Heidelberg Repatriation Hospital

Optimal positioning in mammography and subsequent image quality can be impacted by thorax variability, breast size and the chosen image receptor (IR) angles. This study aims to explore the impact of the female thoracic size, breast size and IR angle on the volume of missing breast tissue (MBT) in mammographic imaging. Sixty-three images were recorded: one craniocaudal (CC) at an IR angle of 0° for three sized breast phantoms attached to three sized thoracic models; and six mediolateral obliques (MLOs) at IR angles of 30°, 40°, 45°, 50°, 55°, 60° for three sized breast phantoms attached to three sized thorax models. Breast size was determined using the posterior nipple line (PNL) measurement and were recorded in millimetres. Breast volume was recorded in cubic centimetres. The breast size and breast tissue volume of a small thorax and large breasts was better visualised with increasing IR angles. Optimal MLO IR angles were determined for the combined average thorax with average breast at 55° and large thorax with large breast at 40° with minimum MBT values of 51.33 cm3 and 75.07 cm3, respectively. Female thoracic size, IR angle, and breast size are significant (p < 0.01) and have a positive impact on the volume of MBT. Optimal MLO IR angles were determined for the three breast phantoms attached to three thoracic models. Female thoracic size positively impacts the volume of MBT and in terms of clinical practice it is vital to adjust the MLO IR angle to ensure maximum breast tissue coverage. These findings can be modelled in current clinical practice on women presented for mammography examinations with varying thorax and breast sizes, allowing optimal IR angle selection and therefore resulting in improved breast tissue inclusion and subsequently a more accurate breast cancer diagnosis.

BackgroundWe aimed to evaluate the acceptability and efficacy of two brief, Internet-delivered cognitive behavioural therapy interventions—MUMentum Pregnancy (study 1) and MUMentum Postnatal (study 2)—in reducing maternal symptoms of anxiety, depression and overall psychological distress compared to usual care in the perinatal period.Methods/DesignWomen who are pregnant (study 1) or < 12 months postpartum (study 2) with current clinically elevated symptoms of anxiety and/or depression according to validated self-report measures, will be recruited via the research arm of a not-for-profit clinical and research unit in Australia and randomised to the intervention group or treatment as usual control group. The minimum sample size for each study (alpha 0.05; power 0.80 for a g of 0.80) was identified as 50 with at least 10% more to be recruited to account for expected attrition. The co-primary outcome measures are the Patient Health Questionnaire 9-item scale and Generalised Anxiety Disorder 7-item scale to measure depression and anxiety symptom severity, respectively, and will be administered at the following primary time-points: baseline; post treatment; and at one-month follow-up. Psychological distress will be measured according to the Kessler-10 psychological distress scale at each primary time-point and will also be completed before each lesson for those in the intervention group. The total trial period nine weeks for study 1 and 11 weeks for study 2. Program efficacy will be determined using intent-to-treat mixed models. Maintenance of gains will be assessed at one-month follow-up.DiscussionThe current randomised controlled trial seeks to extend the literature by evaluating the efficacy of a self-help intervention for women in the perinatal period. If efficacious, the MUMentum programs have the potential to be easily disseminated via https://thiswayup.org.au/ to large numbers of women across Australia as an intervention for women screening positive for anxiety, depressive or distress symptoms during pregnancy or postpartum.Trial registrationAustralian New Zealand Clinical Trials Registry, ACTRN12616000560493; ACTRN12616000559415. Registered on 2nd May 2016.

This study used ambulatory polysomnography (PSG) to investigate post-traumatic nightmares of post-traumatic stress disorder (PTSD). The key research question was whether post-traumatic nightmares occur in both rapid eye movement (REM) and non-REM sleep, and if so, whether nightmares in each sleep stage differed in content, phenomenology, and heart rate response. Underlying sleep disorders were investigated in an exploratory way. Thirty-five treatment-seeking veterans, current serving military members, and emergency service personnel undertook full PSG using the Compumedics (Melbourne, Australia) SomtePSG V1 system, during an inpatient psychiatric admission. The PSG recording included an event button to be pressed when a nightmare occurred, allowing us to determine the stage of sleep, changes in heart rate, and associated sleep events. The content and phenomenological features of participants' nightmares were recorded. Of the 35 participants, 29 reported a nightmare during their sleep study, but only 21 pressed the event button and could recall the content of one or more nightmare. This yielded sleep and nightmare data for 24 nightmares. Of the 24, 10 nightmares arose from REM sleep and 14 from non-REM (stages N1 and N2). Seven were accurate trauma replays and 17 were non-replay or a mixture of replay and non-replay. Most nightmares were associated with respiratory or leg movement events and increase in heart rate on awakening. Post-traumatic nightmares of PTSD occur in both REM and non-REM sleep and are commonly associated with other sleep disturbances. These findings have important treatment implications.

