Making an accurate diagnosis of anterior mediastinal lesions: a proposal for a new diagnostic algorithm from the BTOG Thymic Malignancies Special Interest Group.

Due to the rising demand in cross-sectional thoracic imaging, anterior mediastinal lesions are being identified with increasing frequency. Following iterative and multidisciplinary discussions, the BTOG Thymic Malignancies Special Interest Group have developed an algorithm to standardise the diagnostic approach for these relatively uncommon but important conditions which span from benign (thymic remnant, thymic hyperplasia and thymic cysts) to suspected localised thymomas to suspected more aggressive malignancy (thymic carcinoma, lymphoma and germ cell tumours). For each condition, we provide a brief description, an overview of the key radiological findings and a description of the proposed algorithm including the rationale behind the recommendations. We also highlight the role of magnetic resonance (MR) imaging for the characterisation of anterior mediastinal masses in specific indications when the necessary local resources and expertise exist. In addition, we hope this provides the rationale for service development in MR of the anterior mediastinum where current resource and expertise requires development. Through this standardised pathway, we hope to drive improvements in patient care by rationalising surveillance schedules, avoiding unnecessary resections of benign entities with their associated morbidity and optimising the diagnostic work-up prior to the appropriate treatment of anterior mediastinal malignancies.

Residual ctDNA after treatment predicts early relapse in patients with early-stage non-small cell lung cancer.

BACKGROUND: Identification of residual disease in patients with localized non-small cell lung cancer (NSCLC) following treatment with curative intent holds promise to identify patients at risk of relapse. New methods can detect circulating tumour DNA (ctDNA) in plasma to fractional concentrations as low as a few parts per million, and clinical evidence is required to inform their use. PATIENTS AND METHODS: We analyzed 363 serial plasma samples from 88 patients with early-stage NSCLC (48.9%/28.4%/22.7% at stage I/II/III), predominantly adenocarcinomas (62.5%), treated with curative intent by surgery (n = 61), surgery and adjuvant chemotherapy/radiotherapy (n = 8), or chemoradiotherapy (n = 19). Tumour exome sequencing identified somatic mutations and plasma was analyzed using patient-specific RaDaR™ assays with up to 48 amplicons targeting tumour-specific variants unique to each patient. RESULTS: ctDNA was detected before treatment in 24%, 77% and 87% of patients with stage I, II and III disease, respectively, and in 26% of all longitudinal samples. The median tumour fraction detected was 0.042%, with 63% of samples <0.1% and 36% of samples <0.01%. ctDNA detection had clinical specificity >98.5% and preceded clinical detection of recurrence of the primary tumour by a median of 212.5 days. ctDNA was detected after treatment in 18/28 (64.3%) of patients who had clinical recurrence of their primary tumour. Detection within the landmark timepoint 2 weeks to 4 months after treatment end occurred in 17% of patients, and was associated with shorter recurrence-free survival [hazard ratio (HR): 14.8, P <0.00001] and overall survival (HR: 5.48, P <0.0003). ctDNA was detected 1-3 days after surgery in 25% of patients yet was not associated with disease recurrence. Detection before treatment was associated with shorter overall survival and recurrence-free survival (HR: 2.97 and 3.14, P values 0.01 and 0.003, respectively). CONCLUSIONS: ctDNA detection after initial treatment of patients with early-stage NSCLC using sensitive patient-specific assays has potential to identify patients who may benefit from further therapeutic intervention.

Use of spatio-temporal habitat suitability modelling to prioritise areas for common carp biocontrol in Australia using the virus CyHV-3.

