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Jun Nakajima
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OA 16 - Treatment Strategies and Follow Up (ID 686)
- Event: WCLC 2017
- Type: Oral
- Track: Early Stage NSCLC
- Presentations: 9
- Moderators:Jun Nakajima, T. Demmy
- Coordinates: 10/18/2017, 14:30 - 16:15, Room 315
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OA 16.01 - Stereotactic Ablative Radiotherapy Versus Surgery in Early Lung Cancer: A Meta-analysis of Propensity Score-Adjusted Studies (ID 8066)
14:30 - 16:15 | Presenting Author(s): Hanbo Chen | Author(s): Joanna M Laba, R..G. Boldt, C.D. Goodman, D.A. Palma, Suresh Senan, Alexander Vincent Louie
- Abstract
- Presentation
Background:
There is currently no completed randomized controlled trial data comparing stereotactic ablative radiotherapy (SABR) and surgery in operable patients with early-stage non-small cell lung cancer (ES-NSCLC). Propensity score methods are increasingly utilized in oncology to balance the baseline characteristics of non-randomized cohorts, mimicking the setting of a clinical trial. No previous meta-analysis of propensity score analyses comparing a surgical and non-surgical modality has been conducted. Our goal was therefore to perform a systematic review and meta-analysis of all propensity score analyses comparing SABR and surgery in patients with ES-NSCLC.
Method:
A systematic review was carried out according to PRISMA guidelines by querying the MEDLINE and Embase databases from inception until December 2016. Hazard ratios (HR) with confidence intervals (CI) for overall survival (OS) and disease-specific survival (DSS) were directly extracted, if available, or estimated from Kaplan-Meier curves. Meta-analysis was carried out with inverse variance-weighted random-effects models.
Result:
After reviewing 1039 records, 17 PS-adjusted studies with a total of 20151 patients were included in the final analysis. Overall survival (OS) favoured surgery over SABR (HR = 1.52 [95% CI: 1.33-1.74], p < 0.001). However, the rate at which patients died from lung cancer (DSS) was not significantly different (HR = 1.13 [95% CI: 0.86-1.49], p = 0.38). On subgroup analysis, OS was superior for both lobectomy (HR = 1.61 [95% CI: 1.27-2.03], p < 0.001) and sublobar resection (HR = 1.33 [95% CI: 1.15-1.55], p < 0.001) versus SABR while DSS again did not significantly differ (HR = 1.35 [95% CI: 0.70-2.62] and HR = 1.18 [95% CI: 0.84-1.67], respectively). On secondary analysis, meta-analysis of proportions revealed a lymph node upstaging rate of 16.0% (95% CI: 13.6%-18.6%) and adjuvant chemotherapy usage rate of 11.5% (95% CI: 8.6%-14.8%) among patients who received surgery. On meta-regression, with every increase of 0.1 in the maximum allowable difference in propensity score within a matched pair - representing increases in imbalance between cohorts, DSS outcomes increasingly favoured surgery by 1.36-fold. Critical appraisal revealed inconsistent reporting of propensity score methods.
Conclusion:
Overall survival favoured surgery over SABR in this meta-analysis of 17 propensity score analyses. However, the effectiveness of SABR was reflected in a similar DSS to surgery, supporting ongoing clinical equipoise. A direct relationship between propensity score methodology and DSS outcomes were demonstrated. Whether this observed benefit in OS for surgery is real or due to limitations in the propensity score methodology requires confirmation through randomized data.
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OA 16.02 - Risk of Recurrence in Stage I Adenocarcinoma of the Lung: A Multi-Institutional Study on Interaction with Type of Surgery and Type of Nodal Staging (ID 9304)
14:30 - 16:15 | Presenting Author(s): Francesco Guerrera | Author(s): F. Lococo, A. Evangelista, O. Rena, L. Ampollini, J. Vannucci, Luigi Ventura, V. Marchese, M. Paci, Pier Luigi Filosso, A. Oliaro, C. Casadio, F. Puma, F. Ardissone, Enrico Ruffini
- Abstract
- Presentation
Background:
In last years, an increasing interest emerges on the role of sub-lobar resection and lobe-specific lymphnode dissection in the treatment of early stage lung cancer. The aim of our study was to define impact on Cumulative incidence of recurrence (CIR) of type of surgical resection and type of nodal staging. Furthermore, we evaluated the effect of interactions between the different kinds of procedure.
