Quantitative background parenchymal enhancement and fibro-glandular density at breast MRI: Association with BRCA status.

OBJECTIVES: To investigate whether MRI-based measurements of fibro-glandular tissue volume, breast density (MRBD), and background parenchymal enhancement (BPE) could be used to stratify two cohorts of healthy women: BRCA carriers and women at population risk of breast cancer. METHODS: Pre-menopausal women aged 40-50 years old were scanned at 3 T, employing a standard breast protocol including a DCE-MRI (35 and 30 participants in high- and low-risk groups, respectively). The dynamic range of the DCE protocol was characterised and both breasts were masked and segmented with minimal user input to produce measurements of fibro-glandular tissue volume, MRBD, and voxelwise BPE. Statistical tests were performed to determine inter- and intra-user repeatability, evaluate the symmetry between metrics derived from left and right breasts, and investigate MRBD and BPE differences between the high- and low-risk cohorts. RESULTS: Intra- and inter-user reproducibility in estimates of fibro-glandular tissue volume, MRBD, and median BPE estimations were good, with coefficients of variation < 15%. Coefficients of variation between left and right breasts were also low (< 25%). There were no significant correlations between fibro-glandular tissue volume, MRBD, and BPE for either risk group. However, the high-risk group had higher BPE kurtosis, although linear regression analysis did not reveal significant associations between BPE kurtosis and breast cancer risk. CONCLUSIONS: This study found no significant differences or correlations in fibro-glandular tissue volume, MRBD, or BPE metrics between the two groups of women with different levels of breast cancer risk. However, the results support further investigation into the heterogeneity of parenchymal enhancement. KEY POINTS: • A semi-automated method enabled quantitative measurements of fibro-glandular tissue volume, breast density, and background parenchymal enhancement with minimal user intervention. • Background parenchymal enhancement was quantified over the entire parenchyma, segmented in pre-contrast images, thus avoiding region selection. • No significant differences and correlations in fibro-glandular tissue volume, breast density, and breast background parenchymal enhancement were found between two cohorts of women at high and low levels of breast cancer risk.

Treatments and Outcomes in Oligometastatic Soft Tissue Soft Sarcoma - A Single Centre Retrospective Analysis.

BACKGROUND/AIM: Distinguishing true oligometastatic disease from early polymetastatic disease is vital in patients with soft tissue sarcoma as contemporary treatment strategies differ significantly. Clinical factors such as tumour biology, organ involved, number of lesions, and patient fitness influence clinical decisions. PATIENTS AND METHODS: A retrospective search of a prospective database identified patients with new distant relapse, treated between 2009 and 2012. RESULTS: A total of 223 patients were included, and oligometastases were diagnosed in 81 (36%) patients, which were pulmonary in just over half of cases. These were treated with local therapy in 66 of 89 cases, and 7 patients received subsequent treatment for additional oligometastases. Metastasectomy was the most common treatment modality. A total of 16/66 patients (24%) underwent active surveillance for >6 months prior to local therapy. CONCLUSION: Patients with oligometastatic disease can experience durable disease control with timely multimodality treatment approaches for evolving metastatic disease, where disease biology allows.

High grade gliomas in young children: The South Thames Neuro-Oncology unit experience and recent advances in molecular biology and targeted therapies.

High grade gliomas (HGG) have a dismal prognosis with survival rates of 15-35%. Approximately 10-12% of pediatric HGG occur in young children and their molecular biology and clinical outcomes differ from those arising at older ages. We report on four children aged <5 years newly diagnosed with non-brainstem HGG between 2011 and 2018 who were treated with surgery and BBSFOP chemotherapy. Two died of tumor progression. The other two are still alive without radiotherapy at 3.8 and 3.9 years from diagnosis: one of whom remains disease-free off treatment; and the other one, whose tumor harbored a KCTD16:NTRK2 fusion, went on to receive larotrectinib. Additionally we review the general management, outcomes and latest updates in molecular biology and targeted therapies for young children with HGG. Infant gliomas can be stratified in molecular subgroups with clinically actionable oncogenic drivers. Chemotherapy-based strategies can avoid or delay the need for radiotherapy in young children with HGG. Harnessing the potential of NTRK, ALK, ROS1 and MET inhibitors offers the opportunity to optimize the therapeutic armamentarium to improve current outcomes for these children.

