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1.
Clin. transl. oncol. (Print) ; 20(11): 1422-1429, nov. 2018. tab, graf
Article in English | IBECS | ID: ibc-173733

ABSTRACT

Purpose: After surgical resection, an ample prognosis variability among stages is observed. Multiple prognostic factors are individually studied and some CRC classifiers have been proposed. Not one have been implemented into clinical practice. Methods/patients: We classified 105 patients with resected CRC (stage I-III) into five molecular subtypes using BRAFV600E and RAS (KRAS; NRAS) status, and the expression of DNA mismatch repair (MMR) proteins (MLH1 and MSH2). Clinicopathological features and DFS) of distincts groups were evaluated. Results and conclusions: RAS and BRAFV600E mutations were detected in 43.8 and 11.4% of patients, respectively. 19% of tumours had lack of expression of any MMR proteins reflecting a system deficiency (dMMR). Patients with any RAS mutation had lower DFS that patients with RAS wild type (wt) (40.23 vs 45.26 months; p value = 0.035). Of a total of five molecular subtypes, three were MMR proficient (pMMR): RAS mutated (39%), BRAFV600E mutated (6.7%) and RAS/BRAFV600E wt (35.2%); and two were dMMR: BRAFV600E mutated (4.8%) and BRAFV600E wt (14.3%). Left side tumours were more frequently observed in pMMR/RAS and BRAFV600E wt subtype, and right side tumours in dMMR subtypes. Among the three pMMR subtypes, a benefit survival was observed for patients without any mutation in BRAFv600E or RAS oncogenes (median of DFS = 45.5 vs 40.98 months in RAS mutated group; p = 0.084 and vs 34.13 in BRAFv600E mutated group; p = 0.031). Molecular classification using these biomarkers can be useful to identify groups with differences in prognosis


No disponible


Subject(s)
Humans , Colorectal Neoplasms/genetics , Biomarkers, Tumor/analysis , Molecular Diagnostic Techniques/methods , Colorectal Neoplasms/pathology , Colorectal Neoplasms/classification , Prognosis , Mutation/genetics , DNA Repair-Deficiency Disorders/genetics , Neoplasm Staging
2.
Clin. transl. oncol. (Print) ; 20(8): 1072-1079, ago. 2018. tab, graf
Article in English | IBECS | ID: ibc-173691

ABSTRACT

Background: Immunotherapy increases overall response rate (ORR) and overall survival (OS) in patients with non-small-cell lung cancer (NSCLC). Prognostic and predictive factors are a high need. Patients and methods: Retrospective review of NSCLC patients treated with nivolumab was performed. Analyzed variables included age, sex, stage, performance status (PS), location of metastases, presence of tumour-related symptoms and comorbidities, number of metastasis locations, previous chemotherapy, anti-angiogenic and radiotherapy treatments, and analytical data from the standard blood count and biochemistry. Results: A total of 175 patients were included. Median age was 61.5 years, 73.1% were men, 77.7% were ECOG-PS 0-1, and 86.7% were included with stage IV disease. Histology was non-squamous in 77.1%. Sixty-five received nivolumab in second line (37.1%). Thirty-eight patients had brain metastasis (22%), and 39 (22.3%) liver metastasis and 126 (72%) had more than one metastatic location. The ORR was 15.7% with median Progression free survival (PFS) 2.8 months and median OS 5.81 months. Stage III vs IV and time since the beginning of the previous line of treatment ≥ 6 vs < 6 months were associated with better response. PS 2, time since the previous line of treatment < 6 vs ≥ 6 months, and more than one metastatic location were independently associated with shorter OS in multivariable analysis (7.8 vs 2.7 months, 11.2 vs 4.6 months, and 9.4 vs 5.1 month). Finally, time since the previous treatment < 6 vs ≥ 6 months and more than one metastatic location were independently associated with shorter PFS in multivariable analysis (4.3 vs 2.3 months and 4.7 vs 2.3 months). Conclusion: Poor PS, short period of time since the previous treatment, and more than one metastatic location were associated with poorer prognostic