Method:
An analysis of 969 consecutive stage I pulmonary adenocarcinoma patients, operated in six Thoracic Surgery Institutions between 2001 and 2013, was conducted. Type of surgical resection included lobectomy and sub-lobar resection; pneumonectomy and bilobectomy were excluded from the analysis. Nodal staging procedures were classified in nodal sampling (NS), lobe-specific lymph node dissection (LS-ND) and systematic lymph node dissection (SND). Multivariable-adjusted comparisons for CIR was performed using Fine and Grey model, taking into account death by any cause as competing event. Test of interaction between type of surgical resection and type of nodal staging was carried out and results presented in a stratified way. Missing data were multiple-imputed, combined estimates were obtained from 5 imputed datasets.
Result:Multivariable-adjusted Fine and Grey model for Comulative Incidence of Recurrence (take into account age, gender, smoking habit, side of intervention, pTNM stage, vascular invasion, pTNM stage, predominant histologic pattern and histologic grade)(Results of test of interaction presented in a stratified way)
Median follow-up was 63 months. Eight-hundred forty-six (87%) patients were submitted to lobectomy, while 123(13%) to sub-lobar resection. Four-hundred fifty-five (47%) patients received SND, 98(10%) LS-ND and 416(43%) NS. Two-hundred forty-seven (26%) patients developed a local/distant recurrence with a 5-year CIR of 24%. Multivariable-adjusted comparisons showed an independent negative effect of sub-lobar resection(HR 1.52;95%CI:1.07-2.17), LS-ND(HR 1.74;95%CI:1.16-2.6) and NS(HR 1.49;95%CI:1.12-1.98) on CIR(Table). Test of interaction showed an homogeneity of results among subgroups.Sub-lobar resection vs. Lobectomy HR (95%CI) P INTERACTION P-value Overall 1.52 (1.07 to 2.17) 0.02 0.268 SND 1.98 (1.14 to 3.42) LS-ND 1.87 (0.94 to 3.74) NS 1.08 (0.61 to 1.93) LS-ND vs SND HR (95%CI) P INTERACTION P-value Overall 1.74 (1.16 to 2.6) 0.007 0.903 Lobectomy 1.66 (1.03 to 2.69) Sub-lobar resection 1.58 (0.75 to 3.32) NS vs. SND HR (95%CI) P INTERACTION P-value Overall 1.49 (1.12 to 1.98) 0.007 0.131 Lobectomy 1.61 (1.18 to 2.19) Sub-lobar resection 0.88 (0.43 to 1.82)
Conclusion:
In our series, lobectomy and systematic lymph node dissection confirmed to be the optimal strategy to achieve a favorable prognosis in stage I adenocarcinoma of the lung. The real value of sub-lobar resection and less aggressive nodal staging should be assessed by randomized clinical trial before being integrated in clinical practice.
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OA 16.03 - Recurrences and 2<Sup>Nd</Sup> Primary Cancers in the IFCT-0302 Trial Assessing a CT-Scan-Based Follow-Up after Lung Cancer Surgery (ID 9006)
14:30 - 16:15 | Presenting Author(s): Virginie Westeel | Author(s): Fabrice Barlesi, P. Foucher, J. Lafitte, J. Domas, P. Girard, J. Trédaniel, M. Wislez, B. Chahine, J. Muir, S. Dehette, J. Virally, M. Grivaux, F. Lebargy, F. Al Freijat, Nicolas Girard, E. Courau, R. Azarian, M. Farny, J. Duhamel, S. Labrune, F. Morin, P.J. Souquet
- Abstract
- Presentation
Background:
The IFCT-0302 trial is the first large randomized phase III multicenter trial which compared two follow-up modalities after surgery for early stage non-small cell lung cancer (NSCLC).
