Search

PURPOSE Genomic tests improve accuracy of risk prediction for early breast cancers but these are expensive. This study evaluated the clinical utility of EndoPredict®, in terms of impact on adjuvant therapy recommendations and identification of parameters to guide selective application. METHODS Patients with ER-positive, HER2-negative, and early-stage invasive breast cancer were tested with EndoPredict®. Two cohorts were recruited: one consecutively and another at clinical team discretion. Systemic treatment recommendations were recorded before and after EndoPredict® results were revealed to the multidisciplinary team. RESULTS 233 patients were recruited across five sites: 123 consecutive and 110 at clinical team discretion. In the consecutive cohort 50.6% (62/123) cases were classified high risk of recurrence by EndoPredict®, compared with 62.7% (69/110) in the selective cohort. A change in treatment recommendation was significantly more likely (p

In this retrospective study, we have explored the anatomical factors that lead to the development of radiation necrosis (RN) in the setting of stereotactic radiosurgery (SRS) for melanoma brain metastases (MBM). Between 2014 and 2018, 137 patients underwent SRS for 311 MBM. Lesions were assessed according to anatomical zones: zone 1—peripheral grey-white matter junction and cortical mantle, zone 2—deep white matter, including tumours located at base of sulci, zone 3—tumours adjacent to ependymal lining or in deep locations such as brainstem, basal ganglia and thalamus. Other anatomical factors including lobes, medial-peripheral, supra or infratentorial locations were also recorded. In all, 12.4% (n = 17) of patients and 6.1% (n = 20) of lesions developed RN, actuarial incidence of RN at 12 and 24 months was 10% and 14.2% respectively. Zone 2 lesions recorded the highest rate of development of RN (n = 7/19; 36%), zone 3 (N = 4/24; 16%) and zone 1 (n = 9/268; 3%). Five of 17 patients developed symptomatic RN and 7/17 patients underwent surgery for RN. This study raises awareness of the increased likelihood of deep lesions particularly in white matter structures to develop RN after SRS. Further studies including larger cohorts would be useful in identifying statistical differences in the rate of development of RN in different anatomical zones.

Background Stereotactic Ablative Body Radiotherapy (SABR) is a non-invasive treatment which allows delivery of an ablative radiation dose with high accuracy and precision. SABR is an established treatment for both primary and secondary liver malignancies, and technological advances have improved its efficacy and safety. Respiratory motion management to reduce tumour motion and image guidance to achieve targeting accuracy are crucial elements of liver SABR. This phase II multi-institutional TROG 17.03 study, Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring (LARK), aims to investigate and assess the dosimetric impact of the KIM real-time image guidance technology. KIM utilises standard linear accelerator equipment and therefore has the potential to be a widely available real-time image guidance technology for liver SABR. Methods Forty-six patients with either hepatocellular carcinoma or oligometastatic disease to the liver suitable for and treated with SABR using Kilovoltage Intrafraction Monitoring (KIM) guidance will be included in the study. The dosimetric impact will be assessed by quantifying accumulated patient dose distribution with or without the KIM intervention. The patient treatment outcomes of local control, toxicity and quality of life will be measured. Discussion Liver SABR is a highly effective treatment, but precise dose delivery is challenging due to organ motion. Currently, there is a lack of widely available options for performing real-time tumour localisation to assist with accurate delivery of liver SABR. This study will provide an assessment of the impact of KIM as a potential solution for real-time image guidance in liver SABR. Trial registration This trial was registered on December 7th 2016 on ClinicalTrials.gov under the trial-ID NCT02984566.

Revision hip arthroplasty in the setting of periacetabular bone loss presents a significant challenge, as options for restoring bone loss are limited. Recombinant human bone morphogenetic protein-2 may offer a solution by promoting bone growth to restore bone stock before implant reimplantation. Here we present a case of a patient with a periprosthetic acetabulum fracture, resulting in pelvic discontinuity as the result of significant periacetabular bone loss. Using a staged approach, periacetabular bone stock was nearly entirely reconstituted using recombinant BMPs and allograft, which resulted in stable fixation, but with abundant heterotopic bone formation. Recombinant BMP-2 offers a useful tool for restoring bone stock in complex hip arthroplasty revision cases with periacetabular bone loss; however, caution must be used as overabundant bone growth as heterotopic ossification may result.

