|
1
|
Kim J, Lim KH. Prognostic Factors for Hyperglycemia in Patients Receiving Chemotherapy. Cancer Nurs 2025; 48:112-120. [PMID: 37991472 DOI: 10.1097/ncc.0000000000001271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2023]
Abstract
BACKGROUND Approximately 10% to 30% of patients who receive chemotherapy experience hyperglycemia, which can affect the adverse reactions and treatment efficacy of chemotherapy. However, there is a paucity of research to explore the factors affecting hyperglycemia and include them in nursing interventions. OBJECTIVE The aim of this study was to understand the prognostic factors of hyperglycemia in cancer patients on chemotherapy. METHODS This retrospective, descriptive study included 134 adult patients with cancer receiving chemotherapy at Keimyeng University Dongsan Hospital in Daegu between July 1, 2021, and March 31, 2022. Data were analyzed using frequency, percentage, average, and standard deviation statistics and compared by t test, χ 2 test, and logistic regression analysis. RESULTS Logistic regression analysis revealed that sex (male) (95% confidence interval [CI], 7.24-745.49; odds ratio [OR], 73.48); education (95% CI, 4.02-201.59; OR, 28.46); exercise durations of 30 to 60 minutes (95% CI, 0.00-0.06; OR, 0.01), 60 to 90 minutes (95% CI, 0.00-0.05, OR = 0.01), and ≥90 minutes (95% CI, 0.00-0.42; OR, 0.03); exercise amount ≥ 2000 kcal/wk (95% CI, 0.01-0.77; OR, 0.06); and daily fat (95% CI, 1.02-1.14; OR, 1.08), protein (95% CI, 0.82-0.95; OR, 0.88), and seaweed (95% CI, 0.85-0.99; OR, 0.92) intake were significant predictors of hyperglycemia. CONCLUSION The prognostic factors of hyperglycemia should be included in nursing interventions to prevent and manage hyperglycemia, which in turn may help reduce adverse reactions related to chemotherapy and improve treatment efficacy. IMPLICATIONS FOR PRACTICE To prevent and manage hyperglycemia in patients on chemotherapy, prognostic factors, including exercise and protein, fat, and seaweed consumption, should be considered in nursing interventions. Particularly, in men and patients with low education levels who are at a high risk of hyperglycemia, nursing interventions for diet and exercise should be individualized.
Collapse
Affiliation(s)
- Jiyeong Kim
- Author Affiliations: College of Nursing (Ms Kim) and Department of Nursing (Dr Lim), Keimyung University, Daegu, South Korea
| | | |
Collapse
|
|
2
|
Natalicchio A, Marrano N, Montagnani M, Gallo M, Faggiano A, Zatelli MC, Argentiero A, Del Re M, D'Oronzo S, Fogli S, Franchina T, Giuffrida D, Gori S, Ragni A, Marino G, Mazzilli R, Monami M, Morviducci L, Renzelli V, Russo A, Sciacca L, Tuveri E, Cortellini A, Di Maio M, Candido R, Perrone F, Aimaretti G, Avogaro A, Silvestris N, Giorgino F. Glycemic control and cancer outcomes in oncologic patients with diabetes: an Italian Association of Medical Oncology (AIOM), Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology (SIE), Italian Society of Pharmacology (SIF) multidisciplinary critical view. J Endocrinol Invest 2024; 47:2915-2928. [PMID: 38935200 PMCID: PMC11549129 DOI: 10.1007/s40618-024-02417-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Accepted: 06/16/2024] [Indexed: 06/28/2024]
Abstract
BACKGROUND Increasing evidence suggests that diabetes increases the risk of developing different types of cancer. Hyperinsulinemia, hyperglycemia and chronic inflammation, characteristic of diabetes, could represent possible mechanisms involved in cancer development in diabetic patients. At the same time, cancer increases the risk of developing new-onset diabetes, mainly caused by the use of specific anticancer therapies. Of note, diabetes has been associated with a ∼10% increase in mortality for all cancers in comparison with subjects who did not have diabetes. Diabetes is associated with a worse prognosis in patients with cancer, and more recent findings suggest a key role for poor glycemic control in this regard. Nevertheless, the association between glycemic control and cancer outcomes in oncologic patients with diabetes remains unsettled and poorly debated. PURPOSE The current review seeks to summarize the available evidence on the effect of glycemic control on cancer outcomes, as well as on the possibility that timely treatment of hyperglycemia and improved glycemic control in patients with cancer and diabetes may favorably affect cancer outcomes.
Collapse
Affiliation(s)
- A Natalicchio
- Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Piazza Giulio Cesare, 11, I-70124, Bari, Italy
| | - N Marrano
- Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Piazza Giulio Cesare, 11, I-70124, Bari, Italy
| | - M Montagnani
- Department of Precision and Regenerative Medicine and Ionian Area, Section of Pharmacology, University of Bari Aldo Moro, Bari, Italy
| | - M Gallo
- Endocrinology and Metabolic Diseases Unit, Azienda Ospedaliero-Universitaria SS Antonio e Biagio e Cesare Arrigo of Alessandria, Alessandria, Italy
| | - A Faggiano
- Endocrinology Unit, Department of Clinical & Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - M C Zatelli
- Section of Endocrinology, Geriatrics and Internal Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy
| | - A Argentiero
- Medical Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy
| | - M Del Re
- Department of Clinical and Experimental Medicine, University of Pisa, 55, Via Roma, 56126, Pisa, Italy
| | - S D'Oronzo
- Interdisciplinary Department of Medicine, University of Bari Aldo Moro, Bari, Italy
| | - S Fogli
- Clinical Pharmacology and Pharmacogenetics Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - T Franchina
- Medical Oncology Unit, Department of Human Pathology "G. Barresi", University of Messina, Messina, Italy
| | - D Giuffrida
- Department of Oncology, Istituto Oncologico del Mediterraneo, Viagrande, Catania, Italy
| | - S Gori
- Oncologia Medica, IRCCS Don Calabria-Sacro Cuore Hospital, Negrar, Verona, Italy
| | - A Ragni
- Endocrinology and Metabolic Diseases Unit, Azienda Ospedaliero-Universitaria SS Antonio e Biagio e Cesare Arrigo of Alessandria, Alessandria, Italy
| | - G Marino
- Internal Medicine Department, Ospedale dei Castelli, Asl Roma 6, Ariccia, Rome, Italy
| | - R Mazzilli
- Endocrinology Unit, Department of Clinical & Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - M Monami
- Diabetology, Careggi Hospital and University of Florence, Florence, Italy
| | - L Morviducci
- Diabetology and Nutrition Unit, Department of Medical Specialties, ASL Roma 1 - S. Spirito Hospital, Rome, Italy
| | - V Renzelli
- Diabetologist and Endocrinologist, Italian Association of Clinical Diabetologists, Rome, Italy
| | - A Russo
- Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy
| | - L Sciacca
- Department of Clinical and Experimental Medicine, Endocrinology Section, University of Catania, Catania, Italy
| | - E Tuveri
- Diabetology, Endocrinology and Metabolic Diseases Service, ASL-Sulcis, Carbonia, Italy
| | - A Cortellini
- Operative Research Unit of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128, Rome, Italy
- Department of Medicine and Surgery, Universitá Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128, Rome, Italy
- Department of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College London, London, UK
| | - M Di Maio
- Department of Oncology, University of Turin, AOU Città Della Salute e della Scienza di Torino, Turin, Italy
| | - R Candido
- Department of Medical Surgical and Health Sciences, University of Trieste, 34149, Trieste, Italy
| | - F Perrone
- Clinical Trials Unit, National Cancer Institute, Naples, Italy
| | - G Aimaretti
- Endocrinology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
| | - A Avogaro
- Department of Medicine, Section of Diabetes and Metabolic Diseases, University of Padova, Padua, Italy
| | - N Silvestris
- Medical Oncology Unit, Department of Human Pathology "G. Barresi", University of Messina, Messina, Italy
| | - F Giorgino
- Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Piazza Giulio Cesare, 11, I-70124, Bari, Italy.
| |
Collapse
|
|
3
|
O'Malley DM, Alavi S, Tsui J, Abraham CM, Ohman-Strickland P. Racial and Ethnic Differences in Diabetes Care Quality in A National Sample of Cancer Survivors Relative to Non-Cancer Controls. J Racial Ethn Health Disparities 2024:10.1007/s40615-024-02156-0. [PMID: 39230653 DOI: 10.1007/s40615-024-02156-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 07/31/2024] [Accepted: 08/25/2024] [Indexed: 09/05/2024]
Abstract
BACKGROUND Among cancer survivors, diabetes is associated with greater morbidity and mortality. The objective of this study is to describe racial/ethnic disparities in diabetes care quality (DCQ) among cancer survivors compared to non-cancer controls. METHODS We used Medical Expenditure Panel Survey Household Component data (2010-2018). Black, non-Hispanic White (NHW), and Hispanic respondents diagnosed with diabetes and cancer were frequency matched 1:5 to non-cancer controls. Multivariable logistic regression estimated associations for specific indices and overall DCQ by race/ethnicity stratified by cancer site/status in partially adjusted (not controlling for socioeconomic indicators) and fully adjusted models. RESULTS The final sample of 4775 included cancer survivors (n = 907 all cancers; n = 401 breast; n = 167 colon; n = 339 prostate) and non-cancer controls (n = 3868) matched by age, race/ethnicity, and year. In partially adjusted models, Black (adjusted odds ratio, AOR) 0.67 [95% CI 0.54-0.83]) and Hispanic (AOR 0.68 [95% CI 0.54-0.87]) non-cancer controls had significant disparities for overall DCQ compared to NHWs. Among cancer survivors, DCQ disparities for Black (AOR 0.62, [95% CI 0.4-0.96]) and Hispanics (AOR 0.60, [95% CI 0.38-0.97]) were identified. Among prostate cancer survivors, DCQ disparities were identified for Blacks (AOR 0.38; [95% CI 0.20-0.72]) and Hispanics (AOR 0.39; [95% CI 0.17-0.89]) compared to NHWs. Racial disparities among Black controls and Black prostate cancer survivors remained significant in fully adjusted models. CONCLUSION Diabetes care disparities are evident among cancer survivors and salient among non-cancer controls. Strategies to promote health equity should target specific care indices among survivors and emphasize equitable DCQ strategies among Black and Hispanic communities.
Collapse
Affiliation(s)
- Denalee M O'Malley
- Department of Family Medicine and Community Health, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
- Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
| | - Sarah Alavi
- Rutgers School of Public Health, Department of Epidemiology and Biostatistics, Piscataway, NJ, USA
| | - Jennifer Tsui
- Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Cilgy M Abraham
- Georgetown University Law Center, Georgetown University, Washington, DC, USA
| | - Pamela Ohman-Strickland
- Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
- Rutgers School of Public Health, Department of Epidemiology and Biostatistics, Piscataway, NJ, USA
| |
Collapse
|
|
4
|
Salgado TM, Birari PB, Alshahawey M, Hickey Zacholski E, Mackler E, Buffington TM, Musselman KT, Irvin WJ, Perkins JM, Le TN, Dixon DL, Farris KB, Sheppard VB, Jones RM. Optimal hyperglycemia thresholds in patients undergoing chemotherapy: a cross sectional study of oncologists' practices. Support Care Cancer 2024; 32:563. [PMID: 39088060 PMCID: PMC11294379 DOI: 10.1007/s00520-024-08756-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Accepted: 07/21/2024] [Indexed: 08/02/2024]
Abstract
PURPOSE Neither the United States nor the European oncology guidelines include details for appropriate management of hyperglycemia in cancer patients. The aim was to identify fasting and random blood glucose thresholds, and hemoglobin A1c (HbA1c) targets used by oncologists in clinical practice when managing hyperglycemia in patients with cancer undergoing chemotherapy. METHODS This national, cross sectional study utilized a questionnaire to collect oncologists' perceptions about optimal blood glucose thresholds and HbA1c targets in patients with cancer undergoing chemotherapy. Descriptive statistics were calculated to summarize glucose thresholds, HbA1c targets, and sample characteristics. Responses to an open-ended question about oncologists' approach to hyperglycemia management were analyzed via thematic analysis using an inductive approach. RESULTS Respondents (n = 229) were on average 52.1 years of age, 67.7% men, and 91.3% White. For patients without diabetes but experiencing hyperglycemia, oncologists targeted lower and upper fasting blood glucose levels between 75-121 mg/dL and 105-135 mg/dL, respectively. For patients with diabetes, the targets for lower and upper fasting blood glucose levels ranged between 100-130 mg/dL and 128-150 mg/dL, respectively. Fasting blood glucose (95.6%) and HbA1c (78.6%) were the most commonly used clinical indicators to consider chemotherapy dose reduction, delay, or discontinuation due to hyperglycemia in patients receiving chemotherapy with curative intent. Among those receiving palliative intent chemotherapy, the preferred clinical parameters were random blood glucose (90.0%), patient-reported blood glucose readings (70.7%), continuous glucose monitoring readings (65.1%), and patient-reported symptoms of hyperglycemia (65.1%). Three main themes emerged about oncologists' approach to hyperglycemia management: 1) identification of high-risk patients; 2) need for early identification, screening, and diagnosis of hyperglycemia; and 3) multiple hyperglycemia management strategies. CONCLUSION Oncologists reported a wide variation of target blood glucose ranges considered appropriate in patients undergoing chemotherapy. Lack of clear guidance for hyperglycemia management during chemotherapy in the United States may be contributing to a lack of consistency in clinical practice.
