Virtual Library

Start Your Search

David Harpole



Author of

  • +

    MA05 - Update on Clinical Trials and Treatments (ID 123)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Mesothelioma
    • Presentations: 1
    • Now Available
    • +

      MA05.03 - Impact of Time to Surgery on Outcomes in Patients Undergoing Outright Resection for Malignant Pleural Mesothelioma (Now Available) (ID 648)

      13:30 - 15:00  |  Author(s): David Harpole

      • Abstract
      • Presentation
      • Slides

      Background

      We hypothesized that a longer interval to surgery would be associated with worse overall survival for patients with malignant pleural mesothelioma (MPM).

      Method

      The National Cancer Database (NCDB) for patients with cT1-3N0-1M0 MPM who underwent surgery without induction therapy. Patients with interval of <1 or >180 days were excluded. Patients were grouped into quartiles based on distribution of time intervals to surgery: Q1 (1-30 days), Q2 (31-50 days), Q3 (51-80 days), and Q4 (>80 days). The primary outcome was overall survival. Secondary outcomes were upstaging to pN2 and margin-positive (>R0) resection rate. Survival was estimated using the Kaplan-Meier and Cox Proportional Hazards methods. Nodal upstaging and >R0 resection rates were modeled with multivariable logistic regression.

      Result

      A total of 812 patients met study criteria. The median interval from diagnosis to surgery was 52 days. The unadjusted median survival for Q1, 2, 3, and 4 was 16, 19, 20, and 27 months, respectively (log-rank p=0.004). In multivariable analysis, increased time to surgery was not associated with worse overall survival (Table 1), and Q4 (>80 days) was independently associated with improved survival compared to Q1. When modeled as a continuous variable, an increased time to surgery was associated with a small but clinically insignificant increase in survival (AHR 0.997; 95%CI 0.995-0.999; p=0.005). In a multivariable regression of factors predicting pathologic upstaging to N2, increased time to surgery was significantly associated with upstaging (adjusted odds ratio [AOR] for Q4 compared to Q1: 2.26; 95%CI 1.04-5.28). In a separate regression of >R0 resection, an increased interval to surgery was not associated with margin-positive resection (AOR 0.70; 95%CI 0.41-1.21).

      Conclusion

      An increasing interval from diagnosis to definitive surgery for MPM was not associated with worse overall survival or margin-positive resection, but was associated with higher likelihood of pathologic nodal upstaging in this analysis.

      Variable

      Adjusted HR

      95% CI

      P value

      Interval (ref:Q1)

      Q2

      Q3

      Q4

      1.07

      0.96

      0.74

      0.84-1.36

      0.76-1.22

      0.58-0.95

      0.61

      0.75

      0.02

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MS07 - Controversies with Stereotactic Radiation in Early Stage Lung Cancer (ID 70)

    • Event: WCLC 2019
    • Type: Mini Symposium
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Now Available
    • +

      MS07.01 - Preoperative Optimazition: Reducing Surgery Complications Through Tobacco Cessation (Now Available) (ID 3474)

      14:00 - 15:30  |  Presenting Author(s): David Harpole

      • Abstract
      • Presentation
      • Slides

      Abstract

      Optimizing Outcomes after Pulmonary Resections with Smoking Cessation

      Data on increased risk of complications after major thoracic surgery for current smokers has been documented for several decades, suggesting that smoking cessation for even a few weeks may significantly reduce this risk based on early return of muco-ciliary clearance of respiratory secretions and decreased risk of atelectasis and pneumonia. Moreover, the awareness of potential lung cancer mortality on patients is a potent “teachable moment” for a smoking intervention. However, the literature is anything but definitive on:

      1. Method of smoking cessation / counseling (including pharmacological and non-pharmacological adjuncts)

      2. Length of time required for maximal risk reduction

      3. Durability of cessation after surgery

      This presentation will review the strongest trials in the literature, as well as recent data on a concerted risk reduction programs of Enhanced Recovery from surgery (ERAS) that include smoking cessation.

