Nuestros investigadores

Eduardo Castañón Álvarez

Publicaciones científicas más recientes (desde 2010)

Autores: Berraondo, Pedro, (Autor de correspondencia); Ochoa, María del Carmen; et al.
ISSN 0007-0920  Vol. 120  Nº 1  2019  págs. 6 - 15
Cytokines are soluble proteins that mediate cell-to-cell communication. Based on the discovery of the potent anti-tumour activities of several pro-inflammatory cytokines in animal models, clinical research led to the approval of recombinant interferon-alpha and interleukin-2 for the treatment of several malignancies, even if efficacy was only modest. These early milestones in immunotherapy have been followed by the recent addition to clinical practice of antibodies that inhibit immune checkpoints, as well as chimeric antigen receptor T cells. A renewed interest in the anti-tumour properties of cytokines has led to an exponential increase in the number of clinical trials that explore the safety and efficacy of cytokine-based drugs, not only as single agents, but also in combination with other immunomodulatory drugs. These second-generation drugs under clinical development include known molecules with novel mechanisms of action, new targets, and fusion proteins that increase half-life and target cytokine activity to the tumour microenvironment or to the desired effector immune cells. In addition, the detrimental activity of immunosuppressive cytokines can be blocked by antagonistic antibodies, small molecules, cytokine traps or siRNAs. In this review, we provide an overview of the novel trends in the cytokine immunotherapy field that are yielding therapeutic agents for clinical trials.
Autores: Baraibar, Iosune; Melero, Ignacio Javier; Ponz-Sarvise, Mariano; et al.
ISSN 0114-5916  Vol. 42  Nº 2  2019  págs. 281 - 294
Immunotherapy has emerged in recent years and has revolutionized the treatment of cancer. Immune checkpoint inhibitors, including anti-cytotoxic T lymphocyte antigen-4 (CTLA-4), anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) agents, are the first of this new generation of treatments. Anti-PD-1/PD-L1 agents target immune cells by blocking the PD-1/PD-L1 pathway. This blockade leads to enhancement of the immune system and therefore restores the tumour-induced immune deficiency selectively in the tumour microenvironment. However, this shift in the balance of the immune system can also produce adverse effects that involve multiple organs. The pattern of toxicity is different from traditional chemotherapy agents or targeted therapy, and there is still little experience in recognizing and managing it. Thus, toxicity constitutes a real clinical management challenge and any new alteration should be suspected of being treatment-related. The most common toxicities occur in the skin, gastrointestinal tract, lungs, and endocrine, musculoskeletal, renal, nervous, haematologic, cardiovascular and ocular systems. Immune-mediated toxic effects are usually manageable, but toxicities may sometimes lead to treatment withdrawal, and even fulminant and fatal events can occur. Oncologists need to collaborate with internists, clinical immunologists and other specialists to understand, manage and prevent toxicity derived from immunotherapy. This review focuses on the mechanisms of toxicity of anti-PD-1/PD-L1 agents, and its diagnosis and management.
Autores: Cano, David; et al.
Revista: PLOS ONE
ISSN 1932-6203  Vol. 14  Nº 5  2019  págs. e0215970
Background Perioperative chemotherapy (CT) or neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced gastric (GC) or gastroesophageal junction cancer (GEJC) has been shown to improve survival compared to an exclusive surgical approach. However, most patients retain a poor prognosis due to important relapse rates. Population pharmacokinetic-pharma-codynamic (PK/PD) modeling may allow identifying at risk-patients. We aimed to develop a mechanistic PK/PD model to characterize the relationship between the type of neoadjuvant therapy, histopathologic response and survival times in locally advanced GC and GEJC patients. Methods Patients with locally advanced GC and GEJC treated with neoadjuvant CT with or without preoperative CRT were analyzed. Clinical response was assessed by CT-scan and EUS. Pathologic response was defined as a reduction on pTNM stage compared to baseline cTNM. Metastasis development risk and overall survival (OS) were described using the population approach with NONMEM 7.3. Model evaluation was performed through predictive checks. Results A low correlation was observed between clinical and pathologic TNM stage for both T (R = 0.32) and N (R = 0.19) categories. A low correlation between clinical and pathologic response was noticed (R = -0.29). The OS model adequately described the observed survival rates. Disease recurrence, cTNM stage >= 3 and linitis plastica absence, were correlated to a higher risk of death. Conclusion Our model adequately described clinical response profiles, though pathologic response could not be predicted. Although the risk of disease recurrence and survival were linked, the identification of alternative approaches aimed to tailor therapeutic strategies to the individual patient risk warrants further research.
