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Objectives: This study aimed to compare the overall survival (OS) of patients with advanced EGFR-mutant NSCLC treated with first-line osimertinib versus earlier-generation EGFR tyrosine kinase inhibitors (TKIs) in a real-world setting. Secondary endpoint included OS in patients with uncommon EGFR mutations. Exploratory aim focused on the impact of TKIs sequencing strategies., Methods: We conducted a retrospective cohort study of patients diagnosed with advanced EGFR-mutant NSCLC who started first-line treatment with either osimertinib or another EGFR TKI (afatinib, erlotinib, or gefitinib) at The Christie (Manchester, UK) from January 2014 to May 2023. Data were extracted from electronic health records, and survival outcomes were analysed using Kaplan-Meier estimates and Cox proportional hazards models., Results: We identified 119 patients treated with first-line osimertinib and 217 with other EGFR TKIs. In the whole population, median age was 69 years (IQR 59.8-77) and 67.3 % of the patients had an ECOG 0-1. With a median follow-up of 73.2 months (95 % CI 66.2-115.7) and 30.6 months (95 % CI 26.0-38.4) in the earlier-generation TKIs and the osimertinib groups, respectively, the median OS was comparable (16.6 vs 16.9 months; HR = 1, p = 0.97). Patients with uncommon EGFR mutations (n = 48; 14.3 %) had poorer survival compared to those with common mutations (HR = 1.664, p = 0.002). Amongst patients who received two treatment lines, those who received osimertinib after another TKI had a shorter OS than those who received osimertinib first-line followed by another line of therapy (HR = 2.062, p = 0.022)., Conclusion: First-line osimertinib showed comparable OS to earlier-generation EGFR TKIs for advanced EGFR-mutant NSCLC. Patients with uncommon EGFR mutations had a poorer survival. Further research is warranted to optimize treatment for patients with uncommon EGFR mutations and to explore the cost-effectiveness of different sequencing approaches., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Igor Gomez-Randulfe reports a relationship with Janssen Pharmaceuticals Inc that includes: consulting or advisory. Raffaele Califano reports a relationship with AstraZeneca Pharmaceuticals LP that includes: consulting or advisory and funding grants. Raffaele Califano reports a relationship with Roche that includes: consulting or advisory and funding grants. Raffaele Califano reports a relationship with The Christie Private Care that includes: equity or stocks. Raffaele Califano reports a relationship with Pfizer Inc that includes: consulting or advisory and funding grants. Raffaele Califano reports a relationship with Clovis Oncology that includes: consulting or advisory and funding grants. Raffaele Califano reports a relationship with Eli Lilly and Company that includes: consulting or advisory and funding grants. Raffaele Califano reports a relationship with MSD that includes: consulting or advisory and funding grants. Raffaele Califano reports a relationship with Bristol Myers Squibb Co that includes: consulting or advisory and funding grants. Raffaele Califano reports a relationship with AbbVie Inc that includes: consulting or advisory and funding grants. Raffaele Califano reports a relationship with Takeda Oncology that includes: consulting or advisory and funding grants. Raffaele Califano reports a relationship with Janssen Pharmaceuticals Inc that includes: consulting or advisory and funding grants. Raffaele Califano reports a relationship with Novartis that includes: consulting or advisory and funding grants. Raffaele Califano reports a relationship with Boehringer Ingelheim Ltd that includes: consulting or advisory. Raffaele Califano reports a relationship with Bayer that includes: consulting or advisory. Yvonne Summers reports a relationship with Roche that includes: consulting or advisory and travel reimbursement. Yvonne Summers reports a relationship with AstraZeneca Pharmaceuticals LP that includes: