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W. Mao
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ORAL 34 - Quality/Survival/Prognosis in Localized Lung Cancer (ID 153)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:B.C. Cho, R.L. Keith
- Coordinates: 9/09/2015, 16:45 - 18:15, 201+203
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ORAL34.03 - Prognostic Factors in Early Stage NSCLC: Analysis of the Placebo Group in the MAGRIT Study (ID 24)
17:07 - 17:18 | Author(s): W. Mao
- Abstract
- Presentation
Background:
The MAGRIT study was a worldwide, multicenter, phase-3 double-blind, randomized trial evaluating efficacy of the MAGE-A3 Cancer Immunotherapeutic in resected non-small cell lung cancer (NSCLC) (www.clinicaltrials.gov NCT00480025). We examined baseline patient and disease characteristics associated with overall survival (OS) and disease-free survival (DFS) among patients assigned to placebo.
Methods:
Study participants were ≥18 years, with histologically proven, MAGE-A3-positive stage IB, II or IIIA NSCLC (AJCC 6.0). Participants had undergone complete anatomical resection of the tumor (lobectomy or pneumectomy) with mediastinal lymph node (LN) dissection or sampling according to standard of care. Up to four cycles of platinum-based adjuvant chemotherapy were allowed. Cox regression models were used to explore characteristics that could predict DFS and OS. Factors statistically significant in univariate analysis (p<0.05) were included in multivariate models using a stepwise approach (p<0.05 to enter/remain in the model).
Results:
There were 757 placebo patients in the total treated population; median age 63 years, 76% male, 53% with squamous cell carcinoma (SCC), 34% with adenocarcinoma, 98% with performance status 0-1, 52% had received adjuvant chemotherapy.In univariate analyses, SCC, lower N-category and earlier disease stage were associated with improved DFS. Lower N-category, earlier stage and smaller tumor size were associated with improved OS. In multivariate analysis, N-category (HR 1.34, 95%CI [1.16-1.55]) and histological type (HR for SCC vs non-SCC 0.64, 95%CI [0.51-0.81]) remained significant for DFS. N-category (HR 1.47, 95%CI [1.21-1.79]) and tumor size (HR by unit increase 1.08, 95%CI [1.01-1.15]) did so for OS. No association was found between DFS or OS and age, gender, race, region, baseline performance status, quantitative MAGE-A3 expression, chemotherapy administration or type of chemotherapy, smoking status or type of LN sampling (minimal/systematic). Among patients with SCC, univariate analysis identified increased number of chemotherapy cycles and operative technique (pneumectomy) as associated with improved DFS (p<0.05). Only operative technique remained in the multivariate model. When including N-category (p<0.10 in univariate analysis) in the multivariate model, N-category and number of chemotherapy cycles were also selected. Lower N-category and smaller tumor size were significantly associated with improved OS, in univariate and multivariate analyses. Among patients with non-SCC, univariate analysis identified younger age, being female, lower N-category and earlier disease stage with improved DFS, and lower N-category, earlier disease stage and region (East Asia) with improved OS. N-category and gender, and N-category and region remained significant in the multivariate analysis for DFS and OS, respectively.
Conclusion:
This is the first prognostic factor analysis in resected NSCLC performed on data from a large, prospective randomized study. It highlighted that in terms of DFS, SCC patients have a better prognosis than non-SCC patients. N-category plays a major role in determining prognosis. Operative technique (pneumectomy), number of chemotherapy cycles (SCC) and gender (non-SCC) are also associated with outcome. Variables predictive for OS are N-category and tumor size (all) and region (non-SCC). These results confirm retrospective studies done within the context of TNM classification, but add that histopathology subtype is a strong determinant for DFS in resected NSCLC.
