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Norihiko Ikeda



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    EP1.01 - Advanced NSCLC (ID 150)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.01-93 - Rare Immune Related Adverse Events by Immune Checkpoint Inhibitors in Clinical Practice (Now Available) (ID 1721)

      08:00 - 18:00  |  Author(s): Norihiko Ikeda

      • Abstract
      • Slides

      Background

      Immune checkpoint inhibitors (ICIs) such as anti-PD-1 and PD-L1 antibodies including nivolumab/pembrolizumab and atezolizumab are available practically in Japan. While ICIs produce excellent antitumor activity and long-term survival, unexpected immune related adverse events (irAEs), which are different from those for cytotoxic drugs, have been reported. We experienced varieties of irAEs which have successfully been treated.

      Method

      We retrospectively analyzed irAEs in 50 NSCLC patients treated with ICIs as clinical practice from January 2016 to November 2018 in TODA Central General hospital.

      Result

      Nivolumab, pembrolizumab and atezolizumab was given in 27, 11 and 12 patients, respectively. The median age was 69 (43-84). Male/female: 40/10 patients, adenocarcinoma/squamous cell carcinoma/unclassified non-small cell carcinoma: 30/15/5 patients. Tissue proportional score for PD-L1 antibody was strongly positive/weakly positive/negative/unknown in 12/4/12/22 patients, respectively. The treatment response was CR/PR/SD/PD/NE in 3/14/2/22/9 patients, respectively. Various types of irAEs have been observed, exacerbation of rheumatoid arthritis: 1, hypothyroidism: 3, secondary adrenocortical insufficiency with ACTH isolated deficiency: 1, pneumonitis: 6, liver dysfunction: 1, neutropenia: 1, diarrhea: 1, rash: 3, infusion reaction: 1. Each irAEs had been basically managed according to algorism, such as treatment discontinuation, irritative treatment, steroid therapy, hormone replacement therapy etc. One patient, who developed multiple irAEs, diarrhea, liver dysfunction and neutropenia at same time, recovered from irAEs quickly by supportive care including steroid pulse therapy.

      Conclusion

      A variety of unexpected irAEs have been experienced in NSCLC patients treated with ICIs, however, excellent tumor response was observed in 10 of 13 patients who developed irAEs. In patient who showed multiple irAEs, tumor size was decreased significantly by nivolumab therapy and tumor progression was not observed 33 months after the final nivolumab administration. IrAEs associated with ICIs are diverse and difficult to predict, so safety management and early detection are important.

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    EP1.04 - Immuno-oncology (ID 194)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.04-26 - Efficacy and Safety of Anti-PD-1 Inhibitors in Elderly Patients with Advanced Non-Small Cell Lung Cancer (Now Available) (ID 2107)

      08:00 - 18:00  |  Author(s): Norihiko Ikeda

      • Abstract
      • Slides

      Background

      Recently, the proportion of elderly patients with advanced non-small cell lung cancer (NSCLC) has increased. However, those patients cannot occasionally continue to receive systemic therapy due to adverse events (AEs) or decreased performance status (PS). There are few reports which address efficacy and safety of anti-PD-1 inhibitors as the second line therapy for such elderly patients. The purpose of this study is to evaluate the efficacy and feasibility of anti-PD-1 inhibitors for elderly patients with advanced NSCLC are controversial.

      Method

      We retrospectively evaluated the efficacy and feasibility of anti-PD-1 inhibitors in 14 elderly patients (≥ 75 years old) with advanced NSCLC, comparing with 53 non-elderly patients (< 75 years old). All patients received anti-PD-1 inhibitors as the second line therapy or later.

