Dietary intervention and physical exercise in prevention and treatment of pharmacological cardiotoxicity during cancer
Importância da intervenção dietética e prática de exercícios físicos na prevenção e tratamento da cardiotoxicidade farmacológica durante o câncer
Palavras-chave:
Cardiovascular diseases, Cancer, Cardiotoxicity, Dietary intervention, Physical exerciseResumo
One of the main priorities in the cardiovascular care of cancer patients is to reduce morbidity and mortality and improve the quality of life of cancer survivors through interdisciplinary efforts. The survival rate in cancer patients has improved dramatically over the last few decades. Even in the midst of achievements and advances, survivors may be more likely to die from long-term cardiovascular disease secondary not only to the potential toxicity of cancer therapy but also to cancer biology. In this context, cardio-oncology has been highlighted as a promising field of medicine, obtaining, through studies in this area, relevant information and promising results. Among the initial data, researchers have highlighted the importance of dietary interventions represented by a healthy diet and correct supplementation, and the practice of physical exercises by cancer survivors, with the aim not only of preventing, but also of treating cardiotoxicity and its consequences in the long term.
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Aboumsallem, J. P., Moslehi, J., & de Boer, R. A. (2020). Reverse cardio-oncology: cancer development in patients with cardiovascular disease. Journal of the American Heart Association, 9(2), e013754.
Andersen, M. R., Sweet, E., Zhou, M., & Standish, L. J. (2015). Complementary and alternative medicine use by breast cancer patients at the time of surgery which increases the potential for excessive bleeding. Integrative Cancer Therapies, 14, 119–124.
Ansund, J., Mijwel, S., Bolam, K. A., Altena, R., Wengström, Y., Rullman, E., et al. (2021). High-intensity exercise during breast cancer chemotherapy - effects on long-term myocardial damage and physical capacity - data from the OptiTrain RCT. Cardio-Oncology, 7(1), 7.
Aune, D., Giovannucci, E., Boffetta, P., et al. (2017). Fruit and vegetable intake and the risk of cardiovascular disease, total cancer and all-cause mortality-A systematic review and dose-response meta-analysis of prospective studies. International Journal of Epidemiology, 46, 1029–1056.
Bjørke, A. C. H., Sweegers, M. G., Buffart, L. M., Raastad, T., Nygren, P., & Berntsen, S. (2019). Which exercise prescriptions optimize V̇O2 max during cancer treatment? A systematic review and meta-analysis. Scandinavian Journal of Medicine & Science in Sports, 29(9), 1274–1287.
Blaes, A., Prizment, A., Koene, R. J., et al. (2017). Cardio-oncology related to heart failure: common risk factors between cancer and cardiovascular disease. Heart Failure Clinics, 13, 367–380.
Bloedon, L. T., Balikai, S., Chittams, J., et al. (2008). Flaxseed and cardiovascular risk factors: results from a double blind, randomized, controlled clinical trial. Journal of the American College of Nutrition, 27, 65–74.
Boyle, P., Autier, P., Bartelink, H., et al. (2003). European code against cancer and scientific justification: Third version (2003). Annals of Oncology, 14, 973–1005.
Bracun, V., Aboumsallem, J. P., van der Meer, P., & de Boer, R. A. (2020). Cardiac biomarkers in patients with cancer: considerations, clinical implications, and future avenues. Current Oncology Reports, 22(7), 67.
Brown, S. A., Ray, J. C., & Herrmann, J. (2020). Precision cardio-oncology: a systems-based perspective on cardiotoxicity of tyrosine kinase inhibitors and immune checkpoint inhibitors. Journal of Cardiovascular Translational Research.
Campbell, K. L., Winters-Stone, K. M., Wiskemann, J., May, A. M., Schwartz, A. L., Courneya, K. S., et al. (2019). Exercise guidelines for cancer survivors: consensus statement from International Multidisciplinary Roundtable. Medicine & Science in Sports & Exercise, 51(11), 2375–2390.
Carter, B. D., Abnet, C. C., Feskanich, D., et al. (2015). Smoking and mortality-beyond established causes. New England Journal of Medicine, 372, 631–640.
Caspersen, C. J., Powell, K. E., & Christenson, G. M. (1985). Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research. Public Health Reports, 100(2), 126–131.
