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C. Ho



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    MA 04 - Advocacy: Listen to the Patients (ID 655)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Patient Advocacy
    • Presentations: 1
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      MA 04.02 - Assessing the Psychosocial Needs of Newly Diagnosed NSCLC Patients: Identifying the Population Most At-Risk (ID 8345)

      11:00 - 12:30  |  Author(s): C. Ho

      • Abstract
      • Presentation
      • Slides

      Background:
      The Psychosocial Screen for Cancer (PSSCAN-R) questionnaire and the Canadian Problem Checklist (CPC) are validated screening tools used to identify the psychosocial needs of patients with cancer. The questionnaire identifies at-risk patients requiring timely psychosocial intervention and the CPC comprises of patient-reported support needs in 6 psychosocial domains. The study goal was to review reported needs of patients with NSCLC to facilitate the development of programs and resources specific to those identified as at-risk for psychosocial distress.

      Method:
      All patients with NSCLC referred to BC Cancer Agency centres from 2011-2015, who completed a prospective PSSCAN-R and CPC questionnaire at the time of their first visit, were included in the study. Demographics and baseline disease characteristics were collected retrospectively. Univariate analysis using the Chi-squared test and Fisher’s exact test were used to compare patient groups based on gender, age and stage of disease.

      Result:
      4313 patients completed the PSSCAN-R and CPC questionnaire. The median age was 70 (21-99), with 50% female and 51% of patients with stage IV disease. 29% of patients live alone with 13% having lost their spouse/partner. However, 93% of patients report regular contact with friends/relatives and 85% have someone who can provide assistance with daily tasks (shopping, cooking, transportation). Female patients, patients aged 65 or younger, and those with advanced disease were more likely to report significantly higher levels of anxiety and depression, and reported higher number of needs on the CPC. Figure 1



      Conclusion:
      Newly diagnosed patients with NSCLC report clinically higher levels of anxiety and depression and have greater number of concerns in multiple psychosocial domains. Resources should be developed for lung cancer patients based on their care needs with careful consideration of patients' age, gender and disease stage to optimally support their psychosocial needs during treatment and follow up.

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    P1.03 - Chemotherapy/Targeted Therapy (ID 689)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Chemotherapy/Targeted Therapy
    • Presentations: 1
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      P1.03-020 - Detection of Hypoxia Using EF5 PET/CT in 10 Patients with Advanced NSCLC Receiving Chemotherapy with and without Bevacizumab (ID 8084)

      09:30 - 16:00  |  Author(s): C. Ho

      • Abstract
      • Slides

      Background:
      Hypoxia is associated with increased resistance to radiation and chemotherapy treatments and may be an important prognostic factor in non-small cell lung cancer (NSCLC). Antiangiogenic drugs such as bevacizumab can have the paradoxical effect of transiently improving perfusion by normalizing blood vessels and reducing interstitial pressure, which may improve chemotherapy delivery and tumor cell killing. The aim of this study was to non-invasively assess tumor hypoxia with [18]F-EF5 PET/CT imaging in patients with advanced-stage NSCLC prior to systemic therapy and to compare changes during and after chemotherapy treatments with and without bevacizumab. [18]F-EF5 is a 2-nitroimidazole-based PET tracer reported as a good surrogate for hypoxia.

      Method:
      Eligibility included patients with incurable stage III/IV NSCLC who were to receive first-line platinum-based doublet chemotherapy alone or in combination with bevacizumab; prior radiation therapy was not allowed. 10 patients completed the study; 5 were treated with standard chemotherapy alone and 5 with chemotherapy plus bevacizumab. Each patient had three [18]F-EF5 PET/CT studies: one baseline pre-treatment, one at day 15 after the first cycle and one post-treatment study after 4-6 cycles of therapy. The investigators reading the PET/CT studies were blinded as to whether patients were treated with bevacizumab or not and no clinical information was available. [18]F-EF5 PET/CT images were acquired from shoulders to upper abdomen and analyzed by calculating tumor-to-muscle (T/M) uptake ratios. A ratio ≥1.50 was considered positive for hypoxia.

