Prognostic value of patient-reported quality of life for survival in oesophagogastric cancer:Analysis from the population-based POCOP study

BACKGROUND: Accumulating evidence of trials demonstrates that patient-reported health-related quality of life (HRQoL) at diagnosis is prognostic for overall survival (OS) in oesophagogastric cancer. However, real-world data are lacking. Moreover, differences in disease stages and tumour-specific symptoms are usually not taken into consideration. The aim of this population-based study was to assess the prognostic value of HRQoL, including tumour-specific scales, on OS in patients with potentially curable and advanced oesophagogastric cancer. METHODS: Data were derived from the Netherlands Cancer Registry and the patient reported outcome registry (POCOP). Patients included in POCOP between 2016 and 2018 were stratified for potentially curable (cT1-4aNallM0) or advanced (cT4b or cM1) disease. HRQoL was measured with the EORTC QLQ-C30 and the tumour-specific OG25 module. Cox proportional hazards models assessed the impact of HRQoL, sociodemographic and clinical factors (including treatment) on OS. RESULTS: In total, 924 patients were included. Median OS was 38.9 months in potentially curable patients (n = 795) and 10.6 months in patients with advanced disease (n = 129). Global Health Status was independently associated with OS in potentially curable patients (HR 0.89, 99%CI 0.82-0.97), together with several other HRQoL items: appetite loss, dysphagia, eating restrictions, odynophagia, and body image. In advanced disease, the Summary Score was the strongest independent prognostic factor (HR 0.75, 99%CI 0.59-0.94), followed by fatigue, pain, insomnia and role functioning. CONCLUSION: In a real-world setting, HRQoL was prognostic for OS in patients with potentially curable and advanced oesophagogastric cancer. Several HRQoL domains, including the Summary Score and several OG25 items, could be used to develop or update prognostic models

Effective Melanoma Immunotherapy in Mice by the Skin-Depigmenting Agent Monobenzone and the Adjuvants Imiquimod and CpG

Background: Presently melanoma still lacks adequate treatment options for metastatic disease. While melanoma is exceptionally challenging to standard regimens, it is suited for treatment with immunotherapy based on its immunogenicity. Since treatment-related skin depigmentation is considered a favourable prognostic sign during melanoma intervention, we here aimed at the reverse approach of directly inducing vitiligo as a shortcut to effective anti-melanoma immunity. Methodology and Principal Findings: We developed an effective and simple to use form of immunotherapy by combining the topical skin-bleaching agent monobenzone with immune-stimulatory imiquimod cream and cytosine-guanine oligodeoxynucleotides (CpG) injections (MIC therapy). This powerful new approach promptly induced a melanoma antigen-specific immune response, which abolished subcutaneous B16. F10 melanoma growth in up to 85% of C57BL/6 mice. Importantly, this regimen induced over 100 days of tumor-free survival in up to 60% of the mice, and forcefully suppressed tumor growth upon re-challenge either 65- or 165 days after MIC treatment cessation. Conclusions: MIC therapy is effective in eradicating melanoma, by vigilantly incorporating NK-, B-and T cells in its therapeutic effect. Based on these results, the MIC regimen presents a high-yield, low-cost and simple therapy, readily applicable in the clini

Th17 Cells and Activated Dendritic Cells Are Increased in Vitiligo Lesions

Vitiligo is a common skin disorder, characterized by progressive skin de-pigmentation due to the loss of cutaneous melanocytes. The exact cause of melanocyte loss remains unclear, but a large number of observations have pointed to the important role of cellular immunity in vitiligo pathogenesis.In this study, we characterized T cell and inflammation-related dermal dendritic cell (DC) subsets in pigmented non-lesional, leading edge and depigmented lesional vitiligo skin. By immunohistochemistry staining, we observed enhanced populations of CD11c+ myeloid dermal DCs and CD207+ Langerhans cells in leading edge vitiligo biopsies. DC-LAMP+ and CD1c+ sub-populations of dermal DCs expanded significantly in leading edge and lesional vitiligo skin. We also detected elevated tissue mRNA levels of IL-17A in leading edge skin biopsies of vitiligo patients, as well as IL-17A positive T cells by immunohistochemistry and immunofluorescence. Langerhans cells with activated inflammasomes were also noted in lesional vitiligo skin, along with increased IL-1ß mRNA, which suggest the potential of Langerhans cells to drive Th17 activation in vitiligo.These studies provided direct tissue evidence that implicates active Th17 cells in vitiligo skin lesions. We characterized new cellular immune elements, in the active margins of vitiligo lesions (e.g. populations of epidermal and dermal dendritic cells subsets), which could potentially drive the inflammatory responses

Monobenzone-induced depigmentation: from enzymatic blockade to autoimmunity

Autoimmune side-effects such as vitiligo regularly occur during melanoma immunotherapy. As vitiligo development is associated with a superior prognosis, the active induction of vitiligo in melanoma patients can be a useful tactic. The potent skin-depigmenting agent monobenzone can be used successfully for this purpose. However, until recently, the mechanism of action behind monobenzone-induced skin depigmentation was unclear. Lately, the mechanistic basis for the augmented immunogenicity of monobenzone-exposed pigmented cells has been unveiled, and their active role in the induction of autoimmune T-cell-mediated vitiligo has become apparent. Here, we provide an immunological framework in which we condense this knowledge to an integrated theory of the generation of monobenzone-induced vitilig

