A randomised phase II study of extended pleurectomy/decortication (e-PD) preceded or followed by chemotherapy in patients (pts) with early-stage pleural mesothelioma (PM): EORTC 1205.

BACKGROUND: The role of surgery in pleural mesothelioma remains controversial. It may be appropriate in highly selected patients as part of a multimodality treatment including chemotherapy. Recent years have seen a shift from extrapleural pleuropneumonectomy toward extended pleurectomy/decortication. The most optimal sequence of surgery and chemotherapy remains unknown. METHODS: EORTC-1205-LCG was a multi-centric, non-comparative phase 2 trial, 1:1 randomising between immediate (arm A) and deferred surgery (arm B), followed or preceded by chemotherapy. Eligible patients (ECOG 0-1) had treatment-naïve, borderline resectable T1-3 N0-1 M0 mesothelioma of any histology. Primary outcome was rate of success at 20 weeks, a composite endpoint containing (1) successfully completing both treatments within 20 weeks; (2) being alive with no signs of progressive disease; and (3) no residual grade 3-4 toxicity. Secondary endpoints were toxicity, OS, PFS, and process indicators of surgical quality. FINDINGS: 69 patients were included in this trial. 56 patients (81%) completed 3 cycles of chemotherapy and 58 patients (84%) underwent surgery. Of the 64 patients in the primary analysis, 21/30 patients in arm A (70.0%; 80% CI: 56.8-81.0) and 17/34 patients (50.0%; 80% CI: 37.8-62.2) in arm B reached the statistical endpoint for rate of success. Median progression-free survival and overall survival were 10.8 [95% CI 8.5-17.2] and 27.1 months [95% CI 22.6-64.3] in arm A, and 8.0 [95% CI 7.2-21.9] and 33.8 months [95% CI 23.8-44.6] in arm B. Macroscopic complete resection was obtained in 82.8% of patients. 30- and 90-day mortality were both 1.7%. No new safety signals were found, but treatment-related morbidity was high. INTERPRETATION: EORTC 1205 did not succeed in selecting a preferred sequence of pre- or postoperative chemotherapy. Either procedure is feasible with a low mortality, albeit consistent morbidity. A shared informed decision between surgeon and patient remains essential.

Dendritic cells loaded with allogeneic tumour cell lysate plus best supportive care versus best supportive care alone in patients with pleural mesothelioma as maintenance therapy after chemotherapy (DENIM): a multicentre, open-label, randomised, phase 2/3 study.

