Confirmed in First Such Study (2005)

ORLANDO, FL—About one in three people who survive childhood cancer will die or develop cardiovascular disease, secondary cancers, or other serious or life-threatening medical conditions over the next 30 years, according to the first study designed to take a snapshot of the chronic health problems faced by adult survivors of childhood cancer. A separate study showed that nearly three fourths of cancer survivors experience depression, anxiety, and other lingering mental health problems.Figure: Kevin C. Oeffinger, MD: “By 30 years after being treated for cancer, 66% of survivors will have at least one health condition, and 33% will have serious, chronic problems or die.”There are currently about 10 million cancer survivors in the United States, with more than 270,000 of them survivors of childhood cancers, noted Kevin C. Oeffinger, MD, who presented the Childhood Cancer Survivor Study at the ASCO Annual Meeting here. The numbers are growing: The five-year survival rate for childhood cancers is now over 78%, compared with just 58% in 1975. As the cure rate improves, so too does the need to monitor patients for secondary medical problems, which are often caused by either the primary cancer itself or the treatment, said Dr. Oeffinger, Professor of Family Medicine at the University of Texas Southwestern Medical Center in Dallas. “By 30 years after being treated for cancer, 66% of survivors will have at least one health condition and 33% will have serious, chronic problems or die.” Compared with their siblings, they are 4.2 times more likely to have a severe or life-threatening medical condition, according to the 16-institution retrospective cohort study. Those at greatest risk: Patients who had Hodgkin's disease or tumors of the central nervous system, or those who received chest radiation with anthracycline, Dr. Oeffinger said. The Childhood Cancer Survivor Study The Childhood Cancer Survivor Study included 10,397 people who were diagnosed with a childhood cancer between 1970 and 1986. They had survived a variety of cancers: 29% had leukemia, 18% had Hodgkin's disease, 13% had CNS tumors, 11% had bone tumors, 10% had sarcoma, 9% had non-Hodgkin's lymphomas, 6% had Wilms' tumor, and 4% had neuroblastoma. “They had to be diagnosed with a common cancer before age 21 and survive at least eight years,” Dr. Oeffinger said. As for therapeutic exposures, two thirds has been on some type of chemotherapy, with 38% receiving an alkylating agent and 30%, anthracycline. Nearly as many patients had been exposed to some type of radiation, with 27% receiving brain, 22% receiving chest, 18% having abdominal, and 15% receiving pelvic irradiation. A total of 3,034 siblings were used as a control group. About half of the people in each arm were women, with the vast majority being non-Hispanic whites. The mean age at the interview was 27 in the survivor group and 29 in the sibling group. Upon enrollment, usually between 1994 and 1998, all the participants filled out a questionnaire that asked about a wide variety of health conditions. Secondary malignancies in the survivors were confirmed by trained pathologists. Using the Common Terminology Criteria for Adverse Events, the researchers then assigned a severity score to each chronic disease. Grade 1 corresponded to mild and Grade 2 to moderate disease. Grade 3, or severe, diseases included: ▪ Congestive heart failure. ▪ Limb amputation. ▪ Cirrhosis. ▪ Gonadal failure while on hormone-replacement therapy ▪ Deep vein thrombosis. Grade 4, or life-threatening and disabling conditions, included: ▪ A second cancer. ▪ Myocardial infarction. ▪ Paralysis of an extremity with major daily limitations. Grade 5 is death.Figure: Steven N. Wolff, MD: “A diagnosis of cancer does not end when treatment begins and the consequences of cancer don't end when treatment ends. These are the issues of survivorship.”Over 75% Have Some Health Condition The study showed that 44% of the survivors had multiple health conditions, in many cases accompanied by scarring or disfigurement. After adjustment for age, sex, and race, the survivors were almost twice as likely to have some health condition compared with their siblings, Dr. Oeffinger said. Also, 2.4 times more survivors had two or more conditions, compared with their siblings. When he looked at Grade 3–4 medical conditions, the prognosis was even bleaker. The childhood survivors were 4.2 times more likely to have a Grade 3 or 4 health problem than their brothers