Epidermal growth factor receptor and epididymis invasion as prognostic biomarkers in clinical stage I testicular germ cell tumours.

BACKGROUND: Inguinal orchiectomy is curative in 70-80% of clinical stage I testicular germ cell tumours (CS I TGCT). The identification of patients who are at low risk of relapse is critical to avoid unnecessary treatment. The aim of this study is to explore EGFR, hMLH-1/hMSH-2 and microsatellite instability (MSI) as potential prognostic factors of recurrence in CS I TGCT. METHODS: Fifty-six CS I TGCT patients who underwent inguinal orchiectomy were included in this study. We analysed the relationship between clinicopathological and molecular factors with survival. Analysis of hMLH1, hMSH2 and EGFR expression was carried out by immunohistochemistry. Methylation status of the hMLH1 promoter was determined by pyrosequencing analysis in selected cases. EGFR exons 19, 20, 21 were analysed by PCR labeled-fragments and MSI status was determined using standard Multiplex MSI assays. RESULTS: Classical pathological factors such as lymphovascular invasion, high percentage of embryonal carcinoma, rete testis invasion or tumour size ≥4 cm showed a significant relationship with a higher risk of relapse. Additionally, it was found that an epididymis invasion proved to be a significant independent poor prognostic factor of recurrence (p = 0.001). hMLH1 or hMSH2 expression showed no significant association with risk of relapse and no MSI was found. EGFR expression was observed in 30.4% of samples and its expression was associated with higher risk of relapse (HR 3.5; 95% CI 1.3-9.8; p = 0.016). None of the cases presented EGFR kinase domain mutations. CONCLUSIONS: Epididymis invasion and EGFR expression, but not hMLH-1/hMSH-2 or MSI, could be potentially useful as new prognostic factors of recurrence for CS I TGCT.

Rates of major complications during neoadjuvant and adjuvant chemotherapy for early breast cancer: An off study population.

OBJECTIVES: To determine the incidence and risk factors for thromboembolic events (TE) and febrile neutropenia (FN) in patients receiving systemic chemotherapy for early breast cancer (EBC). METHODS: 325 patients received FEC75, FEC100-T or ECaP for EBC in 2013. RESULTS: TE occurred in 7.4% and FN in 19.1% of patients. Risk factors for TE were: central venous catheter (p = 0.011). Risk factors for FN were: FEC100-T treatment versus FEC75 and ECaP (p ≤ 0.001); lower pre-treatment neutrophil count (p = 0.009) and poorer performance status (p = 0.012). Two patients died from treatment-related toxicities. CONCLUSION: In real-world experience, the majority of patients completed adequate treatment, despite significant complications.

Febrile Neutropenia Rates According to Body Mass Index and Dose Capping in Women Receiving Chemotherapy for Early Breast Cancer.

AIMS: Studies suggest worse outcomes in obese women with breast cancer than in non-obese women. One potential reason may be that oncologists 'dose cap' adjuvant chemotherapy in obese patients in order to avoid excessive toxicity. Reductions from standard dosing may compromise survival outcomes in the curative setting. Here we describe the body mass index (BMI) distribution of patients in a non-trial population, the frequency with which oncologists dose cap and its effect on febrile neutropenia chemotherapy toxicity. MATERIALS AND METHODS: In this non-randomised study, electronic patient records retrospectively identified patients with early breast cancer who initiated neoadjuvant or adjuvant chemotherapy at the Royal Marsden Hospital between 1 January and 31 December 2013. Baseline data included age, BMI, performance status, tumour characteristics, granulocyte colony-stimulating factor and comorbidities. Chemotherapy doses, rates of dose capping across BMI groups and rates of febrile neutropenia were reported. RESULTS: In total, 325 patients were eligible: 79 (24.5%) were obese (BMI ≥ 30), 109 (33.5%) were overweight (BMI ≥25 - <30) and 137 (42%) were normal bodyweight (BMI < 25). Sixteen patients (20.5%) in the obese group received dose-capped chemotherapy. Overall, 62 patients (19%) had an episode of febrile neutropenia. Obese patients receiving uncapped chemotherapy did not experience a significant difference in febrile neutropenia rates when compared with overweight or normal bodyweight groups (P = 0.5798). The febrile neutropenia rate in obese patients receiving capped chemotherapy was 6.5%, compared with 24% in obese patients receiving uncapped chemotherapy (P = 0.1216). CONCLUSION: In a non-trial population of obese patients, dose capping is frequently used. Obese patients receiving uncapped chemotherapy do not experience increased febrile neutropenia rates when compared with uncapped overweight or normal bodyweight patients. Furthermore, dose capping was associated with a trend towards lower rates of febrile neutropenia than in other groups and may indicate relative under-dosing of chemotherapy. This supports international guidelines that state that obese patients should not be dose capped.

