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Yue Yang
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MA27 - Novel Drugs and PDX Models (ID 931)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 13:30 - 15:00, Room 206 BD
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MA27.11 - Genomic Sequencing and Editing Revealed the GRM8 Signaling Pathway as Potential Therapeutic Targets of Squamous Cell Lung Cancer (ID 12246)
14:40 - 14:45 | Author(s): Yue Yang
- Abstract
Background
Lung cancer is the leading cause of cancer death worldwide. Squamous cell carcinoma (LUSC) is one subtype of non-small-cell lung cancer (NSCLC), and ranks at the second of lung cancer incidence. Although targeting receptor tyrosine kinases (RTKs) had already brought better clinical outcomes to NSCLC patients carrying corresponding mutations, very few mutated targets had been identified in LUSC subtype, probably because of the lack of mutation hotspot and functional validation of mutated candidate.
a9ded1e5ce5d75814730bb4caaf49419 Method
The whole exome (WES) and whole genome (WGS) sequencing and CRISPR-Cas9 genome editing techniques were integrated to explore and validate novel targeting candidates from 11 groups of LUSC primary tumors and corresponding patient-derived xenografts (PDXs).
4c3880bb027f159e801041b1021e88e8 Result
The WES data revealed high homologies on the mutation types and signatures among primary tumor and different passages of PDX tumor samples. Nine significant genes carrying single nucleotide variations (SNVs) and three carrying copy number variations (CNVs) were identified as targeting candidates from WES and WGS data based on the mutation frequency and driver gene analysis. The oncogenic or tumor suppressor functions of those 12 candidates were validated through CRISPR-Cas9 loss-of-function system in tumor cells derived from PDX tissues carrying corresponding mutations and in normal bronchial epithelial cell-line. Furthermore, using CRISPRa transcriptionally activating system, one novel candidate, Metabotropic glutamate receptor 8 (GRM8) was elucidated to promote the survival of LUSC tumor cell through inhibiting cAMP pathway and activating MAPK pathway.
8eea62084ca7e541d918e823422bd82e Conclusion
The components of GRM8 signaling pathway could serve as potential targets of squamous cell lung cancer.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P1.05 - Interventional Diagnostics/Pulmonology (Not CME Accredited Session) (ID 937)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.05-23 - Evaluation of the 8th Edition of the TNM Classification for Lung Cancer at a Single Institution (ID 13730)
16:45 - 18:00 | Author(s): Yue Yang
- Abstract
Background
The 7th edition has been used more than10 y ears and has proven reliable, but various problems had been indicated.The latest (8th) edition of the lung cancer staging classification was published in 2017. The purpose of this retrospective study is to make a external validation to the 8th edition of the lung cancer staging system.
a9ded1e5ce5d75814730bb4caaf49419 Method
Subjects included 3,229 patients who underwent pulmonary resection for primary non-small cell lung cancer.Survival characteristics were compared using the 7th and 8th editions of the staging system.
4c3880bb027f159e801041b1021e88e8 Result
8eea62084ca7e541d918e823422bd82e Conclusion
According to the 7th edition, there was no significant difference between pStages IIB and IIIA(P = 0.650), however, according to the 8th edition, there were significant differences between each adjacent stage group. Moreover, to the T descriptor(tumor size), which got most emphasis in the 8th edition, there were significant differences between each adjacent pT classification, either according to the 7th edition or the 8th edition.
The UICC 8th edition staging system is considered valid for non-small cell lung cancer patients and appears to be superior in defining different prognostic groups than the 7th edition.
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P1.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 948)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 2
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.16-23 - Long-Term Survival Analysis of Surgery in Potential Stereotactic Ablative Radiotherapy Candidates of Non-Small Cell Lung Cancer (ID 14436)
16:45 - 18:00 | Author(s): Yue Yang
- Abstract
Background
The aims of this study were to evaluate the long-term survival outcomes and strengthen the primacy of surgery in potential stereotactic body radiotherapy candidates.
a9ded1e5ce5d75814730bb4caaf49419 Method
A total of 541 patients with clinical stage I peripheral non-small cell lung cancer from January 2005 to December 2014 were enrolled in the current study. All patients who were potential stereotactic ablative radiotherapy candidates underwent lobectomy and systematic lymph node dissection including level 13 and 14 without preoperative therapy. According to the recommendation of the 8th edition of TNM stage, combined with our own experience, we divided the N stage into N1a (only level 13-14 positive), N1b (level 10-12 positive), N2a1 (skip single N2), N2a2 (single N2 with N1) and N2b (multiple N2). Survival curves were estimated by the Kaplan–Meier method.
