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Odd Terje Brustugun



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    EP1.01 - Advanced NSCLC (ID 150)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 2
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.01-30 - Clinico-Pathological Profile of Adenocarcinoma of the Lung – A Prospective Study in a Nepalese Population (Now Available) (ID 722)

      08:00 - 18:00  |  Author(s): Odd Terje Brustugun

      • Abstract
      • Slides

      Background

      Lung cancer represents the most common cause of cancer related mortality in developing countries including Nepal where patients (pts) often present in advanced stage. The purpose of this study was to determine the incidence and clinico-pathological profile of pts with adenocarcinoma of the lung (ACL) presented to a tertiary care center of Nepal.

      Method

      An IRB approved prospective study was conducted in pts with ACL over a period of 15 months from April 2017 to July 2018 at a tertiary care center, Bir Hospital, Kathmandu. Demographic data, history of smoking, histological type, presence and type of epidermal growth factor receptor (EGFR) mutations were studied. EGFR-analysis was performed using TheraScreen EGFR mutation kit.

      Result

      A total of 253 pts were diagnosed with lung cancer in the period. Of the 83 (33%) diagnosed with ACL, 45 (54%) were males and 38 (46%) females. The mean age at diagnosis was 59.4 years, and 74 (89%) were in stage III/IV. Forty eight (58%) pts were smoker of whom 30 (63%) pts had less than 10 pack years. Sixty one percent (61%) were illiterate. Eighteen (22%) pts had wrongly received anti-tuberculosis treatment before the diagnosis of ACL was made. All ACL pts were tested for EGFR-mutations which were found in 24 (29%) pts, the most common mutation being exon 21 (L858R) (42%) followed by exon 19 deletion (38%). Exon 18 and exon 20 (T790M) mutation were found in 2 pts (8%) each. One pt had dual mutation in exon 20 (T790M) and exon 21 (L858R).

      Conclusion

      The frequency of EGFR-mutations in ACL in this Nepalese cohort was lower than in Eastern Asian studies, but higher than in western population. EGFR mutation testing of ACL has to be encouraged in developing countries like Nepal as presence of these mutations predict durable response to oral tyrosine kinase inhibitors. Interestingly, lung cancer is often mistreated as tuberculosis leading to delay in diagnosis and treatment.

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      EP1.01-40 - Outcome of EGFR-Mutated and Non-Mutated Lung Adenocarcinoma Receiving Standard Therapy - A Nepalese Cohort (Now Available) (ID 941)

      08:00 - 18:00  |  Author(s): Odd Terje Brustugun

      • Abstract
      • Slides

      Background

      Lung cancer represents major health challenges worldwide including Nepal where patients (pts) often present in advanced stage. The purpose of this study was to compare the objective response rates (ORR), progression free survival (PFS), and quality of life (QoL) of EGFR-mutated (EGFR-mut) and non-mutated (EGFR-wt) pts with adenocarcinoma of the lung (ACL) receiving standard therapy.

      Method

      An IRB approved comparative analytical study was performed in pts with ACL. Newly diagnosed stage IV ACL pts were enrolled and ORR, PFS and QoL was compared between EGFR-mut and EGFR-wt (33 pts in each arm) pts. EGFR-mut pts were given gefitinib and EGFR-wt pts were given systemic chemotherapy (pemetrexed/cisplatin or cisplatin/etoposide). Response evaluation was done using RECIST criteria in both arms. PFS was calculated from the date of starting treatment to the date of progression and QoL was evaluated using EORTC QLQ-C30 (version 3) questionnaire and compared between two arms. Adverse effects were assessed using CTCAE criteria. Pts were followed for 1 year.

      Result

      Complete response (CR) was achieved in 9.1% vs 3.0 % (p=0.46), and ORR was 27.3% vs 15.2% (p=0.23) in EGFR-mut vs EGFR-wt. The median PFS was 11 and 9 months for EGFR-mut and EGFR-wt respectively (p = 0.045). The mean score of global health status from EORTC QLQ-C30 was 68.1 vs 61.6 in EGFR-mut pts vs EGFR-wt pts (p = 0.036). Skin toxicities were more common in pts receiving gefitinib. One pt had grade 3 skin toxicity. Febrile neutropenia and peripheral neuropathy (either grade 1 or grade 2) were the most common toxicities in pts receiving standard chemotherapy.

      kaplan meier-pfs.jpg

      Conclusion

      EGFR-mut pts treated with EGFR-TKI had improved ORR, PFS and QoL in comparison with EGFR-wt pts treated with chemotherapy. EGFR-mutational analysis and EGFR-directed therapy is feasible and provides survival benefit, also in developing countries as Nepal.

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    EP1.18 - Treatment of Locoregional Disease - NSCLC (ID 208)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.18-12 - The Neutrophil and Platelet to Lymphocyte Ratios and Glasgow Prognostic Score as a Predictor for Relapse After Stereotactic Radiation for Lung Cancer (Now Available) (ID 440)

      08:00 - 18:00  |  Author(s): Odd Terje Brustugun

      • Abstract
      • Slides

      Background

      Chronic inflammation plays an important role in lung carcinogenesis. The neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte ratios (PLR) and modified Glasgow Prognostic Score (mGPS) have been associated with overall mortality and PLR greater than 250 with non-local failures in non-small cell lung cancer (NSCLC) patients. We hypothesised that NLR, PLR and mGPS were higher in patients developing non-local failures within the first year after stereotactic body radiation therapy (SBRT) than in those without non-local failures.

      Method

      Medically inoperable stage I NSCLC patients were included in a prospective, observational, single centre study from February 2014 until December 2017. Follow up included physical examination, CT scans and blood samples at baseline, 6 weeks, 3, 6, 9 and 12 months after SBRT. Most patients took baseline blood samples within mean 7 days before treatment. Differences in NLP, PLR and mGPS between the groups (with and without non-local failures) were calculated using Mann-Whitney-Wilcoxon U-test.

