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Erschienen in: Pathology & Oncology Research 4/2015

01.09.2015 | Research

Bone Metastases and the EGFR and KRAS Mutation Status in Lung Adenocarcinoma - The Results of Three Year Retrospective Analysis

verfasst von: Nóra Bittner, Zoltán Balikó, Veronika Sárosi, Terézia László, Erika Tóth, Miklós Kásler, Lajos Géczi

Erschienen in: Pathology & Oncology Research | Ausgabe 4/2015

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Abstract

Lung cancer is a heterogeneous group of disease and mutational profiling of lung adenocarcinomas is a routine practice in thoracic oncology. Kirsten-RAS (KRAS) and EGFR mutations play an important role in the carcinogenesis of a subset of lung adenocarcinomas. Our aim was to investigate the correlation between bone metastases and EGFR and KRAS mutation status in lung adenocarcinoma patients. Retrospectively we analysed 224 patients with recurrent or metastatic lung adenocarcinomas. Patients were treated with standard chemotherapy as first line therapy and with EGFR-TK inhibitors as a second or third line therapy. 72 of 224 patients (32 %) had verified bone metastases. Bone metastases and Skeletal Related Events (SRE) were more frequent in men, heavy smokers and without treatment of EGFR TK inhibitors. We have found that EGFR and KRAS mutation status are both predictive factors for the treatment efficacy and prognostic factors for the disease progression. However there were no significant correlation between mutation status and the presence of bone metastases (P = 0, 59). In our study the presence of bone metastases proved to be an independent prognostic factor related to poor performance status and worse Quality of Life (QL).
Literatur
1.
Zurück zum Zitat Jemal A, Siegel R, Ward E, Hao Y (2009) Cancer statistic, 2009. CA Cancer J Clin 59:225–249CrossRefPubMed Jemal A, Siegel R, Ward E, Hao Y (2009) Cancer statistic, 2009. CA Cancer J Clin 59:225–249CrossRefPubMed
2.
Zurück zum Zitat Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR (2011) International Association for the Study of Lung Cancer /American Thoracic Society / European Respiratory Society International multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 6:2244–2285 Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR (2011) International Association for the Study of Lung Cancer /American Thoracic Society / European Respiratory Society International multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 6:2244–2285
4.
Zurück zum Zitat Schiller JH, Harrington D, Belani CP, Langer C, Sandler A (2002) Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 346:92–98CrossRefPubMed Schiller JH, Harrington D, Belani CP, Langer C, Sandler A (2002) Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 346:92–98CrossRefPubMed
5.
Zurück zum Zitat NSCLC Meta-Analyses Collaborative Group (2008) Chemotherapy in addition to supportive care improves survival in advanced non-small-cell lung cancer: a systematic review and meta-analysis of individual patient data from 16 randomized controlled trials. J Clin Oncol 26:4617–4625PubMedCentralCrossRef NSCLC Meta-Analyses Collaborative Group (2008) Chemotherapy in addition to supportive care improves survival in advanced non-small-cell lung cancer: a systematic review and meta-analysis of individual patient data from 16 randomized controlled trials. J Clin Oncol 26:4617–4625PubMedCentralCrossRef
6.