Chaar, M., Kamta, J., & Ait-Oudhia, S. (2018). Mechanisms, monitoring, and management of tyrosine kinase inhibitors-associated cardiovascular toxicities. OncoTargets and Therapy, 11, 6227–6237.
Chait, A., & den Hartigh, L. J. (2020). Adipose tissue distribution, inflammation and its metabolic consequences, including diabetes and cardiovascular disease. Frontiers in Cardiovascular Medicine, 7, 1–41.
Chajes, V., Jenab, M., Romieu, I., et al. (2011). Plasma phospholipid fatty acid concentrations and risk of gastric adenocarcinomas in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST). The American Journal of Clinical Nutrition, 94(5), 1304–1313.
Chang, H. M., Okwuosa, T. M., Scarabelli, T., Moudgil, R., & Yeh, E. T. H. (2017). Cardiovascular complications of cancer therapy: Best practices in diagnosis, prevention, and management: part 2. Journal of the American College of Cardiology, 70(20), 2552–2565.
Dashwood, R. H., Myzak, M. C., & Ho, E. (2006). Dietary HDAC inhibitors: time to rethink weak ligands in cancer chemoprevention? Carcinogenesis, 27, 344–349.
de Souza, R. J., Mente, A., Maroleanu, A., et al. (2015). Intake of saturated and trans unsaturated fatty acids and risk of all-cause mortality, cardiovascular disease, and type 2 diabetes: Systematic review and meta-analysis of observational studies. BMJ, 351, h3978.
Dikaiou, P., Björck, L., Adiels, M., et al. (2020). Obesity, overweight and risk for cardiovascular disease and mortality in young women. European Journal of Preventive Cardiology.
DiLoreto, R., & Murphy, C. T. (2015). The cell biology of aging. Molecular Biology of the Cell, 26(25), 4524–4531.
Dueregger, A., Heidegger, I., Ofer, P., et al. (2014). The use of dietary supplements to alleviate androgen deprivation therapy side effects during prostate cancer treatment. Nutrients, 6, 4491–4519.
Ferrara, N. (2002). VEGF and the quest for tumour angiogenesis factors. Nature Reviews Cancer, 2, 795–803.
Fretts, A. M., Follis, J. L., Nettleton, J. A., et al. (2015). Consumption of meat is associated with higher fasting glucose and insulin concentrations regardless of glucose and insulin genetic risk scores: a meta-analysis of 50,345 Caucasians. The American Journal of Clinical Nutrition, 102, 1266–1278.
Friedenreich, C. M., Stone, C. R., Cheung, W. Y., & Hayes, S. C. (2020). Physical activity and mortality in cancer survivors: a systematic review and meta-analysis. JNCI Cancer Spectrum, 4(1), pkz080.
Gallagher, E. J., & LeRoith, D. (2015). Obesity and diabetes: The increased risk of cancer and cancer-related mortality. Physiological Reviews, 95, 727–748.
Genkinger, J. M., Li, R., Spiegelman, D., et al. (2012). Coffee, tea, and sugar-sweetened carbonated soft drink intake and pancreatic cancer risk: A pooled analysis of 14 cohort studies. Cancer Epidemiology, Biomarkers & Prevention, 21, 305–318.
Gérard, C., & Brown, K. A. (2018). Obesity and breast cancer – Role of estrogens and the molecular underpinnings of aromatase regulation in breast adipose tissue. Molecular and Cellular Endocrinology, 466, 15–30.
Ghasemi, A., Saeidi, J., Azimi-Nejad, M., et al. (2019). Leptin-induced signaling pathways in cancer cell migration and invasion. Cellular Oncology, 42, 243–260.
Giavridis, T., van der Stegen, S. J. C., Eyquem, J., Hamieh, M., Piersigilli, A., & Sadelain, M. (2018). CAR T cell-induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade. Nature Medicine, 24(6), 731–738.
Giovannucci, E., Harlan, D. M., Archer, M. C., et al. (2010). Diabetes and cancer: A consensus report. Diabetes Care, 33, 1674–1685.
