White Paper. Understanding the Scope and Challenges of Childhood Cancer. Introduction

Transcription

1 White Paper Understanding the Scope and Challenges of Childhood Cancer Introduction Imagine a world without childhood cancer. No painful chemotherapy treatments. No emotional stress on children and their families. No financial sacrifice. CURE Childhood Cancer is dedicated to discovering a cure for childhood cancer through cutting edge research and providing support to patients and their families through our innovative programming. Since its inception in 1975, CURE has focused on improving the care, quality of life, and survival rate of children with cancer. The founders parents and a dedicated pediatric oncologist joined forces to support laboratory research that would translate into immediate care for children with cancer. Research is at the core of CURE s drive to cure childhood cancer. The accomplishments of childhood cancer research teams across the U.S. and the world have made excellent inroads into understanding how to fight this devastating disease. Since the mid-1950s, survival rates have risen from less than 10 percent to almost 80% overall for children with cancer. 1 Only about 3% of federal funding for cancer research is directed at solving cancers that impact our children. The objective of this White Paper is to help you understand the basics of childhood cancer where we have come from and the challenges ahead in curing this horrible disease. The content of this document has been sourced from the primary children s cancer research centers including CureSearch (uniting the Children s Oncology Group and the National Childhood Cancer Foundation), the National Cancer Institute and the National Institute of Health. While this white paper provides a good starting point in helping you understand the challenges ahead, we encourage you to visit the websites of these organizations and institutions for more details. You will see that while we have made excellent progress, we have a lot more to do in letting children live cancer free. 1

2 The State of Childhood Cancer Cancer is the No. 1 disease killer of children in the U.S. and the second overall killer of children, behind car accidents. We tend to talk about it in hushed tones instead of screaming for help. But scream we should. Cancer is the leading cause of death by disease among U.S. children between infancy and age Nearly 30% of the U.S. popoulation is under the age of 20. Helen Jonsen, Senior Editor, Forbes.com, 9/08 Approximately 12,400 new cases of pediatric cancer were diagnosed in children 0 20 years of age in A newborn male has a 1 in 300 chance (0.32%) of developing cancer by the age of 20. Similarly, a newborn female has a 1 in 333 chance (0.30%) of developing cancer by age Although the incidence of invasive cancer in children has increased slightly over the past 30 years, mortality has declined dramatically for many childhood cancers. The combined 5 year survival rate for all childhood cancers has improved from less than 50 % before the 1970s to 80 % today. The ten year survival rate is almost 75%. 4 While these statistics are promising, certain types of childhood cancers, such as brain tumors and neuroblastoma, for instance, remain very difficult to beat. While the incidents of childhood cancer have steadily increased, the number of deaths has been reduced over a 20-year period. Cancer for children, unfortunately, is not one disease type. There are about 25 different types of childhood cancers. Childhood cancers vary by type of histology (tumor type), site of disease origin, race, sex and age. The most common forms of cancer in children (accounting for more than half of new cases) are: Leukemias (blood cell cancers) Brain and other central nervous system tumors 2

3 Only more recently has it been realized that the intense effort to care for and cure a child with cancer does not end with survival. Continued surveillance and a variety of interventions may, in many cases, be needed to identify and care for consequences of treatment that can appear early or only after several decades and impair survivors' health and quality of life. There is an additional dimension of childhood cancer that is important to consider survivorship. It is estimated that there are more than 270,000 cancer survivors in the United States today who were diagnosed with cancer under the age of 21. As a consequence, understanding the long term health implications of these childhood cancer survivors is critical to understanding the therapies and treatments being used today and being developed for tomorrow. The incidence of childhood cancer peaks in the first year of life. Incidence is higher for children under five and for those ages 15-19, and lower for children ages Where have the primary advancements come from in curing childhood cancer? They have come from very specific, targeted research on the many elements and dimensions that make up this complex disease. Each and every cancer type represents its own unique set of challenges. The primary obstacles are time and money. As an example, the research required to bring a single, new targeted therapy drug can take years. While the knowledge database developed and shared by childhood cancer researchers increases daily, the size of the task continues to be large and complex in scope. For children with cancer, time is never on their side. 3

