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X. Fu
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ORAL 36 - Translational Science/Radiation (ID 151)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:E. Vokes, B. Kavanagh
- Coordinates: 9/09/2015, 16:45 - 18:15, Mile High Ballroom 2c-3c
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ORAL36.01 - Prognostic Value of Tumor-Infiltrating Lymphocytes for Patients with Completely Resected Stage IIIA(N2) Non-Small Cell Lung Cancer (ID 1061)
16:45 - 18:15 | Author(s): X. Fu
- Abstract
Background:
Patient prognosis after complete resection for pathologic stage IIIA(N2) non-small cell lung cancer (NSCLC) remains a significant concern. Accumulating evidence suggests that the host immune response might determine tumor behavior and influence the survival prognosis; however, the clinical relevance of the host immune response to NSCLC has yet to be established. We aimed to investigate the prognostic value of tumor-infiltrating lymphocytes (TILs) in a uniform cohort of patients with completely resected stage IIIA(N2) NSCLC.
Methods:
From January 2005 to June 2012, all consecutive patients with pathologic stage IIIA(N2) NSCLC who underwent complete resection in our hospital were retrospectively reviewed. Inclusion criteria for this study were as follows: complete resection through a surgical procedure of either lobectomy or pneumonectomy with microscopically tumor-free resection margins; systematic nodal dissection with a minimum of three N2 stations dissected; and histologically proven NSCLC of stage pT1-3N2M0 (according to the 7th UICC TNM classification). Patients who received neoadjuvant chemotherapy and/or radiotherapy were excluded. Full-face hematoxylin- and eosin-stained sections from surgical specimens from each case were evaluated for the density of TILs by two qualified specialized pathologists. A published recommended TILs scoring scale was followed. The degree of lymphocyte infiltration into the tumor was scored as none (score 0), low (score 1), moderate (score 2), or high (score 3). Patients were stratified into TIL-negative (none to low infiltration) or TIL-positive (moderate to high infiltration) group based on pathologic evaluation.
Results:
Of the eligible 320 patients included in the analysis, 135 (42%) patients were categorized as TIL-positive; and the 185 (58%) patients were defined as TIL-negative. The median follow-up duration was 30.8 months (range, 12-101.4 months) for the living patients. In the entire cohort, the median survival time (MST) was 42.5 months, and the 1-, 3-, and 5-year overall survival (OS) rates were 90.9%, 54.3%, and 35%, respectively. For the patients in the TIL-negative and TIL-positive groups, the MST was 35.7 and 45.5 months, respectively. The 1-, 3-, and 5-year OS rates were 88.6%, 49.5%, and 34%, respectively, in the TIL-negative group and 94.1%, 61.2%, and 35.6%, respectively, in the TIL-positive group. A higher density of TILs (TIL-positive) was associated with improved OS and the differences trended toward significance (P=0.06). Multivariate analyses confirmed that TIL-positive was an independent prognostic factor for improved OS (HR=0.70, 95%CI 0.50-0.99, P=0.05). Subgroup analyses indicated that this positive effect was the greatest for patients with squamous cell carcinoma (SCC; HR=0.44, 95%CI 0.21-0.94, P=0.03). Of the 93 patients with SCC, TIL-positive was significantly associated with improved distant metastasis-free survival (DMFS; P=0.02) and OS (P=0.03). The TIL-positive was a strong prognostic factor in the multivariate model, both for prolonged DMFS (HR=0.39, 95%CI 0.17-0.87, P=0.02) and OS (HR=0.47, 95%CI 0.22-1.00, P=0.05).
Conclusion:
Our data suggested a potential role of TILs in predicting the survival prognosis of patients with completely resected stage IIIA(N2) NSCLC. The beneficial effects of TILs were more pronounced for the prediction of DMFS and OS in patients with SCC. Studies assessing outcomes and therapeutic efficacies in prospective clinical trials should consider stratification for this immunological parameter.
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P1.07 - Poster Session/ Small Cell Lung Cancer (ID 221)
- Event: WCLC 2015
- Type: Poster
- Track: Small Cell Lung Cancer
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.07-010 - Hyperfractionated Versus Hypofractionated Radiotherapy for Limited-Stage SCLC: A Retrospective Comparison of Two Prospective Studies (ID 592)
09:30 - 17:00 | Author(s): X. Fu
- Abstract
Background:
The optimal thoracic radiation dose/fraction for limited-stage small cell lung cancer (SCLC) is not yet established at present. This study mainly aims to retrospectively compare the impact on local/regional control of different thoracic radiation dose/fraction schedules from two prospective trials.
