Chemotherapy negatively impacts the tumor immune microenvironment in NSCLC: an analysis of pre- and post-treatment biopsies in the multi-center SAKK19/09 study.

BACKGROUND: Over the past few years, immune checkpoint inhibitors have changed the therapeutic landscape of non-small-cell lung cancer (NSCLC). Response to immune checkpoint inhibitors correlates with a pre-existing anti-tumoral immune response. Checkpoint inhibitors have been introduced as second-line therapy and are only very recently used as monotherapy or in combination with chemotherapy as first-line treatment of NSCLC. However, the effect of conventional first-line platinum-based chemotherapy on the immune infiltrate in the tumor is largely unknown. METHODS: We measured the gene expression of a custom set of 201 cancer- and immune-related genes in 100 NSCLC tumor biopsies collected before chemotherapy and 33 re-biopsies after platinum-based chemotherapy at the time point of progression. For 29 patients matched pre- and post-chemotherapy samples could be evaluated. RESULTS: We identified a cluster of 47 co-expressed immune genes, including PDCD1 (PD1) and CD274 (PD-L1), along with three other co-expression clusters. Chemotherapy decreased the average gene expression of the immune cluster while no effect was observed on the other three cluster. Within this immune cluster, CTLA4, LAG3, TNFRSF18, CD80 and FOXP3 were found to be significantly decreased in patient-matched samples after chemotherapy. CONCLUSION: Our results suggest that conventional platinum-based chemotherapy negatively impacts the immune microenvironment at the time point of secondary progression.

A cost-effectiveness analysis of consolidation immunotherapy with durvalumab in stage III NSCLC responding to definitive radiochemotherapy in Switzerland.

BACKGROUND: Consolidation immunotherapy with the programmed death ligand 1 (PD-L1) inhibitor durvalumab improves survival in patients with stage III non-small-cell lung cancer responding to radiochemotherapy. The aim of this study was to assess the cost-effectiveness of durvalumab in Switzerland based on the most recent PACIFIC survival follow-up. MATERIALS AND METHODS: We constructed a Markov model based on the 3-year follow-up data of the PACIFIC trial and compared consolidation durvalumab with observation. We used published utility values and assessed costs for treatment strategies from the perspective of the Swiss health care payers. Cost-effectiveness was tested both in the intention-to-treat population of the PACIFIC trial unselected for PD-L1 tumor expression and in patients with PD-L1-expressing tumors (≥1%). RESULTS: In the unselected/PD-L1-positive patients, durvalumab showed an incremental effectiveness of 0.76/1.18 quality-adjusted life year (QALY) and incremental costs of Swiss Francs (CHF) 67 239/78 177, resulting in incremental cost-effectiveness ratios of CHF 88 703/66 131 per QALY gained, respectively. The most influential factors for the incremental cost-effectiveness ratio were the utility before first progression, costs for durvalumab, and the hazard ratio for overall survival under durvalumab versus observation. The cost-effectiveness of durvalumab was better than CHF 100 000 per QALY gained in 75% of the simulations in probabilistic sensitivity analysis. CONCLUSION: Assuming a willingness-to-pay threshold of CHF 100 000 per QALY gained, consolidation durvalumab is likely to be cost-effective both in patients with inoperable stage III non-small-cell lung cancer (NSCLC) unselected for PD-L1 status and in patients with PD-L1-expressing tumors in Switzerland.