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P1.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 224)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.08-030 - Increasing the Interval between Neoadjuvant Chemoradiotherapy and Surgery in Esophageal Cancer. A Meta-Analysis of Published Studies (ID 2472)
09:30 - 09:30 | Author(s): W. Mao
- Abstract
Background:
Neoadjuvant chemordiotherapy followed by surgery was the most common approach for patients with resectable esophageal cancer. Operation was performed within 2 to 8 weeks after nCRT were completed. The aim of this meta-analysis was to clarify whether a longer interval between the end of neoadjuvant chemoradiotherapy (nCRT) and surgery was associated with a better overall survival in esophageal cancer.
Methods:
We performed a systematic literature search in MEDLINE, EMBASE, Cochrane Central Register of Contralled Trials (CENTRAL/CCTR), Clinical Trials from January 2000 to December 2014. Eligible studies were prospective or retrospective studies of esophageal cancer that assessed the effects of intervals longer or shorter than 7 to 8 weeks between the end of nCRT and surgery. The primary endpoint was the overall survival (OS) and pathologic complete response (pCR). Secondary endpoints were anastomotic leak, R0 resection and postoperative mortality rate. A meta-analysis was performed to estimate odds ratios (ORs) , using the fixed- or random-effects model, with review manager 5.2.
Results:
Five studies met the eligibility requirements, including 1016 patients, with 520 in the shorter interval group (≦7~8 weeks) and 496 in the longer interval group (＞7～8 weeks). The results of our meta-analysis showed that the longer interval between nCRT and surgery may be at a disadvantage in 2-year overall survival (OR =1.40 ,95% CI: 1.09–1.80, P=0.010) and R0 resection rate (OR =1.71, 95%CI:1.14-2.22, P=0.009 ). The pCR, anastomotic leak rate and postoperative morbidity were similar in the two groups.
Conclusion:
A longer waiting interval (more than the classical 6–8 weeks) from the end of preoperative CRT is not an increases the rate of pCR in esophageal cancer, with similar anastomotic leak rate and postoperative mortality rates. However, the longer interval between nCRT and surgery may be at a disadvantage in the long-term overall survival, thus it may be reasonable to perform surgery for patients at the esrliest opportunity after adequate recovery form nCRT, especially, who have clinical pCR. These results should be validated prospectively in a randomized trial.
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P2.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 225)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.08-026 - Molecular Markers of Resected Esophageal Squamous Cell Cancer and Its Correlation with Clinical Outcome (ID 2495)
09:30 - 09:30 | Author(s): W. Mao
- Abstract
Background:
The tumor related molecular markers in esophageal squamous cell cancer(ESCC) remains unknown and requires further investigation in order to promote effiicient and rapid development of therapeutic methods. The aim of our study was to evaluate if molecular markers of ESCC correlates with patients’ prognosis and the outcome.
Methods:
Protein expressions of EGFR, C-MET, HER2 were detected by immunohistochemistry (IHC) in 180 paraffin-embedded tissue samples from stage IIB-IIIC ESCC patients with esophagectomy at the Zhejiang Cancer Hospital between January 2007 and December 2012. Log-rank test was used for univariate analysis, and Cox’s proportional hazards model was used for multivariate analysis. Assessed factors were age, gender, somking, alcohol use , tumor location, stage, differentiation, venous or nerve invasion, radiation, chemotherapy and expressions of EGFR, C-MET, HER2.