      References:

      Stokes SM, Wakeam E, Antonoff MB, Backhus LM, Meguid RA, Ordell D, Varghese TK. Optimizing health before elective thoracic surgery: systematic review of modifiable risk factors. J Thorac Dis 11: S537-554; 2109

      Sardari NP, Weyler J, Colpaert C. Prognostic value of smoking status in operated NSCLC. Lung Cancer 47:351-9; 2005

      Mills E, Eyawo O, Lockhart I. Smoking cessation reduces perioperative complications: A systematic review and meta-analysis. Am J Med 124:144-8; 2011

      Kozower BD, Lau CL, Philllips JV. Thoracic surgeon-directed tobacco cessation intervention. Ann Thorac Surg 89:926-30, 2010

      Thomasen T, Abrishami A, Yang Y. Interventions for perioperative smoking cessation. Cochrane Database Syst review 3:CD002299; 2014

      Lugg ST, Tikka T, Agostini PJ, Kerr A, Kalkat MS et al. Smoking and timing of cessation on postoperative complications after curative-intent lung cancer surgery. J Cardiothorac Surg 12:52-60; 2017

      Rodriguez M, Gomez-Hernandez MT, Novoa N, Jimenez MF, Aranda JL. Refraining from smoking shortly before lobectomy has no influence on the risk of pulmonary complications. Eur J Cardiothorac Surg 51:498-503; 2017

      Zaman M, Bilal H, Mahmood S, Tang A. Does getting smokers to stop smoking before lung resections reduce their risk? Interact Cardiovasc Thorac Surg. 14:320-323; 2012

      Gemine RE, Ghosal R, Collier G, Parry D, Campbell I, Davies G, Lewis KE. Longitudinal study to assess impact of smoking at diagnosis and quitting on 1-year survival for people with NSCLC. Lung Cancer 129:1-7; 2019

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    OA13 - Ideal Approach to Lung Resection and Novel Perioperative Therapy (ID 146)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Now Available
    • +

      OA13.01 - SPECS2 Lung Cancer Consortium Prospective Multicenter Validation of Prognostic Signature for Early Stage Squamous Lung Cancer (Now Available) (ID 2723)

      11:30 - 13:00  |  Author(s): David Harpole

      • Abstract
      • Presentation
      • Slides

      Background

      Squamous Lung Cancer (SC) which constitutes 30% of all non-small cell lung cancers (NSCLC) has few targeted therapy options for advanced disease. Surgery for early SC is the best treatment strategy; however, even patients who undergo surgery for stage IA or IB disease are still at a substantial risk for recurrence and death. Adjuvant therapy is not currently indicated for stage I SC smaller than 4 cm. Prior reports suggest gene expression-based signatures that may predict recurrence in patients with stage I SC, but none has been validated or is in clinical use. The SPECS2 Lung Cancer Consortium was assembled to compare and attempt to validate previously published prognostic signature(s) according to the guidelines proposed by Subramanian and Simon (J Natl Cancer Inst 2010; 7:327).

      Method

      The multi-institutional team assembled 249 frozen SC samples representing six participating institutions (cohort 1). These samples were fully annotated in a redcap database hosted by the independent statistical core. Cohort 2 was assembled utilizing 234 frozen SC samples from a prospective multi-institutional NCTN lung biobanking protocol (NCT00899782). RNA was extracted and profiled with U133A microarrays (Affymetrix) in independent core facilities. The data was transferred directly to the SPECS2 Lung statistical core in collaboration with the Alliance Statistical core and the performance of 6 most promising candidate signatures was evaluated relative to a base model that included only age, gender and AJCC stage (editions 6, 7, 8).

      Result

      Analysis of Cohort 1 demonstrated that only one signature (Raponi et al, Cancer Res 2006; 66:7466) significantly enhanced prognosis relative to the base model, independent of AJCC edition. This was also observed in Cohort 2, where Uno’s C index associated with AJCC 8th edition stage, sex and age (0.561; 0.468-0.654) was significantly (p <0.05) increased when the prognostic signature was added to the model (0.683; 0.611-0.755).

      Conclusion

      The SPECS2 Lung Cancer Consortium was successful in validating a previously published prognostic molecular signature for early stage SC using rigorous experimental design. To our knowledge, this is the first unbiased validation of a lung cancer prognostic signature using multi-institutional prospective specimens. These results support a clinical trial designed to evaluate the potential role of adjuvant therapy in completely resected early stage SC.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P1.18 - Treatment of Locoregional Disease - NSCLC (ID 190)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
    • +

      P1.18-02 - The AEGEAN Phase 3 Trial of Neoadjuvant/Adjuvant Durvalumab in Patients with Resectable Stage II/III NSCLC (ID 1375)