Postretinal Detachment Retinal Displacement: How Best to Detect It?

PURPOSE: The reported incidence of postretinal detachment (RD) macular displacement varies markedly (14-72%). This may in part be due to the imaging modalities used. We compared the ability of 2 types of fundus autofluorescence (FAF) imaging modalities to detect this phenomenon. METHODS: Prospective study of 70 eyes with macula-involving RDs. 8 weeks postoperatively, patients underwent FAF imaging with 2 machines: a confocal scanning laser ophthalmoscope (cSLO) and a digital fundus camera (FC). Images were graded for the presence of hyperautofluorescent RPE (retinal pigment epithelium) ghost vessels, indicative of retinal displacement, by 2 masked, independent graders. RESULTS: In total, 87.1% of FC images were gradable versus 88.6% of cSLO images. Retinal displacement was detectable in 61.4% of FC images versus 52.8% of cSLO images. Vessel shift often appeared more autofluorescent on FC imaging, but choroidal vessels were more visible. Cohen's agreement between the imaging modalities was 0.50, rated as moderate agreement. For both imaging modalities, the inter- and intragrader agreement was substantial, representing good test-retest reliability. CONCLUSIONS: Detection of post-RD retinal displacement was similar between FC and cSLO FAF imaging, with only moderate agreement between both modalities.

Aspirin as an adjuvant treatment for cancer: feasibility results from the Add-Aspirin randomised trial.

BACKGROUND: Preclinical, epidemiological, and randomised data indicate that aspirin might prevent tumour development and metastasis, leading to reduced cancer mortality, particularly for gastro-oesophageal and colorectal cancer. Randomised trials evaluating aspirin use after primary radical therapy are ongoing. We present the pre-planned feasibility analysis of the run-in phase of the Add-Aspirin trial to address concerns about toxicity, particularly bleeding after radical treatment for gastro-oesophageal cancer. METHODS: The Add-Aspirin protocol includes four phase 3 randomised controlled trials evaluating the effect of daily aspirin on recurrence and survival after radical cancer therapy in four tumour cohorts: gastro-oesophageal, colorectal, breast, and prostate cancer. An open-label run-in phase (aspirin 100 mg daily for 8 weeks) precedes double-blind randomisation (for participants aged under 75 years, aspirin 300 mg, aspirin 100 mg, or matched placebo in a 1:1:1 ratio; for patients aged 75 years or older, aspirin 100 mg or matched placebo in a 2:1 ratio). A preplanned analysis of feasibility, including recruitment rate, adherence, and toxicity was performed. The trial is registered with the International Standard Randomised Controlled Trials Number registry (ISRCTN74358648) and remains open to recruitment. FINDINGS: After 2 years of recruitment (October, 2015, to October, 2017), 3494 participants were registered (115 in the gastro-oesophageal cancer cohort, 950 in the colorectal cancer cohort, 1675 in the breast cancer cohort, and 754 in the prostate cancer cohort); 2719 (85%) of 3194 participants who had finished the run-in period proceeded to randomisation, with rates consistent across tumour cohorts. End of run-in data were available for 2253 patients; 2148 (95%) of the participants took six or seven tablets per week. 11 (0·5%) of the 2253 participants reported grade 3 toxicity during the run-in period, with no upper gastrointestinal bleeding (any grade) in the gastro-oesophageal cancer cohort. The most frequent grade 1-2 toxicity overall was dyspepsia (246 [11%] of 2253 participants). INTERPRETATION: Aspirin is well-tolerated after radical cancer therapy. Toxicity has been low and there is no evidence of a difference in adherence, acceptance of randomisation, or toxicity between the different cancer cohorts. Trial recruitment continues to determine whether aspirin could offer a potential low cost and well tolerated therapy to improve cancer outcomes. FUNDING: Cancer Research UK, The National Institute for Health Research Health Technology Assessment Programme, The MRC Clinical Trials Unit at UCL.