      Result:
      A total of 64 lesions were analyzed on baseline [18]F-EF5 PET/CT scans: 42 in the bevacizumab group and 22 in the control group. 51 of these lesions were positive for hypoxia (79.7%): 37 in the bevacizumab group (88.1%) and 14 in the control group (63.6%). Using a Dunn’s multiple comparisons test, there was a significant decrease in [18]F-EF5 uptake only on post-treatment study versus baseline in the group treated with chemotherapy alone (p=0.009). On the other hand, in the group treated with chemotherapy plus bevacizumab, T/M ratios obtained after one cycle of chemotherapy and after treatment completion were statistically lower when compared to baseline (p<0.0001).

      Conclusion:
      Preliminary data suggest that many advanced NSCLC are hypoxic and that the combination of bevacizumab and chemotherapy leads to a greater decrease in [18]F-EF5 accumulation compared to chemotherapy alone in primary tumors and metastatic lymph nodes. Further studies are necessary to understand the clinical significance of this finding and to explore this as a potential predictive marker for the use of bevacizumab.

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    P2.05 - Early Stage NSCLC (ID 706)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Early Stage NSCLC
    • Presentations: 1
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      P2.05-003 - Stage by Stage Comparison of Radiotherapy versus Surgery in NSCLC: The Influence of Prognostic Factors on Survival Outcome (ID 8261)

      09:30 - 16:00  |  Author(s): C. Ho

      • Abstract
      • Slides

      Background:
      Curative intent therapy of stage I-III NSCLC may include surgical resection or definitive radiotherapy. Primary management with surgery or radiotherapy may be influenced by patient and disease characteristics. We sought to perform a stage by stage comparison of patients receiving surgery or radical radiation therapy as their curative treatment, and explore the impact of known prognostic factors on outcome.

      Method:
      A retrospective review was completed of all patients with stage I-III NSCLC referred to the BC Cancer Agency from 2005-2012. Cases were filtered to identify those receiving curative intent therapy including surgery, radiotherapy, and combined chemo-radiation. Information was collected on known prognostic and predictive factors. The primary outcome measure was overall survival.

      Result:
      A total of 3873 patients were referred. Of these, 1744 (45%) received curative therapy (713 surgery, 1031 radiotherapy); 592 (34%) presented with stage I disease, 386 (22%) with stage II, and 766 (44%) with stage III. At the time of analysis, 1199 (69%) patients had died. Median overall survival in stage-matched cohorts was significantly shorter in the radiotherapy group compared to the surgery group (stage I 34.9 mo vs 44.8 mo, p=0.003, stage II 27.6 mo vs 42.7 mo, p=0.014, stage III 26.5 mo vs 38.7 mo, p=0.001). However, in a multivariable analysis incorporating age, sex, weight loss, smoking history, and ECOG status, the survival difference between radiotherapy and surgery disappeared for stage I and II disease and persisted for stage III.

      Univariate and multivariate analysis of prognostic factors and treatment group on survival
      Stage I Stage II Stage III
      UVA HR p-value MVA HR p-value UVA HR p-value MVA HR p-value UVA HR p-value MVA HR p-value
      Age at diagnosis 1.03 <0.001 1.03 <0.001 1.03 <0.001 1.03 <0.001 1.02 <0.001 1.02 0.002
      Male vs female 1.31 0.01 1.24 0.04 1.30 0.04 1.12 0.39 1.14 0.11 1.00 0.99
      Weight loss 5-10% vs <5% >10% vs <5% 2.01 1.40 <0.001 0.11 1.96 1.15 <0.001 0.51 0.96 1.44 0.81 0.06 0.87 1.18 0.46 0.39 1.33 1.56 0.02 0.001 1.35 1.28 0.02 0.08
      Smoking status Former vs never Current vs never 1.78 1.65 0.01 0.04 1.58 1.72 0.06 0.03 2.39 2.73 0.02 0.006 1.85 2.62 0.10 0.01 1.64 1.60 0.003 0.004 1.44 1.32 0.03 0.10
      ECOG >=2 vs 0-1 1.39 0.002 1.18 0.14 1.45 0.007 1.31 0.05 2.06 <0.001 1.98 <0.001
      Radiotherapy vs surgery 1.36 0.003 1.09 0.44 1.37 0.02 1.27 0.07 1.41 0.001 1.36 0.004


      Conclusion:
      In stage I and II NSCLC, the performance of radical radiotherapy and surgery were comparable after controlling for known prognostic factors. Superior survival was observed with surgery in stage III disease however; this may be related to disease characteristics. Surgery and radiotherapy are both viable options for curative intent treatment and selection of the primary modality may relate to underlying patient and disease characteristics.

