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Michele Orain



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    MA18 - Advances in Diagnosis of Common Types of NSCLC (ID 145)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Pathology
    • Presentations: 1
    • Now Available
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      MA18.06 - Gene Expression and Clustering of Pulmonary Neuroendocrine Tumors at the Border of Low/Intermediate and High Grade Morphology (Now Available) (ID 1096)

      11:30 - 13:00  |  Author(s): Michele Orain

      • Abstract
      • Presentation
      • Slides

      Background

      The WHO classification of lung tumors is based on several features such as cell morphology, cell size, growth patterns, mitotic rate and presence of necrosis. Pulmonary neuroendocrine tumors are stratified into two categories, namely, low/intermediate grade (pulmonary carcinoid tumors) and high grade (pulmonary neuroendocrine carcinomas). Mitotic rate assessment on H&E stained slides play a crucial role in morphological classification of pulmonary carcinoids and high grade neuroendocrine carcinomas. Neuroendocrine tumors with 0-10 mitoses/ 2 mm² are classified as carcinoids and those with mitotic rate higher than 10 mitoses/ 2 mm² as neuroendocrine carcinomas. However, rare tumors which lie on the border of the spectrum with mitotic rates exceeding 10 mitoses/ 2 mm² but falling far below the average mitotic rates of high grade neuroendocrine carcinomas may actually share more molecular characteristics with carcinoids than high grade neuroendocrine carcinomas. The objective of the project was to explore gene expression of those tumors and a potential utility of molecular features in their classification. The study was based on the next generation RNA-sequencing.

      Method

      Five borderline tumors that exceeded the threshold of 10 mitoses/ 2 mm² in 3 hot-spot areas but remained on the lowest end of the spectrum of malignity for large cell neuroendocrine carcinomas (LCNECs) were selected from institutional archives. These tumors were defined by mitotic counts of 11 to 30 mitoses/ 2 mm². Besides, one case with higher mitotic rate in hot-spot zone (42 mitoses/ 2 mm²) but lower than 30 mitoses/ 2 mm² in the other areas was included in a group of borderline tumors. Seven pulmonary carcinoids and 6 LCNECs were selected for control groups. Ki-67 proliferation index and expression of p53 and pRB proteins were assessed by immunohistochemistry. Next generation RNA-sequencing was performed on fresh frozen tissues from all 18 samples on Illumina platform. Then, unsupervised hierarchical clustering was used to stratify the cases.

      Result

      Pulmonary carcinoids and LCNECs clustered into 2 different groups with no overlap. Borderline tumors presented as a heterogenous group where 3 tumors clustered with carcinoids and the other two with LCNECs. Tumors that clustered with LCNECs expressed higher mitotic rate and presented more prominent necrosis. One of 2 cases that clustered with LCNECs had abnormal p53 expression. There were no cases with pRB loss among borderline tumors. For comparison, p53 and pRB expression was preserved in all carcinoid tumors. A subset of tumors in LCNEC group had abnormal p53 expression (strong diffuse expression or complete loss) and pRB loss.

      Conclusion

      Next generation RNA-sequencing coupled with hierarchical clustering analysis allowed to demonstrate that a subset of borderline tumors classified as LCNEC by the current morphology-based WHO classification shows gene expression that is more compatible with pulmonary carcinoids. The data add to the evidence that molecular classification would prove to be a useful tool in stratification of low/intermediate and high grade pulmonary neuroendocrine tumors. However, immunohistochemistry for p53 and pRB is not sufficient for differentiation between pulmonary carcinoid and LCNEC.

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    P1.04 - Immuno-oncology (ID 164)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.04-01 - Body Mass Index and Age Do Not Influence Survival in Patients with Lung Cancers Treated with PD1/PDL1 Immune Checkpoint Inhibitors (ID 2333)

      09:45 - 18:00  |  Author(s): Michele Orain

      • Abstract

      Background

      Age and body mass index (BMI) are important factors in patients treated with chemotherapy. However, in the era of immune checkpoint inhibitors (ICI), the importance of these baseline characteristics is unclear. For example, pooled analysis of age did not influence the clinical response to ICI, whereas patients with BMI >35 had better outcomes in melanoma and renal cell carcinoma. More data are needed to clarify the role of these two characteristics in non-small cell lung cancer (NSCLC) patients amenable ICI.

      Method

      We conducted a retrospective analysis of patients treated with anti-PD1 ICI for advanced NSCLC at the Dijon Cancer Center (n=177), University of Montreal University Hospital (n=106) and Quebec Heart and Lung Institute (n=98). BMI and age were considered as continuous or categorical variables. Patients’ baseline characteristics were compared using the Chi-squared test. Survival curves were estimated by the Kaplan-Meier method and compared with the Log-rank test in a univariate analysis. Multivariate cox regression model was used to determine hazard ratios and 95% confidence intervals for progression-free survival (PFS) and overall survival (OS) between the groups, adjusting for other clinicopathologic features.

      Result

      Among 381 patients included, the median BMI was 24.5 (range 16.2-43.4) and 32.7% and 13.6% were classified as overweight or obese respectively. The median age was 66 (range 37-89) and 29% were older than 70 years-of-age. Considering BMI and age as continuous or categorical variables, they were not associated with PFS or OS, with the exception of BMI in the Dijon cohort (continuous: HR=0.95, 95%CI[0.91-0.99]; < 25 vs > 25: HR=0.68, 95%CI[0.47-0.99]). Subgroup analysis and multivariate cox regression did not reveal significant interaction of these two factors with outcomes. There was no difference in toxicity between the groups. ECOG performance status was the only significant factor in the three cohorts.

      Conclusion

      Unlike previously described in the era of chemotherapy, obesity and age were not associated with outcomes in NSCLC patients treated with ICI.