(Vienna, 03 February 2017) A new study, jointly conducted by MedUni Vienna and scientists from Hungary, has now shown, for the first time, that mutations in the KRAS gene (Kirsten rat sarcoma viral oncogene homolog) are prognostically relevant in patients with advanced lung cancer and bone metastasis. Survival in this subgroup was found to be significantly poorer than in patients with bone metastasis without this specific mutation.
In Austria, approximately 5,000 people a year develop lung cancer and approximately 70% of these are already at an advanced stage at the time of diagnosis. Lung cancer is by far the commonest cause of death from cancer in men and the trend is rising. Due to changes in smoking habits, more women are likely to develop lung cancer in future than has hitherto been the case.
The most prevalent subgroup of lung cancers – adenocarcimoma – exhibits a mutation in the KRAS gene in approximately 30% of cases. Such mutations lead to certain changes in cell biology and are associated with aggressive tumour growth. Despite the relatively high proportion of lung cancers with KRAS mutations, there is currently no specific treatment licensed for clinical use to combat these mutation-related changes. Moreover, previous studies failed to clarify whether patients with KRAS-mutated adenocarcinoma of the lung generally have a poorer prognosis.
Within the framework of the recently published study, the clinical and molecular data for 500 patients with metastasised adenocarcinoma of the lung were examined and divided into various subgroups according to the tumour spread in the body; these subgroups were then correlated with the molecular pathological investigations into KRAS mutation. Patients with EGFR mutation were excluded from the analysis.
Thomas Klikovits from MedUni Vienna's Division of Thoracic Surgery, one of the study's two lead authors, explains: "As has already been reported in several studies, the presence of a KRAS mutation does not influence the survival of the entire cohort. However, for the first time, we were able to show that patients with KRAS-mutated lung cancer and bone metastasis survive for a significantly shorter time than those without this specific mutation. However, the presence of KRAS mutation does not influence the prognosis of patients with metastases in other organs."
Balazs Döme, Head of the Programme for Translational Thoracic Oncology (TTO) at MedUni Vienna's Division of Thoracic Surgery and Balazs Hegedus (former Head of the Laboratory for TTO, currently working group leader at Duisburg-Essen University), both joint lead investigators, add: "In this cohort, the primary tumour had most frequently spread to other parts of the lung, the second most frequent spread taking the form of bone metastases. Patients with lung metastases exhibit a significantly higher rate of KRAS mutations. On the other hand, metastases on the pleura and in the liver were associated with fewer KRAS mutations. That is particularly important, since several drugs that target changes in cell biology due to KRAS mutation are currently being trialled."
The study arose from a joint project run by various institutions in Hungary and the Laboratory for Translational Thoracic Oncology (Heads: Mir Alireza Hoda and Viktoria Laszlo) at the Medical University of Vienna. The results were published in the journal "Scientific Reports" and, in future, these should simplify decision-making in the individual treatment and prognosis of these patients.
Service: Scientific Reports
Lohinai Z, Klikovits T, Moldvay J, Ostoros G, Raso E, Timar J, Fabian K, Kovalszky I, Kenessey I, Aigner C, Renyi-Vamos F, Klepetko W, Dome B, Hegedus B. KRAS-mutation incidence and prognostic value are metastatic site-specific in lung adenocarcinoma: poor prognosis in patients with KRAS mutation and bone metastasis. Scientific Reports. 2017 Jan 4;7:39721. doi: 10.1038/srep3972.