2nd ESMO Consensus Conference on Lung Cancer : non-small-cell lung cancer first-line/second and further lines in advanced disease

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines in advanced disease, early stage disease and locally-advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on 1st line / 2nd and further lines of treatment in advanced disease. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Palliative care and other physicians’ knowledge, attitudes and practice relating to the law on withholding/withdrawing life-sustaining treatment: Survey results

Background: To effectively care for people who are terminally ill, including those without decision-making capacity, palliative care physicians must know and understand the legal standing of Advance Care Planning (ACP) in their jurisdiction of practice. This includes the use of advance directives/living wills (ADs) and substitute decision-makers (SDMs) who can legally consent to or refuse treatment if there is no valid AD. Aim: The study aimed to investigate the knowledge, attitudes and practices of medical specialists most often involved in end-of-life care in relation to the law on withholding/ withdrawing life-sustaining treatment (WWLST) from adults without decision-making capacity. Design/participants: A pre-piloted survey was posted to specialists in palliative, emergency, geriatric, renal and respiratory medicine, intensive care and medical oncology in three Australian States. Surveys were analysed using SPSS20 and SAS 9.3. Results: The overall response rate was 32% (867/2702); 52% from palliative care specialists. Palliative Care specialists and Geriatricians had significantly more positive attitudes towards the law (χ242 = 94.352; p < 0.001) and higher levels of knowledge about the WWLST law (χ27 = 30.033; p < 0.001), than did the other specialists, while still having critical gaps in their knowledge. Conclusions: A high level of knowledge of the law is essential to ensure that patients’ wishes and decisions, expressed through ACP, are respected to the maximum extent possible within the law, thereby according with the principles and philosophy of palliative care. It is also essential to protect health professionals from legal action resulting from unauthorised provision or removal of treatment.

Doctors’ perspectives on law and life-sustaining treatment: Survey design and recruitment strategies for a challenging cohort

- Background Palliative medicine and other specialists play significant legal roles in decisions to withhold and withdraw life-sustaining treatment at the end of life. Yet little is known about their knowledge of or attitudes to the law, and the role they think it should play in medical practice. Consideration of doctors’ views is critical to optimizing patient outcomes at the end of life. However, doctors are difficult to engage as participants in empirical research, presenting challenges for researchers seeking to understand doctors’ experiences and perspectives. - Aims To determine how to engage doctors involved in end-of-life care in empirical research about knowledge of the law and the role it plays in medical practice at the end of life. - Methods Postal survey of all specialists in palliative medicine, emergency medicine, geriatric medicine, intensive care, medical oncology, renal medicine, and respiratory medicine in three Australian states: New South Wales, Victoria, and Queensland. The survey was sent in hard copy with two reminders and a follow up reminder letter was also sent to the directors of hospital emergency departments. Awareness was further promoted through engagement with the relevant medical colleges and publications in professional journals; various incentives to respond were also used. The key measure is the response rate of doctors to the survey. - Results Thirty-two percent of doctors in the main study completed their survey with response rate by specialty ranging from 52% (palliative care) to 24% (medical oncology). This overall response rate was twice that of the reweighted pilot study (16%). - Conclusions Doctors remain a difficult cohort to engage in survey research but strategic recruitment efforts can be effective in increasing response rate. Collaboration with doctors and their professional bodies in both the development of the survey instrument and recruitment of participants is essential.

Estilos de Pensamento da assistência médica aos pacientes oncológicos na rede pública de saúde do Município do Rio de Janeiro

O objetivo principal da pesquisa é descrever os Estilos de Pensamento que operam em duas das principais clínicas envolvidas na assistência clínica ao paciente oncológico em uma Rede Estadual de Alta Complexidade em Oncologia do Sistema Único de Saúde brasileiro: a oncologia e os cuidados paliativos. Para atingir esses objetivo, a proposta é desenvolver uma pesquisa qualitativa a fim de depreender como se configura o objeto de intervenção clínica nos discursos e nas práticas desses Coletivos de Pensamento. A metodologia escolhida foi a entrevista semi-estruturada. Parte-se, inicialmente, da origem e dos elementos que caracterizam a racionalidade biomédica e o modelo de cuidado integral em saúde, analisando as implicações desses modelos no entendimento dos doenças oncológicas e no seu tratamento. Em seguida, desenvolve-se os conceitos de "Estilo de Pensamento" e "Coletivo de Pensamento" de Ludwik Fleck e o do conceito de "enactment" de Annemarie Mol. Utilizo esses conceitos para refletir sobre a construção do conhecimento e da prática médica, em especial nos seus aspectos sociais, ligados à formação e à especialização. Logo após, faz-se uma descrição histórica dos grupos profissionais estudados: a oncologia e os cuidados paliativos. Pro fim, segue-se a descrição da pesquisa de campo e dos resultados coletados nas entrevistas realizadas. O estudo evidenciou que os Estilos de Pensamento dos Paliativistas e oncologistas são muito distintos, quase incomensuráveis, porém também foi possível identificar preocupações e valores comuns e possíveis campos de interseção entre esses dois grupos.

