Neoadjuvant gemcitabine, docetaxel, and capecitabine followed by gemcitabine and capecitabine/radiation therapy and surgery in locally advanced, unresectable pancreatic adenocarcinoma.

BACKGROUND: This prospective study was undertaken to assess toxicity, resectability, and survival in pancreatic adenocarcinoma patients presenting with locally advanced, unresectable disease treated with neoadjuvant gemcitabine, docetaxel, and capecitabine (GTX) and gemcitabine and capecitabine (GX)/radiation therapy (RT). METHODS: All patients presenting to the Pancreas Center were evaluated for eligibility. Forty-five patients (mean age, 64 years; range, 44-83 years)-34 patients deemed unresectable because of arterial involvement and 11 patients deemed unresectable because of extensive venous involvement-were treated with 6 cycles of GTX. Those with arterial involvement were treated with GX/RT after chemotherapy. RESULTS: The GTX and GX/RT treatments were tolerated with the expected drug-related toxicities. There were no bowel perforations, cases of pancreatitis, or delayed strictures. Among those with arterial involvement, 29 underwent subsequent resection, with 20 (69%) achieving R0 resections. All 11 patients with venous-only involvement underwent resection, with 8 achieving R0 resections and 3 achieving complete pathologic responses. For the arterial arm, the 1-year survival rate was 71% (24 of 34 patients), and the median survival was 29 months (95% confidence interval, 21-38 months). Thirteen patients (38%) have not relapsed (range, 5-49+ months). For the venous arm, the median survival has not been reached at more than 42 months. Six patients (55%) in the venous arm did not experience recurrence (range, 6.2-42+ months). CONCLUSIONS: GTX plus GX/RT is an effective neoadjuvant regimen that can be safely administered to patients up to at least the age of 83 years. It is associated with a high response rate, a high rate of R0 resections, and prolonged overall survival.

Breast cancer molecular subtype as a predictor of the utility of preoperative MRI.

OBJECTIVE: The purpose of this study was to discern whether breast cancer molecular subtype, a known prognostic indicator, can be used to select patients with the highest likelihood of having clinically significant additional findings on breast MRI. MATERIALS AND METHODS: A database review from January 2010 through December 2013 identified 299 patients who underwent preoperative breast MRI with tumors classifiable into molecular subtypes. Subtypes were classified on the basis of immunohistochemical staining surrogates as luminal A (hormone receptor [ER or PR] positive, ERBB2 [formerly HER2 or HER2/neu] negative, luminal B (hormone receptor positive, ERBB2 positive), ERBB2 (hormone receptor negative, ERBB2 positive), or basal (hormone receptor and ERBB2 negative). Univariate and multivariate logistic regression analyses were used to determine the association between subtype and additional breast MRI findings, including multicentric or multifocal disease, contralateral disease, chest wall involvement, skin and nipple involvement, and internal mammary and axillary lymphadenopathy. RESULTS: The subtype distribution was luminal A, 70.6% (211/299); luminal B, 14.1% (42/299); ERBB2, 5.4% (16/299); and basal, 10.0% (30/299). ERBB2 and luminal B sub-types were more often associated with multicentric disease (25.0% and 26.2%), multifocal disease (37.5% and 35.7%), and axillary disease (50.0% and 45.2%) than were luminal A cancers (multicentric disease, 10.9%; multifocal disease 20.4%; axillary disease, 22.7%) (p < 0.001). In multivariate analysis, after control for patient age, tumor size, and nuclear grade, patients with ERBB2-overexpressing tumors were 2.4 times as likely as patients with luminal A tumors to have multicentric disease (p = 0.016), 2.0 times as likely to have multifocal disease (p = 0.024), 1.7 times as likely to have skin and nipple involvement (p = 0.013), and 1.9 times as likely to have axillary disease (p = 0.011). CONCLUSION: Preoperative MRI may most benefit patients with tumors with ERBB2 overexpression because of the increased likelihood of the presence of additional disease.

