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Hisao Asamura
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EP1.18 - Treatment of Locoregional Disease - NSCLC (ID 208)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.18-16 - Surgery for Locally Advanced Lung Cancer Invading the Spine After Chemoradiotherapy (Now Available) (ID 2371)
08:00 - 18:00 | Author(s): Hisao Asamura
- Abstract
Background
Treatment for locally-advanced lung cancer invading the spine remains challenging, and multimodality treatment should be considered. The aim of this study was to clarify surgical outcomes following induction chemoradiotherapy (CRT) for lung cancer invading the spine following chemoradiotherapy.
Method
We retrospectively reviewed clinical and pathological data of locally-advanced lung cancer patients with vertebral invasion, in who we have performed total or partial vertebrectomy after induction CRT between 2011 and 2017.
Result
A total of 4 patients were extracted. All patients were diagnosed as cT4N0M0 disease based on chest computed tomography (CT) and positron emission tomography (PET)-CT, and vertebral invasion was evaluated by chest computed tomography (CT) and magnetic resonance imaging. The histologic type included adenocarcinoma in 3 patients and squamous cell carcinoma in one patient, respectively. Average dose of radiation was 50 Gy. Total vertebrectomy was performed in 3 patients and transverse-process resection in one patient. Average Median operation time and blood loss were 800 minutes and 878 ml, respectively. In all 4 cases, complete R0 resection was performed. There was no perioperative and in-hospital death, and complication occurred in one patient. Median follow-up period was 39 months (range, 16-63 months), and median overall survival time and relapse free survival time were 39 months (range, 16-63 months) and 29months (range, 7-63 months).
Conclusion
The current preliminary result indicated that lung cancer surgery combined with vertebrectomy after induction CRT was feasible. Although our series were small, this multimodal treatment strategy might be a option for cT4N0M0 lung cancer invading to the spine. Further study should be conducted to confirm the current result with a large sample size.
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IBS25 - Optimal GGO Management (Ticketed Session) (ID 56)
- Event: WCLC 2019
- Type: Interactive Breakfast Session
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/10/2019, 07:00 - 08:00, Melbourne (1991)
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IBS25.01 - Eastern Perspective (Now Available) (ID 3392)
07:00 - 08:00 | Presenting Author(s): Hisao Asamura
- Abstract
- Presentation
Abstract
The term “ground glass opacity (GGO)” is being used more often to describe the CT appearance of a focal, non-calcified lesion with a slight/moderate increase in CT density. Usually, GGO is characterized on high-resolution CT scan images with a slice thickness of 1-3mm. The CT appearance of GGO is characterized by “focal, transparent” lesion. First, GGO refers to the localized or focal lesion regardless of the multicentricity, and the diffuse ground glass appearance seen for interstitial pneumonitis should be excluded from this category. Second, GGO lesions is well-characterized by a slight/mild increase in CT density, which does not obscure preexisting lung structures such as blood vessels and bronchi. This apperance refers to the CT-transparency. When the shape of the pulmonary vessels in the nodules is not recognized in the nodule, the lesion is no longer considered GGO, and instead is called a “solid” lesion. GGO lesion can be either homogeneous or heterogeneous. The GGO lesions are classified according to the absence/presence of the solid part. In case the GGO lesions are homogeneous, and does not contain solid part, it is called “non-solid GGO” or “pure GGO”. In case the GGO lesions contain a solid, cystic, or linear part inside the nodule, it is called “non-solid GGO” or “complex GGO”. The solid part is more likely to be located in the center of the nodule, and surrounded by the GGO part, which is a so-called “fried egg” appearance. The solid part might be scant or prominent with various proportions of solid to GGO parts. In the classic, solid tumor, the GGO part has no longer exist within the nodule.