Collapse
Affiliation(s)
- Teresa M Salgado
- Department of Pharmacotherapy & Outcomes Science, School of Pharmacy and Massey Cancer Center, Virginia Commonwealth University, 410 N. 12Th Street PO Box 98053, Richmond, VA, 23298, USA.
| | - Poorva B Birari
- Department of Pharmacotherapy & Outcomes Science, School of Pharmacy, Virginia Commonwealth University, 410 N. 12Th Street PO Box 98053, Richmond, VA, 23298, USA
| | - Mona Alshahawey
- Department of Pharmacotherapy & Outcomes Science, School of Pharmacy, Virginia Commonwealth University, 410 N. 12Th Street PO Box 98053, Richmond, VA, 23298, USA
- Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Organization of African Unity St, El-Qobba Bridge, El Weili, Cairo Governorate, 4393005, Egypt
| | - Erin Hickey Zacholski
- Department of Pharmacotherapy & Outcomes Science, School of Pharmacy, Virginia Commonwealth University, 410 N. 12Th Street PO Box 98053, Richmond, VA, 23298, USA
| | - Emily Mackler
- Michigan Oncology Quality Consortium (MOQC) and Michigan Institute for Care Management and Transformation (MICMT), 4251 Plymouth Road Arbor Lakes, Building 3, Floor 3, Ann Arbor, MI, 48105, USA
| | - Tonya M Buffington
- Bon Secours Mercy Health, 611 Watkins Centre Parkway, Suite 250, Midlothian, VA, 23114, USA
| | - Kerri T Musselman
- Emcara Health and PopHealthCare, 113 Seaboard Lane, Suite B200, Franklin, TN, 37067, USA
| | - William J Irvin
- Bon Secours St Francis, 14051 St Francis Blvd Suite 2210, Midlothian, VA, 23114, USA
| | - Jennifer M Perkins
- Division of Endocrinology, University of California San Francisco Medical Center, 400 Parnassus Ave., Suite A-550, San Francisco, CA, 94143, USA
| | - Trang N Le
- Division of Endocrinology, Diabetes & Metabolism, Department of Internal Medicine, School of Medicine, Virginia Commonwealth University, 1101 E. Marshall St. Sanger Hall Suite 1-030, Richmond, VA, 23298, USA
| | - Dave L Dixon
- Department of Pharmacotherapy & Outcomes Science, School of Pharmacy, Virginia Commonwealth University, 410 N. 12Th Street PO Box 98053, Richmond, VA, 23298, USA
| | - Karen B Farris
- Department of Clinical Pharmacy Translational Sciences, College of Pharmacy and Michigan Institute for Care Management and Transformation (MICMT), University of Michigan, 428 Church St, Ann Arbor, MI, 48109, USA
| | - Vanessa B Sheppard
- Department of Social and Behavioral Sciences, School of Public Health, and Massey Cancer Center, Virginia Commonwealth University, 830 East Main Street, Richmond, VA, 23219, USA
| | - Resa M Jones
- Department of Epidemiology and Biostatistics, College of Public Health, and Fox Chase Cancer Center, Temple University, 1301 Cecil B. Moore Avenue Ritter Annex, 9Th Floor, Suite 917, Philadelphia, PA, 19122, USA
| |
Collapse
|
|
5
|
Fang TZ, Wu XQ, Zhao TQ, Wang SS, Fu GMZ, Wu QL, Zhou CW. Influence of blood glucose fluctuations on chemotherapy efficacy and safety in type 2 diabetes mellitus patients complicated with lung carcinoma. World J Diabetes 2024; 15:645-653. [PMID: 38680689 PMCID: PMC11045413 DOI: 10.4239/wjd.v15.i4.645] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 12/15/2023] [Accepted: 02/21/2024] [Indexed: 04/11/2024] Open
Abstract
BACKGROUND Patients with type 2 diabetes mellitus (T2DM) have large fluctuations in blood glucose (BG), abnormal metabolic function and low immunity to varying degrees, which increases the risk of malignant tumor diseases and affects the efficacy of tumor chemotherapy. Controlling hyperglycemia may have important therapeutic implications for cancer patients. AIM To clarify the influence of BG fluctuations on chemotherapy efficacy and safety in T2DM patients complicated with lung carcinoma (LC). METHODS The clinical data of 60 T2DM + LC patients who presented to the First Affiliated Hospital of Ningbo University between January 2019 and January 2021 were retrospectively analyzed. All patients underwent chemotherapy and were grouped as a control group (CG; normal BG fluctuation with a mean fluctuation < 3.9 mmol/L) and an observation group (OG; high BG fluctuation with a mean fluctuation ≥ 3.9 mmol/L) based on their BG fluctuations, with 30 cases each. BG-related indices, tumor markers, serum inflammatory cytokines and adverse reactions were comparatively analyzed. Pearson correlation analysis was performed to analyze the correlation between BG fluctuations and tumor markers. RESULTS The fasting blood glucose and 2-hour postprandial blood glucose levels in the OG were notably elevated compared with those in the CG, together with markedly higher mean amplitude of glycemic excursions (MAGE), mean of daily differences, largest amplitude of glycemic excursions and standard deviation of blood glucose (P < 0.05). In addition, the OG exhibited evidently higher levels of carbohydrate antigen 19-9, carbohydrate antigen 125, carcinoembryonic antigen, neuron-specific enolase, cytokeratin 19, tumor necrosis factor-α, interleukin-6, and high-sensitivity C-reactive protein than the CG (P < 0.05). Pearson analysis revealed a positive association of MAGE with serum tumor markers. The incidence of adverse reactions was significantly higher in the OG than in the CG (P < 0.05). CONCLUSION The greater the BG fluctuation in LC patients after chemotherapy, the more unfavorable the therapeutic effect of chemotherapy; the higher the level of tumor markers and inflammatory cytokines, the more adverse reactions the patient experiences.
Collapse
Affiliation(s)
- Tian-Zheng Fang
- Department of Thoracic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
| | - Xian-Qiao Wu
- Department of Thoracic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
| | - Ting-Qi Zhao
- Department of Endocrine, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
| | - Shan-Shan Wang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
| | - Guo-Mei-Zhi Fu
- Department of Thoracic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
| | - Qing-Long Wu
- Department of Thoracic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
| | - Cheng-Wei Zhou
- Department of Thoracic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
| |
Collapse
|
|
6
|
Moore-Vasram S, Sawhney M, Houlden RL, Groome PA, Goldie C, Li W, Hay AE, Tranmer J. Determining the Associations Between Glucocorticoid Use During Hematologic Chemotherapy Treatment and New-onset Diabetes and Hyperglycemia and Mortality: A Population-based Cohort Study. Can J Diabetes 2024; 48:195-203.e1. [PMID: 38211830 DOI: 10.1016/j.jcjd.2024.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 08/09/2023] [Accepted: 01/04/2024] [Indexed: 01/13/2024]
Abstract
OBJECTIVES The aim of this study was to determine the associations between glucocorticoid administration during chemotherapy for hematologic malignancy and hyperglycemia, new-onset diabetes, and mortality in Ontario, Canada. Hospitalization and emergency room utilization during the chemotherapy treatment period were also described. METHODS We conducted a retrospective cohort study using health administrative data from ICES, Ontario, to assess risk of new-onset diabetes, new-onset hyperglycemia, and hyperglycemia for individuals with leukemia, non-Hodgkin lymphoma (NHL), and Hodgkin lymphoma (HL) receiving glucocorticoids during chemotherapy between 2006 and 2016. Using multivariable regression models, we determined the associations between glucocorticoid exposure and our outcomes of interest, controlling for age, sex, marginalization, and comorbidities. RESULTS Our cohort included 19,530 individuals; 71.1% (n=13,893) received a glucocorticoid. The highest proportion of hyperglycemia occurred with leukemia (25.4%, n=1,301). Of the 15,580 individuals with no history of diabetes, those with leukemia had the highest rate of new-onset diabetes (7.1%, n=279) and new-onset hyperglycemia (18.1%, n=641), and glucocorticoid exposure increased the risk of new-onset diabetes (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.01 to 1.64, p=0.04) and new-onset hyperglycemia (HR 1.28, 95% CI 1.09 to 1.5, p=0.003). Hyperglycemia during chemotherapy increased the risk of all-cause mortality for the combined (HR 1.18, 95% CI 1.09 to 1.27, p<0.0001) and NHL (HR 1.16, 95% CI 1.04 to 1.28, p=0.007) cohorts. CONCLUSIONS Hyperglycemia is common during hematologic chemotherapy treatment and is associated with a modest increased risk of all-cause mortality. Routine screening, monitoring, and management of hyperglycemia should be an integral part of treatment plans for leukemia, NHL, or HL, with or without glucocorticoid administration.
Collapse
Affiliation(s)
| | - Monakshi Sawhney
- School of Nursing, Queen's University, Kingston, Ontario, Canada
| | - Robyn L Houlden
- Division of Endocrinology and Metabolism, Queen's University, Kingston Health Sciences Centre, Kingston, Ontario, Canada
| | - Patti A Groome
- Division of Cancer Care and Epidemiology, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada; ICES, formerly the Institute for Clinical Evaluative Sciences, Queen's University Site, Kingston, Ontario, Canada
| | - Catherine Goldie
- School of Nursing, Queen's University, Kingston, Ontario, Canada
| | - Wenbin Li
- ICES, formerly the Institute for Clinical Evaluative Sciences, Queen's University Site, Kingston, Ontario, Canada
| | - Annette E Hay
- Division of Hematology, Queen's University, Kingston, Ontario, Canada
| | - Joan Tranmer
- School of Nursing, Queen's University, Kingston, Ontario, Canada; ICES, formerly the Institute for Clinical Evaluative Sciences, Queen's University Site, Kingston, Ontario, Canada
| |
Collapse
|
|
7
|
Tyebally S, Sia CH, Chen D, Abiodun A, Dalakoti M, Chan PF, Koo CY, Tan LL. The intersection of heart failure and cancer in women: a review. Front Cardiovasc Med 2024; 11:1276141. [PMID: 38481958 PMCID: PMC10933022 DOI: 10.3389/fcvm.2024.1276141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 01/22/2024] [Indexed: 11/02/2024] Open
Abstract
Cancer and cardiovascular disease represent the two leading causes of morbidity and mortality worldwide. Women continue to enjoy a greater life expectancy than men. However, this comes at a cost with more women developing diabetes, hypertension and coronary artery disease as they age. These traditional cardiovascular risk factors not only increase their lifetime risk of heart failure but also their overall risk of cancer. In addition to this, many of the cancers with female preponderance are treated with potentially cardiotoxic therapies, adding to their increased risk of developing heart failure. As a result, we are faced with a higher risk population, potentially suffering from both cancer and heart failure simultaneously. This is of particular concern given the coexistence of heart failure and cancer can confer a worse prognosis than either a single diagnosis of heart failure or cancer alone. This review article explores the intersection of heart failure and cancer in women at multiple levels, including traditional cardiovascular risk factors, cardiovascular toxicity derived from antineoplastic and radiation therapy, shared pathophysiology and HF as an oncogenic process. This article further identifies opportunities and strategies for intervention and optimisation, whilst highlighting the need for contemporary guidelines to better inform clinical practice.
Collapse
Affiliation(s)
- Sara Tyebally
- Division of Cardiology, Department of Medicine, Ng Teng Fong General Hospital, Singapore, Singapore
- Institute of Cardiovascular Science, University College London, London, United Kingdom
| | - Ching-Hui Sia
- Department of Cardiology, National University Heart Centre Singapore, Singapore, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Daniel Chen
- Hatter Cardiovascular Institute, University College London, London, United Kingdom
- Department of Cardiology, Princes of Wales Hospital, Sydney, NSW, Australia
| | - Aderonke Abiodun
- Institute of Cardiovascular Science, University College London, London, United Kingdom
| | - Mayank Dalakoti
- Division of Cardiology, Department of Medicine, Ng Teng Fong General Hospital, Singapore, Singapore
- Department of Cardiology, National University Heart Centre Singapore, Singapore, Singapore
- Department of Cardiology, NUS Cardiovascular Metabolic Disease Translational Research Program, Singapore, Singapore
| | - Po Fun Chan
- Division of Cardiology, Department of Medicine, Ng Teng Fong General Hospital, Singapore, Singapore
| | - Chieh-Yang Koo
- Department of Cardiology, National University Heart Centre Singapore, Singapore, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Li Ling Tan
- Department of Cardiology, National University Heart Centre Singapore, Singapore, Singapore
| |
Collapse
|
|
8
|
Al-Taie A, Sheta N. Clinically Approved Monoclonal Antibodies-based Immunotherapy: Association With Glycemic Control and Impact Role of Clinical Pharmacist for Cancer Patient Care. Clin Ther 2024; 46:e29-e44. [PMID: 37932154 DOI: 10.1016/j.clinthera.2023.10.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Revised: 08/17/2023] [Accepted: 10/13/2023] [Indexed: 11/08/2023]
Abstract
PURPOSE Compared with more conventional, nonspecific therapy options, such as radiotherapy and chemotherapy, monoclonal antibodies (mAbs) constitute a crucial approach of cancer treatment. Multiple autoimmune diseases have been observed during treatment with mAb medications, including autoimmune diabetes mellitus (DM). This study provides a narrative review of clinically approved mAbs in cancer treatment and focuses on the development of hyperglycemia and DM arising from using these therapies. Furthermore, it highlights the critical role of oncology clinical pharmacists in the management of autoimmune DM and patient care while using these medications in an oncology setting. METHODS An extensive literature search was conducted using various sources of electronic databases, such as Scopus, Embase, Web of Science, and PubMed, and search engines, such as Google Scholar, for studies on mAb classification, types, mechanisms of action, pharmacokinetic properties, current clinical applications, and the associated common adverse effects with significant recommendations for patient care in an oncology setting, along with focusing on the proposed mechanisms and clinical studies that reported the association of DM after the use of these therapies. FINDINGS There are 4 types (murine, chimeric, humanized, and human) and 3 classes (unconjugated, conjugated, and bispecific) of mAbs with several mechanisms of action that can destroy cancer cells, including preventing tumor cell survival cascades, inhibiting tumor growth by interfering with tumor angiogenesis, evading programmed cell death, and bypassing immune checkpoints. However, multiple endocrinopathies, autoimmune diseases, and complications were reported from the use of these medications, including the development of autoimmune DM and diabetic ketoacidosis. These autoimmune disorders were reported most with the use of immune checkpoint inhibitors, including inhibitors of the programmed cell death protein 1 (nivolumab and pembrolizumab), its ligand (atezolizumab, avelumab, and durvalumab), and cytotoxic T-lymphocyte-associated protein 4 (ipilimumab). IMPLICATIONS mAbs are considered important approaches for the treatment of many cancer types. However, a high incidence of hyperglycemia, type 1 DM, and diabetic ketoacidosis is observed with the use of these medications, particularly immune checkpoint inhibitors. It is important for oncologic clinical pharmacists to be involved in addressing these autoimmune disorders from the use of these immunotherapies via the provision of patient education, medication adherence support, close monitoring, and follow-up, which will lead to better health-related outcomes and improved patient quality of life.
Collapse
Affiliation(s)
- Anmar Al-Taie
- Clinical Pharmacy Department, Faculty of Pharmacy, Istinye University, Istanbul, Türkiye.
| | - Najat Sheta
- Clinical Pharmacy Department, Faculty of Pharmacy, Istinye University, Istanbul, Türkiye
| |
Collapse
|
|
9
|
Dong H, Guo H, Du J, Cheng Y, Wang D, Han J, Yuan Z, Yao Z, An R, Wu X, Poulsen KL, Wang Z, Shao S, Fan X, Wang Z, Zhao J. The classification of obesity based on metabolic status redefines the readmission of non-Hodgkin's lymphoma-an observational study. Cancer Metab 2023; 11:24. [PMID: 38057929 DOI: 10.1186/s40170-023-00327-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Accepted: 11/28/2023] [Indexed: 12/08/2023] Open
Abstract
BACKGROUND The relationship between obesity and non-Hodgkin's lymphoma (NHL) was controversial, which may be due to the crudeness definition of obesity based on body mass index (BMI). As obesity and metabolic abnormalities often coexist, we aimed to explore whether the classification of obesity based on metabolic status can help to evaluate the real impact of obesity on the readmission of NHL. METHODS In this retrospective cohort study, utilizing the 2018 Nationwide Readmissions Database, we identified NHL-related index hospitalizations and followed them for non-elective readmission. The patients with NHL were classified as metabolically healthy non-obese (MHNO) and obese (MHO) and metabolically unhealthy non-obese (MUNO) and obese (MUO). Readmission rates for each phenotype were calculated at 30-day intervals. Multiple COX regression was used to analyze the association of metabolic-defined obesity with 30-day, 90-day, and 180-day readmission rates in patients with NHL. RESULTS There were 22,086 index hospitalizations with NHL included. In the multivariate COX regression, MUNO was associated with increased 30-day (HR = 1.113, 95% CI 1.036-1.195), 90-day (HR = 1.148, 95% CI 1.087-1.213), and 180-day readmission rates (HR = 1.132, 95% CI 1.077-1.189), and MUO was associated with increased 30-day (HR=1.219, 95% CI: 1.081-1.374), 90-day (HR = 1.228, 95% CI 1.118-1.348), and 180-day readmission rates (HR = 1.223, 95% CI 1.124-1.33), while MHO had no associations with readmission rates. CONCLUSIONS The presence of metabolic abnormalities with or without obesity increased the risk of non-selective readmission in patients with NHL. However, obesity alone had no associations with the risk of non-selective readmission, suggesting that interventions for metabolic abnormalities may be more important in reducing readmissions of NHL patients.
