Visual and semi-quantitative analysis of 6-[18F]FDOPA PET/CT in patients with brain tumors and suspected tumor recurrence versus radionecrosis.

INTRODUCTION: Amino acid PET is a tool recommended by the main neuroimaging societies in the differential diagnosis between radionecrosis (RNC) and umour recurrence (TR) in brain tumours, but its use in our country is still limited. The aim of this work is to present our experience with 6-[18F]FDOPA PET/CT (FDOPA) in brain tumours (primary and M1), comparing these results with other published results. MATERIAL AND METHODS: Retrospective study of 62 patients with suspected tumour recurrence (TR): 42 brain metastases (M1) and 20 primary, who underwent FDOPA. Images were analysed visually and semi-quantitatively, obtaining SUVmax and SUVmaxlesion/SUVmaxstriatum (L/S) and SUVmaxlesion/SUVmaxcortex (L/C) ratios. The diagnostic validity of PET was analysed and the best performing cut-off points were calculated. PET results were compared with clinical-radiological follow-up and/or histopathology. RESULTS: TR was identified in 49% of M1 and 76% of brain primaries. The best performing FDOPA interpretation was visual and semi-quantitative, with a sensitivity and specificity in primaries of 94% and 80% and in M1s of 96% and 72% respectively. The cut-off points with the best diagnostic performance were L/C1.44 in M1 and L/C1.55 in primaries. There are discrepant results with other published results. CONCLUSION: FDOPA PET/CT is a useful tool in the differential diagnosis between recurrence and RNC in brain tumours. It is needed a standardization to contribute to homogenise FDOPA results a inter-centre level.

Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study.

BACKGROUND: Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). METHODS: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4 mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (ß-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. RESULTS: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with ß-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. CONCLUSION: In patients with PCa and bone metastases treated with ZA, ß-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially important.

Extended-schedule dose-dense temozolomide in refractory gliomas.

This multicenter phase II study conducted by the Spanish Neuro-Oncology Group evaluated the activity of an extended, dose-dense temozolomide regimen in patients with temozolomide-refractory malignant glioma. Adult patients (at least 18 years of age) with WHO grade III or IV glioma and a Karnofsky Performance Status of 60 or higher were treated with temozolomide (85 mg/m(2)/day) for 21 consecutive days every 28-day cycle until disease progression or unacceptable toxicity. All patients had developed progressive disease either during or less than 3 months after completing previous temozolomide treatment. Forty-seven patients were treated with a median of 2 (range, 1-13) cycles of temozolomide. Before study entry, patients had received a median of 6 cycles of temozolomide: 39 (83%) as part of initial therapy and 23 (49%) as second-line therapy. Three patients (6.4%) had a partial response with durations of 8.0, 3.5, and 3.2 months; 15 patients (31.9%) had stable disease with a median duration of 2.1 months, including 2 patients with stable disease (SD) for greater than 6 months (14 and 16 months). Median time to progression was 2 months, and median overall survival from study entry was 5.1 months. The 6-month progression-free survival rate was 16.7%. The most common hematologic toxicities were lymphopenia, thrombocytopenia, and leukopenia. Lymphopenia occurred in 83% of patients and was grade 3 in 28%, but no opportunistic infections occurred. In conclusion, this extended dose-dense schedule of temozolomide appears to have modest activity in patients refractory to previous treatment with temozolomide and is associated with manageable toxicity.

SEOM clinical guideline of diagnosis and management of low-grade glioma (2017).

Diffuse infiltrating low-grade gliomas include oligodendrogliomas and astrocytomas, and account for about 5% of all primary brain tumors. Treatment strategies for these low-grade gliomas in adults have recently changed. The 2016 World Health Organization (WHO) classification has updated the definition of these tumors to include their molecular characterization, including the presence of isocitrate dehydrogenase (IDH) mutation and 1p/19p codeletion. In this new classification, the histologic subtype of grade II-mixed oligoastrocytoma has also been eliminated. The precise optimal management of patients with low-grade glioma after resection remains to be determined. The risk-benefit ratio of adjuvant treatment must be weighed for each individual.

