PIONEER-Panc: a platform trial for phase II randomized investigations of new and emerging therapies for localized pancreatic cancer.

BACKGROUND: Personalized and effective treatments for pancreatic ductal adenocarcinoma (PDAC) continue to remain elusive. Novel clinical trial designs that enable continual and rapid evaluation of novel therapeutics are needed. Here, we describe a platform clinical trial to address this unmet need. METHODS: This is a phase II study using a Bayesian platform design to evaluate multiple experimental arms against a control arm in patients with PDAC. We first separate patients into three clinical stage groups of localized PDAC (resectable, borderline resectable, and locally advanced disease), and further divide each stage group based on treatment history (treatment naïve or previously treated). The clinical stage and treatment history therefore define 6 different cohorts, and each cohort has one control arm but may have one or more experimental arms running simultaneously. Within each cohort, adaptive randomization rules are applied and patients will be randomized to either an experimental arm or the control arm accordingly. The experimental arm(s) of each cohort are only compared to the applicable cohort specific control arm. Experimental arms may be added independently to one or more cohorts during the study. Multiple correlative studies for tissue, blood, and imaging are also incorporated. DISCUSSION: To date, PDAC has been treated as a single disease, despite knowledge that there is substantial heterogeneity in disease presentation and biology. It is recognized that the current approach of single arm phase II trials and traditional phase III randomized studies are not well-suited for more personalized treatment strategies in PDAC. The PIONEER Panc platform clinical trial is designed to overcome these challenges and help advance our treatment strategies for this deadly disease. TRIAL REGISTRATION: This study is approved by the Institutional Review Board (IRB) of MD Anderson Cancer Center, IRB-approved protocol 2020-0075. The PIONEER trial is registered at the US National Institutes of Health (ClinicalTrials.gov) NCT04481204 .

Clinicopathological correlation of radiologic measurement of post-therapy tumor size and tumor volume for pancreatic ductal adenocarcinoma.

OBJECTIVES: Tumor size measurement is critical for accurate tumor staging in patients with pancreatic ductal adenocarcinoma (PDAC). However, accurate tumor size measurement is challenging in patients who received neoadjuvant therapy before resection, due to treatment-induced fibrosis and tumor invasion beyond the grossly identified tumor area. In this study, we evaluated the correlation between the tumor size and tumor volume measured on post-therapy computed tomography (CT) scans and the pathological measurement. Also, we investigated the correlation between these measurements and clinicopathological parameters and survival. MATERIALS AND METHODS: Retrospectively, we evaluated 343 patients with PDAC who received neoadjuvant therapy, followed by pancreaticoduodenectomy and had pre-operative pancreatic protocol CT imaging. We measured the longest tumor diameter (RadL) and the radiological tumor volume (RadV) on the post-therapy CT scan, then we categorized RadL into four radiologic tumor stages (RTS) based on the current AJCC staging (8th edition) protocol and RadV based on the median. Pearson correlation or Spearman's coefficient (δ), T-test and ANOVA was used to test the correlation between the radiological and pathological measurement. Chi-square analysis was used to test the correlation with the tumor pathological response, lymph-node metastasis and margin status and Kaplan-Meier and Cox-proportional hazard for survival analysis. P-value < 0.05 was considered significant. RESULTS: As a continuous variable, RadL showed a positive linear correlation with the post-therapy pathologic tumor size in the overall patient population (Pearson correlation coefficient: 0.72, P < 0.001) and RadV (δ: 0.63, p < 0.0001). However, there was no correlation between RadL and pathologic tumor size in patients with ypT0 and those with pathologic tumor size of ≤1.0 cm. Post-therapy RTS and RadV group correlated with ypT stage, tumor response grades using either CAP or MDA grading system, distance of superior mesenteric artery margin and tumor recurrence/metastasis. CONCLUSION: Although RadL tends to understage ypT in PDAC patients who had no radiologically detectable tumor or small tumors (RTS0 or RTS1), radiologic measurement of post-therapy tumor size may be used as a marker for the pathologic tumor staging and tumor response to neoadjuvant therapy.

