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Andrea Bezjak



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    MA18 - Modelling, Decision-Making and Population-Based Outcomes (ID 920)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/25/2018, 13:30 - 15:00, Room 201 F
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      MA18.07 - Awareness of the Harms of Continued Smoking Among Lung Cancer (LC) Survivors (Now Available) (ID 12024)

      14:05 - 14:10  |  Author(s): Andrea Bezjak

      • Abstract
      • Presentation
      • Slides

      Background

      Continued smoking after a LC diagnosis is associated with poorer cancer outcomes including increased risk of treatment-related side-effects, reduced treatment efficacy and poorer prognosis. Smoking cessation is an integral part of LC survivorship by improving both cancer and non-cancer outcomes. To enhance survivorship education, clinicians should understand patient awareness of the harms of continued smoking.

      Method

      LC survivors from Princess Margaret Cancer Centre, Toronto (2014-2017) were surveyed with respect to self-awareness of the harms of continued smoking on cancer-related outcomes. Univariable and multivariable logistic regression models assessed factors associated with awareness and whether awareness was associated with cessation among current smokers at diagnosis.

      Result

      Of 553 patients, 181 were lifetime never-smokers. Among those smoking during the peri-diagnosis period (n=177), 65% quit after diagnosis. Among all, few patients were aware that smoking negatively impacts treatment-related outcomes [complications from cancer surgery (only 41% aware), radiation side-effects (30%), quality-of-life on chemotherapy (44%) and treatment efficacy (36%)]; half were aware that smoking negatively impacts cancer prognosis (51% aware) and risk of developing second primaries (50%). Compared to ex-smokers/never-smokers at diagnosis, current smokers at diagnosis were less aware of the impact of smoking on radiation side-effects (22% vs 31% aware, P=0.01), prognosis (44% vs 55%, P=0.02) and risk of second primaries (42% vs 55%, P=0.007). Among sociodemographic variables, only those speaking English at home were consistently found more likely unaware that smoking negatively impacts these outcomes (ORs=1.52-2.20, P<0.04). Patients with early stage disease were more likely unaware that smoking negative impacts radiation side-effects (OR=1.60, 95%CI[1.09-2.35], P=0.02); while patients on curative treatment (OR=1.53[1.08-2.17], P=0.02) and those exposed to second-hand smoke (SHS) were more likely unaware that smoking impacts quality-of-life on chemotherapy (OR=1.64[1.05-2.58], P=0.03). Exposure to SHS, treatment intent and stage were not associated with awareness of impact on prognosis or second primaries (P>0.11). Among smokers in the peri-diagnosis period, awareness of the impact of smoking on surgical complications (aOR=2.09 [0.96-4.54], P=0.06), quality-of-life while receiving chemotherapy (aOR=2.60[1.17-5.79], P=0.02) and on treatment efficacy (aOR =2.24[0.97-5.20], P=0.06) were each associated with subsequent quitting, adjusted for marital status, pack-years, self-rated health and SHS exposure.

      Conclusion

      Many LC patients are unaware of the harms of continued smoking on cancer outcomes, particularly those smoking at diagnosis. Awareness of some of these outcomes was associated with subsequent tobacco cessation. Patient education on the health benefits of smoking cessation may increase quit rates and improve outcomes for LC patients.

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    OA11 - Thymic and Other Thoracic Tumours: Targeted Therapies, Biomarkers and Neo/Adjuvant Radiotherapy (ID 919)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Thymoma/Other Thoracic Malignancies
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/25/2018, 13:30 - 15:00, Room 205 BD
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      OA11.06 - Two BRM Promoter Polymorphisms Do Not Predict Susceptibility or Prognosis of Thymoma (Now Available) (ID 12745)

      14:25 - 14:35  |  Author(s): Andrea Bezjak

      • Abstract
      • Presentation
      • Slides

      Background

      Brahma (BRM) is a critical protein subunit in chromatin remodeling, and insertions/deletions at its two polymorphic promotor sites (BRM-741 and BRM-1321) have been reported as susceptibility and/or prognostic markers in lung, head and neck, esophageal, pancreatic, and liver cancers. There is also early evidence of potential association with immune-related diseases such as ulcerative colitis and rheumatoid arthritis. As epigenetic silencing of BRM can be pharmacologically reversed, BRM polymorphisms in cancer might have therapeutic implications. Thymoma is a unique cancer in that it has immunological disease associations. We evaluated whether BRM-741 and BRM-1321 polymorphisms influence overall risk, survival, and time-to-progression of thymoma.