Eye-tracking analyses of physician face gaze patterns in consultations

Face gaze is a fundamental non-verbal behaviour and can be assessed using eye-tracking glasses. Methodological guidelines are lacking on which measure to use to determine face gaze. To evaluate face gaze patterns we compared three measures: duration, frequency and dwell time. Furthermore, state of the art face gaze analysis requires time and manual effort. We tested if face gaze patterns in the first 30, 60 and 120 s predict face gaze patterns in the remaining interaction. We performed secondary analyses of mobile eye-tracking data of 16 internal medicine physicians in consultation with 100 of their patients. Duration and frequency of face gaze were unrelated. The lack of association between duration and frequency suggests that research may yield different results depending on which measure of face gaze is used. Dwell time correlates both duration and frequency. Face gaze during the first seconds of the consultations predicted face gaze patterns of the remaining consultation time (R2 0.26 to 0.73). Therefore, face gaze during the first minutes of the consultations can be used to predict face gaze patterns over the complete interaction. Researchers interested to study face gaze may use these findings to make optimal methodological choices

Prediction models for patients with esophageal or gastric cancer: A systematic review and meta-analysis

Clinical prediction models are increasingly used to predict outcomes such as survival in cancer patients. The aim of this study was threefold. First, to perform a systematic review to identify available clinical prediction models for patients with esophageal and/or gastric cancer. Second, to evaluate sources of bias in the included studies. Third, to investigate the predictive performance of the prediction models using meta-analysis. MEDLINE, EMBASE, PsycINFO, CINAHL, and The Cochrane Library were searched for publications from the year 2000 onwards. Studies describing models predicting survival, adverse events and/or health-related quality of life (HRQoL) for esophageal or gastric cancer patients were included. Potential sources of bias were assessed and a meta-analysis, pooled per prediction model, was performed on the discriminative abilities (c-indices). A total of 61 studies were included (45 development and 16 validation studies), describing 47 prediction models. Most models predicted survival after a curative resection. Nearly 75% of the studies exhibited bias in at least 3 areas and model calibration was rarely reported. The meta-analysis showed that the averaged c-index of the models is fair (0.75) and ranges from 0.65 to 0.85. Most available prediction models only focus on survival after a curative resection, which is only relevant to a limited patient population. Few models predicted adverse events after resection, and none focused on patient's HRQoL, despite its relevance. Generally, the quality of reporting is poor and external model validation is limited. We conclude that there is a need for prediction models that better meet patients' information needs, and provide information on both the benefits and harms of the various treatment options in terms of survival, adverse events and HRQo

Communicating treatment risks and benefits to cancer patients: a systematic review of communication methods

Purpose: Cancer patients are increasingly involved in decision-making processes. Hence, clinicians need to inform patients about the risks and benefits of different treatment options in order for patients to make well informed decisions. The aim of this review is to determine the effects of methods of communicating prognostic information about (1) disease progression (survival, progression, recurrence and remission), (2) side effects and complications and (3) health-related quality of life (HRQL) on cognitive, affective and behavioral outcomes in cancer patients. Methods: A literature search was performed to select articles that were published up to November 2019 and that examined verbal and/or visual risk communication interventions in an oncological clinical setting. Results: The search yielded 14,875 studies; 28 studies were ultimately included. For disease progression information, we found that framing affects treatment choice. Furthermore, limiting the amount of progression information in a graphical display could benefit patients’ understanding of risks and benefits. For prognostic information about side effects and complications, precise and defined risk information was better understood than information presented in words. When displaying HRQL data, no consensus was found on which graph type to use. Conclusion: Great heterogeneity in the results and methodology and in the compared communication formats precluded us from drawing any further conclusions. Practical implications for clinicians are to consider the effects that different types of framing might have on the patient and to not rely exclusively on words to describe risks, but rather include at least some form of numbers or visualization

Health-related quality of life in curatively-treated patients with esophageal or gastric cancer: A systematic review and meta-analysis

Surgery and chemoradiotherapy can potentially cure esophageal and gastric cancer patients, although they may impact health-related quality of life (HRQoL). We aim to systemically review and meta-analyze literature to determine the effect of curative treatments on HRQoL in esophageal and gastric cancer.— A systematic search was performed identifying studies assessing HRQoL. Meta-analyses were performed on baseline and subsequent time-points.— From the 6067 articles retrieved, 49 studies were included (61 % low quality). Meta-analyses showed short-term HRQoL differences between esophageal cancer patients receiving definitive chemoradiotherapy (dCRT), neoadjuvant chemo(radio)therapy (nC(R)T), or surgery alone (p < 0.001), with better HRQoL with nC(R)T and surgery compared to dCRT. Over the course of 12 months, no HRQoL difference was identified between treatments in esophageal cancer (p = 0.633). Esophagectomy, but not gastrectomy, resulted in a clinically relevant decline in HRQoL. No long-term HRQoL differences were identified between curative treatments in esophageal and gastric cancer. More high-quality HRQoL studies are warranted

Inflammasome-Dependent Induction of Adaptive NK Cell Memory

Monobenzone is a pro-hapten that is exclusively metabolized by melanocytes, thereby haptenizing melanocyte-specific antigens, which results in cytotoxic autoimmunity specifically against pigmented cells. Studying monobenzone in a setting of contact hypersensitivity (CHS), we observed that monobenzone induced a long-lasting, melanocyte-specific immune response that was dependent on NK cells, yet fully intact in the absence of T- and B cells. Consistent with the concept of "memory NK cells," monobenzone-induced NK cells resided in the liver and transfer of these cells conferred melanocyte-specific immunity to naive animals. Monobenzone-exposed skin displayed macrophage infiltration and cutaneous lymph nodes showed an inflammasome-dependent influx of macrophages with a tissue-resident phenotype, coinciding with local NK cell activation. Indeed, macrophage depletion or the absence of the NLRP3 inflammasome, the adaptor protein ASC or interleukin-18 (IL-18) abolished monobenzone CHS, thereby establishing a non-redundant role for the NLRP3 inflammasome as a critical proinflammatory checkpoint in the induction of hapten-dependent memory NK cell