A multicentre randomised phase III trial comparing pembrolizumab versus single-agent chemotherapy for advanced pre-treated malignant pleural mesothelioma: the European Thoracic Oncology Platform (ETOP 9-15) PROMISE-meso trial.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive malignancy characterised by limited treatment options and a poor prognosis. At relapse after platinum-based chemotherapy, single-agent chemotherapy is commonly used and single-arm trials of immune-checkpoint inhibitors have demonstrated encouraging activity. PATIENTS AND METHODS: PROMISE-meso is an open-label 1:1 randomised phase III trial investigating the efficacy of pembrolizumab (200 mg/Q3W) versus institutional choice single-agent chemotherapy (gemcitabine or vinorelbine) in relapsed MPM patients with progression after/on previous platinum-based chemotherapy. Patients were performance status 0-1 and unselected for programmed cell death ligand 1 (PD-L1) status. At progression, patients randomly assigned to receive chemotherapy were allowed to crossover to pembrolizumab. The primary end point was progression-free survival (PFS), assessed by blinded independent central review (BICR). Secondary end points were overall survival (OS), investigator-assessed PFS, objective response rate (ORR), and safety. Efficacy by PD-L1 status was investigated in exploratory analyses. RESULTS: Between September 2017 and August 2018, 144 patients were randomly allocated (pembrolizumab: 73; chemotherapy: 71). At data cut-off [20 February 2019, median follow-up of 11.8 months (interquartile range: 9.9-14.5)], 118 BICR-PFS events were observed. No difference in BICR-PFS was detected [hazard ratio = 1.06, 95% confidence interval (CI): 0.73-1.53; P = 0.76], and median BICR-PFS (95% CI) for pembrolizumab was 2.5 (2.1-4.2), compared with 3.4 (2.2-4.3) months for chemotherapy. A difference in ORR for pembrolizumab was identified (22%, 95% CI: 13% to 33%), over chemotherapy (6%, 95% CI: 2% to 14%; P = 0.004). Forty-five patients (63%) assigned to chemotherapy received pembrolizumab at progression. With follow-up to 21 August 2019 [17.5 months: (14.8-19.7)], no difference in OS was detected between groups (HR = 1.12, 95% CI: 0.74-1.69; P = 0.59), even after adjusting for crossover. Pembrolizumab safety was consistent with previous observations. Exploratory efficacy analyses by PD-L1 status demonstrated no improvements in ORR/PFS/OS. CONCLUSION: This is the first randomised trial evaluating the efficacy of pembrolizumab in MPM patients progressing after/on previous platinum-based chemotherapy. In biologically unselected patients, although associated with an improved ORR, pembrolizumab improves neither PFS nor OS over single-agent chemotherapy.

Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry.

BACKGROUND: Anti-PD1/PD-L1 directed immune checkpoint inhibitors (ICI) are widely used to treat patients with advanced non-small-cell lung cancer (NSCLC). The activity of ICI across NSCLC harboring oncogenic alterations is poorly characterized. The aim of our study was to address the efficacy of ICI in the context of oncogenic addiction. PATIENTS AND METHODS: We conducted a retrospective study for patients receiving ICI monotherapy for advanced NSCLC with at least one oncogenic driver alteration. Anonymized data were evaluated for clinicopathologic characteristics and outcomes for ICI therapy: best response (RECIST 1.1), progression-free survival (PFS), and overall survival (OS) from ICI initiation. The primary end point was PFS under ICI. Secondary end points were best response (RECIST 1.1) and OS from ICI initiation. RESULTS: We studied 551 patients treated in 24 centers from 10 countries. The molecular alterations involved KRAS (n = 271), EGFR (n = 125), BRAF (n = 43), MET (n = 36), HER2 (n = 29), ALK (n = 23), RET (n = 16), ROS1 (n = 7), and multiple drivers (n = 1). Median age was 60 years, gender ratio was 1 : 1, never/former/current smokers were 28%/51%/21%, respectively, and the majority of tumors were adenocarcinoma. The objective response rate by driver alteration was: KRAS = 26%, BRAF = 24%, ROS1 = 17%, MET = 16%, EGFR = 12%, HER2 = 7%, RET = 6%, and ALK = 0%. In the entire cohort, median PFS was 2.8 months, OS 13.3 months, and the best response rate 19%. In a subgroup analysis, median PFS (in months) was 2.1 for EGFR, 3.2 for KRAS, 2.5 for ALK, 3.1 for BRAF, 2.5 for HER2, 2.1 for RET, and 3.4 for MET. In certain subgroups, PFS was positively associated with PD-L1 expression (KRAS, EGFR) and with smoking status (BRAF, HER2). CONCLUSIONS: : ICI induced regression in some tumors with actionable driver alterations, but clinical activity was lower compared with the KRAS group and the lack of response in the ALK group was notable. Patients with actionable tumor alterations should receive targeted therapies and chemotherapy before considering immunotherapy as a single agent.

[Strategies to Overcome Acquired Resistance to EGFR-TKI Therapy Based on T790M Specific Substances using Osimertinib as an Example]. / Strategien zur Überwindung der erworbenen EGFR-TKI-Resistenz durch T790M spezifische Substanzen am Beispiel von Osimertinib.

Tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) are widely used in non-small cell lung cancer patients harboring activating EGFR mutations. However, resistance mechanisms, particularly the T790 M mutation, hamper longer-term therapeutic success of first and second generation EGFR-TKIs. To address this unmet medical need, EGFR-TKIs of the third generation are under clinical development. Relevant clinical efficacy with mainly mild to moderate class-specific side effects has been shown for third-generation EGFR-TKIs. Molecular testing is of major importance in deciding for treatment with third generation EGFR-TKIs. This article elucidates the developmental state of third generation EGFR-TKIs with its focus on Osimertinib, the first and currently the only compound in this class which is approved in Germany. Additionally, the medical importance of molecular diagnosis using tumor tissue and circulating tumor DNA is discussed.

Lung cancer patients with HER2 mutations treated with chemotherapy and HER2-targeted drugs: results from the European EUHER2 cohort.

BACKGROUND: HER2 mutations have been identified as oncogenic drivers in lung cancers and are found in 1-2% of lung adenocarcinomas. There is, to date, no standard of care for these patients. We thus aim to study the therapeutic outcomes of patients harboring HER2 mutations and establish the efficacy of various drug regimens. PATIENTS AND METHODS: This retrospective cohort study in European centers assessed patients with advanced non-small-cell lung cancer (NSCLC), a known HER2 exon-20 insertion, treated with chemotherapy and/or HER2-targeted drugs. RESULTS: We identified 101 eligible patients from 38 centers: median age 61 years (range: 30-87), 62.4% women, 60.4% never-smokers. All tumors were adenocarcinomas. Concomitant EGFR mutations, ALK translocations, and ROS translocations were observed in 5, 1, and 1 patients, respectively. The median number of treatment lines was 3 (range: 1-11). The median overall survival was 24 months. Overall response rate (ORR) and the median progression-free survival (PFS) with conventional chemotherapy (excluding targeted therapies) were 43.5% and 6 months in first-line (n = 93), and 10% and 4.3 months in second-line (n = 52) therapies. Sixty-five patients received HER2-targeted therapies: trastuzumab = 57, neratinib = 14, afatinib = 9, lapatinib = 5, T-DM1 = 1. ORR was 50.9% and PFS was 4.8 months with trastuzumab or T-DM1. CONCLUSION: This series shows the chemosensitivity of HER2-driven NSCLC, and the potential interest of HER2-targeted agents. Our results should help to define the best therapeutic strategy for these patients and to orient future clinical trials.

External Ventricular Catheter Placement: How to Improve.

This cadaveric study outlines the efficiency, safety and precision of cerebral ventricular catheter placement comparing classical freehand technique using anatomical landmarks, neuronavigation and XperCT-guided assistance.

Correlation of pain, functional impairment, and health-related quality of life with radiological grading scales of lumbar degenerative disc disease.

BACKGROUND: It is generally believed that radiological signs of lumbar degenerative disc disease (DDD) are associated with increased pain and functional impairment as well as lower health-related quality of life (HRQoL). Our aim was to assess the association of the Modic and Pfirrmann grading scales with established outcome questionnaires and the timed-up-and-go (TUG) test. METHODS: In a prospective two-center study with patients scheduled for lumbar spine surgery, visual analogue scale (VAS) for back and leg pain, Roland-Morris Disability Index, Oswestry Disability Index and HRQoL, as determined by the Short-Form (SF)-12 and the Euro-Qol, were recorded. Functional mobility was measured with the TUG test. Modic type (MOD) and Pfirrmann grade (PFI) of the affected lumbar segment were assessed with preoperative imaging. Uni- and multivariate logistic regression analysis was performed to estimate the effect size of the relationship between clinical and radiological findings. RESULTS: Two hundred eighty-four patients (mean age 58.5, 119 (42 %) females) were enrolled. None of the radiological grading scales were significantly associated with any of the subjective or objective clinical tests. There was a tendency for higher VAS back pain (3.48 vs. 4.14, p = 0.096) and lower SF-12 physical component scale (31.2 vs. 29.4, p = 0.065) in patients with high PFI (4-5) as compared to patients with low PFI (0-3). In the multivariate analysis, patients with MOD changes of the vertebral endplates were 100 % as likely as patients without changes to show an impaired TUG test performance (odds ratio (OR) 1.00, 95 % confidence interval (CI) 0.56-1.80, p = 0.982). Patients with high PFI were 145 % as likely as those with low PFI to show an impaired TUG test performance (OR 1.45, 95 % CI 0.79-2.66, p = 0.230). CONCLUSIONS: There was no association between established outcome questionnaires of symptom severity and two widely used radiological classifications in patients undergoing surgery for lumbar DDD.

