Early detection and treatment are critical for improving the outcome of patients with cancer
. Understanding the largely uncharted biology of carcinogenesis requires deciphering molecular processes ...in premalignant lesions, and revealing the determinants of the intralesional immune reaction during cancer development. The adaptive immune response within tumours has previously been shown to be strongest at the earliest stage of carcinoma
. Here we show that immune activation and immune escape occur before tumour invasion, and reveal the relevant immune biomarkers of the pre-invasive stages of carcinogenesis in the lung. We used gene-expression profiling and multispectral imaging to analyse a dataset of 9 morphological stages of the development of lung squamous cell carcinoma, which includes 122 well-annotated biopsies from 77 patients. We identified evolutionary trajectories of cancer and immune pathways that comprise (1) a linear increase in proliferation and DNA repair from normal to cancerous tissue; (2) a transitory increase of metabolism and early immune sensing, through the activation of resident immune cells, in low-grade pre-invasive lesions; (3) the activation of immune responses and immune escape through immune checkpoints and suppressive interleukins from high-grade pre-invasive lesions; and, ultimately, (4) the activation of the epithelial-mesenchymal transition in the invasive stage of cancer. We propose that carcinogenesis in the lung involves a dynamic co-evolution of pre-invasive bronchial cells and the immune response. These findings highlight the need to develop immune biomarkers for early detection as well as immunotherapy-based chemopreventive approaches for individuals who are at high risk of developing lung cancer.
To assess the impact of cell type, age, and gender in addition to pathologic tumor, node, metastasis (TNM) stage in surgically managed stage I-IIIA non-small cell lung cancer (NSCLC) cases from the ...international staging database of the International Association for the Study of Lung Cancer.
From the 67,725 cases of NSCLC submitted to the staging database, 9137 surgically managed cases were selected for which all the following variables were available: pathologic stage, age, gender, and specific histologic cell type. Performance status and smoking history were examined in subsets. Methods used were Cox proportional hazards regression and recursive partitioning and amalgamation (RPA) analyses.
Pathologic TNM stage, age, and gender were all independently prognostic for survival. The bronchioloalveolar carcinoma (BAC) subtype had superior survival over other cell types despite the potential for heterogeneity in this group. Adjusted comparisons revealed a small survival advantage for squamous cell carcinomas over non-BAC adenocarcinoma histology and also over large cell, though the effect appeared to be limited to the male patients. RPA revealed the importance of TNM stage primarily, and age was prognostic within stage groups. Cell type was not found to add prognostic value in the RPA analysis. Prognostic groups were formed based on the RPA output, and the prognostic value of these groupings was validated using the North American Surveillance, Epidemiology, and End Results Registries. Performance status and smoking history were prognostic in the subsets where data were available. Effects of other variable were not influenced by the inclusion of smoking status in regression models.
Age and gender are confirmed as important prognostic factors in surgically resected NSCLC. Cell type is less important, although the small population of cases classified as BAC have a survival advantage over other histologies, and there may be a small survival advantage for squamous cell carcinomas over non-BAC adenocarcinomas. Imbalances between stage, gender, and cell type at presentation may lead to a misleading result with respect to cell type in unadjusted analyses. Pathologic TNM category is the most important prognostic factor in this analysis.
This article proposes codes for the primary tumor categories of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) and a uniform way to measure tumor size in part-solid tumors ...for the eighth edition of the tumor, node, and metastasis classification of lung cancer. In 2011, new entities of AIS, MIA, and lepidic predominant adenocarcinoma were defined, and they were later incorporated into the 2015 World Health Organization classification of lung cancer. To fit these entities into the T component of the staging system, the Tis category is proposed for AIS, with Tis (AIS) specified if it is to be distinguished from squamous cell carcinoma in situ (SCIS), which is to be designated Tis (SCIS). We also propose that MIA be classified as T1mi. Furthermore, the use of the invasive size for T descriptor size follows a recommendation made in three editions of the Union for International Cancer Control tumor, node, and metastasis supplement since 2003. For tumor size, the greatest dimension should be reported both clinically and pathologically. In nonmucinous lung adenocarcinomas, the computed tomography (CT) findings of ground glass versus solid opacities tend to correspond respectively to lepidic versus invasive patterns seen pathologically. However, this correlation is not absolute; so when CT features suggest nonmucinous AIS, MIA, and lepidic predominant adenocarcinoma, the suspected diagnosis and clinical staging should be regarded as a preliminary assessment that is subject to revision after pathologic evaluation of resected specimens. The ability to predict invasive versus noninvasive size on the basis of solid versus ground glass components is not applicable to mucinous AIS, MIA, or invasive mucinous adenocarcinomas because they generally show solid nodules or consolidation on CT.
