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M. Okada



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    MINI 01 - Pathology (ID 93)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      MINI01.06 - Pathological Second-Predominant Component Predicts Recurrence in Lung Adenocarcinoma (ID 1070)

      10:45 - 12:15  |  Author(s): M. Okada

      • Abstract
      • Presentation
      • Slides

      Background:
      Lung adenocarcinoma is pathologically subdivided according to its predominant component. Approximately 50–70% of invasive adenocarcinomas are diagnosed as adenocarcinomas of either papillary or acinar predominant subtype. The prognostic difference between these subtypes has not been revealed, and these 2 similar subtypes may further be classified. This study aimed to investigate whether the pathological second-predominant component that follows the most predominant component predict recurrence in adenocarcinoma.

      Methods:
      We retrospectively reviewed 347 consecutive cN0 lung adenocarcinoma cases resected between April 2006 and December 2010 at Hiroshima University Hospital and Kanagawa Cancer Center. We further classified papillary and acinar predominant adenocarcinomas into either the papillary/acinar-lepidic type (Pap/Aci-Lep type) or the papillary/acinar-nonlepidic type (Pap/Aci-NonLep type). Tumor recurrence and the frequency of each invasion status such as lymphatic, vascular, and pleural invasion were compared between Pap/Aci-Lep type and Pap/Aci-NonLep type adenocarcinomas. In addition, we estimated the correlation between the radiological and pathological characteristics of these subtypes. Whole-tumor size, ground-glass opacity (GGO) ratio, solid size, and tumor disappearance ratio (TDR) on high-resolution computed tomography and maximum standardized uptake value (SUVmax) on positron emission tomography (CT) were measured as radiological parameters.

      Results:
      Papillary (n = 70) and acinar predominant adenocarcinomas (n = 61) were subdivided into the Pap/Aci-Lep type (n = 72) and Pp/Aci-NonLep type (n = 59). Compared with the Pap/Aci-NonLep type, the Pap/Aci-Lep type showed a significantly higher disease-free survival rate (5-year DFS: 89.4% vs 70.6%, p = 0.0374) and fewer cases of lymphatic invasion (15.3% vs 30.5%, p = 0.037), vascular invasion (15.3% vs 33.9%, p = 0.013), and pleural invasion (9.72% vs 25.4%, p = 0.031). Furthermore, radiological findings significantly differ between the Pap/Aci-Lep and Pap/Aci-NonLep types as follows: GGO ratio (μ ± 1 ´ SD: 34.4% ± 25.2% vs 3.81% ± 18.0%, p < 0.01), CT solid size (μ ± 1 ´ SD: 1.35 ± 0.65 cm vs 1.73 ± 0.55 cm, p = 0.015), TDR (μ ± 1 ´ SD: 41.8% ± 26.7% vs 17.5% ± 22.6%, p < 0.01), and SUVmax (μ ± 1 ´ SD: 2.37 ± 2.15 vs 3.96 ± 3.06, p < 0.01). Significant recurrence-free survival and prevalences of lymphatic and vascular invasion were observed between the lepidic predominant type (n = 109) and Pap/Aci-Lep type.

      Conclusion:
      The pathological second-predominant component allows for subclassification of papillary and acinar predominant adenocarcinomas with prognostic significance. Pathological features of these subtypes can be represented on clinical imaging. Not only the most predominant component but also the second-predominant component should be given clinical and pathological attention in order to predict malignant potential or decide indication for adjuvant therapy.

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    ORAL 01 - Chemotherapy Developments for Lung Cancer (ID 88)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      ORAL01.01 - Randomized Phase III Study of Nedaplatin plus Docetaxel versus Cisplatin plus Docetaxel for Advanced Squamous Cell Lung Cancer (WJOG5208L) (ID 621)

      10:45 - 12:15  |  Author(s): M. Okada

      • Abstract
      • Presentation
      • Slides

      Background:
      Nedaplatin (N) is a second-generation platinum compound with lower nausea/vomiting and nephrotoxicity than cisplatin (C). Nedaplatin plus docetaxel (ND) showed a promising efficacy with acceptable toxicity for advanced squamous cell lung cancer (SqLC) in the previous phase II study.

      Methods:
      Eligible patients (pts) were those with pathologically proven SqLC with stage IIIB/IV or postoperative recurrence, aged 20-74 years and ECOG PS 0-1. Pts were randomized 1:1 to ND (N 100 mg/m[2] and docetaxel (D) 60mg/m[2] iv, q3w, up to 6 cycles) or C plus D (CD) (C 80 mg/m[2] and D 60mg/m[2] iv, q3w, up to 6 cycles) according to stage, gender and institution. The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), response rate (RR) and adverse events (AEs). Target sample size of 350 provided 90% statistical power to detect a hazard ratio of 0.71 with one-sided type I error of 0.05.