Collapse
Affiliation(s)
- Hang Dong
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, 250021, China
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
- "Chuangxin China" Innovation Base of stem cell and Gene Therapy for endocrine Metabolic diseases, Jinan, Shandong, 250021, China
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
- Department of Mechanical and Aerospace Engineering, Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
| | - Honglin Guo
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, 250021, China
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
- "Chuangxin China" Innovation Base of stem cell and Gene Therapy for endocrine Metabolic diseases, Jinan, Shandong, 250021, China
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
- Department of Mechanical and Aerospace Engineering, Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
| | - Jing Du
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China
- Department of Endocrinology, The First Affiliated Hospital of Baotou Medical College, Baotou, 014010, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, 250021, China
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
- "Chuangxin China" Innovation Base of stem cell and Gene Therapy for endocrine Metabolic diseases, Jinan, Shandong, 250021, China
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
- Department of Mechanical and Aerospace Engineering, Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
| | - Yiping Cheng
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, 250021, China
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
- "Chuangxin China" Innovation Base of stem cell and Gene Therapy for endocrine Metabolic diseases, Jinan, Shandong, 250021, China
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
- Department of Mechanical and Aerospace Engineering, Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
| | - Dawei Wang
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, 250021, China
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
- "Chuangxin China" Innovation Base of stem cell and Gene Therapy for endocrine Metabolic diseases, Jinan, Shandong, 250021, China
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
- Department of Mechanical and Aerospace Engineering, Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
| | - Junming Han
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, 250021, China
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
- "Chuangxin China" Innovation Base of stem cell and Gene Therapy for endocrine Metabolic diseases, Jinan, Shandong, 250021, China
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
- Department of Mechanical and Aerospace Engineering, Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
| | - Zinuo Yuan
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, 250021, China
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
- "Chuangxin China" Innovation Base of stem cell and Gene Therapy for endocrine Metabolic diseases, Jinan, Shandong, 250021, China
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
- Department of Mechanical and Aerospace Engineering, Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
| | - Zhenyu Yao
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, 250021, China
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
- "Chuangxin China" Innovation Base of stem cell and Gene Therapy for endocrine Metabolic diseases, Jinan, Shandong, 250021, China
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
- Department of Mechanical and Aerospace Engineering, Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
| | - Ran An
- Department of Mechanical and Aerospace Engineering, Case Western Reserve University, Cleveland, OH, USA
| | - Xiaoqin Wu
- Department of Integrative Biology and Pharmacology, McGovern Medical School at UTHealth, Houston, TX, USA
| | - Kyle L Poulsen
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Zhixiang Wang
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, 250021, China
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
- "Chuangxin China" Innovation Base of stem cell and Gene Therapy for endocrine Metabolic diseases, Jinan, Shandong, 250021, China
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
- Department of Mechanical and Aerospace Engineering, Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
| | - Shanshan Shao
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, 250021, China
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
- "Chuangxin China" Innovation Base of stem cell and Gene Therapy for endocrine Metabolic diseases, Jinan, Shandong, 250021, China
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
- Department of Mechanical and Aerospace Engineering, Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China
| | - Xiude Fan
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China.
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, 250021, China.
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China.
- "Chuangxin China" Innovation Base of stem cell and Gene Therapy for endocrine Metabolic diseases, Jinan, Shandong, 250021, China.
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China.
- Department of Mechanical and Aerospace Engineering, Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China.
| | - Zhen Wang
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China.
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, 250021, China.
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China.
- "Chuangxin China" Innovation Base of stem cell and Gene Therapy for endocrine Metabolic diseases, Jinan, Shandong, 250021, China.
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China.
- Department of Mechanical and Aerospace Engineering, Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China.
| | - Jiajun Zhao
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China.
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, 250021, China.
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China.
- "Chuangxin China" Innovation Base of stem cell and Gene Therapy for endocrine Metabolic diseases, Jinan, Shandong, 250021, China.
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China.
- Department of Mechanical and Aerospace Engineering, Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China.
| |
Collapse
|
|
10
|
Kristjanson M, Lambert P, Decker KM, Bruin S, Tingey E, Skrabek P. Steroid-Induced Hyperglycemia and Its Effect on Outcomes of R-CHOP Chemotherapy for Diffuse Large B-Cell Lymphoma. Curr Oncol 2023; 30:10142-10151. [PMID: 38132372 PMCID: PMC10742719 DOI: 10.3390/curroncol30120738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Revised: 11/10/2023] [Accepted: 11/21/2023] [Indexed: 12/23/2023] Open
Abstract
Large doses of steroids are integral to R-CHOP, a first-line systemic therapy for diffuse large B-cell lymphoma (DLBCL), an aggressive form of non-Hodgkin Lymphoma (NHL). Patients on R-CHOP often develop clinically significant hyperglycemia from steroids. There is evidence of harms from steroid-induced hyperglycemia in the context of chemotherapy which are associated with a reduction in overall survival. The objective of our study was to characterize the effect of steroid-induced hyperglycemia on the outcomes of R-CHOP chemotherapy for DLBCL. METHODS We performed a retrospective chart review of 188 patients with DLBCL treated with R-CHOP through CancerCare Manitoba (CCMB) from 1 January 2010 to 31 December 2014. Patients diagnosed with DLBCL were identified using the Manitoba Cancer Registry. The CCMB electronic medical record was reviewed to examine the association between steroid-induced hyperglycemia and subsequent infection, including febrile neutropenic events and overall survival (OS). RESULTS Patients who developed hyperglycemia with steroid exposure became hyperglycemic during their first R-CHOP cycle. No significant differences in OS or rates of infection were found between euglycemic and hyperglycemic subjects. CONCLUSIONS Patients destined to develop steroid-induced hyperglycemia declare themselves early in the course of steroid exposure. No statistically significant reduction in overall survival attributable to steroid-induced hyperglycemia was found.
Collapse
Affiliation(s)
- Mark Kristjanson
- Department of Family Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0W2, Canada
- Urgent Cancer Care, CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, MB R3E 0V9, Canada
| | - Pascal Lambert
- Paul Albrechtsen Research Institute CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, MB R3E 0V9, Canada; (P.L.); (K.M.D.)
- Department of Epidemiology and Cancer Registry, CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, MB R3E 0V9, Canada
| | - Kathleen M. Decker
- Paul Albrechtsen Research Institute CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, MB R3E 0V9, Canada; (P.L.); (K.M.D.)
- Department of Epidemiology and Cancer Registry, CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, MB R3E 0V9, Canada
- Department of Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, 750 Bannatyne Avenue, Winnipeg, MB R3E 0W2, Canada
| | - Sonja Bruin
- Ongomiizwin Health Services Institute of Indigenous Health and Healing, 745 Bannatyne Avenue, Winnipeg, MB R3E 3N4, Canada;
| | - Elizabeth Tingey
- Max Rady College of Medicine, Rady Faculty of Health Sciences 750 Bannatyne Avenue, Winnipeg, MB R3E 0W2, Canada;
| | - Pamela Skrabek
- Department of Medical Oncology & Hematology, CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, MB R3E 0V9, Canada;
- Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0W2, Canada
| |
Collapse
|
|
11
|
Paris J, Legris P, Devaux M, Bost S, Gueneau P, Rossi C, Manfredi S, Bouillet B, Petit JM, Pistre P, Boulin M. Impact of a Tripartite Collaboration between Oncologist, Pharmacist and Diabetologist in the Management of Patients with Diabetes Starting Chemotherapy: The ONCODIAB Trial. Cancers (Basel) 2023; 15:4544. [PMID: 37760514 PMCID: PMC10526306 DOI: 10.3390/cancers15184544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 08/30/2023] [Accepted: 09/08/2023] [Indexed: 09/29/2023] Open
Abstract
BACKGROUND Diabetes negatively impacts cancer prognosis. The objective of this work was to evaluate a tripartite oncologist-pharmacist-diabetologist collaboration in the management of patients with diabetes starting chemotherapy. PATIENTS AND METHODS The prospective ONCODIAB study (NCT04315857) included 102 adults with diabetes starting chemotherapy by whom a continuous glucose monitoring device was worn for fourteen days from the first day of the first and second chemotherapy cycles. The primary outcome was to assess pharmacist and diabetologist interventions. The secondary outcome was to evaluate the impact of the ONCODIAB follow-up on individualized patient glycemic targets at 6 months. RESULTS A total of 191 (2 per patient) were made either by clinical pharmacists (n = 95) or diabetologists (n = 96) during the first two chemotherapy cycles. The anatomic therapeutic chemical drug classes most frequently involved in pharmacist interventions were cardiovascular system (23%), alimentary tract and metabolism (22%), and anti-infectives for systemic use (14%). Diabetologists modified the antidiabetic treatment in 58 (62%) of patients: dose reduction (34%), drug discontinuation (28%), drug addition (24%), and dose increase (15%). Glycated hemoglobin decreased from 7.6 ± 1.7% at baseline to 7.1 ± 1.1% at 6 months (p = 0.02). Compared to individualized targets, HbA1c was higher, in the interval, or lower in 29%, 44%, and 27% of patients at baseline vs. in 8%, 70%, and 22% of patients at 6 months, respectively (p < 10-3). CONCLUSIONS In our study, a close collaboration between oncologists, pharmacists, and diabetologists helped by continuous glucose monitoring led to overall medication optimization and better glycemic control in patients with diabetes starting chemotherapy.
Collapse
Affiliation(s)
- Justine Paris
- Department of Pharmacy, University Hospital, 21000 Dijon, France; (J.P.); (M.D.); (S.B.); (P.G.); (P.P.)
| | - Pauline Legris
- Department of Endocrinology, Diabetes and Metabolic Disorders, University Hospital, 21000 Dijon, France; (P.L.); (B.B.); (J.-M.P.)
| | - Madeline Devaux
- Department of Pharmacy, University Hospital, 21000 Dijon, France; (J.P.); (M.D.); (S.B.); (P.G.); (P.P.)
| | - Stephanie Bost
- Department of Pharmacy, University Hospital, 21000 Dijon, France; (J.P.); (M.D.); (S.B.); (P.G.); (P.P.)
| | - Pauline Gueneau
- Department of Pharmacy, University Hospital, 21000 Dijon, France; (J.P.); (M.D.); (S.B.); (P.G.); (P.P.)
| | - Cedric Rossi
- Department of Clinical Hematology, University Hospital and SAPHIIT UMR 1231, University of Burgundy & Franche Comte, 21000 Dijon, France;
| | - Sylvain Manfredi
- Department of Hepatogastroenterology and Digestive Oncology, University Hospital and EPICAD LNC UMR 1231, University of Burgundy & Franche Comte, 21000 Dijon, France;
| | - Benjamin Bouillet
- Department of Endocrinology, Diabetes and Metabolic Disorders, University Hospital, 21000 Dijon, France; (P.L.); (B.B.); (J.-M.P.)
- PADYS LNC UMR 1231, University of Burgundy & Franche Comte, 21000 Dijon, France
| | - Jean-Michel Petit
- Department of Endocrinology, Diabetes and Metabolic Disorders, University Hospital, 21000 Dijon, France; (P.L.); (B.B.); (J.-M.P.)
- PADYS LNC UMR 1231, University of Burgundy & Franche Comte, 21000 Dijon, France
| | - Pauline Pistre
- Department of Pharmacy, University Hospital, 21000 Dijon, France; (J.P.); (M.D.); (S.B.); (P.G.); (P.P.)
| | - Mathieu Boulin
- Department of Pharmacy, University Hospital, 21000 Dijon, France; (J.P.); (M.D.); (S.B.); (P.G.); (P.P.)
- EPICAD LNC UMR 1231, University of Burgundy & Franche Comte, 21000 Dijon, France
| |
Collapse
|
|
12
|
Kanbour S, Yenokyan G, Abusamaan M, Laheru D, Alam A, El Asmar ML, Virk Z, Hardenbergh D, Mathioudakis N. Association of Long-Term, New-Onset, and Postsurgical Diabetes With Survival in Patients With Resectable Pancreatic Cancer: A Retrospective Cohort Study. Pancreas 2023; 52:e309-e314. [PMID: 37890159 PMCID: PMC11913223 DOI: 10.1097/mpa.0000000000002257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/29/2023]
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Identifying modifiable risk factors, such as diabetes, is crucial. In the context of PDAC diagnosis, diabetes manifests as long-term (LTD), new-onset (NOD), or postsurgical (PSD) phenotypes. The link between these diabetes phenotypes and PDAC survival is debated. MATERIALS AND METHODS We performed a retrospective study on patients with resectable PDAC who underwent pancreatectomy at Johns Hopkins Hospital from 2003 to 2017. We utilized the National Death Index and electronic medical records to determine vital status. We categorized diabetes as LTD, NOD, or PSD based on the timing of diagnosis relative to pancreatic resection. Using multivariable Cox models, we assessed hazard ratios (HRs) for survival times associated with each phenotype, considering known PDAC prognostic factors. RESULTS Of 1556 patients, the 5-year survival was 19% (95% CI, 17-21). No significant survival differences were observed between diabetes phenotypes and non-diabetic patients. NOD and PSD presented nonsignificant increased risks of death (aHR: 1.14 [95% CI, 0.8-1.19] and 1.05 [95% CI, 0.89-1.25], respectively). LTD showed no survival difference (aHR, 0.98; 95% CI, 0.99-1.31). CONCLUSIONS No link was found between diabetes phenotypes and survival in resectable PDAC patients. Comprehensive prospective studies are required to validate these results.
Collapse
Affiliation(s)
- Sarah Kanbour
- From the Division of Endocrinology, Diabetes, and Metabolism
| | - Gayane Yenokyan
- Johns Hopkins Biostatistics Center, Department of Biostatistics
| | | | - Daniel Laheru
- Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Ayman Alam
- From the Division of Endocrinology, Diabetes, and Metabolism
| | | | - Zunaira Virk
- From the Division of Endocrinology, Diabetes, and Metabolism
| | | | | |
Collapse
|
|
13
|
Hyperglycemia and Glycemic Variability Associated with Glucocorticoids in Women without Pre-Existing Diabetes Undergoing Neoadjuvant or Adjuvant Taxane Chemotherapy for Early-Stage Breast Cancer. J Clin Med 2023; 12:jcm12051906. [PMID: 36902693 PMCID: PMC10004215 DOI: 10.3390/jcm12051906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 02/22/2023] [Accepted: 02/24/2023] [Indexed: 03/04/2023] Open
Abstract
Glucocorticoids, which are administered with chemotherapy, cause hyperglycemia. Glycemic variability among breast cancer patients without diabetes is not well known. A retrospective cohort study was conducted involving early-stage breast cancer patients without diabetes who received dexamethasone prior to neoadjuvant or adjuvant taxane chemotherapy between August 2017-December 2019. Random blood glucose levels were analyzed, and steroid-induced hyperglycemia (SIH) was defined as a random glucose level of >140 mg/dL. A multivariate proportional hazards model was used to identify the risk factors of SIH. Out of 100 patients, the median age was 53 years (IQR: 45-63.5). A total of 45% of patients were non-Hispanic White, 28% Hispanic, 19% Asian, and 5% African American. The incidence of SIH was 67%, and glycemic fluctuations were highest in those with glucose levels of >200 mg/dL. Non-Hispanic White patients represented a significant predictor for time to SIH, with a hazard ratio of 2.5 (95% CI: 1.04, 5.95, p = 0.039). SIH was transient in over 90% of the patients, and only seven patients remained hyperglycemic after glucocorticoid and chemotherapy completion. Pretaxane dexamethasone-induced hyperglycemia was observed in 67% of the patients, with the greatest glycemic lability in those patients with blood glucose levels of >200 mg/dL. The non-Hispanic White patients had a higher risk of developing SIH.
