Challenges and opportunities associated with the MD Anderson IMPACT2 randomized study in precision oncology.

We investigated the challenges of conducting IMPACT2, an ongoing randomized study that evaluates molecular testing and targeted therapy (ClinicalTrials.gov: NCT02152254). Patients with metastatic cancer underwent tumor profiling and were randomized between the two arms when eligibility criteria were met (Part A). In Part B, patients who declined randomization could choose the study arm. In Part A, 69 (21.8%) of 317 patients were randomized; 78.2% were not randomized because of non-targetable alterations (39.8%), unavailability of clinical trial (21.8%), other reasons (12.6%), or availability of US Food and Drug Administration (FDA)-approved drugs for the indication (4.1%). In Part B, 32 (20.4%) of 157 patients were offered randomization; 16 accepted and 16 selected their treatment arm; 79.0% were not randomized (patient's/physician's choice, 29.3%; treatment selection prior to genomic reports, 16.6%; worsening performance status/death, 12.7%; unavailability of clinical trials, 6.4%; other, 6.4%; non-targetable alterations, 5.7%; or availability of FDA-approved drugs for the indication, 1.9%). In conclusion, although randomized controlled trials have been considered the gold standard for drug development, the execution of randomized trials in precision oncology in the advanced metastatic setting is complicated. We encountered various challenges conducting the IMPACT2 study, a large precision oncology trial in patients with diverse solid tumor types. The adaptive design of IMPACT2 enables patient randomization despite the continual FDA approval of targeted therapies, the evolving tumor biomarker landscape, and the plethora of investigational drugs. Outcomes for randomized patients are awaited.

Interactive Multimedia Reporting Technical Considerations: HIMSS-SIIM Collaborative White Paper.

Despite technological advances in the analysis of digital images for medical consultations, many health information systems lack the ability to correlate textual descriptions of image findings linked to the actual images. Images and reports often reside in separate silos in the medical record throughout the process of image viewing, report authoring, and report consumption. Forward-thinking centers and early adopters have created interactive reports with multimedia elements and embedded hyperlinks in reports that connect the narrative text with the related source images and measurements. Most of these solutions rely on proprietary single-vendor systems for viewing and reporting in the absence of any encompassing industry standards to facilitate interoperability with the electronic health record (EHR) and other systems. International standards have enabled the digitization of image acquisition, storage, viewing, and structured reporting. These provide the foundation to discuss enhanced reporting. Lessons learned in the digital transformation of radiology and pathology can serve as a basis for interactive multimedia reporting (IMR) across image-centric medical specialties. This paper describes the standard-based infrastructure and communications to fulfill recently defined clinical requirements through a consensus from an international workgroup of multidisciplinary medical specialists, informaticists, and industry participants. These efforts have led toward the development of an Integrating the Healthcare Enterprise (IHE) profile that will serve as a foundation for interoperable interactive multimedia reporting.

Multispecialty Enterprise Imaging Workgroup Consensus on Interactive Multimedia Reporting Current State and Road to the Future: HIMSS-SIIM Collaborative White Paper.

Diagnostic and evidential static image, video clip, and sound multimedia are captured during routine clinical care in cardiology, dermatology, ophthalmology, pathology, physiatry, radiation oncology, radiology, endoscopic procedural specialties, and other medical disciplines. Providers typically describe the multimedia findings in contemporaneous electronic health record clinical notes or associate a textual interpretative report. Visual communication aids commonly used to connect, synthesize, and supplement multimedia and descriptive text outside medicine remain technically challenging to integrate into patient care. Such beneficial interactive elements may include hyperlinks between text, multimedia elements, alphanumeric and geometric annotations, tables, graphs, timelines, diagrams, anatomic maps, and hyperlinks to external educational references that patients or provider consumers may find valuable. This HIMSS-SIIM Enterprise Imaging Community workgroup white paper outlines the current and desired clinical future state of interactive multimedia reporting (IMR). The workgroup adopted a consensus definition of IMR as "interactive medical documentation that combines clinical images, videos, sound, imaging metadata, and/or image annotations with text, typographic emphases, tables, graphs, event timelines, anatomic maps, hyperlinks, and/or educational resources to optimize communication between medical professionals, and between medical professionals and their patients." This white paper also serves as a precursor for future efforts toward solving technical issues impeding routine interactive multimedia report creation and ingestion into electronic health records.

