Search

Background This Phase 2 multicentre trial in localised non-gastric marginal zone lymphoma (MZL) evaluated the effectiveness and safety of radiotherapy and documented markers of autoimmunity and Helicobacter pylori infection. Patients and methods Eligible patients had Stages I and II or paired-organ, non-gastric MZL. Bone marrow evaluation, autoantibody panel, and H. pylori evaluation were mandatory. Involved-field or involved-site radiotherapy was delivered to 24–30.6 Gy. Detected H. pylori infections underwent eradication. Results Between 2006 and 2014, six centres enrolled 70 patients, and 68 commenced treatment. The median age was 59 (range: 23–84) years, and 31 (46%) were male. Overall, 55 patients had Stage I disease, nine patients had Stage II disease, and four patients had paired organ–confined disease. Involved extranodal sites with three or more cases were orbital (n = 18), conjunctiva (n = 13), lacrimal (n = 8), skin (n = 8), salivary (n = 7), and muscle (n = 4). Eight patients had primary nodal MZL. At the median follow-up of 5 years (range 0.7–9.4), progression-free survival and overall survival were 79% and 95%, respectively. One lymphoma-related death and two in-field failures (after 25 and 30 Gy, respectively) occurred. Distant relapse sites were skin (n = 2), lymph nodes (n = 2), duodenum, stomach, muscle, and conjunctiva (1 each). No paired-organ MZL relapsed. Apart from cataracts (n = 18), only three treatment-related late grade ≥3 adverse events occurred. Autoantibodies or autoimmune events were detected in 26 of 68 patients (38%). H. pylori infection was detected in 15 of 63 patients (24%) tested. Neither autoimmunity nor H. pylori was detected in 27 of 68 patients (40%). Conclusions Radiotherapy was a potentially curative treatment with low toxicity in localised non-gastric MZL. Autoimmunity, H. pylori infection or both were detected in 60% of patients.

Background and purpose To investigate the role of multi-parametric magnetic resonance imaging (MP-MRI) as a biomarker for squamous cell carcinoma of the anal canal (SCCAC). Materials and methods From January 2013 to January 2017, 25 patients with non-metastatic SCCAC were enrolled in a multi-centre prospective clinical trial, of whom 20 completed protocol treatment. MP-MRIs, incorporating diffusion weighted magnetic resonance imaging (DW-MRI) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) sequences, were performed before (baseline), during the second and fourth weeks of chemo-radiotherapy (CRT), and 8 weeks following treatment completion. Histogram analysis of multi-parametric maps generated maximum, mean, median, minimum, skewness, kurtosis, and standard deviation metrics. Exact logistic regression and ROC AUC analyses were performed for each metric at every timepoint. An elastic net LASSO logistic regression was also performed using all measures at each timepoint. Results With a median follow up of 17.1 months, 3/20 patients had a local recurrence, and 5/20 had any recurrence. Several apparent diffusion coefficient (ADC) metrics extracted from DW-MRIs correlated with local recurrence and demonstrated excellent discrimination: baseline skewness (p = 0.04, ROC AUC 0.90) and standard deviation (SD) (p = 0.02, ROC AUC 0.90), week 2 skewness (p = 0.02, ROC AUC 0.91) and SD (p = 0.01, ROC AUC 0.94), week 4 kurtosis (p = 0.01, AUC 0.92) and SD (p = 0.01, ROC AUC 0.96). Changes in minimum ADC between baseline and week 2 (p = 0.02, ROC AUC 0.94) and baseline and week 4 (p = 0.02, ROC AUC 0.94) were prognostic for local recurrence. For prediction of any recurrence, ADC minimum (p = 0.02, ROC AUC 0.87) and SD (p = 0.01, ROC AUC 0.85) at baseline, and ADC maximum (p = 0.03, ROC AUC 0.77) and SD (p = 0.02, ROC AUC 0.81) at week 4 were significant. On LASSO logistic regression, ADC minimum and SD at baseline were retained for any recurrence. The only significant finding for DCE-MRI was a correlation of k-trans min at the second follow-up with local recurrence (p = 0.05, AUC 0.84). Conclusion Several ADC parameters at various time points correlate with recurrence suggesting DW-MRI is a potential biomarker for SCCAC.

INTRODUCTION Fatigue is a commonly reported symptom in men receiving radiation therapy and androgen deprivation therapy (ADT) for prostate cancer. Despite this, the complex mechanisms remain unclear. This study aims to investigate factors which correlate with development of fatigue. METHODS Twenty-seven men with high-risk prostate cancer undergoing radiation therapy and 18 months of ADT were assessed for fatigue, haemoglobin (Hb), testosterone, magnetic resonance imaging (MRI) fat fraction (FF) and apparent diffusion coefficient (ADC), at baseline and at intervals after radiotherapy. Changes from baseline were analysed using paired t-tests. Linear time trends were assessed using linear mixed effect models. RESULTS Overall, mean fatigue score increased from baseline to the 18-month time interval (difference 4.5, P = 0.0114). The mean value for Hb significantly decreased (P

