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1.
Rev. clín. esp. (Ed. impr.) ; 221(6): 359-368, jun.- jul. 2021. tab, graf
Article Es | IBECS | ID: ibc-226482

Estudios epidemiológicos recientes han demostrado que el consumo de alcohol puede aumentar el riesgo de hipertensión arterial, fibrilación auricular y de cáncer digestivo y de mama, por lo que diversos estamentos están promoviendo la abstinencia. Sin embargo, también han vuelto a confirmar que el consumo ligero de alcohol puede reducir el riesgo de infarto de miocardio y de diabetes, no quedando claro el efecto en la enfermedad cerebrovascular. Por ello, la decisión del consumo de alcohol debe ser individual y basada en factores personales. Un nivel de consumo<100g/semana en hombres (menor en mujeres), parece que no aumenta la mortalidad por cualquier causa, mientras que consumos elevados o en forma de atracón (binge) incrementan significativamente el riesgo de mortalidad, por lo cual deben aplicarse todas las medidas para prevenir este tipo de consumo, especialmente en la población más joven. Hay datos que apuntan una ventaja del vino frente a las otras bebidas, pero no son concluyentes (AU)


Recent epidemiological studies have shown that alcohol consumption can increase the risk of arterial hypertension, atrial fibrillation and gastrointestinal and breast cancer. Various sectors are therefore promoting abstinence from alcohol. However, light alcohol consumption has once again been shown to reduce the risk of myocardial infarction and diabetes but with an unclear effect on cerebrovascular disease. The decision to consume alcohol should therefore be an individual one based on personal factors. A level of consumption <100g/week for men (less for women) appears not to increase all-cause mortality, while high consumption or binge drinking significantly increases mortality risk. All measures to prevent this type of consumption, especially among the younger population, should therefore be applied. There are data indicating an advantage of wine over other beverages, but they are not conclusive (AU)


Humans , Alcoholism/complications , Cardiovascular Diseases/etiology , Risk Factors
2.
Rev Clin Esp (Barc) ; 221(6): 359-368, 2021.
Article En | MEDLINE | ID: mdl-34059235

Recent epidemiological studies have shown that alcohol consumption can increase the risk of arterial hypertension, atrial fibrillation and gastrointestinal and breast cancer. Various sectors are therefore promoting abstinence from alcohol. However, light alcohol consumption has once again been shown to reduce the risk of myocardial infarction and diabetes but with an unclear effect on cerebrovascular disease. The decision to consume alcohol should therefore be an individual one based on personal factors. A level of consumption <100 g/week for men (less for women) appears not to increase all-cause mortality, while high consumption or binge drinking significantly increases mortality risk. All measures to prevent this type of consumption, especially among the younger population, should therefore be applied. There are data indicating an advantage of wine over other beverages, but they are not conclusive.


Cardiovascular Diseases , Wine , Alcohol Drinking/adverse effects , Alcohol Drinking/epidemiology , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Ethanol , Female , Humans , Male , Risk Factors
3.
Rev Clin Esp ; 2019 Jul 25.
Article En, Es | MEDLINE | ID: mdl-31353015

Recent epidemiological studies have shown that alcohol consumption can increase the risk of arterial hypertension, atrial fibrillation and gastrointestinal and breast cancer. Various sectors are therefore promoting abstinence from alcohol. However, light alcohol consumption has once again been shown to reduce the risk of myocardial infarction and diabetes but with an unclear effect on cerebrovascular disease. The decision to consume alcohol should therefore be an individual one based on personal factors. A level of consumption <100g/week for men (less for women) appears not to increase all-cause mortality, while high consumption or binge drinking significantly increases mortality risk. All measures to prevent this type of consumption, especially among the younger population, should therefore be applied. There are data indicating an advantage of wine over other beverages, but they are not conclusive.