Precision medicine: preliminary results from the Initiative for Molecular Profiling and Advanced Cancer Therapy 2 (IMPACT2) study.

Precision medicine is associated with favorable outcomes in selected patients with cancer. Herein, we report an interim analysis of IMPACT2, an ongoing randomized study evaluating genomic profiling and targeted agents in metastatic cancer. Patients with metastatic cancer underwent tumor genomic profiling (ClinialTrials.gov: NCT02152254), and 69 patients met the criteria for randomization. Tumor board and multidisciplinary review of molecular alterations optimized treatment selection. From 5/2014 to 4/2017, 320 patients (median age, 63 years; men, 47%) had tumor molecular aberrations, and 213 (66.56%) received anticancer therapy. The most frequently mutated genes were TP53 (42%), KRAS (16%), PIK3CA (12%), and CDKN2A (11%). The median OS was 10.9 months (95% CI, 8.8-12.9). OS was shorter in patients with higher tumor mutational burden. Independent factors associated with shorter OS were age ≥60 years, liver metastases, low albumin levels, high LDH levels, and KRAS and TP53 mutations. Outcomes for randomized patients will be reported after completion of the study.

A phase I clinical trial of hepatic arterial infusion of oxaliplatin and oral capecitabine, with or without intravenous bevacizumab, in patients with advanced cancer and predominant liver involvement.

BACKGROUND: We investigated hepatic arterial infusion (HAI) oxaliplatin combined with capecitabine +/- bevacizumab in advanced cancer with predominant liver involvement. METHODS: Patients received HAI oxaliplatin (140 mg/m2) and escalating doses of capecitabine (500, 750, and 1000 mg/m2), with (Group 1) or without (Group 2) bevacizumab (10 mg/kg IV). A 3 + 3 dose design was used, followed by an expansion phase. RESULTS: From 9/2009 to 2/2014, 61 patients (34 men, 27 women) were enrolled (Group 1 = 44; Group 2 = 17). Patients were treated in Group 2 if they had contraindications to bevacizumab (n = 13) or if there was no opening in Group 1 (n = 4). The median age was 60 years (range, 20-88). The most common cancers were colorectal (22 patients), liver (12), pancreatic (7), breast (4), and biliary tract (4). The median number of prior therapies was 3 (range, 1-12); 32 (53%) patients had received oxaliplatin. The dose-limiting toxicity was Grade 3 diarrhea and occurred in 2 patients receiving 1000 mg/m2 capecitabine. The maximum tolerated dose was HAI oxaliplatin 140 mg/m2, capecitabine 750 mg/m2, and bevacizumab 10 mg/kg. The most common toxicities were nausea/vomiting, anemia, thrombocytopenia, neutropenia, and hypomagnesemia. The rates of partial response and stable disease ≥ 4 months were 22% and 39% (Group 1) and 9% and 0% (Group 2). The respective median time to treatment failure and overall survival were 3 and 6.9 months (Group 1) and 1.5 and 5.9 months (Group 2). CONCLUSION: HAI oxaliplatin combined with capecitabine +/- bevacizumab was well-tolerated and was associated with favorable outcomes in selected patients.

Comparative study of computational visual attention models on two-dimensional medical images.

