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K. Yoh
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P1.05 - Poster Session with Presenters Present (ID 457)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.05-063 - Multicenter Observational Study of Patients with Resected Early-Staged NSCLC, Who Were Excluded from an Adjuvant Chemotherapy Trial (ID 4713)
14:30 - 15:45 | Author(s): K. Yoh
- Abstract
Background:
From Nov. 2008 to Dec. 2013, the Japan Clinical Oncology Group (JCOG) conducted a randomized phase III trial (JCOG0707), which compared the survival benefit of UFT and S-1 for completely resected pathological (p-) stage I (T1>2 cm and T2 in the 6th TNM classification) NSCLC and a total of 963 patients were enrolled. Recently, there is a growing concern that those who participated in clinical trials are highly selected and do not represent the “real-world” population. Hereby, we conducted a multicenter observational study of patients excluded from JCOG0707 trial during the study period.
Methods:
We retrospectively collected and analyzed the patients’ backgrounds, tumor profiles, post-surgical treatment of the patients who underwent R0 resection of p-stage I (T1>2cm and T2 in TNM 6th) NSCLC by lobectomy or larger lung resection but were excluded from JCOG0707 from Japanese multi-centers.
Results:
Of the 48 institutions which took part in JCOG0707, 34 (enrolling 917 or 95.2% of all JCOG0707 patients) participated in this multicenter study, and 5006 patients were enrolled. Among them, 2617 (52.3%) patients fulfilled the eligibility criteria, but were not enrolled to JCOG0707 mainly due to patients’ decline (69.2%), or physicians’ discretion (20.5%). The accrual rate to JCOG0707 was various by institutions (4.1 to 46.1%), but was 25.9% (917 / [917+2617]) as a whole. Total number of p-stage I and eligible patients at each institution did not correlate the accrual rate (R2=0.003 and 0.046). In the remaining 2389 (47.7%) patients, main ineligible reasons included the existence of active multiple cancer (29.1%), physicians’ decision based on the patients’ comorbidities (19.4%), delayed recovery from surgery (14.1%), and high age ≥81 years (10.7%). Majority of patients received no adjuvant chemotherapy (n = 3338, 66.7%). This proportion differed according to p-T factor (T1: 75.3% vs. T2 : 57.8%, p<0.001) and the JCOG0707 eligibility (ineligible population: 77.6% vs. eligible population: 56.7%, p<0.001). Standard UFT and experimental S-1 were given in 1550 (31.0%) and 21 (0.4%) patients, respectively. Among those who received adjuvant UFT, 971 (62.6%) took UFT for one year or longer.
Conclusion:
Only selected population of candidate patients, even if they met the eligibility criteria, were enrolled to JCOG0707 adjuvant chemotherapy trial for early-stage NSCLC. The “excluded” patients were mainly treated with observation alone or standard UFT treatment. Further analysis of this “excluded” population, including long-term survival, should be necessary for external validation of the randomized trial results.
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P3.01 - Poster Session with Presenters Present (ID 469)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 2
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.01-016 - Factors Influencing the Concordance of Histological Subtype Diagnosis by Biopsy and Resected Specimens of Lung Adenocarcinoma (ID 5018)
14:30 - 15:45 | Author(s): K. Yoh
- Abstract
Background:
Lung adenocarcinoma is heterogeneous, characterized by various histological subtypes. Determination of the predominant histological subtype (lepidic, papillary, acinar or solid-predominant) has been shown to correlate with genetic abnormalities and clinicopathological features. Although subtyping using small biopsy samples is important for tailored approaches to clinical management, limited data exist on the concordance of predominant subtype between resected specimens and biopsy specimens.
Methods:
We compared the diagnosed predominant subtypes in resected specimens and matched biopsy specimens in a series of 327 lung adenocarcinomas. Histological subtyping of preoperative material was made by review of archived hematoxylin and eosin stain slides that had originally been prepared for diagnosis before surgery. The histological subtype of surgically resected tumors was obtained from the pathological case records for each surgical resection specimen. The accuracy of preoperative diagnosis by biopsy and the factors that influence concordance with resected specimen analysis were examined.
Results:
In 211 of the 326 patients (66.0%), the predominant adenocarcinoma subtype diagnosed from biopsy matched the findings of resection analysis. Concordance rate was highest in papillary pattern (82%), followed by lepidic pattern (75%), solid pattern (66%), and acinar pattern (39%). Overall, the concordance rate in biopsy samples with larger tumor areas (≥0.7 mm[2]) was significantly higher than in those with smaller tumor area (<0.7 mm[2]; 71% vs 58%, respectively; p = 0.02). Other factors in biopsy samples, such as number of biopsies, or the small biopsy type, did not have significant influence on the concordance between preoperative and postoperative diagnosis. In the biopsy samples with smaller tumor areas, the concordance rate was 77% in lepidic subtype, 71% in papillary subtype, 60% in solid subtype, and 40% in acinar subtype. Concordance rate in the biopsy samples with larger tumor area was higher in papillary and solid subtypes (88% and 76%, respectively), but remained low in acinar subtype (37%).
Conclusion:
These results indicate that accuracy of adenocarcinoma subtyping based on small biopsy samples is influenced by tumor area. Our study also suggests that subtyping of acinar histology using biopsy specimen is particularly error-prone.
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P3.01-033 - Changes in the Tumor Microenvironment during Lymphatic Metastasis of Lung Squamous Cell Carcinoma (ID 6341)
14:30 - 15:45 | Author(s): K. Yoh
- Abstract
Background:
Metastasis and growth in neoplastic lesions requires the multi-step regulation of microenvironmental factors. We aimed to elucidate the microenvironmental changes in the process of lymphatic metastasis of lung squamous cell carcinoma.
Methods:
We examined the morphological characteristics of 102 cases of Primary Tumor (PT), 50 of intralymphatic tumor (ILT), 51 of lymph node (LN) micrometastasis (LN-Mic; less than 2 mm in size) and 82 of LN Macrometastasis (LN-Mac; greater than 10 mm in size). Afterwards we evaluated the expression of nine molecules (EGFR, FGFR2, CD44, ALDH1, Podoplanin, E-cadherin, S100A4, geminin and ezrin) in matched PT, ILT, LN-Mic and LN-Mac from 23 of these cases.
Results:
The number of smooth muscle actin α-positive fibroblasts, CD34-positive microvessels and CD204-positive macrophages were also examined. As a result, the mitotic index of cancer cells was significantly lower in ILT and LN-Mic than PT and LN-Mac (p<0.001). Moreover stromal reaction in ILT and LN-Mic was less prominent than in PT and LN-Mac (p<0.001). Immunohistochemical study revealed that EGFR expression level and frequency of geminin positive cells in ILT and LN-Mic were significantly lower than in PT and LN-Mac (p<0.05). The number of stromal cells indicated by staining of CD34, CD204 and smooth muscle actin α in ILT and LN-Mic also was significantly lower than in PT and LN-Mac (p<0.05).
Conclusion:
In lung squamous cell carcinoma, drastic microenvironmental changes (e.g., growth factor receptor expression and proliferative capacity of cancer cells and structural changes in stromal cells) occur during both the process of lymphatic permeation and the progression into macrometastases.
