Objectives To assess how often harm is quantified in randomised trials of cancer screening.Design Two authors independently extracted data on harms from randomised cancer screening trials. Binary outcomes were described as proportions and continuous outcomes with medians and interquartile ranges.Data sources For cancer screening previously assessed in a Cochrane review, we identified trials from their reference lists and updated the search in CENTRAL. For cancer screening not assessed in a Cochrane review, we searched CENTRAL, Medline, and Embase.Eligibility criteria for selecting studies Randomised trials that assessed the efficacy of cancer screening for reducing incidence of cancer, cancer specific mortality, and/or all cause mortality.Data extraction Two reviewers independently assessed articles for eligibility. Two reviewers, who were blinded to the identity of the study’s authors, assessed whether absolute numbers or incidence rates of outcomes related to harm were provided separately for the screening and control groups. The outcomes were false positive findings, overdiagnosis, negative psychosocial consequences, somatic complications, invasive follow-up procedures, all cause mortality, and withdrawals because of adverse events.Results Out of 4590 articles assessed, 198 (57 trials, 10 screening technologies) matched the inclusion criteria. False positive findings were quantified in two of 57 trials (4%, 95% confidence interval 0% to 12%), overdiagnosis in four (7%, 2% to 18%), negative psychosocial consequences in five (9%, 3% to 20%), somatic complications in 11 (19%, 10% to 32%), use of invasive follow-up procedures in 27 (47%, 34% to 61%), all cause mortality in 34 (60%, 46% to 72%), and withdrawals because of adverse effects in one trial (2%, 0% to 11%). The median percentage of space in the results section that reported harms was 12% (interquartile range 2-19%).Conclusions Cancer screening trials seldom quantify the harms of screening. Of the 57 cancer screening trials examined, the most important harms of screening—overdiagnosis and false positive findings—were quantified in only 7% and 4%, respectively.
BACKGROUND: Germ-cell cancer (GCC) patients aged 40 years have a two-fold higher GCC-specific mortality. It has been hypothesized that reduced treatment intensity combined with increased treatment related toxicity could be the explanation. The objective was to analyze chemotherapy intensity, treatment related toxicity and survival in patients aged 40 years treated with standard chemotherapy for GCC compared with a younger control group that received similar treatment during the same period. METHODS: From 1984 to 2011, 135 patients aged 40 years with disseminated GCC treated with bleomycin, etoposide and cisplatin (BEP). A control-group of 135 patients aged 18-35 years was randomly selected matched on year of BEP treatment. Cumulated doses of BEP as well as bone marrow toxicity, renal-and lung functions were recorded before, during and after termination of treatment. All patients were followed until death or October 1, 2011. RESULTS: The cumulated doses of BEP were comparable between the two groups, however, more patients aged 40 years were reduced in bleomycin doses based on a decrease in carbon monoxide diffusion capacity corrected for haemoglobin (P 5 0.03). No differences between the two groups were found regarding bone marrow toxicity or mean percentage changes in lung-or renal function. Patients aged 40 year had increased cancer specific mortality, HR 5 4.8 (P 5 0.005). In particular patients with disease progression after first line chemotherapy had increased mortality (P 5 0.015). Moreover, the 5-year overall survival for patients aged 40 years was 82.5% compared to the expected 5-year survival of the background population of 96.3% (P <0.001). CONCLUSIONS: Treatment related toxicity could not explain the increased cancer specific mortality in patients aged 40 years compared to a younger control-group, and while there were no differences in the administrated doses of cisplatin/ etoposide, a decreased number of bleomycin doses were administered in the older patients. Apart from this, the inferior prognosis could be related to tumour biology, increased co-morbidity, or more severe toxicity in relation to second line treatment. Cancer 2014;120:43-51.
4532 Background: The aim was to analyze treatment related toxicity and survival in patients aged 40 years or above (40+) treated with standard chemotherapy for germ-cell cancer (GCC). Methods: The study population comprised 135 40+ patients with disseminated GCC treated between 1984 – 2011 with either 3 or 4 cycles bleomycin, etoposide and cisplatin (BEP). A control-group of 135 patients aged 18-35 years was randomly selected matched on year of BEP treatment. All patients were followed until death or October 1st2011. Cumulated doses of BEP as well as bone-marrow toxicity, renal- and lung functions were recorded before, during and after termination of treatment. The expected mortality was calculated by extracting survival data for each patient matched on the date and age at the time of diagnosis. The cause of death was categorized as GCC, other malignancy or other. Results: The cumulated doses of BEP were comparable between the two groups and, generally, BEP was equally well tolerated. 40+ patients had increased cancer specific mortality, HR = 4.8 (P = 0.005). Especially patients with disease progression after first line chemotherapy had increased mortality (P = 0.015). The year of treatment (P = 0.32), histology (P = 0.30), CCI (P = 0.99), tobacco use (P = 0.16), alcohol consumption (P = 0.21), prophylactic G-CSF (P = 0.61), reduced doses of bleomycin (P = 0.11) and decreased renal function (P = 0.18) were not significantly associated with GCC mortality. However, patients with impaired lung function (<80% of expected) prior to treatment had an increased risk of GCC mortality (FVC (P = 0.03), DLCO (P = 0.01) and FEV1(P = 0.05)). Moreover, the 5-year overall survival in the 40+ group was 82.5% compared to the expected 5-year survival of the background population of 96.2% (P <0.001) and the estimated 5-year survival of 97.0% in the control-group (P <0.001). Conclusions: Reduced treatment intensity, or treatment related toxicity could not explain the increased mortality in 40+ GCC patients compared to a younger control-group. The 40+ group has a significantly lower response rate to BEP and a significantly higher mortality in case of disease progression. The worse prognosis could be related to tumor biology or increased co-morbidity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.