Bioluminescence image-guided irradiation and tumor monitoring in a preclinical pancreatic cancer mouse model.

192 Background: Preclinical pancreatic cancer animal models for radiation research are far from optimal because they utilize nonlocalized, single-beam irradiation of large fields due to lack of accurate targeting and delivery. We report on a novel preclinical pancreatic cancer research model that utilizes bioluminescence imaging (BLI)-guided irradiation (RT) of orthotopic xenograft tumors, sparing of surrounding normal tissues and quantitative, noninvasive longitudinal assessment of treatment response. Methods: In accordance with institutional guidelines, luciferase-expressing MiaPaCa-2 pancreatic carcinoma cells were used to generate orthotopic pancreatic tumors in nude mice. BLI of tumors were correlated to PET/CT and necropsy specimens using Pearson correlation. BLI was compared to cone-beam CT (CBCT) to determine the location of the tumor centroid and estimate an appropriate margin for radiation planning. Off-line fusion of BLI with CBCT was performed to guide radiation delivery to tumors using our small animal radiation research platform (SARRP). RT-induced DNA damage was assessed by γ-H2Ax and p-ATM foci. BLI was used to longitudinally monitor radiation treatment response and was correlated to necropsy specimen. Results: BLI accurately predicted tumor volume (R2 = 0.9961) and correlated well with PET/CT imaging of tumors (R2 = 0.97). BLI centroid accuracy was 3.5 mm relative to that of the CBCT. Irradiated pancreatic tumors stained positively for γ-H2Ax and p-ATM, while surrounding organs were spared. Longitudinal assessment of irradiated (5 Gy) tumors with BLI revealed a significant tumor growth delay of 20 days relative to untreated controls. This was also confirmed pathologically as mean tumor volume of irradiated mice was 30.2% that of unirradiated mice (p < 0.05). Conclusions: We have developed a bioluminescent, orthotopic preclinical pancreas cancer model that allows noninvasive 1) normalizing of pretreatment tumor burden; 2) treatment planning and image-guided focal RT therapy; and 3) longitudinal assessment of treatment response. This unique translational model offers a means to investigate targeted and systemic agents with focused RT for pancreatic cancer. No significant financial relationships to disclose.

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TH-CD-204-02: Longitudinal Assessment of Radiation Treatment Response in Non-Small Cell Lung Cancer Using Intravoxel Incoherent Motion Model Diffusion-Weighted MRI

Medical Physics ◽

10.1118/1.4926249 ◽

2015 ◽

Vol 42 (6Part43) ◽

pp. 3732-3732

Author(s):

K Karki ◽

G Hugo ◽

J Ford ◽

E Weiss

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Treatment Response ◽

Radiation Treatment ◽

Small Cell ◽

Motion Model ◽

Diffusion Weighted Mri ◽

Longitudinal Assessment ◽

Small Cell Lung ◽

Model Diffusion

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Pretreatment [18F] FDG-PET texture analysis to predict local response of pancreatic cancer to radiotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.375 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 375-375 ◽

Cited By ~ 1

Author(s):

Richard Tuli ◽

Benedick Fraass ◽

Wensha Yang ◽

Howard Mark Sandler ◽

Andrew Hendifar ◽

...

Keyword(s):

Pancreatic Cancer ◽

Treatment Response ◽

Fdg Pet ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Texture Features ◽

Pathologic Response ◽

Textural Features ◽

Pet Ct ◽

Pet Scans

375 Background: Accurate assessment of radiographic response following radiotherapy (RT) for pancreatic adenocarcinoma is challenging. Morphologic and textural features of FDG-PET have been shown to correlate with pathologic response and clinical outcomes in other solid tumors (PMID 23204495). The goal of this study was to develop a predictive algorithm derived from textural features of PET scans to predict response to RT. Methods: With IRB approval, we reviewed 10 patients with locally advanced pancreatic cancer treated with stereotactic body radiation therapy (25-30 Gy in 5 daily fractions). 18FDG-PET/CT scans were obtained 2 weeks pre-RT and 6 weeks post-RT. Pre-RT PET/CT images were deformably registered to the RT planning CT. Tumor volumes of interest were divided into (4.8mm)^3 subvolumes and characterized by mean SUV uptake, RT dose and comprehensive texture analysis. These pre-RT variables were correlated to post-RT mean SUV to identify potential predictors of treatment response. Response prediction was modeled by logistic regression with the Lasso algorithm and validated by 10-fold cross-validation. Model performance was assessed using cross-validated area under the receiver operating characteristic curves (AUC). Results: Mean uptake, RT dose and 6 texture features (energy, correlation, variance, sum mean, cluster tendency, and inverse variance) on pre-RT PET scans were significant in predicting treatment response (AUC 0.85). Within this model, each of the above noted variables was predictive of post-RT response (p<.05). Conclusions: Subvolume-based metabolic and texture features of pre-treatment PET scans were predictive of response following RT. Studies are ongoing to further correlate these variables to RECIST and pathologic response. This should serve as a useful model to help direct response-driven adaptive radiotherapy in patients with locally advanced pancreatic cancer.