Method:
After complete resection of a stage pI, II, IIIA or T4 (pulmonary nodules in the same lobe) N0-2 NSCLC (TNM 6[th] edition), patients were randomized (1/1) between 2 follow-up programs: - arm 1, clinical examination and Chest X-ray, - arm 2, clinical examination, Chest X-ray, thoraco-abdominal CT-scan plus bronchoscopy (optional for adenocarcinomas). In both arms, procedures were repeated every 6 months after randomization during the first 2 years, and yearly until 5 years. The primary endpoint was overall survival (OS). Distinction between lung recurrences and 2[nd] primary lung cancer was assessed by investigators, using the Martini and Melamed definition (J Thorac Cardiovasc Surg 1975).
Result:
1775 patients were randomized (arm 1: 888; arm 2: 887). Patient characteristics were well-balanced between the two arms: males 76.3%, median age 63 years (range: 34-88), squamous and large cell carcinomas 39.5%, stage I 68.1%, stage II 13.7%, stage III 18.3%, lobectomy or bilobectomy 86,6%. OS and DFS were not significantly different between arms (OS: HR=0.92, 95% CI: 0.8-1.07; p=0.27). Median disease-free survival was 4.95 years (95% CI: 4.4- not reached) in arm 1 and not reached in arm 2, respectively. A recurrence was diagnosed in 245 patients (27.6%) in arm 1, and in 291 patients (32.8%) in arm 2. Recurrences were symptomatic in 203 (82.9%) and 163 (56.0%) patients, respectively. The most frequent sites of recurrence were: ipsilateral lung (42.0 and 33.0%), brain (29.4 and 23.4%), and contralateral lung (24.9 and 22.3%), respectively. Treatment of recurrence achieved complete remission in 25 (10.2%) and 52 (17.9%) patients (p=0.01), respectively. Second primary cancers (SPC) were diagnosed in 101 patients (11.4%) in arm 1, and 97 patients (10.9%) in arm 2, with symptoms at diagnosis in 64 (63.4%) and 37 (38.1%) patients, respectively. The most frequent sites of SPC were: lung (25.7 and 41.2%), prostate (14.8 and 11.3%), and ENT (11.9 and 7.2%), respectively. Treatment of SPC achieved complete remission in 30 (29.7%) and 40 (41.2%) patients (p=0.10), respectively.
Conclusion:
Although OS and DFS were not significantly increased by thoraco-abdominal CT-scan-based follow-up, recurrences or SPCs were more frequently asymptomatic and amenable to curative treatment in patients followed by thoraco-abdominal CT scan compared to those followed by chest X-ray only.
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OA 16.04 - Efficacy and Safety of Erlotinib vs Vinorelbine/Cisplatin as Adjuvant Therapy for Stage IIIA EGFR Mutant NSCLC Patients (ID 8717)
14:30 - 16:15 | Presenting Author(s): Dongsheng Yue | Author(s): S. Xu, Q. Wang, X. Li, Y. Shen, H. Zhao, C. Chen, W. Mao, W. Liu, J. Liu, L. Zhang, H. Ma, Q. Li, Y. Yang, Y. Liu, H. Chen, C. Wang
- Abstract
- Presentation
Background:
Adjuvant chemotherapy remains the most important treatment for stage IIIA non-small cell lung cancer (NSCLC) after radical operation, but its benefits has reached plateau and high risk of recurrence. Previous studies SELECT and RADIANT have suggested a trend of improving DFS of erlotinib as adjuvant therapy for patients with activating mutations. This study is designed as prospective, open-label, randomized, multicenter phase II trial to investigate the efficacy and safety of erlotinib (E) as adjuvant therapy in comparison with vinorelbine/cisplatin (NP) chemotherapy in completely resected stage IIIA EGFR mutant patients.