[Cervical disc herniation--diagnosis and treatment]. / Hernie discale cervicate--diagnostic et prise en charge.

A cervical disc herniation (CDH) is a frequently encountered pathology in primary care medicine. It may give rise to a compression of a nerve root (a radiculopathy, with or without sensory-motor deficit) or of the spinal cord (myelopathy). The majority of CDHs can be supported by means of a conservative treatment. When a radiculopathy is found and a clinico-radiological correlation is present, a moderate neurological deficit appears suddenly, or if it is progressive under conservative treatment or if pain is poorly controlled by well-conducted conservative treatment performed during 6 to 8 months, surgery is then recommended. A symptomatic cervical myelopathy is, by itself, an indication for a surgical treatment.

[Minimally invasive spine surgery: past and present]. / Chirurgie du rachis lombaire minimalement invasive: passé et present d'une technique pleine d'avenir.

In the early twentieth century, the understanding of spine biomechanics and the advent of surgical techniques of the lumbar spine, led to the currently emerging concept of minimal invasive spine surgery, By reducing surgical access, blood loss, infection rate and general morbidity, functional prognosis of patients is improved. This is a real challenge for the spine surgeon, who has to maintain a good operative result by significantly reducing surgical collateral damages due to the relatively traumatic conventional access.

Early detection of lung cancer: a statement from an expert panel of the Swiss university hospitals on lung cancer screening.

The discussion about setting up a program for lung cancer screening was launched with the publication of the results of the National Lung Screening Trial, which suggested reduced mortality in high-risk subjects undergoing CT screening. However, important questions about the benefit-harm balance and the details of a screening program and its cost-effectiveness remain unanswered. A panel of specialists in chest radiology, respiratory medicine, epidemiology, and thoracic surgery representing all Swiss university hospitals prepared this joint statement following several meetings. The panel argues that premature and uncontrolled introduction of a lung cancer screening program may cause substantial harm that may remain undetected without rigorous quality control. This position paper focuses on the requirements of running such a program with the objective of harmonizing efforts across the involved specialties and institutions and defining quality standards. The underlying statement includes information on current evidence for a reduction in mortality with lung cancer screening and the potential epidemiologic implications of such a program in Switzerland. Furthermore, requirements for lung cancer screening centers are defined, and recommendations for both the CT technique and the algorithm for lung nodule assessment are provided. In addition, related issues such as patient management, registry, and funding are addressed. Based on the current state of the knowledge, the panel concludes that lung cancer screening in Switzerland should be undertaken exclusively within a national observational study in order to provide answers to several critical questions before considering broad population-based screening for lung cancer.

[Lumbar disc herniation--diagnosis and treatment]. / Hernie discale lombaire--diagnostic et prise en charge.

A lumbar disc herniation (LDH) is a condition frequently encountered in primary care medicine. It may give rise to a compression of one or more nerve roots, which can lead to a nerve root irritation, a so-called radiculopathy, with or without a sensorimotor deficit. The majority of LDHs can be supported by means of a conservative treatment consisting of physical therapy, ergotherapy, analgetics, anti-inflammatory therapy or corticosteroids, which may be eventually administered by infiltrations. If a clinico-radiological correlation is present and moderate neurological deficit appears suddenly, if it is progressive under conservative treatment or if pain is poorly controlled by well-conducted conservative treatment performed during four to six months, surgery is then recommended.

Patterns of progression on first line osimertinib in patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC): A Swiss cohort study.