4.
Ann Oncol ; 29(8): 1658-1686, 2018 08 01.
Article En | MEDLINE | ID: mdl-30113631

The European Society for Medical Oncology (ESMO) consensus conference on testicular cancer was held on 3-5 November 2016 in Paris, France. The conference included a multidisciplinary panel of 36 leading experts in the diagnosis and treatment of testicular cancer (34 panel members attended the conference; an additional two panel members [CB and K-PD] participated in all preparatory work and subsequent manuscript development). The aim of the conference was to develop detailed recommendations on topics relating to testicular cancer that are not covered in detail in the current ESMO Clinical Practice Guidelines (CPGs) and where the available level of evidence is insufficient. The main topics identified for discussion related to: (1) diagnostic work-up and patient assessment; (2) stage I disease; (3) stage II-III disease; (4) post-chemotherapy surgery, salvage chemotherapy, salvage and desperation surgery and special topics; and (5) survivorship and follow-up schemes. The experts addressed questions relating to one of the five topics within five working groups. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel. A consensus vote was obtained following whole-panel discussions, and the consensus recommendations were then further developed in post-meeting discussions in written form. This manuscript presents the results of the expert panel discussions, including the consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.


Medical Oncology/standards , Neoplasm Recurrence, Local/prevention & control , Neoplasms, Germ Cell and Embryonal/therapy , Practice Guidelines as Topic , Testicular Neoplasms/therapy , Aftercare/methods , Aftercare/standards , Cancer Survivors/psychology , Chemoradiotherapy, Adjuvant/methods , Chemoradiotherapy, Adjuvant/standards , Consensus Development Conferences as Topic , Europe , Humans , Male , Medical Oncology/methods , Neoadjuvant Therapy/methods , Neoadjuvant Therapy/standards , Neoplasm Recurrence, Local/epidemiology , Neoplasm Staging , Neoplasms, Germ Cell and Embryonal/diagnosis , Neoplasms, Germ Cell and Embryonal/pathology , Orchiectomy/psychology , Palliative Care/methods , Palliative Care/standards , Prognosis , Quality of Life , Risk Factors , Salvage Therapy/methods , Salvage Therapy/standards , Societies, Medical/standards , Survivorship , Testicular Neoplasms/diagnosis , Testicular Neoplasms/pathology , Testis/diagnostic imaging , Testis/pathology , Testis/surgery
5.
Ann Oncol ; 28(9): 2213-2218, 2017 Sep 01.
Article En | MEDLINE | ID: mdl-28651338

BACKGROUND: EORTC 24971 was a phase III trial demonstrating superiority of induction regimen TPF (docetaxel, cisplatin, 5-fluorouracil) over PF (cisplatin/5-fluorouracil), in terms of progression-free (PFS) and overall survival (OS) in locoregionally advanced unresectable head and neck squamous cell carcinomas. We conducted a retrospective analysis of prospectively collected data aiming to evaluate whether only HPV(-) patients (pts) benefit from adding docetaxel to PF, in which case deintensifying induction treatment in HPV(+) pts could be considered. PATIENTS AND METHODS: Pretherapy tumor biopsies (blocks or slides) were assessed for high-risk HPV by p16 immunohistochemistry, PCR and quantitative PCR. HPV-DNA+ and/or p16+ tumors were subjected to in situ hybridization (ISH) and HPV E6 oncogene expression qRT-PCR analysis. Primary and secondary objectives were to evaluate the value of HPV/p16 status as predictive factor of treatment benefit in terms of PFS and OS. The predictive effect was analyzed based on the model used in the primary analysis of the study with the addition of a treatment by marker interaction term and tested at two-sided 5% significance level. RESULTS: Of 358, 119 pts had available tumor samples and 58 of them had oropharyngeal cancer. Median follow-up was 8.7 years. Sixteen of 119 (14%) evaluable samples were p16+ and 20 of 79 (25%) evaluable tumors were HPV-DNA+. 13 of 40 pts (33%) assessed with HPV-DNA ISH and 12 of 28 pts (43%) assessed for HPV E6 mRNA were positive. The preplanned analysis showed no statistical evidence of predictive value of HPV/p16 status for PFS (P = 0.287) or OS (P = 0.118). CONCLUSIONS: The incidence of HPV positivity was low in the subset of EORTC 24971 pts analyzed. In this analysis only powered to detect a large treatment by marker interaction, there was no statistical evidence that treatment effect found overall was different in magnitude in HPV(+) or HPV(-) pts. These results do not justify selection of TPF versus PF according to HPV status.


Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Cisplatin/administration & dosage , Fluorouracil/administration & dosage , Head and Neck Neoplasms/drug therapy , Papillomaviridae/isolation & purification , Taxoids/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Squamous Cell/virology , DNA, Viral/genetics , Docetaxel , Female , Head and Neck Neoplasms/virology , Humans , In Situ Hybridization , Male , Papillomaviridae/genetics , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck , Survival Analysis
6.
Clin Transl Oncol ; 18(12): 1187-1196, 2016 Dec.
Article En | MEDLINE | ID: mdl-27815687

Testicular cancer represents the most common malignancy in males aged 15-34 years and is considered a model of curable neoplasm. Maintaining success, reducing treatment burden, and focusing on survivorship are then key objectives. Inguinal orchiectomy is the first recommended maneuver that has both diagnostic and therapeutic aims. Most patients are diagnosed with stage I disease (confined to the testicle). Close surveillance and selective, short-course adjuvant chemotherapy are accepted alternatives for these cases. In patients with more advanced disease (stages II and III), 3-4 courses of cisplatin-based chemotherapy (according to IGCCCG risk classification) followed by the judicious surgical removal of residual masses represent the cornerstone of therapy. Poor-risk patients and those failing a first-line therapy should be referred to specialized tertiary centers. Paclitaxel-based conventional chemotherapy and high-dose chemotherapy plus autologous hematopoietic support can cure a proportion of patients with relapsing or refractory disease.


Neoplasms, Germ Cell and Embryonal/diagnosis , Neoplasms, Germ Cell and Embryonal/therapy , Practice Guidelines as Topic , Testicular Neoplasms/diagnosis , Testicular Neoplasms/therapy , Adolescent , Adult , Humans , Male , Neoplasm Staging , Risk Factors , Spain , Young Adult
7.
Ann Oncol ; 26(5): 833-838, 2015 May.
Article En | MEDLINE | ID: mdl-25378299

Testicular cancer (TC) is the most common neoplasm in males aged 15-40 years. The majority of patients have no evidence of metastases at diagnosis and thus have clinical stage I (CSI) disease [Oldenburg J, Fossa SD, Nuver J et al. Testicular seminoma and non-seminoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013; 24(Suppl 6): vi125-vi132; de Wit R, Fizazi K. Controversies in the management of clinical stage I testis cancer. J Clin Oncol 2006; 24: 5482-5492.]. Management of CSI TC is controversial and options include surveillance and active treatment. Different forms of adjuvant therapy exist, including either one or two cycles of carboplatin chemotherapy or radiotherapy for seminoma and either one or two cycles of cisplatin-based chemotherapy or retroperitoneal lymph node dissection for non-seminoma. Long-term disease-specific survival is ∼99% with any of these approaches, including surveillance. While surveillance allows most patients to avoid additional treatment, adjuvant therapy markedly lowers the relapse rate. Weighing the net benefits of surveillance against those of adjuvant treatment depends on prioritizing competing aims such as avoiding unnecessary treatment, avoiding more burdensome treatment with salvage chemotherapy and minimizing the anxiety, stress and life disruption associated with relapse. Unbiased information about the advantages and disadvantages of surveillance and adjuvant treatment is a prerequisite for informed consent by the patient. In a clinical scenario like CSI TC, where different disease-management options produce indistinguishable long-term survival rates, patient values, priorities and preferences should be taken into account. In this review, we provide an overview about risk factors for relapse, potential benefits and harms of adjuvant chemotherapy and active surveillance and a rationale for involving patients in individualized decision making about their treatment rather than adopting a uniform recommendation for all.


Antineoplastic Agents/therapeutic use , Decision Support Techniques , Neoplasms, Germ Cell and Embryonal/therapy , Patient Participation , Personal Autonomy , Seminoma/therapy , Testicular Neoplasms/therapy , Watchful Waiting , Adolescent , Adult , Antineoplastic Agents/adverse effects , Chemotherapy, Adjuvant , Choice Behavior , Disease Progression , Humans , Male , Neoplasm Recurrence, Local , Neoplasm Staging , Neoplasms, Germ Cell and Embryonal/pathology , Orchiectomy/adverse effects , Patient Selection , Predictive Value of Tests , Radiotherapy, Adjuvant , Risk Factors , Seminoma/pathology , Testicular Neoplasms/pathology , Time Factors , Treatment Outcome , Young Adult
8.
Clin Transl Oncol ; 16(11): 959-65, 2014 Nov.
Article En | MEDLINE | ID: mdl-24719184

