No abstract

Following surgical removal of the primary tumour, patients with stage I non-seminomatous germ cell tumours of the testis (NSGCTT-'testicular teratoma') have an overall risk of developing metastatic disease of 30% (Cullen, 1991). However, a subgroup of these patients, which can be identified histologically, has an increased risk of distant recurrence of 50% (Freedman et al., 1987). A recent MRC study has demonstrated that two courses of chemotherapy, administered not more than 6 weeks after surgery, will increase relapse-free and long-term survival rates to more than 98% in this 'high-risk' subgroup (Cullen et al., 1996). Stage I cases who are managed in a surveillance programme, with chemotherapy (typically four courses) reserved for those patients who relapse, enjoy an identical long-term survival rate (Read et al., 1992). Thus, there is a choice of two different management approaches for high-risk stage I teratoma patients; either immediate adjuvant chemotherapy, or the surveillance programme with chemotherapy only given on relapse. Both approaches lead to the same, excellent, survival prospects for this group of patients, but their attendant shortcomings are different.It is clear that some patients experience anxiety as a result of the uncertainty of surveillance (Moynihan, 1987). Prompted by this, we sought to investigate which management approach patients prefer. Newly diagnosed teratoma patients were asked to imagine risks of recurrence ranging from 10% to 90% and then to choose between: immediate adjuvant chemotherapy (AC); surveillance (S); or for the doctor to make the decision (DD), at each risk level.We also presented the same hypothetical scenario to different groups of controls, namely: subjects with the 'ultimate' experience, i.e. patients with testicular teratoma who have been through a surveillance programme, and others who have been treated with chemotherapy; those who might be considered to have the 'ultimate' knowledge, i.e. specialist testicular tumour oncologists; and two other groups of noncancer controls. Subjects and methodsNine separate groups, which might reasonably be expected to respond differently owing to varying experience or knowledge, were studied: 1. Newly diagnosed patients with stage I NSGCTT (New; n = 18). For this group it was a 'real-life' situation. surveillance, but then relapsed and undergone BEP chemotherapy and were in remission, presumed cured (Relsurv; n = 9). 7. Non-cancer controls-1; medical students having just had a lecture on NSGCTT (Students; n = 56). 8. Non-cancer controls -2; firemen (Firemen; n = 37). All the available officers at one fire station were selected. 9. Non-cancer controls -3; Specialist testicular tumour oncologists (Oncol; n = 18). These were all the oncologist members of the MRC testicular tumour working party responsible for managing the vast majority of cases in the UK.A specifically trained oncology nurse was responsible for administering a detailed information sheet and questionnaire to Correspondence: MH Cullen

Background: The independent review of the UK National Health Service Breast Screening Programme reported recently on the benefits and harms of breast screening (The Lancet, Volume 380, Issue 9855, Pages 1778 - 1786, 17 November 2012). This concluded that breast screening saves lives but acknowledged the existence of overtreatment. Consequently, randomized trials were recommended to elucidate the appropriate treatment of screen-detected ductal carcinoma in situ (DCIS) and to gain a better understanding of its natural history. The LORIS trial will address these issues in low and low/intermediate grade screen detected (low risk) DCIS. Trial Design: LORIS is a phase III, multicentre, 2 arm study, with a built in 2 year feasibility phase, in women confirmed by central pathology review to have low risk DCIS. Comprehensive site training will be complimented by a patient friendly DVD designed to ensure consistent and appropriate use of terminology. Patients will be randomised between standard surgery and active monitoring with annual mammography. Follow-up will be for a minimum of 10 years. Eligibility Criteria: 1) Female, age ≥ 46 years 2) Screen-detected or incidental microcalcification (with no mass lesion clinically or on imaging) 3) Low risk DCIS on large volume vacuum-assisted biopsy, confirmed by central pathology review 4) Patient fit to undergo surgery 5) No previous breast cancer or DCIS diagnosis 6) Written informed consent Specific Aims: The LORIS Trial aims to establish whether patients with newly diagnosed low risk DCIS can safely avoid surgery without detriment to their wellbeing (psychological and physical) and whether those patients who do require surgery can be identified by pathological and radiological means. Primary endpoint: Ipsilateral invasive breast cancer free survival rate at 5 years Secondary endpoints: Overall survival; mastectomy rate; time to mastectomy; time to surgery; patient reported outcomes; health resource utilisation and assessment of predictive biomarkers. A digital image data repository and tissue bank will provide a prospective resource for both translational and imaging studies. Statistical Methods: A total of 932 patients will be randomized to a non-inferiority design to test the null hypothesis that active monitoring of women diagnosed with low risk DCIS is not non-inferior in terms of 5 year ipsilateral invasive breast cancer free survival (iiBCFS) rate compared to treatment with surgery. The iiBCFS rate will be compared across the two arms on a per protocol and intent-to-treat basis, using a 1-sided (α = 0.05) log-rank test for non-inferiority. The iiBCFS rate is assumed to be 97.5% in the surgery arm giving 80% power to exclude a difference of more than 2.5% in the active monitoring arm at 5 years. Present Accrual and Target Accrual: 20 UK sites have been identified to contribute to the feasibility phase of the trial. Enrolment of the first patient is expected in late 2013/early 2014. A further 40 sites will be recruited upon successful completion of the feasibility phase. For further information, please contact the LORIS Trial Office LORIS@trials.bham.ac.uk. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT2-3-01.