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    P3.01 - Advanced NSCLC (ID 621)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 3
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      P3.01-013 - CNS Metastases in EGFR Mutation Positive NSCLC: Impact on Health Resource Utilization (ID 8584)

      09:30 - 16:00  |  Author(s): C. Ho

      • Abstract

      Background:
      EGFR mutation positive (EGFRm) NSCLC patients commonly progress in the CNS. We reviewed CNS disease development and its impact on resource utilization and outcomes in EGFRm patients who received first-line EGFR TKI.

      Method:
      Methods: A retrospective review was completed of all advanced EGFR+ patients referred to the BC Cancer Agency and treated with a first/second-generation EGFR TKI from 2010-2015. Baseline characteristics, systemic treatment and CNS management was collected. Comparison was made between the CNS positive (CNS+) and negative (CNS-) patients’ health resource utilization from median time of CNS+ diagnosis to death/last follow-up (8.9 m) and for no CNS metastases group, 9 months preceding death/last follow-up, using the Chi squared test and t-test.

      Result:
      499 patients were identified. Baseline characteristics: Female 68%, median age 66 (30-90), adenocarcinoma 89%, Asian 51%, never/former/current smoker 67/24/9%, exon 19/21/other/not specified 57/37/3/3%. 229/499 patients (46%) developed CNS+; 39% at diagnosis, 61% during the course of disease. Systemic treatment: first-line EGFR TKI 95%, first-line platinum doublet 5%; 40% (202/499) second-line EGFR TKI 24%, second -line platinum doublet 56%, single agent chemo 13%, osimertinib 7%, third-line therapy 47%. CNS+ management: surgery+/-WBXRT 13%, WBXRT alone 73%, SRS+/-WBXRT 5%, no CNS directed therapy 9%. Median time from diagnosis to CNS+ was 7.6 m. Median time from development of CNS+ diagnosis to death was 8.9 m. Median OS was 24m in CNS+ versus 33m in CNS- (p<0.001).

      Events in 9m preceding death or last follow-up (consistent with median time from CNS+ to death) No CNS Metastases n=270 CNS Metastases n=229 p value
      Average number of clinic visits 8.53 12.71 <0.001
      Average number of hospitalizations 0.43 0.76 <0.001
      Average number of CNS imaging investigations 0.52 2.65 <0.001
      Average number of ER visits 0.03 0.14 0.001
      Palliative Care Unit admission 22 (8%) 22 (10%) 0.64
      Hospice admission 9 (3%) 43 (19%) <0.001


      Conclusion:
      The incidence of CNS+ in EGFRm patients is high and associated with increased Health Resource Utilization. Prevention or delay of CNS+ with newer systemic therapy options may result in decreased interactions with health care providers, which may translate into lower resource utilization and cost savings.

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      P3.01-015 - Differential Outcomes between First and Second Generation TKIs in Patients with Activating EGFR Mutations in NSCLC (ID 8667)

      09:30 - 16:00  |  Author(s): C. Ho

      • Abstract
      • Slides

      Background:
      Both first and second generation EGFR tyrosine kinase inhibitors (TKIs) have efficacy in NSCLC with activating EGFR mutations (EGFRM+). Previous studies showed a differential benefit of second generation TKIs based on mutational subtypes but failed to show a difference in overall survival (OS). We aimed to characterize the patterns of use and outcomes of first and second generation TKIs and describe any differences with mutation subtype in the real world setting.

      Method:
      A retrospective review of all advanced EGFRM+ NSCLC patients treated with TKIs between the years 2010-2015 at the British Columbia Cancer Agency was performed. All time to event analyses were performed from date of diagnosis of metastatic disease. Multivariate regressions were performed to examine for associations of OS, treatment and mutation subtypes.