No disponible


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Antibodies, Monoclonal, Humanized/pharmacokinetics , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Retrospective Studies , Neoplasm Recurrence, Local/prevention & control
4.
Clin Transl Oncol ; 20(11): 1422-1429, 2018 Nov.
Article in English | MEDLINE | ID: mdl-29802524

ABSTRACT

PURPOSE: After surgical resection, an ample prognosis variability among stages is observed. Multiple prognostic factors are individually studied and some CRC classifiers have been proposed. Not one have been implemented into clinical practice. METHODS/PATIENTS: We classified 105 patients with resected CRC (stage I-III) into five molecular subtypes using BRAFV600E and RAS (KRAS; NRAS) status, and the expression of DNA mismatch repair (MMR) proteins (MLH1 and MSH2). Clinicopathological features and DFS) of distincts groups were evaluated. RESULTS AND CONCLUSIONS: RAS and BRAFV600E mutations were detected in 43.8 and 11.4% of patients, respectively. 19% of tumours had lack of expression of any MMR proteins reflecting a system deficiency (dMMR). Patients with any RAS mutation had lower DFS that patients with RAS wild type (wt) (40.23 vs 45.26 months; p value = 0.035). Of a total of five molecular subtypes, three were MMR proficient (pMMR): RAS mutated (39%), BRAFV600E mutated (6.7%) and RAS/BRAFV600E wt (35.2%); and two were dMMR: BRAFV600E mutated (4.8%) and BRAFV600E wt (14.3%). Left side tumours were more frequently observed in pMMR/RAS and BRAFV600E wt subtype, and right side tumours in dMMR subtypes. Among the three pMMR subtypes, a benefit survival was observed for patients without any mutation in BRAFv600E or RAS oncogenes (median of DFS = 45.5 vs 40.98 months in RAS mutated group; p = 0.084 and vs 34.13 in BRAFv600E mutated group; p = 0.031). Molecular classification using these biomarkers can be useful to identify groups with differences in prognosis.


Subject(s)
Adenocarcinoma/diagnosis , Adenocarcinoma/genetics , Biomarkers, Tumor/genetics , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/pathology , Colorectal Neoplasms/therapy , DNA Mismatch Repair/genetics , Female , Genes, ras , Humans , Male , Middle Aged , Molecular Diagnostic Techniques , Mutation , Neoplasm Staging , Prognosis , Proto-Oncogene Proteins B-raf/genetics , Treatment Outcome
5.
Clin Transl Oncol ; 20(8): 1072-1079, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29368144

ABSTRACT

BACKGROUND: Immunotherapy increases overall response rate (ORR) and overall survival (OS) in patients with non-small-cell lung cancer (NSCLC). Prognostic and predictive factors are a high need. PATIENTS AND METHODS: Retrospective review of NSCLC patients treated with nivolumab was performed. Analyzed variables included age, sex, stage, performance status (PS), location of metastases, presence of tumour-related symptoms and comorbidities, number of metastasis locations, previous chemotherapy, anti-angiogenic and radiotherapy treatments, and analytical data from the standard blood count and biochemistry. RESULTS: A total of 175 patients were included. Median age was 61.5 years, 73.1% were men, 77.7% were ECOG-PS 0-1, and 86.7% were included with stage IV disease. Histology was non-squamous in 77.1%. Sixty-five received nivolumab in second line (37.1%). Thirty-eight patients had brain metastasis (22%), and 39 (22.3%) liver metastasis and 126 (72%) had more than one metastatic location. The ORR was 15.7% with median Progression free survival (PFS) 2.8 months and median OS 5.81 months. Stage III vs IV and time since the beginning of the previous line of treatment ≥ 6 vs < 6 months were associated with better response. PS 2, time since the previous line of treatment < 6 vs ≥ 6 months, and more than one metastatic location were independently associated with shorter OS in multivariable analysis (7.8 vs 2.7 months, 11.2 vs 4.6 months, and 9.4 vs 5.1 month). Finally, time since the previous treatment < 6 vs ≥ 6 months and more than one metastatic location were independently associated with shorter PFS in multivariable analysis (4.3 vs 2.3 months and 4.7 vs 2.3 months). CONCLUSION: Poor PS, short period of time since the previous treatment, and more than one metastatic location were associated with poorer prognostic.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/secondary , Carcinoma, Squamous Cell/secondary , Lung Neoplasms/pathology , Neoplasm Recurrence, Local/pathology , Aged , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Squamous Cell/drug therapy , Female , Follow-Up Studies , Humans , Lung Neoplasms/drug therapy , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local/drug therapy , Nivolumab , Prognosis , Retrospective Studies , Survival Rate
6.
Clin. transl. oncol. (Print) ; 18(4): 405-412, abr. 2016. tab, ilus, graf
Article in English | IBECS | ID: ibc-150456