BACKGROUND:The PORTEC-3 trial investigated the benefit of combined adjuvant chemotherapy and radiotherapy versus pelvic radiotherapy alone for women with high-risk endometrial cancer. We updated the analysis to investigate patterns of recurrence and did a post-hoc survival analysis.METHODS:In the multicentre randomised phase 3 PORTEC-3 trial, women with high-risk endometrial cancer were eligible if they had International Federation of Gynaecology and Obstetrics (FIGO) 2009 stage I, endometrioid grade 3 cancer with deep myometrial invasion or lymphovascular space invasion, or both; stage II or III disease; or stage I-III disease with serous or clear cell histology; were aged 18 years and older; and had a WHO performance status of 0-2. Participants were randomly assigned (1:1) to receive radiotherapy alone (48·6 Gy in 1·8 Gy fractions given on 5 days per week) or chemoradiotherapy (two cycles of cisplatin 50 mg/m2 given intravenously during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2 given intravenously), by use of a biased coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage, and histological type. The co-primary endpoints were overall survival and failure-free survival. Secondary endpoints of vaginal, pelvic, and distant recurrence were analysed according to the first site of recurrence. Survival endpoints were analysed by intention-to-treat, and adjusted for stratification factors. Competing risk methods were used for failure-free survival and recurrence. We did a post-hoc analysis to analyse patterns of recurrence with 1 additional year of follow-up. The study was closed on Dec 20, 2013; follow-up is ongoing. This study is registered with ISRCTN, number ISRCTN14387080, and ClinicalTrials.gov, number NCT00411138.FINDINGS:Between Nov 23, 2006, and Dec 20, 2013, 686 women were enrolled, of whom 660 were eligible and evaluable (330 in the chemoradiotherapy group, and 330 in the radiotherapy-alone group). At a median follow-up of 72·6 months (IQR 59·9-85·6), 5-year overall survival was 81·4% (95% CI 77·2-85·8) with chemoradiotherapy versus 76·1% (71·6-80·9) with radiotherapy alone (adjusted hazard ratio [HR] 0·70 [95% CI 0·51-0·97], p=0·034), and 5-year failure-free survival was 76·5% (95% CI 71·5-80·7) versus 69·1% (63·8-73·8; HR 0·70 [0·52-0·94], p=0·016). Distant metastases were the first site of recurrence in most patients with a relapse, occurring in 78 of 330 women (5-year probability 21·4%; 95% CI 17·3-26·3) in the chemoradiotherapy group versus 98 of 330 (5-year probability 29·1%; 24·4-34·3) in the radiotherapy-alone group (HR 0·74 [95% CI 0·55-0·99]; p=0·047). Isolated vaginal recurrence was the first site of recurrence in one patient (0·3%; 95% CI 0·0-2·1) in both groups (HR 0·99 [95% CI 0·06-15·90]; p=0·99), and isolated pelvic recurrence was the first site of recurrence in three women (0·9% [95% CI 0·3-2·8]) in the chemoradiotherapy group versus four (0·9% [95% CI 0·3-2·8]) in the radiotherapy-alone group (HR 0·75 [95% CI 0·17-3·33]; p=0·71). At 5 years, only one grade 4 adverse event (ileus or obstruction) was reported (in the chemoradiotherapy group). At 5 years, reported grade 3 adverse events did not differ significantly between the two groups, occurring in 16 (8%) of 201 women in the chemoradiotherapy group versus ten (5%) of 187 in the radiotherapy-alone group (p=0·24). The most common grade 3 adverse event was hypertension (in four [2%] women in both groups). At 5 years, grade 2 or worse adverse events were reported in 76 (38%) of 201 women in the chemoradiotherapy group versus 43 (23%) of 187 in the radiotherapy-alone group (p=0·002). Sensory neuropathy persisted more often after chemoradiotherapy than after radiotherapy alone, with 5-year rates of grade 2 or worse neuropathy of 6% (13 of 201 women) versus 0% (0 of 187). No treatment-related deaths were reported.INTERPRETATION:This updated analysis shows significantly improved overall survival and failure-free survival with chemoradiotherapy versus radiotherapy alone. This treatment schedule should be discussed and recommended, especially for women with stage III or serous cancers, or both, as part of shared decision making between doctors and patients. Follow-up is ongoing to evaluate long-term survival.FUNDING:Dutch Cancer Society, Cancer Research UK, National Health and Medical Research Council, Project Grant, Cancer Australia Grant, Italian Medicines Agency, and the Canadian Cancer Society Research Institute.

5533 Background: NOX66 is a new formulation of the small molecule, idronoxil. The primary mechanism of action of idronoxil stems from its binding to the transmembrane enzyme ENOX2 expressed on cancer cells, resulting in reduced S1P and increased ceramide levels, thereby promoting apoptosis. Additional intracellular effects include the inhibition of DNA repair mechanisms. There is growing evidence that S1P is a promotor of tumour resistance to immune cell infiltration, highlighting NOX66’s potential to modulate the immune response against cancer. Methods: This two-part phase 1b open-label study enrolled patients with late-stage progressive mCRPC. Part 1 was a dose-escalation safety assessment of three doses of NOX66 (400 mg, n = 4; 800 mg, n = 6 and 1200 mg, n = 15) administered daily for 14 days with radiation therapy (20 Gy) delivered in 5 fractionated doses to one or more symptomatic lesion/s. Part 2 was an expansion cohort with NOX66 at 1200 mg in conjunction with radiation therapy. The primary endpoint of safety was assessed by the frequency and grade of treatment-emergent adverse events (TEAEs). At 6 weeks, 3- and 6-month follow up, treatment response was assessed radiographically by RECIST1.1 and by PSA >50% reduction. Results: 25 patients received and completed treatment. TEAEs considered related to NOX66 alone were mild (Grade 1) cases of dry mouth and oral mucositis; mild (Grade 1) fatigue was considered related to both NOX66 and radiation. None of the 21 Grade ≥3 TEAEs were considered related to NOX66. At 6 months, of the 15 evaluable patients by RECIST1.1, 9 had SD and 1 had PR and these same patients had maintained this response from 3 months. Five of the 16 PSA-evaluable patients achieved a PSA response (61-98% PSA reduction) at 6 months, which again was maintained from 3 months. Conclusions: NOX66 in combination with low-dose radiation therapy was found to be safe and well tolerated with promising signals of durable efficacy in patients with late-stage mCRPC. Responses of lesions outside the radiation field are being reviewed. Clinical trial information: NCT03307629 .

Carminia Lapuz,1–3 Anoop K Enjeti,2,4 Peter C O’Brien,1,2 Anne L Capp,1,2 Elizabeth G Holliday,2,5 Sanjiv A Gupta1,2 1Department of Radiation Oncology, Calvary Mater Newcastle, Newcastle, NSW, Australia; 2Faculty of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia; 3Department of Radiation Oncology, Olivia Newton-John Cancer Centre, Austin Health, VIC, Australia; 4Department of Haematology, Calvary Mater Newcastle, Newcastle, NSW, Australia; 5Faculty of Public Health, Hunter Medical Research Institute, Newcastle, NSW, Australia Background: This study evaluated relapse patterns and survival in advanced Hodgkin lymphoma (HL) patients treated with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) with positron emission tomography (PET) used for staging and response assessment. Patients and methods: Patients aged 18 years or above with newly diagnosed histologically proven Stage III or IV HL treated with ABVD at Calvary Mater Newcastle from January 2005 to December 2012 were included in this study. All patients underwent pre-chemotherapy staging with 18F-fluorodeoxyglucose PET or PET/computed tomography and post-chemotherapy PET or PET/computed tomography for the assessment of response. Results: Forty-three patients were included in the study. The 5-year disease-free survival, progression-free survival and overall survival were 88%, 74% and 86%, respectively. PET complete response was seen in 35 patients (81%), and the 5-year overall survival for this group was 94%. Relapse following a PET complete response was low (three patients) and occurred predominantly at the initial sites of disease. Four of five patients with bulky disease received consolidative radiotherapy and no in-field relapses were observed. Conclusion: Advanced stage HL with a PET complete response following ABVD is associated with an excellent prognosis. Keywords: Hodgkin lymphoma, advanced, PET scan

Introduction Retrospective analysis was performed at a single institution to assess the responsiveness of mantle cell lymphoma (MCL) to involved-field radiotherapy (IFRT). Methods All patients treated with IFRT to at least one site of MCL between 1998 and 2012 were included. There were 25 patients who received radiotherapy to 60 disease sites. Primary endpoint was overall response rate (ORR) infield for the first site of MCL treated per patient. Predictors of ORR were analysed for the primary endpoint. Time to local progression (TLP) infield and progression-free survival were calculated from the start of the first treatment course. Analysis of all sites collectively was also undertaken. Survival analysis was conducted by the Kaplan–Meier method. Results ORR rate was 84% for the first site treated per patient. Complete response and partial response rates were 68% and 16% respectively. Median TLP following radiotherapy to the first site was not reached. Infield control rate was 91% at 12 months (95% confidence interval 69–97%). When analysis was performed on all 60 sites, ORR was 85%. Symptomatic improvement occurred after IFRT to 93% of all sites. Systemic progression outside the radiotherapy field was the predominant form of failure following IFRT. Conclusion Radiotherapy generally induced a clinical response at all levels of dose administered, ranging from 3 to 36 Gy. However, increased durability of local control was suggested with higher doses. Radiotherapy is an effective treatment for palliation of MCL with objective and symptomatic responses seen over a range of radiotherapy doses.

