E. Dalah

Variability of Target and Normal Structure Delineation Using Multimodality Imaging for Radiation Therapy of Pancreatic Cancer

PURPOSE To explore the potential of multimodality imaging (dynamic contrast-enhanced magnetic resonance imaging [DCE-MRI], apparent diffusion-coefficient diffusion-weighted imaging [ADC-DWI], fluorodeoxyglucose positron emission tomography [FDG-PET], and computed tomography) to define the gross tumor volume (GTV) and organs at risk in radiation therapy planning for pancreatic cancer. Delineated volumetric changes of DCE-MRI, ADC-DWI, and FDG-PET were assessed in comparison with the finding on 3-dimensional/4-dimensional CT with and without intravenous contrast, and with pathology specimens for resectable and borderline resectable cases of pancreatic cancer. METHODS AND MATERIALS We studied a total of 19 representative patients, whose DCE-MRI, ADC-DWI, and FDG-PET data were reviewed. Gross tumor volume and tumor burden/active region inside pancreatic head/neck or body were delineated on MRI (denoted GTVDCE, and GTVADC), a standardized uptake value (SUV) of 2.5, 40%SUVmax, and 50%SUVmax on FDG-PET (GTV2.5, GTV40%, and GTV50%). Volumes of the pancreas, duodenum, stomach, liver, and kidneys were contoured according to CT (VCT), T1-weighted MRI (VT1), and T2-weighted MRI (VT2) for 7 patients. RESULTS Significant statistical differences were found between the GTVs from DCE-MRI, ADC-DW, and FDG-PET, with a mean and range of 4.73 (1.00-9.79), 14.52 (3.21-25.49), 22.04 (1.00-45.69), 19.10 (4.84-45.59), and 9.80 (0.32-35.21) cm(3) for GTVDCE, GTVADC, GTV2.5, GTV40%, and GTV50%, respectively. The mean difference and range in the measurements of maximum dimension of tumor on DCE-MRI, ADC-DW, SUV2.5, 40%SUVmax, and 50%SUVmax compared with pathologic specimens were -0.84 (-2.24 to 0.9), 0.41 (-0.15 to 2.3), 0.58 (-1.41 to 3.69), 0.66 (-0.67 to 1.32), and 0.15 (-1.53 to 2.38) cm, respectively. The T1- and T2-based volumes for pancreas, duodenum, stomach, and liver were generally smaller compared with those from CT, except for the kidneys. CONCLUSIONS Differences exists between DCE-, ADC-, and FDG-PET-defined target volumes for RT of pancreatic cancer. Organ at risk volumes based on MRI are generally smaller than those based on CT. Further studies combined with pathologic specimens are required to identify the optimal imaging modality or sequence to define GTV.

Recommendations for MRI-based contouring of gross tumor volume and organs at risk for radiation therapy of pancreatic cancer

PURPOSE Local recurrence is a common and morbid event in patients with unresectable pancreatic adenocarcinoma. A more conformal and targeted radiation dose to the macroscopic tumor in nonmetastatic pancreatic cancer is likely to reduce acute toxicity and improve local control. Optimal soft tissue contrast is required to facilitate delineation of a target and creation of a planning target volume with margin reduction and motion management. Magnetic resonance imaging (MRI) offers considerable advantages in optimizing soft tissue delineation and is an ideal modality for imaging and delineating a gross tumor volume (GTV) within the pancreas, particularly as it relates to conformal radiation planning. Currently, no guidelines have been defined for the delineation of pancreatic tumors for radiation therapy treatment planning. Moreover, abdominal MRI sequences are complex and the anatomy relevant to the radiation oncologist can be challenging. The purpose of this study is to provide recommendations for delineation of GTV and organs at risk (OARs) using MRI and incorporating multiple MRI sequences. METHODS AND MATERIALS Five patients with pancreatic cancer and 1 healthy subject were imaged with MRI scans either on 1.5T or on 3T magnets in 2 separate institutes. The GTV and OARs were contoured for all patients in a consensus meeting. RESULTS An overview of MRI-based anatomy of the GTV and OARs is provided. Practical contouring instructions for the GTV and the OARs with the aid of MRI were developed and included in these recommendations. In addition, practical suggestions for implementation of MRI in pancreatic radiation treatment planning are provided. CONCLUSIONS With this report, we attempt to provide recommendations for MRI-based contouring of pancreatic tumors and OARs. This could lead to better uniformity in defining the GTV and OARs for clinical trials and in radiation therapy treatment planning, with the ultimate goal of improving local control while minimizing morbidity.

