Diversity of oncopharmacogenetic profile within Spanish population.

Consensus guidelines for genotype-guided fluoropyrimidine dosing based on variation in the dihydropyrimidine dehydrogenase (DPYD) gene before treatment have been firmly established. The prior pharmacogenetic report avoids the serious toxicity that inevitably occurred in a non-negligible percentage of the treated patients. The precise description of the allelic distribution of the variants of interest in our reference populations is information of great interest for the management of the prescription of these antineoplastic drugs. We characterized the allelic distribution of the UGT1A1*28 variant (rs3064744), as well as the DPYD*2A (rs3918290) variant, c.1679T>G (rs55886062), c.2846A>T (rs67376798) and c.1129-5923C>G (rs75017182; HapB3) in series of 5251 patients who are going to receive treatment with irinotecan and fluoropyrimidines, representative of Valencian, Aragonese and Western Andalusian populations.

Sex differences in the diagnosis, treatment and prognosis of cancer: the rationale for an individualised approach

Background Precision medicine in oncology aims to identify the most beneficial interventions based on a patient’s individual features and disease. However, disparities exist when providing cancer care to patients based on an individual’s sex. Objective To discuss how sex differences impact the epidemiology, pathophysiology, clinical manifestations, disease progression, and response to treatment, with a focus on data from Spain. Results Genetic and environmental factors (social or economic inequalities, power imbalances, and discrimination) that contribute to these differences adversely affect cancer patient health outcomes. Increased health professional awareness of sex differences is essential to the success of translational research and clinical oncological care. Conclusions The Sociedad Española de Oncología Médica created a Task Force group to raise oncologists’ awareness and to implement measures to address sex differences in cancer patient management in Spain. This is a necessary and fundamental step towards optimizing precision medicine that will benefit all individuals equally and equitably (AU)

Maintenance of angiogenesis inhibition with aflibercept after progression to bevacizumab in metastatic colorectal cancer: real life study in the Valencian community

Introduction The second-line chemotherapy in metastatic colorectal cancer (mCRC) with FOLFIRI-aflibercept demonstrated an increase in survival compared with FOLFIRI in patients previously treated with oxaliplatin-based regimens. Few data are available in patients treated previously with bevacizumab. Our objective is to evaluate the efficacy and safety of FOLFIRI-aflibercept in second-line treatment in patients who have previously received bevacizumab. Patients and methods This is a observational, retrospective study of patients with mCRC treated with FOLFIRI-aflibercept in 2nd line in eight hospitals in the Valencian Community. Survival, response, and toxicity were analyzed. Result 122 patients with a median age of 61 years were included. 89% of patients had PS 0–1. The median of PFS (progression free survival) and OS (overall survival) was 5.45 (95% CI 4.74–6.15 months) and 10.15 (95% CI 7.47–12.82 months), respectively. Disease control rate 59.8%. The most common grade 3–4 adverse events were neutropenia (13,1%) and asthenia (9%). The presence of hypertension during treatment with FOLFIRI-aflibercept was associated with a survival benefit. Median of OS was 14.45 (95% CI 11.58–17.32) in patients with hypertension vs 7.78 (95% CI 5.02–10.54) in patients without hypertension (p = .001). Our results suggest that the presence of PS 0, primary tumor surgery, metachronous metastases, and the presence of only 1 metastatic location, are favorable prognostic factors associated with better OS. Conclusions Our results confirm the value of maintaining angiogenesis inhibition with FOLFIRI-aflibercept in mCRC after progression to a first-line treatment with bevacizumab. The development of hypertension during treatment is a possible predictive marker of response (AU)

Sex differences in the diagnosis, treatment and prognosis of cancer: the rationale for an individualised approach.

BACKGROUND: Precision medicine in oncology aims to identify the most beneficial interventions based on a patient's individual features and disease. However, disparities exist when providing cancer care to patients based on an individual's sex. OBJECTIVE: To discuss how sex differences impact the epidemiology, pathophysiology, clinical manifestations, disease progression, and response to treatment, with a focus on data from Spain. RESULTS: Genetic and environmental factors (social or economic inequalities, power imbalances, and discrimination) that contribute to these differences adversely affect cancer patient health outcomes. Increased health professional awareness of sex differences is essential to the success of translational research and clinical oncological care. CONCLUSIONS: The Sociedad Española de Oncología Médica created a Task Force group to raise oncologists' awareness and to implement measures to address sex differences in cancer patient management in Spain. This is a necessary and fundamental step towards optimizing precision medicine that will benefit all individuals equally and equitably.

Long term control stereotactic body radiotherapy (SBRT) for oligometastatic colorectal cancer: a single center study.

BACKGROUND: To evaluate survival after stereotactic body radiotherapy (SBRT) as radical treatment for metastases of colorectal cancer (CRC) and to identify prognostic factors after treatment. METHODS: Patients with metastatic CRC treated with SBRT on metastatic lesions were retrospectively analyzed between February 2012 and August 2016 at the General University Hospital of Valencia. The follow-up was carried out until July 15, 2018. The data have been collected in a database. Patients may have received prior systemic therapy and/or resection of metastatic disease. Endpoints were timed from end of SBRT and included overall survival (OS) and progression-free survival (PFS). Univariate and multivariate analysis using Cox proportional hazard modeling was used to identify prognostic factors. RESULTS: A total of 49 patients were identified. Before SBRT, 77.5% of the patients have received systemic therapy and 65.2% surgery for metastatic disease. Of metastatic lesions treated with SBRT 53.1% were located in the lung, 30.6% in the liver and 16.3% in other locations. Median survival were: PFS after treatment with SBRT was 9.9 months (95% CI: 4.64-15.1) and the median OS was 28.9 months (95% CI: 19.0-38.7). No relapses were observed in 20% of the patients after SBRT. The treatment was well tolerated and no patient had grade 3 or 4 adverse effects. Right colon [HR 16.53 (95% CI: 3.11-87.87), P value 0.001] and higher tumor stage (III-IV) [HR 12.30 (95% CI: 2.10-71.92), P value 0.005] showed a lower OS in a multivariate analysis. CONCLUSIONS: SBRT for oligometastatic disease is an effective option for patients with advanced CRC, with encorauging survival outcomes. However, a definitive validation in large randomized studies is required.

