To review the reports of subsequent neoplasms (SNs) in the Childhood Cancer Survivor Study (CCSS) cohort that were made through January 1, 2006, and published before July 31, 2008, and to discuss the ...host-, disease-, and therapy-related risk factors associated with SNs.
SNs were ascertained by survivor self-reports and subsequently confirmed by pathology findings or medical record review. Cumulative incidence of SNs and standardized incidence ratios for second malignant neoplasms (SMNs) were calculated. The impact of host-, disease-, and therapy-related risk factors was evaluated by Poisson regression.
Among 14,358 cohort members, 730 reported 802 SMNs (excluding nonmelanoma skin cancers). This represents a 2.3-fold increase in the number of SMNs over that reported in the first comprehensive analysis of SMNs in the CCSS cohort, which was done 7 years ago. In addition, 66 cases of meningioma and 1,007 cases of nonmelanoma skin cancer were diagnosed. The 30-year cumulative incidence of SMNs was 9.3% and that of nonmelanoma skin cancer was 6.9%. Risk of SNs remains elevated for more than 20 years of follow-up for all primary childhood cancer diagnoses. In multivariate analyses, risks differ by SN subtype, but include radiotherapy, age at diagnosis, sex, family history of cancer, and primary childhood cancer diagnosis. Female survivors whose primary childhood cancer diagnosis was Hodgkin's lymphoma or sarcoma and who received radiotherapy are at particularly increased risk. Analyses of risk associated with radiotherapy demonstrated different dose-response curves for specific SNs.
Childhood cancer survivors are at a substantial and increasing risk for SNs, including nonmelanoma skin cancer and meningiomas. Health care professionals should understand the magnitude of these risks to provide individuals with appropriate counseling and follow-up.
The issues involved in transition from pediatric cancer care to adult-focused care differ from those in other childhood diseases, because malignant disease itself is no longer a problem. However, the ...potential for fatal outcome places a greater dependence on the pediatric oncology setting and delays this transition process, often beyond adolescence. Adverse long-term physical and psychological effects accompany survival for many of the cured children, and because these effects may not become manifest until adulthood, programs that support transition for childhood cancer survivors require the expertise of many subspecialists.
To describe the issues and barriers to successful transition programs for childhood cancer survivors when they are ready for adult-focused care.
We reviewed the literature and discuss the barriers to transition at the survivor, provider, and health care system levels for survivors of childhood cancer. We also critically assess the elements of successful transition programs.
Education of survivors and providers regarding long-term health risks is necessary for a successful transition. This process should be gradual to address the educational needs of survivors, families, and health care professionals, determine "readiness" for transition, and address financial and insurance concerns. Because little is known regarding adverse long-term health-related sequelae beyond the fourth decade of life, research is needed to quantify and reduce the consequences of these morbidities.
Transition programs for pediatric cancer survivors require experts who are knowledgeable regarding the long-term follow-up needs of childhood cancer survivors and who can provide a bridge between pediatric oncology and primary care that is risk based.
The Childhood Cancer Survivor Study found a high rate of illness owing to chronic health conditions among more than 10,000 adult survivors of childhood cancer.
The Childhood Cancer Survivor Study ...found a high rate of illness owing to chronic health conditions among more than 10,000 adult survivors of childhood cancer.
As a result of advances in treatment, almost 80% of children and adolescents who receive a diagnosis of cancer become long-term survivors.
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In the United States, there are approximately 270,000 survivors of pediatric cancer, or about 1 of every 640 adults between the ages of 20 and 39 years.
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The large number of survivors has prompted studies of the long-term health consequences of treatments for childhood cancer.
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It is now clear that damage to the organ systems of children caused by chemotherapy and radiation therapy may not become clinically evident for many years.
To understand fully the health risks . . .
Survival for childhood cancer has increased dramatically over the last 40 years with 5-year survival rates now approaching 80%. For many diagnostic groups, rapid increases in survival began in the ...1970s with the broader introduction of multimodality approaches, often including combination chemotherapy with or without radiation therapy. With this increase in rates of survivorship has come the recognition that survivors are at risk for adverse health and quality-of-life outcomes, with risk being influenced by host-, disease-, and treatment-related factors. In 1994, the US National Cancer Institute funded the Childhood Cancer Survivor Study, a multi-institutional research initiative designed to establish a large and extensively characterized cohort of more than 14,000 5-year survivors of childhood and adolescent cancer diagnosed between 1970 and 1986. This ongoing study, which reflects the single most comprehensive body of information ever assembled on childhood and adolescent cancer survivors, provides a dynamic framework and resource to investigate current and future questions about childhood cancer survivors.