Autores: Salterain, Nahikari; Castañón, Eduardo; Rodeiro, P.; et al.
ISSN 1388-9842  Vol. 21  Nº Supl. 1  2019  págs. 288 - 289
Autores: Carmona-Bayonas, A. , (Autor de correspondencia); Jimenez-Fonseca, P.; Fernandez-Somoano, A.; et al.
ISSN 1699-048X  Vol. 20  Nº 8  2018  págs. 954 - 965
Observational studies using registry data make it possible to compile quality information and can surpass clinical trials in some contexts. However, data heterogeneity, analytical complexity, and the diversity of aspects to be taken into account when interpreting results makes it easy for mistakes to be made and calls for mastery of statistical methodology. Some questionable research practices that include poor analytical data management are responsible for the low reproducibility of some results; yet, there is a paucity of information in the literature regarding specific statistical pitfalls of cancer studies. In addition to proposing how to avoid or solve them, this article seeks to expose ten common problematic situations in the analysis of cancer registries: convenience, dichotomization, stratification, regression to the mean, impact of sample size, competing risks, immortal time and survivor bias, management of missing values, and data dredging.
Autores: Berraondo, Pedro, (Autor de correspondencia); Aznar, María Ángela; Perez-Ruiz, E.; et al.
ISSN 0340-7004  Vol. 67  Nº 11  2018  págs. 1809 - 1813
Autores: Jimenez-Fonseca, P., (Autor de correspondencia); Carmona-Bayonas, A.; Font, C.; et al.
ISSN 1699-048X  Vol. 20  Nº 2  2018  págs. 230 - 242
To assess the prevalence and prognostic significance of additional intrathoracic findings (AIFs) in patients with cancer and pulmonary embolism (PE). AIFs were considered alterations other than the characteristic ones intrinsic to PE or changes in cardiovascular morphology. Subjects have been taken from a Spanish national multidisciplinary and multicenter study of PE and cancer who were treated between 2004 and 2015. The endpoint was the appearance of serious complications or death within 15 days. The registry contains 1024 eligible patients; 41% diagnosed by computed tomography pulmonary angiography versus 59% by non-angiographic CT. Serious complications occurred within 15 days in 18.9%, [95% confidence interval (CI), 16.6-21.4%] and 9.5% (95% CI 7.9-11.5%) died. At least one AIF was seen in 72.6%. The most common AIFs were as follows: pulmonary nodules (30.9%), pleural effusion (30.2%), tumor progression (28.3%), atelectasis (19.0%), pulmonary infarct (15.2%), emphysema (13.4%), pulmonary lymphangitic carcinomatosis (4.5%), and pneumonia (6.1%). Patients with AIF exhibited a higher complication rate at 15 days: 21.9% versus 13.0%, odds ratio (OR) 1.8 (95% CI 1.2-2.8), P = 0.03, and 15-day mortality: 15.0% versus 7.3%, OR 1.9 (95% CI 1.1-3.2), P = 0.020. Patients with pneumonia, pneumothorax, pulmonary edema, pulmonary nodules, tumor progression, pulmonary fibrosis, and pleural effusion showed an excess of adverse events. Additional intrathoracic findings are highly prevalent and significantly impact prognosis in patients with PE and cancer, making them germane to the classification of this population.
Autores: Rodríguez, Javier; Castañón, Eduardo; Pérez, José Luis; et al.
ISSN 2051-1426  Vol. 6  2018  págs. 96
Surgically resectable synchronic and metachronic liver metastases of colon cancer have high risk of relapse in spite of standard-of-care neoadjuvant and adjuvant chemotherapy regimens. Dendritic cell vaccines loaded with autologous tumor lysates were tested for their potential to avoid or delay disease relapses (NCT01348256). Patients with surgically amenable liver metastasis of colon adenocarcinoma (n = 19) were included and underwent neoadjuvant chemotherapy, surgery and adjuvant chemotherapy. Fifteen patients with disease-free resection margins were randomized 1: 1 to receive two courses of four daily doses of dendritic cell intradermal vaccinations versus observation. The trial had been originally designed to include 56 patients but was curtailed due to budgetary restrictions. Follow-up of the patients indicates a clear tendency to fewer and later relapses in the vaccine arm (median disease free survival -DFS-) 25.26 months, 95% CI 8. 74-n.r) versus observation arm (median DFS 9.53 months, 95% CI 5.32-18.88).
