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M. Toda



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    P1.02 - Poster Session/ Treatment of Localized Disease – NSCLC (ID 209)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 2
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      P1.02-001 - Predictive Factors of Distant and Local Recurrence in Patients with Surgically Resected Stage 1 NSCLC (ID 730)

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

      • Abstract
      • Slides

      Background:
      Surgical treatment is the most efficient therapy for early non-small lung cancer (NSCLC). However, after radical surgery many patients relapse or progress to systemic disease, even in stage I NSCLC. The objective of this study was to examine the recurrence predictors, especially focused on location of recurrence (local or distant), in patients who underwent potentially curative resection for stage 1NSCLC.

      Methods:
      The study included 371 consecutive patients who underwent lobectomy with radical mediastinum lymph node dissection from 1998 to 2011 without any preoperative therapy. For analysis of recurrence, 342 patients were enrolled after excluding patients with non-cancer related death or loss of their follow-up within 3 years of resection. Disease recurrence at the surgical margin, ipsilateral pleural dissemination, ipsilateral hilum, and/or mediastinum was considered as local recurrence. The median follow-up was 62 months. There were 205 males and 137 females with a median age of 69 years. Two hundred and forty-four patients had adenocarcinoma, 86 had squamous cell carcinoma, and 12 had other types. On pathologic staging 194 patients were in stage IA and 148 in stage IB. Lymph/vascular invasion were detected in 123, moderate/poor degree of tumor differentiation in 210, and 129 were non-smokers. The patients were divided into two groups: recurrence (n = 70) and non-recurrence (n = 272) within 3 years.

      Results:
      The 1, 3, and 5-year overall survival was 97%, 85% and 74%, respectively. Postoperative recurrence within 1, 2 and 3 years was observed in 26 (7.1%), 58 (16.6%) and 70 (20.4%) patients, respectively. Recurrence in local tissue only within 1, 2 and 3 years was observed in 4 (15%), 14 (24%) and 17 (24%) cases, respectively. Age, sex, smoking history, pathologic stage (IB), lymphatic/vascular invasion, and the degree of tumor differentiation were also significantly different between recurrence and non-recurrence group. Regarding tumor markers, the serum concentrations of SLX, CEA and CYFRA21-1 in the recurrence group were significantly higher than those in the non-recurrence group (p = 0.003, 0.030, and 0.006, respectively). By multivariate analysis, independent predictors of recurrence within 3 years were age more than 75 years (HR 2.51; 1.27–4.96), lymph/vascular invasion (HR 1.95; 1.06–3.63), stage IB (vs IA; HR 2.17; 1.14–4.18) and SLX (HR 1.04; 1.01-1.08). Although the rate of distant recurrence within 3 years was higher in stage IB (p = 0.032), there was no significant difference in age, sex, smoking history, lymphatic/vascular invasion, degree of tumor differentiation, CEA and CYFRA between distant and local recurrence group. The serum tumor marker SLX was also significantly higher in the distant metastasis group than in the local recurrence group (mean 29.8 and 21.4U/ml, respectively; p = 0.007)

      Conclusion:
      Early recurrence predictors after complete resection in patients with pathological stage 1 NSCLC were age (over 75 years), lymph/vascular invasion, stage 1B and high serum concentration of SLX. Furthermore, SLX is potentially useful to predict distant metastasis. Adjuvant chemotherapy might be considered in patients who are positive for these predictive factors.

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      P1.02-004 - Accurate Assessment of Vessel Invasion Using D2-40 and Victoria Blue Predicts Recurrence in Patients with Pathological Stage I NSCLC (ID 880)

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

      • Abstract
      • Slides

      Background:
      It is difficult to estimate lymphatic vessel invasion (LVI) and blood vessel invasion (BVI) by Hematoxylin-Eosin (HE) staining for lung cancer specimens. The aim of this study was to compare HE with D2-40 and Victoria blue staining for detection of LVI and BVI, respectively, and to assess the relationship between these measurements and recurrence in patients with pathological stage I non-small cell lung cancer (NSCLC).

      Methods:
      We retrospectively analyzed 251 patients who underwent complete resection for pathological stage I NSCLC from 1997 to 2008. This study included 152 males and 99 females with a median age of 69 years (range, 20–93 years). Using criteria detailed in the seventh edition of the TNM classification for lung cancer, 129 cases were pathological stage IA and 122 cases were IB. Histologically, 175 adenocarcinomas, 67 squamous cell carcinomas, and 9 other subtypes of carcinomas were found. There were 81 well-differentiated carcinomas and 170 moderate or poorly differentiated carcinomas. The median follow-up across the cohort was 70.2 months and the 5-year survival rate was 72.2%. The paraffin-embedded sections were stained with HE, D2-40, and Victoria blue. Specimens with each staining were reevaluated and classified into three grades according to numbers of vessel invasion in one section: Ly0/V0, no invasion; Ly1/V1, one or two invasions; and Ly2/V2, more than three invasions.

      Results:
      Assessment of vessel invasion by HE revealed the following distribution of LVI grades: Ly0=125 (49.8%); Ly1=104 (41.4%); Ly2=22 (8.8%), and BVI grades: V0=224 (89.2%); V1=24 (9.6%); and V2=3 (1.2%). In contrast, segregation of patients according to reassessment of LVI and BVI by D2-40 and Victoria blue, respectively, resulted in the following distributions: Ly0=177 (70.5%); Ly1=53 (21.1%); Ly2=21 (8.4%); V0=186 (74.1%); V1=53 (21.1%); and V2=12 (4.8%). After reassessment using D2-40 and Victoria blue, 50% (11 of 22) of Ly2 cases by HE changed to Ly0, and 22.7% (5 of 22) of Ly2 cases by HE changed to Ly1, 66% (2 of 3) of V2 cases by HE changed to V0 and V1, respectively. According to accurate assessment of vessel invasion using D2-40 and Victoria blue, there was no significant difference in disease-free survival between patients who were negative and positive for LVI or BVI (p=0.1062 and 0.1849, respectively); however, when patients were divided according to the intensity of LVI/BVI (Ly0&1/V0&1 vs. Ly2/V2), there was a significant difference in disease-free survival (p=0.0281 and p<0.0001, respectively). A recurrence of lung cancer was discovered in 50 patients (19.9%) within 3 years. On multivariate analysis, the independent recurrence factors were pleural invasion (HR 2.64; 1.40–4.86) and V2 based on Victoria blue (HR 8.54; 3.46–19.1).

      Conclusion:
      Our study suggests that accurate reassessment of LVI and BVI using D2-40 and Victoria blue staining, used to assess not only presence but also intensity, is important to predict the postoperative recurrence in patients with pathological stage I NSCLC. If the predictive factors of pleural invasion and V2 based on Victoria blue staining were recognized, adjuvant chemotherapy might be considered for these patients.

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