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

Ahmed M. Amer; Mohamed Zaid; Baishali Chaudhury; Dalia Elganainy; Yeonju Lee; Christopher T. Wilke; Jordan Cloyd; Huamin Wang; Anirban Maitra; Robert A. Wolff; Gauri Varadhachary; Michael J. Overman; Jeffery E. Lee; Jason B. Fleming; Ching Wei Tzeng; Matthew H. Katz; Emma B. Holliday; Sunil Krishnan; Bruce D. Minsky; Joseph M. Herman; Cullen M. Taniguchi; Prajnan Das; Christopher H. Crane; Ott Le; Priya Bhosale; Eric P. Tamm; Eugene J. Koay

doi:10.1002/cncr.31251

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

Ahmed M. Amer, Mohamed Zaid, Baishali Chaudhury, Dalia Elganainy, Yeonju Lee, Christopher T. Wilke, Jordan Cloyd, Huamin Wang, Anirban Maitra, Robert A. Wolff, Gauri Varadhachary, Michael J. Overman, Jeffery E. Lee, Jason B. Fleming, Ching Wei Tzeng, Matthew H. Katz, Emma B. Holliday, Sunil Krishnan, Bruce D. Minsky, Joseph M. HermanCullen M. Taniguchi, Prajnan Das, Christopher H. Crane, Ott Le, Priya Bhosale, Eric P. Tamm, Eugene J. Koay

Radiation Oncology

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1701-1709
Number of pages	9
Journal	Cancer
Volume	124
Issue number	8
DOIs	https://doi.org/10.1002/cncr.31251
State	Accepted/In press - Jan 1 2018

Bibliographical note

Funding Information:
This work was supported by the Andrew Sabin Family Fellowship, the Center for Radiation Oncology Research, the Sheikh Ahmed Center for Pancreatic Cancer Research, institutional funds from The University of Texas MD Anderson Cancer Center, GE Healthcare, Philips Healthcare, and Cancer Center Support (Core) grant CA016672 from the National Cancer Institute to the University of Texas MD Anderson Cancer Center. Eugene Koay was also supported by the National Institutes of Health (U54CA210181-01, U54CA143837, U01CA200468, and U01CA196403), the Pancreatic Cancer Action Network (14-20-25-KOAY and 16-65-SING), and the Radiological Society of North America (RSD1429). Sunil Krishnan reports grants from the National Institutes of Health, the US. Department of Defense, The University of Texas MD Anderson Cancer Center, the Focused Ultrasound Surgery Foundation, Shell Oil, the Malaysian Palm Oil Board, the Dunn Foundation, Elekta, Celgene, and Genentech; royalties from Taylor and Francis, all outside the submitted work; and owns the license on patent pending for radiosensitization with nanoparticles (from The University of Texas MD Anderson Cancer Center). Prajnan Das reports personal fees from Eisai Medical Research outside the submitted work. Eric P. Tamm reports an in-kind grant from General Electric to The University of Texas MD Anderson Cancer Center and research grants from Siemens Healthcare outside the submitted work. Eugene J. Koay reports royalties from Taylor and Francis and personal fees from Augmenix outside the submitted work. The remaining authors made no disclosures.

Funding Information:
This work was supported by the Andrew Sabin Family Fellowship, the Center for Radiation Oncology Research, the Sheikh Ahmed Center for Pancreatic Cancer Research, institutional funds from The University of Texas MD Anderson Cancer Center, GE Healthcare, Philips Healthcare, and Cancer Center Support (Core) grant CA016672 from the National Cancer Institute to the University of Texas MD Anderson Cancer Center. Eugene Koay was also supported by the National Institutes of Health (U54CA210181-01, U54CA143837, U01CA200468, and U01CA196403), the Pancreatic Cancer Action Network (14-20-25-KOAY and 16-65-SING), and the Radiological Society of North America (RSD1429).