To evaluate the reliability of the International Classification of Retinoblastoma (ICRB) for predicting treatment success with chemoreduction (CRD).
Noncomparative interventional case series.
Two ...hundred forty-nine consecutive eyes.
All eyes were treated with CRD and were classified according to the ICRB: group A included those eyes with retinoblastoma </=3 mm; group B included those eyes with retinoblastoma >3 mm, macular location, or minor subretinal fluid; group C included those eyes with retinoblastoma with localized seeds; group D included those eyes with retinoblastoma with diffuse seeds; group E included those eyes with massive retinoblastoma necessitating enucleation. The CRD regimen included vincristine, etoposide, and carboplatin for 6 cycles plus local consolidation with thermotherapy or cryotherapy.
Chemoreduction success, defined as avoidance of external beam radiotherapy or enucleation.
Of the 249 eyes, 23 (9%) were in group A, 96 (39%) were in group B, 21 (8%) were in group C, and 109 (44%) were in group D. In this series, group E eyes were managed with enucleation. Treatment success was achieved in 100% of group A, 93% of group B, 90% of group C, and 47% of group D eyes.
The ICRB can be of assistance in predicting CRD success for retinoblastoma. Additional treatment methods are necessary to salvage more group D eyes.
Background The occurrence of subsequent neoplasms has direct impact on the quantity and quality of life in cancer survivors. We have expanded our analysis of these events in the Childhood Cancer ...Survivor Study (CCSS) to better understand the occurrence of these events as the survivor population ages. Methods The incidence of and risk for subsequent neoplasms occurring 5 years or more after the childhood cancer diagnosis were determined among 14 359 5-year survivors in the CCSS who were treated from 1970 through 1986 and who were at a median age of 30 years (range = 5–56 years) for this analysis. At 30 years after childhood cancer diagnosis, we calculated cumulative incidence at 30 years of subsequent neoplasms and calculated standardized incidence ratios (SIRs), excess absolute risks (EARs) for invasive second malignant neoplasms, and relative risks for subsequent neoplasms by use of multivariable Poisson regression. Results Among 14 359 5-year survivors, 1402 subsequently developed 2703 neoplasms. Cumulative incidence at 30 years after the childhood cancer diagnosis was 20.5% (95% confidence interval CI = 19.1% to 21.8%) for all subsequent neoplasms, 7.9% (95% CI = 7.2% to 8.5%) for second malignant neoplasms (excluding nonmelanoma skin cancer), 9.1% (95% CI = 8.1% to 10.1%) for nonmelanoma skin cancer, and 3.1% (95% CI = 2.5% to 3.8%) for meningioma. Excess risk was evident for all primary diagnoses (EAR = 2.6 per 1000 person-years, 95% CI = 2.4 to 2.9 per 1000 person-years; SIR = 6.0, 95% CI = 5.5 to 6.4), with the highest being for Hodgkin lymphoma (SIR = 8.7, 95% CI = 7.7 to 9.8) and Ewing sarcoma (SIR = 8.5, 95% CI = 6.2 to 11.7). In the Poisson multivariable analysis, female sex, older age at diagnosis, earlier treatment era, diagnosis of Hodgkin lymphoma, and treatment with radiation therapy were associated with increased risk of subsequent neoplasm. Conclusions As childhood cancer survivors progress through adulthood, risk of subsequent neoplasms increases. Patients surviving Hodgkin lymphoma are at greatest risk. There is no evidence of risk reduction with increasing duration of follow-up.
Background: Subsequent primary neoplasms of the central nervous system (CNS) have frequently been described as late events following childhood leukemia and brain tumors. However, the details of the ...dose–response relationships, the expression of excess risk over time, and the modifying effects of other host and treatment factors have not been well defined. Methods: Subsequent primary neoplasms of the CNS occurring within a cohort of 14 361 5-year survivors of childhood cancers were ascertained. Each patient was matched with four control subjects by age, sex, and time since original cancer diagnosis. Tumor site–specific radiation dosimetry was performed, and chemotherapy information was abstracted from medical records. Conditional logistic regression was used to estimate odds ratios (ORs), to calculate 95% confidence intervals (CIs), and to model the excess relative risk (ERR) as a function of radiation dose and host factors. For subsequent gliomas, standardized incidence ratios (SIRs) and excess absolute risks (EARs) were calculated based on Surveillance, Epidemiology, and End Results data. Results: Subsequent CNS primary neoplasms were identified in 116 individuals. Gliomas (n = 40) occurred a median of 9 years from original diagnosis; for meningiomas (n = 66), it was 17 years. Radiation exposure was associated with increased risk of subsequent glioma (OR = 6.78, 95% CI = 1.54 to 29.7) and meningioma (OR = 9.94, 95% CI = 2.17 to 45.6). The dose response for the excess relative risk was linear (for glioma, slope = 0.33 95% CI = 0.07 to 1.71 per Gy, and for meningioma, slope = 1.06 95% CI = 0.21 to 8.15 per Gy). For glioma, the ERR/Gy was highest among children exposed at less than 5 years of age. After adjustment for radiation dose, neither original cancer diagnosis nor chemotherapy was associated with risk. The overall SIR for glioma was 8.7, and the EAR was 19.3 per 10 000 person-years. Conclusions: Exposure to radiation therapy is the most important risk factor for the development of a new CNS tumor in survivors of childhood cancers. The higher risk of subsequent glioma in children irradiated at a very young age may reflect greater susceptibility of the developing brain to radiation.
