• The South West Area Mesothelioma and Pemetrexed trial: a multicentre prospective observational study evaluating novel markers of chemotherapy response and prognostication.

    14 February 2018

    BACKGROUND: Robust markers that predict prognosis and detect early treatment response in malignant pleural mesothelioma (MPM) would enhance patient care. METHODS: Consecutive patients with MPM who were considered fit for first-line chemotherapy were prospectively recruited. Patients of similar performance status opting for best supportive care were included as a comparator group. Baseline and interval CT, PET-CT and serum markers (mesothelin, fibulin-3 and neutrophil-lymphocyte ratio (NLR)) were obtained, and patients followed up for a minimum 12 months. FINDINGS: Seventy-three patients were recruited (58 chemotherapy/15 comparator arm). Baseline TGV (total glycolytic volume on PET-CT) was an independent predictor of worse overall survival (OS) (P=0.001). Change in interval TGV(baseline/after two cycles of chemotherapy) did not predict OS or chemotherapy response on CT. Baseline NLR<4 was an independent predictor of better OS (median survival 453 (IQR 272-576) days vs NLR⩾4, 257 (IQR 147-490), P=0.002). Although baseline serum mesothelin did not predict OS, a falling level at 8 weeks significantly predicted longer time to progression (TTP) (P<0.001). INTERPRETATION: Neutrophil-lymphocyte ratio and baseline TGV predict prognosis in malignant pleural mesothelioma (MPM), but PET-CT is unhelpful in monitoring chemotherapy response. Serum mesothelin is a useful early treatment response marker when measured serially during chemotherapy and may have a role in evaluating patients' treatment response.

  • The effect of chemotherapy on health-related quality of life in mesothelioma: results from the SWAMP trial.

    14 February 2018

    BACKGROUND: The effect of chemotherapy on health-related quality of life (HRQoL) in malignant pleural mesothelioma (MPM) is poorly understood. Patient-individualised prognostication and prediction of treatment response from chemotherapy is useful but little evidence exists to guide practice. METHOD: Consecutive patients with MPM who were fit for first-line chemotherapy with pemetrexed and cisplatin\carboplatin were recruited and followed up for a minimum of 12 months. This study focussed on the HRQoL outcomes of these patients using the EQ-5D, EORTC QLQ-C30 and LC13. RESULTS: Seventy-three patients were recruited of which 58 received chemotherapy and 15 opted for best supportive care (BSC). Compliance with HRQoL questionnaires was 98% at baseline. The chemotherapy group maintained HRQoL compared with the BSC group whose overall HRQoL fell (P=0.006) with worsening dyspnoea and pain. The impact of chemotherapy was irrespective of histological subtype although those with non-epithelioid disease had worse HRQoL at later time points (P=0.012). Additionally, those with a falling mesothelin or improvement on modified-RECIST CT at early follow-up had a better HRQoL at 16 weeks. CONCLUSIONS: HRQoL was maintained following chemotherapy compared with a self-selected BSC group. Once chemotherapy is initiated, a falling mesothelin or improved RECIST CT findings infer a quality-of-life advantage.

  • The impact of the 21-gene assay on adjuvant treatment decisions in oestrogen receptor-positive early breast cancer: a prospective study.

    15 December 2017

    BACKGROUND: International guidelines, including NICE, recommend using the 21-gene Recurrence Score assay for guiding adjuvant treatment decisions in ER+, HER2-negative early breast cancer (BC). We investigated the impact of adding this assay to standard pathological tests on clinicians'/patients' treatment decisions and on patients' decisional conflict in the United Kingdom. METHODS: In this prospective multicentre study, eligibility criteria included: ER+ HER2-negative BC (N0/Nmic for patients ⩽50 years; ⩽3 positive lymph nodes for patients >50 years) and being fit for chemotherapy. Physicians'/patients' treatment choices and patients' decisional conflict were recorded pre- and post testing. RESULTS: The analysis included 137 patients. Overall, adjuvant treatment recommendations changed in 40.7% of patients, with the direction of the change consistent with the Recurrence Score results (net decrease in chemotherapy recommendation rate in low Recurrence Score patients and net increase in high Recurrence Score patients). Patients' choices were generally consistent with physicians' recommendations. Post-testing, patients' decisional conflict decreased significantly (P<0.0001). In the 67 patients meeting the NICE criteria for testing, the recommendation change rate was 49.3%. CONCLUSIONS: Recurrence Score testing significantly influenced treatment recommendations overall and in the subgroup of patients meeting the NICE criteria, suggesting that this test could substantially alter treatment patterns in the United Kingdom.

  • The mutational frequency of BRAF and KRAS in low-grade serous testicular neoplasms-a case series.

    5 February 2018

    AIMS: Low-grade serous neoplasms of the testis are rare neoplasms that show striking morphological similarities with the better-understood ovarian neoplasms. This study is to see if there are similar molecular abnormalities in these two tumours. The cell of origin, relationship with serous ovarian tumour and the pathogenesis of these neoplasms are not fully established. METHODS AND RESULTS: As low-grade serous ovarian neoplasms are known to harbour mutations in the MAPK pathway, we investigated the involvement of BRAF and KRAS mutations in low-grade testicular serous tumour by performing mutational analysis of seven cases. Mutational analysis was performed by melting curve analysis followed by bidirectional sequencing. Our findings showed BRAF and/or KRAS mutations in three of the seven cases, which is similar to the proportions reported in low-grade ovarian serous neoplasms. Of these three cases, one showed co-mutation of BRAF and KRAS. CONCLUSION: The findings of this study are in support of a role of aberrant signalling of the MAPK pathway in the pathogenesis of low-grade serous testicular neoplasms, and provide a genetic link between low-grade testicular and ovarian serous tumours.

  • Effect of Hot Tea Consumption and Its Interactions With Alcohol and Tobacco Use on the Risk for Esophageal Cancer: A Population-Based Cohort Study.

    15 February 2018

    Background: Although consumption of tea at high-temperatures has been suggested as a risk factor for esophageal cancer, an association has not been observed consistently, and whether any relationship is independent of alcohol and tobacco exposure has not been evaluated. Objective: To examine whether high-temperature tea drinking, along with the established risk factors of alcohol consumption and smoking, is associated with esophageal cancer risk. Design: China Kadoorie Biobank, a prospective cohort study established during 2004 to 2008. Setting: 10 areas across China. Participants: 456 155 persons aged 30 to 79 years. Those who had cancer at baseline or who reduced consumption of tea, alcohol, or tobacco before baseline were excluded. Measurements: The usual temperature at which tea was consumed, other tea consumption metrics, and lifestyle behaviors were self-reported once, at baseline. Outcome was esophageal cancer incidence up to 2015. Results: During a median follow-up of 9.2 years, 1731 incident esophageal cancer cases were documented. High-temperature tea drinking combined with either alcohol consumption or smoking was associated with a greater risk for esophageal cancer than hot tea drinking alone. Compared with participants who drank tea less than weekly and consumed fewer than 15 g of alcohol daily, those who drank burning-hot tea and 15 g or more of alcohol daily had the greatest risk for esophageal cancer (hazard ratio [HR], 5.00 [95% CI, 3.64 to 6.88]). Likewise, the HR for current smokers who drank burning-hot tea daily was 2.03 (CI, 1.55 to 2.67). Limitation: Tea consumption was self-reported once, at baseline, leading to potential nondifferential misclassification and attenuation of the association. Conclusion: Drinking tea at high temperatures is associated with an increased risk for esophageal cancer when combined with excessive alcohol or tobacco use. Primary Funding Source: National Natural Science Foundation of China and National Key Research and Development Program.