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H. Ueoka
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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): H. Ueoka
- 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: 2
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.03-002 - Surgery for Locally Advanced Lung Cancer after Induction Concurrent Chemo-Radiation Therapy (ID 693)
09:30 - 17:00 | Author(s): H. Ueoka
- Abstract
Background:
The prognosis of locally advanced non-small-cell lung cancer is very poor. According to the American Cancer Society website, 5-year observed survival rate of Stage IIIA is 14%, and that of IIIB is 5%. A highly effective treatment strategy is needed to improve it. Surgery after induction concurrent chemo-radiation therapy for locally advanced non-small-cell lung cancer in our hospital over the last 8 years was retrospectively reviewed.
Methods:
Our standard induction chemo-radiation therapy consisted of cisplatin 40 mg/m[2] and docetaxel hydrate 40 mg/m[2] given on days 1, 8, 29, and 36 plus concurrent irradiation of 46 Gy (2 Gy/day) to the tumor, hilum, and mediastinum. Surgery was performed between 4 and 6 weeks after completion of the radiotherapy. 37 consecutive patients with 21 cases of lobectomy and 16 cases of pneumonectomy were reviewed. The median age at surgery was 62 (41 – 74) years old. There were 6 females and 31 males. Adenocarcinoma was present in 18, squamous cell carcinoma in 13, large cell neuroendocrine carcinoma in 2, adenosquamous cell carcinoma in 1, giant cell carcinoma in 1, NSCLC in 1, and atypical carcinoid which was preoperatively diagnosed as squamous cell carcinoma in 1. The pretreatment stage was IIIB in 11, IIIA in 20, IIB in 3, IIA in 1, and IB in 2. The pretreatment very high tumor marker levels in blood were as follows: CEA 367, 337, 266, 180, 154, 151, 105 ng/ml, CYFRA 47, 23, 20 ng/ml, and SCC 15, 10 ng/ml. Survival was calculated using the Kaplan-Meier method, and analyzed by the Log-Lank test.
Results:
Toxicity was manageable, and no serious complication was noted. All 37 cases were R0 resection. The median operation time of 21 cases of lobectomy and 16 cases of pneumonectomy were 5 hr 4 min and 4 hr 35 min, respectively. The median bleeding time of 21 cases of lobectomy and 16 cases of pneumonectomy were 200 ml and 175 ml, respectively. A pathologically complete response was obtained in 11 (30%) patients. The pathological stage was complete response in 11, IIIB in 3, IIIA in 6, IIB in 5, IIA in 4, IB in 2, and IA in 6. All abnormal blood tumor marker levels went down to normal. At a median follow-up period of 3 years 4 months (5 months - 8 years 8 month), 5-year survival rate of all 37 patients was 80%, and that of 21 lobectomy patients was 63%. Although 2 patients had recurrent tumors, 16 pneumonectomy patients were all alive without oxygen therapy. The prognosis of pneumonectomy was significantly better than lobectomy (p < 0.05).
Conclusion:
Surgery after induction concurrent chemo-radiation therapy for locally advanced non-small-cell lung cancer is feasible and highly effective. This treatment strategy has greatly improved the prognosis of locally advanced non-small-cell lung cancer.
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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): H. Ueoka
- 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