BACKGROUND: Brain metastases of testicular germ cell tumor (TGCT) are a rare event. Prognostic is poor and there is not much evidence on optimal management of these patients. PATIENTS AND METHODS: A review of case records of germ cell tumor patients within the Spanish Germ Cell Cancer Group data base from 1994 to 2012 was conducted. RESULTS: Thirty-three out of 6,200 cases (0.5 %). Nineteen patients (57 %) group 1: synchronous, 13 (40 %) group 2: metachronous and only one developed brain metastasis during cisplatin-based chemotherapy (excluded from the analysis). Median serum BHCG levels at initial diagnosis was higher in group 1, whereas elevated AFP serum levels were more common in group 2. Histology in the primary tumor: chorionic carcinoma for group 1 versus embryonal carcinoma for group 2. Mainly solitary brain metastasis in group 2 (54 versus 21 %, respectively). The median overall survival from the diagnosis of central nervous system involvement was 16 months for group 1 (CI 95 % 13.9-18) and 23 months (95 % CI 0-165) for group 2 (log rank p = 0.84). Long-term survivors were practically identical in the two groups (38.9 % group 1 versus 38.5 % group 2). Regardless of the timing of brain metastasis, those patients that achieved complete response to the treatment had better survival (log rank p 0.003). CONCLUSION: Although some distinctive clinical characteristics have been found between patients with synchronous versus metachronous brain metastasis from TGCT, the timing of brain metastasis did not seem to have prognostic influence, but due to the retrospective nature of the analysis and the results should be interpreted with caution.


Brain Neoplasms/secondary , Neoplasms, Germ Cell and Embryonal/secondary , Testicular Neoplasms/pathology , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Neoplasms/drug therapy , Brain Neoplasms/mortality , Humans , Male , Middle Aged , Neoplasms, Germ Cell and Embryonal/drug therapy , Neoplasms, Germ Cell and Embryonal/mortality , Survival Analysis , Testicular Neoplasms/drug therapy , Testicular Neoplasms/mortality , Young Adult
9.
Ann Oncol ; 24(4): 878-88, 2013 Apr.
Article En | MEDLINE | ID: mdl-23152360

In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377-1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478-496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497-513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues. The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, ∼50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements.


Neoplasms, Germ Cell and Embryonal/pathology , Neoplasms, Germ Cell and Embryonal/therapy , Europe , Follow-Up Studies , Humans , Neoplasm Metastasis , Neoplasm Staging , Neoplasms, Germ Cell and Embryonal/classification , Neoplasms, Germ Cell and Embryonal/diagnosis , Survival Rate
10.
Ann Oncol ; 23(1): 59-64, 2012 Jan.
Article En | MEDLINE | ID: mdl-21460378

BACKGROUND: 2-¹8fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) has been recommended in international guidelines in the evaluation of postchemotherapy seminoma residuals. Our trial was designed to validate these recommendations in a larger group of patients. PATIENTS AND METHODS: FDG-PET studies in patients with metastatic seminoma and residual masses after platinum-containing chemotherapy were correlated with either the histology of the resected lesion(s) or the clinical outcome. RESULTS: One hundred and seventy seven FDG-PET results were contributed. Of 127 eligible PET studies, 69% were true negative, 11% true positive, 6% false negative, and 15% false positive. We compared PET scans carried out before and after a cut-off level of 6 weeks after the end of the last chemotherapy cycle. PET sensitivity, specificity, negative predictive value (NPV), and positive predictive value were 50%, 77%, 91%, and 25%, respectively, before the cut-off and 82%, 90%, 95%, and 69% after the cut-off. PET accuracy significantly improved from 73% before to 88% after the cut-off (P=0.032). CONCLUSION: Our study confirms the high specificity, sensitivity, and NPV of FDG-PET for evaluating postchemotherapy seminoma residuals. When carried out at an adequate time point, FDG-PET remains a valuable tool for clinical decision-making in this clinical setting and spares patients unnecessary therapy.


