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Title: Evaluation of Late Adverse Events in Long-Term Wilms' Tumor Survivors

Abstract

Purpose: To evaluate the prevalence and severity of adverse events (AEs) and treatment-related risk factors in long-term Wilms' tumor (WT) survivors, with special attention to radiotherapy. Methods and Materials: The single-center study cohort consisted of 185 WT survivors treated between 1966 and 1996, who survived at least 5 years after diagnosis. All survivors were invited to a late-effects clinic for medical assessment of AEs. AEs were graded for severity in a standardized manner. Detailed radiotherapy data enabled us to calculate the equivalent dose in 2 Gy fractions (EQD{sub 2}) to compare radiation doses in a uniform way. Risk factors were evaluated with multivariate logistic regression analysis. Results: Medical follow-up was complete for 98% of survivors (median follow-up, 18.9 years; median attained age, 22.9 years); 123 survivors had 462 AEs, of which 392 had Grade 1 or 2 events. Radiotherapy to flank/abdomen increased the risk of any AE (OR, 1.08 Gy{sup -1} [CI, 1.04-1.13]). Furthermore, radiotherapy to flank/abdomen was associated with orthopedic events (OR, 1.09 Gy{sup -1} [CI, 1.05-1.13]) and second tumors (OR, 1.11 Gy{sup -1} [CI, 1.03-1.19]). Chest irradiation increased the risk of pulmonary events (OR, 1.14 Gy{sup -1} [CI, 1.06-1.21]). Both flank/abdominal and chest irradiation were associated with cardiovascularmore » events (OR, 1.05 Gy{sup -1} [CI, 1.00-1.10], OR, 1.06 Gy{sup -1} [CI, 1.01-1.12]) and tissue hypoplasia (OR, 1.17 Gy{sup -1} [CI, 1.10-1.24], OR 1.10 Gy{sup -1} [CI, 1.03-1.18]). Conclusion: The majority of AEs, overall as well as in irradiated survivors, were mild to moderate. Nevertheless, the large amount of AEs emphasizes the importance of follow-up programs for WT survivors.« less

Authors:
 [1];  [1]; ;  [2]
  1. Department of Radiation Oncology, Academic Medical Center (AMC), Amsterdam (Netherlands)
  2. Outpatient Clinic for Late Effects (Polikliniek Late Effecten Kindertumoren, PLEK)/AMC, Amsterdam (Netherlands)
Publication Date:
OSTI Identifier:
21436175
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 78; Journal Issue: 2; Other Information: DOI: 10.1016/j.ijrobp.2009.08.016; PII: S0360-3016(09)02956-3; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ABDOMEN; CHEST; NEOPLASMS; RADIATION DOSES; RADIATION HAZARDS; RADIOTHERAPY; REGRESSION ANALYSIS; BODY; DISEASES; DOSES; HAZARDS; HEALTH HAZARDS; MATHEMATICS; MEDICINE; NUCLEAR MEDICINE; RADIOLOGY; STATISTICS; THERAPY

