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Kazuhiro Yasufuku
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ES 07 - Recent Advances in Diagnostics and Interventional Bronchoscopy (ID 516)
- Event: WCLC 2017
- Type: Educational Session
- Track: Pulmonology/Endoscopy
- Presentations: 1
- Moderators:Stephen Lam, N. Kurimoto
- Coordinates: 10/18/2017, 11:00 - 12:30, Room 503
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ES 07.01 - Endoscopic Staging of Lung Cancer (ID 7610)
11:00 - 12:30 | Presenting Author(s): Kazuhiro Yasufuku
- Abstract
- Presentation
Abstract:
Endoscopic Staging of Lung Cancer Kazuhiro Yasufuku During the management of patients with lung cancer, accurate lymph node staging is important not only to determine the prognosis but also to decide the most suitable treatment plan. Non-invasive staging such as computed tomography (CT) and positron emission tomography (PET) indicate size and metabolic activity, respectively. However imaging alone is inaccurate and therefore tissue sampling is the preferred and most reliable. Surgical staging by mediastinoscopy has been the gold standard for mediastinal lymph node staging but requires general anesthesia and complications cannot be ignored. Endoscopic ultrasound techniques provide a minimally invasive alternative for surgical staging and have become available for oncologists around the world. The current available endoscopic ultrasound techniques for mediastinal staging include transesophageal endoscopic ultrasound guided fine needle aspiration (EUS-FNA) and endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA). Both procedures are performed in an outpatient setting under local anesthesia. EUS-FNA is a sensitive and safe method of evaluating the inferior mediastinal nodes (stations 7, 8, and 9) and some parts of the anterior mediastinal nodes if the lymph nodes are accessible from the esophagus. However, in spite of the strength of EUS-FNA for evaluating the inferior mediastinal nodes, its ability to evaluate lesions anterior to the trachea is limited. On the other hand, EBUS-TBNA has reach to the paratracheal and subcarinal (stations 2R, 2L, 4R, 4L, 7), as well as the N1 lymph nodes (stations 10, 11, 12). In experienced hands, EBUS can be used through the esophagus for a EUS-like approach to sample inferior mediastinal lymph nodes. With the transvascular approach, AP window lymph nodes (station 5) can be sampled by EUS-FNA and/or EBUS-TBNA. Specialized centers have reported the sampling of station 6 via EUS-FNA. Thus, EUS-FNA and EBUS-TBNA are complementary methods for lymph node staging in lung cancer and most of the mediastinum and the hilum can be evaluated with these endoscopic procedures beyond the reach of mediastinoscopy. Based on the current evidence, EBUS-TBNA and EUS-FNA presents a minimally invasive endoscopic procedure of choice for mediastinal staging of NSCLC with discrete N2 or N3 lymph node enlargement, provided negative results are confirmed by surgical staging. When combined the techniques offer safe and accurate assessment of mediastinum, with accuracy surpassing that of the pervious gold standard – cervical mediastinoscopy. EBUS-TBNA and/or EUS-FNA can also be repeated with ease and have been used for mediastinal restaging in patients who underwent neoadjuvant therapy in preparation for definitive surgical intervention. New size needles are now available for sampling of the lymph nodes during EBUS-TBNA including 25-gauge and 19-gauge needles. Smaller needles may provide greater reach with good quality samples, whereas larger 19-gauge needle may provide bigger tissue for histological evaluation of the lymph nodes samples. There are limitations of using cytological samples obtained during EBUS-TBNA or EUS-FNA for PD-L1 expression. The use of the 19-gauge needle may solve this problem.