Method:
Patients aged between 18 – 75 with ECOG PS 0–1, stage IIIA, EGFR-activating mutation (exon 19 or exon 21 L858R), reached R0 resection NSCLC were eligible. And patients were randomized(1:1) into either erlotinib (orally 150mg/day for 2 years, util relapse or unacceptable toxicity) or NP (vinorelbine 25mg/m[2] i.v. day 1, 8 and cisplatin 75mg/m[2] i.v. day 1, every 3 weeks for 4 cycles) group. Random assignment was stratified by EGFR mutation type (exon 19 vs exon 21), histology (adenocarcinoma vs non- ) and smoking status (smoker vs non-). The primary endpoint was 2-year disease free survival rate (DFSR), secondary endpoints include disease free survival (DFS), overall survival (OS), safety (NCI CTCAE 4.0) and quality of life (QoL), and exploratory biomarker analysis.
Result:
From Sep, 2012 to May, 2015, in total 102 patients from 16 centers across China were randomized to receive E (N=51) or NP (N=51). Median follow-up time was 33 months for E and 28 months for NP. Baseline characteristics of age, sex, PS, histology, smoking status, EGFR mutation subtypes were well balanced in each arm. Two-year DFSR was 81.35% (95%CI: 69.63-93.08) in E arm and 44.62% (95%CI: 26.86-62.38) in NP arm respectively (P<0.001) in ITT population. DFS was significantly prolonged with E vs NP (median, 42.41 vs 20.96 months, HR 0.271, 95% CI: 0.137-0.535; P<0.001). OS data from our trial are still immature. In current, the number of death events were 2 (E) and 13 (NP) arm. Safety profile was similar to previous studies of each agent in NSCLC, no new unexpected AE were observed in each arms.
Conclusion:
As compared with NP, E showed superior efficacy and should be considered therapeutic option for patients with R0 resected stage IIIA NSCLC with EGFR-activating mutation. (EVAN, NCT01683175).
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OA 16.05 - Discussant - OA 16.01, OA 16.02, OA 16.03, OA 16.04 (ID 10782)
14:30 - 16:15 | Presenting Author(s): In Kyu Park
- Abstract
- Presentation
Abstract not provided
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OA 16.06 - Mediastinal Staging by Videomediastinoscopy in Clinical N1 Non-Small Cell Lung Cancer: A Prospective Multicentre Study (ID 8454)
14:30 - 16:15 | Presenting Author(s): Herbert Decaluwe | Author(s): C. Dooms, X.B. D'Journo, S. Call, D. Sanchez-Lorente, B. Haager, R. Beelen, V. Kara, T. Klikovits, C. Aigner, K. Tournoy, J. Moons, G. Brioude, J.C. Trujillo, B. Bethe, W. Klepetko, A. Turna, B. Passlick, L. Molins, Ramon Rami-Porta, P. Thomas, Paul De Leyn
- Abstract
- Presentation
Background:
A fourth of patients with cN1-NSCLC based on PET-CT imaging are at risk for occult mediastinal nodal involvement. In a previous prospective study, endosonography alone had an unsatisfactory sensitivity (38%) to detect mediastinal nodal disease. This prospective multicenter trial investigated the sensitivity of preoperative mediastinal staging by video-assisted mediastinoscopy (VAM) in patients with cN1 (suspected) NSCLC.
Method:
Consecutive patients with operable and resectable cN1 (suspected) non-small cell lung cancer (NSCLC) underwent a VAM or VAM-lymphadenectomy (VAMLA). All patients underwent FDG–PET and CT-scan. The primary study outcome was sensitivity to detect N2-disease. Secondary endpoints were the prevalence of N2-disease, negative predictive value (NPV) and accuracy of VAM(LA).