To evaluate cervix brachytherapy dosimetry with the introduction of magnetic resonance (MR) based treatment planning and volumetric prescriptions and propose a method for plan evaluation in the transition period. The treatment records of 69 patients were reviewed retrospectively. Forty one patients were treated using computed tomography (CT)-based, Point A-based prescriptions and 28 patients were treated using magnetic resonance (MR)-based, volumetric prescriptions. Plans were assessed for dose to Point A and organs at risk (OAR) with additional high-risk clinical target volume (HR-CTV) dose assessment for MR-based brachytherapy plans. ICRU-38 point doses and GEC-ESTRO recommended volumetric doses (D2cc for OAR and D100, D98 and D90 for HR-CTV) were also considered. For patients with small HR-CTV sizes, introduction of MR-based volumetric brachytherapy produced a change in dose delivered to Point A and OAR. Point A doses fell by 4.8 Gy (p = 0.0002) and ICRU and D2cc doses for OAR also reduced (p 0.01). Mean Point A doses for MR-based brachytherapy treatment plans were closer to those of HR-CTV D100 for volumes less than 20 cm(3) and HR-CTV D98 for volumes between 20 and 35 cm(3), with a significant difference (p 0.0001) between Point A and HR-CTV D90 doses in these ranges. In order to maintain brachytherapy dose consistency across varying HR-CTV sizes there must be a relationship between the volume of the HR-CTV and the prescription dose. Rather than adopting a 'one size fits all' approach during the transition to volume-based prescriptions, this audit has shown that separating prescription volumes into HR-CTV size categories of less than 20 cm(3), between 20 and 35 cm(3), and more than 35 cm(3) the HR-CTV can provide dose uniformity across all volumes and can be directly linked to traditional Point A prescriptions.

The detection of circulating tumor cells (CTCs) provides important prognostic information in men with metastatic prostate cancer. We aim to determine the rate of detection of CTCs in patients with high-risk non-metastatic prostate cancer using the CellSearch® method. Samples of peripheral blood (7.5 mL) were drawn from 36 men with newly diagnosed high-risk non-metastatic prostate cancer, prior to any initiation of therapy and analyzed for CTCs using the CellSearch® method. The median age was 70 years, median PSA was 14.1, and the median Gleason score was 9. The median 5-year risk of progression of disease using a validated nomogram was 39 %. Five out of 36 patients (14 %, 95 % CI 5–30 %) had CTCs detected in their circulation. Four patients had only 1 CTC per 7.5 mL of blood detected. One patient had 3 CTCs per 7.5 mL of blood detected, which included a circulating tumor microemboli. Both on univariate analysis and multivariate analysis, there were no correlations found between CTC positivity and the classic prognostic factors including PSA, Gleason score, T-stage and age. This study demonstrates that patients with high-risk, non-metastatic prostate cancer present infrequently with small number of CTCs in peripheral blood. This finding is consistent with the limited literature available in this setting. Other CTC isolation and detection technologies with improved sensitivity and specificity may enable detection of CTCs with mesenchymal phenotypes, although none as yet have been validated for clinical use. Newer assays are emerging for detection of new putative biomarkers for prostate cancer. Correlation of disease control outcomes with CTC detection will be important.

The aims of this study were to evaluate the impact of cosmetic and functional outcomes after breast-conserving surgery (BCS) and radiation on quality of life (QOL). In this exploratory analysis; baseline, 5 and 10 years data of patient's assessment of breast cosmesis, arm swelling/pain, limitation of movement, loss of feeling in fingers and breast sensitivity/tenderness were dichotomized and their impact on QOL (QLQ-C30) were assessed. Multivariable modelling was also performed to assess associations with QOL. The St. George and Wollongong randomized trial randomized 688 patients into the boost and no boost arms. 609, 580, and 428 patients had baseline, 5 and 10 years cosmetic data available, respectively. Similar numbers had the various functional assessments in the corresponding period. By univariate analysis, cosmesis and a number of functional outcomes were highly associated with QOL. Adjusted multivariate modelling showed that cosmesis remained associated with QOL at 5 and 10 years. Breast sensitivity, arm pain, breast separation, age and any distant cancer event were also associated with QOL on multivariate modelling at 10 years. This study highlights the importance of maintaining favorable cosmetic and functional outcomes following BCS. In addition, the clinically and statistically significant relationship between functional outcomes and QOL shows the importance for clinicians and allied health professionals in identifying, discussing, managing, and limiting these effects in women with breast cancer in order to maintain QOL.

Introduction: This study evaluated digital photographs as a method of providing auditable source documentation for radiotherapy-induced skin toxicity and the possibility therefore of centralised, blinded scoring for a multicentre randomised controlled trial. Methods: Digital photograph sets from the first five patients from each of 12 participating centres were audited. Minimum camera specifications and photograph requirements were protocol specified. Three readers rated photographs for four key quality items. They also scored skin reactions according to National Cancer Institute Common Terminology Criteria (CTC) v3.0 acute skin score and also for the presence of any moist desquamation. Results: Five hundred fifty-two images were available. Field of view was scored as inadequate in 1-10%, focus inadequate in 0.4-4%, lighting inadequate in 0.2-3% and dividing line marking inadequate for scoring of skin reactions within sectors in 18-23% of photographs by three readers. Reader pairwise inter-observer agreement was 83-88% for CTC acute skin scores, but the kappa value ranged from 0.58 to 0.73. The percentage of image sectors not scored by readers due to difficulty in assessing was 1-10%. Moist desquamation was scored by clinicians in 8 (medial)-13% (lateral) of patients compared with 3-5% and 5-11% by readers. Conclusion: Photo reader inter-observer agreement is only moderate. Photo readers tended to underscore the frequency of moist desquamation, but the trend by sector parallels the clinical scorers. Photographs are useful source documents for auditing and monitoring, but not a replacement for clinical scoring.

Background: The aim of this study is to determine whether immunohistochemical (IHC) assessment of Ki67 and p53 improves prognostication of oestrogen receptor-positive (ER+) breast cancer after breast-conserving therapy (BCT). In all, 498 patients with invasive breast cancer from a randomised trial of BCT with or without tumour bed radiation boost were assessed using IHC. Methods: The ER+ tumours were classified as ‘luminal A' (LA): ER+ and/or PR+, Ki-67 low, p53−, HER2− or ‘luminal B' (LB): ER+ and/or PR+and/or Ki-67 high and/or p53+ and/or HER2+. Kaplan–Meier and Cox proportional hazards methodology were used to ascertain relationships to ispilateral breast tumour recurrence (IBTR), locoregional recurrence (LRR), distant metastasis-free survival (DMFS) and breast cancer-specific survival (BCSS). Results: In all, 73 patients previously LA were re-classified as LB: a greater than four-fold increase (4.6–19.3%) compared with ER, PR, HER2 alone. In multivariate analysis, the LB signature independently predicted LRR (hazard ratio (HR) 3.612, 95% CI 1.555–8.340, P=0.003), DMFS (HR 3.023, 95% CI 1.501–6.087, P=0.002) and BCSS (HR 3.617, 95% CI 1.629–8.031, P=0.002) but not IBTR. Conclusion: The prognostic evaluation of ER+ breast cancer is improved using a marker panel, which includes Ki-67 and p53. This may help better define a group of poor prognosis ER+ patients with a greater probability of failure with endocrine therapy.