      Result

      Of the 14 elderly patients, 11 patients had PS score 0 or 1. Anti-PD-1 inhibitors included nivolumab in 11 patients and pembrolizumab in 3 patients, and the median courses of anti-PD-1 inhibitors was 7 (1-27). There was no difference in patient background between the elderly group and the non-elderly group. The objective response rate (ORR) was 43% in the elderly group, while the rate was 30% in the non-elderly group (p = 0.33). The median progression-free survival (PFS) was 12.1 and 11.1 months in the elderly and non-elderly group, respectively (p = 0.86). The median overall survival (OS) was 14.3 and 29.6 months in the elderly and the non-elderly group, respectively (p = 0.53). Immune related AEs (irAEs) of grade 2 or higher were significantly observed in 50% of the elderly group, comparing with 17% of the non-elderly group (p = 0.048).

      肺癌学会2018 発表用(田中).jpg

      Conclusion

      The anti-PD-1 inhibitors led to good prognosis for the elderly patients with advanced NSCLC while the rate of irAEs was higher. The follow-up or management of irAE should be careful.

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    EP1.09 - Pathology (ID 199)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Pathology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.09-16 - A Case of Pulmonary Primary Enteric Adenocarcinoma Diagnosed Preoperatively (Now Available) (ID 1376)

      08:00 - 18:00  |  Author(s): Norihiko Ikeda

      • Abstract
      • Slides

      Background

      Pulmonary primary enteric adenocarcinoma(PEA) is a extremely rare subtype of lung cancer, which is defined in the new edition of 2015 WHO classification. Its histopathological and immunohistochemical feature is close to colorectal carcinoma, and it is important to distinguish between PEA and metastasis from colorectal carcinoma. In the paper, we present a case of PEA diagnosed before surgery.

      Method

      Case report

      Result

      A 72-year-old male was attending our hospital for rheumatoid arthritis, Thirty eight mm nodule in diameter was pointed out at the right S9 lung area by follow-up CT of interstitial pneumonia. The patient was refered to our department and TBLB was performed. Histopathological examination revealed that the tumor formes ducts composed of tall columnar cells. Immunohistochemical stains demonstrated positive for CK20, Cdx-2 and negative for CK7, TTF-1 and NapsinA. These findings were suggested metastatic colorectal carcinoma of the lung. However, additional clinical examinations, including FDG-PET/CT, gastroscopy and colonoscopy, did not reveal any existance of tumor elsewhere. The CEA level was 20 ng/ml. The patient was given a diagnosis of primary lung cancer, Pulmonary primary enteric adenocarcinoma staged as cT2aN0M0 stageIB was considered and right lower lobectomy with systemic lymph node dissection was performed. Final histopathological findings of the tumor was same as colorectal carcinoma. Immunohistochemical examinations were also the same as TBLB specimens. The final diagnosis was PEA and the staged as pT2aN0M0 stageIB.

      Conclusion

      PEA is difficult to confirm histopathologically or immunohistologically, and it is necessary to deny the existence of gastro intestinal carcinoma. At present, treatment of PEA should be conducted as primary lung cancer, including operation. It is thought that the biologic and clinical feature of PEA becomes crear by accumulation of more cases.

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    EP1.14 - Targeted Therapy (ID 204)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.14-23 - Comparison of Molecular Testing Using Various Specimens for Non-Small Cell Lung Cancers (Now Available) (ID 2767)

      08:00 - 18:00  |  Author(s): Norihiko Ikeda

      • Abstract
      • Slides

      Background

      The effectiveness of various molecular target drugs such as EGFR-TKI for non-small lung cancers came to be shown. So we performed a genetic tests to make plan for suitable therapy individually. For the cases that an operation was carried out for the lung cancer, I inspected the usefulness of the liquid biopsy. The somatic cell variation rate of detection in blood was low, and, in the relatively early non-small-cell lung cancer patient targeted for the operation, the tumor volume was shown in the rule factor when it was. I examined it including the lung cancer case that moved an object as well as an early case this time.