4 Understanding the Types of Childhood Cancer There are about 25 different types of childhood cancer. This section covers the most common types of childhood cancers. Remember that childhood cancers not only vary by type, but by age, sex and race. The table below is derived from content from the Children s Oncology Group (CureSearch) and the National Cancer Institute websites. 6 Category and Types of Childhood Cancer Description Leukemia: cancer of the bone marrow and the tissues that produce the circulating blood cells. Acute Lymphoblastic Leukemia (ALL) The most common childhood cancer. Almost 75% of children with leukemia have ALL, a cancer of the lymphoid cells in the bone marrow and the lymphoid Acute Myelogenous Leukemia (AML) organs of the body (in the body s immune system). AML (also called acute myeloid leukemia, acute nonlymphatic leukemia or ANLL) is cancer of the myeloid blood cells which are produced in the bone marrow and which help fight bacterial infections. Central Nervous System Brain tumors The central nervous system (CNS) is made up of the brain and the spinal cord. Together, these important organs control functions necessary to sustain life, such as breathing, heart rate, movement, thinking and learning. Important substances produced in the brain (hormones) stimulate and control many other organs in the body. Brain tumors that develop have many unique properties and symptoms. Types of brain tumors include: Meduloblastoma, Ependymoma and Gliomas. Neuroblastoma: Neuroblastoma is a solid tumor or cancer. It occurs in the developing cells of the sympathetic nervous system, called neuroblasts. The sympathetic nervous system is responsible for involuntary actions of the body, such as blushing, increasing heart rate, and dilating the pupils of the eye. The majority of tumors (65%) are located above the kidney. However, tumors can begin anywhere in the body. Other common sites are the chest, neck or pelvis. The disease often spreads from its "primary" location to the bone marrow, bones or lymph nodes. Sarcomas: cancerous tumors of the bones and soft tissues Bone Cancers Osteosarcoma: The most common type of bone sarcoma. These tumors often are located at the growing end of the long bones of the extremities, close to the joints. 4

5 Ewings Sarcoma: A bone cancer that often appears in the middle of the bone. Commonly found in the thighs, hipbones, upper arms and ribs. Soft Tissue Sarcomas Rhabdomyosarcoma A soft tissue sarcoma that develops in muscles. Most often found in the head, neck, kidneys, bladder, arms and legs. Lymphomas: Lymphoma is a tumor of the lymph tissues (part of the immune system). Hodgkin disease or Hodgkin's Affects lymph nodes nearer to the body s surface, lymphoma: such as in the neck, armpit and groin area. Non-Hodgkin Lymphoma: Affect lymph nodes found deep within the body. There are many types of lymphoma, including Burkitt's, non-burkitt's, and lymphoblastic lymphoma. Liver Cancers: Liver cancer is an abnormal growth (tumor) in the liver Hepatoblastoma Tumor of the liver especially of infants and young children. Hepatocellular carcinoma Cancer from the parenchymal cells of the liver. A type of adenocarcinoma, the most common type of liver tumor. Cancers of the Kidney Wilms tumor (also called Most common type of kidney tumor. A disease in nephroblastoma) which malignant (cancer) cells are found in the kidney, and may spread to the lungs, liver or nearby lymph nodes. Wilms tumor usually occurs in children younger than 5 years old. Clear Cell Sarcoma Other types of Cancers Retinoblastoma: Germ Cell Tumors: A rare type of kidney cancer, in which the inside of the cells look clear when viewed under a microscope. Clear cell sarcoma can spread from the kidney to other organs, most commonly the bone, but also including the lungs, brain and soft tissues. A malignant tumor of the retina. Retinoblastoma is a rare cancer, occurring in about one in 20,000 children. It originates in a part of the eye called the retina, a thin layer of nerve tissue that coats the back of the eye that allows a person to see. Retinoblasts (immature cells of the retina) multiply during gestation and early life, to make enough cells to create the retina. As children age, the cells mature and are no longer able to divide and multiply, a process called differentiation. Germ cell tumors appear most commonly in the testes, the ovaries, at the bottom of the spine (sacrococcygeal) and in the middle of the brain, chest or abdomen. 5

