Background We explored the influence of BRAF and PIK3CA mutational status on the efficacy of bevacizumab or cetuximab plus 5-fluorouracil/leucovorin and irinotecan (FOLFIRI) as first-line therapy in patients with RAS wild-type metastatic colorectal cancer (mCRC). Patients and methods VISNÚ-2 was a multicentre, randomised, phase II study. Patients with RAS wild-type mCRC and <3 circulating tumour cells/7.5 ml blood were stratified by BRAF / PIK3CA status (wild-type versus mutated) and number of affected organs (1 versus >1), and allocated to bevacizumab (5 mg/kg every 2 weeks) or cetuximab (400 mg/m 2 then 250 mg/m 2 weekly) plus FOLFIRI [irinotecan 180 mg/m 2 , leucovorin 400 mg/m 2 , 5-fluorouracil 400 mg/m 2 (bolus) then 2400 mg/m 2 (46-h continuous infusion) every 2 weeks]. The primary endpoint was progression-free survival (PFS). All analyses were exploratory. Results Two hundred and forty patients with BRAF / PIK3CA wild-type ( n = 196) or BRAF- and/or PIK3CA- mutated tumours ( n = 44) were enrolled. Median PFS was 12.7 and 8.8 months in patients with BRAF / PIK3CA wild-type and BRAF / PIK3CA -mutated tumours, respectively [hazard ratio (HR) = 1.22; 95% confidence interval (CI) 0.80-1.85; P = 0.3602]. In the BRAF- and/or PIK3CA -mutated cohort, median PFS was 2.8, 8.8 and 15.0 months in patients with BRAF / PI3KCA -mutated ( n = 8), BRAF -mutated/ PI3KCA wild-type ( n = 16) and BRAF wild-type/ PI3KCA -mutated ( n = 20) tumours, respectively ( P = 0.0002). PFS was similar with bevacizumab plus FOLFIRI versus cetuximab plus FOLFIRI in BRAF / PIK3CA wild-type (HR = 0.99; 95% CI 0.67-1.45; P = 0.9486) and BRAF / PIK3C A-mutated tumours (HR = 1.11; 95% CI 0.53-2.35; P = 0.7820). The most common grade 3/4 treatment-related adverse events were neutropenia, diarrhoea and asthenia in both treatment groups. Conclusions BRAF ...
e16550 Background: To evaluate outcome, failure patterns, prognostic factors and radiotherapy (RT) toxicity after postoperative RT for EC in Tarragona Province (Spain). Methods: A retrospective population-based review on 232 patients (pts) between 1997 and 2000 from different gynaecological Dpt. and in a single oncologist institution with RT Units. Multivariate analysis of disease-free survival (DFS), overall survival (OS), adjuvant RT, RT toxicity (RTOG), prognostic factors for survival, and the distance in Km to the RT Units. Results: Mean age: 64 years (35–88). Distance to RT Units >70 Km in 15% pts. Median follow-up: 70 months (2–132). FIGO Stage (S): 8.2% IA; 36.2% IB; 19% IC; 7.8% IIA; 6.5% IIB; 7.3% IIIA; 1.3% IIIB; 3.4% IIIC; 2.6% IVA; 2.2 IVB. Pathology: endometrioid 74.5%, papillary 3.9%, serous 3.4%, clear-cell 2.2%, squamous cell 3%, adenosquamous 1.3%, mixed 3.9%. Grade (G): 35.7% G1, 45.3% G2, 19% G3; miometrial invasion: 44.1% >50%, 46% <50%, 9.9% not invasion. Treatment: 1) Surgery in 93.5%, 49.6% lymph nodes dissection. 2) RT in 73.5%: 47% external beam radiotherapy (EBI) and brachytherapy (BT), 9.4% BT alone, 17.1% EBI alone. 3) Chemotherapy in 11.1% and hormonal treatment in 6.9%. 3). Grade 3 and 4 toxicity: 12 (9%) pts, 6 early and 6 late. Relapses: 26/232 (11.6%), S-I: 11/26 (42%), S-II: 1/26 (3.8%), S-III: 5/26 (19.2%), S-IV: 3/26 (11.5%). Metastasis: 28/232 (12.5%). Survivals at 5 years: 1) OS in all stages was 78.8% and 83%, 89.6%, and 76% for SI, SII, and SIII, respectively. 2) DFS was 76.5% for all pts and 82.3%, 86.22%, and 68.24% for SI, SII, and SIII, respectively. Multivariate analysis: significant prognostic factors for poor outcome were age (p < 0.01), lymph nodes dissection (p < 0.001), pathologic subtype (p < 0.001), grade of differentiation (p < 0.001), and deep myometrial invasion (p < 0.005). Conclusions: Survivals, RT toxicity and relapse sites were similar to the other reported series. Predictors of poor outcome were age, lymph nodes dissection, pathology subtype, grade of differentiation, and deep myometrial invasion. Patients of Tarragona Province are in need of a better accessibility to the radiation units. No significant financial relationships to disclose.
Liquid biopsy has improved significantly over the last decade and is attracting attention as a tool that can complement tissue biopsy to evaluate the genetic landscape of solid tumors. In the present study, we evaluated the usefulness of liquid biopsy in daily oncology practice in different clinical contexts. We studied ctDNA and tissue biopsy to investigate EGFR, KRAS, NRAS, and BRAF mutations from 199 cancer patients between January 2016 and March 2021. The study included 114 male and 85 female patients with a median age of 68 years. A total of 122 cases were lung carcinoma, 53 were colorectal carcinoma, and 24 were melanoma. Liquid biopsy was positive for a potentially druggable driver mutation in 14 lung and colorectal carcinoma where tissue biopsy was not performed, and in two (3%) lung carcinoma patients whose tissue biopsy was negative. Liquid biopsy identified nine (45%) de novo EGFR-T790M mutations during TKI-treatment follow-up in lung carcinoma. BRAF-V600 mutation resurgence was detected in three (12.5%) melanoma patients during follow-up. Our results confirm the value of liquid biopsy in routine clinical oncologic practice for targeted therapy, diagnosis of resistance to treatment, and cancer follow-up.
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