consulting or advisory. Yvonne Summers reports a relationship with AbbVie Inc that includes: consulting or advisory. Yvonne Summers reports a relationship with Bristol Myers Squibb Co that includes: consulting or advisory. Yvonne Summers reports a relationship with MSD that includes: consulting or advisory. Yvonne Summers reports a relationship with Takeda Oncology that includes: consulting or advisory and travel reimbursement. Yvonne Summers reports a relationship with Eli Lilly and Company that includes: consulting or advisory. Yvonne Summers reports a relationship with Amgen Inc that includes: consulting or advisory. Fiona Blackhall reports a relationship with Amgen Inc that includes: consulting or advisory and speaking and lecture fees. Fiona Blackhall reports a relationship with AstraZeneca Pharmaceuticals LP that includes: consulting or advisory and speaking and lecture fees. Fiona Blackhall reports a relationship with Roche that includes: consulting or advisory. Colin R Lindsay reports a relationship with Amgen Inc that includes: consulting or advisory, non-financial support, and speaking and lecture fees. Colin R Lindsay reports a relationship with Hanson Wade Limited that includes: consulting or advisory. Colin R Lindsay reports a relationship with Revolution Medicines Inc that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)

Objectives: IMbrella A is a Phase III extension study that allowed rollover from Roche/Genentech-sponsored atezolizumab trials, including IMpower133, a Phase I/III trial of first-line atezolizumab or placebo plus carboplatin/etoposide in extensive-stage small cell lung cancer. We report outcomes from an exploratory analysis of IMpower133 with extended time-to-event data for patients who rolled over to IMbrella A., Materials and Methods: IMpower133 patients could roll over to IMbrella A to receive atezolizumab 1200 mg intravenously every three weeks if they continued to receive atezolizumab at IMpower133 closure or were in survival follow-up after atezolizumab discontinuation. Overall survival and safety were assessed; only serious adverse events and AEs of special interest were collected in IMbrella A., Results: Eighteen of 26 eligible patients rolled over to IMbrella A. At clinical cutoff (March 16, 2023), median follow-up in the atezolizumab plus carboplatin/etoposide arm (IMpower133 and IMbrella A) was 59.4 months. The three-, four-, and five-year overall survival (95 % CI) estimates were 16 % (11 %-21 %), 13 % (8 %-18 %), and 12 % (7 %-17 %), respectively. In IMbrella A, serious adverse events occurred in three patients (16.7 %), and one adverse event of special interest was reported (grade two hypothyroidism)., Conclusion: This long-term analysis of patients from IMbrella A previously enrolled in IMpower133 provides the first report of five-year overall survival outcomes in patients with extensive-stage small cell lung cancer treated with first-line cancer immunotherapy and chemotherapy. While limited by small patient numbers and lack of long-term data for the IMpower133 control arm, exploratory overall survival analyses in patients treated with atezolizumab plus carboplatin/etoposide compared favorably with historical data with chemotherapy alone. NCT03148418., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All authors report editorial support funded by the Sponsor. Martin Reck reports receiving consulting fees, honoraria and travel support from Amgen, AstraZeneca, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, GSK, Mirati, Merck, MSD, Lily, Novartis, Pfizer, Sanofi, Roche, and Regeneron; and participation on a data safety monitoring or advisory board for Sanofi and Daiichi Sankyo. Rafal Dziadziuszko reports receiving honoraria from Roche, AstraZeneca, Amgen, Novartis, MSD, Bristol Myers Squibb, Takeda, and Pfizer; and materials from Novartis. Shunichi Sugawara reports receiving grants (to institution) from AstraZeneca, Chugai Pharma, MSD, Bristol Myers Squibb, and Ono Pharmaceutical; and honoraria from