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Takashi Ohtsuka



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    MA 05 - Immuno-Oncology: Novel Biomarker Candidates (ID 658)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      MA 05.04 - Distinct Immunosuppressive Microenvironment Determines Poor Prognosis of Nonsmokers with Adenocarcinoma of Non-Small Cell Lung Cancer (ID 7388)

      15:45 - 17:30  |  Author(s): Takashi Ohtsuka

      • Abstract
      • Presentation
      • Slides

      Background:
      Recent clinical trials have demonstrated the efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer (NSCLC). However, not all the patients receive survival benefit from these immunotherapies. In an attempt to refine the current strategy of cancer immunotherapy to treat NSCLC, we examined the influence of tumor-infiltrating lymphocytes (TILs) on postoperative survival.

      Method:
      We evaluated the prognostic significance of TILs (CD4[+], CD8[+], and FOXP3[+]) comprehensively by immunohistochemical (n = 234) and immune-related gene expression analysis (n = 58), and explored the relationship between immune features and clinical characteristics including histological types, smoking habit, epidermal growth factor receptor mutation, and postoperative survival.

      Result:
      Compared with non-adenocarcinoma (non-AD) patients, adenocarcinoma (AD) tumors had significantly higher number of tumor-infiltrating CD4[+] T cells (P < 0.05) but lower CD8[+] T cells and FOXP3[+] T cells (P < 0.01). We found higher accumulation of CD8[+] T cells in non-AD patients was correlated with longer survival, indicating it is a better prognostic factor (P < 0.02). On the contrary, high accumulation of CD8[+] T cells and FOXP3[+] T cells were identified as unfavorable prognostic factors (P < 0.05) in AD patients, particularly in AD nonsmokers (P < 0.02). The expression of activated T cell-related genes including interferon gamma and granzyme was associated with CD8[+] T-cell accumulation in non-AD patients, but not in AD patients, especially in AD nonsmokers. Infiltrating CD8[+] T cells were significantly less activated in immunosuppressive microenvironment with high expression of immunoregulation related genes including GATA3, IL13, CCR4 and CCL17 in AD nonsmokers (P < 0.05). In AD nonsmokers, there are possibly immunodysfunctional CD8[+] GATA3[+] T cells (P < 0.01) and immunoregulatory CD8[+] FOXP3[+] T cells (P < 0.01), accompanied by immunoregulatory CD4[+] FOXP3[+] CCR4[+] T cells (P < 0.01) that may be recruited by CCL17 produced by tumor-associated CD163[+] macrophages (P < 0.05) in IL13-associated tumor microenvironments (P < 0.05).

      Conclusion:
      In contrast to presence of activated CD8[+] T cells in non-AD, CD8[+] T cells are not activated, and may include dysfunctional and immunoregulatory T cells, accompanied by FOXP3[+] regulatory T cells and M2-like macrophages in IL13-associated tumor microenvironment of AD nonsmokers. Our study suggests that modulation of such immunosuppressive condition may be an attractive strategy for treatment of AD nonsmokers including immune-checkpoint blockade.

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    MA 16 - Mediastinal, Tracheal and Esophageal Tumor: Multimodality Approaches (ID 675)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 1
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      MA 16.09 - Discussant - MA 16.06, MA 16.07, MA 16.08 (ID 10855)

      15:45 - 17:30  |  Presenting Author(s): Takashi Ohtsuka

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    P1.05 - Early Stage NSCLC (ID 691)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Early Stage NSCLC
    • Presentations: 2
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      P1.05-005 - Percutaneous Cryoablation for Lung Cancer Patients with Idiopathic Pulmonary Fibrosis (ID 9128)

      09:30 - 16:00  |  Presenting Author(s): Takashi Ohtsuka

      • Abstract
      • Slides

      Background:
      Lung cancer patients concomitant with interstitial pulmonary fibrosis (IPF) sometimes develop a life-threatening acute exacerbation after surgery or radiotherapy. Percutaneous cryoablation is evolving as a potentially less invasive local treatment for lung cancer. The purpose of this study is to retrospectively analyze the outcomes of cryoablation for clinical T1N0M0 non-small cell lung cancer (NSCLC) patients for whom surgery or radiotherapy is contraindicated because of IPF.