According to the recent studies on the relationship between CT appearance and histopathology of GGOs, not all, but considerable portion of these lesions correspond to the preivasive, non-invasive, or early forms of neoplastic growths, especially those on the adenocarcinoma lineage. The clinicopathological entity of these tumors are being established only recently, and it has never been the subject of clinical studies. The histopathology of GGO has been also studied, and they are either neoplastic or inflammatory. A focal inflammation of the lung panrenchyma sometimes presents with GGO on the CT image, and pathologically it is described as “organizing pneumonia”. These changes are more likely to be temporary. In contrast, the persisting GGOs are more likely to be neoplastic. According to the WHO histological classification of lung and pleural tumors, GGO lesions are associated with three pathological entities. “Atypical adenomatous hyperplasia (AAH)” is described as a preinvasive lesion, in which slightly atypical tumor cells line the involved alveoli and respiratory bronchioles. Adenocarcinoma in situ (AIS) is an adenocarcinoma with Clara cells and/or type II pneumocytes growing along alveolar walls and without stromal invasion. The important feature of AIS is “non-invasive” growth of the tumor, and therefore this lesion could be considered in situ carcinoma. The third category is adenocarcinoma with mixed subtypes, which shows a mixture of the histologic subtypes as well as obvious invasive growth.
The intervention strategy for GGO lesions are being established very recently, and some of them still need future clincal trials. Several factors are related to the management stragety; the size of lesions, image characteristics (non-solid versus part-solid), and the history of previous lung cancer. Especially, the indolent nature of the small-sized, non-solid GGOs needs to be stressed. For these tumors, the immediate surgical intervention should be rather avoided. Furthermore, the physical condition of the patiets such as age, co-existing medical conditions also must be taken into consideration. When thinking of surgical interventions, the location of the lesion (outer versus inner) is also an iomportant issue from the technical point of view. For tumors located deeply in the lung parenchyma, the sublobar resection is generally amenable because of the lack in the enough surgical margin.
1. Non-solid GGOs less than 15 mm in diameter. These small lesions without any solid part in the nodule termed as non-solid GGO are basically watched carefully with the repeated high-resolution CT. The appropriate intervals between repeated CTs have not been clearly demonstrated. It might rage from 3 to 6 moths. If the overt growth in size or the newly developping solid component is shown, the surgical intervention should be considered.
2. Part-solid GGOs less than 15 mm in diameter. The solid component in the part-solid GGOs represents the fiborotic scar and/or collapse of the lung in which the proliferation of the collagen fibers and actrive gibroblast is generally seen, and thiese findings indicate the features of invasive growth. Therefore, tumors of this category should be resected, The careful watching should be indicated only for the poor physical conditions compromising the surgical resection. However, considering their minimally invasive nature and small size, the sublobar resection could be reasonablly choosed. For these tumors, the segementectomy rather than wedge resection is preferrable. The location of the tumor should be carefully evaluated. When the tumor is located in the inner two thirds of the lung panrenchyma, the segemetal resection shoul be reapected as amenable. The segmentectomy for this location cannot ensure the safe surgical margin. For such locations, the lobectomy, instead of segmentectomy, must be chosen.
3. Non-solid GGOs larger than 15 mm in diameter. As non-solid GGOs of smaller size category, these lesions should not be resected immediately. However, the larger GGOs are known to be more likely to grow faster even if the lesions still do not contain solid part. There fore, if the lesion persists at least in the same size, after the appropriate follow-up period of 3-6 motnths, these GGOs should be resected. Similarly, the resection should be performed with sublobar resection.
