Immune checkpoint inhibition (ICI) immunotherapy has revolutionized the approach to metastatic non-small-cell lung cancer (NSCLC). In particular, antibodies blocking the inhibitory immune checkpoints ...programmed death 1 (PD-1) and its ligand (PD-L1) are associated with higher response rates, improved overall survival and better tolerability as compared with conventional cytotoxic chemotherapy. Recently, ICI has moved from the second-line to the first-line setting for many patients with non-oncogene-addicted NSCLC, either alone or in combination with chemotherapy. The next logical step is to examine this therapy in patients with non-metastatic NSCLC to improve long-term overall survival and cure rates. For patients with unresectable stage III NSCLC, ICI with durvalumab after concurrent chemoradiotherapy has brought a major improvement in 2-year progression-free and overall survival, which holds promise for an improved cure rate. As the relapse pattern in patients with completely resected early-stage NSCLC is predominantly systemic, high expectations rest on the integration of ICI therapy in their treatment approach. A large number of studies with adjuvant or neo-adjuvant ICI are ongoing and will be discussed here. The advent of stereotactic ablative radiotherapy has brought a valid alternative treatment of patients unfit for or not willing to undergo surgery. Data on combining systemic therapy and stereotactic ablative radiotherapy are virtually non-existent, but there is a strong biological rationale to combine radiotherapy and ICI therapy. Early findings in small feasibility studies are promising and now need to be explored in well-designed phase III trials.
Urban communities were established in the 12th and 13th century with the aid of legal concepts that comprised early notions of the rule of law. Cities were envisaged as "communes", which referred to ...popular sovereignty. In a first period, urban citizenship was flexible and closely related to place of residence. From around 1220 this model came under increasing pressure. In order to safeguard the interests of the most affluent citizens, large guilds were established. Status determined rights, and there were significant inequalities even among citizens. Ideas of democratic democracy and the civic virtues of citizenship were fostering reforms after 1250. Existing urban governments were expanded to include councils and burgomasters. A framework of checks and balances developed because the commune, now considered as the body of citizens and residents, was seen as a force coexisting with metropolitan institutions. The medieval examples show that, in response to economic and even global conditions, community-building and rule-of-law thinking were solutions offering a "unity-in-diversity".
•This ESMO Clinical Practice Guideline provides key recommendations for managing small-cell lung cancer (SCLC).•It covers clinical and pathological diagnosis, staging and risk assessment, treatment ...and follow-up.•Treatment algorithms for limited- and extensive-stage and recurrent SCLC are provided.•All recommendations were compiled by a multidisciplinary group of experts.•Recommendations are based on available scientific data and the authors' collective expert opinion.
The standard first-line treatment for non-oncogene driven metastatic non-small cell lung cancer (NSCLC) is an immune checkpoint inhibitor (ICI) based strategy. Although guidelines increasingly advise ...adding local radical treatment (LRT) to patients with synchronous oligometastatic (sOMD) NSCLC responding to systemic therapy, this recommendation is based on the studies without ICI. Furthermore, the majority of published oligometastatic studies were not on an intention-to-treat basis, resulting in selection bias. Moreover, staging Positron Emission Tomography-Computed Tomography (PET-CT) and brain imaging were often not mandatory and definitions of oligometastatic were heterogeneous. Therefore, this study focused on a single centre retrospective series, including all adequately staged patients with sOMD NSCLC according to the European Organisation for Research and Treatment of Cancer definition (maximum of 5 metastases in 3 organs) that were treated with induction (chemo)-ICI and compared outcomes to those treated with chemotherapy only, with and without LRT. The primary end-points were median progression-free survival (PFS) and overall survival (OS) for patients treated with induction (chemo)-ICI versus chemotherapy. Out of 68 included patients, 38 (56%) eventually received LRT.
With a median follow-up of 26.7 months, the median PFS was 19.0 months for (chemo)-ICI (n = 18) versus 6.8 for chemotherapy-only (n = 50) (HR 0.5, p = 0.03), the median OS was 19.3 versus 15.7 months, respectively (HR 0.8, p = 0.4). In patients having received LRT, median PFS was 19.0 months for (chemo)-ICI versus 8.3 for chemotherapy-only (HR 0.6, p = 0.2). In conclusion, an ICI-based systemic treatment is feasible and may result in superior survival outcomes. This should be investigated in prospective trials. Strategies to improve response rates to systemic treatment are also needed.
•Largest and well-defined oligometastatic series on an intention-to-treat basis.•Adequate staging of synchronous oligometastatic NSCLC based on the EORTC definition.•PFS significantly longer in the (chemo)-immuno group compared with chemo only.•PFS numerically longer for (chemo)-immuno versus chemo-only when LRT.
To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on ...Lung Cancer was held on 11–12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines of treatment in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on locally advanced disease.
Concurrent chemotherapy and radiotherapy (CCRT) followed by durvalumab immune therapy in appropriate patients is considered to be the standard of care in most fit stage III non-small-cell lung cancer ...(NSCLC) patients. However, CCRT is a toxic treatment that affects all organ systems and may cause acute and permanent side effects, some of which may be lethal. Supportive care is therefore of utmost importance in this clinical setting. A group of experts from the European Society for Therapeutic Radiology and Oncology (ESTRO) and the European Society of Medical Oncology (ESMO) identified the following items of importance for further improvement of supportive care: smoking cessation; nutrition before and during CCRT (including treatment and prevention of anorexia); physical exercise before and during CCRT; prevention and treatment of acute esophagitis and dysphagia; treatment of cough and dyspnea; treatment of skin reactions; treatment of fatigue; prophylaxis of nausea and emesis; prevention, diagnosis, and treatment of cardiac disease and damage; and optimization of radiotherapy techniques and chemotherapy adjustments to reduce toxicity in the era of immune therapy. The resulting recommendations are summarized in this manuscript and knowledge gaps identified, in which future investments are needed to improve supportive care and hence quality of life and survival for our stage III NSCLC patients.
•Supportive care is an integral part of CCRT.•All aspects are important.•A multi-disciplinary approach is mandatory.
Background: Patients with stage III non-small-cell lung cancer (NSCLC) and limited disease small-cell lung cancer are excluded from concurrent chemoradiation mostly on the basis of comorbidity and ...age. The purpose of this prospective study was to get insight in what proportion of patients with locally advanced lung cancer would be suitable for concurrent chemoradiation.
Patients and methods: From 2002 to 2005, all patients with a pathological diagnosis of lung cancer and with locally advanced disease in the Maastricht Cancer Registry, the Netherlands, comorbidity were prospectively assessed. Patients were regarded as noneligible for concurrent chemoradiation if they had one or more important comorbidity or were 75 years or older.
Results: In all, 711 patients were included, 577 with NSCLC and 134 with SCLC. Overall, 166 patients (23.3%) were 75 years or older. Of the 526 patients <75 years, comorbidities were as follows: 278 (52.9%) 0, 188 (35.7%) 1, and 56 (11.4%) 2 or more. In all, 408/686 (59%) of the whole patient group were considered as ineligible for concurrent chemoradiation.
Conclusions: More than half of patients with stage III lung cancer were theoretically not eligible for concurrent chemoradiation. Less toxic alternatives are needed for these patients.
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