Pain and disability often persist following hip (THR) and knee replacement (TKR) surgery predisposing patients to increased risk of falling. This study identified pre-operative predictors for post-operative falls in TKR and THR patients, and the incidence and circumstances of falls in the 12months post-surgery. A survey was undertaken of patients before THR and TKR, and was repeated 12months post-operation. The survey included (1) medical history and medications usage, (2) pain and function, (3) health-related and physical activity and (4) fear of falls and history of falls questionnaires. Patients were classified as 'fallers' (≥1 fall) or 'non-fallers' based on prospectively documented falls in the 12months post-surgery. Binary logistic regression was conducted to identify independent pre-operative predictors of incident falls status. Eighty-two of the 243 participants (33.7%) reported ≥1 fall in the 12months post-operatively [60 (34.1%) patients following TKR and 22 (32.8%) following THR]. The logistic regression model was statistically significant, χ 2=24.731, p<0.001, the model explaining 22% of the variance in falls, and correctly classifying 73.7% of cases as fallers or non-fallers. Reduced SF-36v2 general health sub-scale, increased planned physical activity and previous falls in the preceding year were predictors of falls. Those reporting ≥1 fall pre-operatively were three times more likely to fall post-operatively. People awaiting hip or knee joint replacement surgery might present with complex conditions that predispose them to greater risk of falling post-operation. Review of general health and history of falling is recommended pre-operatively to identify patients at risk.

4101 Background: Pancreatic cancer remains a devastating disease, with the diagnosis typically being made late. ctDNA has shown promise as a screening test for various tumor types. The detection of ctDNA post curative intent surgery has been associated with a high risk of recurrence in multiple solid tumors. We explored the potential of ctDNA to improve pancreatic cancer outcomes. Methods: Data from separate US and Australian series were combined. Plasma samples were collected prior to surgery in both studies and post-operative samples were collected in Australia from cases undergoing curative intent surgery. Clinicians were blinded to ctDNA results and adjuvant therapy was at clinician discretion. Tissue samples from both series were analyzed at Johns Hopkins University. Next generation sequencing was used to search for somatic KRAS mutations in the primary tumors and in cell-free DNA in the plasma. Clinico-pathologic, treatment and outcome data were collected. Results: 119 pts had a ctDNA sample at diagnosis (median age 67 years, 56.3% male). Sixty six pts (55.5 %) had detectable ctDNA, including 3/7 (42.9%) with stage I disease, 54/99 (54.5%) with stage II disease, 4/8 (50%) with stage III disease and 5/5 (100%) with metastases. Specific codon 12 KRAS (G12D, G12V or G12R) mutations were identified in the tumor tissue of 12/16 (75%) patients who had a ctDNA sample collected post-surgery. At a median follow-up of 15.2 months, 7/12 (58.3%) pts had recurred, including 3/8 (37.5%) with no detectable ctDNA and 4/4 (100%) with detectable ctDNA post-surgery (HR 4.9, p = 0.04). Detectable ctDNA post-surgery was significantly associated with poor overall survival (HR 6.93, p = 0.006), with a median of 8 months for pts with detectable ctDNA. Conclusions: ctDNA shows promise as a pancreatic cancer screening test, being detectable in a high proportion of pts with early stage disease. The detection of ctDNA post operatively predicts a very high risk of recurrence. The clinical utility of ctDNA to guide adjuvant therapy decision making, and its potential as a real-time marker of treatment effect, are being explored in further studies. Clinical trial information: ACTRN12612000763842.