      09:45 - 18:00  |  Author(s): David Harpole

      • Abstract

      Background

      For patients (pts) with early stage non-small cell lung cancer (NSCLC) (Stages I–IIIA) surgery is the primary treatment. Adjuvant and neo-adjuvant chemotherapy (CTx) are both accepted approaches for resectable NSCLC, and result in modest but clinically meaningful improvements in overall survival (OS) compared with surgery alone; nevertheless, recurrence rates remain high and improved therapies are needed. Checkpoint inhibitors that block programmed death 1 (PD-1)/PD ligand 1 (PD-L1) have shown benefit as monotherapy and in combination with CTx in NSCLC. Durvalumab (durva), a selective, high-affinity, human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80, significantly improved progression-free survival and OS in pts with unresectable Stage III NSCLC who did not progress following chemoradiotherapy (Antonia et al, NEJM 2017; 2018). The AEGEAN study (NCT03800134) will assess the activity and long-term clinical outcomes of durva plus CTx prior to surgery, as well as further administration of durva post-surgery, in pts with resectable Stages II and III NSCLC.

      Method

      The AEGEAN trial is a Phase 3, double-blind, placebo-controlled, multi-center study. Approximately 300 pts with resectable Stage II and III NSCLC will be randomized 1:1 to receive either durva (1500 mg intravenously) or placebo every 3 weeks (wks) alongside platinum-based CTx (4 cycles) prior to surgery, followed by either durva or placebo alone every 4 wks for an additional 12 cycles post-surgery. Pts will be stratified by disease stage and PD-L1 expression levels (<1% vs ≥1%); the number of pts with EGFR/ALK mutations will be capped at 20%. Tumor size (according to RECIST v1.1 criteria) will be evaluated at completion of neo-adjuvant CTx prior to surgery, every 12 wks for the first year; every 24 wks for 2–4 years; then yearly thereafter. The primary endpoint is major pathological response (≤10% residual viable tumor in the resected primary lung tumor after neoadjuvant treatment) in the full analysis set (FAS). Secondary endpoints include safety assessments, a range of efficacy measures including complete pathological response (FAS and PD-L1-TC ≥1%) and OS, pt-reported outcomes, durva pharmacokinetics and immunogenicity. This trial is currently recruiting.

      Result

      Section not applicable

      Conclusion

      Section not applicable

  • +

    P2.06 - Mesothelioma (ID 170)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Mesothelioma
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
    • +

      P2.06-03 - Timing of Surgery After Induction Therapy for Malignant Pleural Mesothelioma: A National Analysis  (ID 649)

      10:15 - 18:15  |  Author(s): David Harpole

      • Abstract

      Background

      The safe window to offer surgery following induction chemotherapy for malignant pleural mesothelioma (MPM) is unknown.

      Method

      The National Cancer Database (NCDB) was queried for patients with cT1-3N0-1M0 MPM undergoing induction chemotherapy followed by definitive surgery. Patients with induction radiation, missing survival data, and time to surgery <1 or >180 days were excluded. Patients were stratified into quartiles based on time from chemotherapy to surgery: Q1 (<85 days), Q2 (85-100 days), Q3 (101-120 days), and Q4 (>120 days). The primary outcome was overall survival, and secondary outcomes were pN2 disease and margin-positive (>R0) resection. Survival was modeled with Kaplan-Meier and Cox Proportional Hazards, and upstaging and >R0 resection with multivariable logistic regression.

      Result

      A total of 205 patients were included, with a median time from induction therapy to surgery of 104 days. There was no difference in unadjusted median survival between the groups: 23 (Q1), 25 (Q2), 25 (Q3), and 20 (Q4) months (log-rank p=0.92). In multivariable regression, increasing time to surgery was not associated with survival examined by quartile (Table) or as a continuous variable (adjusted hazard ratio [AHR] 1.00; 95% confidence interval [CI] 0.99-1.01). Increasing time to surgery was also not associated with increased pathologic upstaging to N2 (adjusted odds ratio [AOR] for Q4 vs. Q1: 1.22; 95%CI 0.33-4.65). In a multivariable regression, increased time from chemotherapy to surgery was not associated with >R0 resection (AOR 0.81; 95%CI 0.23-2.87 for Q4 vs. Q1).

      Conclusion

      Increased time from induction therapy to surgery for MPM was not associated with worse survival, nodal upstaging, or margin-positive resection in this study. Patients with MPM can be safely offered surgery even three months after induction chemotherapy.

      Variable

      Adjusted HR

      95% CI

      P value

      Interval (ref:Q1)

      Q2

      Q3

      Q4

      0.83

      0.92

      1.08

      0.49-1.40

      0.55-1.53

      0.61-1.92

      0.49

      0.74

      0.79