Impact of Diabetes and Insulin Use on Prognosis in Patients With Resected Pancreatic Cancer: An Ancillary Analysis of NRG Oncology RTOG 9704

Danielle S. Bitterman; Kathryn A. Winter; Theodore S. Hong; Charles S. Fuchs; William F. Regine; Ross A. Abrams; Howard Safran; John P. Hoffman; Al B. Benson; Timothy Kasunic; Mary Mulcahy; James F. Strauss; Thomas DiPetrillo; Philip J. Stella; Yuhchyau Chen; John P. Plastaras; Christopher H. Crane

doi:10.1016/j.ijrobp.2020.08.042

Impact of Diabetes and Insulin Use on Prognosis in Patients With Resected Pancreatic Cancer: An Ancillary Analysis of NRG Oncology RTOG 9704

Danielle S. Bitterman^*, Kathryn A. Winter, Theodore S. Hong, Charles S. Fuchs, William F. Regine, Ross A. Abrams, Howard Safran, John P. Hoffman, Al B. Benson, Timothy Kasunic, Mary Mulcahy, James F. Strauss, Thomas DiPetrillo, Philip J. Stella, Yuhchyau Chen, John P. Plastaras, Christopher H. Crane

^*Corresponding author for this work

Medicine, Hematology Oncology Division

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

5 Scopus citations

Abstract

Purpose: Diabetes mellitus (DM) has been proposed to be tumorigenic; however, prior studies of the association between DM and survival are conflicting. The goal of this ancillary analysis of RTOG 9704, a randomized controlled trial of adjuvant chemotherapy in pancreatic cancer, was to determine the prognostic effects of DM and insulin use on survival. Methods and Materials: Eligible patients from RTOG 9704 with available data on DM and insulin use were included. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, and variable levels were compared using log-rank test. Cox proportional hazards models were created to assess the associations among DM, insulin use, and body mass index phenotypes on outcomes. Results: Of 538 patients enrolled from 1998 to 2002, 238 patients were eligible with analyzable DM and insulin use data. Overall 34% of patients had DM and 66% did not. Of patients with DM, 64% had insulin-dependent DM, and 36% had non–insulin-dependent DM. On univariable analysis, neither DM nor insulin dependence were associated with OS or DFS (P >.05 for all). On multivariable analysis, neither DM, insulin use, nor body mass index were independently associated with OS or DFS. Nonwhite race (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.35-3.50; P =.0014), nodal involvement (HR, 1.74; 95% CI, 1.24-2.45; P =.0015), and carbohydrate antigen 19-9 (CA19-9) ≥90 U/mL (HR, 3.61; 95% CI, 2.32-5.63; P <.001) were associated with decreased OS. Nonwhite race (HR, 1.67; 95% CI, 1.05-2.63; P =.029) and CA19-9 ≥90 U/mL (HR, 2.86; 95% CI, 1.85-4.40; P <.001) were associated with decreased DFS. Conclusions: DM and insulin use were not associated with OS or DFS in patients with pancreatic cancer in this study. Race, nodal involvement, and increased CA19-9 were significant predictors of outcomes. These data might apply to the more modern use of neoadjuvant therapies for potentially resectable pancreatic cancer.

Original language	English (US)
Pages (from-to)	201-211
Number of pages	11
Journal	International Journal of Radiation Oncology Biology Physics
Volume	109
Issue number	1
DOIs	https://doi.org/10.1016/j.ijrobp.2020.08.042
State	Published - Jan 1 2021