Results:
The median survival of all patients was 46 months. Of the all 180 patients, the positive rates of EGFR, C-MET, HER2 were 94.4%, 87.2% and 11.1%, respectively. The high expression rates of EGFR and MET were 47.8% and 46.7%, respectively. On univariate analysis ( Tabel 1 ), stage and high expression MET were the statistically significant unfavorable factors for overall survival, meanwhile, a nonsignificant trend toward dcreased overall survival was found with non chemotherapy patients. The multivariate analysis indicated that independent prognostic risk factors included MET ( P=0.029 ) , chemotherapy (P=0.046) and late stage ( p=0.000 ) with very high statistical significance. In subgroub of the patients with MET high expression, tumor location ( p=0.029 ), non chemotherapy ( p=0.043 ) and late stage (p=0.014) had been the statistically significant unfavorable factors, analyzed by Cox proportional hazards model. In subgroub of the patients with C-MET low or negative expression, non chemotherapy ( p=0.043 ) and late stage ( p=0.014 ) had been the statistically significant unfavorable factors.Table.1 Prognostic factors for overall survival in univariate analyses
Factors Category P-value Age ≤65 (vs.＞65) 0.130 Gender Male (vs. Female) 0.486 Smoking Nonsmokers (vs. Smokers) 0.148 Alcohol use Non use (vs. Use) 0.977 Tumor location Upper and middle (vs. Lower) 0.193 Stage IIA-IIIA (vs. IIIB-IIIC) 0.000 Differentiation Well (vs. moderate and poor) 0.265 Venous or nerve in invasion Non invasion (vs. Invasion) 0.613 Radiation Non radiation (vs. Radiation) 0.957 Chemotherapy Non chemotherapy (vs. Chemotherapy) 0.090 EGFR >median (vs. ≦median) 0.347 C-MET >median (vs. ≦median) 0.018 HER2 Positive (vs. Negative) 0.142
Conclusion:
In the Chinese population, HER2 expression rate was very low. The high expressions of HER2 and EGFR was not correlated with prognosis. High expression of C-MET may be prognostic factors for IIB-IIIC ESCC patients who underwent esophagectomy. ESCC with high expression of C-MET might be a poorer prognosis than those with C-MET low expression. In conclusion, C-MET is a important molecular marker in esophageal squamous cell cancer(ESCC) and further studies are necessary to explore the role of C-MET.
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P3.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 214)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.03-026 - Analysis of Clinical and Dosimetric Factors Influencing Radiation-Induced Lung Injury in Patients with Lung Cancer (ID 3215)
09:30 - 09:30 | Author(s): W. Mao
- Abstract
Background:
Dose escalation of thoracic radiation is limited by the occurrence of radiation-induced lung injury (RILI). This study investigated the clinical and dosimetric factors influencing RILI in lung-cancer patients receiving chemoradiotherapy.
Methods:
A retrospective analysis was carried out on 161 patients with non-small-cell or small-cell lung cancer (NSCLC and SCLC, respectively), who underwent chemoradiotherapy between April 2010 and May 2011 with a median follow-up time of 545 days (range: 39–1453). Chemotherapy regimens were based on the histological type (squamous cell carcinoma, adenocarcinoma, or SCLC), and radiotherapy was delivered in 1.8–3.0 Gy fractions, once daily, to a total of 39–66 Gy (median, 60). Univariate analysis was performed to analyze clinical and dosimetric factors associated with RILI. Multivariate analysis using logistic regression identified independent risk factors correlated to RILI.
Results:
The incidence of symptomatic RILI (≥grade 2) was 31.7%. Univariate analysis showed that V5, V20, and mean lung dose (MLD) were significantly associated with RILI incidence (P=0.029, 0.048, and 0.041, respectively). The association was not statistically significant for histological type (NSCLC vs. SCLC, P = .092) or radiation technology (IMRT vs. 3DCRT, P = .095). Multivariate analysis identified MLD as an independent risk factor for symptomatic RILI (OR=1.249, 95%CI=1.055–1.48, P= .01). The incidence of bilateral RILI in cases where the tumor was located unilaterally was 22.7% (32/141) and all dosimetric-parameter values were higher (P< .05) for bilateral versus ipsilateral injury, but only for grade-1 (low) RILI. The RILI grade was higher in cases of ipsilateral lung injury than in bilateral cases (Mann-Whitney U test, z=8.216, P< .001).
Conclusion:
The dosimetric parameter, MLD, was found to be an independent predictive factor for RILI. Contralateral injury does not seem to be correlated with increased RILI grade under the condition of conventional radiotherapy treatment planning.
