Virtual Library

 x 
My Library Virtual Library FAQ

Start Your Search

Y. Sakao



Author of

  • +

    P1.07 - Poster Session 1 - Surgery (ID 184)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 1
    • +

      P1.07-021 - The risk factor of late recurrence in patients with completely resected non-small cell lung cancer (ID 1542)

      09:30 - 16:30  |  Author(s): Y. Sakao

      • Abstract

      Background
      Recurrences in patients with completely resected non-small cell lung cancer (NSCLC) rarely occur more than 5 years after operation. Various follow-up programs for postoperative patients are recommended in each guideline. The purpose of this study is to clarify the risk factor of late recurrence and to determine which patients might benefit from routine computed tomography (CT) follow-up more than 5 years after operation.

      Methods
      Between January 1995 and December 2006, 1,437 consecutive patients with NSCLC underwent pulmonary resections at our institution. Of these, 617 patients remained recurrence-free for 5 years after resection. We retrospectively analyzed the clinicopathological features of these patients. Disease free survival (DFS) was defined as endpoint and was analyzed using Cox proportional hazards model. Variables for univariate analysis were as follows: age, gender, smoking history, carcinoembryonic antigen, operative procedure, pathological type, pathological stage, and pleural lavage cytology (PLC).

      Results
      At the median follow-up time of 7.5 years, 20 patients (3.2%) developed late recurrence more than 5 years after resection. Distant metastasis occurred in 15 patients and locoregional recurrence occurred in 5 patients (Table 1). There were 3 patients (15%) with positive PLC in late recurrence group and 7 patients (1.2%) in recurrence free group. In univariate analysis, only PLC was significant. In a multivariate analysis, PLC was a significant predictor of late recurrence. The Hazard ratio (HR) for positive PLC in comparison to negative PLC was 5.75 (95% CI 1.16–19.26; p=0.04)Figure 1.

      Conclusion
      PLC is a strong independent factor for late recurrence. Patients with positive PLC might be good candidates for routine chest CT more than 5 years after resection.

  • +

    P1.12 - Poster Session 1 - NSCLC Early Stage (ID 203)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
    • +

      P1.12-012 - A Comparison of Clinicopathologic Features and Survival Outcomes between the Lung Cancer Patients with Adenocarcinoma and Squamous Cell Carcinoma: Stage I Disease of Squamous Cell Carcinoma is there? (ID 1811)

      09:30 - 16:30  |  Author(s): Y. Sakao

      • Abstract

      Background
      Patients with lung cancer should be treated differently based on their histologic subtypes because of the disparities in tumor aggressiveness and treatment response. In addition to epidermal growth factor receptor tyrosine kinase inhibitor, recent chemotherapeutic agents such as pemetrexed and bevacizumab have dissimilar activities between adenocarcinoma (AD) and squamous cell carcinoma (SQ). Therefore, it would be important to reevaluate the clinicopathologic features of the two major subtypes, both of which were classified as non-small cell lung cancer.

      Methods
      Between 1995 through 2012, 2412 patients with primary lung cancer underwent pulmonary resection in Nagoya University and Aichi Cancer Center Hospital. For the present study, a total of 2057 patients with AD and SQ who underwent complete resection were extracted, and their clinicopathological features and outcomes were evaluated.

      Results
      The cohort consists of 1585 ADs (77%) and 472 SQs (23%). Female sex, no history of smoking and smaller size of the tumor were distinct characteristics of AD patients, and higher age was that of SQ patients (p < 0.0001). Pathological stage I disease was found in 70% of AD patients and 41% of SQ patients. Significant difference was observed for overall survival with the 5-year survival rate of 78% in AD patients and 63% in SQ patients. Limited to stage I disease, SQ patients also showed significant worse outcomes (p < 0.0001). Since no survival difference was observed between pN0 and pN1 patients with SQ (p = 0.39), we tried to regard the pN0 patients as pN1 and restage them according to the newly defined N status. Thirty-seven stage IA and 42 stage IB patients were upstaged to stage IIA, 36 stage IB patients to stage IIB, and 47 stage IIB patients to stage IIIA. As a result, comparable survival curves were obtained between AD and SQ patients in stage II and IIIA.

      Conclusion
      We identified some significant differences between patients with AD and SQ in the large-scale Japanese cohort. Especially, patients with stage I SQ showed a significantly worse outcome. Newly defined stage grouping applied for SQ patients provided comparable outcomes with those of AD patients. Therefore, stage I disease of SQ may not be there.

  • +

    P2.18 - Poster Session 2 - Pathology (ID 176)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 1
    • +

      P2.18-008 - Transformation to sarcomatoid carcinoma in ALK-rearranged adenocarcinoma which developed acquired resistance to crizotinib and received subsequent chemotherapies (ID 1723)

      09:30 - 16:30  |  Author(s): Y. Sakao

      • Abstract

      Background
      Non-small-cell lung cancers (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangement are highly sensitive to the ALK kinase inhibitor crizotinib, but drug resistance invariably emerges. Morphological transformation from adenocarcinoma to SCLC represents one acquired resistance mechanism to epidermal growth factor receptor tyrosine kinase inhibitors. We present the case of transformation to sarcomatoid carcinoma in ALK-rearranged adenocarcinoma which developed acquired resistance to crizotinib.