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Interim metabolic tumor volume to predict response in diffuse large B-cell lymphoma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.7557 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 7557-7557

Author(s):

Prioty Islam ◽

Jordan Goldstein ◽

Ila Sethi ◽

Daniel Lee ◽

Christopher Flowers

Keyword(s):

Treatment Response ◽

Predictive Value ◽

Tumor Volume ◽

Post Treatment ◽

Ct Scans ◽

Fdg Uptake ◽

Interim Pet ◽

End Of Treatment ◽

Pet Ct ◽

Pre Treatment

7557 Background: DLBCL is a heterogeneous disease with varied clinical outcomes following treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). [18F] fluorodeoxyglucose (FDG) – positron emission tomography (PET)/computed tomography (CT) imaging is ubiquitously used in monitoring of DLBCL. PET-derived metrics for analysis of tumor FDG uptake include: tumor maximum standardized uptake value (SUV); metabolically active tumor volume (MTV); and total lesion glycolysis (TLG), calculated from the intensity of FDG uptake in tumor volume. We evaluated the predictive value of interim SUV, MTV and TLG for patients (pts) with DLBCL treated with R-CHOP. Methods: Pts with DLBCL treated at Emory University 2005-2016 were eligible. Cases were included if there was a diagnosis of DLBCL confirmed by record review, available information on date of diagnosis, date of last contact or date of death. Analyses were restricted to patients who received R-CHOP and had PET/CT scans available at baseline, Cycle 2 or 4 and end of treatment. Maximum SUV, MTV, and TLG were calculated using MIM software for tumor with an SUV threshold of > 4. Logistic regression analysis was used to calculate the predictive value of interim PET/CT metrics on end of treatment response. Results: Pre-treatment PET/CT scans for 42 patients were identified, along with 28 interim and 31 post-treatment scans. The mean pre-treatment MTV was 303ml (range 4 – 1,327) and mean TLG was 3188 (range 28 – 16,176). MTV and TLG were undetectable in 79% of interim scans and 74% of the post-treatment scans. A Deauville score of 3 or less was observed in 71% of the interim PET/CT scans and 56% of the post-treatment scans. A positive interim MTV was correlated with a positive post-treatment MTV and post-treatment Deauville score at 0.58 and 0.66, respectively, and a positive interim MTV result was a significant predictor of a positive post-treatment MTV result (p = 0.02). Conclusions: PET-derived metrics of assessing interim tumor response to therapy offer significant predictive value for end of treatment response, and can guide a response-adapted treatment approach for DLBCL pts that builds on the R-CHOP backbone.

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Use of tumor volume as measured on F18FDG-PET/CT scan as a predictive biomarker for head and neck cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e17019 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e17019-e17019

Author(s):