Complications of hyperglycaemia with PI3K-AKT-mTOR inhibitors in patients with advanced solid tumours on Phase I clinical trials.

BACKGROUND: PI3K-AKT-mTOR inhibitors (PAMi) are promising anticancer treatments. Hyperglycaemia is a mechanism-based toxicity of these agents and is becoming increasingly important with their use in larger numbers of patients. METHODS: Retrospective case-control study comparing incidence and severity of hyperglycaemia (all grades) between a case group of 387 patients treated on 18 phase I clinical trials with PAMi (78 patients with PI3Ki, 138 with mTORi, 144 with AKTi and 27 with PI3K/mTORi) and a control group of 109 patients treated on 10 phase I clinical trials with agents not directly targeting the PAM pathway. Diabetic patients were excluded in both groups. RESULTS: The incidence of hyperglycaemia was not significantly different between cases and controls (86.6% vs 80.7%, respectively, P=0.129). However, high grade (grade 3-4) hyperglycaemia was more frequent in the PAMi group than in controls (6.7% vs 0%, respectively, P=0.005). The incidence of grade 3-4 hyperglycaemia was greater with AKT and multikinase inhibitors compared with other PAMi (P<0.001). All patients with high-grade hyperglycaemia received antihyperglycemic treatment and none developed severe metabolic complications (diabetic ketoacidosis or hyperosmolar hyperglycemic nonketotic state). High-grade hyperglycaemia was the cause of permanent PAMi discontinuation in nine patients. CONCLUSIONS: PI3K-AKT-mTOR inhibitors are associated with small (6.7%) but statistically significant increased risk of high-grade hyperglycaemia compared with non-PAM targeting agents. However, PAMi-induced hyperglycaemia was not found to be associated with severe metabolic complications in this non-diabetic population of patients with advanced cancers.

Controversial issues in early-stage breast cancer: a global collaborative survey, supported by the European Society for Medical Oncology (ESMO).

BACKGROUND: To explore the current clinical management of early-stage breast cancer (BC) patients, identify areas of controversy, and interrogate how treating physicians implement latest advances. METHODS: We conducted a 27-item survey, disseminated in two stages: paper distribution at selected BC sessions at the ESMO 2012 Congress, and dedicated mailings to ESMO members. Descriptive statistical analysis and logistic regression analysis were applied to explore potential associations between the demographic characteristics of the participants and replies. RESULTS: A total of 512 physicians from 79 countries participated in the study, accounting for 465 (91%) fully completed questionnaires. The majority of the participants were ESMO members (66%), medical oncologists (86.5%), and working in multidisciplinary teams (91.6%). Heterogeneous results were captured, such as the following: 40.9% of the participants consider no genetic test useful for making adjuvant treatment decisions; 15.3% consider PET-CT a useful imaging modality for staging; 68.8% consider that postmenopausal patients with hormone receptor positive disease should always be offered an aromatase inhibitor as part of their adjuvant therapy; 78.7% prefer to administer trastuzumab concurrently with the taxane component of chemotherapy; and 27% would consider bevacizumab in the neoadjuvant setting. The logistic regression analysis did not identify any strong predictor of the probability of giving a reply fully compatible with evidence in the literature. CONCLUSION: This survey captures clinical practice and whether the latest research advances are implemented in the treatment of early-stage BC by an extended number of physicians. Significant individual differences were found. Areas of controversy were detected, and they deserve further exploration in order to generate 'tailored' educational tools, with the final goal being the standardization of the treatment of early-stage BC patients.

Pertuzumab: new hope for patients with HER2-positive breast cancer.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) overexpression is detected in approximately 15% to 20% of all breast cancers (BCs). A revolutionary change in the prognosis of this subgroup of patients has occurred since trastuzumab therapy was introduced into daily clinical practice. However, because trastuzumab resistance is common, new molecules with complementary and/or synergistic mechanisms of action have been developed. Pertuzumab is a new anti-HER2 humanized monoclonal antibody that prevents the formation of HER2 dimers. MATERIAL AND METHODS: A computer-based literature search was carried out using PubMed (keywords: breast neoplasm, dimerization, HER-2, pertuzumab); data reported at international meetings are included. RESULTS: This paper describes pertuzumab's mechanism of action, safety, and role in HER2-positive BCs. It also explores the role of pertuzumab as a single agent or combined with trastuzumab by reviewing data from preclinical research to ongoing clinical trials. Recently published trials, particularly the CLEOPATRA study, highlight the efficacy, tolerability, and increase in disease-free survival associated with this novel agent when combined with trastuzumab. CONCLUSION: The pertuzumab and trastuzumab anti-HER2 dual blockade is likely to represent a substantial advance for patients with HER2-positive BCs and a new milestone on the way to personalized medicine.