      Method

      Patients provided written informed consent for use of the samples were participated in this prospective research. EGFR mutation was examined using blood, a liquid cytological specimen, biopsy specimen. These patients was suspected lung cancer and bronchoscopy was performed. We collected blood, the cytodiagnosis specimen using liquid fixed vial for Cellprep and biopsy specimen. I examined EGFR mutations by three kinds of specimens using Cobas EGFR variation detection kit v2.0. We compared results of EGFR mutation,

      Result

      One-hundred fifty-eight patients were registered to this study. Among those patients, 77 patients with matched set of samples were enrolled to this study. EGFR mutation rates in tissue, cytology, and plasma were 37.7, 29.9 and 16.9 %, respectively. Overall agreement rate of the cytology specimens and the plasma specimens against the tissue samples were 87.0 and 75.3%, respectively. All eightT790M mutation positive cases were perfectly matched between tissue and cytology specimens.

      Conclusion

      We previously reported that detection of mutations in cfDNA of patients with disease at stage IA or IB or at T2a or lower is difficult. Tumor volume is a determining factor for the feasibility of mutation detection with cfDNA. In this study, advanced lung cancer patients were included. Biopsy specimen were the most feasible sample for detecting mutations. Since high specificities were confirmed in both cytology and plasma specimens, the results are reliable if the mutation results were positive. Choosing cytology or plasma specimens for EGFR testing can be the considerations for the patients who have difficulties in collecting tissue samples in the real world setting.

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    EP1.17 - Treatment of Early Stage/Localized Disease (ID 207)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.17-36 - Skin Fluorescence Following Photodynamic Therapy with Talaporfin Sodium (Now Available) (ID 1471)

      08:00 - 18:00  |  Author(s): Norihiko Ikeda

      • Abstract
      • Slides

      Background

      The purpose of this study was to establish a sensing to estimate relative talaporfin sodium concentrations in the skin using percutaneous fluorescence spectroscopy, to evaluate the risk of photosensitivity after photodynamic therapy (PDT) for lung cancer.Therefore, we conducted a prospective study to investigate whether talaporfin sodium fluorescence intensity in the skin after PDT could be measured effectively in human lung cancer patients to improve their management during their photosensitive period.

      Method

      Talaporfin sodium fluorescence was measured on the inside of the arm using the fluorescence sensing system that we established prior to and 5 and 10 min after talaporfin sodium administration, as well as at the time of PDT (4–5 h after administration), at discharge (2 or 3 days after PDT), and at 1 or 2 weeks after PDT.

      A total of 10 patients with lung cancer were analyzed. All measurements of talaporfin sodium fluorescence in the skin were obtained without any complications. Spectral peaks were detected at the time of discharge (2–3 days after administration) in most patients or at 1 or 2 weeks after PDT.

      Result

      The fluorescence peak increased with time after talaporfin sodium injection and decreased after a certain peak that was found 48-72 h after talaporfin sodium. The integration of the differential spectrum between obtained spectrum and reference spectrum was calculated to evaluate talaporfin sodium fluorescence in skin tissue.

      Conclusion

      The fluorescence of talaporfin sodium in the skin was readily detected in human patients using our newly established fluorescence sensing system. Furthermore, measuring the relative concentrations of talaporfin sodium indirectly in the skin by measuring fluorescence intensity may be useful for predicting the period of skin photosensitivity after PDT.

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    MA06 - Challenges in the Treatment of Early Stage NSCLC (ID 124)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 2
    • Now Available
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      MA06.05 - Predictive Performance of Quantitative Metabolic Metrics of FDG-PET/CT on Survival and the Effect of Adjuvant Chemotherapy in Lung Cancer (Now Available) (ID 1294)

      13:30 - 15:00  |  Author(s): Norihiko Ikeda

      • Abstract
      • Presentation
      • Slides

      Background

      Growing evidence suggests metabolic metrics of tumors, maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on FDG-PET/CT, reflect the malignancy of early-staged lung cancer. We aimed to investigate the role of metabolic metrics in predicting prognosis and response to adjuvant chemotherapy in pathological stage I (the 7th Edition of TNM Staging of Lung Cancer) lung adenocarcinoma (p-I Ad).