BACKGROUND: Dendritic cell immunotherapy has proven to be safe and induces an immune response in humans. We aimed to establish the efficacy of dendritic cells loaded with allogeneic tumour cell lysate (MesoPher, Amphera BV, 's-Hertogenbosch, Netherlands) as maintenance therapy in patients with pleural mesothelioma. METHODS: In this open-label, randomised, phase 2/3 study, patients with histologically confirmed unresectable pleural mesothelioma, aged 18 years or older, with an Eastern Cooperative Oncology Group performance status score of 0-1, and non-progressing disease after four to six cycles of standard chemotherapy (with pemetrexed 500 mg/m2 plus platinum [cisplatin 75 mg/m2 or carboplatin area under the curve of 5]) were recruited from four centres in Belgium, France, and The Netherlands. Participants were randomly assigned (1:1), using block randomisation (block size of 4), stratified by centre and histology (epithelioid vs other), to MesoPher treatment plus best supportive care or best supportive care alone. Patients received up to a maximum of five MesoPher infusions, with treatment administered on days 1, 15, and 29, and weeks 18 and 30. At each timepoint, participants received an injection of 25 × 106 dendritic cells (two-thirds of the dendritic cells were administered intravenously and a third were injected intradermally). Best supportive care was per local institutional standards. The primary endpoint was overall survival, assessed in all participants randomly assigned to treatment (full analysis set) and safety assessed in all randomly assigned participants, and who underwent leukapheresis if they were in the MesoPher group. This study is registered with ClinicalTrials.gov, NCT03610360, and is closed for accrual. FINDINGS: Between June 21, 2018, and June 10, 2021, 176 patients were screened and randomly assigned to the MesoPher group (n=88) or best supportive care alone group (n=88). One participant in the MesoPher group did not undergo leukapheresis. Mean age was 68 years (SD 8), 149 (85%) of 176 were male, 27 (15%) were female, 173 (98%) were White, two were Asian (1%), and one (1%) was other race. As of data cutoff (June 24, 2023), after a median follow up of 15·1 months (IQR 9·5-22·4), median overall survival was 16·8 months (95% CI 12·4-20·3; 61 [69%] of 88 died) in the MesoPher group and 18·3 months (14·3-21·9; 59 [67%] of 88 died) in the best supportive care group (hazard ratio 1·10 [95% CI 0·77-1·57]; log-rank p=0·62). The most common grade 3-4 treatment-emergent adverse events were chest pain (three [3%] of 87 in the MesoPher group vs two [2%] of 88 in the best supportive care group), dyspnoea (none vs two [2%]), anaemia (two [2%] vs none), nausea (none vs two [2%]), and pneumonia (none vs two [2%]). No deaths due to treatment-emergent adverse events were recorded. Treatment-related adverse events consisted of infusion-related reactions (fever, chills, and fatigue), which occurred in 64 (74%) of 87 patients in the MesoPher group, and injection-site reactions (itch, erythema, and induration), which occurred in 73 (84%) patients, and all were grade 1-2 in severity. No deaths were determined to be treatment related. INTERPRETATION: MesoPher did not show improvement in overall survival in patients with pleural mesothelioma. Immune checkpoint therapy is now standard of care in pleural mesothelioma. Further randomised studies are needed of combinations of MesoPher and immune checkpoint therapy, which might increase efficacy without adding major toxicities. FUNDING: Amphera BV and EU HORIZON.

Long-Term Outcomes After Concurrent Once- or Twice-Daily Chemoradiation in Limited-Stage Small Cell Lung Cancer: A Brief Report From the CONVERT Trial.

PURPOSE: CONVERT was a phase 3 international randomized clinical trial comparing once-daily (OD) and twice-daily (BD) radiation therapy (RT). This updated analysis describes the 6.5-year outcomes of these regimens delivered with conformal techniques. METHODS AND MATERIALS: CONVERT (NCT00433563) randomized patients 1:1 between OD RT (66 Gy/33 fractions/6.5 weeks) and BD RT (45 Gy/30 fractions/3 weeks), both delivered with concurrent cisplatin/etoposide. Three-dimensional conformal RT was mandatory, intensity-modulated RT was permitted, and elective nodal irradiation was not allowed. Prophylactic cranial irradiation was delivered at the discretion of treating clinicians. RT treatment planning was subject to central quality assurance. RESULTS: Five hundred forty-seven patients were recruited at 73 centers. The median follow-up for the surviving cohort (n = 164) was 81.2 months. The median survival for the OD and BD arms were 25.4 months (95% CI, 21.1-30.9) and 30.0 months (95% CI, 25.3-36.5; hazard ratio, 1.13; 95% CI, 0.92-1.38; P = .247). Performance status and tumor volume were associated with survival on multivariate analysis. No treatment-related deaths occurred subsequent to the initial analysis performed in 2017. Regarding late toxicity, 7 patients in the OD arm developed grade 3 esophagitis, 4 of which went on to develop stricture or fistulation, compared with no patients in the BD arm. Grade 3 pulmonary fibrosis occurred in 2 and 3 patients in the OD and BD arms, respectively. CONCLUSIONS: As the CONVERT trial did not demonstrate the superiority of OD RT and this regimen had a slightly worse toxicity profile after 80 months of follow-up, 45 Gy BD should remain the standard of care in limited stage small cell lung cancer.

Determining the clinical utility of a breath test for screening an asbestos-exposed population for pleural mesothelioma: baseline results.