Autores: Baraibar, Iosune; Romano, P. M. ; et al.
ISSN 0923-7534  Vol. 29  Nº Supl. 6  2018  págs. 21 - 22
Autores: Melero, Ignacio Javier; Castañón, Eduardo; Mau-Sorensen, M.; et al.
ISSN 0923-7534  Vol. 29  Nº Supl. 8  2018 
Autores: Sánchez-Bayona, Rodrigo; Chang-Azancot, L.; Álvarez de Mon, Miguel Ángel; et al.
ISSN 0923-7534  Vol. 29  Nº Supl. 8  2018  págs. 711
Background: In the era of big data, the presence of cancer in social media is undeniable. Twitter is one of the biggest networks worldwide, therefore, it establishes an enormous real-world data field of interest when studying health issues. As far as we know, there are no exploratory studies about the content or the authorship of tweets related to breast cancer. Methods: Tweets (original and re-tweets) with the hashtag #BreastCancer posted on Twitter during a 7-day period were collected. For the analysis, tweets were categorised based on their content (medical vs non medical and if medical, appropriate vs inappropriate), user information (private account vs institution or public account), the aim of the tweet (patients¿ experience, relatives¿ experience, advertising, scientific content, fund-raising and patient advocacy) and also on the extent to which they indicated a stigmatising attitude towards cancer. Tweets were further grouped into subthemes: diagnosis, treatment, prognosis and prevention (life-style and other risk factors). Results: A total of 6341 tweets were collected (3703 original and 2638 re-tweets). When analysing original tweets, only 31% had medical content and in these, 90% were considered to have appropriate content. A stigmatising attitude towards cancer was identified in 14.8% of the tweets classified as non-medical content. 60% of the tweets came from private accounts and 40% from institutions or public accounts. Most of the tweets came from patients¿ experiences (30.7%), followed by patient advocacy (25.3%). When considering subthemes, the most common topic was cancer prevention (44.5%). Description of tweets (%) containing #BreastCancer in a 7-day period.
Autores:  et al.
ISSN 0923-7534  Vol. 29  Nº Supl.3  2018 
Autores: Baraibar, Iosune; Martin-Romano, P.; et al.
ISSN 0923-7534  Vol. 29  Nº Supl. 8  2018 
Autores: Carmona Bayonas, A.; Jimenez Fonseca, P.; Font, C.; et al.
ISSN 0007-0920  Vol. 116  Nº 8  2017  págs. 994 - 1001
Background: Our objective was to develop a prognostic stratification tool that enables patients with cancer and pulmonary embolism (PE), whether incidental or symptomatic, to be classified according to the risk of serious complications within 15 days. Methods: The sample comprised cases from a national registry of pulmonary thromboembolism in patients with cancer (1075 patients from 14 Spanish centres). Diagnosis was incidental in 53.5% of the events in this registry. The Exhaustive CHAID analysis was applied with 10-fold crossvalidation to predict development of serious complications following PE diagnosis. Results: About 208 patients (19.3%, 95% confidence interval (CI), 17.1-21.8%) developed a serious complication after PE diagnosis. The 15-day mortality rate was 10.1%, (95% CI, 8.4-12.1%). The decision tree detected six explanatory covariates: Hestia-like clinical decision rule (any risk criterion present vs none), Eastern Cooperative Group performance scale (ECOG-PS; <2 vs >= 2), O-2 saturation (<90 vs >= 90%), presence of PE-specific symptoms, tumour response (progression, unknown, or not evaluated vs others), and primary tumour resection. Three risk classes were created (low, intermediate, and high risk). The risk of serious complications within 15 days increases according to the group: 1.6, 9.4, 30.6%; P<0.0001. Fifteen-day mortality rates also rise progressively in low-, intermediate-, and high-risk patients: 0.3, 6.1, and 17.1%; P<0.0001. The cross-validated risk estimate is 0.191 (s.e. = 0.012). The optimism-corrected area under the receiver operating characteristic curve is 0.779 (95% CI, 0.717-0.840). Conclusions: We have developed and internally validated a prognostic index to predict serious complications with the potential to impact decision-making in patients with cancer and PE.