and sisters did. When looked at by type of cancer, survivors of Hodgkin's disease fared the worst: They were 5.8 times more likely to have a Grade 3 or Grade 4 condition than their siblings, he said. Also, survivors of tumors of the CNS were 5.3 times more likely to have a Grade 3 or Grade 4 condition than their siblings. Treatment-wise, patients who received any radiation therapy were 3.3 times more likely to have a Grade 3 or 4 condition than their siblings were. Patients who got pelvic, chest, and abdominal radiation were about four times more likely to have a Grade 3 or 4 condition than their siblings were, he added. Any type of chemotherapy upped the risk of a Grade 3 or 4 condition by 290%, with either anthracycline or an alkylating agent alone increasing the risk about that amount as well. More dangerous were epipodophyllotoxin and bleomycin, which raised the risk by 390% and 370%, respectively. But combinations of various therapeutic modalities were associated with the highest risks of all. Survivors who received both an anthracycline and an alkylating agent were over five times more likely to have a Grade 3 or 4 condition than their siblings were. Other dangerous combos: chest radiation plus abdominal or pelvic radiation; abdominal or pelvic radiation plus an alkylating agent, and chest radiation plus anthracycline. All of these increased the risk of a Grade 3 or 4 condition by about 700%. Children Today at Lower Risk Sandra J. Horning MD, ASCO's 2005–2006 President, a cancer survivor who is Professor of Medicine at Stanford University School of Medicine, noted that some “fairly dramatic changes” in doses and delivery of radiation as well as in chemotherapy regimens place children today at lower risk of secondary health problems. Since the 1970s and 1980s, “there has been a tremendous change in diagnostics so that the radiation is more targeted, right to the area of a tumor,” she said. “Also, we use lower doses and have lessened the duration of some chemotherapy regimens.” At the same time, Dr. Oeffinger said, drugs like anthracycline, which account for a significant amount of morbidity, are still a mainstay of treatment. “Most clinicians only have about three or four cancer survivors in their entire practice, so there's no reason for them to know” the dismal prognosis unless oncologists get the word out, he said. “We recommend these patients have annual checkups.” He urged oncologists to visit www.survivorshipguidelines.org, an evidence-based Web site of the Children's Oncology Group that offers recommendations for the screening and management of late effects that may arise as the result of therapeutic exposures used during the treatment of pediatric cancers. Over Half Say Emotional Needs Hardest to Deal With In a separate survey, 53% of cancer survivors said that their “emotional needs are harder than their physical needs” and 70% reported depression due to their cancer. Despite this, an alarming 70% said their physicians were “unable to assist with non-medical issues,” reported Steven N. Wolff, MD, Professor of Medicine at Meharry Medical College. The survey of more than 1,000 cancer survivors, half of whom were men, was conducted by the nonprofit Lance Armstrong Foundation. The average age of the survivors was about 50 years. “A diagnosis of cancer does not end when treatment begins, and the consequences of cancer don't end when treatment ends. These are the issues of survivorship,” Dr. Wolff said. Money too is a huge issue, with almost one in 10 survivors reporting debt of more than $25,000 and about the same number saying they are without health insurance. “As treating oncologists, we need to focus more on these issues,” he said. Dr. Horning agreed: “The increase in survivors is accompanied by an increase in needs, many of which are not being met. This requires education of medical professionals as well as patients.” David H. Johnson, MD, ASCO's 2004–2005 President who is also a cancer survivor, said he's not surprised by the results. “After I completed treatment with one of the best doctors I know, I asked what to do next and he said, “I don't know.' “This is an unacceptable answer. Now that we have identified the scope of the problem, we have to figure out what to do,” said Dr. Johnson, Deputy Director of Vanderbilt-Ingram Cancer Center. A good first step, he said, are studies, such as two presented at the meeting (see page 18), looking at whether lifestyle interventions can fend off recurrences among patients with cancer.