ABSTRACT

Purpose: To analyse the prognostic role of the immunohistochemical expression of pKDR in patients with advanced colorectal cancer treated with oxaliplatin and fluoropyrimidines combination chemotherapy with or without bevacizumab. Methods: Retrospective multicentre study, carried out at four hospitals in the Valencian Community (Spain). Patients evolution was compared based on the immunohistochemical expression of pKDR, classified using 4 categories: 0 (undetectable), 1 (mild), 2 (moderate) and 3 (high intensity). Patients were divided into two groups for the analysis: group 1 with low expression (0-1) vs. group 2 with high expression (2-3). Results: Histological samples for the pKDR analysis were available for 84 of the 112 patients selected. Seven (8.3 %) had undetectable or mild expression of pKDR (Group 1) and 77 (91.7 %) showed moderate or high expression of pKDR (Group 2). Response rate in Group 1 was 100 %compared to 54.2 % in Group 2 (p = 0.019). Progression-free survival (PFS) (15 vs. 12 months, p = 0.4) and overall survival (OS) (28 vs. 22 months, p = 0.09) were numerically but not significantly higher in patients from Group 1 vs. Group 2. Patients from Group 2 who received bevacizumab presented a significantly higher PFS (13 vs. 11, p = 0.015) and a numerically higher OS (23 vs. 17 months, p = 0.27) than those treated exclusively with chemotherapy. Conclusions: Our results suggest that the absence or low expression of pKDR is associated with a better prognostic profile in patients with advanced colorectal cancer treated with chemotherapy and bevacizumab. Patients with a high pKDR expression benefit from the combination of chemotherapy with bevacizumab (AU)


No disponible


Subject(s)
Humans , Male , Female , Colorectal Neoplasms/complications , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/drug therapy , Biomarkers/analysis , Prognosis , Antibodies, Monoclonal/therapeutic use , Protein Kinases/analysis , Immunohistochemistry/methods , Immunohistochemistry/standards , Immunohistochemistry , Retrospective Studies , Survivorship
7.
Clin Transl Oncol ; 18(4): 405-12, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26307753

