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Gallbladder cancer is a highly fatal disease with poor prognosis; indeed, a high proportion of tumours are diagnosed at an advanced stage. Metastases are commonly detected in regional lymph nodes, liver and peritoneum, but unusual sites of spread such as thyroid and breast have also been described in the literature.We report a case of unsuspected muscle metastases, associated to pulmonary metastases, detected by FDG-PET/CT in a patient with previously removed gallbladder cancer and persistent episodes of haemoptysis. [ABSTRACT FROM AUTHOR]

Background: Breast conserving surgery (BCS) plus external beam radiotherapy (EBRT) is considered the standard treatment for early breast cancer. We have investigated the possibility of irradiating the residual gland, using an innovative nuclear medicine approach named IART® (Intra-operative Avidination for Radionuclide Therapy). Aim: The objective of this study was to determine the optimal dose of avidin with a fixed activity (3.7 GBq) of 90Y-biotin, in order to provide a boost of 20 Gy, followed by EBRT to the whole breast (WB) at the reduced dose of 40 Gy. Local and systemic toxicity, patient's quality of life, including the cosmetic results after the combined treatment with IART® and EBRT, were assessed. Methods: After tumour excision, the surgeon injected native avidin diluted in 30 ml of saline solution into and around the tumour bed (see video). Patients received one of three avidin dose levels: 50 mg (10 pts), 100 mg (15 pts) and 150 mg (10 pts). Between 12 to 24 h after surgery, 3.7 GBq 90Y-biotin spiked with 185 MBq 111In-biotin was administered intravenously (i.v.). Whole body scans and SPECT images were performed up to 30 h post-injection for dosimetric purposes. WB-EBRT was administered four weeks after the IART® boost. Local toxicity and quality of life were evaluated. Results: Thirty-five patients were evaluated. No side effects were observed after avidin administration and 90Y-biotin infusion. An avidin dose level of 100 mg resulted the most appropriate in order to deliver the required radiation dose (19.5 ± 4.0 Gy) to the surgical bed. At the end of IART®, no local toxicity occurred and the overall cosmetic result was good. The tolerance to the reduced EBRT was also good. The highest grade of transient local toxicity was G3, which occurred in 3/32 pts following the completion of WB-EBRT. The combination of IART®+EBRT was well accepted by the patients, without any changes to their quality of life. Conclusions: These preliminary results support the hypothesis that IART® may represent a valid approach to accelerated WB irradiation after BCS. We hope that this nuclear medicine technique will contribute to a better management of breast cancer patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: In women with breast cancer, sentinel-lymph-node biopsy (SLNB) provides information that allows surgeons to avoid axillary-lymph-node dissection (ALND) if the SLN does not have metastasis, and has a favourable effect on quality of life. Results of our previous trial showed that SLNB accurately screens the ALN for metastasis in breast cancers of diameter 2 mm or less. We aimed to update this trial with results from longer follow-up. METHODS: Women with breast tumours of diameter 2 cm or less were randomly assigned after breast-conserving surgery either to SLNB and total ALND (ALND group), or to SLNB followed by ALND only if the SLN was involved (SLN group). Analysis was restricted to patients whose tumour characteristics met eligibility criteria after treatment. The main endpoints were the number of axillary metastases in women in the SLN group with negative SLNs, staging power of SLNB, and disease-free and overall survival. FINDINGS: Of the 257 patients in the ALND group, 83 (32%) had a positive SLN and 174 (68%) had a negative SLN; eight of those with negative SLNs were found to have false-negative SLNs. Of the 259 patients in the SLN group, 92 (36%) had a positive SLN, and 167 (65%) had a negative SLN. One case of overt clinical axillary metastasis was seen in the follow-up of the 167 women in the SLN group who did not receive ALND (ie, one false-negative). After a median follow-up of 79 months (range 15-97), 34 events associated with breast cancer occurred: 18 in the ALND group, and 16 in the SLN group (log-rank p=0.6). The overall 5-year survival of all patients was 96.4% (95% CI 94.1-98.7) in the ALND group and 98.4% (96.9-100) in the SLN group (log-rank p=0.1). INTERPRETATION: SLNB can allow total ALND to be avoided in patients with negative SLNs, while reducing postoperative morbidity and the costs of hospital stay. The finding that only one overt axillary metastasis occurred during follow-up of patients who did not receive ALND (whereas eight cases were expected) could be explained by various hypotheses, including those from cancer-stem-cell research. [ABSTRACT FROM AUTHOR]