Guida, J. L., Ahles, T. A., Belsky, D., Campisi, J., Cohen, H. J., DeGregori, J., ... & Gallicchio, L. (2019). Measuring aging and identifying aging phenotypes in cancer survivors. Journal of the National Cancer Institute, 111(12), 1245–1254.
Hernandez, C., Huebener, P., & Schwabe, R. F. (2016). Damage-associated molecular patterns in cancer: a double-edged sword. Oncogene, 35(46), 5931–5941.
Hooper, L., Summerbell, C. D., Thompson, R., et al. (2012). Reduced or modified dietary fat for preventing cardiovascular disease. Cochrane Database of Systematic Reviews, 5, CD002137.
Hornsby, W. E., Douglas, P. S., West, M. J., Kenjale, A. A., Lane, A. R., Schwitzer, E. R., et al. (2014). Safety and efficacy of aerobic training in operable breast cancer patients receiving neoadjuvant chemotherapy: a phase II randomized trial. Acta Oncologica, 53(1), 65–74.
Huang, T., Xu, M., Lee, A., et al. (2015). Consumption of whole grains and cereal fiber and total and cause-specific mortality: Prospective analysis of 367,442 individuals. BMC Medicine, 13, 59.
Islam, M. A., Amin, M. N., Siddiqui, S. A., et al. (2019). Trans fatty acids and lipid profile: A serious risk factor to cardiovascular disease, cancer and diabetes. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 13, 1643–1647.
Jamal, F. A., & Khaled, S. K. (2020). The cardiovascular complications of chimeric antigen receptor T cell therapy. Current Hematologic Malignancy Reports, 15(2), 130–132.
Johnson, C. B., Davis, M. K., Law, A., et al. (2016). Shared risk factors for cardiovascular disease and cancer: implications for preventive health and clinical care in oncology patients. Canadian Journal of Cardiology, 32, 900–907.
Kang, D. W., Fairey, A. S., Boule, N. G., Field, C. J., Wharton, S. A., & Courneya, K. S. (2021). Effects of exercise on cardiorespiratory fitness and biochemical progression in men with localized prostate cancer under active surveillance: The ERASE randomized clinical trial. JAMA Oncology.
Kang, Y. S., Park, Y. G., Kim, B. K., et al. (2006). Angiotensin II stimulates the synthesis of vascular endothelial growth factor through the p38 mitogen-activated protein kinase pathway in cultured mouse podocytes. Journal of Molecular Endocrinology, 36, 377–388.
Kirkham, A. A., Eves, N. D., Shave, R. E., Bland, K. A., Bovard, J., Gelmon, K. A., et al. (2018). The effect of an aerobic exercise bout 24 h prior to each doxorubicin treatment for breast cancer on markers of cardiotoxicity and treatment symptoms: a RCT. Breast Cancer Research and Treatment, 167(3), 719–729.
Koene, R. J., Prizment, A. E., Blaes, A., et al. (2016). Shared risk factors in cardiovascular disease and cancer. Circulation, 32, 900–907.
Kris-Etherton, P. M., Hu, F. B., Ros, E., & Sabate, J. (2008). The role of tree nuts and peanuts in the prevention of coronary heart disease: multiple potential mechanisms. The Journal of Nutrition, 138, 1746S–1751S.
Lampe, J. W. (1999). Health effects of vegetables and fruit: Assessing mechanisms of action in human experimental studies. The American Journal of Clinical Nutrition, 70, S475–S490.
Le, R. Q., Li, L., Yuan, W., Shord, S. S., Nie, L., Habtemariam, B. A., ... & Kochenderfer, J. N. (2018). FDA approval summary: tocilizumab for treatment of chimeric antigen receptor T cell-induced severe or life-threatening cytokine release syndrome. The Oncologist, 23(8), 943–947.
Leerink, J. M., de Baat, E. C., Feijen, E. A. M., et al. (2020). Cardiac disease in childhood cancer survivors. J Am Coll Cardiol CardioOnc, 2(3), 363–378.
Lenihan, D. J., Fradley, M. G., Dent, S., et al. (2019). Proceedings from the Global Cardio-Oncology Summit. Journal of the American College of Cardiology CardioOnc, 1, 256–272.
