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V. Rusch
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ED05 - The 8th Edition of the TNM Staging System (ID 268)
- Event: WCLC 2016
- Type: Education Session
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:P. Goldstraw, R. Rami-Porta
- Coordinates: 12/05/2016, 16:00 - 17:30, Hall C1
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ED05.02 - Update on the Mesothelioma Staging System (ID 6444)
16:25 - 16:45 | Author(s): V. Rusch
- Abstract
- Presentation
Abstract:
The initial TNM staging classification for malignant pleural mesothelioma (MPM), published in the 6th edition of the UICC and AJCC staging manuals, was derived from analyses of small retrospective surgical series. It has been criticized for being insufficiently evidence-based and difficult to apply to clinical staging. To identify potential deficits in the MPM staging classification, the IASLC Staging and Prognostic Factors Committee (ISPC), in collaboration with members of the International Mesothelioma Interest Group (IMIG), initiated a large multinational database in 2009. This approach was modeled on methods used by the IASLC to revise the lung cancer staging system. Data were submitted on 3,101 patients from 15 centers on 4 continents, all of whom had some form of surgical management, and an initial analysis was published in 2012. Overall survival (OS) data largely supported continued use of the original MPM staging classification but identified several important areas for improvement, particularly for the T and N components. To address issues raised by this initial analysis, a second iteration of the IASLC MPM database was started in 2013 to inform revisions for the 8th edition of the AJCC / UICC staging systems. The data dictionary was revised to provide more granular information for the T, N and M descriptors and a new electronic data capture (EDC), housed at the biostatistical center CRAB (Cancer Research and Biostatistics, Seattle, WA, USA), was developed. Additional investigators who could provide valid information on patients with tumors staged clinically and managed non-surgically were recruited. Data to inform revisions for the 8th edition of the MPM staging classification originated from 29 centers on 4 continents and included 3,519 cases of which 2,460 passed the initial eligibility screen. As planned, this dataset included both patients managed surgically and non-surgically. OS examined for T categories according to the current 7th edition staging classification showed a clear difference between all clinically staged categories except for T1a versus T1b and T3 versus T4. Pathological staging failed to demonstrate a survival difference between adjacent categories with the exception of T3 versus T4. Performance improved with collapse of T1a and T1b into a single T1 category. Analyses suggested that all current T descriptors should be maintained. Tumor thickness and morphology were also significantly associated with OS. Consequently, a recommendation was made to collapse both clinical and pathological T1a and T1b into a T1 category. Because simple measurement of pleural thickness had prognostic significance, it was felt that this should be examined further with a view to incorporation into future revisions of the staging classification. With respect to the N categories (as defined in the 7th edition staging classification), there was no significant difference in OS between cN0, cN1 and cN2, likely reflecting the inaccuracies of current methods for clinical lymph node staging in MPM. For pathologically staged tumors, patients with pN1 or pN2 tumors had a worse OS than those with pN0 tumors but no OS difference was noted between those with pN1 and pN2. Exploratory analyses found that tumors with both pN1 and pN2 nodal involvement had a poorer OS than those with pN2 only. Consequently, a recommendation was made to collapse N1 and N2 into a new N1 category and to relabel the current N3 category as N2. Larger numbers of well staged cases are needed to determine whether this new N1 category should be subdivided in the future according to the number of involved lymph node stations. Of the 3,519 submitted cases, 84 were cM1 at diagnosis. Median OS for cM1 was significantly worse than for T4 or N3 (as defined in the 7th edition) supporting inclusion of only cM1 in the stage IV group. Exploratory analyses suggested a possible difference in OS for single versus multiple site cM1 but additional data are needed in the future to determine the validity of this finding. Candidate stage groups were developed using a recursive partitioning and amalgamation (RPA) algorithm applied to all cM0 cases. Based on these analyses, optimal stage groupings proposed for the 8th edition of the staging classification were: stage IA (T1N0), stage IB (T2-3N0), stage II (T1-2N1), stage IIIA (T3N1), stage IIIB (T1-3N2 or any T4) and stage IV (any M1). These new stage groupings are substantially different from what is currently used in the 7th edition. The IASLC database is the largest available multinational database in this rare malignancy and has provided the first evidence-based revisions of the TNM classification for MPM leading to substantial changes in the T and N components and the stage groupings. Continued efforts to accrue to this database will be important to inform further changes for the 9th edition of the staging classification.[1-7] Reference List (1) Rusch VW, The International Mesothelioma Interest Group. A proposed new international TNM staging system for malignant pleural mesothelioma. Chest 1995;108:1122-8. (2) Rusch VW, Giroux D, Kennedy C, Ruffini E, Cangir AK, Rice D, et al. Initial analysis of the International Association for the Study of Lung Cancer Mesothelioma Database. J Thorac Oncol 2012;7:1631-9. (3) Pass HI, Giroux D, Kennedy C, Ruffini E, Cangir AK, Rice D, et al. Supplementary prognostic variables for pleural mesothelioma: A report from the IASLC Staging Committee. J Thorac Oncol 2014;9(6):856-64. (4) Pass HI, Giroux D, Kennedy C, Ruffini E, Cangir AK, Rice D, et al. The IASLC Mesothelioma Database: Improving staging of a rare disease through international participation. J Thorac Oncol. In press 2016. (5) Nowak AK, Chansky K, Rice DC, Pass HI, Kindler HL, Shemanski L, et al. The IASLC Mesothelioma Staging Project: Proposals for revisions of the T descriptors in the forthcoming eighth edition of the TNM classification for mesothelioma. J Thorac Oncol. In press 2016. (6) Rice DC, Chansky K, Nowak AK, Pass HI, Kindler HL, Shemanski L, et al. The IASLC Mesothelioma Staging Project: Proposals for revisions of the N descriptors in the forthcoming eighth edition of the TNM classification for malignant pleural mesothelioma. J Thorac Oncol. In press 2016. (7) Rusch VW, Chansky K, Kindler HL, Nowak A, Pass HI, Rice DC, et al. The IASLC Malignant Mesothelioma Staging Project: Proposals for the M descriptors and for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for mesothelioma. J Thorac Oncol. In press 2016.