Background and purpose Dose planning requires a CT scan which provides the electron density distribution for dose calculation. MR provides superior soft tissue contrast compared to CT and the use of MR-alone for prostate planning would provide further benefits such as lower cost to the patient. This study compares the accuracy of MR-alone based dose calculations with bulk electron density assignment to CT-based dose calculations for prostate radiotherapy. Materials and methods CT and whole pelvis MR images were contoured for 39 prostate patients. Plans with uniform density and plans with bulk density values assigned to bone and tissue were compared to the patient’s gold standard full density CT plan. The optimal bulk density for bone was calculated using effective depth measurements. The plans were evaluated using ICRU point doses, dose volume histograms, and Chi comparisons. Differences in spatial uniformity were investigated for the CT and MR scans. Results The calculated dose for CT bulk bone and tissue density plans was 0.1 ± 0.6% (mean ± 1 SD) higher than the corresponding full density CT plan. MR bulk bone and tissue density plans were 1.3 ± 0.8% lower than the full density CT plan. CT uniform density plans and MR uniform density plans were 1.4 ± 0.9% and 2.6 ± 0.9% lower, respectively. Paired t -tests performed on specific points on the DVH graphs showed that points on DVHs for all bulk electron density plans were equivalent with two exceptions. There was no significant difference between doses calculated on Pinnacle and Eclipse. The dose distributions of six patients produced Chi values outside the acceptable range of values when MR-based plans were compared to the full density plan. Conclusions MR-alone bulk density planning is feasible provided bone is assigned a density, however, manual segmentation of bone on MR images will have to be replaced with automatic methods. The major dose differences for MR bulk density plans are due to differences in patient external contours introduced by the MR couch-top and pelvic coil.

Purpose To assess the accuracy of the initial CT plan dose–volume histograms (DVH's) for prostate, rectum and bladder by comparison to delivered doses determined from cone beam CT (CBCT) scans acquired during image-guided treatment. Materials and methods Twelve prostate patients were treated using daily implanted fiducial guidance and following local protocol for bladder and rectal preparation. CBCT scans were acquired twice weekly and contoured for prostate, rectum and bladder. The planned beams were applied to all CBCT scans to determine the delivered doses. Prostate dose coverage was assessed by the proportion of the CTV fully encompassed by the 95% and 98% isodose lines. Rectal and bladder volumes receiving 40Gy, 60Gy and 70Gy at treatment were compared to the initial plan, with significance determined using the one-sample t -test. Results Four patients showed marginally compromised CTV coverage by the 95% isodose at all CBCT plans. For nine patients the initial plan rectal DVH was significantly outside the range of the treatment DVH's. Conclusions Dose coverage of the prostate was not achieved for all patients. Observed rectal and bladder doses were higher than predicted. The initial treatment plan cannot be assumed to represent accurate normal tissue doses.

A prospective clinical trial was conducted to evaluate the feasibility of a novel approach to the treatment of patients with high risk prostate cancer (HRPC) through the use of a nomogram to tailor radiotherapy target volumes. Twenty seven subjects with HRPC were treated with a mildly hypofractionated radiotherapy regimen using image-guided IMRT technique between Jun/2013-Jan/2015. A set of validated prognostic factors were inputted into the Memorial-Sloan-Kettering Cancer Center (MSKCC) prostate cancer nomogram to estimate risk of loco-regional spread (LRS). The nomogram risk estimates for extra-capsular extension (ECE), seminal vesicles involvement (SVI), and pelvic lymph nodes involvement (LNI) were used to adapt radiotherapy treatment volumes based on a risk threshold of ≥15 % in all cases. A planning guide was used to delineate target volumes and organs at risk (OAR). Up to three dose levels were administered over 28 fractions; 70Gy for gross disease in the prostate +/− seminal vesicles (2.5Gy/fraction), 61.6Gy for subclinical peri-prostatic disease (2.2Gy/fraction) and 50.4Gy to pelvic nodes (1.8Gy/fraction). Data regarding protocol adherence, nomogram use, radiotherapy dose distribution, and acute toxicity were collected. Nomogram use 100 % of patients were treated for ECE, 88.9 % for SVI, and 70.4 % for LNI. The three areas at risk of LRS were appropriately treated according to the study protocol in 98.8 % cases. The MSKCC nomogram estimates for LRS differed significantly between the time of recruitment and analysis. Contouring protocol compliance Compliance with the trial contouring protocol for up to seven target volumes was 93.0 % (159/171). Compliance with protocol for small bowel contouring was poor (59.3 %). Dose constraints compliance Compliance with dose constraints for target volumes was 97.4 % (191/196). Compliance with dose constraints for OAR was 88.2 % (285/323). Acute toxicity There were no grade 3 acute toxicities observed. 20/27 (74.1 %) and 6/27 (22.2 %) patients experienced a grade 2 genitourinary and gastrointestinal toxicity respectively. We have demonstrated the feasibility of this novel risk-adapted radiation treatment protocol for HRPC. This study has identified key learning points regarding this approach, including the importance of standardization and updating of risk quantification tools, and the utility of an observer to verify their correct use. ClincialTrials.gov identifier NCT01418040 . Hunter New England Human Research Ethics Committee (HNEHREC) reference number 12/08/15/4.02

Inverse planned intensity-modulated radiation therapy (IMRT) has been applied to patients in a conformal fashion in order to avoid the lacrimal gland. In the present study, we report a patient in which a potential planned dose of 63 Gy to the lacrimal gland for a conventional plan was reduced to 12 Gy to the lacrimal gland for the IMRT plan. Dose objective inverse planning was provided using a Pinnacle treatment planning computer and treatment was delivered using a Varian dynamic multileaf collimator (MLC) on a Varian linear accelerator. Because multiple MLC segments are used to deliver the modulated treatment, conventional dose checks by manual calculation are not practical. To aid in an alternative dosimetric verification process, the Pinnacle planning computer has two unique dose tools, which provide axial and beams eye view doses on user-specified check phantoms. The combined field axial dose tool matched our ion chamber dose checks within +/- 2.4% at the isocentre. The individual beams eye view dose tool matched film dose maps within +/- 3% in the umbra.

Intensity modulated radiotherapy (IMRT) is a complex form of external beam radiation therapy, which is not called on commonly for palliative therapy. However, its use in day-to-day therapy is becoming more wide-spread with the increasing incorporation of new imaging and planning technologies into radiotherapy departments, together with the increasing availability of multileaf collimators and electronic portal imaging devices. In the clinical setting, IMRT is being used in a number of tumour settings where dose escalation is desirable or where there are dose-limiting organs in close proximity to the tumour. The clinical evidence and basis for treatment is discussed.