Perfusion reduction at transcatheter intraarterial perfusion MR imaging: a promising intraprocedural biomarker to predict transplant-free survival during chemoembolization of hepatocellular carcinoma.

PURPOSE: To investigate the predictive value of transcatheter intraarterial perfusion (TRIP) magnetic resonance (MR) imaging-measured tumor perfusion changes during transarterial chemoembolization on transplant-free survival (TFS) in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This HIPAA-compliant prospective study was approved by the institutional review board. Written informed consent was obtained from all patients. Fifty-one consecutive adult patients with surgically unresectable single or multifocal measurable HCC and adequate laboratory parameters who underwent chemoembolization in a combined MR imaging-interventional radiology suite between February 2006 and June 2010 were studied. Tumor perfusion changes during chemoembolization were measured by using TRIP MR imaging with area under the time-signal intensity curve calculation. The end point of the study was TFS. The authors assessed the correlation between the percentage perfusion reduction in the tumor during chemoembolization and TFS by using univariate and multivariate analyses. RESULTS: Fifty patients (mean age, 61 years; 39 men aged 42-87 years [mean age, 61 years] and 11 women aged 49-83 years [mean age, 62 years]) were eligible for the analysis. Patients with 35%-85% intraprocedural tumor area under the time-signal intensity curve reduction (n = 32) showed significantly improved median TFS compared with patients with an area under the time-signal intensity curve reduction outside this range (n = 18) (16.6 months [95% confidence interval: 11.2, 22.0 months] vs 9.3 months [95% confidence interval: 6.6, 12.0 months], respectively; P = .046; hazard ratio: 0.46; 95% confidence interval: 0.21, 1.00). The cumulative TFS rates in the 35%-85% and less than 35% or more than 85% perfusion reduction groups at 1, 2, and 5 years after chemoembolization were 66.4%, 42.2%, and 28.2% versus 33.8%, 16.9%, and 0%, respectively. CONCLUSION: The study shows evidence of an association between intraprocedural tumor perfusion reduction during chemoembolization and TFS and suggests the utility of TRIP MR imaging- measured tumor perfusion reduction as an intraprocedural imaging biomarker during chemoembolization.

Locoregional chemoembolic delivery: prediction with transcatheter intraarterial perfusion MRI.

OBJECTIVE: To our knowledge there is currently no quantitative preprocedural method for predicting the distribution and selectivity of delivery of chemoembolic material during trans-arterial chemoembolization. Transcatheter intraarterial perfusion MRI has been developed as a method of quantifying hepatic arterial perfusion. The purpose of this study was to investigate whether findings at transcatheter intraarterial perfusion MRI before chemoembolization can be used to predict uptake of the chemoembolic material delivered during chemoembolization. SUBJECTS AND METHODS: We compared quantitative prechemoembolization transcatheter intraarterial perfusion MRI parameters with analogous postchemoembolization CT chemoembolic distribution parameters and analyzed correlation using the Pearson correlation coefficient. These MRI and CT parameters included volume of distribution (a metric for volumetric liver perfusion or therapeutic agent delivery) and chemoembolic delivery selectivity factor (a ratio of volume-normalized tumor to background signal intensity that indicates the selectivity of chemoembolic delivery). RESULTS: Twenty-four hepatocellular carcinomas were targeted in 18 patients (14 men, four women; mean age, 66 years), and segmental or lobar chemoembolization with intraprocedural transcatheter intraarterial perfusion MRI was successful in all 18. Transcatheter intraarterial perfusion MRI and CT volume of distribution did not differ significantly (MRI, 233 cm(3); CT, 235 cm(3); p = 0.857). Transcatheter intraarterial perfusion MRI selectivity factor was an underestimate of CT selectivity factor (MRI, 0.20; CT, 0.25; p = 0.005). Prechemoembolization transcatheter intraarterial perfusion MRI and postchemoembolization CT volume of distribution (r = 0.93; p < 0.001) and selectivity factor (r = 0.95; p < 0.001) showed significant correlation. CONCLUSION: Tumor perfusion measured with transcatheter intraarterial perfusion MRI is predictive of uptake of chemoembolic material before delivery. This MRI technique may have utility as a method of quantifying delivery of the therapeutic agent during chemoembolization and, potentially, other liver-directed locoregional therapies.