Pleural mesothelioma (PM) is an aggressive cancer of the serosal lining of the thoracic cavity, predominantly caused by asbestos exposure. Due to nonspecific symptoms, PM is characterized by an advanced-stage diagnosis, resulting in a dismal prognosis. However, early diagnosis improves patient outcome. Currently, no diagnostic biomarkers or screening tools are available. Therefore, exhaled breath was explored as this can easily be obtained and contains volatile organic compounds, which are considered biomarkers for multiple (patho)physiological processes. A breath test, which differentiates asbestos-exposed (AEx) individuals from PM patients with 87% accuracy, was developed. However, before being implemented as a screening tool, the clinical utility of the test must be determined. Occupational AEx individuals underwent annual breath tests using multicapillary column/ion mobility spectrometry. A baseline breath test was taken and their individual risk of PM was estimated. PM patients were included as controls. In total, 112 AEx individuals and six PM patients were included in the first of four screening rounds. All six PM patients were correctly classified as having mesothelioma (100% sensitivity) and out of 112 AEx individuals 78 were classified by the breath-based model as PM patients (30% specificity). Given the large false positive outcome, the breath test will be repeated annually for three more consecutive years to adhere to the 'test, re-test' principle and improve the false positivity rate. A low-dose computed tomography scan in those with two consecutive positive tests will correlate test positives with radiological findings and the possible growth of a pleural tumor. Finally, the evaluation of the clinical value of a breath-based prediction model may lead to the initiation of a screening program for early detection of PM in Aex individuals, which is currently lacking. This clinical study received approval from the Antwerp University Hospital Ethics Committee (B300201837007).

Health Outcomes with Curative and Palliative Therapies in Real World: Role of the Quality of Life Summary Score in Thoracic Oncology Patients.

BACKGROUND: For patients receiving therapy with curative or palliative intent for a thoracic malignancy, prediction of quality of life (QOL), once therapy starts, remains challenging. The role of health assessments by the patient instead of the doctor herein remains ill-defined. AIMS: To assess the evolution of QOL in patients with thoracic malignancies treated with curative and palliative intent, respectively. To identify factors that determine QOL one year after the start of cancer therapy. To identify factors that affect survival. METHODS: We prospectively included consecutive patients with a thoracic malignancy who were starting anti-cancer therapy and measured QOL with QLQ-C30 before the start of therapy, and thereafter at regular intervals for up to 12 months. A multivariate regression analysis of the global health score (GHS) and QOL summary scores (QSS) one year after the start of therapy was conducted. A proportional hazards Cox regression was conducted to investigate the effects of case-mix variables on survival. RESULTS: Of 587 new patients, 375 started different forms of therapy. Most had non-small cell lung cancer (n = 298), 35 had small cell lung cancer, and 42 had other thoracic malignancies or were diagnosed on imaging alone. There were 203 who went for a curative intent and 172 for a palliative intent strategy. The WHO score of 0-1 was more prevalent in the former group (p = 0.02), and comorbidities were equally distributed. At baseline, all QOL indices were better in the curative group (p < 0.05). The curative group was characterized by a significant worsening of GHS and QSS (p < 0.05). The palliative group was characterized by an improvement in GHS and emotional health (p < 0.05), while other dimensions of functioning remained stable. GHS at 12 months was estimated in a multivariate linear regression model (R2 = 0.23-p < 0.001) based on baseline GHS, QSS, and comorbidity burden. QSS at 12 months was estimated (R2 = 0.31-p < 0.001) by baseline QSS and therapeutic intent strategy (curative vs. palliative). The prognostic factors for overall survival were the type of therapy (curative vs. palliative intent, p < 0.001) and occurrence of early toxicity-related hospitalization (grade ≥ 3, p = 0.001). CONCLUSION: Patients with thoracic malignancies treated with curative intent experience a worsening of their QOL in the first year, whereas those receiving palliative anti-cancer therapy do not. QOL one year after the start of therapy depends on the baseline health scores as determined by the patient, comorbidity burden, and therapeutic strategy. Survival depends on therapeutic strategy and early hospitalization due to toxicity.