Publisher Copyright:
© 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society

Keywords

Cytotoxic therapy
Imaging biomarker
Pancreatic cancer
Response
Response Evaluation Criteria in Solid Tumors (RECIST)

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/cncr.31251

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Amer, A. M., Zaid, M., Chaudhury, B., Elganainy, D., Lee, Y., Wilke, C. T., Cloyd, J., Wang, H., Maitra, A., Wolff, R. A., Varadhachary, G., Overman, M. J., Lee, J. E., Fleming, J. B., Tzeng, C. W., Katz, M. H., Holliday, E. B., Krishnan, S., Minsky, B. D., ... Koay, E. J. (Accepted/In press). Imaging-based biomarkers: Changes in the tumor interface of pancreatic ductal adenocarcinoma on computed tomography scans indicate response to cytotoxic therapy. Cancer, 124(8), 1701-1709. https://doi.org/10.1002/cncr.31251

Amer, AM, Zaid, M, Chaudhury, B, Elganainy, D, Lee, Y, Wilke, CT, Cloyd, J, Wang, H, Maitra, A, Wolff, RA, Varadhachary, G, Overman, MJ, Lee, JE, Fleming, JB, Tzeng, CW, Katz, MH, Holliday, EB, Krishnan, S, Minsky, BD, Herman, JM, Taniguchi, CM, Das, P, Crane, CH, Le, O, Bhosale, P, Tamm, EP & Koay, EJ 2018, 'Imaging-based biomarkers: Changes in the tumor interface of pancreatic ductal adenocarcinoma on computed tomography scans indicate response to cytotoxic therapy', Cancer, vol. 124, no. 8, pp. 1701-1709. https://doi.org/10.1002/cncr.31251

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

abstract = "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.",

keywords = "Cytotoxic therapy, Imaging biomarker, Pancreatic cancer, Response, Response Evaluation Criteria in Solid Tumors (RECIST)",

author = "Amer, {Ahmed M.} and Mohamed Zaid and Baishali Chaudhury and Dalia Elganainy and Yeonju Lee and Wilke, {Christopher T.} and Jordan Cloyd and Huamin Wang and Anirban Maitra and Wolff, {Robert A.} and Gauri Varadhachary and Overman, {Michael J.} and Lee, {Jeffery E.} and Fleming, {Jason B.} and Tzeng, {Ching Wei} and Katz, {Matthew H.} and Holliday, {Emma B.} and Sunil Krishnan and Minsky, {Bruce D.} and Herman, {Joseph M.} and Taniguchi, {Cullen M.} and Prajnan Das and Crane, {Christopher H.} and Ott Le and Priya Bhosale and Tamm, {Eric P.} and Koay, {Eugene J.}",

note = "Funding Information: This work was supported by the Andrew Sabin Family Fellowship, the Center for Radiation Oncology Research, the Sheikh Ahmed Center for Pancreatic Cancer Research, institutional funds from The University of Texas MD Anderson Cancer Center, GE Healthcare, Philips Healthcare, and Cancer Center Support (Core) grant CA016672 from the National Cancer Institute to the University of Texas MD Anderson Cancer Center. Eugene Koay was also supported by the National Institutes of Health (U54CA210181-01, U54CA143837, U01CA200468, and U01CA196403), the Pancreatic Cancer Action Network (14-20-25-KOAY and 16-65-SING), and the Radiological Society of North America (RSD1429). Sunil Krishnan reports grants from the National Institutes of Health, the US. Department of Defense, The University of Texas MD Anderson Cancer Center, the Focused Ultrasound Surgery Foundation, Shell Oil, the Malaysian Palm Oil Board, the Dunn Foundation, Elekta, Celgene, and Genentech; royalties from Taylor and Francis, all outside the submitted work; and owns the license on patent pending for radiosensitization with nanoparticles (from The University of Texas MD Anderson Cancer Center). Prajnan Das reports personal fees from Eisai Medical Research outside the submitted work. Eric P. Tamm reports an in-kind grant from General Electric to The University of Texas MD Anderson Cancer Center and research grants from Siemens Healthcare outside the submitted work. Eugene J. Koay reports royalties from Taylor and Francis and personal fees from Augmenix outside the submitted work. The remaining authors made no disclosures. Funding Information: This work was supported by the Andrew Sabin Family Fellowship, the Center for Radiation Oncology Research, the Sheikh Ahmed Center for Pancreatic Cancer Research, institutional funds from The University of Texas MD Anderson Cancer Center, GE Healthcare, Philips Healthcare, and Cancer Center Support (Core) grant CA016672 from the National Cancer Institute to the University of Texas MD Anderson Cancer Center. Eugene Koay was also supported by the National Institutes of Health (U54CA210181-01, U54CA143837, U01CA200468, and U01CA196403), the Pancreatic Cancer Action Network (14-20-25-KOAY and 16-65-SING), and the Radiological Society of North America (RSD1429). Publisher Copyright: {\textcopyright} 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society",