Zurück zum Zitat Azolli CG, Baker S Jr, Temin S, Pao W, Aliff T, Brahmer J (2009) American Society of Clinical Oncology Clinical Practice Guideline update on chemotherapy for stage IV non-small-cell lung cancer. J Clin Oncol 36:6251–6266CrossRef Azolli CG, Baker S Jr, Temin S, Pao W, Aliff T, Brahmer J (2009) American Society of Clinical Oncology Clinical Practice Guideline update on chemotherapy for stage IV non-small-cell lung cancer. J Clin Oncol 36:6251–6266CrossRef
7.
Zurück zum Zitat Paz-Ares L (2012) PARAMOUNT final overall survival (OS) result of the phase III study of maintenance pemetrexed (pem) plus best supportive care (BSC) versus placebo (plb) plus BSC immediatly following induction treatment with pem plus cisplatin (cis) for advanced nonsquamosus (NS) non-small cell lung cancer (NSCLC). J Clin Oncol 30:(Suppl, abstr LBA 7507) Paz-Ares L (2012) PARAMOUNT final overall survival (OS) result of the phase III study of maintenance pemetrexed (pem) plus best supportive care (BSC) versus placebo (plb) plus BSC immediatly following induction treatment with pem plus cisplatin (cis) for advanced nonsquamosus (NS) non-small cell lung cancer (NSCLC). J Clin Oncol 30:(Suppl, abstr LBA 7507)
8.
Zurück zum Zitat Gazdar AF (2009) Activating and resistance mutations of EGFR in nonsmall- cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors. Oncogene 28(Suppl 1):S24–S31PubMedCentralCrossRefPubMed Gazdar AF (2009) Activating and resistance mutations of EGFR in nonsmall- cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors. Oncogene 28(Suppl 1):S24–S31PubMedCentralCrossRefPubMed
9.
Zurück zum Zitat Fukuoka M, Wu Y (2011) Biomarker Analyses and Final Overall Survival results From a Phase III, randomised, open an label, First-line Study of Gefitinib versus carboplatin/Paclitaxel in Clinically Selected Patients with Advanced Non-Small-Cell Lung cancer in Asia (IPASS). J Clin Oncol 29:2866–2874CrossRefPubMed Fukuoka M, Wu Y (2011) Biomarker Analyses and Final Overall Survival results From a Phase III, randomised, open an label, First-line Study of Gefitinib versus carboplatin/Paclitaxel in Clinically Selected Patients with Advanced Non-Small-Cell Lung cancer in Asia (IPASS). J Clin Oncol 29:2866–2874CrossRefPubMed
10.
Zurück zum Zitat Bittner N, Ostoros G, Geczi L (2014) New treatment options for lung adenocarcinoma- in view of molecular background. Pathol Oncol Res 20:11–25CrossRefPubMed Bittner N, Ostoros G, Geczi L (2014) New treatment options for lung adenocarcinoma- in view of molecular background. Pathol Oncol Res 20:11–25CrossRefPubMed
11.
Zurück zum Zitat Cappuzzo F, Ciuleanu T, Stelmakh L, Cicenas S (2010) Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol 11:521–529CrossRefPubMed Cappuzzo F, Ciuleanu T, Stelmakh L, Cicenas S (2010) Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol 11:521–529CrossRefPubMed
12.
Zurück zum Zitat Alice Tsang S, Mehra R (2013) Clinical activity of the ALK inhibitor LDK378 in advanced, ALK-positive NSCLC. J Clin Oncol 31 Alice Tsang S, Mehra R (2013) Clinical activity of the ALK inhibitor LDK378 in advanced, ALK-positive NSCLC. J Clin Oncol 31
13.
Zurück zum Zitat Delea TE, McKiernan J, Brandman J, Edelsberg J, Sung J (2006) Impact of skeletal complications on total medical care costs among patients with bone metastases of lung cancer. J Thorac Oncol 1:571–576CrossRefPubMed Delea TE, McKiernan J, Brandman J, Edelsberg J, Sung J (2006) Impact of skeletal complications on total medical care costs among patients with bone metastases of lung cancer. J Thorac Oncol 1:571–576CrossRefPubMed
14.
Zurück zum Zitat Sun JM, Ahn JS, Lee S, Kim JA, Lee J (2011) Predictors of skeletalrelated events in non-small cell lung cancer patients with bone metastases. Lung Cancer 71:89–93CrossRefPubMed Sun JM, Ahn JS, Lee S, Kim JA, Lee J (2011) Predictors of skeletalrelated events in non-small cell lung cancer patients with bone metastases. Lung Cancer 71:89–93CrossRefPubMed