Quantitative 4D transcatheter intraarterial perfusion MRI for standardizing angiographic chemoembolization endpoints.

OBJECTIVE: The purpose of this study was to test the hypothesis that subjective angiographic endpoints during transarterial chemoembolization (TACE) of hepatocellular carcinoma are consistent and correlate with objective intraprocedural reductions in tumor perfusion determined with quantitative 4D transcatheter intraarterial perfusion MRI. SUBJECTS AND METHODS: In this prospective study, 18 consecutively registered patients underwent TACE in a combined MRI-interventional radiology suite. Three board-certified interventional radiologists independently graded the angiographic endpoint of each procedure using a previously described subjective angiographic chemoembolization endpoint scale. A consensus endpoint rating was established for each patient. Patients underwent quantitative 4D transcatheter intraarterial perfusion MRI immediately before and after TACE, and mean whole tumor perfusion was calculated from the images. Consistency of subjective angiographic endpoint ratings between observers was evaluated with the intraclass correlation coefficient. The relation between the endpoint ratings and intraprocedural transcatheter intraarterial perfusion MRI changes was evaluated with the Spearman rank correlation coefficient. RESULTS: The subjective angiographic chemoembolization endpoint rating scale showed very good consistency among all observers (intraclass correlation coefficient, 0.80). The consensus endpoint rating correlated significantly with both absolute (r = 0.54, p = 0.022) and percentage (r = 0.85, p < 0.001) reduction in intraprocedural perfusion. CONCLUSION: The subjective angiographic chemoembolization endpoint rating scale shows very good consistency between raters and significantly correlates with objectively measured intraprocedural perfusion reductions during TACE. These results support the use of the scale as a standardized alternative method in quantitative 4D transcatheter intraarterial perfusion MRI to classify patients on the basis of embolic endpoints of TACE.

Chemoembolization endpoints: effect on survival among patients with hepatocellular carcinoma.

OBJECTIVE: The purpose of this study was to investigate the relation between angiographic embolic endpoints of transarterial chemoembolization (TACE) and the survival of patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This study was a retrospective assessment of the cases of 105 patients with surgically unresectable HCC who underwent TACE. The cases were classified according to a previously established subjective angiographic chemoembolization endpoint scale. Only one patient had endpoint level I embolization and was excluded from all subsequent analysis. Survival was evaluated with Kaplan-Meier analysis. The Cox proportional hazards model was used to determine independent prognostic risk factors of survival. RESULTS: The overall median survival period was 21.1 months (95% CI, 15.9-26.4 months). Patients with embolization to subjective angiographic chemoembolization endpoint levels II and III were aggregated and had a significantly longer median survival period (25.6 months; 95% CI, 16.2-35.0 months) than patients with embolization to level IV (17.1 months; 95% CI, 13.3-20.9 months) (p = 0.035). The results of multivariate analysis indicated that all of the following factors were independent negative prognostic indicators of survival: subjective angiographic chemoembolization endpoint level IV (hazard ratio [HR], 2.49; 95% CI, 1.41-4.42; p = 0.002), European Cooperative Oncology Group performance status greater than 0 (HR, 1.97; 95% CI, 1.15-3.37; p = 0.013), American Joint Committee on Cancer stage III or IV (HR, 2.42; 95% CI, 1.27-4.60; p = 0.007), and Child-Pugh class B (HR, 1.94; 95% CI, 1.09-3.46; p = 0.025). CONCLUSION: Embolization to an intermediate, substasis endpoint (subjective angiographic chemoembolization endpoint levels II and III) during TACE improves survival compared with embolization to a higher, stasis endpoint (level IV). Interventional oncologists should consider aiming for these intermediate, substasis angiographic endpoints during TACE.

