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K. Aoe
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ORAL 14 - Biology 2 (ID 112)
- Event: WCLC 2015
- Type: Oral Session
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:T. Nakano, P. Baas
- Coordinates: 9/07/2015, 16:45 - 18:15, 702+704+706
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ORAL14.02 - Clinical Significance of Soluble CD26 in Malignant Pleural Mesothelioma (ID 354)
16:45 - 18:15 | Author(s): K. Aoe
- Abstract
- Presentation
Background:
There is no established diagnostic marker for malignant pleural mesothelioma (MPM). CD26 is a 110 kDa, multifunctional, membrane-bound glycoprotein on the surface of many cell types that has dipeptidyl peptidase IV (DPPIV) enzyme activity. The aim of this study was to evaluate the clinical significance of soluble CD26 in patients with MPM.
Methods:
The study included 80 MPM patients, 79 subjects with past asbestos exposure (SPE), and 134 patients with other benign pleural diseases (OPD) that were included as a control group. Soluble CD26 levels and DPPIV activity in serum and/or pleural fluid were determined using an ELISA kit. To make a comparative review of the usefulness of sCD26, we determined serum and pleural fluid soluble mesothelin-related peptides (SMRP). SMRP was measured by the chemiluminescent enzyme immunoassay (CLEIA) based on 2-step sandwich method.
Results:
Serum sCD26 levels and DPPIV enzyme activity in patients with MPM were significantly decreased compared with those in the SPE group (P=0.000). The level of serum sCD26 was significantly decreased in patients with advanced stages of MPM compared with those with earlier stages (P=0.047). The median OS of patients with MPM who had higher DPPIV enzyme activity was significantly longer than that of those with lower DPPIV enzyme activity (P=0.032). The sCD26 levels in the pleural fluid of MPM patients with an epithelioid subtype were significantly increased compared with the OPD cohort (P=0.012). Moreover, DPPIV enzyme activity in the pleural fluid of patients with MPM with an epithelioid subtype were significantly increased compared with those in the OPD cohort (P=0.009). Patients with MPM who had lower specific DPPIV activity, determined as DPPIV/sCD26, showed significantly prolonged survival compared with those with higher specific DPPIV activity (P=0.028). Median values of serum and pleural fluid SMRP in MPM patients were 0.43 and 15.37 mmol/l, respectively. Median value of pleural fluid SMRP in epithelioid MPM was 17.28 mmol/l. Median values of serum SMRP in SPE and pleural fluid SMRP in OPD were 0.90 and 0.43 mmol/l, respectively. Pleural fluid SMRP in MPM was significantly higher than in OPD (P=0.000) and serum SMRP in MPM was significantly higher than in SPE (P=0.000).
Conclusion:
Serum sCD26 and DPPIV enzyme activity appear to be useful biomarkers for differentiating patients with MPM from SPE. The sCD26 levels or DPPIV enzyme activity in pleural fluid appear to be biomarkers in patients with an epithelioid subtype of MPM. DPPIV activity in serum or pleural fluid appears to be predictive for the prognosis of patients with MPM.
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P1.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 224)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.08-001 - Rituximab for Treatment of Lymphoma Induced Marked Regression of Malignant Mesothelioma with Dynamic Changes of Serum Cytokine Profiles (ID 1192)
09:30 - 17:00 | Author(s): K. Aoe
- Abstract
Background:
Malignant mesothelioma (MM) is a highly aggressive tumor with poor prognosis. As an effective therapy remains to be established, increased attention has been given to immunotherapy in MM.
Methods:
We experienced a patient with malignant lymphoma and MM who showed marked regression of MM after the anti-CD20 monoclonal antibody rituximab therapy. Here we investigated the mechanism underlying this response by immunohistochemical staining and serum cytokine assay.
Results:
A 78-year-old man with diffuse large B-cell lymphoma and epithelioid MM was treated with rituximab for malignant lymphoma. The lymphoma responded well to rituximab, and the pleural thickening of MM regressed markedly after this treatment without therapy for mesothelioma. Immunohistochemical stainings revealed negative expression of CD20 on mesothelioma cells, indicating that rituximab did not directly attack the mesothelioma cells. The serum levels of 27 cytokines were measured 12 days before and 16, 45 and 54 days after this treatment to compare with those in 24 untreated MPM patients. The serum levels of cytokines of this patient including IL-12, INF-g, TNF-a, VEGF and IP-10 were higher than those of other mesothelioma patients before the rituximab treatment. Notably, during the treatment the level of IL-12 increased approximately 10-fold, relative to its baseline level. In addition, the levels of IL-2, Eotaxin, G-CSF, and TNF-a transiently increased several fold as compared with their baseline levels. In contrast, the levels of VEGF, PDGF, IP-10, and IL-8 which are associated with mesothelioma proliferation, decreased after the treatment. These results suggest that the mechanism of mesothelioma regression in this case involves antitumor immunity enhanced with high baseline levels of IL-12 and other Th1 cytokines and B-cell depletion by the rituximab treatment.