Common carp (Cyprinus carpio) are an invasive species of the rivers and waterways of south-eastern Australia, implicated in the serious decline of many native fish species. Over the past 50 years a variety of control options have been explored, all of which to date have proved either ineffective or cost prohibitive. Most recently the use of cyprinid herpesvirus 3 (CyHV-3) has been proposed as a biocontrol agent, but to assess the risks and benefits of this, as well as to develop a strategy for the release of the virus, a knowledge of the fundamental processes driving carp distribution and abundance is required. To this end, we developed a novel process-based modelling framework that integrates expert opinion with spatio-temporal datasets via the construction of a Bayesian Network. The resulting weekly networks thus enabled an estimate of the habitat suitability for carp across a range of hydrological habitats in south-eastern Australia, covering five diverse catchment areas encompassing in total a drainage area of 132,129 km2 over a period of 17-27 years. This showed that while suitability for adult and subadult carp was medium-high across most habitats throughout the period, nevertheless the majority of habitats were poorly suited for the recruitment of larvae and young-of-year (YOY). Instead, high population abundance was confirmed to depend on a small number of recruitment hotspots which occur in years of favourable inundation. Quantification of the underlying ecological drivers of carp abundance thus makes possible detailed planning by focusing on critical weaknesses in the population biology of carp. More specifically, it permits the rational planning for population reduction using the biocontrol agent, CyHV-3, targeting areas where the total population density is above a "damage threshold" of approximately 100 kg/ha.

Neutrophil-Lymphocyte Ratio and Absolute Lymphocyte Count as Prognostic Markers in Patients Treated with Curative-intent Radiotherapy for Non-small Cell Lung Cancer.

AIMS: The neutrophil-lymphocyte ratio (NLR) and the absolute lymphocyte count (ALC) have been proposed as prognostic markers in non-small cell lung cancer (NSCLC). The objective of this study was to examine the association of NLR/ALC before and after curative-intent radiotherapy for NSCLC on disease recurrence and overall survival. MATERIALS AND METHODS: A retrospective study of consecutive patients who underwent curative-intent radiotherapy for NSCLC across nine sites in the UK from 1 October 2014 to 1 October 2016. A multivariate analysis was carried out to assess the ability of pre-treatment NLR/ALC, post-treatment NLR/ALC and change in NLR/ALC, adjusted for confounding factors using the Cox proportional hazards model, to predict disease recurrence and overall survival within 2 years of treatment. RESULTS: In total, 425 patients were identified with complete blood parameter values. None of the NLR/ALC parameters were independent predictors of disease recurrence. Higher pre-NLR, post-NLR and change in NLR plus lower post-ALC were all independent predictors of worse survival. Receiver operator curve analysis found a pre-NLR > 2.5 (odds ratio 1.71, 95% confidence interval 1.06-2.79, P < 0.05), a post-NLR > 5.5 (odds ratio 2.36, 95% confidence interval 1.49-3.76, P < 0.001), a change in NLR >3.6 (odds ratio 2.41, 95% confidence interval 1.5-3.91, P < 0.001) and a post-ALC < 0.8 (odds ratio 2.86, 95% confidence interval 1.76-4.69, P < 0.001) optimally predicted poor overall survival on both univariate and multivariate analysis when adjusted for confounding factors. Median overall survival for the high-versus low-risk groups were: pre-NLR 770 versus 1009 days (P = 0.34), post-NLR 596 versus 1287 days (P ≤ 0.001), change in NLR 553 versus 1214 days (P ≤ 0.001) and post-ALC 594 versus 1287 days (P ≤ 0.001). CONCLUSION: NLR and ALC, surrogate markers for systemic inflammation, have prognostic value in NSCLC patients treated with curative-intent radiotherapy. These simple and readily available parameters may have a future role in risk stratification post-treatment to inform the intensity of surveillance protocols.

Predicting the Risk of Disease Recurrence and Death Following Curative-intent Radiotherapy for Non-small Cell Lung Cancer: The Development and Validation of Two Scoring Systems From a Large Multicentre UK Cohort.