Adjuvant chemotherapy in elderly patients with breast cancer: a survey of the Breast International Group (BIG).

BACKGROUND: To collect oncologists' experience and opinion on adjuvant chemotherapy in elderly breast cancer patients. MATERIALS AND METHODS: A questionnaire was circulated among the members of the Breast International Group. RESULTS: A total of 277 oncologists from 28 countries participated in the survey. Seventy years is the age cut-off commonly used to define a patient as elderly. Biological age and the biological characteristics of the tumor are the most frequently used criteria to propose adjuvant chemotherapy to an elderly patient. Combination therapy with cyclophosphamide, methotrexate and fluorouracil on days 1 and 8 is the most frequently prescribed regimen. Great interest exists in oral chemotherapy. CONCLUSION: There is interest among those who responded to the survey to validate a comprehensive geriatric assessment for use as a predictive instrument of toxicity and/or activity of anticancer therapy and to evaluate the role of a treatment option that is potentially less toxic and possibly as effective as polychemotherapy.

Guidelines on the standards for the training of specialised health professionals dealing with breast cancer.

According to EUSOMA position paper 'The requirements of a specialist breast unit', each breast unit should have a core team made up of health professionals who have undergone specialist training in breast cancer. In this paper, on behalf of EUSOMA, authors have identified the standards of training in breast cancer, to harmonise and foster breast care training in Europe. The aim of this paper is to contribute to the increase in the level of care in a breast unit, as the input of qualified health professionals increases the quality of breast cancer patient care.

An integrated approach to the prediction of chemotherapeutic response in patients with breast cancer.

BACKGROUND: A major challenge in oncology is the selection of the most effective chemotherapeutic agents for individual patients, while the administration of ineffective chemotherapy increases mortality and decreases quality of life in cancer patients. This emphasizes the need to evaluate every patient's probability of responding to each chemotherapeutic agent and limiting the agents used to those most likely to be effective. METHODS AND RESULTS: Using gene expression data on the NCI-60 and corresponding drug sensitivity, mRNA and microRNA profiles were developed representing sensitivity to individual chemotherapeutic agents. The mRNA signatures were tested in an independent cohort of 133 breast cancer patients treated with the TFAC (paclitaxel, 5-fluorouracil, adriamycin, and cyclophosphamide) chemotherapy regimen. To further dissect the biology of resistance, we applied signatures of oncogenic pathway activation and performed hierarchical clustering. We then used mRNA signatures of chemotherapy sensitivity to identify alternative therapeutics for patients resistant to TFAC. Profiles from mRNA and microRNA expression data represent distinct biologic mechanisms of resistance to common cytotoxic agents. The individual mRNA signatures were validated in an independent dataset of breast tumors (P = 0.002, NPV = 82%). When the accuracy of the signatures was analyzed based on molecular variables, the predictive ability was found to be greater in basal-like than non basal-like patients (P = 0.03 and P = 0.06). Samples from patients with co-activated Myc and E2F represented the cohort with the lowest percentage (8%) of responders. Using mRNA signatures of sensitivity to other cytotoxic agents, we predict that TFAC non-responders are more likely to be sensitive to docetaxel (P = 0.04), representing a viable alternative therapy. CONCLUSIONS: Our results suggest that the optimal strategy for chemotherapy sensitivity prediction integrates molecular variables such as ER and HER2 status with corresponding microRNA and mRNA expression profiles. Importantly, we also present evidence to support the concept that analysis of molecular variables can present a rational strategy to identifying alternative therapeutic opportunities.

Standardizing clinical trials workflow representation in UML for international site comparison.