Few validated prognostic factors are available for survival in patients with lung cancer. 18F-fluoro-2-deoxy-d-glucose positron emission tomography has been shown to be of additional value to ...conventional imaging for staging lung cancer. The prognostic value of this lung tumor metabolic activity was studied in a first systematic review of studies published until 2006.
As further studies have appeared since 2006, this report has as objective to confirm and to estimate with less variability the prognostic value of primary tumor standardized uptake value (SUV) measured with 18F-fluoro-2-deoxy-d-glucose positron emission tomography on the basis of an updated search of eligible studies.
Ten additional studies were eligible for the updated review and eight of them provided, in the publication, data allowing survival results aggregation. All together, 21 studies were analyzed. Comparing patients with low and high SUV, using preferentially the median SUV value of each study as threshold, we obtained a poor prognostic value for high SUV compared with low SUV with an overall combined hazard ratio of 2.08, significantly different from one with a 95% confidence interval ranging from 1.69 to 2.56. No interaction between older and newer studies was detectable (P = 0.60) as well as between studies having selected non metastatic patients or studies without selection criterion related to stage (P = 0.46).
We confirmed the results of our previous review showing that SUV is potentially a very interesting factor for predicting patient outcome. We believe that a meta-analysis based on individual patient data would be of great value as allowing to assess the independent prognostic value, to take into account some factors responsible for heterogeneity between studies (SUV assessment method, disease stage, and histology), and to update survival data. We are planning to conduct such a meta-analysis on behalf of the International Association for the Study of Lung Cancer Staging Project.
In the context of the European Respiratory Society (ERS) plan for thoracic oncology 1, in 2014 the European Respiratory Journal (ERJ) initiated a series of reviews called "Challenges and ...controversies in thoracic oncology" 2. The following questions were addressed. The specific contribution of each thoracic staging and treatment modality has not always been unequivocally established: which grey areas remain? Concerning screening programmes for lung cancer, is it time for large-scale screening via chest computed tomography? Is multidisciplinary team management in thoracic oncology more than a concept? Considering tumour tissue sampling for lung cancer management at the era of personalised therapy, what is enough for molecular testing? Which approaches should be used for small sized lung cancer: lobectomy, sublobectomy or stereotactic irradiation? What is the place of multimodality management of malignant pleural mesothelioma? How can non-inferiority trials influence practice in thoracic oncology without valid conclusions? How should advanced nonsmall cell lung cancer (NSCLC) be treated: by targeted therapy, personalised chemotherapy or standard chemotherapy? What is the exact role of palliative care in the patient's management? What should be the approach to the staging of lung cancer, with regard to noninvasive, minimally invasive and invasive techniques? Which examinations (and at what time) should take place during the follow-up of the patient after lung cancer resection? What is the best management option for a patient with NSCLC, with an epidermal growth factor receptor activating mutation or with an Alk translocation?
ESR/ERS white paper on lung cancer screening Kauczor, Hans-Ulrich; Bonomo, Lorenzo; Gaga, Mina ...
The European respiratory journal,
07/2015, Letnik:
46, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Lung cancer is the most frequently fatal cancer, with poor survival once the disease is advanced. Annual low dose computed tomography has shown a survival benefit in screening individuals at high ...risk for lung cancer. Based on the available evidence, the European Society of Radiology and the European Respiratory Society recommend lung cancer screening in comprehensive, quality-assured, longitudinal programmes within a clinical trial or in routine clinical practice at certified multidisciplinary medical centres. Minimum requirements include: standardised operating procedures for low dose image acquisition, computer-assisted nodule evaluation, and positive screening results and their management; inclusion/exclusion criteria; expectation management; and smoking cessation programmes. Further refinements are recommended to increase quality, outcome and cost-effectiveness of lung cancer screening: inclusion of risk models, reduction of effective radiation dose, computer-assisted volumetric measurements and assessment of comorbidities (chronic obstructive pulmonary disease and vascular calcification). All these requirements should be adjusted to the regional infrastructure and healthcare system, in order to exactly define eligibility using a risk model, nodule management and quality assurance plan. The establishment of a central registry, including biobank and image bank, and preferably on a European level, is strongly encouraged.
To respond to the legitimate questions raised by the application of invasive methods of monitoring and life-support techniques in cancer patients admitted in the ICU, the European Lung Cancer Working ...Party and the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique, set up a consensus conference. The methodology involved a systematic literature review, experts’ opinion and a final consensus conference about nine predefined questions
1. Which triage criteria, in terms of complications and considering the underlying neoplastic disease and possible therapeutic limitations, should be used to guide admission of cancer patient to intensive care units?
