BackgroundThe EORTC QLQ-LC13 assesses quality of life (QoL) in patients with lung cancer (LC) and was the first EORTC module developed for use in international clinical trials. Since its publication in 1994, major treatment advances have occurred. This calls for an update of the module to improve the assessment and management of side effects, symptom burden, and quality of life. The paper presents results from the international psychometric validation study of the updated module. MethodsThis was an international, observational field study to investigate the psychometric properties of the updated LC-module. Psychometric analyses included confirmatory factor analysis and methods from classical test theory. Findings 523 patients with confirmed diagnosis of lung cancer (either NSCLC or SCLC; 270 [51•6%] NSCLC IV, 315 [60•2%] male, Karnofksy Performance Status median 80 [IQR = 20]) from 19 centers in 12 countries participated. The updated module consists of 29 items, keeping 12 from the previous QLQ-LC13. Confirmatory factor analysis suggested five multi-item scales (Coughing, Shortness of breath, Fear of progression, Hair problems, Surgery-related symptoms ) and 15 single items: RMSEA = 0•075, GFI = 0•934, NFI = 0•877, CFI = 0•901.Analyses of convergent and divergent validity confirmed this solution. Internal consistencies of all multi-item scales ranged between 0•73 and 0•86. Test-retest reliabilities ranged between 0•82 and 0•97. Four of the five multi-item scales yielded known group differences when patients with lower vs. higher Karnofsky Performance Status were contrasted (p < 0•007); so did 10 of the 15 single items. Three of the five multi-item scales showed responsiveness to change over time (p < 0•050); so did 9 out of 15 single symptoms. InterpretationThe Phase 4 study determined the psychometric properties of the updated LC module, which is ready for use in international clinical lung cancer studies.

The role of oxidative stress in cancer is complex. While the pathological alterations induced by oxidative stress may be involved in the induction of tumours, in the late stages of tumour development, it can facilitate the loss of tumour cells and might even prevent metastasis. Tumour cells show metabolic alterations, often inducing an increased production of reactive oxygen species, which makes these cells particularly vulnerable to additional oxidative stress. This is an important mode of action in the use of many chemotherapeutics and in the application of ionizing radiation. Uveal melanoma is the most frequent primary tumour in the adult eye. For metastasis of this tumour, which affects about 50 % of the patients, no appropriate treatment is currently available. However, the primary tumour can efficiently be treated with ionizing radiation. A frequent side effect of this treatment is radiation retinopathy, which is treated with vascular endothelial growth factor (VEGF) antagonists. A therapy of the primary tumour with VEGF antagonists is under discussion. So far, little data is available on this subject, however, a paradoxical worsening of the situation has been found in a mouse model of uveal melanoma treated with bevacizumab. We have investigated the effect of VEGF and of the VEGF-antagonist bevacizumab on the survival of five different melanoma cell lines under oxidative stress treatment with hydrogen peroxide. In addition, we investigated the expression of relevant proteins and the effect of bevacizumab on the proliferation of the cells as well as its effect on the angiogenic behaviour of endothelial cells, co-cultured with uveal melanoma cells. Our study showed that not only VEGF but also, paradoxically, the VEGF-antagonist bevacizumab is able to protect uveal melanoma cells from oxidative stress-induced cell death. Bevacizumab did not influence the proliferation of the cells and showed only limited effectiveness to reduce angiogenic structures. Considering that oxidative stress is the mode of action for ionizing radiation to induce cell death, a protective effect of bevacizumab on uveal melanoma cells against oxidative stress is worrisome and argues against the use of VEGF in uveal melanoma.

Background: Overall survival is the ultimate criterion for the therapy of lung cancer, but psychosocial care, which helps the patient to cope with the disease, becomes a more and more important issue in the treatment of this life-threatening disease. Methods: We report the satellite project within a prospective, international, cross-cultural, multicenter study to validate the EORTC QLQ-LC29, a new designed module to assess the quality of life of lung cancer patients. The participants filled in the EORTC QLQ-C30, the recently updated lung cancer module QLQ-LC29 and the Hornheide questionnaire (HSI). Results: A total of 81 patients (32 female and 49 male, mean age 65.2 years, SD = 9.7) were enrolled in this study by completing the questionnaires. Fatigue (mean 55.4, SD = 26.3) and dyspnea (mean 46.3, SD = 36.2) were the most prominent symptoms. Thirty-nine patients (48.1%) according to the HSI needed psychosocial support. When using the EORTC questionnaires as screening instrument with 50 as cut-off in contrast only 29.5% of our patients needed psychosocial support. The need for psychosocial support according to the HSI correlated most with the EORTC scales "fatigue" (38.3% overlap between the two questionnaires), "existential fear" (38.3% overlap between the two questionnaires) and worse "global quality of life" (27.2% overlap between the two questionnaires). Conclusion: If psychosocial distress is at the core, the HSI is a suitable instrument for quick screening. The EORTC measures help to specify impaired quality of life areas and also cover somatic symptoms that are specific for cancer patients. Once psychosocial distress has been ascertained, clinicians should be particularly aware of specific problems regarding "fatigue", "existential fear" and diminished "global quality of life".