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Xing Wang
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OA 16 - Treatment Strategies and Follow Up (ID 686)
- Event: WCLC 2017
- Type: Oral
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:Jun Nakajima, T. Demmy
- Coordinates: 10/18/2017, 14:30 - 16:15, Room 315
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OA 16.08 - A Modified Pathological N1 Classification Strategy Based on Systematic Dissection of N1 Nodes from Level 10 to 14 for Non-Small Cell Lung Cancer (ID 9157)
15:45 - 15:55 | Author(s): Xing Wang
- Abstract
- Presentation
Background:
It is necessary to apply a precise standard to predict the oncological outcomes among heterogeneous subgroups of N1 disease ranging from level 10 to 14. Although International Association for the Study of Lung Cancer (IASLC) proposed a new N descriptor in the 8[th] edition of the TNM Classification, lack of dissection on level 13 and level 14 may affect the efficacy of new classification. In this study, we tested a hypothesized classification strategy based on systematic dissection of N1 node from level 10 to level 14.
Method:
From March 2007 to December 2014, 156 consecutive patients of non-small cell lung cancer, treating with lobectomy and systematic mediastinal lymphadenectomy, were investigated. Nodes from level 10 to 12 were dissected during operation. Intrapulmonary lymph nodes (level 13-14) were retrieved after surgery. The data were prospectively collected and retrospectively analyzed. All cases were divided into two categories according to the 8[th] edition of the TNM Classification: pN1a was defined as N1 at a single station, while pN1b was defined as N1 at multiple stations. Then, in our proposed classification, N1a (modified) was defined as single level of N1 station involved (not including single level 10 or 11 spread) or level 13 and/or 14 involved, while N1b (modified) was defined as single level 10 or 11 spread or multiple levels of N1 node involvement (not including level 13 and 14 spread). The association between the N1 subgroup status and survival was explored separately using 8[th] IASLC classification and hypothesized classification.
Result:
In the whole cohort, a mean±SD of 13.1±7.1 N2 nodes and 12.0+5.2 N1 nodes per case were collected.There were 4.7±3.1 nodes from level 13 and 14. The difference in 5-year overall survival between pN1a and pN1b was not significant (73.9% versus 65.7%, p=0.371). However, the difference in 5-year overall survival between N1a (modified) and N1b (modified) was significant (79.1% versus 60.2%, p=0.018). Multivariate analysis showed the revised N1 classification was an independent prognostic factor for NSCLC (versus N1a, the hazard ratio [HR] of N1b for OS was 2.120, 95% confidence interval [CI]: 1.083-4.151, p=0.028). However, the 8[th] edition IASLC N1 descriptors was not an independent prognostic factor (versus pN1a, HR of pN1b was 1.419, 95% CI: 0.710-2.837, p=0.322).
Conclusion:
The hypothesized N1 classification in present study was shown to be a better descriptor to express the outcome than 8[th] edition of the TNM Classification of IASLC. More data are needed to validate this proposal.
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-022 - Protein Tyrosine Phosphatase Interacting Protein 51 Might Improve EGFR-TKI Sensitivity in Non-Small-Cell Lung Cancer (ID 8043)
09:30 - 09:30 | Presenting Author(s): Xing Wang
- Abstract
Background:
Epidermal growth factor receptor (EGFR) -mutant tumors define a subset of Non-small-cell lung cancer (NSCLC), tumors that harbor EGFR mutation are highly sensitive to EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib. However, acquired resistance develops in most NSCLC patients with EGFR mutations after 10-14 months of treatment. In this study we aimed to testify the tumor suppressing function of Protein tyrosine phosphatase interacting protein 51 (PTPIP51), an apoptosis related protein and its effect in improving EGFR-TKI sensitivity.
Method:
Tumor tissues and matched adjacent normal tissues of 154 patients undergoing surgery in the department of Thoracic Surgery II of Beijing Cancer Hospital during 2006–2011 were tested. Patient-derived xenograft mice (PDX model) carrying primary tumor was prepared and Gefitinib/adenovirus-PTPIP51 were used for treatment in vivo and vitro.
