The Impact of Serum Glucose, Anti-Diabetic Agents, and Statin Usage in Non-small Cell Lung Cancer Patients Treated With Definitive Chemoradiation

Overview

Journal Front Oncol

Specialty Oncology

Date 2018 Aug 14

PMID 30101126

Citations 5

Authors

Nick A Iarrobino

Beant S Gill

Mark Bernard

Rainer J Klement

Maria Werner-Wasik

Colin E Champ

Affiliations

Soon will be listed here.

Abstract

Epidemiologic data indicate diabetes confers an augmented risk of lung cancer development, yet the relationship between hyperglycemia, metabolic agents, and prognosis is unclear. We analyzed the impact of hyperglycemia, anti-diabetic agents, and statins on outcomes in non-small cell lung cancer (NSCLC) patients undergoing chemoradiation. In total, data from 170 patients with stage III NSCLC treated at the University of Pittsburgh Medical Center between 2001 and 2014 were obtained for analysis. Kaplan-Meier survival analysis was used to estimate time-to-event for overall survival (OS), disease-free survival, distant metastasis (DM), and loco-regional control (LRC). Blood glucose values ( = 2870), statins, and diabetic medications were assessed both continuously and categorically in univariable and multivariable Cox proportional hazard regression models to estimate hazard ratios and identify prognostic factors. Tumor volume was a negative prognostic factor for OS, disease-free survival, DM, and LRC ( = 0.001). Tumor stage and treatment time were associated with increased all-cause mortality. Any glucose measurement ≥ 130 mg/dl during treatment (2-year estimate 49.9 vs. 65.8%, = 0.095) was borderline significant for decreased LRC, with similar trends on multivariable analysis (HR 1.636, = 0.126) and for OS (HR 1.476, = 0.130). Statin usage was associated with improved 2-year LRC (53.4 vs. 62.4%, = 0.088) but not with improvements in survival. Other glycemic parameters, comorbid diabetes diagnosis, or anti-diabetic medications were not significantly associated with outcomes. There were trends for blood glucose value over 130 mg/dl and statin nonuse being associated with inferior prognosis for LRC in stage III NSCLC patients; glycemic state, statin usage, and glucose-modulating medications were not associated with survival outcomes in multivariable analysis in this retrospective database.

Citing Articles

Beta Blockers with Statins May Decrease All-Cause Mortality in Patients with Cardiovascular Diseases and Locally Advanced Unresectable Non-Small-Cell Lung Cancer after Chemoradiotherapy.

Zaborowska-Szmit M, Szmit S, Olszyna-Serementa M, Badurak P, Zajda K, Janowicz-Zebrowska A Cancers (Basel). 2023; 15(4).

PMID: 36831618 PMC: 9954027. DOI: 10.3390/cancers15041277.

Tumor acidity: From hallmark of cancer to target of treatment.

Bogdanov A, Bogdanov A, Chubenko V, Volkov N, Moiseenko F, Moiseyenko V Front Oncol. 2022; 12:979154.

PMID: 36106097 PMC: 9467452. DOI: 10.3389/fonc.2022.979154.

Lipid-lowering medication use and cancer-specific survival among endometrial or lung cancer patients: an Australian nationwide cohort study.

Feng J, Qin X Eur J Clin Pharmacol. 2020; 77(3):399-407.

PMID: 33030570 DOI: 10.1007/s00228-020-03009-5.

Poor glycemic control might compromise the efficacy of chemotherapy in non-small cell lung cancer patients with diabetes mellitus.

Zeng X, Xu C, Cheng J, Sun C, Wang Z, Gong Z Cancer Med. 2019; 9(3):902-911.

PMID: 31830375 PMC: 6997083. DOI: 10.1002/cam4.2750.

Cdc42: A Novel Regulator of Insulin Secretion and Diabetes-Associated Diseases.

Huang Q, Lai X, Qian X, Lv L, Li J, Duan J Int J Mol Sci. 2019; 20(1).

PMID: 30621321 PMC: 6337499. DOI: 10.3390/ijms20010179.

References

Crawford A, Cote C, Couto J, Daskiran M, Gunnarsson C, Haas K . Prevalence of obesity, type II diabetes mellitus, hyperlipidemia, and hypertension in the United States: findings from the GE Centricity Electronic Medical Record database. Popul Health Manag. 2010; 13(3):151-61. DOI: 10.1089/pop.2009.0039. View

Peairs K, Barone B, Snyder C, Yeh H, Stein K, Derr R . Diabetes mellitus and breast cancer outcomes: a systematic review and meta-analysis. J Clin Oncol. 2010; 29(1):40-6. PMC: 3055858. DOI: 10.1200/JCO.2009.27.3011. View

Mayer A, Vaupel P, Struss H, Giese A, Stockinger M, Schmidberger H . Strong adverse prognostic impact of hyperglycemic episodes during adjuvant chemoradiotherapy of glioblastoma multiforme. Strahlenther Onkol. 2014; 190(10):933-8. DOI: 10.1007/s00066-014-0696-z. View