Purpose: The superior image quality of 3 tesla (3T) magnetic resonance (MR) imaging in cervical cancer offers the potential to use a single image set for brachytherapy. This study aimed to determine a suitable single sequence for contouring tumour and organs at risk, applicator reconstruction, and treatment planning. Material and methods: A 3T (Skyra, Siemens Healthcare AG, Germany) MR imaging system with an 18 channel body matrix coil generated HDR cervical cancer brachytherapy planning images on 20 cases using plastic-based treatment applicators. Seven different T2-weighted Turbo Spin Echo (TSE) sequences including both 3D and contiguous 2D scans based on sagittal, axial (transverse), and oblique planes were analysed. Each image set was assessed for total scanning time and usefulness in tumour localization via inter- and intra-observer analysis of high-risk clinical target volume (HR CTV) contouring. Applicator reconstruction in the treatment planning system was also considered. Results: The intra-observer difference in HR CTV volumes between 2D and 3D axial-based image sets was low with an average difference of 3.1% for each observer. 2D and 3D sagittal image sets had the highest intra- and inter observer differences (over 15%). A 2D axial ‘double oblique’ sequence was found to produce the best intra- (average difference of 0.6%) and inter-observer (mean SD of 9.2%) consistency and greatest conformity (average 0.80). Conclusions: There was little difference between 2D and 3D-based scanning sequences; however the increased scanning time of 3D sequences have potential to introduce greater patient motion artifacts. A contiguous 2D sequence based on an axial T2-weighted turbo-spin-echo (TSE) sequence orientated in all planes of the treatment applicator provided consistent tumour delineation whilst allowing applicator reconstruction and treatment planning. J Contemp Brachytherapy 2014; 6, 1: 3–9 DOI: 10.5114/jcb.2014.41528

Purpose Multichannel vaginal applicators allow treatment of a more conformal volume compared with a single, central vaginal channel. There are several optimization methods available for use with multichannel applicators, but no previous comparison of these has been performed in the treatment of superficial vaginal tumors. Accordingly, a feasibility study was completed to compare inverse planning by simulated annealing (IPSA), dose point optimization (DPO), and graphical optimization for high-dose-rate brachytherapy using a multichannel, intracavitary vaginal cylinder. Methods and Materials This comparative study used CT data sets from five patients with superficial vaginal recurrences of endometrial cancer treated with multichannel intracavitary high-dose-rate brachytherapy. Treatment plans were generated using DPO, graphical optimization, surface optimization with IPSA (surf IPSA), and two plans using volume optimization with IPSA. The plans were evaluated for target coverage, conformal index, dose homogeneity index, and dose to organs at risk. Results Best target coverage was achieved by volume optimization with IPSA 2 and surf IPSA with mean V100 values of 93.89% and 91.87%, respectively. Doses for the most exposed 2-cm 3 of the bladder (bladder D2cc) was within tolerance for all optimization methods. Rectal D2cc was above tolerance for one DPO plan. All volume optimization with IPSA plans resulted in higher vaginal mucosa doses for all patients. Greatest homogeneity within the target volume was seen with surf IPSA and DPO. Highest conformal indices were seen with surf IPSA and graphical optimization. Conclusions Optimization with surf IPSA was user friendly for the generation of treatment plans and achieved good target coverage, conformity, and homogeneity with acceptable doses to organs at risk.

Purpose A previous, unblinded study demonstrated that an alcohol-free barrier film containing an acrylate terpolymer (ATP) was effective in reducing skin reactions compared with a 10% glycerine cream (sorbolene). The different appearances of these products precluded a blinded comparison. To test the acrylate terpolymer principle in a double-blinded manner required the use of an alternative cream formulation, a moisturizing durable barrier cream (MDBC); the study was conducted by the Trans Tasman Radiation Oncology Group (TROG) as protocol 04.01. Methods and Materials A total of 333 patients were randomized; 1 patient was ineligible and 14 patients withdrew or had less than 7 weeks' observations, leaving 318 for analysis. The chest wall was divided into medial and lateral compartments, and patients were randomized to have MDBC applied daily to the medial or lateral compartment and sorbolene to the other compartment. Weekly observations, photographs, and symptom scores (pain and pruritus) were collected to week 12 or resolution of skin reactions if earlier. Skin dose was confirmed by centrally calibrated thermoluminescent dosimeters. Results Rates of medial and lateral compartment Common Toxicity Criteria (CTC), version 3, greater than or equal to grade 3 skin reactions were 23% and 41%, but rates by skin care product were identical at 32%. There was no significant difference between MDBC and sorbolene in the primary endpoint of peak skin reactions or secondary endpoints of area-under-the-curve skin reaction scores. Conclusions The MDBC did not reduce the peak skin reaction compared to sorbolene. It is possible that this is related to the difference in the formulation of the cream compared with the film formulation. Skin dosimetry verification and double blinding are essential for radiation skin care comparative studies.

To estimate the prevalence of rectal and urinary dysfunctional symptoms using image guided radiation therapy (IGRT) with fiducials and magnetic resonance planning for prostate cancer.During the implementation stages of IGRT between September 2008 and March 2010, 367 consecutive patients were treated with prostatic irradiation using 3-dimensional conformal radiation therapy with and without IGRT (non-IGRT). In November 2010, these men were asked to report their bowel and bladder symptoms using a postal questionnaire. The proportions of patients with moderate to severe symptoms in these groups were compared using logistic regression models adjusted for tumor and treatment characteristic variables.Of the 282 respondents, the 154 selected for IGRT had higher stage tumors, received higher prescribed doses, and had larger volumes of rectum receiving high dosage than did the 128 selected for non-IGRT. The follow-up duration was 8 to 26 months. Compared with the non-IGRT group, improvement was noted in all dysfunctional rectal symptoms using IGRT. In multivariable analyses, IGRT improved rectal pain (odds ratio [OR] 0.07 [0.009-0.7], P=.02), urgency (OR 0.27 [0.11-0.63], P=.01), diarrhea (OR 0.009 [0.02-0.35], P.01), and change in bowel habits (OR 0.18 [0.06-0.52], P.010). No correlation was observed between rectal symptom levels and dose-volume histogram data. Urinary dysfunctional symptoms were similar in both treatment groups.In comparison with men selected for non-IGRT, a significant reduction of bowel dysfunctional symptoms was confirmed in men selected for IGRT, even though they had larger volumes of rectum treated to higher doses.

