Energy Balance and Cancer Series Editor: Nathan A. Berger Case Western Reserve University Cleveland, OH, USA For further volumes: http://www.springer.com/series/8282 wwwwwwwwwwwww Cornelia M. Ulrich (cid:129) Karen Steindorf Nathan A. Berger Editors Exercise, Energy Balance, and Cancer Editors Cornelia M. Ulrich Karen Steindorf National Center for Tumor Diseases German Cancer Research Center Heidelberg, Germany Heidelberg, Germany Nathan A. Berger Center for Science, Health & Society Case Western Reserve University School of Medicine Cleveland , OH , USA ISBN 978-1-4614-4492-3 ISBN 978-1-4614-4493-0 (eBook) DOI 10.1007/978-1-4614-4493-0 Springer New York Heidelberg Dordrecht London Library of Congress Control Number: 2012946728 © Springer Science+Business Media New York 2013 This work is subject to copyright. 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Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) Contents 1 Exercise, Energy Balance and Cancer .................................................. 1 Cornelia M. Ulrich , Karen Steindorf , and Nathan A. Berger 2 Impact of Exercise, Reactive Oxygen and Reactive Nitrogen Species on Tumor Growth ...................................................... 7 Andreas N. Kavazis and Scott K. Powers 3 Exercise Associated Regulation of Tumor Promoters, Hormones and Cytokines in Cancer Control ....................................... 21 Nora L. Nock and Nathan A. Berger 4 Exercise Impact on Immune Regulation of Cancer ............................. 37 Huicui Meng and Connie J. Rogers 5 Biological Pathways Impacting Cancer Survival: Exercise as a Countermeasure for the Development and Progression of Cachexia .................................................................. 59 James A. Carson and Melissa J. Puppa 6 Physical Activity and Primary Cancer Prevention .............................. 83 Karen Steindorf , Michael F. Leitzmann , and Christine M. Friedenreich 7 Bene fi ts and Rationale for Exercise During Cancer Therapy ............ 107 Morten Quist and Lee W. Jones 8 Exercise During Stem Cell Transplantation ......................................... 119 Joachim Wiskemann and Cornelia M. Ulrich 9 Physical Exercise in Advanced Malignant Diseases ............................. 143 Winfried Banzer , Ezster Füzeki , Markus Bernhörster , and Elke Jäger 10 Exercise in Pediatric Cancer Patients ................................................... 159 Luisa Soares-Miranda , Carmen Fiuza-Luces , and Alejandro Lucia 11 Exercise in Elderly Cancer Survivors ................................................... 181 Anna L. Schwartz and Kerri Winters-Stone v vi Contents 12 Bene fi ts of Aerobic and Resistance Exercise for Cancer Survivors ............................................................................... 199 Melinda L. Irwin 13 Exercise Behavior, Motivation, and Maintenance Among Cancer Survivors ....................................................................... 215 Jeff Vallance , Lauren Spark , and Elizabeth Eakin Index ................................................................................................................. 233 Chapter 1 Exercise, Energy Balance and Cancer Cornelia M. Ulrich , Karen Steindorf , and Nathan A. Berger Energy balance in living organisms is a complex process in which energy input, determined by quantity and quality of caloric intake, is balanced by energy expenditure, which includes physical activity, exercise, and thermogenesis. These processes are exquisitely regulated by environmental, physiologic and genetic in fl uences, as well as by biobehavioral in fl uences including appetite, satiety and sleep, to facilitate normal growth, development and function. Abnormalities in any aspect of these processes may result in underweight and malnutrition or overweight and obesity and a variety of comorbid conditions. Obesity can be associated with multiple comorbidities including diabetes, cardiovascular diseases and a variety of malig- nancies. In contrast, physical activity and exercise have been associated with pre- vention of these disorders and with bene fi cial effects in their therapy and outcomes. More speci fi cally, physical activity and exercise are associated with reduced risk of some malignancies, with evidence considered convincing for colon cancer, probable for endometrial and post-menopausal breast cancer and limited for lung, and pan- creatic cancers [1 ] . Carefully designed programs of moderate to aggressive physical activity and exercise in patients with cancer can lead to improved quality of life, reduced cancer related fatigue, improved cardiovascular fi tness, reduced visceral fat C. M. Ulrich , Ph.D. (*) Preventive Oncology, DKFZ , National Center for Tumor Diseases (NCT) , Im Neuenheimer Feld 460 , 69120 Heidelberg , Germany e-mail: [email protected] K. Steindorf , Ph.D. Unit of Physical Activity and Cancer, Preventive Oncology and Environmental Epidemiology , German Cancer Research Center (DKFZ) , Im Neuenheimer Feld 280 , 69120 Heidelberg , Germany e-mail: [email protected] N. A. Berger , M.D. Hanna-Payne Professor of Experimental Medicine, Center for Science, Health and Society , Case Western Reserve University , 10900 Euclid Avenue , Cleveland , OH 44106-4971 , USA e-mail: [email protected] C.M. Ulrich et al. (eds.), Exercise, Energy Balance, and Cancer, Energy Balance and Cancer 6, 1 DOI 10.1007/978-1-4614-4493-0_1, © Springer Science+Business Media New York 2013 2 C.M. Ulrich et al. mass and improved bone mineral density [ 2, 3 ] . Moreover, exercise has more recently been shown to improve both overall and, in some cases, cancer-speci fi c survival [ 4 ] . Yet concern exists that exhaustive exercise may cause suf fi cient increase in oxidative stress to increase in fl ammation, impair immune function and allow for increased tumor growth [5 , 6 ] . Thus, careful examination of the risks and bene fi ts associated with exercise interventions and their potential mechanisms of action is a central theme in considerations of energy balance and cancer. Various aspects of the relations between exercise and cancer have been considered in earlier volumes of Energy Balance and Cancer including Volume 1, Cancer and Energy Balance, Epidemiology and Overview; Volume 2, Insulin Resistance and Cancer: Epidemiology, Cellular and Molecular