BACKGROUND: Lymphoedema develops after axillary clearance (ANC) in 25% of patients. This prospective, multi-centre study compared multi-frequency bioimpedance spectroscopy (BIS) with arm volume measurement to: (1) determine which test has better diagnostic accuracy, (2) identify factors predicting development of lymphoedema, and its effect on quality-of-life. METHODS: Participants (N = 1100) underwent measurements pre and post-ANC surgery for breast cancer. Relative arm volume increase (RAVI) of >10% diagnosed lymphoedema. Predictors of lymphoedema were determined using logistic regression. Optimal diagnostic method was assessed using diagnostic accuracy. Quality-of-life was assessed using the FACT B + 4 questionnaire. RESULTS: Lymphoedema was diagnosed in 22.8% women using RAVI > 10%, 45.6% using BIS criteria, while 24.5% underwent compression sleeve application by 24 months. BMI > 30 was an independent factor for both development (p = 0.005) and progression (p = 0.015) of lymphoedema. RAVI at 1 month, BMI > 30 and number of involved nodes contributed to a novel scoring model to predict lymphoedema by 36 months. Larger decreases in QoL scores post-surgery occurred in lymphoedema patients (p < 0.001). Progression to moderate lymphoedema occurred in 15% patients after sleeve application. CONCLUSIONS: RAVI measurement was the best diagnostic tool for lymphoedema. BIS alone is not appropriate for lymphoedema screening or diagnosis. BMI > 30 predicted lymphoedema diagnosis and progression.

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Cancer stem-like cells (CSC) contribute to therapy resistance and recurrence. Focal adhesion kinase (FAK) has a role in CSC regulation. We determined the effect of FAK inhibition on breast CSC activity alone and in combination with adjuvant therapies. FAK inhibition reduced CSC activity and self-renewal across all molecular subtypes in primary human breast cancer samples. Combined FAK and paclitaxel reduced self-renewal in triple negative cell lines. An invasive breast cancer cohort confirmed high FAK expression correlated with increased risk of recurrence and reduced survival. Co-expression of FAK and CSC markers was associated with the poorest prognosis, identifying a high-risk patient population. Combined FAK and paclitaxel treatment reduced tumour size, Ki67, ex-vivo mammospheres and ALDH+ expression in two triple negative patient derived Xenograft (PDX) models. Combined treatment reduced tumour initiation in a limiting dilution re-implantation PDX model. Combined FAK inhibition with adjuvant therapy has the potential to improve breast cancer survival.

Summary Background Current published asthma predictive tools have moderate positive likelihood ratios (+LR) but high negative likelihood ratios (−LR) based on their recommended cut‐offs, which limit their clinical usefulness. Objective To develop a simple clinically applicable asthma prediction tool within a population‐based birth cohort. Method Children from the Manchester Asthma and Allergy Study (MAAS) attended follow‐up at ages 3, 8 and 11 years. Data on preschool wheeze were extracted from primary‐care records. Parents completed validated respiratory questionnaires. Children were skin prick tested (SPT). Asthma at 8/11 years (school‐age) was defined as parentally reported (a) physician‐diagnosed asthma and wheeze in the previous 12 months or (b) ≥3 wheeze attacks in the previous 12 months. An asthma prediction tool (MAAS APT) was developed using logistic regression of characteristics at age 3 years to predict school‐age asthma. Results Of 336 children with physician‐confirmed wheeze by age 3 years, 117(35%) had school‐age asthma. Logistic regression selected 5 significant risk factors which formed the basis of the MAAS APT: wheeze after exercise; wheeze causing breathlessness; cough on exertion; current eczema and SPT sensitisation(maximum score 5). A total of 281(84%) children had complete data at age 3 years and were used to test the MAAS APT. Children scoring ≥3 were at high risk of having asthma at school‐age (PPV > 75%; +LR 6.3, −LR 0.6), whereas children who had a score of 0 had very low risk(PPV 9.3%; LR 0.2). Conclusion MAAS APT is a simple asthma prediction tool which could easily be applied in clinical and research settings.

Introduction and objectivesReliable predictors of survival in malignant pleural effusions (MPE) have far reaching applications in clinical practice, not least tailoring individual treatment strategies. The ‘LENT’ score (pleural fluid Lactate dehydrogenase; Eastern Cooperative Oncology Group performance score; Neutrophil-to-lymphocyte ratio; Tumour type) was developed and validated as a clinical prognostic scoring system from three international prospective patient databases.1 The aim of this study was to evaluate the LENT score in a further UK population of patients with MPE, geographically separate from those in the original study.MethodsOur hospital is a large tertiary centre for a physician-led pleural service (including medical thoracoscopy), a regional mesothelioma centre and a regional thoracic surgical centre. A retrospective study of all patients with positive (i.e. diagnostic for malignancy) pleural cytology or histology from 2010 to 2014 was undertaken. This timeframe allowed a minimum of 12 months follow-up for all patients. Survival data was obtained from national death registries. All patients in whom all LENT criteria were available were included in the analysis. A Kaplan-Meier curve and a Cox regression model were used to assess the LENT risk category. Harrell’s C statistic was used to assess the accuracy of the regression model and mortality rates at time points of interest were calculated.ResultsThe LENT score was calculated for 101 patients diagnosed with MPE. The median survival (days, IQR) for the low (n = 18), medium (n = 54) and high risk (n = 29) groups were: 254 (152–602), 102 (40–301) and 16 (7–42). In the high risk group, only 31% of patients survived 1 month and 7% survived 6 months. There is a statistically significant difference in the survival times in the different risk groups according to the log-rank test (p < 0.001). Harrell’s C statistic in this cohort is 0.69 (see Figure 1).Abstract P185 Figure 1 ConclusionsThe LENT scoring system has again been shown to be a good tool for predicting survival in patients with MPE when applied to a geographically distinct cohort of patients to the original study. The LENT score continues to be a clinically valuable tool in the assessment of patients with MPE.Reference1 Clive AO, et al. Thorax 2014;69(12):1098–104

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Background Excess adiposity at diagnosis and weight gain during chemotherapy is associated with tumour recurrence and chemotherapy toxicity. We assessed the efficacy of intermittent energy restriction (IER) vs continuous energy restriction (CER) for weight control and toxicity reduction during chemotherapy. Methods One hundred and seventy-two women were randomised to follow IER or CER throughout adjuvant/neoadjuvant chemotherapy. Primary endpoints were weight and body fat change. Secondary endpoints included chemotherapy toxicity, cardiovascular risk markers, and correlative markers of metabolism, inflammation and oxidative stress. Results Primary analyses showed non-significant reductions in weight (−1.1 (−2.4 to +0.2) kg, p = 0.11) and body fat (−1.0 (−2.1 to +0.1) kg, p = 0.086) in IER compared with CER. Predefined secondary analyses adjusted for body water showed significantly greater reductions in weight (−1.4 (−2.5 to −0.2) kg, p = 0.024) and body fat (−1.1 (−2.1 to −0.2) kg, p = 0.046) in IER compared with CER. Incidence of grade 3/4 toxicities were comparable overall (IER 31.0 vs CER 36.5%, p = 0.45) with a trend to fewer grade 3/4 toxicities with IER (18%) vs CER (31%) during cycles 4–6 of primarily taxane therapy (p = 0.063). Conclusions IER is feasible during chemotherapy. The potential efficacy for weight control and reducing toxicity needs to be tested in future larger trials. Clinical trial registration ISRCTN04156504.

Frequency of obstetric fistula during the first pregnancy is not increased among women who experience their first pregnancy within 2 years of menarche.