PET-based Treatment Response Assessment for Neoadjuvant Chemoradiation in Pancreatic Adenocarcinoma: An Exploratory Study

PURPOSE: Performance of anatomical metrics of Response Evaluation Criteria in Solid Tumors (RECIST1.1) versus Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST1.0) for neoadjuvant chemoradiation (nCR) of pancreatic adenocarcinoma was evaluated based on the pathological treatment response (PTR) data. METHODS AND MATERIALS: The pre- and post-nCR CT and PET data for 14 patients with resectable or borderline resectable pancreatic head adenocarcinoma treated with nCR followed by surgery were retrospectively analyzed. These data were compared with the PTR which were graded according to tumor cell destruction (cellularity), with Grade 0, 1, 2 or 3 (G0, G1, G2 or G3) for complete, moderate, minimal and poor responses, respectively. Maximum standardized uptake value (SUVmax) was defined using body-weight (SUVbw). PERCIST1.0 was defined using lean-body mass normalized SUV (SUVlb or SUL). RECIST1.1 was defined by contouring the whole pancreas head on the CT image. Pre- and post-SUL-peak and SUVmax, RECIST1.1 and PETRECIST1.0 were correlated with PTR using Pearson’s correlation coefficient test. RESULTS: The average mean and SD in SUL-peak for all patients analyzed were lower in post-nCR (3.63±1.06) compared to those at pre-nCR (4.29±0.89). Using PERCIST1.0, 62% of patients showed stable metabolic disease (SMD), 23% partial metabolic response (PMR), and 15% progressive metabolic disease (PMD). Using RECIST1.1, 85% of patients showed stable disease (SD), 8% partial response (PR), and 7% progressive diseases (PD). A poor insignificant correlation was established between PRT and PERECIST1.0 (r=0.121), whereas no correlation was seen with RECIST1.1. CONCLUSIONS: PERCIST1.0 appears to increase the chance of detecting patients with progressive disease compared to the conventional anatomical-based assessment of RECIST1.1. The integration of these additional radiographic metrics in assessing treatment response to nCR for pancreatic adenocarcinoma may provide a promising strategy to better select patients that are most suitable for therapeutic intensification.

TU‐G‐BRA‐06: PET‐Based Treatment Response Assessement for Neoadjuvent Chemoradiation for Pancreatic Adenocarcinoma

Purpose: To address the limitations of the conventional response evaluation criteria in solid tumors (RECIST), and validate PET response criteria in solid tumors (PERCIST1.0). We analyze the relationship between the pathological treatment response (PTR) and PERCIST1.0 for patients treated with neoadjuvent chemoradiation (nCR) for pancreatic adenocarcinoma. Methods: The pre- and post-nCR CT and PET data for a total of 8 patients with resectable, or borderline resectable pancreatic head adenocarcinoma treated with nCR were retrospectively analyzed. These data were compared with the PTR which were graded according to tumor cell destruction (cellularity), with Grade1, 2 or 3 (G1, G2 or G3) for good, moderate, and poor responses, respectively. RECIST-based PET (RECISTPET), and PERCIST1.0 were defined using lean body mass normalized SUV (nSUVlb). RECIST-based CT (RECISTCT) was defined by contouring the whole pancreas head (CTPH). Pre- and post-nSUVlb and SUVbw, PERCIST 1.0, were correlated with PTR using Pearson’s correlation coefficient test. Results: The average mean and SD in nSUVlb for all 8 patients analyzed were lower in post-nCR (1.35±0.34) compared to those at pre-nCR (1.38±0.20). Using PERCIST1.0, 5/8 patients showed stable metabolic disease (SMD), 2/8 partial metabolic response (PMR), and 1/8 progressive metabolic disease (PMD). Using RECISTPET 4/8 showed stable disease (STD), 4/8 partial response (PR), whereas 8/8 showed stable disease (STD) using RECISTCT. PTR were correlated with PERCIST1.0 (R=0.3780/P=0.6071). Pathological tumor size was correlated with RECISTCT (R=0.0727/P=0.8679), and RECISTPET, R=−0.3333/P=0.3798. Conclusion: Chemoradiation treatment response assessment based on metabolic tumor activities using PRECIST1.0 and RECISTPET appears to provide better agreement with pathological assessment as compared to the conventional CT-based assessment using RECISTCT. The integration of these additional radiographic metrics in assessing treatment response to nCR for pancreatic adenocarcinoma may provide a promising strategy to better select those patients most suitable for therapeutic intensification.

