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Ramon Rami-Porta
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ES 01 - New TNM and WHO Classification (ID 510)
- Event: WCLC 2017
- Type: Educational Session
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:M. Noguchi, Peter Goldstraw
- Coordinates: 10/16/2017, 11:00 - 12:30, Room 301 + 302
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ES 01.01 - New TNM Classification (ID 7583)
11:00 - 11:20 | Presenting Author(s): Ramon Rami-Porta
- Abstract
- Presentation
Abstract:
Introduction The new tumor, node and metastasis (TNM) classification of lung cancer –the 8[th] edition– has already been discussed in the two previous World Conferences of Lung Cancer. (J Thorac Oncol 2015; 10 (Supp 2): s69; J Thorac Oncol 2017; 12 (Supp 1): s2-s3.) The purpose of this educational session is to revise the innovations of the 8[th] edition, to point out its lights and shadows, and to highlight how they can affect our clinical practice. The innovations introduced in the 8[th] edition were based on sound statistical analyses of 70,189 patients with non-small cell lung cancer and 6,189 with small cell lung cancer diagnosed from 1999 to 2010. (1) Although a large number of patients was registered in the International Association for the Study of Lung Cancer database, data originated mainly from Asia and Europe and the other geographic regions of the world were scarcely represented. The innovations are applicable to both types of carcinomas (2) and also to bronchopulmonary carcinoids. (3) Rules to classify lung cancers with multiple lesions were provided based on data where data were available or on multidisciplinary consensus. (4) Primary tumor (T component) New T categories were introduced based on tumor size: T1a 1-2cm, T1c >2-3cm, T2a >3-4cm, T2b >4-5cm, T3 >5-7cm and T4 >7cm. In addition, endobronchial location less than 2 cm from the carina and total atelectasis /pneumonitis were reclassified as T2, while invasion of the diaphragm was reclassified as T4 and invasion of the mediastinal pleural was deleted as a T descriptor. The definition of visceral pleural invasion proposed for the 7[th] edition, i.e., the invasion of its elastic layer, was confirmed for the 8[th] edition and the recommendation to use elastic stains was reinforced. (5, 6) Codes for adenocarcinoma in situ –Tis(AIS) – and minimally invasive adenocarcinoma –T1mi– were defined, too. (7) Because tumor size has more prognostic relevance, its measurement must be as accurate as possible. The recommendation is to measure it on computed tomography with the lung window, because the mediastinal window may underestimate it. The registered size should be the greatest dimension in any of the available projections: axial, coronal or saggital. For part-solid non-mucinous adenocarcinomas, only does the size of the solid part on computed tomography at clinical staging or the size of the invasive part at pathologic examination count to assign a T category based on tumor size. (7) Nodal involvement (N component) The present N categories (NX, N0, N1, N2 and N3) and their descriptors remain unchanged. An important confirmation in the analyses of survival was that quantification of nodal disease at pathologic staging impacts prognosis: the more involved nodal stations, the worse the prognosis. (8) Therefore, identifying the number of involved nodal stations is important both at clinical and pathologic staging, although it is difficult to determine them accurately at clinical staging unless a lymphadenectomy is performed at the time of mediastinoscopy. The proposed subclassification of the N categories for prospective testing are: N1a – involvement of a single N1 station; N1b – involvement of multiple N1 stations; N2a1 – involvement of a single N2 station without N1; N2a2 – involvement of a single N2 station with N1; and N2b – involvement of multiple N2 stations. N1b and N2a1 have similar prognosis. Metastatic disease (M component) Intrathoracic metastases (M1a: malignant pleural and pericardial effusions and/or nodules, and contralateral separate tumor nodules) remain the same. Extrathoracic metastases were divided into single extrathoracic metastasis (the redefined M1b category) and multiple extrathoracic metastases in one or in several organs (the new M1c category). (9) These innovations imply that counting the number of metastases is important, at least from the prognostic point of view, but also from the therapeutic, because single extrathoracic metastasis can be the base to define oligometastatic disease, the treatment of which is aimed to be radical, with whatever therapeutic means are available, instead of palliative, as it usually is the case with polymetastatic disease. Stage grouping More stages have been created to accommodate the new T1 (T1a N0 M0 is stage IA1, T1b N0 M0 is stage IA2 and T1c N0 M0 is stage IA3) categories; to isolate locally advanced tumors (T3-T4 N3 M0 are now stage IIIC); or to separate metastatic disease (M1a and M1b are stage IVA and M1c is stage IVB). (10) Some tumors have shifted their positions. Tumors that are stage shifters should be treated according to evidence and not according to the treatment for those stages in which they now are based on prognosis, because a mere change in taxonomy does not imply a change in treatment. Clinical judgment in the multidisciplinary team discussions should led to the best therapeutic option for these patients whose tumors have moved from one stage to another. Conclusion The 8[th] edition facilitates the indication of prognosis and the stratification of tumors in future clinical trial, but requires more discipline from us when measuring tumor size, quantifying nodal disease and determining the number of extrathoracic metastasis. References 1. Rami-Porta R, Bolejack V, Giroux DJ et al. J Thorac Oncol 2014; 9: 1618-1624. 2. Nicholson AG, Chansky K, Crowley J et al. J Thorac Oncol 2016; 11: 300-311. 3. Travis WD, Giroux DJ, Chansky K, et al. J Thorac Oncol 2008; 3: 1213-1223. 4. Detterbeck FC, Nicholson AG, Franklin WA et al. J Thorac Oncol 2016; 11: 539-650. 5.Travis WD, Brombilla E, Rami-Porta R et al. J Thorac Oncol 2008; 3: 1384-1390. 6. Rami-Porta R, Bolejack V, Crowley J et al. J Thorac Oncol 2015; 10: 990-1003. 7. Travis WD, Asamura H, Bankier A et al. J Thorac Oncol 2016; 11: 1204-1223. 8. Asamura H, Chansky K, Crowley J et al. J Thorac Oncol 2015; 10: 1675-1684. 9. Eberhardt WEE, Mitchell A, Crowley J et al. J Thorac Oncol 2015; 10: 1515-1522. 10. Goldstraw P, Chansky K, Crowley J et al. J Thorac Oncol 2016; 11: 39-51.
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OA 16 - Treatment Strategies and Follow Up (ID 686)
- Event: WCLC 2017
- Type: Oral
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:Jun Nakajima, T. Demmy
- Coordinates: 10/18/2017, 14:30 - 16:15, Room 315
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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)
15:25 - 15:35 | Author(s): Ramon Rami-Porta
- 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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P1.05 - Early Stage NSCLC (ID 691)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.05-019 - Effects of Tumor Stroma and Inflammation on Survival of Stage I-IIp Lung Cancer (ID 8443)
09:30 - 09:30 | Author(s): Ramon Rami-Porta
- Abstract
Background:
In lung cancer (LC) TNM classification allows an estimation of patient prognosis, but a third of patients with initial stages will relapse within three years. Molecular markers may increase prognostic accuracy and identify subgroups with high risk of progression.
Method:
Stromal (fibrous stroma and α-actin) and inflammation markers (IL1β, TNF-α and COX-2) were examined by immunohistochemistry in tumor tissue from a cohort of 222 patients with early-stage (I-IIp) LC recruited in Spain for the International Association for the Study of Lung Cancer TNM-16 staging project.
