Usefulness of CA125 and its kinetic parameters and positron emission tomography/computed tomography (PET/CT) with fluorodeoxyglucose ([18F] FDG) in the detection of recurrent ovarian cancer / Utilidad del CA125 y sus parámetros cinéticos y de la tomografía por emisión de positrones/tomografía computarizada (PET/TC) con fluorodesoxiglucosa ([18F]FDG) en la detección de la recidiva del cáncer de ovario

Background and objective: To assess the usefulness of cancer antigen 125 (CA125) serum levels and kinetic values, velocity (CA125vel) and doubling time (CA125dt), as well as fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT), in the detection of ovarian cancer recurrence. To assess the optimal cut-off for CA125, CA125vel and CA125dt to detect relapse with [18F]FDG-PET/CT. Material and methods: A retrospective analysis was performed of 59 [18F]FDG-PET/CT (48 patients) for suspected recurrence of ovarian cancer. Receiver operating characteristic (ROC) curves were plotted and area-under-the curve (AUC) statistics were computed for CA125, CA125vel and CA125dt. The results obtained in the group with normal and high (>35U/ml) CA125 levels were compared. Results: Forty-four cases of recurrence were diagnosed (7 had CA125 ≤35U/ml), whereas 15 showed no disease. All of them were correctly catalogued by PET/CT. In ROC analysis, the discriminatory power of CA125 was relatively high (AUC 0.835) and the optimal cut-off point to reflect active disease was 23.9U/ml. The ROC analyses for the CA125vel and CA125dt showed an AUC of 0.849 and 0.728, respectively, with an optimal cut-off point of 1.96U/ml/month and 0.76 months, respectively. In patients with normal CA125 and recurrence of ovarian cancer, the CA125vel was significantly higher than in patients without recurrence (p=0.029). Conclusion: [18F]FDG-PET/CT is more accurate than CA125 parameters in the detection of ovarian cancer recurrence. CA125 serum levels are essential; nevertheless, CA125 kinetic values must be considered to detect relapse. Particularly in patients with CA125 within normal values, in which a higher CA125vel is indicative of recurrence

Fundamento y objetivo: Valorar en la recidiva del cáncer de ovario la utilidad del CA125 y sus parámetros cinéticos, velocidad (CA125vel) y tiempo de duplicación (CA125td), y de la tomografía por emisión de positrones/tomografía computarizada (PET/TC) con fluorodesoxiglucosa ([18F]FDG). Determinar el valour óptimo del CA125, CA125vel y CA125td para detectar recidiva con [18F]FDG-PET/TC. Material y métodos: Análisis retrospectivo de 59 estudios [18F]FDG-PET/TC en 48 pacientes con sospecha de recidiva de cáncer de ovario platino-sensible. Realizamos un análisis ROC (Receiver operating characteristic) y el área bajo la curva (AUC) para el CA125, CA125vel, CA125td. Comparamos los resultados entre los grupos con CA125 dentro de la normalidad y CA125 patológico (>35U/ml). Resultados: Fueron diagnosticados de recidiva 44 casos (7 con CA125 ≤35U/ml), mientras que 15 no mostraron recurrencia. Todos ellos fueron correctamente catalogados mediante la PET/TC. La curva ROC demostró una capacidad discriminatoria del CA125 relativamente alta (AUC 0.835), con un valour óptimo de referencia de 23.9U/ml. El análisis ROC para la CA125vel y el CA125td mostró un AUC de 0.849 y 0.728, con un valour de referencia de 1.96U/ml/mes y 0.76 meses, respectivamente. En las pacientes con CA125 en límites normales la CA125vel fue significativamente mayor en las pacientes con recidiva que en aquellas sin enfermedad (p=0.029). Conclusión: La [18F]FDG-PET/TC es más exacta que los parámetros de CA125 en la detección de recurrencia de cáncer de ovario. Los niveles séricos de CA125 resultan esenciales, no obstante, los parámetros cinéticos deben ser tenidos en cuenta en la detección de la recidiva

Value of [18F]FDG-PET/CT and CA125, serum levels and kinetic parameters, in early detection of ovarian cancer recurrence: Influence of histological subtypes and tumor stages.