Image Quality Assessment of Abdominal CT by Use of New Deep Learning Image Reconstruction: Initial Experience.

OBJECTIVE. The purpose of this study was to perform quantitative and qualitative evaluation of a deep learning image reconstruction (DLIR) algorithm in contrast-enhanced oncologic CT of the abdomen. MATERIALS AND METHODS. Retrospective review (April-May 2019) of the cases of adults undergoing oncologic staging with portal venous phase abdominal CT was conducted for evaluation of standard 30% adaptive statistical iterative reconstruction V (30% ASIR-V) reconstruction compared with DLIR at low, medium, and high strengths. Attenuation and noise measurements were performed. Two radiologists, blinded to examination details, scored six categories while comparing reconstructions for overall image quality, lesion diagnostic confidence, artifacts, image noise and texture, lesion conspicuity, and resolution. RESULTS. DLIR had a better contrast-to-noise ratio than 30% ASIR-V did; high-strength DLIR performed the best. High-strength DLIR was associated with 47% reduction in noise, resulting in a 92-94% increase in contrast-to-noise ratio compared with that of 30% ASIR-V. For overall image quality and image noise and texture, DLIR scored significantly higher than 30% ASIR-V with significantly higher scores as DLIR strength increased. A total of 193 lesions were identified. The lesion diagnostic confidence, conspicuity, and artifact scores were significantly higher for all DLIR levels than for 30% ASIR-V. There was no significant difference in perceived resolution between the reconstruction methods. CONCLUSION. Compared with 30% ASIR-V, DLIR improved CT evaluation of the abdomen in the portal venous phase. DLIR strength should be chosen to balance the degree of desired denoising for a clinical task relative to mild blurring, which increases with progressively higher DLIR strengths.

Dual-Energy CT: Lower Limits of Iodine Detection and Quantification.

Background Assessments of the quantitative limitations among the six commercially available dual-energy (DE) CT acquisition schemes used by major CT manufacturers could aid researchers looking to use iodine quantification as an imaging biomarker. Purpose To determine the limits of detection and quantification of DE CT in phantoms by comparing rapid peak kilovoltage switching, dual-source, split-filter, and dual-layer detector systems in six different scanners. Materials and Methods Seven 50-mL iohexol solutions were used, with concentrations of 0.03-2.0 mg iodine per milliliter. The solutions and water sample were scanned five times each in two phantoms (small, 20-cm diameter; large, 30 × 40-cm diameter) with six DE CT systems and a total of 10 peak kilovoltage settings or combinations. Iodine maps were created, and the mean iodine signal in each sample was recorded. The limit of blank (LOB) was defined as the upper limit of the 95% confidence interval of the water sample. The limit of detection (LOD) was defined as the concentration with a 95% chance of having a signal above the LOB. The limit of quantification (LOQ) was defined as the lowest concentration where the coefficient of variation was less than 20%. Results The LOD range was 0.021-0.26 mg/mL in the small phantom and 0.026-0.55 mg/mL in the large phantom. The LOQ range was 0.07-0.50 mg/mL in the small phantom and 0.20-1.0 mg/mL in the large phantom. The dual-source and rapid peak kilovoltage switching systems had the lowest LODs, and the dual-layer detector systems had the highest LODs. Conclusion The iodine limit of detection using dual-energy CT systems varied with scanner and phantom size, but all systems depicted iodine in the small and large phantoms at or below 0.3 and 0.5 mg/mL, respectively, and enabled quantification at concentrations of 0.5 and 1.0 mg/mL, respectively. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Hindman in this issue.

Imaging-based biomarkers: Changes in the tumor interface of pancreatic ductal adenocarcinoma on computed tomography scans indicate response to cytotoxic therapy.