Glucose-6-Phosphate/analogs & derivatives , Positron-Emission Tomography , Radiopharmaceuticals , Seminoma/diagnostic imaging , Testicular Neoplasms/diagnostic imaging , Humans , Male , Retrospective Studies , Sensitivity and Specificity
11.
Oncology ; 80(3-4): 219-22, 2011.
Article En | MEDLINE | ID: mdl-21734411

PURPOSE: To determine the activity and toxicity of temozolomide in a phase II multicenter trial in patients diagnosed with relapsed or cisplatin-refractory germ cell tumors. PATIENTS AND METHODS: During a recruitment period of 30 months, 20 patients received temozolomide 150 mg/m(2)/day p.o. for 5 days every 4 weeks, escalating to 200 mg/m(2)/day if grade II toxicity was not observed in the first cycle. Eligibility criteria were tumor progression or relapse after previous cisplatin and ifosfamide-containing chemotherapy, creatinine clearance of >40 ml/min, and a performance status of 0-2. RESULTS: The median age was 38 years (range 27-56). Seventeen patients had nonseminomatous tumors, and 3 had seminomatous tumors. Six of the patients had extragonadal primary tumors (3 retroperitoneal and 3 mediastinal). The median number of prior cisplatin-containing cycles was 11 (range 7-20). Eight patients received prior high-dose chemotherapy and 14 were refractory or absolutely refractory to cisplatin. A total of 45 cycles were administered. Two partial responses lasting 9 and 3.5 months (overall response rate 10%, 95% CI 1.2-31.7) were observed. One of these responses was seen in a patient with a cisplatin-refractory tumor that had previously been treated with high-dose chemotherapy. The median time to progression and the median overall survival were 1.5 and 3.1 months, respectively. Grade III hematological toxicity consisted of thrombocytopenia in 2 patients and anemia in 1 patient. No grade IV toxicity was observed. CONCLUSIONS: Temozolomide had some activity in heavily pretreated patients resistant to cisplatin-based chemotherapy.


Antineoplastic Agents/therapeutic use , Cisplatin/therapeutic use , Dacarbazine/analogs & derivatives , Mediastinal Neoplasms/drug therapy , Neoplasms, Germ Cell and Embryonal/drug therapy , Retroperitoneal Neoplasms/drug therapy , Testicular Neoplasms/drug therapy , Adult , Antineoplastic Agents/adverse effects , Dacarbazine/adverse effects , Dacarbazine/therapeutic use , Drug Resistance, Neoplasm , Humans , Male , Middle Aged , Survival Analysis , Temozolomide , Treatment Outcome
12.
Ann Oncol ; 16(12): 1915-20, 2005 Dec.
Article En | MEDLINE | ID: mdl-16126737

BACKGROUND: The Spanish Germ Cell Group is composed of 60 centres. Our challenge was to define a surveillance protocol that would be safe and suitable regardless of population size or geographic coverage. METHODS: From January 1994 to January 2004, 589 patients with stage I non-seminomatous germ cell tumours entered a risk-adapted surveillance protocol after orchiectomy. Patients with vascular or local invasion of adjacent structures (231/589; 39%) received two cycles of BE400P (bleomycin 30 U/week, etoposide 100 mg/m2 x4, cisplatinum 25 mg/m2 x4). Other patients (358/589; 61%) were kept on close follow-up (chest X-ray; serum tumour markers: first year every 2 months, second year every 3 months, third year every 4 months; abdominal computed tomography scans at every other outpatient control). The outcomes selected for the study were feasibility, relapse rate and number of patients lost to follow-up and mortality. RESULTS: Median follow-up was 40 months. In the surveillance group, 21 patients were lost to follow-up. In the chemotherapy group, two patients relapsed at 12 and 14.5 months and they are presently free of disease. In the surveillance group, 71 (19%) patients relapsed, of which 55 (71%) relapsed within the first year. Five (1.4%) patients died of their cancer. Factors associated with relapse were embryonal carcinoma and vascular invasion in patients who refused chemotherapy. CONCLUSIONS: Our risk-adapted surveillance protocol provided a low rate of recurrences.


Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Risk Management , Testicular Neoplasms/drug therapy , Adolescent , Adult , Biomarkers, Tumor/blood , Bleomycin/administration & dosage , Carcinoma, Embryonal/drug therapy , Carcinoma, Embryonal/metabolism , Carcinoma, Embryonal/surgery , Chemotherapy, Adjuvant , Choriocarcinoma/drug therapy , Choriocarcinoma/metabolism , Choriocarcinoma/surgery , Etoposide/administration & dosage , Feasibility Studies , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Invasiveness/pathology , Neoplasm Recurrence, Local , Orchiectomy , Prognosis , Seminoma/drug therapy , Seminoma/metabolism , Seminoma/surgery , Survival Rate , Teratoma/drug therapy , Teratoma/metabolism , Teratoma/surgery , Testicular Neoplasms/metabolism , Testicular Neoplasms/surgery
13.
Ann Oncol ; 15(9): 1377-99, 2004 Sep.
Article En | MEDLINE | ID: mdl-15319245

Germ cell tumour is the most frequent malignant tumour type in young men with a 100% rise in the incidence every 20 years. Despite this, the high sensitivity of germ cell tumours to platinum-based chemotherapy, together with radiation and surgical measures, leads to the high cure rate of > or = 99% in early stages and 90%, 75-80% and 50% in advanced disease with 'good', 'intermediate' and 'poor' prognostic criteria (IGCCCG classification), respectively. The high cure rate in patients with limited metastatic disease allows the reduction of overall treatment load, and therefore less acute and long-term toxicity, e.g. organ sparing surgery for specific cases, reduced dose and treatment volume of irradiation or substitution of node dissection by surveillance or adjuvant chemotherapy according to the presence or absence of vascular invasion. Thus, different treatment options according to prognostic factors including histology, stage and patient factors and possibilities of the treating centre as well may be used to define the treatment strategy which is definitively chosen for an individual patient. However, this strategy of reduction of treatment load as well as the treatment itself require very high expertise of the treating physician with careful management and follow-up and thorough cooperation by the patient as well to maintain the high rate for cure. Treatment decisions must be based on the available evidence which has been the basis for this consensus guideline delivering a clear proposal for diagnostic and treatment measures in each stage of gonadal and extragonadal germ cell tumour and individual clinical situations. Since this guideline is based on the highest evidence level available today, a deviation from these proposals should be a rare and justified exception.


Neoplasms, Germ Cell and Embryonal/diagnosis , Neoplasms, Germ Cell and Embryonal/therapy , Testicular Neoplasms/diagnosis , Testicular Neoplasms/therapy , Europe , Humans , Magnetic Resonance Imaging , Male , Neoplasm Staging , Orchiectomy , Salvage Therapy , Testis/pathology , Time Factors , Tomography, X-Ray Computed
15.
Br J Cancer ; 88(6): 879-86, 2003 Mar 24.
Article En | MEDLINE | ID: mdl-12644825

This study was undertaken to investigate the expression and predictive value for outcome of multidrug resistance-associated (MDR) proteins P-glycoprotein (Pgp), MRP1, BCRP, and LRP, in advanced testicular germ-cell tumours (TGCT). Paraffin-embedded sections from 56 previously untreated patients with metastatic TGCT were immunostained for Pgp, MRP1, BCRP, and LRP. All patients received platinum-based chemotherapy after orchidectomy. Immunostaining was related to clinicopathological parameters, response to chemotherapy, and outcome. Strong and intermediate expressions of the different MDR-related proteins were: 27 and 41% (Pgp), 54 and 37% (MRP1), 86 and 7% (BCRP), and 14 and 29% (LRP). P-glycoprotein and MRP1 associated, respectively, to low AFP (P=0.026) and high LDH levels (P=0.014), whereas LRP expression associated with high beta-hCG levels (P=0.003) and stage IV tumours (P=0.029). No correlation was found between Pgp, MRP1, and BCRP expression and response to chemotherapy and survival. In contrast, patients with LRP-positive tumours (strong or intermediate expression) had shorter progression-free (P=0.0006) and overall survival (P=0.0116) than LRP-negative patients, even after individual log-rank adjustments by statistically associated variables. Our data suggest that a positive LRP immunostaining at the time of diagnosis in metastatic TGCT is associated with an adverse clinical outcome.


