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Young Tae Kim
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MA 06 - Lung Cancer Biology I (ID 660)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Biology/Pathology
- Presentations: 1
- Moderators:N. Motoi, Keith M Kerr
- Coordinates: 10/16/2017, 15:45 - 17:30, Room 501
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MA 06.04 - Development of Next-Generation Sequencing Based Cancer Panel and Its Clinical Implications in Lung Cancer (ID 9003)
15:45 - 17:30 | Author(s): Young Tae Kim
- Abstract
- Presentation
Background:
To search actionable driver mutations, various cancer panels using next-generation target sequencing technologies are rapidly developed and adopted in the treatment of lung cancer. We developed a new cancer panel to detect 313 coding gene mutations, 30 fusion and 3 exon-skipping genes including either known or potential target genes. Performance of the panel was tested on our archived lung cancer tissue bank samples.
Method:
Two hundreds and two samples were tested (male 118, female 84, median age 63 (30-84) years). Histologic cell types were mainly adenocarcinoma (adenocarcinoma 158, squamous cell 25, large cell 6, sarcomatous 3, small cell 1, and mixed cell types 9).
Result:
With our cancer panel, 139 samples (68.8%) were identified to have mutations including 88 EGFR, 23 KRAS, 8 MET mutations, 7 ALK, 6 RET, 3 ROS1, 6 rare fusions (PTEN, BRAF, MET, CBFB, EWSR1, BCR), and 18 CNV alterations. Medical records revealed that traditional single-site tests including Sanger sequencing of EGFR, KRAS mutations and either immunohistochemical stain or FISH test for ALK or RET fusion had been performed in 191 patients. Among those patients, we identified 102 pathogenic mutations (53.4%) including 80 EGFR, 14 KRAS mutations, 6 ALK, and 2 RET fusions. Conventional single-site test results matched with that of cancer panel in 139 samples (72.8%). Cancer panel detected additional mutations in 48 samples (25.1%; 38 from the single-site test negative and 10 from positive samples). In two samples, the results showed discrepancy while in the other two, mutations were detected only in single-site test. However additional tests revealed cancer panel results to be correct. Excluding 4 patients with M1 stage, 198 patients’ long-term survival were analyzed according to the mutational status. In Cox’s proportional hazard model, presence of EGFR mutation was the only prognostic marker that predicted long-term survival along with clinical variables such as age, pT-stage, and pN-stage.
Conclusion:
In our results, we confirmed superior accuracy of our cancer panel compared to the traditional single-site tests. Furthermore, the new cancer panel discovered novel mutations, of which significance requires future functional investigation and potential development of new target agents.
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P1.13 - Radiology/Staging/Screening (ID 699)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.13-011d - Risk of Pleural Recurrence After Percutaneous Transthoracic Needle Biopsy in Stage I Non-Small Cell Lung Cancer: A Large Center Experience (ID 10019)
09:30 - 16:00 | Author(s): Young Tae Kim
- Abstract
Background:
To determine whether percutaneous transthoracic needle biopsy (PTNB) increase the risk of (a) isolated pleural recurrence and (b) concomitant pleural seeding and metastasis in stage I non-small cell lung cancer (NSCLC).
Method:
In this institutional review board-approved retrospective study, medical records of total of 830 consecutive patients with stage I NSCLC who underwent curative resection between 2004 and 2010 were reviewed. Median duration of follow-up was 1843 days (interquartile range, 1006-2734). Multiple logistic regression analyses were performed to identify risk factors of pleural recurrence.
Result:
Of 830 patients, 540 patients (65.1%) underwent PTNB before surgery, while 290 patients (34.9%) underwent non-PTNB procedures including bronchoscopic biopsy or exploratory thoracotomy. An isolated pleural recurrence was found in 26 patients (3.1%, [95%CI, 2.1-4.6%]) (20 in PTNB group, 6 in non-PTNB group). There was no significant association between PTNB and isolated pleural recurrence (P=0.197). Concomitant pleural recurrence occurred in 42 patients (5.1%, [95%CI, 3.8-6.8%]) (34 in PTNB group, and 8 in non-PTNB group). Subpleural location (p=0.007), tumor consistency (solid, part-solid, nonsolid) (p=0.046), PTNB (p=0.027), pathologic T stage (p<0.001), microscopic pleural invasion (p<0.001) and microscopic lymphatic invasion (p=0.019) were associated with concomitant pleural recurrence. The most significant factor of pleural recurrence was only microscopic pleural invasion (Odds Ratio, 4.28; 95% CI, 2.20 to 8.29) (P<0.001) on multiple logistic analysis. Among 540 patients undergoing PTNB, transfissural approach did not have significant association with pleural recurrence (P=0.220), while the most sole significant factor was microscopic pleural invasion (Odds Ratio, 3.40; 95% CI, 1.54 to 7.51) (P=0.002).