To assess the diagnostic accuracy of CA125, its kinetic values and positron emission tomography/computed tomography with 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG-PET/CT), in relation with tumor characteristics for suspected recurrence of ovarian cancer. To evaluate the performance of CA125-related parameters as a selection criteria to perform a [F]FDG-PET/CT.A retrospective analysis of 69 [F]FDG-PET/CT for suspected recurrence of ovarian cancer was performed. All patients had 2 measurements of CA125, before PET/CT, to calculate kinetic values, as CA125vel (CA125vel = [CA125a - CA125b]/time) and CA125dt (CA125dt = [log2 × time]/[logCA125a - CA125b]). Maximum standard uptake value (SUVmax) was calculated. The diagnostic accuracy was calculated for all the variables and the optimal cut-off value of each of them by the receiver-operating characteristics (ROC) analysis. All the tests were compared with tumor characteristics and clinical-radiological evolution during follow-up of at least 6 months.Fifty-five cases were diagnosed of recurrence (11 with CA125 <35 U/mL), while 14 showed no disease (11 with CA125 < 35 U/mL). All of them were correctly cataloged by PET/CT. CA125, CA125vel, and SUVmax showed higher levels in recurrent patients (mean 129.54 U/mL, 24.58 U/mL per mo, and 8.69 g/mL, respectively) than in nonrecurrent (mean 20.35 U/mL, 0.60 U/mL per mo, and 0.64 g/mL, respectively). No statistical differences in CA125dt were found. Patients with recurrence of high-grade serous carcinoma (HGSC) showed higher CA125 and CA125vel, without differences in the rest of subtypes and International Federation of Gynecology and Obstetrics stages. The ROC analyses for CA125, CA125vel, and CA125dt showed an area under the curve (AUC) of 0.873 (95% confidence interval [CI] 0.77-0.969), 0.903 (95% CI 0.813-0.994), and 0.727 (95% CI 0.542-0.913), respectively, with an optimal cut-off point of 23.95 U/mL, 4.49 U/mL per mo, and 3.36 months, respectively, while for the SUVmax the AUC was of 0.982 (95% CI 0.948-1.000), and the cut-off point of 2. Multivariate regression analysis identified CA125 and CA125vel as predictors of recurrence.[F]FDG-PET/CT is more accurate than the parameters obtained from the CA125 to detect early recurrence. CA125vel is the most suitable parameter, mainly in HGSC. Levels of CA125vel ≥ 4.49 U/mL per mo facilitate earlier detection by the execution of a [F]FDG-PET/CT. The calculation of these parameters is independent of tumor stage at diagnosis.

Usefulness of CA125 and its kinetic parameters and positron emission tomography/computed tomography (PET/CT) with fluorodeoxyglucose ([18F] FDG) in the detection of recurrent ovarian cancer.

BACKGROUND AND OBJECTIVE: To assess the usefulness of cancer antigen 125 (CA125) serum levels and kinetic values, velocity (CA125vel) and doubling time (CA125dt), as well as fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT), in the detection of ovarian cancer recurrence. To assess the optimal cut-off for CA125, CA125vel and CA125dt to detect relapse with [18F]FDG-PET/CT. MATERIAL AND METHODS: A retrospective analysis was performed of 59 [18F]FDG-PET/CT (48 patients) for suspected recurrence of ovarian cancer. Receiver operating characteristic (ROC) curves were plotted and area-under-the curve (AUC) statistics were computed for CA125, CA125vel and CA125dt. The results obtained in the group with normal and high (>35U/ml) CA125 levels were compared. RESULTS: Forty-four cases of recurrence were diagnosed (7 had CA125 ≤35U/ml), whereas 15 showed no disease. All of them were correctly catalogued by PET/CT. In ROC analysis, the discriminatory power of CA125 was relatively high (AUC 0.835) and the optimal cut-off point to reflect active disease was 23.9U/ml. The ROC analyses for the CA125vel and CA125dt showed an AUC of 0.849 and 0.728, respectively, with an optimal cut-off point of 1.96U/ml/month and 0.76 months, respectively. In patients with normal CA125 and recurrence of ovarian cancer, the CA125vel was significantly higher than in patients without recurrence (p=0.029). CONCLUSION: [18F]FDG-PET/CT is more accurate than CA125 parameters in the detection of ovarian cancer recurrence. CA125 serum levels are essential; nevertheless, CA125 kinetic values must be considered to detect relapse. Particularly in patients with CA125 within normal values, in which a higher CA125vel is indicative of recurrence.