4. Part-solid GGOs larger than 15 mm in diameter. The part-solid GGOs of this size are more likely to be an invasive adenocarcinomas. Especially when the solid part exceeds 50% of the whole area of the lesion, the invasive features become more common. Therefore, the lobectomy might be better selected as the mode of resection. The evaluation of the hilar/mediastinal lymph nodes should be also performed during surgery.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MA06 - Challenges in the Treatment of Early Stage NSCLC (ID 124)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Now Available
- Moderators:Florentino Hernando-Trancho, Ayten Kayi Cangir
- Coordinates: 9/08/2019, 13:30 - 15:00, Colorado Springs (1994)
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MA06.06 - A Phase III Study of Adjuvant Chemotherapy in Patients with Completely Resected, Node-Negative Non-Small Cell Lung Cancer (Now Available) (ID 285)
13:30 - 15:00 | Author(s): Hisao Asamura
- Abstract
- Presentation
Background
Post-operative UFT (tegafur/uracil) has been shown to prolong survival of Japanese patients with completely resected, p-stage I (T1> 2 cm) non-small cell lung cancer (NSCLC). This trial, the Japan Clinical Oncology Group (JCOG) 0707, aimed at estimating the efficacy of S-1 (tegafur/gimeracil/oteracil) compared to UFT as adjuvant therapy in this population.
Method
Eligible patients had received complete resection with lymph node dissection for p-stage I (T1-2N0M0, T1> 2 cm, by 5thEdition UICC TNM) NSCLC, within 56 days of enrollment. Patients were randomized to receive: oral UFT 250mg/m2/day for 2 years (Arm A), or oral S-1 80mg/m2/day for 2 weeks and 1 week rest, for 1 year (Arm B). The initial primary endpoint was overall survival (OS). Based upon the monitoring in Jun. 2013, which showed the combined OS of the 2 arms better than expected (4-year OS of 91.6% vs. presumed 5-year OS of 70-76.5%), it was judged to be underpowered. The study protocol was amended so that the primary endpoint is relapse-free survival (RFS). With the calculated sample size of 960, this study would detect the superiority of Arm B over Arm A with power 80% and one-sided type I error of 0.05, assuming the 5-year RFS of 75% in Arm A and the hazard ratio of 0.75.
Result
From Nov. 2008 to Dec. 2013, 963 patients were enrolled (Arm A : 482, Arm B : 481): median age 66 (range: 33 to 80), male 58%, adenocarcinoma 80%, p-T1/T2 46%/54%. Only 2 received pneumonectomy. >Grade 3 toxicities (hematologic/nonhematologic) were observed in 15.9 (1.5/14.7) % in Arm A, and in 14.9 (3.6/12.1) % in Arm B, respectively. 60.0% of the patients in Arm A and 54.7% of them in Arm B completed the protocol treatment (p=0.10). There were 4 cases of deaths during protocol treatment, probably of cardio-vascular origin, with 1 in Arm A and 3 in Arm B. At the data cut-off of Dec. 2018, the hazard ratio (HR, Arm B vs. Arm A) of RFS was 1.06 (95% confidence interval (C.I.): 0.82-1.36), showing no superiority of S-1 over UFT. The HR of OS was 1.10 (95% C.I.: 0.81-1.50). The 5-year RFS/OS rates were 79.4%/88.8% in Arm A and 79.5%/89.7% in Arm B, respectively. Pre-specified subset analyses for gender, age, smoking, stage, tumor side, lymph node dissection area, pleural invasion and histology revealed no remarkable results; S-1 arm was not superior to UFT arm in each analysis. Of the 77 and 85 OS events for Arm A/Arm B, 45 each (58%/53%, respectively) were due to the NSCLC. During the follow-up period, secondary malignancy was observed in 85 (17.8%) and 84 (17.8%) in Arm A and Arm B, respectively.
Conclusion
Post-operative adjuvant therapy with oral S-1 was not superior to that with UFT in stage I (T>2 cm) NSCLC after complete resection. UFT remains standard in this population. Future investigation should incorporate identification of high-risk population for recurrence, since survival of each arm was so good with substantial number of OS events due to other causes of deaths in this trial.
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P1.11 - Screening and Early Detection (ID 177)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.11-10 - Serum MicroRNA Biomarkers for Screening of Resectable Lung Cancer (ID 2253)
09:45 - 18:00 | Author(s): Hisao Asamura
- Abstract
Background
An accurate early screening method for lung cancer would be a powerful tool for decreasing lung cancer–related mortality. Computed tomography (CT) scanning is an effective method for lung cancer screening in high-risk populations. However, screening by CT scan has a limitation of low specificity (61%) for detection of lung cancer, resulting in unnecessary follow-up CT scans or invasive lung biopsies. In this study, we investigated the diagnostic potential of serum microRNAs (miRNAs) for detection of resectable lung cancer.
