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L. Zubiri
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MINI 23 - Lung Cancer Risk: Genetic Susceptibility and Airway Biology (ID 135)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:P.E. Postmus, R. Young
- Coordinates: 9/08/2015, 16:45 - 18:15, 401-404
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MINI23.04 - Familial Clustering of Lung Cancer (LC) Cases in a South European Population (sEp) (ID 2540)
17:00 - 17:05 | Author(s): L. Zubiri
- Abstract
- Presentation
Background:
The National Lung Cancer Screening Trial found, after 6.5 years, a 20% reduction in LC mortality in high-risk patients (pts) screened with low-dose computed tomography compared to chest x-ray. However, LC screening programs (SP) result controversial due to potential cost-effectiveness issues. Familial LC aggregation (fLCa) has been described previously. The estimated relative risk of LC is ∼1.8 for offspring of parents with LC. Linkage analysis has mapped a dominant locus to chromosome 6 in LC pedigrees. Therefore, in this high-risk subpopulation, SP may have clear advantages. This is the first study to investigate the incidence of fLCa conducted in a sEp.
Methods:
Overall, 509 cancer pts of Spanish (n = 473) or Portuguese (n = 36) origin were included in the analysis. A cohort of 236 consecutive pts (cases) diagnosed with LC was studied for family history (FH) of any type of cancer including LC. Another cohort of 273 pts (controls) with similar demographic characteristics diagnosed with cancer types other than LC was also studied for FH of cancer. We investigated whether LC pts show a higher incidence of fLCa than subjects with other solid tumors.
Results:
Among LC pts with a positive FH for LC, 36.7% showed one of their parents as the only LC relative, 26.5% showed one or more siblings, 18.4% one or more either uncle or aunt, 6.1% their grandfather/grandmother and 12.2% other combinations. Regarding the number of relatives affected, in our LC cohort one relative was the most frequent finding with 42/49 pts (85.7%), 2 in 3 cases (6.2%) and > 3 relatives in 4 subjects (8.1%). We studied the overall incidence of any type of family cancer among cases and controls. No differences were found between groups (72.9% vs 67.4%; p = 0.18). However, in our cohort of LC cases, 49/236 pts (20.8%) had a FH of LC in first or second degree whereas among cancer controls only 29/273 pts (10.6%) showed a LC FH (p = 0.002).
Conclusion:
This is the first estimation of LC FH in a non-selected sEp with LC. 20.8% of LC cases showed a positive FH for LC, being significantly higher (twofold) compared to other cancer pts. Therefore, the usefulness of directed SP for subjects with positive FH of LC should be prospectively evaluated and potential genomic drivers studied.Table 1. Comparison of incidence of any type of familial cancer and fLCa between a cohort of LC patients and a cohort of subjects with other solid tumors LC patients Other solid tumor patients p value N= 236 N=273 Familial cancer (any type) (n (%)) Yes 172 (72.9) 184 (67.4) 0.18 No 64 (27.1) 89 (32.6) Familial Lung Cancer (n (%)) Yes 49 (20.8) 29 (10.6) 0.002* No 187 (79.2) 244 (89.4) *Statistically significance at p < 0.05 fLCa: familial lung cancer; LC: lung cancer
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P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.01-013 - EGFR Mutations and Targeted Treatment Reverse the Bad Prognosis of Stage IV NSCLC Associated to Liver Metastasis (ID 2961)
09:30 - 09:30 | Author(s): L. Zubiri
- Abstract
Background:
Liver metastases appear in 20-30% of patients diagnosed with non-small cell lung cancer (NSCLC) and represent a poor prognosis feature of NSCLC and a possibly more treatment-resistant condition. Potential clinical outcome differences in NSCLC patients with liver metastases harboring molecular alterations in EGFR, KRAS and EML4-ALK genes are still to be determined. This study aims to evaluate the incidence of liver metastasis in a single population and look for potential correlations between molecular profile, liver infiltration and response to treatment. response to Liver metastases appear in 20-30% of patients diagnosed with non-small cell lung cancer (NSCLC) and represent a poor prognosis feature of NSCLC and a possibly more treatment-resistant condition. Potential clinical outcome differences in NSCLC patients with liver metastases harboring molecular alterations in EGFR, KRAS and EML4-ALK genes are still to be determined. This study aims to evaluate the incidence of liver metastasis in a single population and look for potential correlations between molecular profile, liver infiltration and response to treatment.
Methods:
A total of 236 consecutive stage IV NSCLC patients treated at the Clínica Universidad de Navarra were analyzed.
Results:
At onset, liver metastases were present in 16.9% of patients conferring them a shorter overall survival (OS) compared to those with different metastatic locations excluding liver infiltration (10 mo. vs. 21 mo.; p =0.001). Patients with EGFR wild-type tumors receiving standard chemotherapy and showing no liver involvement presented a superior median OS compared to those with liver metastases (23 mo. vs 13 mo.; p=0.001). Conversely, patients with EGFR-mutated tumors treated with EGFR tirosin-kinase inhibitors (TKI’s) presented no significant differences in OS regardless of liver involvement (median OS not reached vs. 25 mo; p=0.81).
Conclusion:
Overall, liver metastases at onset negatively impact OS of NSCLC patients. EGFR TKIs however, may reverse the effects of an initial negative prognosis in first-line treatment of EGFR mutated tumors and, more interestingly, in patients with EGFR wild-type NCSLC receiving EGFR TKIs after progression to chemotherapy. Table 1. Multivariate regression model.Variable HR p Sex 1.28 0.32 Age 1 0.9 N 1.28 0.06 EGFR 0.24 0.001 TKIs (after progression) 0.44 0.03 Liver metastases at onset 1.5 0.28 Liver metastases during disease 1.28 0.43 Bone metastases at onset 1.6 0.22 Bone metastases during disease 1.19 0.64 Skin metastases at onset 2.2 0.31 Adrenal metastases at onset 1.37 0.29
