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Alexandra Rice



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

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Mesothelioma
    • Presentations: 1
    • Now Available
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      MA05.01 - Second or Third Line Anti-PD-1 Therapy After Multimodality Therapy Including Total Pleurectomy in Malignant Pleural Mesothelioma (Now Available) (ID 1955)

      13:30 - 15:00  |  Author(s): Alexandra Rice

      • Abstract
      • Presentation
      • Slides

      Background

      Surgical resection plays an important role in the management of selected patients with malignant pleural mesothelioma (MPM). Early experience with anti-PD-1 immunotherapy showed promise in MPM, but it is yet uncertain if it can improve outcomes when tumour relapses following surgical resection, radiotherapy and chemotherapy. We reviewed our experience in patients who received Pembrolizumab or Nivolumab following multimodality therapy.

      Method

      Retrospective study including patients with histologically-proven MPM having completed multimodality therapy and received anti-PD-1 immunotherapy as 2nd or 3rd line treatment. Data were retrieved from a prospective mesothelioma database. Histopathology, BAP1, MTAP and PD-L1 (22C3) immunohistochemistry were performed on surgical specimens and reported by a senior pathologist. All patients had chest computed tomography and positron emission tomography (PET-CT) as part of their normal follow-up. Response evaluation was determined using RECIST 1.1 criteria.

      Result

      16 patients received anti-PD-1 immunotherapy between August 2015 and March 2019. All patients had total pleurectomy/decortication, prophylactic radiotherapy (21Gy/3) and systemic chemotherapy based on pemetrexed and platinum. Median age was 68.5 years, with male predominance (13/16). 56% had epithelioid type, 44% had biphasic type. Median time to starting immunotherapy was 20 months (range 11-42) following surgery. Median ECOG performance status was 0. Twelve patients received Pembrolizumab and 4 received Nivolumab. Median number of cycles of anti-PD-1 therapy received was 5 (range 1-33). Disease control rate at 12 weeks was 56.2% and 7 (43.7%) patients had disease progression. Adverse events were observed in 6 patients (one Grade 3). Eight patients were alive by 1st April 2019. Median OS from starting immunotherapy was 13.5 months. Three patients received treatment for 14 months or more. Five patients started further therapy after discontinuing immunotherapy.

      Conclusion

      In our cohort, second or third-line anti-PD-1 immunotherapy showed efficacy with DCR comparable to non-surgical setting. Further studies are warranted to validate our preliminary findings.

      wclc 2019 figure 1anti pd1.jpg

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    MA12 - New Frontiers from Pathology to Genomics (ID 138)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Mesothelioma
    • Presentations: 1
    • Now Available
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      MA12.02 - Growth Patterns in Epithelioid Malignant Pleural Mesothelioma: A Clinicopathological Review of 614 Cases Over 15 Years (Now Available) (ID 1595)

      14:00 - 15:30  |  Author(s): Alexandra Rice

      • Abstract
      • Presentation
      • Slides

      Background

      Nuclear grading system has been validated as a powerful prognostic tool for epithelioid malignant pleural mesothelioma (MPM) whilst growth patterns had demonstrated prognostic value in earlier studies. We aim to externally validate the previous findings and evaluate the utility of a composite architecture-nuclear grade scoring system.

      Method

      We retrospectively reviewed 614 consecutive cases of epithelioid MPM diagnosed at our institution over a 15-year period. Clinicopathological information including predominant growth pattern (Solid, Tubulo-papillary, Trabecular, Micropapillary, Microcystic, Discohesive, Pleomorphic) and 2-tier nuclear grade were retrieved from an institutional mesothelioma database. The tumours were categorised into High Grade (Solid, Micropapillary, Score=1) and Low Grade (All others, Score=0). A composite score (0-2) was generated based on growth pattern and 2-tier nuclear grade (0-1). Survival analysis was performed using Kaplan-Meier method.

      Result

      Pleomorphic epithelioid MPM was associated with the worst median overall survival (5.4 months), followed by micropapillary- (6.2 months), solid- (10.5 months), microcystic- (15.3 months), discohesive- (16.1 months), trabecular- (17.6 months) and tubulo-papillary- (18.6 months) patterns. The composite scoring system further improved stratification of overall survival based on 2-tier nuclear grade (19.8 vs. 13.4 vs. 8.1 months, p<0.001).

      growth patterns (except cribriform_wdpm).jpg

      composite architecture-ng score v2.jpg

      Conclusion

      Epithelioid MPM growth patterns predicted survival in our cohort. Composite architecture-nuclear grade scoring system further improved prognostic stratification.