AIM: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved for patients with EGFR mutated non-small cell lung cancer as first-line treatment. However, treatment resistance inevitably emerges and may present as oligo-progressive disease (OPD) or systemic progressive disease (SPD). The incidence of OPD on first-line osimertinib is unknown. METHODS: We retrospectively analyzed patients who received first-line osimertinib at 13 Swiss centers. The rate of OPD (PD in ≤ 5 lesions) and treatment outcomes were analyzed. RESULTS: The median age of the 148 patients was 68.2 years (range. 38.0-93.3). There were 62 % females, 83 % with a PS ≤ 1, 59 % never smokers, 57 % of patients with an EGFR exon 19 deletion and 37 % with EGFR p.L858R exon 21. 77 % experienced OPD. Median overall survival (OS) was 51.6 months (95 % CI, 38.4-65.0). Median progression-free survival (PFS) was 19.2 (95 % CI, 14.3-23.5) and 8.7 (95 % CI, 2.8-15.6) months for patients with common and uncommon EGFR mutations. Patients with OPD compared to SPD had a significantly longer time to treatment failure and longer OS of (22.9 vs. 10.8 months, p < 0.001 and 51.6 vs. 26.4 months, p = 0.004, respectively). The most common organ sites of PD were lung (62 %), brain (30 %), lymph nodes (30 %), bone (27 %) and pleura (27 %). Twenty-six patients (45 %) with OPD received local ablative treatment (LAT). The OS of OPD patients with LAT was 60.0 (95 % CI, 51.6-NA) vs. 51.4 (95 % CI 38.4-65.3) months (p = 0.43) without LAT. CONCLUSION: The rate of OPD of patients receiving first line osimertinib was 77 %. Patients with OPD had a significantly better OS compared to patients with SPD (51.6 vs. 26.4 months). Patients with OPD receiving LAT had the longest median OS (60.0 months).

Immune checkpoint blockers in solid organ transplant recipients and cancer: the INNOVATED cohort.

BACKGROUND: Patients with solid organ transplant (SOT) and solid tumors are usually excluded from clinical trials testing immune checkpoint blockers (ICB). As transplant rates are increasing, we aimed to evaluate ICB outcomes in this population, with a special focus on lung cancer. METHODS: We conducted a multicenter retrospective cohort study collecting real data of ICB use in patients with SOT and solid tumors. Clinical data and treatment outcomes were assessed by using retrospective medical chart reviews in every participating center. Study endpoints were: overall response rate (ORR), 6-month progression-free survival (PFS), and grade ≥3 immune-related adverse events. RESULTS: From August 2016 to October 2022, 31 patients with SOT (98% kidney) and solid tumors were identified (36.0% lung cancer, 19.4% melanoma, 13.0% genitourinary cancer, 6.5% gastrointestinal cancer). Programmed death-ligand 1 expression was positive in 29% of tumors. Median age was 61 years, 69% were males, and 71% received ICB as first-line treatment. In the whole cohort the ORR was 45.2%, with a 6-month PFS of 56.8%. In the lung cancer cohort, the ORR was 45.5%, with a 6-month PFS of 32.7%, and median overall survival of 4.6 months. The grade 3 immune-related adverse events rate leading to ICB discontinuation was 12.9%. Allograft rejection rate was 25.8%, and risk of rejection was similar regardless of the type of ICB strategy (monotherapy or combination, 28% versus 33%, P = 1.0) or response to ICB treatment. CONCLUSIONS: ICB could be considered a feasible option for SOT recipients with some advanced solid malignancies and no alternative therapeutic options. Due to the risk of allograft rejection, multidisciplinary teams should be involved before ICB therapy.

Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild-type KRAS, locally advanced rectal cancer (LARC): a randomized, multicenter, phase II trial SAKK 41/07.

BACKGROUND: We conducted a randomized, phase II, multicenter study to evaluate the anti-epidermal growth factor receptor (EGFR) mAb panitumumab (P) in combination with chemoradiotherapy (CRT) with standard-dose capecitabine as neoadjuvant treatment for wild-type KRAS locally advanced rectal cancer (LARC). PATIENTS AND METHODS: Patients with wild-type KRAS, T3-4 and/or N+ LARC were randomly assigned to receive CRT with or without P (6 mg/kg). The primary end-point was pathological near-complete or complete tumor response (pNC/CR), defined as grade 3 (pNCR) or 4 (pCR) histological regression by Dworak classification (DC). RESULTS: Forty of 68 patients were randomly assigned to P + CRT and 28 to CRT. pNC/CR was achieved in 21 patients (53%) treated with P + CRT [95% confidence interval (CI) 36%-69%] versus 9 patients (32%) treated with CRT alone (95% CI: 16%-52%). pCR was achieved in 4 (10%) and 5 (18%) patients, and pNCR in 17 (43%) and 4 (14%) patients. In immunohistochemical analysis, most DC 3 cells were not apoptotic. The most common grade ≥3 toxic effects in the P + CRT/CRT arm were diarrhea (10%/6%) and anastomotic leakage (15%/4%). CONCLUSIONS: The addition of panitumumab to neoadjuvant CRT in patients with KRAS wild-type LARC resulted in a high pNC/CR rate, mostly grade 3 DC. The results of both treatment arms exceeded prespecified thresholds. The addition of panitumumab increased toxicity.

