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Morihito Okada
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MA01 - Early Stage Lung Cancer: Questions and Controversies (ID 894)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 10:30 - 12:00, Room 202 BD
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MA01.06 - Evaluation of Safety and Efficacy in Surgical Treatment for Octogenarian Lung Cancer Patients by Multicenter Prospective Study: JACS1303 (ID 13117)
11:05 - 11:10 | Author(s): Morihito Okada
- Abstract
- Presentation
Background
The percentage of octogenarian lung cancer patients have increased on the background of the aging of Japan’s demographics. Although some retrospective studies reported clinicopathological scoring systems for predicting postoperative complications and survival outcomes for elderly lung cancer patients, optimized scoring systems remain controversial. This study (JACS1303) aims to evaluate the clinical factors to develop a comprehensive operative risk scoring (RS) system for octogenarian patients with lung cancer.
a9ded1e5ce5d75814730bb4caaf49419 Method
JACS conducted a nationwide multicenter prospective cohort and enrolled a total of 1,019 octogenarians with medically operable lung cancer. Details of the clinical factors, comorbidities, and comprehensive geriatric assessment were recorded for 895 patients to develop a comprehensive risk scoring (RS) system capable of predicting severe complications.
4c3880bb027f159e801041b1021e88e8 Result
Operative (30 days) and hospital mortality rates were 1.0% and 1.6%, respectively. Complications were observed in 308 (34%) patients, of whom 81 (8.4%) had grade 3–4 severe complications. Pneumonia was the most common severe complication, observed in 27 (3.0%) patients. The following five predictive factors: gender, comprehensive geriatric assessment (CGA)75: memory, Simplified Comorbidity Score (SCS): diabetes mellitus, Alb, and %VC were identified as independent predictive factors for severe postoperative complications (odds ratio = 2.73, 1.86, 1.54, 1.66, and 1.61, respectively) through univariate and multivariate analyses. A 5-fold cross validation was performed as an internal validation to reconfirm these five predictive factors (average AUC: 0.70). We developed a simplified RS system as follows: RS = 3 (Gender: male) + 2 (CGA75: memory: yes) + 2 (Alb: <3.8 ng/ml) + 1 (%VC: ≤90) + 1 (SCS: Diabetes mellitus: yes).
8eea62084ca7e541d918e823422bd82e Conclusion
The current study shows that octogenarians can be successfully treated for lung cancer with surgical resection with an acceptable rate of severe complications and mortality. We propose a simplified RS system to predict severe complications in octogenarian patients with medically operative lung cancer.
6f8b794f3246b0c1e1780bb4d4d5dc53Only 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.
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OA08 - Mesothelioma: Immunotherapy and microRNA for Diagnosis and Treatment (ID 907)
- Event: WCLC 2018
- Type: Oral Abstract Session
- Track: Mesothelioma
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 15:15 - 16:45, Room 201 BD
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OA08.01 - Long-Term Efficacy and Safety of Nivolumab in Second- or Third-Line Japanese Malignant Pleural Mesothelioma Patients (Phase II: MERIT Study) (ID 11833)
15:15 - 15:25 | Author(s): Morihito Okada
- Abstract
- Presentation
Background
Malignant Pleural Mesothelioma (MPM) is a rare and highly aggressive malignancy with poor prognosis and no treatment is approved for patients (pts) progressing after 1st line pemetrexed-platinum doublet. Here, we report latest analysis of MERIT study in previously treated Japanese MPM pts to update the previous report (WCLC 2017, Goto Y, et al).
a9ded1e5ce5d75814730bb4caaf49419 Method
This open-label study enrolled advanced or metastatic MPM pts previously treated with up to two regimens of chemotherapy including pemetrexed-platinum doublet. Enrollment criteria also included histologically-confirmed, unresectable MPM without prior surgery, measurable lesion and ECOG performance status 0-1. There was no restriction of PD-L1 status. Pts received Nivolumab 240 mg flat dose Q2W until progression or unacceptable toxicity. Primary endpoint was objective response rate (ORR) (modified RECIST by independent review committee, expected response rate was 19.2%); secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS) and safety.
4c3880bb027f159e801041b1021e88e8 Result
Thirty-four pts received Nivolumab in this study. Males: 85.2%, median age: 68.0 years (range 43-78), PS 1: 61.8%, epithelial/sarcomatoid/biphasic: 79.4%/8.8%/11.8%, 1 prior regimen: 70.6% and PD-L1 (≧1%)/PD-L1 (<1%)/not evaluable: 58.8%/35.3%/5.9%. At a median follow-up of 16.8 months (range: 1.8-20.2), ORR was 29.4 % (n=10, 95%CI: 16.8-46.2). DCR was 67.6% (n=23, 95%CI: 50.8-80.9). Median DOR was 11.1 months (95%CI: 3.5-16.2). Median PFS was 6.1 months (95%CI: 2.9-9.9) in all pts, 7.2 months (2.8-15.0) in PD-L1 (≧1%) and 2.9 months (1.4-9.3) in PD-L1 (<1%). Median OS was 17.3 months (95%CI: 11.5-NR) in all pts, 17.3 months (8.2-NR) in PD-L1 (≧1%), 11.6 months (5.8-NR) in PD-L1 (<1%), across tissue types, 15.7 months (95%CI: 8.0-NR) in epithelioid and not reached in sarcomatoid/biphasic pts. Six- and 12-month survival rates were 85.3% (95%CI: 68.2-93.6) and 58.8% (95%CI: 40.6-73.2). Twenty-six (76.5%) pts experienced treatment-related adverse event (TRAE), and 11 (32.4%) experienced grade 3/4 TRAEs. Most commonly reported TRAEs were skin disorder (n=6, 17.6%), elevated lipase (n=5, 14.7%), elevated amylase and diarrhea (n=4, 11.8%). Four pts required dose discontinuation because of interstitial pneumonia (n=2, grade2 and 3) and pneumonitis (n=2, grade3).