year = "2018",

month = jan,

day = "1",

doi = "10.1002/cncr.31251",

language = "English (US)",

volume = "124",

pages = "1701--1709",

journal = "Cancer",

issn = "0008-543X",

publisher = "John Wiley and Sons Inc.",

number = "8",

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TY - JOUR

T1 - Imaging-based biomarkers

T2 - Changes in the tumor interface of pancreatic ductal adenocarcinoma on computed tomography scans indicate response to cytotoxic therapy

AU - Amer, Ahmed M.

AU - Zaid, Mohamed

AU - Chaudhury, Baishali

AU - Elganainy, Dalia

AU - Lee, Yeonju

AU - Wilke, Christopher T.

AU - Cloyd, Jordan

AU - Wang, Huamin

AU - Maitra, Anirban

AU - Wolff, Robert A.

AU - Varadhachary, Gauri

AU - Overman, Michael J.

AU - Lee, Jeffery E.

AU - Fleming, Jason B.

AU - Tzeng, Ching Wei

AU - Katz, Matthew H.

AU - Holliday, Emma B.

AU - Krishnan, Sunil

AU - Minsky, Bruce D.

AU - Herman, Joseph M.

AU - Taniguchi, Cullen M.

AU - Das, Prajnan

AU - Crane, Christopher H.

AU - Le, Ott

AU - Bhosale, Priya

AU - Tamm, Eric P.

AU - Koay, Eugene J.

N1 - Funding Information: This work was supported by the Andrew Sabin Family Fellowship, the Center for Radiation Oncology Research, the Sheikh Ahmed Center for Pancreatic Cancer Research, institutional funds from The University of Texas MD Anderson Cancer Center, GE Healthcare, Philips Healthcare, and Cancer Center Support (Core) grant CA016672 from the National Cancer Institute to the University of Texas MD Anderson Cancer Center. Eugene Koay was also supported by the National Institutes of Health (U54CA210181-01, U54CA143837, U01CA200468, and U01CA196403), the Pancreatic Cancer Action Network (14-20-25-KOAY and 16-65-SING), and the Radiological Society of North America (RSD1429). Sunil Krishnan reports grants from the National Institutes of Health, the US. Department of Defense, The University of Texas MD Anderson Cancer Center, the Focused Ultrasound Surgery Foundation, Shell Oil, the Malaysian Palm Oil Board, the Dunn Foundation, Elekta, Celgene, and Genentech; royalties from Taylor and Francis, all outside the submitted work; and owns the license on patent pending for radiosensitization with nanoparticles (from The University of Texas MD Anderson Cancer Center). Prajnan Das reports personal fees from Eisai Medical Research outside the submitted work. Eric P. Tamm reports an in-kind grant from General Electric to The University of Texas MD Anderson Cancer Center and research grants from Siemens Healthcare outside the submitted work. Eugene J. Koay reports royalties from Taylor and Francis and personal fees from Augmenix outside the submitted work. The remaining authors made no disclosures. Funding Information: This work was supported by the Andrew Sabin Family Fellowship, the Center for Radiation Oncology Research, the Sheikh Ahmed Center for Pancreatic Cancer Research, institutional funds from The University of Texas MD Anderson Cancer Center, GE Healthcare, Philips Healthcare, and Cancer Center Support (Core) grant CA016672 from the National Cancer Institute to the University of Texas MD Anderson Cancer Center. Eugene Koay was also supported by the National Institutes of Health (U54CA210181-01, U54CA143837, U01CA200468, and U01CA196403), the Pancreatic Cancer Action Network (14-20-25-KOAY and 16-65-SING), and the Radiological Society of North America (RSD1429). Publisher Copyright: © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Cytotoxic therapy

KW - Imaging biomarker

KW - Pancreatic cancer

KW - Response

KW - Response Evaluation Criteria in Solid Tumors (RECIST)

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DO - 10.1002/cncr.31251

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JF - Cancer

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ER -

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

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

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