Focal white matter lesions are the defining pathological and imaging hallmark of the multiple sclerosis. Until recently, elucidation of the pathophysiology of lesion formation, progression and repair has relied on point neuropathological observations. Here, we review current and emerging concepts of the MRI-defined multiple sclerosis lesion phenotype, advanced longitudinal imaging techniques that permit in-vivo exploration of dynamic microstructural change within lesions and emerging MRI measures of lesion repair.Novel MRI techniques have elucidated dynamic features of the active multiple sclerosis lesion, defined imaging surrogates for chronic active lesions and revealed progressive microstructural change within chronic inactive lesions. Lesion-related anterograde, retrograde and trans-synaptic neurodegenerative mechanisms are being unravelled in vivo through MRI. An array of myelin-imaging techniques have emerged and in some cases have already been integrated into Phase 2 remyelination trials.MRI has shed new light on dynamic processes that occur over the lifespan of the multiple sclerosis lesion, and reaffirms the critical role of focal pathology as a determinant of disease progression. The development of robust, longitudinal biomarkers of lesion microstructure, such as advanced diffusion imaging, will be especially important as the era of neurorepair trials in multiple sclerosis dawns.

Background: Alemtuzumab is a highly effective treatment for relapsing-remitting multiple sclerosis (MS) but requires ongoing pathology monitoring for autoimmune adverse effects. The Alemtuzumab in MS Safety Systems (AMS3) study evaluated the implementation of an automated pathology-monitoring system. Objectives: To develop an efficient automated clinical decision support system (CDSS) to electronically prompt and track pathology collection and to provide prescribers and patients with customised alerts of abnormal results for identified risks. Methods: A total of 10 patients with relapsing-remitting MS treated with alemtuzumab were enrolled to test the system. Standard care laboratory monitoring was performed and compared to the performance of the CDSS. Results: The automated CDSS, an integrated patient smartphone application and an additional pre-screening tool were all successfully developed. Compliance with pathology monitoring was 96.7%. The automated analysis of pathology results was significantly faster than standard care neurologist review ( p Conclusion: We successfully developed automated pathology monitoring with a CDSS, demonstrating real-world benefits of high compliance and timely alerting of important results.

Adequate coverage of sites harbouring potential microscopic disease is paramount, where the clinical decision has been made to include regional lymph node radiotherapy for patients with breast cancer. This must be achieved in balance with minimising dose to normal tissues. Several international consensus guidelines detailing clinical target volumes (CTVs) are available, but there is currently no agreement as to which is most appropriate for a given clinical situation. Contouring guidelines are beneficial for routine practice and essential for clinical trial quality assurance. The aims of this study were as follows: to provide a single point of comparison of four commonly used contouring guidelines, including one used in a current Trans-Tasman Radiation Oncology Group trial; and to undertake a systematic review of existing studies which map sites of breast cancer recurrence against contouring guidelines. Two international consensus guidelines (European Society for Radiotherapy and Oncology, and Radiation Therapy Oncology Group) were compared with two clinical trial guidelines (TROG 12.02 PET LABRADOR and the Proton/Photon trial NCT02603341 RADCOMP). Comprehensive literature search for patterns of failure studies was undertaken using Embase and Pubmed. We detail the small but significant differences between the breast consensus guidelines, particularly the supraclavicular (SCF) and internal mammary chain CTVs. Seven series were found mapping recurrence patterns. These results are discussed in the context of the contouring guidelines. Several studies found the SCF CTV is the area at greatest risk of geographical 'miss'. This review will facilitate further discussion about guideline selection and modification, particularly for future clinical trials in Australia and New Zealand.