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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
- Moderators:Yoichi Nakanishi, P. Mitchell
- Coordinates: 10/16/2017, 15:45 - 17:30, Room 303 + 304
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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): Kazuhiro Yasufuku
- Abstract
- Presentation
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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OA 15 - Diagnostic Radiology, Staging and Screening for Lung Cancer II (ID 684)
- Event: WCLC 2017
- Type: Oral
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:Y. Satoh, Jin Mo Goo
- Coordinates: 10/18/2017, 14:30 - 16:15, Room 303 + 304
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OA 15.01 - Lung Cancer Screening: Participant Selection by Risk Model – the Pan-Canadian Study (ID 8466)
14:30 - 16:15 | Author(s): Kazuhiro Yasufuku
- Abstract
- Presentation
Background:
Retrospective studies indicate that selecting individuals for low dose computed tomography (LDCT) lung cancer screening based on a highly predictive risk model is superior to applying National Lung Screening Trial (NLST)-like criteria, which use only categorized age, pack-year and smoking quit-time information. The Pan-Canadian Early Detection of Lung Cancer Study (PanCan Study) was designed to prospectively evaluate whether individuals at high risk for lung cancer could be identified for screening using a risk prediction model. This paper describes the study design and results.
Method:
2537 individuals were recruited through 8 centers across Canada based on a ≥2% of lung cancer risk estimated by the PanCan model, a precursor to the validated PLCOm2012 model. Individuals were screened at baseline and 1 and 4 years post-baseline.
Result:
At a median 5.5 years of follow-up, 164 individuals (6.5%) were diagnosed with 172 lung cancers. This was a significantly greater percentage of persons diagnosed with lung cancers than was observed in the NLST(4.0%)(p<0·001). Compared to 57% observed in the NLST, 77% of lung cancers in the PanCan Study were early stage (I or II) (p<0.001) and to 25% in a comparable population, age 50-75 during 2007-2009 in Ontario, Canada’s largest province, (p<0·001).
Conclusion:
Enrolling high-risk individuals into a LDCT screening study or program using a highly predictive risk model, is efficient in identifying individuals who will be diagnosed with lung cancer and is compatible with a strong stage shift – identifying a high proportion at early, potentially curable stage. Funding This study was funded by the Terry Fox Research Institute and Canadian Partnership Against Cancer. ClinicalTrials.gov number, NCT00751660
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P1.02 - Biology/Pathology (ID 614)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.02-034 - Non-Invasive Qualitative Diagnosis of Lung Cancer Enabled by Spectrum Analysis of Ultrasound (ID 9376)
09:30 - 16:00 | Author(s): Kazuhiro Yasufuku
- Abstract
Background:
Ultrasound has been widely utilized in clinical to visualize the internal structure of the objective non-invasively. However ultrasound image can’t distinguish malignant lesion from the normal tissue. Spectrum analysis of ultrasound is a newly developed technology which may reflect on the histological feature. We examine if the spectrum analysis is able to distinguish malignant tissue from normal tissue.
Method:
Spectrum was measured using a prototype ultrasound processor EUME5 given by Olympus Japan. three parameters of spectrum such as Midband-fit(M), Intercept(I), and Slope(S) were measured for the objective tissue. In animal study, human lung cancer Xenograft were created in nude mice for each lung cancer cell line (A549, H460, HCC827, and H3122). In clinical setting, surgically excised lungs including lung cancers were examined spectrum analysis for both lung cancers (n=19, 106 slices) and normal lungs (n=17, 65 slices).
Result:
Four different Xenografts exhibited significant differences of spectrum data. In the clinical study, the mean value of M, I and S of both lung cancers and normal lungs were M: -43.22 ±4.09 vs -39.31±3.87(p<0.01,) I: -55.28±3.19 vs -54.13±2.4 (N.S), S: -1.43±0.35 vs -1.73±0.30 (p<0.01)
Conclusion:
Each lung cancer Xenograft of different histology showed different spectrum value. Spectrum analysis is likely to reflect the histological feature. In clinical, M and S showed statistically different values between lung cancer and normal lung. Based on spectrum value, a malignant tumor can be distinguished from the normal lung in the ultrasound image.