2. Which ventilatory support High Flow Oxygenation, Non-invasive Ventilation (NIV), Invasive Mechanical Ventilation (IMV), Extra-Corporeal Membrane Oxygenation (ECMO) should be used, for which complications and in which environment?
3. Which support should be used for extra-renal purification, in which conditions and environment?
4. Which haemodynamic support should be used, for which complications, and in which environment?
5. Which benefit of cardiopulmonary resuscitation in cancer patients and for which complications?
6. Which intensive monitoring in the context of oncologic treatment (surgery, anti-cancer treatment …)?
7. What specific considerations should be taken into account in the intensive care unit?
8. Based on which criteria, in terms of benefit and complications and taking into account the neoplastic disease, patients hospitalized in an intensive care unit (or equivalent) should receive cellular elements derived from the blood (red blood cells, white blood cells and platelets)?
9. Which training is required for critical care doctors in charge of cancer patients?
The 2-18F-fluoro-2-deoxy-d-glucose positron emission tomography is an imaging tool for assessing clinical tumor, node, metastasis in non-small cell lung cancer (NSCLC). Primary tumor standardized ...uptake value (SUV) has been studied as a potential prognostic factor for survival. However, the sample sizes are limited leading to conduct a meta-analysis to improve the precision in estimating its effect.
We performed a systematic literature search. For each publication, we extracted an estimate of the hazard ratio (HR) for comparing patients with a low and a high SUV and we aggregated the individual HRs into a combined HR, using a random-effects model.
We found 13 eligible studies dedicated to NSCLC. Most of them included patients with stages I to III/IV and used a SUV assessment corrected for body weight. Number of patients ranged from 38 to 315 (total: 1474); 11 studies identified a high SUV as a poor prognostic factor for survival although two studies found no significant correlation between SUV and survival. SUV measurement and SUV threshold for defining high SUV were study dependent, eight studies looked for a so-called best cutoff (maximizing the logrank test statistic) without adjusting the p value for multiplicity. Overall, the combined HR for the 13 reports was 2.27 (95% confidence interval CI: 1.70–3.02); excluding the studies proposing a “best” cutoff, it was 2.08 (95% CI: 1.431–3.04).
Our meta-analysis suggests that the primary tumor SUV measurement has a prognostic value in NSCLC; these results should be confirmed in a meta-analysis on individual patients’ data.
Lung cancer is one of the most frequently occurring neoplasms and usually has a poor prognosis because most of the patients present with advanced or metastatic disease at the time of diagnosis. ...Numerous prognostic factors (PFs) have been studied, but the two most prominent, having both prognostic and operational values, are disease stage and performance status. Even if the literature on PFs in lung cancer is impressive, the number of publications specifically dealing with PFs in stage III non-small cell lung cancer (NSCLC) is limited. We reviewed the literature on this topic and separated the available information into three groups: conventional PFs, metabolic criteria (standardized uptake value SUV measured on18F-FDG-PET) and new biomarkers. Performance status and the distinction between stage IIIA and IIIB confirmed their prognostic value in stage III NSCLC. Other conventional PFs have been suggested such as age, weight loss, response to treatment and some characteristics describing the locoregional extension of the tumour. There is a place for the SUV as a PF for survival in early NSCLC, but its role in stage III NSCLC has to be further assessed. Some new biomarkers involved in cell cycle regulation or in apoptosis have been shown to have potential value. Their role needs to be confirmed in large prospective studies including conventional PFs to determine their independent value as a PF in stage III NSCLC. In conclusion, few PFs have been well evaluated in stage III NSCLC. New studies, taking into account the modifications derived from the 7th international staging system of the UICC, have to be performed.
Climate change policies have stimulated a shift towards renewable energy sources such as biomass. The economic crisis of 2008 has also increased the practice of household biomass burning as it is ...often cheaper than using oil, gas or electricity for heating. As a result, household biomass combustion is becoming an important source of air pollutants in the European Union.This position paper discusses the contribution of biomass combustion to pollution levels in Europe, and the emerging evidence on the adverse health effects of biomass combustion products.Epidemiological studies in the developed world have documented associations between indoor and outdoor exposure to biomass combustion products and a range of adverse health effects. A conservative estimate of the current contribution of biomass smoke to premature mortality in Europe amounts to at least 40 000 deaths per year.We conclude that emissions from current biomass combustion products negatively affect respiratory and, possibly, cardiovascular health in Europe. Biomass combustion emissions, in contrast to emissions from most other sources of air pollution, are increasing. More needs to be done to further document the health effects of biomass combustion in Europe, and to reduce emissions of harmful biomass combustion products to protect public health.
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