Correction to: SEOM clinical guideline of diagnosis and management of low-grade glioma (2017).

The original version of this article unfortunately contained a mistake. Figure 3 was incorrect.

Delay in starting radiotherapy due to neoadjuvant therapy does not worsen survival in unresected glioblastoma patients.

PURPOSE: We retrospectively examined the potential effect on overall survival (OS) of delaying radiotherapy to administer neoadjuvant therapy in unresected glioblastoma patients. PATIENTS AND METHODS: We compared OS in 119 patients receiving neoadjuvant therapy followed by standard treatment (NA group) and 96 patients receiving standard treatment without neoadjuvant therapy (NoNA group). The MaxStat package of R identified the optimal cut-off point for waiting time to radiotherapy. RESULTS: OS was similar in the NA and NoNA groups. Median waiting time to radiotherapy after surgery was 13 weeks for the NA group and 4.2 weeks for the NoNA group. The longest OS was attained by patients who started radiotherapy after 12 weeks and the shortest by patients who started radiotherapy within 4 weeks (12.3 vs 6.6 months) (P = 0.05). OS was 6.6 months for patients who started radiotherapy before the optimal cutoff of 6.43 weeks and 19.1 months for those who started after this time (P = 0.005). Patients who completed radiotherapy had longer OS than those who did not, in all 215 patients and in the NA and NoNA groups (P = 0.000). In several multivariate analyses, completing radiotherapy was a universally favorable prognostic factor, while neoadjuvant therapy was never identified as a negative prognostic factor. CONCLUSION: In our series of unresected patients receiving neoadjuvant treatment, in spite of the delay in starting radiotherapy, OS was not inferior to that of a similar group of patients with no delay in starting radiotherapy.

[Study of the binding of thyroxine by thyroxine-binding prealbumin by a dialysis method using a fixed free concentration of ligand (author's transl)]. / Etude de la liaison thyroxine-thyroxine-binding prealbumin par une methode de dialyse a concentration libre imposee.

In order to study ligand-protein binding in solution, a dialysis method was used in which the free concentration of ligand can be controlled. The method has certain advantages and was applied to the binding of thyroxine by thyroxine-binding prealbumin, a system about which the results found in the literature are not in good agreement. From the isotherm drawn according to the Scatchard plot, it was found that thyroxine-binding prealbumin only presents a single binding site for thyroxine per molecule, the association constant being 1.7 . 10(8) M-1.

A phase II study of feasibility and toxicity of bevacizumab in combination with temozolomide in patients with recurrent glioblastoma.

PURPOSE: The aim of this prospective and multicentric phase II study was to evaluate the efficacy and safety of temozolomide (TMZ) and bevacizumab (BV) in patients (pts) with recurrent glioblastoma (GB), previously treated with chemoradiotherapy and at least three cycles of adjuvant TMZ. PATIENTS AND METHODS: Patients with GB at first relapse received BV 10 mg/kg day every 2 weeks and TMZ 150 mg/m(2) days 1-7 and 15-21, every 28 days. Patients underwent brain magnetic resonance imaging every 8 weeks. RESULTS: Thirty-two evaluable pts were recruited in 8 sites. Fourteen pts (44%) had gross total resection. O(6)-methylguanine-DNA methyltransferase (MGMT) promoter was methylated in 12 pts, unmethylated in 6 pts, and missing in 14 pts. The estimated 6-month progression free survival (PFS) rate was 21.9% (95% CI 9.3-40.0%). The median PFS and overall survival (OS) were 4.2 months (95% CI 3.6-5.4 months) and 7.3 months (95% CI 5.8-8.8 months), respectively. No significant association with MGMT status was found in terms of OS or PFS. Six of 32 pts (19%; 95% CI 7.2-36.4) were long-term survivors, with a median PFS and OS (50% events) of 9.5 months (95% CI 7.9-23.6) and 15.4 (95% CI 8.9-NA), respectively: no differences in baseline characteristics were identified in comparison with total population. No unexpected toxicities or treatment-related deaths were observed. CONCLUSIONS: This regimen showed to be feasible and well tolerated in pts with recurrent GB pretreated with TMZ. Further investigation is warranted to identify subpopulations that are more likely to benefit from addition of BV to GB therapy.