Autores: Carmona-Bayonas, A.; Jimeénez-Fonseca, P. ; Castañón, Eduardo; et al.
ISSN 1699-048X  Vol. 19  Nº 2  2017  págs. 236 - 250
Long-term cancer survivors develop special health issues and specific needs. Chronic pain, whether the consequence of their cancer or as a side effect of treatment, is one of their most prevalent concerns. We conducted a review of the English-language literature on long-term cancer survivorship and chronic opioid therapy, with the objective of determining the efficacy, safety and tolerability in this group of patients. Practical management recommendations are made on the basis of this review. Pain syndromes encountered in the long-term cancer survivors are diverse. Opioid receptor pathways possess complex and pleiotropic functions and continuous over-activation may lead to de novo endocrinopathies, immunosuppression, neurocognitive impairment, or cell cycle disturbances with potential clinical connotations. However, there are insufficient data to support evidence-based decision making with respect to patient selection, doses, administration, monitoring and follow-up. Data about long-term treatment effectiveness and safety are limited and often aggravated by the overlapping of several diseases prevalent among long-term cancer survivors, as well as chronic opiate-induced toxicity. Chronic opioid therapy is frequent in long-term cancer survivors, and may negatively affect the immune system, and produce health problems such as endocrinopathies, osteoporosis, neurological or cardiopulmonary effects, alterations of cell cycle kinetics, abuse and addiction. This review highlights the need for specialized teams to treat chronic pain in long-term cancer survivors from an integrative perspective.
Autores: Castañón, Eduardo; Soltermann, A.; et al.
ISSN 0304-3835  Vol. 402  2017  págs. 43 - 51
Id1 promotes carcinogenesis and metastasis, and predicts prognosis of non-small cell lung cancer (NSCLC)-adenocarcionoma patients. We hypothesized that Id1 may play a critical role in lung cancer colonization of the liver by affecting both tumor cells and the microenvironment. Depleted levels of Id1 in LLC (Lewis lung carcinoma cells, LLC shId1) significantly reduced cell proliferation and migration in vitro. Genetic loss of Id1 in the host tissue (Id1(-/-) mice) impaired liver colonization and increased survival of Id1 animals. Histologically, the presence of Idl in tumor cells of liver metastasis was responsible for liver colonization. Microarray analysis comparing liver tumor nodules from Id1(+/+) mice and Idl(-/-) mice injected with LLC control cells revealed that Id1 loss reduces the levels of EMT-related proteins, such as vimentin. In tissue microarrays containing 532 NSCLC patients' samples, we found that Idl significantly correlated with vimentin and other EMT-related proteins. Idl loss decreased the levels of vimentin, integrin beta 1, TGF beta 1 and snail, both in vitro and in vivo. Therefore, Id1 enables both LLC and the host microenvironment for an effective liver colonization, and may represent a novel therapeutic target to avoid NSCLC liver metastasis. (C) 2017 Elsevier B.V. All rights reserved.
Autores: Font, C.; Carmona Bayonas, A.; Beato, C.; et al.
ISSN 0903-1936  Vol. 49  Nº 1  2017  págs.  1600282
The study aimed to identify predictors of overall 30-day mortality in cancer patients with pulmonary embolism including suspected pulmonary embolism (SPE) and unsuspected pulmonary embolism (UPE) events. Secondary outcomes included 30- and 90-day major bleeding and venous thromboembolism (VTE) recurrence.The study cohort included 1033 consecutive patients with pulmonary embolism from the multicentre observational ambispective EPIPHANY study (March 2006-October 2014). A subgroup of 497 patients prospectively assessed for the study were subclassified into three work-up scenarios (SPE, truly asymptomatic UPE and UPE with symptoms) to assess outcomes.The overall 30-day mortality rate was 14%. The following variables were associated with the overall 30-day mortality on multivariate analysis: VTE history, upper gastrointestinal cancers, metastatic disease, cancer progression, performance status, arterial hypotension <100¿mmHg, heart rate >110¿beats·min-1, basal oxygen saturation <90% and SPE (versus overall UPE).The overall 30-day mortality was significantly lower in patients with truly asymptomatic UPE events (3%) compared with those with UPE-S (20%) and SPE (21%) (p<0.0001). Thirty- and 90-day VTE recurrence and major bleeding rates were similar in all the groups.In conclusion, variables associated with the severity of cancer and pulmonary embolism were associated with short-term mortality. Our findings may help to develop pulmonary embolism risk-assessment models in this setting
Autores: Jimenez Fonseca, P.; Carmona Bayonas, A.; Lorenzo, M. L. S.; et al.
