Prognostic value of18 f-choline pet/ct in patients with metastatic castration-resistant prostate cancer treated with radium-223

We aimed to investigate the role of positron emission computed tomography (PET/CT) with F-18-choline for predicting the outcome of metastatic castration-resistant prostate cancer (mCRPC) submitted to treatment with Radium-223 (Ra-223-therapy). Clinical records of 20 mCRPC patients submitted to PET/CT with F-18-choline before Ra-223-therapy were retrospectively evaluated. The following PET-derived parameters were calculated: number of lesions, maximum and mean standardized uptake values (SUVmax, SUVmean), lean body mass corrected SUV peak (SULpeak), metabolic tumor volume (MATV), and total lesion activity (TLA). After Ra-223-therapy, all patients underwent regular follow-up until death. The predictive power of clinical and PET-derived parameters on overall survival (OS) was assessed by Kaplan-Meier analysis and the Cox proportional hazard method. All the patients showed F-18-choline-avid lesions at baseline PET/CT. Among the enrolled subjects, eleven (55%) completed all the six scheduled cycles of Ra-223-therapy; seven (35%) were responders according to imaging and biochemical parameters. Mean OS was 12.7 +/- 1.4 months: by Kaplan-Meier analysis, number of lesions, PSA level and TLA were significantly correlated with OS. In multivariate Cox analysis, TLA remained the only significant predictor of survival (p = 0.003; hazard ratio = 7.6, 95% confidence interval = 1.9-29.5 months). F-18-choline PET may be useful for patients' stratification before Ra-223-therapy. In particular, high metabolically active tumor burden (i.e., TLA) was predictive of poor outcome

Acute myeloid leukemia in patients previously diagnosed with breast cancer: Experience of the GIMEMA group

Objective: To evaluate in a multicenter retrospective study, the clinical and laboratory characteristics and the outcome of patients with acute myeloid leukemia (sAML) previously diagnosed with breast cancer (BC) among an adult acute leukemia population. Patients and methods: Between June 1992 and July 1996, 3934 new cases of adults with acute leukemia were recorded in GIMEMA Archive of Adult Acute Leukemia (2964 AML, 901 ALL, 69 acute leukemia expressing both myeloid and lymphoid surface markers). Results: Two hundred patients (5.1%) presented with a history of previous malignancy (21 of them were affected by ALL and 179 by AML). Among sAML, 37 patients (29%) had a previous breast cancer. They consisted of 36 females and 1 male, median age 56 years, range 34-87. The median latency between the 2 malignancies was 54 months (range 5-379). Twenty-seven patients received chemo- and/or radiotherapy for breast cancer (7 only chemotherapy, 6 only radiotherapy, and 14 combined treatment). All patients were surgically treated but in 10 patients surgical debridement was the sole therapy for breast cancer. The drugs most frequently employed were alkylating agents (18 patients), topoisomerase II inhibitors (9 patients), antimetabolites (20 patients) (CMF, CEF and MMM combinations). At onset of sAML the median WBC count was 7.7 × 109/1 (0.8-153) and the median platelet count was 33.5 × 109/1 (3-305). Considering morphological features, FAB subtypes were 4 M0, 5 M1, 11 M2, 5 M3, 8 M4, 3 M5, and 1 M6. Cytogenetic study was performed on 28 patients and 12 of them presented abnormalities. It is noteworthy that chromosome 5 or 7 abnormalities (typically observed in those patients treated with alkylating agents) were present only in three cases. Thirty-four patients received chemotherapy for sAML, and twenty-five of them achieved a CR (74%), with a median duration of twenty-eight weeks (5-280+). The overall survival was 8 months (1-80+). Discussion: The high number of sAML we observed in patients with a previous breast cancer, may be due to the fact that this malignancy is the most frequent neoplasm in women and by the high probability of cure with a consequent long disease-free survival. Our results suggest that the risk of sAML after recovery from breast cancer is increasing due to the rise in the number of patients cured from breast cancer, and in the future could be a relevant problem for haematologists