Conclusion:
PTNB did not increase the risk of isolated or concomitant pleural recurrence in early stage NSCLC. Higher incidence of concomitant pleural seeding in PTNB group was presumably attributed to peripheral lung cancer, potentially accompanying microscopic pleural invasion.
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P2.02 - Biology/Pathology (ID 616)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.02-059 - Genomic Mutation Patterns Detected with Cancer Panel Can Predict Postoperative Prognosis in Clinical Stage I Adenocarcinoma (ID 9024)
09:30 - 16:00 | Author(s): Young Tae Kim
- Abstract
Background:
Recent development of cancer panels based on target sequencing technology can detect genomic mutations which are useful to choose target agents for advanced stage lung cancer. We investigated if the result of panel-detected mutation patterns can predict prognosis of early stage lung cancer.
Method:
Among the 350 cases whose postoperative tissues were tested with cancer panel, we selected 338 cases excluding 9 recurrent tumors and 3 cases who received neo-adjuvant treatment. The mean age was 60.7+/-11.4 years (Male 197, female 141). Adenocarcinoma (293) was the most common followed by squamous cell (26), larger cell (5) and others (14). We classified the mutations patterns into three group; SN group (n=126) where a single nucleotide mutation (EGFR, KRAS, NRAS, CTNNB1) was detected, SV group (n=117) where a structural variation (SV) (indel, fusion, splicing) was present, and NO group (n=95) where no significant mutation was found. We investigated the association of mutation patterns with various clinical variables and their impact on the prognosis.
Result:
The mutation was rarely found in squamous cell cancer and the SVs were more frequently found in never-smoked patients. The 5 year overall survival was 73.8+/-3.1% and the 5 year disease-free survival was 46.3+/-3.2%. The disease-free survival of SV group was inferior to that of SN group (p=0.029). When we selected only adenocarcinoma patients and stratified them by clinical stage, the SV group showed poorer disease-free survival to that of SN group in clinical stage I (p=0.017). However, when stratified by pathologic stage, there was no difference. When we investigated discrepancies between clinical and pathologic stages, up-stage from clinical stage I to pathologic N2 was more frequently found in SV group. Figure 1
Conclusion:
Our observation suggests that if structural variations are detected in clinical stage I adenocarcinoma, more aggressive mediastinal lymph node evaluation is mandatory and a different treatment strategy may be investigated.
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P3.09 - Mesothelioma (ID 725)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Mesothelioma
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.09-008 - Role of Surgery in the Multimodality Treatment of Malignant Pleural Mesothelioma (ID 9827)
09:30 - 16:00 | Author(s): Young Tae Kim
- Abstract
Background:
The treatment of malignant pleural mesothelioma is challenging and multimodality treatment including surgery is recommended, although there are debates about the role of surgery. We analyzed the outcomes of surgery in MPM in the context of multimodality treatment focusing on extrapleural pneumonectomy (EPP).
Method:
Total 29 patients had pathologically proven malignant pleural mesothelioma from April 1998 to July 2015 were retrospectively reviewed. The overall survival rates of surgery group (any type of curative surgical treatment) and medical group (medical treatment only) were compared. Prognoses of EPP subgroup and medical group were also compared
Result:
Among 29 patients, 16 patients underwent surgery for curative intent, 12 patients underwent definitive chemotherapy, and one patient refused treatment. Epithelioid type (n=11, 68.8%) was the most common pathologic type in surgery group. Only 4 (33.3%) patients of medical group were epithelioid type. Half of surgery group patients were clinical stage I/II and there was no clinical stage I/II in medical group. Pulmonary functions of both group were not significantly different. In surgery group, 11 patients underwent EPP and one patient underwent pleurectomy/decortication. Four patients misdiagnosed as lung cancer preoperatively underwent lobectomy with chest wall resection. There were no postoperative 30-day nor in-hospital mortality. The median follow-up duration was 10.6 (1.0-78) months. The median survival time (MST) was 10.6 months, and the 3-year overall survival rate (3yr-OS) was 25 %. There was no statistical difference in overall survival between surgery and medical group (MST = 10.6 vs. 8.4 months, 3yr-OS = 31.1 % vs 16.7%, p=0.47) EPP subgroup (MST = 13.3 months, 3yr-OS = 45.5 %) also showed statistically similar survival with medical group (p=0.23). (Fig 1)Figure 1
Conclusion:
Multimodality treatment incorporating surgery was not superior compared with medical treatment in MPM. EPP with multimodality treatment also failed to show meaningful superior prognosis compared with non-surgical treatment in MPM.