KIR Genes and Their Ligands Predict the Response to Anti-EGFR Monoclonal Antibodies in Solid Tumors.

Killer-cell immunoglobulin-like receptors (KIRs) regulate the killing function of natural killer cells, which play an important role in the antibody-dependent cell-mediated cytotoxicity response exerted by therapeutic monoclonal antibodies (mAbs). However, it is unknown whether the extensive genetic variability of KIR genes and/or their human leukocyte antigen (HLA) ligands might influence the response to these treatments. This study aimed to explore whether the variability in KIR/HLA genes may be associated with the variable response observed to mAbs based anti-epidermal growth factor receptor (EGFR) therapies. Thirty-nine patients treated with anti-EGFR mAbs (trastuzumab for advanced breast cancer, or cetuximab for advanced colorectal or advanced head and neck cancer) were included in the study. All the patients had progressed to mAbs therapy and were grouped into two categories taking into account time to treatment failure (TTF ≤6 and ≥10 months). KIR genotyping (16 genetic variability) was performed in genomic DNA from peripheral blood by PCR sequence-specific primer technique, and HLA ligand typing was performed for HLA-B and -C loci by reverse polymerase chain reaction sequence-specific oligonucleotide methodology. Subjects carrying the KIR/HLA ligand combinations KIR2DS1/HLAC2C2-C1C2 and KIR3DS1/HLABw4w4-w4w6 showed longer TTF than non-carriers counterparts (14.76 vs. 3.73 months, p < 0.001 and 14.93 vs. 4.6 months, p = 0.005, respectively). No other significant differences were observed. Two activating KIR/HLA ligand combinations predict better response of patients to anti-EGFR therapy. These findings increase the overall knowledge on the role of specific gene variants related to responsiveness to anti-EGFR treatment in solid tumors and highlight the importance of assessing gene polymorphisms related to cancer medications.

Epidemiology and characteristics of febrile neutropenia in oncology patients from Spanish tertiary care hospitals: PINNACLE study.

Febrile neutropenia (FN) is one of the most common adverse events associated with myelosuppressive chemotherapy for cancer treatment. The objective of this study was to describe the incidence of hospitalization due to FN in Spanish tertiary care hospitals (PINNACLE study). This epidemiological, retrospective, multicenter, nationwide study involved 119 patients from oncology units of 10 Spanish tertiary care hospitals who were admitted for FN. The primary endpoint was to assess the epidemiology and characteristics of FN. The incidence of admissions due to FN in oncology patients was 2.0% (interquartile range [IQR], 1.6-3.0). In terms of fever and absolute neutrophil count (ANC), 37.0% of the patients had a temperature of ≥38.2°C and an ANC of ≤500/m3. The number of patients who received prophylactic treatment with granulocyte colony-stimulating factor (G-CSF) was significantly higher in the palliative group (32.6%) compared with that in the non-palliative group (13.5%). The hospital length of stay was significantly shorter in patients who received prophylactic G-CSF compared with those who did not (5.0 days; IQR, 4.0-9.0 vs. 7.0 days; IQR, 5.0-11.0, respectively). The hospital length of stay was also significantly shorter in patients receiving palliative treatment (5.0 days; IQR, 3.0-7.0) compared with those receiving non-palliative therapy (7.0 days; IQR, 5.0-12.0). In conclusion, the incidence of admissions due to FN in oncology patients was 2.0% and the duration of hospital stay was 7.0 days. Prophylactic G-CSF treatment was found to be associated with better outcomes and shorter hospital stays. Therefore, the use of this treatment becomes relevant for achieving better clinical outcomes and reducing hospitalization cost in the management of FN.

Polimorfismo de ABCB1 en pacientes diagnosticados enfermedad de Charcot-Marie Tooth. Una posible relación con la neurotoxicidad a tratamiento citostático / ABCB1 polymorphisms in patients with Charcot-Marie Tooth disease. A possible relationship with neurotoxicity due to cytostatic treatment

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Clinical practice guidelines on antiemetics in oncology.

