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Jhingook Kim
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MA08 - Pawing the Way to Improve Outcomes in Stage III NSCLC (ID 127)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Now Available
- Moderators:Simon Ekman, Helena A Yu
- Coordinates: 9/08/2019, 15:15 - 16:45, Tokyo (1982)
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MA08.03 - Adjuvant Pembrolizumab in N2 Positive NSCLC Treated with Concurrent Chemoradiotherapy Followed by Surgery: Phase II, Prospective Study (Now Available) (ID 1744)
15:15 - 16:45 | Author(s): Jhingook Kim
- Abstract
- Presentation
Background
The standard treatment option for stage IIIA-N2 subgroup is still under discussion with controversies. We hypothesize that immune checkpoint inhibitor consolidation therapy could have an additional role in prolongation of the disease-free survival (DFS) for stage IIIA-N2 NSCLC treated with tri-modalities therapy.
Method
This is a phase 2 study evaluating the clinical efficacy of pembrolizumab treatment after CCRT with curative resection in stage IIIA-N2 NSCLC pts (NCT03053856). Pathologically confirmed pts were treated with five cycles of CCRT, weekly paclitaxel (50mg/m2) and cisplatin (25mg/m2) combined with radiotherapy (total of 44Gy over 22 fractions) followed by curative resection. Adjuvant Pembrolizumab (200mg fixed dose) is applied every three weeks up to 2 years or until disease recurrence. The primary objective is disease-free survival of more than 20 months. The first patient was recruited in October 2017, and the data for this abstract was locked at 20th of January, 2019.
Result
Total of 40 pts were screened, and 37 pts received treatment. Median age was 64 years (range 39-74), and twenty-three pts were male (62.2%). As a curative surgery, pts received lobectomy (n=34), bi-lobectomy (n=2), or pneumonectomy (n=1). Adenocarcinoma was predominant (n=27, 73.0%). After the neoadjuvant CCRT, down-staging were observed in nine pts (24.3%). The median follow-up duration was 10.6 months (range 3.1-17.2), and pts received a median of 11 cycles (range 1-22) of adjuvant pembrolizumab. DFS is not reached. Fourteen patients discontinued treatment due to disease progression (n=9), adverse events (n=4) and withdraw consent (n=1). There was a case of grade 4 pneumonitis and a case of grade 3 autoimmune hepatitis which lead to discontinuation of the treatment. Otherwise, grade 1-2 hypothyroidism (n=6), pneumonitis (n=5), skin rash (n=3) were observed. Patients with severe immune-related adverse event showed a significantly high percentage of Ki-67 + cells among CD8 T-cells in peripheral blood.
Conclusion
This study is the first study to demonstrate the feasibility of adjuvant pembrolizumab monotherapy in stage IIIA-N2 patients. Updated clinical outcome will be presented at the conference.
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MS03 - Workup and Management of Small Anterior Mediastinal Masses/Lesions (ID 66)
- Event: WCLC 2019
- Type: Mini Symposium
- Track: Thymoma/Other Thoracic Malignancies
- Presentations: 1
- Now Available
- Moderators:Meinoshin Okumura, Pier Luigi Filosso
- Coordinates: 9/08/2019, 13:30 - 15:00, Amsterdam (2011)
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MS03.05 - Relevance of Nodal Involvement and the Thymic Lymph Node Map (Now Available) (ID 3453)
13:30 - 15:00 | Presenting Author(s): Jhingook Kim
- Abstract
- Presentation
Abstract
Thymic epithelial tumors (TET) including thymoma, thymic carcinoma, and thymic neuroendocrine tumors are rare cancers, accounting for less than 1% of all tumors. No official staging system was defined by the Union Internationale Contre le Cancer and the American Joint Commission on Cancer (AJCC) until 2017. This led to several proposals being published over the years, but few received clinical validation. Unlike lung cancer, where regional spread through the lymphatics has been proved, most common patterns of recurrence in TET are local failure, or dissemination into the pleural or pericardial spaces. Therefore, the role of additional intraoperative nodal assessment is uncertain in TET, for which total thymectomy is the standard procedure.