ABSTRACT

PURPOSE: To analyse the prognostic role of the immunohistochemical expression of pKDR in patients with advanced colorectal cancer treated with oxaliplatin and fluoropyrimidines combination chemotherapy with or without bevacizumab. METHODS: Retrospective multicentre study, carried out at four hospitals in the Valencian Community (Spain). Patients evolution was compared based on the immunohistochemical expression of pKDR, classified using 4 categories: 0 (undetectable), 1 (mild), 2 (moderate) and 3 (high intensity). Patients were divided into two groups for the analysis: group 1 with low expression (0-1) vs. group 2 with high expression (2-3). RESULTS: Histological samples for the pKDR analysis were available for 84 of the 112 patients selected. Seven (8.3 %) had undetectable or mild expression of pKDR (Group 1) and 77 (91.7 %) showed moderate or high expression of pKDR (Group 2). Response rate in Group 1 was 100 % compared to 54.2 % in Group 2 (p = 0.019). Progression-free survival (PFS) (15 vs. 12 months, p = 0.4) and overall survival (OS) (28 vs. 22 months, p = 0.09) were numerically but not significantly higher in patients from Group 1 vs. Group 2. Patients from Group 2 who received bevacizumab presented a significantly higher PFS (13 vs. 11, p = 0.015) and a numerically higher OS (23 vs. 17 months, p = 0.27) than those treated exclusively with chemotherapy. CONCLUSIONS: Our results suggest that the absence or low expression of pKDR is associated with a better prognostic profile in patients with advanced colorectal cancer treated with chemotherapy and bevacizumab. Patients with a high pKDR expression benefit from the combination of chemotherapy with bevacizumab.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/metabolism , Colorectal Neoplasms/pathology , Liver Neoplasms/secondary , Vascular Endothelial Growth Factor Receptor-2/metabolism , Adult , Aged , Aged, 80 and over , Bevacizumab/administration & dosage , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Immunoenzyme Techniques , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Phosphorylation , Prognosis , Retrospective Studies , Survival Rate
8.
Oncología (Barc.) ; 29(1): 39-42, ene. 2006. ilus, tab
Article in Es | IBECS | ID: ibc-042875

ABSTRACT

Presentamos un paciente con un timoma invasor como hallazgo en un estudio radiológico por disneaprogresiva. Tras el diagnóstico histológico fue tratado con quimioterapia (Qt) neoadyuvante consiguiendo unareducción del volumen tumoral del 25%. El tratamiento quirúrgico consistió en una exéresis en bloque deltimoma junto con el pulmón izquierdo por afectación de los vasos pulmonares. La combinación de la Qtneoadyuvante con la cirugía posibilitan un tratamiento con intención curativa


We present a patient suffering from an invasive thymoma discovered in a chest roentgenogram because ofprogressive dyspnea. Neoadjuvant chemotherapy was used after histological diagnosis, observing a tumorvolume decrease of 25 %. The surgical treatment consisted of the thymoma en bloc resection, and a left sidepneumonectomy due to affected pulmonary vessels. The combination of neoadjuvant chemotherapy andsurgery is applied as a curative intention therapy


Subject(s)
Male , Middle Aged , Humans , Thymoma/therapy , Thymus Neoplasms/therapy , Neoadjuvant Therapy/methods , Pneumonectomy , Dyspnea/etiology
9.
Allergol Immunopathol (Madr) ; 28(3): 136-43, 2000.
Article in Spanish | MEDLINE | ID: mdl-10867384

ABSTRACT

The leukotriene antagonists have represented the first novelty in the treatment of asthma over the last 20 years. Their easy oral administration that favours a suitable completion of the treatment, especially on children, together with the proven efficiency and their apparent safety, gave rise to the fact in 1999 the asthma committee of the Spanish Society of Clinical Immunology and Paediatric Allergology (SSCIPA) in the bronchial asthma treatment guide that was presented a year ago during the XXIII National Congress of our Society, considered the antileukotrienes, together with the chromones, as important medicines for stage 2 asthma (frequent episodes) and as useful medicines to reduce the need to take corticoides in cases of persistent asthma. A year later, in our study we proposed to value too suitability or non suitability of this positioning, in the light of the new investigations published and from our own experience. We believe that the bibliography available to date shows that the agonist cysteinyl-leukotrienes are anti-inflammatory medicines, that have an efficiency similar to that of low doses of inhaled corticoids, equally efficient in controlling bronchospasm-induced exercise and they have a good safety profile. We present two studies that are the result of our own experience, one carried out on children with persistent asthma and the other on children with frequent episodic asthma, from which we can apparently deduce that both nedocromil (2 inhalations every 8 hours) and montelukast (5 mg every 24 hours) are medicines that have similar efficacy in the control of asthma. We conclude that the antileukotrienes, together with the chromones, should be seen as important medicines when treating infant asthma.