AIMS: There is a paucity of evidence on which to produce recommendations on neither the clinical nor the imaging follow-up of lung cancer patients after curative-intent radiotherapy. In the 2019 National Institute for Health and Care Excellence lung cancer guidelines, further research into risk-stratification models to inform follow-up protocols was recommended. MATERIALS AND METHODS: A retrospective study of consecutive patients undergoing curative-intent radiotherapy for non-small cell lung cancer from 1 October 2014 to 1 October 2016 across nine UK trusts was carried out. Twenty-two demographic, clinical and treatment-related variables were collected and multivariable logistic regression was used to develop and validate two risk-stratification models to determine the risk of disease recurrence and death. RESULTS: In total, 898 patients were included in the study. The mean age was 72 years, 63% (562/898) had a good performance status (0-1) and 43% (388/898), 15% (134/898) and 42% (376/898) were clinical stage I, II and III, respectively. Thirty-six per cent (322/898) suffered disease recurrence and 41% (369/898) died in the first 2 years after radiotherapy. The ASSENT score (age, performance status, smoking status, staging endobronchial ultrasound, N-stage, T-stage) was developed, which stratifies the risk for disease recurrence within 2 years, with an area under the receiver operating characteristic curve (AUROC) for the total score of 0.712 (0.671-0.753) and 0.72 (0.65-0.789) in the derivation and validation sets, respectively. The STEPS score (sex, performance status, staging endobronchial ultrasound, T-stage, N-stage) was developed, which stratifies the risk of death within 2 years, with an AUROC for the total score of 0.625 (0.581-0.669) and 0.607 (0.53-0.684) in the derivation and validation sets, respectively. CONCLUSIONS: These validated risk-stratification models could be used to inform follow-up protocols after curative-intent radiotherapy for lung cancer. The modest performance highlights the need for more advanced risk prediction tools.

A multicentre randomised phase III trial comparing pembrolizumab versus single-agent chemotherapy for advanced pre-treated malignant pleural mesothelioma: the European Thoracic Oncology Platform (ETOP 9-15) PROMISE-meso trial.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive malignancy characterised by limited treatment options and a poor prognosis. At relapse after platinum-based chemotherapy, single-agent chemotherapy is commonly used and single-arm trials of immune-checkpoint inhibitors have demonstrated encouraging activity. PATIENTS AND METHODS: PROMISE-meso is an open-label 1:1 randomised phase III trial investigating the efficacy of pembrolizumab (200 mg/Q3W) versus institutional choice single-agent chemotherapy (gemcitabine or vinorelbine) in relapsed MPM patients with progression after/on previous platinum-based chemotherapy. Patients were performance status 0-1 and unselected for programmed cell death ligand 1 (PD-L1) status. At progression, patients randomly assigned to receive chemotherapy were allowed to crossover to pembrolizumab. The primary end point was progression-free survival (PFS), assessed by blinded independent central review (BICR). Secondary end points were overall survival (OS), investigator-assessed PFS, objective response rate (ORR), and safety. Efficacy by PD-L1 status was investigated in exploratory analyses. RESULTS: Between September 2017 and August 2018, 144 patients were randomly allocated (pembrolizumab: 73; chemotherapy: 71). At data cut-off [20 February 2019, median follow-up of 11.8 months (interquartile range: 9.9-14.5)], 118 BICR-PFS events were observed. No difference in BICR-PFS was detected [hazard ratio = 1.06, 95% confidence interval (CI): 0.73-1.53; P = 0.76], and median BICR-PFS (95% CI) for pembrolizumab was 2.5 (2.1-4.2), compared with 3.4 (2.2-4.3) months for chemotherapy. A difference in ORR for pembrolizumab was identified (22%, 95% CI: 13% to 33%), over chemotherapy (6%, 95% CI: 2% to 14%; P = 0.004). Forty-five patients (63%) assigned to chemotherapy received pembrolizumab at progression. With follow-up to 21 August 2019 [17.5 months: (14.8-19.7)], no difference in OS was detected between groups (HR = 1.12, 95% CI: 0.74-1.69; P = 0.59), even after adjusting for crossover. Pembrolizumab safety was consistent with previous observations. Exploratory efficacy analyses by PD-L1 status demonstrated no improvements in ORR/PFS/OS. CONCLUSION: This is the first randomised trial evaluating the efficacy of pembrolizumab in MPM patients progressing after/on previous platinum-based chemotherapy. In biologically unselected patients, although associated with an improved ORR, pembrolizumab improves neither PFS nor OS over single-agent chemotherapy.