BACKGROUND: The assessment of pancreatic ductal adenocarcinoma (PDAC) response to therapy remains challenging. The objective of this study was to investigate whether changes in the tumor/parenchyma interface are associated with response. METHODS: Computed tomography (CT) scans before and after therapy were reviewed in 4 cohorts: cohort 1 (99 patients with stage I/II PDAC who received neoadjuvant chemoradiation and surgery); cohort 2 (86 patients with stage IV PDAC who received chemotherapy), cohort 3 (94 patients with stage I/II PDAC who received protocol-based neoadjuvant gemcitabine chemoradiation), and cohort 4 (47 patients with stage I/II PDAC who received neoadjuvant chemoradiation and were prospectively followed in a registry). The tumor/parenchyma interface was visually classified as either a type I response (the interface remained or became well defined) or a type II response (the interface became poorly defined) after therapy. Consensus (cohorts 1-3) and individual (cohort 4) visual scoring was performed. Changes in enhancement at the interface were quantified using a proprietary platform. RESULTS: In cohort 1, type I responders had a greater probability of achieving a complete or near-complete pathologic response (21% vs 0%; P = .01). For cohorts 1, 2, and 3, type I responders had significantly longer disease-free and overall survival, independent of traditional covariates of outcomes and of baseline and normalized cancer antigen 19-9 levels. In cohort 4, 2 senior radiologists achieved a κ value of 0.8, and the interface score was associated with overall survival. The quantitative method revealed high specificity and sensitivity in classifying patients as type I or type II responders (with an area under the receiver operating curve of 0.92 in cohort 1, 0.96 in cohort 2, and 0.89 in cohort 3). CONCLUSIONS: Changes at the PDAC/parenchyma interface may serve as an early predictor of response to therapy. Cancer 2018;124:1701-9. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Intermanufacturer Comparison of Dual-Energy CT Iodine Quantification and Monochromatic Attenuation: A Phantom Study.

Purpose To determine the accuracy of dual-energy computed tomographic (CT) quantitation in a phantom system comparing fast kilovolt peak-switching, dual-source, split-filter, sequential-scanning, and dual-layer detector systems. Materials and Methods A large elliptical phantom containing iodine (2, 5, and 15 mg/mL), simulated contrast material-enhanced blood, and soft-tissue inserts with known elemental compositions was scanned three to five times with seven dual-energy CT systems and a total of 10 kilovolt peak settings. Monochromatic images (50, 70, and 140 keV) and iodine concentration images were created. Mean iodine concentration and monochromatic attenuation for each insert and reconstruction energy level were recorded. Measurement bias was assessed by using the sum of the mean signed errors measured across relevant inserts for each monochromatic energy level and iodine concentration. Iodine and monochromatic errors were assessed by using the root sum of the squared error of all measurements. Results At least one acquisition paradigm per scanner had iodine biases (range, -2.6 to 1.5 mg/mL) with significant differences from zero. There were no significant differences in iodine error (range, 0.44-1.70 mg/mL) among the top five acquisition paradigms (one fast kilovolt peak switching, three dual source, and one sequential scanning). Monochromatic bias was smallest for 70 keV (-12.7 to 15.8 HU) and largest for 50 keV (-80.6 to 35.2 HU). There were no significant differences in monochromatic error (range, 11.4-52.0 HU) among the top three acquisition paradigms (one dual source and two fast kilovolt peak switching). The lowest accuracy for both measures was with a split-filter system. Conclusion Iodine and monochromatic accuracy varies among systems, but dual-source and fast kilovolt-switching generally provided the most accurate results in a large phantom. © RSNA, 2017 Online supplemental material is available for this article.

Computed Tomography Image Quality Evaluation of a New Iterative Reconstruction Algorithm in the Abdomen (Adaptive Statistical Iterative Reconstruction-V) a Comparison With Model-Based Iterative Reconstruction, Adaptive Statistical Iterative Reconstruction, and Filtered Back Projection Reconstructions.

