phase, the enhanced pattern of target lesions varied. The conspicuity of target lesions and accuracy of identifying the active site of target lesions was significantly improved on CEUS compared to B-mode US (p < 0.05). The three BMI groups had significant differences in conspicuity of target lesions after using CEUS (p < 0.05). The high BMI group had a greater change in conspicuity of lesions compared to the normal BMI group or the low BMI group (p < 0.05). The sensitivity, specificity, and accuracy of this technique for the diagnosis of FLL were 92.8%, 100%, and 93.4%, respectively. CONCLUSION: Real-time CEUS-guided coaxial needle biopsy can be very useful for FLL that are inconspicuous or cannot be accurately identified the active site on B-mode US.

Value of Ultrasonographic Features for Assessing Malignant Potential of Complex Cystic Breast Lesions.

OBJECTIVES: To assess the value of ultrasonography (US) features for determining the malignant potential of complex cystic lesions. METHODS: Seventy-nine complex cystic lesions were reviewed retrospectively. They were classified into four types according to US features in type I, the masses have a thick outer wall, thick internal septa, or both; in type II, the masses are an intracystic type with one or more discrete solid mural lesions within a cyst; in type III, the masses contain mixed cystic and solid components and are at least 50% cystic portion in a mass; in type IV, there are predominantly (at least 50%) solid masses with eccentric or central cystic foci. Positive predictive values were calculated for all types. RESULTS: The frequency of malignancy was higher among type III and IV lesions than among the other two types. Lesions with a diameter greater than or equal to 20 mm, margins not circumscribed, resistance index greater than or equal to 0.7, and axillary abnormal nodes had a high probability of malignancy. CONCLUSIONS: US is an important adjunct to evaluate the malignant potential of complex cystic lesions.