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P3.16 - Surgery (ID 732)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Surgery
- Presentations: 2
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.16-013 - Prognostic Effect of EGFR Gene Mutation for Recurrence in Completely Resected Lung Adenocarcinoma (ID 9798)
09:30 - 16:00 | Author(s): Young Tae Kim
- Abstract
Background:
Prognostic effect of EGFR gene mutation in disease progression which affecting recurrence pattern and recurrence dynamics after complete resection of lung adenocarcinoma has not been well established. We investigated the relationship between EGFR gene mutation and recurrence dynamics in completely resected lung adenocarcinoma.
Method:
We retrospectively review 527 patients who underwent curative surgery for lung adenocarcinoma from January 2006 to December 2009. Demographics, clinic-pathologic data, and prognosis data were obtained by review of medical records. The EGFR gene mutation was analyzed by nested polymerase chain reaction followed by bidirectional direct sequencing in case of recurrence. Adenocarcinoma patients who experienced recurrence and had data of EGFR mutation were included in the analysis. Pathologic stage IV were excluded. Patients were divided into M group (mutant EFGR gene) or W group (wild-type EGFR gene). Sites of recurrence and disease-free times (DFT) of two groups were compared.
Result:
Median follow-up duration was 72 months. Overall 5-year survival rate was 80.1%. Recurrence was detected in 153 patients and 5-year disease-free rate was 58.2%. EGFR gene sequencing was performed in 118 (77.1%) patients. There were 38 (32.2%) loco-regional recurrences and 80 (67.8%) distant metastases. Any mutation of EGFR gene was detected in 66 (59.9%) patients (M group) and 52 patients had wild-type EGFR gene (W group). Sites of recurrence in M group were loco-regional in 25 (37.9%) and distant metastasis in 41 (62.1%) patients. Site of recurrence in W group were loco-regional in 13 (25%) and distant metastasis in 39 (75%) patients. Sites of recurrence of both groups were not significantly different. (p=0.14) Median DFT of two groups were significantly different (M = 20.3 months vs W = 15.1 months, p=0.039). Visceral pleura invasion (p=0.045) and EGFR gene mutation (p=0.039) were prognostic factor for DFT in univariable analysis. In multivariable analysis, EGFR gene mutation was the only prognostic factor for DFT. (HR – 0.676, 95% CI – 0.371 ~ 0.986, p=0.042) No significant factor for DFT was identified in loco-regional recurrence. EGFR gene mutation, however, was the only significant prognostic factor for DFT of distant metastasis (HR – 0.561, 95% CI – 0.356 ~ 0.885, p=0.013) in univariable and multivariable analysis.
Conclusion:
In recurrent lung adenocarcinoma, EGFR gene mutation group showed longer DFT than wild-type EGFR group. EGFR gene mutation is a prognostic factor in lung adenocarcinoma and slow-growing nature of adenocarcinoma with EGFR gene mutation should be considered in surveillance after surgery.
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P3.16-026 - Clinical Implication of Occult Lymph Node Metastasis in the Remaining Lobes After Lobectomy in Non-small Cell Lung Cancer (ID 8993)
09:30 - 16:00 | Presenting Author(s): Young Tae Kim
- Abstract
Background:
The presence of lymph node metastasis in the ipsilateral remaining lobe and its clinical implication after lobectomy have not been evaluated or discussed.
Method:
We sampled station 12 node of the remaining lobe during the surgery and completely dissected all the segmental nodes if cancer cell metastasis was either confirmed or suspicious. We retrospectively reviewed such patients and analyzed clinicopathologic characteristics.