      Method

      Thymoma cases and matched healthy controls were recruited in a comprehensive cancer centre. Study participants’ peripheral blood samples were collected and genotyped for BRM promoter polymorphisms. Multivariable logistic regression assessed risk of thymoma in case-control analyses. Association of BRM variants with overall survival (OS) and time-to-progression or recurrence (TTP) was assessed by multivariable Cox regression.

      Result

      Of 237 cases of histologically diagnosed thymoma and 948 age- and gender-matched healthy controls, thymoma patients had median age of 53 (range: 17-84) years; 121 (51%) were male; 76 (32%) had a history of myasthenia gravis. Median follow-up time was 7 years. 79% of patients were recurrence- and progression-free at 10-year follow-up (95% CI: 74-86%), and 81% of patients were alive at 10 years post-diagnosis (95% CI: 75-87%). Frequency of homozygous variants for either gene was not significantly different between thymoma cases and controls: homozygous BRM-741genotype (OR=1.0; 95%CI:0.6-1.8; P=0.95), homozygous BRM-1321 (OR=0.59; 95%CI:0.3-1.0; P=0.07) or double homozygous variants in both loci (OR=0.69; 95%CI:0.3-1.4; P=0.29). No association between BRM-741/BRM-1321 and OS and TTP was detected (For homozygous BRM-741, OS P=0.74, TTP P=0.93; for homozygous BRM-1321 OS P=0.39, TTP P=0.93). Consistently, there was also no association between double homozygous variants and OS and TTP (Double homozygous, OS P=0.64, TTP P=0.48). Heterozygous variants were also not associated with either risk or outcome.

      Conclusion

      Results of this study do not support use of BRM promoter polymorphisms as susceptibility or prognostic markers for thymoma. Molecular biologic mechanisms of risk and prognosis remain elusive in malignant thymoma.

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    OA13 - Therapeutics and Radiation for Small Cell Lung Cancer (ID 927)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/26/2018, 10:30 - 12:00, Room 203 BD
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      OA13.05 - Prophylactic Cranial Irradiation (PCI) for Limited-Stage Small-Cell Lung Cancer: Results from the Phase 3 CONVERT Trial (Now Available) (ID 13762)

      11:15 - 11:25  |  Author(s): Andrea Bezjak

      • Abstract
      • Presentation
      • Slides

      Background

      PCI is considered standard of care in limited-stage small-cell lung cancer (LS-SCLC) patients. However the impact of the dose and fractionation of thoracic radiotherapy (RT) on the risk of developing brain metastasis (BM) has not been evaluated prospectively.

      Method

      CONVERT is an international, phase 3 trial that randomly assigned patients to receive twice-daily (BD 45Gy in 30 fractions) or once-daily (OD 66Gy in 33 fractions) RT starting on day 22 of chemotherapy (CT) cycle 1 (NCT00433563). PCI was offered, if indicated. Data on thoracic and brain RT delivery and timing, rate of BM and overall survival (OS) in patients treated with PCI was analysed. The association of the risk of developing BM/OS and predictor variables, using a competing risk regression model developed by Fine and Gray for BM or the standard Cox proportional hazards model for OS, was investigated.