Computational modeling of visual attention is an active area of research. These models have been successfully employed in applications such as robotics. However, most computational models of visual attention are developed in the context of natural scenes, and their role with medical images is not well investigated. As radiologists interpret a large number of clinical images in a limited time, an efficient strategy to deploy their visual attention is necessary. Visual saliency maps, highlighting image regions that differ dramatically from their surroundings, are expected to be predictive of where radiologists fixate their gaze. We compared 16 state-of-art saliency models over three medical imaging modalities. The estimated saliency maps were evaluated against radiologists' eye movements. The results show that the models achieved competitive accuracy using three metrics, but the rank order of the models varied significantly across the three modalities. Moreover, the model ranks on the medical images were all considerably different from the model ranks on the benchmark MIT300 dataset of natural images. Thus, modality-specific tuning of saliency models is necessary to make them valuable for applications in fields such as medical image compression and radiology education.

CT Imaging Findings of Metastatic Spindle Cell Sarcoma of Prostate: A Case Report and Review of the Literature.

Sarcomas of the prostate are rare tumors. Imaging plays an important role in the management and diagnosis of patients with prostate sarcomas. Their clinic-pathologic features are well described, but the imaging features of these tumors have rarely been documented in the literature and have appeared mainly as case reports. Herein, we present a rare case of metastatic spindle cell sarcoma of prostate with computed tomography imaging findings.

In vivo CT dosimetry during CT colonography.

OBJECTIVE: The purpose of this study was to develop a method of measuring rectal radiation dose in vivo during CT colonography (CTC) and assess the accuracy of size-specific dose estimates (SSDEs) relative to that of in vivo dose measurements. MATERIALS AND METHODS: Thermoluminescent dosimeter capsules were attached to a CTC rectal catheter to obtain four measurements of the CT radiation dose in 10 volunteers (five men and five women; age range, 23-87 years; mean age, 70.4 years). A fixed CT technique (supine and prone, 50 mAs and 120 kVp each) was used for CTC. SSDEs and percentile body habitus measurements were based on CT images and directly compared with in vivo dose measurements. RESULTS: The mean absorbed doses delivered to the rectum ranged from 8.8 to 23.6 mGy in the 10 patients, whose mean body habitus was in the 27th percentile among American adults 18-64 years old (range, 0.5-67th percentile). The mean SSDE error was 7.2% (range, 0.6-31.4%). CONCLUSION: This in vivo radiation dose measurement technique can be applied to patients undergoing CTC. Our measurements indicate that SSDEs are reasonable estimates of the rectal absorbed dose. The data obtained in this pilot study can be used as benchmarks for assessing dose estimates using other indirect methods (e.g., Monte Carlo simulations).

Segmentation in virtual colonoscopy using a geometric deformable model.

The Geometric Deformable Model is developed for accurate colon lumen segmentation as part of an automatic Virtual Colonoscopy system. The deformable model refines the lumen surface found by an automatic seed location and thresholding procedure. The challenges to applying the deformable model are described, showing the definition of the stopping function as the key to accurate segmentation. The limitations of current stopping criteria are examined and a new definition, tailored to the task of colon segmentation, is given. First, a multiscale edge operator is used to locate high confidence boundaries. These boundaries are then integrated into the stopping function using a distance transform. The hypothesis is that the new stopping function results in a more accurate representation of the lumen surface compared to previous monotonic functions of the gradient magnitude. This hypothesis is tested using observer ratings of colon surface fidelity at 100,000 randomly selected locations in each of four datasets. The results show that the surfaces determined by the modified deformable model better represent the lumen surface overall.

Computed tomographic colonography (virtual colonoscopy): a multicenter comparison with standard colonoscopy for detection of colorectal neoplasia.