High-dose etoposide and cyclophosphamide in adults and children with primary refractory and multiply relapsed acute leukaemias: The Royal Marsden experience.

INTRODUCTION: For patients with primary refractory and relapsed acute leukaemias allogeneic stem cell transplantation is the only hope for cure, but morphological remission is not always achieved after standard salvage regimens. Here we review the experience with high-dose etoposide and cyclophosphamide (HD-Et/Cy) in relapsed/refractory acute leukaemias at the Royal Marsden Hospital. PATIENTS AND METHODS: Twenty-three patients (15 adults, 8 children) with refractory/relapsed acute myeloblastic (n = 18; 78%), lymphoblastic (n = 4; 17%) or biphenotypic (n = 1; 4%) leukaemia who had failed to respond to at least one previous line of chemotherapy received HD-Et/Cy at our institution between 2006 and 2015. RESULTS: Overall response rate was 21.7% (95%CI 4.0-40.0). Median overall survival was 14.8 months (95%CI 9.1-49.1). Eight (35%) patients (7 AML, 1 biphenotypic leukaemia) proceeded to allogeneic transplant after one cycle of HD-Et/Cy: four of them (50%; 3 adults, 1 child) in complete remission and another four children (50%) with aplastic bone marrow with scattered blasts. Among the transplant recipients, three with AML (38%), ie. one adult (responder) and two children with aplastic bone marrow with scattered blasts, became long-term survivors 9.8, 4.4 and 2.5 years post-HD-Et/Cy, respectively. Toxicity profile was comparable to similar regimens with no treatment-related deaths. The most common grade 3-4 toxicity was febrile neutropenia (96%). CONCLUSIONS: HD-Et/Cy can salvage patients with refractory/relapsed AML who remain candidates for allogeneic stem cell transplantation after failure of standard salvage regimens and do not have access to clinical trials.

Post-radiotherapy apparent diffusion coefficient (ADC) in children and young adults with high-grade gliomas and diffuse intrinsic pontine gliomas.

Objectives: Diffusion-weighted magnetic resonance imaging (DW-MRI) offers potential to monitor response and predict survival in high-grade gliomas (HGG) and diffuse intrinsic pontine gliomas (DIPG). We hypothesized that post-radiotherapy DW-MRI may provide prognostic imaging biomarkers in children and young adults with these tumors. Methods: Patients aged ≤21 years diagnosed between 2005 and 2012 were eligible. The tumor median apparent diffusion coefficient (ADC) and its 5th percentile (C5-ADC) were determined at the first post-radiotherapy scan and at the time of radiological progression. DW-MRI parameters were correlated with survival endpoints, temozolomide use and pseudoprogression, when it occurred. Results: Out of 40 patients (20 HGG, 20 DIPG), 23 had evaluable DW-MRI post-radiotherapy and 25 at radiological progression. There were 6 episodes of pseudoprogression. Hazard ratios (95%CI) for progression-free survival were 0.998 (0.993-1.003) for median ADC and 1.003 (0.996-1.010) for C5-ADC. Hazard ratios (95%CI) for overall survival were 1.0009 (0.996-1.006) for median ADC and 0.998 (0.992-1.004) for C5-ADC. Post-radiotherapy median and C5-ADC values were not significantly different between patients treated with radiotherapy alone versus radiotherapy/temozolomide. The median and C5-ADC values were not significantly different at the time of pseudoprogression compared to those at tumor progression. Conclusions: Post-radiotherapy median ADC and C5-ADC were not prognostic, nor able to differentiate radiosensitization with temozolomide or occurrence of pseudoprogression in this cohort of HGG and DIPG patients. Further exploration of alternative DW parameters, study timepoints or data modeling may contribute to the development of prognostic/predictive imaging biomarkers for children and young adults with HGG or DIPG.