Quantitative 4D transcatheter intraarterial perfusion MRI for monitoring chemoembolization of hepatocellular carcinoma.

PURPOSE: To develop a fully quantitative 4D transcatheter intraarterial perfusion (TRIP) magnetic resonance imaging (MRI) technique and prospectively test the hypothesis that quantitative 4D TRIP-MRI can be used clinically to monitor intraprocedural liver tumor perfusion reductions during transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS: TACE was performed within an x-ray digital subtraction angiography (DSA)-MRI procedure suite in 16 patients with hepatocellular carcinoma. Quantitative 4D TRIP-MRI with targeted radiofrequency field mapping and dynamic longitudinal relaxation rate mapping was used to monitor changes in tumor perfusion during TACE. First-pass perfusion analysis was performed to produce intraprocedural blood flow (Frho) maps. Mean liver tumor perfusions before and after TACE were compared with a paired t-test (alpha = 0.05). RESULTS: Perfusion reductions were successfully measured with quantitative 4D TRIP-MRI in 22 separate tumors during 18 treatment sessions. Mean tumor perfusion Frho decreased from 16.3 (95% confidence interval [CI]: 10.7-21.9) before TACE to 5.0 (95% CI: 3.5-6.5) (mL/min/100 mL) after TACE. Tumor perfusion reductions were statistically significant (P < 0.0005), with a mean absolute perfusion change of 11.4 (95% CI: 5.6-17.1) (mL/min/100 mL) and a mean percentage reduction of 61.0% (95% CI: 48.3%-73.6%). CONCLUSION: Quantitative 4D TRIP-MRI can be successfully performed within clinical interventional settings to monitor intraprocedural changes in liver tumor perfusion during TACE.

Intraprocedural transcatheter intra-arterial perfusion MRI as a predictor of tumor response to chemoembolization for hepatocellular carcinoma.

RATIONALE AND OBJECTIVES: To prospectively test the hypothesis that transcatheter intraarterial perfusion magnetic resonance imaging (TRIP-MRI) measured semiquantitative perfusion reductions during transcatheter arterial chemoembolization of hepatocellular carcinoma (HCC) are associated with tumor response. MATERIALS AND METHODS: Twenty-eight patients (mean age 63 years; range 47-87 years) with 29 tumors underwent chemoembolization in a combined magnetic resonance interventional radiology suite. Intraprocedural tumor perfusion reductions during chemoembolization were monitored using TRIP-MRI. Pre- and postchemoembolization semiquantitative area under the time-signal enhancement curve (AUC) tumor perfusion was measured. Mean tumor perfusion pre- and postchemoembolization were compared using a paired t-test. Imaging follow-up was performed 1-3 months after chemoembolization. We studied the relationship between short-term tumor imaging response and intraprocedural perfusion reductions using univariate and multivariate analysis. RESULTS: Intraprocedural AUC perfusion value decreased significantly after chemoembolization (342.1 vs. 158.6 arbitrary unit, P < .001). Twenty-six patients with 27 HCCs (n = 27) had follow-up imaging at mean 39 days postchemoembolization. Favorable response was present in 67% of these treated tumors according to necrosis criteria. Fifteen of 16 (94%) tumors with 25%-75% perfusion reductions showed necrosis treatment response compared to only 3 of 11 (27%) tumors with perfusion reductions outside the above range (P = .001). Multivariate logistic regression indicated that intraprocedural tumor perfusion reduction and Child-Pugh class were independent factors associated significantly with tumor response (P = .012 and .047, respectively). CONCLUSION: TRIP-MRI can successfully measure semiquantitative changes in HCC perfusion during chemoembolization. Intraprocedural tumor perfusion reductions are associated with future tumor response.