Session 3 Radiation protection of patients and staff in radiotherapy including brachytherapy ABAZA et al RADIOTHERAPY INDUCED CATARACT AMONG CHILDHOOD CANCER SURVIVORS; INCIDENCE AND PROTECTION A. ABAZA Email: [email protected] G. EL- SHANSHOURY Email: [email protected] H. EL- SHANSHOURY Email: [email protected] Nuclear and Radiological Regulatory Authority, Cairo, Egypt Abstract The increased number of cancer survivors has shifted attention to the possible risk of subsequent treatment-related morbidities, including cataracts. Recently, it is known that cataracts can be developed with lens doses exceeding a threshold of 5- 8 Gy. The aim was to study retrospectively the role of radiation protection measurements in the incidence of radiotherapy induced cataract among childhood cancer survivors during the period of study (4 years) using statistical analysis. In follow-up clinic, 495 childhood cancer patients (leukemia, Lymphoma, soft tissue sarcoma and Wilms’ tumor) were examined after 5years of starting treatment. The file of patients was revised for clinic-epidemiologic data. A questionnaire that included questions on cataracts, the surgical procedures related and the using of radiation protection measurements during radiotherapy was answered by the patients and their relatives. The Results indicate a strong association between ocular exposure to ionizing radiation and long-term risk of pre-senile cataract. It is possible to significantly reduce the risk of radiation cataract through the use of appropriate eye protection concluding that the increasing awareness among those at risk, better adoption and increased usage of protective measures, radiation cataract can become preventable despite lowering of dose limits. Keywords: Cataract, Radiotherapy, Cancer survivors, Radiation Protection 1. INTRODUCTION The increased number of survivors has shifted attention to the possible long-term adverse effects of cancer treatments (1). Long-term survivors are at risk for developing a broad spectrum of adverse outcomes, which may include early death, second neoplasms, and damage to the heart (15,26,28,14). Additionally, neurosensory complications affecting the auditory, ocular such as cataracts, olfactory, or speech systems are commonly reported by childhood cancer survivors. Although some of these effects have a minor effect on the survivors’ quality of life, others, such as blindness and cataract, may have various important consequences. (14,39,1) Fortunately, radiotherapy (RT) is a major element in the treatment and improved survival of childhood cancers (26), including cranial or craniospinal RT. It is nevertheless associated with an increased risk of adverse outcomes such as second cancers and sensory or psychosocial problems (28). Since a child’s visual system is immature and develops during the initial years of life, the consequences of future visual deprivation caused by cataracts and aphakia in children can be important and include anisometropia, aniseikonia and lack of accommodation (5). Moreover, compared to adults, pediatric cataract surgery tends to be more complicated, requiring additional treatments to decrease the postoperative inflammation, secondary glaucoma, refractive instability of the developing eye and early and severe visual axis opacification. Most of the reported studies in pediatric cancer patients were limited by relatively small sample sizes and a lack of quantitative assessment of lens dose (13). Whelan et al. (39) found an increased risk of cataract at doses greater than 2 Gy to the eye after evaluating the risk of developing late ocular complications in specific cancer treatments five or more years after diagnosis in the Childhood Cancer Survivor Study (CCSS). Other studies have suggested that cataracts are associated with doses below 2 Gy. Therefore, it is classified as stochastic rather than deterministic outcomes (9,27,18,8,). A fair degree of consistency exists in the radiogenic risks for cataract in different groups exposed to radiation (16,29,42,9,27,23). Since the 1950s, the prevailing view has been that only relatively high doses of at least several grays induce vision-impairing cataracts. However, the incidence of cataract induced by RT and cytotoxic chemotherapy (CT) among survivors of childhood cancer is often underestimated and underreported. Few previous IAEA- CN-255/91 studies (29,10,39) addressed the question of cataract after childhood RT for cancer. One retrospective study of retinoblastoma survivors (10) showed that eyes exposed to a therapeutic radiation dose of 5 Gy or more had a 6-fold increased risk for cataract extraction compared with eyes exposed to 2.5 Gy or less. Another study found that the dose of radiation to the eye was significantly associated with the risk for cataract (29,39). On the other hand, Whelan et al (39) have also shown an increased risk for cataract in survivors who were treated with prednisone. Unfortunately, these studies have not provided findings on the risk for cataract for each of the main alkylating agents. To date, the possibility of interactions between exposure to specific groups of cytotoxic drugs and to ionizing radiation to the eyes also has not been considered (1). The aim of the current work was to study retrospectively the role of radiation protection measurements in the incidence of RT induced cataract among childhood cancer survivors attending the follow up clinic in multi-cancer centers during the period of study (from January 2013 till January 2017). 