Late somatic sequelae after treatment of childhood cancer in Slovenia

Abstract

BackgroundThis is a long-term follow-up clinical study of adolescents and adults, survivors of childhood cancer. We evaluate and analyze the late somatic sequelae of childhood cancer treatment. Many such studies are susceptible to a strong selection bias, i.e., they employ a limited non-systematic sample of patients, based on a clinical hospital that provided the cancer treatment or performed the follow-up. To address the issue of selection bias, we perform here an analysis of late sequelae on a systematic database of the entire population of the children treated for cancer in Slovenia. Due to the specifics of cancer treatment procedures in Slovenia, they have all been treated and followed-up in the same clinic.MethodsThe data are based on the centralized registry of cancer patients in Slovenia and present a controlled and homogeneous collection. Late sequelae are evaluated following a modified CTCAE, i.e., the National Cancer Institute’s Common Terminology Criteria for Adverse Events version 3.0. We use survival analysis method to estimate the incidence of and risk for late sequelae, where the time variable is measured in years from the diagnosis date, while we follow the event of incidence of late sequelae scored other than none. Survival analysis is performed using KaplanMeier estimator and Cox regression model.ResultsThe incidence of mild, moderate, or severe late sequelae of childhood cancer treatment significantly decreased from 75% in the group of patients diagnosed before 1975 to 55% for those diagnosed after 1995. The Cox regression analysis of the risk factors for the incidence of late sequelae identifies three significant factors: treatment modalities, age at diagnosis, and primary diagnosis.ConclusionsThe change of treatment modalities in terms of replacement of surgery and radiotherapy with chemotherapy is the main reason for the decrease of the incidence and the risk for late sequelae of childhood cancer treatment; treatment modalities including surgery significantly increase the risk ratio of late sequelae, while those based on chemotherapy only significantly decreases the risk. Risk of late sequelae increases with the diagnosis age: younger children are more susceptible to late effects of treatment. Finally, primary diagnosis significantly influences the risk for late sequelae, but mostly due to the dependency of the treatment modality on the primary diagnosis.

The Dutch LATER physical outcomes set for self-reported data in survivors of childhood cancer

“…Comparison to the SJLIFE adapted CTCAE for grading of clinically ascertained data showed that more of our core outcomes were missing and that 24 clinically relevant conditions corresponded to grade 2 or even grade 1. Hence, our results support previous authors, concluding that the CTCAE in its current form is not optimal to grade severity of (self-reported) long-term physical morbidity outcomes for CCS [ 41 – 43 ]. To our knowledge, this is the first comprehensive proposal to define a core outcome set for self-reported long-term physical outcomes in CCS.…”

“…Because the CTCAE criteria were originally designed for grading acute adverse events during adult cancer trials [ 54 ], the current CTCAE version 4.03 [ 40 ] does not cover the complete spectrum of long-term morbidity that CCS might encounter [ 42 ]. Several authors have already stated that relevant outcomes were missing for CCS and use adapted versions [ 41 – 43 ]. Comparison of our core set of long-term self-reported physical outcomes to the commonly used CTCAE showed that 36% of the outcomes were not present in the CTCAE.…”

“…Definitions of long-term morbidity outcomes also vary, for example, authors reporting on cardiovascular conditions generally report on heart failure, myocardial infarction, and hypertension, but some also include stroke as a cardiovascular condition [ 10 , 14 , 17 , 18 , 36 ]. While many authors do not grade the severity of the reported long-term morbidity in CCS, others use the Common Terminology Criteria for Adverse Events (CTCAE) [ 40 ], either in its original form or an adapted version incorporating specific additional outcomes that authors considered missing [ 41 – 43 ]. This lack of uniformity in types of outcomes, outcome definitions, and outcome grading—even among studies that use similar data ascertainment methods—limits interpretation, comparability, and generalizability of studies investigating the burden of long-term morbidity in CCS.…”

Health status of Polish children and adolescents after cancer treatment

“…The latest data from EUROCARE-5 focused on adolescents and young adults diagnosed between 2000 and 2007 exhibited improved survival in children and adolescents, but relatively poorer in adolescents and young adults than in children [ 31 ]. Similarly, in a Slovenian study, older age at diagnosis decreased the risk for late sequelae [ 10 ].…”

Impairment of lung diffusion capacity—a new consequence in the long-term childhood leukaemia survivors

“…An American multi-institutional study reported that over 60% of cancer survivors after oncology therapy in childhood had at least one, and 20% had multiple chronic health conditions [4, 6]. Observations from Europe are similar and show that more than 50% of the survivors present at least one side effect, with a growing prevalence and severity with time after the completion of oncology treatment [2, 7–10]. The nationwide study performed in the largest cohort of Polish childhood cancer survivors showed that over 80% of them had one or more symptoms of organ dysfunction [11].…”