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After the results of two large, randomized trials, the global implementation of lung cancer screening is of outmost importance. However, COVID-19 infections occurring at heightened levels during the current global pandemic, and also other respiratory infections, can influence scan interpretation, and screening safety and uptake. Several respiratory infections can lead to lesions that mimic malignant nodules and other imaging changes suggesting malignancy, leading to an increased level of follow-up procedures or even invasive diagnostic procedures. In periods of increased rates of respiratory infections such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) there is also a risk of transmission of these infections to the health care providers, the screenees and patients. This became very clear and evident for the SARS-CoV-2 pandemic and led to a temporary global stop of lung cancer and other cancer screening programs. Data about the optimal management of these situations are not available. The pandemic is still ongoing and there will come further periods of increased respiratory infections, where practical guidance would be helpful. The aim of this report is a) to summarize the data available for possible false positive results due to respiratory infections, b) to evaluate the safety concerns for screening during times of increased respiratory infections, especially during a regional outbreak or an epidemic or pandemic event, c) to provide guidance for these situations and d) to stimulate research and discussions about these scenarios.

After the results of two large, randomized trials, the global implementation of lung cancer screening is of utmost importance. However, coronavirus disease 2019 infections occurring at heightened levels during the current global pandemic and also other respiratory infections can influence scan interpretation and screening safety and uptake. Several respiratory infections can lead to lesions that mimic malignant nodules and other imaging changes suggesting malignancy, leading to an increased level of follow-up procedures or even invasive diagnostic procedures. In periods of increased rates of respiratory infections from severe acute respiratory syndrome coronavirus 2 and others, there is also a risk of transmission of these infections to the health care providers, the screenees, and patients. This became evident with the severe acute respiratory syndrome coronavirus 2 pandemic that led to a temporary global stoppage of lung cancer and other cancer screening programs. Data on the optimal management of these situations are not available. The pandemic is still ongoing and further periods of increased respiratory infections will come, in which practical guidance would be helpful. The aims of this report were: (1) to summarize the data available for possible false-positive results owing to respiratory infections; (2) to evaluate the safety concerns for screening during times of increased respiratory infections, especially during a regional outbreak or an epidemic or pandemic event; (3) to provide guidance on these situations; and (4) to stimulate research and discussions about these scenarios.

Screening with low-dose computed tomography of high-risk individuals with a smoking history reduces lung cancer mortality. Current screening guidelines and eligibility criteria can miss more than 50% of lung cancers, and in some geographic areas, such as East Asia, a large proportion of the missed lung cancers are in never-smokers. Although randomized trials revealed the benefits of screening for people who smoke, these trials generally excluded never-smokers. Thus, the feasibility and effectiveness of lung cancer screening of individuals who never smoked are uncertain. Several known and suspected risk factors for lung cancers in never-smokers such as exposure to secondhand smoke, occupational carcinogens, radon, air pollution, and pulmonary diseases, such as chronic obstructive pulmonary disease and interstitial lung diseases, and intrinsic factors, such as age, are well noted. In this regard, knowledge of risk factors may make possible quantification and prediction of lung cancer risk in never smokers. It is worth considering if and how never smokers could be included in population-based screening programs. As the implementation of these programs is challenging in many countries owing to multiple factors and the epidemiologic differences by global regions, these issues will need to be evaluated in each country taking into account various factors, including accuracy of risk assessment and cost-effectiveness of screening in never smokers. This report aims to outline current knowledge on risk factors for lung cancer in never smokers to propose research strategies for this topic and initiate a broader discussion on lung cancer screening of never smokers. Similar considerations can be made in current and ex-smokers, which do not fulfill the current screening inclusion criteria, but otherwise are at increased risk. Although screening of never smokers may in the future be effectively conducted, current evidence to support widespread implementation of this practice is lacking.