Result:
Figure 1 Out of 105 patients with cN1 on imaging, 26% eventually had N2-disease. Invasive mediastinal staging with VAM(LA) reached sensitivity of 73% to detect N2-disease. The median number of assessed lymph node stations during VAM(LA) was 4. In 96% ≥3 stations were assessed. VAMLA was performed in 31%, 69% underwent VAM.N Prevalence of mediastinal disease Sensitivity OR(95%CI) Negative Predictive Value OR(95%CI) Negative Posttest probability OR(95%CI) Dooms et al. Chest. 2014; 147(1): 209–15. Endosonography alone 100 24% 0.38 (0.18-0.57) 0.81 (0.71-0.91) 0.19 (0.13-0.27) Endosonograpy, if negative followed by mediastionoscopy 0.73 (0.55-0.91) 0.91 (0.83-0.98) 0.09 (0.04-0.17) Current Study Mediastinoscopy 105 26% 0.73 (0.54-0.86) 0.92 (0.83-0.97) 0.08 (0.03-0.17)
Conclusion:
VAM(LA) has a satisfactory sensitivity of 73% to detect mediastinal nodal disease in cN1-NSCLC and could be the technique of choice for pre-resection mediastinal lymph node assessment in this patient group with 26% chance of occult positive mediastinal nodes after negative PET-CT. (ClinicalTrials.gov NCT02222194)
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OA 16.07 - Radiological Feature on TSCT for Predicting a Pathological Less-Invasive Lung Cancer According to the 8th TNM Classification (ID 8608)
14:30 - 16:15 | Presenting Author(s): Shinya Katsumata | Author(s): Keiju Aokage, T. Sakai, S. Okada, K. Sekihara, T. Miyoshi, K. Tane, G. Ishii, M. Tsuboi
- Abstract
- Presentation
Background:
The limited resection for lung cancer has become more prevalent for patients who show a compromised pulmonary or cardiac function. As of now standard care of lung cancer is lobectomy with lymph node dissection or sampling even for early lung cancer. Japan clinical oncology group (JCOG) study 0201 has proposed the criteria to diagnose pathological less-invasive lung adenocarcinoma by using consolidation to tumor ratio (CTR) on preoperative thin-sliced computed tomography (TSCT) scan. Three clinical trials have been ongoing based on this result, but the TNM classification was drastically revised in 2016, especially in T category. The aim of this study is to propose the new radiological criteria to predict pathological less-invasive lung cancer before surgery in accordance with the new TNM classification.
Method:
We analyzed the 744 patients who have peripheral Tis-T1cN0M0 non-small cell lung cancer with 3cm or less in size and underwent complete resection by lobectomy from 2003 to 2011. We defined a lung cancer with no nodal involvement and no vessel invasion pathologically as a pathological less-invasive cancer, and investigated the radiological criteria corresponding to the new T category by using TSCT to predict a pathological less-invasive cancer with the specificity of 97% or more. We also re-evaluated the criteria by adding the parameter of CTR and presence of ground-glass opacity (GGO), and prognostic parameters; overall survival (OS) and relapse-free survival (RFS).
Result:
The cTis/T1ami/T1a patients showed no pathological invasive cancer except for only 1 patient (specificity: 99%). In the cT1b/T1c patients, the specificity of cT1b with CTR 0.5 or less, cT1b with C/T ratio 0.75 or less, and cT1b with GGO presence were 100%, 97.1%, 94.4%, respectively. The new criteria of cT1a or less and cT1b with CTR 0.75 or less showed excellent prognosis for OS and RFS.
Conclusion:
As most of the patients with cTis/T1ami/T1a and cT1b with CTR 0.75 or less showed pathological less-invasive cancers and extremely good survival, they will be more likely to be obtained good outcomes by sublobar resection including wide-wedge resection as well. The further prospective study will be required to confirm the hypothesis.