SU-E-J-228: MRI-Based Planning: Dosimetric Feasibility of Dose Painting for ADCDefined Intra-Prostatic Tumor

Purpose: Apparent diffusion coefficient (ADC) map may help to delineate the gross tumor volume (GTV) in prostate gland. Dose painting with external beam radiotherapy for GTV might increase the local tumor control. The purpose of this study is to explore the maximum boosting dose on GTV using VMAT without sacrificing sparing of organs at risk (OARs) in MRI based planning. Methods: VMAT plans for 5 prostate patients were generated following the commonly used dose volume (DV) criteria based on structures contoured on T2 weighted MRI with bulk electron density assignment using electron densities derived from ICRU46. GTV for each patient was manually delineated based on ADC maps and fused to T2-weighted image set for planning study. A research planning system with Monte Carlo dose engine (Monaco, Elekta) was used to generate the VMAT plans with boosting dose on GTV gradually increased from 85Gy to 100Gy. DV parameters, including V(boosting-dose) (volume covered by boosting dose) for GTV, V75.6Gy for PTV, V45Gy, V70Gy, V72Gy and D1cc (Maximum dose to 1cc volume) for rectum and bladder, were used to measure plan quality. Results: All cases achieve at least 99.0% coverage of V(boosting-dose) on GTV and 95% coverage of V75.6Gy to the PTV. All the DV criteria, V45Gy≤50% and V70Gy≤15% for bladder and rectum, D1cc ≤77Gy (Rectum) and ≤80Gy (Bladder), V72Gy≤5% (rectum and bladder) were maintained when boosting GTV to 95Gy for all cases studied. Except for two patients, all the criteria were also met when the boosting dose goes to 100Gy. Conclusion: It is dosimetrically feasible safe to boost the dose to at least 95Gy to ADC defined GTV in prostate cancer using MRI guided VMAT delivery. Conclusion: It is dosimetrically feasible safe to boost the dose to at least 95Gy to ADC defined GTV in prostate cancer using MRI guided VMAT delivery. This research is partially supported by Elekta Inc.

SU‐E‐J‐268: Change of CT Number During the Course of Chemoradiation Therapy for Pancreatic Cancer

Purpose: It has been observed radiation can induce changes in CT number (CTN) inside tumor during the course of radiation therapy (RT) for several tumor sites including lung and head and neck, suggesting that the CTN change may be potentially used to assess RT response. In this study, we investigate the CTN changes inside tumor during the course of chemoradiation therapy (CRT) for pancreatic cancer. Methods: Daily diagnostic-quality CT data acquired during IGRT for 17 pancreatic head cancer patients using an in-room CT (CTVision, Siemens) were analyzed. All patients were treated with a radiation dose of 50.4 in 1.8 Gy per fraction. On each daily CT set, The contour of the pancreatic head, included in the treatment target, was generated by populating the pancreatic head contour from the planning CT or MRI using an auto-segmentation tool based on deformable registration (ABAS, Elekta) with manual editing if necessary. The CTN at each voxel in the pancreatic head contour was extracted and the 3D distribution of the CTNs was processed using MATLAB. The mean value of CTN distribution was used to quantify the daily CTN change in the pancreatic head. Results: Reduction of CTN in pancreatic head was observed during the CRT delivery in 14 out the 17 (82%) patients studied. Although the average reduction is only 3.5 Houncefield Unit (HU), this change is significant (p<0.01). Among them, there are 7 patients who had a CTN drop larger than 5 HU, ranging from 6.0 to 11.8 HU. In contrast to this trend, CTN was increased in 3 patients. Conclusion: Measurable changes in the CT number in tumor target were observed during the course of chemoradiation therapy for the pancreas cancer patients, indicating this radiation-induced CTN change may be used to assess treatment response.

SU-E-J-136: Multimodality-Image-Based Target Delineation for Dose Painting of Pancreatic Cancer

PURPOSE Dose escalated RT may provide improved disease local-control for selected unresectable pancreatic cancer. Accurate delineation of the gross tumor volume (GTV) inside pancreatic head or body would allow safe dose escalation considering the tolerances of adjacent organs at risk (OAR). Here we explore the potential of multi-modality imaging (DCE-MRI, ADC-MRI, and FDG-PET) to define the GTV for dose painting of pancreatic cancer. Volumetric variations of DCE-MRI, ADC-MRI and FDG-PET defined GTVs were assessed in comparison to the findings on CT, and to pathology specimens for resectable and borderline reseactable cases of pancreatic cancer. METHODS A total of 19 representative patients with DCE-MRI, ADC-MRI and FDG-PET data were analyzed. Of these, 8 patients had pathological specimens. GTV, inside pancreatic head/neck, or body, were delineated on MRI (denoted GTVDCE, and GTVADC), on FDG-PET using SUV of 2.5, 40% SUVmax, and 50% SUVmax (denoted GTV2.5, GTV40%, and GTV50%). A Kruskal-Wallis test was used to determine whether significant differences existed between GTV volumes. RESULTS Significant statistical differences were found between the GTVs defined by DCE-MRI, ADC-MRI, and FDG-PET, with a mean and range of 4.73 (1.00-9.79), 14.52 (3.21-25.49), 22.04 (1.00-45.69), 19.10 (4.84-45.59), and 9.80 (0.32-35.21) cm3 (p<0.0001) for GTVDCE, GTVADC, GTV2.5, GTV40%, and GTV50%, respectively. The mean difference and range in the measurements of maximum dimension of GTVs based on DCE-MRI, ADC-MRI, SUV2.5, 40% SUVmax, and 50% SUVmax compared with pathologic specimens were -0.84 (-2.24 to 0.9), 0.41 (-0.15 to 2.3), 0.58 (-1.41 to 3.69), 0.66 (-0.67 to 1.32), and 0.15 (-1.53 to 2.38) cm, respectively. CONCLUSION Differences exists between DCE, ADC, and PET defined target volumes for RT of pancreatic cancer. Further studies combined with pathological specimens are required to identify the optimal imaging modality and/or acquisition method to define the GTV.