Calcifying pseudoneoplasms of the neuraxis (CAPNON): clinical features and therapeutic options.

INTRODUCTION: Calcifying pseudoneoplasms of the neuraxis (CAPNON) are rare, slow-growing lesions occurring anywhere in the central nervous system (CNS). Since their first description in 1978, only 39 cases have been reported in the literature. METHODS: The cases of two patients with histopathologically verified diagnoses of CAPNON are presented. Thereafter, we review all reports published so far with respect to study type, number of patients, anatomical area (intracranial, spinal, or both), clinical presentation, radiological presentation, therapy, duration of follow-up, incidence and type of complication, and outcome. Furthermore, current recommendations for the management of spinal and cerebral CAPNON are discussed. RESULTS: A total of 19 retrospective articles were identified and selected for review: 6 case series (31.6 %) and 13 reports of single cases (68.4 %). The 19 articles and our two additional cases added up to a total of 19 patients with spinal CAPNON and 22 patients with intracranial CAPNON. All patients were treated surgically. A follow-up was provided in 13 patients with spinal (68.4 %) and in 16 patients with intracranial CAPNON (72.7 %), respectively. The follow-up showed no signs of recurrence in 12 of 13 patients with spinal CAPNON (92.3 %) and in 15 of 16 patients with intracranial CAPNON (93.7 %). One-tailed Fisher's exact test revealed no significant difference between complete and incomplete resection in terms of disease recurrence (spinal: p = 0.6842; intracranial: p = 0.3749). Analysis of the literature did not reveal any deaths directly associated with CAPNON. CONCLUSIONS: Calcifying pseudoneoplasms are rare benign lesions of the CNS of yet unknown origin. Because of the increasing number of reports, this clinical entity should be taken into consideration in the differential diagnosis of intracranial and intraspinal calcified lesions.

[Lung cancer - on the way to a molecular classification]. / Das Bronchialkarzinom - auf dem Wegzu einer molekularen Klassifikation.

Treatment options for patients with advanced lung cancer have greatly improved in recent years. New molecular-targeted drugs are avaliable based on predictive biomarkers. Molecular diagnostics are key to successful therapy. Guidelines and recommendations for lung cancer testing and treatment are evolving, and it is increasingly challenging to stay up-to-date. In view of the rapid development in the lung cancer field, the current article discusses the current evidence for lung cancer classification and testing, and illustrates new perspectives in modern oncology.

[Chemotherapy for malignant tumors of lung and pleura]. / Chemotherapie bei Tumoren der Lunge und Pleura - was darf von welchem Therapieansatzerwartet werden.

Lung Cancer is the leading cause of cancer-related mortality worldwide, with nearly 1.4 million deaths each year. There has been an overall decrease in the incidence of lung cancer in men, although in women this trend has only been noted very recently in the United States and in many countries in Western Europe. In contrast, in many parts of the world the number of cases and deaths related to lung cancer is on the rise. These increased death rates are in close correlation to smoking habits in the different countries. It is also increasingly becoming a disease of the elderly, with a median age at diagnosis of 70 years. In Switzerland about 2'500 men and 1'200 women are yearly diagnosed with lung cancer. Lung cancer is diagnosed at an advanced stage in a majority of patients, which explains the high mortality rate associated with this disease. In the current review we give on overview on the current treatment practice for small cell lung cancer (SCLC) as well as on non-small cell lung cancer (NSCLC). The main focus is on the novel treatment options for advanced, metastatic NSCLC and the current use of predictive biomarkers in order to personalize therapy. Malignant pleural mesothelioma is a rare cancer occurring mainly in older men who have been exposed to asbestos, although it occurs decades after exposure (20 - 40 years later). The disease is difficult to treat and median overall survival is only about one year.

[Oncological emergencies with special consideration of the side effects of checkpoint inhibitors]. / Onkologische Notfälle mit besonderer Berücksichtigung der Nebenwirkungen von Checkpoint-Inhibitoren.

Oncological patients are already exceedingly burdened due to their underlying disease, so that another complication can quickly cause significant deterioration of the state of health. Febrile neutropenia should be rapidly treated with anti-infective agents and malignant hypercalcemia requires a rapid diagnosis. In the case of suspected checkpoint inhibitor-associated toxicity, an interdisciplinary consultation is often necessary.