ISSN 1436-3291  Vol. 20  Nº 3  2017  págs. 465 - 474
Trastuzumab significantly improves overall survival (OS) when added to cisplatin and fluoropyrimidine as a treatment for HER2-positive advanced gastric cancers (AGC). The aim of this study was to evaluate the impact of the gradual implementation of HER2 testing on patient prognosis in a national registry of AGC. This Spanish National Cancer Registry includes cases who were consecutively recruited at 28 centers from January 2008 to January 2016. The effect of missing HER2 status was assessed using stratified Cox proportional hazards (PH) regression. The rate of HER2 testing increased steadily over time, from 58.3 % in 2008 to 92.9 % in 2016. HER2 was positive in 194 tumors (21.3 %). In the stratified Cox PH regression, each 1 % increase in patients who were not tested for HER2 at the institutions was associated with an approximately 0.3 % increase in the risk of death: hazard ratio, 1.0035 (CI 95 %, 1.001-1.005), P = 0.0019. Median OS was significantly lower at institutions with the highest proportions of patients who were not tested for HER2. Patients treated at centers that took longer to implement HER2 testing exhibited worse clinical outcomes. The speed of implementation behaves as a quality-of-care indicator. Reviewed guidelines on HER2 testing should be used to achieve this goal in a timely manner.
Autores: Carmona-Bayonas, A.; Jimenez-Fonseca, P.; Virizuela, J.; et al.
ISSN 1699-048X  Vol. 19  Nº 3  2017  págs. 386 - 395
The clinical index of stable febrile neutropenia (CISNE) can contribute to patient safety without increasing the complexity of decision-making. However, febrile neutropenia (FN) is a diverse syndrome. The aim of this analysis is to assess the performance of CISNE according to the type of tumor and infection and to characterize these patients. We prospectively recruited 1383 FN episodes in situations of apparent clinical stability. Bonferroni-adjusted z tests of proportions were used to assess the association between the infections suspected at the time of onset and the type of tumor with the risk of serious complications and mortality. The performance of CISNE was appraised in each category using the Breslow-Day test for homogeneity of odds ratios and Forest Plots. 171 patients had a serious complication (12.3 %, 95 % confidence interval 10.7-14.2 %). The most common initial assumptive diagnoses were: fever without focus (34.5 %), upper respiratory infection (14.9 %), enteritis (12.7 %), stomatitis (11.8 %), and acute bronchitis (10.7 %). Lung and breast were the most common tumors, accounting for approximately 56 % of the series. The distribution of complications, mortality, and bacteremia varies for each of these categories. However, Breslow-Day tests indicate homogeneity of the odds ratio of the dichotomized CISNE score to predict complications in all infection and tumor subtypes. Despite FN's clinical and microbiological heterogeneity, the CISNE score was seen to be consistent and robust in spite of these variations. Hence, it appears to be a safe tool in seemingly stable FN.
Autores: Aristu, José Javier; Castañón, Eduardo; et al.
ISSN 1699-3055  Vol. 18  Nº 3  2016  págs. 259 - 268
Introduction: Lung cancer is the most frequent neoplasm in humans. Surgery is considered the best therapeutic approach for stage I non-small lung cell cancer (NSCLC). However, a remarkable amount of patients are considered as inoperable. Stereotactic body radiotherapy (SBRT) has risen as an option for those patients, rendering excellent results in quality of life and survival. Materials and methods: We analyzed clinical studies published between 2002 and 2015 which included SBRT as a treatment modality. Our own clinical series was analyzed as well. The patterns of failure following SBRT were investigated, together with the outcomes and the toxicity observed. Results: SBRT has proven to maintain an excellent local control. The analysis showed the tumor size and the histology as determinant factors for the response to treatment. Conclusion: According to the published evidence as well as our own experience, SBRT is a safe and feasible approach for early NSCLC. Its results may be comparable with surgery treatment.
Autores: Castañón, Eduardo; Rolfo, C.; Viñal, D.; et al.