Citation Formats

Dijk, Irma van, E-mail: i.w.vandijk@amc.uva.n, Oldenburger, Foppe, Cardous-Ubbink, Mathilde C., and Geenen, Maud M.. Evaluation of Late Adverse Events in Long-Term Wilms' Tumor Survivors. United States: N. p., 2010. Web. doi:10.1016/j.ijrobp.2009.08.016.
Dijk, Irma van, E-mail: i.w.vandijk@amc.uva.n, Oldenburger, Foppe, Cardous-Ubbink, Mathilde C., & Geenen, Maud M.. Evaluation of Late Adverse Events in Long-Term Wilms' Tumor Survivors. United States. doi:10.1016/j.ijrobp.2009.08.016.
Dijk, Irma van, E-mail: i.w.vandijk@amc.uva.n, Oldenburger, Foppe, Cardous-Ubbink, Mathilde C., and Geenen, Maud M.. 2010. "Evaluation of Late Adverse Events in Long-Term Wilms' Tumor Survivors". United States. doi:10.1016/j.ijrobp.2009.08.016.
@article{osti_21436175,
title = {Evaluation of Late Adverse Events in Long-Term Wilms' Tumor Survivors},
author = {Dijk, Irma van, E-mail: i.w.vandijk@amc.uva.n and Oldenburger, Foppe and Cardous-Ubbink, Mathilde C. and Geenen, Maud M.},
abstractNote = {Purpose: To evaluate the prevalence and severity of adverse events (AEs) and treatment-related risk factors in long-term Wilms' tumor (WT) survivors, with special attention to radiotherapy. Methods and Materials: The single-center study cohort consisted of 185 WT survivors treated between 1966 and 1996, who survived at least 5 years after diagnosis. All survivors were invited to a late-effects clinic for medical assessment of AEs. AEs were graded for severity in a standardized manner. Detailed radiotherapy data enabled us to calculate the equivalent dose in 2 Gy fractions (EQD{sub 2}) to compare radiation doses in a uniform way. Risk factors were evaluated with multivariate logistic regression analysis. Results: Medical follow-up was complete for 98% of survivors (median follow-up, 18.9 years; median attained age, 22.9 years); 123 survivors had 462 AEs, of which 392 had Grade 1 or 2 events. Radiotherapy to flank/abdomen increased the risk of any AE (OR, 1.08 Gy{sup -1} [CI, 1.04-1.13]). Furthermore, radiotherapy to flank/abdomen was associated with orthopedic events (OR, 1.09 Gy{sup -1} [CI, 1.05-1.13]) and second tumors (OR, 1.11 Gy{sup -1} [CI, 1.03-1.19]). Chest irradiation increased the risk of pulmonary events (OR, 1.14 Gy{sup -1} [CI, 1.06-1.21]). Both flank/abdominal and chest irradiation were associated with cardiovascular events (OR, 1.05 Gy{sup -1} [CI, 1.00-1.10], OR, 1.06 Gy{sup -1} [CI, 1.01-1.12]) and tissue hypoplasia (OR, 1.17 Gy{sup -1} [CI, 1.10-1.24], OR 1.10 Gy{sup -1} [CI, 1.03-1.18]). Conclusion: The majority of AEs, overall as well as in irradiated survivors, were mild to moderate. Nevertheless, the large amount of AEs emphasizes the importance of follow-up programs for WT survivors.},
doi = {10.1016/j.ijrobp.2009.08.016},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 78,
place = {United States},
year = 2010,
month =
}
  • Purpose: To evaluate the prevalence and severity of clinical adverse events (AEs) and treatment-related risk factors in childhood cancer survivors treated with cranial radiation therapy (CRT), with the aim of assessing dose-effect relationships. Methods and Materials: The retrospective study cohort consisted of 1362 Dutch childhood cancer survivors, of whom 285 were treated with CRT delivered as brain irradiation (BI), as part of craniospinal irradiation (CSI), and as total body irradiation (TBI). Individual CRT doses were converted into the equivalent dose in 2-Gy fractions (EQD{sub 2}). Survivors had received their diagnoses between 1966 and 1996 and survived at least 5 yearsmore » after diagnosis. A complete inventory of Common Terminology Criteria for Adverse Events grade 3.0 AEs was available from our hospital-based late-effect follow-up program. We used multivariable logistic and Cox regression analyses to examine the EQD{sub 2} in relation to the prevalence and severity of AEs, correcting for sex, age at diagnosis, follow-up time, and the treatment-related risk factors surgery and chemotherapy. Results: There was a high prevalence of AEs in the CRT group; over 80% of survivors had more than 1 AE, and almost half had at least 5 AEs, both representing significant increases in number of AEs compared with survivors not treated with CRT. Additionally, the proportion of severe, life-threatening, or disabling AEs was significantly higher in the CRT group. The most frequent AEs were alopecia and cognitive, endocrine, metabolic, and neurologic events. Using the EQD{sub 2}, we found significant dose-effect relationships for these and other AEs. Conclusion: Our results confirm that CRT increases the prevalence and severity of AEs in childhood cancer survivors. Furthermore, analyzing dose-effect relationships with the cumulative EQD{sub 2} instead of total physical dose connects the knowledge from radiation therapy and radiobiology with the clinical experience.« less