8eea62084ca7e541d918e823422bd82e Conclusion
Nivolumab shows durable long term efficacy and manageable safety profile in Japanese 2nd/3rd line MPM pts.
6f8b794f3246b0c1e1780bb4d4d5dc53Only 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.
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P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.01-97 - Prognostic Factors in Resected Lung Mucinous Adenocarcinoma: Clinical and Pathological Features (ID 13241)
16:45 - 18:00 | Author(s): Morihito Okada
- Abstract
Background
Mucinous adenocarcinoma is rare subtype of lung adenocarcinoma. This study aimed to discover which factors influenced prognosis of resected lung mucinous adenocarcinoma.
a9ded1e5ce5d75814730bb4caaf49419 Method
From April 1997 to March 2017, we retrospectively reviewed the clinical and pathological features in resected lung mucinous adenocarcinoma patients. We specially focused on KRAS mutation and NRG1 fusion, which were reported that MA often harbored them. We also examined CT findings (solitary type or pneumonic type) and spread through air space(STAS). The Kaplan-Meier method and log -rank test were used for the survival analyses.
4c3880bb027f159e801041b1021e88e8 Result
57 patients were enrolled to the study. We detected KRAS mutation in 32 patients (56.1%) and NRG1 fusion in one patient (1.8%). G12D was the most common in terms of amino acid change of KRAS mutation (78%). There were no significant differences in overall survival (OS) and disease-free survival (DFS) between patients with KRAS wild type and those with KRAS mutation (p=0.70 and p=0.85[Office1] , respectively). In point of CT finding, there were 42 solitary type of tumors and 15 pneumonic type of tumors. OS and DFS were significantly worse in pneumonic type patients (p<0.01 and p<0.01[Office2] , respectively). STAS was observed in 32 patients. DFS was significantly shorter in patient with STAS(p=0.03) although OS was not(p=0.07).[Office3] Multivariate analysis revealed that CT finding (pneumonic type) was an independent prognostic factor of DFS.
8eea62084ca7e541d918e823422bd82e Conclusion
Pneumonic type on CT finding was an independent prognostic factor in patients with completely resected lung mucinous adenocarcinoma. KRAS status was not significantly related to the prognosis in our cohort.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.03 - Biology (Not CME Accredited Session) (ID 952)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.03-14 - PKCι-PAK1 Pathway Modulates Sensitivity to Therapy in EGFR, KRAS Mutant and Squamous Cell Non-Small Cell Lung Cancer (NSCLC) (ID 12342)
16:45 - 18:00 | Author(s): Morihito Okada
- Abstract
Background
To understand intrinsic and acquired resistance to different MAPK signaling inhibitors, we explored PKCι-PAK1 signaling in EGFR, KRAS and Squamous cell carcinoma (SCC) cell lines.
a9ded1e5ce5d75814730bb4caaf49419 Method
Three lung cancer cell lines were used: HCC827 and H23 lung adenocarcinoma cells that carry EGFR and KRAS mutations, respectively, and H520 PAK1 amplified squamous NSCLC cells. Cell viability assays and western blotting were applied to evaluate the effect of auranofin (PKCi inhibitor) plus IPA-3 (PAK1 inhibitor). Since IPA-3 is only for laboratory use, we also tested auranofin in combination with OTSSP167 (a MELK inhibitor in phase I trials), which, in our experience, inhibits pPAK1 (Thr423 and Thr212 in the HCC827 cell line).
4c3880bb027f159e801041b1021e88e8 Result
Auranofin plus IPA-3 was highly synergistic (CI less than 0.4) in EGFR mutant (HCC827), KRAS mutant (H23) and SCC with PAK1 amplification (H520 cells). Similar synergism was found with the combination of auranofin plus OTSSP167 in the 3 cell lines (Figure). the combination of auranofin with either IPA-3 or OTSSP167 ablated EGFR phosphorylation and downstream signaling pathways: ERK, AKT, STAT3, YAP1 and inhibited the expression of RTKs: AXL, MET and CDCP1. We created EGFR mutant gefitinib and osimertinib resistant cell lines (PC9-GR3, GR4, OR2, OR4). Auranofin plus IPA-3 was highly synergistic in all cell lines.
