[Tobacco cessation - the underused potential in clinical routine]. / Tabakentwöhnung ­ die bisher wenig genutzte Chance im ärztlichen Alltag.

Tobacco control, psychosocial and medical assistance regarding tobacco cessation is still a hidden potential within the German health care system. So far doctors rarely talk to their patients about their smoking status and physical and psychological benefits of quitting.This paper focusses on recommended current diagnostic and treatment standards, as well as evidence-based methods to address the topic on how to stop smoking and its association with certain diseases such as COPD, lung cancer and COVID-19 infection. The role of e-cigarettes as a cessation tool and its health related risks are critically examined. Consequences and advice how to implement smoking cessation procedures into daily practice are presented.

[Tobacco cessation: one of the most effective medical measures]. / Tabakentwöhnung ­ eine der effektivsten medizinischen Maßnahmen.

Tobacco smoking is widespread in Germany. An increase in the number of teenagers and young adults that smoke has recently been a cause for concern. The high prevalence in Germany is contrasted by inadequate preventive measures compared to international standards. Smoking behavior should always be inquired about and documented in the same way as vital signs. All smokers, regardless of the reason for contact and motivation, should receive short, low-threshold advice, e.g. using the ABC approach (ask, brief advice, cessation). In addition to repeated advice and referral to further services, the use of nicotine replacement or drug therapy is essential for the success of quitting. The combination of long- and short-acting nicotine replacement products doubles the success rate. Electronic nicotine delivery systems are not recommended for smoking cessation.

Survey on the working, training, and research conditions of resident physicians in internistic and rheumatological continuing education-BEWUSST.

BACKGROUND: Data on the training and continuing education situation of residents in the field of internal medicine and rheumatology are not available for Germany. For this reason, the Commission for Education and Training of the German Society of Rheumatology (DGRh) initiated the BEWUSST survey on the working, training and research conditions of residents in rheumatology. METHODS: A total of 102 questions on the topics of working conditions in everyday professional life, continuing medical education and training, compatibility of career and family, compatibility of work and research, perspectives as a rheumatologist and practical activities were included in an online questionnaire. RESULTS: A total of 102 participants took part in the survey. Of the respondents 48.1% were satisfied with their professional situation, 40.2% of the participants were supervised by a specialist mentor and 54.9% were working as scientists during their work as a physician. A compatibility of family and career was possible for 34.7%. After completion of the residency 52.9% of the respondents aspired to a combined clinical and outpatient activity. CONCLUSION: Half of the trainee rheumatologists are satisfied with their professional activities, although mentoring of the assistants in training should be further improved. With respect to the desired combined clinical and outpatient activity, the existing options should be expanded or new professional fields of activity should be established, so that the specialty remains attractive for the upcoming generations.

[Survey on the working, training, and research conditions of resident physicians in internistic and rheumatological continuing education-BEWUSST]. / Befragung zu den Arbeits-, Weiterbildungs- und Forschungsbedingungen von Assistenzärztinnen und -ärzten in der internistisch-rheumatologischen Weiterbildung ­ BEWUSST.

BACKGROUND: Data on the training and continuing education situation of residents in the field of internal medicine and rheumatology are not available for Germany. For this reason, the Commission for Education and Training of the German Society of Rheumatology (DGRh) initiated the BEWUSST survey on the working, training and research conditions of residents in rheumatology. METHODS: A total of 102 questions on the topics of working conditions in everyday professional life, continuing medical education and training, compatibility of career and family, compatibility of work and research, perspectives as a rheumatologist and practical activities were included in an online questionnaire. RESULTS: A total of 102 participants took part in the survey. Of the respondents 48.1% were satisfied with their professional situation, 40.2% of the participants were supervised by a specialist mentor and 54.9% were working as scientists during their work as a physician. A compatibility of family and career was possible for 34.7%. After completion of the residency 52.9% of the respondents aspired to a combined clinical and outpatient activity. CONCLUSION: Half of the trainee rheumatologists are satisfied with their professional activities, although mentoring of the assistants in training should be further improved. With respect to the desired combined clinical and outpatient activity, the existing options should be expanded or new professional fields of activity should be established, so that the specialty remains attractive for the upcoming generations.

