BreathEase: rationale, design and recruitment of a randomised trial and embedded mixed-methods study of a multiprofessional breathlessness service in early palliative care.

BACKGROUND: The Munich Breathlessness Service has adapted novel support services to the German context, to reduce burden in patients and carers from breathlessness in advanced disease. It has been evaluated in a pragmatic fast-track randomised controlled trial (BreathEase; NCT02622412) with embedded qualitative interviews and postal survey. The aim of this article is to describe the intervention model and study design, analyse recruitment to the trial and compare sample characteristics with other studies in the field. METHODS: Analysis of recruitment pathways and enrolment, sociodemographic and clinical characteristics of participants and carers. RESULTS: Out of 439 people screened, 253 (58%) were offered enrolment and 183 (42%) participated. n=97 (70%) carers participated. 186 (42%) people did not qualify for inclusion, mostly because breathlessness could not be attributed to an underlying disease. All participants were self-referring; 60% through media sources. Eligibility and willingness to participate were associated to social networks and illness-related activities as recruitment routes. Mean age of participants was 71 years (51% women), with COPD (63%), chronic heart failure (8%), interstitial lung disease (9%), pulmonary hypertension (6%) and cancer (7%) as underlying conditions. Postal survey response rate was 89%. Qualitative interviews were conducted with 16 patients and nine carers. CONCLUSION: The BreathEase study has a larger and more heterogeneous sample compared to other trials. The self-referral-based and prolonged recruitment drawing on media sources approximates real-world conditions of early palliative care. Integrating qualitative and quantitative components will allow a better understanding and interpretation of the results of the main effectiveness study.

Prognostic and predictive value of PD-L1 expression and tumour infiltrating lymphocytes (TiLs) in locally advanced NSCLC treated with simultaneous radiochemotherapy in the randomized, multicenter, phase III German Intergroup lung Trial (GILT).

OBJECTIVES: Immune checkpoint inhibition after radiochemotherapy (RTCT) has become a new standard of care for locally advanced non-small cell lung cancer with programmed death-ligand 1 (PD-L1) expression. However, little is known about the prognostic role of immune response markers in this setting. We analysed PD-L1 expression and tumour infiltrating lymphocytes (TiLs) in tumour biopsies from the multicenter German Intergroup Lung Trial (GILT), which previously randomised patients with stage III NSCLC to RTCT with or without consolidation chemotherapy. MATERIALS AND METHODS: We retrospectively analyzed tumour biopsies from patients treated in the GILT trial. PD-L1 expression was analysed using the Ventana SP263 assay and TiL score (low, intermediate, high) and pattern (excluded, inflamed, desert) were assessed. The primary endpoint of the biomarker analysis was PFS in patients with PD-L1 ≥ 1% vs. PD-L1 < 1% NSCLC. Secondary endpoints explored the prognostic relevance of additional PD-L1 expression levels and TiL score and pattern. RESULTS: Biopsies were available from 92 patients treated with RTCT. Patients with available tumor tissue did not differ significantly from the whole study population. PD-L1 scores from 78 samples were available for analysis. There was no difference in PFS in the PD-L1 < 1% vs. PD-L1 ≥ 1% subgroups. TiL score was available in 66 patients. Patients with high TiL score showed favourable overall survival compared to the low TiL subgroup. This trend was most pronounced in those patients treated with consolidative chemotherapy. CONCLUSION: In this analysis, PD-L1 expression did not correlate with PFS following RTCT. However, patients with TiLs > 10% were found to have longer overall survival, especially for those patients treated with consolidation chemotherapy after the end of RTCT. Further analyses to explore the prognostic and predictive relevance of TiLs in the context of consolidative checkpoint inhibition with durvalumab are required.

Effectiveness of a specialised breathlessness service for patients with advanced disease in Germany: a pragmatic fast-track randomised controlled trial (BreathEase).