AstraZeneca, Chugai Pharma, MSD, Bristol Myers Squibb, and Ono Pharmaceutical. Steven Kao reports receiving grants (to institution) from AstraZeneca; honoraria from AstaZeneca, Pfizer, MSD, Bristol Myers Squibb, Roche, Amgen, Beigene, and Boehringer Ingelheim; and travel support from MSD. Maximilian Hochmair reports receiving honoraria from MSD, Roche, Lilly, AstraZeneca, Takeda, Bristol Myers Squibb, and Amgen. Florian Huemer declares no conflict of interest. Gilberto de Castro, Jr reports receiving consulting fees from Daiichi-Sankyo; honoraria from AstraZeneca, Bristol Myers Squibb, Jannsen, Lilly, MSD, Novartis, Roche, Amgen, and Daiichi-Sankyo; travel support from Roche, Amgen, Daiichi-Sankyo, MSD, AstraZeneca, and Bristol Myers Squibb; and participation on a data safety monitoring or advisory board for GlaxoSmithKline, AstraZeneca, MSD, and Novartis. Libor Havel declares no conflict of interest. Reyes Bernabé Caro reports receiving an investigational grant from Roche; honoraria from Roche, Bristol Myers Squibb, Pfizer, MSD, Amgen, Takeda, and AstraZeneca; and participation in a data safety monitoring or advisory board for Takeda, Roche, Bristol Myers Squibb, and AstraZeneca. György Losonczy and Jong-Seok Lee declare no conflict of interest. Dariusz M. Kowalski reports participation on an advisory board and consultancy for Roche, Boehringer Ingelheim, Novartis, Bristol Myers Squibb, MSD, Sanofi-Aventis, Takeda, Pfizer, and Johnson & Johnson. Zoran Andric declares no conflict of interest. Raffaele Califano reports receiving grants (to institution) from Roche and MSD; consulting fees from Roche, MSD, Bristol Myers Squibb, and AstraZeneca; and honoraria from Roche, MSD, and AstraZeneca; membership in the EORTC lung cancer group and ESMO educational publication working group; and stock or stock options in The Christie Private Care and Supportive Care UK. Andrea Veatch, Gregory Gerstner, and Marta Batus declare no conflicts of interest. Stefanie Morris reports employment with and stock or stock options in Roche. Monika Kaul, Vaikunth Cuchelkar, Huafei Li, Bradford J. Danner, and Barzin Y. Nabet report employment with Roche. Stephen V. Liu reports receiving grants from AbbVie, Alkermes, Elevation Oncology, Ellipses, Genentech, Gilead, Merck, Merus, Nuvalent, RAPT, and Turning Point Therapeutics; and consulting fees from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Catalyst, Daiichi Sankyo, Eisai, Elevation Oncology, Genentech/Roche, Gilead, Guardant Health, Janssen, Jazz Pharmaceuticals, Merck, Merus, Mirati, Novartis, Pfizer, Regeneron, Sanofi, Takeda, and Turning Point Therapeutics; and participation on a data safety monitoring for Candel Therapeutics., (Copyright © 2024. Published by Elsevier B.V.)

Therapeutic options for patients with relapsed SCLC are limited, and the prognosis in this setting remains poor. While clinical outcomes for frontline treatment have modestly improved with the introduction of immunotherapy, treatment in the second-line setting persists almost unchanged. In this review, current treatment options and recent advances in molecular biology are described. Emerging therapeutic options in this setting, and potential strategies to improve clinical outcomes of these patients are also addressed., Competing Interests: Declaration of Competing Interest AA reports research grants from Celgene, BMS, Ipsen, Roche; honoraria for advisory board participation from BMS, MSD, ROCHE, AstraZeneca, Eli-Lilly. LB received research funding from AstraZeneca, Amgen, Jazz Pharmaceuticals; served as an advisor/consultant for Merck Sharp & Dohme Corp., Arrowhead Pharmaceuticals, Chugai Pharma, AstraZeneca, Abbvie, BeiGene, Jazz Pharmaceuticals, Genentech. RC reports honoraria, consulting or advisory role from AstraZeneca, BMS, Roche, MSD, Boehringer Ingelheim, Takeda, Bayer, Sanofi, Pharmamar, Lilly Oncology, Janssen, Amgen and Novartis. LM, BZ and GL declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., (Copyright © 2020. Published by Elsevier B.V.)

