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S. Shin
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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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MA06.03 - Recurrence Dynamics after Trimodality Therapy (Neoadjuvant Chemoradiotherapy and Surgery) in Stage IIIa(N2) Lung Cancer (ID 4963)
16:00 - 17:30 | Author(s): S. Shin
- Abstract
- Presentation
Background:
In IIIa(N2) Non-small cell lung cancer (NSCLC), various strategies to cure have been tried but the major cause of mortality is still the recurrence. Therefore, understanding of the dynamics of recurrence is important to improve the treatment outcome. We investigated the timing and patterns of recurrence after treatment of IIIA(N2) NSCLC with trimodality treatment (neoadjuvant chemoradiotherapy and surgery).
Methods:
An institutional database of consecutive patients between 1997 and 2013 (N = 574) was reviewed retrospectively. Eligible patients had pathologically proven N2 disease of NSCLC and completion of a planned trimodality treatment. First events involving the development of loco-regional recurrence, distant metastases or both were considered. The hazard rate function was used to evaluate the dynamics of recurrence.
Results:
The 5-year overall survival rate was 47% and the 5-year recurrence free survival rate was 29%. Among the 299 patients (52.1% of total) who experienced recurrence, 26 (8.7%) had loco-regional recurrences, 248 (82.9%) had distant metastases, and 25 (8.4%) had both. The most frequent sites of distant metastases were lung (n=102, 41%), brain (n=63, 25%), and bone (n=63, 25%). The hazard rate function for the overall recurrence revealed the peak at approximately 8 months after surgery then the down-slope pattern before 38 months. A similar risk pattern was found in distant metastasis but low and steady risk pattern was detected in loco-regional recurrence. In distant metastases, similar patterns were found in individual organs, however, earlier peak at approximately 5 months presented in brain metastasis. A comparison of histology showed that adenocarcinoma exhibited higher recurrence hazard rate of distant metastasis than squamous cell carcinoma with similar pattern of recurrence (p=0.03). The status of nodal clearance after induction therapy exhibited that ypN2 patients (n= 229, 39.9%) had highest hazard rate (p=0.03). The recurrence hazard rate of ypN0 was the least, but the extent was not smaller, they showed approximately one of third of ypN2 at peak.
Conclusion:
The hazard rate of loco-regional failure after trimodality therapy was low. But the hazard rate of distant metastasis was considerably high yet and shifted to left with the peak within 12 moths after surgery. This study guides the intensive surveillance immediate after completion of trimodality therapy to identify risk groups of early recurrence and to develop therapeutic strategy.
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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: 2
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.05-041 - Dynamics of Brain Metastasis for Curatively Resected Stage I or II Non-Small Cell Lung Cancer Patients (ID 5933)
14:30 - 15:45 | Author(s): S. Shin
- Abstract
Background:
Development of brain metastasis results in a significant impairment in overall survival. The aim of this study to investigate the timing and manifestation of brain recurrence event during follow-up in patients undergoing surgery for stage I or II non–small-cell lung cancer (NSCLC).
Methods:
Between 2008 and 2012, medical records for patient who underwent curative surgery for stage I or II NSCLC at our institution were reviewed retrospectively. Event dynamics including brain metastasis, distant metastasis and non-brain distant metastasis, based on the hazard rate, were evaluated.
Results:
A total of 2389 eligible patients were identified. At a median follow-up of 50.6 months (IQR, 37.8–60.3 months), 573 patients developed recurrence. Among those, 457 patients had distant metastasis including 70 patients had brain metastasis as the first relapse site. The hazard rate curve for brain metastasis is similar from those of all distant metastasis and non-brain distant metastasis. The distinct surge was noted in 8.3 months in the brain metastasis. Subgroup analysis according to pathologic stage revealed that patients with stage II have distinct surge in 10 months, while the surge of stage I patients is more gradual and low. Hazard rate for brain metastasis is similar for each stage since 34months.
Conclusion:
Brain recurrence dynamics of resected stage I or II early-stage NSCLC displays a similar pattern compared to other distant metastasis. The overall risk reached high less than 1 year postoperative period regardless of stage. Our findings would be helpful to make a strategy to surveillance for brain metastasis after surgical resection for early stage NSCLC.