A method for measuring testosterone-estradiol-binding globulin--new analysis of experimental data and comparison with two commercially available kits.

Some binding assays have been suggested to measure serum testosterone--estradiol-binding globulin (TeBG) concentration. They have led to discrepant results. This study brought to surface the lack of these methods and the interest of a method using an accurate analysis of the binding isotherm. These observations led us to propose an absolute reference method especially suitable for the radioimmunological assays standardization. Our method used Con A Sepharose as a solid phase and DHT as a radioligand. We succeeded in solving the difficulties related to binding methods by evaluating the non-specific binding of the ligand and ligand--albumin binding. A careful analysis of experimental data, by setting equations specific to this DHT-TeBG system permitted the systematic errors to be corrected and allowed a precise determination of the serum TeBG concentration (27.3 +/- 6.0 nmol/l for 30 healthy men; 40 +/- 13 nmol/l for 15 healthy women). Moreover, the affinity constant of the ligand for the protein was accurately evaluated KDHT = (0.7 +/- 0.1)10(9) (mol/l-1) at 20 degrees C, which was not permitted by other methods. Two lines of evidence supported our assumptions and results. On the one hand, using estradiol as a radioligand instead of dihydrotestosterone, we found the same value for serum TeBG concentration; on the other hand, our assay favourably compared with two different kits commercially available. The correlation (r = 0.89) with 3H-SBP kit Merieux was good though this kit was not suitable for correctly assaying serum TeBG concentrations between 30 nmol/l and 60 nmol/l. An excellent correlation (r = 0.97) with SHBG IRMA Kit Farmos was found. This antibody-based assay and our binding assay yielded quite similar values that mutually validated both methods.

Correlation of free thyroxine index and thyroxine: thyroxine-binding globulin ratio with the free thyroxine concentration as measured by the thyroxine and thyroxine-binding globulin radioimmunoassays.

The concentration of thyroxine-binding globulin in the serum can now be measured by a simple and specific radioimmunoassay. Triiodothyronine uptake and measurement of total thyroxine have been combined to yield a free thyroxine index which has been found to correlate with the clinical state of the patients. An estimate of the free thyroxine concentration, as measured by the thyroxine and thyroxine-binding globulin radioimmunoassays, provided a good correlation with the free thyroxine index and the thyroxine: thyroxine-binding globulin ratio. However, the thyroxine: thyroxine-binding globulin ratio is inaccurate when thyroxine-binding globulin concentrations are high or low.

[Infections due to herpes-varicella viruses in Hodgkin's disease (author's transl)]. / Infecciones por herpes virus-varicela en la enfermedad de Hodgkin.

The infections due to herpes-varicella viruses occurring in 191 patients with Hodgkin's disease form the basis of this report. There were overall 41 episodes (26.7%) in 40 patients, distributed as follows: varicella in three cases, atypical herpes-varicella in two cases, and herpes zoster in 36 cases, the latter showing systemic spread in seven instances, one to the central nervous system (myelitis) and six to the skin. The mortality was 2.5% of all infections, and 33% of the varicella cases. Morbidity was apparent as postherpetic neuralgia in seven patients (19.4%), postherpetic paraplegia in one case (2.5%), and severe thrombocytopenia in another case (2.5%). The statistical study of the factors contributing to the development of reactivation episodes demonstrated that neither age, sex, or previous splenectomy were influential. The results obtained in relation to the stage and histologic type of Hodgkin's disease can not be fully evaluated because of the artifact introduced by other variables such as type of therapy and observation time. There was a clear relationship with the aggressiveness of therapy, because 81.7% of the viral episodes occurred in patients submitted to total radiotherapy with or without chemotherapy, or with partial radiotherapy plus chemotherapy. In the patients with systemic spread there was a clear relationship with prior splenectomy (p less than 0.005). The clinical features of these patients are commented upon.