      Result:
      500 patients were eligible for analysis: 283 patients had an exon 19 deletion (del19), 185 had an exon 21 L858R mutation and 32 were not specified or have mutational variants such as G719var. Patient characteristics in the del19 vs. L858R group were similar: 69%/66% were female, 66%/71% were never smokers, 90%/89% were adenocarcinoma, 20%/20% had CNS metastases at diagnosis, 85%/84% had de novo metastatic disease and 41%/37% received ≥2 lines of therapy (all p>0.05). The del19 cohort had less Asians (46% vs 58%, p=0.02) and were younger (median age 63 vs. 69, p=0.02) compared to L858R group. In the del19/L858R cohorts, 81%/19% and 84%/16% received a first and second generation TKI respectively. 43% of patients receiving a second generation TKI required a dose reduction to manage the toxicity and one patient discontinued the medication. OS in the entire cohort was 26 months, with the del19 group surviving longer compared to the L858R cohort (27 vs. 22 months, p<0.01). In multivariate analysis, factors associated with improved OS were del19 (HR0.7, p<0.01 95%CI0.6-0.9), treatment with a second generation TKI (HR0.6, p=0.01 95%CI0.5-0.9) and absence of CNS metastases (HR0.7, p<0.01 95%CI0.5-0.9). First line treatment with a second generation TKI was associated with better OS compared to a first generation TKI (HR0.6, p=0.04 95%CI0.3-1.0). This was statistically significant only in the del19 subgroup (HR0.4, p=0.04 95%CI0.2-1.0).

      Conclusion:
      Use of a second generation TKI in EGFRM+ advanced NSCLC is associated with improved OS in multivariate analyses controlling for other prognostic factors. This was significant in the entire group and in the del19 cohort, supporting the use of mutational subtype to guide therapy decisions.

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      P3.01-030 - CNS Metastases in EGFR Mutation Positive (EGFRm) NSCLC Patients: The Prognostic Relevance of Presenting Symptoms (ID 9135)

      09:30 - 16:00  |  Author(s): C. Ho

      • Abstract

      Background:
      The overall survival (OS) of patients with EGFR mutation positive (EGFRm) lung cancer has changed dramatically due to the combined benefit of targeted systemic therapy, local management of oligometastatic disease and incorporation of judicious use of radiotherapy. We reviewed EGFRm NSCLC patients who were diagnosed with CNS metastasis to determine the prognostic importance of the initial CNS presentation.

      Method:
      A retrospective review was conducted of EGFR+ referred to the BC Cancer Agency between 2010 and 2015, treated with a first/second-generation EGFR TKI who developed CNS metastases (CNSm). Baseline characteristics, presenting symptoms and CNS-targeted treatment data was collected. Cox regression was conducted to determine the prognostic implications of the most common clinical presentations on OS.

      Result:
      229 patients were identified; 90 presented with CNSm and 139 developed CNSm during the course of their disease. Method of CNSm detection: CT only 61%, MRI only 8%, CT and MRI 30%, PET 1%. 80% of patients were symptomatic at CNSm diagnosis. Baseline characteristics: female 66%, median age 62 (34-90), Asian 51%, exon 19/exon 21/rare mutation/not specified 56/39/3/2%. CNS management: 13% surgery+/- whole brain radiotherapy (WBRT), 73% WBRT alone, 5% stereotactic radiosurgery (SRS)+/-WBRT, 9% no CNS directed therapy. OS was 21.6 months in patients who presented with CNSm vs. 27.1 months in those who developed CNSm during the course of disease (p=0.39). On multivariate analysis, the only presenting symptom associated with increased risk of death was cognitive dysfunction.

      Frequency of symptom at presentation Univariate Analysis Multivariate Analysis
      HR P value HR P value
      Cognitive Dysfunction 19% 1.26 0.01 1.21 0.04
      Motor Dysfunction 18% 1.04 0.69
      Balance and Ataxia 11% 1.04 0.46
      Cranial Nerve Changes 8% 0.94 0.65
      Headache and Dizziness 30% 0.94 0.41
      Nausea and Vomiting 13% 0.92 0.48
      Visual Disturbance 10% 0.99 0.97
      Speech and Aphasia 10% 1.19 0.16
      Seizures 7% 0.75 0.09 0.78 0.13
      Leptomeningeal disease 12% 1.25 0.04 1.20 0.10


      Conclusion:
      The most common symptoms at initial presentation of CNSm in EGFRm patients were headache and dizziness, cognitive dysfunction and motor dysfunction. In multivariate analysis, only cognitive dysfunction was associated with poorer survival. Clinicians should have a low threshold for CNS screening based on the varied clinical symptoms experienced by patients