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P1.05-048 - Effect of Adjuvant Chemotherapy on the Patterns and Dynamics of Recurrences in Resected Stage II(N1) Lung Adenocarcinoma (ID 4990)
14:30 - 15:45 | Author(s): S. Shin
- Abstract
Background:
Although the complete surgical resection in most cases of the non-small cell lung carcinoma with N1 involvement is feasible, a considerable number of patients develop recurrence and the disease course is highly variable. Timing and pattern of recurrence are essential to explain strong prognostic heterogeneity, however, research focusing on these subjects have rarely been reported. We investigated the patterns of recurrences and event rates over time in patients with completely resected N1-stageII lung adenocarcinoma.
Methods:
We retrospectively reviewed the medical records of 333 patients who underwent a complete surgical resection for N1-stage II lung adenocarcinoma. Survival curves were generated using the Kaplan-Meier method, and the event dynamics was estimated using the hazard function.
Results:
The median recurrence-free survival was 36.8 months. The life table survival analysis showed that the 1-year, 3-year and 5-year recurrence free survival rates were 85.1%, 50.2% and 36.6%, respectively. Approximately 151(45.2%) patients experienced recurrence, and the patterns of recurrences included loco-regional in 41 patients (27.2%), distant in 68 (45.0%), and both in 42 (27.8%). Most commonly involved organs were the lung (n=77, 47.0%), followed by lymph nodes (n=41, 27.2%), bone (n=31, 20.5%), and brain (n=30, 19.9%). There were 228 patients received adjuvant chemotherapy. Patients treated with adjuvant chemotherapy showed better recurrence free survival (chemotherapy group vs non-chemotherapy group; median survival 42.5 months vs 25.4 months), and post-recurrence survival(chemotherapy group vs non-chemotherapy group; median survival 39.8 months vs 22.6 months) compared to those of patients without adjuvant chemotherapy. The multivariate analysis revealed that adjuvant chemotherapy was significantly correlated with recurrence free survival (p=0.004) and post recurrence survival (p=0.001). Patients underwent adjuvant chemotherapy had less distant (p=0.014) and less lung (p=0.045) recurrence, while there is no difference in loco-regional (p=0.837) and brain (p=0.997) recurrence. The recurrence hazard curve demonstrated similarly shaped and sized initial and second peak at 16 and 24months, followed by a smaller peak at 40months. The temporal distribution of the recurrence risk varied depending on adjuvant chemotherapy. A visual inspection of the hazard curves suggested that the patients without adjuvant chemotherapy exhibited earlier and higher first peaks with higher hazard rate over time.
Conclusion:
In the patients who underwent completely resected N1-stageII lung adenocarcinoma, adjuvant chemotherapy not only reduced the recurrence hazard, but also delayed the recurrence, altered pattern of recurrence and improved post-recurrence survival.
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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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P2.06-043 - 3-Dimensional High Throughput Multi-Drug Screening Using Patient-Derived Tumor Cells (PDC) Established from Surgical Specimens of NSCLC (ID 5942)
14:30 - 15:45 | Author(s): S. Shin
- Abstract
Background:
To investigate the clinical applicability of the high throughput screening (HTS) using patient-derived tumor cells (PDC) which were established from patients with non-small cell lung cancer undergoing surgery.
Methods:
PDCs were isolated and cultured from surgical specimen from NSCLC at Samsung Medical Center. We performed the HTS for 24 drugs (23 targeted agents and 1 positive control drug) with a micropillar/microwell chip platform using PDCs. Scanned images of the live cells were obtained using an optical fluorescence. With 6 dosages per drug in 7 replicates, the dose response curves and corresponding IC~50~ values were calculated from the scanned images.
Results:
From October 2015 to February 2016, 15 samples from patients with non-small cell lung cancer were collected. PDCs were successfully established in 12 (80%) patients, and nine of 12 cases were successfully cultured in 3-d suitable for 23-drug HTS platform. Three PDCs demonstrated a sensitivity to Neratinib (HER-2/EGFR inhibitor). These PDCs are currently being profiled to elucidate the underlying molecular mechanisms for neratinib sensitivity.
Conclusion:
Differential chemosensitivity were observed which suggests that this HTS platform based on 3D culture with micropillar/microwell chips and PDC model could potentially provide a preclinical tool for predicting the efficacy of targeted agents in lung cancer.