BACKGROUND: The effectiveness of the Munich Breathlessness Service (MBS), integrating palliative care, respiratory medicine and physiotherapy, was tested in the BreathEase trial in patients with chronic breathlessness in advanced disease and their carers. METHODS: BreathEase was a single-blinded randomised controlled fast-track trial. The MBS was attended for 5-6 weeks; the control group started the MBS after 8 weeks of standard care. Randomisation was stratified by cancer and the presence of a carer. Primary outcomes were patients' mastery of breathlessness (Chronic Respiratory Disease Questionnaire (CRQ) Mastery), quality of life (CRQ QoL), symptom burden (Integrated Palliative care Outcome Scale (IPOS)) and carer burden (Zarit Burden Interview (ZBI)). Intention-to-treat (ITT) analyses were conducted with hierarchical testing. Effectiveness was investigated by linear regression on change scores, adjusting for baseline scores and stratification variables. Missing values were handled with multiple imputation. RESULTS: 92 patients were randomised to the intervention group and 91 patients were randomised to the control group. Before the follow-up assessment after 8 weeks (T1), 17 and five patients dropped out from the intervention and control groups, respectively. Significant improvements in CRQ Mastery of 0.367 (95% CI 0.065-0.669) and CRQ QoL of 0.226 (95% CI 0.012-0.440) score units at T1 in favour of the intervention group were seen in the ITT analyses (n=183), but not in IPOS. Exploratory testing showed nonsignificant improvements in ZBI. CONCLUSIONS: These findings demonstrate positive effects of the MBS in reducing burden caused by chronic breathlessness in advanced illness across a wide range of patients. Further evaluation in subgroups of patients and with a longitudinal perspective is needed.

Comprehensive serial biobanking in advanced NSCLC: feasibility, challenges and perspectives.

BACKGROUND: Availability of tumor material at baseline and disease progression is increasingly important for patient management in non-small-cell lung cancer (NSCLC), especially for the application of targeted therapies like tyrosine kinase inhibitors and for immune checkpoint inhibitor treatment. Here we report the experience of prospective biomaterial acquisition in advanced NSCLC from a pilot project. METHODS: Main objective was the longitudinal collection of high-quality, cryoconserved biopsies in addition to formalin-fixed paraffin-embedded (FFPE) biopsies required for routine diagnostics, along with blood samples and detailed clinical annotation using standardized questionnaires. RESULTS: Over five years, 205 patients were enrolled for the project, yielding 387 cryoconserved biopsies and 1,098 serum, plasma and buffy-coat samples. The feasibility of obtaining the cryoconserved biopsies in addition to the FFPE biopsies was 89% for newly diagnosed cases, but dropped down to 56% and 47% at first and second disease progression, respectively. While forceps biopsy was the preferred procedure for tissue acquisition, the highest tissue amounts were received using the cryobiopsy method. Biopsies had a median tumor cellularity of 34% and yielded in median 13.6 µg DNA and 12 µg RNA (median RIN =8). During the five-year project, a maximum of 38 follow-up blood samples per patient were assembled in up to four therapy lines. CONCLUSIONS: Despite the poor condition and limited prognosis of most NSCLC patients, this serial biomaterial acquisition including routine collection of cryoconserved biopsies is feasible to support individualized management. The standardized collection of high-quality material has enabled and enriched several translational research studies that can advance therapeutic options.

Orphan Drugs in Development for the Treatment of Small-Cell Lung Cancer: Emerging Data on Lurbinectedin.

Lung cancer is the leading cause of death of all cancer entities and small-cell lung cancer (SCLC) is the most malignant subtype. Despite good initial response to chemotherapy, many patients relapse early and success of second line treatment remains poor. For years, no relevant improvement of second line treatment has been achieved in the field of SCLC. Lurbinectedin, a novel RNA-polymerase II inhibitor has shown promising results in pretreated SCLC patients as single agent and in combination with other chemotherapeutic drugs leading to an orphan drug designation from the FDA. This article reviews the current data on this emerging substance and its impact on the treatment of SCLC.

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.

How much primary tumor metabolic volume reduction is required to improve outcome in stage III NSCLC after chemoradiotherapy? A single-centre experience.

