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J.H. Cho
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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)
16:12 - 16:18 | Author(s): J.H. Cho
- 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 - 14:30 | Author(s): J.H. Cho
- 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 - 14:30 | Author(s): J.H. Cho
- 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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P2.02 - Poster Session with Presenters Present (ID 462)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Locally Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.02-044 - Impact of N2 Extent and Nodal Response on Survival after Trimodal Treatment for Stage IIIA-N2 Non-Small Cell Lung Cancer (ID 4662)
14:30 - 14:30 | Author(s): J.H. Cho
- Abstract
Background:
Mediastinal nodal downstaging is an important prognostic factor of neoadjuvant concurrent chemoradiotherapy (CCRT) for stage IIIA-N2 non-small cell lung cancer (NSCLC) and the role of trimodal treatment remains controversial in patients with persistent N2 disease. We aimed to investigate survival outcomes based on the extent of pre-CCRT nodal involvement and mediastinal nodal response in patients who underwent neoadjuvant CCRT for stage IIIA-N2 NSCLC.
Methods:
A retrospective review of patients with N2 disease who underwent neoadjuvant CCRT followed by surgery at our institution was performed and survival outcomes were compared according to the extent of pre-CCRT mediastinal nodal involvement and mediastinal nodal response to CCRT. Extensive lymph node involvement was defined by short-axis diameter of lymph nodes > 2cm measured at computed tomography or involvement of 2 or more mediastinal lymph node stations.
Results:
From 2003 to 2013, 407 patients underwent curative-intent surgery after neoadjuvant CCRT for NSCLC with pathologically proven N2 disease. The mean age was 59 years (314 men, 77%) and histologic type included adenocarcinoma in 233 patients (57%), squamous cell carcinoma in 141 (35%), and large cell carcinoma in 11 (2.7%). Seventy-nine patients (19%) had extensive N2 disease on pre-CCRT imaging tests. The extent of surgery included lobectomy in 311 patients (76%), pneumonectomy in 43 (11%), and sleeve resection in 15 (3.7%). Post-CCRT pathologic nodal status was ypN0 in 155 patients (38%), ypN1 in 56 (14%), and ypN2 in 196 (48%). With a mean follow-up of 41 months, median overall survival (OS) and recurrence-free survival (RFS) were 73 months and 18 months, respectively. The 5-year OS and RFS rates were 61% and 42% in ypN0-1 and 40% and 13% in ypN2, respectively (OS, p=0.0032; RFS, p<0.0001). For patients with ypN0-1, the 5-year OS and RFS rates were 60% and 52% in extensive N2 disease and 61% and 40% in non-extensive N2 disease, respectively (OS, p=0.8106; RFS, p=0.1218). For patients with ypN2, the 5-year OS and RFS rates were 22% and 12% in extensive N2 disease and 47% and 12% in non-extensive N2 disease, respectively (OS, p=0.0403; RFS, p=0.4842).
Conclusion:
Pre-CCRT non-extensive N2 disease was associated with better OS, but was not with better RFS in patients with persistent N2 disease. Patients who achieved mediastinal downstaging showed acceptable OS and RFS regardless of N2 extensiveness. Considering heterogeneity of N2, the indication of neoadjuvant CCRT needs to be differentiated according to the extent of pre-CCRT nodal involvement and post-CCRT mediastinal nodal response.
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P2.02-053 - Does the Method of Mediastinal Staging Cause the Mediastinal Nodal Clearance Following Trimodality Therapy? (ID 4048)
14:30 - 14:30 | Author(s): J.H. Cho
- Abstract
Background:
Outcomes of trimodality therapy for patients with persistent N2 have been well-known as grave. The aim of our study was to investigate whether the method of mediastinal staging could influence the mediastinal nodal clearance following trimodality therapy.
Methods:
We retrospectively reviewed medical records of 574 patients with clinical stage IIIA-N2 non-small cell lung cancer who underwent surgery after neoadjuvant CCRT from 1997 to 2013. Clinical outcomes were analyzed and compared in those who had EBUS (n = 147), Mediastinoscopy (n =341), and others (n=86) after neoadjuvant CCRT in a single institution.
Results:
The median number of dissected lymph node during the operation was 20 (range, 0-50) in EBUS, 14 (range, 1-52) in mediastinoscopy, and 18 (range, 4-40) in others (p<0.001). The median number of lymph node metastases was 2 (range, 0-23) in EBUS, 1 (range, 0-26) in mediastinoscopy, and 0 (range,0-14) in others (p<0.001). There were no differences of age, sex ratio, cell type, surgical extent, clinical T stage, and bulk N2 between these groups. The mediastinal nodal clearance rate (ypN0/1) after surgery was 36 % (54/147) in EBUS, 58% (198/341) in mediastinoscopy, and 60.5% (52/86) in others (p<0.001). The ypN0 rate was 28.6% (42/147) in EBUS, 41.9% (143/341) in mediastinoscopy, and 51.2% (44/86) in others (p=0.001).