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P1.12 - Pulmonology/Endoscopy (ID 698)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Pulmonology/Endoscopy
- Presentations: 2
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.12-002 - Nanoparticle Targeted Folate Receptor 1 Enhanced Photodynamic Therapy for Lung Cancer (ID 8471)
09:30 - 16:00 | Author(s): Kazuhiro Yasufuku
- Abstract
Background:
Despite modest improvements, the prognosis of lung cancer patients has still remained poor and new treatment are urgently needed. Photodynamic therapy (PDT), the use of light-activated compunds (photosensitizers) is a treatment option but its use has been restricted to central airway lesions. Here, we report the use of novel porphyrin-lipid nanoparticles (porphysomes) targeted to folate receptor 1 (FOLR1) to enance the efficacy and specificity of PDT that may translate into a minimally-invasive intervention for peripheral lung cancer and metastatic lymph nodes of advanced lung cancer.
Method:
The frequency of FOLR1 expression in primary lung cancer and metastatic lymph nodes was first analyzed by human tissue samples from surgery and endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS-TBNA). Confocal fluorescence microscopy was then used to confirm the cellular uptake and fluorescence activation in lung cancer cells, and the photocytotoxicity was evaluated using a cell viability assay. In vivo fluorescence activation and quantification of uptake were investigated in mouse lung orthotopic tumor models, followed by the evaluation of in vivo PDT efficacy.
Result:
FOLR1 was highly expressed in metastatic lymph node samples from patients with advanced lung cancer and was mainly expressed in lung adenocarcinomas in primary lung cancer. Expression of FOLR1 in lung cancer cell lines corresponded with the intracellular uptake of folate-porphysomes in vitro. When irradiated with a 671 nm laser at a dose of 10 J/cm2, folate-porphysomes showed marked therapeutic efficacy compared with untargeted porphysomes (28% vs. 83% and 24% vs. 99% cell viability in A549 and SBC5 lung cancer cells, respectively. Systemically-administered folate-porphysomes accumulated in lung tumors with significantly enhanced disease-to-normal tissue contrast. Folate-porphysomes mediated PDT successfully inhibited tumor cell proliferation and activated tumor cell apoptosis.
Conclusion:
Folate-porphysome based PDT shows promise in selectively ablating lung cancer based on FOLR1 expression in these preclinical models.
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P1.12-003 - Photothermal Ablation of Lung Cancer by Low Power Near-Infrared Laser and Topical Injection of Indocyanine Green; A Preliminary Animal Study (ID 8994)
09:30 - 16:00 | Author(s): Kazuhiro Yasufuku
- Abstract
Background:
Surgical resection by lobectomy with systematic lymph node dissection is the gold standard of treatment for early stage non-small cell lung cancer. However, minimally invasive tumor ablation can be an alternative treatment for patients not eligible for surgery due to comorbidities. The present study was designed to evaluate the efficacy of photothermal ablation therapy for lung cancer by low power near-infrared laser and topical injection of Indocyanine green (ICG).
Method:
6 New Zealand white rabbits were employed for the study. Tumor suspension containing VX2 cancer cells with growth factor reduced Matrigel was inoculated into the lung using an ultrathin bronchoscope. 3 rabbits were treated by laser ablation therapy with topical injection of ICG. Another 3 rabbits were treated by laser ablation alone. All tumors were irradiated with a laser with 500 mW output at 808 nm for 15 min. The tumors were examined histopathologically to assess the ablated areas.
Result:
Figure 1The maximum surface temperature of the tumor in rabbits treated by ICG/laser and laser alone were more than 58°C and less than 40°C, respectively. The ablated areas in the rabbits using ICG/laser were statistically larger than those in the rabbits using laser alone (ICG/laser: 0.49±0.27 cm[2] vs laser alone: 0.02±0.002 cm[2]) (p < 0.05).
Conclusion:
We clarified the efficacy of the photothermal treatment by low power near-infrared laser and topical injection of ICG using a rabbit VX2 orthotopic lung cancer model. This system may be able to be applied for transbronchial laser ablation of peripheral lung cancers.