6 Where We ve Come From Cooperative Research Multi-institution clinical trials by cancer clinical researchers are the most efficient way to apply new laboratory discoveries to advance diagnosis, selection of the most appropriate treatment and, increasingly, to prevent cancer. Today, there are 63 member hospitals in the NCI research network. What is Chemotherapy? Chemotherapy is a cancer treatment that uses drugs to destroy cancer cells. Chemotherapy can be used to: Destroy cancer cells Stop cancer cells from spreading Slow the growth of cancer cells Chemotherapy can be given alone or with other treatments. It is interesting to note that chemotherapy was first used on children with cancer. Today, chemotherapy is generally a regular part of cancer treatment. Cancer research dates back well over 100 years. By the 1930 s, the U.S. Congress recognized the importance of studying and researching the causes and cures for cancer. The National Cancer Act of 1937 allocated funds to form The National Cancer Institute (NCI). NCI s mandate was to: Conduct and foster cancer research; Revise and approve grant-in-aid applications to support promising research projects on the causes, prevention, diagnosis and treatment of cancer; Collect, analyze and disseminate the results of cancer research conducted in the United States and in other countries; and Provide training and instruction in the diagnosis and treatment of cancer. NCI has been instrumental in establishing a nationwide network of cancer researchers, health professionals, patients and their families, and the general public to share information. An important part of NCI s charter was training and cross-training new researchers to join in the fight against cancer. In the mid-1950 s, NCI formed a treatment initiative among seven research hospitals to treat acute leukemia, the most common childhood cancer. These hospitals agreed to cooperate in clinical trials of several new drugs, including chemotherapy. By 1955, clinical trials of chemotherapy had begun. Chemotherapy was found effective for children with acute leukemia by eliminating leukemia cells from the bone marrow and circulating blood. Based on this success, chemotherapy was tried against the cancers of solid organs. The strategy entailed combining surgery, chemotherapy and radiation therapy in treating the solid malignant tumors of children. 6

7 What is a clinical trial? A clinical trial is a research study whose purpose is to determine the most effective treatment for a particular disease. Each trial is based on a detailed evaluation of factors involved in the standard treatment (the current best treatment) and factors that could lead to better survival rates or a reduction in side effects or late effects of treatment. The original group of research hospitals that had been formed originally to test chemotherapy for leukemia was reorganized to include the principal medical disciplines needed to diagnose and treat solid tumors of children as well as leukemia. Kidney and muscle cancers, which occurred mainly in children, followed in the research path. Combined treatment types including surgery, chemotherapy and radiation therapy in treating solid malignant tumors were found to produce the best results. As a result, advances were made in the treatment of pediatric kidney and muscle cancers. Over the years, cancer researchers across the U.S. have focused on understanding the inner workings of cancer. The cooperative research efforts of many NCI affiliated researchers and institutions have yielded a body of important knowledge contributing to: Understanding how normal cells transform into cancer cells and how to develop therapies to overcome that process without harm to normal cells and tissues. These are called target therapies. The discovery of the first tumor suppressor gene which was discovered in childhood cancer cells. The principle of multi-drug therapy, which was pioneered in childhood cancer. What is a targeted therapy? Targeted therapies are treatments that directly affect only cancer cells. Where We Are Today Significant strides have been made in understanding the nature of childhood cancers. The cooperative efforts of many research organizations have improved the survival rates for certain types of childhood cancer dramatically from less than 10% to almost 80%. 7 Cure rates, though, still vary according to each specific type of childhood cancer and certain types of childhood cancers remain very tough to conquer. As the research horizon expands, new treatments based on immunology, bone marrow and stem cell transplantation and newer treatments derived from molecular biology and genetics are now in increasingly wider use. 7

