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K. Yoshida



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    MO08 - NSCLC - Early Stage (ID 117)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO08.11 - The role of aggressive local therapy and prognostic factors in postoperative recurrent non-small cell lung cancer: Is oligorecurrence state potential curable disease? (ID 925)

      17:15 - 17:20  |  Author(s): K. Yoshida

      • Abstract
      • Presentation
      • Slides

      Background
      Non-small cell lung cancer (NSCLC) with postoperative recurrence (POR) is generally believed to have an incurable disease. However, several studies have indicated that only a limited number of distant recurrences (oligorecurrence) may benefit from local therapy to the distant site of disease. We investigated factors associated with postrecurrence survival (PRS) in recurrent NSCLC, and particularly the role of local therapy to the metastatic site.

      Methods
      From 2000 through 2009, a total of 1542 patients with NSCLC underwent complete surgical resection. Of those, we reviewed the records of 356 patients with POR.

      Results
      Type of POR included locoregional only in 114 (32%), distant in 242 (68%). Of the 242, there were 65 oligorecurrences. Initial recurrence therapy found local treatment for 68 (surgery 5, radiation 12, surgery with chemotherapy and/or radiation 12, chemoradiotherapy 39). Multivariate analysis demonstrated that older age (HR1.522), advanced stage (HR1.371), shorter disease-free interval (DFI; HR1.733), non-adenocarcinoma (HR1.442), systemic treatment (-) (HR1.481), EGFR-TKIs (-) (HR1.563), local treatment (-) (HR1.705) and bone metastases (HR2.140) had a significant association with poor PRS, and oligorecurrences state appeared as an independent PRS factor in patient with distant recurrence (HR1.836). Median PRS times were 36.3 months for 37 patients with DFI > 16 months and receiving local treatment, and 16.0 months for other (p<0.001) in all patients (Fig.1), and 36.5 months for 29 patients with DFI > 16 months and oligorecurrence, and 14.6 months for other (p<0.001) in patient with distant recurrence (Fig.2). There was no significant difference in survival for the patients with oligorecurrence according to whether or not receiving local treatment. Figure 1Figure 2

      Conclusion
      This study showed that local therapy improved PRS in patients with POR. Optimization of personalized systemic treatment depends on patient selection, and therapeutic strategy for adding an aggressive local treatment options based on a careful follow-up is important.

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    P1.07 - Poster Session 1 - Surgery (ID 184)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 2
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      P1.07-006 - Lung cancer resection in patients with chronic renal failure on hemodialysis (ID 2104)

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

      • Abstract

      Background
      The number of patients with malignant tumors receiving long-term hemodialysis (HD) has been increasing. Patients on HD who undergo surgery represent a high-risk group requiring careful perioperative management to avoid electrolyte imbalance and hemodynamic instability. This retrospective study analyzed the postoperative outcome in terms of complications and survival of a group of patients on HD who underwent pulmonary resection for non-small cell lung cancer.

      Methods
      Between January 1995 and March 2013, 10 patients (7 men, 3 women; median age, 71.5 years) with non-small cell lung cancer who were also receiving HD underwent radical pulmonary resection by open thoracotomy or video-assisted thoracic surgery at Tokyo Medical University Hospital. We retrospectively evaluated their postoperative clinical outcomes and survival results. Most patients had comorbidities, including cardiovascular disease (5), diabetes (3), and brain infarction (1). The distribution of clinical staging was IA in 2 cases, IB in 5, IIB in 1, and IIIA in 2. Procedures included 8 lobectomies and 2 segmentectomies. We performed 4 systematic lymph node dissections and 6 selective lymph node dissections.

      Results
      The median intraoperative time was 215.5 minutes (range, 101-308). The median blood loss was 55 mL (range, 0-478 mL). Blood transfusion was not necessary. There was no intraoperative mortality. There were major perioperative complications in 4 patients, including atrial fibrillation (3), cardiac failure (1), shunt failure (1), and pneumonia (1). The median length of hospital stay was 21 days (range, 11-47). Thoracic drainage removal was at 4.5 postoperative days (range, 3-9). Pathological staging was IA in 3 cases, IB in 2, IIA in 2, IIB in 1, and IIIA in 2. Two cases were upstaged from the preoperative period to the final period. Seven of the 10 patients are currently alive and recurrence-free. Two patients had mediastinal lymph node and lung recurrence. One patient died from mediastinal lymph node recurrence at 8 months after surgery, and the other patient died at 26 months after surgery from malignant lymphoma.

      Conclusion
      Patients with chronic renal failure on HD who undergo lung resection have a high rate of postoperative complications (40%). Surgical treatment remains one of the effective treatments for patients on HD with lung cancer.