[Smoking cessation in hospitalised patients - Initiate among inpatients, continue when outpatients - A Position Paper by the German Respiratory Society (DGP) Taskforce for Smoking Cessation]. / Tabakentwöhnung bei hospitalisierten Patienten:innen ­ Stationär einleiten, ambulant fortführen.

Tobacco smoking is the greatest preventable health risk. The effects are serious, both individually and societal. Nevertheless, the current prevalence of tobacco smokers in Germany is still high at around 35 %. A recent strong increase in actively smoking adolescents (14- to 17-year-olds, current prevalence approx. 16 %) and young adults (18- to 24-year-olds, current prevalence approx. 41 %) is also a cause for concern. About a third of all inpatients continue smoking while being treated. The hospitalization of active smokers in acute and rehabilitation hospitals serves as a "teachable moment" for initiation of cessation offers. An intervention that begins in hospital and continues for at least a month after discharge results in about 40 % additional smokefree patients. It is scientifically well-researched, effective and cost-efficient. After initiation in hospital these measures can be continued via ambulatory cessation programs, rehabilitation facilities, an Internet or telephone service. In Germany, there are structured and quality-assured cessation offers, both for the inpatient and for the outpatient area. The biggest obstacle to broad establishment of such offers is the lack of reimbursement. Two feasible ways to change this would be the remuneration of the existing OPS 9-501 "Multimodal inpatient treatment for smoking cessation" and the establishment of quality contracts according to §â€Š110a SGB V. An expansion of tobacco cessation measures in healthcare facilities would reduce smoking prevalence, associated burden of disease and consecutive costs.

Management, risk factors and prognostic impact of checkpoint-inhibitor pneumonitis (CIP) in lung cancer - A multicenter observational analysis.

INTRODUCTION: Checkpoint-inhibitor pneumonitis (CIP) represents a major immune-related adverse event (irAE) in patients with lung cancer. We aimed for the clinical characterization, diagnostics, risk factors, treatment and outcome in a large cohort of patients from everyday clinical practice. PATIENTS AND METHODS: For this retrospective analysis, 1,376 patients having received checkpoint inhibitors (CPI) in any line of therapy from June 2015 until February 2020 from three large-volume lung cancer centers in Berlin, Germany were included and analyzed. RESULTS: With a median follow-up of 35 months, all-grade, high-grade (CTCAE ≥ 3) and fatal CIP were observed in 83 (6.0%), 37 (2.7%) and 12 (0.9%) patients, respectively, with a median onset 4 months after initiation of CPI therapy. The most common radiologic patterns were organizing pneumonia (OP) and non-specific interstitial pneumonia (NSIP) (37% and 31%). All except 7 patients with G1-2 CIP interrupted treatment. Corticosteroids were administered to 74 patients with a median starting dose of 0.75 mg/kg. After complete restitution (n = 67), re-exposure to CPI (n = 14) led to additional irAE in 43% of the cases. Thoracic radiotherapy targeting the lung was the only independent risk factor for CIP (odds ratio 2.8, p < 0.001) and pretherapeutic diffusing capacity for carbon monoxide inversely correlated with CIP severity. Compared with patients without CIP and non-CIP irAE, CIP was associated with impaired overall survival (hazard ratios 1.23, p = 0.24 and 2.01, p = 0.005). CONCLUSIONS: High-grade CIP accounts for almost half of all CIP cases in an allcomer lung cancer population. A continuous vigilance, rapid diagnostics and adequate treatment are key to prevent disease progression associated with impaired survival.

Self-Assessment and Learning Motivation in the Second Victim Phenomenon.

INTRODUCTION: The experience of a second victim phenomenon after an event plays a significant role in health care providers' well-being. Untreated; it may lead to severe harm to victims and their families; other patients; hospitals; and society due to impairment or even loss of highly specialised employees. In order to manage the phenomenon, lifelong learning is inevitable but depends on learning motivation to attend training. This motivation may be impaired by overconfidence effects (e.g., over-placement and overestimation) that may suggest no demand for education. The aim of this study was to examine the interdependency of learning motivation and overconfidence concerning second victim effects. METHODS: We assessed 176 physicians about overconfidence and learning motivation combined with a knowledge test. The nationwide online study took place in early 2022 and addressed about 3000 German physicians of internal medicine. Statistics included analytical and qualitative methods. RESULTS: Of 176 participants, 83 completed the assessment. Analysis showed the presence of two overconfidence effects and in-group biases (clinical tribalism). None of the effects correlated directly with learning motivation, but cluster analysis revealed three different learning types: highly motivated, competent, and confident "experts", motivated and overconfident "recruitables", and unmotivated and overconfident "unawares". Qualitative analysis revealed four main themes: "environmental factors", "emotionality", "violence and death", and "missing qualifications" contributing to the phenomenon. DISCUSSION: We confirmed the presence of overconfidence in second victim management competencies in about 3% of all persons addressed. Further, we could detect the same three learning motivation patterns compared to preceding studies on learning motivation in other medical competencies like life support and infection control. These findings considering overconfidence effects may be helpful for safety managers, medical teachers, curriculum developers and supervisors to create preventive educational curricula on second victim recognition and management.