This paper deals with power flow management within a hybrid fuel cell-powered vehicle during real-time operation. The aim is the real-time control of the power distribution between the fuel cell and its associated energy storage to optimize the global hydrogen consumption while maintaining drivability. An original concept to convert the electrical power flow into equivalent hydrogen cost is proposed. On that basis, the previously developed control strategy (the equivalent consumption minimization strategy) is used to determine the real-time optimal power distribution by simple minimization of a univariate form. The approach presented has been applied to and implemented on a real fuel cell-supercapacitor-powered vehicle. Experimental and simulation results are presented, demonstrating that this approach provides an improvement of fuel efficiency along with robustness and ease of implementation. [Copyright &y& Elsevier]

Deals with a surgical oncology study that compares sentinel node biopsy with routine axillary dissection in breast cancer patients. Clinical function of sentinel node biopsy as a diagnostic test; Percentage of the accuracy of sentinel node biopsy among the randomly selected patients.

We report the case of a 71-year-old woman who was referred to our institute with a solid nodule in the right thyroid lobe and hypercalcemia. Ultrasound revealed a well-vascularized right thyroid nodule that was identified as a cold area by 99mTc-sodium pertechnetate scan. Fine-needle aspiration showed a follicular lesion and blood tests revealed hypercalcemia and hyperparathyroidism. A 99mTc-methoxyisobutylisonitrile (99mTc-Sestamibi) scan was subsequently performed revealing a focal area of increased uptake in the right thyroid lobe, within the cold area detected by the thyroid scan. A right emithyroidectomy and right superior and inferior parathyroidectomy was performed and histopathological examination showed a parathyroid carcinoma (immunohistochemistry positive for PTH and chromogranin A, Ki-67 10%) associated with follicular hyperplasia. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the clinical value of 68Ga-PSMA PET/CT negativity in patients with biochemical recurrent prostate cancer (BCR). Methods: One hundred three BCR patients (median age, 70 years; median PSA, 0.47 ng/mL) with negative 68Ga-PSMA PET/CT, followed up for at least 1 year, were retrospectively identified in a database of 1003 consecutive patients undergoing 68Ga-PSMA PET/CT for BCR. Clinical recurrence (CR) was determined or excluded on follow-up imaging selected as per clinical practice. Clinical recurrence-free survival (CRFS) was computed from the date of negative 68Ga-PSMA PET/CT to the date of evident disease; frequencies of CRFS were described as per ISUP patient subset (subset 1: ISUP grades 1 and 2; subset 2: ISUP grade 3; subset 3: ISUP grades 4 and 5) and other conventional variables. Results: In 57 patients out of 103 (55.3%), CR was detected in the prostatic fossa (45.6%), nodes (38.6%), and bone (15.8%). The median CRFS was 15.4 months (range, 12.1–20.5), with a CRFS at 12 months in 61.4% of cases (range, 50.9–70.4) whereas the 24-month CRFS was 34.8% (range, 24–45.8). ISUP subset 1 benefited from significantly longer CRFS compared to subset 2 and subset 3 (median CRFS, 20.5 months, 12.6 months, and 12.1 months, respectively). ISUP subset 3 had significantly poorer 24-month CRFS (9.3%) compared to subset 1 (47.8%) and subset 2 (33.5%). At the univariate and multivariate analyses, the ISUP subset was the only significant risk factor for clinical relapse; ISUP subset 3 and subset 2 patients held a higher risk of CR compared to subset 1 patients (HR of 2.75 [1.35–5.57] for subset 3 versus subset 1; HR of 2.08 [1.11–3.88] for subset 2 versus subset 1). Conclusion: 68Ga-PSMA PET/CT negativity in early BCR patients (PSA < 0.5 ng/mL) with low-grade primary prostate cancer (ISUP1 and 2) may support the exploration of a clinical surveillance approach in future prospective studies. [ABSTRACT FROM AUTHOR]

Cyclic voltammetry measurements at the anode have been carried out and reveal the presence of carbon monoxide in steady-state operation, with pure hydrogen. Experiments have been performed both in single cell and in stack to find out its origin. The contamination of the anode catalyst is partly due the reverse-water gas shift (RWGS) with carbon dioxide from the cathode. However, this study shows a temperature-activated and time-related corrosion mechanism which appears under humidified hydrogen. Due to this degradation mechanism, a reversible 25 mV-loss of performances is observed and can be recovered by oxidizing carbon monoxide on the anode. [ABSTRACT FROM AUTHOR]

