Surveillance and screening for new neoplasms in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS)
Reviewer: Christine Hill-Kayser, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 10, 2009
Presenter: Paul Nathan, MD, MSc Presenter's Affiliation: The Hospital for Sick Children, Toronto, Canada Type of Session: Scientific
Series of clinical trials in pediatric oncology, examining outcomes in multiple disease sites, have resulted in overall survival rates approaching 80%.
Currently, over 325,000 childhood cancer survivors are living in the United States, and this number is expected to grow as survival rates after childhood cancer continue to increase. Currently, one in 640 adults aged 20-39 years in the US is a childhood cancer survivor.
Unfortunately, prior studies have demonstrated that approximately 60% of adult survivors of childhood cancer report having a chronic health condition, and 28% report having a severe or life-threatening medical condition.
Among severe health problems encountered by survivors of childhood cancer are second malignant neoplasms. In all likelihood, increased risk of second malignancy is multifactorial in this population, and results from alkalating chemotherapies, radiation therapy, and potential higher risk for cellular mutation and damage that may result in malignant transformation.
The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort study examining patients who have survived at least 5 years after diagnosis of childhood cancer. Patients have been enrolled from 26 institutions across the US and Canada, and data is maintained and accumulated via review of medical records as well as healthcare provider and survivor survey-based reporting. The database is publicly accessible for research purposes.
Among the CCSS cohort, the 30-year cumulative incidence of second malignant neoplasm (SMN) is 9.3%.
SMN is the leading cause of death in survivors living 20 years or more after cancer diagnosis, with a standardized incidence ratio of 9.0 and a standardized mortality ratio of 15.2.
Previous groups have demonstrated that adult cancer survivors are less likely to receive recommended cancer screening for cancers other than those previously diagnosed (Earle, Cancer, 2008).
The study described here was designed to assess adherence to published cancer surveillance guidelines by survivors of pediatric cancer at recognized risk for breast, colorectal, or skin cancer resulting from previous therapy, as well as to compare adherence of pediatric cancer survivors to national screening guidelines for breast, colorectal, and cervical cancer with the general population.
Materials and Methods
20,602 CCSS participants were originally indentified, 3035 of whom have been lost to follow-up. As a result, 17,567 participants were contacted regarding participation in this study. Of these, 3197 declined to participate, 1541 were deceased, and 990 were excluded based on known presence of SMN or unknown race/ethnicity. This resulted in 8318 survivors participating in this study.
The mean age at cancer diagnosis was 7.8 years.
12.5% had been seen at a cancer center in the last two years
Primary cancer diagnoses were leukemia (35%), CNS (13%), Hodgkin’s lymphoma (10%), non-Hodgkin’s lymphoma (8%), Wilm’s tumor (10%), Neuroblastoma (7%), soft tissue sarcoma (9%), and primary bone cancer (8%).
Information on health behaviors was gathered via telephone interview.
8318 individuals were matched to these survivors from the 2003 National Health Interview Study by age, gender, and race/ethnicity and served as a population control.
51.9% of individuals in the survivor and control populations were male, and 88.7% were Caucasian.
Mean age at interview was 31.2 years in the survivor population, and 32.7 years in the control population.
Risk definitions and recommended surveillance guidelines were based on guidelines set by the Children’s Oncology Group:
High-risk for colorectal cancer:
30 Gray (Gy) or more delivered to abdomen, pelvis, or spine (n = 794)
Recommended screening: Colonoscopy every 5 years starting at age 35.
High-risk for breast cancer:
Female, having received 20 Gy or more to breast tissue (n = 521)
Recommended screening: Annual mammogram starting at age 25, or 8 years following radiotherapy, which ever is later.
High risk for skin cancer:
Any radiotherapy (n = 4,833)
Recommended screening: Annual dermatologic exam of irradiated areas.
Recommendations for general cancer screening among normal-risk populations were based on the United States Preventive Services Task Force Cancer Screening Recommendations:
Screening mammography every 1-2 years for women aged 40 and older.
Colonoscopy at intervals of 10 years between 50 and 75 years.