Introduction LAL deficiency (LALd) is a rare autosomal recessive condition of deficiency or underexpression of the enzyme LAL which leads to the excessive accumulation of cholesteryl esters and triglycerides in various organs especially the liver. Patients often present with hepatosplenomegaly, deranged liver function tests (LFTs), hyperlipidaemia, gastrointestinal symptoms, and hepatic failure. LALd is often misdiagnosed as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), cryptogenic cirrhosis or type IIa or b hyperlipoproteinaemia. Aim To develop a model for LALd testing in the hepatology and metabolic clinics using dried blood spotting (DBS). Method We carried out a systematic literature review and worked closely with paediatricians, hepatologists, metabolic consultants and endocrinologists to develop a screening algorithm for LALd. With the support of industry partners, we obtained DBS test kits and started testing suitable patients. The DBS tests were sent for processing to an external laboratory in Glasgow. Results To date we have tested 122 adult patients (M:F 2.4:1). The mean LAL levels were 0.56 nmol/punch/hour (range 0.08–1.26 nmol/punch/hour) (Figure 1). We identified 27 (22.5%) patients with LAL levels below the reference range (0.37–2.30 nmol/punch/hr). Almost half of these patients were eventually diagnosed with NAFLD/NASH (48.15%) (Figure 2). The control enzyme, beta galactosidase, was used on two occasions to test sample quality and one sample was regarded as of poor quality. Conclusion The genotype to phenotype presentation has not been clearly elucidated for LALd. More than 40 mutations have been identified each leading to variable enzymatic expression. Traditionally, if the LAL levels are less than 0.15, control enzymes are used to test sample quality. In good quality samples, levels of Disclosure of Interest None Declared

Summary Lysosomal acid lipase deficiency is a rare, autosomal recessive condition caused by mutations in the gene encoding lysosomal acid lipase ( LIPA ) that result in reduced or absent activity of this essential enzyme. The severity of the resulting disease depends on the nature of the underlying mutation and magnitude of its effect on enzymatic function. Wolman's disease is a severe disorder that presents during infancy, resulting in failure to thrive, hepatomegaly, and hepatic failure, and an average life expectancy of less than 4 months. Cholesteryl ester storage disorder arises later in life and is less severe, although the two diseases share many common features, including dyslipidaemia and transaminitis. The prevalence of these diseases has been estimated at one in 40 000 to 300 000, but many cases are undiagnosed and unreported, and awareness among clinicians is low. Lysosomal acid lipase deficiency—which can be diagnosed using dry blood spot testing—is often misdiagnosed as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), hereditary dyslipidaemia, or cryptogenic cirrhosis. There are no formal guidelines for treatment of these patients, and treatment options are limited. In this Review we appraise the existing literature on Wolman's disease and cholesteryl ester storage disease, and discuss available treatments, including enzyme replacement therapy, oral lipid-lowering therapy, stem-cell transplantation, and liver transplantation.

The anti-PD-1 antibodies nivolumab and pembrolizumab are active in metastatic melanoma; however, there is limited data on combining anti-PD-1 antibody and radiotherapy (RT). We sought to review clinical outcomes of patients receiving RT and anti-PD-1 therapy. All patients receiving anti-PD-1 antibody and RT for metastatic melanoma were identified. RT and systemic treatment, clinical outcome, and toxicity data were collected. Fifty-three patients were included; 35 patients received extracranial RT and/or intracranial stereotactic radiosurgery (SRS) and 21 received whole brain radiotherapy (WBRT) (three of whom also received SRS/extracranial RT). Patients treated with extracranial RT or SRS received treatment either sequentially (RT then anti-PD-1, n = 11), concurrently (n = 16), or concurrent “salvage” treatment to lesions progressing on anti-PD-1 therapy (n = 15). There was no excessive anti-PD-1 or RT toxicity observed in patients receiving extracranial RT. Of six patients receiving SRS, one patient developed grade 3 radiation necrosis. In 21 patients receiving WBRT, one patient developed Stevens–Johnson syndrome, one patient developed acute neurocognitive decline, and one patient developed significant cerebral edema in the setting of disease. Response in irradiated extracranial/intracranial SRS lesions was 44% for sequential treatment and 64% for concurrent treatment (p=0.448). Likewise there was no significant difference between sequential or concurrent treatment in lesional response of non-irradiated lesions. For progressing lesions subsequently irradiated, response rate was 45%. RT and anti-PD-1 antibodies can be safely combined, with no detectable excess toxicity in extracranial sites. WBRT and anti-PD-1 therapy is well tolerated, although there are rare toxicities and the role of either anti-PD-1 or WBRT in the etiology of these is uncertain.

