An international field study for the reliability and validity of the EORTC communication questionnaire EORTC QLQ-COMU26.

BACKGROUND: The EORTC Quality of Life Group has developed a questionnaire to evaluate cancer patients' perception of their communication with healthcare professionals (HCPs): the EORTC QLQ-COMU26. In this study we test the validity and reliability of this novel measure in an international and culturally diverse sample of cancer patients. METHODS: Cancer patients completed the following EORTC questionnaires at two time points (before and during treatment): the QLQ-COMU26 (including a debriefing questionnaire), the QLQ-C30, and specific IN-PATSAT32 scales. These data were used to assess: the cross-cultural applicability, acceptability, scale structure, reliability, convergent/divergent validity, known-groups validity, and responsiveness to change of the QLQ-COMU26. RESULTS: Data were collected from 498 patients with various cancer diagnoses in 10 European countries, Japan, Jordan and India (overall 5 cultural regions). At most, only 3% of patients identified an item as confusing and 0.6% as upsetting, which indicates that the questionnaire was clear and did not trigger negative emotional responses. Confirmatory factor analysis and multi-trait scaling confirmed the hypothesised QLQ-COMU26 scale structure comprising six multi-item scales and four single items (RMSEA = 0.025). Reliability was good for all scales (internal consistency > 0.70; test-retest reliability > 0.85). Convergent validity was supported by correlations of ≥ 0.50 with related scales of the IN-PATSAT32 and correlations < 0.30 with unrelated QLQ-C30 scales. Known-groups validity was shown according to sex, education, levels of anxiety and depression, satisfaction with communication, disease stage and treatment intention, professional evaluated, and having a companion during the visit. The QLQ-COMU26 captured changes over time in groups that were defined based on changes in the item of satisfaction with communication. CONCLUSION: The EORTC QLQ-COMU26 is a reliable and valid measure of patients' perceptions of their communication with HCPs. The EORTC QLQ-COMU26 can be used in daily clinical practice and research and in various cancer patient groups from different cultures. This questionnaire can help to improve communication between patients and healthcare professionals.

Aprepitant for Cough in Lung Cancer. A Randomized Placebo-controlled Trial and Mechanistic Insights.

Rationale: Effective cough treatments are a significant unmet need in patients with lung cancer. Aprepitant is a licensed treatment for nausea and vomiting, which blocks substance P activation of NK-1 (neurokinin 1) receptors, a mechanism also implicated in cough.Objectives: To assess aprepitant in patients with lung cancer with cough and evaluate mechanisms in vagal nerve tissue.Methods: Randomized double-blind crossover trial of patients with lung cancer and bothersome cough. They received 3 days of aprepitant or matched placebo; after a 3-day washout, patients crossed to the alternative treatment. The primary endpoint was awake cough frequency measured at screening and Day 3 of each treatment; secondary endpoints included patient-reported outcomes. In vitro, the depolarization of isolated guinea pig and human vagus nerve sections in grease-gap recording chambers, indicative of sensory nerve activation, was measured to evaluate the mechanism.Measurements and Main Results: Twenty patients with lung cancer enrolled, with a mean age 66 years (±7.7); 60% were female and 80% had non-small cell cancer, 50% had advanced stage, and 55% had World Health Organization performance status 1. Cough frequency improved with aprepitant, reducing by 22.2% (95% confidence interval [CI], 2.8-37.7%) over placebo while awake (P = 0.03), 30.3% (95% CI, 12.7-44.3) over 24 hours (P = 0.002), and 59.8% (95% CI, 15.1-86.0) during sleep (P = 0.081). Patient-reported outcomes all significantly improved. Substance P depolarized both guinea pig and human vagus nerve. Aprepitant significantly inhibited substance P-induced depolarization by 78% in guinea pig (P = 0.0145) and 94% in human vagus (P = 0.0145).Conclusions: Substance P activation of NK-1 receptors appears to be an important mechanism driving cough in lung cancer, and NK-1 antagonists show promise as antitussive therapies.