8 Research in cellular and molecular biology, genetics, immunology and epidemiology has become an important aspect of cooperative group cancer research. Research organizations across the country are improving diagnostic evaluation, developing new treatments and evaluating how they affect cancer cells. Human Genome Project There are about 20,000 to 25,000 genes in the human body. In 1990, an international research project began to decipher the sequence of chemical base pairs that make up DNA. In 2003, researchers released a working draft of the genome (full set of chromosomes or genes). The important discoveries found through the Human Genome Project will be instrumental in leading to better diagnosis and treatments of childhood cancers. The key advancements in understanding and curing childhood cancer have come through targeted research efforts at research hospitals across the nation. Here are some highlights of progress that has been made: 8 Decreased childhood cancer mortality by 25%. Improved survival of acute lymphoblastic leukemia from 70% to 80%. Improved survival of acute non-lymphoblastic leukemia from 35% to 50%. Improved survival of the most common form of non- Hodgkin s lymphoma from 70% to 90%. Improved survival of widespread childhood neuroblastoma from 10% to 45%. Reduced by 50% or more the need for radiation therapy for the following groups of patients, thereby reducing risks of long-term effects of radiotherapy: o acute lymphoblastic leukemia o infants under 3 years of age with brain tumors o adolescent females with Hodgkin s disease Established efficacy of 8 new anti-cancer agents and combinations of such agents for the first time in pediatric cancers. Shortened the treatment time for the most common form of non-hodgkin s lymphoma, Hodgkin's disease, and all forms of childhood acute non-lymphoblastic leukemia by 30%-50%. Successfully evaluated several agents that reduce the side effects of pediatric cancer treatment (i.e. G-CSF, Dexrazoxane). Published recommendations for long-term follow-up care for all cancers of children and adolescents. Established the first broad effort to develop new treatments for cancers common to adolescents and young adults, and demonstrated the superiority of pediatric treatment protocols over adult treatment protocols for several cancers of young adults. 8

9 Where We Are Going While tremendous progress has been made in understanding and treating childhood cancers, a great deal still needs to be done. Some of the broad goals outlined by the Children s Oncology Group are: Increase the survivor rate above 85% in the short term. Reduce deaths from childhood cancer by 20%. Focus on the types of childhood cancers that are the most difficult to cure. Escalate research to develop treatments that cure the child while causing the least possible side effects and long-term effects. Link biology and laboratory investigations to clinical trials to better identify new options for improved and less toxic therapy Evaluate short- and long-term consequences of cancer and anti-cancer therapy in patients who are cured to improve the quality of life during and after treatment. Gene Expression Array: What happens that causes normal cells to turn into cancer cells? One type of laboratory study is called a gene expression array. Using special techniques, researchers can identify those genes that are active in the cancer cells, but not in the normal cells. This allows them to focus attention on those genes to discover their role in causing cancer. Special drugs, called biologic agents, can then be developed to target those specific genes. The modern definition of cure for children goes far beyond achieving disappearance of the evidences of cancer. It now includes the goals of psychosocial, educational, and occupational reintegration of the child into a successful life. In social terms, the impact of this achievement is considerable: The cure of a child saves an entire lifetime. 9 Survivorship studies are looking carefully at the long term impact of the drugs and therapies on children that have had childhood cancer. There are about 270,000 childhood cancer survivors in the U.S., or about 1 in every 900 young adults. A University of Minnesota study, which looked at 14,358 survivors of childhood leukemia, central nervous system tumors, Hodgkin's and non-hodgkin's lymphoma, kidney tumors, bone cancers, neuroblastoma and soft-tissue sarcoma, determined that childhood cancer survivors are 5- to-10 times more likely to develop heart disease. "This study clearly shows for children, and particularly children treated with radiation therapy to the chest or certain drugs that are particularly toxic to the heart, there are 9

10 significant risks of cardiovascular disease at a far youngerthan-expected age," said Dr. Richard Schilsky of the University of Chicago. Children have often had to accept medicines and treatments based on what is known to work in adults. we should not agree to this "hand-me-down" approach. Many efforts are being made to provide proper research for children, to find the best treatments, drugs, and devices for them. 11 The cancer survivors were 10 times more likely to have clogged arteries, 5.7 times more likely to have heart failure, 4.9 times more likely to have heart attacks, 6.3 times more likely to have pericardial disease -- affecting the sac surrounding the heart -- and 4.8 times more likely to have diseased heart valves compared with their siblings. Heart problems are just one example of the long term adverse health consequences that commonly arise from conventional treatments. Research Funding While funding for cancer research has steadily grown at The National Cancer Institute, the percentage dedicated to childhood cancer is surprisingly small. The NCI budget in 2007 was $4.8 billion. This encompassed the research of all cancer types, for all ages. NCI s budget for pediatric cancer research in 2007 was $172.7 million. Only 3% of the NCI total budget was dedicated to solving cancers affecting children. "Children are not little adults. They are unique." Dr. Renee Jenkins, Pediatrician, American Academy of Pediatrics President, Three percent is a disproportionate amount compared to research efforts for adults. Worse still, the current economic climate has forced cutbacks recently at NCI that have impacted the amount of research funding allocated to childhood cancer. In response to the most recent cutbacks, the National Cancer Institute has decreased funding which especially impacts childhood cancer research. As a result, the Children s Oncology Group (COG), the world s pre-eminent childhood cancer research organization, has been forced to put 20 new studies on hold and decrease enrollment in new clinical trials by more than 400 children next year. 10 We cannot afford to cut back on the research that drives finding a cure to childhood cancers. Our children with cancer cannot afford not to be, at minimum, very high on the list. Keep in mind that many advances in treatments for adult cancer have been pioneered through research efforts focused on childhood cancers. 10

