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L. Thiberville



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    MO03 - Thymic Malignancies (ID 123)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO03.03 - RYTHMIC: a nationwide network for thymic malignancies in France (ID 2631)

      10:30 - 12:00  |  Author(s): L. Thiberville

      • Abstract
      • Presentation
      • Slides

      Background
      RYTHMIC (Réseau tumeurs THYMiques et Cancer) is a nationwide network for thymic malignancies, which was appointed in 2012 by the French National Cancer Institute, as part of its rare cancer program. The objectives of the network include a territorial coverage by regional expert centers, the dissemination of highest standards for the diagnostic and therapeutic management of patients, and the promotion of collaborative research. Registration in RYTHMIC of all patients diagnosed with thymic malignancy is recommended as part of good clinical practice for oncologists.

      Methods
      Starting January 2012, the management of all patients diagnosed with thymic malignancy in France has been discussed on a real-time basis at a reference national multidisciplinary tumor board (MTB), which is organized twice a month using a web-based conferencing system. Decision-making is based on consensual recommendations, that were originally established using available evidence, and are updated and approved each year by all members of the network. A prospective database of all patients is hosted by the French Thoracic Cancer Intergroup. We report the characteristics and treatment modalities of patients included during the first year.

      Results
      From January to December 2012, 257 patients were enrolled in RYTHMIC. There were 126 (49%) men and 131 (51%) women; mean age at diagnosis was 54.5 years. Among 214 cases, histology was thymoma for 146 (56%) patients (11 (5%) type A, 28 (13%) type AB, 22 (10%) type B1, 35 (16%) type B2, 24 (11%) type B3, 26 (12%) mixed type), and thymic carcinoma for 33 (15%) patients, 8 of which were neuroendocrine carcinomas; other histologies were diagnosed for 35 (16%) patients. Among 144 cases, Masaoka-Koga stage was I, IIA, IIB, III, IVA, and IVB in 34 (24%), 19 (13%), 20 (14%), 22 (15%), 35 (24%), and 14 (10%) patients, respectively. 44 (17%) patients presented with autoimmune disorder, consisting of myasthenia gravis in 28 cases. Surgery was performed for 166 patients, mostly using a median sternotomy approach (52% of cases). Postoperative radiotherapy was delivered to 42 patients; 71 patients received perioperative chemotherapy. Exclusive chemotherapy/radiotherapy was administered to 20 and 4 patients, respectively. Mature data will be presented at the meeting.

      Conclusion
      This first analysis of the RYTHMIC prospective cohort demonstrates the feasibility of a national MTB for thymic malignancies, that, besides ensuring all patients an equal access to highly specialized treatment, provides with a comprehensive tool to monitor dedicated actions to improve the management of patients in the future, increase the quality-of-care, and screen patients for future translational research and clinical trials. Supported by Institut National du Cancer

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    O28 - Endoscopy (ID 124)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Pulmonology + Endoscopy/Pulmonary
    • Presentations: 1
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      O28.04 - DISCUSSANT (ID 3978)

      10:30 - 12:00  |  Author(s): L. Thiberville

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    P2.05 - Poster Session 2 - Preclinical Models of Therapeutics/Imaging (ID 158)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.05-023 - In vivo micro-imaging of apoptosis in a murine xenograft model of human lung adenocarcinoma (ID 3324)

      09:30 - 16:30  |  Author(s): L. Thiberville

      • Abstract

      Background
      Resistance to apoptosis is a hallmark of cancer that can be reversed by several chemotherapy drugs and targeted therapies, including cisplatin and erlotinib. In vivo imaging of apoptosis would be of great interest to study molecular mechanisms of drug activity and resistance. The aim of this study is to investigate whether in vivo micro-imaging of apoptosis could be used for early assessment of treatment response in a murine xenograft model of human lung cancer.

      Methods
      A549 (EGFR wild type), H1650 (carrying EGFR exon 19 deletion that confers sensitivity to Erlotinib) and H1975 (carrying EGFR mutations L858R and T790M, resistant to Erlotinib) cell lines were used to induce subcutaneous tumors in Nude mice. In vivo micro-imaging of apoptosis was performed using fibered confocal fluorescence microscopy (FCFM) after intra-venous injection of a fluorogenic caspase 3 substrate. Tumors were treated by cisplatin (10mg/kg) (5 mice, A549 xenografts), erlotinib (25mg/kg) (6 mice, 2 A549, 2 H1650, 2 H1975), or vehicle (6 mice, 2 A549, 2 H1650, 2 H1975).

      Results
      In A549 xenografts treated by cisplatin, apoptosis was detected in vivo at 24h post-treatment. Fluorescence intensity ratio (FIR) was significantly higher than in untreated tumors (16.9+/-3.1 vs 4.8+/-2.1 respectively, p<0.001). 24h after treatment by erlotinib, FIR in H1650 erlotinib sensitive tumors was significantly higher than in A549 tumors, and than in H1975 erlotinib resistant tumors (12.2+/-2.4 vs 6.1+/-1.2 vs 1.9+/-0.7 respectively, p<0.01, Figures 1 and 2). Results were confirmed ex vivo on harvested tumor xenografts by TUNEL assay and immunohistochemistry for activated caspase 3, and on cell lines in vitro by flow cytometry and fluorescence microscopy. Figure 1 Figure 2

      Conclusion
      Early in vivo micro-imaging of apoptosis using FCFM makes it possible to differentiate sensitive from resistant tumors to Erlotinib in a murine xenograft model of human lung adenocarcinoma.