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., Competing Interests: Declaration of Competing Interest MF reports advisor fees (paid to institution) from BMS, MSD, AstraZeneca, Boehringer Ingelheim, Roche, Takeda and institutional research grants from BMS and AstraZeneca CP: none MR reports honoraria for lectures and consultancy from Abbvie, Amgen, AstraZenece, BMS, Boehringer-Ingelheim, Lilly, Merck, MSD, Novartis, Pfizer, Roche, Samsung. FB: none RC reports honoraria and consultancy fees from AstraZeneca, Boeringer Ingelheim, Lilly Oncology, Roche, Pfizer, MSD, Bristol Myers Squibb, Takeda and Novartis; institutional grands for conduct of clinical trials or contracted research from Roche, AstraZeneca, Pfizer, Clovis, Lilly Oncology, MSD, BMS, Abbvie, Takeda and Novartis; stock ownership of The Christie Private Care. FC reports consultation and participation in advisory boards and lectures for Roche, AstraZeneca, Pfizer, BMS, Takeda, Lilly, MSD, Bayer. BB reports institutional grants from Abbvie, Amgen, AstraZeneca, BeiGene, Blueprint Medicines, BMS, Boehringer Ingelheim, Celgene, Cristal Therapeutics, Daiichi-Sankyo, Eli Lilly, GSK, Ignyta, IPSEN, Inivata, Janssen, Merck KGaA, MSD, Nektar, Onxeo, OSE immunotherapeutics, Pfizer, Pharma Mar, Roche-Genentech, Sanofi, Servier, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma, Tolero Pharmaceuticals. PG reports speaker and/or advisory fees for Roche, AstraZeneca, BMS, Guardant Health, MSD, Pfizer, Janssen, Boehringer Ingelheim, Novartis, Gilead, Rovi, Abbvie, Lilly, Takeda, Sysmex, Blueprint Medicines, and Bayer. EF reports personal fees from Abbvie, AstraZeneca, Blue Print Medicines, Boehringer Ingelheim, BMS, Eli Lilly, Guardant Health, Jannsen, Medscape, Merck KGaA, Merck Sharp & Dohme, Novartis, Pfizer, Prime Oncology, Roche, Samsung, Takeda, Touchtime, GSK, Bayer; grants from Grant for Oncology Innovation (GOI), Fundacion Merck Salud, outside the submitted work; and Grifols: Independent Member of the Board. MOB reports advisory board work for MSD, BMS, BI and Pierre Fabre. LP-A is a board member of Genomica and Altum Sequencing, and has received honoraria from Roche/Genentech, Eli Lilly, Pfizer, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp and Dohme, AstraZeneca, Merck Serono, Pharmamar, Novartis, Celgene, Sysmex, Amgen, Blueprint and Incyte; and travel, accommodations or expenses from Roche, AstraZeneca, AstraZeneca Spain, Merck Sharp and Dohme, Bristol-Myers Squibb, Eli Lilly and Pfizer. FdM reports fees as consultant/advisor role for AstraZeneca, Bristol Myers Squibb, Roche, Genentech, Pfizer and MSD VW reports personal fees and other from Roche, personal fees and other from BMS, personal fees and other from Astra Zeneca, personal fees from MSD, personal fees from Takeda, other from Pfizer, personal fees and other from Boehringer Ingelheim, personal fees from Lilly, outside the submitted work. DDR reports outside of this project advisor fees from Bristol-Myers Squibb, Celgene, Merck/Pfizer, Roche/Genentech, AstraZeneca, MSD, Seattle genetics; institutional research funding from Boehringer Ingelheim, Bristol-Myers Squibb, AstraZeneca, Philips, Olink. PMP reports speaker fees from Janssen and institutional educational grants from AstraZeneca and Celgene., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Despite the highly immunogenic potential of small cell lung cancer (SCLC), progress in evaluating the therapeutic value of immune checkpoint agents has lagged behind that of non-small cell lung cancer. Results from a number of phase I-III clinical trials that specifically address the use of anti-PD-1, anti-PD-L1 and anti-CTLA-4 agents in SCLC have now been reported. This review will focus on the available evidence for immune checkpoint blockade in SCLC and review current biomarker strategies with the aim of providing perspective and interpretation of this data for clinical practice., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The development of PD-1, PD-L1 and CTLA-4 immune checkpoint inhibitors (CPI) has revolutionised the treatment of advanced non-small cell lung cancer (NSCLC). The potential of immunotherapy (IO) to induce durable responses for a subset of patients represents a therapeutic milestone. After the approval of front-line single agent pembrolizumab, IO-based combinations are rapidly entering clinical practice resulting in a fast change of treatment algorithms for advanced NSCLC. We hereby summarize the recent first-line phase 3 trials evaluating PD-(L)1 blockade plus chemotherapy (ChT) and PD-1 plus CTLA-4 CPI for advanced NSCLC and provide potential treatment recommendations., (Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)