Drug Resistance, Multiple , Gene Expression Regulation, Neoplastic , Germinoma/drug therapy , Germinoma/genetics , Neoplasm Proteins/biosynthesis , Testicular Neoplasms/drug therapy , Testicular Neoplasms/genetics , Vault Ribonucleoprotein Particles/biosynthesis , ATP Binding Cassette Transporter, Subfamily B, Member 1/analysis , ATP Binding Cassette Transporter, Subfamily B, Member 1/biosynthesis , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols , Cisplatin/administration & dosage , Disease-Free Survival , Germinoma/pathology , Germinoma/surgery , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Proteins/analysis , Orchiectomy , Prognosis , Testicular Neoplasms/pathology , Testicular Neoplasms/surgery
16.
Eur Urol ; 42(6): 553-62; discussion 562-3, 2002 Dec.
Article En | MEDLINE | ID: mdl-12477650

OBJECTIVE: To describe the clinical characteristics and treatment results obtained with the application of a homogeneous treatment protocol in 1490 patients with germ-cell tumours (GCT) registered in the 55 hospitals belonging to the Spanish Germ-Cell Cancer Group (GG) during the period between January 1994 and April 2001. METHODS: In general, surveillance was the common policy for stage I patients without local poor prognosis factors, whereas they received adjuvant chemotherapy in case those factor were present. Chemotherapy schedules used in advanced cases were cisplatin and etoposide (EP) for seminoma and BEP or BOMP-EPI in non-seminoma, according to whether the patient was in the good or poor prognosis IGCCCG (International Germ-Cell Cancer Collaborative Group) group. Excision of residual masses was mandatory in non-seminomatous germ-cell tumour (NSGCT). RESULTS: Initial local symptomatology was increased testis size in 90% of cases. Sonography was an excellent diagnostic tool to suggest tumour. Non-seminoma (64.2%) was more frequent than seminoma (35.8%). Approximately 10% had the antecedent of cryptorchidism. Non-seminoma patients were 7 years younger than seminoma. Right testis was involved predominantly. Pre-orchidectomy tumour markers were elevated in 21% of seminoma (betaHGC) and 79% in non-seminoma (alphaFP and/or betaHGC). Scrotum violation occurred in only 1.8%. There were significant differences among stage I and the IGCCCG prognosis groups related to a longer interval between the first symptom and orchiectomy. Eighteen percent of non-seminomatous germ-cell tumour belonged to the poor prognosis IGCCCG group. With a median follow-up to 33 months, this series has achieved a 3 year overall survival of 98% for seminoma and 94% for non-seminoma. Only 10% of excised residual masses present after chemotherapy contained malignant cells. CONCLUSION: Spanish GCT have a similar clinical pattern to that described in the other occidental countries except for a slight increased proportion of non-seminoma upon seminoma. Co-operative groups as GG are unique structures to obtain quick and wide experience on the treatment of testis tumours, contributing to achieve a high cure rate.


Germinoma/diagnosis , Germinoma/therapy , Testicular Neoplasms/diagnosis , Testicular Neoplasms/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Humans , Male , Middle Aged
18.
Ann Oncol ; 12(4): 487-91, 2001 Apr.
Article En | MEDLINE | ID: mdl-11398880

PURPOSE: To evaluate the efficacy and toxicity of primary chemotherapy with the schedule E400P in the treatment of patients with early stage II (IIa and IIb) and advanced seminoma of good prognosis according to the international classification (IGCCCG). PATIENTS AND METHODS: Sixty-four patients were included. E400P consisted of cisplatin 25 mg/m2/day and etoposide 100 mg/m2/day for four days, every three weeks. Royal Marsden stages were IIab: 53% and IIc-IV: 47%. Twenty-three percent had high BHCG levels, twenty-seven percent had LDH > 2 x N. Sixty-two patients were of good prognosis according to the Medical Research Council classification. RESULTS: Response rate was 98% (69% complete remission, 29% residual disease). After a median follow-up of 34 months, treatment failure was seen in 7 patients (11%). Neutropenia (32%) was the most relevant grade 3-4 toxicity. Other important grade 3-4 side effects were found in less than 5%. Three-year time to treatment failure (TTF) was 89% (95% confidence intervals (CI): 80%-97%) for all patients, 91% (95% CI: 80%-99%) for stages IIa-b, and 87% (95% CI: 74%-99%) for stages IIc-IV. Three-year overall survival (OS) was 97% (95% CI: 93%-99%) for all patients and 95% (95% CI: 85%-99%) for stages IIa-b. CONCLUSIONS: E400P was a very active and safe regimen in good-prognosis advanced seminoma, with low toxicity rates. Definitive comparisons of this regimen with radiotherapy in stages IIa-b or with the more standard E500P or BEP, could be of interest.


Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Seminoma/drug therapy , Testicular Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Cisplatin/administration & dosage , Disease-Free Survival , Etoposide/administration & dosage , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Quality of Life , Seminoma/classification , Seminoma/pathology , Testicular Neoplasms/classification , Testicular Neoplasms/pathology , Treatment Outcome
19.
J Clin Oncol ; 19(10): 2647-57, 2001 May 15.
Article En | MEDLINE | ID: mdl-11352956

PURPOSE: To assess the value of postsurgery chemotherapy in patients with disseminated nonseminomatous germ-cell tumors (NSGCTs) and viable residual disease after first-line cisplatin-based chemotherapy. PATIENTS AND METHODS: The outcome of 238 patients was reviewed. Tumor markers had normalized in all patients before resection. A multivariate analysis of survival was performed on 146 patients. RESULTS: The 5-year progression-free survival (PFS) rate was 64% and the 5-year overall survival (OS) rate was 73%. Three factors were independently associated with both PFS and OS: complete resection (P <.001), < 10% of viable malignant cells (P =.001), and a good International Germ Cell Consensus Classification (IGCCC) group (P =.01). Patients were assigned to one of three risk groups: those with no risk factors (favorable group), those with one risk factor (intermediate group), and those with two or three risk factors (poor-risk group). The 5-year OS rate was 100%, 83%, and 51%, respectively (P <.001). The 5-year PFS rate was 69% (95% confidence interval [CI], 62% to 76%) and 52% (95% CI, 40% to 64%) in postoperative chemotherapy recipients and nonrecipients, respectively (P <.001). No significant difference was detected in 5-year OS rates. After adjustment on the three prognostic factors, postoperative chemotherapy was associated with a significantly better PFS (P <.001) but not with better OS. Patients in the favorable risk group had a 100% 5-year OS, with or without postoperative chemotherapy. Postoperative chemotherapy appeared beneficial in both PFS (P <.001) and OS (P =.02) in the intermediate-risk group but was not statistically beneficial in the poor-risk group. CONCLUSION: A complete resection may be more critical than recourse to postoperative chemotherapy in the setting of postchemotherapy viable malignant NSGCT. Immediate postoperative chemotherapy or surveillance alone with chemotherapy at relapse may be reasonable options depending on the completeness of resection, IGCCC group, and percent of viable cells. Validation is necessary.


Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Germinoma/drug therapy , Mediastinal Neoplasms/drug therapy , Retroperitoneal Neoplasms/drug therapy , Testicular Neoplasms/drug therapy , Adult , Analysis of Variance , Combined Modality Therapy , Disease-Free Survival , Germinoma/mortality , Germinoma/pathology , Germinoma/surgery , Humans , Male , Mediastinal Neoplasms/mortality , Mediastinal Neoplasms/pathology , Mediastinal Neoplasms/surgery , Multicenter Studies as Topic , Prognosis , Retroperitoneal Neoplasms/mortality , Retroperitoneal Neoplasms/pathology , Retroperitoneal Neoplasms/surgery , Retrospective Studies , Testicular Neoplasms/mortality , Testicular Neoplasms/pathology , Testicular Neoplasms/surgery
20.
Arch Esp Urol ; 53(6): 460-8, 2000.
Article Es | MEDLINE | ID: mdl-11002513

OBJECTIVE: To review the utility of tumor markers in the treatment of germ cell testicular tumors. METHODS: The literature on this subject was reviewed. RESULTS/CONCLUSIONS: The tumor markers alpha-fetoprotein, beta-HCG and LDH are essential in the management of germ cell tumors. They are useful for the initial diagnosis and postoperatively, particularly in the detection of residual disease following surgery in stage I tumors. Their role as a prognostic marker has been clearly established in the IGCCCG classification. Furthermore, these markers are useful for follow-up, detection of tumor recurrence and for monitoring response to therapy. Spurious increases of marker levels unrelated with tumor progression may occur and should be recognized. The increase in alpha-fetoprotein levels can be caused by liver damage and tumor lysis, and the increase in beta-HCG levels can be caused by hypogonadism, tumor lysis, or may be a discordant increase or hook effect.


Germinoma/diagnosis , Testicular Neoplasms/diagnosis , Biomarkers, Tumor/blood , Chorionic Gonadotropin/blood , Follow-Up Studies , Humans , L-Lactate Dehydrogenase/blood , Male , Monitoring, Physiologic , Prognosis , alpha-Fetoproteins/analysis
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