4c3880bb027f159e801041b1021e88e8 Result
Among all patients, 25.0% had occult lymph node involvement, 12.8% were N1 and 12.2% were N2. Among 32 T1a patients only 1 case (3.0%) patients had N1a positive without other N positive. In 104 cases of T1b, the positive rates of N1a, N1b, N2a1, N2a2 and N2b were 0.8%, 5.9%, 0.8%, 2.5% and 1.7%, respectively. Among the 86 patients with T1c, the positive rate of each station was 5.4%, 11.5%, 3.8%, 8.5%, and 4.6%, respectively. Of the 184 patients with T2a, N1 accounted for 14.6% , and N2 accounted for 11.5%. The 3-year, 5-year and 10-year disease free survival (DFS) of all 541 clinical stage I patients were 82.8%, 74.0%, 64.7%, and the overall survival (OS) were 91.3%, 85.4% and 77.0% respectively. The 3-year, 5-year and 10-year DFS of postoperatively pathological stage I patients were 90.0%, 81.0%, 72.5%, and the OS were 94.4%, 91.1% and 85.0%, respectively.
8eea62084ca7e541d918e823422bd82e ConclusionT ／N category
N0
N1a
N1b
N2a1
N2a2
N2b
1a
32(97.0%)
1（3.0%）
0
0
0
0
1b
104(88.1%)
1（0.8%）
7（5.9%）
1（0.8%）
3（2.5%）
2（1.7%）
1c
86(66.2%)
7（5.4%）
15（11.5%）
5（3.8%）
11（8.5%）
6（4.6%）
2a
184(70.8%)
13（5.0%）
25（9.6%）
8（3.1%）
12（4.6%）
18（6.9%）
In view of the high rate of lymph node metastasis in clinical stage I lung cancer, surgical resection is still the preferred treatment.
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P1.16-61 - Intermittent Chest Tube Clamping Shortens Chest Tube Duration After Lung Cancer Surgery: An Interim Analysis of Randomized Clinical Trial (ID 11919)
16:45 - 18:00 | Author(s): Yue Yang
- Abstract
Background
Postoperative pleural drainage markedly influences the length of hospital stay and the financial costs of medical care. Our previous retrospective study proved the safety and effectiveness of chest tube clamping in the term of shortening chest tube duration. This study aims to determine if intermittent chest tube clamping could decrease chest tube duration and total drainage volume after lung cancer surgery in randomized clinical trial. This trial is registered with ClinicalTrials.gov (NCT03379350).
a9ded1e5ce5d75814730bb4caaf49419 Method
All the patients were managed with gravity drainage (water seal only, without suction) during the first 12–24 h (depending on the time of surgery completion) after surgery. Once a radiograph confirmed re-expansion of the lung on the morning of the POD1 and no air leak was detected, patients were randomly assigned to intermittent chest tube clamping as study arm or traditional chest tube management as control arm. Patients in control arm were unchangeably managed with gravity drainage. In clamping arm, the chest tube would be clamped, and the nurses would check the patient every 6 h. If the patient had no problems with compliance, the clamp was removed for 30 minutes in the morning to record the drainage volume every 24 h. The criterion for chest tube removal was drainage volume <250 mL in 24 h.
4c3880bb027f159e801041b1021e88e8 Result
Seven-two consecutive patients with operable lung cancer treated using lobectomy were randomized, all of them were eligible and evaluable. Thirty-seven and 35 patients were randomly assigned to clamping arm and control arm, respectively. There were no significant differences between two groups in terms of demographics, such of age, gender and the percentage of neoadjuvant treatment. Analyses were performed to compare drainage duration between two groups. Chest tube drainage duration was significantly shorter in clamping group than in control group (2.3±0.5 days vs. 2.7±0.9 days, p = 0.011). Total drainage volume was significantly less in clamping group than in control group (411.0±183.1 ml vs. 553.7±333.6 ml, p = 0.030). Only one patient in clamping group underwent thoracocentesis after chest tube removal due to chylothorax, which was probably caused by excess high-fat diet. No pyrexia relevant to chest tube clamping occurred. There was some degree of improvement on plasma albumin declination at discharge in clamping group over control group (7.5±2.5 g/L vs. 8.6±3.6 g/L, p = 0.119), but without a significant statistical difference.
