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Andre Luis Moreira
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GR03 - Problem Areas for the Next WHO Classification of Lung Cancers (ID 31)
- Event: WCLC 2019
- Type: Grand Rounds Session
- Track: Pathology
- Presentations: 1
- Now Available
- Moderators:Ming Sound Tsao, Johan Botling
- Coordinates: 9/09/2019, 15:45 - 17:15, Toronto (1985)
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GR03.05 - Grading of NSCLCs - Problems and Solutions (Now Available) (ID 3313)
15:45 - 17:15 | Presenting Author(s): Andre Luis Moreira
- Abstract
- Presentation
Abstract
Background
Tumor grading has been a traditional component of the pathologic evaluation and in many organ systems, tumor grading offers guideline to therapy and patient management. The latter has not been applied to NSCLC. However, considering the new advances in therapy modalities for NSCLC and advances in adenocarcinoma classification, it is now clear that there are different types of adenocarcinomas and these tumors should not be treated the same way. The 2015 WHO classification of pulmonary adenocarcinoma based on the predominant histological pattern has consistently been found to correlate with prognosis. There is broad agreement that the five histological patterns (lepidic, acinar, papillary, solid and micropapillary) are important prognostic indicators. Recent studies have proposed the inclusion of a number of additional pathologic features (the role of secondary patterns, non-traditional pattern such as cribriform and complex glandular patterns, nuclear grade, mitotic counts, presence of spread through alveolar space (STAS), and necrosis.) that also have prognostic value. The addition of these histological features to the predominant pattern could offer greater refinement of a grading scheme. Supplementing the classification of lung adenocarcinomas with an objective grading system will help define prognostic groups that could benefit from the changing landscape of emerging management and treatment options.
Contrary to adenocarcinoma, there has been little advancements in the histological prognostic indicators in squamous cell carcinoma of the lung. Isolated reports have suggested that the presence of tumor budding into the stroma is the sole indicator of poor prognosis. Keratinization, which has been traditionally used to grade these tumors, does not appear to have prognostic value. However, a systematic evaluation of prognostic markers in these tumors have not been carried out. A summary of the current efforts in squamous cell carcinoma will be discussed.
The IASLC pathology panel has proposed a systematic study to evaluate a set of histological criteria that have been described as prognostic indicators in adenocarcinoma aimed at establishing an objective grading system of invasive lung adenocarcinoma.
Design
A multi-institutional study involving well-annotated multiple cohorts of stage 1 adenocarcinomas with at least five years of follow up were evaluated. Annotation included an estimate of the percentage for each histological pattern present for each case; nuclear grade, cytology grade; and mitotic counts with pattern hot-spot association, presence of STAS, and necrosis. A cohort of 284 cases was used as a training set. Univariate analysis was performed to identify significant associations of histological features with recurrence-free survival and overall survival. ROC curve analysis was used to select the best model based on combinations of several features and its association with disease recurrence or death of disease. The results were validate on independent cohorts of 212 cases.
Results
Review of the literature showed that there are many variation in the classification and definitions on non-traditional patterns. In our cohorts, cribriform and complex glandular patterns followed similar curve as traditional high grade patterns (solid and micropapillary), therefore these non-traditional pattern were defined as patterns of high grade in the model. Another are of variation is the percentage of high grade pattern that can influence outcome. Therefore, the cut-off for a high grade pattern associated with recurrence or death of disease was also established in the training cohort and correspond to 20%. Therefore, amounts smaller than 20% of high grade pattern did not influence outcome.
In the training cohort (n=284) all parameters tested, predominant patterns, mitotic count, nuclear grade, cytological grade, and STAS (but not necrosis) were found to have significant prognostic value on a univariate analysis. A Baseline Model composed of Age + Gender + Race + Type of surgery + Pathological Stage; showed an AUC of 0.673. In an attempt to improve this curve, histological parameters were added to the model.