2. MATERIAL AND METHODS Full clinical examination was done to 495 patients 5 years after starting the treatment in 4 types of cancer survivors (158 leukemic patients, 183 Lymphoma, 89 soft tissue sarcoma and 65 Wilms’ tumor) laying stress on eye examination. The file of patients was revised about all clinical data including the radiation dose, the other RT data including radiation protection measurement used and the occurrence of cataract or not. By doing a questionnaire that answered by the patients and their relatives we can catch the data that can be missed in the file. Patients received RT alone or in combination with CT and other modality treatments. Chemotherapy used are classified according to their known mechanisms of action in cells laying stress on corticosteroids which were prescribed for a median duration of 29 days per course in the form of dexamethasone with a median dose of 8 mg (dose range, 1 mg-40 mg). 2.1 Statistical analysis The data are analyzed using some statistical tools. The analysis tools are confirmed in chi-square test (x2- test), cumulative incidence (CI), relative risk (RR), odds ratio (OR) and their confidence intervals. The IBM SPSS for Windows (version 23.0) is used to fit cumulative incidence using Kaplan-Meier and cumulative hazard using Cox’s proportional hazards regression model for cataract according to lens dose among five-year survivors. Attained age is used as the primary time scale. The Kaplan-Meier method for estimating survival functions and the Cox proportional hazards regression model for estimating the effects of covariates on the hazard of the occurrence of the event are commonly used statistical methods for the analysis of survival data. Estimating the incidence of an event as a function of follow-up time provides important information on the absolute risk of an event. In the absence of competing risks, the Kaplan-Meier estimate of the survival function is frequently used for estimating the survival function. One minus the Kaplan-Meier estimate of the survival function provides an estimate of the cumulative incidence of events over time. In the case study that follows, the incidence of cataract in patients is examined (3). 2.1.1 Cumulative incidence (CI) or incidence proportion is a measure of frequency, where it is a measure of disease frequency during a period of time (40). CI is an estimate of risk. It is the proportion of individuals who experience the event in a defined time period (24). Event/Number during some time T = cumulative incidence 2.1.2 Relative risk (Risk Ratio) (RR) is a measure of the risk of a certain event happening in one group compared to the risk of the same event happening in another group. In cancer research, risk ratios are used in prospective studies, such as cohort studies and clinical trials. A risk ratio of one means there is no difference between two groups in terms of their risk of cancer, based on whether or not they were exposed to a certain substance or factor, or how they responded to two treatments being compared. RR is the ratio of the risk or probability of an event occurring in group 1 (P1) versus the probability of the event in group 2 (P2). Then the relative risk is 푅푅 = 푃1 (35) 푃2 2.1.3 The Confidence interval (CIs) indicates the level of uncertainty is associated with the estimate of the intervention (the precision or accuracy of the estimate) (17). Confidence intervals are used because a study recruits only a small sample of the overall population so by having an upper and lower confidence limit we can infer that the true population effect lies between these two points. Most studies report the 95% confidence interval (95%CIs). The 95% confidence interval of Relative Risk as follows (32). 95% CIs= exp(ln(RR)-1.96× SE[ln(RR)]) to exp(ln(RR)+1.96× SE[ln(RR)]) Where, SE is the Standard Error ABAZA et al 2.1.4 Odd ratio (OR) is the “measure of association” for a case-control study. It is a measure of the relative magnitude of the odds of exposure among individuals who have the disease (cases) and the odds of exposure among individuals who do not have the disease (controls). It quantifies the relationship between an exposure and a disease or outcome in a case-control study (19). i.e. to quantify how strongly the presence or absence of property A is associated with the presence or absence of property B in a given population (41).