CONTEXT Improved survival of children with cancer has been accompanied by multiple treatment-related complications. However, most studies in survivors of childhood cancer focused on only 1 late ...effect. OBJECTIVE To assess the total burden of adverse health outcomes (clinical or subclinical disorders “adverse events”) following childhood cancer in a large cohort of childhood cancer survivors with long-term and complete medical follow-up. DESIGN, SETTING, AND POPULATION Retrospective cohort study of 1362 five-year survivors of childhood cancer treated in a single institution in the Netherlands between 1966 and 1996. All survivors were invited to a late-effects clinic for medical assessment of adverse events. Adverse events occurring before January 2004 were graded for severity in a standardized manner. MAIN OUTCOME MEASURES Treatment-specific prevalence of adverse events (according to severity) at end of follow-up and relative risk of high or severe burden of disease (≥2 severe or ≥1 life-threatening or disabling adverse events) associated with various treatments. RESULTS Medical follow-up was complete for 94.3% of survivors (median follow-up, 17.0 years). The median attained age at end of follow-up was 24.4 years. Almost 75% of survivors had 1 or more adverse events, and 24.6% had 5 or more adverse events. Furthermore, 40% of survivors had at least 1 severe or life-threatening or disabling adverse event. A high or severe burden of adverse events was observed in 55% of survivors who received radiotherapy only and 15% of survivors treated with chemotherapy only, compared with 25% of survivors who had surgery only (adjusted relative risks, 2.18 95% confidence interval, 1.62–2.95 and 0.65 95% confidence interval, 0.46–0.90, respectively). A high or severe burden of adverse events was most often observed in survivors of bone tumors (64%) and least often in survivors of leukemia or Wilms tumor (12% each). CONCLUSIONS In young adulthood, a substantial proportion of childhood cancer survivors already has a high or severe burden of disease, particularly after radiotherapy. This underscores the need for lifelong risk-stratified medical surveillance of childhood cancer survivors.
To establish 1) further psychometric properties of the information preference for radiotherapy patients scale (IPRP); 2) what information new radiotherapy patients want to receive; 3) which patients ...have a lower information need.
Eligible patients (n = 159; response rate 54%) of 15 radiation oncologists completed the IPRP and provided background characteristics before their first radiotherapy consultation. Exclusion criteria were: age <18 years, having undergone radiotherapy before, unable to read and write Dutch, cognitive problems or a brain tumor.
Reliability (Cronbach's alpha 0.84-0.97) and concurrent validity (r from .39 to .57, p < 0.001) of the subscales of the IPRP were good. New radiotherapy patients want extensive information about their disease, treatment, procedures, side effects, and prognosis (mean scores between 4.1 and 4.4 on a scale from 1 to 5) but less information about psychosocial issues (mean = 3.4). Patients who are older and male, have lung or rectal cancer, more difficulty understanding and a higher trait anxiety level, need less information.
The IPRP can reliably and validly address information needs of patients undergoing radiation treatment. Most new radiotherapy patients want much information. Yet, information giving should be tailored according to their background, understanding and anxiety.
Childhood cancer survivors (CCSs) have an increased risk of morbidity and mortality. The prevalence and risk factors of pulmonary function impairment were investigated in a large cohort of CCSs ...treated with potentially pulmotoxic therapy with a minimal follow-up of 5 years after diagnosis.
The study cohort consisted of all adult 5-year CCSs who were treated with bleomycin, pulmonary radiotherapy and/or pulmonary surgery in the Emma Children's Hospital/Academic Medical Center between 1966 and 1996. Pulmonary function tests were performed to diagnose obstructive and restrictive pulmonary function impairment, and diffusion capacity impairment.
The study population consisted of 220 out of 248 eligible CCSs, of whom 193 (87.7%) had performed a pulmonary function test at a median follow-up of 18 years after diagnosis. 85 (44.0%) out of 193 CCSs developed a pulmonary function impairment. Pulmonary function impairments occurred in all treatment groups. Most prevalent were restrictive pulmonary function impairment (17.6%) and a decreased carbon monoxide diffusion capacity (39.9%). Multivariate logistic regression models showed that, compared with bleomycin treatment only, treatment with radiotherapy, radiotherapy combined with bleomycin and radiotherapy combined with surgery were associated with the highest risk of pulmonary function impairment.
The prevalence of pulmonary function impairment in long-term adult CCSs who received potentially pulmotoxic therapy is high. Bleomycin, pulmonary radiotherapy and pulmonary surgery are all associated with pulmonary function impairment. Pulmonary radiotherapy, especially in combination with bleomycin or surgery, is the most important risk factor. This emphasises the need for adequate counselling and follow-up for this patient population.
