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BACKGROUND: The Kirsten rat sarcoma virus (KRAS) is a prominent proto-oncogene. Several treatments for KRAS mutations have been developed. However, KRAS amplification, a KRAS alteration, is poorly understood, and there is currently no appropriate treatment other than conventional chemotherapy. This study aimed to elucidate the role of KRAS amplification in different types of cancers. METHODS: From October 2019 to June 2023, we performed next-generation sequencing using Trusight Oncology 500 on 3895 patients with 37 different cancer types at the Samsung Medical Center. We analyzed the distribution of KRAS amplification according to cancer type and its correlation with tumor mutation burden (TMB). Concomitant KRAS mutations were also identified. RESULTS: Of the total 3895 patients, 99 (2.5â¯%) had KRAS amplification. The highest frequency of KRAS amplification was detected in 2â¯% (27/1350) of patients with colorectal cancer, followed by 3.48â¯% (32/920) of patients with gastric cancer and 3.88â¯% (9/232) patients with of pancreatic cancer. MSI-High was not detected in patients with KRAS amplification. There was no correlation between KRAS copy number variation and TMB status. Among patients with KRAS amplification, 27.3â¯% (27/99) had a concomitant KRAS mutation. More than 50â¯% of patients had G12D or G12V mutations. In gastric cancer, patients with both KRAS amplification and mutation were extremely rare at 3.1â¯% (1/32); however, in colorectal cancer, more than half of the patients had KRAS amplification and mutation (51.9â¯%, 14/27). KRAS amplification and mutations are associated with mutations in tumor suppressor genes TP53, BRCA2, ARID1B, and PTCH1. CONCLUSIONS: Of the 3895 patients with metastatic solid tumors, 99 (2.5â¯%) had KRAS amplification, and next-generation sequencing analysis provided a deeper understanding of KRAS amplification.
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PTCL-EBV is a disease entity newly recognized in the WHO-HAEMS5 and the ICC of Mature Lymphoid neoplasms classification. Previously, it was classified as a subtype within PTCL-NOS and was known to have a poor prognosis. However, the clinical feature and treatment outcomes are not well known. This retrospective observational study was conducted on patients diagnosed with PTCL-EBV at Samsung Medical Center through a pathology review from 2000 to 2020. We analyzed clinical data from 14 patients. We conducted an investigation of patients with PTCL-EBV into immunohistochemistry and analysis of survival outcomes for each treatment regimen. We analyzed both overall survival and progression-free survival for each treatment regimen. 25% were beta-F1 positive, and 67% were TCRγ positive. TIA-1 and granzyme B exhibited positive results in all cases, whereas the NK cell marker CD56 was negative in only 11% of patients. The CD3 was observed in all of patients. And, the CD4 was 43% positive. The CD8 were investigated in 8 patients, with 37.5% positive. Hepatosplenomegaly was observed in 55% of patients, and 70% of patients displayed B symptoms at the time of diagnosis. Patients who received CHOP or CVP treatment had a median PFS of 2.2 months (95% CI 1.9-2.5 months), and patients who received other treatments had a median PFS of 5.1 months (NA). The objective response rate (ORR) for ICE/dexa as the first or second line treatment was 100% (3 out of 3). But, ORR of CHOP or CVP as the first line treatment was 33.3% (3 out of 9). The median overall survival (OS) for the group that received HSCT after achieving a response was 34.6 months (95% CI 0-74.6 months), and the median OS for the group that did not receive HSCT was 5.0 months (95% CI 2.1-7.9 months) (p=0.04). In conclusion, in the context of PTCL-EBV, despite a limited sample size, the ICE/Dexa regimen shows potential benefits in terms of ORR and PFS. Furthermore, the application of HSCT following the attainment of a complete response may prove advantageous.