[Evidence of positive care effects by digital health apps-methodological challenges and approaches]. / Nachweis positiver Versorgungseffekte von digitalen Gesundheitsanwendungen ­ methodische Herausforderungen und Lösungsansätze.

Since 2020, digital health applications (DiGA) can be prescribed at the expense of the German statutory health insurance (SHI) system after undergoing an approval procedure by the Federal Institute for Drugs and Medical Devices (BfArM). DiGA can be approved provisionally for 1 year (with the option of extension) or permanently. The latter is dependent on scientific evidence of a positive effect on care, which can be a medical benefit or a patient-relevant structural and procedural improvement in care. However, it is apparent that the investigation of DiGA in scientific studies is challenging, as they are often complex interventions whose success also includes user and prescriber factors. In addition, health services research data underpinning the benefits of DiGA are lacking to date. In the current article, methodological considerations for DiGA research are presented, and a selection of internal medicine DiGAs is used to critically discuss current research practice.

Physicians' responsibility toward environmental degradation and climate change: A position paper of the European Federation of Internal Medicine.

The current data on climate change and environmental degradation are dramatic. The consequences of these changes are already having a significant impact on people's health. Physicians - as advocates of the patients, but also as citizens - have an ethical obligation to be involved in efforts to stop these changes. The European Federation of Internal Medicine (EFIM) strongly encourages the Internal Medicine societies and internists across Europe to play an active role in matters related to climate change and environmental degradation. At a national level, this includes advocating the adoption of measures that reduce greenhouse gas (GHG) emissions and environmental degradation and contributing to policy decisions related to these issues. At a hospital level and in clinical practice, supporting actions by the health sector to reduce its ecological footprint is vital. At the level of EFIM and its associated internal societies, promoting educational activities and developing a toolkit to prepare internists to better care for citizens who suffer from the consequences of climate change. In addition to advocating and implementing effective actions to reduce the ecological footprint of the health industry, recommending the introduction of these themes in scientific programs of Internal Medicine meetings and congresses and the pre- and postgraduate medical training. At a personal level, internists must be active agents in advocating sustainable practices for the environment, increasing the awareness of the community about the health risks of climate change and environmental degradation, and being role models in the adoption of environmentally friendly behaviour.

Recurrence patterns and impact of brain metastases in synchronous single organ oligometastatic lung cancer following local ablative treatment - A multicenter analysis.

INTRODUCTION: Local ablative therapy (LAT) improves survival in oligometastatic lung cancer (OMD), but there is limited information on recurrence patterns, re-treatments and in particular the role of brain metastases during the course of disease. We therefore conducted a retrospective multicenter analysis to evaluate course of disease, sequence of therapies and predictors for long-term disease-control in the brain and survival endpoints. PATIENTS AND METHODS: Clinical data of patients with synchronous, single organ OMD with ≤4 metastases were collected from 5 certified German lung cancer centers. All patients underwent thorough initial staging including a 18FDG-PET/CT scan, brain imaging and mediastinal staging, if necessary, and received LAT to all sites of disease. RESULTS: In total, 164 patients were included (median age 62 years [range 41-84], non-squamous histology 80%, N0-1 64%, single metastasis 84%), 103 had brain (cohort A), 61 extracranial metastases (cohort B). With a median follow-up of 66 months, 115 patients (70%) experienced recurrent disease with a different distribution of sites: In cohort A vs. B, brain relapses occurred in 56% vs. 18% and new distant metastases in 5% vs. 40%. In total, LAT for every relapse was possible for 25% (29/115) of the patients. Patients with initial and secondary onset brain metastases experienced long-term disease-control in the brain and subsequently favorable survival with the application of repeated LAT (disease in the brain controlled vs. not-controlled, HR 0.21, p < 0.001). Comparable long-term overall survival was observed in patients with no or isolated brain relapses (5-years OS 74% and 92%) in contrast to patients with extracranial relapses (5-years OS 19.6%, p < 0.001). CONCLUSIONS: Repeated LAT for recurrent synchronous single organ OMD results in a long-term favorable outcome. Disease control in the brain appears crucial and likely determines survival.