Y. Choi ◽

M. Song ◽

Y. Seol ◽

B. Kwon ◽

H. Shin ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Treatment Response ◽

Neck Cancer ◽

Tumor Volume ◽

Disease Free Survival ◽

Metabolic Tumor Volume ◽

Free Survival ◽

Pet Ct ◽

Disease Free

e17019 Background: Functional imaging, PET and its fusion with anatomical modalities, PET/CT promise to improve detection and characteristic disease. The objective of this study was to evaluate metabolic tumor volume as measured on F-18 FDG-PET/CT and its association with treatment response and prognosis in patients with head and neck cancer. Methods: The study population consisted of patients received neoadjuvant chemotherapy for a maximum of three cycles followed by radiation therapy. Before treatment patients were taken FDG-PET/CT scan, SUVmax, tumor volume, metastasis were recorded. Results: We enrolled 59 patients with stage III ann IV head and neck cancer. The median age was 66 years (range 47–81). There were 32 patients with stage III and 27 with stage IV. The mean SUVmax was 8.8 (range, 1.478). The mean tumor volume was 21.3 cm3 (range, 0.2–170). There was no correlation between tumor volume and SUVmax (correlation coefficient 0.295). Higher SUVmax was not associated with an increased risk of lymph node and distant metastasis at diagnosis (p = 0.968). But higher tumor volume was associated with an increased risk of lymph node and distant metastasis at diagnosis (p = 0.063). The metabolic tumor volume as measured on PET/CT scans was predictor of treatment response and disease -free survival. The response rate were 84% (21/25) for an SUVmax <5.5, 55% (19/34) for an SUVmax > 5.5 (p = 0.038). The disease free survival were 31.1month for an SUVmax <5.5, 4.6months for an SUVmax > 5.5 (p = 0.025). Conclusions: The metabolic tumor volume as measured on F-18FDG-PET/CT is a predictive biomarker of treatment response and disease free survival for patients with head and neck cancer. No significant financial relationships to disclose.

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18F-fluorothymidine (FLT) PET-CT for early response assessment in advanced pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e21093 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e21093-e21093

Author(s):

Amarnath Challapalli ◽

Harpreet S Wasan ◽

Adil Al-Nahhas ◽

Eric Aboagye ◽

Charles Coombes ◽

...

Keyword(s):

Pancreatic Cancer ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Standardized Uptake Value ◽

Response To Therapy ◽

Pancreatic Tumors ◽

Metastatic Tumors ◽

Flt Pet ◽

Pet Ct ◽

The Mean

e21093 Background: Advanced pancreatic cancer has a poor prognosis with a median survival of 6-10 months. There is a need for early non-invasive assessment of treatment response. We evaluated FLT PET-CT combined with a kinetic spatial filtering method (FLT-PETKSF) for detecting response to gemcitabine-based chemotherapy in advanced pancreatic cancer. Methods: Dynamic FLT PET-CT data were collected from patients with confirmed locally advanced or metastatic pancreatic cancer before and 2 weeks after the first cycle of chemotherapy. Changes in tumor FLT-PET variables with treatment were determined. Standardized uptake value (SUV) reduction of 18% was taken as cut-off for response. Voxel quantification of each tumor volume was performed on the filtered data. Each voxel-intensity was normalised by injected dose, body weight and decay corrected to obtain the SUV for the voxel. Changes in high intensity voxels (HiVox: SUV ≥ 2) - were computed. Results: Results of the first 5 patients are discussed. There were 4 primary and 9 metastatic tumors. FLT-PETKSF improved tumor-to-background ratio and enabled visualisation of all the primary and metastatic tumors. The mean (± SD) average and maximum SUV at 60 min (SUV60, av & SUV60, max) of the primary lesions was 2.10 (±0.38) & 4.85 (±1.55) and that of the metastatic lesions was 3.74 (±1.49) & 6.90 (±2.05) respectively. The mean (± SD) percentage reduction in the SUV60, av & SUV60, max, HIVox was 26 (±44), 18 (±38) and 23 (±50) respectively. The changes in the voxel occurrences correlated strongly with the changes in both SUV60, av & SUV60, max (Pearson r-0.9, p=0.001) .Overall, there were 2 partial responders and 3 with stable disease. These responses concurred with response evaluation on mid-treatment CT scan. Conclusions: FLT-PET and FLT-PETKSF enables visualisation of the pancreatic tumors and the liver metastases, and could be used to monitor response to therapy.

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Pretreatment metabolic tumor volume (MTV) as a predictor of survival in borderline resectable pancreatic cancers treated with neoadjuvant therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.310 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 310-310

Author(s):

Alex Cruz ◽

Dung-Tsa Chen ◽

William J. Fulp ◽

Michael Chuong ◽

Sarah Hoffe ◽

...