      Method:
      Between December 2003 and June 2017, 215 patients underwent computer tomography guided percutaneous cryoablation for lung tumors at our institution. Of these, 11 histologically proven clinical T1N0M0 NSCLC patients, for whom surgery or radiotherapy was considered contraindicated because of severe IPF, were retrospectively reviewed. Complications, local progression-free survival and clinicopathological factors were evaluated.

      Result:
      The cohort was composed of 11 men with a mean age of 74 years (range: 68 to 82). The median follow-up time was 24 months (range: 15 to 65 months). The mean Krebs von den Lungen-6 (KL-6) level was 1608 ±1025 U/mL. The mean tumor size was 24 ± 7mm. The mean percentage of predicted diffusing capacity for carbon monoxide (DLCO) was 37±27%. Thirty and 90-day mortality was 0 and 18%, respectively. Two patients required chest tube drainage because of severe pneumothorax. Acute exacerbation of IPF occurred in two patients (18%). The use of oral steroids and need for chest tube drainage were predictors of higher mortality (p < 0.05) and higher incidence of acute exacerbation of IPF (p < 0.05). However, higher level of KL-6 and low percentage of DLCO were not significant risk factors of mortality or acute exacerbation of IPF. Local progression-free survival at 1, 2 and 3 year was 51, 41 and 31%, respectively.

      Conclusion:
      Percutaneous cryoablation for lung cancer patients with IPF provoked acute exacerbation of IPF in 18% of patients. The use of oral steroids and need for chest tube drainage were predictors of higher mortality and higher incidence of acute exacerbation of IPF.

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      P1.05-009 - Analysis of Postoperative Prognosis in Terms of the Difference Between the Invasive Growth Area and the Total Tumor Diameter (ID 9888)

      09:30 - 16:00  |  Author(s): Takashi Ohtsuka

      • Abstract

      Background:
      In the 8[th] edition of the TNM classification of lung cancer, the T descriptor reflects the invasive growth area, which is not always equal to the total tumor diameter. In this study, we analyzed the difference in postoperative prognosis between tumors for which the invasive growth area was equal to the total tumor diameter and those for which the invasive growth area was smaller than the total tumor diameter.

      Method:
      One hundred forty-two patients with pathological stage I lung adenocarcinoma that was completely resected in our institute were enrolled. Adenocarcinoma in situ and minimally invasive adenocarcinoma were excluded. The average age at operation was 67.8±9.7 years, 87 patients were male, the average total tumor diameter was 1.9±0.6 cm, and the average invasive growth area was 1.6±0.6 cm. In 61 patients, the invasive growth area was smaller than the total tumor diameter (Group A), and in the remaining 81, the invasive growth area was equal to the total tumor diameter (Group B). The postoperative prognosis was compared between Groups A and B.

      Result:
      The estimated 5-year recurrence-free survival (RFS) probabilities by the Kaplan-Meier method in Groups A and B were 94.4% and 70.1%, respectively (p = 0.002, log-rank test). By a log-rank test, T factor (p < 0.001) and lymphatic permeation (p = 0.031) were also significantly associated with RFS. By a multivariate COX proportional hazards model, Group B (p = 0.045) and a pathological T descriptor of T1c or more (p = 0.001) were independently associated with RFS. Group B had a higher percentage of smokers (p = 0.004) and a higher percentage of cases in which the predominant histological subtype was other than a lepidic pattern (p < 0.001).

      Conclusion:
      Tumors for which the invasive growth area is equal to the total tumor diameter are associated with smoking and a predominant subtype of other than a lepidic pattern, and have a worse prognosis than tumors for which the invasive growth area is smaller than the total tumor diameter.

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    P1.13 - Radiology/Staging/Screening (ID 699)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Radiology/Staging/Screening
    • Presentations: 1
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      P1.13-011b - Nodal Status Based on the Anatomical Location or the Number of Lymph Nodes Metastasis (ID 9012)

      09:30 - 16:00  |  Author(s): Takashi Ohtsuka

      • Abstract

      Background:
      The 8th edition of the TNM staging system for lung cancer has been published. In the new staging system, the N component remains the same as in the previous version. However, the number of involved nodal stations has been previously shown to be correlated with patient outcomes. In the present study, we retrospectively investigated the correlations between the anatomical location versus the total number of metastatic lymph nodes and the outcomes of patients with non-small cell lung cancer.