PURPOSE: We analysed a correlation between pre- to post-treatment primary tumour metabolic volume (PT-MV) reduction on 18F-FDG-PET/CT and survival in non-small cell lung cancer (NSCLC) patients treated with chemoradiotherapy (CRT). METHODS: Sixty consecutive patients with NSCLC stage IIIA-B (UICC 7th edition), treated with chemoradiotherapy, who underwent 18F-FDG-PET/CT at the same institution before and 6 weeks after treatment, were analysed. Different metabolic response values were investigated on their correlation with survival parameters: complete response (100% PT-MV reduction); major response (80-99% PT-MV reduction); moderate response (50-79% PT-MV reduction); minor response (1-49% PT-MV reduction) and non-response (no change or increase in uptake). RESULTS: From 60 patients, 52 (87%) had repeat PET/CT scans 6 weeks after completion of CRT. Complete metabolic response (CR) was reached in ten (17%), whereas major and moderate metabolic responses occurred in 16 (27%) and 15 (25%) patients, respectively. Four patients (7%) had minor metabolic response. Non-response was documented in seven patients (12%). Median overall survival (MS) for the entire cohort was 17 months (95% CI: 11.9-22.1 months). MS according to the different metabolic response values was as follows: 34 months (95% CI: 0-84.1); 22 months (95% CI: 14.2-29.8); 12 months (95% CI: 0.4-23.6); 11 months (95% CI: 0.2-21.8) and 17 months in patients with complete, major, moderate, minor and non-response (95% CI: 6.7-27.3), respectively (p = 0.008). On multivariate analysis, significant predictors of survival included ECOG performance status (p = 0.035, HR 0.49, 95% CI: 0.25-0.95) as well as complete and major metabolic response as a continuous variable with PT-MV reduction of at least 80% (p = 0.021, HR 0.36, 95% CI: 0.15-0.86). Moderate metabolic response did not correlate with improved outcome (p = 0.522). CONCLUSIONS: In this homogeneous locally-advanced NSCLC single-centre patient cohort, a PT-MV reduction of at least 80% (complete and major metabolic response) following CRT was necessary to significantly improve patient outcome.

Daily Chronic Intermittent Hypobaric Hypoxia Does Not Induce Chronic Increase in Pulmonary Arterial Pressure Assessed by Echocardiography.

Chronic hypoxia causes pulmonary vascular remodeling resulting in persistently increased pulmonary arterial pressures (PAP) even after return to normoxia. Recently, interest in chronic intermittent hypobaric hypoxia (CIHH) was raised because it occurs in subjects working at high altitude (HA) but living in lowland. However, effects of daily CIHH on PAP are unknown. In this pilot study, we included 8 healthy subjects working at (2650 m) each workday for 8-9 h while living and sleeping at LA and 8 matched control subjects living and working at LA. Cardiorespiratory measurements including echocardiography at rest and during exercise were performed at LA (Munich, 530 m) and HA (Zugspitze, 2650 m). Hemoglobin was higher in CIHH subjects. LA echocardiography showed normal right and left cardiac dimensions and function in all subjects. Systolic PAP (sPAP) and tricuspid annular plane systolic excursion (TAPSE) at rest were similar in both groups. Resting blood gas analysis (BGA) at HA revealed decreased pCO2 in CIHH compared to controls (HA: 28.4 versus 31.7 mmHg, p=0.01). During exercise, sPAP was lower in CIHH subjects compared to controls (LA: 28.7 versus 35.3 mmHg, p=0.02; HA: 26.3 versus 33.6 mmHg, p=0.04) and peripheral oxygen saturation (SpO2) was higher. In sum, subjects exposed to CIHH showed no signs of pulmonary vascular remodeling.

Correction to: Analysis of primary tumor metabolic volume during chemoradiotherapy in locally advanced non-small cell lung cancer.

Correction to: Strahlenther Onkol 2017 https://doi.org/10.1007/s00066-017-1229-3 Unfortunately, an incorrect reference was provided in Table 4.The corrected version of Table 4 can be found below.We apologize for any inconvenience ….

NSCLC Patients Harbouring Rare or Complex EGFR Mutations Are More Often Smokers and Might Not Benefit from First-Line Tyrosine Kinase Inhibitor Therapy.