Genetic lesions disrupting calreticulin 3′-untranslated region in JAK2 mutation-negative polycythemia vera

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Effects of phlebotomy-induced reduction of body iron stores on metabolic syndrome: results from a randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Metabolic syndrome (METS) is an increasingly prevalent but poorly understood clinical condition characterized by insulin resistance, glucose intolerance, dyslipidemia, hypertension, and obesity. Increased oxidative stress catalyzed by accumulation of iron in excess of physiologic requirements has been implicated in the pathogenesis of METS, but the relationships between cause and effect remain uncertain. We tested the hypothesis that phlebotomy-induced reduction of body iron stores would alter the clinical presentation of METS, using a randomized trial.</p> <p>Methods</p> <p>In a randomized, controlled, single-blind clinical trial, 64 patients with METS were randomly assigned to iron reduction by phlebotomy (n = 33) or to a control group (n = 31), which was offered phlebotomy at the end of the study (waiting-list design). The iron-reduction patients had 300 ml of blood removed at entry and between 250 and 500 ml removed after 4 weeks, depending on ferritin levels at study entry. Primary outcomes were change in systolic blood pressure (SBP) and insulin sensitivity as measured by Homeostatic Model Assessment (HOMA) index after 6 weeks. Secondary outcomes included HbA1c, plasma glucose, blood lipids, and heart rate (HR).</p> <p>Results</p> <p>SBP decreased from 148.5 ± 12.3 mmHg to 130.5 ± 11.8 mmHg in the phlebotomy group, and from 144.7 ± 14.4 mmHg to 143.8 ± 11.9 mmHg in the control group (difference -16.6 mmHg; 95% CI -20.7 to -12.5; <it>P </it>< 0.001). No significant effect on HOMA index was seen. With regard to secondary outcomes, blood glucose, HbA1c, low-density lipoprotein/high-density lipoprotein ratio, and HR were significantly decreased by phlebotomy. Changes in BP and HOMA index correlated with ferritin reduction.</p> <p>Conclusions</p> <p>In patients with METS, phlebotomy, with consecutive reduction of body iron stores, lowered BP and resulted in improvements in markers of cardiovascular risk and glycemic control. Blood donation may have beneficial effects for blood donors with METS.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01328210">NCT01328210</a></p> <p>Please see related article: <url>http://www.biomedcentral.com/1741-7015/10/53</url></p

The incidence of secondary leukemias.

Background and Objectives. The term secondary leukemia is usually employed to indicate both forms of acute myeloid leukemia (AML) evolving from previous myelodysplasia and forms of acute leukemia developing after exposure to environmental or therapeutic toxins or radiation (therapy-related). Secondary leukemias account for 10-30% of all AML. The majority of secondary leukemias resulting from the use of cytotoxic drugs can be divided into two well defined groups depending on whether the patient has received 1) alkylating agents or 2) drugs binding to the enzyme DNA-topolsomerase II. Alkylating agents related leukemias are very similar to post MDS leukemias being characterized frequently by a preleukemic phase, trilineage dysplasia, frequent cytogenetic abnormalities involving chromosomes 5 and 7 and a poor prognosis. Secondary leukemias related to therapy with topoisomerase II inhibitors are not preceded by a preleukemic phase and show frequently balanced translocations involving chromosome 11q23. Among therapy-related leukemias, AML is generally a second neoplasm, thus a predisposition to malignancy, independently from previous chemotherapy, cannot be excluded. This review article examines the incidence of all secondary AMLs and the risk of therapy-related leukemia in relation to the different primary malignancies and treatments. Information Sources. The authors have been working in this field, both experimentally and at clinical level, contributing original papers for many years. In addition, the material examined in this review includes articles published in journals covered by MedLine, reviews in journals with high impact factor and recent reports presented at the Secondary Leukemia. An Update Symposium held in Rome in November 1998. State of Art and Perspectives. The incidence of secondary leukemias is increasing because of aging of the population (MDS is more frequent in elderly people) and widespread and successful use of chemoradiotherapy in cancer patients. In the GIMEMA archive of adult acute leukemia (2,964 AML pts from June 1992 to June 1996) an antecedent hematologic disorder (AHD) and/or MDS was found in 8% of all patients (10% of 2,118 patients aged more than 45 years and in 4% of 848 patients aged less than 45). In this series of patients, 6% of all myeloid leukemias were therapy-related leukemia. Therapy-related leukemias are a major problem in patients treated for Hodgkin's disease, non-Hodgkin's lymphoma, myeloma, polycythemia, breast cancer, ovarian carcinoma, or testicular carcinoma. In the GIMEMA archive more than 50% of patients with secondary AML have breast cancer, NHL, or HD. Alkylating agents, nitrosureas and procarbazine appear to have the highest leukemogenic potential. Furthermore aggressive chemotherapy and radiotherapy followed or not by hematopoietic stem cell infusion will produce a more and more prolonged survival but also a greater incidence of secondary AML. Assessment of the risk of secondary leukemia should become part of any therapeutic plan for cancer patients. Avoidance of drugs with more leukemogenic potential will produce a marked reduction of secondary AM

