International Journal of
Radiation Oncology biology
physics
www.redjournal.org
Physics Contribution
Variability of Target and Normal Structure Delineation Using Multimodality Imaging for Radiation Therapy of Pancreatic Cancer Entesar Dalah, PhD,* Ion Moraru, PhD,* Eric Paulson, PhD,*,y Beth Erickson, MD,* and X. Allen Li, PhD* Departments of *Radiation Oncology and yRadiology, Medical College of Wisconsin, Milwaukee, Wisconsin Received Oct 3, 2013, and in revised form Feb 10, 2014. Accepted for publication Feb 24, 2014.
Summary This work explores the potential of using various magnetic resonance imaging, positron emission tomography, and computed tomography techniques to define treatment targets and organs at risk for radiation therapy of pancreatic cancer. Significant differences exist in the gross tumor volumes defined by these imaging modalities and sequences. Further studies are required to establish reliable imaging modalities and/or techniques for the accurate target delineation, which will be crucial particularly in dose escalation and/or dose painting for pancreatic cancer.
Purpose: To explore the potential of multimodality imaging (dynamic contrast eenhanced 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 DCEMRI, 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) cm3 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
Reprint requests to: X. Allen Li, PhD, Department of Radiation Oncology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226. Tel: (414) 805-4362; E-mail: [email protected] Int J Radiation Oncol Biol Phys, Vol. -, No. -, pp. 1e8, 2014 0360-3016/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ijrobp.2014.02.035
This work is partially supported by MCW Cancer Center Meinerz Foundation and by Elekta Inc. Conflict of interest: none.
2
International Journal of Radiation Oncology Biology Physics
Dalah et al.
generally smaller compared with those from CT, except for the kidneys. Conclusions: Differences exists between DCE-, ADC-, and FDG-PETedefined 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. Ó 2014 Elsevier Inc.
Introduction The local relapse rates after definitive radiation therapy (RT) for locally advanced pancreatic carcinoma (LAPC) patients are high, ranging from 42% to 68% (1), and may be even more of a challenge than controlling distant metastases, at least for certain groups of patients (2). This poor local control is thought to be dose dependent, with insufficient standard doses of 45-50 Gy imposed by the tolerance of the surrounding organs at risk (OARs). With the pancreas in close proximity to many critical structures, there is an increased need for improved accuracy in gross tumor volume (GTV) delineation to define and escalate dose to the GTV while selectively sparing the adjacent OARs. Inadequate tumor control from current RT regimes, combined with recent indications for radiation dose escalation (3), is providing strong motivation for growing interest in dose escalation protocols in patients with unresectable LAPC (4, 5). A recent trial, however, did not show an improvement in survival over chemotherapy alone, but doses of only 53-54 Gy were used and thus part of the limitation of the study (6). Advanced RT techniques (eg, respiration motion management [7] and adaptive RT strategies [8, 9]) improve the safe delivery of higher doses, with tighter margins for better normal tissue sparing. The optimal imaging modality to accurately define the GTV for RT of pancreatic cancer is unknown. With computed tomography (CT), primary pancreatic tumors often appear as hypoattenuating lesions with poorly defined borders. Computed tomography scans with specific contrast protocols, however, offer the best possible visualization to assess tumor resectability according to the vascular anatomy/tumor interface. Recently evidence has emerged showing a discrepancy between pancreatic tumor measurements obtained from pathologic specimens and CT (10), as well as dynamic contrasteenhanced (DCE) T1weighted gradient echo magnetic resonance imaging (MRI) (11). In principle, the use of multimodality imaging is intended to synthesize and integrate information provided by individual imaging modalities, aiming to provide more accurate tumor volume delineation that could enable dose escalation and eventually more durable definitive local control. In this work, we address the agreement between the GTVs defined with fluorodeoxyglucose positron emission tomography (FDG-PET) using 3 different thresholds, DCE, apparent diffusion-coefficient (ADC) maps obtained from
diffusion-weighted (DW) MRI, and 3-dimensional (3D)/4dimensional (4D) CT with and without intravenous contrast. Additionally, differences between OAR volumes determined on MRI and CT are assessed. The divergence between tumor-defined maximum dimension (MD) from all imaging modalities is assessed against pathologic specimens in resectable and borderline resectable cases.
Methods and Materials Patient characteristics Imaging and pathologic data for a total of 19 patients with histologic confirmation of pancreatic adenocarcinoma were retrospectively reviewed. Patient staging was classified into 3 categories according to whether tumor was surgically resectable, borderline resectable, or locally advanced. Of these 19 patients, 89.5% of the patients had tumors in the pancreatic head/neck and 10.5% in the pancreatic body. All 19 patients had DCE, ADC, and FDG-PET.