BACKGROUND: Generally, tyrosine kinase inhibitor (TKI) therapy is recommended in first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) harbouring a classic epidermal growth factor receptor (EGFR) mutation. However, the response of patients with rare or complex EGFR mutations to TKI treatment is not predictable, nor is the prognosis for such patients. OBJECTIVES: In cases of rare or complex EGFR mutations, the right approach to therapy remains challenging. That is why we sought to analyse the characteristics as well as the prognosis and the response to TKI treatment of patients with rare or complex EGFR mutations. PATIENTS AND METHODS: 343 NSCLC patients tested for EGFR mutation at a German lung cancer centre were analysed for age, gender, and smoking status as well as for the mutation status. For 12 patients with rare and complex mutations, response to TKI treatment was described. RESULTS: 282 of all patients had a wild-type EGFR, whereas 61 harboured an EGFR mutation. 32 of these were classic mutations, followed by 16 rare and 7 complex mutations. EGFR mutations were significantly more frequent in women. Patients with rare or complex mutations were significantly more often smokers compared to those with classic EGFR mutations. Furthermore, rare and complex mutations were less responsive to TKI therapy. CONCLUSION: Patients with rare or complex EGFR mutations differ from those with classic mutations in terms of smoking status and response to TKIs. As these mutations may not respond well to TKI therapy, first-line TKIs should not be automatically chosen based on the sole presence of an EGFR mutation.

Analysis of primary tumor metabolic volume during chemoradiotherapy in locally advanced non-small cell lung cancer.

PURPOSE: Positron emission tomography with 2­deoxy-2-[fluorine-18] fluoro-d-glucose integrated with computed tomography (18F-FDG-PET/CT) has an established role in the initial diagnosis and staging of lung cancer. However, a prognostic value of PET/CT during multimodality treatment has not yet been fully clarified. This study evaluated the role of primary tumor metabolic volume (PT-MV) changes on PET/CT before, during, and after chemoradiotherapy (CRT). METHODS: A total of 65 patients with non-small-cell lung cancer (NSCLC) UICC stage IIIA/B (TNM 7th Edition) were treated with definitive chemoradiotherapy (sequential or concurrent setting). PET/CT was acquired before the start, at the end of the third week, and 6 weeks following CRT. RESULTS: Median overall survival (OS) for the entire cohort was 16 months (95% confidence interval [CI]: 12-20). In all, 60 (92.3%) patients were eligible for pre-treatment (pre-PT-MV), 28 (43%) for mid-treatment (mid-PT-MV), and 53 (81.5%) for post-treatment (post-PT-MV) volume analysis. Patients with pre-PT-MV >63 cm3 had worse OS (p < 0.0001). A reduction from mid-PT-MV to post-PT-MV of >15% improved OS (p = 0.001). In addition, patients with post-PT-MV > 25 cm3 had significantly worse outcome (p = 0.001). On multivariate analysis, performance status (p = 0.002, hazard ratio [HR] 0.007; 95% CI 0.00-0.158), pre-PT-MV1 < 63 cm3 (p = 0.027, HR 3.98; 95% CI 1.17-13.49), post-PT-MV < 25 cm3 (p = 0.013, HR 11.90; 95% CI 1.70-83.27), and a reduction from mid-PT-MV to post-PT-MV > 15% (p = 0.004, HR 0.25; 95% CI 0.02-0.31) correlated with improved OS. CONCLUSIONS: Our results demonstrated that pre- and post-treatment PT-MV, as well as an at least 15% reduction in mid- to post-PT-MV, significantly correlates with OS in patients with inoperable locally advanced NSCLC.

Frequency and clinical relevance of EGFR mutations and EML4-ALK translocations in octogenarians with non-small cell lung cancer.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) have improved response rates in some patients with non-small cell lung cancer (NSCLC), and testing for EGFR mutation and ALK translocation is recommended for all patients with advanced lung adenocarcinoma. The frequency of driver mutations in elderly and very elderly patients has not been described. PATIENTS AND METHODS: We reviewed EGFR and ALK in patients over the age of 70 years diagnosed and treated at our center in 2015 (subgroups: 70-74, 75-79 and >80 years). We then assessed a second cohort, including all patients with lung cancer over the age of 80 years diagnosed in 2014. We also analyzed smoking history, treatment and response. RESULTS: In the 2015 cohort of 179 patients, 16 were 80 years or older at diagnosis. Six of eight (75%) octogenarians with non-squamous NSCLC were EGFR or ALK positive. The 2014 cohort confirmed the high rate of driver alterations in octogenarians. Of 334 patients, 32 were 80 years or older and, of these, 10 had non-squamous histology and were tested for driver alterations (four of 10 [40%] EGFR or ALK positive). Rates of genetic drivers were somewhat lower in patients with non-squamous NSCLC aged 70-74 years (27.0%) and 75-79 years (26.7%). When treated with a TKI, octogenarians had high response rates and progression-free survival. Most octogenarians with lung adenocarcinoma were never smokers, with an inverse correlation of pack-years smoked to age at diagnosis. CONCLUSION: Very elderly patients with non-squamous NSCLC show high rates of driver alterations in EGFR and ALK. This, often frail and comorbid, population may not be fit for treatment with cytotoxic chemotherapy and may benefit from targeted treatments. Testing for EGFR and ALK alterations should not be restricted to younger patients. The biology of lung cancer in the very elderly may differ from that of moderately elderly patients, as longevity may select for individuals more resistant to, or with little exposure to, environmental carcinogens.