8eea62084ca7e541d918e823422bd82e Conclusion
These observations suggest that the combination of auranofin with OTSSP167 can be used for treatment of different subclasses NSCLC with driver EGFR or KRAS mutations, as well as SCC with PAK1 amplification.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.06 - Mesothelioma (Not CME Accredited Session) (ID 955)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.06-11 - A Phase I/II Study of Intrapleural Ad-SGE-REIC Administration in Patients with Refractory Malignant Pleural Mesothelioma (ID 11328)
16:45 - 18:00 | Author(s): Morihito Okada
- Abstract
Background
Reduced expression in immortalized cell (REIC)/Dickkopf-3 (Dkk-3) is a tumor-suppressor gene and REIC/Dkk-3 expression was markedly downregulated in various human cancer cells. REIC/Dkk-3 protein is also known as a key player, namely an antagonist of the Wnt signaling pathway. Ad-SGE-REIC is an adenoviral vector carrying REIC/Dkk-3 that mediates cancer cell death induction and anti-cancer immunity augmentation.
a9ded1e5ce5d75814730bb4caaf49419 Method
We conducted a phase I/II, 3+3 design, dose escalation study in malignant pleural mesothelioma (MPM) patients (pts) with measurable lesions. Pts with refractory to or unsuitable for standard chemotherapy received 2 intrapleural administrations of Ad-SGE-REIC on days1 and 4. Three escalating doses of level (DL) 1: 3.0×1011, DL2: 1.0×1012 and DL3: 3.0×1012 viral particles were employed. This dosage and regimen were set by considering the reason of manufacturing and neutralizing anti-body for adenovirus. The safety and dose-limiting toxicities (DLTs) of Ad-SGE-REIC were evaluated for 32 days. Continuous safety and efficacy were assessed for 172 days using modified RECIST (mRECIST). The concentrations of REIC/Dkk-3 in pleural fluid also were measured as indirect indication of targeted gene expressions.
4c3880bb027f159e801041b1021e88e8 Result
From 07/2015 to 09/2017, a total of 13 pts have been treated at DL1 (n=4 included one fatal case within 32 days), DL2 (n=3) and DL3 (n=6). Male: 100%; median age 70; PS 0: 23%, 1: 69%, 2: 8%; epithelial/biphasic histology: 69%/15%; Stage III-IV: 77%; previous chemotherapy use with platinum-pemetrexed: 92%. Treatment-related AEs (TRAEs) were all Grade 1-2 and no DLTs occurred. The most frequent TRAEs were fever and CRP increase based on adenovirus infection. Tumor responses assessed by independent central review showed that there was no objective response and DCR was 62% (8/13 pts). Median PFS was 3.4 months at all groups and 5.7 months at DL3. A remarkable increase of REIC/Dkk-3 concentration in pleural fluid was determined (6/13 pts, prominently high in DL3).
8eea62084ca7e541d918e823422bd82e Conclusion
The intrapleural administration of Ad-SGE-REIC up to 2 cycles was safe and well tolerated in MPM pts and promising results of efficient REIC/Dkk-3 expression and durable disease control were obtained. We are planning phase II study using repeated intrapleural or intratumoral administration.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 965)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.16-11 - Prognostic Role of Combined Pulmonary Fibrosis and Emphysema (CPFE) in Patients with Clinical Stage I Lung Cancer. (ID 11264)
16:45 - 18:00 | Author(s): Morihito Okada
- Abstract
Background
The prognostic role of CPFE in lung cancer is not fully understood. The purpose of this study is to evaluate the prognostic role of combined pulmonary fibrosis and emphysema (CPFE) in patients with clinical stage I primary lung cancer with interstitial pneumonia (IP).
a9ded1e5ce5d75814730bb4caaf49419 Method
CPFE was defined as the presence of both emphysema and IP on high-resolution computed tomography (HRCT). Of 836 consecutive patients with clinical stage I primary lung cancer who underwent complete resection between April 2007 and March 2016, 65 patients with CPFE were identified. The log-rank tests and Cox proportional hazard models were used to test for survival differences.
4c3880bb027f159e801041b1021e88e8 Result
There was a significant difference in overall survival (OS) between patients with CPFE (n = 65: 5 y-OS rates, 62.6%) and those without CPFE (n = 771: 5 y-OS rates, 86.5%, P <0.001). However, in patients with interstitial pneumonia on HRCT (n = 115), there was no significant difference in OS between patients with CPFE (n = 65: 5 y-OS rates, 62.5%) and those without CPFE (n = 50: 5 y-OS rates, 59.4%, P = 0.84). In patients with interstitial pneumonia, multivariable backward stepwise Cox analysis revealed that histology, %DLCO, radiologic IP pattern, and surgical procedure were independent prognostic factors for OS, but the presence of CPFE was not.
8eea62084ca7e541d918e823422bd82e Conclusion
CPFE was not an independent prognostic factor for OS in patients with clinical stage I lung cancer with IP. The presence of interstitial pneumonia pattern may explain poor survival in patients with CPFE.
6f8b794f3246b0c1e1780bb4d4d5dc53