Pap smear beginning within 3 years of sexual activity or age 21, whichever is earlier, and screening at least every 3 years.
Of defined high risk populations, compliance with recommended surveillance tests was as follows:
Of survivors at high risk for colorectal cancer, 11.5% were compliant with recommended guidelines.
Survivors at older age at the time of interview were more likely to have undergone recommended colonoscopies [RR 1.08 (1.00 – 1.17)].
Of survivors at high risk for breast cancer, 46.3% were compliant.
Survivors at older age, as well as those receiving follow-up care at a dedicated cancer center were more likely to have undergone recommended mammography [RR 1.09 (1.04-1.13) and RR 1.7 (1.04 – 2.76), respectively].
Of survivors at high risk for skin cancer, 26.7% were compliant.
Patients who were non-white were less likely to have undergone dermatologic screening examination [RR 0.63 (1.04 – 2.76)].
Those receiving care at a dedicated cancer center, as well as those with a printed treatment summary were more likely to have undergone dermatologic screening examination [RR 1.55 (1.22 – 1.96) and RR 1.30 (1.07 – 1.58), respectively].
Cancer survivors without known elevated risk were more likely than the general population to have undergone recommended screening tests for breast and cervical cancer.
Survivors underwent recommended mammography in 66.8% of cases, compared to 58.1% of the general population (RR 1.29, p < 0.0001).
Survivors underwent recommended cervical cancer screening in 82.3% of cases, compared to 69.6% of the general population (RR 1.17, p < 0.001).
Being “married or living as married” predicted for PAP smear compliance.
Survivors of normal risk were equally likely to have undergone colon cancer screening as were members of the control population:
Survivors underwent screening colonoscopy in 23.5% of cases compared to 24.1% of the control population (p = 0.95).
Detailed analysis was not possible due to too few survivors over 50 years of age.
The authors conclude that rates of colonoscopy, mammography, and skin exams in high-risk survivors of childhood cancer are very low.
They note that care at a cancer center modestly increases surveillance for breast and skin cancer, and recommend that patients and physicians need to be educated about recommended surveillance.
Conclusions also include that cancer survivors are more likely to undergo mammography and pap smear than is the general population, but that compliance rates are very low for colonoscopy and only moderate for mammography.
The authors have performed an interesting and well-conducted study that is an important contribution to the literature.
The rates of compliance with screening for second malignant neoplasm reported in this study are startlingly low, and indicate a severe deficit in survivorship care. Although many clinicians caring for adult survivors of childhood cancer may not be experienced in screening high-risk populations with colonoscopy, mammography, and skin examination, guidelines are available via the Children’s Oncology Group website, www.curesearch.org. Clinicians and survivors alike should be encouraged to utilize this website to ensure that recommended screening is undertaken.
Along these lines, of interest is the fact that survivors provided with a detailed treatment summary were more likely to receive appropriate screening. This indicates that increased survivor and clinician awareness of treatments received may increase use of screening tools, and that such treatment summaries may increase communication among physicians. Further, treatment summaries may empower survivors to seek indicated care.
In addition, survivors receiving care at a dedicated cancer center were more likely to receive adequate screening care; this may result from increased attention to survivor needs at cancer centers, and again points to a communication deficit that may be most severe among clinicians outside of cancer centers.
Although survivors of normal risk were equally or more likely than the general population to receive cancer screening exams, the number undergoing these tests still remains too low.
In addition to communication issues within the medical community, other factors are likely influential in decreasing care of survivors of pediatric cancer, including cost, insurance issues, and survivor fear of recurrence.
The entire oncology community bears the responsibility of educating survivors and other medical practitioners regarding survivor needs. Much progress has been made thus far; however, studies such as this one demonstrate that more is certainly needed.
Jun 7, 2011 - Childhood cancer survivors have an increased risk of developing subsequent digestive and genitourinary primary neoplasms after the age of 40, according to a study published in the June 8 cancer-themed isssue of the Journal of the American Medical Association to coincide with the annual meeting of the American Society of Clinical Oncology, held from June 3 to 7 in Chicago.