15.
Zurück zum Zitat Reinersman JM, Johnson ML, Riely GJ, Chitale DA, Nicastri AD (2011) Frequency of EGFR and KRAS mutations in lung adenocarcinomas in African Americans. J Thorac Oncol 6:28–31PubMedCentralCrossRefPubMed Reinersman JM, Johnson ML, Riely GJ, Chitale DA, Nicastri AD (2011) Frequency of EGFR and KRAS mutations in lung adenocarcinomas in African Americans. J Thorac Oncol 6:28–31PubMedCentralCrossRefPubMed
16.
Zurück zum Zitat Roberts PJ, Stinchcombe TE (2013) KRAS mutation: should we test for it, and does it matter? J Clin Oncol 31:1112–1121CrossRefPubMed Roberts PJ, Stinchcombe TE (2013) KRAS mutation: should we test for it, and does it matter? J Clin Oncol 31:1112–1121CrossRefPubMed
17.
Zurück zum Zitat Cserepes M, Ostoros G, Lohinai Z, Raso E, Barbai T (2014) Subtype-specific KRAS mutations in advanced lung adenocarcinoma: a retrospective study of patients treated with platinum-based chemotherapy. Eur J Cancer 50:1819–1828CrossRefPubMed Cserepes M, Ostoros G, Lohinai Z, Raso E, Barbai T (2014) Subtype-specific KRAS mutations in advanced lung adenocarcinoma: a retrospective study of patients treated with platinum-based chemotherapy. Eur J Cancer 50:1819–1828CrossRefPubMed
18.
Zurück zum Zitat Normanno N, Luca D, Aldinucci D, Maiello MR, Mancino M (2005) Gefitinib inhibits the ability of human bone marrow stromal cells to induce osteoclast differentiation: implications for the pathogenesis and treatment of bone metastasis. Endocr Relat Cancer 12:471–482CrossRefPubMed Normanno N, Luca D, Aldinucci D, Maiello MR, Mancino M (2005) Gefitinib inhibits the ability of human bone marrow stromal cells to induce osteoclast differentiation: implications for the pathogenesis and treatment of bone metastasis. Endocr Relat Cancer 12:471–482CrossRefPubMed
19.
Zurück zum Zitat Lu X, Wang Q, Hu G, Van Poznak C, Fleisher M (2009) ADAMTS1 and MMP1 proteolytically engage EGF-like ligands in an osteolytic signaling cascade for bone metastasis. Genes Dev 23:1882–1894PubMedCentralCrossRefPubMed Lu X, Wang Q, Hu G, Van Poznak C, Fleisher M (2009) ADAMTS1 and MMP1 proteolytically engage EGF-like ligands in an osteolytic signaling cascade for bone metastasis. Genes Dev 23:1882–1894PubMedCentralCrossRefPubMed
20.
Zurück zum Zitat Nagata M, Kudoh S, Mitsuoka S, Suzumura T, Umekawa K (2013) Skeletal-related events in advanced lung adenocarcinoma patients evaluated EGFR mutations. Osaka City Med J 59:45–52PubMed Nagata M, Kudoh S, Mitsuoka S, Suzumura T, Umekawa K (2013) Skeletal-related events in advanced lung adenocarcinoma patients evaluated EGFR mutations. Osaka City Med J 59:45–52PubMed
21.
Zurück zum Zitat Bae HM, Lee SH, Kim TM, Kim DW, Yang SC (2012) Prognostic factor for non-small cell lung cancer with bone metastases at the time of diagnosis. Letters to the editor. Lung Cancer 78:167–170CrossRef Bae HM, Lee SH, Kim TM, Kim DW, Yang SC (2012) Prognostic factor for non-small cell lung cancer with bone metastases at the time of diagnosis. Letters to the editor. Lung Cancer 78:167–170CrossRef
Metadaten
Titel
Bone Metastases and the EGFR and KRAS Mutation Status in Lung Adenocarcinoma - The Results of Three Year Retrospective Analysis
verfasst von
Nóra Bittner
Zoltán Balikó
Veronika Sárosi
Terézia László
Erika Tóth
Miklós Kásler
Lajos Géczi
Publikationsdatum
01.09.2015
Verlag
Springer Netherlands
Erschienen in
Pathology & Oncology Research / Ausgabe 4/2015
Print ISSN: 1219-4956
Elektronische ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-015-9955-2

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