Vivek Gowdra Halappa

Neuroendocrine Liver Metastasis Treated by Using Intraarterial Therapy: Volumetric Functional Imaging Biomarkers of Early Tumor Response and Survival

PURPOSE To determine if volumetric changes of diffusion-weighted and contrast material-enhanced magnetic resonance (MR) imaging can help assess early tumor response to intraarterial therapy (IAT) in neuroendocrine liver metastasis (NELM). MATERIALS AND METHODS This retrospective single-center comprehensive imaging analysis was performed in compliance with HIPAA and was institutional review board approved. Informed patient consent was waived. Seventy-one patients (39 men; mean age, 62.3 years) with NELM treated with IAT were analyzed retrospectively. MR studies were performed before and 3-4 weeks after therapy. The index lesion was segmented to provide volumetric functional analysis of apparent diffusion coefficient (ADC) and contrast-enhanced MR imaging in the hepatic arterial phase (HAP) and portal venous phase (PVP). Tumor response was defined as increase in volumetric ADC of 15% or greater and decrease in volumetric enhancement of 25% or greater during the HAP or of 50% or greater during the PVP. Patient overall survival was the primary end point after therapy initiation. Univariate analysis included Kaplan-Meier survival curves. The Cox proportional hazards regression model was used to detect interactions between volumetric ADC and contrast-enhanced MR imaging and to calculate the hazard ratio. RESULTS There was significant increase in mean volumetric ADC (27%, P < .0001) and significant decrease in mean volumetric enhancement during the HAP (-25.3%, P < .0001) and the PVP (-22.4%, P < .0001) in all patients. Patients who had 15% or greater volumetric ADC increase (n = 49) after therapy had better prognosis than those who had less than 15% increase in volumetric ADC (n = 22) (log-rank test, P < .002). Patients who had 25% or greater decrease in volumetric arterial enhancement (n = 40) or 50% or greater decrease in venous enhancement (n = 18) had better prognosis than those who had less than 25% decrease in volumetric arterial enhancement (n = 31) or less than 50% decrease in venous enhancement (n = 53) (log-rank test, P < .02). CONCLUSION Volumetric functional MR imaging criteria may act as biomarkers of early response, indicating that these criteria may be important to incorporate in future NELM clinical trials.

Intrahepatic Cholangiocarcinoma Treated with Local-Regional Therapy: Quantitative Volumetric Apparent Diffusion Coefficient Maps for Assessment of Tumor Response

PURPOSE To evaluate volumetric changes in apparent diffusion coefficient (ADC) and contrast material enhancement on contrast-enhanced (CE) magnetic resonance (MR) images in hepatic arterial and portal venous phases for assessing early response in cholangiocarcinoma treated with transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS Twenty-nine patients with unresectable cholangiocarcinoma, including 11 men (mean age, 60 years; standard deviation, 16.8) and 18 women (mean age, 63 years; standard deviation, 11.5) were included in this retrospective institutional review board-approved, HIPAA-compliant study; informed consent was waived. Sixty-nine TACE procedures were performed during the observational time (range, one to five TACE sessions). No patients received another form of therapy after treatment with TACE. MR Imaging was performed before and 3-4 weeks after TACE, and images were analyzed with a semiautomatic volumetric software package. Patients were stratified as responders and nonresponders on the basis of overall survival (OS) as the primary end point. Differences between responders and nonresponders were analyzed with paired t tests, and OS was calculated with the Kaplan-Meier method. Significant differences were analyzed with the log-rank test. RESULTS Mean volumetric ADC increased from 1.54×10(-3) mm2/sec to 1.92×10(-3) mm2/sec (P<.0001), with no significant decrease in mean volumetric enhancement in hepatic arterial (40.6% vs 37.5%, P=.546) and portal venous (79.0% vs 70.0%, P=.105) phases. Patients who demonstrated improved survival of 10 months or more had a significant increase in mean volumetric ADC and volumetric ADC above the threshold level of 1.60×10(-3) mm2/sec (P<.002). Patients with 45% or greater (n=21; log-rank test, P<.02) and 60% or greater (n=12; log-rank test, P<.009) ADC changes for the whole tumor volume demonstrated better OS compared with patients in whom these ADC changes were not achieved. CONCLUSION Patients with percentage tumor volume increase in ADC of 45% or greater and 60% or greater above the threshold level of 1.60×10(-3) mm2/sec had favorable response to therapy and improved survival.