OBJECTIVE: The purpose of this study was to compare abdominopelvic computed tomography images reconstructed with adaptive statistical iterative reconstruction-V (ASIR-V) with model-based iterative reconstruction (Veo 3.0), ASIR, and filtered back projection (FBP). METHODS AND MATERIALS: Abdominopelvic computed tomography scans for 36 patients (26 males and 10 females) were reconstructed using FBP, ASIR (80%), Veo 3.0, and ASIR-V (30%, 60%, 90%). Mean ± SD patient age was 32 ± 10 years with mean ± SD body mass index of 26.9 ± 4.4 kg/m. Images were reviewed by 2 independent readers in a blinded, randomized fashion. Hounsfield unit, noise, and contrast-to-noise ratio (CNR) values were calculated for each reconstruction algorithm for further comparison. Phantom evaluation of low-contrast detectability (LCD) and high-contrast resolution was performed. RESULTS: Adaptive statistical iterative reconstruction-V 30%, ASIR-V 60%, and ASIR 80% were generally superior qualitatively compared with ASIR-V 90%, Veo 3.0, and FBP (P < 0.05). Adaptive statistical iterative reconstruction-V 90% showed superior LCD and had the highest CNR in the liver, aorta, and, pancreas, measuring 7.32 ± 3.22, 11.60 ± 4.25, and 4.60 ± 2.31, respectively, compared with the next best series of ASIR-V 60% with respective CNR values of 5.54 ± 2.39, 8.78 ± 3.15, and 3.49 ± 1.77 (P <0.0001). Veo 3.0 and ASIR 80% had the best and worst spatial resolution, respectively. CONCLUSIONS: Adaptive statistical iterative reconstruction-V 30% and ASIR-V 60% provided the best combination of qualitative and quantitative performance. Adaptive statistical iterative reconstruction 80% was equivalent qualitatively, but demonstrated inferior spatial resolution and LCD.

Potential Application of Dual-Energy CT in Gynecologic Cancer: Initial Experience.

OBJECTIVE: The purpose of this article is to review the use of dual-energy CT (DECT) in the assessment of gynecologic cancer. CONCLUSION: DECT has the potential to improve diagnostic performance, may improve the ability to differentiate between simple cystic lesions and primary ovarian cancer, and may also improve the detection of musculoskeletal and liver metastases. Additional studies will be needed to determine the direction of future developments and the degree to which DECT will affect the imaging and management of gynecologic cancer.

Evaluation of Abdominal Computed Tomography Image Quality Using a New Version of Vendor-Specific Model-Based Iterative Reconstruction.

PURPOSE: To qualitatively and quantitatively compare abdominal computed tomography (CT) images reconstructed with a new version of model-based iterative reconstruction (Veo 3.0; GE Healthcare) to those created with Veo 2.0. MATERIALS AND METHODS: This retrospective study was approved by our institutional review board and was Health Insurance Portability and Accountability Act compliant. The raw data from 29 consecutive patients who had undergone CT abdomen scanning was used to reconstruct 4 sets of 3.75-mm axial images: Veo 2.0, Veo 3.0 standard, Veo 3.0 5% resolution preference (RP), and Veo 3.0 20% RP. A slice thickness optimization of 3.75 mm and texture feature was selected for Veo 3.0 reconstructions.The images were reviewed by 3 independent readers in a blinded, randomized fashion using a 5-point Likert scale and 5-point comparative scale.Multiple 2-dimensional circular regions of interest were defined for noise and contrast-to-noise ratio measurements. Line profiles were drawn across the 7 lp/cm bar pattern of the CatPhan 600 phantom for spatial resolution evaluation. RESULTS: The Veo 3.0 standard image set was scored better than Veo 2.0 in terms of artifacts (mean difference, 0.43; 95% confidence interval [95% CI], 0.25-0.6; P < 0.0001), overall image quality (mean difference, 0.87; 95% CI, 0.62-1.13; P < 0.0001) and qualitative resolution (mean difference, 0.9; 95% CI, 0.69-1.1; P < 0.0001). Although the Veo 3.0 standard and RP05 presets were preferred across most categories, the Veo 3.0 RP20 series ranked best for bone detail. Image noise and spatial resolution increased along a spectrum with Veo 2.0 the lowest and RP20 the highest. CONCLUSION: Veo 3.0 enhances imaging evaluation relative to Veo 2.0; readers preferred Veo 3.0 image appearance despite the associated mild increases in image noise. These results provide suggested parameters to be used clinically and as a basis for future evaluations, such as focal lesion detection, in the oncology setting.