Lymph node metastasis in TET is more common with thymic carcinoma. Kondo et al. reported in their retrospective study (n=1320) that lymphogenous spread with or without distant metastasis was found in 3.2% of thymomas, and more commonly in 33% of thymic carcinomas.1 In particular, anterior mediastinal lymph nodes were thought to be the primary drainage location for TET. Anterior mediastinal lymph nodes were involved in approximately 90% of thymomas, 70% of thymic carcinomas, and 90% of thymic neuroendocrine tumors with lymph node metastasis. Furthermore, a cadaveric study found that the anterior mediastinal nodes are the primary drainage basin and the intrathoracic lymph node group are secondary.2
In 2017, the first TNM classification of TET was announced in the 8thedition of the AJCC Cancer Staging Manual, based on proposals made through a collaboration between IASLC and ITMIG.3 A new N category was presented based on the lymph node drainage pattern found in anatomic studies and international databases. Prominent nodes defined by anatomic studies are included as regional nodes in the lymph node map (Table 1).2 In addition, the IASLC lymph node map of lung cancer and AAO-HNS/ASHNS node map were referenced to define boundaries. This new N category classifies the node involvement into three groups according to a region-based system: N0, N1 (anterior region: anterior mediastinal and anterior cervical nodes), and N2 (deep region: middle mediastinal and deep cervical nodes) (Fig. 1). However, this classification is limited by the fact that the amount of data included was too limited to determine statistical significance.2,4,5
Although the first official N category has been published, controversy still remains over the lymph node involvement in TET. The prognosis with nodal metastasis is clearly poor, but the clinical significance of the criterion dividing the current N1, and N2 groups is uncertain. Moreover, the treatment strategy according to each stage is not yet fully defined. ITMIG recommends removal of anterior mediastinal nodes at the time of resection for thymoma.6 This fits into the generally accepted definition of an extended thymectomy which includes anterior mediastinal nodes. For locally advanced thymomas (Masaoka stage III or IVA) and thymic carcinoma, a systematic removal of intrathoracic nodes is encouraged (i.e., those corresponding to the deep region). However, for minimally invasive surgery, which is currently in widespread use, the extent and level of lymph node removal should be discussed further. It also remains to be determined whether different treatment strategies should be adopted according to the histological classification of thymomas, as well as whether it is appropriate to apply the same staging for the different TET pathological entities (i.e. thymoma, thymic carcinoma, and thymic neuroendocrine tumor). Therefore, the current official staging system will play a major role in settling these debates through collection from appropriate databases under uniform definitions. Further research is needed to establish the relevance of the node map, the prognostic role of nodal involvement, and the clinical implications of node dissection.
Reference
1. Kondo K, Monden Y. Lymphogenous and hematogenous metastasis of thymic epithelial tumors. Ann Thorac Surg. 2003;76(6):1859–64
2. Bhora FY, Chen DJ, Detterbeck FC, et al. The ITMIG/IASLC Thymic Epithelial Tumors Staging Project: A Proposed Lymph Node Map for Thymic Epithelial Tumors in the Forthcoming 8th Edition of the TNM Classification of Malignant Tumors. J Thorac Oncol. 2014;9(9):S88–S96.
3. Amin MB, Edge SB, Greene FL, et al, eds. AJCC Cancer Staging Manual. 8th ed. New York:Springer; 2017
4. Detterbeck FC, Stratton K, Giroux D, et al. The IASLC/ITMIG Thymic Epithelial Tumors Staging Project: Proposal for an Evidence-Based Stage Classification System for the Forthcoming (8th) Edition of the TNM Classification of Malignant Tumors. J Thorac Oncol.2014;9(9):S65–S72.
5. Kondo K, Van Schil P, Detterbeck FC, et al. The IASLC/ITMIG Thymic Epithelial Tumors Staging Project: proposals for the N and M components for the forthcoming (8th) edition of the TNM classification of malignant tumors. J Thorac Oncol. 2014;9(9 Suppl 2):S81–7.