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    P1.06 - Mesothelioma (ID 169)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Mesothelioma
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.06-08 - WDPM-Like but Not Cribriform as Secondary Growth Patterns Modify Survival in Epithelioid Malignant Pleural Mesothelioma (ID 1609)

      09:45 - 18:00  |  Author(s): Alexandra Rice

      • Abstract
      • Slides

      Background

      The presence of well differentiated papillary mesothelioma (WDPM)- like and cribriform growth patterns in otherwise unequivocally invasive, tubulo-papillary-predominant epithelioid malignant pleural mesothelioma (MPM) is recognised in clinical practice, but their prognostic impact is largely uncertain. We hypothesise they modify prognosis as secondary patterns.

      Method

      We retrospectively reviewed the tubulo-papillary-predominant, invasive epithelioid MPM (n=269) as a subset of 614 consecutive epithelioid MPM diagnosed at our institution over a 15-year period. The diagnostic criteria for WDPM-like and cribriform patterns were inferred from those of canonical WDPM and lung adenocarcinoma. Survival analysis was performed using Kaplan-Meier method.

      Result

      We identified 10 cases of tubulo-papillary-predominant epithelioid exhibiting WDPM-like pattern, and one case being predominantly WDPM-like (Estimated incidence 4.1%). They are associated with significantly prolonged median overall survival (78.7 months vs. 18.0 months, p=0.001). On the other hand cribriform neither as predominant (n=9, 3.3%, p=0.672) or secondary growth patterns (n=46, 17.1%, p=0.952) achieved statistical significance in univariate setting compared with tubulo-papillary epithelioid MPM without such pattern.

      wdpm-like.jpg

      cribriform pattern (predominant and secondary).jpg

      Conclusion

      We propose tubulo-papillary-predominant epithelioid MPM with WDPM-like features as a rare and favourable prognostic group. Further molecular analysis is planned. Cribriform pattern does not appear to be prognostically relevant. We recommend external validation of our findings for both growth patterns.

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    P1.13 - Staging (ID 181)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Staging
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.13-11 - An Audit on IASLC Compliance of Lymph Nodes Dissection and Impact on Survival After Surgery for Non-Small Cell Lung Cancer (ID 196)

      09:45 - 18:00  |  Author(s): Alexandra Rice

      • Abstract
      • Slides

      Background

      The IASLC proposed minimal criteria for 6 nodes / stations to ascertain certainty status of complete (R0) resection after lung cancer surgery and in 2017, Edwards et al presented that failure of compliance leading to R0 (un) status was associated with poorer survival.

      The aims of this audit are to assess compliance of the IASLC recommendations on lymph node staging and determine the impact of R0 (un) status on prognosis in an independent cohort.

      Method

      We included patients who underwent lobectomy or pneumonectomy for primary lung cancer. Data was obtained from electronic records and survival status obtained from NHS Spine.

      Result

      From January 2010 to December 2017, 2,521 patients underwent lung resection for primary lung cancer staged using TNM7. The mean age (SD) was 67 (10) and 1,235 (49%) were men, the primary diagnoses were either adenocarcinoma or squamous carcinoma in 2,057 (82%).

      The IASLC compliance with 6 node / stations was 627 (25%) and when sub-carinal station was mandatory it was 608 (24%). After exclusions, we were left with 1,859 patients and on adjustment of T and N category, there was no difference between IASLC non-compliance R0 (un) on overall survival with a hazard ratio of 0.95 (95% CI 0.74 to 1.21; P=0.657) compared to R0 compliant.

      After adjusting for T and N category there was no significant difference in total lymph nodes stations harvested with a HR 1.01 (0.97 to 1.04, P=0.712) or number of positive stations HR 1.04 (0.92 to 1.16; P=0.543) in survival.

      lymph node.png

      Conclusion

      Independent validation of R0 (un) status did not concur with poorer survival. The designation carries uncertainty and likely to be influenced by the extent of N2 dissection. When adjusted for stage, there was no difference on number of stations harvested nor the total number of positive stations on survival.

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