Cancellous screws are designed to optimize fixation in metaphyseal bone environments; however, certain clinical situations may require the substitution of cortical screws for use in cancellous bone, such as anatomic constraints, fragment size, or available instrumentation. This study compares the biomechanical properties of commercially available cortical and cancellous screw designs in a synthetic model representing various bone densities. Commercially available, fully threaded, 4.0-mm outer-diameter cortical and cancellous screws were tested in terms of pullout strength and maximum insertion torque in standard-density and osteoporotic cancellous bone models. Pullout strength and maximum insertion torque were both found to be greater for cancellous screws than cortical screws in all synthetic densities tested. The magnitude of difference in pullout strength between cortical and cancellous screws increased with decreasing synthetic bone density. Screw displacement prior to failure and total energy absorbed during pullout strength testing were also significantly greater for cancellous screws in osteoporotic models. Stiffness was greater for cancellous screws in standard and osteoporotic models. Cancellous screws have biomechanical advantages over cortical screws when used in metaphyseal bone, implying the ability to both achieve greater compression and resist displacement at the screw-plate interface. Surgeons should preferentially use cancellous over cortical screws in metaphyseal environments where cortical bone is insufficient for fixation. [ Orthopedics. 2016; 39(5):e828–e832.]

Objective: Several female sub-populations of the healthcare industry, including radiologists, radiology technicians, and orthopedic surgeons, display an increased prevalence of breast cancer. Female plastic surgeons have a similar exposure to possible risk factors such as radiation exposure, late parturition, and overnight shifts. Therefore, this study aimed to evaluate the risk of breast cancer and overall cancer in female plastic surgeons. Methods: A two-page survey designed to collect data on respondent demographics, cancer incidence and exposure to social and occupational risk factors as identified in the current literature was mailed to 612 currently practicing female plastic surgeons identified by the American Society of Plastic Surgeons (ASPS). Prevalence rates for breast cancer and cancer in general were calculated. Only melanoma and internal cancers that were diagnosed within 15 years of the survey date were included, enabling us to compare the results with data from the National Institute’s Surveillance Epidemiology and End Results (SEER 11) Program. Standardized prevalence ratios (SPR), confidence intervals, and exact p-values were calculated. Results: Fourteen of the 352 respondents had been diagnosed with cancer, including three breast cancer cases, within 15 years preceeding the survey. These numbers are not signficantly lower than the expected prediction of 16 cancer and six breast cancer cases, based on the sex and race-specific prevalences in the general U.S. population. SPRs were 0.89 [95%CI: 0.49 to 1.5] for all cancers and 0.54 [95%CI: 0.11, 1.57] for breast cancer. Conclusion: Despite similarities to subpopulations with increased breast and overall cancer prevalence, the subpopulation of female plastic surgeons had no evdience of excess cancers compared to age and race-adjusted women in the general US population.

Filamentous aggregates of the protein tau are a prominent feature of Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). However, the extent to which the molecular structure of the tau in these aggregates is similar or differs between these diseases is unclear. We approached this question by examining these disorders with a panel of antibodies that represent different structural, conformational, and cleavage-specific tau epitopes. Although each of these antibodies reveals AD pathology, they resolved into three classes with respect to PSP and CBD: AD2 and Tau-46.1 stained the most tau pathology in all cases; Tau-1, 2, 5, and 12 exhibited variable reactivity; and Tau-66 and MN423 did not reveal any tau pathology. In addition, hippocampal neurofibrillary tangles in these cases showed a predominantly PSP/CBD-like, rather than AD-like, staining pattern. These results indicate that the patterns of the tau epitopes represented by this panel that reside in the pathological aggregates of PSP and CBD are similar to each other but distinct from that of AD.