Collapse
|
|
14
|
Mailliez A, Ternynck C, Duhamel A, Mailliez A, Ploquin A, Desauw C, Lemaitre M, Bertrand N, Vambergue A, Turpin A. Diabetes is associated with high risk of severe adverse events during chemotherapy for cancer patients: A single-center study. Int J Cancer 2023; 152:408-416. [PMID: 36054752 PMCID: PMC10087807 DOI: 10.1002/ijc.34268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Revised: 05/31/2022] [Accepted: 06/02/2022] [Indexed: 02/01/2023]
Abstract
Diabetes mellitus (DM) is a common comorbidity among cancer patients, but its impact on chemotherapy tolerance has not been widely studied. We aimed to compare the occurrence of severe grade 3/4 adverse events (G3/4 AEs) within 90 days of starting chemotherapy between patients with and without diabetes. We conducted a retrospective single-center study in Lille University Hospital Oncology Department, France. Patients who received the first cycle of chemotherapy for gastrointestinal, gynecological or cancer of unknown primary source between 1 May 2013 and 1 May 2016, were included. Overall, 609 patients were enrolled: 490 patients without diabetes (80.5%) and 119 patients with diabetes (19.5%). Within 90 days of starting chemotherapy, patients with diabetes had a significantly higher occurrence of AEs G3/4 compared to those with no diabetes (multivariate odds ratio [OR]: 1.57 [1.02-2.42], P = .04). More frequent G3/4 AEs in patients with diabetes were infection (26%), hematological disorders (13%), endocrine disorders (13%) and deterioration of the general condition (13%). In the year following the beginning of chemotherapy, patients with diabetes were twice as likely to be hospitalized as those without diabetes (univariate OR: 2.1 [1.40-3.15], P = .0003). After multivariate adjustment, diabetes was no longer significantly associated with the risk of hospitalization (P = .051). There were no differences between patients with and without diabetes regarding dose reduction and chemotherapy treatment delays (P = .61 and P = .30, respectively). Our study suggests the need for better consideration of DM in the personalized care plan to improve chemotherapy tolerance and quality of life of patients with DM.
Collapse
Affiliation(s)
- Aurélie Mailliez
- Department of Geriatrics, CHU Lille, Lille, France.,U1167-RID-AGE-Facteurs de Risque et Déterminants Moléculaires des Maladies Liées au Vieillissement, Université de Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France
| | - Camille Ternynck
- ULR 2694-METRICS: Évaluation Des Technologies De Santé Et Des Pratiques Médicales, Université de Lille, CHU Lille, Lille, France
| | - Alain Duhamel
- ULR 2694-METRICS: Évaluation Des Technologies De Santé Et Des Pratiques Médicales, Université de Lille, CHU Lille, Lille, France
| | - Audrey Mailliez
- Medical Oncology Department, Breast Cancer Unit, Oscar Lambret Center, Lille, France
| | - Anne Ploquin
- Medical Oncology Department, CHU Lille, ULR 2694 METRICS, University of Lille, Lille, France
| | - Christophe Desauw
- Medical Oncology Department, CHU Lille, ULR 2694 METRICS, University of Lille, Lille, France
| | - Madleen Lemaitre
- CHU Lille, Department of Diabetology, Endocrinology, Metabolism and Nutrition, Lille University Hospital, Lille, France.,European Genomic Institute for Diabetes, Lille University School of Medicine, Lille, France
| | - Nicolas Bertrand
- Medical Oncology Department, CHU Lille, ULR 2694 METRICS, University of Lille, Lille, France
| | - Anne Vambergue
- CHU Lille, Department of Diabetology, Endocrinology, Metabolism and Nutrition, Lille University Hospital, Lille, France.,European Genomic Institute for Diabetes, Lille University School of Medicine, Lille, France
| | - Anthony Turpin
- CHU Lille, Institut Pasteur de Lille, UMR9020-UMR-S 1277-Canther-Cancer Heterogeneity, Plasticity and Resistance to Therapies, University of Lille, CNRS, Inserm, Lille, France.,Medical Oncology Department, CHU Lille, University of Lille, Lille, France
| |
Collapse
|
|
15
|
Pinheiro LC, Cho J, Rothman J, Zeng C, Wilson M, Kern LM, Tamimi RM, Safford MM. Diabetes and cancer co-management: patient-reported challenges, needs, and priorities. Support Care Cancer 2023; 31:145. [PMID: 36729259 PMCID: PMC9892662 DOI: 10.1007/s00520-023-07604-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Accepted: 01/20/2023] [Indexed: 02/03/2023]
Abstract
INTRODUCTION Twenty percent of breast cancer survivors have co-occurring diabetes and face a 50% greater risk of 10-year mortality compared to survivors without diabetes. Individuals with cancer are often overwhelmed during cancer treatment and have less time for their diabetes, contributing to worse outcomes. We elicited perspectives of breast cancer survivors with diabetes regarding their specific needs for diabetes and cancer co-management. METHODS We conducted semi-structured interviews with women with breast cancer aged 40 + years at three New York City hospitals from May 2021 to March 2022. Eligible participants had type 2 diabetes or pre-diabetes. Interviews were audio-recorded, professionally transcribed, and coded by two independent reviewers. RESULTS We conducted interviews with 15 females with breast cancer of mean age 61.5 years (SD 7.2); 70% were Black, Hispanic, or Asian/Pacific Islander, and 20% had only a high school education. Most (73%) patients were insured by Medicaid or Medicare, and 73% underwent chemotherapy as part of their cancer care. Of the 15 participants, 60% reported that their glucose levels were of control during cancer treatment and nearly 50% reported glucose levels > 200 mg/dL. We identified distinct themes that reflect patient-reported challenges (worse glucose control after initiation of cancer treatment, lack of information on co-managing diabetes, negative psychosocial effects, burden of diabetes management during cancer care) and needs/priorities (designated provider to help, educational resources specific to diabetes and cancer, and individualized care plans). CONCLUSIONS Patients co-managing diabetes and cancer face challenges and have unmet needs that should be addressed to improve diabetes control during cancer treatment. Our findings can directly inform interventions aimed at improving glucose control in this population.
Collapse
Affiliation(s)
- Laura C. Pinheiro
- grid.5386.8000000041936877XDivision of General Internal Medicine, Department of Medicine, Weill Cornell Medicine, 420 East 70th Street, Box 331, New York, NY USA ,grid.5386.8000000041936877XDivision of Epidemiology, Department of Population Health Science, Weill Cornell Medicine, New York, NY USA
| | - Jacklyn Cho
- grid.36425.360000 0001 2216 9681Renaissance School of Medicine at Stony Brook University, NY Stony Brook, USA
| | - Julia Rothman
- grid.5386.8000000041936877XCornell University, Ithaca, NY USA
| | - Caroline Zeng
- grid.5386.8000000041936877XDivision of General Internal Medicine, Department of Medicine, Weill Cornell Medicine, 420 East 70th Street, Box 331, New York, NY USA
| | - Micayla Wilson
- grid.266093.80000 0001 0668 7243University of California Irvine, Irvine, CA USA
| | - Lisa M. Kern
- grid.5386.8000000041936877XDivision of General Internal Medicine, Department of Medicine, Weill Cornell Medicine, 420 East 70th Street, Box 331, New York, NY USA
| | - Rulla M. Tamimi
- grid.5386.8000000041936877XDivision of Epidemiology, Department of Population Health Science, Weill Cornell Medicine, New York, NY USA
| | - Monika M. Safford
- grid.5386.8000000041936877XDivision of General Internal Medicine, Department of Medicine, Weill Cornell Medicine, 420 East 70th Street, Box 331, New York, NY USA
| |
Collapse
|
|
16
|
Kandil I, Keely E. Glucocorticoid-Induced Hyperglycemia in Oncologic Outpatients: A Narrative Review Using the Quadruple Aim Framework. Can J Diabetes 2022; 46:730-739. [PMID: 36055914 DOI: 10.1016/j.jcjd.2022.02.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 01/04/2022] [Accepted: 02/28/2022] [Indexed: 10/18/2022]
Abstract
Glucocorticoids are a central part of cancer treatment protocols. Their use in patients receiving chemotherapy increases patient risk of hyperglycemia and associated adverse outcomes. Despite this, there have been few published protocols that guide the management of this patient group. In this narrative review, we use the quadruple aim as a framework to evaluate the current literature, including interventions, on glucocorticoid-induced hyperglycemia in patients receiving oncologic treatment, with a focus on the outpatient setting. Findings were drawn from published review articles, observational studies, qualitative reports and costing data. Results were synthesized using the framework's 4 dimensions of care: population health, provider experience, patient experience and cost. Prospective studies proposing an intervention on oncologic patients receiving glucocorticoids were identified as intervention studies. Management of glucocorticoid-induced hyperglycemia in oncologic patients is a complex problem with no published interventions addressing all components of the quadruple aim. Most evidence on this population is based on retrospective studies. Six prospective intervention studies were identified and highlighted in this review, and only 2 were exclusively in the outpatient context. Challenges included lack of standardization in screening strategies and a paucity of interventions that have examined impact on patient and provider experience. There is limited evaluation of the impact of interventions targeting glycemic management on clinical outcomes and cost of care delivery, especially in the outpatient context. We propose a conceptual framework for evaluation of quality improvement programs. Management of glucocorticoid-induced hyperglycemia in the outpatient setting is complex and requires well-designed intervention studies evaluated across the quadruple aim.
Collapse
Affiliation(s)
- Ihab Kandil
- Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Erin Keely
- Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Division of Endocrinology and Metabolism, The Ottawa Hospital, Ottawa, Ontario, Canada.
| |
Collapse
|
|
17
|
Toyoshima MTK, Cukier P, Souza ABCD, Pereira J, Hoff AO, Nery M. Effects of glucocorticoids on interstitial glucose concentrations in individuals with hematologic cancer and without known diagnosis of diabetes: a pilot study. EINSTEIN-SAO PAULO 2022; 20:eAO8031. [PMID: 35830152 PMCID: PMC9262279 DOI: 10.31744/einstein_journal/2022ao8031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 12/02/2021] [Indexed: 01/08/2023] Open
Abstract
Objective To analyze interstitial glucose behavior during glucocorticoid use in non-diabetic patients receiving chemotherapy for hematologic malignancies. Methods Prospective pilot study carried out to assess interstitial glucose levels in 15 non-diabetic individuals with hematologic malignancies who received glucocorticoids in combination with chemotherapy. The FreeStyle Libre flash monitoring system (Abbott Diabetes Care) was used for up to 14 days to measure interstitial glucose. Results Median age and body mass index were 53 (42-61) years and 25 (23-28) kg/m2 respectively. Interstitial glucose levels >180mg/dL lasting at least one hour were detected in 60% of participants. Interstitial glucose profile parameters (median and peak interstitial glucose levels and percentage of time during which interstitial glucose levels were >180mg/dL) were significantly (p<0.01) higher during glucocorticoid use (115mg/dL, 218mg/dL and 10% respectively) than after glucocorticoid discontinuation (97mg/dL, 137mg/dL and 0% respectively). Mean interstitial glucose levels increased in the afternoon and at night during glucocorticoid use. Conclusion This pilot study was the first to evaluate interstitial glucose levels in non-diabetic individuals using glucocorticoids in treatment of hematologic cancer. Glucocorticoid use during chemotherapy significantly increases interstitial glucose levels in these patients.
Collapse
|
|
18
|
Joharatnam-Hogan N, Morganstein DL. Diabetes and Cancer - optimising glycaemic control. J Hum Nutr Diet 2022; 36:504-513. [PMID: 35748508 DOI: 10.1111/jhn.13051] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 05/31/2022] [Indexed: 01/08/2023]
Abstract
Diabetes and cancer are both common and increasingly prevalent conditions, but emerging epidemiological evidence confirms that the risk of developing a number of common cancers is increased in those with type 2 diabetes. The risk of cancer in type 1 diabetes is less clearly defined, and therefore this review will focus on type 2 diabetes. Emerging evidence also supports an influence of diabetes on outcomes of cancer treatment. However, this relationship is bi-directional, with cancer and its treatment impacting on glucose control, whilst there is also emerging evidence that diabetes care can deteriorate after a cancer diagnosis (summarised in Figure 1). Despite these clear links there is a lack of evidence to guide clinicians in how to manage patients with diabetes during their cancer treatment. Although recent UK guidelines have started to address this, with the development of guidance for the management of hyperglycaemia in cancer, there is a clear need for wider guidance on the management of multi-morbidity during cancer, including diabetes and obesity, to incorporate nutritional management We have therefore undertaken a narrative review of the evidence of links between type 2 diabetes and cancer incidence and outcomes, and discuss the challenges to diabetes care during cancer treatment. This article is protected by copyright. All rights reserved.
Collapse
Affiliation(s)
| | - Daniel L Morganstein
- Royal Marsden Hospital, Fulham Roal, London, SW3 6JJ, UK.,Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK
| |
Collapse
|
|
19
|
Risk of diabetes and the impact on preexisting diabetes in lymphoma patients treated with steroid-containing immunochemotherapy. Blood Adv 2022; 6:4427-4435. [PMID: 35679481 DOI: 10.1182/bloodadvances.2021006859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 05/29/2022] [Indexed: 01/08/2023] Open
Abstract
First-line treatments for lymphomas often include high doses of prednisolone, but the risks of new-onset diabetes mellitus (DM) or worsening of pre-existing DM following treatment with cyclic high dose corticosteroids is unknown. This cohort study matched non-Hodgkin lymphoma (NHL) patients treated with steroid-containing immunochemotherapy, i.e. R-CHOP(-like) and R-CVP, between 2002 and 2015 to individuals from the Danish population to investigate the risks of new-onset DM. For patients with pre-existing DM, the risks of insulin dependency and anthracycline-associated cardiovascular diseases (CVD) were assessed. In total, 5,672 NHL patients and 28,360 matched comparators were included. Time-varying incidence rate ratios (IRRs) showed increased risk of DM in the first year after treatment compared to matched comparators with the highest IRR being 2.7. The absolute risks were higher among patients in the first two years, but the difference was clinically insignificant. NHL patients with pre-existing DM had increased risks of insulin prescriptions with 0.5-, 5-, and 10-year cumulative risk differences of insulin treatment of 15.3, 11.8, and 6.0 percentage units as compared to the DM comparators. In a landmark analysis at one year, DM patients with lymphoma had decreased risks of insulin dependency compared to comparators. Time-varying IRRs showed a higher CVD risk for NHL patients with DM as compared to comparators in the first year after treatment. NHL patients treated with steroid-containing immunochemotherapy regimens have a clinically insignificant increased risk of DM in the first year following treatment, and patients with pre-existing DM have a temporary increased risk of insulin prescriptions and CVD.
Collapse
|
|
20
|
Factors leading to alpelisib discontinuation in patients with hormone receptor positive, human epidermal growth factor receptor-2 negative breast cancer. Breast Cancer Res Treat 2022; 192:303-311. [PMID: 35000092 DOI: 10.1007/s10549-021-06476-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Accepted: 12/02/2021] [Indexed: 11/02/2022]
Abstract
PURPOSE Alpelisib is a phosphoinositide-3-kinase inhibitor approved for hormone-receptor-positive, PIK3CA-mutated metastatic breast cancer. However, length of drug exposure, maximum-tolerated dose, and therefore clinical response can vary significantly outside of the trial setting. This study evaluates our center's "real world" experience with alpelisib and focuses on duration of therapy and factors associated with cancer progression. METHODS Patients receiving alpelisib at our center between 2019 and 2021 were identified. We evaluated duration of alpelisib therapy and the causative reasons for drug discontinuation. The association of drug duration and dose with subsequent cancer progression were assessed, along with the association between hyperglycemia during alpelisib therapy and cancer progression. RESULTS Sixty-two women prescribed alpelisib were included (mean age 61 years). Disease progression was the most common reason for drug discontinuation, while discontinuation within 30 days was primarily attributed to adverse events (AEs). Among those who progressed, median time to progression was longer in those on alpelisib for > 90 days compared with those on alpelisib for ≤ 90 days (187 vs. 77 days, p < 0.001). At 200 days, freedom from progression was greater for those on alpelisib for > 90 days compared to those receiving therapy for ≤ 90 days (59% vs. 19%, p = 0.001). Median blood glucose as a continuous variable was associated with disease progression (HR 1.01, 95% CI 1.00-1.02, p = 0.02). CONCLUSION While progression of disease is the largest contributor to alpelisib discontinuation, AEs are the leading cause for early drug cessation. Shorter alpelisib exposure is associated with greater cancer progression. Further studies are needed to determine the impact of sustained hyperglycemia on cancer progression.