Effectiveness of Immune Checkpoint Inhibition vs Chemotherapy in Combination With Radiation Therapy Among Patients With Non-Small Cell Lung Cancer and Brain Metastasis Undergoing Neurosurgical Resection.

Importance: Patients with brain metastases from non-small cell lung cancer (NSCLC) have regularly been excluded from prospective clinical trials that include therapy with immune checkpoint inhibitors (ICIs). Clinical data demonstrating benefit with ICIs, specifically following neurosurgical brain metastasis resection, are scarce. Objective: To evaluate and compare the association of radiation therapy with ICIs vs classic therapy involving radiation therapy and chemotherapy regarding overall survival in a cohort of patients who underwent NSCLC brain metastasis resection. Design, Setting and Participants: This single-center 1:1 propensity-matched comparative effectiveness study at the largest neurosurgical clinic in Germany included individuals who had undergone craniotomy with brain metastasis resection from January 2010 to December 2021 with histologically confirmed NSCLC. Of 1690 patients with lung cancer and brain metastasis, 480 were included in the study. Key exclusion criteria were small-cell lung cancer, lack of tumor cells by means of histopathological analysis on brain metastasis resection, and patients who underwent biopsy without tumor resection. The association of overall survival with treatment with radiation therapy and chemotherapy vs radiation therapy and ICI was evaluated. Exposures: Radiation therapy and chemotherapy vs radiation therapy and ICI following craniotomy and microsurgical brain metastasis resection. Main Outcomes and Measures: Median overall survival. Results: From the whole cohort of patients with NSCLC (N = 384), 215 (56%) were male and 169 (44%) were female. The median (IQR) age was 64 (57-72) years. The 2 cohorts of interest included 108 patients (31%) with radiation therapy and chemotherapy and 63 patients (16%) with radiation therapy and ICI following neurosurgical metastasis removal (before matching). Median (IQR) follow-up time for the total cohort was 47.9 (28.2-70.1) months with 89 patients (23%) being censored and 295 (77%) dead at the end of follow-up in December 2021. After covariate equalization using propensity score matching (62 patients per group), patients receiving radiation therapy and chemotherapy after neurosurgery had significantly lower overall survival (11.8 months; 95% CI; 9.1-15.2) compared with patients with radiation therapy and ICIs (23.0 months; 95% CI; 20.3-53.8) (P < .001). Conclusions and Relevance: Patients with NSCLC brain metastases undergoing neurosurgical resection had longer overall survival when treated with radiation therapy and ICIs following neurosurgery compared with those receiving platinum-based chemotherapy and radiation. Radiation and systemic immunotherapy should be regularly evaluated as a treatment option for these patients.

[Tobacco Cessation - The Underused Potential in Clinical Routine]. / Tabakentwöhnung ­ die bisher wenig genutzte Chance im ärztlichen Alltag.

Tobacco control, psychosocial and medical assistance regarding tobacco cessation is still a hidden potential within the German health care system. So far doctors rarely talk to their patients about their smoking status and physical and psychological benefits of quitting.This paper focusses on recommended current diagnostic and treatment standards, as well as evidence-based methods to address the topic on how to stop smoking and its association with certain diseases such as COPD, lung cancer and COVID-19 infection. The role of e-cigarettes as a cessation tool and its health related risks are critically examined. Consequences and advice how to implement smoking cessation procedures into daily practice are presented.

[Practical use of digital health applications (DiGA) in internal medicine]. / Praktische Anwendung digitaler Gesundheitsanwendungen (DiGA) in der Inneren Medizin.

