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S. Shiono
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OA19 - Translational Research in Early Stage NSCLC (ID 402)
- Event: WCLC 2016
- Type: Oral Session
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:G. Heller, G. Goss
- Coordinates: 12/07/2016, 11:00 - 12:30, Schubert 3
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OA19.07 - Difference of Postoperative Survival Due to the Type of EGFR Gene Mutation in Surgically Resected Lung Adenocarcinomas (ID 4726)
12:05 - 12:15 | Author(s): S. Shiono
- Abstract
- Presentation
Background:
Epidermal growth factor receptor (EGFR) gene mutation is a robust prognostic factor in patients with advanced lung adenocarcinomas. Recently, on the other hand, there are some reports proposing the difference of survival due to the type of EGFR mutation. In this study, we analyzed the difference of postoperative survivals between two most common mutations, that is, exon 19 deletions (DEL) and exon21 L858R (PM), using multi-institutional data of patients with surgically resected lung adenocarcinomas.
Methods:
We retrospectively collected 1,063 consecutive patients who underwent surgical resections for lung adenocarcinoma between 2005 and 2012 in five institutions, and who were examined their EGFR mutation status. The patients with minor EGFR mutations were excluded. We compared their clinicopathological characteristics among DEL, PM, and wild type (WT) group. We also analyzed postoperative recurrence-free survival (RFS) and overall survival (OS) according to the type of EGFR mutation.
Results:
The number of patients with DEL, PM, and WT was 218 (20.5%), 301 (28.3%), and 544 (51.2%) respectively, and their median follow-up period was 47.6 months. The patients of PM were older and earlier pathological staged than those with DEL, whereas no significant difference was observed among other clinicopathological factors. Five-year RFS and OS of DEL, PM, and WT were 67.3/85.9%, 76.4/88.6%, 59.2/71.5%, respectively, and both survivals of each mutant were significantly better than those of WT. Regarding the difference between DEL and PM, RFS curve of DEL was significantly worse than that of PM (p = 0.027), but OS curves of both mutant weren’t significantly different. (p = 0.16). In multivariate analysis, the type of EGFR mutation (DEL vs PM) was not an independent factor both in RFS and OS.
Conclusion:
Exon 21 L858R might be a more favorable recurrence-risk factor than exon 19 deletions in patients with surgically resected lung adenocarcinomas.
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P3.01 - Poster Session with Presenters Present (ID 469)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.01-002 - The Clinical Impact of Spread through Air Spaces (STAS) in Surgically Resected pStage I Lung Squamous Cell Carcinoma (ID 3904)
14:30 - 14:30 | Author(s): S. Shiono
- Abstract
Background:
Spread through air spaces (STAS) is identified as a newly invasive pattern in lung adenocarcinoma. It contributes to the significantly increased recurrence rate for patients with small adenocarcinoma. But the presence of STAS and its clinical impact has remained uncertain in squamous cell carcinoma (SQCC.) The purpose of this study is to analyze whether STAS happens in surgically resected pathological Stage I (pStage I) lung SQCC.
Methods:
We retrospectively reviewed 141 pStage I patients of SQCC (Female/Male, 13/128; Smoker/Never smoker, 135/6; pStage IA/IB, 93/48). Tumor STAS was defined as tumor cells within the air spaces in the lung parenchyma beyond the edge of the main tumor. Statistical analyses were conducted to investigate the relationship between its presence and the clinicopathological background factors, including the clinical outcome.