Management of Progressive Pulmonary Nodules Found during and outside of CT Lung Cancer Screening Studies.

Although the effectiveness of screening for lung cancer remains controversial, it is a fact that most lung cancers are diagnosed at an advanced stage outside of lung cancer screening programs. In 2013, the U.S. Preventive Services Task Force revised its lung cancer screening recommendation, now supporting lung cancer screening by low-dose computed tomography in patients at high risk. This is also endorsed by many major medical societies and advocacy group stakeholders, albeit with different eligibility criteria. In Europe, population-based lung cancer screening has so far not been recommended or implemented, as some important issues remain unresolved. Among them is the open question of how enlarging pulmonary nodules detected in lung cancer screening should be managed. This article comprises two parts: a review of the current lung cancer screening approaches and the potential therapeutic options for enlarging pulmonary nodules, followed by a meeting report including consensus statements of an interdisciplinary expert panel that discussed the potential of the different therapeutic options.

Metronomic treatment of advanced non-small-cell lung cancer with daily oral vinorelbine - a Phase I trial.

MICRO-ABSTRACT: In a Phase I dose-finding study of metronomic daily oral vinorelbine in advanced non-small-cell lung cancer, a recommended dose was established for this therapeutic approach. In addition, this trial revealed promising efficacy data and an acceptable tolerability profile. The observed vinorelbine blood concentrations suggest continuous anti-angiogenic coverage. INTRODUCTION: We present a Phase I dose-finding study investigating metronomic daily oral vinorelbine (Navelbine® Oral, NVBo) in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with stage III/IV NSCLC received daily NVBo at fixed dose levels of 20-50 mg/d for 21 days of each 4-week cycle. Primary end point was the maximum tolerated dose. Secondary end points included tumor response, time to progression (TTP), overall survival (OS) and tolerability. RESULTS: Twenty-seven patients with advanced NSCLC were enrolled. Most of them were extensively pretreated. Daily NVBo was well tolerated up to 30 mg/d. At 40 mg/d, two of five patients experienced dose-limiting toxicities (DLTs). Three of six patients had DLTs at the 50 mg/d level. The recommended dose was established at 30 mg/d in cycle 1, with escalation to 40 mg/d in cycle 2, if tolerated. Pharmacokinetic analyses showed continuous blood exposure over 21 days and only marginal accumulation. The tolerability profile was acceptable (all dose levels - all grades: decreased appetite 33%, diarrhea 33%, leukopenia 33%, nausea 30%, vomiting 26%; ≥grade 3: leukopenia 30%, lymphopenia 19%, neutropenia 19%, febrile neutropenia 15%). Disease control rate, OS and TTP signaled a treatment effect. CONCLUSION: Daily metronomic NVBo therapy in extensively pretreated patients with advanced NSCLC is feasible and safe at the recommended dose of 30 mg/d. Escalation to 40 mg/d in the second cycle is possible. The blood concentrations of vinorelbine after daily metronomic dosing reached lower peaks than intravenous or oral conventional dosing. Blood concentrations were consistent with anti-angiogenic or immune modulating pharmacologic properties of vinorelbine. Further studies are warranted to evaluate the safety and efficacy of this novel approach in specific patient populations.

Clinical relevance of the M1b and M1c descriptors from the proposed TNM 8 classification of lung cancer.

