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Vivianne Ding



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    MA06 - Challenges in the Treatment of Early Stage NSCLC (ID 124)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Now Available
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      MA06.09 - Timing of Driver Mutation Development and the Genetic Evolution of Semi-Solid Lung Nodules into Early NSCLC (Now Available) (ID 2980)

      13:30 - 15:00  |  Author(s): Vivianne Ding

      • Abstract
      • Presentation
      • Slides

      Background

      The genetic changes that drive the appearance of a ground glass opacity and subsequent development of an invasive solid component within a semi-solid lesion (SSL) are not well understood. Biomarkers that predict the transition to invasive cancer are needed to determine when ground glass lesions will evolve into invasive cancer.

      Method

      From a prospective database 65 patients with surgically resected SSL between 2011-2018 were identified. Clinical characteristics and disease free survival was compared between SSL and 155 stage I adenocarcinomas resected during the same time period. Paraffin tissue blocks were obtained from 22 of the SSL and areas of normal lung (NL) ground glass (GG) and solid (S) tumor were identified and microdissected separately from within the same lesion. Next generation sequencing (NGS) was performed on DNA extracted from 19 nineteen matched GG and S samples on twenty-five common lung cancer driver mutations. Affymetrix microarray of over 48,000 transcripts was performed on S, GG, and NL samples from eight patients with SSL.

      Result

      No patients with a resected SSL has recurred to date with significant differences in 5-year disease free survival verses stage I adenocarcinomas from the same time period (100% vs 80.9%, log-rank p-value 0.007). Driver mutations in the solid component of SSL were EGFR mutation (43%; L858R 26% and exon 19 deletion 11%), KRAS mutation (21%), and no mutation identified (42%). All driver mutations present in S component of SSL were also identified in GG regions of the same lesion with very similar gene expression profiles. Only 32 transcripts were significantly different between GG and S areas of the same tumor. The greatest difference observed between GG and S portions of the same tumor was significantly higher expression of secreted phosphoprotein 1 (SPP1) in the invasive solid portion suggesting that SPP1 may serve as a biomarker of invasive potential.

      Conclusion

      This is the first study to examine the systems genetics of mutations and gene expression from the microenvironments of solid and ground glass areas within the same tumor. Mutations are present in the ground glass portion of a semi-solid tumor suggesting early development of driver mutations. Increased expression of SPP1 emerged as the most promising biomarker of invasive potential of a semi-solid lesion. In other studies SPP1 has been shown to correlate with poor prognosis and is a biomarker that warrants further study.

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    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
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      P2.06-09 - Drop the Scalpel: Long-Term Survival in Mesothelioma Without Extrapleural Pneumonectomy or Pleurectomy Decortication (ID 2610)

      10:15 - 18:15  |  Author(s): Vivianne Ding

      • Abstract

      Background

      Survival times following multimodality treatment with extrapleural pneumonectomy (EPP) and pleurectomy decortication (P/D) for malignant pleural mesothelioma (MPM) are poor with a need to identify factors that predict long-term survival.

      Method

      A retrospective single-institution review was performed on all patients who underwent EEP or P/D for histologically confirmed MPM between 1996 and 2015. Patients who underwent a diagnostic biopsy or limited tumor excision were included for survival comparison in a non-operative group (NO). Clinical characteristics, perioperative outcomes, stage, nodal disease, R1 versus R2 resection, treatment modalities, and survival data were collected. The top decile of patients with longest overall survival were studied in subgroup analysis as “long-term survivors.”

      Result

      A total of 206 patients with MPM underwent any type of operations with a median survival time of 13 months (range, 0-134 months) and a 3-year and 5-year survival rates of 15.9% and 8.1% respectively among all patients. Median survival times following EPP (n=28), P/D (n=102) and NO (n=76) were 14 months, 13 months, and 11 months respectively. Better survival was observed in patients with epithelial histology (16 months, n=146) than biphasic histology (7 months, n=28) or sarcomatoid histology (5 months, n=27) (logrank p<.001). Patients with epithelial histology had the greatest median survival times, EPP (29 months, n=23), P/D (16 months, n=77) and NO (16 months, n=46). Three-year and 5-year overall survival rates among patients with epithelial histology were 34.7%, 14.9% after EPP, 16.7, 10.4% after PD and 25.9%, 8.1% after NO, with the patients in the NO group presenting with the most advanced disease. The top decile of long-term survivors all had epitheliod histology and were treated with a variety of chemotherapy regimens leading to a median survival of 64 months with a mean of 71 months. Patients with disease too advanced for surgical resection in the NO group were equally likely to become long-term survivors (9.2%, median survival 57 months) compared with patients who underwent major surgical resection like EPP or P/D (10.0%, median survival 72 months).

      Conclusion

      In this non-randomized retrospective review, patients with MPM too advanced for EPP or PD, who instead underwent palliative limited operations as part of a multimodality treatment regimen had long-term survival rates of approximately 10% that were equivalent to rates of long-term survival following major resections like EPP or P/D. Long-term survival is mesothelioma is therefore more likely determined by outside factors such as disease biology and pace of tumor growth than it is major surgical resection.