Keyword(s):

Pancreatic Cancer ◽

Radiation Therapy ◽

Surgical Resection ◽

Tumor Volume ◽

Metabolic Tumor Volume ◽

Post Treatment ◽

Ct Scans ◽

Borderline Resectable ◽

Pet Ct ◽

Pre Treatment

310 Background: A higher initial metabolic tumor burden is associated with lower median survival in locally advanced pancreatic cancer (LAPC), yet the prognostic utility of PET/CT is not defined in the setting of borderline resectable pancreatic cancer (BRPC). Methods: We performed a retrospectivereview of our institutional experience treating BRPC. Initial staging included endoscopic ultrasound as well as pancreatic protocol CT and PET/CT scans. All patients underwent neoadjuvant gemcitabine-based chemotherapy and radiation therapy (RT). RT was delivered using standard fractionation intensity modulated radiation therapy (IMRT) or stereotactic body radiation therapy (SBRT). Restaging CT and PET/CT scans were obtained approximately 4 weeks following RT completion. We measured the significance of the pre-treatment and post-treatment SUV maximum and metabolic tumor volume (MTV) 2.5 to 5.0, which was defined as the MTV above a threshold SUV of 2.5, 3.0, 4.0 and 5.0. Cox regression models were used to evaluate the significance between these parameters and disease free survival (DFS) and overall survival (OS). Results: We evaluated a total of 72 BRPC patients. Median follow up was 12.7 months. 56 patients (77%) received induction chemotherapy with gemcitabine, docetaxel and capecitabine (GTX). 43 (59.7 %) underwent surgical resection. Significant predictors for OS in the whole cohort included pre-treatment SUV maximum (p=0.0042), post-treatment SUV maximum (p=0.0183), pre-treatment MTV 2.5 (p=0.0016) and pre-treatment MTV 4.0 (p=0.0111). In addition, the difference between the MTV 4.0 pre-treatment and post-treatment was significant (p=0.0285). In patients who underwent surgical resection, there was a significant correlation between OS with pre-treatment SUV max (p=0.0229) and post-treatment SUV maximum (p=0.0325) but not pre-treatment MTV 2.5 (p=0.0654) nor MTV 4.0 (p=0.0928) nor the differences between each variable pre (0.1482) or post-treatment (0.0959). Conclusions: This is the first study to suggest that pre and post treatment PET activity is prognostic for BRPC.

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Fiducial markers coupled with 3D PET/CT offer more accurate radiation treatment delivery for locally advanced esophageal cancer

Endoscopy International Open ◽

10.1055/s-0043-104861 ◽

2017 ◽

Vol 05 (06) ◽

pp. E496-E504 ◽

Cited By ~ 2

Author(s):

Jasmine Oliver ◽

Puja Venkat ◽

Jessica Frakes ◽

Jason Klapman ◽

Cynthia Harris ◽

...

Keyword(s):

Esophageal Cancer ◽

Tumor Volume ◽

Radiation Treatment ◽

Locally Advanced ◽

Standardized Uptake Value ◽

Pathologic Response ◽

Mucosal Inflammation ◽

Fiducial Markers ◽

Median Distance ◽

Pet Ct

Abstract Background and aims The role of three-dimensional positron emission tomography/computed tomography (3 D PET/CT) in esophageal tumors that move with respiration and have potential for significant mucosal inflammation is unclear. The aim of this study was to determine the correlation between gross tumor volumes derived from 3 D PET/CT and endoscopically placed fiducial markers. Methods This was a retrospective, IRB approved analysis of 40 patients with esophageal cancer with fiducials implanted and PET/CT. The centroid of each fiducial was identified on PET/CT images. Distance between tumor volume and fiducials was measured using axial slices. Image features were extracted and tested for pathologic response predictability. Results The median adaptively calculated threshold value of the standardized uptake value (SUV) to define the metabolic tumor volume (MTV) border was 2.50, which corresponded to a median 23 % of the maximum SUV. The median distance between the inferior fiducial centroid and MTV was – 0.60 cm (– 3.9 to 2.7 cm). The median distance between the superior fiducial centroid and MTV was 1.25 cm (– 4.2 to 6.9 cm). There was no correlation between MTV-to-fiducial distances greater than 2 cm and the gastroenterologist who performed the fiducial implantation. Eccentricity demonstrated statistically significant correlations with pathologic response. Conclusions There was a stronger correlation between inferior fiducial location and MTV border compared to the superior extent. The etiology of the discordance superiorly is unclear, potentially representing benign secondary esophagitis, presence of malignant nodes, inflammation caused by technical aspects of the fiducial placement itself, or potential submucosal disease. Given the concordance inferiorly and the ability to more precisely set up the patient with daily image guidance matching to fiducials, it may be possible to minimize the planning tumor volume (PTV) margin in select patients, thereby, limiting dose to normal structures.

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