8eea62084ca7e541d918e823422bd82e Conclusion
Intermittent postoperative chest tube clamping decreases chest tube duration and total drainage volume while maintaining patient safety. Further investigation is warranted.
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P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.01-67 - The Prognostic Analysis of Lung Cancer Patients with Occult Malignant Pleural Disease at Thoracotomy (ID 13270)
16:45 - 18:00 | Author(s): Yue Yang
- Abstract
Background
This study aims to determine the clinicopathological prognostic factors for occult malignant pleural disease (MPD) first detected at thoracotomy in patients with non-small cell lung cancer (NSCLC) and assess the outcome of surgical intervention.
a9ded1e5ce5d75814730bb4caaf49419 Method
A total of 120 patients with MPD at thoracotomy from January 2006 to October 2016 were evaluated. Survival curves were estimated by the Kaplan–Meier method, and Cox regression analysis was performed to validate the selected risk factors. Clinical and pathologic parameters were balanced by propensity score matching when assessing surgical intervention.
4c3880bb027f159e801041b1021e88e8 Result
With a median follow-up of 34 months, the 5-year overall survival of 120 patients was 28.0%. Multivariate analyses showed male (p=0.044), advanced T stages (p<0.001), advanced N stages (p=0.02), pleural invasion in image (p=0.005), pleural effusion (p=0.027), surgical intervention (p=0.008) and EGFR status (p=0.003) were independent predictors of survival. The 5-year survival rate and median survival time (MST) for 21 patients with lobectomy were 71.6% and undefined, compared with 25.6% and 40.0 months in 46 patients with sublobectomy. When 53 patients only subjected to open-close surgery, their 5-year survival rate and MST were 23.4% and 30.2 months. After propensity score matching, both 21 patients were included in lobectomy group and sublobectomy /open-close group. The overall survival of lobectomy group was better than the control group (p=0.046).
8eea62084ca7e541d918e823422bd82e Conclusion
The prognosis of MPD patients first detected at thoracotomy was affected by gender, stage, pleural invasion, pleural effusion, surgical intervention and EGFR status. Lobectomy maybe confers better survival compared with sublobectomy and exploratory thoracotomy.
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P2.09 - Pathology (Not CME Accredited Session) (ID 958)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.09-20 - Minor Components of Solid Pattern is a Significant Poor Prognostic Factor in Pathological Stage I Lung Adenocarcinoma (ID 12606)
16:45 - 18:00 | Author(s): Yue Yang
- Abstract
Background
Lung adenocarcinoma with solid pattern (SP) predominant subtype was reported to be associated with poor prognosis. However, whether minor components of SP predict poor prognosis remains unknown. The present study aimed to clarify the influence of different proportion of SP on the prognosis of pathological stage I lung adenocarcinoma.
a9ded1e5ce5d75814730bb4caaf49419 Method
Tumors of 341 patients who underwent radical resections were classified according to the IASLC/ATS/ERS classification. Patient contained less than 5% SP in the tumor was determined SP negative and SP positive patients were reclassified to SP minor (5-50%) and SP major (≥50%) groups. Survival analyses were used to determine the association between each group with patient survival.
4c3880bb027f159e801041b1021e88e8 Result
50 (15%) patients were SP positive and compared to SP negative group they showed a significantly lower five-year disease-free survival (DFS) rate (85.2 vs. 55.4%, p<0.001) and overall survival (OS) rate (97.3 vs. 66.7%, p<0.001). Multivariate analysis for DFS showed that SP positive, lepidic pattern negative, KRAS mutation and pathological stage IB were independent poor prognostic factors. In addition, higher proportions (<5%, 5–50% and ≥50%) of SP components were associated with a poorer prognosis (85.2, 76.6, and 40.0% of 5y-DFS, respectively; p<0.001).
8eea62084ca7e541d918e823422bd82e Conclusion
Solid pattern is a significant poor prognostic factor and an indicator of early recurrence after radical resection for early stage lung adenocarcinoma. Patients with tumors harboring a higher ratio of SP components have worse survival.
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P2.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 965)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.16-45 - Should Patients with Stage IB Non-Small Cell Lung Cancer Receive Adjuvant Chemotherapy? (ID 11211)
16:45 - 18:00 | Author(s): Yue Yang
- Abstract
Background
There’re much controversy over the necessity of adjuvant chemotherapy to stage IB non-small cell lung cancer (NSCLC) . The aim of this study is to compare the efficacy of platinum-based adjuvant chemotherapy for patients with stage IB NSCLC according to the 8th and 7th editions of the TNM staging system who underwent complete surgical resection and systemic mediastinal lymph node dissection.
a9ded1e5ce5d75814730bb4caaf49419 Method
Subjects were 569 patients who underwent pulmonary resection for primary NSCLC. Survival characteristics were compared using the 8th and 7th editions of the TNM classification.