9071Background: BRG is a kinase inhibitor approved for the treatment of patients (pts) with ALK+ metastatic NSCLC; specific details for BRG use vary by indication and country. We report long-term efficacy and safety results of the Phase 1/2 and Phase 2 (ALTA) trials of BRG. Methods: The Phase 1/2 study was a single-arm, open-label trial (NCT01449461) of BRG 30?300 mg/d in pts with advanced malignancies. ALTA (NCT02094573) randomized pts with CRZ-refractory ALK+ NSCLC to receive BRG at 90 mg qd (arm A) or 180 mg qd with 7-d lead-in at 90 mg (arm B). For the Phase 1/2 study, investigator assessments of confirmed objective response rate (cORR; RECIST v1.1), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety in pts with ALK+ NSCLC are reported. The primary endpoint of ALTA was cORR per investigator; secondary endpoints included cORR per independent review committee (IRC), DoR, PFS, and OS. Results: In the Phase 1/2 study, 137 pts received BRG; of these, 79 pts had ALK+ NSCLC (71/79 had prior CRZ; 28/79 received 180 mg qd [7-d lead-in at 90 mg]; 14/79 received 90 mg qd). In ALTA, 222 pts with CRZ-refractory ALK+ NSCLC were randomized (n = 112/110, arm A/B). At the end of the Phase 1/2 study (Feb 18, 2020), with median 27.7 mo follow-up (?67 mo after last pt enrolled), 4 pts remained on BRG. At the end of ALTA (Feb 27, 2020), with median 19.6/28.3 mo follow-up in arm A/B (?53 mo after last pt enrolled), 10/17 pts in arm A/B were still on treatment. Table shows efficacy results from final analyses with long-term follow-up. In ALTA, the IRC-assessed intracranial cORR in pts with measurable baseline brain metastases was 50% (13/26) in arm A and 67% (12/18) in arm B; Kaplan-Meier (KM) estimated median intracranial DoR was 9.4 mo (95% CI, 3.7, not reached [NR]) in arm A and 16.6 mo (3.7, NR) in arm B. With long-term follow-up, no new safety signals were identified. Treatment-emergent adverse events led to dose interruption (Phase 1/2: 59%; ALTA arm A/B: 49%/61%), dose reduction (13%; 8%/33%), or discontinuation (10%; 4%/13%). Conclusions: BRG showed sustained long-term activity, PFS, and manageable safety in pts with CRZ-refractory ALK+ NSCLC. The 180 mg/d dose after 7-d lead-in at 90 mg/d led to numerically higher median PFS and OS. Final results are similar to those reported for other approved ALK tyrosine kinase inhibitors in this setting. Clinical trial information: NCT01449461, NCT02094573.Phase 1/2(n = 79)ALTA: A(n = 112)ALTA: B(n = 110)cORR, n (%) [95% CI]Per investigator53 (67) [56, 77]51 (46) [36, 55]63 (57) [48, 67]Per IRC?58 (52) [42, 61]62 (56) [47, 66]Median DoR (95% CI),a moPer investigator14.9 (9.9, 29.5)12.0 (9.2, 19.4)13.8 (10.8, 17.6)Per IRC?19.4 (9.2, 24.9)15.7 (13.6, 22.1)Median PFS (95% CI),a moPer investigator14.5 (10.8, 21.2)9.2 (7.4, 11.1)15.6 (11.1, 18.5)Per IRC?9.9 (7.4, 12.8)16.7 (11.6, 21.4)Median OS (95% CI),a mo47.6 (28.6, NR)25.9 (18.2, 45.8)40.6 (32.5, NR)OS at 5 yearsa42%31%43%aKM estimates.

After the results of two large, randomized trials, the globalimplementation of lung cancer screening is of utmostimportance. However, coronavirus disease 2019 infectionsoccurring at heightened levels during the current globalpandemic and also other respiratory infections can influence scan interpretation and screeningsafetyanduptake.Severalrespiratoryinfectionscanleadtolesionsthatmimicmalignantnodules and other imaging changes suggestingmalignancy, leading to an increased level of follow-up procedures or even invasive diagnostic procedures. In periodsof increased rates of respiratory infections from severeacute respiratory syndrome coronavirus 2 and others, thereis also a risk oftransmission of these infections to the healthcare providers, the screenees, and patients. This becameevident with the severe acute respiratory syndrome coronavirus 2 pandemic that led to atemporary global stoppageof lung cancer and other cancer screening programs. Dataon the optimal management of these situations arenotavailable. The pandemic is still ongoing and further periodsof increased respiratory infections will come, in whichpractical guidance would be helpful. The aims of this reportwere: (1) to summarize the data available for possible falsepositive results owing to respiratory infections; (2) toevaluate the safety concerns for screening during times ofincreased respiratoryinfections, especially during aregional outbreak or an epidemic or pandemic event; (3) toprovide guidance on these situations; and (4) to stimulateresearch and discussions about these scenarios.