• Choice of second-line systemic therapy in stage IV small cell lung cancer (SCLC) - A decision-making analysis amongst European lung cancer experts

      Fruh, M.; Panje, C. M.; Reck, M.; Blackhall, Fiona H; Califano, Raffaele; Cappuzzo, F.; Besse, B.; Novello, S.; Garrido, P.; Felip, E.; et al. (2020)
      OBJECTIVES: Stage IV small cell lung cancer (SCLC) is associated with short survival and progression after first-line systemic therapy frequently occurs within months. Although topotecan is approved for second-line treatment, its efficacy is limited, and treatment heterogeneity exists. MATERIAL AND METHODS: The decision-making patterns for second line treatment of 13 European medical oncologists with expertise in SCLC were analyzed. RESULTS: The two criteria most relevant to decision-making were the performance status and the interval of recurrence since first-line treatment. With an interval of less than 3 months since the end of first-line chemotherapy, 62 % of the experts recommended cyclophosphamide, doxorubicin and vincristine (CAV) for fit patients and 54 % recommended topotecan for unfit patients. For an interval of more than 6 months, a clear consensus for a re-challenge with a platinum doublet was achieved (92 %). However, there was no consensus on the second-line therapy with an interval of 3-6 months since the end of first-line therapy. CONCLUSION: Real world practice may differ from recommendations in general guidelines and cannot always be directly derived from trial results as other factor such as habits, patient's preference, convenience or costs have to be factored in.
    • Neutrophil-lymphocyte ratio and absolute lymphocyte count as prognostic markers in patients treated with curative-intent radiotherapy for non-small cell lung cancer

      Punjabi, A.; Barrett, E.; Cheng, A.; Mulla, A.; Walls, G.; Johnston, D.; McAleese, J.; Moore, K.; Hicks, J.; Blyth, K.; et al. (2021)
      Aims: The neutrophil-lymphocyte ratio (NLR) and the absolute lymphocyte count (ALC) have been proposed as prognostic markers in non-small cell lung cancer (NSCLC). The objective of this study was to examine the association of NLR/ALC before and after curative-intent radiotherapy for NSCLC on disease recurrence and overall survival. Materials and methods: A retrospective study of consecutive patients who underwent curative-intent radiotherapy for NSCLC across nine sites in the UK from 1 October 2014 to 1 October 2016. A multivariate analysis was carried out to assess the ability of pre-treatment NLR/ALC, post-treatment NLR/ALC and change in NLR/ALC, adjusted for confounding factors using the Cox proportional hazards model, to predict disease recurrence and overall survival within 2 years of treatment. Results: In total, 425 patients were identified with complete blood parameter values. None of the NLR/ALC parameters were independent predictors of disease recurrence. Higher pre-NLR, post-NLR and change in NLR plus lower post-ALC were all independent predictors of worse survival. Receiver operator curve analysis found a pre-NLR > 2.5 (odds ratio 1.71, 95% confidence interval 1.06-2.79, P < 0.05), a post-NLR > 5.5 (odds ratio 2.36, 95% confidence interval 1.49-3.76, P < 0.001), a change in NLR >3.6 (odds ratio 2.41, 95% confidence interval 1.5-3.91, P < 0.001) and a post-ALC < 0.8 (odds ratio 2.86, 95% confidence interval 1.76-4.69, P < 0.001) optimally predicted poor overall survival on both univariate and multivariate analysis when adjusted for confounding factors. Median overall survival for the high-versus low-risk groups were: pre-NLR 770 versus 1009 days (P = 0.34), post-NLR 596 versus 1287 days (P ≤ 0.001), change in NLR 553 versus 1214 days (P ≤ 0.001) and post-ALC 594 versus 1287 days (P ≤ 0.001). Conclusion: NLR and ALC, surrogate markers for systemic inflammation, have prognostic value in NSCLC patients treated with curative-intent radiotherapy. These simple and readily available parameters may have a future role in risk stratification post-treatment to inform the intensity of surveillance protocols.
    • Predicting the risk of disease recurrence and death following curative-intent radiotherapy for non-small cell lung cancer: the development and validation of two scoring systems from a large multicentre UK cohort