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- Abstract
- Presentation
Background:
It is necessary to apply a precise standard to predict the oncological outcomes among heterogeneous subgroups of N1 disease ranging from level 10 to 14. Although International Association for the Study of Lung Cancer (IASLC) proposed a new N descriptor in the 8[th] edition of the TNM Classification, lack of dissection on level 13 and level 14 may affect the efficacy of new classification. In this study, we tested a hypothesized classification strategy based on systematic dissection of N1 node from level 10 to level 14.
Method:
From March 2007 to December 2014, 156 consecutive patients of non-small cell lung cancer, treating with lobectomy and systematic mediastinal lymphadenectomy, were investigated. Nodes from level 10 to 12 were dissected during operation. Intrapulmonary lymph nodes (level 13-14) were retrieved after surgery. The data were prospectively collected and retrospectively analyzed. All cases were divided into two categories according to the 8[th] edition of the TNM Classification: pN1a was defined as N1 at a single station, while pN1b was defined as N1 at multiple stations. Then, in our proposed classification, N1a (modified) was defined as single level of N1 station involved (not including single level 10 or 11 spread) or level 13 and/or 14 involved, while N1b (modified) was defined as single level 10 or 11 spread or multiple levels of N1 node involvement (not including level 13 and 14 spread). The association between the N1 subgroup status and survival was explored separately using 8[th] IASLC classification and hypothesized classification.
Result:
In the whole cohort, a mean±SD of 13.1±7.1 N2 nodes and 12.0+5.2 N1 nodes per case were collected.There were 4.7±3.1 nodes from level 13 and 14. The difference in 5-year overall survival between pN1a and pN1b was not significant (73.9% versus 65.7%, p=0.371). However, the difference in 5-year overall survival between N1a (modified) and N1b (modified) was significant (79.1% versus 60.2%, p=0.018). Multivariate analysis showed the revised N1 classification was an independent prognostic factor for NSCLC (versus N1a, the hazard ratio [HR] of N1b for OS was 2.120, 95% confidence interval [CI]: 1.083-4.151, p=0.028). However, the 8[th] edition IASLC N1 descriptors was not an independent prognostic factor (versus pN1a, HR of pN1b was 1.419, 95% CI: 0.710-2.837, p=0.322).
Conclusion:
The hypothesized N1 classification in present study was shown to be a better descriptor to express the outcome than 8[th] edition of the TNM Classification of IASLC. More data are needed to validate this proposal.
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OA 16.09 - Discussant - OA 16.06, OA 16.07, OA 16.08 (ID 10783)
14:30 - 16:15 | Presenting Author(s): Marcin Zielinski
- Abstract
- Presentation
Abstract not provided
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Author of
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MTE 01 - Management of Small Nodules Detected by CT Screening (Sign Up Required) (ID 550)
- Event: WCLC 2017
- Type: Meet the Expert
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 07:00 - 08:00, Room 301 + 302
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MTE 01.01 - Management of Small Nodules Detected by CT Screening; A Surgeon's Perspective (ID 7774)
07:00 - 08:00 | Presenting Author(s): Jun Nakajima
- Abstract
- Presentation
Abstract:
Along with the prevalence of screening with computed tomography (CT), small pulmonary ground-glass density nodules (GGN) have been detected more frequently. A GGN is a round area of increased pulmonary opacity with intact bronchial and vascular structures. GGNs showing no or slow growth during follow-up period are most likely to be “early” adenocarcinomas showing lepidic pattern pathologically. There are three problems in diagnostics and therapeutics of GGNs. First, should they be treated or not? They might not change for years. We might take a risk of postoperative comorbidity for a harmless disease. Some large prospective observational studies on these pulmonary small GGNs have been performed: From clinical practice performed in these clinical trials, We found that 5-30% of GGN were resected during the observation period, because of the increased size or appearance of solid part in the GGN. Almost all of the pathologies of the resected GGN were adenocarcinomas. Part-solid GGNs were more likely to be diagnosed as invasive adenocarcinomas than pure GGNs. That is, we can correctly diagnose small pulmonary GGNs