Mihaly Cserepes1, Gyula Ostoros2, Zoltan Lohinai3, Erzsebet Raso4, Tamas Barbai5, Jozsef Timar4, Anita Rozsas3, Judit Moldvay6, Ilona Kovalszky7, Katalin Fabian6, Marton Gyulai8, Bahil Ghanim9, Viktoria Laszlo10, Thomas Klikovits10, Mir Alireza Hoda9, Michael Grusch11, Walter Berger11, Walter Klepetko10, Balazs Hegedus12, Balazs Dome13. 1. Department of Tumor Biology, National Koranyi Institute of Pulmonology, Budapest, Hungary; Department of Pulmonology VIII, National Koranyi Institute of Pulmonology, Budapest, Hungary; Division of Thoracic Surgery, Medical University of Vienna, Austria. 2. Department of Pulmonology VIII, National Koranyi Institute of Pulmonology, Budapest, Hungary. 3. Department of Tumor Biology, National Koranyi Institute of Pulmonology, Budapest, Hungary; Division of Thoracic Surgery, Medical University of Vienna, Austria. 4. 2nd Department of Pathology, Semmelweis University, Budapest, Hungary; Tumor Progression Research Group, Hungarian Academy of Sciences-Semmelweis University, Budapest, Hungary. 5. 2nd Department of Pathology, Semmelweis University, Budapest, Hungary. 6. Department of Pulmonology, Semmelweis University, Budapest, Hungary. 7. 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary. 8. County Hospital of Pulmonology, Torokbalint, Pest County, Hungary. 9. Division of Thoracic Surgery, Medical University of Vienna, Austria; Institute of Cancer Research and Comprehensive Cancer Center, Department of Internal Medicine I, Medical University of Vienna, Austria. 10. Division of Thoracic Surgery, Medical University of Vienna, Austria. 11. Institute of Cancer Research and Comprehensive Cancer Center, Department of Internal Medicine I, Medical University of Vienna, Austria. 12. Division of Thoracic Surgery, Medical University of Vienna, Austria; 2nd Department of Pathology, Semmelweis University, Budapest, Hungary; Tumor Progression Research Group, Hungarian Academy of Sciences-Semmelweis University, Budapest, Hungary. 13. Department of Tumor Biology, National Koranyi Institute of Pulmonology, Budapest, Hungary; Division of Thoracic Surgery, Medical University of Vienna, Austria; Department of Thoracic Surgery, National Institute of Oncology-Semmelweis University, Budapest, Hungary. Electronic address: balazs.dome@meduniwien.ac.at.
Abstract
BACKGROUND: Platinum-based chemotherapy is the most common treatment in advanced-stage lung adenocarcinoma. Because the clinical significance of KRAS mutational status in this setting has not yet been clearly determined, a mutation subtype-specific analysis was performed in the so far largest cohort of Caucasian patients with KRAS mutant advanced-stage lung adenocarcinoma treated with platinum-based chemotherapy. METHODS: 505 Caucasian stage III-IV lung adenocarcinoma patients with known amino acid substitution-specific KRAS mutational status and treated with platinum-based chemotherapy were included. The correlations of subtype-specific KRAS mutations with smoking status, progression-free and overall survival (PFS and OS, respectively) and therapeutic response were analysed. RESULTS: Among 338 KRAS wild-type, 147 codon 12 mutant and 20 codon 13 mutant patients, there were no mutation-related significant differences in PFS or OS (P values were 0.534 and 0.917, respectively). Eastern Cooperative Oncology Group (ECOG) status and clinical stage were significant independent prognostic factors. KRAS mutation showed a significant correlation with smoking status (P=0.018). Importantly, however, G12V KRAS mutant patients were significantly more frequent among never-smokers than all other codon 12 KRAS mutant (G12x) subtypes (P=0.016). Furthermore, this subgroup tended to have a higher response rate (66% versus 47%; P=0.077). A modestly longer median PFS was also found in the G12V mutant cohort (233days; versus 175days in the G12x group; P=0.145). CONCLUSIONS: While KRAS mutation status per se is neither prognostic nor predictive in stage III-IV lung adenocarcinoma, subtype-specific analysis may indeed identify clinically relevant subgroups of patients that may ultimately influence treatment decisions.
BACKGROUND:Platinum-based chemotherapy is the most common treatment in advanced-stage lung adenocarcinoma. Because the clinical significance of KRAS mutational status in this setting has not yet been clearly determined, a mutation subtype-specific analysis was performed in the so far largest cohort of Caucasian patients with KRAS mutant advanced-stage lung adenocarcinoma treated with platinum-based chemotherapy. METHODS: 505 Caucasian stage III-IV lung adenocarcinomapatients with known amino acid substitution-specific KRAS mutational status and treated with platinum-based chemotherapy were included. The correlations of subtype-specific KRAS mutations with smoking status, progression-free and overall survival (PFS and OS, respectively) and therapeutic response were analysed. RESULTS: Among 338 KRAS wild-type, 147 codon 12 mutant and 20 codon 13 mutant patients, there were no mutation-related significant differences in PFS or OS (P values were 0.534 and 0.917, respectively). Eastern Cooperative Oncology Group (ECOG) status and clinical stage were significant independent prognostic factors. KRAS mutation showed a significant correlation with smoking status (P=0.018). Importantly, however, G12VKRAS mutant patients were significantly more frequent among never-smokers than all other codon 12 KRAS mutant (G12x) subtypes (P=0.016). Furthermore, this subgroup tended to have a higher response rate (66% versus 47%; P=0.077). A modestly longer median PFS was also found in the G12V mutant cohort (233days; versus 175days in the G12x group; P=0.145). CONCLUSIONS: While KRAS mutation status per se is neither prognostic nor predictive in stage III-IV lung adenocarcinoma, subtype-specific analysis may indeed identify clinically relevant subgroups of patients that may ultimately influence treatment decisions.
Authors: Nóra Bittner; Zoltán Balikó; Veronika Sárosi; Terézia László; Erika Tóth; Miklós Kásler; Lajos Géczi Journal: Pathol Oncol Res Date: 2015-06-09 Impact factor: 3.201
Authors: Nakul P Valsangkar; Thun Ingkakul; Camilo Correa-Gallego; Mari Mino-Kenudson; Ricard Masia; Keith D Lillemoe; Carlos Fernández-del Castillo; Andrew L Warshaw; Andrew S Liss; Sarah P Thayer Journal: Surgery Date: 2015-02 Impact factor: 3.982
Authors: Anna Biernacka; Peter D Tsongalis; Jason D Peterson; Francine B de Abreu; Candice C Black; Edward J Gutmann; Xiaoying Liu; Laura J Tafe; Christopher I Amos; Gregory J Tsongalis Journal: Cancer Genet Date: 2016-03-18
Authors: Ahmet Yilmaz; Nehad Mohamed; Kara A Patterson; Yan Tang; Konstantin Shilo; Miguel A Villalona-Calero; Michael E Davis; Xiao-Ping Zhou; Wendy Frankel; Gregory A Otterson; Weiqiang Zhao Journal: Int J Environ Res Public Health Date: 2014-08-25 Impact factor: 3.390