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
| العنوان: | 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 |
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| المؤلفون: | Isaksson, Johan, Berglund, Anders, Louie, Karly, Willen, Linda, Hamidian, Arash, Edsjo, Anders, Enlund, Fredrik, Planck, Maria, Vikström, Anders, Johansson, Mikael, Hallqvist, Andreas, Wagenius, Gunnar, Botling, Johan |
| المصدر: | Clinical Lung Cancer. 24(6):507-518 |
| مصطلحات موضوعية: | NSCLC, Real-world data, Prognostic, KRAS mutation, NGS |
| الوصف: | In a nation-wide cohort of NSCLC patients, reflex tested for driver mutations by NGS, we present detailed results on demographics, clinical baseline characteristics and survival associated with KRAS mutation status. We demonstrate significant differences between patients with KRAS G12C and other KRAS mutations related to male-female sex distribution, metastatic patterns associated with CNS disease, and impact on overall survival. Background: Real-world data on demographics related to KRAS mutation subtypes are crucial as targeted drugs against the p.G12C variant have been approved. Method: We identified 6183 NSCLC patients with reported NGSbased 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). Results: The 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 KRASG12C 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. Conclusion: The 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. |
| وصف الملف: | electronic |
| URL الوصول: | https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-198245 https://liu.diva-portal.org/smash/get/diva2:1801862/FULLTEXT01.pdf |
| قاعدة البيانات: | SwePub |
Full Text via ClinicalKey | تدمد: | 15257304 19380690 |
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| DOI: | 10.1016/j.cllc.2023.05.002 |