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Importance: Over the past 10 years, treatment of non-small cell lung cancer (NSCLC) has been continually revolutionized. However, standard clinical trials may not reflect current multiple lines of treatment and corresponding outcomes in a timely manner. Objective: To investigate outcomes associated with new treatment of NSCLC in a clinical setting. Design, Setting, and Participants: This cohort study included patients with NSCLC between January 1, 2010, and November 30, 2020, who received any anticancer treatment at Samsung Medical Center in Korea. Data were analyzed from November 2021 through February 2022. Exposures: Clinical and pathological stage, histology, and major druggable sequence variation, including epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS1, RET, MET exon 14 skipping, BRAF V600E, KRAS G12C, and NTRK between 2 periods (period I: 2010-2015 vs period II: 2016-2020). Main Outcomes and Measures: The primary outcome was the 3-year survival rate of NSCLC. Secondary outcomes included median overall survival, progression-free survival, and recurrence-free survival. Results: Among 21â¯978 patients with NSCLC (median [range] age at diagnosis, 64.1 [57.0-71.0] years; 13â¯624 males [62.0%]), there were 10â¯110 patients in period I and 11â¯868 patients in period II; adenocarcinoma (AD) was the predominant histology (7112 patients [70.3%] in period I and 8813 patients [74.3%] in period II). There were 4224 never smokers [41.8%] in period I and 5292 never smokers [44.6%] in period II. Compared with patients in period I, patients during period II were more likely to undergo molecular tests in the AD (5678 patients [79.8%] vs 8631 patients [97.9%]) and non-AD (1612 of 2998 patients [53.8%] and 2719 of 3055 patients [89.0%]) groups. In patients with AD in period I, 3-year survival rates were 92.8% (95% CI, 91.8%-93.7%), 72.4% (95% CI, 68.3%-76.8%), 56.7% (95% CI, 53.4%-60.2%), and 28.7% (95% CI, 27.0%-30.4%) for stage I, II, III, and IV, respectively. In period II, 3-year survival rates of patients with AD were 95.1% (95% CI, 94.4%-95.9%), 82.5% (95% CI, 79.1%-86.1%), 65.1% (95% CI, 61.8%-68.6%), and 42.4% (95% CI, 40.3%-44.7%) for each stage, respectively. In patients without AD, 3-year survival rates were 72.0% (95% CI, 68.8%-75.3%), 60.0% (95% CI, 56.2%-64.1%), 38.9% (95% CI, 35.6%-42.5%), and 9.7% (95% CI, 7.9%-12.1%) for each stage in period I. In period II, the 3-year survival rates of patients without AD were 79.3% (95% CI, 76.3%-82.4%), 67.3% (95% CI, 62.8%-72.1%), 48.2% (95% CI, 44.5%-52.3%), and 18.1% (95% CI, 15.1%-21.6%) for each stage. Conclusions and Relevance: In this cohort study of 10 years of clinical data, survival outcomes were improved across all stages, with larger increases in patients with stage III to IV disease. The incidence of never-smokers and the use of molecular testing increased.
Subject(s)
Adenocarcinoma , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Male , Humans , Middle Aged , Aged , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Survival Rate , Protein-Tyrosine Kinases , Cohort Studies , Mutation , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/therapeutic use , Molecular Diagnostic Techniques , Republic of Korea/epidemiologyABSTRACT
Background: In non-small cell lung cancer (NSCLC), the epidermal growth factor receptor (EGFR) mutation is a representative oncogenic driver mutation. Only about 12% of EGFR mutation patients have the exon 20 insertion mutation, which is the third most frequent mutation among EGFR mutation NSCLC. Amivantamab, an EGFR and MET proto-oncogene, receptor tyrosine kinase (MET) bispecific antibody, was approved for NSCLC patients with the EGFR exon 20 insertion (E20I) mutation. In this study, we described the real-world, single-center efficacy and safety data of amivantamab in E20I mutation patients. Methods: This study included metastatic NSCLC patients with EGFR E20I mutations. From January 2018 to June 2022, patients with EGFR E20I mutations who were treated with amivantamab were analyzed at Samsung Medical Center as part of the clinical trial or the early access program (EAP). We collected the patients' characteristics [age, sex, smoking history, location of mutation, sites of metastasis, programmed death-ligand 1 (PD-L1) expression status, etc.] and analyzed progression-free survival (PFS) and overall survival (OS) stratified by PD-L1 expression status, co-mutation such as tumor protein p53 (TP53), and metastasis sites. Results: A total of 42 patients were analyzed, of which 16 patients were enrolled in the phase 1 study, and 26 patients received amivantamab through EAP. There were 14 (33%) patients with partial remission, 18 (43%) patients with stable disease, and 10 (24%) patients with disease progression. The objective response rate (ORR) was 33%, and the disease control rate (DCR) was 76%. PFS was analyzed by dividing the near and far loop for 31 patients whose mutation location was known. The two groups had no statistically significant difference in PFS [median (range): 11.8 (2.3-21.3) vs. 11.3 (3.4-19.2) months, P=0.69]. For 29 patients with TP53 mutation data, there was no significant difference in PFS between the two groups [median (range): 5.9 (0-18.0) vs. 12.6 (6.9-18.3) months, P=0.11]. When analyzing PFS in 37 patients with PD-L1 expression data, PD-L1 (+) patients showed a poor prognosis [median (range): 11.3 (5.0-17.6) vs. 19.5 (5.3-33.7) months, P=0.04; hazard ratio (HR), 0.44; 95% confidence interval (CI): 0.20-0.98]. Conclusions: The efficacy of amivantamab was confirmed for the real-world population for EGFR E20I-mutated NSCLC. PD-L1 status could be a poor predictive factor, which should be further validated.
