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X. Fu
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MA06 - Locally Advanced NSCLC: Risk Groups, Biological Factors and Treatment Choices (ID 379)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:P. Van Houtte, M. Zemanová
- Coordinates: 12/05/2016, 16:00 - 17:30, Strauss 2
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MA06.06 - Tumor Microenvironment and Brain Metastases in Completely Resected Stage IIIA(N2) Non-Small Cell Lung Cancer (ID 5115)
16:36 - 16:42 | Author(s): X. Fu
- Abstract
- Presentation
Background:
Tumor-infiltrating lymphocytes (TILs) and tumor budding were all the markers of tumor microenvironment. This study aimed to explore the potential association of tumor microenvironment with brain metastases (BM) in patients with completely resected stage IIIA(N2) NSCLC.
Methods:
301 consecutive patients with pathological stage IIIA(N2) NSCLC who underwent complete surgery were reviewed between January 2005 and July 2012. Full-face hematoxylin and eosin-stained sections from surgical specimens for each case were evaluated for the density of TILs. Patients were stratified into TIL- and TIL+ groups based on pathologic evaluation. Tumor budding was defined as single cancer cells and clusters composed of up to four cancer cells. According to the number of tumor budding per field, the cases were classified into two groups: grade 1, up to five budding foci; and grade 2, six or more budding foci. The relationship between tumor microenvironment and BM at the initial presentation was analyzed.
Results:
Brain was the most common site of distant failure, and 92.5% BM developed in 3 years after the complete resection. 53 (17.6%) patients had BM as the first failure. Although, univariate analysis showed that TIL was not significantly associated with an increased risk of developing BM as the first site of failure in 3 years (P=0.196), a higher density of TILs was associated with improved postoperative survival time (P=0.058). Patients with the tumor budding >5 experienced increased BM in 3 years versus patients with the tumor budding ≤5 (P=0.068). Multivariate analysis showed that adenocarcinomas and multiple N2 stations were significantly associated with the high risk of BM as the initial site of failure in 3 years. Figure 1
Conclusion:
In patients with completely resected stage IIIA(N2) NSCLC, tumor budding >5 had a tendency to experience more BM. TIL seems to be a potential role in predicting survival of patients in completely resected stage IIIA(N2) NSCLC.
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P2.01 - Poster Session with Presenters Present (ID 461)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.01-057 - Association of Tumor Infiltrating Lymphocytes Quantification with EGFR Mutations in Completely Resected Stage IIIA(N2) Lung Adenocarcinoma (ID 5269)
14:30 - 14:30 | Author(s): X. Fu
- Abstract
Background:
Accumulating data suggests that the extent of lymphocytic infiltrations into the tumor provides prognostic value in non-small cell lung cancer (NSCLC). However, the factors that influence the status of tumor immune environment remain poorly defined and need investigation. The aim of this study was to assess whether the density of tumor infiltrating lymphocytes (TILs) was related to tumor molecular characteristics in completely resected stage IIIA(N2) lung adenocarcinoma.
Methods:
We retrospectively screened consecutive patients with pathologic stage IIIA(N2) pulmonary adenocarcinomas, who had undergone complete resection in our hospital between 2005 and 2012. Patients who received neoadjuvant chemotherapy and/or radiotherapy were excluded. DNA of EGFR and KRAS was extracted and purified from paraffin-embedded primary lung cancer tissue samples. EGFR (exons 18-21) and KRAS (exons 2, 3) mutation analyses were performed by the DNA sequencing. The density of TILs was evaluated by full-face hematoxylin- and eosin-stained sections from surgical specimens for each case by two specialized pathologists. The degree of lymphocyte infiltration into the tumor was scored as none, low, moderate, or high. Patients were stratified into TIL- (none to low infiltration) or TIL+ (moderate to high infiltration) group based on pathologic evaluation. We investigated the association of densities of TILs with tumor-cell mutation status.
Results:
Among the 192 eligible patients included, 96 (50%) patients were male and 123 (64%) were never/light ex-smokers, and the median age of all patients was 59 years (range, 22–84 years). There were 84 (43.8%) EGFR mutated and 21 (10.9%) KRAS mutated cases. Among the 84 patients with activating EGFR mutations, there were 30 patients harboring mutations in the exon 19 deletions, 35 patients in the exon 21 L858R mutations, and 1 patient with concurrent exon 19 deletion and L858R mutation. The proportion of patients who had higher density of TILs (TIL+) was lower in the EGFR mutation-positive subgroup (42.9% versus 53.7%, P=0.14) and this difference was significantly observed in the patients with L858R mutation and/or exon 19 deletion subgroup (P=0.026). The proportion of patients who had higher density of TILs (TIL+) was significantly lower in the 66 patients harboring L858R mutation and/or exon 19 deletion (37.9% versus 54.8%, P=0.026).
Conclusion:
There existed association between the lower density of TILs and activating EGFR mutation status in lung adenocarcinoma, underlying the interactions between cancer cells and their microenvironment. Further studies are warranted to validate these results and clarify the potential molecular mechanisms responsible for regulation of lymphocytic infiltration by activating EGFR pathway.
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P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03b-006 - Distinct MR Imaging Features of Metastatic Lesions in Brain with Non-Small Cell Lung Cancer According to EGFR Mutation Status (ID 4131)
14:30 - 14:30 | Author(s): X. Fu
- Abstract
Background:
It is often difficult to evaluate the status of EGFR mutation in non-small cell lung cancer (NSCLC) patients with brain metastases either from primary or metastatic lesions. Is it possible to ascertain the EGFR status and to guide the usefulness of TKI according to the MR imaging features of metastatic lesions in brain?
Methods:
Patients diagnosed with NSCLC from June 2014 through May 2015 were identified synchronous brain metastases based on enhanced magnetic resonance imaging (MRI). The variables of metastatic brain tumor included the numbers and the size of the brain lesions, the size of the associated peritumoral brain edema (PTBE) measured with brain MRI. The information was obtained mainly by transbronchial lung biopsy, percutaneous needle lung biopsy or cervical lymph nodes biopsy about EGFR mutation status.
Results:
Among 156 patients, 41 had the exon 19 deletion, 48 had the exon 21 L858R point mutation, and 67 had the wild-type EGFR. The exon 19 deletion group and exon 21 point mutation group had smaller peritumoral brain edema than did the wild-type group (P = 0.002 and P = 0.010, respectively). Different from the wild-type group, the exon 21 point mutation group showed more multiple brain tumors (P = 0.020). There was no significant difference about the size of the largest brain tumors in either exon 19 deletion group or exon 21 point mutation group when compared with the wild-type group (P = 0.077 and P = 0.051, respectively), but the metastatic brain lesions were inclined to smaller in EGFR mutation groups.
Conclusion:
Specific features of MRI in brain metastatic lesions were found in NSCLC with EGFR mutation，including smaller peritumoral brain edema and more lesions than did those with wild-type EGFR. Meanwhile, there was the trend that the size of the largest brain lesion was smaller in EGFR mutation groups. Accumulation of more knowledge was needed to depend on radiomics to make a quantifying analysis of EGFR mutation status.