Interobserver agreement of semi-automated and manual measurements of functional MRI metrics of treatment response in hepatocellular carcinoma.

PURPOSE To assess the interobserver agreement in 50 patients with hepatocellular carcinoma (HCC) before and 1 month after intra-arterial therapy (IAT) using two semi-automated methods and a manual approach for the following functional, volumetric and morphologic parameters: (1) apparent diffusion coefficient (ADC), (2) arterial phase enhancement (AE), (3) portal venous phase enhancement (VE), (4) tumor volume, and assessment according to (5) the Response Evaluation Criteria in Solid Tumors (RECIST), and (6) the European Association for the Study of the Liver (EASL). MATERIALS AND METHODS This HIPAA-compliant retrospective study had institutional review board approval. The requirement for patient informed consent was waived. Tumor ADC, AE, VE, volume, RECIST, and EASL in 50 index lesions was measured by three observers. Interobserver reproducibility was evaluated using intraclass correlation coefficients (ICC). P<0.05 was considered to indicate a significant difference. RESULTS Semi-automated volumetric measurements of functional parameters (ADC, AE, and VE) before and after IAT as well as change in tumor ADC, AE, or VE had better interobserver agreement (ICC=0.830-0.974) compared with manual ROI-based axial measurements (ICC=0.157-0.799). Semi-automated measurements of tumor volume and size in the axial plane before and after IAT had better interobserver agreement (ICC=0.854-0.996) compared with manual size measurements (ICC=0.543-0.596), and interobserver agreement for change in tumor RECIST size was also higher using semi-automated measurements (ICC=0.655) compared with manual measurements (ICC=0.169). EASL measurements of tumor enhancement in the axial plane before and after IAT ((ICC=0.758-0.809), and changes in EASL after IAT (ICC=0.653) had good interobserver agreement. CONCLUSION Semi-automated measurements of functional changes assessed by ADC and VE based on whole-lesion segmentation demonstrated better reproducibility than ROI-based axial measurements, or RECIST or EASL measurements.

Unresectable Hepatocellular Carcinoma: MR Imaging after Intraarterial Therapy. Part I. Identification and Validation of Volumetric Functional Response Criteria

PURPOSE To identify and validate the optimal thresholds for volumetric functional MR imaging response criteria to predict overall survival after intraarterial treatment (IAT) in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS Institutional review board approval and waiver of informed consent were obtained. A total of 143 patients who had undergone MR imaging before and 3-4 weeks after the first cycle of IAT were included. MR imaging analysis of one representative HCC index lesion was performed with proprietary software after initial treatment. Subjects were randomly divided into training (n = 114 [79.7%]) and validation (n = 29 [20.3%]) data sets. Uni- and multivariate Cox models were used to determine the best cutoffs, as well as survival differences, between response groups in the validation data set. RESULTS Optimal cutoffs in the training data set were 23% increase in apparent diffusion coefficient (ADC) and 65% decrease in volumetric enhancement in the portal venous phase (VE). Subsequently, 25% increase in ADC and 65% decrease in VE were used to stratify patients in the validation data set. Comparison of ADC responders (n = 12 [58.6%]) with nonresponders (n = 17 [34.5%]) showed significant differences in survival (25th percentile survival, 11.2 vs 4.9 months, respectively; P = .008), as did VE responders (n = 9 [31.0%]) compared with nonresponders (n = 20 [69.0%]; 25th percentile survival, 11.5 vs 5.1 months, respectively; P = .01). Stratification of patients with a combination of the criteria resulted in significant differences in survival between patients with lesions that fulfilled both criteria (n = 6 [20.7%]; too few cases to determine 25th percentile), one criterion (n = 9 [31.0%]; 25th percentile survival, 6.0 months), and neither criterion (n = 14 [48.3%]; 25th percentile survival, 5.1 months; P = .01). The association between the two criteria and overall survival remained significant in a multivariate analysis that included age, sex, Barcelona Clinic for Liver Cancer stage, and number of follow-up treatments. CONCLUSION After IAT for unresectable HCC, patients can be stratified into significantly different survival categories based on responder versus nonresponder status according to MR imaging ADC and VE cutoffs.