  • Purpose: To investigate adverse events after samarium Sm 153 lexidronam and the effect of pre- and post-samarium Sm 153 lexidronam external beam radiation therapy (EBRT) and/or chemotherapy on myelosuppression in patients who received samarium Sm 153 lexidronam for osseous metastases. Methods and Materials: We performed a single-institution retrospective review of 139 patients treated with samarium Sm 153 lexidronam between November 1997 and February 2008. New-onset adverse events after samarium Sm 153 lexidronam were reported. The effect of samarium Sm 153 lexidronam on platelet and peripheral white blood cell counts and the duration of myelosuppression after samarium Sm 153 lexidronam plusmore » EBRT and/or chemotherapy were calculated. Differences in the prevalence of adverse events among patients with varying treatment histories were evaluated with the Pearson chi-square test. Results: Hematologic follow-up was available for 103 patients. Chemotherapy and/or EBRT had no effect on the magnitude or duration of myelosuppression. The most common nonhematologic adverse events were acute lower extremity edema (n = 27) and acute and transient neuropathy (n = 29). Patients treated with chemotherapy after samarium Sm 153 lexidronam had a higher prevalence of lower extremity edema (9 of 18 [50%]) than those who were not treated with chemotherapy after samarium Sm 153 lexidronam (18 of 85 [21.2%]) (p = 0.01, chi-square test). No adverse events were correlated with EBRT. Conclusions: Our observation of new-onset, acute and transient edema and neuropathy after samarium Sm 153 lexidronam and of a relationship between edema and post-samarium Sm 153 lexidronam chemotherapy suggests the need for re-examination of patients in past series or for a prospective investigation with nonhematologic adverse events as a primary endpoint.« less
  • Purpose: Cervical cancer treatment is associated with a risk of urinary adverse events (UAEs) such as ureteral stricture and vesicovaginal fistula. We sought to measure the long-term UAE risk after surgery and radiation therapy (RT), with confounding controlled through propensity-weighted models. Methods and Materials: From the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we identified women ≥66 years old with nonmetastatic cervical cancer treated with simple surgery (SS), radical hysterectomy (RH), external beam RT plus brachytherapy (EBRT+BT), or RT+surgery. We matched them to noncancer controls 1:3. Differences in demographic and cancer characteristics were balanced by propensity weighting. Grade 3 tomore » 4 UAEs were identified by diagnosis codes plus treatment codes. Cumulative incidence was measured using Kaplan-Meier methods. The hazard associated with different cancer treatments was compared using Cox models. Results: UAEs occurred in 272 of 1808 cases (17%) and 222 of 5424 (4%) controls; most (62%) were ureteral strictures. The raw cumulative incidence of UAEs was highest in advanced cancers. UAEs occurred in 31% of patients after EBRT+BT, 25% of patients after RT+surgery, and 15% of patients after RH; however, after propensity weighting, the incidence was similar. In adjusted Cox models (reference = controls), the UAE risk was highest after RT+surgery (hazard ratio [HR], 5.07; 95% confidence interval [CI], 2.32-11.07), followed by EBRT+BT (HR, 3.33; 95% CI, 1.45-7.65), RH (HR, 3.65; 95% CI, 1.41-9.46) and SS (HR, 0.99; 95% CI, 0.32-3.01). The higher risk after RT+surgery versus EBRT+BT was statistically significant, whereas, EBRT+BT and RH were not significantly different from each other. Conclusions: UAEs are common after cervical cancer treatment, particularly in patients with advanced cancers. UAEs are more common after RT, but these women tend to have the advanced cancers. After propensity weighting, the risk after RT was similar to that after surgery.« less
  • Three children with malignant primary CNS tumors treated with craniospinal radiotherapy developed intraparenchymal hemorrhages a median of 5 years following therapy in sites distant from the primary tumor. Radical surgical procedures disclosed fresh and old hematoma, gliosis, and necrosis in all 3 patients and an aggregation of abnormal microscopic blood vessels in two. No tumor was found. All 3 patients remain in long-term (greater than 10 years) continuous remission.
  • Outcome of pregnancy was reported by 99 patients who were cured of childhood Wilms' tumor at seven pediatric cancer centers during 1931 to 1979. These patients carried or sired 191 singleton pregnancies of at least 20 weeks in duration. Among the 114 pregnancies in women who had received abdominal radiotherapy for Wilms' tumor, an adverse outcome occurred in 34 (30%). There were 17 perinatal deaths (five in premature low-birth-weight infants) and 17 other low-birth-weight infants. Compared with white women in the United States, the irradiated women had an increased perinatal mortality rate (relative risk, 7.9) and an excess of low-birth-weightmore » infants (relative risk, 4.0). In contrast, an adverse outcome was found in two (3%) of the 77 pregnancies in nonirradiated female patients with Wilms' tumor and wives of male patients. The high risk of adverse pregnancy outcome should be considered in the counseling and prenatal care of women who have received abdominal radiotherapy for Wilms' tumor.« less