as adenocarcinomas when their CT images are changed. However, it is still unclear whether surgical intervention will contribute to increased survival from lung cancer. Second, how to detect pulmonary GGOs at surgery, if they are located deep in lung parenchyma? GGNs are difficult to identify even by bimanual palpation through open thoracotomy, because they are as soft as lung parenchyma if they show pure GGN appearance. Preoperative marking of these GGN is mandatory to ensure a definite resection. Many methods for detecting small pulmonary nodules have been developed: Preoperative hookwire placement under CT observation has been most widely performed. The punctured hook wire with thread can easily be identified that excisional biopsy may be done through thoracoscopy. However, arterial air embolism is reported to be occasionally associated with the placement of hookwire which can cause lethal results. Instead, dye marking, or fiducial placement through bronchoscopy has been revived to replace the hookwire method. We have recently developed Virtual-assisted lung mapping (VAL-MAP), a relatively brand-new lung marking technique using dye multiple dye markings through bronchoscope. Before bronchoscopy, we create a virtual 3-D bronchoscope map with CT and plan where to mark. Multiple dye markings enable us to determine the extent of resection with safe margin from the tumor. Actually safer margin from the tumor was shown to be secured by this method. Third, how to determine the extent of pulmonary resection for these small GGNs? Still there is no evidence other than lobectomy and lymph node dissection for early non-small cell lung cancer (NSCLC), clinical trials have been performed to prove feasibility and no-inferiority of sublobar resections (wedge resection and segmentectomy) for small NSCLC, especially those ≤2cm in diameter. In Japan and USA, prospective randomized studies are on the way to obtain more reliable evidence. In conclusion, management of small pulmonary nodules suspected of an early carcinoma includes the determination of operative indication, detection technique of the tumor, aiming to safer and effective treatment of these tumors.
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P1.07 - Immunology and Immunotherapy (ID 693)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.07-017 - Assessment of Cancer Immunity Status in Each Patient Using Immunogram (ID 9115)
09:30 - 16:00 | Author(s): Jun Nakajima
- Abstract
Background:
For successful cancer immunotherapy, comprehensive profiling of cancer-immune system interaction is required for each individual patient. To this end, we developed an immunogram reflecting the cancer immunity cycle and applied it to real patients with lung cancer.
Method:
Whole-exome sequencing and RNA-Seq were performed in 25 non-small cell lung cancer patients (13 adenocarcinoma, 11 squamous cell carcinoma, and 1 large cell neuroendocrine carcinoma). The number of somatic mutations and the expression of genes related to cancer-immunity were assessed and normalized using TCGA-LUAD and LUSC data (n=1035). Immunogram of each patient was drawn in a radar chart composed of 9 axes reflecting 7 steps of cancer-immunity cycle.
Result:
Various patterns of immunogram were observed in all 25 lung cancer patients, suggesting that each patient has their own pattern of immunosuppressive microenvironment (Figure 1). The hierarchical clustering using each scores of immunogram showed four clusters of patients characterized by T cell phenotype (inflamed vs non-inflamed) and tumor antigenicity (high vs low) (Figure 2). T cell-inflamed tumors (Clusters 3&4) had gene signatures of abundant T cells and interferon gamma (IFNG) response, as well as inhibitory cells and checkpoint molecules, suggesting the presence of counter regulatory immunosuppressive microenvironment. Unleashing of counter regulations by checkpoint inhibitors, for example, may be indicated for these patients. Each scores of immunogram had no correlation with histology. This result was consistent with previous studies of checkpoint blockade that clinical responses were not easily predicted solely by the histology. Patient age, gender and TNM stage also did not correlate with each immunogram scores. Figure 1
Conclusion:
The landscape of the tumor microenvironment in each patient can be appreciated by utilizing immunogram. Immunogram for the cancer-immunity cycle can be used for the assessment and visualization of cancer immunity status in each patient, and thus may become a helpful resource toward optimal personalized immunotherapy.