Result:
Between 2010 and 2016, we found 20 cases where a complete lymph node dissections of the remaining lobes were performed (male 19, female 1, median age 55 (29-71) years). The location of primary cancer was predominantly in the RLL (RLL 17, RML 2 and LLL 1) and the surgical procedure performed were mainly bi-lobectomy (RLL and RML 11, RLL 6, RML 2, LLL 1). The site of lymph nodes in the other lobe were predominantly located in the RUL (RUL 18, RUL and RML 1, LUL 1). Clinical N-stages were N0 in 6, N1 in 9, and N2 in 15 patients. Preoperative CT and PET-CT failed to predict presence of metastasis of other lobe lymph nodes. The pathologic N-stages were N0 in 3, N1 in 4 and N2 in 13. The metastasis in the other lobe was present in 14 patients whereas, 6 were negative. Twelve out of 14 patients with positive lymph node in the other lobe had mediastinal lymph node metastasis (85.7%). The overall survival rates were 94.4% at one year and 74.4% at 2 years. However, as many as 8 patients (40%) recurred at the time of the study. Figure 1
Conclusion:
In conclusion, we found some patients possessed occult metastasis in N1 nodes of the remaining lobe especially in lower lobe cancers and the majority had occult N2 metastasis as well. The prognostic and clinical implication of knowing lymph node status of the remaining lobe needs further investigations.
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PC 01 - 1-2. What is the Role of Local Therapy in Non-CNS Oligometastatic NSCLC? (ID 592)
- Event: WCLC 2017
- Type: Pros & Cons
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:David L Ball, H. Date
- Coordinates: 10/16/2017, 16:45 - 17:30, Room 502
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PC 01.04 - There is a Role of Surgery in Non-CNS Oligometastatic Disease (ID 7825)
16:45 - 17:30 | Presenting Author(s): Young Tae Kim
- Abstract
- Presentation
Abstract:
For certain extra-pulmonary malignancies, such as colorectal cancer or sarcomas, the existence of curable oligometastatic disease state has been well established. Oligometastasis is a state of stage IV disease associated with limited spread of disease at the time of diagnosis. This condition may reflect a more indolent phenotype than that associated with more widespread disease at presentation. Recently, it becomes more clear that the patients with Stage IV NSCLC are heterogenous and hence, some patients have high disease burden whereas others have isolated metastatic lesions. In the 8th TNM staging system, M-stage was reclassified into M1a, M1b, M1c, and the patients with M1b may represents the oligometastatic status of NSCLC. It has been demonstrated that the predominant pattern of failure in patients with oligometastasis treated with the first-line systemic chemotherapy was mainly a local failure, the fact which leads an idea that the local treatment may improve cure rates in such patients. The incidence of oligometastasis in NSCLC has been reported 7-26% of NSCLC [1, 2], with the major sites of metastases being bone, brain, adrenal glands and liver. In general, the successful treatment of patients with oligometastasis requires the ability to eradicate the primary site, the ability to image all sites of metastatic disease, the ability to ablate all metastatic sites, and having effective systemic therapy to eradicate undetected micrometastatic disease. Recently, routine use of improved diagnostic imaging tools such as PET-CT or Brain MRI, can better detect latent metastases in patients who would otherwise have been thought to have a localized disease, and hence, the diagnosis of “true” oligometastatic disease may be increasing [3]. Development of local treatment modalities such as minimally invasive surgery (MIS) or stereotactic radiotherapy (SABR) enabled effective local abrasion of the metastatic sites without major morbidities. Above all, rapid development of effective molecular target agents and immune check point agents in the treatment of NSCLC are encouraging to reconsider surgery for the treatment of oligometastatic NSCLC patients. Most evidence of treatment effect of local treatment for oligometastasis derives from the survival data from retrospective patients groups. For brain metastases, 5-year survival rates have been reported 6.6-35% and adrenal gland metastases showed similar results (5-year survival rates 12-40%). In a well-designed propensity score matching study suggested an improvement in survival favoring local abrasive therapy, but definite conclusions on the efficacy of local therapy for the treatment of extra-cranial oligometastatic NSCLC could not be reached [4]. A meta-analysis which included 49 studies, suggested overall median overall survival of 19 months after local ablative treatment (5.9-52 months)[5]. Most recent study by Gomez and colleagues demonstrated a progression free survival benefit favoring local consolidative therapy [6]. Hopefully, ongoing prospective trials may provide more strong evidence of the effect of local ablative therapy for oligometastasis in