Collapse
|
|
21
|
Yang J, Zhao B, Zhou H, Jia B, Chen L. Blood glucose related adverse drug reaction of antitumor monoclonal antibodies: a retrospective analysis using Vigibase. BRAZ J PHARM SCI 2022. [DOI: 10.1590/s2175-97902020000118893] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Jincheng Yang
- Chinese Academy of Medical Sciences and Peking Union Medical College, China
| | - Bin Zhao
- Chinese Academy of Medical Sciences & Peking Union Medical College, China
| | - Haiyan Zhou
- Chinese Academy of Medical Sciences and Peking Union Medical College, China
| | - Bei Jia
- Chinese Academy of Medical Sciences and Peking Union Medical College, China
| | - Lianzhen Chen
- Chinese Academy of Medical Sciences and Peking Union Medical College, China
| |
Collapse
|
|
22
|
Sublethal concentrations of high glucose prolong mitotic arrest in a spindle assembly checkpoint activity dependent manner in budding yeast. Biologia (Bratisl) 2021. [DOI: 10.1007/s11756-021-00912-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
|
|
23
|
Yim C, Mansell K, Hussein N, Arnason T. Current cancer therapies and their influence on glucose control. World J Diabetes 2021; 12:1010-1025. [PMID: 34326951 PMCID: PMC8311484 DOI: 10.4239/wjd.v12.i7.1010] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 04/11/2021] [Accepted: 06/25/2021] [Indexed: 02/06/2023] Open
Abstract
This review focuses on the development of hyperglycemia arising from widely used cancer therapies spanning four drug classes. These groups of medications were selected due to their significant association with new onset hyperglycemia, or of potentially severe clinical consequences when present. These classes include glucocorticoids that are frequently used in addition to chemotherapy treatments, and the antimetabolite class of 5-fluorouracil-related drugs. Both of these classes have been in use in cancer therapy since the 1950s. Also considered are the phosphatidyl inositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR)-inhibitors that provide cancer response advantages by disrupting cell growth, proliferation and survival signaling pathways, and have been in clinical use as early as 2007. The final class to be reviewed are the monoclonal antibodies selected to function as immune checkpoint inhibitors (ICIs). These were first used in 2011 for advanced melanoma and are rapidly becoming widely utilized in many solid tumors. For each drug class, the literature has been reviewed to answer relevant questions about these medications related specifically to the characteristics of the hyperglycemia that develops with use. The incidence of new glucose elevations in euglycemic individuals, as well as glycemic changes in those with established diabetes has been considered, as has the expected onset of hyperglycemia from their first use. This comparison emphasizes that some classes exhibit very immediate impacts on glucose levels, whereas other classes can have lengthy delays of up to 1 year. A comparison of the spectrum of severity of hyperglycemic consequences stresses that the appearance of diabetic ketoacidosis is rare for all classes except for the ICIs. There are distinct differences in the reversibility of glucose elevations after treatment is stopped, as the mTOR inhibitors and ICI classes have persistent hyperglycemia long term. These four highlighted drug categories differ in their underlying mechanisms driving hyperglycemia, with clinical presentations ranging from potent yet transient insulin resistant states [type 2 diabetes mellitus (T2DM) -like] to rare permanent insulin-deficient causes of hyperglycemia. Knowledge of the relative incidence of new onset hyperglycemia and the underlying causes are critical to appreciate how and when to best screen and treat patients taking any of these cancer drug therapies.
Collapse
Affiliation(s)
- Carly Yim
- Department of Medicine, University of Saskatchewan, Saskatoon S7N 0W8, Saskatchewan, Canada
| | - Kerry Mansell
- College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon S7N 5E5, Saskatchewan, Canada
| | - Nassrein Hussein
- Department of Medicine, Division of Endocrinology, University of Saskatchewan, Saskatoon S7N 0W8, Saskatchewan, Canada
| | - Terra Arnason
- Departments of Anatomy and Cell Biology and Medicine, Division of Endocrinology, University of Saskatchewan, Saskatoon S7N 0W8, Saskatchewan, Canada
| |
Collapse
|
|
24
|
Lee EK, Koo B, Hwangbo Y, Lee YJ, Baek JY, Cha YJ, Kim SY, Sim SH, Lee KS, Park IH, Lee H, Joo J, Go S, Heo SC, Moon MK. Incidence and disease course of new-onset diabetes mellitus in breast and colorectal cancer patients undergoing chemotherapy: A prospective multicenter cohort study. Diabetes Res Clin Pract 2021; 174:108751. [PMID: 33722701 DOI: 10.1016/j.diabres.2021.108751] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 02/24/2021] [Accepted: 03/05/2021] [Indexed: 10/21/2022]
Abstract
AIMS To investigate the incidence of and risk factors for new-onset type 2 diabetes mellitus (DM) developed during chemotherapy that included steroids in cancer patients without DM. METHODS This multicenter, prospective, and observational cohort study enrolled 299 cancer patients without DM (aged > 18 years), planning 4-8 cycles of adjuvant chemotherapy. The endpoints were the incidence, remission rate, and independent determinants of new-onset DM during chemotherapy. RESULTS Between April 2015 and March 2018, 270 subjects with colorectal cancer or breast cancer (mean age, 51.0 years) completed the follow up (mean 39 months). Of whom, 17 subjects (6.3%) developed DM within a median time of 90 days (range, 17-359 days). Male sex (hazard ratio [HR], 15.839; 95% confidence interval [CI], 2.004-125.20) and impaired fasting glucose (IFG) at baseline (HR, 8.307; CI, 1.826-37.786) were independent risk factors. Six months after chemotherapy completion, 11/17 subjects (64.7%) experienced DM remission, associated with a significantly higher C-peptide level at baseline (C-peptide levels, 1.3 ng/mL in subjects with remission and 0.9 ng/mL in subjects without remission, age- and sex-adjusted P = 0.007). CONCLUSIONS DM incidence was 6.3% in patients who received chemotherapy with dexamethasone. Close monitoring for hyperglycemia is recommended, especially for men with IFG. TRIAL REGISTRATION ClinicalTrials.gov (NCT03062072).
Collapse
Affiliation(s)
- Eun Kyung Lee
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Thyroid Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Bokyung Koo
- Division of Endocrinology, Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yul Hwangbo
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Thyroid Cancer, National Cancer Center, Goyang, Republic of Korea
| | - You Jin Lee
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Thyroid Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Ji Yeon Baek
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Colorectal Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Yong Jun Cha
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Colorectal Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Sun Young Kim
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Colorectal Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Sung Hoon Sim
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Breast Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Keun Seok Lee
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Breast Cancer, National Cancer Center, Goyang, Republic of Korea
| | - In Hae Park
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Breast Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Hyewon Lee
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea
| | - Jungnam Joo
- Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, USA
| | - Sujeong Go
- Center for Thyroid Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Seung Chul Heo
- Department of Surgery, Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Min Kyong Moon
- Division of Endocrinology, Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
| |
Collapse
|
|
25
|
Ahn HR, Kang SY, Youn HJ, Jung SH. Hyperglycemia during Adjuvant Chemotherapy as a Prognostic Factor in Breast Cancer Patients without Diabetes. J Breast Cancer 2020; 23:398-409. [PMID: 32908790 PMCID: PMC7462816 DOI: 10.4048/jbc.2020.23.e44] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Accepted: 06/26/2020] [Indexed: 12/22/2022] Open
Abstract
Purpose Breast cancer treatments, including chemotherapy, administered in combination with glucocorticoids can induce hyperglycemia. This study aimed to investigate the effect of hyperglycemia during adjuvant chemotherapy on the prognosis of breast cancer patients without a known history of diabetes. Methods In this study, 936 patients who underwent breast cancer surgery from 2010 to 2015 were initially selected as participants. Chemotherapy-related hyperglycemia was defined as fasting plasma glucose levels ≥ 100 mg/dL or random blood glucose levels ≥ 140 mg/dL during 2 or more cycles of adjuvant chemotherapy. After dividing the patients into the euglycemia and hyperglycemia groups, univariate and multivariate analyses were performed, and survival outcomes were analyzed by propensity score matching. Results The mean age of the patients was 47.4 ± 7.7 years, and the median follow-up period was 70.1 months. Eighty-two patients (19.4%) were diagnosed as having hyperglycemia. There were significant differences between the euglycemia and hyperglycemia groups with respect to age, hypertension, body mass index, axillary surgery extents, nodal stage, and total steroid dosage. T stage, vascular invasion, and hyperglycemia were identified as prognostic factors of relapse-free survival (RFS). The 5-year RFS rates were 92.0% and 82.3% in the euglycemia and hyperglycemia groups, respectively, and there was a statistically significant difference between the 2 groups (p = 0.011). The 5-year overall survival rates were 94.6% and 92.0% in the euglycemia and hyperglycemia groups, respectively, showing no statistically significant difference between the 2 groups (p = 0.113). Conclusion These data suggest that hyperglycemia during adjuvant chemotherapy is a prognostic factor for RFS in breast cancer patients without diabetes.
Collapse
Affiliation(s)
- Ha Rim Ahn
- Department of Surgery, Research Institute of Clinical Medicine, Jeonbuk National University Hospital, Jeonbuk National University and Biomedical Research Institute, Jeonju, Korea
| | - Sang Yull Kang
- Department of Surgery, Research Institute of Clinical Medicine, Jeonbuk National University Hospital, Jeonbuk National University and Biomedical Research Institute, Jeonju, Korea
| | - Hyun Jo Youn
- Department of Surgery, Research Institute of Clinical Medicine, Jeonbuk National University Hospital, Jeonbuk National University and Biomedical Research Institute, Jeonju, Korea
| | - Sung Hoo Jung
- Department of Surgery, Research Institute of Clinical Medicine, Jeonbuk National University Hospital, Jeonbuk National University and Biomedical Research Institute, Jeonju, Korea
| |
Collapse
|
|
26
|
The role of metabolic diseases in cardiotoxicity associated with cancer therapy: What we know, what we would know. Life Sci 2020; 255:117843. [PMID: 32464123 DOI: 10.1016/j.lfs.2020.117843] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 05/16/2020] [Accepted: 05/22/2020] [Indexed: 12/12/2022]
Abstract
Metabolic diseases, such as obesity and type 2 diabetes, are known risk factors for cardiovascular (CV) diseases. Thus, patients with those comorbidities could be at increased risk of experiencing cardiotoxicity related to treatment with Anthracyclines and the other new generation targeted anticancer drugs. However, investigations addressing the mechanisms underlying the development of CV complications and poor outcome in such cohort of patients are still few and controversial. Given the importance of a personalized approach against chemotherapy-induced cardiomyopathy, this review summarizes our current knowledge on the pathophysiology of chemotherapy-induced cardiomyopathy and its association with obesity and type 2 diabetes. Along with clinical evidences, future perspectives of preclinical research around this field and its role in addressing important open questions, including the development of more proactive strategies for prevention, and treatment of cardiotoxicity during and after chemotherapy in the presence of metabolic diseases, is also presented.
Collapse
|
|
27
|
Marić A, Miličević T, Vučak Lončar J, Galušić D, Radman M. Patterns of Glucose Fluctuation are Challenging in Patients Treated for Non-Hodgkin's Lymphoma. Int J Gen Med 2020; 13:131-140. [PMID: 32346306 PMCID: PMC7167272 DOI: 10.2147/ijgm.s245779] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Accepted: 03/25/2020] [Indexed: 12/13/2022] Open
Abstract
Purpose This cohort study aimed to determine patterns of glycemic fluctuation and changes in metabolic parameters during and after corticosteroid administration in newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP chemotherapy. Patients and Methods The study was performed in 20 patients of whom 11 had diabetes and 9 were nondiabetics. Anthropometric parameters were collected, and blood samples were taken four times during the study to analyze metabolic parameters. Capillary glucose was measured seven times a day (fasting, before mean meals, postprandial, and before bedtime) to evaluate the glycemic profile. Results In all 20 patients, acute glucocorticoid administration resulted in the elevation of average glucose levels, dominantly postprandial in the afternoon which correlates with corticosteroid peak action. In 7 out of 11 diabetics, prandial insulin was started during corticosteroid administration and discontinued afterward. Although none of our nondiabetic patients met diabetes criteria, evident is the elevation in average glycemia levels six weeks after corticosteroid administration. Potentially, even transient corticosteroid administration reduces insulin sensitivity and contributes to later glycemic disturbances. HbA1c levels were higher at the end of the study while fructosamine levels were higher during the study. Conclusion Patients and health-care professionals need to be aware of corticosteroid-induced hyperglycemia. We recommend identifying risk factors, measuring glycemia before, during, and after corticosteroid administration, and starting the adequate therapy as soon as possible.
Collapse
Affiliation(s)
- Andreja Marić
- Department of Internal Medicine, County Hospital Čakovec, Čakovec 40000, Croatia
| | - Tanja Miličević
- Department of Internal Medicine, University Hospital Center Split, Split 21000, Croatia
| | - Jelena Vučak Lončar
- Department of Internal Medicine, County Hospital Zadar, Zadar 23000, Croatia
| | - Davor Galušić
- Department of Internal Medicine, University Hospital Center Split, Split 21000, Croatia
| | - Maja Radman
- Department of Internal Medicine, University Hospital Center Split, Split 21000, Croatia
| |
Collapse
|
|
28
|
Determining the Impact of a Cancer Diagnosis on Diabetes Management: A Systematic Literature Review. Am J Clin Oncol 2020; 42:870-883. [PMID: 31592804 DOI: 10.1097/coc.0000000000000612] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVES Cancer patients with comorbid diabetes have a 50% increased risk of all-cause mortality compared with cancer patients without diabetes. Less attention to diabetes management (glucose control, medication adherence, and diabetes self-management behaviors) during active cancer treatment is hypothesized as an explanation for worse outcomes among diabetic cancer patients. The objective of this systematic review is to determine and quantify how a cancer diagnosis impacts diabetes management. METHODS Quantitative and qualitative studies evaluating diabetes management among patients were identified by searching 4 databases: MEDLINE, EMBASE, The Cochrane Library, and Web of Science. Two independent reviewers extracted data and summarized results from eligible studies. Study quality was formally assessed. RESULTS Thirty-six studies met all inclusion criteria. We observed heterogeneity across studies in terms of study design, sample size, cancer site, type of diabetes management evaluated, and quality. Numerous articles discussed that overall, glucose control, medication adherence, and diabetes self-management behaviors declined following a cancer diagnosis. However, findings were inconsistent across studies. CONCLUSIONS Although the effects of a cancer diagnosis on diabetes management are mixed, when results across studies were synthesized together, diabetes management appeared to generally decline after a cancer diagnosis. Declines in diabetes management seem to be primarily due to shifts in the priority of care from diabetes management to cancer. A next critical step in this line of work is to identify patient and provider level predictors of better or worse diabetes management to design and test interventions aimed at improving effective diabetes management for cancer patients.