Preclinical evaluation of CDK4 phosphorylation predicts high sensitivity of pleural mesotheliomas to CDK4/6 inhibition.

Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited therapeutic options. We evaluated the impact of CDK4/6 inhibition by palbociclib in 28 MPM cell lines including 19 patient-derived ones, using various approaches including RNA-sequencing. Palbociclib strongly and durably inhibited the proliferation of 23 cell lines, indicating a unique sensitivity of MPM to CDK4/6 inhibition. When observed, insensitivity to palbociclib was mostly explained by the lack of active T172-phosphorylated CDK4. This was associated with high p16INK4A (CDKN2A) levels that accompany RB1 defects or inactivation, or (unexpectedly) CCNE1 overexpression in the presence of wild-type RB1. Prolonged palbociclib treatment irreversibly inhibited proliferation despite re-induction of cell cycle genes upon drug washout. A senescence-associated secretory phenotype including various potentially immunogenic components was irreversibly induced. Phosphorylated CDK4 was detected in 80% of 47 MPMs indicating their sensitivity to CDK4/6 inhibitors. Its absence in some highly proliferative MPMs was linked to very high p16 (CDKN2A) expression, which was also observed in public datasets in tumours from short-survival patients. Our study supports the evaluation of CDK4/6 inhibitors for MPM treatment, in monotherapy or combination therapy.

The need for a comprehensive and integrated approach to lung cancer policy in Europe.

Lung cancer is the leading cause of cancer-related deaths in Europe. Europe's Beating Cancer Plan calls for a comprehensive approach to the disease in general but not specifically to lung cancer. Such a comprehensive approach, integrating efforts to strengthen anti-tobacco policies, early detection and underlying models of care, is sorely needed for lung cancer - particularly considering disruptions to care during the COVID-19 pandemic. In a recently published think piece, a multidisciplinary group of experts proposed four key policy priority areas. First, to reduce stigma and improve awareness of potential symptoms, there is a need to foster a better understanding of lung cancer - among the public and healthcare professionals. Second, opportunities for early detection should be enhanced, and the implementation of targeted screening through low-dose computed tomography should be encouraged as a complement to smoking cessation services. This complementarity should be recognised and built into joint policy proposals, with development and better integration of screening and smoking cessation programmes on the ground. Third, the socioeconomic inequalities underpinning disparities in outcomes in people with lung cancer must be addressed, with targeted approaches to overcome barriers to access Finally, the overall quality of lung cancer care must be improved, making multidisciplinary care available to all and ensuring survivorship is given due attention.

How Can the EU Beating Cancer Plan Help in Tackling Lung Cancer, Colorectal Cancer, Breast Cancer and Melanoma?

Cancer is the second leading cause of mortality in EU countries, and the needs to tackle cancer are obvious. New scientific understanding, techniques and methodologies are opening up horizons for significant improvements in diagnosis and care. However, take-up is uneven, research needs and potential outstrip currently available resources, manifestly beneficial practices-such as population-level screening for lung cancer-are still not generalised, and the quality of life of patients and survivors is only beginning to be given attention it merits. This paper, mainly based on a series of multistakeholder expert workshops organised by the European Alliance for Personalised Medicine (EAPM), looks at some of those specifics in the interest of planning a way forward. Part of this exercise also involves taking account of the specific nature of Europe and its constituent countries, where the complexities of planning a way forward are redoubled by the wide variations in national and regional approaches to cancer, local epidemiology and the wide disparities in health systems. Despite all the differences between cancers and national and regional resources and approaches to cancer care, there is a common objective in pursuing broader and more equal access to the best available care for all European citizens.

New Implications of Patients' Sex in Today's Lung Cancer Management.

This paper describes where and how sex matters in today's management of lung cancer. We consecutively describe the differences between males and females in lung cancer demographics; sex-based differences in the immune system (including the poorer outcomes in women who are treated with immunotherapy but no chemotherapy); the presence of oncogenic drivers and the response to targeted therapies according to sex; the greater benefit women derive from lung cancer screening and why they get screened less; and finally, the barriers to smoking cessation that women experience. We conclude that sex is an important but often overlooked factor in modern-day thoracic oncology practice.

