Fifth Dimension Catalog Contact Us
|
|||
|
Childhood and Adolescent Cancer Survivorship |
||
|
|||
|
Over the last four decades, there has been a dramatic improvement in the survivorship of those with both childhood and adolescent cancers, in part due to improved research and treatment , development of new and better drugs, and a better understanding of the complications and morbidity of cancer treatment. The current five-year survival is approximately 80%, but survivors face many new problems due to the complications and side effects from therapy and long- and late-term toxicity and comorbidities.1 The National Cancer Institute funded the Childhood Cancer Survivor Study to address these problems, and the May 2009 issue of the Journal of Clinical Oncology is devoted to reviewing the results of this study. The Childhood Cancer Survivor Study was established in 1994 with the goal of improving survivorship. The results have shown an improvement in survival from about 30% in 1960 to approximately 80% in 2004 through knowledge of potential problems in the future, and how best to treat them through improved supportive care, including both physical and psychosocial issues. It is important to improve the survival rate. Long-term survivors have the risk of toxic side effects, which are now being seen as survivors are living longer, and often includes impaired cognitive function, fertility problems, psychosocial and employment problems as these children and adolescents advance into extemnded (up to 30 years) adulthood years. Long-Term Survivors Following successful treatment, a new and different life develops. Through research, we now better understand some of the consequences of treatment, toxic side effects, which can occur late (up to 30 years) and the risk of disease recurrence as some of the problems that are now being faced. Fortunately, a consortium of institutions treating childhood and adolescent cancers in the United States and Canada are now working together to help study and resolve problems. Together, they are addressing the major issues facing young adults, including prevention of comorbid diseases, reproductive infertility issues, second malignancies, secondary toxic problems from chemotherapy, surgery or radiation, neurologic and neuropsychiatric problems, as well as problems of cancer control. This is being accomplished through a cooperative effort, involving systematic surveillance of these potential problems. This large cooperative of centers specializing in childhood cancers has been able to improve survivorship for these young people as they mature into and through adulthood through the resources of the scientific community at these specialized centers. The goal is to improve the well-being of cancer survivors through the efforts of pediatric oncologists, primary care physicians, and cancer researchers. The goals, in part, have been attained, and future improvements are planned for better survivorship. Studies years ago, as therapy was being developed for childhood cancers, detected a variety of late side effects of therapy. With expansion of the cooperative of the Childhood Cancer Survivors Study, knowledge and data are being acquired and analyzed to help improve a healthier survivorship. It is a new field, requiring the cooperation of many institutes ten years following diagnosis to better appreciate potential problems.2 The CCSS, being a cooperative of many childhood cancer centers in the U.S. and Canada, has appreciated the heterogeneity of both the follow-up, as well as the consequences of therapy. The success of the CCSS after twenty-five years in the United States and one in Canada, is a more accurate follow-up on the health of childhood and adolescent
Outcomes of Therapy Chemotherapeutic Problems Approximately 42 different chemotherapeutic agents are used in treating childhood and adolescent cancers, and subsequent problems relate to the duration of therapy and the cumulative dose used. Agents, such as anthracyclines or alkylating, have well-known side effects, which were reviewed by a panel to reach a consensus on potential and actual toxicities. For example, cardiac toxicity from anthracyclines for potential congestive heart failure (CHF) was validated in one study, showing 292 survivors. Telephone and Internet follow-up and self-reporting methods were utilized. With the success of the CCSS, we will end up with a better understanding of the risks and sequelae of treatment and have the opportunity of developing focused interventions, improved screening and follow-up surveillance. With childhood cancer survivors now living longer with about an 80% five-year survival rate, they have become vulnerable to late morbidity and mortality secondary to either cancer recurrence of the primary disease, second malignancies, or toxicities from surgery, radiotherapy and chemotherapy. The improvement in diagnosis and therapy has contributed to the increased survival rate, with a growing population of long-term survivors. The results are late long-term morbidity and mortality.3 Liu has reported an 83% overall survival at twenty years. Certain