Radiation-associated breast cancers in a late-effects cohort: Long-term surveillance is essential.

AIMS: Survivors of childhood, adolescent, and young adulthood malignancies have an increased risk of subsequent primary malignancies, particularly after exposure to therapeutic radiation. This study aims to evaluate the mode of surveillance and surveillance compliance, incidence and mode of detection of breast cancer, breast cancer phenotype, and outcomes after radiation-associated breast cancer (RBC) in a late-effects cohort. METHODS: Women exposed to therapeutic radiation attending the late effects service from 1st January 2000 to 20th February 2013. All invasive and in-situ cancers, benign tumors, and deaths were evaluated. The incidence of breast cancer was compared to the Australian general population. Compliance with breast surveillance recommendations, clinicopathological features, and management of breast cancers were examined. RESULTS: The prevalence of RBC was 17.1%. Twenty-eight cases of RBC occurred in 24 women, out of 140 women exposed to chest radiation. Patients whose first attendance was ≥15 years after radiation exposure experienced the highest incidence of RBC at 23%. The incidence of breast cancer was 11.2 times the general population (P < .001). Compliance with surveillance mammography was observed in 18.4%. Breast cancers diagnosed after the first attendance to the service were more likely screen-detected (P = .002). Most were hormone receptor positive (84.0%), invasive ductal carcinomas (82.1%), and managed with mastectomy (89.3%). CONCLUSIONS: Patients attending a dedicated late effects service have a high burden of subsequent malignancies generally occurring after long latency. Judicious management with adherence to long-term surveillance guidelines is advocated.

Radiation-Associated Thyroid Cancer Surveillance and Management in a Cohort of Late Effects Patients.

BACKGROUND AND AIMS: Compared to the general population, the incidence of thyroid cancer in childhood and adolescent and young adult malignancy survivors is increased 14.0-18.0 times (CI 11.7-23.8). The cumulative incidence is variably reported as 0.5% by age 45 with 30-year incidence of 1.3% in women and 0.6% in men. This study aims to evaluate the incidence of radiation-associated thyroid cancer amongst patients treated with prior radiation to the thyroid followed up in a late effects service. A secondary aim was to assess screening compliance in this cohort. METHODS: The medical records of all patients attending the late effects service from 1 January 2000 to 20 February 2013 were interrogated to identify patients exposed to thyroid irradiation. The screening compliance and incidence of thyroid cancer were assessed for the duration whilst under the guidance of the late effect service. Mode of diagnosis, all imaging and cytology were retrieved from the institutional electronic record. Cytology was categorized according to Bethesda. RESULTS: Four hundred and sixty-five patients were exposed to direct or scatter neck irradiation. Compliance with thyroid surveillance was observed in 76.9%. 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%). However, cytological assessment was not performed in 45.6% of operative cases. Thirty-three patients had thyroid carcinoma of which 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. The incidence of thyroid cancer was elevated 57.6 times compared to the Australian general population (p < 0.001). CONCLUSION: Due to the high incidence of thyroid cancer, this study supports screening in this cohort. However, due to the risk of overtreatment, we endorse further investigation of thyroid nodules with ultrasound-guided fine-needle aspiration cytology based on sonographic criteria as for the general population and American Thyroid Association guidelines.

Management and Prevention of Breast Cancer After Radiation to the Chest for Childhood, Adolescent, and Young Adulthood Malignancy.

BACKGROUND: Women treated with chest irradiation for childhood, adolescent, and young adulthood (CAYA) malignancies, in particular Hodgkin's lymphoma, have an increased risk of developing second cancers of the breast (SCB). However, there are few uniform guidelines regarding surveillance and prevention for this high-risk group. METHODS: A systematic search using PUBMED and OVID MEDLINE was performed. Publications listed under the terms "breast neoplasm", "neoplasm, radiation-induced", "therapeutic radiation-induced breast cancer", "screening", "surveillance", "prevention", and "prophylaxis" between January 1992 and January 2015 were assessed. RESULTS: A total of 138 publications were reviewed. Factors associated with increased SCB risk include young age at irradiation, prolong duration since irradiation (peak relative risk 13.87 at 15-19 years postradiation), and increased radiation dose and field. Early menopause reduces SCB risk. Annual screening mammography and breast MRI is recommended from age 25 or 8 years posttreatment for women treated with ≥20 Gy chest radiation before age 30 years. Compared with sporadic primary breast cancers (PBC), SCB more often are bilateral (6-34 %), managed with mastectomy (56-100 %), hormone receptor-negative (27-49 %), and high-grade (35 %). Women with SCB have a similar breast cancer event-free survival and breast cancer-specific survival compared to women with PBC. However, their overall survival is worse due to comorbid conditions. There is paucity of information regarding secondary prevention of SCB. CONCLUSIONS: Survivors of CAYA malignancy are at risk of many late effects, including iatrogenic breast cancer from chest irradiation. They are best managed in a multidisciplinary late-effects setting where tailored risk management can be provided.