TPS3619 Background: Cancer stem cells are considered to be fundamentally important for resistance to therapy, recurrence and metastasis. Napabucasin is a first-in-class cancer stemness inhibitor in development identified by its ability to inhibit STAT3-driven gene transcription and spherogenesis of cancer stem cells (Li et al, PNAS 112(6):1839, 2015). Preclinically, napabucasin sensitizes cancer cells to chemotherapeutics, including 5-FU and irinotecan. Encouraging anticancer activity in advanced CRC was observed in a phase Ib/II (Bendell et al, GI ASCO 2017) study of 63 pts with disease control rate (DCR) of 93% (28/30) and overall response rate (ORR) of 33% (10/30) in FOLFIRI-naïve pts who have had an on-study RECIST evaluation. On the basis of these data, a phase III trial is being conducted in North America, Europe, Australia, and Asia. Methods: This study (ClinicalTrials.gov NCT02753127) will assess the efficacy of napabucasin+FOLFIRI vs FOLFIRI in pts with mCRC (n = 1250). Addition of bevacizumab (bev) is permissible per investigator choice. Pts must have failed 1 prior line of therapy with oxaliplatin and a fluoropyrimidine +/- bev for metastatic disease. Pts are randomized 1:1 to receive napabucasin 240 mg PO BID plus FOLFIRI bi-weekly, or FOLFIRI bi-weekly (bev may be added to FOLFIRI by investigator choice) and stratified by geography, time to progression on 1st-line therapy, RAS mutation status, bev as part of study treatment and primary tumor location. Treatment will continue until disease progression, or another discontinuation criterion. Primary endpoint is overall survival (OS) in the general study population (ITT) (HR 0.80 for OS improvement from 12.54 to 15.68 months); secondary endpoints include OS in the biomarker positive (biomarker+) population, progression free survival (PFS) in the ITT population, PFS in biomarker+ population, ORR and DCR in the ITT and in biomarker+ populations, safety and quality of life. Also, blood and tumor archival tissue will be assessed for PK and biomarker analyses. Global enrollment is underway. Clinical trial information: NCT02753127.

3555 Background: There is minimal data on the efficacy and improvement of quality of life (QoL) of these targeted therapies, like cetuximab, in elderly CRC patients (≥70yo). We analyzed outcomes from two randomized phase III clinical trials from the Canadian Clinical Trials Group, CO.17 and CO.20. Methods: CO.17 and CO.20 were retrospectively analyzed. CO.17 compared cetuximab (CETUX) with best supportive care (BSC), CO.20 compared CETUX + brivanib (BRIV) with CETUX + placebo. Key eligibility criteria were similar between each trial. Patients were dichotomized by age (≥70yo/ &lt; 70yo) for comparisons. Outcomes included overall survival (OS), progression free survival (PFS), adverse events (AEs), and QoL deterioration. In CO.17, only patients with wild type K-RAS were included in analysis. Multivariate analysis with Cox regression controlled for additional variables. Results: 980 patients were included in this analysis. 257 (26.2%) were ≥70yo at the time of enrollment. In CO.17, OS and PFS were similar between young and elderly patients treated with CETUX (OS 9.7m vs 8.0m, p = 0.45; HR 0.73 95%CI 0.39-1.37). Compared to the BSC arm, elderly patients treated with CETUX had a non-significant increase in OS (8.0m vs 5.1m, p = 0.11). In patients treated with CETUX, grade 3/4 AEs were similar between age groups, however elderly patients had a faster deterioration in global QoL than younger patients (3.6m vs 5.7m p = 0.046). In CO.20, younger patients had longer OS than elderly (9.2m vs 7.6m, p = 0.02; HR 0.81 95% 0.68-0.97, p = 0.02). AEs in the BRIV+CETUX arm were higher in the elderly than young (88% vs 77%, p = 0.03). Both young and elderly treated with BRIV+CETUX had more rapid decreases in global QoL than the CETUX arm. Conclusions: Age was neither prognostic nor predictive of response to targeted therapy in the single agent CO.17 trial. In CO.20, age conferred a worse prognosis. Elderly patients who are eligible for clinical trials may garner similar survival benefits as younger patients with single agent therapy, but may not derive the same improvement in QoL.

We have investigated the potential use of β-conglutin protein isoforms from narrow-leafed lupin (Lupinus angustifolius L.) as a diabetes treatment. We produced purified recombinant β1-, β2-, β3-, β4-, and β6-conglutin proteins and showed that β1, β3, and β6 could bind to insulin. To assess β-conglutin proteins modulatory effect on insulin activation meditated kinases, whole blood and peripheral blood mononuclear cell cultures from type 2 diabetes (T2D) and healthy control subjects (C) were incubated with conglutin proteins. The treatment of peripheral blood mononuclear cells from T2D patients with β1, β3, and β6 proteins increased up to threefold mRNA and protein levels of genes important in insulin signaling pathways, namely insulin receptor substrate 1/p85/AKT/glucose transporter type 4. This was accompanied by a comparable fold-change decrease in the mRNA expression level of pro-inflammatory genes (iNOS and IL-1β) and proteins compared to healthy controls. The β2 and β4 isoforms had no effect on the insulin signaling pathway. However, these β-conglutin proteins elicited pro-inflammatory effects since levels of mRNA and proteins of inducible nitric oxide synthase and IL 1 beta were increased. Our results raise the possibility of using these particular β-conglutin proteins in the prevention and treatment of diabetes, as well as their potential as anti-inflammatory molecules.