Abstract Background and Purpose For the radiation treatment of prostate cancer high dose should be delivered for optimal biochemical control. Treatment can be given by dose-escalated external beam ...radiotherapy (EBRT) or external beam radiotherapy combined with a radioactive seed implantation (EBSeeds) or high-dose rate (HDR) brachytherapy (EBTI). Differences in outcome between the modalities were assessed by a systematic review. Materials and methods A systematic search was performed resulting in 40 articles to be used. Data were extracted on biochemical control and overall survival at 3, 5, and 8 years and other time points mentioned in the articles. Also known prognostic parameters were noted. Comparison of the modalities was done by a Weibull survival analysis and estimation of Hazard Ratio’s (HR) was done with 95% confidence intervals (95% CIs). Results The HR for biochemical recurrence was 1.40 (95% CI 1.31–1.51) for EBRT relative to EBTI, and was 1.37 (95% CI 1.26–1.49) for EBSeeds relative to EBTI. The HR for overall survival was 1.50 (95% CI 1.29–1.73) for EBRT relative to EBTI, and was 2.33 (95% CI 2.04–2.66) for EBSeeds relative to EBTI. Conclusion The combination of external beam radiotherapy and HDR brachytherapy results in a superior biochemical control and overall survival found in a systematic review on radiotherapy for prostate cancer.
Impaired glomerular function is one of the health problems affecting childhood cancer survivors (CCS). It is unclear whether glomerular function deteriorates or recovers. We investigated time trends ...and predictors of glomerular function in CCS.
We evaluated repeated observations of estimated glomerular filtration rate (GFR) and glomerular dysfunction (GFR <90 mL/min/1.73 m(2)) among adult five-year CCS treated in the EKZ/AMC between 1966 and 2003. Ifosfamide, cisplatin, carboplatin, high-dose (HD) methotrexate, HD-cyclophosphamide, radiotherapy to the kidney region, and nephrectomy (i.e., potentially nephrotoxic therapy) were investigated as predictors of glomerular function patterns over time in multivariable longitudinal analyses.
At a median follow-up of 21 years after diagnosis, glomerular function was assessed in 1,122 CCS aged ≥18 years. CCS treated with potentially nephrotoxic therapy had a significantly lower GFR and higher glomerular dysfunction probability up to 35 years after cancer diagnosis compared with CCS treated without nephrotoxic therapy (P < 0.001). Especially ifosfamide, cisplatin, and nephrectomy were associated with worse glomerular function that persisted during the entire follow-up period (P < 0.001). Glomerular function deteriorated over time in all CCS (P < 0.001). CCS treated with higher doses of cisplatin seem to have a higher deterioration rate as compared with other CCS (P < 0.005).
The loss in glomerular function starts early, especially for CCS treated with ifosfamide, higher doses of cisplatin, and nephrectomy, and seems to be persistent. We have an indication that CCS treated with higher doses of cisplatin experience faster decline than other CCS.
As glomerular function continues to deteriorate, CCS are at risk for premature chronic renal failure.
Background The thentest design aims to detect and control for recalibration response shift. This design assumes (1) more consistency in the content of the cognitive processes underlying patients' ...quality of life (QoL) between posttest and thentest assessments than between posttest and pretest assessments; and (2) consistency in the time frame and description of functioning referenced at pretest and thentest. Our objective is to utilize cognitive interviewing to qualitatively examine both assumptions. Methods We conducted think-aloud interviews with 24 patients with cancer prior to and after radiotherapy to elicit cognitive processes underlying their assessment of seven EORTC QLQ-C30 items at pretest, posttest and thentest. We used an analytic scheme based on the cognitive process models of Tourangeau et al. and Rapkin and Schwartz that yielded five cognitive processes. We subsequently used this input for quantitative analysis of count data. Results Contrary to expectation, the number of dissimilar cognitive processes between posttest and thentest was generally larger than between pretest and posttest across patients. Further, patients considered a range of time frames when answering the thentest questions. Moreover, patients' description at the thentest of their pretest functioning was often not similar to that which was noted at pretest. Items referring to trouble taking a short walk, overall health and QoL were most often violating the assumptions. Conclusions Both assumptions underlying the thentest design appear not to be supported by the patients' cognitive processes. Replacing the conventional pretest-posttest design with the thentest design may simply be replacing one set of biases with another.
