Chronic medical conditions, health status, and health care practices at 25 years in 5-year survivors of Wilms tumor: A report from the Childhood Cancer Survivor Study
Reporter: Samuel Swisher-McClure, MD
The Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 7 de junio del 2010
Presenter: A. M. Termuhlen, The Ohio State University College of Medicine, Nationwide Children's Hospital, Columbus, OH
- Wilms tumor (WT) is the most common pediatric abdominal tumor.
- The development of more effective therapy for WT has translated into marked improvements in overall survival since the 1960's, and currently over 90% of children with WT are alive at least 5 years after diagnosis.
- WT patients are typically treated with a combination of surgery, chemotherapy, ± irradiation (RT), which are associated with risks of long-term toxicities.
- Published long term results from the National Wilms Tumor Studies (NWTS) indicate that long term WT survivors are at increased risk for development of congestive heart failure (CHF), renal failure, hypertension, pregnancy complications, and second malignancy.
- Green et al. (JCO, 2001) found that the cumulative frequency of CHF among patients enrolled on NWTS-1 through NWTS-4 trials was 4.4% at 20 years for the overall population. This risk was increased by 4-6 fold in patients having been treated with doxorubicin and/or thoracic radiation
- Breslow et al. (JCO, 1995) reported a 1.6% cumulative 15-year risk of second cancers among patients enrolled in the NWTS trials.
- Aging adult survivors of childhood cancer require screening and intervention strategies to address potential long-term health problems that may arise following treatment.
- The current study reports outcomes of chronic medical conditions, health status, and health care practices of WT patients within the Childhood Cancer Survivor Study.
- This study uses data from the Childhood Cancer Survivor Study, a large, multi-institutional, retrospective, cohort study analyzing health outcomes of pediatric cancer survivors.
- The analysis included WT survivors diagnosed between 1970-1986 as well as a sibling comparison group.
- Survivors were defined as being alive at least 5 years after diagnosis.
- Baseline characteristics of the study group including diagnosis, stage, and treatments received were previously obtained from review of patient medical records.
- Self-reported outcomes from patient surveys were used for follow-up regarding chronic medical conditions (CMCs), health status, and health care practices.
- The risk of specific CMCs was analyzed by specific treatments patients received.
- 137 separate CMC's were recorded according to the NCI CTCAE v. 3.0
- 1,256 WT survivors and 4,023 individuals within the sibling comparison group were identified for analysis.
- Median follow-up was approximately 20 years after diagnosis
- The median age was 25.3 in the WT survivor group and 31.9 in the sibling comparison group.
- 47% of the study group was male and 53% female.
- The cumulative incidence at 25 yrs of any CMC within the WT survivor group was 51%, and 11% of patients reported a severe or disabling CMC.
- Compared to the siblings, WT survivors were twice as likely to report a CMC (hazard ratio [HR]=2.0, 95% confidence interval (CI), 1.8-2.4) and almost five- times more likely to have a severe/disabling CMC (HR=4.7, 95%CI, 3.6-6.1).
- The Hazard Ratios of specific CMCs among WT survivors were:
- Congestive heart failure (CHF) 23.6 (95% CI, 10.8- 51.5)
- Renal failure 50.7 (95% CI, 14.5-177.4)
- Hypertension (HTN) 8.2 (95% CI, 6.4-10.5).
- Radiation involving the heart increased the likelihood of reporting CHF without doxorubicin (HR=6.6, 95% CI, 1.6-28.3), with ? 250 mg/m2 (HR=13.0, 95% CI, 1.9-89.7), and with > 250 mg/m2 (HR=18.3, 95% CI, 3.8-88.2).
- Doxorubicin without RT did not significantly increase the likelihood of CHF.
- RT to the contralateral kidney did not increase the likelihood of reporting renal failure or HTN.
- The prevalence ratio (PR) of reported adverse health status was significantly different from the sibling group for general overall health (PR 1.7, p=0.001), functional impairment (PR 3.3, p<0.001) and activity limitations (PR 1.9, p<0.001), but not for mental health status (PR 1.2, p=0.09).
- WT survivors and the siblings showed no differences in self or professional screening for cancer.
- An exception to this was female WT survivors <30 yrs, who were more likely to report having had a mammogram (PR 1.6, p=0.008) than their sibling counterparts.
- Having said this, of female WT survivors who received chest RT, only 13% <30 yrs and 57% ?30 yrs reported having had a mammogram.
- WT survivors <30 yrs old reported more general medical exams (PR 1.1, p<0.001) than did their siblings.
- Survivors of WT have an almost five-fold increased risk of severe chronic medical conditions and an almost two-fold increased risk of adverse health status than their sibling cohort.
- Overall health care practices of WT survivors were similar to their siblings, despite their increased risk of CMCs.
- Strategies for screening and intervention are therefore needed.
- A high percentage of WT patients are now cured of their disease with multi-modality therapy, and there is a growing group of aging adult WT survivors.
- WT survivors have an elevated risk of long-term treatment related toxicities and are at particular risk for development of CHF, renal failure, and HTN.
- The current study is a large retrospective cohort study examining self-reported health outcomes in long-term WT survivors.
- Strengths of the study include the large number of patients examined, and a median follow-up of over 20 years, which is important to characterize risks of many late toxicities.
- Limitations of the study include:
- All data regarding patient health outcomes are self-reported, including information about CHF, renal failure, and hypertension. Patient self-reported data may be less reliable than direct review of health care provider records.
- The study results report outcomes of patients treated for WT between 1970-1986. However, information regarding health outcomes of patients receiving more modern therapy is not yet available. Analysis of a more modern cohort of patients treated between 1987-1999 is currently ongoing.
- The study is retrospective in nature and therefore results are subject to potential inherent bias.
- This study provides further information about long-term health risks for WT survivors and helps to identify patient groups at highest risk based upon specific therapy received.
- The study confirms the findings reported in other studies that the combination of thoracic RT and high dose doxorubicin significantly increase risk of developing CHF
- The study reports that WT survivors are no more likely to undergo cancer screening than their sibling counterparts, despite an increased risk of second malignancy. Rates of mammographic screening in female survivors having received chest radiation are shockingly low, especially because these patients fall into a cohort recommended by cooperative groups to have aggressive screening with mammography and breast MRI due to previous chest radiation.
- These results highlight the need for screening and intervention strategies to address the long-term health of these patients.
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