Islet Cell Liver Metastases: Assessment of Volumetric Early Response with Functional MR Imaging after Transarterial Chemoembolization

PURPOSE To assess early response to transarterial chemoembolization by using volumetric functional magnetic resonance (MR) imaging in patients with islet cell liver metastases (ICLMs). MATERIALS AND METHODS This retrospective institutional review board-approved HIPAA-compliant study included 215 ICLMs in 26 patients (15 men, 11 women; mean age, 59.7 years; age range, 37-79 years). Volumetric measurements were performed by an experienced radiologist on diffusion-weighted and contrast material-enhanced MR images at baseline and 1-month follow-up. Measurements included mean change (three-dimensional [3D] mean apparent diffusion coefficient [ADC], 3D mean enhancement) and percentage of tumor with change above a predetermined threshold (3D threshold ADC, 3D threshold enhancement). Response by volumetric measurements at 1-month follow-up was compared with Response Evaluation Criteria in Solid Tumors (RECIST) at 6-month follow-up. Lesions that had complete or partial response were considered responders, while those with stable or progressive disease were considered nonresponders. Statistical analysis included the t test, receiver operating characteristic (ROC) curve analysis, and logistic regression analysis. RESULTS RECIST criteria at 6-month follow-up indicated 78 (36.3%) lesions responded, while 137 (63.7%) did not. The increase in 3D mean ADC was significantly higher in responders than in nonresponders (median, 26.2% vs 10.9%; P<.001). The 3D threshold ADC was 71.1% in responders and 47.6% in nonresponders (P<.001). Decrease in 3D mean arterial enhancement (AE) was significantly higher in responders than in nonresponders (median, 40.5% vs 18.0%; P<.001). Decrease in 3D mean venous enhancement (VE) was significantly higher in responders than in nonresponders (median, 28.0% vs 10.0%; P<.001). The 3D threshold VE and 3D threshold AE did not differ between responders and nonresponders. In unadjusted logistic regression analyses, 3D mean ADC and 3D threshold ADC had the highest odds ratio (1.02 and 1.03, respectively) and the largest area under the ROC curve (0.698 and 0.695, respectively). CONCLUSION Volumetric functional MR imaging could be used to predict early response of hepatic ICLMs to therapy and to distinguish between responders and nonresponders.

Rectal imaging: Part 1, high-resolution MRI of carcinoma of the rectum at 3 T

OBJECTIVE MRI is currently the imaging modality of choice for the detection, characterization, and staging of rectal cancer. A variety of examinations have been used for preoperative staging of rectal cancer, including digital rectal examination, endorectal (endoscopic) ultrasound, CT, and MRI. Endoscopic ultrasound is the imaging modality of choice for small and small superficial tumors. MRI is superior to CT for assessing invasion to adjacent organs and structures, especially low tumors that carry a high risk of recurrence. CONCLUSION High-resolution MRI is an accurate and sensitive imaging method delineating tumoral margins, mesorectal involvement, nodes, and distant metastasis. In this article, we will review the utility of rectal MRI in local staging, preoperative evaluation, and surgical planning. MRI at 3 T can accurately delineate the mesorectal fascia involvement, which is one of the main decision points in planning treatment.