Abstract Background Childhood cancer survivors (CCS) are a growing group of young individuals with a high risk of morbidity and mortality. We evaluated the prevalence and risk factors of hepatic late ...adverse effects, defined as elevated liver enzymes, in a large cohort of CCS. Methods The cohort consisted of all five-year CCS treated in the EKZ/AMC between 1966 and 2003, without hepatitis virus infection and history of veno-occlusive disease (VOD). Liver enzyme tests included serum levels of alanine aminotransferase (ALT) for hepatocellular injury and gamma-glutamyltransferase (γGT) for biliary tract injury. We performed multivariable linear and logistic regression analyses. Results The study population consisted of 1404 of 1795 eligible CCS, of whom 1362 performed liver enzyme tests at a median follow-up of 12 years after diagnosis. In total, 118 (8.7%) of 1362 CCS had hepatic late adverse effects defined as ALT or γGT above the upper limit of normal. Abnormal ALT and γGT levels were found in 5.8% and 5.3%, respectively. In multivariable regression analyses treatment with radiotherapy involving the liver, higher body mass index, higher alcohol intake and longer follow-up time were significantly associated with elevated ALT and γGT levels; older age at diagnosis was only significantly associated with elevated γGT levels (all p < 0.05). Conclusion One in twelve CCS showed signs of hepatic late adverse effects after a median follow-up of 12 years. Several risk factors have been identified. Future studies should focus on the course of long-term liver related outcomes and on the influence of radiotherapy and chemotherapy dose.
Little is known about renal function and blood pressure (BP) in long-term childhood cancer survivors. This cross-sectional study evaluated prevalence of these outcomes and associated risk factors in ...long-term childhood cancer survivors at their first visit to a specialized outpatient clinic.
Estimated GFR; percentages of patients with albuminuria, hypomagnesemia, and hypophosphatemia; and BP were assessed in 1442 survivors ≥5 years after diagnosis. Multivariable logistic regression analyses were used to estimate effect of chemotherapy, nephrectomy, and radiation therapy on the different outcomes.
At a median age of 19.3 years (interquartile range, 15.6-24.5 years), 28.1% of all survivors had at least one renal adverse effect or elevated BP. The median time since cancer diagnosis was 12.1 years (interquartile range, 7.8-17.5 years). High BP and albuminuria were most prevalent, at 14.8% and 14.5%, respectively. Sixty-two survivors (4.5%) had an estimated GFR <90 ml/min per 1.73 m(2). Survivors who had undergone nephrectomy had the highest risk for diminished renal function (odds ratio, 8.6; 95% confidence interval CI, 3.4-21.4). Combined radiation therapy and nephrectomy increased the odds of having elevated BP (odds ratio, 4.92; 95% CI, 2.63-9.19), as did male sex, higher body mass index, and longer time since cancer treatment.
Almost 30% of survivors had renal adverse effects or high BP. Therefore, monitoring of renal function in high-risk groups and BP in all survivors may help clinicians detect health problems at an early stage and initiate timely therapy to prevent additional damage.
The purpose of this study was to determine survival, local and distant control, toxicity, and prognostic factors in patients with stage III non-small cell lung cancer (NSCLC) treated with concurrent ...chemoradiation therapy (CCRT).
Consecutive patients with stage IIIA and IIIB NSCLC (N = 154) staged with 18F-fluorodeoxyglucose positron emission tomography/computed tomography were retrospectively selected (2005-2015). CCRT consisted of daily low-dose cisplatin (6 mg/m2) combined with 24 fractions of 2.75 Gy to a total dose of 66 Gy.
During a median follow-up period of 22 months (range, 1-92 months) the median overall survival was 36 months. The 1-, 2-, 3-, and 5-year survival rates were 79% (95% confidence interval CI, 73%-86%), 61% (95% CI, 54%-70%), 52% (95% CI, 43%-60%), and 40% (95% CI, 31%-51%), respectively. The local relapse-free survival at 5 years was 55% (95% CI, 44%-69%). Metastasis-free survival at 5 years was 53% (95% CI, 44%-65%). The incidence of severe gastrointestinal disorders (grade 3-5) was 11%, among which grade 3 radiation esophagitis was 8.4%. The incidence of severe respiratory, thoracic, and mediastinal disorders (grade 3-5) was 8.4%, among which grade 3 radiation pneumonitis was 1.3%. Predictors of overall survival were lymph node gross tumor volume (GTV) (hazard ratio HR, 1.007; 95% CI, 1.000-1.012) and sex (HR, 0.500; 95% CI, 0.320-0.870) in favor of women. Although lymph node GTV was a predictor of treatment toxicity (HR, 1.010; 95% CI, 1.000-1.013), tumor GTV was the predictor for distant metastasis during follow-up (HR, 1.002; 95% CI, 1.001-1.003).
CCRT with daily low-dose cisplatin for locally advanced stage III NSCLC resulted in promising overall survival (3-year survival rate of 52% and 5-year survival rate of 40%) with low toxicity. Lymph node GTV, tumor GTV, and sex were predictors of overall survival, treatment toxicity, and distant metastasis.
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