ESMO Management and treatment adapted recommendations in the COVID-19 era: Lung cancer.

The COVID-19 pandemic, characterised by a fast and global spread during the first months of 2020, has prompted the development of a structured set of recommendations for cancer care management, to maintain the highest possible standards. Within this framework, it is crucial to ensure no disruption to essential oncological services and guarantee the optimal care.This is a structured proposal for the management of lung cancer, comprising three levels of priorities, namely: tier 1 (high priority), tier 2 (medium priority) and tier 3 (low priority)-defined according to the criteria of the Cancer Care Ontario, Huntsman Cancer Institute and Magnitude of Clinical Benefit Scale.The manuscript emphasises the impact of the COVID-19 pandemic on lung cancer care and reconsiders all steps from diagnosis, staging and treatment.These recommendations should, therefore, serve as guidance for prioritising the different aspects of cancer care to mitigate the possible negative impact of the COVID-19 pandemic on the management of our patients.As the situation is rapidly evolving, practical actions are required to guarantee the best patients' treatment while protecting and respecting their rights, safety and well-being. In this environment, cancer practitioners have great responsibilities: provide timely, appropriate, compassionate and justified cancer care, while protecting themselves and their patients from being infected with COVID-19. In case of shortages, resources must be distributed fairly. Consequently, the following recommendations can be applied with significant nuances, depending on the time and location for their use, considering variable constraints imposed to the health systems. An exceptional flexibility is required from cancer caregivers.

Assessment of Breathlessness in Lung Cancer: Psychometric Properties of the Dyspnea-12 Questionnaire.

CONTEXT: The Dyspnea-12 (D-12) Questionnaire is a well-validated instrument in respiratory illnesses for breathlessness assessment, but its psychometric properties have not been tested in lung cancer. OBJECTIVE: To demonstrate the psychometric properties of the D-12 in lung cancer patients. METHODS: Baseline data from a lung cancer feasibility trial were adopted for this analysis. D-12 and a series of patient-reported tools, including five Numeric Rating Scales (NRS), the Hospital Anxiety and Depression Scale (HADS), and the Lung Cancer Symptom Scale (LCSS), were used for the psychometric assessment. Spearman's correlation coefficients (rs) were used to estimate the convergent validity of the D-12 with the NRS, HADS, and LCSS. Exploratory factor analysis was performed to examine construct validity. Reliability was tested by Cronbach's alpha and item-to-total correlations. D-12 score difference between patients with or without anxiety, depression, and chronic obstructive pulmonary disease (COPD) was explored to identify its discriminate performance. RESULTS: One hundred and one lung cancer patients were included. There were significantly positive correlations between the D-12 and the HADS, LCSS, and NRS measuring breathlessness severity and its associated affective distress. Factor analysis clearly identified two components (physical and emotional) of the D-12. Cronbach's alpha for D-12 total, physical, and emotional subscales was 0.95, 0.92, and 0.94, respectively. Patients with anxiety or depression demonstrated significantly higher D-12 scores than those without it, and patients with COPD reported significantly more severe breathlessness than those without COPD. CONCLUSION: The D-12 is a valid and reliable self-reported questionnaire for use in breathlessness assessment in lung cancer patients.

Management of the respiratory distress symptom cluster in lung cancer: a randomised controlled feasibility trial.

BACKGROUND: Breathlessness, cough and fatigue are distressing symptoms for patients with lung cancer. There is evidence that these three symptoms form a discreet symptom cluster. This study aimed to feasibly test a new non-pharmacological intervention for the management of the Respiratory Distress Symptom Cluster (breathlessness-cough-fatigue) in lung cancer. METHOD: This was a multi-centre, randomised controlled non-blinded parallel group feasibility trial. Eligible patients (patients with primary lung cancer and 'bothered' by at least two of the three cluster symptoms) received usual care plus a multicomponent intervention delivered over two intervention training sessions and a follow-up telephone call or usual care only. Follow-up was for 12 weeks, and end-points included six numerical rating scales for breathlessness severity, Dyspnoea-12, Manchester Cough in Lung Cancer scale, FACIT-Fatigue scale, Hospital Anxiety and Depression scale, Lung Cancer Symptom Scale and the EQ-5D-3L, collected at baseline, week 4 and week 12. RESULTS: One hundred seven patients were randomised over 8 months; however, six were removed from further analysis due to protocol violations (intervention group n = 50 and control group n = 51). Of the ineligible patients (n = 608), 29 % reported either not experiencing two or more symptoms or not being 'bothered' by at least two symptoms. There was 29 % drop-out by week 4, and by week 12, a further two patients in the control group were lost to follow-up. A sample size calculation indicated that 122 patients per arm would be needed to detect a clinically important difference in the main outcome for breathlessness, cough and fatigue. CONCLUSIONS: The study has provided evidence of the feasibility and acceptability of a new intervention in the lung cancer population and warrants a fully powered trial before we reach any conclusions. The follow-on trial will test the hypothesis that the intervention improves symptom cluster of breathlessness, cough and fatigue better than usual care alone. Full economic evaluation will be conducted in the main trial.

Assessment of Intervention Fidelity and Recommendations for Researchers Conducting Studies on the Diagnosis and Treatment of Chronic Cough in the Adult: CHEST Guideline and Expert Panel Report.

