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G. Rossi
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P1.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 224)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.08-021 - Role of Surgery in Sarcomatoid Tumors of the Lung: A Multicentre Analysis (ID 44)
09:30 - 09:30 | Author(s): G. Rossi
- Abstract
Background:
Sarcomatoid lung carcinoma (SaLC) is a very rare and aggressive subtype of non-small cell lung cancer (NSCLC). To better understand the long-term results after surgical treatment and the main prognostic factors of such rare entities, we have revisited the clinical records of patients affected by SaLC in a large multicentre surgical series.
Methods:
Among 6569 patients who underwent curative resection for NSCLC from 01/2003 to 12/2013 in 5 Institutions, 148 patients (2.2%) had sarcomatoid carcinoma. Clinical and pathological data were retrospectively reviewed. Kaplan-Meier method, log-rank test and Cox-regression analysis were used for the statistical analysis when indicated.
Results:
Mean age and male/female ratio were 66.6±9.9 yrs and 120/28, respectively. The main clinical, surgical and pathological features of the population are summarized in Table 1. Thirty-six pts (24.3%) had pathologic stage-I disease and 70 pts (47.3%) presented with mixed histological tumor (SaLC combined with NSCLC). The overall median and 5-year (LTS) survivals were 17 months and 11.3%, respectively. During follow-up, 101 patients (68.2%) experienced a relapse of disease (84 pts (57%) at distance). Log-rank analysis identified the administration of pre-op PET/CT scan (LTS: yes=17.9% vs no=5.5%; p=0.040), the surgical radicality (LTS: R0=13.2% vs R+=0%, p<0.001), the pStage (LTS: p-I=13.2%, p-II=10.6%, p-III=6.3%, p-IV=0%; p<0.001) as prognostic factors in SaLC patients. Finally, Cox regression analysis confirmed the administration of pre-op PET/CT scan (p=0.021), the surgical radicality (p<0.001) and the p-Stage (p=0.022) as independent prognostic factors in such cohort of patients.
Conclusion:
Primary SaLC presented a poor prognosis after surgical treatment (overall 5-yr survival=11.3%), even in early stages (LTS: 13.2% in pStage-I). Such results imply that the role of surgery for primary SaLC is questionable and eventually limited (after an accurate preoperative staging) to “early-stage” tumors only. In this framework, stronger efforts should be made for target therapies development for such rare entity. Figure 1
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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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P3.04-015 - Immunohistochemistry With 3 ALK Antibodies and Thymidylate Synthase Evaluation of FISH-Positive ALK-Rearranged Lung Adenocarcinomas (ID 1430)
09:30 - 09:30 | Author(s): G. Rossi
- Abstract
Background:
ALK-rearranged lung tumors represent approximately 2-7% of all Non-Small-Cell Lung Cancers (NSCLCs). Young age, never/light smoking habit, adenocarcinoma (ADK) histology and good response to chemotherapy with pemetrexed characterize ALK-positive patients (pts). Current treatment strategies in this molecular setting are based on ALK-kinase inhibition with small molecules including first (crizotinib/CZT) and second generation TKIs. The FDA-approved companion diagnostic test for CZT treatment is the Vysis break-apart FISH probe, but several works support the immunohistochemistry (IHC) as a sensitive and specific test. The European Medical Agency (EMA) recently approved CZT for second-line treatment of ALK-rearranged NSCLC as detected by "an accurate and validated ALK assay", thus endorsing IHC for eligibility purposes. Here, we retrospectively assessed ALK status in 28 pts with known FISH-positive ALK-rearranged NSCLC performing IHC with 3 different antibodies in order to assess their diagnostic accuracy as compared to the FISH assay. Moreover, we evaluated thymidylate synthase (TS) expression using real-time polymerase chain reaction (RT-PCR) given the conflicting literature data on pemetrexed sensitivity in those tumors. As a secondary end point we will compare molecular and clinical outcomes.
Methods:
FISH was performed with Vysis break-apart FISH probe. IHC was performed with 3 different antibodies: ALK1 (DAKO), 5A4 (Novocastra) and D5F3 (Ventana/Cell Signaling Technology). For ALK1 and 5A4 an IHC scoring value between 0+ and 3+ was used, as previously proposed, while a positive or negative score was used with D5F3 and Ventana KIT. TS gene expression was measured through Real Time PCR, TaqMan method.
Results:
28 specimens of ALK-rearranged ADK diagnosed between 2010 and 2013 from 7 different Italian Oncology Centres were evaluated. Pts median age at diagnosis was 55 (range: 25-78), 9 pts were female. 25/28 (89.3%) specimens were D5F3 positive. 13/28 (46.4%) had 5A4 3+ positivity, 12 (42.8%) showed 2+ positivity while the remaining 3 were negative. 3/28 specimens (10.7%) had ALK1 3+ score, 9 (32.1%) 2+, 13 (46.5%) 1+ and the remaining 3 (10.7%) were negative. Among the 3 FISH-positive and IHC-negative cases, 2 pts underwent CZT treatment, both progressing within 2 weeks and with low percentage of rearranged tumor cells at FISH testing (16-20%) When considering 3+ and 2+ scores as positive, 12 specimens (42.8%) resulted to be positive with all the 3 antibodies, while score 1+ was observed only with ALK1 in 13 (46.4%). Only 3 cases resulted strongly positive with all clones. TS gene expression median value on 25 cases was 6.27 (range 2,8-14-94). 65% of cases had low expression as compared to a population of ALK-negative lung ADK (personal data).
Conclusion:
IHC proved to be a reliable tool to diagnose ALK-rearranged lung tumors, especially with D5F3 and 5A4 antibodies. As the two IHC negative and FISH positive patients who received CZT didn’t respond to treatment, IHC should be used as screening tool or a confirmatory test in case of low-rearranged FISH-positive cases. TS expression appeared to be lower in ALK-positive lung tumors as compared to ALK-negative lung ADK. Further comparisons between clinical and molecular data are ongoing.