      Result

      We included 46 patients with median age 75 years, of which 67% were men. Comorbidities were common, and 80% had chronic obstructive pulmonary disease (COPD). Six patients were diagnosed with non-local failures within the first year of follow-up. Multiple metastases were identified in the mediastinum (2 patients), contralateral lung (2 patients) and in the liver and bone (2 patients).

      Marker

      Non-local failures (n=6)

      Without non-local failures (n=40)

      P-value

      NLR

      3.3

      3.5

      0.83

      PLR

      246

      158

      0.35

      mGPS

      0.67

      0.33

      0.27

      Conclusion

      Our study found no statistically significant association between increased NLR, PLR, mGPS and the identification of non-local failures within the first year after SBRT. This is a relatively small cohort of patients, and the patients suffered from serious chronic medical comorbidities such as COPD, chronical renal and cardiac disease. These medical conditions can also influence NLR, PLR, mGPS and can explain our finding.

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    P1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 186)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.16-22 - Reduced Delays in Diagnostic Pathways for Non-Small Cell Lung Cancer After Local and National Interventions (Now Available) (ID 415)

      09:45 - 18:00  |  Author(s): Odd Terje Brustugun

      • Abstract
      • Slides

      Background

      Patients with non-small cell lung cancer (NSCLC) may experience progression and stage shift due to delays in a complex and time-consuming diagnostic work-up. We have analyzed the impact of both a local and national intervention on total time to treatment (TTT) for a population-based cohort of NSCLC patients.

      Method

      All patients diagnosed with NSCLC at a county hospital in Kristiansand, Norway, 2007-2016 were reviewed. The period 2007-12 before the interventions was defined as baseline. Local bottlenecks in the diagnostic pathways were identified and a new, locally developed diagnostic algorithm introduced from 2013. From 2015 National diagnostic cancer pathways were implemented and local adjustments were made accordingly. TTT defined as time from referral of the primary physician to treatment was compared in the three diagnostic time periods; baseline period (2007-12), local initiative (2013-14) and the national initiative (2015-16). Multivariable quantile regression was used to correct for possible confounding factors.

      Result

      A total of 780 NSCLC patients were included in the study. The median TTT decreased from 46 days in the first period to 35 days in the last period. Among patients treated with curative intent the median TTT decreased by 21 days, from 64 to 43 days (p<0.001) while the mean number of procedures increased from 3,5 to 3,9. In median regression analysis, the local intervention was associated with a reduction of 7.7 days (95% CI 3.2, 12.3) in TTT, while the national intervention had a reduction of 14.9 days (95% CI 10.2, 19.6) compared to the baseline group. Examining the 75thand 90thpercentile, the last period had 22 days and 27 days shorter TTT than the first period, respectively. Covariates associated with longer TTT were stage I (21.3 days compared to stage IV), use of PET-CT (10.6 days), diagnostic procedure at external hospital (13.0 days), and additional number of diagnostic procedures (5.3 days per procedure).

      Conclusion

      Both interventions, the local and national initiatives introduced to this population significantly reduced TTT in NSCLC despite more diagnostic procedures being added to the work-up. The effect was most pronounced among patients with disease available for curative treatment.

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    P2.04 - Immuno-oncology (ID 167)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.04-74 - Radiotherapy Prior to Immunotherapy Is Associated with Durable Disease Control in Advanced NSCLC (ID 1581)

      10:15 - 18:15  |  Author(s): Odd Terje Brustugun

      • Abstract

      Background

      In an unselected patient cohort response rates for immune checkpoint inhibitors in advanced NSCLC are around 20 %1-3. To enhance this proportion several treatment combinations are under investigation. Radiotherapy combined with immunotherapy has shown promising results in preclinical trials and clinical trials using this combination are in progress, assessing safety and optimal dosage/timing of radiotherapy4.

      Method

      Between May and September 2015 fifty-seven patients with advanced NSCLC were treated with nivolumab (3 mg/kg every 2nd week) at The Norwegian Radium Hospital in a named-patient-use-program. Clinical information, including dosage and timing of radiotherapy given prior to immunotherapy, has been collected and correlated to clinical outcome.

      Result

      figure_1.pngMedian follow-up time for those with no event when data was collected was 43.4 months (range 42.4-44.1 months) and overall survival 14%. Eight patients died of other causes than lung cancer. Radiotherapy administered at different time intervals before the first dose of nivolumab was correlated to progression free survival (PFS) and overall survival (OS) using cox regression analysis. We found poor PFS (HR 3.1 p=0.034) and OS (HR 3.7 p=0.015) for those who received radiotherapy between 1-2 months prior to nivolumab. The indication for radiotherapy in late stage lung cancer is most often symptomatic metastases. Hence, recent radiotherapy is usually associated with more advanced disease and poor prognosis. When patients were divided into groups according to prognosis we found that many in the group with short PFS had received radiotherapy shortly before immunotherapy but the proportion was even higher in the group with durable response (figure 1).

      Conclusion

      Our findings support the hypothesis that radiotherapy can trigger a tumor-directed immune response which can be enhanced by immunotherapy and result in long-lasting disease control. We will validate our results in an additional cohort and will assess and include PD-L1 expression in our analysis.

      1. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med 2015;373(2):123-35.

      2. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med 2015;373(17):1627-39.

      3. Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 2015;372(21):2018-28.

      4. Ngwa W, Irabor OC, Schoenfeld JD, et al. Using immunotherapy to boost the abscopal effect. Nat Rev Cancer 2018;18(5):313-22.