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H. Sasaki



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    MO03 - Thymic Malignancies (ID 123)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO03.10 - A multicenter prospective study of carboplatin and paclitaxel for advanced thymic carcinoma: West Japan Oncology Group 4207L (ID 987)

      10:30 - 12:00  |  Author(s): H. Sasaki

      • Abstract
      • Presentation
      • Slides

      Background
      Thymic carcinoma (TC) is a rare malignant tumor originated within the thymus gland and is associated with a poor prognosis, differing from thymoma which is the most common type of thymic malignant neoplasm. No results of clinical trials focusing on TC have been reported. This single-arm study evaluated carboplatin and paclitaxel (CbP) in previously untreated patients (pts) with advanced TC.

      Methods
      Pts with Masaoka’s stage III to IVb TC, ECOG PS 0 to 1, and more than 20 years old were eligible. The study treatment consisted of carboplatin (AUC 6) and paclitaxel (200 mg/m2) every 3 weeks for a maximum of 6 cycles. The primary endpoint was objective response rate (ORR) by extramural assessment. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and safety. All pts were followed-up until 24 months (mo) after last enrollment. Based on the SWOG 2-stage design, the planned sample size of 40 pts was determined to reject the ORR of 20% under the expectation of 40% with a power of 0.85 and a type I error of 0.05.

      Results
      From May 2008 to November 2010, 40 pts were enrolled from 21 centers. Of 39 evaluable for analysis, the median age was 62 years (range, 36–84); 23/16 males/females; 3/10/26 with Masaoka’s stage III/IVa/IVb; 9/11/19 with squamous cell carcinoma/poorly differentiated neuroendocrine carcinoma/other types. The median number of cycles was 6. There was 1/13 complete/partial responses with an ORR of 36% (95% confidence interval [CI], 21-53%; P = 0.031). The median PFS was 7.5 mo (6.2-12.3 mo) while OS did not reach the median value. The 1-year and 2-year survival rates were 85% (95% CI, 69-93%) and 71% (95% CI, 54-83%), respectively. Major adverse event was grade 3-4 neutropenia in 34 pts (87%). Two cases (5%) of grade 3 febrile neutropenia, neuropathy, and arthralgia were observed, respectively. There was no treatment-related death.

      Conclusion
      CbP showed high efficacy in advanced TC. Our results established that CbP, one of the standard treatments for non-small cell lung cancer, also serves as a key chemotherapy regimen for TC.

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    P3.02 - Poster Session 3 - Novel Cancer Genes and Pathways (ID 149)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.02-001 - KIF5B/RET fusion gene in surgically-treated Japanese adenocarcinoma of the lung (ID 33)

      09:30 - 16:30  |  Author(s): H. Sasaki

      • Abstract

      Background
      Recently, a novel fusion gene resulting from linkage between the kinesin family member 5B gene (KIF5B; 10p11.22) and rearranged during transfection gene (RET; 10q11.21) was identified in non-small cell lung cancer (NSCLC). RET translocation was previously reported in thyroid cancer, as CCD6/RET translocation. However, the correlation between KIF5B/RET fusion gene status and clinicopathologic features of surgically-treated lung cancer has not been well characterized.

      Methods
      We have investigated KIF5B/RET fusion gene status in 371 surgically treated NSCLC (270 were adenocarcinoma and 101 were squamous cell carcinoma), 60 breast cancers, 11 metastatic lung cancers from colon cancers and thyroid papillary adenocarcinoma case at Nagoya City University Hospital. The fusion gene and CCD6/RET statuses were analyzed by RT-PCR based assay and direct sequencing. We have performed immunohistochemical (IHC) analysis using C-ternimal specific anti RET antibody (EPR2871, 1:250) (Epitomics Inc., Burlingame, CA, USA, n=86) with Dako linker kit using intercalated antibody-enhanced polymer (iAEP) method. Cytoplasm was stained either granular (G1) or diffuse (G2). G2 staining was defined as positive staining.

      Results
      We detected 3 of 270 cases of KIF5B/RET fusion genes in adenocarcinomas (1.5 %) from the present study; all were mixed subtype adenocarcinomas and three were female and never-smokers. The fusion genes were exclusive with the other mutations, such as EGFR, Kras, Braf, erbB2 mutations, and EML4-ALK fusion. KIF5B/RET fusion was not detected in the cases with squamous cell carcinoma or other types of cancers. Of the 3 cases, 2 cases were KIF5B (exon15): RET (exon12) fusions with papillary dominant and 1 cases were KIF5B (exon22): RET (exon12) fusion with solid dominant adenocarcinoma. Matched normal lung tissues did not show translocation. In the present study, we did not detect CCD6/RET fusion genes. as a driver somatic mutation of lung adenocarcinomas. Although all 3 had positive IHC staining, 35/86 had more than 10% staining and 15/86 had more than 50% staining.

      Conclusion
      In the present study, we reported KIF5B/RET fusion genes as a possible new driver somatic mutation of lung adenocarcinomas. Cinico-pathological backgrounds of the KIF5B/RET fusion positive patients were similar with that of the EML4/ALK fusion positive patients. The chimeric oncogene might be as a promising molecular target for the personalized diagnosis and treatment of NSCLC. However, the chimeric oncogene might not be determined using IHC analysis.