Novel 18-gene signature for predicting relapse in ER-positive, HER2-negative breast cancer.

BACKGROUND: Several prognostic signatures for early oestrogen receptor-positive (ER+) breast cancer have been established with a 10-year follow-up. We tested the hypothesis that signatures optimised for 0-5-year and 5-10-year follow-up separately are more prognostic than a single signature optimised for 10 years. METHODS: Genes previously identified as prognostic or associated with endocrine resistance were tested in publicly available microarray data set using Cox regression of 747 ER+/HER2- samples from post-menopausal patients treated with 5 years of endocrine therapy. RNA expression of the selected genes was assayed in primary ER+/HER2- tumours from 948 post-menopausal patients treated with 5 years of anastrozole or tamoxifen in the TransATAC cohort. Prognostic signatures for 0-10, 0-5 and 5-10 years were derived using a penalised Cox regression (elastic net). Signature comparison was performed with likelihood ratio statistics. Validation was done by a case-control (POLAR) study in 422 samples derived from a cohort of 1449. RESULTS: Ninety-three genes were selected by the modelling of microarray data; 63 of these were significantly prognostic in TransATAC, most similarly across each time period. Contrary to our hypothesis, the derived early and late signatures were not significantly more prognostic than the 18-gene 10-year signature. The 18-gene 10-year signature was internally validated in the TransATAC validation set, showing prognostic information similar to that of Oncotype DX Recurrence Score, PAM50 risk of recurrence score, Breast Cancer Index and IHC4 (score based on four IHC markers), as well as in the external POLAR case-control set. CONCLUSIONS: The derived 10-year signature predicts risk of metastasis in patients with ER+/HER2- breast cancer similar to commercial signatures. The hypothesis that early and late prognostic signatures are significantly more informative than a single signature was rejected.

Randomized Trial of Tablet Computers for Education and Learning in Children and Young People with Low Vision.

SIGNIFICANCE: Mobile devices such as tablet computers have become widely available as mainstream devices and are also used in some schools, but there is an absence of robust information regarding the efficacy of any optical/electronic low vision device or tablet computer in supporting education of young people with low vision. PURPOSE: A randomized controlled trial (RCT) is needed to measure the impact of tablet computers on education, specifically on independent access to educational material, in children and young people with low vision. We conducted a pilot RCT to determine the feasibility of conducting a full-scale trial. METHODS: This was a randomized multicenter pilot trial across two sites in the United Kingdom and one site in India. Forty children and young people aged 10 to 18 years with low vision (best-corrected visual acuity for distance between <20/60 [0.48 logMAR] and 20/400 [1.30 logMAR] in the better eye) in the United Kingdom (n = 20) and India (n = 20) were randomized to two parallel arms, with a 1:1 allocation ratio, to control (n = 20) or intervention (n = 20). Control group participants received standard low vision care. The intervention group received a tablet computer (iPad) with low vision applications and instruction in its use, including accessibility features. Four primary outcomes included (1) 6-month recruitment rate, (2) retention of participants for 3 months, (3) acceptance/usage of device, and (4) accessibility of device. RESULTS: Nineteen participants (95%) enrolled within 6 months in the United Kingdom, and 20 participants (100%), in India. Retention at 3 months was 85% (n = 17) in the United Kingdom and 95% (n = 19) in India. More than one half of participants reported using a tablet computer at school at least once every day. The majority (90%) found it easily accessible. CONCLUSIONS: This study demonstrated that it is feasible to recruit children and young people with low vision into an international multicenter RCT of electronic assistive technology. Regardless of geographical location, children and young people with low vision reported using tablet computers at least once a day at school and accessed them easily.

Comparison of Immediate versus Delayed DIEP Flap Reconstruction in Women Who Require Postmastectomy Radiotherapy.