      Method

      The study included 452 patients with p-I Ad who underwent FDG-PET/CT followed by complete resection between July 2012 and December 2017. In this study, MTV is defined as the total tumor volume with an SUV > 2.5 while TLG is calculated as mean of SUV x MTV. The three metabolic metrics measured by a three-dimensional workstation and clinico-pathological factors were analyzed to identify the factors associated with unfavorable overall survival (OS) and recurrence-free survival (RFS). We assessed whether the metabolic metrics were associated with response to oral adjuvant chemotherapy with uracil-tegafur (AC with UFT) in patients with p-I Ad amenable to the treatment.

      Result

      All the three metabolic metrics were significantly correlated with unfavorable OS and RFS on univariate analyses (SUVmax; p=0.047 / p<0.001, MTV2.5; p=0.003 / p<0.001, TLG2.5; p=0.005 / p<0.001). On multivariate analyses, smoking status (p=0.043), the value of serum CEA (p < 0.001), and SUVmax (p=0.001) were independent determinants for poorer RFS while gender (p=0.013) and MTV2.5 (p=0.028) were independent significant factors for unfavorable OS. The receiver operating characteristic areas under the curves for SUVmax, MTV2.5, and TLG2.5 relevant to recurrence were 0.901, 0.849, and 0.872, respectively. Among 239 patients who fitted the criteria of AC with UFT (p-IA > 2cm or p-IB), 80 patients (33.4%) received the treatment (250 mg of tegafur per square meter of body-surface area per day). Although the administration of AC with UFT did not significantly affect RFS and OS (p=0.411 and 0.753), patients with TLG2.5 > 12.8, which value corresponded to the cut-off level, who were not given AC with UFT exhibited worse RFS than those who received the treatment (5-year RFS rate of 72.1% vs. 92.7%; p=0.041).figure.png

      Conclusion

      Metabolic metrics on FDG-PET/CT such as SUVmax, MTV, and TLG enable us to estimate survival outcomes and the effectiveness of AC with UFT in patients with p-I Ad. Patients with metabolically active tumors should be considered high risk, and this information can be useful for the selection of appropriate therapeutic strategy including AC with UFT.

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      MA06.06 - A Phase III Study of Adjuvant Chemotherapy in Patients with Completely Resected, Node-Negative Non-Small Cell Lung Cancer  (Now Available) (ID 285)

      13:30 - 15:00  |  Author(s): Norihiko Ikeda

      • Abstract
      • Presentation
      • Slides

      Background

      Post-operative UFT (tegafur/uracil) has been shown to prolong survival of Japanese patients with completely resected, p-stage I (T1> 2 cm) non-small cell lung cancer (NSCLC). This trial, the Japan Clinical Oncology Group (JCOG) 0707, aimed at estimating the efficacy of S-1 (tegafur/gimeracil/oteracil) compared to UFT as adjuvant therapy in this population.

      Method

      Eligible patients had received complete resection with lymph node dissection for p-stage I (T1-2N0M0, T1> 2 cm, by 5thEdition UICC TNM) NSCLC, within 56 days of enrollment. Patients were randomized to receive: oral UFT 250mg/m2/day for 2 years (Arm A), or oral S-1 80mg/m2/day for 2 weeks and 1 week rest, for 1 year (Arm B). The initial primary endpoint was overall survival (OS). Based upon the monitoring in Jun. 2013, which showed the combined OS of the 2 arms better than expected (4-year OS of 91.6% vs. presumed 5-year OS of 70-76.5%), it was judged to be underpowered. The study protocol was amended so that the primary endpoint is relapse-free survival (RFS). With the calculated sample size of 960, this study would detect the superiority of Arm B over Arm A with power 80% and one-sided type I error of 0.05, assuming the 5-year RFS of 75% in Arm A and the hazard ratio of 0.75.

