A new automated radiogrammetric method to estimate bone mineral density (BMD) from a single radiograph of the hand and forearm is described. Five regions of interest in radius, ulna and the three middle metacarpal bones are identified and approximately 1800 geometrical measurements from these bones are used to obtain a BMD estimate of the distal forearm, referred to as BMDDXR (from digital X-ray radiogrammetry, DXR). The measured dimensions for each bone are the cortical thickness and the outer width, in combination with an stimate of the cortical porosity. The short-term in vivo precision of BMDDXR was observed to be 0.60% in a clinical study of 24 women and the in vitro variation over 12 different radiological clinics was found to be 1% of the young normal BMDDXR level. In a cohort of 416 women BMDDXR was found to be closely correlated with BMD at the distal forearm measured by dual-energy X-ray absoptiometry (r = 0.86, p < 0.0001) and also with BMD at the spine, total hip and femoral neck (r = 0.62, 0.69 and 0.73, respectively, p<0.0001 for all). The annual decline was estimated from the cohort to be 1.05% in the age group 55-65 years. Relative to this age-related loss, the reported short-term precision allows for monitoring intervals of 1.0 years and 1.6 years in order to detect expected age-related changes with a confidence of 80% and 95%, respectively. It is concluded that the DXR method offers a BMD estimate with a good correlation with distal forearm BMD, a low variation between geographical sites and a precision that potentially allows for relatively short observation intervals.

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BackgroundNeoadjuvant therapy is increasingly the standard of care in the management of locally advanced adenocarcinoma of the oesophagus and junction (AEG). In randomised controlled trials (RCTs), the MAGIC regimen of pre- and postoperative chemotherapy, and the CROSS regimen of preoperative chemotherapy combined with radiation, were superior to surgery only in RCTs that included AEG but were not powered on this cohort. No completed RCT has directly compared neoadjuvant or perioperative chemotherapy and neoadjuvant chemoradiation. The Neo-AEGIS trial, uniquely powered on AEG, and including comprehensive modern staging, compares both these regimens.MethodsThis open label, multicentre, phase III RCT randomises patients (cT2-3, N0-3, M0) in a 1:1 fashion to receive CROSS protocol (Carboplatin and Paclitaxel with concurrent radiotherapy, 41.4Gy/23Fr, over 5 weeks). The power calculation is a 10% difference in favour of CROSS, powered at 80%, two-sided alpha level of 0.05, requiring 540 patients to be evaluable, 594 to be recruited if a 10% dropout is included (297 in each group). The primary endpoint is overall survival, with a minimum 3-year follow up. Secondary endpoints include: disease free survival, recurrence rates, clinical and pathological response rates, toxicities of induction regimens, post-operative pathology and tumour regression grade, operative in-hospital complications, and health-related quality of life. The trial also affords opportunities for establishing a bio-resource of pre-treatment and resected tumour, and translational research.DiscussionThis RCT directly compares two established treatment regimens, and addresses whether radiation therapy positively impacts on overall survival compared with a standard perioperative chemotherapy regimen Sponsor: Irish Clinical Research Group (ICORG).Trial registration NCT01726452. Protocol 10-14. Date of registration 06/11/2012.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3386-2) contains supplementary material, which is available to authorized users.

4004 Background: The optimum combination curative approach to locally advanced adenocarcinoma of the esophagus and esophago-gastric junction (AEG) is unknown. A key question is whether neoadjuvant multimodal therapy, specifically CROSS (carboplatin/paclitaxel, 41.4Gy radiation therapy), is superior to optimum peri-operative chemotherapeutic regimens including modified MAGIC (epirubicin, cisplatin (oxaliplatin), 5-FU (capecitabine)) and more latterly FLOT (docetaxel, 5-FU, leucovorin, oxaliplatin). Neo-AEGIS was designed as the first randomised controlled trial to address this question. Methods: 377 patients with cT2-3N0-3M0 AEG were randomly assigned to CROSS or peri-operative chemotherapy (ECF/ECX/EOF/EOX pre-2018, FLOT option 2019/20) at 24 sites (Ireland, UK, Denmark, France, Sweden). The primary outcome was overall survival. The initial power calculation was based on CROSS superiority of 10%. This was modified after the first futility analysis (70 events) to a non-inferiority margin of 5%. Secondary end points included toxicity, pathologic measures of response, and postoperative complications as per the Esophageal Complications Consensus Group (ECCG) definitions and Clavien-Dindo severity grade. Results: Of 362 evaluable patients, 178 CROSS, 184 MAGIC/FLOT (157/27), 90% were male, median (range) age 64 (35-83), 84% were cT3, and 58% cN1. At a median (range) follow up of 24.5 (1-92) months, at the second futility analysis (60% of planned events), there were 143 deaths, 70 CROSS and 73 MAGIC/FLOT arm, with 3-year estimated survival probability of 56% (95% CI 47,64) and 57% (95% CI 48,65), respectively [(HR 1.02 (95%CI. 0.74-1.42))]. Based on the absence of futility evidenced in this data the DSMB recommended closure of recruitment in December 2020. Conclusions: This RCT reveals no evidence that peri-operative chemotherapy is unacceptably inferior to multimodal therapy, notwithstanding greater proxy markers of local tumour response in the CROSS arm. Oncologic and operative outcomes were consistent with optimum modern benchmarks. These data strongly suggest non-inferiority and support equipoise in decision making in modern practice. Clinical trial information: NCT01726452. [Table: see text]