The tolerability of chemotherapy has been significantly improved by the advent of effective drugs and protocols for the amelioration of chemotherapy-induced nausea and vomiting. Variables such as the timing of nausea and vomiting (acute, delayed or anticipatory) and the emetogenicity of the chemotherapy must be taken into account in developing guidelines for antiemetic prophylaxis and treatment. Although there are a number of 5-hydroxytryptamine antagonists available, the clinical differences between them are small. The use of drugs with a different mechanism of action, such as the recently introduced neurokinin-1 receptor antagonist aprepitant, may be a useful adjunct to 5-hydroxytryptamine-3 receptor antagonists or steroid prophylaxis. The addition of aprepitant to standard antiemetic regimens increases the proportion of complete responses to antiemetic therapy. For the use of highly emetogenic chemotherapy in oncology a combination of 5-hydroxytryptamine-3 receptor antagonist, dexamethasone and aprepitant is recommended in the acute phase, and dexamethasone plus aprepitant during the subsequent days (many patients do not have their symptoms controlled by 5-hydroxytryptamine-3 receptor antagonist and steroid alone). In either case, lorazepam can be added as required. For moderately emetogenic chemotherapy, a regimen of 5-hydroxytryptamine, dexamethasone and aprepitant is recommended in the acute phase, followed by aprepitant alone in the delayed phase. Alternatively, a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone can be used in the acute phase, followed by dexamethasone for prophylaxis in the delayed phase. For chemotherapy with a low emetogenicity, either dexamethasone, metoclopramide, prochlorperazine or triethyperazine alone is recommended. No prophylaxis is generally required during the delayed phase and indeed may not be necessary during the acute phase either.

A phase II trial of gemcitabine and weekly high-dose 5-fluorouracil in a 48-hour continuous-infusion schedule in patients with advanced pancreatic carcinoma. A study of the Spanish Cooperative Group for Gastrointestinal Tumour Therapy (TTD)

Aim. A multi-centred, open-labelled, phase II study containing 46 patients was conducted to evaluate the clinical benefit of gemcitabine (1,400 mg/m2) combined with 5-FU (3 g/m2) in a 48h continuous infusion (CI). Methods. Both drugs were administered on days 1, 8 and 15 of every 4 week cycle in chemotherapy-naïve patients with locally advanced un-resectable metastatic pancreatic carcinoma. The minimum follow-up was 6 months. Results. Clinical benefit response was the primary endpoint and this was achieved by 24.4% of the patients. Quality of life (QoL) improved in 16.6% of patients. Objective response was observed in 7% of the patients. The median progression-free survival (PFS) was 14.4 weeks and the median overall survival (OS) time was 22.7 weeks. One-year survival was 25%. The most frequent grade 3-4 toxicities were neutropenia (45%), mucositis (7.5%) and hyperbilirubinaemia (10.5%). Conclusions. This schedule was not superior in terms of clinical benefit, response rate, PFS and OS than standard gemcitabine treatment

Pseudomembranous colitis associated with chemotherapy with 5-fluorouracil.

Pseudomembranous colitis is frequently associated with antibiotics and more rarely with chemotherapeutic agents such as 5-fluorouracil. The objective of this study is to show that it is possible to confuse this infection with chemotherapy associated toxicity. We present a 54 year old woman who underwent surgery for colorectal cancer and in the first cycle of chemotherapy with 5-fluorouracil developed pseudomembranous colitis. We detected the toxin B of Clostridium difficile in stools and we began early antibiotic treatment. Thus, in patients with post chemotherapy neutropenia and diarrhoea that develop negatively, we have to rule out this infection.

Pseudomembranous colitis associated with chemotherapy with 5-fluorouracil

Pseudomembranous colitis is frequently associated with antibiotics and more rarely with chemotherapeutic agents such as 5-fluorouracil. The objective of this study is to show that it is possible to confuse this infection with chemotherapy associated toxicity. We present a 54 year old woman who underwent surgery for colorectal cancer and in the first cycle of chemotherapy with 5-fluorouracil developed pseudomembranous colitis. We detected the toxin B of Clostridium difficile in stools and we began early antibiotic treatment. Thus, in patients with post chemotherapy neutropenia and diarrhoea that develop negatively, we have to rule out this infection

A panel discussion of controversies and challenges in the adjuvant treatment of colon cancer.