Funding

This project was supported by grants U10CA180868 ( NRG Oncology Operations ), U10CA180822 ( NRG Oncology SDMC ), U10CA180820 ( ECOG-ACRIN ), and U10CA180888 ( SWOG ) from the National Cancer Institute (NCI) and Eli Lilly and Company. This project is funded, in part, under a grant from the Pennsylvania Department of Health . The department specifically disclaims responsibility for any analyses, interpretations, or conclusions. Disclosures: A.B.B. reports an advisor role with Envision, Guardant, DavaOnc, LSK, Therabionic, PreCOG, Terumo, Lexicon, Incyte, ACCC, and ECOG-ACRIN; a Data Monitor Committee role with Bristol-Myers Squibb; research with Acerta, Celgene, Advanced Accelerator Applications, Novartis, Infinity Pharmaceuticals, Merck Sharp and Dohme, Talho Pharmaceutical, Bristol-Myers Squibb, Medimmune/AstraZeneca, Xencor, and Amgen; and other with NCCN, outside the submitted work. D.S.B. reports personal fees from Agios Pharmaceuticals, outside the submitted work; D.S.B.’s spouse is an employee at Agios Pharmaceuticals. Y.C. reports institutional grant funding from National Cancer Institute to RTOG for clinical trial case enrollment during the conduct of the study. C.S.F. reports personal fees from Agios, Bain Capital, Bayer, Celgene, Dicerna, Eli Lilly, Five Prime Therapeutics, Genentech, Gilead Sciences, KEW, Merck, Merrimack, Pfizer, Sanofi, Talho, and Unum, and personal fees and other from CytomX and Entrinsic Health, outside the submitted work. J.F.S. reports stock and other ownership interests from Abbvie, Abbott Laboratories, Bristol-Myers Squibb, Intuitive Surgical, Johnson & Johnson, and Merck; a consulting or advisory role with Tempus; and other relationships with Dialectic Therapeutics.

ASJC Scopus subject areas

Radiation
Oncology
Radiology Nuclear Medicine and imaging
Cancer Research

UN SDGs

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

Access to Document

10.1016/j.ijrobp.2020.08.042

Cite this

Bitterman, D. S., Winter, K. A., Hong, T. S., Fuchs, C. S., Regine, W. F., Abrams, R. A., Safran, H., Hoffman, J. P., Benson, A. B., Kasunic, T., Mulcahy, M., Strauss, J. F., DiPetrillo, T., Stella, P. J., Chen, Y., Plastaras, J. P., & Crane, C. H. (2021). Impact of Diabetes and Insulin Use on Prognosis in Patients With Resected Pancreatic Cancer: An Ancillary Analysis of NRG Oncology RTOG 9704. International Journal of Radiation Oncology Biology Physics, 109(1), 201-211. https://doi.org/10.1016/j.ijrobp.2020.08.042

@article{94a6bdb7e9fa49a9b7a30f2c63ce0fac,

title = "Impact of Diabetes and Insulin Use on Prognosis in Patients With Resected Pancreatic Cancer: An Ancillary Analysis of NRG Oncology RTOG 9704",

abstract = "Purpose: Diabetes mellitus (DM) has been proposed to be tumorigenic; however, prior studies of the association between DM and survival are conflicting. The goal of this ancillary analysis of RTOG 9704, a randomized controlled trial of adjuvant chemotherapy in pancreatic cancer, was to determine the prognostic effects of DM and insulin use on survival. Methods and Materials: Eligible patients from RTOG 9704 with available data on DM and insulin use were included. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, and variable levels were compared using log-rank test. Cox proportional hazards models were created to assess the associations among DM, insulin use, and body mass index phenotypes on outcomes. Results: Of 538 patients enrolled from 1998 to 2002, 238 patients were eligible with analyzable DM and insulin use data. Overall 34% of patients had DM and 66% did not. Of patients with DM, 64% had insulin-dependent DM, and 36% had non–insulin-dependent DM. On univariable analysis, neither DM nor insulin dependence were associated with OS or DFS (P >.05 for all). On multivariable analysis, neither DM, insulin use, nor body mass index were independently associated with OS or DFS. Nonwhite race (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.35-3.50; P =.0014), nodal involvement (HR, 1.74; 95% CI, 1.24-2.45; P =.0015), and carbohydrate antigen 19-9 (CA19-9) ≥90 U/mL (HR, 3.61; 95% CI, 2.32-5.63; P <.001) were associated with decreased OS. Nonwhite race (HR, 1.67; 95% CI, 1.05-2.63; P =.029) and CA19-9 ≥90 U/mL (HR, 2.86; 95% CI, 1.85-4.40; P <.001) were associated with decreased DFS. Conclusions: DM and insulin use were not associated with OS or DFS in patients with pancreatic cancer in this study. Race, nodal involvement, and increased CA19-9 were significant predictors of outcomes. These data might apply to the more modern use of neoadjuvant therapies for potentially resectable pancreatic cancer.",

