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S. Maehara



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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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      O28.06 - Comprehensive management of central type early lung cancer (ID 1558)

      11:25 - 11:35  |  Author(s): S. Maehara

      • Abstract
      • Presentation
      • Slides

      Background
      Tumor localization and the precise evaluation of tumor invasion are most important for the management of central type early stage lung cancer (CELC) and Photodynamic therapy (PDT) has come to be considered as the first choice of treatment for CELC. The present guidelines of PDT for CELC were established based mainly on the data obtained from studies since 1980’s. CELCs less than 1 cm in diameter showed a favorable cure rate by PDT, thus this was a good standard to decide the indications of PDT. To obtain complete response (CR) by PDT, evaluation of each lesion is extremely important, including the extent of the tumor on the bronchial surface and the depth of invasion in the bronchial wall. We postulate that the combination of comprehensive diagnosis and the new generation of photosensitizers may increase the CR rate and expand the indications of PDT for larger tumors.

      Methods
      Autofluorescence bronchoscopy (AFB) has been used in the objective evaluation of the margin of the tumor before endoscopic treatment and Endobronchial ultrasonography (EBUS) has been employed to determine the depth of tumor invasion. Ooptical coherence tomography (OCT) has been investigated for clinical use as well. Also, the relatively newer photosensitizer NPe6, which has a stronger antitumor effect than Photofrin has been extensively used for PDT. We routinely used these diagnostic methodologies and NPe6 since 2004.

      Results
      A total of 122 consecutive CELCs were treated by PDT using NPe6 in Tokyo Medical University and CR was obtained in 115 lesions (CR rate 94.3%). Of the 122 lesions examined in this study, 78 had a diameter of ≦1.0 cm and the rest of the 44 cancer lesions were >1.0 cm in size. The CR rate of CELC ≦1.0 cm in diameter was 93.6% (73/78) and for those >1.0 cm in diameter, 95.5% (42/44), respectively. There was no significant difference between tumor size and clinical response. The CR rate to NPe6-PDT is higher than that of Photofrin-PDT in our previous studies. This early result suggests that PDT with NPe6 has a stronger antitumor effect than Photofrin therefore similar treatment outcome even for larger tumors >1.0 cm in diameter should be possible.

      Conclusion
      Objective evaluation by a comprehensive approach using AFB and EBUS enables to select the optimal therapeutic strategy for CELC. These results suggest that PDT with NPe6 may have a similar treatment outcome regardless of tumor size, as long sufficient laser illumination of the entire tumor is possible.

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    P3.03 - Poster Session 3 - Technology and Novel Development (ID 152)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.03-001 - The overxpression of TS protein induced by NPe6-PDT (ID 1339)

      09:30 - 09:30  |  Author(s): S. Maehara

      • Abstract

      Background
      Malignant pleural mesothelioma(MPM) is a locally aggressive disease characterized by a poor prognosis and increasing. MPM tumors are usually related to asbestos exposure, and the incidence is anticipated to peak between 2020 and 2030 because of the lag time between asbestos expousere and the development of the malignancy. MPM is difficult to detect at an early stage, and surgical and radiotherapeutic approaches are ineffective when used independently, because MPM spreads diffusely in the surrounding chest wall. No universally accepted treatment approach currently exists.

      Methods
      We examined whether combination treatment consisting of pemetrexed chemotherapy and photodynamic therapy (PDT) using the photosensitizer, NPe6, enhanced the antitumor effect in vitro and in vivo models. We also investigated preclinical treatment schedules. Four human malignant mesothelioma cell line, (MSTO-211H, H2052, H2452and H28) were assayed using the WST assy after treatment with pemetrexed and NPe6-PDT. The treatment schedule for the combination treatment was examined using nude mice.

      Results
      In nude mice injected with MSTO-211H cells and then treared using a combination of pemetrexed and NPe6-PDT (10 mg/kg NPe6, 10 J/cm2 laser irradiation), the tumor volume decreased by 50% but subsequently increased, reaching the pretreatment value after 14 days. Pemetrexed treatment followed by NPe6-PDT resulted in an 80% reduction in the tumor size and inhibited re-growth. NPe6-PDT followed by pemetrexed treatment resulted in a 60% reduction in tumor size but did not inhibit re-growth.

      Conclusion
      Pemetrexed reportedly inhibits multiple enzymes in the folate metabolic pathway, with TS being the main target. In non-small cell lung cancer cell line, high baseline TS expression levels confer resistance to pemetrexed, and the TS level is correlated with pemetrexed efficacy in a variety of solid tumors. These results suggest that the overexpression of TS protein induced by NPe6-PDT may be associated with the failure of pemetrexed to exert a tumoricidal action. Therefore, we concluded that NPe6-PDT followed by pemetrexed did not enhance tumor cell lethality in the in vivo model. Combination treatment, consisting of pemetrexed followed by NPe6-PDT, should be further investigated as a new treatment modality for malignant pleural mesothelioma. In the future, this combination treatment may contribute to a reduction in local recurrence and a prolonged survival period in patients with malignant pleural mesothelioma.