Sequential RAS mutations evaluation in cell-free DNA of patients with tissue RAS wild-type metastatic colorectal cancer: the PERSEIDA (Cohort 2) study.

PURPOSE: RAS (KRAS/NRAS) mutational status on a tumor biopsy is mandatory to guide the best treatment in metastatic colorectal cancer (mCRC). Determining the RAS mutational status by tumor-tissue biopsy is essential in guiding the optimal treatment decision for mCRC. RAS mutations are negative predictive factors for the use of EGFR monoclonal antibodies. Cell-free DNA (cfDNA) analysis enables minimally invasive monitoring of tumor evolution. METHODS/PATIENTS: PERSEIDA was an observational, prospective study assessing cfDNA RAS, BRAF and EGFR mutations (using Idylla™) in first-line mCRC, RAS wild-type (baseline tumor-tissue biopsy) patients (cohort 2). Plasma samples were collected before first-line treatment, after 20 ± 2 weeks, and at disease progression. RESULTS: 117 patients were included (103 received panitumumab + chemotherapy as first-line treatment). At baseline, 7 (6.8%) patients had RAS mutations, 4 (3.9%) BRAF mutations and no EGFR mutations were detected (cfDNA, panitumumab + chemotherapy subpopulation [panitumumab + Ch]). The baseline RAS mutational status concordance between tissue and liquid biopsies was 94.0% (93.2%, panitumumab + Ch). At 20 weeks, only one patient in the study (included in the panitumumab + Ch) had an emerging cfDNA RAS mutation. No emerging BRAF or EGFR mutations were reported. At disease progression, 6 patients had emergent mutations not present at baseline (RAS conversion rate: 13.3% [6/45]; 15.0% [6/40], panitumumab + Ch). CONCLUSIONS: The concordance rate between liquid and solid biopsies at baseline was very high, as previously reported, while our results suggest a considerable emergence of RAS mutations during disease progression. Thus, the dynamics of the genomic landscape in ctDNA may provide relevant information for the management of mCRC patients.

Treatment change comparisons between skeletal Class I and II white adolescents with 3 different vertical divergencies-Part 2: Holdaway difference.

INTRODUCTION: The Holdaway difference represents the relationship of the NB line to the mandibular incisor (NB-L1) and the bony pogonion (NB-Pog). This study aimed to evaluate treatment changes of NB-L1, NB-Pog, and the Holdaway difference in patients with skeletal Class I and II relationships with 3 different skeletal divergencies. METHODS: This retrospective study was the second part of treatment outcome assessments of 135 white adolescent patients (females, n = 69; males, n = 66; mean age, 12.8 ± 1.4 years pretreatment and 15.0 ± 1.4 years posttreatment). The NB-L1, NB-Pog, and Holdaway differences (NB-L1 - NB-Pog) were measured. The mixed-model analysis of variance was used to assess within- and between-subject effects responding to horizontal and vertical skeletal discrepancies. RESULTS: For the group with favorable profile changes, the means of the Holdaway difference were maintained in the hypodivergent and normodivergent subgroups and reduced in the hyperdivergent subgroups for patients with skeletal Class I and II relationships. The means of NB-L1 and Holdaway difference were significantly larger in the skeletal Class II group and became greater as skeletal vertical divergencies increased. The NB-Pog means were significantly different only between the hypodivergent and hyperdivergent subgroups. CONCLUSIONS: Based on the findings of this study, the Holdaway difference should be adjusted to individualize the incisor positions, considering not only the anteroposterior but also the vertical skeletal relationships of the patients.