European Respiratory Society guideline on various aspects of quality in lung cancer care.

This European Respiratory Society guideline is dedicated to the provision of good quality recommendations in lung cancer care. All the clinical recommendations contained were based on a comprehensive systematic review and evidence syntheses based on eight PICO (Patients, Intervention, Comparison, Outcomes) questions. The evidence was appraised in compliance with the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Evidence profiles and the GRADE Evidence to Decision frameworks were used to summarise results and to make the decision-making process transparent. A multidisciplinary Task Force panel of lung cancer experts formulated and consented the clinical recommendations following thorough discussions of the systematic review results. In particular, we have made recommendations relating to the following quality improvement measures deemed applicable to routine lung cancer care: 1) avoidance of delay in the diagnostic and therapeutic period, 2) integration of multidisciplinary teams and multidisciplinary consultations, 3) implementation of and adherence to lung cancer guidelines, 4) benefit of higher institutional/individual volume and advanced specialisation in lung cancer surgery and other procedures, 5) need for pathological confirmation of lesions in patients with pulmonary lesions and suspected lung cancer, and histological subtyping and molecular characterisation for actionable targets or response to treatment of confirmed lung cancers, 6) added value of early integration of palliative care teams or specialists, 7) advantage of integrating specific quality improvement measures, and 8) benefit of using patient decision tools. These recommendations should be reconsidered and updated, as appropriate, as new evidence becomes available.

Initiation of a new anti-cancer medical treatment in ICU: a retrospective study.

PURPOSE: The purpose of our study is to evaluate the characteristics of patients whose medical anti-cancer treatment has been initiated at the ICU and to release prognostic factors for hospital mortality in these patients. MATERIAL AND METHODS: We analyzed retrospectively all the records of cancer patients admitted between 01/01/2007 and 31/12/2017 in our ICU and for whom a new anti-cancer medical treatment was initiated during their ICU stay. RESULTS: Our study includes 147 patients, 78 men (53%) and 69 women (47%), with a median age of 58 years. Eighty patients (54%) had a solid tumor and 67 (46%) a hematological malignancy. ICU mortality was 23% and hospital mortality 32%. The poor prognostic factors for hospital mortality were: higher SOFA, higher Charslon comorbidity index and the presence of a therapeutic limitation (introduced at the time of admission or within 24 hours of admission to the ICU). One-year survival for patients who survived hospital stay was 37% (17% for those with a solid tumor and 61% for the ones with a hematological malignancy). CONCLUSION: Initiation of an anti-cancer medical treatment is feasible and can lead to good 1 year survival rate, especially for those with a hematological tumor.

Critically ill cancer patient's resuscitation: a Belgian/French societies' consensus conference.

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 questions1. 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?

Sepsis and Septic Shock Definitions in Patients With Cancer Admitted in ICU.

INTRODUCTION: In 2016, a new definition of sepsis and septic shock was adopted. Some studies based on the general population demonstrated that the Sequential Organ Failure Assessment (SOFA) score is more accurate than the systemic inflammatory response syndrome (SIRS) criteria to predict hospital mortality of infected patients requiring intensive care. PATIENTS AND METHOD: We have analyzed all the records of patients with cancer admitted for a suspected infection between January 1, 2013, and December 31, 2016, in our oncological intensive care unit (ICU). Sequential Organ Failure Assessment score and quick SOFA (qSOFA) score as well as SIRS criteria were calculated. We analyzed the accuracy of each score to predict hospital mortality in the setting of the new and old definitions of septic shock. RESULTS: Our study includes 241 patients with a solid tumor and 112 with a hematological malignancy. The hospital mortality rate is 37% (68% in patients with septic shock according to the new definition and 60% according to old definition) between 2013 and 2016. To predict hospital mortality, the SOFA score has an area under the receiver operating characteristic curve of 0.74 (95% confidence interval [CI], 0.68-0.79), the qSOFA of 0.65 (95% CI, 0.59-0.70), and the SIRS criteria of 0.58 (95% CI, 0.52-0.63). In multivariate analysis, a higher SOFA score or a higher qSOFA score indicates poor prognosis: odds ratio (OR) per 1-point increase by 1.28 (95% CI, 1.18-1.39) and 1.48 (95% CI, 1.04-2.11), respectively. Complete remission is a good prognostic factor for hospital mortality: OR 0.39 (95% CI, 0.22-0.67). CONCLUSION: The new definition of sepsis and septic shock is applicable in an ICU oncological population with the same reliability as in the general population. The SOFA score is more accurate than qSOFA and SIRS criteria to predict hospital mortality.

Bullous Lupus Under Nivolumab Treatment for Lung Cancer: A Case Report With Systematic Literature Review.