Methods:
Patients received thoracic radiotherapy consisted of 1.5 Gy twice a day in 30 fractions over a 19-day period to a total of 45 Gy (hyperfractionated arm, BED=53.3 Gy) or 2.5 Gy daily in 22 fractions over a 30-day period to a total of 55 Gy (hypofractionated arm, BED=62.6 Gy) combined with concurrent chemotherapy were included into this study. A statistical software package SPSS 13.0 was applied, and Kaplan-Meier method was used to estimate survival data. Fisher’s exact test was used for comparisons of categorical data.
Results:
From 2005 to 2014, nighty-two patients were accrued into to the hyperfractionated arm. From 2005 to 2012, nighty-one patients were accrued into the hypofractionated arm. The 1-year, 2-year local/regional progression free survival rates of hyperfractionated arm and hypofractionated arm were 82.1%, 60.7% and 83.8%, 67.9%, respectively (P=0.33). The median survival time (months) of hyperfractionated arm and hypofractionated arm were 27.9 (95% CI: 15.7-40.1) and 22.0 (95% CI: 16.4-27.5) respectively, while 1-year, 3-year, 5-year overall survival rates of the two arms were 85.2%, 39.4%, 26% and 77.1%, 34.4%, 26.9% respectively (P=0.48). Grade 2 and 3 acute radiation esophagitis were observed in 28.3%, 8.7% and 15.5%, 2.1% of patients in hyperfractionated arm and hypofractionated arm (P=0.009). Figure 1 Figure 2
Conclusion:
This study indicated that the use of hypofractionated radiotherapy failed to significantly improve the local regional control rate and overall survival time compared with hyperfractionated radiotherapy. However, the incidence of grade 2 and 3 acute radiation induced esophagitis was significantly more common in the hyperfractionated arm than in hypofractionated arm.
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P3.06 - Poster Session/ Screening and Early Detection (ID 220)
- Event: WCLC 2015
- Type: Poster
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.06-028 - Risk Factors of Brain Metastases in Completely Resected Stage IIIA(N2) Pulmonary Adenocarcinomas (ID 2369)
09:30 - 17:00 | Author(s): X. Fu
- Abstract
Background:
Previous studies show that adenocarcinomas is the main high risk factor of brain metastases (BM) in NSCLC, and 90% of BM developes in 3 years. In patients with completely resected stage IIIA(N2) pulmonary adenocarcinomas, we aimed to identify the risk factors of BM as the first site of failure in 3 years on the basis of the new lung adenocarcinoma classification and molecular biology information.
Methods:
Patients with IIIA(N2) pulmonary adenocarcinomas, who had undergone radical surgery in our hospital from January 2005 to July 2012 were retrospectively reviewed. We observed the correlation among clinical factors, the new lung adenocarcinoma classification, lymph node status, microenvironmental factors, gene mutation status and BM to find out the risk factors of BM. DNA of EGFR and KRAS was extracted and purified from primary tumors embedded in paraffin blocks. KRAS and EGFR mutation analyses were performed by using DNA sequencing. Main outcome measure was BM as the first site of failure in 3 years.The cumulative incidence of BM as the first site of failure were determined using the Kaplan–Meier analyiss. The log-rank test was used for univariate analysis, and Cox regression was used for multivariate analysis.
Results:
179 patients with completely resected stage IIIA(N2) pulmonary adenocarcinomas were included in this study. EGFR and KRAS mutations were found in tumors 41.3% and 11.7%, respectively. The most common EGFR mutations were deletions in exon 19 and the p.L858R point mutation in exon 21. The most common KRAS mutations were G-T or G-C point mutation in codon 12. Brain was the most common site of distant failure as the first failure, and 93.3% BM developed in 3 years after the complete resection. Multivariate analysis showed that the extra-capsular extension（ECE）, cN2 and KRAS mutations were significantly associated with the high risk of BM as the initial site of failure in 3 years, while EGFR 19 exon mutations were the low risk of BM. The risk of BM in patients with KRAS mutations were significantly higher than patients with EGFR 19 exon mutations or other EGFR mutaions (P=0.018). Figure 1
Conclusion:
In patients with completely resected stage IIIA(N2) pulmonary adenocarcinomas, ECE, cN2 and KRAS mutations were independent high risk factors for BM as the initial failure in 3 years. The EGFR 19 exon mutation may be a protective factor of BM. The new lung adenocarcinoma classification and tumor microenvironment were not statistically significant factors in our series.