4c3880bb027f159e801041b1021e88e8 Result
For patients in the observation and adjuvant groups, 5-year overall survival was 76.9% and 83.5%, respectively (p=0.044). In univariate analysis, lymphovascular invasion, TNM stage and performance status (PS) were risk factors for overall survival. In multivariate analysis, TNM stage (hazard ratio=5.808, 95% confidence interval 3.980-8.475, p<0.001), PS (hazard ratio=4.804, 95% confidence interval 3.113-7.413, p<0.001) and adjuvant chemotherapy (hazard ratio=1.565, 95% confidence interval 1.069-2.291, p=0.021) were risk factors for overall survival. Subset analysis showed that for patients with stage IB NSCLC, 5-year overall survival was 87.6% in the observation group (n=265) and 82.4% in the adjuvant group (p=0.021). For patients with stage IIA NSCLC, 5-year overall survival was 48.1% in the observation group and 87.7% in the adjuvant group (p<0.001). For patients with Eastern Cooperative Oncology Group (ECOG) 0, 5-year overall survival was 79.3% in the observation group and 91.6% in the adjuvant group(p=0.001). For patients with ECOG 1, 5-year overall survival was 58.6% in the observation group and 17.2% in the adjuvant group (p=0.021).
8eea62084ca7e541d918e823422bd82e Conclusion
For NSCLC patients with surgically treated, platinum-based adjuvant chemotherapy might result in worse survival than observation alone to stage IB but improve survival to stage IIA. Moreover, patients with good PS (ECOG 0) benefit fromadjuvant chemotherapy.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P3.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 982)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 3
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.16-34 - The Impact of Preoperative Exercise Therapy on the Surgical Outcomes of Patients with Lung Cancer and COPD: A Systematic Review and Meta-Analysis (ID 12034)
12:00 - 13:30 | Author(s): Yue Yang
- Abstract
Background
Although isolated studies have looked at the impact of preoperative exercise on patients with lung cancer and chronic obstructive pulmonary disease (COPD), a comprehensive meta-analysis of the available data has hitherto been lacking.
a9ded1e5ce5d75814730bb4caaf49419 Method
Articles were searched from PubMed, Embase, and Cochrane library, with the following criteria: lung cancer patients with or without COPD; undergoing resection; receiving preoperative exercise training. Key outcomes were analyzed using meta-analysis.
4c3880bb027f159e801041b1021e88e8 Result
Seven studies containing 404 participants were included. Patients receiving preoperative exercise training had a lower incidence of postoperative pulmonary complications (PPCs) (Odds Ratio (OR) 0.35, 95% Confidence Interval (CI) 0.21 to 0.59) and shorter length of hospital stay (Standard Mean Difference −1.02 days, 95% CI −1.31 to −0.74 days). Exceptionally, incidence of pneumonia remained unchanged. Patients with COPD could not obviously benefit from exercise training to reduce PPCs（OR 0.44, 95% CI 0.18 to 1.08）but still might achieve faster recovery. No significant difference in pulmonary function was observed between the two groups. However, 6-minutes walking distance and VO2 peak were significantly improved after exercise training.
8eea62084ca7e541d918e823422bd82e Conclusion
Preoperative exercise training might not reduce PPCs for COPD patients undergoing lung cancer resection, but still facilitate faster recovery. Muscle capacity was strengthened after rehabilitation, which emphasized the possible mechanism of the protocol design.
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P3.16-35 - Stair Climbing Exercise May Ameliorate Pulmonary Function Impairment in Patients at One Month After Lung Cancer Resection (ID 12136)
12:00 - 13:30 | Author(s): Yue Yang
- Abstract
Background
Surgical resection remains the primary treatment for patients with localized non-small cell lung cancer (NSCLC). Despite the possibility of a cure, lung resection is associated with an immediate pulmonary function impairment.