Background: The role of consolidative thoracic radiotherapy (TRT) in stage IV small cell lung cancer (SCLC) is not uniformly accepted., Methods: We obtained a list of 13 European medical oncologists from the International Association for the Study of Lung Cancer (IASLC) and 13 European radiation oncologists from the European Society for Therapeutic Radiation Oncology (ESTRO). The strategies in decision making for TRT in stage IV SCLC were collected. Decision trees were created representing these strategies. Frequencies of recommending TRT were analysed for various parameter combinations based on the objective consensus methodology., Results: The factors associated with the recommendation for TRT included fitness of the patient, limited extrathoracic tumour burden, initial bulky thoracic disease and response to chemotherapy. The highest consensus for TRT was in fit patients with limited extrathoracic tumour burden and initial bulky disease with either a complete extrathoracic response or partial thoracic response (92% recommend TRT). For these patients the recommendations were the same for medical and radiation oncologists. In the setting of partial response (intra- and extra-thoracically) without initial bulky thoracic disease radiation oncologists were more likely to recommend TRT than medical oncologists. For unfit patients or for patients with poor overall response to chemotherapy, the majority did not recommend TRT., Conclusion: European radiation and medical oncologists specializing in lung cancer recommend TRT in selected patients with stage IV SCLC and restrict its use primarily to fit patients who responded to chemotherapy with limited extrathoracic tumour burden., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Due to conflicting results between major trials the role of prophylactic cranial irradiation (PCI) in stage IV small cell lung cancer (SCLC) is controversial., Methods: We obtained a list of 13 European experts from both the European Society for Therapeutic Radiation Oncology (ESTRO) and the International Association for the Study of Lung Cancer (IASLC). The strategies in decision making for PCI in stage IV SCLC were collected. Decision trees were created representing these strategies. Analysis of consensus was performed with the objective consensus methodology., Results: The factors associated with the recommendation for the use of PCI included the fitness of the patient, young age and good response to chemotherapy. PCI was recommended by the majority of experts for non-elderly fit patients who had at least a partial response (PR) to chemotherapy (for complete remission (CR) 85% of radiation oncologists and 69% of medical oncologists, for PR: 85% of radiation oncologists and 54% of medical oncologists). For patients with stable disease after chemotherapy, PCI was recommended by 6 out of 13 (46%) radiation oncologists and only 3 out of 13 medical oncologists (23%). For elderly fit patients with CR, a majority recommended PCI (62%) and no consensus was reached for patients with PR., Conclusion: European radiation and medical oncologists specializing in lung cancer recommend PCI in selected patients and restrict its use primarily to fit, non-elderly patients who responded to chemotherapy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Brain metastases are common events in the natural course of many advanced solid cancers like breast, lung and renal cancer or melanoma with a cumulative risk of 10-30% in adults [1-3]. Non-small cell lung cancer (NSCLC) is associated with an increased risk for the development of brain metastases and the prognosis until recently has been poor except for some patients' subgroups and depending on the disease-specific GPA prognostic factors [4]. For patients receiving only best supportive care, average survival is about 3 months and it is assumed that through additional whole brain radiotherapy average survival may be improved up to 6-9 months in selected patients [5]. In recent years, complex treatment strategies for different solid tumors have been developed and this has impacted on the general management of brain metastases. Most of the studies on brain metastases have included different histological subtypes and therefore have made tumor- specific recommendations difficult. In this review, we discuss the current evidence on management of brain metastases and incorporate specific recent data on oncogenic-driven NSCLC in order to suggest recommendations on the optimal management of brain metastases in this subgroup of NSCLC where formal level I evidence is lacking., (Copyright © 2018. Published by Elsevier B.V.)