Early interplay of intra-hepatic iron and insulin resistance in children with non-alcoholic fatty liver disease

Background &amp; Aims: The liver is a crucial organ at the crossroads of iron and glucose metabolism. The aim of the study was to assess intra-hepatic iron in young patients with non-alcoholic fatty liver disease (NAFLD) and its association with insulin resistance and severity of liver damage. Methods: Intrahepatic iron content was assessed (Pearl's stain grade) in 66 patients (41 males, age 3.3-17.6 years) with biopsy-proven NAFLD. Mutations of the Hereditary Hemochromatosis (HFE) gene were determined by sequence allele-specific polymerase chain reaction. Insulin resistance was estimated by means of the Oral Glucose Tolerance Test and the Insulin Sensitivity Index (ISI); the Insulino-Genic Index was also calculated. Tumor necrosis factor-alpha and interleukin-6 were measured. Results: Low-mild intra-hepatic iron deposition was observed in one out of five children (n = 15, 22%), and it was not associated with HFE mutations, carried by 17 patients (26%). Among carriers of HFE mutations, four had siderosis. No abnormalities were observed in systemic indices of iron balance. Serum ferritin was within normal adult ranges in all patients (33.6 ± 7.6 ng/ml), but it was correlated with ISI (ro= -0.361; p = 0.003). No significant difference was observed in insulin sensitivity, iron balance, inflammatory milieu, and liver histology between patients with and without hepatic siderosis. Conclusions: In young obese individuals with NAFLD, despite normal peripheral iron parameters, mild intra-hepatic iron deposition is a frequent finding, but it is not associated with insulin resistance or severity of liver damage. Longitudinal studies are required to define the long-term relevance of these findings

Early interplay of intra-hepatic iron and insulin resistance in children with nonalcoholic fatty liver disease

Background & Aims: The liver is a crucial organ at the crossroads of iron and glucose metabolism. The aim of the study was to assess intra-hepatic iron in young patients with non-alcoholic fatty liver disease (NAFLD) and its association with insulin resistance and severity of liver damage. Methods: Intrahepatic iron content was assessed (Pearl's stain grade) in 66 patients (41 males, age 3.3-17.6 years) with biopsy-proven NAFLD. Mutations of the Hereditary Hemochromatosis (HFE) gene were determined by sequence allele-specific polymerase chain reaction. Insulin resistance was estimated by means of the Oral Glucose Tolerance Test and the Insulin Sensitivity Index (ISI); the Insulino-Genic Index was also calculated. Tumor necrosis factor-alpha and interleukin-6 were measured. Results: Low-mild intra-hepatic iron deposition was observed in one out of five children (n = 15, 22%), and it was not associated with HFE mutations, carried by 17 patients (26%). Among carriers of HFE mutations, four had siderosis. No abnormalities were observed in systemic indices of iron balance. Serum ferritin was within normal adult ranges in all patients (33.6 +/- 7.6 ng/ml), but it was correlated with ISI (r(o) = -0.361: p = 0.003). No significant difference was observed in insulin sensitivity, iron balance, inflammatory milieu, and liver histology between patients with and without hepatic siderosis. Conclusions: In young obese individuals with NAFLD, despite normal peripheral iron parameters, mild intra-hepatic iron deposition is a frequent finding, but it is not associated with insulin resistance or severity of liver damage. Longitudinal studies are required to define the long-term relevance of these findings

