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David Small



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    MA09 - Lung Cancer Surgical and Molecular Pathology (ID 908)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Pathology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 15:15 - 16:45, Room 202 BD
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      MA09.09 - EBUS-TBNA in Assessing PD-L1 Expression in NSCLC (ID 13471)

      16:15 - 16:20  |  Author(s): David Small

      • Abstract
      • Presentation
      • Slides

      Background


      Pembrolizumab is the only immunotherapy approved as a first line agent for metastatic NSCLC in patients with high programmed death‐ligand 1 (PD‐L1) expression. The standard samples for PD-L1 testing are considered surgical or core biopsies. In this study, our primary objective is to identify the adequacy of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS TBNA) tumor samples in detecting PD-L1 expression.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Between July 2016 and April 2017 a total of 1352 consecutive cases of non-small cell lung cancer (NSCLC) were identified. 29 specimens were deemed inadequate (less than 100 viable tumor cells) and were excluded. 1323 specimens analyzed included surgical samples (N=238), small biopsy (N=744) and cytology cell blocks (N=341). Cytology cell blocks were from EBUS-TBNA (N=190), fine needle aspiration (FNA) (N=61) and pleural/pericardial fluid (N=90). PD-L1 expression was examined by staining with Dako PD-L1 IHC 22C3 pharmDx kit. A Tumor Proportion Score (TPS) was categorized as <1%, 1-49% and ≥ 50% tumor cells.

      4c3880bb027f159e801041b1021e88e8 Result

      Most of the 1323 specimens (84%) were non-squamous carcinomas. Overall yield for TPS > 50% was 36%. Rate of PD-L1 positivity was no different in non-squamous (37%) compared to squamous (32%). Diagnostic yield of PD-L1 for different sample types varied substantially (Table 1). The EBUS-TBNA samples had the highest yield for TPS ≥ 50% (p=0.025).

      TPS Surgical resection Small biopsy EBUS-TBNA FNA Fluid cytology Total
      Adequacy 100% 99% 98% 96% 92% 98%
      ≥ 50% 69 (29) 269 (36) 84 (44) 21 (34) 38 (42) 481
      1-49% 87 (37) 274 (37) 57 (30) 22 (36) 22 (24) 462
      <1% 82 (35) 201 (27) 49 (26) 18 (30) 30 (33) 380
      Total 238 744 190 61 90 1323
      8eea62084ca7e541d918e823422bd82e Conclusion

      Our results show that cytology cell blocks could be considered as a valuable resource for PD-L1 testing in advanced NSCLC. Future studies are warranted to explore clinical correlation of PD-L1 on EBUS-TBNA samples and immunotherapy outcome.

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    P1.04 - Immunooncology (Not CME Accredited Session) (ID 936)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.04-16 - Comparison of Clinical Response to Checkpoint Inhibitors in Advanced NSCLC with High PD-L1 Expression Tested on Cytology Versus Biopsy Samples (ID 12525)

      16:45 - 18:00  |  Author(s): David Small

      • Abstract
      • Slides

      Background

      PD-L1 immunohistochemistry (IHC) expression correlates with clinical response to checkpoint inhibitors in advanced-stage NSCLC. PD-L1 IHC testing is usually performed on tissue blocks from core needle biopsy or surgical resection, but appears to be feasible on cytology cell blocks as well. In this retrospective study, we assessed the clinical response to checkpoint inhibitors in patients with NSCLC and high PDL1 IHC expression on cytology specimens in comparison with tissue biopsy specimens.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Between August 2015 and April 2018, 116 patients with NSCLC received immunotherapy at our institution. Only cases with known PD-L1 expression from IHC testing performed on small biopsies or cytology cell blocks were included. A total of 65 consecutive cases were reviewed, including 40 small biopsies and 25 cytology samples. A Tumor Proportion Score (TPS) was categorized as high (≥ 50% tumor cell staining) or low (<50%). Response to treatment was categorized as disease control (DC, including complete and partial response and stable disease) or progression (PD). The primary outcome was the rate of disease control.

      4c3880bb027f159e801041b1021e88e8 Result

      Patients were mostly current or ex-smokers (91%), Caucasians (82%) and non-squamous carcinomas (85 %). High TPS was seen in 44 (68%) cases. Immunotherapy was given in the first line setting in 20 (31%) patients, the second line in 36 (55%), and the third line in 9 (14%). 50 (77%) patients received Pembrolizumab, 10 (15%) Nivolumab and 5 (8%) others received immunotherapies on RCTs. Overall, there was DC in 40 (62%) patients and PD in 17 (26%). There was no significant difference in DC rate between the cytology and the small biopsy groups in high TPS group.

      table 1.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      PD-L1 expression on cytology cell blocks and on small biopsies appears to have similar clinical significance. Further prospective trials are needed to confirm these findings.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.09 - Pathology (Not CME Accredited Session) (ID 958)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.09-07 - Does Metastatic Site Matter for PD-L1 Testing in Stage IV NSCLC? (ID 13385)

      16:45 - 18:00  |  Author(s): David Small

      • Abstract
      • Slides

      Background

      Stage IV non-small cell lung cancer (NSCLC) often presents with metastasis to multiple distant sites. Currently PD-L1 expression by immunohistochemistry (IHC) testing with Tumor Proportion Score (TPS) ≥ 50% and ≥1% is required for first- and second-line Pembrolizumab treatment respectively. However, it is not well known if PD-L1 expression differs in NSCLC specimens sampled from different distant metastatic sites. In this study, we evaluate PD-L1 expression in distant metastatic sites.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A total of 400 NSCLC specimens from distant metastatic sites are included in this study. The metastatic sites include brain, bone, non-regional lymph nodes, serous membranes (pleura, pericardium and peritoneum) and organs outside the chest (liver, adrenal gland, skin, soft tissue). The samples are either cytology cell blocks, small biopsies or surgical resections. IHC was performed using Dako PD-L1 IHC 22C3 pharmDx. A total of 100 viable tumor cells is required for adequacy. TPS≥ 50% and 1-49% are defined as high and low PD-L1 expression respectively.

      4c3880bb027f159e801041b1021e88e8 Result

      Overall, the rate of TPS >50% ranges from 36-47% in different metastatic organ sites (Table 1). The prevalence of PD-L1 high and low expression is similar for all distant metastatic sites (P=0.91). Brain metastases have a slightly lower rate of high PD-L1 expression but the difference is not statistically significant.

      Table 1. PD-L1 expression in different metastatic sites

      Metastatic sites

      Tumor Proportion Score (TPS)

      Total

       

      ≥50%

      n (%)

      1-49%

      n (%)

      0%

      n (%)

      n (%)

      Brain

      13(36%)

      9 (25%)

      14(39%)

      36 (100%)

      Bone

      21(44%)

      11(23%)

      16(33%)

      48 (100%)

      Nonregional lymph nodes

      6(40%)

      3(20%)

      6 (40%)

      15 (100%)

      Serous membranes

      91(40%)

      62(27%)

      74(33%)

      227 (100%)

      Organ outside chest

      35(47%)

      20(27%)

      19(26%)

      74 (100%)

      Total

      166(42%)

      105(26%)

      129(32%)

      400 (100%)

      P=0.91

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our results suggest that the specimens for PD-L1 IHC testing can be sampled from any accessible distant metastatic site.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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