Collapse
|
|
29
|
Kesh K, Mendez R, Abdelrahman L, Banerjee S, Banerjee S. Type 2 diabetes induced microbiome dysbiosis is associated with therapy resistance in pancreatic adenocarcinoma. Microb Cell Fact 2020; 19:75. [PMID: 32204699 PMCID: PMC7092523 DOI: 10.1186/s12934-020-01330-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Accepted: 03/12/2020] [Indexed: 12/14/2022] Open
Abstract
Resistance to therapy is one of the major factors that contribute to dismal survival statistics in pancreatic cancer. While there are many tumor intrinsic and tumor microenvironment driven factors that contribute to therapy resistance, whether pre-existing metabolic diseases like type 2 diabetes (T2D) contribute to this has remained understudied. It is well accepted that hyperglycemia associated with type 2 diabetes changes the gut microbiome. Further, hyperglycemia also enriches for a "stem-like" population within the tumor. In the current study, we observed that in a T2D mouse model, the microbiome changed significantly as the hyperglycemia developed in these animals. Our results further showed that, tumors implanted in the T2D mice responded poorly to gemcitabine/paclitaxel (Gem/Pac) standard of care compared to those in the control group. A metabolomic reconstruction of the WGS of the gut microbiota further revealed that an enrichment of bacterial population involved in drug metabolism in the T2D group. Additionally, we also observed an increase in the CD133+ tumor cells population in the T2D model. These observations indicated that in an animal model for T2D, microbial dysbiosis is associated with increased resistance to chemotherapeutic compounds.
Collapse
Affiliation(s)
- Kousik Kesh
- Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA
- Sylvester Comprehensive Cancer Center, Miami, FL, USA
| | - Roberto Mendez
- Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA
- Sylvester Comprehensive Cancer Center, Miami, FL, USA
- Miami Integrative Metabolomics Research Center, University of Miami, Miami, FL, USA
| | - Leila Abdelrahman
- Miami Integrative Metabolomics Research Center, University of Miami, Miami, FL, USA
| | - Santanu Banerjee
- Sylvester Comprehensive Cancer Center, Miami, FL, USA.
- Miami Integrative Metabolomics Research Center, University of Miami, Miami, FL, USA.
- Department of Surgery, Miller School of Medicine, University of Miami, Biomedical Research Building Suite 516, 1501, NW 10th Ave, Miami, FL, 33156, USA.
| | - Sulagna Banerjee
- Sylvester Comprehensive Cancer Center, Miami, FL, USA.
- Department of Surgery, Miller School of Medicine, University of Miami, Biomedical Research Building, Suite 508, 1501, NW 10th Ave, Miami, FL, 33156, USA.
| |
Collapse
|
|
30
|
Pinheiro LC, Soroka O, Kern LM, Leonard JP, Safford MM. Diabetes care management patterns before and after a cancer diagnosis: A SEER-Medicare matched cohort study. Cancer 2020; 126:1727-1735. [PMID: 31999848 DOI: 10.1002/cncr.32728] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Revised: 12/16/2019] [Accepted: 12/28/2019] [Indexed: 12/20/2022]
Abstract
BACKGROUND Diabetes places patients with cancer at an increased risk of infections, hospitalizations, and mortality. The objective of the current study was to characterize diabetes care management patterns among patients with cancer in the year before and, separately, after cancer diagnosis. The authors hypothesized that diabetes care declines after a diagnosis of cancer. METHODS The Surveillance, Epidemiology, and End Results (SEER) cancer registry linked to Medicare claims data was used. The authors included diabetic beneficiaries aged ≥65 years who were diagnosed with incident, nonmetastatic breast, prostate, or colorectal cancer between 2008 and 2013. Controls were diabetic Medicare beneficiaries in SEER regions who did not have cancer. Cases were matched to controls based on age, sex, Charlson Comorbidity Index, and diabetes severity. Primary outcomes were diabetes care received over 12 months: 1) hemoglobin A1c testing; 2) eye examination; and 3) low-density lipoprotein testing. Using a difference-in-difference (DID) approach, the authors examined use differences 12 months before to after diagnosis for patients with cancer and controls. To avoid capturing testing related to diagnosis and not diabetes management, the authors implemented a 90-day washout period (45 days before and/or after diagnosis). RESULTS A total of 32,728 diabetic patients with cancer and 32,728 matched noncancer controls were included. After diagnosis, patients with cancer were found to have modest, but significantly lower, rates of diabetes care use compared with controls. Patients with cancer had greater declines in hemoglobin A1c testing (DID, 2.4%; 95% CI, 1.7%-3.0%), low-density lipoprotein testing (DID, 4.3%; 95% CI, 3.6%-5.0%), and receipt of all diabetes indicators (DID, 2.7%; 95% CI, 1.8%-3.5%) 12 months before to after diagnosis. CONCLUSIONS Compared with controls, less diabetes care use was observed among patients with cancer in the year after diagnosis. Understanding and addressing the reasons for this may improve outcomes in this population.
Collapse
Affiliation(s)
- Laura C Pinheiro
- Division of General Internal Medicine, Department of Medicine, Weill Cornell Medicine, New York, New York
| | - Orysya Soroka
- Division of General Internal Medicine, Department of Medicine, Weill Cornell Medicine, New York, New York
| | - Lisa M Kern
- Division of General Internal Medicine, Department of Medicine, Weill Cornell Medicine, New York, New York
| | - John P Leonard
- Division of Hematology and Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York
| | - Monika M Safford
- Division of General Internal Medicine, Department of Medicine, Weill Cornell Medicine, New York, New York
| |
Collapse
|
|
31
|
Paviglianiti A. Endocrine and Metabolic Disorders after Hematopoietic Cell Transplantation. Turk J Haematol 2019; 37:111-115. [PMID: 31876135 PMCID: PMC7236409 DOI: 10.4274/tjh.galenos.2019.2019.0248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2022] Open
Abstract
Chemotherapy treatment and autologous and allogeneic cell transplantations are often complicated by the onset of metabolic and endocrine disorders. Autoimmune disorders, metabolic diseases, and hormonal dysfunctions are some of the endocrine complications observed during or after treatment with immunotherapy (mostly novel agents) and/or chemotherapy conditioning for transplantation. Although successful treatment of the underlying hematological condition often improves the dysfunction, endocrinopathies can have an impact on prognosis and are associated with poor survival; therefore, it is important to detect and treat them as early as possible. An increased incidence of cardiovascular diseases and metabolic syndrome has been observed after transplantation mostly in long-term survivors. In addition, chemotherapy and radiation along with the prolonged use of corticosteroids can contribute to the onset of thyroid and gonadal dysfunctions. The aim of this article is to describe metabolic dysfunctions occurring in patients who underwent allogeneic cell transplantation.
Collapse
Affiliation(s)
- Annalisa Paviglianiti
- Saint Antoine Hospital, Department of Hematology and Cell Therapy, AP-HP, Paris, France
| |
Collapse
|
|
32
|
Madsen ML, Due H, Ejskjær N, Jensen P, Madsen J, Dybkær K. Aspects of vincristine-induced neuropathy in hematologic malignancies: a systematic review. Cancer Chemother Pharmacol 2019; 84:471-485. [PMID: 31214762 PMCID: PMC6682573 DOI: 10.1007/s00280-019-03884-5] [Citation(s) in RCA: 74] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Accepted: 06/04/2019] [Indexed: 01/09/2023]
Abstract
PURPOSE Vincristine is widely used as anticancer therapy for a variety of hematological malignancies. The treatment is limited by progressive vincristine-induced neuropathy, possibly including both peripheral sensory and motor nerves, autonomic nervous functions, and the central nervous system. This dose-limiting side-effect can diminish quality of life and, furthermore, cause discontinuation of vincristine treatment. The present review elucidates the current knowledge regarding vincristine-induced neuropathy in hematologic malignancies, focusing on neuropathy assessment, clinical and molecular predictive markers, drug-drug interference, prevention, and treatment. METHODS This review is conducted by a systematic search strategy for the identification of relevant literature in the PubMed and Embase databases. RESULTS No clinical parameters displayed convincing potential as predictors of vincristine-induced neuropathy; however, preexisting neuropathy was consistently reported to be associated with an increased risk of neurotoxicity. In contrast, molecular markers, including polymorphisms in genes involved in the pharmacodynamics and pharmacokinetics of vincristine, displayed great potential as predictive markers of neuropathy incidence and severity. Furthermore, antifungal drugs, such as itraconazole and voriconazole, decrease the metabolism of vincristine and consequently lead to severe neuropathy when co-administered with vincristine, underscoring why fluconazole should be the antifungal drug of choice. CONCLUSION Reports from the 71 included studies clearly emphasize the lack of consistency in neuropathy assessment, grading systems, and reporting, making it difficult to interpret results between studies. Thus, truer clinical and molecular markers could emerge if the consistency of neuropathy detection and reporting increases by the use of conventional standardized neuropathy assessment tools and grading scales.
Collapse
Affiliation(s)
- Marie Lindhard Madsen
- Department of Hematology, Aalborg University Hospital, Sdr. Skovvej 15, 9000, Aalborg, Denmark
| | - Hanne Due
- Department of Hematology, Aalborg University Hospital, Sdr. Skovvej 15, 9000, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Sdr. Skovvej 15, 9000, Aalborg, Denmark
| | - Niels Ejskjær
- Department of Clinical Medicine, Aalborg University, Sdr. Skovvej 15, 9000, Aalborg, Denmark.,Steno Diabetes Center North Denmark, Aalborg University Hospital, 9000, Aalborg, Denmark
| | - Paw Jensen
- Department of Hematology, Aalborg University Hospital, Sdr. Skovvej 15, 9000, Aalborg, Denmark.,Clinical Cancer Research Center, Aalborg University Hospital, Sdr. Skovvej 15, 9000, Aalborg, Denmark
| | - Jakob Madsen
- Department of Hematology, Aalborg University Hospital, Sdr. Skovvej 15, 9000, Aalborg, Denmark
| | - Karen Dybkær
- Department of Hematology, Aalborg University Hospital, Sdr. Skovvej 15, 9000, Aalborg, Denmark. .,Department of Clinical Medicine, Aalborg University, Sdr. Skovvej 15, 9000, Aalborg, Denmark. .,Clinical Cancer Research Center, Aalborg University Hospital, Sdr. Skovvej 15, 9000, Aalborg, Denmark.
| |
Collapse
|
|
33
|
Zylla D, Gilmore G, Eklund J, Richter S, Carlson A. Impact of diabetes and hyperglycemia on health care utilization, infection risk, and survival in patients with cancer receiving glucocorticoids with chemotherapy. J Diabetes Complications 2019; 33:335-339. [PMID: 30717892 DOI: 10.1016/j.jdiacomp.2018.12.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Revised: 12/13/2018] [Accepted: 12/22/2018] [Indexed: 01/11/2023]
Abstract
BACKGROUND Glucocorticoids are commonly used in chemotherapy regimens and may lead to hyperglycemia and increased infection rates. METHODS We performed a retrospective analysis on 1781 patients who received intravenous chemotherapy with glucocorticoids between 2010 and 2015. Data was obtained using electronic medical record, billing modules, and tumor registry. We compared new infections and survival between patients with and without diabetes, after adjusting for demographic and cancer-related variables. RESULTS In the first 12 months following chemotherapy, patients with diabetes (n = 330) had higher rates of hospital admissions (70.9% vs 57.4%), more infection-related admissions (37.0% vs 29.2%), and increased rates of new infections (61.2% vs 49.2%) when compared to patients without diabetes (n = 1451). One-year survival was worse among patients with diabetes (67.3% vs 78.3%), and in patients with at least one elevated glucose following chemotherapy (60.8% vs 78.5). After adjusting for cancer stage, age, and gender, diabetes history increased the odds of dying within one year after diagnosis by 86% (OR 1.86, 95% CI (1.37-2.52)) and of new infections by 68% (OR 1.68, 95% CI (1.26-2.24)). CONCLUSIONS Among patients with cancer receiving intravenous chemotherapy with glucocorticoids we demonstrate those with diabetes have more hospital admissions, increased rates of infections, and worse survival.
Collapse
Affiliation(s)
- Dylan Zylla
- Park Nicollet Oncology Research, Frauenshuh Cancer Center, HealthPartners, Minneapolis, MN, USA; HealthPartners Institute, HealthPartners, Minneapolis, MN, USA.
| | - Grace Gilmore
- Park Nicollet Oncology Research, Frauenshuh Cancer Center, HealthPartners, Minneapolis, MN, USA
| | - Justin Eklund
- Park Nicollet Oncology Research, Frauenshuh Cancer Center, HealthPartners, Minneapolis, MN, USA; HealthPartners Institute, HealthPartners, Minneapolis, MN, USA
| | - Sara Richter
- Professional Data Analysts, Inc., Minneapolis, MN, USA
| | - Anders Carlson
- International Diabetes Center, Park Nicollet, Minneapolis, MN, USA
| |
Collapse
|
|
34
|
Abstract
BACKGROUND Patients who receive autologous hematopoietic cell transplantation (HCT) for the treatment of hematologic malignancies are at risk of serious adverse outcomes including infections and death. Hyperglycemia following the HCT is associated with increased risk of these adverse outcomes. However, limited information is available on demographic and clinical characteristics that contribute to changes in blood glucose levels following HCT. OBJECTIVE The objective of this study was to determine the trajectories of fasting blood glucose (FBG) levels as well as the demographic and clinical characteristics that predicted interindividual differences in these FBG trajectories. METHODS A sample of adult patients with hematologic malignancies who were scheduled to receive autologous HCT (n = 53) was enrolled in the study. Patients with preexisting diabetes were excluded. Demographic and clinical characteristics were abstracted from electronic medical records. Morning fasting laboratory tests (ie, FBG and absolute neutrophil counts) were obtained. Data were analyzed using hierarchical linear modeling from the day of HCT (day 0) through 14 days post-HCT. RESULTS Among 8 characteristics evaluated, pre-HCT FBG was associated with variability in both the initial levels and the trajectories of FBG. Body mass index was only associated with initial levels of FBG. CONCLUSIONS The large amount of interindividual variability in the trajectories of FBG levels following autologous HCT suggests that glucose control in these patients warrants ongoing assessments and preemptive tailoring. IMPLICATIONS FOR PRACTICE Fasting blood glucose monitoring is warranted. Additional research with larger samples is warranted to identify additional modifiable and nonmodifiable characteristics associated with interindividual variability in FBG levels.
Collapse
|
|
35
|
Schultz H, Pedersen-Bjergaard U, Jensen AK, Engelholm SA, Kristensen PL. The influence on survival of glucocorticoid induced diabetes in cancer patients with metastatic spinal cord compression. Clin Transl Radiat Oncol 2018; 11:19-25. [PMID: 30014043 PMCID: PMC6019865 DOI: 10.1016/j.ctro.2018.04.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND AND PURPOSE The influence of glucocorticoid induced hyperglycemia on survival in patients with metastatic spinal cord compression (MSCC) is unknown. MATERIALS AND METHODS In a prospective, observational cohort study 131 patients with MSCC referred to radiotherapy, 30 Gray (Gy) in 10 fractions, and treated with ≥100 mg prednisolone a day were followed with daily blood glucose measurements during radiotherapy. RESULTS During follow-up a total of 56 patients 43% (95% CI = 35-52%) presented plasma glucose values diagnostic of diabetes. Sixteen patients who developed diabetes were treated with insulin, 12% (95% CI = [6%; 18%]) of the total population. The patients developing diabetes with need for insulin therapy during glucocorticoid therapy had a significantly increased mortality compared to those with normal glucose metabolism and with diabetes without need for therapy, hazard ratio = 2.1 (95% CI = 1.08-4.09, p = 0.0285). DISCUSSION To our knowledge this is the first prospective study to describe the influence of glucocorticoid induced diabetes on survival in patients with MSCC from different primary tumors. CONCLUSIONS The results indicate that development of diabetes during high-dose glucocorticoid therapy needing insulin treatment in patients with MSCC from different primary tumors is associated with reduced survival.