Many burns surgeons avoid excision and direct closure of acute burns owing to concerns over wound dehiscence, scarring and infection. There is no evidence in the literature to support this practice. We present outcomes of a prospective series of 100 patients who underwent excision and direct closure of 138 burns over a 2-year period, along with results from a survey sent to 33 senior burns surgeons to gauge attitudes towards direct closure in burns surgery. 47% of survey respondents never perform direct closure. Dehiscence was cited as the most common concern, followed by hypertrophic scarring (HTS). In our cohort, the superficial dehiscence rate was 12% and the HTS rate was 16%, with no scarring contractures. Patients with healing time greater than 14 days were more likely to develop HTS (p = 0.008), as were those with wound dehiscence (p = 0.014). Patients undergoing part-grafting in addition to direct closure took significantly longer to heal than those undergoing direct closure alone (p = 0.0002), with the donor site or graft delaying healing in the majority. Excision and direct closure of acute burn wounds avoids donor site morbidity and has an acceptable complication rate. It is a safe and effective treatment for full thickness burns in selected cases.

s / The Breast 23 (2014) S1eS6 S2 A CARDIAC SPARING TECHNIQUE FOR BREAST CANCER RADIATION TREATMENT Christopher Kelly, Kirsten Stuart, Tim Wang, Drew Latty, Verity Ahern. Crown Princess Mary Cancer Centre (CPMCC), and Breast Cancer Institute NSW, Westmead Hospital, Australia Background: Historically left-sided breast cancer radiation treatment has been associatedwith an excess risk of cardiac deaths1, and every additional 1Gy mean cardiac dose results in a relative increase in cardiac events of 7.4%2. Methods: A deep inspiratory breath hold (DIBH) techniquewas introduced as a method of reducing the volume of heart in breast / chest wall tangential radiation treatment at CPMCC in 2010, one of the few centres using this technique in Australia. This study evaluates the impact of DIBH on cardiac radiation dose. Results: A total of 51 patients underwent an attempt at radiation treatment simulation by DIBH as well as the conventional ‘free breathing’ (FB) approach between December 2010 and April 2013. Thirty eight patients proceeded to treatment delivery by DIBH. Thirteen patients did not undergo treatment by DIBH, either because DIBH did not reduce the cardiac dose (6 patients) or because they were not able to follow instructions for DIBH (7 patients). For the 38 patients who underwent DIBH, the simulated size of the heart measured as a volume varied between FB and DIBH by 72% 115%. The mean irradiated heart dose calculated by simulation was 6.2Gy by the DIBH technique and higher by the FB technique for all 38 patients .It was a mean of 7.0Gy for the 13 patients treated by FB .Six of 38 patients underwent fluoroscopic imaging of one radiation field during treatment on at least two occasions. For the six patients as a group, the heart moved between 1 and 6mm during the fluoroscopic imaging. Conclusions: DIBH is a suitable technique to reduce the cardiac volume irradiated for some patients with left sided breast cancer. We are now exploring the best method of measuring cardiac position during treatment, and how we can help more women cope with this procedure. References [1] Darby SC, McGale P, Taylor CW et al. Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: Prospective study of about 300,000 women in US SEER cancer registries, Lancet Oncol 2005;6:557-565. [2] Feng M, Moran JM, Koelling T et al. Development and validation of a heart atlas to study cardiac exposure to radiation following treatment for breast cancer. Int J Radiat Oncol Biol Phys 2011;79:10-18. INTRA-OPERATIVE ULTRASOUND REFINES BREAST CONSERVING SURGERY FOR PALPABLE BREAST CANCERS G.A. Regalo, C.J. O'Neill, C. Douglas, D.A. Clark. The Breast & Endocrine Centre, Gateshead, New South Wales, Australia Background and purpose: Excision of a breast cancer with a tumour-free margin is the principle aim of breast-conserving surgery. Tumourinvolved margins of up to 41% are reported with palpation-guided excision. Satisfactory cosmetic outcome is an important secondary aim, with poor cosmesis associated with excision volumes greater than 85cm3. Intra-operative ultrasound (US) has the potential to reduce positive margin rates and tissue volume for palpable breast cancers. The purpose of this study is to report outcomes of a five-year experience in the use of this technique. Methods: A retrospective review was conducted of 176 consecutive