Anaplastic lymphoma kinase rearrangement (ALK+) occurs in approximately 2-7% of patients with non-small cell lung cancer (NSCLC), contributing to a considerable number of patients with ALK+ NSCLC worldwide. Ceritinib is a next generation ALK inhibitor (ALKi), approved by the European Medicines Agency in 2015. In the first-in-human, phase I study, ceritinib demonstrated rapid and durable responses in ALK patients previously treated with a different ALKi and in those who were ALKi-naive. As ceritinib is starting to be used routinely for the treatment of patients with ALK+ NSCLC, experience is growing with regard to ideal therapy management. In this review we provide a brief background to the development of ceritinib. The optimal treatment management and adverse events associated with ceritinib in clinical trials and in clinical practice are then discussed in detail, and where applicable, an expert consensus on specific recommendations are made. In clinical trials, the most common adverse events related to ceritinib are nausea, vomiting, and diarrhea. However, the majority of these are mild and, in the opinion of the authors, can be effectively managed with dose modifications. Based on clinical data, ceritinib has demonstrated efficacy as a first-line therapy and in patients who have relapsed on crizotinib, including those with brain metastases at baseline. Unfortunately, at some point, all patients experience progressive disease, with the central nervous system being a common site of metastases. Recommendations are made for continuing treatment beyond disease progression as long as a clinical benefit to patients is observed. Here, we review management of ceritinib treatment and adverse events and make recommendations on optimal management of patients., (Copyright © 2017. Published by Elsevier B.V.)

Background: Early stage Non-Small Cell Lung Cancer (NSCLC) is potentially curable with surgery. ESMO guidelines recommend cisplatin-based adjuvant chemotherapy (CT) for completely resected stage II-III NSCLC. There is limited evidence for the use of adjuvant CT and/or radiotherapy (RT) in incompletely resected (R1) early stage NSCLC., Materials and Methods: A European survey of thoracic oncologists was conducted to evaluate use of adjuvant CT and RT for R1-resected NSCLC and to identify factors influencing treatment decisions. Demographics and information on clinical stage, regimens, cycles planned, radiotherapy sites, multidisciplinary management and discussion about inconclusive evidence with the patient were collected. Univariate and multivariate analyses were performed., Results: 768 surveys were collected from 41 European countries. 82.9% of participants were medical oncologists; 49.3% ESMO members; 37.1% based in University Hospitals; 32.6% practicing oncology for over 15 years and 81.4% active in research. 91.4% of participants prescribed adjuvant CT and mostly cisplatin/vinorelbine (81.2%) or cisplatin/gemcitabine (42.9%). 85% discussed limited clinical evidence with the patient. In the univariate analysis, a statistically significant association with CT prescription was found for medical oncology specialty (p<0.001), ESMO membership (p<0.001), activity in clinical research (p=0.002) and increased frequency of ESMO guidelines consultation (p for trend <0.001). 48.3% of participants prescribed adjuvant RT and its prescription were associated with radiation oncology specialty (p<0.001), not being an ESMO member (p<0.001), years practicing specialty (p for trend=0.001), workload of lung cancer patients (p for trend=0.027) and decreased frequency in consulting ESMO guidelines (p<0.001). In the multivariate analysis, medical oncology and radiation oncology were the best discriminator for prescription of adjuvant CT and RT, respectively., Conclusion: This survey demonstrates that adjuvant CT and RT are commonly used in clinical practice for R1-resected NSCLC despite limited evidence. Prospective trials are necessary to clarify optimal management in this setting., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Omitting elective nodal irradiation (ENI) in limited-stage disease small cell lung cancer (LD-SCLC) is expected to result in smaller radiation fields. We report on data from a randomised phase II trial that omitted ENI in patients receiving concurrent chemo-radiotherapy for LD-SCLC. 38 patients with LD-SCLC were randomised to receive once-daily (66 Gy in 33 fractions) or twice-daily (45 Gy in 30 fractions) radiotherapy (RT). 