Ligibel, J. A., Barry, W. T., Alfano, C., Hershman, D. L., Irwin, M., Neuhouser, M., ... & Thomson, C. A. (2017). Randomized phase III trial evaluating the role of weight loss in adjuvant treatment of overweight and obese women with early breast cancer (Alliance A011401): Study design. NPJ Breast Cancer, 3, 37.
Liu, P. H., Wu, K., Ng, K., et al. (2019). Association of obesity with risk of early-onset colorectal cancer among women. JAMA Oncology, 5, 37–44.
Lyman, G. H., Carrier, M., Ay, C., Di Nisio, M., Hicks, L. K., Khorana, A. A., ... & Morgan, R. L. (2021). American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer. Blood Advances, 5(4), 927–974.
MacMahon, S., Duffy, S., Rodgers, A., et al. (2007). Blood cholesterol and vascular mortality by age, sex, and blood pressure: A meta-analysis of individual data from 61 prospective studies with 55 000 vascular deaths. The Lancet, 370, 1829–1839.
Maginador, G., Lixandrão, M. E., Bortolozo, H. I., Vechin, F. C., Sarian, L. O., Derchain, S., et al. (2020). Aerobic exercise induced changes in cardiorespiratory fitness in breast cancer patients receiving chemotherapy: a systematic review and meta-analysis. Cancers, 12(8), E2240.
Mahmood, S. S., Fradley, M. G., Cohen, J. V., Nohria, A., Reynolds, K. L., Heinzerling, L. M., ... & Moslehi, J. (2018). Myocarditis in patients treated with immune checkpoint inhibitors. Journal of the American College of Cardiology, 71(16), 1755–1764.
Maude, S. L., Barrett, D., Teachey, D. T., & Grupp, S. A. (2014). Managing cytokine release syndrome associated with novel T cell-engaging therapies. Cancer Journal, 20(2), 119–122.
McCall, D. O., McGartland, C. P., McKinley, M. C., et al. (2009). Dietary intake of fruits and vegetables improves microvascular function in hypertensive subjects in a dose-dependent manner. Circulation, 119, 2153–2156.
McTiernan, A., Friedenreich, C. M., Katzmarzyk, P. T., Powell, K. E., Macko, R., Buchner, D., et al. (2019). Physical activity in cancer prevention and survival: a systematic review. Medicine & Science in Sports & Exercise, 51(6), 1252–1261.
Mensink, R. P., Zock, P. L., Kester, A. D., & Katan, M. B. (2003). Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: A meta-analysis of 60 controlled trials. The American Journal of Clinical Nutrition, 77, 1146–1155.
Miller, K. D., Siegel, R. L., Lin, C. C., et al. (2016). Cancer treatment and survivorship statistics, 2016. CA: A Cancer Journal for Clinicians, 66, 271–289.
Monroe, K. R., Murphy, S. P., Henderson, B. E., et al. (2007). Dietary fiber intake and endogenous serum hormone levels in naturally postmenopausal Mexican American women: The Multiethnic Cohort Study. Nutrition and Cancer, 58, 127–135.
Morris, P. B., Ference, B. A., Jahangir, E., et al. (2015). Cardiovascular effects of exposure to cigarette smoke and electronic cigarettes: clinical perspectives from the Prevention of Cardiovascular Disease Section Leadership Council and Early Career Councils of the American College of Cardiology. Journal of the American College of Cardiology, 66, 1378–1391.
Mozaffarian, D., & Ludwig, D. S. (2015). The 2015 US dietary guidelines: Lifting the ban on total dietary fat. JAMA, 313, 2421–2422.
Nathan, P. C., Greenberg, M. L., Ness, K. K., et al. (2008). Medical care in long-term survivors of childhood cancer: a report from the childhood cancer survivor study. Journal of Clinical Oncology, 26, 4401–4409.
Navi, B. B., Reiner, A. S., Kamel, H., Iadecola, C., Okin, P. M., Elkind, M. S., ... & DeAngelis, L. M. (2017). Risk of arterial thromboembolism in patients with cancer. Journal of the American College of Cardiology, 70(8), 926–938.
Norat, T., Scoccianti, C., Boutro-Rouault, M. C., et al. (2015). European Code Against Cancer 4th Edition: Diet and cancer. Cancer Epidemiology, 39(1), S56–S66.