BACKGROUND: The authors investigated aesthetic outcome and patient satisfaction in women who have undergone deep inferior epigastric artery perforator (DIEP) flap reconstruction in the setting of postmastectomy radiotherapy. Patients who underwent DIEP flap reconstruction without postmastectomy radiotherapy were the control group. METHODS: Participants who had undergone DIEP flap reconstruction between September 1, 2009, and September 1, 2014, were recruited, answered the BREAST-Q, and underwent three-dimensional surface-imaging. A panel assessed the aesthetic outcome by reviewing these images. RESULTS: One hundred sixty-seven women participated. Eighty women (48 percent) underwent immediate DIEP flap reconstruction and no postmastectomy radiotherapy; 28 (17 percent) underwent immediate DIEP flap reconstruction with postmastectomy radiotherapy; 38 (23 percent) underwent simple mastectomy, postmastectomy radiotherapy, and DIEP flap reconstruction; and 21 (13 percent) underwent mastectomy with temporizing implant, postmastectomy radiotherapy, and DIEP flap reconstruction. Median satisfaction scores were significantly different among the groups (p < 0.05). Post hoc comparison demonstrated that women who had an immediate DIEP flap reconstruction were significantly less satisfied if they had postmastectomy radiotherapy. In women requiring radiotherapy, those undergoing delayed reconstruction after a simple mastectomy were most satisfied, but there was no significant difference between the immediate DIEP flap and temporizing implant groups. Median panel scores differed among groups, being significantly higher if the immediate reconstruction was not subjected to radiotherapy. There was no significant difference in panel assessment among the three groups of women who had received radiotherapy. CONCLUSIONS: Patients who avoid having their immediate DIEP flap reconstruction irradiated are more satisfied and have better aesthetic outcome than those who undergo postmastectomy radiotherapy. In women requiring radiotherapy and who wish to have an immediate or "delayed-immediate" reconstruction, there were no significant differences in panel or patient satisfaction. Therefore, immediate DIEP flap reconstruction or mastectomy with temporizing implant then DIEP flap surgery are acceptable treatment pathways in the context of post-mastectomy radiotherapy.

Validation of the Vectra XT three-dimensional imaging system for measuring breast volume and symmetry following oncological reconstruction.

PURPOSE: Three-dimensional surface imaging (3D-SI) of the breasts enables the measurement of breast volume and shape symmetry. If these measurements were sufficiently accurate and repeatable, they could be used in planning oncological breast surgery and as an objective measure of aesthetic outcome. The aim of this study was to validate the measurements of breast volume and symmetry provided by the Vectra XT imaging system. METHODS: To validate measurements, breast phantom models of true volume between 100 and 1000 cm3 were constructed and varying amounts removed to mimic breast tissue 'resections'. The volumes of the phantoms were measured using 3D-SI by two observers and compared to a gold standard. For intra-observer repeatability and inter-observer reproducibility in vivo, 16 patients who had undergone oncological breast surgery had breast volume and symmetry measured three times by two observers. RESULTS: A mean relative difference of 2.17 and 2.28% for observer 1 and 2 respectively was seen in the phantom measurements compared to the gold standard (n = 45, Bland Altman agreement). Intra-observer variation over ten repeated measurements demonstrated mean coefficients of variation (CV) of 0.58 and 0.49%, respectively. The inter-observer variation demonstrated a mean relative difference of 0.11% between the two observers. In patients, intra-observer variation over three repeated volume measurements for each observer was 3.9 and 3.8% (mean CV); the mean relative difference between observers was 5.78%. For three repeated shape symmetry measurements using RMS projection difference between the two breasts, the intra-observer variations were 8 and 14% (mean CV), the mean relative difference between observers was 0.43 mm for average symmetry values that ranged from about 3.5 to 15.5 mm. CONCLUSION: This first validation of breast volume and shape symmetry measurements using the Vectra XT 3D-SI system suggests that these measurements have the potential to assist in pre-operative planning and also as a measure of aesthetic outcome.