ISSN 1479-5876  Vol. 13  2015  págs. 257
Objectives: Liver metastases appear in 20-30% of patients diagnosed with non-small cell lung cancer (NSCLC) and represent a poor prognosis feature of NSCLC and a possibly more treatment-resistant condition. Potential clinical outcome differences in NSCLC patients with liver metastases harboring molecular alterations in EGFR, KRAS and EML4-ALK genes are still to be determined. This study aims to evaluate the incidence of liver metastasis in a single population and look for potential correlations between EGFR mutations, liver infiltration and clinical outcomes. Methods: A total of 236 consecutive stage IV NSCLC patients treated at the Clinica Universidad de Navarra were analyzed. Results: At onset, liver metastases were present in 16.9% of patients conferring them a shorter overall survival (OS) compared to those with different metastatic locations excluding liver infiltration (10 vs. 21 months; p = 0.001). Patients with EGFR wild-type tumors receiving standard chemotherapy and showing no liver involvement presented a superior median OS compared to those with liver metastases (23 vs. 13 months; p = 0.001). Conversely, patients with EGFR-mutated tumors treated with EGFR tyrosin-kinase inhibitors (TKI's) presented no significant differences in OS regardless of liver involvement (median OS not reached vs. 25 months; p = 0.81). Conclusion: Overall, liver metastases at onset negatively impact OS of NSCLC patients. EGFR TKIs however, may reverse the effects of an initial negative prognosis of liver metastasis in first-line treatment of EGFR mutated NSCLC patients.
Autores: Murillo Jaso, L.; Rodríguez-Spiteri, Natalia; et al.
ISSN 0732-183X  Vol. 33  Nº 15 Supl.  2015  págs. e11617
Background: Amplification of the HER-2 gene occurs in 20% of breast cancer (BC) patients (pts). Trastuzumab administered concurrently with chemotherapy (CT) is the standard of care in the neoadjuvant setting. Moreover, the use of a combination of antiHER2 therapies with CT are related to an increased pCR, which could be a surrogate marker for survival. Methods: We retrospectively analyzed three historic cohorts with overexpressing HER2 BC. They received neoadjuvant CT based on dose dense anthracyclines followed by three schedules of antiHER2 therapy: 1) docetaxel plus trastuzumab (DT; n = 33 pts); 2) DT plus CBDCA (DTP; n = 17 pts); and 3) DT plus double blockade with triweekly pertuzumab or daily L (750mg/day; n = 12) (DTD; n = 14) before surgery. Study endpoints were safety, pCR (breast + axilla) based on Miller&Payne criteria and DFS. Results: Sixty-four pts with HER2 overexpressing BC were studied since 2005. Baseline characteristics were well balanced. The median age was 48 (range 23-80). Coexpression of ER and HER2 in each cohort was 48% in DT, 53%% in DTP and 57% DTD (p = 0.855) as well as initial BC stages (p = 0.64). Grade 3-4 toxicity in DT, DTP and DTD were respectively: asthenia 0%, 5.8% and 0% (p = 0.71), hand-foot syndrome 3%, 5.8% and 0% in DT, DTP and DTD (p = 0.719), anemia 0%, 5.8% and 0% (p = 0.71) leukopenia 6%, 11.7% and 0% in DTD (p = 0.60) and diarrhea in 35.7% in DTD (p = 0.002). We did not find differences in pCR (42.4% in the DT, 29.4%% in the DTP and 42.8% in DTD cohorts; p = 0.67), axillar response (type D) was significantly superior in the DTD cohort with the followed distribution of 51.1%, 52.9% and 85.7% respectively (p = 0.04). However breast responses were similar in the three cohorts (p = 0.9). With a median follow-up of 72, 90 and 21 months respectively, the number of pts who progressed were 12.1%, 11.7% and 0% in DT, DTP and DTD. Conclusions: We did not find differences in pCR in any cohort. The best significant axillary responses were in the DTD cohort, however this fact did not impact in total pCR. DTD cohort has more gastrointestinal toxicity. To date, median survival has not been reached.
Autores: Ponz-Sarvise, Mariano; Castañón, Eduardo; et al.