Acute leukemia following a previous malignancy: do acute lymphoid leukemia and acute myeloid leukemia have a common risk factors ?

Introduction: Within the framework of the GIMEMA Study Group, the characteristics of acute lymphoid leukemia and acute myeloid leukemia occurring in patients who have su\u80ered a previous malignancy were studied. Assessment was also made of the clinical course, laboratory features and overall outcome of these conditions. Materials and methods: A four-year, multi-center retrospective study was conducted to evaluate the e\u80ect of treatment for previous hematological malignancy on the development of secondary leukemia. The study collected in the GIMEMA Archive of Adult Acute Leukemia 3934 new cases of acute leukemia (2964 AML, 901 ALL, 60 acute biphenotypic leukemia). Among these cases, data were evaluated from patients with a personal history of a previous malignancy, and included inquiring into demographic data, history of neoplastic diseases in the 1st degree relatives, type and treatment of the previous malignancy, latency until the development of a secondary acute leukemia diagnosis, laboratory features, treatment and outcome at the onset of secondary acute leukemia. Results: Approximately 200 (5.1%) patients presented a previous malignancy. Twenty-one were a\u80ected by ALL and 179 by AML. The proportion of patients with secondary AML was higher than that of patients with secondary ALL (179/2964 vs 21/901, O.R. 2.69 ± 95% C.I. 1.66 ± 4.39, P50.001). The median latency, from the onset of the previous malignancy to the development of secondary ALL was 27 months and to the development of secondary AML was 52 months (P50.05). Furthermore, of patients who previously received chemotherapy more developed a second AML (66/127 sAML vs 5/21 sALL; O.R. 3.46 ± 95% C.I. 1.10 ± 11.56, P50.01). Conclusion: In most cases, chemotherapy treatment for a previous malignancy can play a role in the development of secondary AML. In almost all cases of secondary ALL, the role of previous drugs does not appear to be relevant. On the basis of our analysis, performed systematically for the ®rst time on a large adult series of acute leukemia, we conclude that in these patients a biological predisposition to cancer may be suspected

Molecular imaging in immuno-oncolog. Current status and translational perspectives

Introduction: Only 20–40% of patients respond to therapy with immune checkpoint inhibitors (ICIs). Therefore, the early identification of subjects that can benefit from such therapeutic regimen is mandatory. Areas covered: The immunobiological mechanisms of ICIs are briefly illustrated. Furthermore, the limitations of traditional radiological approaches are covered. Then, the pros and cons of molecular imaging through positron emission computed tomography (PET/CT) are reviewed, with a particular focus on 18f-fluorodeoxyglucose (18F-FDG) and PET-derived metabolic parameters. Lastly, translational perspective of radiopharmaceuticals others than 18F-FDG such as 89zirconium (89Zr) or fluorine-18 (18F) labeled monoclonal antibodies (e.g.89Zr-atezolizumab, 89Zr-nivolumab) binding to specific biomarkers are discussed. Expert opinion: Molecular imaging presents a prominent role for the management of oncological patients treated with ICIs. Preliminary clinical data indicate that PET/CT with 18F-FDG is useful for assessing the response to treatment and for the imaging of immune-related adverse effects. Nevertheless, the methodological approach (iPERCIST, PERCIMT, or others) to be used for an optimal diagnostic accuracy and patients’ evaluation is still a debated issue. PET/CT with radioligands directed toward ICIs biomarkers, although is still in a translational phase, holds the promise of accurately predicting the response to treatment and revealing the acquired resistance to immunotherapy