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H. Niwa
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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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P1.05-020 - Opposing Prognostic Roles of CD73 and A2A Adenosine Receptor in Non-Small-Cell Lung Cancer (ID 5139)
14:30 - 14:30 | Author(s): H. Niwa
- Abstract
Background:
CD73 (otherwise known as ecto-5’-nucleotidase) is an important molecule in the adenosine pathway because it generates adenosine by enzymatically dephosphorylating extracellular AMP, which results in immunosuppressed niche within the tumor microenvironment. A2A adenosine receptor (A2AR) acts as a predominant receptor for adenosine in immune cells and can also be expressed in lung tumor cells. However, the clinical impact of the adenosine pathway in non-small-cell lung cancer (NSCLC) has yet to be uncovered, although the pathway has been shown to have a pivotal role in the regulation of anti-tumor immunity and is considered as one of the promising future treatment targets.
Methods:
We investigated CD73 and A2AR protein expression profiles using immunohistochemistry in tissue microarrays containing 642 resected NSCLC specimens. The expression levels were assessed using the H-score method that ranged from 0 to 300, and cutoffs were determined using the minimum P-value method for overall survival (OS). The associations between their expression levels and clinicopathological and molecular characteristics as well as patients’ prognoses were retrospectively analyzed.
Results:
The median age of patients was 68 years old (range, 23–88) and 440 (68.5%) patients were male. 438 (68.2%) patients had smoking history and 420 (65.4%) patients had adenocarcinoma histology. Significantly higher expression of both CD73 and A2AR was observed in female than male, in never smokers than ever smokers, and in adenocarcinomas than squamous cell carcinomas. Among adenocarcinomas, both high CD73 and A2AR expression were significantly associated with TTF-1 positivity and EGFR mutations. ALK-positive adenocarcinomas showed significantly higher expression levels of CD73 than ALK-negative tumors. High CD73 expression was an independent indicator of a poor prognosis for NSCLC patients in multivariate Cox regression analyses for OS (hazard ratio (HR), 2.19; 95% confidence interval (CI), 1.38–3.47) and disease-specific survival (DSS) (HR, 2.97; 95% CI, 1.78–4.95). Contrary, high A2AR expression was an independent favorable predictor of prognosis for OS (HR, 0.69; 95% CI, 0.49–0.97) and DSS (HR, 0.51; 95% CI, 0.33–0.79). Among adenocarcinomas, high CD73 expression was an independent poor prognostic marker for OS (HR, 2.73; 95% CI, 1.61–4.63) and DSS (HR, 4.57; 95% CI, 2.54–8.23), whereas high A2AR expression was an independent favorable prognostic marker for DSS (HR, 0.56; 95% CI, 0.32–0.98).
Conclusion:
Both CD73 and A2AR expression was associated with TTF-1-positive and EGFR-mutant adenocarcinoma. Nonetheless, they had opposing prognostic significance in resected NSCLC.
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P2.06 - Poster Session with Presenters Present (ID 467)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.06-037 - A Feasibility Study of Concurrent Chemoradiation Followed by Surgery for Pathologically-Proven Clinical IIIA-N2 Non-Small Cell Lung Cancer (ID 4700)
14:30 - 14:30 | Author(s): H. Niwa
- Abstract
Background:
The standard treatment for stage IIIA-N2 non-small cell lung cancer (NSCLC) is definitive chemoradiotherapy. However, the strategy for resectable IIIA-N2 disease remains controversial. This phase II multi-institutional trial (WJOG5308L) was designed to evaluate the feasibility for neoadjuvant chemoradiotherapy followed by surgery (tri-modality) in patients with pathologically-proven N2 NSCLC.
Methods:
Patients with resectable IIIA-N2 (pathologically proven N2) were eligible. Neoadjuvant chemotherapy consisted of weekly paclitaxel (40mg/m2) plus carboplatin (AUC 2) for 5 weeks. Concurrent radiotherapy (RT) was prescribed with 50 Gy in 25 fractions to the mediastinum and primary tumor. Patients underwent surgical resection, unless PD disease, followed by two courses of paclitaxel plus carboplatin consolidation chemotherapy. The primary endpoint was complete resection (R0) rate. Secondary endpoints were progression-free survival, overall survival, response rate, protocol completion rate and morbidity/mortality.
Results:
From December 2011 to November 2013, 40 patients were enrolled. The median follow-up time was 33.97 (7.2-46.3) months. The radiological responses to neoadjuvant chemoradiotherapy were as follows: no complete response, 23 (57.5%) partial response, 16 (40.0%) stable disease and one (2.5%) progression. 34 of 40 patients underwent surgery. Reasons for not receiving surgery were radiation pneumonitis (n=4), PD (n=1) and delay of protocol (n=1). Of 34 resections, twenty-eight were lobectomies, three were bilobectomies, two were pneumonectomies, and one was exploratory thoracotomy. Six patients underwent sleeve lobectomy, without any complication. Thirty-two patients achieved the primary endpoint, complete resection (R0) rate 80% (32/40). Pathological complete response (PCR) rate was 30.3%. Finally, 20 patients (50%) completed all planned tri-modality treatment. The 2-year progression-free and overall survival rates for all patients were 62.5% and 75.0%, respectively. The 2-year recurrence-free survival for patients who received R0 was 61.5%. Neutropenia was the main grade 3/4 morbidity and tolerable. 30-days mortality rate was 0 %. Two treat-related deaths (late bronchial fistula) occurred. Sites of first disease recurrences were mediastinal lymphnodes (n=9, 22.5%), lung (n=8, 20%), and brain (n=4, 10%).
Conclusion:
Tri-modality treatment, neoadjuvant chemoradiotherapy followed by surgery, for resectable IIIA-N2 NSCLC seems feasible and promising.