External Validation of a Breath-Based Prediction Model for Malignant Pleural Mesothelioma.

During the past decade, volatile organic compounds (VOCs) in exhaled breath have emerged as promising biomarkers for malignant pleural mesothelioma (MPM). However, as these biomarkers lack external validation, no breath test for MPM has been implemented in clinical practice. To address this issue, we performed the first external validation of a VOC-based prediction model for MPM. The external validation cohort was prospectively recruited, consisting of 47 MPM patients and 76 asbestos-exposed (AEx) controls. The predictive performance of the previously developed model was assessed by determining the degree of agreement between the predicted and actual outcome of the participants (patient/control). Additionally, to optimise the performance, the model was updated by refitting it to the validation cohort. External validation revealed a poor performance of the original model as the accuracy was estimated at only 41%, indicating poor generalisability. However, subsequent updating of the model improved the differentiation between MPM patients and AEx controls significantly (73% accuracy, 92% sensitivity, and 92% negative predictive value), substantiating the validity of the original predictors. This updated model will be more generalisable to the target population and exhibits key characteristics of a potential screening test for MPM, which could significantly impact MPM management.

Lung Cancer Screening: New Perspective and Challenges in Europe.

Randomized-controlled trials have shown clear evidence that lung cancer screening with low-dose CT in a high-risk population of current or former smokers can significantly reduce lung-cancer-specific mortality by an inversion of stage distribution at diagnosis. This paper will review areas in which there is good or emerging evidence and areas which still require investment, research or represent implementation challenges. The implementation of population-based lung cancer screening in Europe is variable and fragmented. A number of European countries seem be on the verge of implementing lung cancer screening, mainly through the implementation of studies or trials. The cost and capacity of CT scanners and radiologists are considered to be the main hurdles for future implementation. Actions by the European Commission, related to its published Europe's Beating Cancer Plan and the proposal to update recommendations on cancer screening, could be an incentive to help speed up its implementation.

Headspace Volatile Organic Compound Profiling of Pleural Mesothelioma and Lung Cancer Cell Lines as Translational Bridge for Breath Research.

Introduction: Malignant pleural mesothelioma (MPM) is a lethal cancer for which early-stage diagnosis remains a major challenge. Volatile organic compounds (VOCs) in breath proved to be potential biomarkers for MPM diagnosis, but translational studies are needed to elucidate which VOCs originate from the tumor itself and thus are specifically related to MPM cell metabolism. Methods: An in vitro model was set-up to characterize the headspace VOC profiles of six MPM and two lung cancer cell lines using thermal desorption-gas chromatography-mass spectrometry. A comparative analysis was carried out to identify VOCs that could discriminate between MPM and lung cancer, as well as between the histological subtypes within MPM (epithelioid, sarcomatoid and biphasic). Results: VOC profiles were identified capable of distinguishing MPM (subtypes) and lung cancer cells with high accuracy. Alkanes, aldehydes, ketones and alcohols represented many of the discriminating VOCs. Discrepancies with clinical findings were observed, supporting the need for studies examining breath and tumor cells of the same patients and studying metabolization and kinetics of in vitro discovered VOCs in a clinical setting. Conclusion: While the relationship between in vitro and in vivo VOCs is yet to be established, both could complement each other in generating a clinically useful breath model for MPM.

Anetumab ravtansine versus vinorelbine in patients with relapsed, mesothelin-positive malignant pleural mesothelioma (ARCS-M): a randomised, open-label phase 2 trial.