Since 2020 physicians can prescribe digital health applications (DiGA), also colloquially known as apps on prescription, which are reimbursed by the statutory health insurance when they are approved by the Federal Institute for Drugs and Medical Devices (BfArM) and are included in the DiGA Ordinance. Currently, there is one approved DiGA (indication obesity) for internal medicine. There are many questions on the practical use of the DiGA, ranging from the prescription, the effectiveness, the complexities and reimbursement as well as the liability risks. The DiGA are innovative new means, which maybe support internal medicine physicians in the diagnostics and treatment in the future. The benefits in this field of indications are limited by unclarified issues, especially on the prescription practice and the currently low number of DiGA available in internal medicine.

Prevalence of Second Victims, Risk Factors, and Support Strategies among German Nurses (SeViD-II Survey).

BACKGROUND: Second victim phenomena (SVP) are critical to workplace and patient safety, and epidemiological data are limited to investigate the causes and impact on German health care. We investigated SVP in German nurses regarding prevalence, causes, and predisposition compared to a preceding study on German physicians (Second Victims in Deutschland/SeViD-I). METHODS: We conducted a nationwide anonymous cross-sectional online study in 2020 using a modified SeViD questionnaire including the BFI-10 (personality traits). Statistical analysis was conducted using chi² tests and binary logistic regression models. RESULTS: Of 332 nurses, 60% reported to experience SVP at least once a working lifetime, with a 12-month prevalence among SVP of 49%. Of the nurses, 24% reported recovery times of more than 1 year. In contrast to physicians from SeViD-I, a main cause for becoming a second victim was aggressive behavior by patients. High neuroticism values, higher age, and medium work life experience, but neither gender nor workplace position, were predisposing for SVP. Like SeViD-I, nurses reported demand for an institutional response in cases of SVP. CONCLUSIONS: SVP is common among German nurses and comprises other causes and a different course than in physicians. Further research should concentrate on specific prevention strategies, e.g., profession- and workplace-based educational programs.

Characteristics and management of asymptomatic SARS-CoV-2 infections.

The coronavirus disease 2019 (COVID-19) pandemic has caused and is still causing tremendous morbidity, mortality, and damage to our societies. The disease course of COVID-19 can be unpredictable ranging from asymptomatic infections to multi-organ failure and death. Transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) from an asymptomatic infected individual to others has been observed early in the pandemic. Asymptomatic individuals have been shown to have quantitative SARS-CoV-2 viral loads, there may or may not be radiological and/or laboratory abnormalities. No antiviral therapy has been approved for the treatment of asymptomatic SARS-CoV2- infection. The management of asymptomatic individuals at home requires that the person can be monitored for any signs and symptoms of deterioration and that the requirements for infection prevention and control measures can be fulfilled. It is crucial to properly diagnose and manage asymptomatic COVID-19 cases with effective testing, contact tracing, quarantine, and isolation strategies. Preventing asymptomatic SARS-CoV-2 infections that have a major role in the unhindered transmission of the virus is a milestone to take control of the pandemic. Vaccination has been proven to be the crucial pillar for preventing asymptomatic infections and real-life data will continue to exhibit the effects of community vaccination in breaking the transmission chain of SARS-CoV-2 infections.

[COVID-19 and Smoking - A Position Paper by the DGP Taskforce for Smoking Cessation]. / COVID-19 und Rauchen.

Tobacco smoking is associated with severe health risks. In 2020, the WHO estimated that 8 million people have died due to smoking. Furthermore, smoking tobacco is a well-known risk factor for various infectious pulmonary diseases. The question raised, whether smoking is facilitating SARS-CoV-2-infections and increases adverse outcomes of COVID-19. To answer these questions a narrative review was conducted, finally including 7 systematic reviews with meta-analyses published in January and February 2021. Tobacco smoking was associated with an increased COVID-19 disease severity (odds ratio range of active vs. never smokers 1.55-2.19 and former vs. never smokers 1.20-2.48) and an increased COVID-19 in-hospital mortality (odds ratio range of active vs. never smokers 1.35-1.51 and former vs. never smokers 1.26-2.58). Beside immediate pulmonary toxic effects through active smoking, the cumulative livelong tobacco exposition and subsequent tobacco-associated diseases seem to predominantly predict adverse outcomes in patients with COVID-19. Data regarding an increased risk of infection among smokers is conflicting. However, a large observational study from England with 2.4 million persons reported an association between tobacco smoking and typical symptoms of COVID-19. For e-cigarettes and vaping less data exist, but experimental and first clinical investigations also suggest an increased risk for adverse outcomes for their use and SARS-CoV-2 infections. Especially during the current SARS-CoV-2 pandemic with limited therapeutic options it is particularly important to advise smokers of their increased risks for unfavourable COVID-19 outcomes. Evidence based support for smoking cessation should be offered. In Germany, the existing and well-established methods to support tobacco cessation need to be reimbursed by statutory health insurances.