Impact of erythropoietin on the reduction of blood transfusions and on survival of lung cancer patients receiving first-line chemotherapy.

INTRODUCTION: Anaemia is a common problem in patients with cancer who receive chemotherapy and is normally associated with a negative impact on patients' quality of life (QOL), poor cancer control and diminished survival. In clinical trials, recombinant human erythropoietin has been shown to correct and prevent anaemia, decrease the need for blood transfusions and improve cancer patients' QOL. METHODS: A retrospective study followed lung cancer patients who received first-line chemotherapy in our hospital in 1998 and in 2005. The incidence of anaemia was analysed, as was the impact of incorporating erythropoietin into the treatment. RESULTS: The incidence of anaemia was 68% (69% of which reported asthenia) in 1998 vs. 54% (60% with asthenia) in 2005. The comparison of anaemia rates (1998 vs. 2005) were grade 1 (16% vs. 32%), grade 2 (36% vs. 16%), grade 3 (16% vs. 5%) and grade 4 (none). Treatment for anaemia included transfusion 52%, intravenous iron 5% and epoetin 4% in 1998. In 2005 anaemia was treated with transfusion 9%, intravenous iron 41%, and epoetin 49%. Median survival (1998 vs. 2005) was 242 days [95% confidence interval (CI) 217-329) vs. 356 days (95% CI 322-382). CONCLUSIONS: Erythropoietin is a valid alternative for cancer patients with anaemia undergoing chemotherapy. It can possibly avoid the need for transfusions without negatively impacting survival.

Impact of erythropoietin on the reduction of blood transfusions and on survival of lung cancer patients receiving first-line chemotherapy

INTRODUCTION: Anaemia is a common problem in patients with cancer who receive chemotherapy and is normally associated with a negative impact on patients' quality of life (QOL), poor cancer control and diminished survival. In clinical trials, recombinant human erythropoietin has been shown to correct and prevent anaemia, decrease the need for blood transfusions and improve cancer patients' QOL. METHODS: A retrospective study followed lung cancer patients who received first-line chemotherapy in our hospital in 1998 and in 2005. The incidence of anaemia was analysed, as was the impact of incorporating erythropoietin into the treatment. RESULTS: The incidence of anaemia was 68% (69% of which reported asthenia) in 1998 vs. 54% (60% with asthenia) in 2005. The comparison of anaemia rates (1998 vs. 2005) were grade 1 (16% vs. 32%), grade 2 (36% vs. 16%), grade 3 (16% vs. 5%) and grade 4 (none). Treatment for anaemia included transfusion 52%, intravenous iron 5% and epoetin 4% in 1998. In 2005 anaemia was treated with transfusion 9%, intravenous iron 41%, and epoetin 49%. Median survival (1998 vs. 2005) was 242 days [95% confidence interval (CI) 217-329) vs. 356 days (95% CI 322-382). CONCLUSIONS: Erythropoietin is a valid alternative for cancer patients with anaemia undergoing chemotherapy. It can possibly avoid the need for transfusions without negatively impacting survival (AU)

No disponible

Estudio retrospectivo en pacientes con diagnóstico de carcinoma de pulmón no microcítico estadio avanzado tratados con la combinación gemcitabina y vinorelbina: valoración de la eficacia terapéutica y factores pronósticos / No disponible