      Method:
      We retrospectively collected 237 samples (16.1%) from patients with pN1 and N2 primary lung cancer who underwent complete resection between 2004 and 2013. In those samples, we divided N1 samples into N1ss (single station N1) and N1ms (multiple station N1). We also divided samples into hilar N1 (#11, #10; N1h) and peripheral N1 (#14, #13, and #12; N1p) subgroups. pN2 lymph nodes were divided into “single station N2 with skip metastasis” (N2ss1), “single station N2 with N1 metastasis” (N2ss2), and N2ms. The clinicopathological factors and outcomes for each group were statistically analyzed.

      Result:
      In this study, per patient, a mean of 17.9 lymph nodes were dissected and the mean number of lymph node metastases was 3.9. The pN1 and pN2 groups consisted of 74 and 163 cases, and their 5-year survival rates were 74.7% and 54.8%, respectively (p = 0.021). The 5-year survival rates of the N1p and N1h groups were 74.7% and 63.6%, respectively. Although the N1h group showed a tendency towards poorer outcomes, no statistically significant difference between the groups was observed (p = 0.114). The 5-year survival rates of the N2ss1 and N2ss2 groups were 65.4% and 62.4%, respectively, and the N2ms group had poorer outcomes (45.0%, p = 0.010). In our cohort of patients with N1 and N2 lymph node metastasis, the number of metastatic lymph nodes was not correlated with patient outcomes.

      Conclusion:
      In the cases of pN1, patients with N1h had poorer outcomes than those with N1p. In the cases of pN2, patients with N2ms had poorer outcomes than those with other subsets of pN2. From a prognostic point of view, classification based on the anatomical location of metastatic lymph nodes may be important. Further accumulation and examination of cases will be necessary to confirm our findings.

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    P3.13 - Radiology/Staging/Screening (ID 729)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Radiology/Staging/Screening
    • Presentations: 1
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      P3.13-031 - Predicting Factor for the Dissociation of the Diameter Between Radiographical Solid Part and Pathological Invasive Part in Lung Adenocarcinoma (ID 10184)

      09:30 - 16:00  |  Author(s): Takashi Ohtsuka

      • Abstract

      Background:
      In part-solid nodule of lung adenocarcinoma, the diameter of the solid part in computed tomography(CT) scan correlates with the diameter of the pathological invasive part. However, there are some cases revealing dissociation between them. We analyzed clinical factors predicting the dissociation of the diameter between radiographical solid part and pathological invasive part in adenocarcinoma less than 3 cm.

      Method:
      Among 291 cases with a lung adenocarcinoma smaller than 3 cm, we identified 91 cases whose solid part in preoperative thin-slice CT scan was less than 5 mm. Based on pathological diagnosis of invasive part, we divided these cases into Adenocarcinoma in situ/Minimally Invasive Adenocarcinoma(AIS/MIA) group (less than 5 mm) and Massive invasion group (5mm or larger), and retrospectively analyzed the clinicopathological factors. We also performed logistic regression analysis to detect the factors predicting the dissociation between radiographical and pathological findings.

      Result:
      Of 91 cases, 67 cases were in AIS/MIA group (AIS: 57, MIA: 10) and 24 cases were in Massive invasion group. In univariative analysis, cases of Massive invasion group were significantly higher in Brinkman index, CEA, age, and total tumor size than those of AIS/MIA group (p = 0.02, 0.01, 0.04, 0.03 respectively). With these detected four factors, we performed logistic regression analysis after determining threshold by ROC curve, which resulted in Brinkman index equal or larger than 400, and age equal or elder than 67 as significant predictive factors for Massive invasion group (p < 0.01, p = 0.05 respectively). Among 11 cases positive for these two factors, 7 cases (63.6 %) were in Massive invasion group.

      Conclusion:
      In the cases of radiographical AIS/MIA, the diameter of pathological invasive part tends to exceed 5 mm if Brinkman index equal or larger than 400, and age equal or elder than 67.