Evaluation of Magnetic Resonance (MR) Biomarkers for Assessment of Response With Response Evaluation Criteria in Solid Tumors: Comparison of the Measurements of Neuroendocrine Tumor Liver Metastases (NETLM) With Various MR Sequences and at Multiple Phases of Contrast Administration.

PURPOSE: Our aim was to compare the interobserver and intraobserver variability for the measurement of the size of liver metastases in patients with carcinoid tumors with various magnetic resonance (MR) series. MATERIALS AND METHODS: In this retrospective institutional review board-approved study, 30 patients with liver metastases from a carcinoid primary had a complete MR examination of the abdomen at 1.5 T with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA). The complete MR examination included T1 (in-phase [IP]/out-of-phase [OOP], T2, diffusion-weighted imaging, pre-Gd-EOB-DTPA and post-Gd-EOB-DTPA 3D gradient echo (4 phases plus 20-minute hepatobiliary phase [HBP] Gd]). Four readers reviewed each series independently. The measurement for each lesion was compared to HBP-Gd images. The sensitivity for detection of each lesion was compared to HBP-Gd. Variance component analysis was used to estimate variance due to patient, lesion within patient, and reader by sequence. Linear mixed model was used to compare lesion size between sequences. RESULTS: The HBP-Gd had the smallest interreader variability. There was no significant difference between series with respect to interreader variability. Lesion sizes measured in diffusion-weighted imaging was significantly higher. T2-weighted imaging was the closest to HBP-Gd. Lesion sizes measured with the other sequences were significantly smaller. There was significant difference in sensitivity of lesion detection of some series when compared to HBP-Gd. CONCLUSION: The HBP-Gd series had the smallest interreader variability and is the recommended series to measure lesion size for evaluation of response to treatment.

Performance evaluation of iterative reconstruction algorithms for achieving CT radiation dose reduction - a phantom study.

The purpose of this study was to characterize image quality and dose performance with GE CT iterative reconstruction techniques, adaptive statistical iterative recontruction (ASiR), and model-based iterative reconstruction (MBIR), over a range of typical to low-dose intervals using the Catphan 600 and the anthropomorphic Kyoto Kagaku abdomen phantoms. The scope of the project was to quantitatively describe the advantages and limitations of these approaches. The Catphan 600 phantom, supplemented with a fat-equivalent oval ring, was scanned using a GE Discovery HD750 scanner at 120 kVp, 0.8 s rotation time, and pitch factors of 0.516, 0.984, and 1.375. The mA was selected for each pitch factor to achieve CTDIvol values of 24, 18, 12, 6, 3, 2, and 1 mGy. Images were reconstructed at 2.5 mm thickness with filtered back-projection (FBP); 20%, 40%, and 70% ASiR; and MBIR. The potential for dose reduction and low-contrast detectability were evaluated from noise and contrast-to-noise ratio (CNR) measurements in the CTP 404 module of the Catphan. Hounsfield units (HUs) of several materials were evaluated from the cylinder inserts in the CTP 404 module, and the modulation transfer function (MTF) was calculated from the air insert. The results were con-firmed in the anthropomorphic Kyoto Kagaku abdomen phantom at 6, 3, 2, and 1mGy. MBIR reduced noise levels five-fold and increased CNR by a factor of five compared to FBP below 6mGy CTDIvol, resulting in a substantial improvement in image quality. Compared to ASiR and FBP, HU in images reconstructed with MBIR were consistently lower, and this discrepancy was reversed by higher pitch factors in some materials. MBIR improved the conspicuity of the high-contrast spatial resolution bar pattern, and MTF quantification confirmed the superior spatial resolution performance of MBIR versus FBP and ASiR at higher dose levels. While ASiR and FBP were relatively insensitive to changes in dose and pitch, the spatial resolution for MBIR improved with increasing dose and pitch. Unlike FBP, MBIR and ASiR may have the potential for patient imaging at around 1 mGy CTDIvol. The improved low-contrast detectability observed with MBIR, especially at low-dose levels, indicate the potential for considerable dose reduction.

