Virtual Library

Start Your Search

Simon Knight



Author of

  • +

    OA08 - Mesothelioma: Immunotherapy and microRNA for Diagnosis and Treatment (ID 907)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Mesothelioma
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 15:15 - 16:45, Room 201 BD
    • +

      OA08.05 - Quantifying Tumour Infiltrating Lymphocytes (TILs) in Malignant Pleural Mesothelioma (MPM) -Defining the Hot, the Warm and the Cold Tumours. (ID 13326)

      16:00 - 16:10  |  Author(s): Simon Knight

      • Abstract
      • Presentation
      • Slides

      Background

      Immunological infiltrates into tumor tissues have been associated with improved prognosis in many cancers including breast, colorectal, cervical, melanoma and lung. While most studies evaluating TILs have been based on evaluation of individual types of T lymphocytes, more recently, a morphological assessment of the TILs based on a simple hematoxylin & eosin (H&E) slide examination has been shown to be an independent positive prognostic factor in HER2 positive early stage breast cancer and lung cancer. We used similar methods to explore the immune microenvironment in a large mesothelioma cohort.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Using full face sections of MPM tumour samples, we assessed lymphocytes infiltrating tumour stroma.TILs score was calculated as a % of stromal area assessed to be covered by TILs by an experienced pathologist. Tissue microarrays (TMA) were constructed and stained with PD-L2, LAG3 and TIM3 antibodies. These data were combined with PD-L1 expression, CD4+ and CD8+ infiltration in the same cohort reported previously. We explored the clinical and pathological correlates of the level of TILs.

      4c3880bb027f159e801041b1021e88e8 Result

      Amongst 329 patients evaluated, 308 samples were evaluable for TILs characterisation. The scores ranged from 0-90 (median 30). Stratified using tertiles, 142 patients had low TILs, 68 had medium and 98 had high TILs. High TILs were seen in patients who were PD-L1 (Chi square test p = 0.002) and PD-L2 positive (Chi square test p <0.0001) and of non-epithelioid histological subtype (Fischer’s exact test p = 0.01). On univariate analysis, PD-L2 positivity (HR = 3.2; CI = 2.2-4.6; Log rank P < 0.0001), high TILs (HR = 2.03; CI = 1.5-2.6; Log rank P < 0.0001), and high TIM3+ lymphocytes (HR = 1.3; CI = 1.0-1.7; Log rank P < 0.04) were found to be related to poorer overall survival (OS). On multivariate analysis, higher TILS was found to remain significantly associated with poorer OS along with non-epithelioid histology and poor physiological status.

      8eea62084ca7e541d918e823422bd82e Conclusion

      High TILs correlated with non-epithelioid histology and greater expression of PD-L1 and PD-L2. In contrast to other tumor types, a high TIL infiltrate was negatively prognostic.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      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.

  • +

    P1.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 948)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
    • +

      P1.16-58 - Hospital Lung Surgery Volume and Patient Outcomes in Victoria (ID 12674)

      16:45 - 18:00  |  Author(s): Simon Knight

      • Abstract

      Background

      Surgical resection remains the primary curative option for early stage non-small cell lung cancer (NSCLC) with lobectomies considered the gold standard due to a reduction in local recurrence and improved overall survival. There has been growing evidence of an association between patient outcomes and the number of cancer surgeries performed at a hospital since the seminal paper by Luft et al in 1979.

      To our knowledge, there are no Australian data on hospital cancer surgery volumes and patient outcomes by procedure, and few data worldwide on specific lung surgery procedures and outcomes. We evaluated the relationship between hospital NSCLC surgery volume and patient outcomes in Victoria.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Victorians with a primary diagnosis of NSCLC between 2008 and 2014 were identified in the Victorian Cancer Registry (n=15,469), 3,420 (22%) of whom had surgery. Primary outcome was death within 90 days of surgery and secondary outcomes were overall survival, use of postoperative ventilation, ≥24hours spent in ICU and length of stay >17days. Hospital volume was measured as the average number of lung surgeries performed per year, with quartiles Q1: 1-17, Q2: 18-34, Q3: 35-58 and Q4: 59+.

      4c3880bb027f159e801041b1021e88e8 Result

      57% (1,941/3,420) lung cancer patients underwent lobectomy, 38% (1,299/3,420) sub-lobar resection and 5% (180/3,420) pneumonectomy. The overall 90-day mortality after lung surgery was 3.5%, and was 2.6% for patients undergoing lobectomy compared with 4.5% for those undergoing sub-lobar resection. There was no difference in 90-day mortality between low- and high-volume centres regardless of procedure. Patients operated in lower volume centres had more admissions to ICU ≥24hours (Q1. 55% vs. Q4. 11%, p-trend <0.001). Median overall survival was 6.2 years, 5.4 years and 5.8 years for lobectomy, sub-lobar resection and pneumonectomy, respectively. The distribution of ASA scores differed between patients attending public and private hospitals. A higher proportion of patients attending private hospitals (19%) had an ASA score of 4 compared with patients attending a public hospital (9%).

      8eea62084ca7e541d918e823422bd82e Conclusion

      We observed no evidence of survival differences between lung cancer patients attending low- and high-volume hospitals for surgery, regardless of surgical procedure. Median overall survival in Victorian is substantially better compared to interstate and international data. Of interest, a higher proportion of patients had an ICU admission ≥24hours in lower volume centres. We also observed a higher proportion of patients with an ASA score of 4 in private hospitals compared to public hospitals; the reasons for this are unclear and warrant further investigation.

      6f8b794f3246b0c1e1780bb4d4d5dc53