Phase Ib study of talimogene laherparepvec in combination with atezolizumab in patients with triple negative breast cancer and colorectal cancer with liver metastases.

BACKGROUND: Talimogene laherparepvec (T-VEC), a first-in-class oncolytic viral immunotherapy, enhances tumor-specific immune activation. T-VEC combined with atezolizumab, which blocks inhibitor T-cell checkpoints, could provide greater benefit than either agent alone. Safety/efficacy of the combination was explored in patients with triple negative breast cancer (TNBC) or colorectal cancer (CRC) with liver metastases. METHODS: In this phase Ib, multicenter, open-label, parallel cohort study of adults with TNBC or CRC with liver metastases, T-VEC (106 then 108 PFU/ml; ≤4 ml) was administered into hepatic lesions via image-guided injection every 21 (±3) days. Atezolizumab 1200 mg was given on day 1 and every 21 (±3) days thereafter. Treatment continued until patients experienced dose-limiting toxicity (DLT), had complete response, progressive disease, needed alternative anticancer treatment, or withdrew due to an adverse event (AE). The primary endpoint was DLT incidence, and secondary endpoints included efficacy and AEs. RESULTS: Between 19 March 2018 and 6 November 2020, 11 patients with TNBC were enrolled (safety analysis set: n = 10); between 19 March 2018 and 16 October 2019, 25 patients with CRC were enrolled (safety analysis set: n = 24). For the 5 patients in the TNBC DLT analysis set, no patient had DLT; for the 18 patients in the CRC DLT analysis set, 3 (17%) had DLT, all serious AEs. AEs were reported by 9 (90%) TNBC and 23 (96%) CRC patients, the majority with grade ≥3 [TNBC, 7 (70%); CRC, 13 (54%)], and 1 was fatal [CRC, 1 (4%)]. Evidence of efficacy was limited. Overall response rate was 10% (95% confidence interval 0.3-44.5) for TNBC; one (10%) patient had a partial response. For CRC, no patients had a response; 14 (58%) were unassessable. CONCLUSIONS: The safety profile reflected known risks with T-VEC including risks of intrahepatic injection; no unexpected safety findings from addition of atezolizumab to T-VEC were observed. Limited evidence of antitumor activity was observed.

In vivo prostate cancer detection and grading using restriction spectrum imaging-MRI.

BACKGROUND: Magnetic resonance imaging (MRI) is emerging as a robust, noninvasive method for detecting and characterizing prostate cancer (PCa), but limitations remain in its ability to distinguish cancerous from non-cancerous tissue. We evaluated the performance of a novel MRI technique, restriction spectrum imaging (RSI-MRI), to quantitatively detect and grade PCa compared with current standard-of-care MRI. METHODS: In a retrospective evaluation of 33 patients with biopsy-proven PCa who underwent RSI-MRI and standard MRI before radical prostatectomy, receiver-operating characteristic (ROC) curves were performed for RSI-MRI and each quantitative MRI term, with area under the ROC curve (AUC) used to compare each term's ability to differentiate between PCa and normal prostate. Spearman rank-order correlations were performed to assess each term's ability to predict PCa grade in the radical prostatectomy specimens. RESULTS: RSI-MRI demonstrated superior differentiation of PCa from normal tissue, with AUC of 0.94 and 0.85 for RSI-MRI and conventional diffusion MRI, respectively (P=0.04). RSI-MRI also demonstrated superior performance in predicting PCa aggressiveness, with Spearman rank-order correlation coefficients of 0.53 (P=0.002) and -0.42 (P=0.01) for RSI-MRI and conventional diffusion MRI, respectively, with tumor grade. CONCLUSIONS: RSI-MRI significantly improves upon current noninvasive PCa imaging and may potentially enhance its diagnosis and characterization.

Novel technique for characterizing prostate cancer utilizing MRI restriction spectrum imaging: proof of principle and initial clinical experience with extraprostatic extension.