SU‐E‐J‐112: Improving Target Delineation by Using Deformably Registered Multi‐Modality Images for Radiation Therapy of Pancreatic Cancer

Purpose: Combined multi‐modality images can provide unsurpassed target recognition, yet the large variation of contour volumes from different modalities prevents accurate contour transfer onto CT images for radiation therapy (RT) planning. This work demonstrates improved agreement between target contours from multi‐modality images after deformable multi‐modality image registration for pancreatic cancer RT. Methods: PET, and various MRI including T1, T2, DWI and DCE, were rigidly registered with CT for representative patients with pancreatic cancer. Gross tumor volume (GTV) and organs at risk (OARs) were delineated on multi‐modality images and were exported into a presently‐developed deformable multi‐modality image registration tool. The derived deformation fields were applied to deform the corresponding modality contours, which were later overlapped onto the planning CT. Results: Substantial variations among contours from multi‐modality images were observed for both GTV and OARs. When using T1 weighted contour volume as nominator, the delineated volumes vary from 0.5 to 1.8 for GTV, from 0.81 to 1.05 for OARs between the image modalities. The overlapping ratio between different modalities varies from 0.22 to 0.74 for GTV, and from 0.65 to 0.84 for OARs. After deformable image registration, the contour volumes are changed by deformation fields by 6% to 11%. These changes do not impact volume variation between different modalities, but improve significantly the overlapping ratio between contours from different modalities, for example, changing from 0.55 to 0.82 for GTV. Conclusion: The deformable image registration of multi‐modality images increases the agreement between contours from different image modalities, improving accuracy for target and normal structure delineation for radiation treatment planning of pancreatic cancer.

SU‐D‐500‐03: A Correction of Partial Volume Effect for Using PET to Define Metabolically Active Tumor Volume for Pancreatic Cancer

PURPOSE Accurate delineation of tumor volume based on PET is affected by partial volume effect (PVE) that has been shown to Result in underestimations of the standardized uptake value (SUV), leading to decreased metabolically-active tumor volume (MATV). Here we assess the impact of a PVE correction on the SUV and the PET defined MATV in patients with pancreatic cancer. METHODS A voxel-by-voxel PVE correction method utilizing a recovery coefficient (RC) approach is implemented for correction in the region of interest (ROI). A profile-analysis study was used to define the ideal-cutoff-values (IDCVs) to threshold PET. The RC and the IDCVs were calculated using NEMA phantom. The pancreas tumor volumes were delineated on the T1 with contrast and diffusion-weighted MRI (DWI), and on the PET using four different cutoff values: 2.5-SUV, tumor-to-background (T/B) ratio, 42% of SUVmax, and IDCVs. The PVE-corrected PET and MATV were compared with the original PET, and the resulted tumor sizes were compared with those from contrast-enhanced CT and MRI. RESULTS For all patients studied, the mean RC was 0.72 (ranging 0.58 - 0.81) based on tumor diameter on the CT (ranging 1.9 - 5.8) cm, and tumor-to-background ratio (ranging 2.4 - 8.7). The mean SUVmax values in the ROI were 8.2 (ranging 3.9 - 13.1) and 10.6 (ranging 5.57 - 16.37) g/ml, respectively, before and after PVE correction. Generally, all of the 2.5-SUV, T/B ratio, and 42% SUVmax showed an increase of up to 34% in the MATV after PVE correction except for the IDCVs MATV was reduced by 21%. The differences between tumor sizes from CT, T1, and DWI and those from PET with PVE-correction were reduced compared to those without correction. CONCLUSION The partial volume effect correction considerably impacts PET SUV and improves the PET-defined metabolic - ally-active tumor volume, particularly for small pancreatic tumors.