Low-cost Kinect Version 2 imaging system for breath hold monitoring and gating: Proof of concept study for breast cancer VMAT radiotherapy.

Voluntary inspiration breath hold (VIBH) for left breast cancer patients has been shown to be a safe and effective method of reducing radiation dose to the heart. Currently, VIBH protocol compliance is monitored visually. In this work, we establish whether it is possible to gate the delivery of radiation from an Elekta linac using the Microsoft Kinect version 2 (Kinect v2) depth sensor to measure a patient breathing signal. This would allow contactless monitoring during VMAT treatment, as an alternative to equipment-assisted methods such as active breathing control (ABC). Breathing traces were acquired from six left breast radiotherapy patients during VIBH. We developed a gating interface to an Elekta linac, using the depth signal from a Kinect v2 to control radiation delivery to a programmable motion platform following patient breathing patterns. Radiation dose to a moving phantom with gating was verified using point dose measurements and a Delta4 verification phantom. 60 breathing traces were obtained with an acquisition success rate of 100%. Point dose measurements for gated deliveries to a moving phantom agreed to within 0.5% of ungated delivery to a static phantom using both a conventional and VMAT treatment plan. Dose measurements with the verification phantom showed that there was a median dose difference of better than 0.5% and a mean (3% 3 mm) gamma index of 92.6% for gated deliveries when using static phantom data as a reference. It is possible to use a Kinect v2 device to monitor voluntary breath hold protocol compliance in a cohort of left breast radiotherapy patients. Furthermore, it is possible to use the signal from a Kinect v2 to gate an Elekta linac to deliver radiation only during the peak inhale VIBH phase.

Development and responses of brain metastases during treatment with trastuzumab emtansine (T-DM1) for HER2 positive advanced breast cancer: A single institution experience.

Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that does not cross an intact blood-brain barrier. In the EMILIA trial of T-DM1 vs capecitabine/lapatinib for HER2 positive advanced breast cancer, all patients had baseline brain imaging, and 9/450 (2%) of patients with negative baseline imaging developed new brain disease during T-DM1. We assessed the frequency of brain progression in clinical practice, without routine baseline imaging. We undertook a retrospective study of all patients treated with T-DM1 at the Royal Marsden Hospital from 2011 to 2016. Data collected included baseline characteristics, previous treatment for advanced breast cancer, sites of metastatic disease, duration of T-DM1, sites of progression, and treatment of CNS progression. Fifty-five patients were identified who had received a median of two prior lines of treatment (range 0-5). All were HER2 positive; 45 patients had IHC 3+ tumors and 10 were ISH positive. Patients received a median of 12 cycles of T-DM1 (range 1-34), and six remain on treatment at the time of analysis. Before commencing T-DM1, 16/55 (29%) had known brain metastases (treated with whole brain [9] stereotactic radiotherapy [6] or both [1]). Brain was the first site of progression in 56% (9/16) patients, with a median time to brain progression of 9.9 months (95% CI 3.9-12.2). In patients without known baseline brain metastases, 17.9% (7/39) developed new symptomatic brain disease during T-DM1, after a median of 7.5 months (95%CI 3.8-9.6). Brain progression was isolated, with control of extra-cranial disease in 4/7 patients. Only one patient was suitable for stereotactic radiotherapy. Median time to extra-cranial progression in all patients was 11.5 months (95% CI 9.1-17.7), and median OS in all patients was 17.8 months (95% CI 14.2-22). In patients not screened for brain metastases at baseline, the brain was the first site of progression in a significant proportion. Baseline brain imaging may have a role in standard practice for patients commencing T-DM1 therapy.

Impact of tumour histological subtype on chemotherapy outcome in advanced oesophageal cancer.