Psychometric properties of the updated EORTC module for assessing quality of life in patients with lung cancer (QLQ-LC29): an international, observational field study.

BACKGROUND: The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) assesses quality of life (QOL) in patients with lung cancer and was the first EORTC module developed for use in international clinical trials. Since its publication in 1994, major treatment advances with possible effects on QOL have occurred. These changes called for an update of the module and its international psychometric validation. We aimed to investigate the scale structure and psychometric properties of the updated lung cancer module, QLQ-LC29, in patients with lung cancer. METHODS: This international, observational field study was done in 19 hospitals across 12 countries. Patients aged older than 18 years with a confirmed diagnosis of lung cancer and no other previous primary tumour, and who were mentally fit with sufficient language skills to understand and complete the questionnaire were included. Patients were asked during a hospital visit to fill in the paper versions of the core questionnaire EORTC QLQ-C30 plus QLQ-LC29, and investigators selected half of these patients to complete the questionnaire again 2-4 weeks later. Our primary aim was to assess the scale structure and psychometric properties of EORTC QLQ-LC29. We analysed scale structure using confirmatory factor analysis; reliability using Cronbach's α value (internal consistency) and intra-class coefficient (test-retest reliability); sensitivity using independent t tests stratified by Karnofsky performance status; and responsiveness to change over time by ANOVA. This study is registered with ClinicalTrials.gov, NCT02745691. FINDINGS: Between April 12, 2016, and Sept 26, 2018, 523 patients with a confirmed diagnosis of either non-small-cell lung cancer (n=442) or small-cell lung cancer (n=81) were recruited. Confirmatory factor analysis provided a solution composed of five multi-item scales (coughing, shortness of breath, fear of progression, hair problems, and surgery-related symptoms) plus 15 single symptom or side-effect items: χ2=370·233, root mean square error of approximation=0·075, and comparative-fit index=0·901. Cronbach's α for internal consistencies of all multi-item scales were above the threshold of 0·70. Intra-class coefficients for test-retest reliabilities ranged between 0·82 and 0·97. Three (shortness of breath, fear of progression, and hair problems) of the five multi-item scales showed responsiveness to change over time (p values <0·05), as did nine of 15 single symptom items. Four (coughing, shortness of breath, fear of progression, and surgery-related symptoms) of the five multi-item scales and ten of the 15 single symptom items were sensitive to known group differences (ie, lower vs higher Karnofsky performance status). INTERPRETATION: Results determined the psychometric properties of the updated lung cancer module, which is ready for use in international clinical studies. FUNDING: EORTC Quality of Life Group.

A cross sectional study to determine the prevalence of cough and its impact in patients with lung cancer: a patient unmet need.

BACKGROUND: There is absence of literature related to cough prevalence and its characteristics in lung cancer patients, with information deriving only from broader symptoms occurrence studies. The aims of this study were to provide a snapshot of the prevalence of all-cause-cough in lung cancer patients and to characterise cough in terms of its impact and severity. METHODS: A cross-sectional study recruiting consecutive lung cancer patients over a pre-defined period of time and using cough-specific validated tools in a tertiary referral centre in the UK, including a cough severity VAS and the Manchester Cough in Lung Cancer scale (MCLCS). RESULTS: Data was collected from 202 patients. All-cause cough prevalence was 57% (through VAS) both in the screened (N = 223) and research (N = 202) population or 67% (through the MCLCS), and cough severity was moderate at a mean of 32 mm (in a 100 mm VAS). Age, sex, smoking status, lung cancer histology, stage and comorbidities were not associated with cough prevalence. The only variable associated with lower cough reports was being 'on anticancer treatment'; fewer patients on treatment reported a cough (40%) compared to those off treatment (54%) (p = 0.04). The impact of cough (as measured by MCLCS) was also significant (mean score = 22). About 18% of patients felt moderate/severe distress from their cough and about 15% often or always reported disturbed sleep due to coughing. Half the patients felt their cough warranted treatment. CONCLUSIONS: Cough is a common symptom in lung cancer with considerable impact on patients' lives. Cough presence and severity should regularly be assessed in clinical practice. There is an urgent need to focus on developing more potent antitussive treatments and improve the management of this complex and distressing symptom.