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OA01 - Risk Assessment and Follow up in Surgical Patients (ID 371)
- Event: WCLC 2016
- Type: Oral Session
- Track: Surgery
- Presentations: 1
- Moderators:W. Zhong, E. Lim
- Coordinates: 12/05/2016, 11:00 - 12:30, Schubert 2
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OA01.03 - Impact of Increasing Age on Cause-Specific Mortality and Morbidity in Stage I NSCLC Patients: A Competing Risk Analysis (ID 4952)
11:20 - 11:30 | Author(s): V. Rusch
- Abstract
- Presentation
Background:
At the time of diagnosis, two-thirds of patients with lung cancer are ≥65 years of age with significant comorbidities. We sought to determine the short- and long-term cancer- and noncancer-specific mortality and morbidity in patients who underwent resection for stage I non-small cell lung cancer (NSCLC).
Methods:
Of 5371 consecutive patients who had undergone curative-intent resection of primary lung cancer (2000–2011), 2186 patients with pStage I NSCLC were included in the analysis. All preoperative clinical variables known to affect outcomes were considered, including, Charlson comorbidity index, predicted postoperative (ppo) diffusion capacity of the lung for carbon monoxide (DLCO), and ppo–forced expiratory volume in 1 second (FEV1). Association between factors and cause-specific mortality was performed using competing risks approach.
Results:
Of 2186 patients, 1532 patients (70.1%) were ≥65 years of age, including 638 patients (29.2%) ≥75 years of age. In patients ≥65 years of age, for up to 2.5 years after resection, noncancer-specific CID was higher than lung cancer–specific CID, the higher noncancer-specific early-phase mortality was enhanced in patients ≥75 years of age compared with 65-74 years of age (Figure 1a). Multivariable analyses adjusted by age, sex, smoking status, comorbidities, tumor size, and surgical procedures showed that low ppoDLCO was an independent predictor for severe morbidity (p<0.001), 1-year mortality (p<0.001), and noncancer-specific mortality (p<0.001), whereas low ppoFEV1 for lung cancer–specific mortality (p=0.002). PpoDLCO can be used for estimation of 5-year cumulative incidence of noncancer death (Figure 1b, right, red curve) because of its linear relation, whereas ppoFEV1 for lung cancer-specific death (Figure 1b, left, black curve).
Conclusion:
In patients undergoing curative-intent resection of stage I NSCLC, noncancer-specific mortality is a significant competing event, with increasing impact as patient age increases. Figure 1
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P2.06 - Poster Session with Presenters Present (ID 467)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.06-019 - A Phase II Study of Atezolizumab as Neoadjuvant and Adjuvant Therapy in Patients (pts) with Resectable Non-Small Cell Lung Cancer (NSCLC) (ID 4642)
14:30 - 14:30 | Author(s): V. Rusch
- Abstract
Background:
There is no curative treatment for patients with NSCLC who develop metastatic disease after resection. Trials of neoadjuvant and adjuvant chemotherapy have demonstrated an absolute survival benefit of 5% for patients with stages IB, II, and IIIA disease. Clearly, developing new treatment strategies to improve survival following resection is critical to improving outcomes for this patient population. Immunotherapy with checkpoint inhibitors such as antibodies to PD-1 and PD-L1 has demonstrated superior survival compared to chemotherapy in randomized clinical trials. PD-L1 expression is being investigated as a predictive biomarker for these therapies, but its ability to predict response has varied in published trials. Atezolizumab is a humanized IgG1 monoclonal PD-L1 antibody that was recently evaluated in the POPLAR trial (NCT01903993), a phase II randomized trial of patients with NSCLC who progressed on platinum based chemotherapy. Atezolizumab therapy improved overall survival compared with docetaxel (12.6 months vs. 9.7 months, HR 0.73 [95% CI 0.53 – 0.99]) with a manageable safety profile. Improvement in survival correlated with PD-L1 immunohistochemistry expression of tumor and tumor-infiltrating immune cells.
Methods:
Trial design: This phase II, open-label, single-arm study is designed to evaluate the efficacy and safety of atezolizumab as a neoadjuvant therapy in patients with Stage IB, II, or IIIA NSCLC prior to curative-intent resection. Approximately 180 patients with NSCLC will be enrolled in this study at 15 academic medical centers in the United States. There are two parts to this study: the first/primary part will evaluate the ability of neoadjuvant atezolizumab to produce objective pathologic responses in patients with early stage NSCLC. Atezolizumab 1200 mg IV will be given every 3 weeks for two doses. Surgical resection of tumors following treatment will allow determination of pathologic response rates and potential predictive biomarkers. Part 2 is exploratory and will evaluate atezolizumab adjuvant therapy for up to 12 months in patients who demonstrate clinical benefit (evidence of pathologic response or absence of radiographic progression) in Part 1. After surgical resection, patients may receive SOC adjuvant chemotherapy (with or without radiation) before starting atezolizumab adjuvant therapy in Part 2. The primary objectives are safety and major pathologic response based on surgical resection. Secondary objectives include overall response rate based on PD-L1 status, mutational load, antigen burden, and RNA-sequencing. This trial presents a unique opportunity to evaluate exploratory biomarkers, including pre- and post-treatment biopsy assessment of evolution of immune related markers associated with response.
Results:
Section not applicable
Conclusion:
Section not applicable