Análisis visual y semicuantitativo del 6-[18F]FDOPA PET/TC en pacientes con tumores cerebrales ante la sospecha de recurrencia tumoral versus radionecrosis / VAnálisis visual y semicuantitativo del 6-[18F]FDOPA PET/TC en pacientes con tumores cerebrales ante la sospecha de recurrencia tumoral versus radionecrosis

Introducción La tomografía por emisión de positrones (PET) con aminoácidos es una herramienta recomendada por las principales sociedades de neuroimagen, en el diagnóstico diferencial entre radionecrosis (RNC) y recurrencia tumoral (RT) en los tumores cerebrales, sin embargo, su uso en nuestro pais aún es limitado. El objetivo de este trabajo es presentar nuestra experiencia con 6-[18F]FDOPA PET/TC (FDOPA) en tumores cerebrales (primarios y M1), comparando estos resultados con otros publicados. Material y métodos Estudio retrospectivo de 62 pacientes con sospecha de RT: 42 metástasis cerebrales (M1) y 20 primarios, a los que se les realizó una FDOPA. Las imágenes fueron analizadas visual y semicuantitativamente, obteniendo el SUVmax y los ratios SUVmaxlesión/SUVmaxestriado (L/E) y SUVmaxlesión/SUVmaxcortex (L/C). Se analizó la validez diagnóstica de la PET y se calcularon los puntos de corte con mayor rendimiento. Los resultados de la PET se compararon con la evolución clínico-radiológica y/o con la histopatología. Resultados Se identificó RT en el 49% de las M1 y en el 76% de los primarios cerebrales. La interpretación de la FDOPA con mejores resultados fue la conjunta; visual y semicuantitativa, con una sensibilidad y especificidad en los primarios del 94 y 80% y en las M1 del 96 y 72%, respectivamente. Los puntos de corte con mejor rendimiento diagnóstico fueron L/C 1,44 en M1 y L/C 1,55 en primarios. Existen resultados discrepantes con otros publicados. Conclusión La FDOPA PET/TC es una herramienta útil en el diagnóstico diferencial entre RT y RNC en tumores cerebrales. Es necesario una estandarización que contribuya a homogeneizar los resultados de la FDOPA a nivel intercentro (AU)

Introduction Amino acid PET is a tool recommended by the main neuroimaging societies in the differential diagnosis between radionecrosis (RNC) and tumour recurrence (TR) in brain tumours, but its use in our country is still limited. The aim of this work is to present our experience with 6-[18F]FDOPA PET/CT (FDOPA) in brain tumours (primary and M1), comparing these results with other published results. Material and methods Retrospective study of 62 patients with suspected tumour recurrence (TR): 42 brain metastases (M1) and 20 primary, who underwent FDOPA. Images were analysed visually and semi-quantitatively, obtaining SUVmax and SUVmaxlesion/SUVmaxstriatum (L/S) and SUVmaxlesion/SUVmaxcortex (L/C) ratios. The diagnostic validity of PET was analysed and the best performing cut-off points were calculated. PET results were compared with clinical-radiological follow-up and/or histopathology. Results TR was identified in 49% of M1 and 76% of brain primaries. The best performing FDOPA interpretation was visual and semi-quantitative, with a sensitivity and specificity in primaries of 94% and 80% and in M1s of 96% and 72% respectively. The cut-off points with the best diagnostic performance were L/C1.44 in M1 and L/C1.55 in primaries. There are discrepant results with other published results. Conclusion FDOPA PET/CT is a useful tool in the differential diagnosis between recurrence and RNC in brain tumours. It is needed a standardization to contribute to homogenise FDOPA results a inter-centre level (AU)

VEGF and TSP1 levels correlate with prognosis in advanced non-small cell lung cancer.