11 Childhood Cancer Research in Georgia Biologic Agents: Laboratory investigators also study the cells to see what proteins are made by the cancer cells but not by normal cells. When they identify specific proteins, they can work to make special agents called antibodies that attack the proteins and make them inactive. These biologic agents must be carefully tested before being used to treat patients. The focus for use of these agents is primarily the more high-risk cancers. Georgia has become one the preeminent research centers for childhood cancer in the country. The Aflac Cancer Center, which is affiliated with Children s Healthcare of Atlanta, has developed an innovative and progressive research program focused on pediatric cancer, hematology and blood and marrow transplant programs. Aflac, the insurance carrier, and its Aflac Field Force have contributed more than $47 million to the Aflac Cancer Center, making the company the largest supporter of Children s Healthcare of Atlanta. 11 The Aflac Cancer Center delivers its services at three hospitals: Children s at Egleston, Children s at Hughes Spalding and Children s at Scottish Rite. Aflac s financial contributions have been used to fund the following critical needs: New inpatient and outpatient facilities at both Children s at Egleston and Children s at Scottish Rite New state-of-the-art pediatric research building Endowments for the Family Support team and hematology/oncology Fellowship program Endowed chairs for the chief medical officer and leaders in innovative therapy, cancer survivorship and sickle cell disease Endowment supporting clinical and basic research program development CURE Childhood Cancer CURE was founded in 1975 by Dr. Abdel Ragab, head of the Division of Pediatric Hematology/Oncology at Emory University. Since there was an urgent need to fund a pediatric oncology research program at Emory, as well as to provide a support group for families afflicted by childhood cancer, Dr. Ragab organized a group of parents who formed CURE Childhood Cancer. In the early years of the relationship, CURE contributed funding to help set up the research lab and provide support 11

12 for training Pediatric Hematology/Oncology fellows during their research rotations. The research lab was originally located at Grady Hospital in downtown Atlanta. In 1981, the laboratory moved to the Emory University campus. Over several years, CURE raised more than $1 million to build and equip a more expansive 3,500 square foot laboratory. This laboratory was dedicated in What is BL22? BL22 is an immunotoxin--a type of targeted therapy that directly attacks leukemic cells in a major type of childhood leukemia. BL22 is a molecule made by genetic engineering and consists of an antibody and toxin linked together. The antibody targets the leukemia cell like a guided missile and delivers the toxin that kills the cell. The first laboratory tests of BL22 against childhood leukemia were funded by CURE at Emory. CURE soon made another significant contribution to the treatment of childhood cancer by promoting passage of an act in the GA legislature titled Calloway s Law. The act was named in memory of Calloway Thrash, an early patient of Dr. Ragab and the son of one of the first presidents of CURE. While being treated for leukemia, Calloway had been unable to obtain insurance coverage for an experimental drug. After Calloway s death from leukemia, his father and CURE successfully lobbied the Georgia legislature in support of a bill that would mandate Georgia insurers support experimental therapies for childhood cancer. The passage of this act in the late 1990 s was a great advance in support of pediatric cancer clinical trials. One of the measures of the success of the research efforts is the number of new therapies that have been tested. Here are some examples: First trial of retinoic acid in pediatric acute myeloid leukemia. First trial of interleukin-2 for stimulating the immune system in childhood cancer patients. In collaboration with the National Cancer Institute, the Childhood Cancer Research Lab at Emory performed the first laboratory testing of a new drug (BL22) targeted at pediatric acute lymphoblastic leukemia (ALL). Using data from this laboratory research, the NCI obtained approval for clinical trial testing BL22 in ALL. Results from this trial have been promising and have led to a trial for a second generation form of BL22 (called HA22), which is now ongoing with even more promising results. Funding from CURE was critical in enabling the Emory-NCI research collaboration which led to these trials. 12