Sensitivity to change of the EORTC quality of life module measuring cancer-related fatigue (EORTC QlQ-Fa12): Results from the international psychometric validation.

OBJECTIVE: The European Organisation for Research and Treatment of Cancer Quality of Life Group (EORTC QLG) has developed a multidimensional instrument measuring cancer-related fatigue, the EORTC QLQ-FA12. The analysis of sensitivity to change is an essential part of psychometric validation. With this study, we investigated the EORTC QLQ-FA12's sensitivity to change. METHODS: The methodology follows the EORTC guidelines of EORTC QLG for phase IV validation of modules. We included cancer patients undergoing curative and palliative treatment at t1 and followed them up prospectively over the course of their treatment (t2) and 4 weeks after completion of treatment (t3). Data were collected prospectively at 17 sites in 11 countries. Sensitivity to change was investigated using analysis of variance. RESULTS: A total sample of 533 patients was enrolled with various tumour types, different stages of cancer, and receiving either curative treatment (n=311) or palliative treatment (n=222). Over time all fatigue scores were significantly higher in the palliative treatment group compared with the curative group (p < .001). Physical fatigue increased with medium effect size over the course of treatment in the curative group (standardized response mean [SRM] (t1,t2) = 0.44]. After treatment physical [SRM (t2,t3) = 0.39], emotional [SRM (t2,t3)= 0.28] and cognitive fatigue (SRM [t2,t3] = 0.22) declined significantly in the curative group. In the palliative group, emotional (SRM [t2,t3] = 0.18) as well as cognitive [SRM [t2,t3] = 0.26) fatigue increases significantly. CONCLUSIONS: The EORTC-QLQ-FA12 proved to identify clinically significant changes in fatigue in the course of curative and palliative cancer treatment.

Use of the lung cancer-specific Quality of Life Questionnaire EORTC QLQ-LC13 in clinical trials: A systematic review of the literature 20 years after its development.

The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) covers 13 typical symptoms of lung cancer patients and was the first module developed in conjunction with the EORTC core quality-of-life (QL) questionnaire. This review investigates how the module has been used and reported in cancer clinical trials in the 20 years since its publication. Thirty-six databases were searched with a prespecified algorithm. This search plus an additional hand search generated 770 hits, 240 of which were clinical studies. Two raters extracted data using a coding scheme. Analyses focused on the randomized controlled trials (RCTs). Of the 240 clinical studies that were identified using the LC13, 109 (45%) were RCTs. More than half of the RCTs were phase 3 trials (n = 58). Twenty RCTs considered QL as the primary endpoint, and 68 considered it as a secondary endpoint. QL results were addressed in the results section of the article (n = 89) or in the abstract (n = 92); and, in half of the articles, QL results were presented in the form of tables (n = 53) or figures (n = 43). Furthermore, QL results had an impact on the evaluation of the therapy that could be clearly demonstrated in the 47 RCTs that yielded QL differences between treatment and control groups. The EORTC QLQ-LC13 fulfilled its mission to be used as a standard instrument in lung cancer clinical trials. An update of the LC13 is underway to keep up with new therapeutic trends and to ensure optimized and relevant QL assessment in future trials.

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.

The experiences and decision making of patients with incurable cancer and health literacy difficulties.

