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K. Yasumoto



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    P1.12 - Poster Session 1 - NSCLC Early Stage (ID 203)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.12-001 - Efficacy of pulmonary resection and gamma knife surgery for non-small cell lung cancer with synchronous brain metastasis (ID 155)

      09:30 - 09:30  |  Author(s): K. Yasumoto

      • Abstract

      Background
      Several studies suggest that pulmonary resection and gamma knife surgery (GKS) protocol prolong survival in patients with thoracic stage I or II non-small cell lung cancer (NSCLC), without extra-cranial or lymph node metastases, and with a limited number of small synchronous brain metastases. According to the Japanese Lung Cancer Society guidelines published in 2012, stereotactic radiosurgery (SRS) or surgery for a single brain metastatic lesion and SRS or stereotactic radiotherapy (SRT) for 2-4 brain metastatic lesions, less than 3 cm in length, are Grade B recommendations. To validate these recommendations, we retrospectively examined the prognosis of patients with NSCLC who underwent GKS for synchronous brain metastasis and pulmonary resection.

      Methods
      We retrospectively reviewed the cases of patients with NSCLC and synchronous brain metastasis who underwent GKS preceding pulmonary resection from January 2006 to December 2012 at our institution. The eligibility criteria were thoracic stage I or II NSCLC, a performance status of 0­­­­­­­­­­­­­­–1, a predicted post-operative forced expiratory volume in 1 second of >600 ml/m[2], no extra-cranial metastasis, and brain metastatic lesions of < 3 cm.

      Results
      In total, 253 patients underwent pulmonary resection for NSCLC between January 2006 and December 2012. Six patients with NSCLC and synchronous brain metastasis underwent GKS preceding pulmonary resection, and received postoperative adjuvant systemic chemotherapy or molecular targeted therapy. All of them were Japanese, 4 were male and 2 were female. The mean age was 63 years (range, 47–78 years). Four patients had neurologic symptoms. The mean size of the primary lung lesion was 35 mm (range, 22–59 mm). The median number of brain metastases was 1 or 2 (range, 1–8) and the mean size was 16 mm (range, 7–28 mm). GKS was performed before pulmonary resection in all patients. The median time between GKS and thoracotomy was 2 weeks (range, 2–8weeks). Combined pulmonary resection was performed in 2 patients because of inter-lobar pleural invasion and lobectomy was performed in 4. Postoperative complications occurred in 1 patient: (thoracic empyema with bronchopleural fistula). Histologically, 4 patients had adenocarcinoma and 2 had large cell carcinoma. None of the patients showed evidence of lymph node metastasis after pulmonary resection (pN0). All patients received either platinum-taxol doublet therapy or molecular targeted therapy as postoperative adjuvant chemotherapy. One patient died 28 months after surgery because of new brain metastasis, and 5 were alive at 15, 18, 30, 66, and 88 months after pulmonary resection.

      Conclusion
      The pulmonary resection and GKS protocol resulted in long-term survival in 5 of 6 patients with synchronous brain metastasis from NSCLC. Although only a small number of cases were studied, this report may provide promising data with regard to a multidisciplinary therapeutic strategy for patients with newly diagnosed thoracic stage I or II NSCLC with brain metastasis. Further analysis and clinical studies are necessary to validate our findings.

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    P3.04 - Poster Session 3 - Tumor Immunology (ID 155)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.04-001 - Combined adjuvant chemoimmunotherapy with CBDCA+GEM and autologous tumor lysate-transduced dendritic cell vaccinations in patients with operable NSCLC (ID 92)

      09:30 - 09:30  |  Author(s): K. Yasumoto

      • Abstract

      Background
      Surgical adjuvant chemotherapy with platinum doublet is effective but not enough to suppress recurrence of NSCLC. We have applied combination chemoimmunotherapy with CBDCA+GEM and autologous tumor lysate transduced dendritic cell vaccination in patients with operable NSCLC in order to clarify that such a treatment can induce tumor specific immune response.

      Methods
      Eight patients with NSCLC whose pathological stages ranging from IB~IV were included in this study. The main purpose of the study is to obtain the principle of concept in which such vaccination can induce cellular immune response against autologous tumor cells detected by ELISPOT assay and establishment of CTL clones to recognize the tumor cell. Autologous tumor lysate was prepared from the surgical specimen aseptically by 5 times of freeze-thaw and sonication . DC cells were prepared from peripheral blood mononuclear cells obtained by apheresis, and in vitro culture with IL-4 and GM-CSF. Matured DC was induced by culture with TNF-α. Autologous tumor lysate-transduced DC was prepared by electroporation using MaxCyte cell loading system(MaxCyte[R]). More than 7x10[6] of the DC were injected intradermally at groin biweekly at 1, 3, 5, 7, 9 and 11week. Combination chemotherapy with CBDCA+GEM was administered at 0, 2, 4, 6, 8 and 10 week.

      Results
      Delayed type hypersensitivity skin reaction to the DC was observed in 5 of 8 patients after completion of the vaccination(6 times). ELISPOT assay revealed specific IFN-γ production in response to autologous tumor lysate-transduced DC following completion of the vaccination in 3 of the 5 patients. In one patient among them, CTL clones could be induced successfully in vitro, and identification of the Ag recognized by the CTL is now underway. No serious adverse effect was observed. Six patients have recurrent disease at 6, 6, 8, 10, 12 and 18months after operation. One patient(N0.6) died of the disease at 13 months after the operation due to systemic metastasis. However, the other patients are alive with(5 patients) or without(2 patients) evidence of the recurrent disease(ranging from 10~22 months as of February, 2013). Figure 1

      Conclusion
      The autologous tumor lysate-transduced DC vaccination is effective to induce tumor specific cellular immune response in some of such patients. Establishment of CTL clones recognizable autologous tumor cells can lead to identification of specific Ag coding genes which can be used as immunological targets.