Results:
STAS was identified in 23 of 141 patients (16.3%) with limited (7.1%) and extensive (9.2%) feature, respectively. Both disease-free survival (DFS) and overall survival (OS) were significantly worse in the patients with STAS in comparison with the patients without STAS (5-year DFS, 35.1% vs. 65.6%, p<0.01; 5-year OS, 41.7% vs. 71.2%, p<0.01, respectively). In multivariate analyses adjusting for sex, year, smoking history and pStage, the presence of STAS was found to be an independent predictive factor of both DFS (HR=3.154, 95%CI: 1.592-6.249; p=0.001) and OS (HR=3.07, 95%CI: 1.595-5.911; p=0.0008). The 141 tumors were divided into patients who underwent limited resection and those who underwent standard resection in order to examine whether the surgical procedure affected the DFS and OS of patients with and without STAS. In the standard resection group, both 5-year DFS and 5-year OS were worse in the patients with STAS in comparison with the patients without STAS (44.1% vs.68.3%, p=0.03; 53.8% vs. 72.3%, p=0.048, respectively). In the limited resection group, both 5-year DFS and 5-year OS were worse in the patients with STAS in comparison with the patients without STAS (0% vs.57.5%, p=0.001; 0% vs. 66.4%, p=0.001, respectively).
Conclusion:
STAS happened in lung SQCC and was found to be an independent predictive factor of both DFS and OS. Both 5-year DFS and 5-year OS were worse in the patients with STAS regardless of surgical procedure.
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P3.04 - Poster Session with Presenters Present (ID 474)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Surgery
- Presentations: 3
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.04-005 - Evaluation of Noninvasive Lung Adenocarcinoma Using 3D-CT Imaging (ID 5150)
14:30 - 14:30 | Author(s): S. Shiono
- Abstract
Background:
Computed tomography (CT) can reveal small pulmonary nodules of ≤ 2 cm. Nodules with a consolidation-to-tumor ratio (C/T ratio) ≤ 0.5 on thin-section chest CT are generally recognized as noninvasive lung cancer. However, estimations of C/T ratios on CT may vary between observers. Three-dimensional (3D) imaging can provide more accurate information than 2D-CT for distinguishing noninvasive lung cancers. The aims of this study were to determine the 3D-C/T ratios of small pulmonary nodules on 3D-CT images and explore the relationship between 3D-C/T ratios and the histopathological invasiveness of lung cancers.
Methods:
This was a retrospective analysis of a total of 82 patients with lung adenocarcinoma who had a ground glass opacity (GGO) on CT and underwent surgery from April 2013 to March 2016. We constructed 3D tumor images and calculated the 3D-C/T ratios of GGOs using a 3D analysis system (SYNAPSE VINCENT[®]; Fuji Film). The relationships between 3D-C/T ratio and histopathological indicators of invasiveness were evaluated. Pathological noninvasive cancer was defined as follows: no lymph node metastasis (n[-]), no lymphatic invasion (ly[-]), no vascular invasion (v[-]), and no pleural invasion (pl[-]).
Results:
10 (12%) of 82 tumors were found to be invasive by histopathology, with the following positive indicators: n(+) in 5 (6%), ly(+) in 3 (4%), v(+) in 2 (2%), and pl(+) in 6 (7%). The median 3D-C/T ratio was 0.39. The mean 3D-C/T ratios by pathological findings were as follows: n(+) 0.74 vs n(-) 0.35 (p < 0.01), ly(+) 0.74 vs ly(-) 0.36 (p = 0.06), v(+) 0.58 vs v(-) 0.37 (p = 0.27), and pl(+) 0.57 vs pl(-) 0.35 (p = 0.04). The 3D-C/T ratios of invasive cancer vs noninvasive cancer were 0.71 and 0.34, respectively (p < 0.01). By ROC curve analysis, a 3D-C/T ratio cutoff value of 0.43 provided a sensitivity and specificity of 100% and 61%, respectively, for the diagnosis of invasive cancer.
Conclusion:
This was a pilot study that evaluated the usefulness of 3D-CT imaging for assessing the invasiveness of small lung adenocarcinomas. A prospective observational study of 3D-CT imaging for diagnosing invasive lung adenocarcinoma is warranted.
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P3.04-014 - Surgical Outcome and Diagnosis of cN1 Lung Cancers after Introducing PET/CT (ID 4692)
14:30 - 14:30 | Author(s): S. Shiono
- Abstract
Background:
The mainstay of therapy for cN1 lung cancer is surgery; however, the pre-operative radiologic assessment of cN1 lung cancer remains challenging and it has been reported that approximately 30% of cN1 cases are pathologically pN2. The aim of this study was to determine the pre-operative evaluation and outcomes of patients with cN1 lung cancer.