OBJECTIVE: Shared decision making is important when decisions are preference sensitive, as in incurable cancer. A prerequisite for shared decision making is health literacy, which is essential to facilitate good understanding of an individual's current situation, the decision to be made, and the options available to them. This study sought to learn about the challenges for shared decision making faced by patients with incurable cancer and health literacy difficulties. METHODS: Semi-structured telephone and video interviews were used to collect data on participants' experiences, decision making, and challenges faced. Study procedures followed health literacy principles, with information offered in various formats to suit individuals' preferences, the use of a verbal consent process, and flexibility in whether interviews were conducted over telephone or video call. Data were analysed using Framework Analysis (Ritchie et al. 2003), with initial verbatim transcription of interviews, iterative development of the analysis framework, indexing using Nvivo 12 software and summarising of the data before systematic categorisation and development of final themes. RESULTS: Twenty participants (aged 31-80, of whom 13 male) with a variety of cancers (including breast, central nervous system, gastrointestinal, gynaecological, lung, head and neck, and urological) and experience of a range of treatments were interviewed. Seven themes were identified, including: supportive staff in an imperfect system, additional pressure from COVID-19, in the expert's hands, treatment not so bad, emotional hurdles, accessing information to further understanding and wanting to be a good patient. CONCLUSION: In order to support patients with incurable cancer and health literacy difficulties to become involved in decisions about their care, we must address the emotional, social and informational challenges they face. Recommendations for achieving this include addressing peoples' emotional needs, facilitating control over information, developing a partnership, involving others, and organisational changes.

Cohort study investigating evolution and factors associated with dyspnoea after anatomic lung resection.

Background: Dyspnoea is common following surgical resection for non-small cell lung cancer (NSCLC). The effects range from reduced quality of life to impact on adjuvant therapy outcomes. Currently, dyspnoea beyond the immediate postoperative phase and risk factors are not well characterised. We hope to assess the evolution of patient-reported dyspnoea after anatomic lung resection and associated factors. Methods: Single-centre cohort study with analysis on data collected longitudinally of 131 patients undergoing anatomic lung resections for NSCLC between September 2014 and December 2018. The European Organization for Research and Treatment Lung Cancer-specific Quality of Life Questionnaire Dyspnoea Scale was used to measure dyspnoea before and after surgery. Multivariable regression analysis was used to identify factors associated with clinically meaningful perioperative changes in dyspnoea at 6-12 months. Results: Mean Dyspnoea Scale scores preoperatively and 6-12 months after resection were 12.6 (standard deviation 17.4) and 17.9 (standard deviation 20.5), respectively. Of all patients 31% experienced a clinically meaningful increase in dyspnoea, defined as >10 points between Dyspnoea Scale scores preoperatively and at 6-12 months. Comparatively, 71% of patients without preoperative symptoms of dyspnoea developed a clinically meaningful increase of dyspnoea postoperatively. After adjusting the analysis for baseline factors and preoperative Dyspnoea Scale score, female sex remained the only patient factor associated with increased postoperative dyspnoea at 6-12 months after surgery (P=0.046). A total of 34% of patients reported increased dyspnoea after lobectomies and 9% after segmentectomies (P=0.014). Segmentectomy (as opposed to larger resections) was the only surgical factor associated with lower risk of increased dyspnoea (P=0.057). Conclusions: A clinically meaningful increase in dyspnoea is frequent after lung resection. Postoperative evolution of dyspnoea is non-predictable using objective baseline factors highlighting the importance of patient reported symptoms and involvement in clinical consultation.

The role of health literacy in cancer care: A mixed studies systematic review.

BACKGROUND: Patients diagnosed with cancer face many challenges and need a good understanding of their diagnosis and proposed treatments to make informed decisions about their care. Health literacy plays an important role in this and low health literacy has been associated with poorer outcomes. The aims of this review are to identify which outcomes relate to health literacy in patients with cancer, and to combine this through a mixed studies approach with the patient experience as described through qualitative studies. METHODS: Four electronic databases were searched in January 2021 to identify records relating to health literacy and patients with cancer. Records were independently screened then assessed for inclusion by two reviewers according to the following criteria: patients aged ≥18 years with cancer, English language publication AND health literacy measured with validated tool and measured outcome associated with health literacy OR qualitative study exploring the role of health literacy as patients make decisions about health. Quality was independently assessed by two reviewers. A narrative synthesis was performed, and findings integrated through concept mapping. This systematic review was registered with PROSPERO, entry CRD42020166454. RESULTS: 4441 records were retrieved. Following de-duplication, 2496 titles and abstracts were screened and full texts of 405 papers were reviewed for eligibility. 66 papers relating to 60 studies met the eligibility criteria. Lower health literacy was associated with greater difficulties understanding and processing cancer related information, poorer quality of life and poorer experience of care. Personal and situational influences contributed to how participants processed information and reached decisions about their care. CONCLUSION: This review highlights the important role of health literacy for patients with cancer. Outcomes are poorer for those who experience difficulties with health literacy. Further efforts should be made to facilitate understanding, develop health literacy and support patients to become more involved in their care.

