In the United Kingdom, current screening guidelines for TP53 germline mutation carriers solely recommends annual breast MRI, despite the wide spectrum of malignancies typically seen in this group. This study sought to investigate the role of one-off non-contrast whole-body MRI (WB MRI) in the screening of asymptomatic TP53 mutation carriers. 44 TP53 mutation carriers and 44 population controls were recruited. Scans were read by radiologists blinded to participant carrier status. The incidence of malignancies diagnosed in TP53 mutation carriers against general population controls was calculated. The incidences of non-malignant relevant disease and irrelevant disease were measured, as well as the number of investigations required to determine relevance of findings. In TP53 mutation carriers, 6 of 44 (13.6, 95% CI 5.2–27.4%) participants were diagnosed with cancer during the study, all of which would be considered life threatening if untreated. Two were found to have two primary cancers. Two participants with cancer had abnormalities on the MRI which were initially thought to be benign (a pericardial cyst and a uterine fibroid) but transpired to be sarcomas. No controls were diagnosed with cancer. Fifteen carriers (34.1, 95% CI 20.5–49.9%) and seven controls (15.9, 95% CI 6.7–30.1%) underwent further investigations following the WB MRI for abnormalities that transpired to be benign (p = 0.049). The cancer detection rate in this group justifies a minimum baseline non-contrast WB MRI in germline TP53 mutation carriers. This should be adopted into national guidelines for management of adult TP53 mutation carriers in addition to the current practice of contrast enhanced breast MRI imaging.Electronic supplementary materialThe online version of this article (doi:10.1007/s10689-017-9965-1) contains supplementary material, which is available to authorized users.

Purpose: To report a planned analysis of the efficacy and toxicity of dose escalation to the intraprostatic dominant nodule identified on multiparametric magnetic resonance imaging using standard and hypofractionated external beam radiation therapy. Methods and Materials: DELINEATE is a single centre prospective phase 2 multicohort study including standard (cohort A: 74 Gy in 37 fractions) and moderately hypofractionated (cohort B: 60 Gy in 20 fractions) prostate image guided intensity modulated radiation therapy in patients with National Comprehensive Cancer Network intermediate-and high-risk disease. Patients received an integrated boost of 82 Gy (cohort A) and 67 Gy (cohort B) to lesions visible on multiparametric magnetic

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E 7 2 7What ' s known on the subject? and What does the study add? Diethylstilbestrol (DES) was the fi rst hormone treatment used for prostate cancer and has also shown effectiveness in castration-resistant disease in small studies; however, concerns over thromboembolic toxicity have restricted its use in the past.Over 200 elderly men with castration-resistant prostate cancer were treated with 1 -3 mg of DES, given with 75 mg aspirin and breast bud irradiation. Almost 30% of men showed a signifi cant PSA response and the median time to PSA progression was 4.6 months. Almost 20% of patients with pain had a signifi cant analgesic benefi t. The most important toxicity was thromboembolism in 10% of men. Overall the drug has an acceptable toxicity profi le and offers a palliative benefi t in frail elderly men who may not be fi t for chemotherapy. OBJECTIVE• To assess the effi cacy and toxicity of diethylstilbestrol (DES) in the management of castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS• A total of 231 patients with CRPC received treatment with DES at the Royal Marsden Hospital between August 1992 and August 2000.• The median pre-treatment prostatespecifi c antigen (PSA) level was 221 ng/mL.• DES was used at a dose of 1 -3 mg daily, with aspirin 75 mg.• The primary endpoint was PSA response rate. RESULTS• The PSA response rate (using PSA Working Group criteria) was 28.9%.• The median time to PSA progression was 4.6 months.• Of patients with bone pain, 18% had an improvement in their European Organisation for the Research and Treatment of Cancer pain score.• Thromboembolic complications were seen in 9.9% of all patients. CONCLUSIONS• DES has signifi cant activity in CRPC and can be of palliative benefi t.• DES has an acceptable toxicity profi le in the management of patients with symptomatic CRPC when used at a dose of 1 -3 mg, combined with aspirin and prophylactic breast bud radiotherapy. KEYWORDS

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