      Methods
      not applicable

      Results
      A 32-year-old man presented with cough and bloody sputum. Computed tomography (CT) showed a mass in the S6 segment and diffuse consolidation throughout the lower lobe of the left lung. Transbronchial lung biopsy revealed adenocarcinoma with lymphangiosis. Immunohistochemistry (IHC) showed ALK protein expression and break-apart fluorescent in-situ hybridization (FISH) showed ALK gene rearrangement. First-line chemotherapy with cisplatin and docetaxel was started. After tumor progression, the patient was enrolled in the clinical trial and was allocated to the pemetrexed arm. Subsequently, he was enrolled in other trial to receive crizotinib in July 2011. After partial response was observed, a nodule in the S9 segment developed to 2cm in February 2012, and crizotinib was discontinued. CT scans performed after 4 cycles of carboplatin and gemcitabine showed a mixed response, with improvements in lymphadenopathy and lymphangiosis but progression of the mass in S9. CT-guided core-needle biopsy revealed ALK-positive atypical cells but it was impossible to distinguish histological types because of degeneration and necrosis. Thereafter, carboplatin, paclitaxel, and bevacizumab were administered, but the same mixed response was observed. The mass in S9 increased rapidly and reached 7 cm. 　Left lower lobectomy was performed. The primary tumor in S6 was diagnosed as adenocarcinoma positive for thyroid transcription factor (TTF)-1 immunostaining, whereas the tumor in S9 was TTF-1-negative sarcomatoid carcinoma. ALK was positive with IHC in both tumors, and FISH revealed high-level gene amplification of the ALK fusion gene only in the sarcomatoid carcinoma. Reverse transcriptase polymerase chain reaction revealed the same variant of echinoderm microtubule-associated protein like 4-ALK (E13; A20) and it indicated that these tumors have the same origin. Moreover, in the sarcomatoid carcinoma, DNA sequencing revealed no additional resistance point mutations from ALK exon 20 to exon 23. Brain metastases occurred 2 months after pulmonary resection and he underwent brain surgery. The tumor was diagnosed as sarcomatoid carcinoma. Ten days later, he died due to exacerbation of lymphangiosis To discuss potential epithelial-to-mesenchymal transition (EMT), we performed E-cadherin and keratin staining as epithelial markers, and vimentin staining as a mesenchymal marker in 4 specimens. The specimens were pre-crizotinib specimen in S6, surgical specimen in S6, rebiopsied specimen in S9 after carboplatin and gemcitabine, and surgical specimen in S9. Rebiopsied specimen in S9 was unevaluable for IHC staining because of degeneration and necrosis. All of the 3 evaluable specimens showed positive expression of vimentin and only surgical specimen in S9 showed negative of epithelial markers.

      Conclusion
      The transformation from adenocarcinoma to sarcomatoid carcinoma could be interpreted as kind of EMT. This transformation might represent a novel acquired resistance mechanism to crizotinib, although there is another possibility that subsequent chemotherapies induced this transformation.

  • +

    P2.19 - Poster Session 2 - Imaging (ID 180)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Imaging, Staging & Screening
    • Presentations: 1
    • +

      P2.19-010 - The association between baseline clinical-radiological characteristics and growth of pulmonary nodules with ground-glass opacity (ID 1729)

      09:30 - 16:30  |  Author(s): Y. Sakao

      • Abstract

      Background
      Pulmonary nodules with ground-glass opacity (GGO) are frequently encountered. We previously reported that, based on natural history of 108 pulmonary nodules that were 3 cm or less and had 50 % or more GGO component, these nodules should be followed for at least 3 years to accurately evaluate lesion growth. However, it remains unclear whether all GGOs should be followed for as long as 3 years. To establish reasonable follow-up plan, it would be useful to if we could predict which of GGO lesions tend to grow by any of clinical-radiographic characteristics. The purpose of this study was to clarify which baseline clinical and radiological characteristics were associated with growth of these nodules.

      Methods
      We retrospectively studied patients between 1999 and 2013 with pulmonary nodules that met the following criteria: (1) lesion diameter of ≤ 3 cm, (2) GGO proportion of ≥ 50%, and (3) observation without treatment in the prior 6 months. We evaluated the changes in lesion size on serial computed tomography. Two endpoints, “Time to 2-mm growth” and “2-mm growth incidence”, were analyzed using Cox proportional hazards and logistic regression models, respectively.Variables for univariate analysis were as follows: age; gender; smoking history; past history of lung cancer; lesion multiplicity; lesion diameter; and solid proportion. Factors for which p-value was < 0.05 in univariate analysis, as well as past history of lung cancer which was reported as a predictor in previous reports, were included in multivariate analysis. To strictly define “no growth”, we excluded lesions which had been observed for less than 3 years in logistic regression analyses.

      Results
      120 pulmonary lesions in 67 patients fulfilled inclusion criteria. At the median observation period of 4.2 years, 34 lesions had become larger by 2mm or more, whereas the remaining 86 had persisted without changing in size. Smoking history and initial lesion diameter were statistically significant in both regression and time-to-event analyses. In terms of time to 2mm growth, hazard ratio (HR) for smoking history was 3.67 (P < 0.01). Compared to those ≤ 1 cm, HRs for 1.1–2 cm and 21-3 cm lesions were 2.23 (P = 0.08) and 5.08 (P = 0.04), respectively. In contrast, odds ratio (OR) for the likelihood of 2mm growth for smoking history was 6.51 (P < 0.01), and OR for lesion diameter of 1.1–3 cm in comparison to ≤ 1 cm was 4.06 (P = 0.02).

      Conclusion
      Smoking history and initial lesion diameter are significantly associated with the growth of these nodules. These results suggested that closer follow up of larger size GGO in smoking patients be recommended.