Developing Symptom Lists for People with Cancer Treated with Targeted Therapies.

BACKGROUND: Targeted therapies (TTs) have revolutionised cancer treatment with their enhanced specificity of action. Compared with conventional therapies, TTs are delivered over a longer period and often have unusual symptom profiles. Patient-reported outcome measures such as symptom side-effect lists need to be developed in a time-efficient manner to enable a rapid and full evaluation of new treatments and effective clinical management OBJECTIVE: The aim of this study was to develop a set of TT-related symptoms and identify the optimal method for developing symptom lists. PATIENTS AND METHODS: Symptoms from TT treatment in the context of Chronic Myeloid Leukaemia (CML), HER2-positive breast cancer, or Gastrointestinal Stromal Tumours (GIST) were identified through literature reviews, interviews with healthcare professionals (HCPs) and patients, and patient focus groups. The symptom set was then pilot tested in patients across the three cancer diagnoses: The number of items derived from each source (literature, patients, or HCPs) were compared. RESULTS: A total of 316 patients and 86 HCPs from 16 countries participated. An initial set of 209 symptoms was reduced to 61 covering 12 symptom categories. Patient interviews made the greatest contribution to the item set. CONCLUSIONS: Symptom lists should be created based on input from patients. The item set described will be applicable to the assessment of new TTs, and in monitoring treatment.

Gender effects on quality of life and symptom burden in patients with lung cancer: results from a prospective, cross-cultural, multi-center study.

BACKGROUND: Lung cancer causes impairment of health-related quality of life (QoL), but little is known about gender aspects in QoL and symptom burden of lung cancer patients. The aim of this study was to investigate gender differences in QoL as assessed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the updated lung cancer module. METHODS: In a prospective, international, cross-cultural, multicenter study that was undertaken to update the lung cancer-specific module EORTC QLQ-LC13, patients filled in the core questionnaire EORTC QLQ-C30 and the updated lung cancer module. Gender differences were calculated for all QoL scores using ANCOVAs that controlled for known and suspected confounders. Comparisons with historic data were drawn. RESULTS: A total of 200 patients (82 female and 118 male, median age 65 years) were recruited. With the exception of coughing (estimated marginal means: women 33.86 and men 43.52, P=0.022) and diarrhea (estimated marginal means: women 26.01 and men 17.93, P=0.038) there were no significant QoL gender differences. Fatigue was the most pronounced symptom in both, men and women, outpacing typical respiratory symptoms. Quite generally, our sample of lung cancer patients showed considerably worse QoL in all scores when compared to EORTC reference data (lung cancer and combined cancer diagnoses, mean differences up to 13.70 and 21.54 score points, respectively) and to a German norm reference sample (up to 35.37 score points). CONCLUSIONS: This study adds to the literature in showing that the typical QoL gender difference effect (women doing worse than men) may not be generalizable across all patient samples.

Developing and testing a web-based intervention to encourage early help-seeking in people with symptoms associated with lung cancer.