BACKGROUND: With the globalization of clinical trials, a growing emphasis has been placed on the standardization of the workflow in order to ensure the reproducibility and reliability of the overall trial. Despite the importance of workflow evaluation, to our knowledge no previous studies have attempted to adapt existing modeling languages to standardize the representation of clinical trials. Unified Modeling Language (UML) is a computational language that can be used to model operational workflow, and a UML profile can be developed to standardize UML models within a given domain. This paper's objective is to develop a UML profile to extend the UML Activity Diagram schema into the clinical trials domain, defining a standard representation for clinical trial workflow diagrams in UML. METHODS: Two Brazilian clinical trial sites in rheumatology and oncology were examined to model their workflow and collect time-motion data. UML modeling was conducted in Eclipse, and a UML profile was developed to incorporate information used in discrete event simulation software. RESULTS: Ethnographic observation revealed bottlenecks in workflow: these included tasks requiring full commitment of CRCs, transferring notes from paper to computers, deviations from standard operating procedures, and conflicts between different IT systems. Time-motion analysis revealed that nurses' activities took up the most time in the workflow and contained a high frequency of shorter duration activities. Administrative assistants performed more activities near the beginning and end of the workflow. Overall, clinical trial tasks had a greater frequency than clinic routines or other general activities. CONCLUSIONS: This paper describes a method for modeling clinical trial workflow in UML and standardizing these workflow diagrams through a UML profile. In the increasingly global environment of clinical trials, the standardization of workflow modeling is a necessary precursor to conducting a comparative analysis of international clinical trials workflows.

The prognosis of incurable cachectic cancer patients on home parenteral nutrition: A multi-centre observational study with prospective follow-up of 414 patients

Background: The role of home parenteral nutrition (HPN) in incurable cachectic cancer patients unable to eat is extremely controversial. The aim of this study is to analyse which factors can influence the outcome. Patients and methods: We studied prospectively 414 incurable cachectic (sub)obstructed cancer patients receiving HPN and analysed the association between patient or clinical characteristics and surviving status. Results: Median weight loss, versus pre-disease and last 6-month period, was 24% and 16%, respectively. Median body mass index was 19.5, median KPS was 60, median life expectancy was 3 months. Mean/median survival was 4.7/3.0 months; 50.0% and 22.9% of patients survived 3 and 6 months, respectively. At the multivariable analysis, the variables significantly associated with 3- and 6-month survival were Glasgow Prognostic Score (GPS) and KPS, and GPS, KPS and tumour spread, respectively. By the aggregation of the significant variables, it was possible to dissect several classes of patients with different survival probabilities. Conclusions: The outcome of cachectic incurable cancer patients on HPN is not homogeneous. It is possible to identify groups of patients with a ≥6-month survival (possibly longer than that allowed in starvation). The indications for HPN can be modulated on these clinical/biochemical indices. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

β-Blocker usage and colorectal cancer mortality:a nested case-control study in the UK Clinical Practice Research Datalink cohort

BACKGROUND: Epidemiological and laboratory studies suggest that β-blockers may reduce cancer progression in various cancer sites. The aim of this study was to conduct the first epidemiological investigation of the effect of post-diagnostic β-blocker usage on colorectal cancer-specific mortality in a large population-based colorectal cancer patient cohort.

PATIENTS AND METHODS: A nested case-control analysis was conducted within a cohort of 4794 colorectal cancer patients diagnosed between 1998 and 2007. Patients were identified from the UK Clinical Practice Research Datalink and confirmed using cancer registry data. Patients with a colorectal cancer- specific death (data from the Office of National Statistics death registration system) were matched to five controls. Conditional logistic regression was applied to calculate odds ratios (OR) and 95% confidence intervals (95% CIs) according to β-blocker usage (data from GP-prescribing records).

RESULTS: Post-diagnostic β-blocker use was identified in 21.4% of 1559 colorectal cancer-specific deaths and 23.7% of their 7531 matched controls, with little evidence of an association (OR = 0.89 95% CI 0.78-1.02). Similar associations were found when analysing drug frequency, β-blocker type or specific drugs such as propranolol. There was some evidence of a weak reduction in all-cause mortality in β-blocker users (adjusted OR = 0.88; 95% CI 0.77-1.00; P = 0.04) which was in part due to the marked effect of atenolol on cardiovascular mortality (adjusted OR = 0.62; 95% CI 0.40-0.97; P = 0.04).

CONCLUSIONS: In this novel, large UK population-based cohort of colorectal cancer patients, there was no evidence of an association between post-diagnostic β-blocker use and colorectal cancer-specific mortality.

CLINICAL TRIALS NUMBER: NCT00888797.