Purpose Prostate radiation therapy dose planning directly on magnetic resonance imaging (MRI) scans would reduce costs and uncertainties due to multimodality image registration. Adaptive planning using a combined MRI-linear accelerator approach will also require dose calculations to be performed using MRI data. The aim of this work was to develop an atlas-based method to map realistic electron densities to MRI scans for dose calculations and digitally reconstructed radiograph (DRR) generation. Methods and Materials Whole-pelvis MRI and CT scan data were collected from 39 prostate patients. Scans from 2 patients showed significantly different anatomy from that of the remaining patient population, and these patients were excluded. A whole-pelvis MRI atlas was generated based on the manually delineated MRI scans. In addition, a conjugate electron-density atlas was generated from the coregistered computed tomography (CT)-MRI scans. Pseudo-CT scans for each patient were automatically generated by global and nonrigid registration of the MRI atlas to the patient MRI scan, followed by application of the same transformations to the electron-density atlas. Comparisons were made between organ segmentations by using the Dice similarity coefficient (DSC) and point dose calculations for 26 patients on planning CT and pseudo-CT scans. Results The agreement between pseudo-CT and planning CT was quantified by differences in the point dose at isocenter and distance to agreement in corresponding voxels. Dose differences were found to be less than 2%. Chi-squared values indicated that the planning CT and pseudo-CT dose distributions were equivalent. No significant differences ( p > 0.9) were found between CT and pseudo-CT Hounsfield units for organs of interest. Mean ± standard deviation DSC scores for the atlas-based segmentation of the pelvic bones were 0.79 ± 0.12, 0.70 ± 0.14 for the prostate, 0.64 ± 0.16 for the bladder, and 0.63 ± 0.16 for the rectum. Conclusions The electron-density atlas method provides the ability to automatically define organs and map realistic electron densities to MRI scans for radiotherapy dose planning and DRR generation. This method provides the necessary tools for MRI-alone treatment planning and adaptive MRI-based prostate radiation therapy.

Dose planning for prostate radiation therapy is performed using computed tomography (CT) scans that provide the electron density information needed for individual patients' radiation dose calculations. For visualising the prostate and determining the target volume for radiation treatment, magnetic resonance imaging (MRI) gives vastly superior soft-tissue contrast. However, currently, MRI scans cannot be used for dose planning, as they do not provide the electron density information. We aimed to develop an alternative and efficient MRI-only image-based workflow, enabling both organ delineation and dose planning to be performed using MRI, with "pseudo-CT scans" generated from MRI scans supplying the information for dose planning. The feasibility of implementing MRI-based prostate radiation therapy planning is being investigated through collaboration between the clinical and medical physics group at the Calvary Mater Newcastle Hospital/University of Newcastle and the biomedical imaging processing group at the CSIRO (Commonwealth Scientific and Industrial Research Organisation) Australian e-Health Research Centre. Results comparing Hounsfield units calculated from CT scans and from MRI-based pseudo-CT scans for 39 patients showed very similar average values for the prostate, bladder, bones and rectum, confirming that pseudo-CT scans can replace CT scans for accurate radiation dose calculations. MRI-based radiotherapy planning can also be used for tumours in other locations, such as head and neck, and breast cancers.

Purpose To determine the clinical utility of intrinsic molecular phenotype after breast-conserving therapy (BCT) with lumpectomy and whole-breast irradiation with or without a cavity boost. Patients and Methods Four hundred ninety-eight patients with invasive breast cancer were enrolled into a randomized trial of BCT with or without a tumor bed radiation boost. Tumors were classified by intrinsic molecular phenotype as luminal A or B, HER-2, basal-like, or unclassified using a five-biomarker panel: estrogen receptor, progesterone receptor, HER-2, CK5/6, and epidermal growth factor receptor. Kaplan-Meier and Cox proportional hazards methodology were used to ascertain relationships to ipsilateral breast tumor recurrence (IBTR), locoregional recurrence (LRR), distant disease-free survival (DDFS), and death from breast cancer. Results Median follow-up was 84 months. Three hundred ninety-four patients were classified as luminal A, 23 were luminal B, 52 were basal, 13 were HER-2, and 16 were unclassified. There were 24 IBTR (4.8%), 35 LRR (7%), 47 distant metastases (9.4%), and 37 breast cancer deaths (7.4%). The overall 5-year disease-free rates for the whole cohort were: IBTR 97.4%, LRR 95.6%, DDFS 92.9%, and breast cancer–specific death 96.3%. A significant difference was observed for survival between subtypes for LRR (P = .012), DDFS (P = .0035), and breast cancer–specific death (P = .0482), but not for IBTR (P = .346). Conclusion The 5-year and 10-year survival rates varied according to molecular subtype. Although this approach provides additional information to predict time to IBTR, LRR, DDFS, and death from breast cancer, its predictive power is less than that of traditional pathologic indices. This information may be useful in discussing outcomes and planning management with patients after BCT.

Purpose We sought to categorize longitudinal radiation-induced rectal toxicity data obtained from men participating in a randomised controlled trial for locally advanced prostate cancer. Materials and methods Data from self-assessed questionnaires of rectal symptoms and clinician recorded remedial interventions were collected during the TROG 96.01 trial. In this trial, volunteers were randomised to radiation with or without neoadjuvant androgen deprivation. Characterization of longitudinal variations in symptom intensity was achieved using prevalence data. An integrated visualization and clustering approach based on memetic algorithms was used to define the compositions of symptom clusters occurring before, during and after radiation. The utility of the CTC grading system as a means of identifying specific injury profiles was evaluated using concordance analyses. Results Seven well-defined clusters of rectal symptoms were present prior to treatment, 25 were seen immediately following radiation and 7 at years 1, 2 and 3 following radiation. CTC grading did not concord with the degree of rectal ‘distress’ and ‘problems’ at all time points. Concordance was not improved by adding urgency to the CTC scale. Conclusions The CTC scale has serious shortcomings. A powerful new technique for non-hierarchical clustering may contribute to the categorization of rectal toxicity data for genomic profiling studies and detailed patho-physiological studies.