      Result

      From Nov. 2008 to Dec. 2013, 963 patients were enrolled (Arm A : 482, Arm B : 481): median age 66 (range: 33 to 80), male 58%, adenocarcinoma 80%, p-T1/T2 46%/54%. Only 2 received pneumonectomy. >Grade 3 toxicities (hematologic/nonhematologic) were observed in 15.9 (1.5/14.7) % in Arm A, and in 14.9 (3.6/12.1) % in Arm B, respectively. 60.0% of the patients in Arm A and 54.7% of them in Arm B completed the protocol treatment (p=0.10). There were 4 cases of deaths during protocol treatment, probably of cardio-vascular origin, with 1 in Arm A and 3 in Arm B. At the data cut-off of Dec. 2018, the hazard ratio (HR, Arm B vs. Arm A) of RFS was 1.06 (95% confidence interval (C.I.): 0.82-1.36), showing no superiority of S-1 over UFT. The HR of OS was 1.10 (95% C.I.: 0.81-1.50). The 5-year RFS/OS rates were 79.4%/88.8% in Arm A and 79.5%/89.7% in Arm B, respectively. Pre-specified subset analyses for gender, age, smoking, stage, tumor side, lymph node dissection area, pleural invasion and histology revealed no remarkable results; S-1 arm was not superior to UFT arm in each analysis. Of the 77 and 85 OS events for Arm A/Arm B, 45 each (58%/53%, respectively) were due to the NSCLC. During the follow-up period, secondary malignancy was observed in 85 (17.8%) and 84 (17.8%) in Arm A and Arm B, respectively.

      Conclusion

      Post-operative adjuvant therapy with oral S-1 was not superior to that with UFT in stage I (T>2 cm) NSCLC after complete resection. UFT remains standard in this population. Future investigation should incorporate identification of high-risk population for recurrence, since survival of each arm was so good with substantial number of OS events due to other causes of deaths in this trial.

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    MA08 - Pawing the Way to Improve Outcomes in Stage III NSCLC (ID 127)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 1
    • Now Available
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      MA08.08 - Discussant - MA08.05, MA08.06, MA08.07 (Now Available) (ID 3745)

      15:15 - 16:45  |  Presenting Author(s): Norihiko Ikeda

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    MS16 - The Interventional Pulmonologist's Contribution to Screen-Detected Nodules: From Diagnosis to Treatment (ID 79)

    • Event: WCLC 2019
    • Type: Mini Symposium
    • Track: Interventional Diagnostics/Pulmonology
    • Presentations: 1
    • Now Available
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      MS16.05 - Optimal Treatment Selection for Screen-Detected Lung Cancers (Now Available) (ID 3534)