primary cancers have a higher death rate, such as acute lymphoblastic leukemia, often seen with central nervous system relapse and disease, often with late mortality. The five-year survival for Hodgkin's lymphoma is about 90%, and the ten-year survival is approximately 50% for all. 4 In 1971, cardiovascular deaths due to myocardial infarction and cerebral vascular accidents had a five-fold increase in incidence. Of 37,324 and the mortality experience of 20,483 survivors, there were 2,821 deaths as of 2002. That is 18.1% at thirty years from diagnosis. The mortality rate is decreasing for recurrence or progression of primary disease, and the increased mortality rate is attributable to subsequent neoplasms, about 15.2%, and death, about 7%. Part of these are related to cardiac deaths and anthracycline therapy and deaths related to radiation therapy, with a relative risk of 2.9, alkylating agent therapy with a relative risk of 2.2, as well as risks to other drugs, and to subsequent malignancies. Cardiac radiation exposure relative risk is 3.3, and high-dose anthracycline exposure relative risk is 3.1 and is related to cardiac deaths. Chronic comorbid diseases Long-term cancer survivors often develop chronic diseases, which involve one or several organ systems. This, in part, is related to their general health, as well as prior treatment risks. 5 Various comorbidities, including endocrine diseases, such as thyroid disorders, disorders of growth and weight, and pubertal maturation, cardiac disease, osteonecrosis, pulmonary and neurological comorbidities, are seen. Outcomes differ for each disease entity. A lot depends on the exposure of the body or an organ to the disease process or the treatments. An example might be having a stroke after neck radiation therapy or disorders of the kidneys or urinary tract, or gastrointestinal tract diseases. Another example might be long-term neurologic sequelae with varied symptomatology, such as seen in childhood brain tumors with both physical and psychological adverse neurological compromises. Thirty years ago, it was noted that there was an increased incidence of second malignant neoplasms in childhood cancer survivors.. This was believed to be related to host disease factors and therapy-related risk factors. Among 14,358 cohort members, there were 730 who reported 802 second malignancies. These excluded non-melanoma skin cancers. That is a 2.3-fold increase in SMs. There is a relationship to both the host as well as the therapy as probable causes of the second malignancies. Non-melanoma skin cancers and meningiomas were more common.6 Potential long-term morbidity and mortality The CCSS evaluated groups with the highest risk for morbidities, who could benefit from risk-based surveillance. This included a wide variety of potential late toxicities based, in part, on sex, race, ethnicity, and age at diagnosis. Some of the toxicities related to radiation therapy plus bleomycin, anthracyclines, chest, abdominal, or pelvic radiation, or alkylating agents. In general, there was at least a ten-fold excess risk of having a severe or life-threatening chronic health condition. Side effects included both cardiopulmonary disease and secondary cancers, which are problems noted in the older age group. Therapy with alkylating agents, abdominal, pelvic or chest radiation, of radiation to the ovaries or testes added the potential for infertility and comorbidities as well. Thyroid abnormalities in function, as well as other endocrinological dysfunctions, were often seen secondary to chest radiation for Hodgkin's disease or brain radiation. Screening for thyroid dysfunction requires annual monitoring of thyroid function via laboratory tests, as well as measurements of growth, reproduction, cardiovascular disease, neurocognitive function, and psychosocial/emotional function, to assess for hypo- and hyperthyroidism. Patients with central nervous system tumors and leukemia, especially those treated with craniospinal radiation therapy, were at risk, and an estimated 40% had a deficit in linear growth and adult stature. There were also abnormalities in both weight and body mass index from the therapies, and there was an increased risk of being overweight or obese. Overweight is a BMI >25, and obese is >30 kg/m2. There were also deficits in sexual development and reproductive function with premature ovarian failure and infertility, as well as the effects of pituitary gland and other glandular failure secondary to cranial radiation therapy. This often resulted in growth hormone deficiency with overweight and obesity. For men, reproductive organ deficiency secondary to radiation of the testes or use of alkylating agents led to testicular dysfunction and often sterility and delayed puberty. Pulmonary toxicity was increased secondary to radiation therapy and/or cumulative chemotherapy drug use, especially for leukemia and Hodgkin's disease, as well as those undergoing bone marrow transplants. Strokes are rare in children and healthy young adults; although, the prevalence of stroke factors was increased in childhood cancer survivors, especially survivors of leukemia and brain tumors. The most prominent treatment risk factor for subsequent stroke was radiation therapy. Health Behaviors, Medical Care, and Interventions to Promote Healthy Living8 Children and adolescents with cancer are at increased risk for serious morbidity and premature mortality. They often have decreased quality of life, depending on their exposure to various treatments, and they are at increased risk for coronary artery disease, cerebrovascular disease, diabetes, hypertension, dyslipidemia, renal insufficiency and subsequent secondary malignancies, as well as potential infections. 