Result:
The diagnosis was non-small cell lung carcinoma (NSCLC) in 199 patients (106 adenocarcinoma and 93 squamous cell carcinoma) who were the target for this study. The participants had a mean age of 69 (SD 9) years, frequent respiratory (108, 54.3%) and cardiac (84, 42.2%) comorbidities, and were staged as IA (53, 26.5%); IB (56, 28.1%); IIA (41, 20.6%); IIB (40, 20.1%) or ≥III (9, 4.5%). After three years 94 patients had died (47.2%). In the bivariate analysis, 3-year mortality showed statistically significant associations with more advanced stage (p <0.001) and a higher proportion of fibrous stroma in the tumor (p = 0.014); and a marginal relationship with cardiac comorbidity (p= 0.07) and higher IL1β levels (p = 0.098). Sensitivity and specificity of fibrous stroma and IL1β were calculated and optimal cut-off points established according to Youden’s index. Using these cut-offs, fibrous stroma in >8% of the tumor sample and IL1β H-score levels above 1356 were significantly related to mortality. In Cox proportional hazards models, adjusting by stage and cardiac morbidity, patients with fibrous stroma levels above 8% had higher 3 year-mortality [HR= 2.03, 95% CI (1.1-3.7), p= 0.021]; and similar results were obtained in patients with IL1β levels above 1356 [HR= 2.05, 95% CI (1.1-3.7), p= 0.019]. Combining both markers, patients with both markers above their established cut-offs had a significantly higher risk of 3 year mortality [HR= 2.95% CI (1.1-3.6), p= 0.022].
Conclusion:
An overrepresentation of fibrous stroma and IL1β in the tumor sample is independently associated with 3 year mortality in NSCLC, confirming that the tumor stroma influences survival in LC. Funded by PII Oncology SEPAR and FIS 12-02040
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PL 02 - Presidential Symposium including Top 3 Abstracts and James Cox Lectureship Award Presentation (ID 585)
- Event: WCLC 2017
- Type: Plenary Session
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:Hisao Asamura, Keunchil Park
- Coordinates: 10/17/2017, 08:15 - 09:45, Plenary Hall (Exhibit Hall D)
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PL 02.06 - The IASLC Lung Cancer Staging Project: Analysis of Resection Margin Status and Proposals for R Status Descriptors for Non-Small Cell Lung Cancer (ID 10325)
09:00 - 09:10 | Author(s): Ramon Rami-Porta
- Abstract
- Presentation
Background:
The residual tumor (R) classification describes the tumor status after treatment. It reflects the effectiveness of treatment, has prognostic impact and may affect further treatment. We analyzed existing and potential R status criteria, including the proposed IASLC definition for “uncertain” resection margin status (2005), from data collected for the IASLC Lung Cancer Staging Project.
Method:
This analysis is based on 14,712 patients undergoing NCSLC surgery, for whom full R status and survival data were available. R status criteria and the following data were evaluated: number of N2 stations explored; lobe-specific systematic lymph node dissection (SLND); extra-capsular extension (ECE); status of the highest station; bronchial carcinoma in situ (cis) at bronchial resection margin (BRM); pleural lavage cytology (PLC). Revised categories of R0, R(un), R1 and R2 were designated and tested for survival impact.
Result:
There were 14,293 R0, 263 R1 and 156 R2 cases, with median survival not reached, 33 and 29 months (p<0.0001). R status correlated with T and N stages (p<0.0001). Greater or equal to 3 N2 stations were explored for 9,290 cases (63%) and lobe-specific SLND in 6,619 (45%), with positive associations for increasing pN2 stage (p<0.0001). ECE was recorded in 61 (20%) of 304 N+ cases evaluated. The highest station was positive in 942 (6.4%) cases. PLC was positive in 59 (3.6%) of 1,646 cases and there was BRM cis in 13 cases. After reassignment according to the IASLC proposed definition, there were 6,103 R0 cases, 8,203 R(un), 250 R1 and 156 R2. Figure 1
Conclusion:
These data confirm the proposed criteria for Uncertain R status, R(un), with a prognosis stratifying between R0 and R1. Further detailed prospective data collection is required to characterize fully the prognostic impact of these criteria. Detailed evaluation of R status is of particular importance in the design and analyses of clinical trials of adjuvant therapies.
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