PURPOSE: There is a need for biomarkers that may help in selecting the most effective anticancer treatments for each patient. We have investigated the prognostic value of a set of angiogenesis, inflammation and coagulation markers in patients treated for advanced non-small cell lung cancer. PATIENTS AND METHODS: Peripheral blood samples were obtained from 60 patients before first line platinum-based chemotherapy ± bevacizumab, and after the third cycle of treatment. Blood samples from 60 healthy volunteers were also obtained as controls. Angiogenesis, inflammation and coagulation markers vascular endothelial growth factor (VEGF), their soluble receptors 1 (VEGFR1) and 2 (VEGFR2), thrombospondin-1 (TSP-1), interleukin-6 (IL6), sialic acid (SA) and tissue factor (TF) were quantified by ELISA. RESULTS: Except for TSP-1, pre- and post-treatment levels of all markers were higher in patients than in controls (p < 0.05). There was a positive and significant correlation between VEGF and VEGFR2 before treatment. VEGF also correlated with inflammatory markers IL-6 and SA. Moreover, there was a positive and significant correlation between levels of VEGFR1 and TF. Decreased levels of TSP-1 and increased levels of VEGF were associated with shorter survival. Bevacizumab significantly modified angiogenesis parameters and caused a decrease of VEGF and an increase of TSP-1. CONCLUSION: Angiogenesis, inflammation and coagulation markers were increased in NSCLC patients. Increased levels of VEGF and low levels of TSP-1 correlated with a poor prognosis.

SEOM clinical guideline of diagnosis and management of low-grade glioma (2017)

Diffuse infiltrating low-grade gliomas include oligodendrogliomas and astrocytomas, and account for about 5% of all primary brain tumors. Treatment strategies for these low-grade gliomas in adults have recently changed. The 2016 World Health Organization (WHO) classification has updated the definition of these tumors to include their molecular characterization, including the presence of isocitrate dehydrogenase (IDH) mutation and 1p/19p codeletion. In this new classification, the histologic subtype of grade II-mixed oligoastrocytoma has also been eliminated. The precise optimal management of patients with low-grade glioma after resection remains to be determined. The risk-benefit ratio of adjuvant treatment must be weighed for each individual (AU)

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Relative value of magnetic resonance spectroscopy, magnetic resonance perfusion, and 2-(18F) fluoro-2-deoxy-D-glucose positron emission tomography for detection of recurrence or grade increase in gliomas.

In a consecutive series of 26 previously operated patients diagnosed with cerebral glioma, magnetic resonance spectroscopy (MRS), 2-((18)F) fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), and perfusion MRI (MRP), were performed at follow-up to distinguish recurrence from radiation necrosis, and to identify tumour upgrading. Discrepancy between techniques was observed in 9 cases. The positive predictive value (PPV) and the negative predictive value (NPV) of each technique to detect the presence of high grade glioma was: MRI, PPV=50%; MRS, PPV=91.6%, NPV=100%; FDG-PET, PPV=75%, NPV=61.1%; MRP, PPV=100%, NPV=100%. In the selected group of nine cases studied to differentiate viable tumour from radiation necrosis, MRS and MRP reached a PPV and a NPV of 100%, whereas for FDG-PET, PPV and NPV were 66.6% and 60%, respectively. To distinguish between viable high-grade glioma and radiation necrosis, gadolinium-enhanced MRI gives a high false-positive rate, while MRS and MRP are superior to FDG-PET in discriminating tumour recurrence, grade increase and radiation necrosis.

Delay in starting radiotherapy due to neoadjuvant therapy does not worsen survival in unresected glioblastoma patients