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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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P1.13-002 - New Clinical T Classification Is Associated with Pathological Stage I Invasive Adenocarcinoma with Solid Histologic Subtype (ID 9209)
09:30 - 16:00 | Author(s): Jun Nakajima
- Abstract
Background:
Recent studies have reported that sublobar resection is not inferior to lobectomy for small-sized non-invasive adenocarcinoma; however, the adequacy for small-sized invasive adenocarcinoma (IAD) remains unclear. We have reported that, in patients with pathological stage I IAD, the presence of ≥ 5% solid (SOL) histologic subtype is a significant predictor of recurrence, especially for the patients undergoing sublobar resection (Figure A). The objective of this study was to identify the clinical factors associated with the presence of SOL in patients with IAD.
Method:
We retrospectively reviewed patients with therapy-naïve, pathological stage I (≤2-cm) lung adenocarcinoma, who had undergone complete resection from 1998-2015. Each tumor was evaluated by comprehensive histologic subtyping according to the 2015 WHO classification and re-evaluated preoperative thin-sliced computed tomography to determine solid size and reclassified them according to the new TNM classification. We defined carcinoembryonic antigen (CEA) cut-off value as 2.2 ng/mL. Recurrence-free probability was estimated using the Kaplan-Meier method.
Result:
IAD patients with available image was 160 cases (94 male and 66 female, 96 smokers, and median age: 69 years). Clinical T classification in the 7th edition was T1a:142, T1b:17, T2a:1, and in the 8th edition Tis:17, T1mi:3, T1a:37, T1b:100, T1c:3. The presence of ≥ 5% solid component (SOL) was identified in 70 patients (44%). In patients with IAD, the presence of ≥ 5% SOL was associated with increased risk of recurrence compared to those with SOL <5% (P=0.001, Figure B). The presence of ≥ 5% SOL was significantly associated with sex, smoking, clinical T classification in the 8th edition, and high CEA level (P = 0.001, P < 0.001, P < 0.001, P = 0.013, respectively).
Conclusion:
In patients with pathological stage I IAD, clinical T classification in the 8th edition, and high CEA level significantly correlated with the presence of ≥ 5% SOL, which was associated with recurrence after surgery. Figure 1
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P3.16 - Surgery (ID 732)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Surgery
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.16-028 - Necrosis Is a Predictor of Recurrence in Patients with Small Lung Adenocarcinoma ≦2cm (ID 10451)
09:30 - 16:00 | Author(s): Jun Nakajima
- Abstract
Background:
The prognostic significance of pathological necrosis in small lung adenocarcinoma has not been investigated. The purpose of this study is to investigate the prognostic role of pathological necrosis in patients with completely resected small lung adenocarcinoma ≦2cm.
Method:
All available tumor slides from patients with surgically resected lung adenocarcinoma ≦2cm in size (1998-2015) were retrospectively reviewed. Exclusion criteria: patients who received induction therapy and lung cancer surgery within preceding 2 years. Recurrence free probability and overall survival were assessed using the Kaplan-Meier method.
Result:
351 patients met inclusion criteria (48% women, median age 67yr (34-86 yrs), 50% never-smokers; 324 Stage IA, 27 Stage IB; 111 and 240 patients underwent sublobar resection and lobectomy, respectively). Presence of pathological necrosis was identified in 32 patients (9%). Presence of pathological necrosis was significantly associated with sex, smoking, clinical T classification in the 8[th] edition and pathological tumor size (p<0.01, p<0.001, p<0.01, p<0.001, respectively). Presence of pathological necrosis correlated with an increased risk of recurrence, compared with those without pathological necrosis (5-year RFP, 70.5%vs 93.8%; p<0.001). Presence of pathological necrosis did not affect OS (5-year OS, 80.8%vs 92.3%; p=0.21).Figure 1
Conclusion:
In patients with small lung adenocarcinoma ≦2cm, presence of pathological necrosis was significantly associated with increased risk of recurrence.
