Virtual Library

Start Your Search

Junichi Murakami



Author of

  • +

    MA12 - Mesothelioma Surgery and Novel Targets for Prognosis and Therapy (ID 913)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Mesothelioma
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 10:30 - 12:00, Room 202 BD
    • +

      MA12.10 - Long-Term Impact of Radiotherapy Before Surgery for Mesothelioma on the Distribution of Memory T Cell Subsets (ID 12728)

      11:35 - 11:40  |  Presenting Author(s): Junichi Murakami

      • Abstract
      • Presentation
      • Slides

      Background

      Postoperative recurrence remains one of the critical issues in treatments for mesothelioma. We previously reported that non-ablative, hypo-fractionated radiation before surgery generated an antigen-specific activation of the immune system and could provide an in situ vaccination with long-term protection against mesothelioma in our murine model. An effective immunological protection depends on memory T cell subset diversification. However, limited work has been done to address the distribution of memory T cell subsets and its effects on the immune system after radiotherapy followed by surgery for mesothelioma.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      C57BL/6 mice bearing AE17-OVA tumor were treated with local radiotherapy (LRT). LRT 5Gy was delivered on days 10, 11 and 12. We performed radical tumor resection 7 days after LRT. The mice were re-challenged under the skin or into thoracic cavity with AE17-OVA 28 days after surgery and defined as immunological protective memory model if the tumors were completely rejected. Memory model received subcutaneous tumor inoculation once again (second rechallenge), samples were harvested on day 0, 3, 10. We investigated memory T cell subsets using flow cytometry. In addition, the harvested total splenocytes (effector) were co-cultured with CFSE-labeled AE17-OVA (target) for three days. Each of their cytotoxic potential was analyzed by evaluating a number of AE17-OVA and its early or late apoptosis.

      4c3880bb027f159e801041b1021e88e8 Result

      8 out of 10 mice completely rejected the subcutaneous tumor in mice treated with LRT and surgery after re-challenged. We observed significantly better survival in the memory model re-challenged into the thoracic cavity compared with no treatment mice. After subcutaneous tumor inoculation, central memory T cells (CD44[+]CD62L[+]KLRG1[-]) on day 0, effector memory T cells (CD44[+]CD62L[-]KLRG1[-]) and terminal effector T cells (CD44[+]CD62L[-]KLRG1[+]) on day 0, 3, 10 increased significantly in CD8[+] splenocytes of memory model compared with no treatment mice. This observation was also seen in draining and non-draining lymph nodes. The MFI of CFSE reflecting a number of AE17-OVA cells decreased, whereas the proportion of early (Annexin V[+]FVD[low]) or late (Annexin V[+]FVD[high]) apoptotic cells in CFSE[+] cells increased, depending on time passage and effector/target ratio after tumor inoculation in both memory model and naïve mice. However, during time passage, memory model always had a stronger cytotoxicity (even at Day 0) as compared to naïve mice.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our data raise an important possibility that non-ablative, hypo-fractionated radiotherapy followed by surgery for mesothelioma contributes to the development and long-term maintenance of memory T cell subsets, which could remain poised to rapidly recall effector functions upon antigen re-exposure.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P1.11 - Screening and Early Detection (Not CME Accredited Session) (ID 943)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
    • +

      P1.11-14 - Radiological Pleura-Tumor Proximity in Pure-Solid Clinical Stage I Lung Cancer: Its Influence on Lymph Node Metastasis and Recurrence (ID 12206)

      16:45 - 18:00  |  Author(s): Junichi Murakami

      • Abstract
      • Slides

      Background

      Lymph node metastasis of lung cancer is an important factor for deciding on surgical indications. Radiological pure-solid lung cancer is a highly aggressive feature, even in small lesions, and it is generally difficult to evaluate lymph node metastasis based on preoperative clinical examinations. We focused on the radiological association between the tumor and pleura and assessed the influence of pleura-tumor proximity on the risk of lymph node metastasis and postoperative recurrence.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively reviewed a consecutive series of 133 patients with clinical stage I lung cancer possessing pure-solid nodule on chest computed tomography who had undergone lobectomy with systematic lymph node dissection between January 2009 and December 2016. Figure shows the definition of positive pleura-tumor proximity. A multiple logistic regression analysis was used to identify the predictors for lymph node metastasis, and a multiple Cox proportional hazards model was used to identify the predictors for postoperative recurrence, with covariates of age, gender, performance status, resected side, pulmonary function, tumor size, pleural tag, pleura-tumor proximity, and maximum standardized uptake on positron emission tomography.

      figure.jpg

      4c3880bb027f159e801041b1021e88e8 Result

      There were 89 men (mean age 70.7 ± 9.6 years). The mean tumor size was 22.9 ± 8.7 mm. Lymph node metastasis was found in 21 patients (15.7%), and postoperative recurrence was found in 24 patients (18%). According to the multivariate analysis, the age (p = 0.013) and positive pleura-tumor proximity (p = 0.036) were the independent predictive factors of lymph node metastasis, and the positive pleura-tumor proximity (p = 0.035) was an independent predictive factor of postoperative recurrence.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Pleura-tumor proximity in radiological pure-solid lung cancer was associated with lymph node metastasis and postoperative recurrence. Such pleura-tumor proximity should therefore be taken into consideration in the therapeutic decision-making for stage I lung cancer possessing pure-solid nodules.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P1.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 948)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
    • +

      P1.16-60 - A High Risk of Recurrence After the Resection of Lower Lobe Adenocarcinoma (ID 12475)

      16:45 - 18:00  |  Author(s): Junichi Murakami

      • Abstract
      • Slides

      Background

      According to previous reports, non-small cell lung cancers arising in the lower lobe are associated with a worse prognosis than those arising in the upper lobe; however, the reason remains to be elucidated. Thus, we attempted to identify high-risk population in patients with lower lobe disease, that may substantially cause poor prognosis of lower lobe disease.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively reviewed a consecutive series of 400 patients with completely resected lung adenocarcinoma who were treated between January 2006 and December 2015. All patients underwent major lung resection and lymph node dissection. The clinicopathological factors that were investigated included the solid component size, the pathological subtype (pre-invasive, minimally invasive/invasive), the epidermal growth factor receptor (EGFR) mutation status, and some other characteristics (TNM 8th edition).

      4c3880bb027f159e801041b1021e88e8 Result

      fig 1.jpgThe proportion of never-smokers among patients with lower lobe disease was significantly higher than that among those with upper lobe disease. According to a multivariate proportional hazards analysis, primary site (upper/lower) was an independent predictor of early recurrence, along with the solid component size, pleural lavage cytology results, pathological pleural invasion, and pathological lymph node metastasis. However, although lower lobe disease was associated with early recurrence in never smokers (Fig 1A), it was not in smokers (Fig 1B). Furthermore, although lower lobe disease was associated with early recurrence in never smokers with EGFR wild-type tumors (Fig 1C), it was not in never smokers with EGFR mutant tumors (Fig 1D). EGFR wild-type tumors were more frequently detected in patients with lower lobe disease than in those with upper lobe disease when the analysis was restricted to never smokers.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Patients with lower lobe cancer, particularly those without a smoking history or those with EGFR wild-type tumors, showed a higher risk of recurrence than their counterparts with upper lobe disease. Further studies that include the molecular profiling of such aggressive lesions, are warranted.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.