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Jun Nakajima
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P1.17 - Treatment of Early Stage/Localized Disease (ID 188)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.17-38 - Does Use of Epidural Anesthesia Affects Survival of Resectable NSCLC? Analysis from a Japanese Nationwide Database (Now Available) (ID 1718)
09:45 - 18:00 | Author(s): Jun Nakajima
- Abstract
Background
Several studies have suggested that epidural anesthesia may increase postoperative survival by reducing the cancer recurrence rate. The rationale for this phenomenon is that epidural anesthesia decreases the surgical stress response by suppressing circulating glucocorticoids, catecholamines and inflammatory mediators, and thus reduces transient immunosuppression during cancer surgery. Moreover, epidural anesthesia can reduce the use of opioids, which are generally thought to be immunosuppressive (suppresion of NK cell cytotoxicity, promotion of VEGF-dependent angiogenesis, and activation of EGF pathway). The topic is still controversial, and there are no previous studies related to lung cancer and thoracic epidural anesthesia. Our study aim is to reveal the probable impact of epidural anesthesia during radical lung cancer surgery on long-term postoperative survival and cancer recurrence.
Method
We used Japanese Diagnosis Procedure Combination database, the national databese which covers 55% of all acute-care hospitalizations in Japan. We retrospectively reviewed the medical records of 34,694 patients who received lobectomy or pneumonectomy for curative intent for non-small cell lung cancer, between July 2010 and March 2016. Propensity score matching and stabilized inverse probability of treatment weighting (IPTW) was used to adjust the patient background. Recurrence-free survival was assessed using Kaplan-Meier curves.
Result
Among the patients, 27,810 received epidural anesthesia during lung cancer surgery and 6,884 underwent the surgery without epidural anesthesia. Video assisted thoracoscopic surgery (VATS) was performed in about 23,682 (81.2%) in epidural anesthesia patients, and 6,180 (85.5%) in non-epidural anesthesia patients (<0.001). According to the Kaplan-Meier curve after baseline adjusting by using propensity score matching and inverse weighting, there was no stastically significant difference in recurrence-free survival between the groups (p=0.89). Stratification according to the cancer stage revealed no significant difference in recurrence-free survival depending on the type of anesthesia administered at each stage.
Conclusion
Oncological outcome after lung cancer surgery was not affected by the use of epidural anesthesia.
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P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.04-55 - Tumor Spread Through Air Spaces Is Associated with the Non-Inflamed Immune Microenvironment in Lung Squamous Cell Carcinoma (ID 2529)
10:15 - 18:15 | Author(s): Jun Nakajima
- Abstract
Background
Tumor spread through air spaces (STAS) is reportedly a poor prognostic factor in non-small cell lung cancer. However, little is known about the molecular background and tumor microenvironment associated with STAS. This study assessed the relationship between STAS and tumor microenvironment in lung squamous cell carcinoma using next generation sequencing data.
Method
RNA-sequencing and whole-exome sequencing were performed in 20 surgically resected lung squamous cell carcinoma cases. Pathological specimens were reviewed to determine the existence of STAS. Somatic mutations, gene expression and gene set enrichment were analyzed and compared between STAS positive and negative tumors.
Result
Among 20 patients, nine were pathological stage I, six stage II and five stage III. In all, eight tumors were positive for STAS and 12 were negative. While STAS was not associated with tumor size, all N2 tumors were positive for STAS. Tumor mutational burden was not associated with STAS.
Hierarchical clustering using the single sample Gene Set Enrichment Analysis score of 4872 immunologic signature gene sets revealed two clusters (Figure 1). Cluster 1 revealed lower expression of immune-related genes, forming a cluster of non-inflamed (cold) tumors. The cluster of non-inflamed tumors showed a tendency to higher STAS positivity (Cluster 1, 67%; Cluster 2, 18%; p=0.065).
Next, we performed Gene Set Enrichment Analysis between STAS positive and negative tumors. Using 50 Hallmark gene sets in the Molecular Signatures Database, gene sets of allograft rejection, IL2-STAT5 signaling, inflammatory response and complement were found to have a significantly lower expression in STAS positive tumors (q <0.05).
We further investigated the expression of each immune-related gene and compared them between STAS positive and negative tumors, which showed that PD-L1 gene expression was significantly lower in STAS positive tumors (p=0.023).
Conclusion
STAS positivity was associated with the non-inflamed tumor-immune microenvironment in lung squamous cell carcinoma. Our findings might partly explain the aggressive behavior of STAS positive tumors. Since the efficacy of immunotherapy might differ between STAS positive and negative tumors, further investigation of immunological and molecular aspects of STAS positive tumors is needed.