Methods:
A prospectively-collected institutional database was used. In the current study, cN1 was defined as hilar lymph nodes 1 cm in the short axis on CT and standardized uptake values > 2.5 on PET/CT. Between January 2004 and March 2016, a total of 1082 lung cancer patients underwent surgery. After excluding patients who received pre-operative treatment or had an incomplete resection, 86 (7.9%) cN1 patients were retrospectively studied. We compared the characteristics and prognosis of cN1 patients with 783 (72.4%) cN0 patients. Because the patients with cN1pN2 were underestimated, we investigated the frequency and predictive factors for cN1pN2.
Results:
The median follow-up time was 48 months. Compared with cN0 patients, the proportion of males, smokers, and squamous cell carcinomas was higher in cN1 patients (p < 0.01). In addition, cN1 patients had elevated CEA levels and increased SUV on PET/CT. Lymph node metastases were noted as follows: cN1pN0, 32 (37.2%); cN1pN1, 37 (43.0%); cN1pN2, 17 (19.8%); cN0pN0, 701 (89.5%); cN0pN1, 50 (6.4%); and cN0pN2, 32 (4.1%). Lymph node metastases were underestimated in 99 cN0 and cN1 patients (11.4%). The incidence of pN2 was higher in cN1 cases (p < 0.01). The 5-year survival for cN1 cases was 51.9%. The 5-year overall survival of the underestimated cases was as follows: cN1pN2, 18.0%; cN0pN1, 63.7%; and cN0pN2, 39.5%. Among the underestimated cases, survival of cN1pN2 patients was significantly reduced (p < 0.01). In addition, univariate analysis showed that smoking (p = 0.04) and peripheral tumors (p < 0.01) were predictive factors for cN1pN2. Multivariate analysis confirmed that cN1 peripheral tumors tended to be pN2. In 44 cases with peripheral tumors and cN1, 14 (31.8%) were pN2.
Conclusion:
PET/CT can decrease the number of underestimated patients with cN1 lung cancer. Amongst cN1 lung cancer patients, pN2 existed in approximately 20% of cases. Especially, since around 30% of peripheral tumors with cN1 were pN2, invasive staging would be warranted before the treatment.
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P3.04-021 - Readmission Rate is Not Increased with Shortened Hospital Stay after Lung Cancer Surgery (ID 4844)
14:30 - 14:30 | Author(s): S. Shiono
- Abstract
Background:
In health economics, keeping costs down is a great concern. Early discharge has been enabled after surgery for lung cancer by clinical pathways, preoperative rehabilitation and the introduction of Enhanced Recovery After Surgery (ERAS) protocols. However, even if a shortened hospitalization has a benefit for hospital management, it has not been clarified whether it has a good influence on the patient’s recovery after surgery. In this study, we examined the relationship between a shortened hospitalization and patient recovery after lung cancer surgery; in particular, we focused on the rate of rehospitalization within 30 days after discharge.
Methods:
We investigated the postoperative course of 318 patients who underwent lung cancer surgery from April 2013 through February 2016. Based on the execution of ERAS, we divided the patients into a shortened group (ERAS performed) and a usual group (ERAS not performed), and compared the rates of rehospitalization and postoperative complications.
Results:
There were 202 men and 116 women, and their median age was 71 years. The shortened group contained 90 cases, and the usual group contained 228 cases. Limited resections were carried out in 19 of 90 patients in the shortened group and in 72 of 228 patients in the usual group (p=0.06). The median duration of postoperative hospitalization was 4 days in the shortened group and 6 days in the usual group (p < 0.001). The incidence of complications was 23.3% (21/90) in the shortened group and 28.0% (64/228) in the usual group (p = 0.38). The rate of rehospitalization within 30 days after surgery was 6.7% (6/90) in the shortened group vs 4.4% (10/228) in the usual group (p = 0.40). In addition, one case in each group required rehospitalization within one week after discharge; thus, there was no significant difference in incidence between groups.
