Virtual Library

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    P1.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session) (ID 944)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.12-07 - Time to the End of Thoracic Radiotherapy Affects to Survival Outcomes Greater than Radiation Dose in Limited Stage Small Cell Lung Cancer (ID 13607)

      16:45 - 18:00  |  Presenting Author(s): Sung-Ja Ahn  |  Author(s): Jae-Uk Jeong, Wan Jeon, Young-Chul Kim, In-Jae Oh, Cheol-Kyu Park, Mee Sun Yoon, Ju-Young Song, Taek-Keun Nam, Woong-Ki Chung

      • Abstract
      • Slides

      Background

      Early thoracic radiotherapy (TRT) concurrent with chemotherapy and radiation doses of 45 Gy given 1.5 Gy bid still has taken a seat as a standard treatment option for limited-stage small cell lung cancer (LS-SCLC). We aim to search the association between radiation parameters and survival outcomes in LS-SCLC patients who undertaken more than 45 Gy of TRT.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      One hundred and one patients with LS-SCLC who completed TRT between August 2005 and March 2014 were reviewed retrospectively. Median age was 64 years (43-80) and male to female was 88 vs. 13. Stage IIIA was 30 and IIIB was 55, respectively. TRT was performed using 3-dimensional conformal radiation therapy (3DCRT) and delivered using 2Gy single fraction per day in 73.2% of patients. The median dose TRT was 50 Gy (45-65), and all patients received concurrent chemoradiotherapy. PCI was combined in 56 (55.4%) patients.

      4c3880bb027f159e801041b1021e88e8 Result

      The median survival for all patients was 26.9 months. Local failure occurred in 41 patients (40.5%), and distant metastasis was noted in 54 patients (53.4%). The 3-year local control, progression-free survival (PFS), and overall survival (OS) rates were 52.0%, 29.5%, and 56.4%, respectively. On univariate analysis, the American Joint Committee on Cancer stage (p<0.001), timing of TRT (≤2 vs, >2 cycles, p=0.017), tumor response (CR vs. PR, p=0.015), the duration from the start date of chemotherapy to the end of TRT (SER) (≤70 vs >70 days, p=0.025), and PCI (p=0.003) were the significant predictors of OS and stage (p<0.001) and PCI (p=0.017) were the significant predictors in PFS. Multivariate analysis revealed that stage (hazard ratio [HR], 3.61; 95% CI, 2.15-6.07) was the only significant factor in PFS and stage (HR, 2.49; 95% CI, 1.56-3.98), SER (HR, 1.93; 95% CI, 1.22-3.07), PCI (HR, 0.52; 95% CI, 0.33-0.84), and tumor response (HR, 1.76; 95% CI, 1.12 – 2.77) were the significant predictors in OS. There was one fatal radiation pneumonitis. Grade 3 radiation pneumonitis and esophagitis was shown in 7 (6.9%) vs. 7 (6.9%) patients, respectively. Grade 3 and 4 leukopenia was shown in 30 (29.7%) vs. 11 (10.8%) patients and febrile neutropenia was 9 (8.9%) vs. 1 (0.9%) patients, respectively.

      8eea62084ca7e541d918e823422bd82e Conclusion

      SER less than 70 days was a significant predictors of OS in LS-SCLC patients who received more than 45 Gy of TRT concurrently with chemotherapy. We could not find any significant positive survival benefits of TRT dose or BED escalation in our patients groups.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P1.12 - Small Cell Lung Cancer/NET (ID 179)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.12-07 - Near Infrared Photoimmunotherapy Targeting DLL3 Against Small Cell Lung Cancer (ID 331)

      09:45 - 18:00  |  Presenting Author(s): Yoshitaka Isobe  |  Author(s): Kazuhide Sato, Kazuomi Takahashi, Shunichi Taki, Hirotoshi Yasui, Yuko Nishinaga, Toshinori Matsui, Yoshinori Hasegawa

      • Abstract

      Background

      Small cell lung cancer (SCLC) has poor prognosis, and its treatment options are limited. Delta-like protein 3 (DLL3) is a promising treatment target for SCLC, and Rovalpituzumab tesirine (Rova-T) is the first antibody drug conjugate targeting DLL3, which is currently in clinical trials. Although DLL3 is ideal target for SCLC, the result of clinical studies has not reached its primary object. Thus, new approaches are still needed.

      Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of intravenously injected antibodies for targeting tumor with the toxicity induced by photosensitizers after exposure to near infrared (NIR) light. This new therapy is now in international Phase III clinical trial against locoregional, recurrent head and neck squamous cell cancer (LUZERA-301).

      Herein, we exploited NIR-PIT to develop new therapy for SCLC with DLL3 antibody. We preclinically evaluates the efficacy of DLL3-targeted-NIR-PIT.

      dll3研究概要.png

      Method

      In vitro and in vivo experiments were conducted with DLL3, GFP, and luciferase-expressing SCLC cell line and/or mouse fibroblast cell line (SBC5-DLL3-luc-GFP and 3T3-DLL3-luc-GFP). An antibody-photosensitizer conjugate consisting of rovalpituzumab (anti-DLL3 humanized monoclonal antibody) and a phthalocyanine dye, IRDye-700DX, was synthesized (rova-IR700) and cells or tumors were exposed to NIR-light. Serial fluorescence microscopic observation was done before and after NIR-PIT. In vitro NIR-PIT cytotoxicity was assessed with dead cell staining by flow cytometry and luciferase activity. In vivo NIR-PIT was performed in mice with tumors implanted in the flank and these were assessed by tumor volume, bioluminescence and overall survival.

      Result

      After exposure to NIR-light, cellular swelling, bleb formation, rupture of the lysosome and dead cell staining were observed in fluorescence microscope. In vitro cytotoxicity of NIR-PIT was light dose dependent. In vivo the antitumor effects of NIR-PIT were confirmed by significant reductions in tumor volume (p < 0.05), luciferase activity (p < 0.01) and overall survival (p = 0.023).

      Conclusion

      These results suggest that DLL3-targeting-NIR-PIT could be a new promising treatment for SCLC.