Machtay M, Hsu C, Komaki R, Sause W, Swann R, Langer C . Effect of overall treatment time on outcomes after concurrent chemoradiation for locally advanced non-small-cell lung carcinoma: analysis of the Radiation Therapy Oncology Group (RTOG) experience. Int J Radiat Oncol Biol Phys. 2005; 63(3):667-71. DOI: 10.1016/j.ijrobp.2005.03.037. View

Qi X, Zheng L, Lee K, Kim D, Kim C, Cai D . HMG-CoA reductase inhibitors induce apoptosis of lymphoma cells by promoting ROS generation and regulating Akt, Erk and p38 signals via suppression of mevalonate pathway. Cell Death Dis. 2013; 4:e518. PMC: 3734846. DOI: 10.1038/cddis.2013.44. View

Arrieta O, Varela-Santoyo E, Soto-Perez-de-Celis E, Sanchez-Reyes R, de la Torre-Vallejo M, Muniz-Hernandez S . Metformin use and its effect on survival in diabetic patients with advanced non-small cell lung cancer. BMC Cancer. 2016; 16:633. PMC: 4983059. DOI: 10.1186/s12885-016-2658-6. View

Derr R, Ye X, Islas M, Desideri S, Saudek C, Grossman S . Association between hyperglycemia and survival in patients with newly diagnosed glioblastoma. J Clin Oncol. 2009; 27(7):1082-6. PMC: 2667812. DOI: 10.1200/JCO.2008.19.1098. View

Han J, Lee S, Yoo N, Hyung L, Moon Y, Yun T . A randomized phase II study of gefitinib plus simvastatin versus gefitinib alone in previously treated patients with advanced non-small cell lung cancer. Clin Cancer Res. 2011; 17(6):1553-60. DOI: 10.1158/1078-0432.CCR-10-2525. View

Cardwell C, Hicks B, Hughes C, Murray L . Statin use after colorectal cancer diagnosis and survival: a population-based cohort study. J Clin Oncol. 2014; 32(28):3177-83. DOI: 10.1200/JCO.2013.54.4569. View

10.

Chubak J, Boudreau D, Wirtz H, McKnight B, Weiss N . Threats to validity of nonrandomized studies of postdiagnosis exposures on cancer recurrence and survival. J Natl Cancer Inst. 2013; 105(19):1456-62. PMC: 3787908. DOI: 10.1093/jnci/djt211. View

11.

Klement R, Champ C . Calories, carbohydrates, and cancer therapy with radiation: exploiting the five R's through dietary manipulation. Cancer Metastasis Rev. 2014; 33(1):217-29. PMC: 3988521. DOI: 10.1007/s10555-014-9495-3. View

12.

Adeberg S, Bernhardt D, Foerster R, Bostel T, Koerber S, Mohr A . The influence of hyperglycemia during radiotherapy on survival in patients with primary glioblastoma. Acta Oncol. 2015; 55(2):201-7. DOI: 10.3109/0284186X.2015.1043397. View

13.

Warita K, Warita T, Beckwitt C, Schurdak M, Vazquez A, Wells A . Statin-induced mevalonate pathway inhibition attenuates the growth of mesenchymal-like cancer cells that lack functional E-cadherin mediated cell cohesion. Sci Rep. 2014; 4:7593. PMC: 4274516. DOI: 10.1038/srep07593. View

14.

Lamkin D, Spitz D, Shahzad M, Zimmerman B, Lenihan D, DeGeest K . Glucose as a prognostic factor in ovarian carcinoma. Cancer. 2009; 115(5):1021-7. PMC: 2649990. DOI: 10.1002/cncr.24126. View

15.

Champ C, Baserga R, Mishra M, Jin L, Sotgia F, Lisanti M . Nutrient restriction and radiation therapy for cancer treatment: when less is more. Oncologist. 2013; 18(1):97-103. PMC: 3556263. DOI: 10.1634/theoncologist.2012-0164. View

16.

Mazzoletti M, Bortolin F, Brunelli L, Pastorelli R, Di Giandomenico S, Erba E . Combination of PI3K/mTOR inhibitors: antitumor activity and molecular correlates. Cancer Res. 2011; 71(13):4573-84. DOI: 10.1158/0008-5472.CAN-10-4322. View

17.

Porporato P . Understanding cachexia as a cancer metabolism syndrome. Oncogenesis. 2016; 5:e200. PMC: 5154342. DOI: 10.1038/oncsis.2016.3. View

18.

Iarrobino N, Gill B, Bernard M, Mishra M, Champ C . Targeting Tumor Metabolism With Statins During Treatment for Advanced-stage Pancreatic Cancer. Am J Clin Oncol. 2018; 41(11):1125-1131. PMC: 6123314. DOI: 10.1097/COC.0000000000000433. View

19.

Pelaia G, Gallelli L, Renda T, Fratto D, Falcone D, Caraglia M . Effects of statins and farnesyl transferase inhibitors on ERK phosphorylation, apoptosis and cell viability in non-small lung cancer cells. Cell Prolif. 2012; 45(6):557-65. PMC: 6496308. DOI: 10.1111/j.1365-2184.2012.00846.x. View

20.

Klement R, Champ C . Corticosteroids compromise survival in glioblastoma in part through their elevation of blood glucose levels. Brain. 2016; 140(3):e16. DOI: 10.1093/brain/aww324. View