Conclusion:
Health economics is different throughout the world. The timing of discharge depends on the discretion of each institution. Although this study was carried out in a non-randomized setting, we revealed that a shortened hospital stay did not increase the postoperative complication and readmission rates of patients who underwent surgery for lung cancer. Shortening of hospital stay by the introduction of ERAS and other challenges could provide a benefit for patient and hospital management.
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SC24 - Management of Indeterminate Pulmonary Nodules (ID 348)
- Event: WCLC 2016
- Type: Science Session
- Track: Pulmonology
- Presentations: 1
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SC24.01 - Risk Assessment in the Management of Pulmonary Nodules (ID 6700)
11:00 - 11:20 | Author(s): S. Shiono
- Abstract
- Presentation
Abstract:
Background Solitary pulmonary nodules are seen on approximately 0.1% of all chest X-ray films.[1] High-resolution computed tomography (HRCT), which is used in lung cancer screening programs, can detect pulmonary nodules that are smaller than those detected by conventional radiography. The radiological diagnosis and treatment of these small pulmonary nodules are now the focus of lung cancer research. The timely detection of lung cancers is essential for successful treatment. The guidelines and recommendations for the management of pulmonary nodules include follow up, nonsurgical biopsy, or surgery; and are based on the size of the nodule, and ground glass opacity (GGO) ratio or size of the solid component.[2-4] Diagnosis The diagnosis of a pulmonary nodule is frequently problematic. The management of pulmonary nodules is based on their characteristics. When a pulmonary nodule is monitored by CT, the important features include not only its size but also its density. According to the guidelines of the American College of Chest Physicians, solid nodules measuring > 8 mm in diameter need further examination.[3] The Fleischner Society for Thoracic Imaging and Diagnosis uses a cutoff diameter of 5 mm for decision making for subsolid nodules.[2] It should be kept in mind that solid nodules that are suspicious for lung cancer are frequently invasive. A subsolid nodule can be classified as a pure ground glass nodule (GGN) or part-solid nodule. Subsolid nodules grow slowly and may develop a solid component. The HRCT findings of early lung adenocarcinomas were significantly correlated with the histopathologic findings of the resected specimens.[5] In the evaluation of subsolid nodules, the features indicating noninvasive lung adenocarcinoma include tumor disappearance rate, diameter of consolidation, and GGO ratio.[6] However, even HRCT cannot accurately assess the areas of solid opacities or GGO, and results might vary between investigators. In the upcoming 8[th] TNM classification, the Lung Cancer Staging Project of the International Association for the Study of Lung Cancer showed that the solid part of a nodule on HRCT represents the clinical T factor, and that measurement of the solid part is essential for lung cancer staging.[5] Positron emission tomography (PET)-CT has a clearly established role in lung cancer clinical practice. Based on the pretest probability, PET-CT should be used for patients with a solid, indeterminate nodule > 8 mm in size.[3,4] For adenocarcinomas in situ (AIS) and minimally invasive adenocarcinomas (MIA) of the lung that show solid opacities on HRCT, the preoperative PET-CT and thin-section CT findings together can provide information on the aggressiveness of the tumor. Our study group found that these modalities used together could detect aggressive lung cancers in clinical stage IA (Fig. 1).[7] However, since PET-CT can show false-negative results for slow-growing and low-grade lung malignancies, we think that HRCT is the best modality for identifying indolent lung cancers. Transthoracic biopsy, bronchoscopy, or surgery is used for obtaining specimens for histopathological diagnosis. The definitive diagnosis of small pulmonary nodules, especially GGO-dominant nodules, is challenging. The diagnostic yields of percutaneous CT-guided fine needle aspiration biopsy for GGO-dominant and solid-dominant lesions were 51.2% and 75.6%, respectively (p = 0.018).