Virtual Library
Start Your Search
J. Chung
Author of
-
+
MA07 - ALK-ROS1 in Advanced NSCLC (ID 385)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
-
+
MA07.07 - Ceritinib in ROS1-Rearranged Non-Small-Cell Lung Cancer: An Update of Korean Nationwide Phase II Study (ID 5953)
11:42 - 11:48 | Author(s): J. Chung
- Abstract
- Presentation
Background:
ROS1 rearrangement is a distinct molecular subset of non-small-cell lung cancer (NSCLC). We investigated the efficacy and safety of ceritinib in patients with ROS1-rearranged NSCLC.
Methods:
We enrolled 32 patients with advanced NSCLC who tested positive for ROS1 rearrangement by fluorescent in situ hybridization (FISH). ROS1 immunohistochemistry (IHC) and next-generation sequencing (NGS) was performed in available tumor samples. Ceritinib 750mg was administered once daily and the primary endpoint was objective response rate (ORR) by central independent radiologic review. The secondary endpoints included disease control rate (DCR), duration of response, progression-free survival (PFS), overall survival (OS), toxicity and concordance between FISH and IHC. ROS1 fusion partners were identified with the use of next-generation sequencing (NGS) in available tumor samples.
Results:
Between June 7, 2013, and February 1, 2016, a total of 404 patients underwent ROS1 prescreening, and 32 ROS1+ (by FISH) patients were enrolled. All patients except two (who did not respond to ceritinib) were crizotinib naïve. The median age of all patients was 62 years, and there were 24 females (75%). The majority of patients (84%) were never smokers, and all had adenocarcinoma histology. The median number of previous treatments before study enrollment was 3 (range, 2-7) and 17 (53%) patients had received three or more lines of chemotherapy. At the time of the data cut-off (April 18, 2016), the median follow-up was 7.5 months, and 15 (47%) patients had discontinued treatment. Of the 32 patients enrolled, 28 patients were evaluable for response by independent radiologic review. ORR was 63% (95% CI, 45.7-79.3), with 1 complete response and 19 partial responses. The median duration of response was 10.0 months (range, 0.4+-18.4+). Among 11 tumors that were tested by NGS, we identified 7 ROS1 fusion partners including ROS1-CD74, ROS1-SLC34A2, and ROS1-EZR. The median progression-free survival was 19.3 months (95% CI, 7.2-not reached), with 17 (53%) patients still in follow-up for progression. The median overall survival was not reached at the time of the data cut-off. Of 5 patients with retrospectively confirmed brain metastases, intracranial disease control was reported in 4 patients (80%). Gastrointestinal adverse events (vomiting, nausea, diarrhea) mostly grade 1-2, were the most frequent adverse events (80%); these events were manageable.
Conclusion:
Ceritinib demonstrated potent clinical activity in patients with advanced, ROS1-rearranged NSCLC, who received at least one prior line of platinum-based chemotherapy. ROS1 rearrangement defines a second molecular subgroup of NSCLC for which ceritinib is highly active (ClinicalTrials.gov number, NCT01964157).
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.
-
+
P3.01 - Poster Session with Presenters Present (ID 469)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 3
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P3.01-018 - Reproducibility in Classification of Small Lung Adenocarcinomas: An International Interobserver Study (ID 5222)
14:30 - 14:30 | Author(s): J. Chung
- Abstract
Background:
The 2015 WHO classification for lung adenocarcinoma (ACA) provides criteria for diagnosis of adenocarcinoma in-situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (INV). Differentiating these entities can be difficult, and as understanding of prognostic significance increases, inconsistent classification is problematic.
Methods:
Sixty cases of lung ACAs (<2cm) were reviewed by an international panel of 6 lung pathologists. One slide reflecting overall morphology of each case was digitally scanned to an internet browser-based viewer. In round one, the panel independently reviewed each case to assess predominant pattern, invasive component size, and final diagnosis (AIS, MIA or INV). After a consensus conference among participants, a second round of independent review of the cases was performed. Additionally, a discussion on interpretation of elastic stain for evaluation of invasion will precede a third round of review with assessment of a concomitant elastic stain for each case. Statistical analysis was performed for each round.
Results:
In round one, the overall kappa value for AIS versus MIA and INV was 0.34 (fair agreement), and that for AIS and MIA versus INV was 0.44 (moderate agreement). The raters had 100% agreement on final diagnosis in 10 cases (AIS, n=2; MIA, n=2; INV, n=6). In 28 cases with poor agreement on final diagnosis and invasive measurement, inconsistent measurement of multifocal invasion led to wide variance in 5 cases, and subjectivity in pattern recognition led to variance in 23 cases. Misinterpretation of the WHO criteria for MIA resulted in 18 instances of misclassification across all raters. A case with a predominant mucinous lepidic pattern had a range of diagnoses (AIS, n=1; MIA, n=1; INV, n=4). In round two, the overall kappa value for AIS versus MIA and INV is 0.40 (fair agreement), and that for AIS and MIA versus INV is 0.36 (moderate agreement). The raters had 100% agreement on final diagnosis in 12 cases (AIS, n=3; MIA n=4; INV, n=5). Misinterpretation of the WHO criteria for MIA was seen in 6 instances. The intraobserver kappa coefficient ranged widely from 0.259 to 0.859.