      Results:
      Between July 2009 and July 2012, 355 pts were randomized. Of 349 for efficacy analysis (ND 177; CD 172), baseline characteristics were well-balanced between two arms. ND had a significantly longer OS (p=0.037, one-sided stratified log-rank test). The OS HR was 0.81 (90%CI, 0.67-0.98) with a median OS of 13.6 months [m] for ND and 11.4 for CD. ND had a longer PFS (p=0.050) with a HR of 0.83 (0.69-1.00) and a median PFS of 4.9 m in ND and 4.5 in CD. RR was 54.5% in ND vs 52.9% in CD (p=0.829). Grade 3 or higher AEs of nausea (4.0% vs 14.3%), fatigue (3.4% vs 10.9%), hyponatremia (13.6% vs 30.3%) and hypokalemia (2.3% vs 8.6%) are more frequent in CD. Grade 3 or higher AEs of neutrophils (82.5% vs 70.3%) and platelets (9.0% vs 0.0%) are more frequent in ND, but there was no difference in grade 3 or higher febrile neutropenia (13.6% vs 15.4%). Treatment related deaths occurred in 4 and 3 pts in ND and CD, respectively.

      Conclusion:
      ND showed a significantly longer OS as compared to CD with different toxicity profile. ND will be considered as a new standard treatment for advanced or relapsed SqLC. Clinical trial information: UMIN000002015.

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    P1.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 212)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Locoregional Disease – NSCLC
    • Presentations: 1
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      P1.03-028 - Multicenter Study of the Usefulness of FDG-PET as a Predictor of the Clinicopathological Characteristics and Prognosis of Lung Cancer (ID 1121)

      09:30 - 17:00  |  Author(s): M. Okada

      • Abstract
      • Slides

      Background:
      This multicenter study aimed to investigate the performance of standardized uptake value (SUV) on [18F]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) as a predictor of the clinicopathological characteristics and prognosis of resected lung cancers.

      Methods:
      A total of 721 patients underwent curative resection with systematic lymph node dissection. The relationship among histological characteristics, pathological staging, prognosis, and SUV on FDG-PET was retrospectively examined.

      Results:
      There were 107 squamous cell carcinomas and 614 adenocarcinomas. The pathological stages of the cases were IA 408, IB 162, IIA 57, IIB 23, IIIA 65, IIIB 1, and IV 5. The SUVmax on FDG-PET/CT was significantly higher in squamous cell carcinoma than in adenocarcinoma (11.98 ± 6.81 vs 4.03 ± 4.99; p < 0.001) and this tendency was similar in all stages. Pathological N1 (n = 19), N2 (n = 9) cases showed a significantly higher SUVmax than N0 (n = 79) in squamous cell carcinoma (15.00 ± 5.42, 17.24 ± 8.10 vs 10.65 ± 6.50). This was also the case with adenocarcinoma N2 (n = 48) 8.58 ± 6.14, N1 (n = 40) 9.15 ± 7.13 vs N0 (n = 526) 3.23 ± 4.16. Cases with pathological tumor invasiveness such as lymphatic, vascular or pleural infiltration showed a significantly higher SUVmax than cases with no invasiveness in squamous cell carcinoma (13.75 ± 6.75 vs 7.21 ± 4.22; p < 0.001) and adenocarcinoma (7.39 ± 6.12 vs 1.94 ± 2.37; p < 0.001). The areas under the receiver operating characteristic curves for SUVmax used to predict the relapse-free survival were 12.3 (p = 0.058) in squamous cell carcinoma and 2.6 (p < 0.001) in adenocarcinoma. The 2-year relapse-free survival was 93%/68% (SUVmax lower/higher than 12.3) in squamous cell carcinoma and 99%/78% (SUVmax lower/higher than 2.6) in adenocarcinoma. Following multivariate analysis, pathological nodal status and SUVmax were found to be independent predictive factors for relapse-free survival.

      Conclusion:
      SUVmax of the primary tumor reflected the biological malignancy of lung cancers. As SUVmax tended to be higher in squamous cell carcinoma than in adenocarcinoma, this should be clinically used separately according to histology. SUVmax is also useful for predicting survival, and multimodality treatment might be indicated if the value is high.

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