s / The Breast 24 (2015) 302e307 304 Resonance Imaging (CEMRI) is currently the most sensitive imaging technique for breast cancer detection; however, it suffers from many drawbacks including high cost, timely accessibility, patient contraindications and low specificity. Previous studies have shown that contrast enhanced spectral mammography (CESM) may have similar diagnostic capability to CEMRI without these associated costs (2). Methods: The study included patients with biopsy proven breast cancer aged 21 years, fit for surgery, and excluded patients with contra-indications to intravenous contrast or CEMRI, candidates for neo-adjuvant chemotherapy, or who had pure in situ carcinoma. Participants underwent both CESM and CEMRI. Studies were independently double read and results benchmarked against the final surgical histopathology, core biopsy histology or one year follow-up imaging. CESM and CEMRI were compared for 1) detection of additional lesions 2) ability to size the index lesion 3) influence on surgical plan and 4) participant satisfaction. Results: A minimum of 19 participants was analysed for each study objective. For the detection of additional lesions (n1⁄421), the addition of CESM to conventional imaging increased sensitivity from 50% to 67% with specificity unchanged (47%). Addition of CEMRI to standard imaging increased sensitivity from 50% to 100% but with considerable reduction in specificity (47% to 7%). The geometric mean of index lesion size at pathology was similar for CESM and CEMRI (n1⁄424). For 19 patients, CESM and CEMRI had identical influence on the surgery plan. Participants preferred CESM to CEMRI (n1⁄434, p1⁄40.0005). Conclusions: Results so far suggest CESM has similar diagnostic capacity to CEMRI and is preferred by patients. References [1] Lobbes M, Smidt M, Houwers J, Tjan-Heijnen V, Wildberger J. Contrast enhanced mammography: Techniques, current results, and potential indications. Clinical Radiology. 2013. [2] Jochelson MS, Dershaw DD, Sung JS, Heerdt AS, Thornton C, Moskowitz CS, et al. Bilateral contrast-enhanced dual-energy digital mammography: feasibility and comparison with conventional digital mammography and MR imaging inwomenwith known breast carcinoma. Radiology. 2013Mar; 266 (3):743-51. PubMed PMID: 23220903. PREDICTORS OF RESPONSES AND SEXUAL FUNCTION FOR WOMEN IN THE ST GEORGE BREAST BOOST RANDOMIZED TRIAL (STGBBT) P.H. Graham, L. Browne , A. Capp , G. Delaney , C. Fox , E.K. Millar , E. Nasser , G. Papadatos . Cancer Care Centre, St George Hospital, Kogarah, Australia; Mater Hospital, Newcastle, Australia; Cancer Therapy Centre, Liverpool Hospital, Liverpool, Australia; Cancer Care Centre, Wollongong Hospital, Wollongong, Australia; Macarthur Cancer Care Centre, Campbelltown Hospital, Campbelltown, Australia Background and purpose: To describe the StGBBT sexual function dataset and associations of response to sexual function assessment. Methods: 688 women participated in the StGBBT as previously reportedi. Quality of life (QOL) and Sexual function data was collected from baseline (pre-radiotherapy) to year 10 annually. Results: 92% completed QOL questionnaires. 81% responded to sexual partner status but responders to other sexual function questions ranged from 59 to 64%. Response rates were maintained to 10 years, were highest in marrieds, lowest in singles, intermediate for divorcees/widows. 97% years and 81% aged 60-79 of married had sexual partners, versus 35% and 5% divorcees, 5% aged 69-79 widows. Of responders, at baseline 60% married versus 75% non-married reported their treated breast did not affect their sexual function. Sexual desire was reported normal in 47% married versus 35% non-married. Sexual frequency never versus at least weekly was reported in 22% and 33% of marrieds, 68% and 17% of non- marrieds. Sexual enjoyment was reported as normal in 60% of married and 47% of non-married. Conclusions: From this unique large long-term Australian data set for sexual function in breast cancer treated women longitudinal data and predictors will be presented. Response rates and sexual partnership status are similar to large community population sexual health surveysii. References [1] Hau E, Browne LH, Khanna S, Cail S, Chin Y, Clark C, Inder S, Swajcer A, Graham PH. Radiotherapy breast boost with reduced whole breast dose is associated with improved cosmesis: The results of a comprehensive assessment from the St George and Wollongong Randomized Breast Boost Trial. Int J Radiat Oncol Biol Phys. 2012; 82(2):682-689. [2] Mercer CH, Tanton C, Prah P, et al. Changes in sexual attitudes and lifestyles in Britain through the life course and over time: findings from the National Surveys of Sexual attitudes and lifestyles (Natsal). Lancet 2013; 382:1781-94 WHAT IS THE VALUE OF AXILLARY STAGING IN ELDERLY WOMEN WITH BREAST CANCER? REVIEW OF FOUR YEARS PROSPECTIVE SERIES FROM A SINGLE INSTITUTION K. Murugappan, B. Dijkstra. Department of surgery, Christchurch Hospital, Christchurch, New Zealand Background and purpose: The optimum management of elderly women with breast cancer is complex. Current guidelines are based on expert panel recommendations due to paucity of major trails. 1 In particular, there is lack of evidence to guide axillary management in elderly women (spe- cifically 80 years). Our aim is to evaluate the role of axillary surgery in the management of women aged 80 with breast cancer and its impact on their outcomes. Method: From 2009 e 2013, 130 patients 80 years were identified. Pa- tient demographics, presentation, diagnosis, surgical and non-surgical management and pathological characteristics were derived from a pro- spective database series. Follow up period was a median of 2 years (range 14) Results: Of the 130 patients, 83 (64%) patients underwent Breast +/- axillary surgery, 39 (30%) patients primary endocrine therapy alone; 4 (3%) had combination of endocrine and radiotherapy, 2 (1.5%) patients had primary radiotherapy, 2 patients refused all treatment. 52 patients (62%) whowere clinically or radiologically negative for axillary metastatic lymph node (LN) involvement underwent SLNBx (36 patients) and ALNDx (13 patients). Positive axillary LN was found in 5 patients from ALNDx group and 8 patients had positive SLNBx with 4 of these patients proceeding to completion ALNDx. Chemotherapy was not offered to anyonewith positive axillary LN. Four patients with positive axillary LN underwent radio- therapy. 38 of 57 patients with clinically node negative disease had recommendation for adjuvant endocrine therapy. Patients’ functional and medical comorbidities were analyzed to determine their impact on adju- vant management plan. Conclusion: The vast majority of patients with clinically node negative disease are undergoing axillary surgery that does not alter their subse- quent adjuvant treatment plan. Elderly patients’ functional status and medical comorbidities plays a crucial role in adjuvant management plan- ning. PET SCANS FOR LOCALLY ADVANCED BREAST CANCER AND DIAGNOSTIC MRI TO DETERMINE THE EXTENT OF OPERATION AND RADIOTHERAPY (PET LABRADOR); TROG 12.02

Purpose: Postmastectomy irradiation provides an excellent model for irradiated skin care practices because of the relatively uniform surface and radiation compared with other situations in which radiation-induced moist desquamation is common. We designed a study to test the effect of prophylactic 3M Cavilon No-Sting Barrier Film (No-Sting) on the rates of moist desquamation compared with sorbolene cream (with 10% glycerin). Methods and Materials: The irradiated chest wall was divided into medial and lateral halves. Sixty-one women were randomized to have No-Sting applied to either the medial or lateral half, with the alternate half treated with sorbolene. Results: For all patients, the skin toxicity, calculated as the area under the curve, mean No-Sting and sorbolene score was 8.1 vs. 9.2, respectively (p 0.005, Wilcoxon signed rank test). The total number of weeks of moist desquamation for the 61 patients was 40 vs. 45, equating to a mean of 0.65 week vs. 0.74 week per patient in the No-Sting and sorbolene–treated areas, respectively. The rates of moist desquamation were 33% vs. 46% (p 0.096, McNemar’s Exact test). For 58 fully assessable patients (minimum of 7 weekly observations), the area under the curve and rates of moist desquamation were significantly different statistically ( p 0.002 and 0.049, respectively). No statistically significant differences were noted in the pain scores. The pruritus scores were significantly reduced in the No-Sting area (area under the curve, p 0.011). Conclusion: No-Sting reduces the duration and frequency of radiation-induced moist desquamation. © 2004 Elsevier Inc.

