Monitoring of RAS mutant clones in plasma of patients with RAS mutant metastatic colorectal cancer

PurposeSome patients with histologically confirmed primary mCRC and mutated RAS reported undetectable RAS mutant clones in plasma after receiving anti-VEGF treatment. The aim was to prospectively assess it with its potential therapeutic implications.MethodsRAS mutant genes in solid biopsy (before first-line treatment: FOLFOX/CAPOX + bevacizumab) were compared in liquid biopsy (before second-line treatment: panitumumab + FOLFIRI), using Idylla™ system. Discordant results between solid/liquid biopsies were assessed by the next-generation sequencing (NGS) test (solid/liquid biopsies).ResultsTwenty-three patients were assessed (seven had RAS mutant discrepancies between solid/liquid biopsies). The NGS test confirmed that 3/23 (13%) patients had undetectable RAS mutant clones in liquid biopsy and 3/23 (13%) presented discrepancies in solid biopsy (Idylla™ system vs. NGS test).ConclusionThirteen percentage of patients had undetectable RAS mutant clones in liquid biopsy after first-line treatment. However, some discrepancies between solid and liquid biopsies have been observed. These results suggest a need to improve accuracy of RAS analyses, especially in solid biopsies.

Monitoring of RAS mutant clones in plasma of patients with RAS mutant metastatic colorectal cancer.

PURPOSE: Some patients with histologically confirmed primary mCRC and mutated RAS reported undetectable RAS mutant clones in plasma after receiving anti-VEGF treatment. The aim was to prospectively assess it with its potential therapeutic implications. METHODS: RAS mutant genes in solid biopsy (before first-line treatment: FOLFOX/CAPOX + bevacizumab) were compared in liquid biopsy (before second-line treatment: panitumumab + FOLFIRI), using Idylla™ system. Discordant results between solid/liquid biopsies were assessed by the next-generation sequencing (NGS) test (solid/liquid biopsies). RESULTS: Twenty-three patients were assessed (seven had RAS mutant discrepancies between solid/liquid biopsies). The NGS test confirmed that 3/23 (13%) patients had undetectable RAS mutant clones in liquid biopsy and 3/23 (13%) presented discrepancies in solid biopsy (Idylla™ system vs. NGS test). CONCLUSION: Thirteen percentage of patients had undetectable RAS mutant clones in liquid biopsy after first-line treatment. However, some discrepancies between solid and liquid biopsies have been observed. These results suggest a need to improve accuracy of RAS analyses, especially in solid biopsies.

[Use of intravitreal bevacizumab for the treatment of choroidal neovascularization secondary to choroidal rupture]. / Bevacizumab intravítreo en el tratamiento de la neovascularización subretiniana secundaria a rotura coroidea.

CASE REPORT: A 28 year-old male attended our Emergency Department with a traumatic choroidal rupture and macular haemorrhage. After pneumatic displacement of the haemorrhage with C(3)F(8) and tissue plasminogen activator, the haemorrhage was reabsorbed and visual acuity (VA) improved. Three months later the patient presented with decreased VA and a juxtafoveal choroidal neovascularisation (CNV) that was treated with intravitreal bevacizumab. One year after a single bevacizumab injection the CNV remained inactive, with a final VA of 0.5. DISCUSSION: Intravitreal bevacizumab injection is a new and effective treatment for traumatic CNV. In our patient, in contrast to other aetiologies, the CNV needed no more than one Avastin(®) injection to be inactivated, after one year of follow-up.

A retrospective observational study on the safety and efficacy of first-line treatment with bevacizumab combined with FOLFIRI in metastatic colorectal cancer.

