Management and outcome of oncological patients under immune checkpoint inhibitors presenting at the emergency department.

INTRODUCTION: With the rising use of immune checkpoint inhibitors (ICIs) in oncology, emergency physicians are increasingly confronted with their immune-related adverse events (irAEs). We described the types of irAEs presenting to the ED of a Belgian cancer centre and determined associations with the development of an irAE and other patient's characteristics. Secondary objectives describe the therapeutic management and determine 7 and 30-day mortality. METHODS: A retrospective chart review of ED visits of patients on ICI from 15 December 2016 to 6 December 2020 was performed. Clinical presentation, cancer characteristics and type of ICI were extracted by a single abstractor. We recorded any suspicion of irAE in the ED and confirmation of an irAE was based on the patient's oncologist report. Outcome was based on mortality at date of last follow-up. RESULTS: 227 patients on ICI presented to the ED, with a total of 451 visits. 54 (12%) of the visits resulted in a diagnosis of irAE. Four clinical features were associated with an irAE: gastrointestinal complaints (p=0.01), skin rashes (p=0.02), acute renal failure (p=0.002) and abnormal liver function (p=0.04). An irAE was also associated with three different factors: a cancer status in remission (OR=5.33, 95% CI 2.57 to 11.04), a combination of two ICIs (OR=4.43, 95% CI 2.09 to 9.42) and a medical history of irAE (OR=2.44, 95% CI 1.27 to 4.68). 30-day mortality was lower in the irAE group (0%) than in the non-irAE group (13%, 95% CI 9% to 19%). CONCLUSIONS: Oncological patients under ICI presenting in the ED are more likely to have an irAE if they present with gastrointestinal and dermatological complaints, acute renal failure and abnormal liver function. This is also true for patients with any history of irAE, a concomitant use of two ICIs and with a cancer status in remission.

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.

PARIS score for evaluation of probability of SARS-CoV-2 infection in cancer patients.

Control of transmissible diseases as COVID-19 needs a testing and an isolation strategy. The PARIS score developed by Torjdman et al. was aimed at improving patient selection for testing and quarantining but was derived from a general population. We performed a retrospective analysis of the validity of the PARIS score in a cancer patient population. We included 164 patients counting for 181 visits at the emergency department of the Jules Bordet Institute between March 10th and May 18th which had a SARS-CoV-2 RT-PCR test at admission. Twenty-six cases (14.3%) were tested positive with a higher proportion of positive tests among hematological patients compared to those with solid tumors (26% vs 11% p = 0.02). No clinical symptoms were associated with a positive SARS-CoV-2 PCR. No association between anticancer treatment and SARS-CoV-2 infection was found. The PARIS score failed to differentiate SARS-CoV-2-positive and SARS-CoV-2-negative groups (AUC 0.61 95% CI 0.48-0.73). The negative predictive value of a low probability PARIS score was 0.89 but this concerned only 11% of the patients. A high probability PARIS score concerned 49% patients but the positive predictive value was 0.18. CT scan had a sensitivity of 0.77, specificity 0.51, a positive predictive value of 0.24, and a negative predictive value of 0.92. The performance of the PARIS score is thus very poor in this cancer population. A low-risk score can be of some utility but this concerns a minority of patients.

Management of Acute Complications of Targeted Therapy in Patients With Cancer: A Review of Cases Managed in ICU.

INTRODUCTION: Targeted therapies, molecules in full expansion, are not free of side effects that can lead patients to intensive care. We performed an extensive review of the published evidence and propose a management strategy for acute complications of targeted therapy in critically ill patients with cancer. METHODS: The literature search was performed in August 2017 using the Ovid Medline system by a scientific librarian and physicians. We made a review of cases admitted in intensive care unit (ICU) and a review of toxicities of grades greater or equal to 3. RESULTS: Our search selected 59 articles. The main cardiovascular side effects requiring ICU are heart failure, which is generally reversible, severe hypertension, thrombotic and ischemic events, and rhythm disturbances. The main pulmonary side effects are interstitial lung disease essentially caused by crizotinib, respiratory infections, pneumothorax, and alveolar hemorrhage. The main gastrointestinal side effects are fulminant hepatitis that may be fatal, colitis that may be complicated by hemorrhage, and perforation. The main neurological side effect is posterior reversible encephalopathy syndrome essentially caused by bevacizumab. The main other side effects are Steven-Johnson syndrome, necrotizing fasciitis, and anaphylactic reactions. CONCLUSIONS: The side effects induced by targeted therapies may be fatal but are generally potentially reversible. The main treatment includes stopping current therapy and symptomatic management. Treatment rechallenge should be discussed on a case-by-case basis.