Palma, S., Hasenoehrl, T., Jordakieva, G., Ramazanova, D., & Crevenna, R. (2021). High-intensity interval training in the prehabilitation of cancer patients: A systematic review and meta-analysis. Supportive Care in Cancer, 29(4), 1781–1794.
Pandey, A., Garg, S., Khunger, M., et al. (2015). Dose-response relationship between physical activity and risk of heart failure: A meta-analysis. Circulation, 132, 1786–1794.
Pollak, M. (2012). The insulin and insulin-like growth factor receptor family in neoplasia: An update. Nature Reviews Cancer, 12, 159–169.
Postigo-Martin, P., Peñafel-Burkhardt, R., Gallart Aragón, T., Alcaide-Lucena, M., Artacho-Cordón, F., Galiano-Castillo, N., et al. (2021). Attenuating treatment-related cardiotoxicity in women recently diagnosed with breast cancer via a tailored therapeutic exercise program: protocol of the ATOPE trial. Physical Therapy, 101(3), pzab014.
Powell, D. R., Suwanichkul, A., Cubbage, M. L., et al. (1991). Insulin inhibits transcription of the human gene for insulin-like growth factor-binding protein-1. Journal of Biological Chemistry, 266, 18868–18876.
Ramin, C., Schaeffer, M. L., Zheng, Z., Connor, A. E., Hoffman-Bolton, J., Lau, B., & Visvanathan, K. (2021). All-cause and cardiovascular disease mortality among breast cancer survivors in CLUE II, a long-standing community-based cohort. Journal of the National Cancer Institute, 113(2), 137–145.
Raygan, F., Rezavandi, Z., Dadkhah Tehrani, S., et al. (2015). The effects of coenzyme Q10 administration on glucose homeostasis parameters, lipid profiles, biomarkers of inflammation and oxidative stress in patients with metabolic syndrome. European Journal of Nutrition.
Renehan, A. G., Zwahlen, M., Minder, C., et al. (2004). Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: Systematic review and meta-regression analysis. The Lancet, 363, 1346–1353.
Rock, E., & De Michele, A. (2003). Nutritional approaches to late toxicities of adjuvant chemotherapy in breast cancer survivors. The Journal of Nutrition, 133, 3785S–3793S.
Rohrmann, S., Linseisen, J., Nöthlings, U., et al. (2013). Meat and fish consumption and risk of pancreatic cancer: results from the European Prospective Investigation into Cancer and Nutrition. International Journal of Cancer, 132, 617–624.
Sattelmair, J., Pertman, J., Ding, E. L., et al. (2011). Dose-response relationship between physical activity and risk of coronary heart disease: A meta-analysis. Circulation, 124, 789–795.
Siegel, R. L., Miller, K. D., & Jemal, A. (2020). Cancer statistics, 2020. CA: A Cancer Journal for Clinicians, 70(1), 7–30.
Schnohr, P., Lange, P., Scharling, H., et al. (2006). Long-term physical activity in leisure time and mortality from coronary heart disease, stroke, respiratory diseases, and cancer: The Copenhagen City Heart Study. European Journal of Cardiovascular Prevention & Rehabilitation, 13, 173–179.
Scott, J. M., Nilsen, T. S., Gupta, D., & Jones, L. W. (2018). Exercise therapy and cardiovascular toxicity in cancer. Circulation, 137(11), 1176–1191.
Scott, L. C., Yang, Q., Dowling, N. F., & Richardson, L. C. (2021). Predicted heart age among cancer survivors — United States, 2013–2017. MMWR Morbidity and Mortality Weekly Report, 70(70), 1–6.
Shah, M. S., & Brownlee, M. (2016). Molecular and cellular mechanisms of cardiovascular disorders in diabetes. Circulation Research, 118, 1808–1829.
Shimabukuro-Vornhagen, A., Gödel, P., Subklewe, M., Stemmler, H. J., Schlößer, H. A., Schlaak, M., ... & von Bergwelt-Baildon, M. (2018). Cytokine release syndrome. Journal for Immunotherapy of Cancer, 6(1), 56.
Shoelson, S. E., Lee, J., & Goldfine, A. B. (2006). Inflammation and insulin resistance. Journal of Clinical Investigation, 116, 1793–1801.