BACKGROUND: Combination of bevacizumab and FOLFIRI has currently become one of the standard therapeutic regimens. However, published information is still limited. The objective of the present retrospective observational study is to analyse the response and toxicity of first-line treatment with FOLFIRI+bevacizumab in patients with metastatic colorectal cancer (mCRC). METHODS: Data were collected from patients from nine Spanish sites diagnosed with mCRC, ECOG≤2, whose first treatment for advanced disease was at least three cycles of FOLFIRI+bevacizumab. RESULTS: A total of 95 patients were enrolled into the study: 64.2% males, median age of 59 years (53.2-67.1 years), ECOG=0-1 in 96.9% of patients. The main site of primary tumour was the colon (69.7%), and most metastases occurred in the liver (71.6%). Clinical benefit was detected in 67.4% (57.0-76.6; 95% confidence interval (CI)), with 8.4% of CR and 42.1% of PR. Median TTP was 10.6 months (10.0-11.3; 95% CI), PFS was 10.6 months (9.8-11.3; 95% CI), and OS was 20.7 months (17.1-24.2; 95% CI). Main grade I-II toxicities included haematological toxicity (35.8%), diarrhea (27.3%), mucositis (25.3%), asthenia (19.0%), haemorrhages (11.6%), and emesis (10.6%). Toxicities reaching grades III-IV were haematological toxicity (9.5%), diarrhea (8.5%), mucositis (5.3%), hepatic toxicity (2.1%), asthenia (2.1%), proteinuria (1.1%), emesis (1.1%), pain (1.1%), and colics (1.1%). CONCLUSION: Results of this study support the beneficial effect of adding bevacizumab to FOLFIRI regimen in terms of efficacy and show a favourable tolerability profile.

[Ultrasound biomicroscopy in deep sclerectomy with a new acrylic implant]. / Biomicroscopía ultrasónica en esclerectomía profunda no perforante con un nuevo implante acrílico.

OBJECTIVE: To describe the ultrasound biomicroscopic (UBM) characteristics seen in patients who have undergone deep phaco-sclerectomy with a new acrylic implant (Esnoper). SUBJECTS, MATERIAL AND METHODS: UBM exploration was performed 12 months after deep phaco-sclerectomy in three patients with chronic open angle glaucoma. RESULTS: One year after surgery, all three patients had intraocular pressure levels under 15 mmHg and were on no treatment. All of them had an intrascleral space in UBM, in which the hyperechogenic implant was visible. CONCLUSIONS: The new non-absorbable implant has proven to be effective in these cases. Information provided by UBM is useful and assists in understanding the mechanism of action of deep sclerectomy.

[Von Willebrand factor as an intermediate between hemostasis and angiogenesis of tumor origin]. / El factor von Willebrand como intermediario entre la hemostasia y la angiogénesis de origen tumoral.

Cancer patients often show an imbalance condition between coagulation system and fibrinolysis which causes a prothrombotic state. Different molecular factors like von Willebrand factor (vWf), presenting higher plasmatic rates in these patients, play an important role in this situation. During active angiogenesis taking place in tumor growth, the vascular endothelial growth factor (VEGF) and the fibroblast growth factor (FGF-2) contribute to the proliferation and differentiation of endothelial tissue, the main vWf producer, promoting increased rates of vWf in the serum of neoplastic patients. Recently vWf's contribution to tumor cells and platelet adhesion has been described. In this process, the discovery of platelet, endothelial and tumor cell membrane integrins and their implication in cellular adhesion has represented a major step in demonstrating how blood clotting and platelet aggregation are mediated by tumor cell and platelet linkage. Migration properties acquired by tumor cells as a result of this binding have been also pointed out. Clinical trials show higher rates of plasmatic vWf in cancer patients the more advanced clinical and radiological stage they present (metastasic versus localized). Moreover, higher pre-surgical serum vWf rates in patients can be used to predict poorer survival after resection surgery. vWf high molecular weight multimers have been also related to a cleavage protease deficiency in the serum of the oncologic population. The promising results of antiaggregation/anticoagulation therapies in these patients permit us to envisage new therapeutic targets.

[Evaluation of the body composition by anthropometry and bioelectric impedance in a group of elderly patients recovering from cerebrovascular accidents]. / Evaluación de la composición corporal por antropometría e impedancia bioeléctrica en un grupo de ancianos en recuperación de accidentes cerebrovasculares.

Body composition was assessed by bioelectrical impedance and anthropometry in 25 subjects, 13 men and 12 women aged 68 +/- 9 with approximately 1 year of recovering from stroke. Most of them with a high independence in their diary activities. The main purpose of this study is to know the body composition of elderly patients with this pathology and how affects the two compartments, fat mass and fat free mass when they are measured by two different techniques anthropometry and BIA. Body Mass Index was higher in women than in men and correlation coefficient (r = 0.6) with body fat per cent was similar with both methods: BIA and anthropometry. The body fat per cent values obtained by BIA showed the same trend to be lower for men than for women and in general were higher than the anthropometric values; the high correlation between the body fat per cent by anthropometry and by BIA support this tendency (r = 0.748, p < 0.01). The comparative studies of ours results in elderly subjects recovered from stroke and the literature data in healthy elderly subjects suggests that this pathology do not lean to important changes in body composition. However, further research is necessary to confirm these results.