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Background: Ramucirumab, an anti-vascular endothelial growth factor receptor (VEGFR) monoclonal antibody (mAb), inhibits angiogenesis and reduces tumor activity. Programmed cell death-ligand 1 (PD-L1) might act upon VEGFR2 to induce cancer cell angiogenesis and metastasis. Herein, we investigated the efficacy of combining ramucirumab and paclitaxel according to the status of PD-L1 expression in patients with advanced gastric cancer (AGC). Methods: This analysis included AGC patients who received ramucirumab plus paclitaxel as 2nd line therapy between December 1, 2018, and February 28, 2022, at Samsung Medical Center. All patient data analyses included an evaluation of PD-L1 expression using the combined positive score (CPS). We analyzed the efficacy and the survival of patients according to their PD-L1 expression. Results: We included 117 patients in this analysis, and 80 patients (68.4%) had a PD-L1 CPS of one or more, 37 (31.6%) had five or more, and 19 (16.2%) had ten or more scores. Progression-free survival (PFS) and overall survival (OS) did not differ significantly between patients with a PD-L1 CPS of less than one and one or more {PD-L1 <1% vs. PD-L1 ≥1%; PFS: median 3.6 months [95% confidence interval (CI): 2.4-4.8 months] vs. median 4.1 months (95% CI: 3.5-4.7 months), P=0.93; PD-L1 <1% vs. PD-L1 ≥1%; OS: median 7.0 months (95% CI: 5.4-8.6 months) vs. median 8.1 months (95% CI: 6.4-9.8 months), P=0.32}. PFS and OS did not differ significantly between patients with a PD-L1 CPS of less than 5 and 5 or more [PD-L1 <5% vs. PD-L1 ≥5%; PFS: 3.9 months (95% CI: 3.3-4.5 months) vs. 4.4 months (95% CI: 3.0-5.8 months), P=0.57; OS: 7.4 months (95% CI: 6.5-8.3 months) vs. 10.0 months (95% CI: 1.1-18.9 months), P=0.07]. Interestingly, with a PD-L1 CPS cutoff of 10, PFS and OS did differ significantly [PD-L1 <10% vs. PD-L1 ≥10%; PFS: 3.8 months (95% CI: 3.3-4.3 months) vs. 5.7 months (95% CI: 4.1-7.3 months), P=0.05; OS: 7.2 months (95% CI: 6.5-7.9 months) vs. 18.9 months (95% CI: 6.5-31.3 months), P=0.04]. Conclusions: No biomarkers have been established to predict survival times after ramucirumab plus paclitaxel treatment. This analysis suggests that a PD-L1 CPS cutoff of 10 might be novel a biomarker to predict the survival of AGC patients treated with ramucirumab and paclitaxel.
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Because sleep comprises one-third of a person's life, using an optimal pillow for appropriate neck support to maintain cervical curve may contribute to improve quality of sleep. Design of orthopedic pillow conforms to orthopedic guidelines to ensure the right support of the cervical curve. The aim of this study was to investigate effect of different pillow shape and content on cervical curve, pillow temperature, and pillow comfort. A feather pillow is regarded as a standard pillow, and a memory foam pillow is one of the most popular pillows among pillow users. We, therefore, compared these two pillows with an orthopedic pillow. Twenty healthy subjects (10 men and 10 women; age range, 21-30 years) participated in the study. Each subject was asked to assume the supine position with 3 different pillows for 30 minute in each trial and then cervical curve, pillow temperature, and pillow comfort were measured. When comparing the cervical curve of the 3 different pillows, that of the orthopedic pillow was significantly higher than that of the other 2 pillows (p < 0.001). The degree of temperature increase was significantly lower for the orthopedic pillow than for the memory foam and feather pillows (p < 0.001). The visual analog scale (VAS) score of pillow comfort was significantly higher in orthopedic pillow than the other 2 pillows. This study shows that pillow shape and content plays a crucial role in cervical curve, pillow temperature, and pillow comfort and orthopedic pillow may be an optimal pillow for sleep quality.
Subject(s)
Bedding and Linens/standards , Cervical Vertebrae/physiology , Sleep/physiology , Supine Position/physiology , Animals , Cervical Vertebrae/diagnostic imaging , Feathers , Female , Geese , Humans , Male , Polypropylenes , Polyurethanes , Radiography , Random Allocation , TemperatureABSTRACT
Conformation selective: A new technique of ultraviolet-ultraviolet hole burning spectroscopy that can be applied to ions stored in a quadrupole ion trap (QIT) is developed and used to obtain the conformation-selective electronic spectra of dibenzo[18]crown-6 complexes with alkali metal cations (M(+), see picture; F(+) = fragment).