author = "Bitterman, {Danielle S.} and Winter, {Kathryn A.} and Hong, {Theodore S.} and Fuchs, {Charles S.} and Regine, {William F.} and Abrams, {Ross A.} and Howard Safran and Hoffman, {John P.} and Benson, {Al B.} and Timothy Kasunic and Mary Mulcahy and Strauss, {James F.} and Thomas DiPetrillo and Stella, {Philip J.} and Yuhchyau Chen and Plastaras, {John P.} and Crane, {Christopher H.}",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2021",

month = jan,

day = "1",

doi = "10.1016/j.ijrobp.2020.08.042",

language = "English (US)",

volume = "109",

pages = "201--211",

journal = "International Journal of Radiation Oncology Biology Physics",

issn = "0360-3016",

publisher = "Elsevier Inc.",

number = "1",

}

Bitterman, DS, Winter, KA, Hong, TS, Fuchs, CS, Regine, WF, Abrams, RA, Safran, H, Hoffman, JP, Benson, AB, Kasunic, T, Mulcahy, M, Strauss, JF, DiPetrillo, T, Stella, PJ, Chen, Y, Plastaras, JP & Crane, CH 2021, 'Impact of Diabetes and Insulin Use on Prognosis in Patients With Resected Pancreatic Cancer: An Ancillary Analysis of NRG Oncology RTOG 9704', International Journal of Radiation Oncology Biology Physics, vol. 109, no. 1, pp. 201-211. https://doi.org/10.1016/j.ijrobp.2020.08.042

Impact of Diabetes and Insulin Use on Prognosis in Patients With Resected Pancreatic Cancer: An Ancillary Analysis of NRG Oncology RTOG 9704. / Bitterman, Danielle S.; Winter, Kathryn A.; Hong, Theodore S. et al.
In: International Journal of Radiation Oncology Biology Physics, Vol. 109, No. 1, 01.01.2021, p. 201-211.

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

TY - JOUR

T1 - Impact of Diabetes and Insulin Use on Prognosis in Patients With Resected Pancreatic Cancer

T2 - An Ancillary Analysis of NRG Oncology RTOG 9704

AU - Bitterman, Danielle S.

AU - Winter, Kathryn A.

AU - Hong, Theodore S.

AU - Fuchs, Charles S.

AU - Regine, William F.

AU - Abrams, Ross A.

AU - Safran, Howard

AU - Hoffman, John P.

AU - Benson, Al B.

AU - Kasunic, Timothy

AU - Mulcahy, Mary

AU - Strauss, James F.

AU - DiPetrillo, Thomas

AU - Stella, Philip J.

AU - Chen, Yuhchyau

AU - Plastaras, John P.

AU - Crane, Christopher H.