The addition of only the predominant pattern to the baseline increases the AUC to 0.698.
A model based on the combination of predominant pattern paired with the second predominant pattern was found to have the highest AUC (0.765), followed by a combination of predominant pattern plus worse pattern (AUC=0.74). Addition of other histological features (nuclear grade, mitotic count, STAS etc.) did not significantly improve the model.
Similar results were found in the validation set (N=212). The combination of the two most predominant patterns showed an AUC = 0.763, followed by a combination of predominant + worse pattern with AUC = 0.766. Addition of other histological features did not show improvement of the model.
There was no statistical difference between the models using the two most predominant patterns and the predominant plus worse. There was good reproducibility scores for the 2 models
Conclusion
Our results suggest that an objective grading system for pulmonary adenocarcinoma is possible. Considering that there is no significant differences between a model that accounts for the 2 most predominant pattern and another composed of the predominant plus worse pattern. The IASLC pathology panel proposes the later to be used, because pathologists traditionally grade tumors by the worse component. Therefore, histologic assessment of the predominant pattern and worse pattern, would represent the most parsimonious and prognostic grading system for stage I lung adenocarcinomas.
The use of the model in two other independent cohorts of adenocarcinomas (stages 1-3), as well as a reproducibility study will be discussed.
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P2.09 - Pathology (ID 174)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Pathology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.09-24 - IASLC Global Survey for Pathologists on PD-L1 Testing for Non-Small Cell Lung Cancer (ID 906)
10:15 - 18:15 | Author(s): Andre Luis Moreira
- Abstract
Background
PD-L1 immunohistochemistry (IHC) is now performed for advanced non-small cell lung cancer (NSCLC) patients to examine their eligibility for pembrolizumab treatment, as well as in Europe for durvalumab therapy after chemoradiation for stage III NSCLC patients. Four PD-L1 clinical trial validated assays (commercial assays) have been FDA/EMA approved or are in vitro diagnostic tests in multiple countries, but high running costs have limited their use; thus, many laboratories utilize laboratory-developed tests (LDTs). Overall, the PD-L1 testing seems to be diversely implemented across different countries as well as across different laboratories.
Method
The Immune biomarker working group of the IASLC international pathology panel conducted an international online survey for pathologists on PD-L1 IHC testing for NSCLC patients from 2/1/2019 to 5/31/2019. The goal of the survey was to assess the current prevalence and practice of the PD-L1 testing and to identify issues to improve the practice globally. The survey included more than 20 questions on pre-analytical, analytical and post-analytical aspects of the PDL1 IHC testing, including the availability/type of PD-L1 IHC assay(s) as well as the attendance at a training course(s) and participation in a quality assurance program(s).
Result
344 pathologists from 310 institutions in 64 countries participated in the survey. Of those, 38% were from Europe (France 13%), 23% from North America (US 17%) and 17% from Asia. 53% practice thoracic pathology and 36%, cytopathology. 11 pathologists from 10 countries do not perform PD-L1 IHC and 7.6% send out to outside facility. Cell blocks are used by 75% of the participants and cytology smear by 9.9% along with biopsies and surgical specimens. Pre-analytical conditions are not recorded in 45% of the institutions. Clone 22C3 is the most frequently used (61.5%) (59% with the commercial assay; 41% with LDT) followed by clone SP263 (45%) (71% with the commercial assay; 29% with LDT). Overall, one or several LDTs are used by 57% of the participants. A half of the participants reported turnaround time as 2 days or less, while 13% reported it as 5 days or more. Importantly, 20% of the participants reported no quality assessment, 15%, no formal training session for PD-L1interpretation and 14%, no standardized reporting system.
Conclusion
There is marked heterogeneity in PD-L1 testing practice across individual laboratories. In addition, the significant minority reported a lack of quality assurance, formal training and/or standardized reporting system that need to be established to improve the PD-L1 testing practice globally.