      Result

      Of 547 patients recruited to the study, 449 (82%) received PCI after completion of CTRT. PCI was delivered to 220/273 participants (81%) in the BD group and 229/270 in the OD group (85%; p=0.49). Pre-CTRT brain imaging consisted of CT-scan in 356/449 patients (79%) and MRI in 83/449 (18%) patients. Total median PCI dose was 25 Gy in both BD and OD groups (p=0.74). PCI was delivered later after CT in the OD group compared to the BD group (median days post CT 37 vs. 35 days, respectively; p=0.04). In patients who received PCI, 75 (17%) developed BM (35 [8%] in OD and 40 [9%] in BD) and 173 (39%) other extracranial progression. In the univariate analysis, GTV was associated with an increased risk of BM (HR: 1.37 [95%CI 1.09-1.73]; p=0.007) or other radiological progression events (HR: 1.43 [95%CI 1.11-1.85]; p=0.006), whereas in a multivariate analysis both GTV and PS were associated with either progression type. The median OS of patients treated with PCI was 29 months (95%CI 25.8-35.7). Median OS was 28 months in BD (95%CI 22-35) and 31 months in OD (95%CI 27-52; p=0.1). In the univariate analysis of OS, PCI timing from end of CT, weight loss >10%, and thoracic GTV were prognostic factors associated with OS. In the multivariate analysis, only thoracic GTV was associated with OS. Delay between end of CT and PCI was not associated with OS (p=0.2).

      Conclusion

      Patients receiving OD or BD thoracic RT have the same risk of developing BM. Larger tumours are associated with a higher risk of BM.

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    P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.01-03 - Quality of Life Outcomes for FDA-Approved Agents in Advanced Non-Small Cell Lung Cancer (Now Available) (ID 14214)

      16:45 - 18:00  |  Author(s): Andrea Bezjak

      • Abstract
      • Slides

      Background

      Symptom control and quality of life (QoL) improvement are among the most important goals of systemic therapy in advanced NSCLC, but they are not required for regulatory approval. We reviewed published QoL data for agents approved for use in advanced NSCLC by the United States Food and Drug Administration (FDA) and explore their potential uses in the era of precision medicine.

      Method

      Through systematic review, we identified 19 agents approved by the FDA for the treatment of advanced NSCLC between 1999 and 2017. Clinical trials associated with regulatory approval of these agents were identified. QoL results were abstracted from study publications, in addition to trial characteristics (phase, sponsor).

      Result

      46 trials were identified supporting the FDA approval of the 19 agents. Of these, 33 (72%) were phase 3 randomized trials (including 3 cooperative group studies) and 13 (28%) were early phase (I/II) trials. QoL data were reported for 27 trials (59%), including all cooperative group trials. Another 5 (11%) measured QoL but results were not published. The remaining 13 (24%) trials did not measure QoL, 8/13 are phase III, 3/13 phase II and 2 phase I. In trials that reported QoL outcomes, better global QoL and cancer-related symptoms were identified in 17/33 (51%) and 18/33 (55%), respectively. Time to symptom deterioration was reported in 18 (55%) studies, with all but one showing benefit for the approved agent. The remaining studies reported no significant difference in QoL between study treatment arms. All studies reporting improved QoL parameters also reported improved response rates. In trials demonstrating OS and PFS improvement, 3/14 and 10/21 reported better QoL outcomes, respectively. ORR was higher in 26 trials, and it was associated with improvement in QoL in 12/26. Of 12 early phase trials leading to drug approval based on response rate and duration, 6 reported improved QoL outcomes. Three have not yet reported QoL data and 3 did not measure QoL.

      Conclusion

      QoL is clearly associated with response rate but improved QoL or symptom control was only demonstrated in17/33 (51%) and 18/33 (55%) of studies supporting regulatory approval. QoL may be a clinically relevant endpoint for drug approval based on early phase trials of agents with high response rates and should be given further consideration by pharmaceutical sponsors and regulators in this era of precision medicine.

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    PR01 - Press Conference (ID 872)

    • Event: WCLC 2018
    • Type: Press Conference
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/23/2018, 16:00 - 17:30, Room 202 BD
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      Preview of the WCLC/Key Themes/Practice-Changing Abstracts (ID 14871)

      16:05 - 16:13  |  Presenting Author(s): Andrea Bezjak

      • Abstract

      Abstract not provided

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      Welcome (ID 13396)

      16:00 - 16:05  |  Presenting Author(s): Andrea Bezjak

      • Abstract

      Abstract not provided