PY - 2021/1/1

Y1 - 2021/1/1

N2 - Purpose: Diabetes mellitus (DM) has been proposed to be tumorigenic; however, prior studies of the association between DM and survival are conflicting. The goal of this ancillary analysis of RTOG 9704, a randomized controlled trial of adjuvant chemotherapy in pancreatic cancer, was to determine the prognostic effects of DM and insulin use on survival. Methods and Materials: Eligible patients from RTOG 9704 with available data on DM and insulin use were included. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, and variable levels were compared using log-rank test. Cox proportional hazards models were created to assess the associations among DM, insulin use, and body mass index phenotypes on outcomes. Results: Of 538 patients enrolled from 1998 to 2002, 238 patients were eligible with analyzable DM and insulin use data. Overall 34% of patients had DM and 66% did not. Of patients with DM, 64% had insulin-dependent DM, and 36% had non–insulin-dependent DM. On univariable analysis, neither DM nor insulin dependence were associated with OS or DFS (P >.05 for all). On multivariable analysis, neither DM, insulin use, nor body mass index were independently associated with OS or DFS. Nonwhite race (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.35-3.50; P =.0014), nodal involvement (HR, 1.74; 95% CI, 1.24-2.45; P =.0015), and carbohydrate antigen 19-9 (CA19-9) ≥90 U/mL (HR, 3.61; 95% CI, 2.32-5.63; P <.001) were associated with decreased OS. Nonwhite race (HR, 1.67; 95% CI, 1.05-2.63; P =.029) and CA19-9 ≥90 U/mL (HR, 2.86; 95% CI, 1.85-4.40; P <.001) were associated with decreased DFS. Conclusions: DM and insulin use were not associated with OS or DFS in patients with pancreatic cancer in this study. Race, nodal involvement, and increased CA19-9 were significant predictors of outcomes. These data might apply to the more modern use of neoadjuvant therapies for potentially resectable pancreatic cancer.

AB - Purpose: Diabetes mellitus (DM) has been proposed to be tumorigenic; however, prior studies of the association between DM and survival are conflicting. The goal of this ancillary analysis of RTOG 9704, a randomized controlled trial of adjuvant chemotherapy in pancreatic cancer, was to determine the prognostic effects of DM and insulin use on survival. Methods and Materials: Eligible patients from RTOG 9704 with available data on DM and insulin use were included. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, and variable levels were compared using log-rank test. Cox proportional hazards models were created to assess the associations among DM, insulin use, and body mass index phenotypes on outcomes. Results: Of 538 patients enrolled from 1998 to 2002, 238 patients were eligible with analyzable DM and insulin use data. Overall 34% of patients had DM and 66% did not. Of patients with DM, 64% had insulin-dependent DM, and 36% had non–insulin-dependent DM. On univariable analysis, neither DM nor insulin dependence were associated with OS or DFS (P >.05 for all). On multivariable analysis, neither DM, insulin use, nor body mass index were independently associated with OS or DFS. Nonwhite race (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.35-3.50; P =.0014), nodal involvement (HR, 1.74; 95% CI, 1.24-2.45; P =.0015), and carbohydrate antigen 19-9 (CA19-9) ≥90 U/mL (HR, 3.61; 95% CI, 2.32-5.63; P <.001) were associated with decreased OS. Nonwhite race (HR, 1.67; 95% CI, 1.05-2.63; P =.029) and CA19-9 ≥90 U/mL (HR, 2.86; 95% CI, 1.85-4.40; P <.001) were associated with decreased DFS. Conclusions: DM and insulin use were not associated with OS or DFS in patients with pancreatic cancer in this study. Race, nodal involvement, and increased CA19-9 were significant predictors of outcomes. These data might apply to the more modern use of neoadjuvant therapies for potentially resectable pancreatic cancer.

UR - http://www.scopus.com/inward/record.url?scp=85091879586&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85091879586&partnerID=8YFLogxK

U2 - 10.1016/j.ijrobp.2020.08.042

DO - 10.1016/j.ijrobp.2020.08.042

M3 - Article

C2 - 32858111

AN - SCOPUS:85091879586

SN - 0360-3016

VL - 109

SP - 201

EP - 211

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

IS - 1

ER -

Impact of Diabetes and Insulin Use on Prognosis in Patients With Resected Pancreatic Cancer: An Ancillary Analysis of NRG Oncology RTOG 9704

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this