Mechanisms and Clinical Implications; Volume 3, Physical Activity, Dietary Calorie Restriction, and Cancer; Volume 4, Energy Balance and Hematologic Malignancies; and Volume 5, Energy Balance and Gastrointestinal Malignancies. This sixth volume now focuses entirely on a transla- tional and transdisciplinary examination of the role of exercise in the relation between energy balance and cancer, its risks and bene fi ts across the age spectrum, potential mechanisms of action, and strategies for implementation and sustainability. The stimulus for this volume derives from a National Center for Tumor Diseases (NCT) Conference on Exercise, Energy Balance and Cancer: De fi ning the Role and Potential of Exercise and Body Weight Maintenance in Cancer Prevention, Treatment and Outcomes, convened in November 2010 in Heidelberg, Germany by Professor, Cornelia M. Ulrich, Director, National Center for Tumor Diseases, and Head, Division of Preventive Oncology, German Cancer Research Center (DKFZ), Professor Karen Steindorf, Head, Physical Activity and Cancer Research Group (DKFZ and NCT), Dr. Joachim Wiskemann, Ph.D., Scienti fi c Coordinator, Physical Activity and Cancer, Division of Preventive Oncology, (DKFZ and NCT) and Professor Dirk Jäger MD, Head Medical Oncology and Director, NCT. The confer- ence featured an international, transdisciplinary series of experts in the fi eld of energy balance and cancer, who discussed their research and clinical experience in multiple areas including the role of physical activity and exercise across the spec- trum from cancer prevention to cancer survivorship; potential mechanisms linking physical activity and exercise to cancer risk and survival; effects of exercise at all stages of anticancer therapy; application of exercise interventions in different clini- cal settings and challenges of sustaining exercise in cancer survivors. The importance of implementing a transdisciplinary approach to better under- stand the role of exercise in cancer risk reduction and to most effectively incorporate exercise into cancer prevention and control strategies was emphasized by Dr. Linda Nebeling, Chief, Health Promotion Research Branch, Behavioral Research Program, Division of Cancer Control and Population Sciences (DCCPS), National Cancer Institute (NCI), and by Dr. Robert Croyle, Director, DCCPS, NCI, who provided an expert overview of the science and organization in the USA focused on exercise, and, more broadly, on energy balance and cancer. These two have provided leader- ship and guidance for the development and ongoing coordination of the innovative US NCI sponsored program on Transdisciplinary Research on Energetics and Cancer (TREC) [7 , 8 ] . 1 Exercise, Energy Balance and Cancer 3 The conference emphasized the important conceptual and practical challenges that occurred in recent years in the application of physical activity and exercise for cancer patients and during cancer therapy. Historically, it was noted that doctors admonished their patients to refrain from strenuous exercise during cancer treat- ment. The standard motto was “no sports or physical activities for cancer patients, they need to save their energy and get plenty of rest and relaxation.” In the 1980s and 1990s patients were still given this admonition in spite of the fact that epidemio- logic studies indicated that the right amount of physical effort had a protective effect that was likely to both reduce the incidence of cancer and bene fi t clinical outcomes in cancer patients. Further research has shown that exercise clearly reduces the risk of certain cancers including colon, breast and probably endometrial, has a salutary bene fi t in patients undergoing cancer therapy, promotes improved quality of life and prolongs survival in cancer patients. A striking contrast at the conference, was the observation that, while clinicians and scientist in the United States were interested in investigating the role of exercise in prevention and therapy of cancer, the Europeans had already signi fi cantly incor- porated exercise into their therapeutic regimens. Commenting on the change in atti- tude in Europe towards incorporation of exercise programs into the approach to cancer patients, one of the presenters, Professor Fernando Dimeo, Charité Campus Benjamin Franklin, Medicine, Berlin, Germany, noted that cancer patients at his institution now question why they are being neglected, if the exercise team does not visit them within a few days of their hospitalization for cancer. Rapid incorporation of exercise into the overall approach to cancer patients in Europe compared to its rather sluggish uptake in the United States was attributed, in part, to the cultural orientation to regular participation in physical activity and sports in Europe versus a more spectator approach to sports in the US. The Heidelberg Conference and this volume address many of the same important questions, including, but not limited to, the following: Is exercise possible and bene fi cial for all types of cancer, across the age spectrum and at every stage of the disease? Which type of physical training is the most effective for cancer prevention and prognosis? What type, how much and at what frequency? What are the biologic mechanisms by which exercise contributes to the well-being of healthy individuals and what are the bene fi ts and the mechanisms by which exercise improves the well- being and survival of cancer patients? What kind of physiological, psychological and social changes can be obtained with exercise programs for cancer patients? What are the best ways to maintain a high level of physical activity over long peri- ods of time in cancer survivors? Answers to these questions, provided in this vol- ume, should contribute to better understanding of the risks and bene fi ts associated with exercise in cancer patients and help to optimize the use of exercise in cancer prevention and control. In preparing this volume we have been fortunate to engage many of the experts and pioneers who participated in the 2010 Heidelberg Conference and to attract other top investigators to share their expertise. In Chap. 2 , Andreas N. Kavazis, University of Mississippi and Scott K. Powers, University of Florida, U.S.A., discuss the impact of free radicals generated by exercise on tumor growth and the