BACKGROUND: Various immune-related adverse events (irAEs) have been reported to be associated with the use of immune checkpoint inhibitors. We report a case of a patient with lung cancer treated with nivolumab who developed a bullous eruption and give a systematic review of the literature on irAEs in patients treated with immune checkpoint inhibitors for lung cancer. CASE REPORT: A patient with lung adenocarcinoma developed a non-specific skin lesion at the time of his cancer diagnosis followed by flare episodes until the eighth cycle of nivolumab, when he developed a bullous lupus. As the first eruption had started a few months after his cancer diagnosis and was exacerbated during immunotherapy, a paraneoplastic origin is discussed. Since the patient also presented with flares under nivolumab, we reviewed reported irAEs. No bullous lupus was found but to date, 33 cases of paraneoplastic lupus and two of lupus erythematosus have been reported. CONCLUSION: To our knowledge, this is the first description of a bullous lupus exacerbated by nivolumab.

Immune evasion before tumour invasion in early lung squamous carcinogenesis.

Early detection and treatment are critical for improving the outcome of patients with cancer1. 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 carcinoma2,3. 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.

Achieving Thoracic Oncology data collection in Europe: a precursor study in 35 Countries.

BACKGROUND: A minority of European countries have participated in international comparisons with high level data on lung cancer. However, the nature and extent of data collection across the continent is simply unknown, and without accurate data collection it is not possible to compare practice and set benchmarks to which lung cancer services can aspire. METHODS: Using an established network of lung cancer specialists in 37 European countries, a survey was distributed in December 2014. The results relate to current practice in each country at the time, early 2015. The results were compiled and then verified with co-authors over the following months. RESULTS: Thirty-five completed surveys were received which describe a range of current practice for lung cancer data collection. Thirty countries have data collection at the national level, but this is not so in Albania, Bosnia-Herzegovina, Italy, Spain and Switzerland. Data collection varied from paper records with no survival analysis, to well-established electronic databases with links to census data and survival analyses. CONCLUSION: Using a network of committed clinicians, we have gathered validated comparative data reporting an observed difference in data collection mechanisms across Europe. We have identified the need to develop a well-designed dataset, whilst acknowledging what is feasible within each country, and aspiring to collect high quality data for clinical research.

ERS statement on harmonised standards for lung cancer registration and lung cancer services in Europe.

The European Respiratory Society (ERS) task force for harmonised standards for lung cancer registration and lung cancer services in Europe recognised the need to create a single dataset for use in pan-European data collection and a manual of standards for European lung cancer services.The multidisciplinary task force considered evidence from two different sources, reviewing existing national and international datasets alongside the results of a survey of clinical data collection on lung cancer in 35 European countries. A similar process was followed for the manual of lung cancer services, with the task force using existing guidelines and national or international recommendations for lung cancer services to develop a manual of standards for services in Europe.The task force developed essential and minimum datasets for lung cancer registration to enable all countries to collect the same essential data and some to collect data with greater detail. The task force also developed a manual specifying standards for lung cancer services in Europe.Despite the wide variation in the sociopolitical landscape across Europe, the ERS is determined to encourage the delivery of high-quality lung cancer care. Both the manual of lung cancer services and the minimum dataset for lung cancer registration will support this aspiration.

A phase III randomised study comparing concomitant radiochemotherapy with cisplatin and docetaxel as induction versus consolidation treatment in patients with locally advanced unresectable non-small cell lung cancer.

OBJECTIVES: To assess if induction radiochemotherapy followed by consolidation chemotherapy (arm A) will improve survival in comparison with the same chemotherapy given as induction followed by consolidation concurrent radiochemotherapy (arm B) in patients with unresectable non-metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy consisted in a combination of cisplatin with docetaxel, with one initial course for each patient, two courses in single modality therapy and weekly administration during chest irradiation (66 Gy). RESULTS: A total of 125 patients were randomised before early closure of the study because of poor accrual and an unplanned blind interim analysis which suggested that the continuation of the study would have been futile. Mature survival results showed no significant difference between both modalities with median survival times, respectively in arms A and B, of 19.6 months and 18.3 months, two years survival rates of 44% and 44% and five years survival rates of 23% and 26%. Toxicity was acceptable. CONCLUSIONS: Our randomised study did not demonstrate survival difference between induction concurrent radiochemotherapy followed by consolidation chemotherapy and induction chemotherapy followed by consolidation concurrent radiochemotherapy.

A Phase III Randomized Study Comparing a Chemotherapy with Cisplatin and Etoposide to a Etoposide Regimen without Cisplatin for Patients with Extensive Small-Cell Lung Cancer.