BACKGROUND: Standard magnetic resonance imaging (MRI) of the prostate lacks sensitivity in the diagnosis and staging of prostate cancer (PCa). To improve the operating characteristics of prostate MRI in the detection and characterization of PCa, we developed a novel, enhanced MRI diffusion technique using restriction spectrum imaging (RSI-MRI). METHODS: We compared the efficacy of our novel RSI-MRI technique with standard MRI for detecting extraprostatic extension (EPE) among 28 PCa patients who underwent MRI and RSI-MRI prior to radical prostatectomy, 10 with histologically proven pT3 disease. RSI cellularity maps isolating the restricted isotropic water fraction were reconstructed based on all b-values and then standardized across the sample with z-score maps. Distortion correction of the RSI maps was performed using the alternating phase-encode technique. RESULTS: 27 patients were evaluated, excluding one patient where distortion could not be performed. Preoperative standard MRI correctly identified extraprostatic the extension in two of the nine pT3 (22%) patients, whereas RSI-MRI identified EPE in eight of nine (89%) patients. RSI-MRI correctly identified pT2 disease in the remaining 18 patients. CONCLUSIONS: In this proof of principle study, we conclude that our novel RSI-MRI technology is feasible and shows promise for substantially improving PCa imaging. Further translational studies of prostate RSI-MRI in the diagnosis and staging of PCa are indicated.

Cowden disease: CT findings in three patients.

Cowden disease, also known as multiple hamartoma syndromes, is an autosomal dominant disease characterized by numerous benign mucocutaneous tumors, hamartomas of multiple organs, and malignancies of the breast and thyroid. In this report, we present the computed tomographic findings in three patients with Cowden disease. In addition to the classic findings, the patients were diagnosed with spinal neurinoma (n=1), meningioma (n=1), and hepatic hemangioma (n=3). We also review current clinical and genetic concepts that unify Cowden disease.

Hepatic MR imaging using ferumoxides: prospective evaluation with surgical and intraoperative sonographic confirmation in 25 cases.

OBJECTIVE: The purpose of our study was to evaluate the sensitivity and accuracy of ferumoxides-enhanced MR imaging in comparison with surgery and intraoperative sonography. SUBJECTS AND METHODS: We prospectively evaluated 25 consecutive studies in 24 patients who underwent ferumoxides-enhanced hepatic MR imaging before surgery and intraoperative sonography. Both 1.5-T scanners (13 cases) and 0.2-T scanners (12 cases) were used. Turbo spin-echo T2-weighted sequences were performed before and after the administration of ferumoxides and the images were compared. Lesions were classified as solid or nonsolid and tabulated on standard liver maps. The liver maps from MR imaging were compared with those from surgery and intraoperative sonography. For lesions greater than 1 cm, the regions of interest were measured and contrast-to-noise ratio was calculated. RESULTS: Of 93 solid lesions found at surgery, 69 were seen on unenhanced MR imaging (sensitivity, 74.2%) and 87 were seen on ferumoxides-enhanced MR imaging (sensitivity, 93.5%) (p < 0.05). Of the seven benign lesions (five cysts, two hemangiomas) found at surgery, all were correctly identified as benign on MR imaging. Two lesions identified as solid before surgery were not found at surgery. Mean lesion contrast-to-noise ratio for the unenhanced scans was 22.9 and 34.5 (p < 0.001) for the ferumoxides-enhanced scans. Subanalysis of 1.5- and 0.2-T MR imaging revealed similar results with significant (p < 0.05) increases in sensitivity for both. The average size of the lesions missed before surgery was 0.7 cm. CONCLUSION: Turbo spin-echo T2-weighted ferumoxides-enhanced MR imaging at either 1.5 or 0.2 T has value in preoperative liver assessment.

MR-guided therapy. Applications in the abdomen.

This article provides an overview of current abdominal interventional applications that use MR imaging guidance and monitoring for diagnostic biopsies, tumor ablations and--owing to the development of new pulse sequences--monitoring the ablation process, and aspiration and drainage of fluid collections. These applications are optimal for patients with lesions that can be localized only by MR imaging or for lesions in suboptimal locations such as the dome of the liver.