BACKGROUND: Few treatment options exist for second-line treatment of malignant pleural mesothelioma. We aimed to assess the antibody-drug conjugate anetumab ravtansine versus vinorelbine in patients with unresectable locally advanced or metastatic disease overexpressing mesothelin who had progressed on first-line platinum-pemetrexed chemotherapy with or without bevacizumab. METHODS: In this phase 2, randomised, open-label study, done at 76 hospitals in 14 countries, we enrolled adults (aged ≥18 years) with unresectable locally advanced or metastatic malignant pleural mesothelioma, an Eastern Cooperative Oncology Group performance status of 0-1, and who had progressed on first-line platinum-pemetrexed chemotherapy with or without bevacizumab. Participants were prospectively screened for mesothelin overexpression (defined as 2+ or 3+ mesothelin membrane staining intensity on at least 30% of viable tumour cells by immunohistochemistry) and were randomly assigned (2:1), using an interactive voice and web response system provided by the sponsor, to receive intravenous anetumab ravtansine (6·5 mg/kg on day 1 of each 21-day cycle) or intravenous vinorelbine (30 mg/m2 once every week) until progression, toxicity, or death. The primary endpoint was progression-free survival according to blinded central radiology review, assessed in the intention-to-treat population, with safety assessed in all participants who received any study treatment. This study is registered with ClinicalTrials.gov, NCT02610140, and is now completed. FINDINGS: Between Dec 3, 2015, and May 31, 2017, 589 patients were enrolled and 248 mesothelin-overexpressing patients were randomly allocated to the two treatment groups (166 patients were randomly assigned to receive anetumab ravtansine and 82 patients were randomly assigned to receive vinorelbine). 105 (63%) of 166 patients treated with anetumab ravtansine (median follow-up 4·0 months [IQR 1·4-5·5]) versus 43 (52%) of 82 patients treated with vinorelbine (3·9 months [1·4-5·4]) had disease progression or died (median progression-free survival 4·3 months [95% CI 4·1-5·2] vs 4·5 months [4·1-5·8]; hazard ratio 1·22 [0·85-1·74]; log-rank p=0·86). The most common grade 3 or worse adverse events were neutropenia (one [1%] of 163 patients for anetumab ravtansine vs 28 [39%] of 72 patients for vinorelbine), pneumonia (seven [4%] vs five [7%]), neutrophil count decrease (two [1%] vs 12 [17%]), and dyspnoea (nine [6%] vs three [4%]). Serious drug-related treatment-emergent adverse events occurred in 12 (7%) patients treated with anetumab ravtansine and 11 (15%) patients treated with vinorelbine. Ten (6%) treatment-emergent deaths occurred with anetumab ravtansine: pneumonia (three [2%]), dyspnoea (two [1%]), sepsis (two [1%]), atrial fibrillation (one [1%]), physical deterioration (one [1%]), hepatic failure (one [1%]), mesothelioma (one [1%]), and renal failure (one [1%]; one patient had 3 events). One (1%) treatment-emergent death occurred in the vinorelbine group (pneumonia). INTERPRETATION: Anetumab ravtansine showed a manageable safety profile and was not superior to vinorelbine. Further studies are needed to define active treatments in relapsed mesothelin-expressing malignant pleural mesothelioma. FUNDING: Bayer Healthcare Pharmaceuticals.

Recent Advances of Immune Checkpoint Inhibition and Potential for (Combined) TIGIT Blockade as a New Strategy for Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) is a fatal cancer type that affects the membranes lining the lungs, and is causally associated with asbestos exposure. Until recently, the first-line treatment consisted of a combination of chemotherapeutics that only had a limited impact on survival, and had not been improved in decades. With the recent approval of combined immune checkpoint inhibition for MPM, promising new immunotherapeutic strategies are now emerging for this disease. In this review, we describe the current preclinical and clinical evidence of various immune checkpoint inhibitors in MPM. We will consider the advantages of combined immune checkpoint blockade in comparison with single agent checkpoint inhibitor drugs. Furthermore, recent evidence suggests a role for T cell immunoglobulin and ITIM domain (TIGIT), an inhibitory immunoreceptor, as a novel target for immunotherapy. As this novel immune checkpoint remains largely unexplored in mesothelioma, we will discuss the potential of TIGIT blockade as an alternative therapeutic approach for MPM. This review will emphasize the necessity for new and improved treatments for MPM, while highlighting the recent advances and future perspectives of combined immune checkpoint blockade, particularly aimed at PD-L1 and TIGIT.