Current issues of adjuvant therapy for colon cancer concern the introduction of drugs other than fluorouracil-5/leucovorin (5-FU/LV), the benefits for stage II patients, the use of new primary endpoints and the influence of age on treatment benefits. These issues were addressed in a panel discussion and the conclusions were the following: FOLFOX4 is the first regimen that shows superiority over 5-FU/LV. The use of 3-year disease-free survival as primary endpoint could encourage the quicker adoption of improved therapeutic strategies into clinical practice. Available data suggest that there are some benefits for stage II patients, and the decision needs to be individualised for each patient. Further, therapeutic decisions based solely on the patient's age are inappropriate, and geriatric assessment tools will help in making this decision. This information would improve patient and physician understanding of the recent data regarding the potential benefits of adjuvant therapy.

Tratamiento del melanoma coroideo. Estudio de 13 casos / Treatment of choroidal melanoma. Study of 13 cases

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A panel discussion of controversies and challenges in the adjuvant treatment of colon cancer

Las controversias actuales referentes al tratamiento adyuvante del cáncer de colon incluyen la introducción de fármacos más allá de 5-FU/LV, el beneficio que ofrece a los pacientes con estadio II, el uso de nuevas variables y la influencia de la edad sobre los beneficios del tratamiento. Estas controversias fueron discutidas en un panel de expertos y las conclusiones fueron las siguientes: FOLFOX4 es el primer régimen que ha demostrado superioridad frente a 5-FU/LV. El uso de la supervivencia libre de enfermedad a 3 años como variable principal de los estudios podrá permitir una adopción más rápida de estrategias terapéuticas. Los datos disponibles sugieren que existe beneficio para los pacientes con estadio II, y la decisión terapéutica debe ser individualizada. Finalmente, también se llegó a la conclusión de que las decisiones basadas únicamente en la edad no son apropiadas, y las herramientas de valoración geriátrica servirán de apoyo. Esta información puede mejorar el entendimiento de pacientes y médicos acerca de los datos recientes relativos a los beneficios del tratamiento adyuvante

Current issues of adjuvant therapy for colon cancer concern the introduction of drugs other than fluorouracil-5/leucovorin (5-FU/LV), the benefits for stage II patients, the use of new primary endpoints and the influence of age on treatment benefits. These issues were addressed in a panel discussion and the conclusions were the following: FOLFOX4 is the first regimen that shows superiority over 5-FU/LV. The use of 3-year disease-free survival as primary endpoint could encourage the quicker adoption of improved therapeutic strategies into clinical practice. Available data suggest that there are some benefits for stage II patients, and the decision needs to be individualised for each patient. Further, therapeutic decisions based solely on the patient's age are inappropriate, and geriatric assessment tools will help in making this decision. This information would improve patient and physician understanding of the recent data regarding the potential benefits of adjuvant therapy

Comparative study of the immunohistochemical phenotype in breast cancer and its lymph node metastatic location.

At present, an important part of prognostic information, together with particular treatment strategies in breast cancer, take into account the immunohistochemical phenotype of the primary tumor location. However, the changing heterogeneity intrinsic to neoplastic cells in general leads us to consider the possibility that the expression of these proteins is modified during tumoral development and dissemination. With this hypothesis as a starting point, 60 patients with breast cancer were studied with immunohistochemistry, the expression of estrogen and progestagenic receptors, proliferation through the Ki-67 expression, and the overexpression of HER-2 and p53 in both the primary location and the lymph node metastases. If we consider significant change to be loss (from positive to negative) or gain (negative to positive) of expression in some of the studied determinations, we find that this is produced in 60% of the tumors studied. These results demonstrate the modification of immunohistochemical expression of the proteins studied between the primary tumor location and the lymph node metastases.

Adjuvant treatment in elderly patients with breast cancer: critical review of clinical practice.

Today the use of adjuvant treatment of breast cancer is unquestionable in the management of this disease. Both chemotherapy and hormonal therapy have proved to be beneficial, not only with respect to the reduction of the risk of recurrence, but also with respect to mortality. However, in elderly patients, this therapeutic approach is occasionally the subject of controversy, due to the undervaluing of the tumoral disease with respect to the multiple pathology frequently present in these patients. This study analyses a retrospective series of 100 patients more than 70 years old with breast cancer who underwent radical surgery between 1990 and 1998, with an extension study without evidence of metastasis and a minimum follow-up of 2 years. As occurs in the population of this age, in our series 77% of the patients presented with concomitant disease under medical treatment, and although the majority received adjuvant treatment with tamoxifen, the principal cause of death in this series was the breast cancer that had been diagnosed.