Agreement and reproducibility of apparent diffusion coefficient measurements of dual-b-value and multi-b-value diffusion-weighted magnetic resonance imaging at 1.5 Tesla in phantom and in soft tissues of the abdomen.

Objective To compare the coefficient of variation (CV) and long-term reproducibility of apparent diffusion coefficient (ADC) in a simple fluid-filled phantom and abdominal organs simultaneously. Materials and Methods Retrospective institutional review board–approved and Health Insurance Portability and Accountability Act–compliant study sequentially selected 100 patients who underwent clinically indicated abdominal magnetic resonance imaging. A subset of 58 patients had repeat scans within 2 to 5 months after the initial magnetic resonance imaging. Two diffusion-weighted imaging techniques (b-values 0–750 mm2/s) were performed to compare the ADC values. Mean ADC values were calculated for 10 locations and the reference phantom. The CV and Bland-Altman plots were calculated for the phantom and soft tissues at each session and location. Results There were no significant differences in the mean ADC values between repeated acquisitions. However, ADC values were statistically higher using dual-b-value than multi-b-value diffusion-weighted imaging. The CV for the phantom was 8.6 versus 10.8 for dual-b-value and multi-b-value, respectively. The CVs for the soft tissues had a wider range compared with that of the phantom (liver, 12.6 vs 9.0; spleen, 11.7 vs 11.2; gallbladder, 11.0 vs 13.6; head of pancreas, 14.6 vs 14.7; body of pancreas, 13.4 vs 13.0; tail of pancreas, 14.8 vs 16.3; right kidney, 9.1 vs 9.6; left kidney, 9.3 vs 9.3; right paraspinal muscle, 7.9 vs 7.5; left paraspinal muscle, 7.3 vs 7.3, respectively). Conclusions A change in ADC less than 11% falls into the range of measurement variability. Paraspinal muscle could potentially be used as an internal reference parameter.

Prevalence of honorary coauthorship in the American Journal of Roentgenology.

OBJECTIVE The objective of our study was to determine the prevalence of honorary authorship in articles published in the American Journal of Roentgenology (AJR) and to evaluate the factors that might influence the perception of honorary authorship. MATERIALS AND METHODS Corresponding authors of 1333 Original Research articles published in AJR between 2003 and 2010 were invited by e-mail to complete a Web-based, self-administered survey. Univariable analysis of sample proportions was performed using the chi-square test. Multivariable logistic regression models were used to assess the independent factors that were associated with the probability of honorary authorship. RESULTS Responses were received from authors of 490 articles (36.8% response rate). Most respondents were aware of the authorship guidelines proposed by the International Committee of Medical Journal Editors (n = 399, 81.4%) and the issue of honorary authorship (n = 353, 72.0%). Authorship was most commonly decided by the first author (n = 256, 52.2%). One hundred twenty-one authors (24.7%) perceived that one or more coauthors listed for the respective article did not make sufficient contributions. Factors most strongly associated with honorary authorship included a work environment where a senior department member was automatically listed (odds ratio [OR], 1.33), the suggestion that an honorary author should be included (OR, 5.96), and the perception that a coauthor performed only a single nonauthor task (i.e., reviewing the manuscript: OR, 1.54). CONCLUSION A substantial proportion of articles had evidence of honorary authorship. The rate of honorary authors was higher among authors who worked in an environment where senior members were routinely added to all manuscripts submitted for publication, authors who perceived that a coauthor listed had only reviewed the manuscript, and authors who reported that someone suggested they should include an honorary author.

