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Tadeusz Orłowski
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P1.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 948)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.16-55 - Surgical Treatment for Lung Cancer. Subaortic (Para-Aortic) Lymph Nodes Involvement - N1 or N2 Disease? (ID 13693)
16:45 - 18:00 | Author(s): Tadeusz Orłowski
- Abstract
Background
In patients with cN2 disease surgical treatment alone is not recommended because it often indicates systemic disease. Qualification to undergo a surgery patients with clinical manifestation of subaortic (#5)/para-aortic (#6) nodes malignant involvement remains controversial. The aim of this study is to compare survivals of patients with single station metastases to #5(#6) lymph nodes, patients with interlobar (#11) and lobar (#12) nodes involvement (pN1) and patients with right lower paratracheal (#4R) and subcarinal (#7) nodes involvement (pN2) after received lung resection.
a9ded1e5ce5d75814730bb4caaf49419 Method
Material was collected rectospectively from an online-survey-based database of the Polish Lung Cancer Group and included patients who underwent a surgical treatment due to lung cancer at multi-institution in Poland between 2007 and 2017. The 8th Edition of the Staging Classification System (TNM, 2017) was used to determine staging.
4c3880bb027f159e801041b1021e88e8 Result
There were 34 870 patients (35,52% females and 64,48% males) who received surgical treatment for lung cancer. 27 321 (78,35%) underwent lobectomy, 1 063 (3,04%) segmentectomy, 4 658 (13,35%) pneumonectomy, 1 768 (5,07%) wedge resection. Histologic types included: non-small cell lung cancer (n= 475), adenocarcinoma (n=13 515), squamous cell carcinoma (n=14 273), large cell carcinoma (2 127), carcinoid (n=1 428) and others (n=2 934). Stage IA1 disease presented 683 (1,97%) patients, IA2 - 4442 (12,79%), IA3 - 3674 (10,58%), IB - 7150 (20,59%). Stage IIA disease presented 2493 (7,18%) patients, IIB - 7442 (21,43%). 6804 (19,59%) patients were in stage IIIA disease, 1529 (4,4%) in IIIB and 475 (1,37%) in IVA, 12 (0,03%) in IVB disease. The majority of patients were diagnosed with N0 disease (n: 24388, 70,23%). N1 disease was reported in 5913 (17,03%) cases, N2 disease in 4 412 (12,71%).
Among patients with N1 disease there were 3543 cases with confirmed metastases only in #11 or #12 nodes. 3-, 5-, 7- and over 7-year survivals in this group were 70,03%, 15,33%, 8,41%, 6,24%. Among patients with N2 disease there were 1202 cases with exclusive involvement of #4R or #7 nodes. 3-, 5-, 7- and over 7-year survivals in this group were 73,21%, 14,14%, 7,74%, 4,91%. Malignant involvement of #5 or #6 nodes were reported in 1047 cases. 3-, 5-, 7- and over 7-year survivals here were 75,17%, 14,04%, 6,59%, 4,2%.
8eea62084ca7e541d918e823422bd82e Conclusion
According to the study there is no significant difference in survival of patients with #5(6) nodes invasion comparing to those with N2 and N1 disease. Controversy followed from classification #5(6) nodes as N2 remains unsettled.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.13-31 - p.(Leu747Pro) Mutation Leads to Misdiagnosis in EGFR Mutation Assessment – Analysis in a Cohort of 1841 Polish NSCLC Patients (ID 14123)
16:45 - 18:00 | Author(s): Tadeusz Orłowski
- Abstract
Background
Epidermal growth factor receptor (EGFR) mutation assessment is essential for targeted therapy of non-small cell lung cancer (NSCLC) as predictive biomarker of the response to EGFR tyrosine kinase inhibitors (EGFR-TKI).
There is a number of well-known actionable mutations in EGFR gene such as a deletions in exon 19 or p.(Leu858Arg), still some others, infrequent or complex are also observed.
Missense substitution p.(Leu747Pro) (c.2239_2240TT>CC) is one of the rare mutations that might be misdiagnosed if EGFR mutation analysis is performed with commercial real-time PCR based kits. The eventual clinical consequences are considerable. While p.(Leu747Pro) substitution is reported as an most likely inhibiting mutation, it might be confused with an activating deletion in exon 19 of EGFR gene.
Up to date, majority of published reports providing data on p.(Leu747Pro) role in resistance towards EGFR-TKI came from Asia.
The frequency of p.(Leu747Pro) in the European population has not been evaluated yet. It was detected accidentally in large NSCLC patients cohorts using varied molecular methods.
The aim of the study was to assess the frequency of p.(Leu747Pro) in a group of 1841 NSCLC patients referred for EGFR mutation analysis between 2015 and 2017 to the National Institute of Tuberculosis and Lung Diseases.
a9ded1e5ce5d75814730bb4caaf49419 Method
EGFR mutation analysis was performed with CE-IVD real-time PCR kit using complementary primer pairs and oligonucleotide probes.
The frequency of EGFR gene mutations was 8,4% (n=155), including deletions in exon 19 (n=84), p.Leu858Arg (n=56), insertions in exon 20 (n=9), p.Glu719X (n=1), p.Glu719X and p.Ser768Ile(n=5).
All samples with a deletion in exon 19 were reanalyzed by PNA-LNA PCR clamp to confirm the test result.
In case of a discrepancy between the outcomes, direct Sanger sequencing was performed.
4c3880bb027f159e801041b1021e88e8 Result
Upon reanalysis, 4 (4,8%) lung adenocarcinoma patients (3 female, 1 male) with initially identified deletion in exon 19 proved to be misdiagnosed. Instead, in all p.(Leu747Pro) substitution was decisively confirmed with direct sequencing.
One patient with p.(Leu747Pro) mutation in EGFR gene gained clinical benefit from EGFR-TKI therapy. She achieved partial response according to RECIST while treated with erlotynib for 7 months.
8eea62084ca7e541d918e823422bd82e Conclusion
Diagnostic laboratories as well as clinicians should be aware of the commercial real-time PCR based test limitations, despite their IVD certification.
New methods such as next generation sequencing may solve misdiagnosis problem with the exon 19 deletion of EGFR gene.
Data concerning rare variants in EGFR gene are limited and results are varied, the mechanism of the p.(Leu747Pro) variant response to EGFR-TKIs needs further investigation.
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