3D-conformal RT was given concurrently with cisplatin and etoposide starting with the second cycle of a total of four cycles. The gross tumour volume was defined as primary tumour with involved lymph nodes (nodes ≥1 cm in short axis) identifiable with CT imaging. ENI was not used. Six recurrence patterns were identified: recurrence within planning target volume (PTV) only, recurrence within PTV+regional nodal recurrence and/or distant recurrence, isolated nodal recurrence outside PTV, nodal recurrence outside PTV+distant recurrence, distant metastases only and no recurrence. At median follow-up 16.9 months, 31/38 patients were evaluable and 14/31 patients had relapsed. There were no isolated nodal recurrences. Eight patients relapsed with intra-thoracic disease: 2 within PTV only, 4 within PTV and distantly and 2 with nodal recurrence outside PTV plus distant metastases. Rates of grade 3+ acute oesophagitis and pneumonitis in the 31 evaluable patients were 23 and 3% respectively. In our study of LD-SCLC, omitting ENI based on CT imaging was not associated with a high risk of isolated nodal recurrence, although further prospective studies are needed to confirm this. Routine ENI omission will be further evaluated prospectively in the ongoing phase III CONVERT trial (NCT00433563)., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

There is paucity of data in the literature regarding the safety of combining granulocyte colony stimulating factor (G-CSF) during chemo-radiotherapy (CTRT) in lung cancer patients. The ASCO 2006 recommendations advise against use of CSFs during concomitant mediastinal CTRT. The only randomised study evaluating CSFs in this context showed significant increase in grade 3/4 thrombocytopenia and an excess of pulmonary toxic deaths. In the context of a phase II trial, 38 patients with limited-stage small cell lung cancer were randomised to receive once-daily (66 Gy in 33 fractions) or twice-daily (45 Gy in 30 fractions) radiotherapy. Radiotherapy (RT) was given concurrently with cisplatin and etoposide. G-CSF was given as primary or secondary prophylaxis or as a therapeutic measure during an episode of febrile neutropenia according to local protocols. Common terminology criteria for adverse events (CTCAE) v3.0 was used to record toxicity. Thirteen (34%) of 38 patients received G-CSF concurrently with RT. With a median follow-up of 16.9 months, there were no treatment related deaths reported. Seven (54%) patients experienced grade 3/4 thrombocytopenia and 5 (38%) experienced grade 3/4 anaemia. Thirty-one percent required platelet transfusions. No episodes of bleeding were observed. There were no cases of grade 3/4 acute pneumonitis. These data suggests that with modern three-dimensional (3D) conformal RT, G-CSF administration concurrently with CTRT does not result in the increase risk of pulmonary toxicity, but does increase the risk of thrombocytopenia. Whether the risks of thrombocytopenia are outweighed by the outcome of timely early concurrent CTRT is being evaluated prospectively in the ongoing phase III CONVERT trial (NCT00433563) in which G-CSF is permitted during thoracic irradiation., (Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: The role of chemotherapy for advanced NSCLC patients and ECOG PS2 remains controversial. We evaluated 4 doses of 3-weekly docetaxel to identify a less toxic, clinically effective dose., Methods: Seventy-three patients with stage III (22%) (unsuitable for radical surgery/radiotherapy) and IV (78%) NSCLC were randomized to receive 4 doses of 3-weekly docetaxel, for 4 cycles: arm (A) 40 mg/m(2) (n=17), arm (B) 50 mg/m(2) (n=17), arm (C) 60 mg/m(2) (n=19), arm (D) 50 mg/m(2) escalated by 10 mg/m(2) to a maximum of 70 mg/m(2) (n=19). Primary endpoints: maximum tolerated dose, RR, duration of response, symptom improvement, toxicity and QoL. Secondary endpoint: overall survival (OS). Patients and disease characteristics were well balanced. Median age was 67 (range 45-81), there were 32 male and 41 female, histology subtype: squamous/adenocarcinoma/mixed/NOS=42%/49%/4%/5%., Results: Seven patients did not receive any treatment because of deterioration in PS or death. 