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R. Manser



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    MA 14 - Diagnostic Radiology, Staging and Screening for Lung Cancer I (ID 672)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Radiology/Staging/Screening
    • Presentations: 1
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      MA 14.09 - Impact of Lung Cancer Perceived Risk, Screening Eligibility and Worry on LDCT Screening Preference - Challenges for Engaging Patients at High Risk (ID 9669)

      15:45 - 17:30  |  Author(s): R. Manser

      • Abstract
      • Presentation
      • Slides

      Background:
      Lung cancer screening is only effective at reducing lung cancer deaths when the highest risk individuals are screened and followed. An individual’s risk of lung cancer, and therefore their screening eligibility, has not been shown to correlate with their perceived risk or intention to participate in screening. While previous studies have suggested many at-risk individuals are supportive of screening, no validated risk perception questionnaire has been used to compare perceived risk and worry with screening preference between eligible and ineligible individuals.

      Method:
      Participants were current or former smokers aged 55 to 80 years old who presented for medical outpatient specialist appointments at three Australian hospitals. The survey included 1) demographics and previous cancer screening participation 2) objective lung cancer risk measured by PLCOm2012 lung cancer risk prediction model 3) perceived lung cancer risk and worry about lung cancer measured by the questionnaire developed by Park et al and validated in sub-set of National Lung Screening Trial (NLST) participants and 4) preference for screening measured by a five point Likert scale. Eligibility for screening was PLCOm2012 risk >1.5%. Ordinal logistic regression identified factors associated with screening preference.

      Result:
      760 people 55-80 years old participated, of which 306 were ever-smokers. The participation rate was 26.9%. 23 did not complete either sufficient smoking details for PLCOm2012 risk or screening preference leaving 283 responses. Mean±SD age was 66.3±6.5, 60.4% (171/283) were male, median (IQR) PLCOm2012 risk was 1.28% (0.44-3.11) and 45.6% (129/283) were eligible for screening. Overall screening preference was high; 72.1% (204/283) either agreed or strongly agreed to having screening if offered. Objective lung cancer risk (PLCOm2012) was weakly correlated with both perceived lung cancer risk (r=0.28, p<0.0001) and worry (r=0.21, p<0.001). In univariate analysis, worry (OR 1.37, 95% CI [1.18-1.60], p<0.001), perceived risk (OR 1.10, 95% CI[1.04-1.16], p=0.002) and PLCOm2012 risk (OR 1.06, 95% CI[1.01-1.12], p=0.02) were associated with higher screening preference, but not associated with higher screening eligibility (OR 1.50, 95%CI[0.97-2.30], p=0.06). Age, gender, smoking status, family history of lung cancer and previous screening practice were not associated with screening preference. Only worry remained significantly associated with screening preference (adj-OR 1.33, [95%CI 1.10-1.60], p=0.003) with multivariate analysis.

      Conclusion:
      Worry about lung cancer appears to be a more important driver for screening preference than eligibility status. This presents a unique challenge when trying to engage with eligible individuals while minimizing screening demand from the ineligible majority.

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    P1.01 - Advanced NSCLC (ID 757)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P1.01-033 - Thrombogenic Biomarkers in Patients with NSCLC – Associations with Thrombosis, Progression, and Survival (ID 8852)

      09:30 - 16:00  |  Author(s): R. Manser

      • Abstract
      • Slides

      Background:
      For patients with NSCLC, the risk of thromboembolism (TE) is high but heterogeneous. We aimed to profile biomarkers among NSCLC patients receiving anticancer therapy to identify patients and time periods of high TE risk where intervention with proven preventative strategies is likely to achieve maximal benefit.

      Method:
      We assessed the association between baseline biomarker levels and longitudinal biomarker changes, with subsequent incidence of TE (venous (VTE) or arterial (ATE)), disease progression and overall survival. Biomarkers (thromboelastography, d-dimer, fibrinogen, haemoglobin, white cell count, platelet count, neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR)) were sequentially assessed at commencement of anticancer therapy (baseline), weeks 1, 4 and 12, and 3-monthly until 12 months.