AIM: To investigate the impact of histology on outcome in advanced oesophageal cancer treated with first-line fluoropyrimidine-based chemotherapy. METHODS: Individual patient data were pooled from three randomised phase III trials of fluoropyrimidine-based chemotherapy ± platinum/anthracycline in patients with advanced, untreated gastroesophageal adenocarcinoma or squamous cell carcinoma (SCC) randomised between 1994 and 2005. The primary endpoint was overall survival of oesophageal cancer patients according to histology. Secondary endpoints were response rates and a toxicity composite endpoint. RESULTS: Of the total 1836 randomised patients, 973 patients (53%) were eligible (707 patients with gastric cancer were excluded), 841 (86%) had adenocarcinoma and 132 (14%) had SCC. There was no significant difference in survival between patients with adenocarcinoma and SCC, with median overall survivals of 9.5 mo vs 7.6 mo (HR = 0.85, 95%CI: 0.70-1.03, P = 0.09) and one-year survivals of 38.8% vs 28.2% respectively. The overall response rate to chemotherapy was 44% for adenocarcinoma vs 33% for SCC (P = 0.01). There was no difference in the frequency of the toxicity composite endpoint between the two groups. CONCLUSION: There was no significant difference in survival between adenocarcinoma and SCC in patients with advanced oesophageal cancer treated with fluoropyrimidine-based chemotherapy despite a trend for worse survival and less chemo-sensitivity in SCC. Tolerance to treatment was similar in both groups. This analysis highlights the unmet need for SCC-specific studies in advanced oesophageal cancer and will aid in the design of future trials of targeted agents.

The potential role of three-dimensional surface imaging as a tool to evaluate aesthetic outcome after Breast Conserving Therapy (BCT).

PURPOSE: To establish whether objective measurements of symmetry of volume and shape using three-dimensional surface imaging (3D-SI) can be used as surrogate markers of aesthetic outcome in patients who have undergone breast conserving therapy (BCT). METHODS: Women who had undergone unilateral BCT in the preceding 1-6 years were invited to participate. Participants completed a satisfaction questionnaire (BREAST-Q) and underwent 3D-SI. Volume and surface symmetry were measured on the images. Assessment of aesthetic outcome was undertaken by a panel of clinicians. The Kruskal-Wallis test was used to assess the relationship between volume and shape symmetry measurements with the panel score. Spearman's rho correlations were used to assess the relationship between the measurements and patient satisfaction. RESULTS: 200 women participated. Median volume symmetry was 87% (IQR 78-93) and shape symmetry was 5.9 mm (IQR 4.2-8.0). The participants were grouped according to panel assessment of aesthetic outcome (poor, fair, good, excellent) and the median volume and shape symmetry was calculated for each group. Volume symmetry significantly differed between the groups. Post hoc pairwise comparisons demonstrated that these differences existed between panel scores of fair versus good and good versus excellent. Median shape symmetry also differed according to patient panel groups with four significant pairwise comparisons between poor versus good, poor versus excellent, fair versus good and fair versus excellent. There was a significant but weak correlation of both volume symmetry and surface asymmetry with BREAST-Q scores (correlation coefficients 0.187 and -0.229, respectively). CONCLUSION: Breast volume and shape symmetry are both associated with panel assessment scores and patient satisfaction. The objective volume and shape symmetry measures were strongly associated with panel assessment scores, such that a 3D-SI tool could replace panel assessment as a faster and more objective method of evaluating aesthetic outcomes.

Initial experience of the BREAST-Q breast-conserving therapy module.

