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KRAS G12C mutant non-small cell lung cancer linked to female sex and high risk of CNS metastasis : Population-based demographics and survival data from the National Swedish Lung Cancer Registry

Isaksson, Johan (författare)
Uppsala University,Uppsala universitet,Centrum för klinisk forskning, Gävleborg,Science for Life Laboratory, SciLifeLab,Cancerprecisionsmedicin,Johan Botling,Uppsala Univ, Sweden; Uppsala Univ Reg Gavleborg, Sweden,Department of Immunology Genetics and Pathology, Science for life laboratory, Uppsala University, Uppsala, Sweden; Center for Research and Development, Uppsala University/Region Gävleborg, Uppsala, Sweden
Berglund, Anders (författare)
Epistat AB, Uppsala, Sweden,EpiStat (Epidemiology & Statistics Consulting) Sweden
Louie, Karly (författare)
Amgen Ltd, England,Amgen Ltd, Uxbridge, United Kingdom
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Willén, Linda, 1979- (författare)
Umeå universitet,Uppsala University,Umeå University,Uppsala universitet,Centrum för klinisk forskning, Gävleborg,Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden,Uppsala Univ Reg Gavleborg, Sweden; Umea Univ, Sweden,Onkologi,Center for Research and Development, Uppsala University/Region Gävleborg, Uppsala, Sweden
Hamidian, Arash (författare)
Amgen Sweden AB, Solna, Sweden
Edsjö, Anders (författare)
Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Institutionen för translationell medicin,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Department of Translational Medicine,Skåne University Hospital,Division of Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden
Enlund, Fredrik (författare)
Diagnost Ctr, Sweden,Diagnostic center, Region Kalmar County, Sweden
Planck, Maria (författare)
Lund University,Lunds universitet,Lungmedicin, allergologi och palliativ medicin,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Forskningsgrupp Lungcancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Bröst/lungcancer,Sektion I,Institutionen för kliniska vetenskaper, Lund,Respiratory Medicine, Allergology, and Palliative Medicine,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Research Group Lung Cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Breast/lungcancer,Section I,Department of Clinical Sciences, Lund,Division of Oncology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden
Vikström, Anders (författare)
Region Östergötland, Lungmedicinska kliniken US,Department of Pulmonary Medicine, Linköping University Hospital, Linköping, Sweden
Johansson, Mikael (författare)
Umeå universitet,Umeå University,Onkologi
Hallqvist, Andreas, 1973 (författare)
Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology,Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
Wagenius, Gunnar (författare)
Karolinska Univ Hosp, Sweden,Cancer Theme, Karolinska University Hospital, Stockholm, Sweden
Botling, Johan (författare)
Gothenburg University,Göteborgs universitet,Uppsala University,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Cancerprecisionsmedicin,Department of Immunology Genetics and Pathology, Science for life laboratory, Uppsala University, Uppsala, Sweden; Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden,Uppsala Univ, Sweden; Univ Gothenburg, Sweden,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Department of Laboratory Medicine
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 (creator_code:org_t)
Elsevier, 2023
2023
Engelska.
Ingår i: Clinical Lung Cancer. - : Elsevier. - 1525-7304 .- 1938-0690. ; 24:6, s. 507-518
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • BackgroundReal-world data on demographics related to KRAS mutation subtypes are crucial as targeted drugs against the p.G12C variant have been approved.MethodWe identified 6183 NSCLC patients with reported NGS-based KRAS status in the Swedish national lung cancer registry between 2016 and 2019. Following exclusion of other targetable drivers, three cohorts were studied: KRAS-G12C (n = 848), KRAS-other (n = 1161), and driver negative KRAS-wild-type (wt) (n = 3349).ResultsThe prevalence of KRAS mutations and the p.G12C variant respectively was 38%/16% in adenocarcinoma, 28%/13% in NSCLC-NOS and 6%/2% in squamous cell carcinoma. Women were enriched in the KRAS-G12C (65%) and KRAS-other (59%) cohorts versus KRAS-wt (48%). A high proportion of KRAS-G12C patients in stage IV (28%) presented with CNS metastasis (vs. KRAS-other [19%] and KRAS-wt [18%]). No difference in survival between the mutation cohorts was seen in stage I-IIIA. In stage IV, median overall survival (mOS) from date of diagnosis was shorter for KRAS-G12C and KRAS-other (5.8 months/5.2 months) vs. KRAS wt (6.4 months). Women had better outcome in the stage IV cohorts, except in KRAS-G12C subgroup where mOS was similar between men and women. Notably, CNS metastasis did not impact survival in stage IV KRAS-G12C, but was associated with poorer survival, as expected, in KRAS-other and KRAS-wt.ConclusionThe KRAS p.G12C variant is a prevalent targetable driver in Sweden and significantly associated with female sex and presence of CNS metastasis. We show novel survival effects linked to KRAS p.G12C mutations in these subgroups with implications for clinical practice.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

NSCLC
Real-world data
Prognostic
KRAS mutation
NGS
Oncology
Onkologi
KRAS mutation
NGS
NSCLC
Prognostic
Real-world data

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