      Result:
      During study follow-up (median 22 months, range 6-31), 129 patients were sequentially assessed over median 5 time points (range 1-9). Patients underwent surgery (n=12), chemo-radiotherapy (CRT, n=47), palliative chemotherapy (CHT, n=36), and single modality radiotherapy (RT, n=34) – only surgical patients received thromboprophylaxis. 24 patients (19%) had documented TE, 19 (15%) VTE and 5 (4%) ATE; 79% occurred within the first 6 months with median time to TE 48 days (range 1-151). Among ambulatory patients (CHT/CRT/RT), an initial model identified as high TE risk those patients with baseline fibrinogen ≥4g/L and d-dimer ≥0.5mg/L, or d-dimer ≥1.5mg/L. Hazard ratio (HR) for TE was 8.0 (p=0.04) for high versus low risk CHT/CRT patients and 6.5 (p=0.07) for high versus low risk for CHT/CRT/RT patients. Comparatively, using an established risk score, HR for TE with Khorana score ≥3 vs. <3 was 1.3 (p=0.68) for CHT/CRT and 1.1 (p=0.91) for CHT/CRT/RT. Considering temporal changes (d-dimer ≥1.5mg/L at week 4), risk assessment was enhanced with 100% sensitivity and 34% specificity for CHT/CRT. Specificity reduced to 27% when including RT patients. NLR, PLR and platelet count were not associated with TE. High TE risk patients (Fib≥4 + d-dimer ≥0.5, d-dimer ≥1.5) also had increased risk of cancer progression (HR 2.3, p<0.01) and mortality (HR 2.5, p<0.01). Baseline NLR≥2.5 and platelet count ≥350 were associated with progression (HR 2.0, p=0.01 and HR 2.0, p<0.01 respectively) and mortality (HR 2.6, p=0.01 and HR 1.9, p=0.01 respectively); PLR was not.

      Conclusion:
      For ambulatory patients with NSCLC, d-dimer and fibrinogen were associated with TE, cancer progression, and prognosis and could easily be applied in a simple algorithm, for real-time decision-making. In spite of low specificity, consideration of thromboprophylaxis is warranted for high risk patients given substantial TE-associated adverse clinical and economic consequences.

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    P1.04 - Clinical Design, Statistics and Clinical Trials (ID 690)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Clinical Design, Statistics and Clinical Trials
    • Presentations: 1
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      P1.04-003 - The International Lung Screen Trial: A Multi-Centre Study to Evaluate LDCT Screening Selection Criteria and Nodule Management (ID 8141)

      09:30 - 16:00  |  Author(s): R. Manser

      • Abstract
      • Slides

      Background:
      There remain important knowledge gaps surrounding the optimal selection criteria of high-risk individuals for low-dose CT (LDCT) screening for lung cancer and the optimal management of screening-detected pulmonary nodules. The International Lung Screen Trial (ILST) is an international, multi-centre prospective cohort study with recruitment sites in Canada and Australia. The rationale and design for the study are presented here. The PLCO~m2012~ risk prediction model[1] may have higher sensitivity and positive predictive value in identifying individuals who develop lung cancer compared to the United States Preventive Services Task Force (USPSTF) criteria. The PanCan model[2] calculates malignancy probability in screen-detected nodules and provides a risk-based approach to managing pulmonary nodules. Both models will be prospectively tested in this study. Primary aims: (a) to define the optimal selection criteria for LDCT screening, (b) to evaluate pulmonary nodule management using the PanCan nodule risk calculator.

      Method:
      We aim to recruit 4,000 high-risk individuals with 5 years follow up. Eligible participants are current or former smokers, aged 55-80 years, with a PLCO~m2012~ lung cancer risk of ≥1.51% over 6 years or USPSTF criteria (age as above, plus ≥30 pack year history of smoking and smoking cessation <15 years ago). Exclusion criteria include: symptoms suspicious of lung cancer, severe co-morbidity, previous lung cancer and chest CT within the last 2 years. Baseline assessment includes interview, smoking status assessment and pulmonary function testing. Eligible individuals are offered a baseline screening LDCT and subsequent interval surveillance LDCTs dependent on the PanCan risk score. Participants with no nodules or nodule risk score of <1.5% will have biennial LDCT screening. Participants with nodule malignancy risk score ≥10%, or significant growth in subsequent scan will be considered suspicious for lung cancer and undergo clinical review for further investigation. The primary outcome is the proportion of lung cancers detected by either selection criteria. Secondary outcomes include: number needed to screen, cancer detection rate, lung cancer mortality, cancer stage distribution, resection rate, number of interval cancers, recall rate, invasive procedure rate, benign biopsy/surgery rate, screening-related adverse events and comprehensive healthcare economic evaluation.

      Result:
      This study is currently in its recruitment phase. Results will be reported in future conferences and peer-reviewed publications.

      Conclusion:
      The ILST trial will provide a clearer understanding on the optimum selection criteria for LDCT screening for lung cancer and prospective validation of the PanCan model. ClinicalTrials.gov number: NCT02871856 References: Tammemägi MC et al (2013). NEJM; 368:728-736. McWilliams A et al (2013). NEJM; 369:910-919.

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