OBJECTIVES: To detail the development method used to produce an online, tailored, theory-based, user-centred intervention to encourage help-seeking for potential lung cancer symptoms. DESIGN: Intervention development was structured around the person-based approach. The feasibility study involved a randomized controlled trial design. METHODS: Intervention development drew on qualitative inquiries, the Theory of Planned Behaviour (TPB), and identifying concrete mechanisms of change to implement in the intervention (Behaviour Change Techniques). The final intervention involved two key features: (1) tailoring and (2) 'TPB components' to target beliefs about help-seeking. In an online feasibility study, we recruited people reporting potential lung cancer symptoms using mailing lists, social media, websites, and Google AdWords. Participants were randomized to the intervention, a tailored comparison group (CG) without TPB-components, an untailored CG with TPB components, or a CG with neither. Following treatment, participants clicked a button to indicate whether they wished to make an appointment and completed a TPB questionnaire. RESULTS: A total of 130 participants reporting relevant symptoms were recruited (24% of website visitors). Participants in the intervention group reported higher intention to seek help than those who received tailored information without TPB components (p = .03). User comments indicate more support is needed for people who sought help for symptoms, but felt dismissed. CONCLUSIONS: The potential for differential dropout in online randomized trials requires careful consideration. Future help-seeking interventions should provide support for those who have previously felt dismissed by health professionals. The feasibility study provides some evidence that our 'TPB components' were effective, but validation in a powered trial is necessary. Statement of contribution What is already known on this subject? People with lung cancer often delay presenting symptoms to health services. Some patients (or their family/friends) look up symptoms online before their diagnosis, to decide whether they should see a doctor. Interventions are needed to ensure people can find useful information online that will encourage them to seek help for relevant symptoms. What does this study add? Theory-mapping and user involvement facilitated systematic intervention development. Lung cancer help-seeking interventions should address salient beliefs and personal relevance. The potential for differential dropout in online randomized trials requires careful consideration.

Cough in Patients With Lung Cancer: A Longitudinal Observational Study of Characterization and Clinical Associations.

BACKGROUND: Cough is common in patients with lung cancer, and current antitussive treatments are suboptimal. There are little published data describing cough in patients with lung cancer or work assessing clinical associations. The aim of this study is to fill that gap. METHODS: This was a longitudinal prospective observational single-cohort study over 60 days. Patients were assessed through self-reported validated scales and, in a subsample, ambulatory cough monitoring at study entry (day 0), day 30, and day 60. RESULTS: At study entry, 177 patients were included and 153 provided data at day 60. The median duration of cough was 52 weeks (interquartile range, 8.5-260). Cough was described as severe enough to warrant treatment in 62% of the patients. Depending on the scale used, performance status was associated with both cough severity and cough impact (P < .001) at study entry, whereas higher cough severity at study entry was associated with female sex (P = .02), asthma (P = .035), and reflux disease (P < .001). Cough impact at study entry was additionally associated with experiencing nausea (P = .018). Cancer characteristics (ie, cancer stage, histology) were not associated with cough severity nor cough impact; neither was smoking or COPD. CONCLUSIONS: This is the first study to describe characteristics of cough in patients with lung cancer and to identify clinical associations that may be relevant for its treatment. Our data suggest that cough is a frequent and distressing symptom and an unmet clinical need. Its association with gastrointestinal symptoms in this study may improve our understanding of pathophysiology and therapeutic options for cough occurring in patients with lung cancer.

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.

International Psychometric Validation of an EORTC Quality of Life Module Measuring Cancer Related Fatigue (EORTC QLQ-FA12).

Background: The European Organisation for Research and Treatment of Cancer (EORTC) Group has developed a new multidimensional instrument measuring cancer-related fatigue to be used in conjunction with the quality of life core questionnaire (EORTC QLQ-C30). The module EORTC QLQ-FA13 assesses physical, cognitive, and emotional aspects of cancer-related fatigue. Methods: The methodology follows the EORTC guidelines for phase IV validation of modules. This paper focuses on the results of the psychometric validation of the factorial structure of the module. For validation and cross-validation confirmatory factor analysis (maximum likelihood estimation), intraclass correlation and Cronbach alpha for internal consistency were employed. The study involved an international multicenter collaboration of 11 European and non-European countries. Results: A total of 946 patients with various tumor diagnoses were enrolled. Based on the confirmatory factor analysis, we could approve the three-dimensional structure of the module. Removing one item and reassigning the factorial mapping of another item resulted in the EORTC QLQ-FA12. For the revised scale, we found evidence supporting good local (indicator reliability ≥ 0.60, factor reliability ≥ 0.82) and global model fit (GFI t1|t2 = 0.965/0.957, CFI t1|t2 = 0.976/0.972, RMSEA t1|t2 = 0.060/0.069) for both measurement points. For each scale, test-retest reliability proved to be very good (intraclass correlation: R t1-t2 = 0.905-0.921) and internal consistency proved to be good to high (Cronbach alpha = .79-.90). Conclusion: Based on the former phase III module, the multidimensional structure was revised as a phase IV module (EORTC FA12) with an improved scale structure. For a comprehensive validation of the EORTC FA12, further aspects of convergent and divergent validity as well as sensitivity to change should be determined.