[9] The diagnostic yield of GGO-dominant lesions < 10 mm was 35.2%. Since invasive biopsy is not without risk, a histopathological diagnosis should be limited to nonsurgical candidates. For cases with high likelihood of lung cancer, a surgical biopsy followed by lung resection might be warranted. Although surgery might be performed on patients with benign nodules, it does provide the definitive diagnosis. If surgery is performed after careful preoperative assessment, the surgical mortality is very low, and the surgical risk may be acceptable. Treatment While lobectomy is the standard procedure for lung cancers, sublobar resection, meaning segmentectomy or wedge resection, might be justified for patients with noninvasive small lung cancers. However, to date, which procedure, sublobar resection or lobectomy, provides a better outcome remains unclear in these cases, since prospective randomized control trials are ongoing (JCOG0802/WJOG4607L[8] and CALGB140503). One of the concerns in sublobar resection is recurrence at the surgical margin (Fig. 2). Recurrence at the surgical margin might be accounted for by tumor cells spreading via air spaces.[10] Accurate intraoperative cytology and adequate surgical margins have been reported to be important for preventing recurrence at the surgical margin. Another concern is lymph node metastasis. In a prospective radiological study for clinical stage IA lung cancer, 47 of 545 (8.6%) patients had lymph node metastasis.[6] Sublobar resection, especially wedge resection, dose not allow evaluation of lymph nodes for metastatic disease. Conclusion HRCT findings play an important role in discriminating the biological behaviors of pulmonary nodules. The definitive diagnosis by HRCT can be difficult, and the combination of HRCT and PET-CT might be beneficial. Randomized control trials should clarify the role of sublobar resection in treating patients with noninvasive lung cancer. Figure 1. Figure 1 Figure 2. Figure 2 References 1. Ost D, Fein AM, Feinsilver SH. The solitary pulmonary nodule. N Engl J Med 2003;348:2535-42. 2. Naidich D, Bankier AA, MacMahon H, Schaefer-Prokop CM, Pistolesi M, Goo JM, et al. Recommendations for the management of subsolid pulmonary nodules detected at CT: A statement from the Fleischner Society. Radiology 2013;266:304-17. 3. Gould MK, Donington J, Lunch WR, Mazzone PJ, Midthun DE, Naidich DP, et al. Evaluation of individuals with pulmonary nodules: when is it lung cancer? Diagnosis and management of lung cancer 3[rd] ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013;143:e93s-120s. 4. National Comprehensive Cancer Network. Guidelines for surveillance following therapy for non-small cell lung cancer Ver 4.2016. Available at: www.nccn.com. 5. Travis WD, Asamura H, Bankier AA, Beaseley MB, Detterbeck F, Flieder DB, et al. The IASLC Lung Cancer Staging Project: Proposals for coding T categories for subsolid nodules and assessment of tumor size in part-solid tumors in the forthcoming eighth edition of the TNM classification of lung cancer. J Thorac Oncol 2016;11:1204-23. 6. Suzuki K, Koike T, Asakawa T, Kusumot M, Asamura H, Nagai K, et al. A prospective radiological study of thin-section computed tomography to predict pathological noninvasiveness in peripheral clinical IA lung cancer (Japan Clinical Oncology Group 0201). J Thorac Oncol 2011;6:751-6. 7. Shiono S, Yanagawa N, Abiko M, Sato T. Detection of non-aggressive stage IA lung cancer using chest computed tomography and positron emission tomography/computed tomography. Interact Cardiovasc Thorac Surg. 2014;21:637-43. 8. Nakamura K, Saji H, Nakajima R, Okada M, Asamura H, Shibata T et al. A phase III randomized trial of lobectomy versus limited resection for smallsized peripheral non-small cell lung cancer (JCOG0802/WJOG4607L). Jpn J Clin Oncol 2010;40:271–4. 9. Shimizu K, Ikeda N, Tsuboi M, Hirano T, Kato H. Percutaneous CT-guided fine needle aspiration for lung cancer smaller than 2 cm and revealed by ground-glass opacity at CT. Lung Cancer 2006;51:173-9. 10. Shiono S, Yanagawa N. Spread through air spaces is a predictive factor of recurrence and a prognostic factor in stage I lung adenocarcinoma. Interact Cardiovasc Thorac Surg. 2016 Jun 26. pii: ivw211.
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