Purifying selection and genetic drift shaped Pleistocene evolution of the mitochondrial genome in an endangered Australian freshwater fish.

Genetic variation in mitochondrial genes could underlie metabolic adaptations because mitochondrially encoded proteins are directly involved in a pathway supplying energy to metabolism. Macquarie perch from river basins exposed to different climates differ in size and growth rate, suggesting potential presence of adaptive metabolic differences. We used complete mitochondrial genome sequences to build a phylogeny, estimate lineage divergence times and identify signatures of purifying and positive selection acting on mitochondrial genes for 25 Macquarie perch from three basins: Murray-Darling Basin (MDB), Hawkesbury-Nepean Basin (HNB) and Shoalhaven Basin (SB). Phylogenetic analysis resolved basin-level clades, supporting incipient speciation previously inferred from differentiation in allozymes, microsatellites and mitochondrial control region. The estimated time of lineage divergence suggested an early- to mid-Pleistocene split between SB and the common ancestor of HNB+MDB, followed by mid-to-late Pleistocene splitting between HNB and MDB. These divergence estimates are more recent than previous ones. Our analyses suggested that evolutionary drivers differed between inland MDB and coastal HNB. In the cooler and more climatically variable MDB, mitogenomes evolved under strong purifying selection, whereas in the warmer and more climatically stable HNB, purifying selection was relaxed. Evidence for relaxed selection in the HNB includes elevated transfer RNA and 16S ribosomal RNA polymorphism, presence of potentially mildly deleterious mutations and a codon (ATP6113) displaying signatures of positive selection (ratio of nonsynonymous to synonymous substitution rates (dN/dS) >1, radical change of an amino-acid property and phylogenetic conservation across the Percichthyidae). In addition, the difference could be because of stronger genetic drift in the smaller and historically more subdivided HNB with low per-population effective population sizes.

Cyprinid herpesvirus 3 as a potential biological control agent for carp (Cyprinus carpio) in Australia: susceptibility of non-target species.

Carp (Cyprinus carpio L.) is a pest species in Australian waterways, and cyprinid herpesvirus 3 (CyHV-3) is being considered as a potential biological control (biocontrol) agent. An important consideration for any such agent is its target specificity. In this study, the susceptibility to CyHV-3 of a range of non-target species (NTS) was tested. The NTS were as follows: 13 native Australian, and one introduced, fish species; a lamprey species; a crustacean; two native amphibian species (tadpole and mature stages); two native reptilian species; chickens; and laboratory mice. Animals were exposed to 100-1000 times the approximate minimum amount of CyHV-3 required to cause disease in carp by intraperitoneal and/or bath challenge, and then examined clinically each day over the course of 28 days post-challenge. There were no clinical signs, mortalities or histological evidence consistent with a viral infection in a wide taxonomic range of NTS. Furthermore, there was no molecular evidence of infection with CyHV-3, and, in particular, all RT-PCRs for viral mRNA were negative. As a consequence, the results encourage further investigation of CyHV-3 as a potential biocontrol agent that is specific for carp.

Assessment and Optimisation of Lung Cancer Patients for Treatment with Curative Intent.

Over the past decade the field of lung cancer management has seen many developments. Coupled with an ageing population and increasing rates of comorbid illness, the work-up for treatments with curative intent has become more complex and detailed. As well as improvements in imaging and staging techniques, developments in both surgery and radiotherapy may now allow patients who would previously have been considered unfit or not appropriate for treatment with curative intent to undergo radical therapies. This overview will highlight published studies relating to investigation and staging techniques, together with assessments of fitness, with the aim of helping clinicians to determine the most appropriate treatments for each patient. We also highlight areas where further research may be required.

Identifying environmental correlates of intraspecific genetic variation.

