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Philippe Joubert
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ES25 - Unmet Need Issues of Current TNM (ID 179)
- Event: WCLC 2020
- Type: Educational Session
- Track: Staging
- Presentations: 1
- Moderators:
- Coordinates: 1/31/2021, 11:45 - 12:45, Scientific Program Auditorium
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ES25.06 - Special Issues: Subsolid Tumors (ID 4005)
11:45 - 12:45 | Presenting Author(s): Philippe Joubert
- Abstract
- Presentation
Abstract
In 2011, the introduction of the lepidic pattern was one of the most notable modifications supported by the International Association for the Study of Lung Cancer (IASLC), the American Thoracic Society (ATS) and the European Respiratory Society (ERS)1. The new concept of invasive versus non-invasive components led to significant revisions in the most recent edition (8th) of the tumor, node and metastasis (TNM) classification2. Among all, the T classifier underwent modifications including the integration of adenocarcinoma in situ (Tis) and minimally invasive adenocarcinoma (T1mi). In addition, the TNM staging system recommended using the invasive size instead of total size when assessing the pathology T descriptor in a resected nonmucinous adenocarcinoma (AC) with a lepidic component. This was based on the acceptance that the size of the invasive patterns of these tumors better predicts the prognosis versus the total size3,4.
Pulmonary AC presenting as subsolid lesions are commonly encountered in the daily practice and are defined as any AC with a ground-glass component. Ground-glass opacity (GGO) is radiologically characterized by hazy increased opacity of the lung that does not obscure underlying bronchial structures or pulmonary vessels on chest computerized tomography (CT) scan5. In pathology, GGO normally corresponds to a lepidic pattern microscopically while the invasive component is visualized as a solid area, which is usually sharply circumscribed and firm. This area is measured using a ruler placed along the largest axis of the tumor. In general, the gross aspect of the invasive component contrasts with the ill-defined, slightly condensed lung parenchyma seen with a lepidic component. The importance to review the preoperative chest-CT before the procedure for a radiology-pathology correlation cannot be overemphasized as it allows to validate that the greatest diameter seen on radiology corresponds to the size assessed on gross examination. In cases where there is a significant discrepancy between these two measures, the pathologist must ensure that the largest diameter was correctly identified in pathology.
Because it is sometimes difficult to distinguish between reactive tissue such as organizing pneumonia and fibrosis that may arise at the periphery of a tumor, and tumor tissue itself, a thorough sampling of the edges of the tumor should be performed for microscopic evaluation. In cases in which there is a prominent fibroinflammatory reaction surrounding the tumor or when a tumor invades a fibrotic scar, an estimation of the percentage of the neoplastic component should be done and the total solid size multiplied by this percentage to obtain the invasive size to be applied for T staging. Therefore, the microscopic evaluation remains a crucial element of the size assessment. Because the scars seen in a cancer are generally thought to be induced by the cancer itself, it is recommended to include these foci of fibrotic tissue in the total measurement of invasive component, unless they seem unrelated to the tumor, as we frequently see in AC developed in association with an apical scar.
In summary, the new modifications proposed in the 8th edition of the TNM led the pathologists to revisit their approach to examine lung cancer specimens in the gross room. Among the most important elements to include in the pathology examination protocol for subsolid lung AC: 1) assess the invasive size (grossly and microscopically) to determine the T descriptor; 2) exclude the reactive elements from the invasion size evaluation.
References:
Travis WD et al. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011;6(2):244-85.
Lim W et al. The 8(th) lung cancer TNM classification and clinical staging system: review of the changes and clinical implications. Quant Imaging Med Surg. 2018;8(7):709-18.
Travis WD 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(1556-1380 (Electronic)):1204-23.
Kameda K et al. Implications of the Eighth Edition of the TNM Proposal: Invasive Versus Total Tumor Size for the T Descriptor in Pathologic Stage I-IIA Lung Adenocarcinoma. J Thorac Oncol. 2018;13(12):1919-29.
Hansell DM et al. Fleischner Society: glossary of terms for thoracic imaging. Radiology. 2008;246(3):697-722.
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FP07 - Pathology (ID 109)
- Event: WCLC 2020
- Type: Posters (Featured)
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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FP07.08 - A Pan-Canadian Validation Study for the Detection of EGFR-T790M Mutations Using Circulating Tumour DNA (ctDNA) from Blood (ID 1294)
00:00 - 00:00 | Author(s): Philippe Joubert
- Abstract
- Presentation
Introduction
In advanced non-small cell lung cancer (NSCLC) patients with resistance to EGFR inhibitors, tumor genotyping to identify T790M resistance mutations is mandated. However, because of challenges such as tumour inaccessibility, tumour heterogeneity and patient morbidity, the measurement of circulating tumour DNA (ctDNA) in peripheral blood has emerged as a promising non-invasive clinical tool to detect this mutation. To facilitate standardization and clinical adoption of ctDNA testing across Canada, we developed a 2-phase multicentre RING study to standardize EGFR-T790M mutation detection using plasma ctDNA testing.
Methods
In Phase 1, commercially available cell-free DNA reference standards including a variety of clinically relevant variants were distributed to nine participating clinical molecular laboratories. Each site employed their existing platforms for mutation detection, including next generation sequencing (ThermoFisher Oncomine Lung cfDNA assay; Illumina TruSight Tumor 15 - TST15 panel), Bio-Rad digital droplet PCR, EntroGen ARMS-based ctEGFR mutation detection kit, Roche cobas EGFR mutation kit and the MassARRAY UltraSEEK Lung Panel). Baseline performance characteristics were established to ensure that the methods at each site were compatible with clinical application. Performance characteristics, including limit of detection, were further tested through distribution of blinded engineered plasma samples spiked with predetermined concentrations of T790M and L858R variants. Six of the labs proceeded to Phase II, where a series of blood samples, collected from local patients with known EGFR activating mutations progressing on treatment, were assayed for the presence of the primary mutation and the T790M variant. A blood sample was also sent out to the reference center using a clinically validated test (ddPCR, Bio-Rad). Blinded results were reported to a central repository to assess the concordance between the results.
Results
All labs in Phase I detected variants (T790M, L858R, Ex19 deletion alone or T790M/L858R) at allele frequencies of 0.5% and 5.0%. Four labs also reported detection of some variants at 0.05%. For the blinded samples, all labs identified the T790M and T790M/L858R variants at 0.5% and 5.0% (100% concordance). No false positives were reported for the EGFR wild type control.
Six labs proceeded to Phase II using local patient-derived samples with the Cobas (Lab1), EntroGen (Labs 2, 4), NGS (Labs 3, 5) and ddPCR (Lab 6) platforms. The concordance between the reference and local labs for detection of both the sensitizing mutation and the resistance mutation was high, with NGS and ddPCR showing the best overall (~100%) concordance. The overall detection rate of T790M in this project was 22%. One lab using the EntroGen assay had lower concordance overall, but the other lab using the same kit had higher concordance, suggesting this could be a lab specific issue. These data suggest that the ability to detect EGFR resistance mutations at clinically relevant limits of detection is generally not only platform specific, but also impacted by lab specific practices.
Conclusion
These results indicate that the NGS and ddPCR platforms yielded the most concordant results for EGFR T790M detection in ctDNA when compared to a clinically validated reference lab. Discrepancies between sending labs using the same assay suggest that lab-specific factors may impact performance.
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.