Method
Using the 3D-Gene® miRNA Labeling kit and the 3D-Gene® Human miRNA Oligo Chip (Toray Industries), we generated comprehensive miRNA profiles (expression levels of 2588 miRNAs) from 3744 serum samples obtained from 1566 patients with resectable lung cancer and 2178 participants with no cancer. We created a reliable diagnostic model for resectable lung cancer based on the combined expression levels of two miRNAs in the discovery set (208 lung cancer patients, 208 non-cancer participants). We then confirmed the diagnostic performance of the model in the validation set (1358 lung cancer patients, 1970 non-cancer participants).
Result
The combination of miR-A and miR-B yielded the best discrimination in the discovery set (AUC, 99.3; sensitivity, 99.0%; specificity, 99.0%). We then confirmed the diagnostic performance of the model in the validation set, and showed that the model was accurate (AUC, 0.973; sensitivity, 95.0%; specificity, 99.0%). According to univariable logistic regression analysis, the odds ratio of the diagnostic model for the presence of lung cancer was 21.76 (95% confidence interval [CI], 15.98–29.63). The diagnostic index exhibited high performance for all pathological stages (IA, 96.1%; IB, 93.7%; IIA, 97.3%; IIB, 96.7%; IIIA, 90.2%; IIIB, 83.3%; IV, 100%), and histological types (adenocarcinoma, 95.1%; squamous cell carcinoma, 94.2%; small-cell lung cancer, 90.9%).
Conclusion
A comprehensive analysis of serum levels of 2588 miRNAs in 1566 patients with lung cancer and 2178 non-cancer participants identified a combination of two miRNAs that could reliably detect resectable lung cancer. This study was the largest of its kind performed to date, and the results confirm that evaluation of serum miRNAs is an effective method for detection of resectable lung cancer. The high sensitivity and specificity of this screening model could help to decrease lung cancer–related mortality, as well as the number of unnecessary follow-up CT scans and invasive lung biopsies.
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WS04 - Staging Workshop Part 1: IASLC Database Challenges and Application (ID 105)
- Event: WCLC 2019
- Type: Workshop
- Track: Staging
- Presentations: 1
- Now Available
- Moderators:Paula Antonia Ugalde, Maria Teresa Tsukazan
- Coordinates: 9/09/2019, 14:00 - 15:30, San Francisco (2009)
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WS04.05 - Developing the IASLC Lung Cancer Staging Database and Recommendations for the 9th Edition (Now Available) (ID 3682)
14:00 - 15:30 | Author(s): Hisao Asamura
- Abstract
- Presentation
Abstract
Developing the IASLC lung cancer staging database and recommendations for the 9th edition
Background
Since the turn of the century, the international database of the IASLC Staging Project has served as the foundation for evidence-based recommendations for revisions to the TNM classification system for lung cancer. These recommendations were adopted by the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC), establishing the IASLC Staging Project as a global resource for lung cancer staging research. The project is currently midway through its third iteration of data collection, which was begun in 2017 and includes lung cancer cases diagnosed from 2011 through 2019, with follow-up for survival through 2021. The preferred mechanism for data collection is direct, online entry into a central database administered by Cancer Research and Biostatistics (CRAB) in Seattle, Washington.