      14:30 - 16:00  |  Presenting Author(s): Norihiko Ikeda

      • Abstract
      • Presentation
      • Slides

      Abstract

      In recent years, the number of early stage lung cancers, especially cases showing ground-glass opacity (GGO) has enormously increased mainly due to frequent use of chest CT in routine practice or screening purpose. The surgical approach has enormously changed to pursue both curability and minimal inavasiveness for such early disease. Increased number of VATS lobectomy and sublobar resection for selected patients is the international trend.Conventional bronchoscopic examination for screening detected tiny cancers shows low diagnostic rate therefore the combination of virtual bronchoscopic navigation (VBN) and EBUS guide-sheath has been employed. A total of 40000 lung cancers were resected in Japan in 2015 and 70% of surgeries were performed by video-assisted1). Although there are a few randomized controlled trial, the evidence of VATS lobectomy is supported many propensity-matched studies, several high quality meta-analyses as well as outcome studies2). Segmentectomy has been performed intentionally mainly for lung cancer 2cm or less in diameter. Several comparative studies between lobectomy and segmentectomy for tumors < 2cm showed no significant difference in survival3). Recently, segmentectomy is selected based on the size, location as well as the consolidation size in the primary lesion in preoperative high resolution CT (HRCT). The proportion of consolidation diameter to tumor diameter (C/T ratio) correlates with biological malignancy and the establishment of robust image criteria predicting non-invasive cancer is desirable to find candidates for segmentectomy. The Japan Clinical Oncology Group (JCOG) conducted a prospective cohort study to recognize the relationship between HRCT finding and pathological non-invasiveness (no lymph node metastasis or vessel invasion) in clicical stage IA cancer (JCOG0201)4). This study revealed that adenocarcinoma <2.0 cm with <0.25 consolidation to the maximum tumor diameter showed pathological non-invasiveness in 98.7% and this criterion could be used to as radiological non-invasive adenocarcinoma5). Based on the result of JCOG0201, two prospective studies were performed and finished recruitment, phase II trial of wide wedge resection for radiological non-invasive adenocarcinoma (tumor diameter 2cm or less and consolidation ratio<0.25) (JCOG0804) and randomised phase III trial for radiological invasive adenocarcinoma (tumor diameter 2cm or less and consolidation ratio>0.25) to evaluate non-inferiority in OS of segmentectomy compared to lobectomy (JCOG0802)6). The indication of segmentectomy will be demonstrated by the results of these studies. Although C/T ratio in the maximum plane of the tumor has been applied clinically as an index of malignancy, objective measurement is sometimes difficult due to the irregular shape of objectives. It should be more accurate to analyze the ratio of the consolidation part volume to whole tumor volume quantitatively by creating 3D-CT image. In our analysis of 252 cases of stage I lung cancer, the solid part volume of the tumor had a statistically significant correlation with prognosis7). In addition, PET-CT has been routinely used for the management of lung cancer and another approach to evaluate the biological aggressiveness. The standardized uptake value (SUV) of the main tumor is recognized to be as a predictor of the clinicopathological characteristics. Our data showed that more accurate prognosis of stage IA adenocarcinoma could be predicted by the combination of SUVmax and solid part volume of the primary tumor8). Since CT reflects the histologic grade of the tumor and SUVmax reflects the intratumoral metabolism, the combined use of these may be expected to evaluate nature of lung cancer more precisely than each alone.The information on the grade of malignancy obtained from preoperative images is useful for selecting appropriate treatment. In the near future, radiomics can analyze the radiologic images and extract important pathological and genomic information non-invasively before treatment. Advances in imaging and quantitative analysis will be powerful support to select interventions of screening detected lung cancer.

      References

      1) Committee for Scientific Affairs The Japanese Association for Thoracic Surgery, Thoracic and cardiovascular surgery in Japan during 2015 : Annual report by the Japanese Association for Thoracic Surgery. Gen Thorac Cardiovasc Surg.2018;66:581-615.

      2) Ikeda N Updates on minimally inavasive surgery in non-small cell lung cancer. Curr. Treat. In Oncol. 2019;20:16 (DOI 10.1007/s11864-019-0614-9)

      3) Okada M, Koike T, Higashiyama M, et al. Radical sublobar resection for small-sized non-small cell lung cancer: a multicenter study. J Thorac Cardiovasc Surg. 2006; 132: 769-775

      4) Suzuki K, Koike T, Asakawa T, et al.: A prospective radiological study of thin-section computed tomography to predict pathological noninvasiveness in peripheral clinical IA lung cancer (Japan Clinical Oncology Group 0201). J Thorac Oncol 2011;6:751-756

      5) Asamura H, Hishida T, Suzuki K, et al. Radiographically determined noninvasive adenocarcinoma of the lung: Survival outcomes of Japan Clinical Oncology Group 0201 J Thorac Cardiovasc Surg 2013;146:24-30

      6) Nakamura K, Saji H, Nakajima R, et.al. A Phase III Randomized Trial of Lobectomy Versus Limited Resection for Small-sized Peripheral Non-small Cell Lung Cancer (JCOG0802/WJOG4607L) Jpn J Clin Oncol 2010;40:271–274