Collapse
Affiliation(s)
- Helga Schultz
- Department of Endocrinology and Nephrology, Nordsjaellands Hospital, Dyrehavevej 29, DK-3400 Hillerød, Denmark
| | - Ulrik Pedersen-Bjergaard
- Department of Endocrinology and Nephrology, Nordsjaellands Hospital, Dyrehavevej 29, DK-3400 Hillerød, Denmark
- Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark
| | - Andreas Kryger Jensen
- Section of Biostatistics, Institute of Public Health, University of Copenhagen, Denmark
| | - Svend Aage Engelholm
- Department of Oncology, Rigshospitalet, University of Copenhagen, Belgdamsvej 9, 2100 Copenhagen N, Denmark
| | - Peter Lommer Kristensen
- Department of Endocrinology and Nephrology, Nordsjaellands Hospital, Dyrehavevej 29, DK-3400 Hillerød, Denmark
| |
Collapse
|
|
36
|
Storey S, Von Ah D, Hammer MJ. Measurement of Hyperglycemia and Impact on Health Outcomes in People With Cancer: Challenges and Opportunities. Oncol Nurs Forum 2018. [PMID: 28632250 DOI: 10.1188/17.onf.e141-e151] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PROBLEM IDENTIFICATION Poor health outcomes have been associated with hyperglycemia in patients with and without diabetes. However, the impact of hyperglycemia on the health-related outcomes of patients with cancer has shown conflicting results. The purpose of this review was to explore definitions and measurement issues related to the assessment of hyperglycemia and the subsequent impact on the findings of health-related outcomes in adults with cancer.
. LITERATURE SEARCH Four electronic databases were searched. DATA EVALUATION A total of 30 articles were reviewed. Quantitative articles were synthesized using integrative review strategies.
. SYNTHESIS Three key gaps were identified in the literature. CONCLUSIONS This review highlights the inconsistencies in measuring or assessing hyperglycemia and the lack of standardized guidelines in treating hyperglycemia. Failure to have a standard approach to the measurement and management of hyperglycemia impedes the ability of healthcare providers to determine the significance of its impact on health outcomes. Further research is needed to establish appropriate measurement guidelines to address hyperglycemia in people with cancer.
. IMPLICATIONS FOR PRACTICE Evidence-based measurement and treatment guidelines are needed to inform and assist healthcare providers with clinical decision making for people with cancer who experience hyperglycemia.
Collapse
|
|
37
|
Hyperglycemia and aberrant O-GlcNAcylation: contributions to tumor progression. J Bioenerg Biomembr 2018; 50:175-187. [DOI: 10.1007/s10863-017-9740-x] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2017] [Accepted: 12/26/2017] [Indexed: 12/17/2022]
|
|
38
|
Lamar ZS, Dothard A, Kennedy L, Isom S, Robinson M, Vaidya R, Hurd D, McClain D, Lesser G. Hyperglycemia during first-line R-CHOP or dose adjusted R-EPOCH chemotherapy for non-Hodgkin lymphoma is prevalent and associated with chemotherapy alteration - a retrospective study. Leuk Lymphoma 2017; 59:1871-1877. [PMID: 29252084 DOI: 10.1080/10428194.2017.1410889] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
High-dose glucocorticoids such as prednisone are combined with cytotoxic chemotherapy in the R-CHOP or dose adjusted R-EPOCH regimens used for non-Hodgkin lymphoma (NHL). In this retrospective study, our primary objective was to evaluate the incidence of hyperglycemia during first-line R-CHOP or DA-EPOCH-R. The secondary objectives were to evaluate the incidence of chemotherapy alteration and overall survival in those with and without hyperglycemia. One hundred and sixty patients were eligible. We found that 47% of all patients had at least one hyperglycemic episode and hyperglycemia was associated with chemotherapy alteration (p = .028). Multivariate analysis revealed international prognostic index (IPI) ≥ 3 (p = .045) and chemotherapy alteration (p = .001) were associated with decreased overall survival. We conclude that hyperglycemia is common during first-line NHL treatment with R-CHOP or DA-EPOCH-R, even in the absence of known diabetes and is associated with alterations of chemotherapy. Baseline pre-PET scan fasting blood glucose of 100 mg/dL or higher may predict hyperglycemia during therapy.
Collapse
Affiliation(s)
- Zanetta S Lamar
- a Department of Internal Medicine - Section of Hematology and Oncology , Wake Forest Baptist Medical Center , Winston-Salem , NC , USA.,b Wake Forest Baptist Comprehensive Cancer Center, Wake Forest Baptist Medical Center , Winston-Salem , NC , USA
| | - Andrew Dothard
- a Department of Internal Medicine - Section of Hematology and Oncology , Wake Forest Baptist Medical Center , Winston-Salem , NC , USA
| | - LeAnne Kennedy
- c Department of Pharmacy , Wake Forest Baptist Medical Center , Winston-Salem , NC , USA
| | - Scott Isom
- a Department of Internal Medicine - Section of Hematology and Oncology , Wake Forest Baptist Medical Center , Winston-Salem , NC , USA.,d Department of Biostatistical Sciences , Wake Forest Baptist Medical Center , Winston-Salem , NC , USA
| | - Mac Robinson
- b Wake Forest Baptist Comprehensive Cancer Center, Wake Forest Baptist Medical Center , Winston-Salem , NC , USA
| | - Rakhee Vaidya
- a Department of Internal Medicine - Section of Hematology and Oncology , Wake Forest Baptist Medical Center , Winston-Salem , NC , USA.,b Wake Forest Baptist Comprehensive Cancer Center, Wake Forest Baptist Medical Center , Winston-Salem , NC , USA
| | - David Hurd
- a Department of Internal Medicine - Section of Hematology and Oncology , Wake Forest Baptist Medical Center , Winston-Salem , NC , USA.,b Wake Forest Baptist Comprehensive Cancer Center, Wake Forest Baptist Medical Center , Winston-Salem , NC , USA
| | - Donald McClain
- e Department of Internal Medicine - Section of Endocrinology and Metabolism , Wake Forest Baptist Medical Center , Winston-Salem , NC , USA
| | - Glenn Lesser
- a Department of Internal Medicine - Section of Hematology and Oncology , Wake Forest Baptist Medical Center , Winston-Salem , NC , USA.,b Wake Forest Baptist Comprehensive Cancer Center, Wake Forest Baptist Medical Center , Winston-Salem , NC , USA
| |
Collapse
|
|
39
|
Al Qahtani A, Holly J, Perks C. Hypoxia negates hyperglycaemia-induced chemo-resistance in breast cancer cells: the role of insulin-like growth factor binding protein 2. Oncotarget 2017; 8:74635-74648. [PMID: 29088813 PMCID: PMC5650368 DOI: 10.18632/oncotarget.20287] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2017] [Accepted: 07/25/2017] [Indexed: 12/11/2022] Open
Abstract
Background Women who suffer from breast cancer and type II diabetes with associated hyperglycaemia respond less well to chemotherapy. We have shown that hyperglycaemia induces resistance to chemotherapy through upregulation of fatty acid synthase (FASN) in breast cancer cells and increased insulin-like binding protein 2 (IGFBP-2) in prostate cancer cells. As a tumour develops the tumour mass can outgrow the blood supply resulting in the cancer cells being exposed to hypoxia that stimulates many tumorigenic signalling pathways. Methods We used MCF-7 and T47D breast cancer cell lines. Trypan blue dye exclusion assay was employed to assess cell death and Western immunoblotting was used to determine changes in protein abundance. Hypoxia was induced both chemically by the addition of cobalt chloride (CoCl2) and using a hypoxia chamber. Results IGFBP-2 abundance increased with increasing concentrations of glucose (0-25 mM) that contributed to hyperglycaemia-induced chemo-resistance as it was abrogated by downregulating IGFBP-2 using siRNA. Production of IGFBP-2 is ER dependent: pre-treatment of MCF-7 cells with β-estradiol increased IGFBP-2 and induced chemo-resistance to doxorubicin. The hyperglycaemia-induced chemo-resistance and increases in FASN and IGFBP-2 were negated in a hypoxic environment, with levels of cell death unaffected by glucose concentrations. Conclusions The sensitivity of breast cancer cells to chemotherapy is reduced in hyperglycaemic conditions but this effect is negated by hypoxia. These effects appear to be mediated via regulation of IGFBP-2 and FASN. Understanding the role of FASN and IGFBP-2 in chemo-resistance could provide a novel target for improving the effectiveness of breast cancer treatment.
Collapse
Affiliation(s)
- Athba Al Qahtani
- IGFs and Metabolic Endocrinology Group, School of Clinical Sciences, University of Bristol, Learning and Research Building, Southmead Hospital, Bristol BS10 1TD, UK
| | - Jeff Holly
- IGFs and Metabolic Endocrinology Group, School of Clinical Sciences, University of Bristol, Learning and Research Building, Southmead Hospital, Bristol BS10 1TD, UK
| | - Claire Perks
- IGFs and Metabolic Endocrinology Group, School of Clinical Sciences, University of Bristol, Learning and Research Building, Southmead Hospital, Bristol BS10 1TD, UK
| |
Collapse
|
|
40
|
Healy SJ, Nagaraja HN, Alwan D, Dungan KM. Prevalence, predictors, and outcomes of steroid-induced hyperglycemia in hospitalized patients with hematologic malignancies. Endocrine 2017; 56:90-97. [PMID: 28058528 DOI: 10.1007/s12020-016-1220-2] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2016] [Accepted: 12/26/2016] [Indexed: 12/18/2022]
Abstract
To determine prevalence, predictors, and outcomes of steroid-induced hyperglycemia in hospitalized patients with hematologic malignancies METHODS: We performed retrospective analysis of patients who were hospitalized on any of the four hematology services or bone marrow transplant service and who received systemic steroids during a 2-month period. Mean glucoses for days 1-4 and maximum glucose were calculated and the total daily steroid dose was converted to equivalent dose of dexamethasone. Hyperglycemia was defined as any glucose >9.917 mmol/l during days 1-4. We examined associations between variables using Spearman's correlations and multivariable linear regression RESULTS: 168 patients were included in the analysis. Mean age was 57.1 ± 14.4 years with 59% males and 90% Caucasians. The prevalence of hyperglycemia was 39%. Eight patients received intravenous insulin. In patients without diabetes, steroid dose equivalent to >12 mg dexamethasone and longer acting steroids caused greater degree of hyperglycemia compared to a dose <12 mg. Maximum glucose was a predictor of hospital length of stay among patients without diabetes (but not those with diabetes), and with acute leukemia or stem cell transplant (but not other hematologic malignancies). There were no significant differences in in mortality or other outcomes between the groups with and without hyperglycemia CONCLUSIONS: Hyperglycemia is common in patients with hematologic malignancies, which require frequent corticosteroids. Higher steroid dose and long-acting steroids caused a greater degree of hyperglycemia. Maximum glucose was a predictor of length of stay but this was only significant for patients without diabetes, those with acute hematologic malignancy or stem cell transplant.
Collapse
Affiliation(s)
- Sara J Healy
- Division of Endocrinology, Diabetes, and Metabolism, The Ohio State University Wexner Medical Center, 5th Floor McCampbell Hall, 1581 Dodd Drive, Columbus, OH, 43210-1296, USA
| | - Haikady N Nagaraja
- Division of Biostatistics, The Ohio State University College of Public Health, Columbus, OH, 43210-1296, USA
| | - Dhuha Alwan
- The Ohio State University College of Public Health, Columbus, OH, 43210-1296, USA
| | - Kathleen M Dungan
- Division of Endocrinology, Diabetes, and Metabolism, The Ohio State University Wexner Medical Center, 5th Floor McCampbell Hall, 1581 Dodd Drive, Columbus, OH, 43210-1296, USA.
| |
Collapse
|
|
41
|
Impact of hyperglycemia on the efficacy of chemotherapy-A systematic review of preclinical studies. Crit Rev Oncol Hematol 2017; 113:235-241. [PMID: 28427512 DOI: 10.1016/j.critrevonc.2017.03.007] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Revised: 01/05/2017] [Accepted: 03/08/2017] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Antineoplastic agents can provoke hyperglycemia in cancer patients with and without diabetes mellitus. We systematically reviewed the impact of hyperglycemia on the efficacy of chemotherapy. METHODS MEDLINE was searched for preclinical intervention studies which compared chemotherapy response in hyperglycemic and euglycemic conditions. RESULTS Thirteen preclinical studies, including 23 cell lines and 2 animal experiments were identified. In 14 cell lines and 2 animal studies, chemotherapy response was lower in a hyperglycemic (>15mmol/L) compared to a euglycemic environment (5mmol/L). The response was similar in 4 cell lines. In the remaining 5 cell lines, the hyperglycemic environment potentiated chemotherapy efficacy. CONCLUSION Hyperglycemia attenuated the antiproliferative effect of chemotherapy in preclinical experiments, but the results are inconsistent. Whether hyperglycemia influences efficacy of chemotherapy in patients needs to be explored.
Collapse
|
|
42
|
Hershey DS, Hession S. Chemotherapy and Glycemic Control in Patients with Type 2 Diabetes and Cancer: A Comparative Case Analysis. Asia Pac J Oncol Nurs 2017; 4:224-232. [PMID: 28695169 PMCID: PMC5473094 DOI: 10.4103/apjon.apjon_22_17] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Objective: Individuals with diabetes who develop cancer have a worse 5-year overall survival rate and are more likely to develop an infection and/or be hospitalized when compared to those without diabetes. Patients with diabetes and cancer receiving chemotherapy have an increased risk for developing glycemic issues. The relationship between chemotherapy and glycemic control is not completely understood. The aim of this study was to explore the relationship between glycemic control, symptoms, physical and mental function, development of adverse events, and chemotherapy reductions or stoppages in adults with Type 2 diabetes (T2D) and cancer. Methods: A prospective 12-week longitudinal cohort study recruited 24 adults with T2D, solid tumor cancer, or lymphoma receiving outpatient intravenous chemotherapy. Eighteen individuals completed baseline data and were included in the analysis. A comparative case analysis was performed to analyze the results. Results: Potential predictors of occurrence of an adverse event include sex (relative risk [RR] = 1.5), treatment with insulin (RR = 2.17), years with diabetes (RR = 3.85), and baseline glycated hemoglobin (HbA1c) (odds ratio [OR] = 1.67). Baseline body mass index (BMI) (OR = 1.16) and HbA1c (OR = 1.61) were potentially predictive of a chemotherapy stoppage. Conclusions: Level of glycemic control at the time an individual begins treatment for cancer appears to contribute to the occurrence of an adverse event, developing an infection and/or being hospitalized during treatment, and the increased risk of having a chemotherapy reduction or stoppage. Clinicians working with patients receiving chemotherapy for a solid tumor cancer who have pre-existing diabetes, need to be aware of how the patients glycemic level at the start of treatment may impact successful treatment completion.