Image acquisition CT imaging Abdominal 3D/4D CTs were collected using a scanner (LightSpeed, GE, Waukesha, Wisconsin, USA) for all patients before the start of RT. Additional CTs with oral and/ or intravenous contrast were acquired on a subset of patients at the discretion of the radiation oncologist to assist with OAR delineation and assessment of vasculature involvement. Images were acquired with 120 kVp, automAs (range, 182-285), 2.5-mm slice thickness, and
Radiation Oncology biology
physics
www.redjournal.org
Physics Contribution
Variability of Target and Normal Structure Delineation Using Multimodality Imaging for Radiation Therapy of Pancreatic Cancer Entesar Dalah, PhD,* Ion Moraru, PhD,* Eric Paulson, PhD,*,y Beth Erickson, MD,* and X. Allen Li, PhD* Departments of *Radiation Oncology and yRadiology, Medical College of Wisconsin, Milwaukee, Wisconsin Received Oct 3, 2013, and in revised form Feb 10, 2014. Accepted for publication Feb 24, 2014.
Summary This work explores the potential of using various magnetic resonance imaging, positron emission tomography, and computed tomography techniques to define treatment targets and organs at risk for radiation therapy of pancreatic cancer. Significant differences exist in the gross tumor volumes defined by these imaging modalities and sequences. Further studies are required to establish reliable imaging modalities and/or techniques for the accurate target delineation, which will be crucial particularly in dose escalation and/or dose painting for pancreatic cancer.
Purpose: To explore the potential of multimodality imaging (dynamic contrast eenhanced 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 DCEMRI, 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) cm3 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
Reprint requests to: X. Allen Li, PhD, Department of Radiation Oncology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226. Tel: (414) 805-4362; E-mail: [email protected] Int J Radiation Oncol Biol Phys, Vol. -, No. -, pp. 1e8, 2014 0360-3016/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ijrobp.2014.02.035
This work is partially supported by MCW Cancer Center Meinerz Foundation and by Elekta Inc. Conflict of interest: none.
2
International Journal of Radiation Oncology Biology Physics
Dalah et al.
generally smaller compared with those from CT, except for the kidneys. Conclusions: Differences exists between DCE-, ADC-, and FDG-PETedefined 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. Ó 2014 Elsevier Inc.
Introduction The local relapse rates after definitive radiation therapy (RT) for locally advanced pancreatic carcinoma (LAPC) patients are high, ranging from 42% to 68% (1), and may be even more of a challenge than controlling distant metastases, at least for certain groups of patients (2). This poor local control is thought to be dose dependent, with insufficient standard doses of 45-50 Gy imposed by the tolerance of the surrounding organs at risk (OARs). With the pancreas in close proximity to many critical structures, there is an increased need for improved accuracy in gross tumor volume (GTV) delineation to define and escalate dose to the GTV while selectively sparing the adjacent OARs. Inadequate tumor control from current RT regimes, combined with recent indications for radiation dose escalation (3), is providing strong motivation for growing interest in dose escalation protocols in patients with unresectable LAPC (4, 5). A recent trial, however, did not show an improvement in survival over chemotherapy alone, but doses of only 53-54 Gy were used and thus part of the limitation of the study (6). Advanced RT techniques (eg, respiration motion management [7] and adaptive RT strategies [8, 9]) improve the safe delivery of higher doses, with tighter margins for better normal tissue sparing. The optimal imaging modality to accurately define the GTV for RT of pancreatic cancer is unknown. With computed tomography (CT), primary pancreatic tumors often appear as hypoattenuating lesions with poorly defined borders. Computed tomography scans with specific contrast protocols, however, offer the best possible visualization to assess tumor resectability according to the vascular anatomy/tumor interface. Recently evidence has emerged showing a discrepancy between pancreatic tumor measurements obtained from pathologic specimens and CT (10), as well as dynamic contrasteenhanced (DCE) T1weighted gradient echo magnetic resonance imaging (MRI) (11). In principle, the use of multimodality imaging is intended to synthesize and integrate information provided by individual imaging modalities, aiming to provide more accurate tumor volume delineation that could enable dose escalation and eventually more durable definitive local control. In this work, we address the agreement between the GTVs defined with fluorodeoxyglucose positron emission tomography (FDG-PET) using 3 different thresholds, DCE, apparent diffusion-coefficient (ADC) maps obtained from
diffusion-weighted (DW) MRI, and 3-dimensional (3D)/4dimensional (4D) CT with and without intravenous contrast. Additionally, differences between OAR volumes determined on MRI and CT are assessed. The divergence between tumor-defined maximum dimension (MD) from all imaging modalities is assessed against pathologic specimens in resectable and borderline resectable cases.
Methods and Materials Patient characteristics Imaging and pathologic data for a total of 19 patients with histologic confirmation of pancreatic adenocarcinoma were retrospectively reviewed. Patient staging was classified into 3 categories according to whether tumor was surgically resectable, borderline resectable, or locally advanced. Of these 19 patients, 89.5% of the patients had tumors in the pancreatic head/neck and 10.5% in the pancreatic body. All 19 patients had DCE, ADC, and FDG-PET.
Image acquisition CT imaging Abdominal 3D/4D CTs were collected using a scanner (LightSpeed, GE, Waukesha, Wisconsin, USA) for all patients before the start of RT. Additional CTs with oral and/ or intravenous contrast were acquired on a subset of patients at the discretion of the radiation oncologist to assist with OAR delineation and assessment of vasculature involvement. Images were acquired with 120 kVp, automAs (range, 182-285), 2.5-mm slice thickness, and