Conclusion:
The relationship between these cytokine profiles and the clinical outcome might provide a potential immunotherapeutic strategy for MM.
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P2.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 213)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.03-013 - A Phase II Study of S-1 and Thoracic Irradiation for Elderly Pts with Locally Advanced Non-Small Cell Lung Cancer: Okayama Lung Cancer Study Group (ID 224)
09:30 - 17:00 | Author(s): K. Aoe
- Abstract
Background:
Although thoracic irradiation (TRT) is one of the standarad therapies in elderly pts with locally advanced non-small cell lung cancer (LA-NSCLC), its treatment outcome is still poor. We previously reported safety profiles of S-1, an oral fluoropyrimidine possesing a radio-sensitizing effect, and concurrent TRT in such population [Lung Cancer 2011]. Here, we investigated the efficacy and safety of S-1 with concurrent TRT for elderly pts with LA-NSCLC.
Methods:
Pts with stage III, aged >75 years and PS 0-1, and without any prior chemotherapy were eligible for this study. Pts were treated with S-1 (40 mg/m2/dose b.i.d on days 1-14 and 29-42) and TRT (60 Gy/30 fr over 6 weeks starting on day 1). Primary endpoint was response rate (RR), and required sample siza was 30 pts.
Results:
Between 2007 and 2012, 30 pts were enrolled (24 men; median age, 79 years; PS 1, 15; IIIa, 20; Sq, 12). Median Charlson score was 1 (range; 0-3). The proportion of actual dose schedule relative to the planned one of S-1 and TRT was 95 and 98%, respectively. Partial response was observed in 19 pts (63%; 95% confidence interval: 45-82%), which did not meet the endpoint. At the time of the analysis, 24 (80%) of the 30 had experienced recurrences; 13 (43%) were locoregional, 6(20%) distant, and 5 (17%) both locoregional and distant. At a median follow-up of 23.7 months, median progression-free survival and MST were 13.0 months and 27.9 months, respectively. Toxicities were generally mild, including G3/4 neutropenia (17%), G3 febrile neutropenia (7%) and G3 pneumonitis (10%). No toxic deaths occurred.
Conclusion:
This study did not meet the primary endpoint. However, concurrent S-1 and TRT yielded favorable survival data. Also, it was well-tolerated in elderly pts with LA-NSCLC
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P2.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 225)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.08-024 - CT Findings of Early Pleural Mesothelioma and Benign Asbestos Pleural Effusion (ID 272)
09:30 - 17:00 | Author(s): K. Aoe
- Abstract
Background:
• Malignant pleural mesothelioma is known as disease of the poor prognoses. • Our purpose is to find useful CT findings for correct differentiation between Malignant Pleural Mesothelioma in the early stage (e-MPM) and Benign Asbestos Pleural Effusion (BAPE) to improve prognosis of MPM.
Methods:
• The BAPE group consisted of 36 patients diagnosed at Okayama Rosai Hospital since Jan 2000. In all BAPE patients thoracoscopic biopsies were conducted to exclude malignant diseases including MPM. • In e-MPM group, 66 patients who were diagnosed mesotheliomas with T1 or T2 (IMIG system) by the CT evaluation were studied. The e-MPM patients were selected from 2,742 mesothelioma death cases of Japanese vital statistics of 2003-05. • We evaluated CT scans taken at the time of diagnosis for each group. The evaluating items were presence of asbestosis, pleural plaque (PQ), rounded atelectasis (RA) and diffuse pleural thickening (DPT), as well as the grade and localization of pleural irregularities.
Results:
• In BAPE group (36 cases), the occurrence rate of asbestos-related lesions was significantly higher than in e-MPM group (66 cases) as follows; prevalence of asbestosis 17%/2% (*), PQ 92%/35% (**), RA 44%/0% (**) and DPT 25%/2% (**). (*P=0.0038 **P<0.001) • As for grade of pleural irregularity, no irregularity was found in 22%/9%, low-level irregularity in 72%/54%, high-level irregularity in 5%/23% and mass formation in 0%/14% of BAPE and e-MPM group patients, respectively. • As for localization (including overlap) of pleural irregularity, irregularity in mediastinal pleura was observed in 30%/74%, basal pleura in 91%/77% and interlobar pleura in 0%/55% of BAPE and e-MPM group patients, respectively. The mediastinal pleural thickening was minimal in BAPE group and found regressed in the follow-up CT scans.
Conclusion:
• In BAPE group the occurrence rate of asbestos-related lesions was higher than in e-MPM group. • Because the 5% of BAPE cases presented irregular pleural thickening, the differentiation with MPM was difficult in such case. • The mediastinal pleural thickening, which is considered to be a characteristic of MPM, was also observed in 30% of BAPE cases. However, the finding disappeared during observation. And no BAPE case with interlobar pleural irregularity was found. These findings can be useful for differentiation BAPE and e-MPM cases.