Genetic variation is critical to the persistence of populations and their capacity to adapt to environmental change. The distribution of genetic variation across a species' range can reveal critical information that is not necessarily represented in species occurrence or abundance patterns. We identified environmental factors associated with the amount of intraspecific, individual-based genetic variation across the range of a widespread freshwater fish species, the Murray cod Maccullochella peelii. We used two different approaches to statistically quantify the relative importance of predictor variables, allowing for nonlinear relationships: a random forest model and a Bayesian approach. The latter also accounted for population history. Both approaches identified associations between homozygosity by locus and both disturbance to the natural flow regime and mean annual flow. Homozygosity by locus was negatively associated with disturbance to the natural flow regime, suggesting that river reaches with more disturbed flow regimes may support larger, more genetically diverse populations. Our findings are consistent with the hypothesis that artificially induced perennial flows in regulated channels may provide greater and more consistent habitat and reduce the frequency of population bottlenecks that can occur frequently under the highly variable and unpredictable natural flow regime of the system. Although extensive river regulation across eastern Australia has not had an overall positive effect on Murray cod numbers over the past century, regulation may not represent the primary threat to Murray cod survival. Instead, pressures other than flow regulation may be more critical to the persistence of Murray cod (for example, reduced frequency of large floods, overfishing and chemical pollution).

Trimodality therapy and definitive chemoradiotherapy for esophageal cancer: a single-center experience and review of the literature.

In the UK, the standard of care for esophageal cancer has generally combined surgery with neoadjuvant chemotherapy, with definitive chemoradiotherapy (dCRT) being reserved for certain subgroups. Chemoradiotherapy followed by surgery (trimodality therapy) has not been widely adopted. The outcomes of patients undergoing dCRT or trimodality therapy at our cancer center between 2004 and 2012 were restrospectively analyzed. Trimodality therapy was offered to selected patients of good performance status (World Health Organisation performance status 0/1), with squamous cell carcinoma or bulky adenocarcinoma. dCRT was offered to patients of good PS but with comorbidities, upper third tumors or at patient's request. Patients received four cycles of chemotherapy with a platinum agent (mostly cisplatin) and a fluoropyrimidine (mostly 5-fluorouracil) over a total of 11 weeks. Cycles 3 and 4 were given concurrently with radiotherapy: 50 Gy in 25 fractions for dCRT and 45 Gy in 25 fractions in the trimodality group. Surgery occurred 8-10 weeks following the completion of chemoradiotherapy. The cut-off length for maximum gross tumor volume length was 10 cm. One hundred two patients were included (47 received dCRT, and 55 received trimodality treatment). The majority of tumors were stage III (80.4%), and two-thirds were located in the distal esophagus (64.7%). Median follow-up was 44 months. The 2-year overall survival (OS) was 57.3% (median OS 39.7 months) for the dCRT group and 77.8% (median not reached) for the trimodality group. The 5-year OS rates were 38% and 58%, respectively. Postoperative mortality rate was low at 1.8%, and the pathological complete response rate was 23.6%. In conclusion, trimodality treatment for patients with esophageal and junctional gastroesophageal tumors offers high rates of 2-year survival, and the potential for long-term cure. dCRT is an established alternative for patients that are not fit or suitable for surgery.

The management of lung cancer: a UK survey of oncologists.

AIMS: This report reviews current radiotherapy practice across the UK in the management of lung cancer, and the way new treatments and technologies are being introduced, where improvements have occurred, and where work is still required. We wanted to determine adherence to both National Radiotherapy Advisory Group and National Institute for Health and Clinical Excellence (NICE) guidance. This survey was conducted on behalf of the Department of Health Lung Cancer & Mesothelioma Advisory Group. MATERIALS AND METHODS: We sent a questionnaire to all UK radiotherapy departments. It covered radical radiotherapy dose fractionation, the use of concurrent or sequential chemotherapy for both non-small cell and small cell lung cancers, the use of continuous hyperfractionated accelerated radiotherapy, new radiotherapy techniques, the use of positron emission tomography/computed tomography for planning purposes and patient accrual into current National Cancer Research Network UK trials. RESULTS: This UK-wide survey of radiotherapy practice for lung cancer showed broad compliance with NICE clinical guidance, but highlighted significant variation in fractionation schedules and the use of concomitant chemoradiotherapy. Clinical trial entry into lung cancer radiotherapy trials was variable and many centres are not fully participating in recruitment into these trials. CONCLUSIONS: This report has shown the variability of radiotherapy provision nationally. Current practice is largely consistent with current and updated NICE recommendations and best practice and should be recognised as such. It has also highlighted areas where improvements are still needed, particularly fractionation and new technologies. One particular aspect of concern is the poor recruitment to current UK-based clinical trials in lung cancer.