Discussion
The data fields in the lung cancer database are extensive, having been revised in 20171 by the IASLC Staging and Prognostic Factors Committee (SPFC) to address specific research questions framed by each of its 15 subcommittees, such as the impact of direct extension into specific anatomic sites on survival, the relative effects of location vs size of involved nodes, or the importance of the size of distant metastases relative to the number of lesions and distant sites. The committee will consider the prognostic value of these anatomic parameters independently and in the context of non-anatomic factors such as sex, comorbidity, laboratory values that correlate with survival, or molecular markers. Existing institutional databases and large registries have traditionally been used to supplement the data contributed using the online system; however, these external sources rarely contain sufficient detail to address all of the committee’s stated objectives.2
The SPFC is chaired by Hisao Asamura, MD, and has separate subcommittees for T, N, M, ground glass opacities and adenocarcinoma in situ, neuroendocrine tumors, stage groupings, lymph node chart, validation and methodology, prognostic factors, R factor (completeness of resection), radiology and imaging, multiple pulmonary nodules, molecular markers, and data quality, as well as a steering committee that provides oversight. SPFC members are expected to demonstrate leadership and promote participation in the project, as well as develop and evaluate proposals for change. The current SPFC membership reflects the diverse geographic representation in the database used to support the most recent (8th edition) recommendations.
As of 5 June 2019, over 3,000 patients from 14 countries have been enrolled directly in the online system. Larger databases designed to be compatible with the project have also been transferred from Japan and the United States.
In the newly redesigned IASLC web site (www.iaslc.org), new participants can sign up online to contribute data by choosing the IASLC Staging Project page under the Research & Education heading. Following the publication of the core recommendations for the 9th edition of TNM, the web site may also be used to submit research proposals for secondary use of the data. Secondary use may be restricted according to agreements with individual sites in some cases. All proposals will be reviewed by the steering committee according to published guidelines.3
Conclusion
In the context of shifting paradigms and rapid advancements in treatments, diagnostics, and molecular technologies, the SPFC is tasked with evaluating and improving TNM staging on a global scale. To this end, we aim to engage a wide variety of research partners and to increase participation in previously underrepresented regions such as Egypt and India, where the first sites from each of these countries have recently been recruited. The collection of a large and comprehensive database will be pivotal to the SPFC’s ability to provide data-informed, universally applicable, and balanced recommendations that will be used world-wide by physicians, researchers, and patients. As we continue to prepare for upcoming analysis of the 9th edition database, the IASLC membership is encouraged to participate through the contribution of data and engagement with the SPFC and its mission. This global effort to improve the TNM staging criteria presents a unique opportunity to collaborate in international public health research.
References
Giroux DJ, Schil PV, Asamura H, et al. The IASLC Lung Cancer Staging Project: A Renewed Call to Participation. J Thorac Oncol 2018;13:801-809.
Rami-Porta R, Bolejack V, Giroux D, et al. The IASLC Lung Cancer Staging Project: The New Database to Inform the Eighth Edition of the TNM Classification of Lung Cancer. J Thorac Oncol 2014;9:1618-1624.
Goldstraw P, Rami-Porta, R, and Crowley J. We Probably Have the Answer: Now What is the Question? J Thorac Oncol 2009;4:939-940.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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WS05 - Staging Workshop Part 2: The Importance of Invasive Nodal Staging in Thoracic Malignancies (ID 106)
- Event: WCLC 2019
- Type: Workshop
- Track: Staging
- Presentations: 1
- Now Available
- Moderators:Jose Maria Matilla, Ricardo Beyruti
- Coordinates: 9/09/2019, 15:45 - 17:15, San Francisco (2009)
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WS05.03 - How to Perform a Proper Systematic Nodal Dissection in Lung Cancer Surgery (Now Available) (ID 3686)
15:45 - 17:15 | Author(s): Hisao Asamura
- Abstract