Subject(s)
Leukotriene Antagonists/therapeutic use , Leukotrienes/metabolism , Acetates/therapeutic use , Administration, Oral , Adrenal Cortex Hormones/therapeutic use , Algorithms , Anti-Asthmatic Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Asthma/drug therapy , Beclomethasone/therapeutic use , Child , Clinical Trials as Topic , Cyclopropanes , Double-Blind Method , Humans , Leukotriene Antagonists/metabolism , Nedocromil/therapeutic use , Quinolines/therapeutic use , Randomized Controlled Trials as Topic , Sulfides , Treatment Outcome
10.
Allergol. immunopatol ; 28(3): 136-142, abr. 2000.
Article in Es | IBECS | ID: ibc-9818

ABSTRACT

Los antagonistas de los leucotrienos han supuesto la primera novedad en el tratamiento del asma en los últimos 20 años. Su fácil administración por vía oral que favorece un adecuado cumplimiento del tratamiento, sobre todo en niños, junto a su eficacia demostrada y su aparente seguridad hicieron que en 1999 el comité de asma de la Sociedad Española de Inmunología Clínica y Alergología Pediátrica (SEICAP) en la guía de tratamiento del asma bronquial que se presentó hace un año en el XXIII congreso nacional de nuestra sociedad situó a los antileucotrienos, junto con las cromonas, como fármacos de primera línea en el asma en estadio dos (episódico frecuente), y como fármacos útiles para la reducción de la necesidad de corticoides en los asmas persistentes. Doce meses después nos proponemos en este trabajo valorar la conveniencia o inconveniencia de dicha situación, a la luz de los nuevos trabajos publicados y de nuestra propia experiencia. Creemos que con la bibliografía hasta ahora disponible queda demostrado que los fármacos agonistas de los cisteinil-leucotrienos son fármacos antiinflamatorios, con una eficacia similar a dosis bajas de corticoides inhalados, eficaces asimismo en el control del broncoespasmo inducido por ejercicio y con un buen perfil de seguridad. Presentamos dos trabajos fruto de nuestra propia experiencia, uno en niños con asma persistente y otros en niños con asma episódica frecuente, en los que parece deducirse que tanto el nedocromil (2 inh/8 horas) como el montelukast (5 mg/24 horas) son fármacos de eficacia similar en el control del asma. Concluimos que los antileucotrienos, junto con las cromonas, deberían ser vistos como fármacos de primera línea en el tratamiento del asma infantil (AU)


The leukotriene antagonists have represented the first novelty in the treatment of asthma over the last 20 years. Their easy oral administration that favours a suitable completion of the treatment, especially on children, together with the proven efficiency and their apparent safety, gave rise to the fact in 1999 the asthma committee of the Spanish Society of Clinical Immunology and Paediatric Allergology (SSCIPA) in the bronchial asthma treatment guide that was presented a year ago during the XxiII National Congress of our Society, considered the antileukotrienes, together with the chromones, as important medicines for stage 2 asthma (frequent episodes) and as useful medicines to reduce the need to take corticoides in cases of persistent asthma. A year later, in our study we proposed to value the suitability or non suitability of this positioning, in the light of the new investigations published and from our own experience. We believe that the bibliography available to date shows that the agonist cysteinyl-leukotrienes are anti-inflammatory medicines, that have an efficiency similar to that of low doses of inhaled corticoids, equally efficient in controlling bronchospasm-induced exercise and they have a good safety profile. We present two studies that are the result of our own experience, one carried out on children with persistent asthma and the other on children with frequent episodic asthma, from which we can apparently deduce that both nedocromil (2 inhalations every 8 hours) and montelukast (5 mg every 24 hours) are medicines that have similar efficacy in the control of asthma. We conclude that the antileukotrienes, together with the chromones, should be seen as important medicines when treating infant asthma (AU)


Subject(s)
Child , Humans , Leukotrienes , Nedocromil , Treatment Outcome , Anti-Asthmatic Agents , Leukotriene Antagonists/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal , Anti-Inflammatory Agents , Quinolines/therapeutic use , Beclomethasone/therapeutic use , Asthma/drug therapy , Clinical Trials as Topic , Double-Blind Method , Acetates/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Administration, Oral , Algorithms
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