6. Toker A, Sonett J, Zielinski M, et al. Standard Terms, Definitions, and Policies for Minimally Invasive Resection of Thymoma. J Thorac Oncol. 2011;6(7):S1739–42.
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OA10 - Sophisticated TNM Staging System for Lung Cancer (ID 136)
- Event: WCLC 2019
- Type: Oral Session
- Track: Staging
- Presentations: 1
- Now Available
- Moderators:Ke-Neng Chen, Pedro Lopez De Castro
- Coordinates: 9/09/2019, 14:00 - 15:30, Toronto (1985)
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OA10.02 - Recommended Change for N Descriptor Proposed by the IASLC: A Validation Study from a Single-Center Experience (Now Available) (ID 2117)
14:00 - 15:30 | Author(s): Jhingook Kim
- Abstract
- Presentation
Background
The International Association for the Study of Lung Cancer (IASLC) recently proposed changes for N descriptor based on the location and number of involved lymph node stations. The aim of our study was to evaluate the discriminatory ability and prognostic performance of the proposed N descriptor in a large independent non-small cell lung cancer (NSCLC) cohort.
Method
IASLC proposals include: a classification of N descriptor by combining the present nodal categories and number of involved lymph node stations into: N0; single-station N1 (N1a); multiple-stations N1 (N1b); single-station N2 without N1 involvement (N2a1); single-station N2 with N1 involvement (N2a2); multiple-stations N2 (N2b) and N3. A total of 1128 patients who underwent major pulmonary resection for pathologic N1 or N2 NSCLC between 2004 and 2014 were analyzed in this study. survival analysis was performed using Cox proportional hazard model to assess the prognostic significance of the N descriptor.
Result
From 2004 to 2014, 7437 patients were operated on for non-small-cell lung carcinoma (NSCLC). Among those, patients who underwent preoperative treatment for stage IIIA-N2 NSCLC were excluded (N=-698, 9.4%). Patients who were confirmed as pathologic N1 (N=676) or N2 (N=452) after surgery were included in this study. Invasive mediastinal staging (EBUS or mediastinoscopy) was done in 614 patients (54.4%). After surgery, adjuvant treatments were performed in 901 patients (81.7%). The mean total number of dissected lymph node was 25.7 ± 11.0, and the mean number of involved (metastatic) lymph node was 3.0 ± 3.2. The 5-year overall survival rate was 64.7 % in N1a, 57.1% in N1b, 68.0% in N2a1, 50.1% in N2a2, and 46.7% in N2b. Based on our study about the overall survival and recurrence-free survival, N2a1 is not clearly divided into N1a and N1b is not clearly divided with N2a2.
Conclusion
Based on the proposed N stage classification by combining the LN station number with the proposed anatomic location in IASLC, all 5 groups were not clearly identified. According to our analysis, it would be better to classify similar prognostic group as 3 or 4 group to divide the group. The new N classifications should be considered for future revisions of TNM staging system for lung cancer.
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P1.18 - Treatment of Locoregional Disease - NSCLC (ID 190)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.18-24 - Neoadjuvant Therapy versus Upfront Surgery for NSCLC Patients with Clinically Suspected Subaortic or Paraaortic Lymph Nodes (ID 2568)
09:45 - 18:00 | Author(s): Jhingook Kim
- Abstract
Background
Subaortic lymph nodes (#LN5) and para-aortic lymph nodes (#LN6) cannot be accessed by routine mediastinoscopy and E(B)US-FNA but need additional invasive surgical staging methods such as VATS or anterior mediastinotomy. Therefore, a considerable number of patients with suspected #LN5 or #LN6 receive multimodal treatment or, upfront surgery based on imaging staging only. We investigated survival outcomes of each therapeutic strategy.
Method
An institutional lung cancer database of consecutive patients between 2007 and 2016 (N=134) was reviewed retrospectively. Eligible patients had pathologically confirmed non-small cell lung cancer with clinically suspected #LN5 or #LN6 involvement by CT or PET-CT without clinical or pathological evidence of other N2 station involvement. Excluded are those with involvement of other N2 stations, unexpected N2, low grade malignancy, and prior history of cancer. Patients in group 1 received neoadjuvant therapy followed by surgery (n=68) and those in group 2 underwent upfront surgery (n=66).