The purpose of this study was to quantify the risk of breast cancer in relation to radiation dose and chemotherapy among survivors of childhood cancer.
We conducted a case-control study of breast ...cancer in a cohort of 6,647 women who were 5-year survivors of childhood cancer and who were treated during 1970 through 1986. One hundred twenty patients with histologically confirmed breast cancer were identified and were individually matched to four selected controls on age at initial cancer and time since initial cancer. Medical physicists estimated radiation dose to the breast tumor site and ovaries on the basis of medical records.
The odds ratio for breast cancer increased linearly with radiation dose, and it reached 11-fold for local breast doses of approximately 40 Gy relative to no radiation (P for trend < .0001). Risk associated with breast irradiation was sharply reduced among women who received 5 Gy or more to the ovaries (P = .002). The excess odds ratio per Gy was 0.36 for those who received ovarian doses less than 5 Gy and was 0.06 for those who received higher doses. Radiation-related risk did not vary significantly by age at exposure. Borderline significantly elevated risks were seen for doxorubicin, dactinomycin, dacarbazine, and carmustine.
Results confirm the radiation sensitivity of the breast in girls age 10 to 20 years but do not demonstrate a strong effect of age at exposure within this range. Irradiation of the ovaries at doses greater than 5 Gy seems to lessen the carcinogenic effects of breast irradiation, most likely by reducing exposure of radiation-damaged breast cells to stimulating effects of ovarian hormones.
Previous studies have indicated that thyroid cancer risk after a first childhood malignancy is curvilinear with radiation dose, increasing at low to moderate doses and decreasing at high doses. ...Understanding factors that modify the radiation dose response over the entire therapeutic dose range is challenging and requires large numbers of subjects. We quantified the long-term risk of thyroid cancer associated with radiation treatment among 12,547 5-year survivors of a childhood cancer (leukemia, Hodgkin lymphoma and non-Hodgkin lymphoma, central nervous system cancer, soft tissue sarcoma, kidney cancer, bone cancer, neuroblastoma) diagnosed between 1970 and 1986 in the Childhood Cancer Survivor Study using the most current cohort follow-up to 2005. There were 119 subsequent pathologically confirmed thyroid cancer cases, and individual radiation doses to the thyroid gland were estimated for the entire cohort. This cohort study builds on the previous case-control study in this population (69 thyroid cancer cases with follow-up to 2000) by allowing the evaluation of both relative and absolute risks. Poisson regression analyses were used to calculate standardized incidence ratios (SIR), excess relative risks (ERR) and excess absolute risks (EAR) of thyroid cancer associated with radiation dose. Other factors such as sex, type of first cancer, attained age, age at exposure to radiation, time since exposure to radiation, and chemotherapy (yes/no) were assessed for their effect on the linear and exponential quadratic terms describing the dose–response relationship. Similar to the previous analysis, thyroid cancer risk increased linearly with radiation dose up to approximately 20 Gy, where the relative risk peaked at 14.6-fold (95% CI, 6.8–31.5). At thyroid radiation doses >20 Gy, a downturn in the dose–response relationship was observed. The ERR model that best fit the data was linear-exponential quadratic. We found that age at exposure modified the ERR linear dose term (higher radiation risk with younger age) (P < 0.001) and that sex (higher radiation risk among females) (P = 0.008) and time since exposure (higher radiation risk with longer time) (P < 0.001) modified the EAR linear dose term. None of these factors modified the exponential quadratic (high dose) term. Sex, age at exposure and time since exposure were found to be significant modifiers of the radiation-related risk of thyroid cancer and as such are important factors to account for in clinical follow-up and thyroid cancer risk estimation among childhood cancer survivors.
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