      Evison, M.; Barrett, E.; Cheng, A.; Mulla, A.; Walls, G.; Johnston, D.; McAleese, J.; Moore, K.; Hicks, J.; Blyth, K.; et al. (2020)
      Aims: There is a paucity of evidence on which to produce recommendations on neither the clinical nor the imaging follow-up of lung cancer patients after curative-intent radiotherapy. In the 2019 National Institute for Health and Care Excellence lung cancer guidelines, further research into risk-stratification models to inform follow-up protocols was recommended. Materials and methods: A retrospective study of consecutive patients undergoing curative-intent radiotherapy for non-small cell lung cancer from 1 October 2014 to 1 October 2016 across nine UK trusts was carried out. Twenty-two demographic, clinical and treatment-related variables were collected and multivariable logistic regression was used to develop and validate two risk-stratification models to determine the risk of disease recurrence and death. Results: In total, 898 patients were included in the study. The mean age was 72 years, 63% (562/898) had a good performance status (0-1) and 43% (388/898), 15% (134/898) and 42% (376/898) were clinical stage I, II and III, respectively. Thirty-six per cent (322/898) suffered disease recurrence and 41% (369/898) died in the first 2 years after radiotherapy. The ASSENT score (age, performance status, smoking status, staging endobronchial ultrasound, N-stage, T-stage) was developed, which stratifies the risk for disease recurrence within 2 years, with an area under the receiver operating characteristic curve (AUROC) for the total score of 0.712 (0.671-0.753) and 0.72 (0.65-0.789) in the derivation and validation sets, respectively. The STEPS score (sex, performance status, staging endobronchial ultrasound, T-stage, N-stage) was developed, which stratifies the risk of death within 2 years, with an AUROC for the total score of 0.625 (0.581-0.669) and 0.607 (0.53-0.684) in the derivation and validation sets, respectively. Conclusions: These validated risk-stratification models could be used to inform follow-up protocols after curative-intent radiotherapy for lung cancer. The modest performance highlights the need for more advanced risk prediction tools.
    • Real-world outcomes with pembrolizumab in patients with treatment-naive advanced/metastatic NSCLC in the UK: multicentre retrospective observational study

      Tokaca, N.; Gomes, Fabio; Lau, S.; Jackson, A.; Gradwell, M.; Gyi, M.; Reinius, M.; Valentine, E.; Winn, E.; Bhosle, J.; et al. (2019)
      Introduction: Anti-PD1 inhibitor pembrolizumab became standard of care therapy for previously untreated advanced/metastatic NSCLC with PD-L1 ≥50% following publication of results from KEYNOTE-001 and KEYNOTE-024 trials, having demonstrated improved overall survival and tolerability over chemotherapy. We evaluated the realworld efficacy and tolerability of first-line pembrolizumab in UK patients. Methods: Multicentre retrospective observational study. Primary endpoint: progression-free survival (PFS). Key secondary endpoints: time to PD-L1 report, overall survival (OS), objective response rate (ORR), prognostic factors associated with PFS and OS, and treatmentrelated toxicities. Results: 219 patients treated with first-line pembrolizumab between 07/2016 and 01/2018 at 27 centres were included (Table 1). Median time from diagnosis of advanced disease to PDL1 report was 18 days. Median time from PD-L1 report to start of pembrolizumab treatment was 23 days. After median follow-up of 5.7 months, there were 90 events of progression or death. ORR was 56.6% (KN-024: 44.8%) with disease-control rate of 76.4%. Median PFS was 8.2 months (KN-024: 10.3mo). 20 patients continued pembrolizumab beyond first documented progression, with median time to further PD of 2.8 months. Median OS was not reached (KN- 024: NR; KN-001: 35mo). 6-month and 1-year OS rates were 73.8% (KN-024: 80.2%) and 68.2% (KN-024: 70.3%), respectively. In the multivariate analysis, poor performance status and presence of a confirmed mutation or unknown mutational status were associated with increased risk of death (p=0.024 and p=0.044). 22.8% patients experienced grade ≥3 treatment-related toxicity (KN-024; 26.6%). 38% experienced any-grade immune-related toxicities (KN-024: 29.2%), the most common being hypothyroidism (7.3%), rash (5.9%) and hyperthyroidism (3.7%). 77 patients (35.2%) required a dose delay and 58 (26.5%) required immunosuppressant therapy.Conclusion: Real-world efficacy and safety of first-line pembrolizumab are comparable to published trial data. Prolonged times to PD-L1 report and start of pembrolizumab treatment likely reflect complex access routes prior to UK NICE approval.
    • Treatment of brain metastases in small cell lung cancer: Decision-making amongst a multidisciplinary panel of European experts

      Putora, P. M.; Fischer, G. F.; Fruh, M.; Califano, Raffaele; Faivre-Finn, Corinne; Van Houtte, P.; McDonald, F.; Nestle, U.; Dziadziuszko, R.; Le Pechoux, C.; et al. (2020)
      Background: Brain metastases (BM) are common in patients with small cell lung cancer (SCLC). In recent years, the role of whole brain radiotherapy (WBRT) for brain metastases in lung cancer is being reevaluated, especially in the context of new systemic treatments available for SCLC. With this analysis, we investigate decision-making in SCLC patients with BM among European experts in medical oncology and radiation oncology. Methods: We analyzed decision-making from 13 medical oncologists (selected by IASLC) and 13 radiation oncologists (selected by ESTRO) specialized in SCLC. Management strategies of individual experts were converted into decision trees and analyzed for consensus. Results and conclusion: In asymptomatic patients, chemotherapy alone is the most commonly recommended first line treatment. In asymptomatic patients with limited volume of brain metastases, a higher preference for chemotherapy without WBRT among medical oncologists compared to radiation oncologists was observed. For symptomatic patients, WBRT followed by chemotherapy was recommended most commonly. For limited extent of BM in symptomatic patients, some experts chose stereotactic radiotherapy as an alternative to WBRT. Significant variation in clinical decision-making was observed among European SCLC experts for the first line treatment of patients with SCLC and BM.