Pancreatic ductal adenocarcinoma radiology reporting template: consensus statement of the society of abdominal radiology and the american pancreatic association.

Pancreatic ductal adenocarcinoma is an aggressive malignancy with a high mortality rate. Proper determination of the extent of disease on imaging studies at the time of staging is one of the most important steps in optimal patient management. Given the variability in expertise and definition of disease extent among different practitioners as well as frequent lack of complete reporting of pertinent imaging findings at radiologic examinations, adoption of a standardized template for radiology reporting, using universally accepted and agreed on terminology for solid pancreatic neoplasms, is needed. A consensus statement describing a standardized reporting template authored by a multi-institutional group of experts in pancreatic ductal adenocarcinoma that included radiologists, gastroenterologists, and hepatopancreatobiliary surgeons was developed under the joint sponsorship of the Society of Abdominal Radiologists and the American Pancreatic Association. Adoption of this standardized imaging reporting template should improve the decision-making process for the management of patients with pancreatic ductal adenocarcinoma by providing a complete, pertinent, and accurate reporting of disease staging to optimize treatment recommendations that can be offered to the patient. Standardization can also help to facilitate research and clinical trial design by using appropriate and consistent staging by means of resectability status, thus allowing for comparison of results among different institutions.

Analysis of free-form radiology dictations for completeness and clarity for pancreatic cancer staging.

PURPOSE: To assess the completeness and clarity of current free-form radiology reports for pancreatic cancer staging by evaluating them against the elements of the RSNA CT oncology primary pancreas mass dictation template. METHODS: This retrospective study was approved by our Institutional Review Board (IRB). 295 free-form computed tomography (CT) reports for baseline staging of pancreatic cancer (PC) generated between August 2008 and December 2010 were evaluated by one of two radiologists with expertise in pancreatic cancer imaging. Reports which indicated that metastatic disease was present were excluded. The completeness and clarity of the reports were analyzed against the elements of the RSNA CT pancreas mass dictation template. Fisher's exact tests were used to analyze differences by year and type of radiologist. RESULTS: Primary lesion location, size, and effect on bile duct (BD) were provided in 93.9% (277/295), 69.8% (206/295), and 67.5% (199/295) of reports, respectively. Standard terms to describe vascular involvement were used in 47.5% (140/295) of reports. In 20.3% (60/295), the resectability status could not be defined based on the report alone. In 36.9% (109/295) of reports, review of CT images was necessary to understand vascular involvement. Radiologists expert in pancreatic oncology had a higher proportion of reports using standardized terminology and reports in which vascular involvement was understood without revisiting the images. CONCLUSIONS: Free-form reports were more likely to use ambiguous terminology and/or require review of the actual images for understanding resectability status. The use of a standardized reporting template may improve the usefulness of pancreatic cancer staging reports.

Multidetector CT detection of peritoneal metastases: evaluation of sensitivity between standard 2.5 mm axial imaging and maximum-intensity-projection (MIP) reconstructions.