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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
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.13-004 - The Role of Lymph Node Staging by EBUS-TBNA in Stereotactic Body Radiation Therapy for patients with Non-Small Cell Lung Cancer. (ID 8070)
09:30 - 16:00 | Author(s): Kazuhiro Yasufuku
- Abstract
Background:
Stereotactic body radiation therapy (SBRT) is an option for treatment of patients with non-small cell lung cancer (NSCLC). Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive, diagnostic modality for mediastinal and hilar staging of NSCLC. We evaluated the diagnostic value of EBUS-TBNA in SBRT candidates and compared it to that of computed tomography (CT) and positron emission tomography (PET) scans.
Method:
Inclusion criteria for this single institutional retrospective study included 1) biopsy-proven or clinically suspicious NSCLC with diameter <6 cm; 2) no evidence of distant metastasis; 3) EBUS-TBNA staging between April 2008 and November 2014; 4) medically SBRT-eligible other than nodal staging. CT and PET positive nodes were defined as short axis ≧1cm and standardized uptake value ≧2.5, respectively. Node positive by clinical-pathologic confirmation (NPCP) was defined as confirmed malignancy by EBUS-TBNA or clinically diagnosed recurrence in hilar or mediastinal lymph nodes within one year after SBRT. The survival after SBRT was compared between CT or PET node-positive but EBUS-TBNA result-negative patients, and a matched cohort (tumor size; radiation dose; operability) who underwent SBRT in our institution within the same time period but without EBUS-TBNA staging.
Result:
There were 35 eligible patients (mean age 77±8.2, 24 male). Thirty-two (91.4%) patients had pathological confirmation of NSCLC (mean diameter 2.5±1.0 cm) (T1a N=12, T1b N=15, T2a N=7, T2b N=1). Thirty (85.7%) patients were medically inoperable. After EBUS-TBNA, 20 out of 24 patients who had positive nodes in CT (N=13) or PET (N=17) were ultimately pathologically N0. All eleven image-negative patients were N0 following EBUS-TBNA. Thirty-one patients (20 image positive plus 11 image negative) underwent SBRT. Sensitivity/specificity of CT, PET and EBUS-TBNA for NPCP were 42.9/64.3%, 100/64.3% and 57.1/100%, respectively. Positive predictive value of CT and PET for NPCP was 23.1% and 41.2%, respectively. Negative predictive value of CT, PET and EBUS for NPCP was 81.8%, 100% and 90.3%, respectively. A 1:4 (Case; N=20, Control; N=76) match was obtained. Regional failure-free survival (p=0.71, HR=0.88 CI 0.45-1.74) and disease-free survival (p=0.77, HR=1.10 CI 0.58-2.11) of the Case were not significantly different from the ones of Control. There were no major complications related to EBUS procedures.
Conclusion:
EBUS-TBNA can be considered for invasive staging in SBRT-eligible NSCLC patients with radiographically positive lymph nodes because of its safety and possibility of false positive imaging. If EBUS-TBNA result is negative, these patients may remain candidates for SBRT with comparable outcomes to those who are conventionally selected for SBRT.
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WS 04 - Minimally Invasive Diagnosis and Staging of Lung Cancer – Interventional Pulmonology Hands-On Workshop (Ticketed Session) (ID 766)
- Event: WCLC 2017
- Type: Workshop
- Track: Pulmonology/Endoscopy
- Presentations: 2
- Moderators:
- Coordinates: 10/15/2017, 13:00 - 17:00, Room 416 + 417
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WS 04.01 - Welcome and Introduction (ID 11036)
13:00 - 17:00 | Presenting Author(s): Kazuhiro Yasufuku
- Abstract
- Presentation
Abstract not provided
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WS 04.02 - EBUS-TBNA – Role in Invasive Mediastinal Staging (ID 11037)
13:00 - 17:00 | Presenting Author(s): Kazuhiro Yasufuku
- Abstract
- Presentation
Abstract not provided
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