      7) Shimada Y, Furumoto H, Imai K, et al. Prognostic value of tumor solid-part size and solid-part volume in parients with clinical stage I non-small cell lung cancer. J Thorac Dis 2018;10:6491-6500

      8) Furumoto H, Shimada Y, Imai K, et al. Prognostic impact of the integration of volumetric quantification of the solid part of the tumor on 3DCT and FDG-PET imaging in clinical stage IA adenocarcinoma of the lung. Lung Cancer 2018;121:91-96

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    P1.04 - Immuno-oncology (ID 164)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.04-07 - Immune Suppressive Microenvironment and Highly Clonal Concordance of TCR Repertoire in Brain Metastases from Non-Small Cell Lung Cancer (ID 2018)

      09:45 - 18:00  |  Author(s): Norihiko Ikeda

      • Abstract
      • Slides

      Background

      The tumor immune microenvironment (TIME) of lung cancer brain metastasis is largely unexplored. We performed immune profiling and sequencing analysis of paired resected primary tumors and brain metastases of non-small cell lung carcinoma (NSCLC).

      Method

      TIME profiling of archival formalin-fixed and paraffin embedded specimens of paired primary tumors and brain metastasis from 39 patients with surgically resected NSCLCs was performed using a 770 immune gene expression panel (NanoString Technologies, Seattle, WA) and by T cell receptor beta repertoire (TCRß) sequencing (Adaptive Biotechnologies, Seattle, WA). Immunohistochemistry was performed for validation. Targeted sequencing was performed to catalog hot spot mutations in cancer genes (ThermoFisher Scientific, Waltham, MA).

      Result

      Somatic hot spot mutations were mostly shared between both tumor sites (28/39 patients; 71%). We identified 161 differentially expressed genes, indicating inhibition of dendritic cell maturation, Th1, and leukocyte extravasation signaling pathways, in brain metastases compared to primary tumors (p < 0.01). The proinflammatory cell adhesion molecule vascular cell adhesion protein 1 was significantly suppressed in brain metastases compared to primary tumors. Brain metastases exhibited lower T cell and elevated macrophage infiltration compared with primary tumors (p < 0.001). T cell clones were expanded in 64% of brain metastases compared with their corresponding primary tumors. Further, while TCR repertoires were largely shared between paired brain metastases and primary tumors, T cell densities were sparse in the metastases.

      Conclusion

      We present findings that the TIME in brain metastases is immunosuppressed when compared to matched primary tumors in NSCLC patients, and that thus may help guide immunotherapeutic strategies for NSCLC brain metastases.

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    P1.17 - Treatment of Early Stage/Localized Disease (ID 188)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.17-02 - The Investigation of Intraoperative Marking by Transbronchial Low Power Laser Irradiation in Human Lung (ID 144)

      09:45 - 18:00  |  Author(s): Norihiko Ikeda

      • Abstract
      • Slides

      Background

      Small lung nodules which appear to be ground glass opacity in peripheral lung are difficult to identify during surgery. In order to identify the site of such lesions, various types of preoperative or intraoperative marking methods have been reported. However, there is no definitive way. Therefore, we have reported a new safe and reliable intraoperative marking method using low power laser light. By irradiating low power laser close to the lesion from a bronchus, the site of the lesion can be identified from the lung surface by looking at the laser light. We conducted an animal experiment and were able to observe the laser light irradiated in bronchus from the lung surface. In this study, we performed laser irradiation to the resected human lung to confirm whether the laser light can actually be observed safely from lung surface.

      Method

      The patient was 70-year-old male (40 pack-years ex-smoker). The adenocarcinoma (55×40mm) was located at right S2 area. Immediately after right upper lobectomy, a plastic cylindrical-type laser probe was inserted into peripheral bronchus of the resected lung. The probe was very thin (0.8mm diameter) and flexible. Therefore, it can be inserted into the peripheral lung. It was developed jointly with Keio University. The probe was induced just below the pleura and 70mW low power laser irradiation was performed. We examined whether laser light could be confirmed from lung surface. The effect of laser irradiation to the lung tissue was evaluated pathologically.