9 Knowing these risks, it is important to utilize behavior modifications that could potentially decrease the risk of subsequent illnesses - comorbidities. Preventive health programs have been developed for Hodgkin's lymphoma and acute lymphoblastic leukemia. Hodgkin's lymphoma patients who had chest radiation have an increased risk of lung cancer. Use of tobacco has been estimated to increase the risk about twenty-fold.9 Strategies to prevent childhood cancer survivors from smoking are important for optimal disease prevention, not only for cancer but also for heart disease, stroke, and secondary cancers. Women who receive chest wall radiation are at risk for breast cancer at a younger age and merit mammograms and follow-up, starting around age twenty-five. Magnetic resonance imaging is recommended and has improved survival. All chemotherapy treatments increase the risk of different comorbidities, including obesity, osteoporosis, insulin resistance, cardiovascular and cerebrovascular diseases, and chronic hepatitis C. Excessive drinking is also a promoter of cancer survivors' risk of comorbidities. Dietary habits with a recommended low-fat, Mediterranean-type diet plus calcium and vitamin D should be promoted. Physical exercise is recommended as part of the healthy lifestyle. Health benefits are achieved through healthy behaviors and lifestyle habits adopted to help promote a healthier longevity. Tobacco In a large study, 28% of survivors reported that they smoked at least 100 cigarettes in their lifetime (19% male and 15% female). In 1999, this compared to 23.5% of the U.S. population admitting to smoking. The current smoking rate is about 20%. Over half of these smokers related there was smoking in their social network, family or friends, and many had a lower level of education and economic status which increases health problems. Smoking cessation programs were common, and 41% of smokers reported that they had joined a quit program over the prior two years. They did have a lot of encouragement from family and friends to stop smoking, but the social networks were often the compromise. Being younger than fourteen, not having graduated from high school and having received brain radiation therapy were associated with failure to quit smoking. Alcohol Use Additional Health Behavior Risk Factors Physical Activity Exercise is important in all versus inactive activity. Those receiving anthracycline drugs have some risk for cardiac failure, and exercise is recommended to reduce risk factors. Dental Problems Dental problems usually occur before five years or with those who receive cranial radiation therapy. Regular dental care is recommended. Approximately 60% of survivors had seen a dentist within a year, due either to lack of health insurance or education of risks. Dental compliance care is, in general, considered suboptimal. Health Care for the Future The CCSS is planning three interventional health studies, and Emmons completed the first intervention study to promote healthy lifestyles and smoking cessation.10 Fifteen percent quit smoking for at least eight months. Conclusion Potential Screening Techniques 1. Cerebrovascular Disease 2. Secondary Neoplasms Radiation exposure was one of the leading causes of secondary neoplasms, especially in females with Hodgkin's disease, or tissue sarcomas, and those treated with alkylating agent chemotherapy. Familial cancer predisposition also played a role for the risk of breast cancer - radiation therapy between age 10 and 16 increased the risk, as this was the time of rapid breast tissue proliferation. Hereditary predisposition also played a role, as well as the association with thyroid disease, especially when the thyroid was treated with radiation, often in high doses.
3. Skin Cancer 4. Additional Cancers Screening is important. Potential tumors are numerous, including breast, thyroid, CNS, bone, skin, and soft tissue. Simple measures, such as avoidance of excess sunshine, can reduce the risk of skin cancer recurrence or secondary malignancy. Following Hodgkin's disease, chest wall radiation therapy, thyroid assessment, as well as screening mammograms starting at age 25, and assessment for potential lung cancer are part of the screening techniques necessary for optimal follow-up.
Summary References
|
|
|
You are welcome to share this © article with friends, but do not forget to include the author name and web address. Permission needed to use articles on commercial and non commercial websites. Thank you. |