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P2.15 - Thymoma/Other Thoracic Malignancies (ID 185)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Thymoma/Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.15-04 - Impact of Prognostic Nutritional Index on Long-Term Outcomes After Surgery for Pulmonary Metastasis from Colorectal Cancer (ID 2013)
10:15 - 18:15 | Author(s): Jun Nakajima
- Abstract
Background
A prognostic nutritional index (PNI), calculated using serum albumin levels and peripheral lymphocyte counts, has been reported as a predictor of prognosis of various cancers. The aim of this study was to investigate the impact of a PNI on postoperative prognosis of lung resection for pulmonary metastasis from colorectal cancer.
Method
Retrospective review of patients who underwent curative surgical resection for pulmonary metastasis from colorectal cancer (01/2008-12/2015). Exclusion criteria: missing data. Preoperative serum albumin (Alb) and peripheral lymphocyte counts were measured within 1 month just before the initial lung surgery. We calculated PNI as follows: PNI = serum albumin levels (g/dl) × 10 + total lymphocyte count (per mm3) × 0.005. We used the median value as the optimal cut-off value for PNI (47.5) and divided patients into two groups. We evaluated overall survival using propensity score matching.
Result
A total of 158 patients underwent 187 lung resections for pulmonary metastasis in this study. One hundred eighteen patients were eligible. Low PNI was significantly associated with older age (P<0.001), wedge resection (P=0.041), open approach (P=0.045) and colon origin (P=0.041). In the non-matched analysis, overall survival was significantly better in high PNI group that low PNI group (77.5% vs 54.0% at 5 years; HR 2.21; 95% CI 1.11-4.39; P=0.024). After propensity score matching accounting for sex, age, surgical procedure, surgical approach and site of origin, there were no significant differences in background between both groups. In the matched analysis, overall survival was significantly better in high PNI group than low PNI group (78.2% vs 43.2% at 5 years; HR 3.46; 95% CI 1.33-8.96; P=0.010).
Conclusion
Preoperative PNI may be a useful biomarker to predict postoperative prognosis of pulmonary metastasis from colorectal cancer.
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P2.17 - Treatment of Early Stage/Localized Disease (ID 189)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.17-22 - Retrospective Analysis of Spread Through Air Spaces and Other Features in Patients with Stage IA Adenocarcinoma by the 8<sup>th</sup> TNM Classification (ID 2246)
10:15 - 18:15 | Author(s): Jun Nakajima
- Abstract
Background
We have recently demonstrated that the presence of the Spread Through Air Spaces (STAS) increased the risk of recurrence after resection for small lung adenocarcinoma (ADC). Currently, the TNM classification of lung cancer was revised and T-factor was changed to be basically determined by its invasive size. The purpose of this study is to examine the impact of presence of STAS in stage IA ADC according to the 8th TNM classification.
Method
Patients with pleural invasion, lymph node metastasis, distant metastasis, and neoadjuvant therapy were excluded. All available tumor slides from patients with surgically resected solitary lung ADC (2000-2015) were reviewed. Patients with stage IA ADC according to the 8th TNM classification were collected. Overall survival (OS) and recurrence-free probability (RFP) were estimated using the Kaplan-Meier method. Propensity score was generated from age, operation year, gender, lymphatic invasion, vascular invasion, the presence of solid component ≥5%, the presence of micropapillary component ≥5%, limited resection, and invasive size. One-by-one nearest neighbor matching by the presence of STAS was adapted to reduce the bias.
Result
In all, 295 patients met study criteria with median age of 68. Male gender comprised 48.8% (n=144), lymphatic invasion positive 4.7% (n=14), and vascular invasion positive 14.9% (n=44). By T-factor (7th edition), 216 (73.2%) were T1a, 53 (18.0%) T1b, 23 (7.8%) T2a, 2 (0.7%) T2b, and 1 (0.3%) T3. By T-factor (8th edition), 100 (33.9%) were T1mi, 111 (37.6%) T1a, 70 (23.7%) T1b, and 14 (4.7%) T1c. By operation method, 241 (81.7%) underwent lobectomy, 15 (5.1%) segmentectomy, and 39 (13.2%) partial resection. Adjuvant chemotherapy was given in 2.7% (n=8) of patients. STAS was seen in 22.7% (n=67) of patients. Five-year OS was 95.3% for STAS-negative and 91.1% for STAS-positive (p=0.0262), and the 5-year RFS was 96.8% and 83.9%, respectively (p=0.0003). In matched cohorts, each cohort included 48 patients and the 5-year OS was 95.0% for STAS-negative and 90.6% for STAS-positive (p=0.3201). The 5-year RFS was 93.3% and 91.3%, respectively (p=0.9363).
Conclusion
Patients with pathologic stage IA ADC with STAS, according to the 8th TNM classification, had a worse prognosis in unmatched cohorts even though adenocarcinoma in situ was excluded. Because of various confounding factors, the propensity score matching revealed the presence of STAS as a non-significant prognostic factor in our matched cohorts. This study was a retrospective analysis, and a prospective study is needed regarding the indication of limited resection.