Prevalence of second victims, risk factors and support strategies among young German physicians in internal medicine (SeViD-I survey).

BACKGROUND: Second victims, defined as healthcare team members being traumatised by an unanticipated clinical event or outcome, are frequent in healthcare. Evidence of this phenomenon in Germany, however, is sparse. Recently, we reported the first construction and validation of a German questionnaire. This study aimed to understand this phenomenon better in a sample of young (<= 35 years) German physicians. METHODS: The electronic questionnaire (SeViD-I survey) was administered for 6 weeks to a sample of young physicians in training for internal medicine or a subspecialty. All physicians were members of the German Society of Internal Medicine. The questionnaire had three domains - general experience, symptoms, and support strategies - comprising 46 items. Binary logistic regression models were applied to study the influence of various independent factors on the risk of becoming a second victim, the magnitude of symptoms and the time to self-perceived recovery. RESULTS: The response rate was 18% (555/3047). 65% of the participants were female, the mean age was 32 years. 59% experienced second victim incidents in their career so far and 35% during the past 12 months. Events with patient harm and unexpected patient deaths or suicides were the most frequent key incidents. 12% of the participants reported that their self-perceived time to full recovery was more than 1 year or have never recovered. Being female was a risk factor for being a second victim (odds ratio (OR) 2.5) and experiencing a high symptom load (OR 2). Working in acute care was promoting a shorter duration to self-perceived recovery (OR 0.5). Support measures with an exceptionally high approval among second victims were the possibility to discuss emotional and ethical issues, prompt debriefing/crisis intervention after the incident and a safe opportunity to contribute insights to prevent similar events in the future. CONCLUSION: The second victim phenomenon is frequent among young German physicians in internal medicine. In general, these traumatic events have a potentially high impact on physician health and the care they deliver. A better understanding of second victim traumatisations in Germany and broad implementation of effective support programs are warranted.

KRASG12C/TP53 co-mutations identify long-term responders to first line palliative treatment with pembrolizumab monotherapy in PD-L1 high (≥50%) lung adenocarcinoma.

BACKGROUND: Pembrolizumab is a standard of care as first line palliative therapy in PD-L1 overexpressing (≥50%) non-small cell lung cancer (NSCLC). This study aimed at the identification of KRAS and TP53-defined mutational subgroups in the PD-L1 high population to distinguish long-term responders from those with limited benefit. METHODS: In this retrospective, observational study, patients from 4 certified lung cancer centers in Berlin, Germany, having received pembrolizumab monotherapy as first line palliative treatment for lung adenocarcinoma (LuAD) from 2017 to 2018, with PD-L1 expression status and targeted NGS data available, were evaluated. RESULTS: A total of 119 patients were included. Rates for KRAS, TP53 and combined mutations were 52.1%, 47.1% and 21.9%, respectively, with no association given between KRAS and TP53 mutations (P=0.24). By trend, PD-L1 expression was higher in KRAS-positive patients (75% vs. 65%, P=0.13). Objective response rate (ORR), median progression-free survival (PFS) and overall survival (OS) in the KRASG12C group (n=32, 51.6%) were 63.3%, 19.8 months (mo.) and not estimable (NE), respectively. Results in KRASother and wild type patients were similar and by far lower (42.7%, P=0.06; 6.2 mo., P<0.001; 23.4 mo., P=0.08). TP53 mutations alone had no impact on response and survival. However, KRASG12C/TP53 co-mutations (n=12) defined a subset of long-term responders (ORR 100.0%, PFS 33.3 mo., OS NE). In contrast, patients with KRASother/TP53 mutations showed a dismal prognosis (ORR 27.3%, P=0.002; PFS 3.9 mo., P=0.001, OS 9.7 mo., P=0.02). CONCLUSIONS: A comprehensive assessment of KRAS subtypes and TP53 mutations allows a highly relevant prognostic differentiation of patients with metastatic, PD-L1 high LuAD treated upfront with pembrolizumab.