Purpose: A method that could enable dose calculations to be performed using magnetic resonance(MR)images for conventional treatment planning and adaptive planning using MR‐accelerator systems would be to apply bulk electron densities to the MRimages. However currently bone must be manually segmented making this impractical. This work develops and tests an atlas‐based method to automatically segment bone on pelvic MRimages for dose calculations. Methods: An MR whole‐pelvic atlas was created using manually delineated scans from 39 patients. Atlas‐based pelvic‐bone auto‐segmentations were then created for 25 patient scans using deformable image registration of the atlas to each patients scan with a leave‐one‐out atlas approach. These and corresponding expert manual segmentations were compared using the Dice similarity coefficient. Bone was assigned a density of 1.19 g/cm3 and all other tissues a water equivalent density. Treatment plans were generated on the whole‐pelvis MRimages and doses compared for the manual and auto‐segmented bone plans. Results: The average Dice coefficient was 0.83 (standard deviation = 0.05). The average manual bone volume was 834.6 cm3 compared to the atlas based average volume of 840.0 cm3, with a mean difference of 5.4 cm3 (0.64%). The average ICRU point dose calculated on the MRimages using the atlas‐based bone segmentations was 0.2% lower (standard deviation 0.3%) than the dose calculated using the manual bone segmentations. Conclusions: The atlas based method for auto‐segmentation of pelvic bone enables MR‐based prostate radiotherapydose calculations for treatment and adaptive planning. This work was partially funded by a Cancer Council New South Wales Grant RG07‐06

commercially available rectal retractor blade (RR); vaginal packing (P) and an intravaginal Foley balloon (FB). All three methods were used in all patients. The first application was performed with the RR and the following two applications were randomly assigned to P and FB. All patients received a CT scan with bladder and rectal contrast and orthogonal X-rays following each application. Dose-volume parameters (D2cc) for rectum, sigmoid, small bowel and bladder were collected for each fraction. The sign test and Wilcoxon signed rank test were used to compare if the ratio of doses or absolute difference in dose were significantly different among the three methods. Results: Twelve patients and 46 CT scans were available for analysis. One patient was unable to have rectal retraction using RR. The mean age (SD) of the patients was 46 (8). The median dose (min, max) in cGy to the rectum using RR, FB and P were: 131 (102, 165), 208 (124, 243) and 211 (149, 298) respectively. There were significant differences in absolute dose to the rectum, sigmoid and small bowel observed using RR compared to FB (median differences -55 cGy, p Z 0.010; -53 cGy, p Z 0.003; and -58 cGy, p Z 0.012, respectively). No differences in dose to the rectum or sigmoid was observed between the packing and Foley balloon methods. There were no significant differences in bladder dose between methods. Conclusions: The rectal retractor significantly reduced the dose to rectum, sigmoid and small bowel compared with Foley balloon and packing. In patients treated under conscious sedation the rectal retractor method provides the best rectal sparing. For patients unable to undergo treatment using the rectal retractor, no significant differences in rectal or sigmoid dose were observed when comparing the other two techniques. Therefore, the Foley balloon method of rectal retraction is a reasonable alternative to vaginal packing. Author Disclosure: S. Quinlan-Davidson: None. S. Voruganti: None. R. Hunter: None. M. Patel: None. G. Pond: None. E. Timotin: None. K. Dhamanaskar: None. R. Sur: None. I. Kong: None.

Aim To determine whether immunohistochemical (IHC) assessment of Ki-67 and p53 improves prognostication of luminal breast cancer after breast-conserving therapy (BCT). Methods 498 patients with invasive breast cancer from a randomised trial of BCT with or without tumour bed radiation boost were assessed using IHC. Luminal tumours were classified as luminal A (LA): ER+ and/or PR+, Ki-67 low, p53–, HER2–; or Luminal B (LB): ER+ and/or PR+, Ki-67 high and/or p53+ and/or HER2+. Kaplan-Meier and Cox proportional hazards methodology were used to ascertain relationships to ispilateral breast tumour recurrence (IBTR), locoregional recurrence (LRR), distant metastasis free survival (DMFS) and breast cancer specific survival (BCSS). Results Seventy-three patients previously LA were re-classified as LB: a greater than four-fold increase (4.6% to 19.3%), compared to ER, PR, HER2 alone. In multivariate analysis the LB signature independently predicted LRR (HR 3.612, 95%CI 1.555–8.340, p = 0.003), DMFS (HR 3.023, 95%CI 1.501–6.087, p = 0.002) and BCSS (HR 3.617, 95%CI 1.629–8.031, p = 0.002). Conclusions The prognostic evaluation of luminal breast cancer is improved using a marker panel which includes Ki-67 and p53. This may help better define a group of poor prognosis ER+ patients with a greater probability of failure with endocrine therapy.

This project develops atlas‐based deformable image registration methods to map electron densities and automatically segment organs on MRI scans. This will enable dose calculations to be performed using the MRI scan without the requirement for an additional CT scan. The method developed uses atlas‐based deformable image registration. An MRI atlas was developed based on whole pelvic MRI scans for 39 patients. The atlas is then registered to an individual patient MRI scan. The registration of the atlas organ contours gives the automatically segmented organs on that patient scan. A CT or electron‐density atlas was also developed that corresponds to the MRI atlas. The deformation vectors that register the MRI‐atlas to the patient MRI scan are applied to the CT‐atlas to produce a pseudo‐CT scan for the patient. This can then be used for dose planning and digitally reconstructed radiographs. The feasibility of the entire workflow has been tested for one patient. The rectum, bladder, prostate and bone were automatically segmented on the MRI scan with Dice coefficient results of 0.82, 0.59, 0.62 and 0.81. The patient's plan was applied to the pseudo‐CT using a commercial treatment planning system. Dose at the normalisation point was 2.9% lower than on the full density CT plan. This method will improve the workflow of prostate radiotherapy planning and will reduce systematic uncertainties introduced by MRI‐CT registration.

Background The use of gold fiducial markers (FM) for prostate image-guided radiotherapy (IGRT) is standard practice. Published literature suggests low rates of serious infection following this procedure of 0-1.3%, but this may be an underestimate. We aim to report on the infection incidence and severity associated with the use of transrectally implanted intraprostatic gold FM. Methods Three hundred and fifty-nine patients who underwent transrectal FM insertion between January 2012 and December 2013 were assessed retrospectively via a self-reported questionnaire. All had standard oral fluoroquinolone antibiotic prophylaxis. The patients were asked about infective symptoms and the treatment received including antibiotics and/or related hospital admissions. Potential infective events were confirmed through medical records. Results 285 patients (79.4%) completed the questionnaire. 77 (27.0%) patients experienced increased urinary frequency and dysuria, and 33 patients (11.6%) reported episodes of chills and fevers after the procedure. 22 patients (7.7%) reported receiving antibiotics for urinary infection and eight patients (2.8%) reported hospital admission for urosepsis related to the procedure. Conclusion The overall rate of symptomatic infection with FM implantation in this study is 7.7%, with one third requiring hospital admission. This exceeds the reported rates in other FM implantation series, but is in keeping with the larger prostate biopsy literature. Given the higher than expected complication rate, a risk-adaptive approach may be helpful. Where higher accuracy is important such as stereotactic prostate radiotherapy, the benefits of FM may still outweigh the risks. For others, a non-invasive approach for prostate IGRT such as cone-beam CT could be considered. Electronic supplementary material The online version of this article (doi:10.1186/s13014-015-0347-2) contains supplementary material, which is available to authorized users.