Slavin, J. L. (2000). Mechanisms for the impact of whole grain foods on cancer risk. Journal of the American College of Nutrition, 19, 300S–307S.
Smetana, K. Jr, Lacina, L., Szabo, P., Dvorankova, B., Broz, P., & Sedo, A. (2016). Ageing as an important risk factor for cancer. Anticancer Research, 36(10), 5009–5017.
Stampfer, M., & Jahn, J. L. (2013). Partnerships for promoting prevention. Circulation, 127, 1267–1269.
Stocks, T., Van Hemelrijck, M., Manjer, J., et al. (2012). Blood pressure and risk of cancer incidence and mortality in the metabolic syndrome and cancer project. Hypertension, 59, 802–810.
Stoltzfus, K. C., Zhang, Y., Sturgeon, K., Sinoway, L. I., Trifiletti, D. M., Chinchilli, V. M., & Zaorsky, N. G. (2020). Fatal heart disease among cancer patients. Nature Communications, 11(1), 2011.
Sturgeon, K. M., Deng, L., Bluethmann, S. M., Zhou, S., Trifletti, D. M., Jiang, C., ... & Zaorsky, N. G. (2019). A population-based study of cardiovascular disease mortality risk in US cancer patients. European Heart Journal, 40(48), 3889–3897.
Sung, H., Siegel, R. L., Rosenberg, P. S., & Jemal, A. (2019). Emerging cancer trends among young adults in the USA: analysis of a population-based cancer registry. The Lancet Public Health, 4, e137–147.
Tini, G., Sarocchi, M., Tocci, G., et al. (2019). Arterial hypertension in cancer: The elephant in the room. International Journal of Cardiology, 281, 133–139.
Toledo, E., Salas-Salvado, J., Donat-Vargas, C., et al. (2015). Mediterranean diet and invasive breast cancer risk among women at high cardiovascular risk in the PREDIMED trial: A randomized clinical trial. JAMA Internal Medicine, 175, 1752–1760.
Tsukuma, H., Hiyama, T., Tanaka, S., et al. (1993). Risk Factors for hepatocellular carcinoma among patients with chronic liver disease. New England Journal of Medicine, 328, 1797–1801.
Unger, M., & Frank, A. (2004). Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Communications in Mass Spectrometry, 18(19), 2273–2281.
Vafeiadou, K., Weech, M., Altowaijri, H., et al. (2015). Replacement of saturated with unsaturated fats had no impact on vascular function but beneficial effects on lipid biomarkers, E-selectin, and blood pressure: results from the randomized, controlled Dietary Intervention and VAScular function (DIVAS) study. The American Journal of Clinical Nutrition, 102, 40–48.
van de Poll-Franse, L. V., Kwan, L., Reiter, R. E., Lee, S. P., & Litwin, M. S. (2008). The influence of cardiovascular disease on health-related quality of life in men with prostate cancer: a 4-year follow-up study. The Journal of Urology, 179(4), 1362–1367.
Wang, F., Chandra, J., & Kleinerman, E. S. (2021). Exercise intervention decreases acute and late doxorubicin-induced cardiotoxicity. Cancer Medicine, 10(21), 7572–7584.
Ward, E., DeSantis, C., Robbins, A., Kohler, B., & Jemal, A. (2014). Childhood and adolescent cancer statistics, 2014. CA: A Cancer Journal for Clinicians, 64, 83–103.
Warns, J., Marwarha, G., Freking, N., et al. (2018). 27-hydroxycholesterol decreases cell proliferation in colon cancer cell lines. Biochimie, 153, 171–180.
Wen, C. P., Wai, J. P. M., Tsai, M. K., et al. (2011). Minimum amount of physical activity for reduced mortality and extended life expectancy: A prospective cohort study. The Lancet, 378, 1244–1253.
Wolin, K. Y., Carson, K., & Colditz, G. A. (2010). Obesity and cancer. The Oncologist, 15, 556–565.
Zaorsky, N. G., Zhang, Y., Tchelebi, L. T., Mackley, H. B., Chinchilli, V. M., & Zacharia, B. E. (2019). Stroke among cancer patients. Nature Communications, 10(1), 5172.