OBJECTIVE: Our purpose was to evaluate the sensitivity of multidetector CT for the detection of peritoneal metastases between standard 2.5 mm axial imaging and maximum-intensity-projection (MIP) reconstructions. MATERIALS AND METHODS: The Institutional Review Board approved this retrospective study and waived the need to obtain patient consent. We retrospectively identified 36 patients with pancreatic adenocarcinoma and peritoneal metastatic disease who underwent a pancreatic protocol CT examination of the abdomen and pelvis between January 2012 and January 2014. Three independent radiologists reviewed a randomized combination of standard axial (2.5 mm reconstructed thickness, 2.5 mm interval) and axial MIP reconstructions (6, 3 mm interval) over two sessions. Each reader recorded metastasis location in PACS. Subsequent consensus review by two radiologists determined the final number and size of metastases. RESULTS: The reviewers found 328 peritoneal implants in 36 patients. After accounting for the size, location, and number of lesions as well as multiple readers, a generalized estimating equations model showed that the statistical combination of MIP with standard technique significantly increased the odds of correctly identifying a lesion (OR 2.16; 95% CI 1.86-2.51; p value < 0.0001) compared to standard technique alone. MIP reconstruction as a standalone technique was less sensitive compared to standard technique alone (OR 0.81; 95% CI 0.65-0.99; p value = 0.0468). When compared to standard axial imaging, evaluation via MIP reconstructions resulted in the identification of an additional 50 (15%), 45 (14%), and 55 (17%) lesions by Readers 1-3, respectively. CONCLUSION: The axial 6 mm MIP series is complimentary in the CT evaluation of peritoneal metastases. MIP reconstruction evaluation identified a significant number of additional lesions, but is not adequate as a standalone technique for peritoneal cavity assessment.

Pancreatic ductal adenocarcinoma radiology reporting template: consensus statement of the Society of Abdominal Radiology and the American Pancreatic Association.

Pancreatic ductal adenocarcinoma is an aggressive malignancy with a high mortality rate. Proper determination of the extent of disease on imaging studies at the time of staging is one of the most important steps in optimal patient management. Given the variability in expertise and definition of disease extent among different practitioners as well as frequent lack of complete reporting of pertinent imaging findings at radiologic examinations, adoption of a standardized template for radiology reporting, using universally accepted and agreed on terminology for solid pancreatic neoplasms, is needed. A consensus statement describing a standardized reporting template authored by a multi-institutional group of experts in pancreatic ductal adenocarcinoma that included radiologists, gastroenterologists, and hepatopancreatobiliary surgeons was developed under the joint sponsorship of the Society of Abdominal Radiologists and the American Pancreatic Association. Adoption of this standardized imaging reporting template should improve the decision-making process for the management of patients with pancreatic ductal adenocarcinoma by providing a complete, pertinent, and accurate reporting of disease staging to optimize treatment recommendations that can be offered to the patient. Standardization can also help to facilitate research and clinical trial design by using appropriate and consistent staging by means of resectability status, thus allowing for comparison of results among different institutions.

Intra-tumoral heterogeneity of gemcitabine delivery and mass transport in human pancreatic cancer.

There is substantial heterogeneity in the clinical behavior of pancreatic cancer and in its response to therapy. Some of this variation may be due to differences in delivery of cytotoxic therapies between patients and within individual tumors. Indeed, in 12 patients with resectable pancreatic cancer, we previously demonstrated wide inter-patient variability in the delivery of gemcitabine as well as in the mass transport properties of tumors as measured by computed tomography (CT) scans. However, the variability of drug delivery and transport properties within pancreatic tumors is currently unknown. Here, we analyzed regional measurements of gemcitabine DNA incorporation in the tumors of the same 12 patients to understand the degree of intra-tumoral heterogeneity of drug delivery. We also developed a volumetric segmentation approach to measure mass transport properties from the CT scans of these patients and tested inter-observer agreement with this new methodology. Our results demonstrate significant heterogeneity of gemcitabine delivery within individual pancreatic tumors and across the patient cohort, with gemcitabine DNA incorporation in the inner portion of the tumors ranging from 38 to 74% of the total. Similarly, the CT-derived mass transport properties of the tumors had a high degree of heterogeneity, ranging from minimal difference to almost 200% difference between inner and outer portions of the tumor. Our quantitative method to derive transport properties from CT scans demonstrated less than 5% difference in gemcitabine prediction at the average CT-derived transport value across observers. These data illustrate significant inter-patient and intra-tumoral heterogeneity in the delivery of gemcitabine, and highlight how this variability can be reproducibly accounted for using principles of mass transport. With further validation as a biophysical marker, transport properties of tumors may be useful in patient selection for therapy and prediction of therapeutic outcome.