      Result

      When the probe was guided to just below the pleura, laser light could be clearly observed from the lung surface. After that, the probe was gradually withdrawn. The laser light could be observed until the depth of 10mm from the pleura. No damage was obtained around the laser irradiated area in pathological findings. The observable depth of laser light was slightly shallow at10mm. The reasons of this were guessed that lung expansion was not sufficiently because harvested lung was used, so the density of lung tissue was increase and pleural thickening and anthracosis were observed in the lung because of his smoking history.

      Conclusion

      It might be possible to confirm the localization of small nodules in peripheral lung using low power laser light during surgery.

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    P2.17 - Treatment of Early Stage/Localized Disease (ID 189)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.17-39 - Relationship Between EGFR Mutation and Pathological Differentiation in Patients with Clinical Stage IA Lung Adenocarcinoma (ID 3008)

      10:15 - 18:15  |  Author(s): Norihiko Ikeda

      • Abstract

      Background

      Pathological differentiation is an established prognostic factor for patients with lung

      adenocarcinoma. There are some correlations between epidermal growth factor receptor

      (EGFR) mutations and pathological differentiation. EGFR mutation-positive

      adenocarcinoma is considered to be highly differentiated types that show development

      of alveolar epithelial substitution. However, the distribution of pathological

      differentiation and the prognostic impact of the presence or absence of EGFR mutations

      in early adenocarcinoma are not clear.

      Method

      We collected the records of 569 patients who underwent surgical resection for clinical

      stage ⅠA lung adenocarcinoma between 2008 and 2015, and were also examined their

      EGFR mutation status.

      Based on the presence or absence of EGFR mutations and pathological differentiation

      (well;G1/moderately;G2/poorly;G3), patients were categorized into 6 groups: EGFR

      mutation positive (E+) with G1, E+ with G2, E+ with G3, EGFR mutation negative (E-)

      with G1, E- with G2, E- with G3. We examined the distribution of each group, 

      clinicopathological features and prognosis.

      Result

      303 lung adenocarcinoma had EGFR mutations. The distribution was

      E+/G1:85,E+/G2:209,E+/G3:9,E-/G1:50,E-/G2:178,E-/G3:38. E+/G3 group was

      significantly fewer (P<0.001). The 5-year recurrence-free survival (RFS) rates were

      95% in E+/G1 group, 78% in E+/G2 group, 33% in E+/G3 group, 100% in E-/G1

      group, 75% in E-/G2 group, 61% in E-/G3 group. The 5-year overall survival (OS) rates

      were 98% in E+/G1 group, 91% in E+/G2 group, 44% in E+/G3 group, 100% in E-/G1

      group, 87% in E-/G2 group, 79% in E-/G3 group. The prognosis was significantly

      worse in the E+/G3 group. There were more women (77%) and non-smokers (89%) in

      the E+/G3 group. Six patients (66%) had recurrence, and in all cases EGFR-TKI was

      administered and the response rate was 100%.

      Conclusion

      Most of the c-IA EGFR positive adenocarcinomas were highly differentiated, and

      significantly fewer poorly differentiated cases. Among the poorly differentiated group,

      EGFR gene mutation positive is particularly poor prognosis. However, The therapeutic

      effect of EGFR-TKI was not different from other EGFR positive patients.

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    S01 - IASLC CT Screening Symposium: Forefront Advances in Lung Cancer Screening (Ticketed Session) (ID 96)

    • Event: WCLC 2019
    • Type: Symposium
    • Track: Screening and Early Detection
    • Presentations: 1
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      S01.22 - Session V - IASLC Leads the International Collaboration on Data Sharing (ELIC) (ID 3647)

      07:00 - 12:00  |  Author(s): Norihiko Ikeda

      • Abstract

      Abstract not provided