[Euthanasia in patients with cancer and the continuous-care providers]. / La eutanasia en el paciente con cáncer y los cuidados continuos.

During the clinical evolution of patients with cancer there are many occasions, or phases of the disease, when there are no specific treatments and, as such, we need to provide maximum comfort following appropriate symptom control; in this stage it is fundamental to respect personal autonomy together with the option to reject futile treatment. With appropriate control of symptoms it is possible to reach the stage where the majority of the patients do not continue to suffer. Continuous-care providers for cancer patients are those who are responsible for providing help to resolve these situations. In palliative medicine there are highly-efficacious procedures to the help in these last hours. Sedation is applied when it is impossible to control symptoms by other means. With appropriate Carer cover, it is not necessary to introduce laws on assisted suicide and/or active voluntary euthanasia, neither because of the magnitude of demand, nor because of the difficulties in achieving appropriate control of symptoms.

[Analysis of tumour-derived DNA in serum in advanced non-microcytic lung cancer: might it be a prognostic factor?]. / Análisis de la concentración sérica del ADN tumoral en el cáncer de pulmón no microcítico y avanzado: 'es útil como factor pronóstico?

INTRODUCTION: Presence of circulating DNA in the serum of patients with cancer makes detection of tumour-specific genetic alterations feasible. OBJECTIVE: To study serum DNA concentration in patients diagnosed as having advanced Non-Small Cell Lung Cancer (NSCLC) and to evaluate its relationship with age, histology, stage, response, time-to-progression (TTP), and survival. METHODS: Serum DNA from 78 patients was purified and spectrophotometrically quantified. RESULTS: No significant correlations were found between serum DNA concentration and age, histology, response and survival. There was a significant correlation with respect to stage (IIIB = 408.75 ng/ml; IV = 478.74 ng/ml; p = 0.02). When patients were grouped according to DNA concentration, significant correlation with TTP was found; establishing a cut-off point at 500 ng/ml ([DNA] < 500 ng/ml TTP = 7.25 months, 95%CI: 3.5-5.25; [DNA ] > or = 500 ng/ml TTP = 4.25 months, 95%CI: 2-6.5; p = 0.05). CONCLUSIONS: Using the present method, DNA concentration quantification appears to be simple, but with certain deficiencies due to inter-sample variability and low specificity. This is because total DNA concentration is measured without distinguishing as to whether it is tumour-related. We suggest that there is a correlation between DNA concentration and prognosis which enables an analysis of the natural history of the disease.

Análisis de la concentración sérica del ADN tumoral en el cáncer de pulmón no microcítico y avanzado: ¿es útil como factor pronóstico? / Analysis of tumour-derived DNA in serum in advanced non-microcytic lung cancer: might it be a prognostic factor?

Introducción. El ADN sérico de pacientes oncológicos puede permitir detectar alteraciones genéticas específicas del tumor. Objetivo. Estudiar la concentración de ADN sérico ([ADN]) en pacientes con cáncer de pulmón no microcítico (CPNM) avanzado. Evaluar su relación con la edad, histología, estadio, respuesta, tiempo a la progresión (TTP) y supervivencia. Métodos. Se purificó el ADN sérico de 78 pacientes y se cuantificó espectrofotométricamente. Resultados. No hubo diferencias significativas entre [ADN] media y edad, histología, respuesta, y supervivencia. Hubo significatividad respecto al estadio (IIIB= 408,75 ng/ml; IV= 478,74 ng/ml; p= 0,02). Agrupando los pacientes según el [ADN] hubo significatividad en TTP estableciendo un punto de corte en 500 ng/ml ([ADN] = 500 ng/ml, TTP=4,25 meses, IC 95% 2-6,5; p= 0,05). Conclusiones. La cuantificación del ADN sérico resulta sencilla mediante este método, pero presenta deficiencias debido a la variabilidad intermuestral y a la baja especificidad, al medirse el [ADN] total sin especificar su asociación o no al tumor. Nuestro estudio sugiere que el [ADN] está relacionado con el pronóstico permitiendo un análisis evolutivo

Introduction. Presence of circulating DNA in the serum of patients with cancer makes detection of tumour-specific genetic alterations feasible. Objective. To study serum DNA concentration in patients diagnosed as having advanced Non-Small Cell Lung Cancer (NSCLC) and to evaluate its relationship with age, histology, stage, response, time-to-progression (TTP), and survival. Methods. Serum DNA from 78 patients was purified and spectrophotometrically quantified. Results. No significant correlations were found between serum DNA concentration and age, histology, response and survival. There was a significant correlation with respect to stage (IIIB = 408.75 ng/ml; IV = 478.74 ng/ml; p = 0.02). When patients were grouped according to DNA concentration, significant correlation with TTP was found; establishing a cut-off point at 500 ng/ml ([DNA] = 500 ng/ml TTP = 4.25 months, 95%CI: 2-6.5; p = 0.05). Conclusions. Using the present method, DNA concentration quantification appears to be simple, but with certain deficiencies due to inter-sample variability and low specificity. This is because total DNA concentration is measured without distinguishing as to whether it is tumour-related. We suggest that there is a correlation between DNA concentration and prognosis which enables an analysis of the natural history of the disease