Radiation-associated breast, thyroid and solid malignancies in patients attending the Peter MacCallum Cancer Centre Late Effects service

Abstract

Background: Survivors of childhood, adolescent and young adulthood (CAYA) malignancies have an increased risk of subsequent primary malignancies, particularly after exposure to therapeutic radiation. The Peter MacCallum Cancer Centre Late Effects (PMCC LE) service provides individualize, multidisciplinary care and surveillance advice for survivors of malignancies, especially CAYA malignancies.

Methods: A retrospective review was performed of patients exposed to therapeutic radiation attending the PMCC LE service from 1st January 2000 to 20th February 2013. All invasive malignancies, in-situ malignancies, benign tumours and deaths were evaluated. Separate time-to-event analyses was performed for radiation-associated breast, thyroid and solid malignancies in patients exposed to chest, thyroid and any therapeutic radiation respectively, measured from the date of first attendance to the PMCC LE service and stratified by the interval from completion of radiation to the first attendance. The incidence of breast and thyroid malignancies was compared to the Australian general population. Compliance with breast and thyroid surveillance recommendations was determined by assessing the number of screen events over the period of attendance to the service. Clinicopathological features and management of radiation-associated breast and thyroid and other solid malignancies was examined. Ultrasound and cytological workup of radiation exposed thyroid nodules was assessed.

Results: After excluding 187 patients, 534 included patients developed 194 invasive malignancies; 147 were radiation-associated and 47 non-radiation associated. The most common malignancies were non-melanoma skin (37.1%), thyroid (17.0%) and breast (12.9%) malignancies. Patients whose first attendance was ≥15+ years after radiation exposure experienced the highest incidence of radiation-associated breast, thyroid and solid malignancies, with 23%, 8% and 27% affected after 10 years of subsequent follow-up respectively. The incidence of breast and thyroid malignancy was elevated 11.2 and 57.6 times respectively compared to the Australian general population (both p<0.001). Compliance with breast surveillance using mammography or any screening modality was observed in 18.4% and 28.6% of women at risk respectively. Twenty-eight radiation-associated breast malignancies occurred in 24 women (16.7% bilaterality). Breast malignancies diagnosed after the first attendance to the PMCC LE service were more likely screen-detected (p=0.002). Most were hormone receptor positive (87.5%), invasive ductal carcinomas (82.1%) managed with mastectomy (89.3%). Compliance with thyroid surveillance was observed in 76.9% of patients at risk. Ultrasound features of microcalcification and increased internal vascularity had a low sensitivity (62.5%) for predicting a malignant nodule, which improved when used in conjunction with a Bethesda IV-VI result (91.7%), although cytological assessment was not performed in 45.6% of operative cases. Thirty-three patients had a radiation-associated thyroid malignancy; 45.4% (n=15) were incidental. The majority were papillary thyroid cancers (88.9%); of which 12.5% were node positive and 34.4% were multifocal. Node positive thyroid cancers were more likely to present symptomatically (p=0.03). There were 36 deaths in the cohort (6.7%), most commonly attributable to radiation-associated malignancies (41.9%), especially brain, breast and sarcomatous malignancies.

Conclusions: Patients attending the PMCC LE service have a high burden of subsequent malignancies that typically occur after a long latency. Ongoing long-term surveillance is essential and judicious management with adherence to guidelines is advocated in this unique population of patients.