Understanding cough and its management in lung cancer.

PURPOSE OF REVIEW: This article summarizes the current understanding of cough in lung cancer, strategies for its management and highlights areas where further research is warranted.Cough is common, severe and distressing for many lung cancer patients. Currently few effective cough interventions exist for lung cancer patients. This review proposes some of the mechanisms that may underlie cough in lung cancer and presents the existing data on antitussive therapy in cancer patients. A greater focus on the cough mechanisms may enable effective antitussives to be developed in the future for lung cancer patients. A brief overview of the validated cough assessment tools is provided. The use of such tools will enable robust clinical endpoints to be determined for future cough intervention studies. A 'cough treatment pyramid' is presented to provide a pragmatic approach to the management of cough in lung cancer patients. RECENT FINDINGS: Despite the small number of publications on cough in lung cancer, some recent research has characterized cough for the first time in lung cancer patients. Its impact on quality of life domains such as psychological, social and physical is significant. The lung cancer symptom cluster of cough, breathlessness and fatigue has also been described. A recently developed cough severity assessment tool has provided researchers with a short well validated seven-item questionnaire to determine this important cough characteristic. In addition, a Cochrane Database Systematic Review on Interventions for Cough in Cancer has also been published. These studies are all described in the present review. Understanding the impact of a symptom such as cough, the assessment of cough and its potential underlying mechanisms is crucial if we are to manage this symptom effectively. SUMMARY: Current cough management in lung cancer patients is lagging behind the management of other cancer symptoms. There is now an increasing need to diagnose and treat cough more effectively, as lung cancer patients are living longer with chronic symptoms such as cough.

Targeted therapies in small cell lung cancer: a review.

Small cell lung cancer (SCLC) is an aggressive form of lung cancer that is characterized by a rapid doubling time, early onset of dissemination and high sensitivity to chemotherapy. Despite the potential for cure in patients with limited disease with concurrent chemoradiation and an initial good response to chemotherapy in extensive disease, there is a high chance of disease relapse with an overall poor median survival for both stages. With increasing translational research and a better understanding of the molecular basis of cancer, a number of molecular targets have been identified in various preclinical studies. This review summarizes potentially viable targets and new agents that have been developed and employed in recent, ongoing and future clinical trials to attempt to improve clinical outcomes in this disease.

Clinical expert guidelines for the management of cough in lung cancer: report of a UK task group on cough.

BACKGROUND: Cough is a common and distressing symptom in lung cancer patients. The clinical management of cough in lung cancer patients is suboptimal with limited high quality research evidence available. The aim of the present paper is to present a clinical guideline developed in the UK through scrutiny of the literature and expert opinion, in order to aid decision making in clinicians and highlight good practice. METHODS: Two systematic reviews, one focusing on the management of cough in respiratory illness and one Cochrane review specifically on cancer, were conducted. Also, data from reviews, phase II trials and case studies were synthesized. A panel of experts in the field was also convened in an expert consensus meeting to make sense of the data and make clinical propositions. RESULTS: A pyramid of cough management was developed, starting with the treatment of reversible causes of cough/specific pathology. Initial cough management should focus on peripherally acting and intermittent treatment; more resistant symptoms require the addition of (or replacement by) centrally acting and continuous treatment. The pyramid for the symptomatic management starts from the simpler and most practical regimens (demulcents, simple linctus) to weak opioids to morphine and methadone before considering less well-researched and experimental approaches. CONCLUSION: The clinical guidelines presented aim to provide a sensible clinical approach to the management of cough in lung cancer. High quality research in this field is urgently required to provide more evidence-based recommendations.