Result
Group 1 consisted of patients with clinically suspected (n=39, 57%), and biopsy-proven #LN5 or #LN6 (n=29, 43%) by VATS (n=19), anterior mediastinotomy (n=6), or EUS-FNA (n=4). They received preoperative chemoradiation (n=62, 91%) and the rest received chemotherapy (n=6, 9%). Nodal down-staging was occurred in 36 (53%) patients whereas persistent N2 in 32 (47%). On the contrary, group 2 consisted of patients with clinically suspected #LN5 or 6 (n=66). After surgery, 30 (45%) patients were confirmed to have pathologic N0 or N1. The rest 36 (55%) patients were confirmed pathologic N2, and 29 (81%) of them received adjuvant therapy: chemoradiation in 23, and chemotherapy in 6. Overall survival rate at 5-year (5YOS) were 50.5% in group 1 versus 58.9% in group 2 (p=0.55); recurrence-free survival at 5-year (5YRFS) was 42.2% versus 46.7% (p=0.98), respectively. In subgroup, the 5YOS were 44.6% in pathologic N2 in group 2, which were similar to persistent N2 (52.8%, p=0.6), down-staged (49.2%, p=0.89), or biopsy-proven N2 (57.8%, p=0.54) in group 1. The 5YRFS were 26.7% in pathologic N2 in group 2, which were similar to persistent N2 (30.3%, p=0.89) and biopsy-proven N2 (43.9%, p=0.15), but lower than down-staged (53%, p=0.03) in group 1.
Conclusion
Upfront surgery or omission of invasive mediastinal staging for #LN5 or 6 may not compromise survival outcomes. Each therapeutic strategy is effective in terms of oncologic outcomes.
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P2.05 - Interventional Diagnostic/Pulmonology (ID 168)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Interventional Diagnostics/Pulmonology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.05-13 - Impact of Diffusing Capacity for Postoperative Pulmonary Complications in Patients Without Obstructive Pulmonary Disease (ID 2314)
10:15 - 18:15 | Author(s): Jhingook Kim
- Abstract
Background
This study evaluated the impact of diffusing capacity of the lungs for carbon monoxide (DLco) on postoperative pulmonary complications (PPCs) after lung resection in patients without obstructive pulmonary disease
Method
We retrospectively reviewed non-small cell lung cancer patients undergoing anatomical lung resection without induction treatment between 2015 and 2016. Of these, 1233 patients without obstructive pulmonary disease were included in the study. We considered the following PPCs as study outcomes: pneumonia, acute respiratory distress syndrome (ARDS), significant atelectasis, empyema, bronchopleural fistula, prolonged air leakage and pneumothorax. The independent effects of DLco on PPCs were evaluated using multivariate logistic regression. Models were adjusted for age, sex, smoking status, comorbidity, histology and type of surgery.
Result
Twenty three percentage of patients showed the decrement of pred % of DLco less than 80. A total of 104 patients (8.4%) developed at least one PPC. More PPCs were occurred in the patients with impaired DLco (6.2% vs 15.7%, p<0.001). In multivariable-adjusted analyses, risk of PPC in patients with impaired DLco was more than 2 times [the adjusted odds ratio (aOR)=2.44 (1.58,3.77)] compared to those in patients with preserved DLco. Also, with every 10% decreasing in % pred DLco, the risk of developing PPC was gradually increased. [DLco ≥ 80 vs. 70≤DLco<80, aOR=2.07 (1.22, 3.49); 60≤DLco<70, aOR=2.79 (1.45, 5.36); DLco<60, aOR=4.69 (1.72, 12.75), p<0.001]
Conclusion
Patients with impaired DLco had more risk of PPCs after lung resection even without airflow obstruction. Assessment of DLco is necessary for the prediction of PPCs in lung resection surgery for NSCLC.