A hybrid zone and bidirectional introgression between two catadromous species: Australian bass Macquaria novemaculeata and estuary perch Macquaria colonorum.

The presence and distribution of hybrid individuals and the existence of a hybrid zone between the catadromous Australian bass Macquaria novemaculeata and estuary perch Macquaria colonorum were investigated throughout the range of both species in Australia. Bayesian analyses and genotypic simulations identified 140 putative hybrids (11·5% of the total sample) with varying levels of introgression. Most hybrids were observed in an area extending from the Snowy River to the Albert River suggesting a hybrid zone in the eastern Bass Strait region. Sixteen hybrids, however, were found outside this zone, possibly reflecting the movement of hybrid offspring between estuaries or their inadvertent release during fish stocking programmes. Biparental backcrossing was found to occur suggesting that hybrids were fertile. These results have implications for the management of the extensive stocking programme in M. novemaculeata and for understanding the potential role of habitat degradation and reduced water flow in facilitating hybridization in species with migratory life histories.

An examination of the divergent general, specific, and other criminogenic risk/needs across neuropathic and psychopathic pathways to homicide.

The social learning theory underlying Andrews and Bonta's Psychology of Criminal Conduct model has generally been seen as guiding risk assessment, with good relevance to mentally ill as well as non-mentally ill offenders. The current study reports a novel approach to qualitative assessment of 26 murderers found not guilty by reason of insanity (NGRI), divided into two groups--neuropathic offenders characterised by frontal lobe deficits and psychosis and psychopathic murderers characterised by high scores on psychopathy and an absence of neuropathic factors. The findings of the present research support the notion that the two pathways are embedded in two diverging theoretical frameworks of psychopathology and social learning theory, with each corresponding to the neuropathic and psychopathic pathways, respectively. Models of social learning theory may have limited utility to the total mentally disordered offender population overall as they apply more specifically to offenders within special offender groups or perhaps more specifically to offenders with psychopathic characteristics. However, the significantly greater association of the other social, physical, and mental health risk/needs with the neuropathic pathway suggests that pathological models are important for understanding the neuropathic pathway in relation to homicide offence and risk of future violence in NGRI samples.

Population genetics of invasive common carp Cyprinus carpio L. in coastal drainages in eastern Australia.

The common carp Cyprinus carpio introduced in two drainages in eastern Australia are largely descended from European common carp, and in a third drainage they descend largely from East Asian common carp. The partial genetic differentiation among the species in those drainages is consistent with their origins.

Matuzumab plus epirubicin, cisplatin and capecitabine (ECX) compared with epirubicin, cisplatin and capecitabine alone as first-line treatment in patients with advanced oesophago-gastric cancer: a randomised, multicentre open-label phase II study.