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      P1.07-037 - Clinical characteristics of completely resected lung cancer with combined pulmonary fibrosis and emphysema (ID 2525)

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

      • Abstract

      Background
      The occurrence of both emphysema and pulmonary fibrosis in the same patient has received increased attention as the syndrome of combined pulmonary fibrosis and emphysema (CPFE). Patients with CPFE show severely impaired DLCO, hypoxemia at exercise, characteristic computed tomography (CT) imaging feature, and high probability of lung cancer. However, the clinical characteristics of lung cancer patients with CPFE are not well known. The aim of this study is to identify clinical characteristics of completely resected lung cancer with CPFE.

      Methods
      A total of 559 consecutive patients who underwent complete surgical resection for lung cancer from January 2008 through December 2010 were reviewed. Based on preoperative chest HRCT findings, patients were categorized into three groups: those with normal lung (N) (except for lung cancer), emphysema without pulmonary fibrosis (E), and CPFE. The HRCT inclusion criteria of CPFE is as follows; 1) Presence of emphysema, defined as well-demarcated areas of decreased attenuation in comparison with contiguous normal lung and marginated by a very thin or no wall, and/or multiple bullae with upper zone predominance. 2) Presence of a diffuse parenchymal lung disease with significant pulmonary fibrosis, defined as reticular opacities with peripheral and basal predominance, honeycombing, architectural distortion and/or traction bronchiectasis or bronchiolectasis. Chest HRCT scans were reviewed separately by two thoracic surgeons and one radiologist. The clinical characteristics of patients with CPFE were compared with those of the other groups.

      Results
      This study cohort included 328 (58.7%) patients in N group, 136 (24.8%) patients in E group, and 95 (17.0%) patient in CPFE group, with median age of 67 years. The 3-year survival rates were 68.4% in CPFE group, 80.2% in E group, and 89.7% in N group (p < 0.001). CPFE group found a positive correlation with each of the following factors compared to N and E groups; > 67 years (p = 0.004), lymph node metastases (p = 0.033), male gender (p < 0.001), tumor size > 3cm (p < 0.001), vascular invasion (p < 0.001), non-adenocarcinoma (p < 0.001), pleural invasion (p < 0.001), elevated preoperative serum CEA level (p < 0.001). The frequency of patients presenting grade 2 or more severe postoperative complication under CTCAE or Clavien-Dindo classification was 28.4% for CPFE group, 24.3% for E group, and 14.9% for N group (p = 0.004), and respiratory complication was higher for CPFE group (22.1%) than N group (5.8%) and E group (11.8%) (p < 0.001).

      Conclusion
      Resected lung cancer patients with CPFE had some different clinical characteristics in comparison with those with emphysema. Intensive postoperative management and a strict follow-up are required because of higher rate of postoperative complications and aggressive malignant behavior in CPFE patients.

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    P1.10 - Poster Session 1 - Chemotherapy (ID 204)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.10-006 - Examination of recurrence predictors in cases receiving UFT as postoperative adjuvant chemotherapy for lung cancer (ID 658)

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

      • Abstract

      Background
      Although the 2012 version of the clinical practice guidelines for lung cancer published by the Japan Lung Cancer Society recommends performing a tegafur-uracil (UFT) compound drug therapy on cases of non-small cell lung cancer for stage 1A and 1B tumors measuring > 2 cm in diameter after surgery, we often encounter cases of recurrence. Therefore, we obtained data on T2a tumors (> 3 cm but < 5 cm in diameter) treated with UFT as postoperative adjuvant chemotherapy at our hospital and examined their recurrence predictors.

      Methods
      Among 2,724 cases of total surgical removal of non-small cell lung cancer performed between January 1997 and December 2007, we examined 168 cases with stage 1B T2a tumors treated with UFT to clarify the recurrence predictors in these cases. We examined age, sex, tumor diameter, vascular invasion, lymphatic involvement, pleural invasion, histologic degree of differentiation, tissue, and CEA.

      Results
      The age range was 38 to 85 years (median 66 years), and there were 108 men and 60 women. The 5-year recurrence-free survival rate was 72.7%. In cases of recurrence, the median time to recurrence was 662 days in 48 of the 168 cases (28.6%). On univariate analysis, vascular invasion (p < 0.001), male sex (p = 0.045), and non-differentiation (p < 0.002) were identified as significant recurrence predictors. On multivariate analysis, vascular invasion (p = 0.009) was found to be a significant recurrence predictors. Please confirm this part as the changes were made based on the original Japanese text.

      Conclusion
      It was inferred that vascular invasion is a primary recurrence predictor in cases receiving UFT as postoperative adjuvant chemotherapy. We need to consider a more careful follow-up during UFT administration as postoperative adjuvant chemotherapy in stage 1B T2a tumors.

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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): K. Yoshida

      • 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.