ISSN 1558-7673  Vol. 12  Nº 2  2014  págs. 87 - 93
Inhibitor of differentiation-1 (Id1) might constitute a novel prognostic factor able to differentiate indolent from aggressive prostate tumors. In this study, 2 cohorts of 52 and 79 prostate cancer patients were selected for Id1 expression analysis. Higher levels of Id1 protein in advanced poor-prognosis patients and a correlation of higher Id1 mRNA expression levels with a lower survival in stage I to III patients were observed. Background: In the prostate-specific antigen era, potentially indolent prostate tumors are radically treated, causing overtreatment. Molecular prognostic factors might differentiate indolent from aggressive tumors, allowing avoidance of unnecessary treatment. Patients and Methods: Fifty-two prostate cancer patients (20 organ-confined and 32 metastatic) were selected. All formalin-fixed and paraffin-embedded primary biopsies and matched metastases of 15 of them were evaluated for tumor and endothelial cell Id1 protein expression. Seventy-nine additional patients with organ-confined prostate cancer were selected for Id1 mRNA in silico analysis. Results: Among metastatic cancer subjects, 48% of primary tumors and 38% of metastases showed Id1 tumor cell expression, and 79% of primary tumors and 81% of metastases showed endothelial immunoreactivity. In the organ-confined group none of them showed Id1 protein tumor cell expression and 50% displayed endothelial expression. In the metastatic patients group, lower levels of Id1 protein predicted a nonsignificant longer overall survival (13 months vs. 7 months; P = .79). In the in silico analysis, however, lower levels of Id1 mRNA predicted a longer disease-free survival (61 months vs. not-reached; P = .018) and the hazard ratio for progression was 0.451 (P = .022) in favor of patients showing lower levels. Conclusion: In our cohort, it seems to be a differential epithelial expression of Id1 protein according to the prognostic features (metastatic/poor prognosis vs. organ-confined/good prognosis). In localized tumors treated with radical prostatectomy, higher Id1 mRNA expression levels might predict a higher hazard ratio for progression and a shorter disease-free survival. Further validation of these results in larger prospective series is warranted.
Autores: Castañón, Eduardo; et al.
ISSN 1479-5876  Vol. 12  2014  págs. 98
In our series, 3R/3R polymorphism correlated with a superior OS. Also, this polymorphism, when associated to wild type EGFR, was related to a higher ORR to pemetrexed. Toxicity was not significantly correlated with a specific TS genotype.
Autores: Aldaz, Azucena; Chopitea, Ana; et al.
ISSN 1969-2420  Vol. 32  Nº 3  2014  págs. S356
Autores: Rodríguez, Javier; Aldaz, Azucena; et al.
ISSN 0732-183X  Vol. 32  Nº Supl. 3  2014  págs. 579
Autores: Castañón, Eduardo; Lopez, I.; et al.
ISSN 1479-5876  Vol. 11  2013 
Background: Inhibitor of DNA binding 1 (Id1) and 3 (Id3) genes have been related with the inhibition of cell differentiation, cell growth promotion and tumor metastasis. Recently, Id1 has been identified as an independent prognostic factor in patients with lung adenocarcinoma, regardless of the stage. Furthermore, Id1 may confer resistance to treatment (both, radiotherapy and chemotherapy). Methods: We have studied, using monoclonal antibodies for immunohistochemistry, the Id1 and Id3 tumor epithelial expression in 17 patients with stage III-N2 non-small cell lung cancer (NSCLC) treated with definitive chemoradiotherapy. Results: Id1 expression is observed in 82.4% of the tumors, whereas Id3 expression is present in 41.2% of the samples. Interestingly, Id1 and Id3 expression are mutually correlated (R = 0.579, p = 0.015). In a subgroup analysis of patients with the most locally advanced disease (T4N2 stage), co-expression of Id1 and Id3 showed to be related with a worse overall survival (45 vs 6 months, p = 0.002). A trend towards significance for a worse progression free survival (30 vs 1 months, p = 0.219) and a lower response rate to the treatment (RR = 50% vs 87.5%, p = 0.07) were also observed. Conclusions: A correlation between Id1 and Id3 protein expression is observed. Id1 and Id3 co-expression seems associated with a poor clinical outcome in patients with locally advanced NSCLC treated with definitive chemoradiotherapy.
Autores: Inoges S; et al.
ISSN 0008-5472  Vol. 72  Nº Sup.24  2012 
Autores: González, Álvaro; García-del-Barrio, MA; Arbea, Leire; et al.
Libro:  Guía inmunotoxicidad: diagnóstico y manejo de los efectos secundarios asociados a inmunoterapia en oncología
2019  págs. 204 - 210