13 Collaborative Research Efforts Each and every school day, 46 children, or more than two full classrooms of kids, are diagnosed with cancer in the United States alone. While doctors and researchers have made serious strides in the battle against so many other types of cancer, the lack of funding and awareness for our children has led to an insignificant improvement in survival rates for pediatric cancer over the past decade. As a result, cancer continues to be the number-one disease killer of children in our country, more than asthma, diabetes, cystic fibrosis and pediatric AIDS combined! Liz Scott, Jay Scott: Atlanta Journal Constitution Editorial, 2008 CURE Childhood Cancer focuses its research investments at the Aflac Cancer Center at Children s Healthcare of Atlanta and Emory University. We believe strongly that our research investment not only focuses our funding locally but assists in the countrywide collaborative research efforts. In the last year, CURE through many donations has committed more than $1.2 million to fund research projects including: Pl-3 Kinase Inhibitor and Other Targeted Therapies for Pediatric Cancer Targeted Agents for Therapy of Neuroblastoma and Acute Lymphoblastic Leukemia Beyond the Cure Promoting Quality of Life for All Survivors of Childhood Cancer Novel Drug Discovery for Treatment of Refractory Leukemia Hypoxia-driven MDM2/VEGF Interaction in Cancer Growth and Metastasis Innovative Concept for the Discovery of a Novel Therapy for Pediatric Neuroblastoma The research above represents the true nuts and bolts science of finding a childhood cancer cure and the complex treatments needed. While helping fund a cure through research, CURE Childhood Cancer also provides critical support to thousands of parents and children who are dealing with the devastating effects of cancer. Here are some of the CURE programs: Providing critical support at the time of diagnosis through our Early Outreach program; Providing more than $100,000 in emergency financial assistance to families this year; Providing hot meals and fellowship to more than 5,500 hospitalized children and their caregivers; Providing critical bereavement care to families who have lost children to cancer. Addressing issues of importance to survivors of childhood cancer. 13

14 Conclusion Imagine a world without childhood cancer. No painful chemotherapy treatments. No emotional stress on children and their families. No financial sacrifice. CURE Childhood Cancer is dedicated to finding cures for all childhood cancers. While the progress in curing childhood cancer has been real and measurable, there is still a long road ahead. We believe that the national investment in pediatric cancer is insufficient to continue to make the progress needed. We believe that investments in targeted research in combination with other national programs will yield results that will allow childhood cancer to be cured in our lifetime. We believe we can make a measurable impact on the difficult journeys patients and their families make in coping with this disease. We encourage you to invest in helping CURE continue to fight childhood cancer through our research and family support initiatives. We know it will yield measurable results. We, at CURE, encourage you to learn more about childhood cancer by visiting these websites: Children s Oncology Group CureSearch: National Cancer Institute, Childhood Cancers: Aflac Cancer Center and Blood Disorders Services: Children s Healthcare of Atlanta: CURE Childhood Cancer: 14

15 Footnotes: 1. CureSearch Website: Progress in Childhood Cancer; 2. CureSearch Website: Our Research page; 3. National Cancer Institute Cancer Incidence and Survival among Children and Adolescents: United States SEER Program, National Cancer Institute website: A Snapshot of Pediatric Cancers 5. CureSearch Website: Cancer Incidence and Survival among Children and Adolescents: United States SEER (Surveillance, Epidemiology, and End Results) Program Ries LAG, Smith MA, Gurney JG, Linet M, Tamra T, Young JL, Bunin GR (eds). Cancer Incidence and Survival among Children and Adolescents: United States SEER Program , National Cancer Institute, SEER Program. NIH Pub. Nol Bethesda, MD CureSearch Website: Types of Childhood Cancer 7. CureSearch website Progress in Childhood Cancer; 8. CureSearch website Progress in Childhood Cancer; 9. CureSearch website Progress in Childhood Cancer: CureSearch Website; CureSearch in the News: Budget Cuts May Hurt Children with Cancer National Heart, Lung and Blood Institute website, Children & Clinical Studies: Children s Healthcare of Atlanta website: How Aflac Support Us 15