Disease burden of psoriatic arthritis compared to rheumatoid arthritis, Hungarian experiment.

The objectives of this study were to assess the costs of psoriatic arthritis (PsA) in Hungary and to identify key cost drivers among demographic and clinical variables and to compare cost-of-illness of PsA and rheumatoid arthritis (RA). Cross-sectional retrospective survey of 183 consecutive patients from eight rheumatology centres was conducted. Mean direct medical, direct non medical, indirect and total costs were 1,876, 794, 2,904 and 5,574 euros/patient/year, respectively. Total costs were in significant linear relationship with health assessment questionnaire score and psoriatic area severity index. Costs of RA were higher in all domains than of PsA. Our study was the first from the Eastern European region that provides cost-of-illness data on PsA. Our study revealed that functional status and severity of skin symptoms were the key cost drivers. The costs of PsA in Hungary were lower than in the high-income European countries.

[The role of biological agents in the treatment of psoriatic arthritis, literature review]. / A biológiai terápia szerepe az arthritis psoriatica gyógykezelésében (irodalmi attekintés).

INTRODUCTION: The recognition of the key pathogenetic role of TNF-alpha in psoriatic arthritis has made it possible to introduce new drugs in the treatment. TNF-alpha inhibitors available in Hungary (infliximab, etanercept, adalimumab) are potential therapies for patients who have not adequately responded to traditional disease-modifying antirheumatic drugs. OBJECTIVE: The aim of the study was to present the epidemiology and progression of psoriatic arthritis in Hungary based on national and international data, to assess the target population for biological therapy and to analyze their effectiveness, reviewing the available literature of randomized controlled trials. METHODS: The prevalence of psoriatic arthritis in Hungary was estimated using international data. Characteristics of psoriatic arthritis population were studied using the database of a rheumatology ward. A systematic literature search was performed to identify each relevant trial. A synthesis and comparison of the results from the 5 identified trials was performed and the average effect of biological agents was calculated. Both the fixed and the random effect model were used for the data synthesis; the results were probed with Mantel-Haenzel test. RESULTS: The prevalence of psoriatic arthritis is about 10.000-20.000 in Hungary. Average disease-duration was 10 years in the sample (n = 189), the most frequent was polyarticular form (51%). Regarding functional status the mean HAQ score was 1.46, with an average progression of 0.05 points/year. The trial data confirmed that biological agents are superior to placebo in improving symptoms (achieving ACR20); risk difference between biological treatments and placebo is 47% (RD = 0.47, 95% CI: 0.42-0.53). The biological treatment of 2 patients improves the status of 1 patient (NNT = 2.1 95% CI 1.9-2.4). There is no significant difference in efficacy between the three biological agents. CONCLUSIONS: TNF-alpha inhibitors are effective treatments of psoriatic arthritis and are safe under strict medical control. The principles of indications, contraindications, administration and control have been worked out by the Rheumatology and Physical Medicine Board.

[Genetics in patients with psoriatic arthritis]. / Arthritis psoriaticaában szenvedo betegek genetikai vizsgálata.

OBJECTIVES: HLA antigens were studied in 100 Hungarian patients suffered from psoriatic arthritis. Genetic markers for the development of different clinical pattern of the disease and skin disorder were identified. METHODS: Determination of class I and class II antigens was performed by using microlymphocytotoxicity assay. RESULTS: The frequency of HLA-Cw6, HLA-B16 (and its split B-39) and HLA-B27 antigens were significantly higher in psoriatic arthritis patients than in the Hungarian general population. No connection was found between HLA-DR4, DR7, B17 antigens and psoriatic arthritis. The patients were classified according to the subgroups proposed by Gladman. The comparisons between the clinical subgroups revealed a significant association of HLA-B27 with spondylitis (Gladman 4, 5, 6, 7). There was no association between HLA DR4 and polyarticular pattern of the disease (Gladman 3, 7). Psoriasis seemed to be significantly associated only with HLA-Cw6. There was a higher frequency of HLA-B38 in psoriatic arthritis patients with erythroderma.