Collapse
Affiliation(s)
| | - Sarah Hession
- Center for Statistical Training and Consulting, Michigan State University, MI, USA
| |
Collapse
|
|
43
|
Hershey DS. Importance of Glycemic Control in Cancer Patients with Diabetes: Treatment through End of Life. Asia Pac J Oncol Nurs 2017; 4:313-318. [PMID: 28966959 PMCID: PMC5559941 DOI: 10.4103/apjon.apjon_40_17] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Cancer patients with diabetes are at increased risk for developing infections, being hospitalized, and requiring chemotherapy reductions or stoppages. While it has been hypothesized that glycemic control increases the risk for these adverse events, few studies have explored this hypothesis. The purpose of this paper is to discuss the importance of glycemic control in patients with diabetes and cancer during treatment through end of life. Glycemic control was found to play a role; the overall level of health-related quality of life experienced by patients with cancer and diabetes, level of symptom severity experienced and can impact the overall survival of the individual. Evidence-based policies and practice guidelines also need to be developed to help clinicians manage these patients during all phases of care. Using diabetes educators and advance practice, nurses to provide management and care coordination services need to be considered. Survivorship care plans should address both cancer and diabetes management. Finally, glycemic control should continue through end of life, with the main goal of avoiding hypoglycemic events.
Collapse
|
|
44
|
Impact of Hyperglycemia on Outcomes among Patients Receiving Neoadjuvant Chemotherapy for Bulky Early Stage Cervical Cancer. PLoS One 2016; 11:e0166612. [PMID: 27851819 PMCID: PMC5113016 DOI: 10.1371/journal.pone.0166612] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Accepted: 11/01/2016] [Indexed: 12/14/2022] Open
Abstract
Background The impact of hyperglycemia on survival of patients undergoing neoadjuvant chemotherapy (NACT) for bulky early stage cervical cancer (BESCC) has not been explored. Method Records of patients who received NACT and radical hysterectomy in our institution between January 2005 and June 2010 were reviewed. Results In total, 347 patients were included. The median follow-up time was 37 months (range: 4–65). Patients with hyperglycemia (fasting blood glucose ≥ 100 mg/dl) had shorter recurrence-free survival (RFS) (univariate hazard ratio [HR] = 1.95, 95% confidence interval [CI] [1.16, 3.28], P = 0.010) and cancer-specific survival (CSS) (univariate HR = 2.24, 95% CI [1.33, 3.78], P = 0.002) compared with those with euglycemia (fasting blood glucose <100 mg/dl). In multivariate analysis, positive surgical margins, parametrium invasion, node metastasis, hyperglycemia and complete response to NACT independently predicted recurrence and cancer-specific death. To further validate the prognostic value of hyperglycemia, we conducted a subgroup analysis based on patient baseline characteristics and prognostic effect of hyperglycemia remained significant in all subgroups. On multivariable logistic regression analysis, euglycemia before NACT, squamous cell tumor and pre-treatment squamous cell carcinoma antigen levels < 3.5 ng/ml were identified as independent predictors of complete response after NACT. Conclusions FBG ≥100 mg/dl is a negative prognostic predictor for cervical cancer patients receiving NACT for BESCC. Patients with hyperglycemia are less likely to achieve complete response after NACT. Our findings underscore the clinical utility of hyperglycemia screening of for cervical cancer patients.
Collapse
|
|
45
|
Gerards MC, de Maar JS, Steenbruggen TG, Hoekstra JBL, Vriesendorp TM, Gerdes VEA. Add-on treatment with intermediate-acting insulin versus sliding-scale insulin for patients with type 2 diabetes or insulin resistance during cyclic glucocorticoid-containing antineoplastic chemotherapy: a randomized crossover study. Diabetes Obes Metab 2016; 18:1041-4. [PMID: 27191794 DOI: 10.1111/dom.12694] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Revised: 04/19/2016] [Accepted: 05/13/2016] [Indexed: 12/15/2022]
Abstract
The aim of this study was to compare the effectiveness and safety of intermediate-acting insulin (IMI) titrated on body weight and glucocorticoid dose with that of short-acting sliding-scale insulin (SSI) in patients on recurrent high-dose glucocorticoid-containing chemotherapy. We enrolled 26 patients with type 2 diabetes mellitus or random blood glucose level >12 mmol/l in a previous cycle of chemotherapy in a randomized crossover study. In two consecutive cycles of glucocorticoid-containing chemotherapy, participants were treated with either IMI or SSI, as add-on to routine diabetes medication. We compared time spent in target range (3.9-10 mmol/l), measured by continuous glucose monitoring (CGM), and the occurrence of hypoglycaemia. IMI resulted in a higher proportion of glucose values within target range than SSI (34.4 vs 20.9%; p < 0.001). There were no severe or symptomatic hypoglycaemic events. Two participants in each group had a subclinical hypoglycaemia detected only by CGM. Once-daily IMI resulted in better glycaemic control than SSI in patients with glucocorticoid-induced hyperglycaemia during chemotherapy. Safety was not compromised as the incidence of hypoglycaemia was low and not different between both regimens.
Collapse
Affiliation(s)
- M C Gerards
- Department of internal medicine, MC Slotervaart, Amsterdam, The Netherlands.
| | - J S de Maar
- Department of internal medicine, Isala, Zwolle, The Netherlands
| | - T G Steenbruggen
- Department of medical oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - J B L Hoekstra
- Department of internal medicine, Academic Medical Centre, Amsterdam, The Netherlands
| | - T M Vriesendorp
- Department of internal medicine, Isala, Zwolle, The Netherlands
| | - V E A Gerdes
- Department of internal medicine, MC Slotervaart, Amsterdam, The Netherlands
| |
Collapse
|
|
46
|
Jeong Y, Han HS, Lee HD, Yang J, Jeong J, Choi MK, Kwon J, Jeon HJ, Oh TK, Lee KH, Kim ST. A Pilot Study Evaluating Steroid-Induced Diabetes after Antiemetic Dexamethasone Therapy in Chemotherapy-Treated Cancer Patients. Cancer Res Treat 2016; 48:1429-1437. [PMID: 26987397 PMCID: PMC5080830 DOI: 10.4143/crt.2015.464] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2015] [Accepted: 02/05/2016] [Indexed: 11/30/2022] Open
Abstract
Purpose Dexamethasone is a mainstay antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting. The aim of this pilot study was to assess the incidence of and factors associated with steroid-induced diabetes in cancer patients receiving chemotherapy with dexamethasone as an antiemetic. Materials and Methods Non-diabetic patients with newly diagnosed gastrointestinal cancer who received at least three cycles of highly or moderately emetogenic chemotherapy with dexamethasone as an antiemetic were enrolled. Fasting plasma glucose levels, 2-hour postprandial glucose levels, and hemoglobin A1C tests for the diagnosis of diabetes were performed before chemotherapy and at 3 and 6 months after the start of chemotherapy. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as an index for measurement of insulin resistance, defined as a HOMA-IR ≥ 2.5. Results Between January 2012 and November 2013, 101 patients with no history of diabetes underwent laboratory tests for assessment of eligibility; 77 of these patients were included in the analysis. Forty-five patients (58.4%) were insulin resistant and 17 (22.1%) developed steroid-induced diabetes at 3 or 6 months after the first chemotherapy, which included dexamethasone as an antiemetic. Multivariate analysis showed significant association of the incidence of steroid-induced diabetes with the cumulative dose of dexamethasone (p=0.049). Conclusion We suggest that development of steroid-induced diabetes after antiemetic dexamethasone therapy occurs in approximately 20% of non-diabetic cancer patients; this is particularly significant for patients receiving high doses of dexamethasone.
Collapse
Affiliation(s)
- Yusook Jeong
- Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Hye Sook Han
- Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Hyo Duk Lee
- Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Jiyoul Yang
- Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Jiwon Jeong
- Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Moon Ki Choi
- Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Jihyun Kwon
- Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Hyun-Jung Jeon
- Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Tae-Keun Oh
- Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Ki Hyeong Lee
- Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Seung Taik Kim
- Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea
| |
Collapse
|
|
47
|
Poręba M, Gać P, Usnarska-Zubkiewicz L, Pilecki W, Kuliczkowski K, Mazur G, Sobieszczańska M, Poręba R. Echocardiographic evaluation of the early cardiotoxic effect of hematopoietic stem cell transplantation in patients with hematologic malignancies. Leuk Lymphoma 2016; 57:2119-25. [PMID: 26762118 DOI: 10.3109/10428194.2015.1122782] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
The purpose was to evaluate the early cardiotoxic effects of the treatment in the course of hematopoietic stem cell transplantation (HSCT) in patients with hematologic malignancies. The studies were conducted on 47 patients qualified for the HSCT. Echocardiography was carried out prior to the HSCT and after the HSCT. It was shown that higher age, administration of cyclophosphamide and higher glucose concentrations represented independent risk factors for the worsening of left ventricular diastolic function. Higher cumulative dose of anthracyclines in the previous cytostatic treatment, higher age and administration of cyclophosphamide represented independent risk factors for worsening of left ventricular systolic function. Peri-transplant therapy in the course of HSCT in patients with hematologic malignancies gives the negative effect on the diastolic and systolic left ventricular function, however, previous treatment is of importance, as higher cumulative dose of anthracyclines represents an independent risk factor for the worsening of left ventricular systolic function.
Collapse
Affiliation(s)
- Małgorzata Poręba
- a Department of Pathophysiology , Wroclaw Medical University , Wroclaw , Poland
| | - Paweł Gać
- a Department of Pathophysiology , Wroclaw Medical University , Wroclaw , Poland
| | - Lidia Usnarska-Zubkiewicz
- b Department of Hematology , Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University , Wroclaw , Poland
| | - Witold Pilecki
- a Department of Pathophysiology , Wroclaw Medical University , Wroclaw , Poland
| | - Kazimierz Kuliczkowski
- b Department of Hematology , Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University , Wroclaw , Poland
| | - Grzegorz Mazur
- c Department of Internal Medicine , Occupational Diseases and Hypertension, Wroclaw Medical University , Wroclaw , Poland
| | | | - Rafał Poręba
- c Department of Internal Medicine , Occupational Diseases and Hypertension, Wroclaw Medical University , Wroclaw , Poland
| |
Collapse
|
|
48
|
Mareschal S, Dubois S, Viailly PJ, Bertrand P, Bohers E, Maingonnat C, Jaïs JP, Tesson B, Ruminy P, Peyrouze P, Copie-Bergman C, Fest T, Jo Molina T, Haioun C, Salles G, Tilly H, Lecroq T, Leroy K, Jardin F. Whole exome sequencing of relapsed/refractory patients expands the repertoire of somatic mutations in diffuse large B-cell lymphoma. Genes Chromosomes Cancer 2015; 55:251-67. [PMID: 26608593 DOI: 10.1002/gcc.22328] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2015] [Revised: 10/18/2015] [Accepted: 10/19/2015] [Indexed: 12/19/2022] Open
Abstract
Despite the many efforts already spent to enumerate somatic mutations in diffuse large B-cell lymphoma (DLBCL), previous whole-genome and whole-exome studies conducted on patients of mixed outcomes failed at characterizing the 30% of patients who will relapse or resist current immunochemotherapies. To address this issue, we performed whole-exome sequencing of normal/tumoral DNA pairs in 14 relapsed/refractory (R/R) patients subclassified by full-transcriptome arrays (six activated B-cell like, three germinal center B-cell like, and five primary mediastinal B-cell lymphomas), from the LNH-03 LYSA clinical trial program. Aside from well-known DLBCL features, gene and pathway level recurrence analyses proposed several interesting leads including TBL1XR1 and activating mutations in IRF4 or in the insulin regulation pathway. Sequencing-based copy number analysis defined 23 short recurrently altered regions involving genes such as REL, CDKN2A, HYAL2, and TP53. Moreover, it highlighted mutations in genes such as GNA13, CARD11, MFHAS1, and PCLO as associated with secondary variant allele amplification events. The five primary mediastinal B-cell lymphomas (PMBL), while unexpected in a R/R cohort, showed a significantly higher mutation rate (P = 0.003) and provided many insights on this classical Hodgkin lymphoma related subtype. Novel genes such as XPO1, MFHAS1, and ITPKB were found particularly mutated, along with various cytokine-based signaling pathways. Among these analyses, somatic events in the NF-κB pathway were found preponderant in the three DLBCL subtypes, confirming its major implication in DLBCL aggressiveness and pinpointing several new candidate genes.
Collapse
Affiliation(s)
| | | | - Pierre-Julien Viailly
- INSERM U918, Centre Henri Becquerel, Rouen, France.,LITIS, INSA EA 4108, Saint-Etienne-du-Rouvray, France
| | | | | | | | | | | | | | - Pauline Peyrouze
- Plate-Forme De Génomique Fonctionnelle Et Structurale, Université De Lille 2, Lille, France
| | | | | | | | - Corinne Haioun
- AP-HP Hôpital Henri Mondor, Unité Hémopathies Lymphoïdes, Créteil, France
| | - Gilles Salles
- CNRS UMR 5239, Hospices Civils De Lyon, Lyon, France
| | - Hervé Tilly
- INSERM U918, Centre Henri Becquerel, Rouen, France
| | | | - Karen Leroy
- AP-HP Hôpital Henri Mondor, INSERM U955, IMRB, Créteil, France
| | | |
Collapse
|
|
49
|
Hammer M, Aouizerat B, Schmidt B, Cartwright F, Wright F, Miaskowski C. Glycosylated Hemoglobin A1c and Lack of Association With Symptom Severity in Patients Undergoing Chemotherapy for Solid Tumors. Oncol Nurs Forum 2015; 42:581-90. [DOI: 10.1188/15.onf.581-590] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
|
|
50
|
Gerards MC, Tervaert ECC, Hoekstra JBL, Vriesendorp TM, Gerdes VEA. Physician's attitudes towards diagnosing and treating glucocorticoid induced hyperglycaemia: Sliding scale regimen is still widely used despite guidelines. Diabetes Res Clin Pract 2015; 109:246-52. [PMID: 26055758 DOI: 10.1016/j.diabres.2015.05.040] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2015] [Revised: 05/04/2015] [Accepted: 05/19/2015] [Indexed: 02/08/2023]
Abstract
AIMS Treatment with glucocorticoids for neoplasms and inflammatory disorders is frequently complicated by glucocorticoid induced hyperglycaemia (GCIH). GCIH is associated with adverse outcomes and its treatment has short term and long term benefits. Currently, treatment targets and modalities depend on local protocols and habits of individual clinicians. We explored current practice of screening and treatment of GCIH in patients receiving glucocorticoid pulse therapy. METHODS A factorial survey with written case vignettes. All vignette patients received glucocorticoid pulse therapy. Other characteristics (e.g., indication for glucocorticoid therapy, pre-existent diabetes) varied. The survey was held between November 2013 and May 2014 on 2 nationwide conferences and in hospitals across The Netherlands. Pulmonologists and internists expressed their level of agreement with statements on ordering capillary glucose testing and treatment initiation. RESULTS Respondents ordered screening for GCIH in 85% of vignette patients and initiated treatment in 56%. When initiating treatment, respondents opt for sliding scale insulin in 62% of patients. Sliding scale insulin was more frequently prescribed in patients with pre-existent insulin dependent diabetes (OR 2.4, CI 1.3-4.2) and by residents (vs. specialists, OR 2.1, CI 1.2-3.5). Sixty-nine percent of clinicians experienced a lack of guidelines for GCIH. CONCLUSIONS Clinicians have a strong tendency to screen for GCIH but subsequent initiation of treatment was low. Sliding scale insulin is still widely used in episodic GCIH despite evidence against its effectiveness. This may be due to lacking evidence on feasible treatment options for GCIH.
Collapse
Affiliation(s)
| | | | | | | | - V E A Gerdes
- Slotervaart Hospital, Amsterdam, The Netherlands
| |
Collapse
|