PURPOSE: The most recently developed module of the BREAST-Q, a validated patient outcome measure, is for patients who have undergone breast-conserving therapy (BCT) for cancer. This aim of this study was to assess patient satisfaction and quality of life after BCT using BREAST-Q, investigate clinical risk factors for lower satisfaction and explore the relationship between patient satisfaction with the appearance of their breasts and the other domains of the BREAST-Q. METHODS: Women who had undergone unilateral BCT in the preceding 1-6 years were invited to participate at the time of their annual surveillance mammogram. Clinicopathological data were collected from an electronic database. Linear regression was used to evaluate risk factors for lower satisfaction. Spearman's rho correlation coefficients were calculated to evaluate the relationship between domains. RESULTS: 200 women completed the questionnaire. Mean age was 60 years (SD 11.1). Time from surgery was 35.5 months (SD 17.8). Median score for 'Satisfaction with breasts' was 68 (interquartile range 55-80). Lowest scores were for 'sexual wellbeing' (57, IQR 45-66). On multivariate analysis, BMI at the time of surgery (p = 0.002), delayed wound healing (p = 0.001) and axillary surgery (p = 0.003) were independent risk factors for lower satisfaction. There was significant correlation between 'Satisfaction with breasts' and all other BREAST-Q domains. CONCLUSION: High BMI, delayed wound healing and axillary surgery are risk factors for lower patient satisfaction. This first publication reporting the whole dataset for the BREAST-Q BCT will serve as a benchmark for future studies of patient satisfaction following BCT.

Pseudoprogression in children, adolescents and young adults with non-brainstem high grade glioma and diffuse intrinsic pontine glioma.

Pseudoprogression (PsP) is a treatment-related phenomenon which hinders response interpretation. Its prevalence and clinical impact have not been evaluated in children/adolescents. We assessed the characteristics, risk factors and prognosis of PsP in children/adolescents and young-adults diagnosed with non-brainstem high grade gliomas (HGG) and diffuse intrinsic pontine gliomas (DIPG). Patients aged 1-21 years diagnosed with HGG or DIPG between 1995 and 2012 who had completed radiotherapy were eligible. PsP was assessed according to study-specific criteria and correlated with first-line treatment, molecular biomarkers and survival. Ninety-one patients (47 HGG, 44 DIPG) were evaluable. Median age: 10 years (range, 2-20). Eleven episodes of PsP were observed in 10 patients (4 HGG, 6 DIPG). Rates of PsP: 8.5 % (HGG); 13.6 % (DIPG). Two episodes of PsP were based on clinical findings alone; nine episodes had concurrent radiological changes: increased size of lesions (n = 5), new focal enhancement (n = 4). Temozolomide, MGMT methylation or H3F3A mutations were not found to be associated with increased occurrence of PsP. For HGG, 1-year progression-free survival (PFS) was 41.9 % no-PsP versus 100 % PsP (p = 0.041); differences in 1-year overall survival (OS) were not significant. For DIPG, differences in 1-year PFS and OS were not statistically significant. Hazard ratio (95 %CI) of PsP for OS was 0.551 (0.168-1.803; p = 0.325) in HGG; and 0.308 (0.107-0.882; p = 0.028) in DIPG. PsP occurred in both pediatric HGG and DIPG patients at a comparable rate to adult HGG. PsP was associated with improved 1-yr PFS in HGG patients. PsP had a protective effect upon OS in DIPG patients.

Extrinsic factors can mediate resistance to BRAF inhibition in central nervous system melanoma metastases.

Here, we retrospectively review imaging of 68 consecutive unselected patients with BRAF V600-mutant metastatic melanoma for organ-specific response and progression on vemurafenib. Complete or partial responses were less often seen in the central nervous system (CNS) (36%) and bone (16%) compared to lung (89%), subcutaneous (83%), spleen (71%), liver (85%) and lymph nodes/soft tissue (83%), P < 0.001. CNS was also the most common site of progression. Based on this, we tested in vitro the efficacy of the BRAF inhibitors PLX4720 and dabrafenib in the presence of cerebrospinal fluid (CSF). Exogenous CSF dramatically reduced cell death in response to both BRAF inhibitors. Effective cell killing was restored by co-administration of a PI-3 kinase inhibitor. We conclude that the efficacy of vemurafenib is variable in different organs with CNS being particularly prone to resistance. Extrinsic factors, such as ERK- and PI3K-activating factors in CSF, may mediate BRAF inhibitor resistance in the CNS.