Result:
PTPIP51 was down-regulated in NSCLC on both RNA and protein level, and high PTPIP51 expression was revealed as a favorable predictor for better outcome of NSCLC patients(Figure A,B), and elevated PTPIP51 expression exhibited a higher objective regression rate(ORR) to EGFR-TKI therapy of patients with EGFR mutation. Sensitivity to EGFR-TKI of PC9 and A549 cell lines were both enhanced after transfection of PTPIP51. After treatment with adenovirus-PTPIP51+placebo, Gefitinib+placebo, and PTPIP51 plus Gefitinib, it suggested that PTPIP51 could significantly improve EGFR-TKI efficacy in PDX model with wild-type NSCLC tumors (Figure C,D), suggesting a potential correlation between PTPIP51 and EGFR signal pathways. Over-expression of PTPIP51 in NSCLC cell lines significantly inhibited the downstream signaling of EGFR, including PI3K/Akt, Ras/Raf/Erk and Jak/Stat3 pathways, and Gefitinib co-effected with PTPIP51 could induce apoptosis of NSCLC cell lines PC9 and A549. Meanwhile, PTPIP51 interacted with PTEN could induce ubiquitylation then degradation of EGFR via lysosome. Figure 1
Conclusion:
Our findings first highlighted PTPIP51 as a novel tumor suppressor gene in NSCLCs, and it might play a potential role in outcome prediction and improvement of EGFR-TKI sensitivity.
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P3.16 - Surgery (ID 732)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Surgery
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.16-023 - Intrapulmonary Lymph Node Metastasis of Non-Small Cell Lung Cancer: Distribution Pattern and Therapeutic Relevance (ID 8687)
09:30 - 09:30 | Author(s): Xing Wang
- Abstract
Background:
Intrapulmonary lymph node retrieval is important for pathological staging and omitting this procedure may affect the outcome evaluation for patients of pN0. In this study, we aim to investigate the incidence and distribution pattern of intrapulmonary nodes involvement (level 13-14) in a pathological N1 cohort. Meanwhile, survival benefit of adjuvant chemotherapy for patients with N1 nodes involvement only limited in intrapulmonary levels was explored.
Method:
From January 2006 to December 2014, 1979 cases admitted to Peking University Cancer Hospital were treated with standard lung resection and systematic lymph node dissection and intrapulmonary lymph nodes retrieval, of which 160 cases of pathological N1 status entered the analysis. Surgeons collected intrapulmonary nodes after operation according to the protocol and all samples were sent for pathological examination. The data was prospectively collected and retrospectively analyzed. For those with N1 nodes involvement only limited in intrapulmonary levels, adjuvant chemotherapy was suggested by oncologists and patients may or may not follow the advice due to insufficient evidence in this condition. The outcome of those receiving adjuvant chemotherapy and those not was compared.
Result:
In this group, 104 cases (65%) reported level 13-14 nodes metastasis and 57 cases (36%) of N1 spreading only limited in level 13-14. The average levels and numbers of intrapulmonary node involvement were 1.09±0.29 and 1.54±0.85, respectively. For peripheral lung cancer, 38 of 89 cases (42.7%) showed non-tumor-located level 13-14 metastasis. Level 13-14 involvement in non-tumor-bearing segment of the right upper lobe was more frequent than that of the lower lobe (44.4% vs 13.3%, p=0.032), but this trend didn't occur in the left side(56.5% vs 45.8%, p=0.464). In 25 cases with tumor diameter ≤ 2cm, 13 cases (52%) presented non-tumor-bear segment metastasis(right side 38.5% vs left side 52.0%). Among 57 cases of pN1(13-14 only), 38 cases showed all three stations' collection and examination from level 10 to 12 in pathological reports, of which 19 had adjuvant chemotherapy and remaining 19 did not. Survival analysis in this 38 cases revealed survival benefit for patients receiving adjuvant chemotherapy (5-year OS 100% vs. 73.7%±11.6%, p = 0.043; 5-year DFS 53.9%±12.8% vs. 74.6%±8.5%, p=0.563).
Conclusion:
High incidence of intrapulmonary node metastasis and frequent spreading to non-tumor-located (sub)segments in pN1 group may indicate the clinical relevance of intrapulmonary node retrieval. The oncological outcome may be improved by adjuvant chemotherapy for those with N1 nodes involvement only limited in intrapulmonary levels.