patients with a palpable breast cancer, undergoing breast-conserving surgery between 2008-2012. All patients underwent intra-operative US localisation followed by specimen US. Sonography was performed by a breast surgeon or breast sonographer. Specimen volumes were calculated and compared to an optimum specimen volume. Results: Thirty-eight (22%) patients had involved margins on final pathology, with 15 (9%) showing invasive carcinoma, and 23 (13%) having DCIS. The rate of tumour-involved margins was higher for lobular carcinoma (29%) than invasive ductal carcinoma (6%). Of those with positive margins, 93% underwent re-excision, with 40% having residual cancer at resection. Specimen interrogation resulted in 25 patients having additional tissue excised. Two had cancer, and four DCIS, in the marginal tissue. The median value for specimen volume was 60cm3, with 23% of patients having excision volumes greater than 85cm3. Conclusions: Use of intra-operative US localisation coupled with specimen interrogation demonstrated a low rate of positive margins. For the majority of patients, specimen volumes remain lower than those associated with cosmetic dissatisfaction. Intra-operative ultrasound is a useful adjunct to breast conserving surgery. RISK FACTORS ASSOCIATED WITH MORTALITY FROM BREAST CANCER IN WAIKATO, NZ e A CASE CONTROL STUDY S.A. Seneviratne, I.D. Campbell, N. Scott, R. Lawrenson, M. Elwood. Waikato Clinical School, University of Auckland, New Zealand Background: New Zealand (NZ) has the seventh highest age standardized breast cancer mortality in theworld1. Maori women fare evenworsewith a 60% higher mortality rate compared to NZ European women2. We performed a case control study to identify key characteristics associated with death from breast cancer in Waikato, NZ. Methods: Women diagnosed with breast cancer during 2002-2010 were identified from theWaikato Breast Cancer Register and NZ Cancer Registry. Cases e All women who died of breast cancer during 2002-2012 with a diagnosis during 2002-2010. Controls e Age (±1 year) and year of diagnosis, matched controls (up to three controls per each case) that were alive on the date of death of the case to which they were being matched Results: 258 women who died of breast cancer and 652 matched controls were identified. Proportion of Maori women among cases was higher compared to controls (17.4% vs. 13.3%). Compared to controls (59.2%) a higher proportion of cases (84.5%) were diagnosed symptomatically. 61% of cases had advanced cancers (stage III and IV) compared to only 14.2% for controls. 50.7% cases were grade-3 cancers compared to 17.5% controls. Significantly higher (p (27.3% vs. 9.6%) and HER-2 positive compared to controls (30.1% vs. 14.8%). Among cases, compared to NZ Europeans, Maori women had advanced staged (p more HER-2 positive (p tumour stage, grade and ER/PR status as tumour factors significantly associated with mortality from breast cancer among Waikato women. Conclusions: Advanced stage, higher grade, ER/PR negativity and HER-2 positivity were found to be significantly associated with mortality from breast cancer. Higher proportion of advanced staged, ER/PR negative and HER-2 positive cancers are likely contributors to mortality inequity seen among Maori women. References [1] Ferlay J, Shin H, Bray F, Forman D, Mathers C, Parkin D. GLOBOCAN 2008 v1.2, Cancer Incidence and Mortality Worldwide IARC Cancer Base 2010. Lyon, France: International Agency for Research on Cancer; 2010. [2] Cancer: New Registrations and Deaths 2009. New Zealand Health In- formation Service, Ministry of Health, Wellington; 2012. DEVELOPMENT OF A REALISTIC MODEL FOR TEACHING BREAST EXAMINATION D. Veitch., M. Bochner . 1 Faculty of Industrial Design, Delft University of Technology (TU Delft), The Netherlands; Breast Endocrine and Surgical Oncology Unit, Royal Adelaide Hospital, Adelaide, S.A., Australia Background and purpose: Breast cancer mortality can be significantly reduced by early detection, however many medical students and doctors report that they feel they could improve their skills in clinical breast ex- amination (CBE). There are more medical students and fewer opportu- nities for them to practice on patients. Realistic simulationmodels can help address this need. Training programs including silicone breast simulators can improve the rate of detection of lumps in patients. (Saslow CA Cancer 2004) Despite this, medical students and trainees typically have low per- formance scores for breast examination. This indicates that current simulation models are not sufficient to provide the training required for