- Presentation
Abstract
In 1960, Cahan first reported lobectomy with regional lymph node dissection, which was called “radical lobectomy.”1 Since then, this procedure has been widely accepted, and systematic nodal dissection (SND) is an internationally accepted standard procedure for lymph node dissection in cases of non-small cell lung cancer (NSCLC). The purpose of SND is aimed at removal of all mediastinal lymph node stations regardless of the anatomical location of the primary tumor in the lobe. The significance of SND can be discussed from the clinical aspects of accurate staging and survival benefit. Metastatic lymph nodes obtained via SND can undergo careful and accurate accurate histopathological evaluation, which offers several clinical advantages. However, the therapeutic effect of SND remains unclear.2-5
Technically, SND involves complete excision of all tissues in a particular anatomical compartment along with a few components of surrounding anatomical structures. An ideal technique involves en bloc removal of all tissue that may contain cancer cells, including lymph nodes and surrounding fatty tissue within pre-defined anatomical landmarks. All of lobectomies for NSCLC are performed via posterolateral incision using minimally invasive open surgery (MIOS) approach in our institution. Common to both sides, the fourth or fifth intercostal space provides better access in SND. During the SND, special care is warranted to prevent interruption of the lymphatic vessels and/or injury to the lymph nodes themselves. Additionally, connective tissue ligation is necessary in a few cases to prevent postoperative chylothorax. Identification of the bilateral recurrent nerves is important because recurrent nerve paralysis can cause serious postoperative complications. Based on AOSOG Z0030 trial, complications of SND include postoperative chylothorax (1.7%), intraoperative bleeding (1.1%), and recurrent laryngeal nerve injury (0.9%).5
Although SND is a standard procedure of lymph node dissection for NSCLC, previous studies have analyzed in detail the lymphatic pathway and the pattern of lymph node involvement based on the primary location by lobe. Asamura et al. 6 reported that right upper lobe tumors and left upper segment tumors tend to metastasize to the superior mediastinum and that these lesions rarely metastasize to the subcarinal nodes without concomitant metastasis to the hilar or superior mediastinal nodes.6 The lobe-specific patterns of nodal metastases are being recognized owing to increasing analyses of the lymph node metastatic pathway.6-9 Based on these results, lobe-specific lymph node dissection is being increasingly performed under certain conditions, for example, based on tumor location, tumor size, cell type, and the percentage of the area of ground glass opacity visualized in the tumor on computed tomography.
References
1. Cahan WG. Radical lobectomy. J Thorac Cardiovasc Surg; 1960;39:555-572.
2. Izbicki JR, Passlick B, Pantel K, et al. Effectiveness of radical systematic mediastinal lymphadenectomy in patients with resectable non small cell lung cancer. Ann Surg 1998;227:138-144.
3. Sugi K, Nawata K, Fujita N, et al. Systematic lymph node dissection for clinically diagnosed peripheral non-small-cell lung cancer less than 2 cm in diameter. World J Surg 1998;22:290-294.
4. Wu Y, Huang ZF, Wang SY, et al. A randomized trial of systematic nodal dissection in resectable non-small cell lung cancer. Lung Cancer 2002;36:1- 6.
5. Wright G, Manser RL, Byrnes G, et al. Surgery for non-small cell lung cancer: systematic review and meta-analysis of randomised controlled trials. Thorax 2006;61:597-603.
6. Asamura H, Nakayama H, Kondo H, Tsuchiya R, Naruke T. Lobe-specific extent of systematic lymph node dissection for non-small cell lung carcinomas based on a retrospective study of metastasis and prognosis. J Thorac Cardiovasc Surg 1999; 117:1102-1111
7. Asamura H, Nakayama H, Kondo H, Tsuchiya R, Naruke T. Lymph node involvement, recurrence, and prognosis in resected small, peripheral non-small cell carcinoma of the lung. Are these carcinomas candidates for video-assisted lobectomy? J Thorac Cardiovasc Surg 1996;111:1125-1134
8. Okada M, Tsubota N, Yoshimura M, et al. Prognosis of completely resected pN2 non-small cell carcinomas: what is the significant node that affects survival? J Thorac Cardiovasc Surg 1999;118:270-275
9. Watanabe S, Suzuki K, Asamura H. Superior and basal segment lung cancers in the lower lobe have different lymph node metastatic pathways and prognosis. Ann Thorac Surg 2008;85:1026-1031.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