Purpose: We retrospectively examined the potential effect on overall survival (OS) of delaying radiotherapy to administer neoadjuvant therapy in unresected glioblastoma patients. Patients and methods: We compared OS in 119 patients receiving neoadjuvant therapy followed by standard treatment (NA group) and 96 patients receiving standard treatment without neoadjuvant therapy (NoNA group). The MaxStat package of R identified the optimal cut-off point for waiting time to radiotherapy. Results: OS was similar in the NA and NoNA groups. Median waiting time to radiotherapy after surgery was 13 weeks for the NA group and 4.2 weeks for the NoNA group. The longest OS was attained by patients who started radiotherapy after 12 weeks and the shortest by patients who started radiotherapy within 4 weeks (12.3 vs 6.6 months) (P = 0.05). OS was 6.6 months for patients who started radiotherapy before the optimal cutoff of 6.43 weeks and 19.1 months for those who started after this time (P = 0.005). Patients who completed radiotherapy had longer OS than those who did not, in all 215 patients and in the NA and NoNA groups (P = 0.000). In several multivariate analyses, completing radiotherapy was a universally favorable prognostic factor, while neoadjuvant therapy was never identified as a negative prognostic factor. Conclusion: In our series of unresected patients receiving neoadjuvant treatment, in spite of the delay in starting radiotherapy, OS was not inferior to that of a similar group of patients with no delay in starting radiotherapy

No disponible

A phase II study of feasibility and toxicity of bevacizumab in combination with temozolomide in patients with recurrent glioblastoma

Purpose. The aim of this prospective and multicentric phase II study was to evaluate the efficacy and safety of temozolomide (TMZ) and bevacizumab (BV) in patients (pts) with recurrent glioblastoma (GB), previously treated with chemoradiotherapy and at least three cycles of adjuvant TMZ. Patients and methods. Patients with GB at first relapse received BV 10 mg/kg day every 2 weeks and TMZ 150 mg/m2 days 1–7 and 15–21, every 28 days. Patients underwent brain magnetic resonance imaging every 8 weeks. Results. Thirty-two evaluable pts were recruited in 8 sites. Fourteen pts (44 %) had gross total resection. O6-methylguanine-DNA methyltransferase (MGMT) promoter was methylated in 12 pts, unmethylated in 6 pts, and missing in 14 pts. The estimated 6-month progression free survival (PFS) rate was 21.9 % (95 % CI 9.3–40.0 %). The median PFS and overall survival (OS) were 4.2 months (95 % CI 3.6–5.4 months) and 7.3 months (95 % CI 5.8–8.8 months), respectively. No significant association with MGMT status was found in terms of OS or PFS. Six of 32 pts (19 %; 95 % CI 7.2–36.4) were long-term survivors, with a median PFS and OS (50 % events) of 9.5 months (95 % CI 7.9–23.6) and 15.4 (95 % CI 8.9–NA), respectively: no differences in baseline characteristics were identified in comparison with total population. No unexpected toxicities or treatment-related deaths were observed. Conclusions. This regimen showed to be feasible and well tolerated in pts with recurrent GB pretreated with TMZ. Further investigation is warranted to identify subpopulations that are more likely to benefit from addition of BV to GB therapy (AU)

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A simple and sensitive solid-phase radioimmunoassay for measuring the transferrin content of human biological fluids: its application to seminal plasma.

A highly sensitive and reproducible radioimmunoassay was established to detect transferrin in human fluids. By this technique, applied to seminal fluid, transferrin levels (micrograms/ml) were found in normozoospermic individuals (64.49 +/- 25.41) at level higher than in oligozoospermic (38.93 +/- 21.35), azoospermic (19.49 +/- 10.23), or vasectomized (19.61 +/- 8.95) subjects. A relationship between transferrin and spermatozoid concentration in sperm was shown. These results reinforce previous findings that seminal transferrin can be used as a reliable clinical marker of Sertoli Cell function.

[Detection of the HBs antigen. Analysis of an interlaboratory of different methods of detection used in the blood banks of the central region]. / Détection de l'antigène HBs. Analyse d'une confrontation interlaboratoires concernant les différentes méthodes de détection utilisées dans les centres de transfusion sanguine de la région Centre.

A one year study has been performed between six blood Banks of the Centre of France in order to evaluate, among a population of donors found to be positive for HBs Ag by a radioimmunoassay, the number of those who were not detected by Enzyme immunoassay or passive hemagglutination. This study provides a good basis for comparing the sensitivities of the different methods used for Hbs Ag testing.