near future. Despite many reports that support local treatment for oligometastasis, the lack of control data in almost all reports is a problematic issue. Since local treatment for the oligometastasis is only performed in selected patients with relatively indolent disease, there is often no actual denominator for the entire group of patients who developed metastasis [7]. Thus, determining the survival advantage of ablative local treatment of oligometastasis compared to palliative systemic therapy is difficult because the majority of existing data are with a substantial degree of selection bias. In the other aspect, however, we have learned that the patient selection is critical for the application of local treatment on the oligometastasis. In general, local treatment is indicated in metastatic NSCLC patients with favorable prognostic factors including absence of mediastinal lymph node metastasis, small number of metastases, complete control of primary lesion, meta-chronous metastasis, and good performance status of the patients. Although there are relatively large numbers of papers on the brain or adrenal metastases, the reports of extra-cranial or extra-adrenal metastases are rare. In a meta-analysis, the 5 year overall survival rates of extra-cranial / extra-adrenal metastasis was 50% and the prognosis was mainly influenced by lymph node metastasis status[ 8]. First used in the literature in 2012 [9], the concept of oligoprogressive disease has been rapidly adopted. It can be best described in patients with tumors harboring actionable mutations who are treated with molecular targeted therapies. Initially, the response rate is great but the duration of response is relatively short, with resistance to therapy generally emerging within a year of start of treatment as a result of various genetic mechanisms. Not uncommonly, disease progression during molecular targeted therapy occurs at a limited number of anatomic sites. Recently, several studies reported improved progression free survival and overall survival in either intra-cranial or extra-cranial oligopregressive diseases by applying local abrasive therapy on those acquired resistant oligoprogressive diseases and by resuming target agents [10]. Furthermore, the combination of immune check point agents and SABR on primary tumor and/or metastatic sites may be promising for treating oligometastatic NSCLC, due to a possible abscopal effect. In conclusion, although current evidence of local treatment of oligometastases is limited in NSCLC, with aid of recent diagnostic tools by which more stringent patient selection is possible, local ablative treatment of metastatic lesions can lead improved survival of patients with oligometastasis in conjunction with molecular target agents or immune check point agents. 1. Albain KS, Crowley JJ, LeBlanc M, et al. Survival determinants in extensive-stage non-small-cell lung cancer: the Southwest Oncology Group experience. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 1991;9:1618-1626. 2. Parikh RB, Cronin AM, Kozono DE, et al. Definitive primary therapy in patients presenting with oligometastatic non-small cell lung cancer. International journal of radiation oncology, biology, physics 2014;89:880-887. 3. Tonnies S, Tonnies M, Kollmeier J, et al. Impact of preoperative 18F-FDG PET/CT on survival of resected mono-metastatic non-small cell lung cancer. Lung cancer (Amsterdam, Netherlands) 2016;93:28-34. 4. Sheu T, Heymach JV, Swisher SG, et al. Propensity score-matched analysis of comprehensive local therapy for oligometastatic non-small cell lung cancer that did not progress after front-line chemotherapy. International journal of radiation oncology, biology, physics 2014;90:850-857. 5. Ashworth A, Rodrigues G, Boldt G, et al. Is there an oligometastatic state in non-small cell lung cancer? A systematic review of the literature. Lung cancer (Amsterdam, Netherlands) 2013;82:197-203. 6. Gomez DR, Blumenschein GR, Jr., Lee JJ, et al. Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy: a multicentre, randomised, controlled, phase 2 study. The Lancet Oncology 2016;17:1672-1682. 7. Fiorentino F, Treasure T. Pulmonary metastasectomy: a call for better data collection, presentation and analysis. Future oncology (London, England) 2015;11:19-23. 8. Salah S, Tanvetyanon T, Abbasi S. Metastatectomy for extra-cranial extra-adrenal non-small cell lung cancer solitary metastases: systematic review and analysis of reported cases. Lung cancer (Amsterdam, Netherlands) 2012;75:9-14. 9. Weickhardt AJ, Scheier B, Burke JM, et al. Local ablative therapy of oligoprogressive disease prolongs disease control by tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 2012;7:1807-1814. 10. Iyengar P, Kavanagh BD, Wardak Z, et al. Phase II trial of stereotactic body radiation therapy combined with erlotinib for patients with limited but progressive metastatic non-small-cell lung cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2014;32:3824-3830.
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