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Impact of epidermal growth factor receptor (EGFR) activating mutations and their targeted treatment in the prognosis of stage IV non-small cell lung cancer (NSCLC) patients harboring liver metastasis.

Castañón E, Rolfo C, Viñal D, López I, Fusco JP, Santisteban M, Martin P, Zubiri L, Echeveste JI, Gil-Bazo I - J Transl Med (2015)

Bottom Line: 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 vs. 13 months; p = 0.001).Conversely, patients with EGFR-mutated tumors treated with EGFR tyrosin-kinase inhibitors (TKI's) presented no significant differences in OS regardless of liver involvement (median OS not reached vs. 25 months; p = 0.81).EGFR TKIs however, may reverse the effects of an initial negative prognosis of liver metastasis in first-line treatment of EGFR mutated NSCLC patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Clínica Universidad de Navarra, Avenida Pío XII, 36, 31008, Pamplona, Spain. ecastanon@unav.es.

ABSTRACT

Objectives: 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 EGFR mutations, liver infiltration and clinical outcomes.

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 vs. 21 months; 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 vs. 13 months; p = 0.001). Conversely, patients with EGFR-mutated tumors treated with EGFR tyrosin-kinase inhibitors (TKI's) presented no significant differences in OS regardless of liver involvement (median OS not reached vs. 25 months; 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 of liver metastasis in first-line treatment of EGFR mutated NSCLC patients.

No MeSH data available.


Related in: MedlinePlus

OS depending on the presence of LM at onset or during disease curse. a At onset, LM presence seems to be a poor prognosis factor detecting an OS of 10 months when LM are present (n = 40) compared to 21 months when no liver metastases are diagnosed at the moment of stage IV NSCLC diagnosis (n = 196). b A better overall survival is achieved in stage IV NSCLC patients who never present liver involvement (n = 144) compared to those patients in whom LM are present during the course of the disease (n = 86).
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Fig1: OS depending on the presence of LM at onset or during disease curse. a At onset, LM presence seems to be a poor prognosis factor detecting an OS of 10 months when LM are present (n = 40) compared to 21 months when no liver metastases are diagnosed at the moment of stage IV NSCLC diagnosis (n = 196). b A better overall survival is achieved in stage IV NSCLC patients who never present liver involvement (n = 144) compared to those patients in whom LM are present during the course of the disease (n = 86).

Mentions: As expected, a significant OS benefit was observed for patients with stage IV NSCLC showing no liver involvement at onset when compared to those exhibiting liver infiltration at the time of stage IV diagnosis [KM survival: 21 months (95% CI 16.9–25.1) vs. 10 months (95% CI 2.8–17.2); p = 0.001], (Fig. 1a). When taken into account the presence of LM at any time-point during the entire disease process, we found a shorter OS [14 months (95% CI 11.6–16.4)] in patients with liver disease, when compared to those patients in which liver was never affected [24 months (95% CI 18.6–29.3), p = 0.038], (Fig. 1b).Fig. 1


Impact of epidermal growth factor receptor (EGFR) activating mutations and their targeted treatment in the prognosis of stage IV non-small cell lung cancer (NSCLC) patients harboring liver metastasis.

Castañón E, Rolfo C, Viñal D, López I, Fusco JP, Santisteban M, Martin P, Zubiri L, Echeveste JI, Gil-Bazo I - J Transl Med (2015)

OS depending on the presence of LM at onset or during disease curse. a At onset, LM presence seems to be a poor prognosis factor detecting an OS of 10 months when LM are present (n = 40) compared to 21 months when no liver metastases are diagnosed at the moment of stage IV NSCLC diagnosis (n = 196). b A better overall survival is achieved in stage IV NSCLC patients who never present liver involvement (n = 144) compared to those patients in whom LM are present during the course of the disease (n = 86).
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4528698&req=5

Fig1: OS depending on the presence of LM at onset or during disease curse. a At onset, LM presence seems to be a poor prognosis factor detecting an OS of 10 months when LM are present (n = 40) compared to 21 months when no liver metastases are diagnosed at the moment of stage IV NSCLC diagnosis (n = 196). b A better overall survival is achieved in stage IV NSCLC patients who never present liver involvement (n = 144) compared to those patients in whom LM are present during the course of the disease (n = 86).
Mentions: As expected, a significant OS benefit was observed for patients with stage IV NSCLC showing no liver involvement at onset when compared to those exhibiting liver infiltration at the time of stage IV diagnosis [KM survival: 21 months (95% CI 16.9–25.1) vs. 10 months (95% CI 2.8–17.2); p = 0.001], (Fig. 1a). When taken into account the presence of LM at any time-point during the entire disease process, we found a shorter OS [14 months (95% CI 11.6–16.4)] in patients with liver disease, when compared to those patients in which liver was never affected [24 months (95% CI 18.6–29.3), p = 0.038], (Fig. 1b).Fig. 1

Bottom Line: 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 vs. 13 months; p = 0.001).Conversely, patients with EGFR-mutated tumors treated with EGFR tyrosin-kinase inhibitors (TKI's) presented no significant differences in OS regardless of liver involvement (median OS not reached vs. 25 months; p = 0.81).EGFR TKIs however, may reverse the effects of an initial negative prognosis of liver metastasis in first-line treatment of EGFR mutated NSCLC patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Clínica Universidad de Navarra, Avenida Pío XII, 36, 31008, Pamplona, Spain. ecastanon@unav.es.

ABSTRACT

Objectives: 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 EGFR mutations, liver infiltration and clinical outcomes.

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 vs. 21 months; 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 vs. 13 months; p = 0.001). Conversely, patients with EGFR-mutated tumors treated with EGFR tyrosin-kinase inhibitors (TKI's) presented no significant differences in OS regardless of liver involvement (median OS not reached vs. 25 months; 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 of liver metastasis in first-line treatment of EGFR mutated NSCLC patients.

No MeSH data available.


Related in: MedlinePlus