INTRODUCTION: In a literature meta-analysis, we showed survival benefits for regimens including cisplatin [hazard ratio (HR) 0.61; 95% confidence interval (CI), 0.57-0.66] and for those including etoposide (HR 0.65; 0.61-0.69). That benefit was mainly observed when etoposide alone or in combination with cisplatin was included in the chemotherapy regimens. Our objective was to determine if chemotherapy with both drugs improves survival in comparison to a non-platinum regimen with etoposide. METHODS: Extensive small-cell lung cancer patients were randomized between cisplatin-etoposide (CE) and ifosfamide + etoposide + epirubicin regimen (IVE) between 2000 and 2013. RESULTS: 176 and 170 eligible patients were allocated to CE and IVE (315 deaths were required before analysis), respectively. Objective response rates were not significantly different: 60% with CE and 59% with IVE. No statistically significant difference in median survival and 1-year and 2-year was observed with rates of 9.6 months, 31 and 5% for CE and 10 months, 39 and 9% for IVE, respectively. HR was 0.84 (95% CI 0.68-1.05, p = 0.16). Only two prognostic factors for survival were retained in multivariate analysis: sex with HR = 0.69 (95% CI 0.49-0.97, p = 0.03) and performance status with HR = 0.53 (95% CI 0.49-0.97, p < 0.0001). After adjustment for these prognostic factors, HR for survival was 0.83 (95% CI 0.65-1.08, p = 0.17). There was more thrombopenia in the CE regimen and more leukopenia with IVE. CONCLUSION: Combination of CE failed to improve survival in comparison to an etoposide-containing regimen without cisplatin. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT00658580?term=ELCWP+01994&rank=1, identifier NCT00658580.

Pain control in thoracic oncology.

This review of pain management in lung cancer is based on the presentation of four cases of thoracic oncology patients with pain at various stages of their disease. The approach will be multidisciplinary, involving a thoracic oncologist, radiologist, thoracic and orthopaedic spine surgeon, radiation therapist, pain medicine specialist, and palliative care specialist. This multispecialty approach to the management of different painful presentations in thoracic oncology will demonstrate the complexity of each case and the improved patient outcomes which result from the involvement of different disciplines working in concert.In the USA, Europe and other countries, palliative care specialists often become rapidly involved in the management of these patients, coordinating social care and providing psychological support.Thoracic and orthopaedic spine subspecialists provide surgical methods to control tumour invasion, and improve quality of life and preservation of function in settings of even diffuse metastatic disease. Similarly, thoracic oncology and radiation therapists utilise both therapeutic and palliative chemotherapeutic and radiation therapy regimens to prolong and improve quality of life.The pain medicine specialist can, in addition to medication management, offer a variety of interventional approaches including unique drug delivery systems such as epidural analgesia, regional anaesthesia techniques, and intrathecal pumps, as well as neuromodulation techniques and neurolytic or neuroablative procedures.In the USA, these specialists complete an additional fellowship year in pain medicine following the completion of an anaesthesiology, physical medicine and rehabilitation, neurology or psychiatry residency. These programmes are accredited by the Accreditation Council for Graduate Medical Education, or ACGME (www.acgme.org).

Autoimmune paraneoplastic syndromes associated to lung cancer: A systematic review of the literature Part 4: Neurological paraneoplastic syndromes, involving the peripheral nervous system and the neuromuscular junction and muscles.

The development of new immune treatment in oncology and particularly for lung cancer may induce new complications, particularly activation or reactivation of auto-immune diseases. In this context, a systematic review on the auto-immune paraneoplastic syndromes that can complicate lung cancer appears useful. This article is the fourth of a series of five and deals mainly with neurological paraneoplastic syndromes involving the peripheral nervous system and the neuromuscular junction and muscles.

Autoimmune paraneoplastic syndromes associated to lung cancer: A systematic review of the literature: Part 5: Neurological auto-antibodies, discussion, flow chart, conclusions.

The development of new immune treatment in oncology and particularly for lung cancer may induce new complications, particularly activation or reactivation of auto-immune diseases. In this context, a systematic review on the auto-immune paraneoplastic syndromes that can complicate lung cancer appears useful. This article is the last of a series of five and deals mainly with onconeural antibodies involved in neurological paraneoplastic syndromes and provides the final discussion.

Autoimmune paraneoplastic syndromes associated to lung cancer: A systematic review of the literature.

The development of new immune treatment in oncology and particularly for lung cancer may induce new complications, particularly activation or reactivation of auto-immune diseases. In this context, a systematic review on the auto-immune paraneoplastic syndromes associated with lung cancer appears useful. This article is the first of a series of five and deals with the methodology applied for the review and with renal and rheumatic syndromes.

Autoimmune paraneoplastic syndromes associated to lung cancer: A systematic review of the literature: Part 3: Neurological paraneoplastic syndromes, involving the central nervous system.