Neuroendocrine tumor liver metastases treated with yttrium-90 radioembolization

OBJECTIVE Yttrium-90 (Y-90) radioembolization is an emerging treatment option for unresectable neuroendocrine liver metastases (NELM). However, the data regarding this treatment are currently limited. This study evaluates the efficacy and tolerability of Y-90 radioembolization and identifies prognostic factors for radiographic response and survival. METHODS AND MATERIALS Thirty-eight patients underwent Y-90 radioembolization for NELM at our institution between April 2004 and February 2012. Patients were assessed radiographically (RECIST criteria, enhancement), serologically, and clinically at 1month, and then at every 3months after treatment for tumor response, toxicity, and survival outcomes. RESULTS Median length of follow-up was 17.0months (IQR, 9.0-37.0). Median survival was 29.2months. Three patients (9%) had a radiographic complete response to treatment, 6 (17%) had a partial response, 21 (60%) had stable disease, and 5 (14%) developed progressive disease. Two factors were significantly associated with a good radiographic response (complete/partial response): islet cell histological subtype (p=0.043) and hepatic tumor burden ≥33% (p=0.031). Multivariate analysis revealed that patients requiring multiple Y-90 treatments (HR 2.9, p=0.035) and patients who had previously failed systemic therapy with octreotide/chemotherapy (HR 4.4, p=0.012) had worse survival. Grade 3 serologic toxicity was observed in 2 patients (5%; hyperbilirubinemia, elevated alkaline phosphatase) after treatment. Grade 3 non-serologic toxicities included abdominal pain (11%), fatigue (11%), nausea/vomiting (5%), ascites (5%), dyspnea (3%), diarrhea (3%), and peripheral edema (3%). No grade 4 or 5 toxicity was reported. CONCLUSIONS Y-90 radioembolization is a promising treatment option for inoperable NELM and is associated with low rates of grade≥3 toxicity.

Functional magnetic resonance imaging response of targeted tumor burden and its impact on survival in patients with hepatocellular carcinoma.

ObjectiveThe aim of this study was to evaluate response of the targeted tumor burden by functional magnetic resonance imaging (MRI) including volumetric diffusion-weighted imaging and volumetric contrast-enhanced MRI (CE-MRI) and its impact on survival in patients with hepatocellular carcinoma treated with intra-arterial therapy (IAT). Materials and MethodsThis institutional review board–approved, Health Insurance Portability and Accountability Act–compliant retrospective study included 157 hepatocellular carcinoma lesions in 97 patients (78 men and 19 women; mean age, 64 years) treated with IAT. All patients had pretreatment and 3- to 4-week follow-up MRI with diffusion-weighted imaging and CE-MRI. All lesions 2 cm or larger that were targeted during the first session of IAT were segmented using research software (MR-Oncotreat) to determine targeted tumor burden relative to liver volume (%). Targeted tumor burden was stratified into low (⩽10%) or high (>10%). Response using volumetric functional apparent diffusion coefficient (ADC; increase by ≥25%) and CE-MRI (decrease by ≥50% and ≥65% in arterial and venous enhancement [VE], respectively) was assessed in all targeted tumors (range, 1–11) using paired t tests. Kaplan-Meier survival analysis was performed and log-rank test was used to compare pairs of survival curves. Multivariate Cox regression analysis was performed to determine the simultaneous effect of treatment response and tumor burden on survival after adjusting for age, sex, and Child Pugh status. ResultsThere was a significant increase in volumetric ADC (median, 15%; P < 0.001) and a decrease in volumetric arterial enhancement (AE) and VE (median AE, −43% and portal venous phase (PVP), −29%, respectively; P < 0.001) 3 to 4 weeks after treatment in the targeted tumor burden. Multivariable Cox regression demonstrated that both ADC response and low tumor burden were independently associated with greater survival (hazard ratios, 0.53 and 0.55; P values, 0.025 and 0.016, respectively) after adjustment for age, sex, and Child Pugh status. Multivariable Cox regression models demonstrated no statistically significant relationship between AE response and survival after adjusting for tumor burden. However, multivariable Cox regression demonstrated that VE response was associated with greater survival only in those with low tumor burden (hazard ratio, 0.10; P = 0.001), indicating a strong interaction between VE response and tumor burden. ConclusionQuantifying targeted tumor burden is important in predicting patient survival when using functional MRI metrics in assessing treatment response.