OBJECTIVE: The TNM 8 lung cancer staging system reclassifies patients with a solitary extrathoracic metastasis as M1b and two or more extrathoracic metastases as M1c. This study investigates the clinical relevance of this change. METHODS: Advanced lung cancer patients were retrospectively restaged according to the TNM8 M1b and M1c classifiers. Overall survival was compared in M1b and M1c patients staged with and without PET-CT. We then summarized the TNM 8 staging classification and the relevant literature on the treatment of oligometastatic lung cancer. RESULTS: In all, 82 patients with metastatic lung cancer were reclassified according to the TNM 8: 14 had M1b and 58 had M1c disease. Those with M1b disease lived significantly longer than those with M1c disease (15.2 vs. 7.3 months, p = 0.0029). Among those with M1b disease, survival was the highest when M1b status was confirmed by PET-CT (21.4 vs. 7 months). M1c patients with 4 or less distant metastases had a trend to longer survival vs. M1c patients with 5 or more metastases (9.4 vs. 7.3 months), especially when PET-CT staging was used (13.9 months). CONCLUSIONS: We confirmed the prognostic value of the M1b and M1c descriptors in a Western European tertiary care population. The use of PET-CT seems to increase the prognostic value of the M descriptor and may define an additional oligometastatic subgroup of M1c patients. Clinical trials investigating the treatment of patients with varying degrees of metastatic disease are needed and should be based on PET-CT staging.

Advanced non-small cell lung cancer (NSCLC) with activating EGFR mutations: first-line treatment with afatinib and other EGFR TKIs.

INTRODUCTION: Based on the results of several randomised controlled trials, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have now replaced platinum-based chemotherapy as first-line therapy for advanced non-small cell lung cancer (NSCLC) harboring an activating EGFR mutation. Areas covered: This review describes the EGFR pathway and its abnormalities in NSCLC and discusses the differential molecular and clinical activity of first and next-generation EGFR TKIs in the first-line treatment of tumors with an activating EGFR mutation, with a special focus on the second-generation agent afatinib. A comprehensive literature search was conducted to identify all relevant clinical trials including abstracts from most recent meetings to provide up-to-date information on this topic. Expert commentary: While the first-generation EGFR TKIs erlotinib and gefitinib exhibited good tolerability and improved progression-free survival compared with a platinum doublet, they failed to improve overall survival (OS). In contrast, clinical trials of afatinib (LUX-Lung 3 and 6) demonstrated a significant OS advantage over a platinum doublet, particularly in patients whose tumors harbored the Del19 mutation. Moreover, in a head-to-head comparison afatinib improved efficacy versus gefitinib in patients with common EGFR mutations across a range of clinically relevant endpoints. Afatinib is therefore a promising first-line option in these patients.

A persistent pneumothorax? 5-year follow-up after diagnosis of Swyer-James-MacLeod syndrome.

Swyer-James-MacLeod syndrome should be considered in healthy patients with unilateral pulmonary hyperlucency http://ow.ly/YWps9.

SCLC-State of the Art and What Does the Future Have in Store?

Worldwide, the total number of diagnosed lung cancer cases amounts to 1.8 million every year. Small-cell lung cancer (SCLC) accounts for about 15% to 17% of all diagnosed lung cancers. Despite all progress made in the field of non-small-cell lung cancer, the prognosis and therapeutic options in SCLC are still limited. The resistance of SCLC to conventional therapy as well as its high recurrence rate can be attributed to the heterogeneous genetic structure of SCLC; however, a targeted therapy approach to SCLC may build on this very heterogeneous genetic structure. SCLC is by now a well-characterized cancer with various genetic alterations; for example, mutations in tumor suppressor genes TP53 and RB1, alterations in chromosome 3p, JAK2, FGFR1, and MYC genes were discovered. Based on these findings, various treatment options (eg, aurora kinase inhibitors, PARP inhibition, immune checkpoint inhibition and vaccine therapy) are currently evaluated with the goal of determining their clinical effectiveness. In this article, we review the existing knowledge of SCLC genetics and the current treatment standards and highlight new approaches of immunotherapy and other targeted therapies, which may yield new treatment options and improve the outcome of patients with SCLC.