The development of new immune treatment in oncology and particularly for lung cancer may induce new complications, particularly activation or reactivation of auto-immune diseases. In this context, a systematic review on the auto-immune paraneoplastic syndromes that can complicate lung cancer appears useful. This article is the third of a series of five and deals mainly with neurological paraneoplastic syndromes involving the central nervous system.

Autoimmune paraneoplastic syndromes associated to lung cancer: A systematic review of the literature: Part 2: Hematologic, cutaneous and vascular syndromes.

The development of new immune treatment in oncology and particularly for lung cancer may induce new complications, particularly activation or reactivation of auto-immune diseases. In this context, a systematic review on the auto-immune paraneoplastic syndromes associated with lung cancer appears useful. This article is the second of a series of five and deals with hematologic, cutaneous and vascular syndromes.

Are Intensive Cares Worthwhile for Breast Cancer Patients: The Experience of an Oncological ICU.

PURPOSE: One among seven women will present with breast cancer for which major therapeutic advances led to a significant increase in survival and cure rates. During or after cancer treatment, severe complications may occur requiring admission in intensive care unit (ICU). Intensivists could be reluctant for accepting cancer patients in the ICU, and there are very few data about causes of admission and prognosis of patients with breast cancer admitted in the ICU for an acute complication. Our study seeks to determine, in a population of patients with breast cancer, the main causes for ICU admission and the predictors of death during hospital stay and prognostic factors for survival after hospital discharge. METHODS: This retrospective study includes all unplanned ICU admissions of patients with breast cancer in a cancer hospital from January 1, 2009 to December 31, 2014. To search for predictive factors of death during hospitalization, Mann-Whitney or Fisher Exact (or chi-square) tests were used for continuous variables or categorical variables, respectively. A logistic regression model was applied for multivariate analysis. Multivariate analysis of prognostic factors for survival after hospital discharge was performed with a Cox's proportional hazards model. RESULTS: Of 1586 ICU admissions during the study period, 282 (18%) concerned breast cancer of which 175 met the inclusion criteria. The main causes of admission were of cardiovascular (26%), respiratory (19%), neurologic (19%), or infectious (14%) origin. ICU death rate was 15% and, overall, 28% of the patients died during hospitalization. The median survival time after hospitalization was 12.8 months (95% CI: 8.2-20.7). Independent predictors of death during hospitalization were the sequential organ failure assessment (SOFA) score (OR 1.36, 95% CI 1.15-1.60), high GPT values (OR 3.70, 95% CI: 1.52-9.03), and cardiovascular disease (OR 0.23, 95% CI: 0.06-0.86). Independent predictors of death after hospital discharge were metastatic disease (HR 7.90, 95% CI 3.69-16.92), high GOT value (HR 3.22 95% CI: 1.93-5.36), simplified acute physiology score (SAPS) (HR 1.95 95% CI: 1.21-3.16), and therapeutic limitations during the first 24 h after ICU admission (HR 8.52 95% CI: 3.66-19.87). CONCLUSION: Independent predictors of death during hospitalization were related to the acute complications (SOFA score, GPT level and cardiovascular-related admission) while cancer parameters retained their prognostic significance for survival after hospital discharge (metastatic disease, therapeutic limitations).

Continuous Renal Replacement Therapy for Acute Renal Failure in Patients with Cancer: A Well-Tolerated Adjunct Treatment.

INTRODUCTION: Acute renal failure (ARF) has a poor prognosis in patients with cancer requiring intensive care unit (ICU) admission. Our aim is finding prognostic factors for hospital mortality in patients with cancer with ARF requiring renal replacement therapy (RRT). METHODS: In this retrospective study, all patients with cancer with ARF treated with continuous venovenous filtration (CVVHDF) in the ICU of the Institut Jules Bordet, between January 1, 2003 and December 31, 2012, were included. RESULTS: One hundred and three patients are assessed: men/women 69/34, median age 62 years, solid/hematologic tumors 68/35, median SAPS II 56. Mortality rate was 63%. Seven patients required chronic renal dialysis. After multivariate analysis, two variables were statistically associated with hospital mortality: more than one organ failure (including kidney) (OR 5.918; 95% CI 2.184-16.038; p < 0.001) and low albumin level (OR 3.341; 95% CI 1.229-9.077; p = 0.02). Only minor complications related to CVVHDF have been documented. CONCLUSION: Despite the poor prognosis associated with ARF, CVVHDF is an effective and tolerable renal replacement technique in patients with cancer admitted to the ICU. Multiple organ failure and hypoalbuminemia, two independent prognostic factors for hospital mortality have to be considered when deciding for introducing RRT.

Thoracic oncology HERMES: European curriculum recommendations for training in thoracic oncology.

Thoracic oncology HERMES: European curriculum recommendations for training in thoracic oncology http://ow.ly/mdqT300NHqO.