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B. Witte
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P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.01-022 - A Prospective Multicenter Study for ALK IHC+ Metastasized NSCLC (ID 2566)
09:30 - 09:30 | Author(s): B. Witte
- Abstract
Background:
Pulmonary adenocarcinomas may harbor driver mutations, that sensitize tumors to drugs that specifically target the genetic alteration. Metastasized NSCLC with an EML4-ALK translocation are sensitive to a range of tyrosine kinase inhibitors, of which crizotinib is most extensively studied. ALK-positive NSCLC was determined in a phase III trial with fluorescence in situ hybridisation (ALK FISH+). ALK immunohistochemistry (IHC) seems to run parallel with ALK FISH positivity. However discrepant cases occur, which include ALK IHC+ FISH-. The aim of this study is to collect cases with ALK IHC+ and compare within this group response to crizotinib treatment of ALK FISH+ cases with ALK FISH- cases.
Methods:
A prospective multicenter investigator initiated research study was started in Europe. This study is supported by Pfizer. Cases diagnosed with ALK IHC+ lung cancer (5A4 or D5F3) treated with crizotinib are collected centrally. Slides are submitted centrally for validation of ALK IHC (with ETOP and Ventana protocol), ALK FISH (with Vysis probes) and DNA analysis.
Results:
The study started on April 1 2014 and is still open. Currently 10 centers are actively participating. 1443 cases have been examined with ALK IHC of which 39 (2.7%) recorded positive. 24 cases have been submitted to the database. The validation process is still ongoing. The fraction of ALK IHC+ FISH- cases is low. Two cases with ALK IHC+ FISH- metastastatic NSCLC responded to crizotinib treatment. In two cases ALK positivity could not be confirmed (ALK IHC- and ALK FISH-). These patients had progressive disease following crizotinib treatment.
Conclusion:
A clinically relevant question what the effect of ALK inhibitor treatment is on metastatic NSCLC ALK IHC+ FISH- compared to ALK IHC+ FISH+ is examined. Other centers with interested collaborating physicians are invited to participate.
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-040 - Comparison of Histology with Genome-Wide Copy Number Profiling in Patients with Metachronous or Synchronous Tumors (ID 3035)
09:30 - 09:30 | Author(s): B. Witte
- Abstract
Background:
Multiple synchronous and metachronous lung tumors are frequently encountered in patients with lung cancer. In addition, tumors of head and neck (usually squamous cell carcinoma) have a chance for a second primary malignancy in the lung. For treatment purposes it is important to know whether tumors are related (clonal = metastases) or not (multiple primaries). Histopathological comparison of the synchronous or metachronous tumors has been associated with molecular analysis. The purpose of this study is to examine the value of histopathological scoring with genome-wide copy number profiling for determination of clonality.
Methods:
From cases in which array CGH for clonality analysis performed between 2006 and 2012 were selected if at least one intrathoracic tumor was present. In the first years genome-wide copy number profiling was performed with arrayCGH and later with shallow sequencing. Results of the genome-wide copy number profiling were compared to histological (sub)typing.
Results:
100 tumor pairs from 59 patients were examined. 32 pairs were discovered simultaneously (synchronous), the other 68 were metachronous. The histopathological diagnosis was similar in 74 cases (74%). genome-wide copy number profiling revealed evidence for clonality in 55% of the pairs, no-clonality in 28% and was undetermined in 17%. Comparing of histology with genome-wide copy number profiling revealed concordancy in 54 pairs ( 74%; 44 clonal en 10 non-clonal). In 18 of the 62 pairs where histology was similar the genome-wide copy number profiling revealed a non-clonal pattern. In 11 out of 21 pairs where histology differed between the pairs, genome-wide copy number profiling revealed a clonal pattern. Thus histology was not prognostic in 29/83 pairs (35%).
Conclusion:
For the determination of clonality in lung cancer histological examination is discordant with genome-wide copy number profiling in 35% of the comparisons. As histology is a poor predictor of clonality, genome-wide copy number profiling is preferred for clonality analysis between tumors.