BACKGROUND: Clinical data showed promising antitumour activity with feasible tolerability for matuzumab plus epirubicin, cisplatin and capecitabine (ECX) chemotherapy in untreated advanced oesophago-gastric (OG) cancer. The aim was to evaluate the efficacy of matuzumab plus ECX versus ECX alone. PATIENTS AND METHODS: In this multicentre, randomised open-label phase II study, 72 patients with metastatic OG cancer were randomly assigned to either 800 mg matuzumab weekly plus epirubicin 50 mg/m², cisplatin 60 mg/m² on day 1 and capecitabine 1250 mg/m² daily in a 21-day cycle (ECX) or the same ECX regimen alone. The primary end point was objective response. Secondary end points included progression-free survival (PFS), overall survival (OS), quality of life, safety and tolerability. RESULTS: Following random assignment, 35 patients (median age 59 years) received ECX/matuzumab and 36 patients (median age 64 years) ECX. The addition of matuzumab to ECX did not improve objective response: 31% for ECX/matuzumab [95% confidence interval (CI) 17-49] compared with 58% for the ECX arm (95% CI 41-74) P = 0.994 (one sided). There was no significant difference in median PFS: 4.8 months (95% CI 2.9-8.1) for ECX/matuzumab versus 7.1 months (95% CI 4.4-8.5) for ECX, or in median OS: 9.4 months (95% CI 7.5-16.2), compared with 12.2 months (95% CI 9.8-13.8 months). Grade 3/4 treatment-related toxicity was observed in 27 and 25 patients in the ECX/matuzumab and ECX groups, respectively. CONCLUSION: Matuzumab 800 mg weekly combined with ECX chemotherapy does not increase response or survival for patients with advanced OG cancer. Therefore, ECX/matuzumab should not be examined further in phase III trials.

Comparison of gemcitabine and carboplatin versus cisplatin and etoposide for patients with poor-prognosis small cell lung cancer.

BACKGROUND: The combination of cisplatin and etoposide (PE) has been a standard treatment for patients with poor-prognosis small cell lung cancer (SCLC). This non-inferiority design trial aimed to determine whether the combination of gemcitabine and carboplatin (GC) results in similar survival but is less toxic with better quality of life. METHODS: Previously untreated patients with SCLC with extensive disease or limited stage with poor prognostic factors were randomly assigned to six 3-weekly cycles of GC or PE. RESULTS: 241 patients (121 GC, 120 PE) were recruited, of which 216 (90%) had died. There was no difference in overall survival (HR 1.01, 95% CI 0.77 to 1.32). Median survival with GC and PE was 8.0 and 8.1 months, respectively. Median progression-free survival was 5.9 months with GC and 6.3 months with PE. Grade 3 or 4 myelosuppressions were more frequent with GC (anaemia: 14% GC vs 2% PE; leucopenia: 32% GC vs 13% PE; thrombocytopenia: 22% GC vs 4% PE), but these were not associated with increased hospital admissions, infections or fatalities. Grade 2-3 alopecia (68% PE vs 17% GC) and nausea (43% PE vs 26% GC) were more frequent with PE. Patients given GC received more chemotherapy as outpatients (89% GC vs 66% PE of treatment cycles). In QoL questionnaires, more patients receiving PE reported being upset by hair loss (p = 0.004) and impaired cognitive functioning (p = 0.04). CONCLUSIONS: GC is as effective as PE in terms of overall survival and progression-free survival and has a toxicity profile more acceptable to patients. TRIAL REGISTRATION NUMBER: ISRCTN 39679215.

Population genetics and management units of invasive common carp Cyprinus carpio in the Murray-Darling Basin, Australia.

Common carp Cyprinus carpio were introduced into Australia on several occasions and are now the dominant fish in the Murray-Darling Basin (MDB), the continent's largest river system. In this study, variability at 14 microsatellite loci was examined in C. carpio (n = 1037) from 34 sites throughout the major rivers in the MDB, from 3 cultured populations, from Prospect Reservoir in the Sydney Basin and from Lake Sorrell in Tasmania. Consistent with previous studies, assignment testing indicated that the Boolara, Yanco and koi strains of C. carpio are present in the MDB. Unique to this study, however, the Prospect strain was widely distributed throughout the MDB. Significant genetic structuring of populations (Fisher's exact test, AMOVA and distribution of the different strains) amongst the MDB sub-drainages was detected, and was strongly associated with contemporary barriers to dispersal and population history. The distributions of the strains were used to infer the history of introduction and spread of C. carpio in the MDB. Fifteen management units are proposed for control programmes that have high levels of genetic diversity, contain multiple interbreeding strains and show no evidence of founder effects or recent population bottlenecks.