CONTEXT: Conventional colonoscopy is the best available method for detection of colorectal cancer; however, it is invasive and not without risk. Computed tomographic colonography (CTC), also known as virtual colonoscopy, has been reported to be reasonably accurate in the diagnosis of colorectal neoplasia in studies performed at expert centers. OBJECTIVE: To assess the accuracy of CTC in a large number of participants across multiple centers. DESIGN, SETTING, AND PARTICIPANTS: A nonrandomized, evaluator-blinded, noninferiority study design of 615 participants aged 50 years or older who were referred for routine, clinically indicated colonoscopy in 9 major hospital centers between April 17, 2000, and October 3, 2001. The CTC was performed by using multislice scanners immediately before standard colonoscopy; findings at colonoscopy were reported before and after segmental unblinding to the CTC results. MAIN OUTCOME MEASURES: The sensitivity and specificity of CTC and conventional colonoscopy in detecting participants with lesions sized at least 6 mm. Secondary outcomes included detection of all lesions, detection of advanced lesions, possible technical confounders, participant preferences, and evidence for increasing accuracy with experience. RESULTS: A total of 827 lesions were detected in 308 of 600 participants who underwent both procedures; 104 participants had lesions sized at least 6 mm. The sensitivity of CTC for detecting participants with 1 or more lesions sized at least 6 mm was 39.0% (95% confidence interval [CI], 29.6%-48.4%) and for lesions sized at least 10 mm, it was 55.0% (95% CI, 39.9%-70.0%). These results were significantly lower than those for conventional colonoscopy, with sensitivities of 99.0% (95% CI, 97.1%->99.9%) and 100%, respectively. A total of 496 participants were without any lesion sized at least 6 mm. The specificity of CTC and conventional colonoscopy for detecting participants without any lesion sized at least 6 mm was 90.5% (95% CI, 87.9%-93.1%) and 100%, respectively, and without lesions sized at least 10 mm, 96.0% (95% CI, 94.3%-97.6%) and 100%, respectively. Computed tomographic colonography missed 2 of 8 cancers. The accuracy of CTC varied considerably between centers and did not improve as the study progressed. Participants expressed no clear preference for either technique. CONCLUSIONS: Computed tomographic colonography by these methods is not yet ready for widespread clinical application. Techniques and training need to be improved.

Virtual colonoscopy using oral contrast compared with colonoscopy for the detection of patients with colorectal polyps.

BACKGROUND & AIMS: Virtual colonoscopy using abdominal spiral computed tomography scanning allows total colonic evaluation with minimal invasiveness. Two-dimensional images and selective 3-dimensional images of the colon are used to detect colorectal lesions. This trial used conventional colonoscopy with segmental unblinding to determine the ability of virtual colonoscopy to identify patients with colorectal lesions who need conventional colonoscopy. METHODS: We studied 205 patients with virtual colonoscopy using oral iodinated contrast preceding conventional colonoscopy. Colonic lavage was achieved with an oral sodium phosphosoda preparation and colonic distention with a carbon dioxide electronic insufflator. RESULTS: The overall sensitivity and specificity of virtual colonoscopy in identifying patients with colorectal lesions was 61.8% and 70.7%, respectively. Virtual colonoscopy was more accurate in identifying patients with lesions >/=6 mm (sensitivity 84.4% and specificity 83.1%) and those with lesions >/=10 mm (sensitivity 90% and specificity 94.6%). The negative predictive value of virtual colonoscopy was 95% for a 6-mm cutoff size and 98.9% for a 10-mm cutoff. Using a 10-mm cutoff, virtual colonoscopy precludes the need for conventional colonoscopy in 86% of patients with a 1% false-negative rate (68% with a 3.4% false-negative rate when using a 6-mm cutoff). CONCLUSIONS: Virtual colonoscopy has a high sensitivity and specificity for detecting patients with significant colorectal lesions. Its high negative predictive value may help reduce the number of negative screening colonoscopies. Further studies are needed to determine what lesion cutoff size is clinically acceptable and the appropriate interval time for repeat virtual colonoscopy when it detects lesions below this cutoff size.

The virtual colonoscopy study: a large multicenter clinical trial designed to compare two diagnostic screening procedures.

This paper reviews the design of a large multicenter clinical trial currently being conducted to test the equivalence of two screening procedures for colorectal polyps. The primary outcome is the sensitivity and specificity of the new and standard procedures for detecting subjects with and without polyps of a size > or =6 mm, respectively. An important secondary outcome is the accuracy of these procedures in detecting individual polyps. A total of 619 participants underwent virtual colonoscopy, the new procedure, followed by conventional colonoscopy, the standard procedure. Strategies for the design and implementation of the study are shared as well as the challenges encountered.