50% of patients in arm D, who received more than one cycle, received dose escalation. There was no statistical difference in the number of cycles administered (arms A, B and D: median 2 cycles and arm C: median 3 cycles) and no difference in RR: arm A=6%, arm B=6%, arm C=10%, and arm D=0%. There was no statistically significant difference in grade 3/4 neutropenia and thrombocytopenia between the four arms. No difference was observed in hospitalization rate, blood transfusions, antibiotics administration and non-haematological toxicity. QoL: no difference in total scores between baseline and cycles 1-4. There was a significant decrease in pain scores from baseline to post cycles 2 and 3 (p=0.025 and p=0.002, respectively). There was no difference in OS (p=0.992). Median survival and 6-month survival were 61, 86, 88 and 97 days and 29%, 33%, 21% and 26% for arms A, B, C, and D, respectively., Conclusions: Clinical efficacy of docetaxel was observed at all dose levels. Higher dose levels were not associated with increased toxicities, use of IV antibiotics or hospitalization rates. However, the median survival observed is shorter than historical data and do not support further evaluation of these doses of single agent docetaxel in this population., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Patients with small-cell lung cancer (SCLC) that progress after first-line chemotherapy have a poor prognosis and the evidence of a benefit from second-line (SL) chemotherapy is limited. Patients relapsing or progressing more than 90 days after completion of first-line treatment are considered platinum sensitive and may be rechallenged with platinum-based chemotherapy. Topotecan is approved as SL treatment independent of time to progression. This retrospective analysis evaluates the clinical outcomes of SCLC patients who received SL chemotherapy after platinum-etoposide chemotherapy., Patients and Methods: We retrospectively reviewed 161 patients who received SL chemotherapy for SCLC. Patients were divided into four subgroups by type of SL treatment: (1) platinum-based rechallenge; (2) anthracycline-based regimens; (3) topotecan; (4) other single agents. The endpoints were overall survival (OS), progression-free survival (PFS) and response rate (RR). Survival curves were plotted using the Kaplan-Meier method. The Cox proportional hazard model was used for multivariate analysis to investigate factors influencing survival., Results: The median age was 63. There were 125 males and 36 females. Eastern Cooperative Oncology Group performance status (ECOG-PS) was 0, 1 and 2 in 12.5%, 62.5% and 25% of patients, respectively. Platinum sensitive/platinum resistant/platinum refractory/unknown=121/29/3/8 patients. Median time to SL chemotherapy was 6.9 months. The median PFS from starting second-line treatment was 4.3 months and median OS was 5.8 months. The overall RR was 22.9%. There was a trend toward higher RR (34.5% vs 17.5%, p for trend: 0.06) and OS (9.2 months vs 5.8 months, p=0.08) for patients with sensitive disease who were rechallenged with platinum-based chemotherapy. A multivariate analysis that adjusted for the time to SL treatment showed that a platinum-containing regimen achieves better RR, PFS and OS independently of the time to SL chemotherapy and that response to first-line treatment and PS at SL are the only independent prognostic factors., Conclusions: The outcome for second-line therapy for SCLC was poor and benefit appeared to be limited to those patients with good PS and rechallenged with platinum-based chemotherapy. Platinum-based rechallenge should be considered as a standard comparator in future randomized controlled trials of SL chemotherapy., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)