Extensive genomic analysis in patients with KRAS-mutated solid tumors shows high frequencies of concurrent alterations and potential targets but has limited clinical impact.

BACKGROUND: This study aimed to investigate the distribution and frequency of concurrent alterations in different cancers across KRAS subtypes and in different KRAS subtypes across cancers, and to identify potentially actionable targets and patients who received targeted treatment matched to their genomic profile (GP). MATERIALS AND METHODS: In this descriptive and single-center study, we included 188 patients with solid tumors harboring KRAS mutations in codon 12, 13, 61, 117, or 146, referred to the Phase 1 Unit, Rigshospitalet, Copenhagen, Denmark from mid-2016 to 2020. Genomic co-alterations were detected with whole-exome sequencing, RNA sequencing, SNP array, and mRNA expression array on fresh biopsies. The study is part of the Copenhagen Prospective Personalized Oncology study (NCT02290522). RESULTS: The majority of patients had colorectal cancer (60.1%), non-small cell lung cancer (11.2%), or pancreatic cancer (10.6%). Most tumors were KRAS-mutated in codon 12 or 13 (93.7%) including G12D (27.1%), G12V (26.6%), G12C (11.7%), and G13D (11.2%). A total of 175 different co-alterations were found, most frequently pathogenic APC and TP53 mutations (55.9% and 46.4%, respectively) and high expression of CEACAM5 (73.4%). Different cancers and KRAS subtypes showed different patterns of co-alterations, and 157 tumors (83.5%) had potentially actionable targets with varying evidence of targetability (assessed using ESMO Scale for Clinical Actionability of molecular Targets). Of the 188 patients included in the study, 15 (7.4%) received treatment matched to their GP (e.g., immunotherapy and synthetic lethality drugs), of whom one had objective partial response according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CONCLUSION: Performing extensive genomic analysis in patients with known KRAS-mutated solid tumors may contribute with information to the genomic landscape of cancers and identify targets for immunotherapy or synthetic lethality drugs, but currently appears to have overall limited clinical impact, as few patients received targeted therapy matched to their GP.

Can Strain Elastography Predict Malignancy of Soft Tissue Tumors in a Tertiary Sarcoma Center?

This study aims to investigate the ability of ultrasound strain elastography as an adjunct to predict malignancy in soft tissue tumors suspect of sarcoma or metastasis in a tertiary reference center for sarcoma. A total of 137 patients were included prospectively. Patients were referred on the basis of clinical or radiological suspicion of malignant soft tissue tumor. All patients had previously undergone diagnostic imaging (MRI, CT or PET-CT). After recording strain elastography cine loops, ultrasound guided biopsy was performed. Three investigators, who were blinded to final diagnosis, reviewed all elastograms retrospectively. For each elastogram, a qualitative, visual 5-point score was decided in consensus and a strain ratio was calculated. Final pathology obtained from biopsy or tumor resection served as gold standard. Eighty-one tumors were benign, and 56 were malignant. t-tests showed a significant difference in mean visual score between benign and malignant tumors. There was no significant difference in mean strain ratio between the two groups. Strain elastography may be a valuable adjunct to conventional B-mode ultrasound, perhaps primarily in primary care, when considering whether to refer to a sarcoma center or to biopsy, although biopsies cannot reliably be ruled out based on the current data.

Cochlear ossification in patients with profound hearing loss following bacterial meningitis.

CONCLUSION: Cochlear ossification following bacterial meningitis is related to causative pathogen, but not age at disease or time point of evaluation. However, progression may occur over time, especially in case of primary signs of ossification. OBJECTIVE: To investigate the occurrence and degree of cochlear ossification on CT and MRI in patients with bilateral profound hearing loss following bacterial meningitis, in relation to causative pathogen, age at disease, and time point of evaluation. Progression of ossification in cases that underwent more than one scan was evaluated. METHODS: In the period 1982-2008, 47 cochlear implantations were performed in 34 consecutive candidates suffering from bilateral profound hearing loss following bacterial meningitis. A retrospective review of patient files and preoperative CT and MR images was performed. RESULTS: Cochlear ossification was observed in 35% of patients and 26% of ears on CT. The corresponding values for MRI were 44 and 30% (difference not significant). Streptococcus pneumoniae infection caused ossification more frequently than Neisseria meningitidis. No difference was found between pediatric and adult cases, and the occurrence of ossification was not related to the time point of evaluation. Signs of progressive ossification were found in cases with two CT scans, especially if ossification was present at the first scan.