Stair-climbing test as a reliable indicator of pulmonary function, is often performed preoperatively to select patients. It also has been reported that stair-climbing yielding greater values of VO2 is a more stressful exercise than cycle ergometry. The benefits of this intervention in postoperative patients remain unclear. Thus, this study aimed to evaluate the effects of performance at the postoperative symptom-limited stair climbing exercise on pulmonary function.
a9ded1e5ce5d75814730bb4caaf49419 Method
We retrospectively analyzed 36 consecutive NSCLC patients undergoing video-assisted thoracoscopic surgery lobectomy and systematic mediastinal lymphadenectomy from November 2017 to January 2018. In the postoperative pulmonary rehabilitation program, all patients were suggested to perform symptom-limited stair climbing exercise in addition to routine physiotherapy (walking, incentive spirometry, breathing) from the first day after surgery. Patients were encouraged to climb gradually to the maximum number of floors at a pace of their own choice, and to stop in case of exhaustion, insufferable pain, limiting dyspnea or leg fatigue. A nursing professional was indispensable for the management of chest drains and supervision of any symptoms. Heart rate, pulse oxygen saturation were continuously measured using a portable pulse oximeter. Stair climbing exercise was performed at least twice a day during and after hospital stay. According to their performance of the exercise, patients could be divided into two groups. Stair climbing group completed the exercise training as planned, while routine physiotherapy group was reluctant to stair climbing exercise except for routine physiotherapy. Pulmonary functions were performed on all patients preoperatively and at one month postoperatively.
4c3880bb027f159e801041b1021e88e8 Result
Totally, 25 patients (15 in stair climbing group and 10 in routine physiotherapy group) were included in the final analysis. The average preoperative and postoperative FEV1 for patients in two groups were 2.69±0.83 L vs. 3.08±0.72 L (p=0.244) and 2.08±0.72 L vs. 2.23±0.60 L (p=0.592), respectively. The difference in FEV1 decline between stair climbing group and routine physiotherapy group was significant (0.61±0.26 L vs. 0.84 ± 0.23 L, p=0.032).
8eea62084ca7e541d918e823422bd82e Conclusion
This study suggested that symptom-limited stair climbing as a more stressful exercise performed postoperatively in patients may ameliorate pulmonary function impairment at one month after lung resection. Prospective randomized controlled trials are therefore warranted.
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P3.16-36 - Adjuvant Chemotherapy May Improve the Outcome of Patients with Non-Small-Cell Lung Cancer with Metastasis of Intrapulmonary Lymph Nodes. (ID 11759)
12:00 - 13:30 | Author(s): Yue Yang
- Abstract
Background
Survival benefit of adjuvant chemotherapy (AC) of patients with intrapulmonary lymph node (IPLN) metastasis (level 12–14) needs investigation. We evaluated the impact of AC on patients whose metastatic nodes were limited to intrapulmonary levels after systematic dissection of N1 nodes.
a9ded1e5ce5d75814730bb4caaf49419 Method
First, 155 consective cases of lung cancer confirmed as pathologic N1 were collected and evaluated. Patients received systematic dissection of N2 and N1 nodes. For patients with IPLN metastasis, survival outcomes were compared between those receiving AC and those not receiving AC.
4c3880bb027f159e801041b1021e88e8 Result
In this group, 112 cases (72.3%) had IPLN metastasis and 55 cases (35.5%) had N1 involvement limited to level 13–14 without further disease spread to higher levels. Patients with IPLN involvement had a better prognosis than that of patients with hilar–interlobar involvement. For the intrapulmonary N1 group (level 12–14-positive, level 10–11-negative or unknown, n = 112), no survival benefit was found between the AC group and non-AC group (5-year overall survival (54.6±1.6 vs. 50.4±2.4 months, p = 0.177, Figure 1A). However, 76 of 112 cases for whom harvesting of level-10 and level-11 nodes was done did not show cancer involvement in pathology reports (level 12–14-positive, level 10–11 both negative), oncologic outcome in this group was better for patients receiving AC than those not receiving AC (5-year OS: 57.3±1.5 vs. 47.1±3.2 months, p = 0.002, Figure 1B). Similarly, survival benefit of AC didn’t exist in patients with lymph node metastasis to level 13–14 (level 13–14-positive, 10-12-negative or unknown, n=55, Figure 1C), but was found in 38 patients with complete examination of N1 nodes (58.3±1.7 vs. 51.0±4.2 months, p = 0.048, Figure 1D).
8eea62084ca7e541d918e823422bd82e Conclusion
Oncologic outcome may be improved by AC for patients with involvement of N1 nodes limited to intrapulmonary levels after complete examination of N1 nodes.
6f8b794f3246b0c1e1780bb4d4d5dc53