A Cross-Sectional Study on the Acceptability of Implementing a Lung Cancer Screening Program in Belgium.

Lung cancer is the most common and deadliest cancer in the world, and its incidence is expected to grow. Nonetheless, this growth can be contained through smoking cessation programs and effective lung cancer screening programs. In 2018, Belgium had the seventh highest incidence of lung cancer in the world, with lung cancer incidence accounting for 11.8% of all cancers diagnosed and 23.8% of all cancer-related deaths that same year. The aims of this study were to determine the overall acceptability of a lung cancer screening program in the Flemish population and to determine the main factors that would influence the overall acceptability of such a program. A questionnaire-based cross-sectional study was performed in the Flemish population and distributed online and on paper. The results are presented with the variables of interest and the main outcome, i.e., the acceptability of participating in such a program if implemented. Odds ratios were used to compare acceptability between subgroups. A multivariate regression model was used to determine the key factors that would have the largest impact on the level of acceptability and, thus, on the possible efficiency of such a program. This study estimated that acceptability of participating in a lung cancer screening program was 92%. Irrespective of the smoking status, levels of acceptability were higher than 89%. The key factors which could significantly influence the acceptability of a lung cancer screening program were individuals with low education, low protective factor knowledge and total knowledge, and lung cancer screening reimbursement, which were significantly associated with acceptability (0.01, 0.001, 0.01, and 0.05 respectively). Low protective factor knowledge decreased the log odds of acceptability 3.08-fold. In conclusion, the acceptability of implementing a lung cancer screening program in Flanders seems to be extremely high and would be well received by all. When implementing such a program, policymakers should aim for it to be reimbursed, campaigns should be gender-specific, focused on those with lower educational and socioeconomic status, and there should be investment in increasing total knowledge about lung cancer and knowledge about protective factors.

Clinical utility of diagnostic biomarkers in malignant pleural mesothelioma: a systematic review and meta-analysis.

Malignant pleural mesothelioma (MPM) is characterised by late-stage diagnosis and poor prognosis. Currently, no screening tool is advocated and diagnosis is based on invasive techniques, which are not well tolerated. Non-invasive diagnostic biomarkers have shown potential and could have a huge clinical benefit. However, despite extensive research, there is no consensus yet on their clinical use, with many articles reporting contradicting results, limiting their clinical implementation. The aim of this systematic review is therefore to explore the different semi- and non-invasive diagnostic markers in several human matrices and identify those that might clinically be relevant. A total of 100 articles were selected through Web of Science and PubMed, with 56 articles included in the quantitative analysis. Although many studies have reported on the diagnostic accuracy of MPM biomarkers such as serum mesothelin and high-mobility group box protein 1 and plasma fibulin-3, none have resulted in a validated test for early detection. Future research should focus on external validation, combinations into biomarker panels, the inclusion of early stage MPM patients and a combination of different biomarker matrices, as well as new markers.

Recent developments in the treatment of small cell lung cancer.

Small cell lung cancer (SCLC) comprises about 15% of all lung cancers. It is an aggressive disease, with early metastasis and a poor prognosis. Until recently, SCLC treatment remained relatively unchanged, with chemotherapy remaining the cornerstone of treatment. In this overview we will highlight the recent advances in the field of staging, surgery, radiotherapy and systemic treatment. Nevertheless, the prognosis remains dismal and there is a pressing need for new treatment options. We describe the progress that has been made in systemic treatment by repurposing existing drugs and the addition of targeted treatment. In recent years, immunotherapy entered the clinic with high expectations of its role in the treatment of SCLC. Unravelling of the genomic sequence revealed new possible targets that may act as biomarkers in future treatment of patients with SCLC. Hopefully, in the near future, we will be able to identify patients who may benefit from targeted therapy or immunotherapy to improve prognoses.