Impact of Acquisition Method and Region of Interest Placement on Inter-observer Agreement and Measurement of Tumor Response to Targeted Therapy Using Dynamic Contrast-Enhanced Ultrasound.

This study evaluated the impact of different acquisition methods, user-directed region of interest placement and post-processing steps on the quantification of dynamic contrast-enhanced ultrasound measurements of blood volume in 29 patients with renal cancer, pre- and post-treatment. Specifically, we compared tumor quantification using multiple planes versus a single plane, breathhold versus free breathing and large region of interest versus a region targeting the area of highest vascularity. Performance was evaluated using area under the receiver operating characteristic curves to identify the method that best predicts progression-free survival. The intra-class correlation coefficient was also used to investigate how the same parameters affect inter-observer agreement. Of the different methods used to quantify blood volume in this study, the combination that had the highest level of inter-observer agreement (intra-class correlation coefficient = 0.8-0.97) and was the best predictor of progression-free survival was the change in blood volume measured (area under receiver operating characteristic curve = 0.77, p = 0.04) by a multiplane average, acquired during quiet breathing, quantified using a region of interest that encompassed the entire tumor.

A phase II trial of second-line axitinib following prior antiangiogenic therapy in advanced hepatocellular carcinoma.

BACKGROUND: Second-line treatment options in advanced hepatocellular carcinoma (HCC) are limited. Axitinib, a selective potent tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor VEGF) receptors 1, 2, and 3, merits exploration in HCC. METHODS: This was a single-arm phase II trial of axitinib in advanced HCC. Eligible patients were Child-Pugh A/B7, with measurable progressive disease after TKIs/antiangiogenic drugs. Axitinib was started at 5 mg twice daily orally, titrated from 2 to 10 mg twice daily as tolerated. The primary end point was tumor control at 16 weeks by RECIST1.1; secondary end points were response rate, comparing response by RECIST1.1 to Choi and modified RECIST, exploring dynamic contrast-enhanced imaging models, safety, progression-free (PFS), and overall survival (OS). RESULTS: Thirty patients were treated. Of 26 patients evaluable for response, there were 3 partial responses (PR) per RECIST1.1; 13 PR by Choi, 6 PR and 1 complete response by modified RECIST. Tumor control rate at 16 weeks was 42.3%. Two-week perfusion changes were noted on functional imaging. Of 21 patients with evaluable α-fetoprotein response, 43% had >50% decrease from baseline. Most common axitinib-related grade 3/4 adverse events (AEs) were hypertension, thrombocytopenia and diarrhea. Of 11 patients with any grade hypertension, 7 had disease control >36 wks. Four patients discontinued treatment due to AEs. Median PFS was 3.6 months. Median OS was 7.1 months. CONCLUSIONS: With 42.3% tumor control at 16 weeks, primary endpoint was met. Axitinib has shown encouraging tolerable clinical activity in VEGF-pretreated HCC patients but further study should be in a selected population incorporating potential biomarkers of response.

Use and misuse of waterfall plots.

BACKGROUND: "Waterfall plots" are used to describe changes in tumor size observed in clinical studies. Here we assess criteria for generation of waterfall plots and the impact of measurement error in generating them. METHODS: We reviewed published waterfall plots to investigate variability in criteria used to define them. We then compared waterfall plots generated by different observers for 24 patients enrolled in a completed phase I study of solid tumors with available computed tomography (CT) scans. Tumor measurements were made independently from CT scans according to Response Evaluation Criteria in Solid Tumors 1.1 by four board-certified radiologists and four medical oncologists. Interobserver variability was quantified and compared with reference measurements reported for the phase 1 study. All statistical tests were two-sided. RESULTS: There was substantial variability in criteria used to generate published waterfall plots. In the internal study, the results were statistically significantly different between all eight readers (P = .01, variance = 197.1, SD = 14.0) and between the oncologists (P = .01, variance = 319.0, SD = 17.9), but not between the radiologists (P = .68, variance = 70.8, SD = 8.4). Different observers classified one to five patients as having a partial response and 12-19 patients as having stable disease. Similar variability in categorization of response was observed when these error rates were applied to published waterfall plots. CONCLUSION: Waterfall plots are subject to substantial variability in criteria used to define them and are influenced by measurement errors; they should be generated by trained radiologists. Caution should be exercised when interpreting results of waterfall plots in the context of clinical trials.

Patterns and signal intensity characteristics of pelvic recurrence of rectal cancer at MR imaging.

Magnetic resonance (MR) imaging is becoming the cross-sectional imaging modality of choice for follow-up of patients with previous rectal cancer to diagnose pelvic recurrence and plan for surgery. The authors conducted a retrospective review of MR imaging examinations performed at their institution for evaluation of local recurrence of rectal cancer in 42 patients. Twenty-six patients had undergone rectal anastomosis and 16 had undergone abdominoperineal resection. The mean interval between initial surgery and recurrence was 2.5 years. Recurrence sites were axial (involving the anastomosis) (n = 19); lateral (sidewall) (n = 6); anterior (prostate or seminal vesicle [n = 2], bladder [n = 4], ureter [n = 3], vagina or uterus [n = 5]); or posterior (presacral fascia [n = 11], sacrum [n = 2]). Other recurrence sites included the pelvic floor (n = 7), sciatic nerve (n = 2), obturator nerve (n = 1), perineum (n = 1), abdominal wall (n = 1), or adnexa (n = 1). Recurrence was confirmed at surgery or by evidence of tumor growth at follow-up imaging. Recurrence patterns, signal intensity characteristics, findings of unresectability, potential MR imaging pitfalls, and the role of MR imaging versus other modalities in evaluating recurrent rectal carcinoma are discussed. Supplemental material available at http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg335115170/-/DC1.