Conclusion:
We found that the mediastinal nodal clearance rate (ypN0/1) after surgery was higher in mediastinoscopy than in EBUS. The method of mediastinal staging could influence ypN stage following trimodality therapy.
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P2.04 - Poster Session with Presenters Present (ID 466)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.04-001 - A Comparative Analysis of Long-Term Outcome of Thymoma between Video-Assisted Surgery and Open Resection from Multi-Center Study Data (ID 6297)
14:30 - 14:30 | Author(s): J.H. Cho
- Abstract
Background:
To compare the oncologic results between video-assisted thoracoscopic surgery and open resection in early and locally advanced thymomas from multi-center study database using propensity score matching analysis.
Methods:
Data from 1546 participants in the Korean Association for Research on the Thymus were used to analysis for video-assisted thoracoscopic surgery(VATS) versus open resection from January 2003 to December 2013. We performed propensity score matching analysis for the outcomes of video-assisted thoracoscopic surgery versus thoracotomy lung resection (based on age, gender, MG symptom, tumor size, WHO histologic type, receiving neoadjuvant chemotherapy).
Results:
We excised the thymoma using VATS in 513 patients, while 1033 patients underwent open procedures. There were not significant differences between the 2 groups for the 5-year overall survival (p=.61), recurrence-free survival (p=.25), and complete resection (p=.38). The operative times, the hospital stay duration, and the chest tube indwelling time were significantly shorter in the VATS group compared to in the open group. Median follow-up duration was 50.13 months (IQR 26.61-79.60). The Masaoka-Koga stage was I/II/III, IV in 556/604/384 patients, respectively. We analyzed on the basis of propensity score matching. There were no significant difference in survival rate (p=0.882/0.632/0.597), recur-free survival (p=0.120/0.104/0.488), and R0 resection (p=0.945/0.656/0.007) between 3 grups in multivariable analysis.
Conclusion:
Patients undergoing VATS thymectomy had shorter the operative time and the hospital stay duration. Moreover, survival rate and recurrence-free survival are equivalent between VATS and open resection. Therefore, video-assisted thoracosopic surgery is feasible approach for early and locally advanced stage thymoma.
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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 - 14:30 | Author(s): J.H. Cho
- 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.
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P3.04 - Poster Session with Presenters Present (ID 474)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Surgery
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.04-026 - A Simultaneous Surgical Strategy for Patients with Lung Cancer and Severe Cardiac Diseases Requiring Surgical Treatment (ID 5666)
14:30 - 14:30 | Author(s): J.H. Cho
- Abstract
Background:
The simultaneous surgical treatment of lung carcinoma and cardiac disease is rare.The aim of the study was to analyze the early and mid-term results of simultaneous surgical treatment for concomitant lung cancer and cardiac diseases which both needs surgical treatment.
Methods:
We performed a retrospective review of 12 patients who underwent pulmonary and cardiac surgery, from 2002 to 2015, in a single institution. We focused on early postoperative morbidity and mortality.
Results:
Total 12 patients were recruited from 2002 to 2015 in the department of cardiothoracic surgery at the Samsung Medical Center in Korea. Nine patients were the diagnosed as concomitant non-small cell lung cancer and coronary artery disease, one patient was diagnosed as concomitant non-small lung cancer and aortic arch aneurysm, one patient was diagnosed as concomitant non-small lung cancer and mitral stenosis with tricuspid regurgitation, one patient was diagnosed as concomitant BALtoma and ASD with pulmonary hypertension. Various cardiac surgeries were performed simultaneously with the pulmonary resection. Ten patients were performed via median sternotomy, and 2 patients were performed via anterior thoracotomy. The mean age of the patients was 62.7 years old. Follow-up ranging from 6 months to 12 years is available for these patients. The lobectomy by median sternotomy rate was 41.6 % (5 patients), the lobectomy by anterior thoracotomy rate was 16.7 % (2 patients), and the wedge resection by median sternotomy rate was 41.6 % (5 patients). There were no mortality or major morbidity, apart from 8 minor complications in four patients (33.3%) (air leak, atrial fibrillation, atelectasis, pneumonia, delirium).
Conclusion:
Simultaneous cardiac surgery and lung resection in this small number of patients were safely performed without life-threatening morbidity and no in-hospital mortality.