Conclusion:
Interobserver agreement on diagnosis of small lung ACAs between raters was fair to moderate, with minimal improvement after a consensus conference. Inconsistent measurement of multifocal invasion, subjectivity in pattern recognition, misinterpretation of the WHO criteria, and subjective interpretation of mucinous ACA have contributed to interobserver discordance. A third round of evaluation is currently ongoing to assess for improvement and the utility of elastic stains.
-
+
P3.01-021 - Reproducibility of Comprehensive Histologic Assessment and Refining Histologic Criteria in P Staging of Multiple Tumour Nodules (ID 5365)
14:30 - 14:30 | Author(s): J. Chung
- Abstract
Background:
Multiple tumor nodules (MTNs) are being encountered, with increasing frequency with the 8[th] TNM staging system recommending classification as separate primary lung cancers (SPLC) or intrapulmonary metastases (IM). Pathological staging requires assessment of morphological features, with criteria of Martini and Melamed supplanted by comprehensive histologic assessment of tumour type, predominant pattern, other histologic patterns and cytologic features. With publication of the 2015 WHO classification of lung tumours, we assessed the reproducibility of comprehensive histologic assessment and also sought to identify the most useful histological features.
Methods:
We conducted an online survey in which pathologists reviewed a sequential cohort of resected multifocal tumours to determine whether they were SPLC, IM, or a combination. Specific histological features for each nodule were entered into the database by the observing pathologist (tumour type, predominant adenocarcinoma pattern, and histological features including presence of lepidic growth, intra-alveolar cell clusters, cell size, mitotic rate, nuclear pleomorphism, nucleolar size and pleomorphism, nuclear inclusions, necrosis pattern, vascular invasion, mucin content, keratinization, clear cell change, cytoplasmic granules¸ lymphocytosis, macrophage response, acute inflammation and emperipolesis). Results were statistically analyzed for concordance with submitting diagnosis (gold standard) and among pathologists. Consistency of each feature was correlated with final determination of SPLC vs. IM status (p staging) by chi square analysis and Fisher exact test.
Results:
Seventeen pathologists evaluated 126 tumors from 48 patients. Kappa score on overall assessment of primary v. metastatic status was 0.60. There was good agreement as measured by Cohen’s Kappa (0.64, p<0.0001) between WHO histological patterns in individual cases with SPLC or IM status but proportions for histology and SPT or IM status were not identical (McNemar's test, p<0.0001) and additional histological features were assessed. There was marked variation in p values among the specific histological features. The strongest correlations (<0.05) between p staging status and histological features were with nuclear pleomorphism, cell size, acinus formation, nucleolar size, mitotic rate, nuclear inclusions, intra-alveolar clusters and necrosis pattern. Correlation between lymphocytosis, mucin content, lepidic growth, vascular invasion, macrophage response, clear cell change, acute inflammation keratinization and emperipolesis did not reach a p value of 0.05.
Conclusion:
Comprehensive histologic assessment shows good reproducibility between practicing lung pathologists. In addition to main tumour type and predominant patterns, nuclear pleomorphism, cell size, acinus formation, nucleolar size, and mitotic rate appear to be useful in distinguishing between SPLC and IM.
-
+
P3.01-061 - Prognostic Significance of Stem Cell-Related Marker Expression and Its Correlation with Histologic Subtypes in Lung Adenocarcinoma (ID 4661)
14:30 - 14:30 | Author(s): J. Chung
- Abstract
Background:
Cancer stem cells (CSCs) are a small subset of tumor cells that exhibit stem cell-like properties and contribute in treatment failure. CSCs can be distinguished from other cancer cells on the basis of specific markers. Although the clinical impact of these markers is unclear, they may have a prognostic or predictive value in NSCLC.
Methods:
To clarify the expression and prognostic significance of several CSC markers in non-small cell lung cancer, we retrospectively analyzed 368 patients with adenocarcinoma (n = 226) or squamous cell carcinoma (n = 142). We correlated the expression of six CSC markers – CD133, CD44, aldehyde dehydrogenase 1 (ALDH1), sex determining region Y-box 2 (SOX2), octamer binding transcription factor 4 (OCT4), and Nanog – with clinicopathologic and molecular variables and survival outcomes.
Results:
In adenocarcinoma, CD133, ALDH1 and CD44 expression was associated with low pathologic stage and absence of lymphovascular invasion, while Nanog expression correlated with high histologic grade, lymphatic invasion and increased expression of Snail-1, a transcription factor associated with epithelial-mesenchymal transition. CSC marker expression was also associated with histologic subtypes in adenocarcinoma. Multivariate analysis showed that high Nanog expression was an independent factor associated with a poor prognosis in adenocarcinoma.
Conclusion:
In conclusion, we have shown that CSC markers may be prognostic factors in NSCLC, and high Nanog expression is an independent prognostic factor for poor survival that may be associated with EMT features in ADC patients. In addition, the clinicopathologic implication of CSC markers in lung ADC differed from those in tumors arising from other organs. Thus, the impact of CSC marker expression should be considered in a tumor/organ specific manner.