Introducción: La Gemcitabina (G), la vinorelbina (V) y su combinación (GV) han demostradosu utilidad en pacientes con Carcinoma de Pulmón no Microcítico (CPNM). El propósito del estudioha sido confirmar la eficacia de GV e identificar factores pronósticos relacionados con los resultadosterapéuticos.Pacientes y Métodos: Se revisó de forma retrospectiva la historia de 144 pacientes conCPNM avanzado tratados entre octubre del 96 y abril del 05 con G (1.000-1.250 mg/m2) + V (25-30mg/m2) administrados el día 1 y 8 cada 21 días.Resultados: El tratamiento fue bien tolerado, desarrollando un 18% de los pacientes leucopeniagrado 3-4 incluyendo un 7% de neutropenia febril como peor toxicidad. La tasa de respuestas objetivasfue del 36,8% (IC al 95: 28,9–44,7) y las medianas de supervivencia libre de progresión y globalfueron de 21 (18–25) y 33 (26–40) semanas respectivamente. En el análisis multivariante sólo la histologíade adenocarcinoma (HR 3; p<,0001), la enfermedad limitada a una o ninguna localización metastática(HR 1,7; p =,02) y el índice Karnofsky (IK) mayor a 70% (HR 1,5; p=,02) tuvieron una asociaciónsignificativa con mayor supervivencia.Conclusiones: La combinación de GV se tolera bien y es eficaz en pacientes con CPNM avanzado.La histología de adenocarcinoma, la enfermedad limitada a una o ninguna localización metastásicay un IK superior a 70% se han identificado como variables independientes relacionadas con unamejor supervivencia

Introduction: Gemcitabine (G), vinorelbine (V) and their combination (GV) have shown to beuseful in patients with non-small cell lung cancer (NSCLC). The purpose of this study is to confirmthe activity of GV administration and to identify prognostic factors related with the clinical outcome.Methods: A retrospective analysis was carried out in relation to 144 patients with NSCL treatedbetween October 1996 and April 2005 with G (1000-1250 mg/m2) + V (25-30 mg/m2) both administeredon days 1 and 8 every three weeks.Results: Treatment was well tolerated, grade 3-4 neutropenia being registered as the worse toxiceffect in 18% cases, including 7% of neutropenic fever. The objective response rate was 36.8% (95%CI: 28.9-44.7) and the median progression free survival and overall survival rates were 21 (18-25) and33 (26-40) weeks respectively. In multivariate analysis only the histology of adenocarcinoma (HR 3;p<0.001), less than two metastatic sites (HR 1.7; p<0.02) and Karnofsky index (KI) above 70% (HR1.5; p<0.02) showed a significant association with longer survival.Conclusion: The GV combination therapy is well tolerated and active in patients with advancedNSCLC. The histology of adenocarcinoma, less than two metastatic sites and KI above 70% were identified as independent variables related with longer survival (AU)

Tratamiento adyuvante en pacientes diagnosticados de carcinoma no microcítico de pulmón: estado de la evidencia científica / Adjuvant treatment of non-small cell lung cancer patients: state of the scientific evidence

La cirugía representa el tratamiento curativo de elección para los pacientes que son diagnosticadosde carcinoma no microcítico de pulmón en estadio local. Sin embargo, gran parte de ellos experimentanuna recurrencia de su enfermedad lo que ha llevado al empleo de opciones terapéuticas tanto localescomo sistémicas con el ánimo de mejorar las posibilidades de curación. Durante las últimas décadasdiversos estudios comparativos heterogéneos y varios meta-análisis publicados en los años 95 y 97no demostraron de forma significativa una ventaja al asociar la quimioterapia y/o radioterapia adyuvantea la cirugía. Desde entonces y hasta nuestros días otros trabajos realizados con un número mayorde pacientes y empleando una quimioterapia más eficaz basada en combinaciones de platino, coincidenen describir un beneficio con su utilización aunque no de forma unánime. Más recientemente, unnuevo meta-análisis recopilando la mayoría de los estudios antes mencionados ha confirmado de formasignificativa una mejoría absoluta del 4% en la supervivencia global de los pacientes sometidos aquimioterapia adyuvante, especialmente en los estadios patológicos II-III tras cirugía y tratados conregímenes que incluyen cisplatino y vinorelbina. Queda por ser determinado el papel que desempeñanotros agentes como el uracilo/tegafur así como la radioterapia en el contexto adyuvante

Surgery is the current treatment of choice in patients with early-stage non-small cell lung cancer.Based on the high rates of recurrence, additional local and systemic treatments have been developed,aimed at improving the cure rates. The comparative studies about the benefits of post-operativeadjuvant chemotherapy and/or radiotherapy, and the meta-analysis studies made during the lastdecades, reviewed in some articles appeared in 95 and 97, did not confirm a significant improvementof the overall survival. Since then, new comparative trials carried out with a higher number of patientsand with more active and standard chemotherapy seem to show a benefit of the administration ofplatinum-based chemotherapy, although it has not gained general acceptance. More recently, a newmeta-analysis, that included the previous studies, has confirmed an overall increase of 4 % in survivalof patients treated by surgery and adjuvant chemotherapy, especially in stages II-III patients receivingschedules of cisplatin and vinorelbine. Further studies are needed to determine the real therapeuticvalue of other agents, as uracil-tegafur and radiotherapy