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Timothy G. Whitsett

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    P2.12 - Small Cell Lung Cancer/NET (ID 180)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.12-14 - A Pilot Study of Serial Plasma Metabolomics in Small Cell Lung Cancer Patients (ID 1623)

      10:15 - 18:15  |  Author(s): Timothy G. Whitsett

      • Abstract


      Small cell lung cancer (SCLC) is among the deadliest cancers. SCLC is characterized by high proliferation and high turn-over metabolism. There are few results of metabolomics analysis correlated with outcomes of SCLC patients.


      This study included 27 patients after excluding eight who were treated with immunotherapy or placebo. Median age of the patients was 65 years (range, 43 to 82), and 23 male patients were included. Three (11%) never-smoker patients were included. Twelve patients were limited disease (LD) and 15 were extensive disease (ED) including three patients with brain metastases. All patients were treated with etoposide and platinum (EP, 20 cisplatin and 7 carboplatin), and nine among 12 patients with LD were treated concurrently with radiotherapy since 3rd cycle of EP chemotherapy. We planned to collect blood samples at diagnosis (T1), after two cycles of chemotherapy (T2) and at the first progression (T3). We analyzed 27 T1 samples, 14 T2 samples, and 18 T3 samples. Metabolomics analysis included 183 metabolites (21 amino acids, 19 biogenic amines, 40 acylcarnitines, 14 lysoglycerophosphocholines, 74 glycerophospholipids, and 14 sphingolipids, 1 hexose) using AbsoluteIDQ® p180 kit (Biocrates Life Sciences AG, Innsbruck, Austria).


      Baseline levels of five acylcarnitines and one glycerophospholipid were associated with progression free survival whereas, the amino acid proline and acylcarnitine (C10:1) were associated to overall survival. In comparison to LD, amino acid, asparagine was elevated while two acylcarnitines (C10:2 and C12:1) were lower in patients with ED. After two cycles of chemotherapy without progression, plasma concentration of 37 lipids (5 LysoPC, 24 glycerophospholipids, 3 sphingolipids and 5 acylcarnitines) were increased. Five mono and poly unsaturated glycerophosphospholipids (PC aa and PC ae) with C42 and C44 fatty acid chains were significantly (adj p < 0.05) lower. Of these, chemotherapy and induction of remission induced change in glycerophospholipid PC ae C42:5 was related to overall survival (p < 0.05). The 7 glycerophospholipids with C42 and C44 fatty acids were elevated when patients relapsed post chemotherapy. Five glycerophospholipid metabolites were significantly lower in response to chemotherapeutic exposure. The metabolites tended to increase towards baseline levels upon relapse.


      With this preliminary exploratory study, we identified association of metabolites and initial status and outcomes of SCLC. We observed significant modulation in glycerophospholipids upon chemotherapy and relapse which may serve as indicators of therapeutic response and resistance. Further exploration and validation is being underway in larger SCLC population.