BACKGROUND: Successful management of chronic cough has varied in the primary research studies in the reported literature. One of the potential reasons relates to a lack of intervention fidelity to the core elements of the diagnostic and/or therapeutic interventions that were meant to be used by the investigators. METHODS: We conducted a systematic review to summarize the evidence supporting intervention fidelity as an important methodologic consideration in assessing the effectiveness of clinical practice guidelines used for the diagnosis and management of chronic cough. We developed and used a tool to assess for five areas of intervention fidelity. Medline (PubMed), Scopus, and the Cochrane Database of Systematic Reviews were searched from January 1998 to May 2014. Guideline recommendations and suggestions for those conducting research using guidelines or protocols to diagnose and manage chronic cough in the adult were developed and voted upon using CHEST Organization methodology. RESULTS: A total of 23 studies (17 uncontrolled prospective observational, two randomized controlled, and four retrospective observational) met our inclusion criteria. These articles included 3,636 patients. Data could not be pooled for meta-analysis because of heterogeneity. Findings related to the five areas of intervention fidelity included three areas primarily related to the provider and two primarily related to the patients. In the area of study design, 11 of 23 studies appeared to be underpinned by a single guideline/protocol; for training of providers, two of 23 studies reported training, and zero of 23 reported the use of an intervention manual; and for the area of delivery of treatment, when assessing the treatment of gastroesophageal reflux disease, three of 23 studies appeared consistent with the most recent guideline/protocol referenced by the authors. For receipt of treatment, zero of 23 studies mentioned measuring concordance of patient-interventionist understanding of the treatment recommended, and zero of 23 mentioned measuring enactment of treatment, with three of 23 measuring side effects and two of 23 measuring adherence. The overall average intervention fidelity score for all 23 studies was poor (20.74 out of 48). CONCLUSIONS: Only low-quality evidence supports that intervention fidelity strategies were used when conducting primary research in diagnosing and managing chronic cough in adults. This supports the contention that some of the variability in the reporting of patients with unexplained or unresolved chronic cough may be due to lack of intervention fidelity. By following the recommendations and suggestions in this article, researchers will likely be better able to incorporate strategies to address intervention fidelity, thereby strengthening the validity and generalizability of their results that provide the basis for the development of trustworthy guidelines.

The Manchester cough in lung cancer scale: the development and preliminary validation of a new assessment tool.

CONTEXT: Cough is a common distressing symptom in lung cancer patients. Its assessment is hampered by the lack of a validated scale to measure the complex cough experience in this population. OBJECTIVES: To describe the development and preliminary validation of a scale to measure cough in lung cancer patients. METHODS: In the first phase, collection of qualitative data from patient interviews, a review of literature, and identification of noncancer cough scales resulted in the development of a pool of 30 items. This item pool was tested for appropriateness of content and breadth of coverage with 18 patients with lung cancer and 25 health care professionals. The second phase was the operationalization/phrasing of items. The final phase was the scale's field testing with 139 patients, 49 of whom repeated the assessment after one week. RESULTS: The first phase led to the deletion of several items and the addition of four, resulting in a final scale for field testing of 21 items. In the field testing, the scale was decreased to 10 items, eliminating items on psychometric grounds. The final scale's Cronbach alpha (internal consistency) was 0.86, item to total correlations ranged from 0.40 to 0.76, and test-retest reliability was high (intraclass correlation=0.83). CONCLUSION: We have developed a promising tool to assess cough in lung cancer, but this needs validation, and future studies should determine whether this is a sensitive and responsive tool. A fully validated tool can be used in the clinical assessment of cough in cancer patients, and as a unidimensional impact scale in the measurement of cough as an outcome in intervention studies.

Guideline on the requirements of external quality assessment programs in molecular pathology.

Molecular pathology is an integral part of daily diagnostic pathology and used for classification of tumors, for prediction of prognosis and response to therapy, and to support treatment decisions. For these reasons, analyses in molecular pathology must be highly reliable and hence external quality assessment (EQA) programs are called for. Several EQA programs exist to which laboratories can subscribe, but they vary in scope, number of subscribers, and execution. The guideline presented in this paper has been developed with the purpose to harmonize EQA in molecular pathology. It presents recommendations on how an EQA program should be organized, provides criteria for a reference laboratory, proposes requirements for EQA test samples, and defines the number of samples needed for an EQA program. Furthermore, a system for scoring of the results is proposed as well as measures to be taken for poorly performing laboratories. Proposals are made regarding the content requirements of an EQA report and how its results should be communicated. Finally, the need for an EQA database and a participant manual are elaborated. It is the intention of this guideline to improve EQA for molecular pathology in order to provide more reliable molecular analyses as well as optimal information regarding patient selection for treatment.

Is serum or plasma more appropriate for intersubject comparisons in metabolomic studies? An assessment in patients with small-cell lung cancer.

In clinical analyses, the most appropriate biofluid should be analyzed for optimal assay performance. For biological fluids, the most readily accessible is blood, and metabolomic analyses can be performed either on plasma or serum. To determine the optimal agent for analysis, metabolic profiles of matched human serum and plasma were assessed by gas chromatography/time-of-flight mass spectrometry and ultrahigh-performance liquid chromatography mass spectrometry (in positive and negative electrospray ionization modes). Comparison of the two metabolomes, in terms of reproducibility, discriminative ability and coverage, indicated that they offered similar analytical opportunities. An analysis of the variation between 29 small-cell lung cancer (SCLC) patients revealed that the differences between individuals are markedly similar for the two biofluids. However, significant differences between the levels of some specific metabolites were identified, as were differences in the intersubject variability of some metabolite levels. Glycerophosphocholines, erythritol, creatinine, hexadecanoic acid, and glutamine in plasma, but not in serum, were shown to correlate with life expectancy for SCLC patients, indicating the utility of metabolomic analyses in clinical prognosis and the particular utility of plasma in relation to the clinical management of SCLC.