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.

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.

Intensive care in thoracic oncology.

The admission of lung cancer patients to intensive care is related to postprocedural/postoperative care and medical complications due to cancer or its treatment, but is also related to acute organ failure not directly related to cancer.Despite careful preoperative risk management and the use of modern surgical and anaesthetic techniques, thoracic surgery remains associated with high morbidity, related to the extent of resection and specific comorbidities. Fast-tracking processes with timely recognition and treatment of complications favourably influence patient outcome. Postoperative preventive and therapeutic management has to be carefully planned in order to reduce postoperative morbidity and mortality.For patients with severe complications, intensive care unit (ICU) mortality rate ranges from 13% to 47%, and hospital mortality ranges from 24% to 65%. Common predictors of in-hospital mortality are severity scores, number of failing organs, general condition, respiratory distress and the need for mechanical ventilation or vasopressors. When considering long-term survival after discharge, cancer-related parameters retain their prognostic value.Thoracic surgeons, anesthesiologists, pneumologists, intensivists and oncologists need to develop close and confident partnerships aimed at implementing evidence-based patient care, securing clinical pathways for patient management while promoting education, research and innovation. The final decision on admitting a patient with lung to the ICU should be taken in close partnership between this medical team and the patient and his or her relatives.

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).

Comparison of next generation sequencing, SNaPshot assay and real-time polymerase chain reaction for lung adenocarcinoma EGFR mutation assessment.

BACKGROUND: The epidermal growth factor receptor (EGFR) mutation status assessment has become increasingly important given the significant impact of tyrosine kinase inhibitors in lung cancer management. Our aim was to compare real life operational characteristics for three EGFR mutation assays - two targeted approaches and a next generation sequencing (NGS) technique. METHODS: EGFR mutation status was assessed for lung adenocarcinoma samples (formalin fixed- paraffin embedded samples) using qPCR, SNaPshot and NGS (Ion Torrent™) techniques. RESULTS: A total of 15 high clinical significance mutations were identified by at least one technique from the total of 64 samples. All mutations were identified by the TaqMan qPCR technique while SNaPshot in conjunction with fragment analysis identified 11 EGFR mutations. The NGS approach followed by an automatic analysis using the default calling parameters identified 10 mutations from the SNaPshot/qPCR panel and other three insertions, five point mutations and 58 silent variants; manual data review identified all 15 high significance mutations. CONCLUSIONS: Performance was similar for high tumor content samples but careful data analysis and post hoc variant calling filter alterations were necessary in order to obtain robust results from low tumor content samples by NGS. NGS is able to generate a comprehensive mutational profile albeit at a higher cost and workload. Result interpretation should take into account not only general run parameters such as mean read depth but also relative coverage and read distribution; currently there is an acute need to define firm recommendations/standards concerning NGS data interpretation and quality control.

Management of EGFR mutated nonsmall cell lung carcinoma patients.

Tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) are common in the therapeutic armentarium of lung cancer today. Initially tested in an unselected population, they have been of limited usefulness until the identification EGFR gene mutations. Activating mutations generate conformational changes that result in a shift toward an active state of the catalytic domain and are associated with sensitivity to first generation EGFR TKI. Other mutations have been associated with resistance to these drugs, but for rare mutations there is limited data concerning their role in predicting response to EGFR TKI. To date, four molecules have been approved for the treatment of EGFR mutated lung cancer. Gefitinib and/or erlotinib are available in almost all countries. Afatinib has been approved by the US Food and Drug Administration and by the European Medicines Agency, and icotinib has been approved only in China. Other, more active, third generation agents with a higher binding affinity for the receptor, or that are directed against specific mutations, are under development. EGFR TKIs have a favourable impact on progression-free survival when given as first line treatment in mutated patients, but may also have a moderate effect as a salvage therapy and in maintenance in an unselected population.