The effects of bisphosphonate and radiation therapy in bone-metastatic lung adenocarcinoma: the impact of KRAS mutation

Peter Radeczky; Zsolt Megyesfalvi; Viktoria Laszlo; Janos Fillinger; Judit Moldvay; Erzsebet Raso; Erzsebet Schlegl; Tamas Barbai; Jozsef Timar; Ferenc Renyi-Vamos; Balazs Dome; Balazs Hegedus

doi:10.21037/tlcr-20-754

The effects of bisphosphonate and radiation therapy in bone-metastatic lung adenocarcinoma: the impact of KRAS mutation

Transl Lung Cancer Res. 2021 Feb;10(2):675-684. doi: 10.21037/tlcr-20-754.

Authors

Peter Radeczky^{1

2}, Zsolt Megyesfalvi^{1

2

3}, Viktoria Laszlo^{2

3}, Janos Fillinger^{1

2}, Judit Moldvay^{2

4}, Erzsebet Raso⁵, Erzsebet Schlegl², Tamas Barbai⁵, Jozsef Timar^{5

6}, Ferenc Renyi-Vamos^{1

2}, Balazs Dome^{1

2

3}, Balazs Hegedus⁷

Affiliations

¹ Department of Thoracic Surgery, National Institute of Oncology-Semmelweis University, Budapest, Hungary.
² National Koranyi Institute of Pulmonology, Budapest, Hungary.
³ Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
⁴ MTA-SE NAP, Brain Metastasis Research Group, Hungarian Academy of Sciences, Budapest, Hungary.
⁵ 2nd Department of Pathology, Semmelweis University, Budapest, Hungary.
⁶ Tumor Progression Research Group, Hungarian Academy of Sciences-Semmelweis University, Budapest, Hungary.
⁷ Department of Thoracic Surgery, Ruhrlandklinik, University Clinic Essen, Essen, Germany.

Abstract

Background: KRAS mutation is the most common genetic alteration in lung adenocarcinoma (LADC) in Western countries and is associated with worse outcome in bone-metastatic cases. Yet, to date, no effective treatment guidelines were developed for these patients. Accordingly, our aim was to investigate the impact of KRAS mutation on bisphosphonate (BTx) and radiation therapy (RTx) in bone-metastatic LADC patients.

Methods: Clinicopathological variables of 134 consecutive LADC patients with bone metastases at diagnosis and known KRAS status were retrospectively analyzed. The effects of BTx, RTx and KRAS mutation on overall survival (OS) were investigated.

Results: Of the total cohort, 93 patients were identified as KRAS wild-type (WT) (69.4%) and 41 (30.6%) as KRAS mutant patients. The presence of KRAS mutation was associated with significantly reduced median OS (5.1 vs. 10.2 months in KRAS WT patients; P=0.008). Irrespective of KRAS mutational status both BTx (P=0.007) and RTx (P=0.021) conferred a significant benefit for OS. Notably, however, when analyzing the patients with KRAS-mutant and KRAS WT tumors separately, the benefit from BTx and RTx on OS remained statistically significant only in KRAS WT patients (P=0.032 and P=0.031, respectively).

Conclusions: KRAS mutation is a strong negative prognostic factor in bone-metastatic LADC patients. Both BTx and RTx can increase the OS with a pronounced benefit for patients with KRAS WT tumors. Altogether, KRAS mutational status should be considered during therapeutic decision making in bone-metastatic LADC patients.

Keywords: Bone metastases; KRAS mutation; bisphosphonate therapy; lung adenocarcinoma (LADC); radiation therapy.