Background: Peptide receptor radionuclide therapy (PRRT) is an effective method for treating neuroendocrine tumors (NETs). It is limited, however, in the prediction of individual tumor response and the precise and early identification of changes in tumor size. Currently, response prediction is based on somatostatin receptor expression and efficacy by morphological imaging and/or chromogranin A (CgA) measurement. The aim of this study was to assess the accuracy of circulating NET transcripts as a measure of PRRT efficacy, and moreover to identify prognostic gene clusters in pretreatment blood that could be interpolated with relevant clinical features in order to define a biological index for the tumor and a predictive quotient for PRRT efficacy. Methods: NET patients ( n = 54), M: F 37:17, median age 66, bronchial: n = 13, GEP-NET: n = 35, CUP: n = 6 were treated with Lu-based-PRRT (cumulative activity: 6.5-27.8 GBq, median 18.5). At baseline: 47/54 low-grade (G1/G2; bronchial typical/atypical), 31/49 FDG positive and 39/54 progressive. Disease status was assessed by RECIST1.1. Transcripts were measured by real-time quantitative reverse transcription PCR (qRT-PCR) and multianalyte algorithmic analysis (NETest); CgA by enzyme-linked immunosorbent assay (ELISA). Gene cluster (GC) derivations: regulatory network, protein:protein interactome analyses. Statistical analyses: chi-square, non-parametric measurements, multiple regression, receiver operating characteristic and Kaplan-Meier survival. Results: The disease control rate was 72 %. Median PFS was not achieved (follow-up: 1-33 months, median: 16). Only grading was associated with response ( p < 0.01). At baseline, 94 % of patients were NETest-positive, while CgA was elevated in 59 %. NETest accurately (89 %, χ = 27.4; p = 1.2 × 10) correlated with treatment response, while CgA was 24 % accurate. Gene cluster expression (growth-factor signalome and metabolome) had an AUC of 0.74 ± 0.08 (z-statistic = 2.92, p < 0.004) for predicting response (76 % accuracy). Combination with grading reached an AUC: 0.90 ± 0.07, irrespective of tumor origin. Circulating transcripts correlated accurately (94 %) with PRRT responders (SD+PR+CR; 97 %) vs. non-responders (91 %). Conclusions: Blood NET transcript levels and the predictive quotient (circulating gene clusters+grading) accurately predicted PRRT efficacy. CgA was non-informative. [ABSTRACT FROM AUTHOR]

Purpose: Precise determination of neuroendocrine tumor (NET) disease status and response to therapy remains a rate-limiting concern for disease management. This reflects limitations in biomarker specificity and resolution capacity of imaging. In order to evaluate biomarker precision and identify if combinatorial blood molecular markers and imaging could provide added diagnostic value, we assessed the concordance between Ga-somatostatin analog (SSA) positron emission tomography (PET), circulating NET gene transcripts (NETest), chromogranin A (CgA), and Ki-67 in NETs. Methods: We utilized two independent patient groups with positive Ga-SSA PET: data set 1 (Ga-SSA PETs undertaken for peptide receptor radionuclide therapy (PRRT), as primary or salvage treatment, n = 27) and data set 2 (Ga-SSA PETs performed in patients referred for initial disease staging or restaging after various therapies, n = 22). We examined the maximum standardized uptake value (SUV), circulating gene transcripts, CgA levels, and baseline Ki-67. Regression analyses, generalized linear modeling, and receiver-operating characteristic (ROC) analyses were undertaken to determine the strength of the relationships. Results: SUV measured in two centers were mathematically evaluated (regression modeling) and determined to be comparable. Of 49 patients, 47 (96 %) exhibited a positive NETest. Twenty-six (54 %) had elevated CgA (χ = 20.1, p < 2.5×10). The majority (78 %) had Ki-67 < 20 %. Gene transcript scores were predictive of imaging with >95 % concordance and significantly correlated with SUV ( R = 0.31, root-mean-square error = 9.4). The genes MORF4L2 and somatostatin receptors SSTR1, 3, and 5 exhibited the highest correlation with SUV. Progressive disease was identified by elevated levels of a quotient of MORF4L2 expression and SUV [ROC-derived AUC ( R = 0.7, p < 0.05)]. No statistical relationship was identified between CgA and Ki-67 and no relationship with imaging parameters was evident. Conclusion: Ga-SSA PET imaging parameters (SUV) correlated with a circulating NET transcript signature. Disease status could be predicted by an elevated quotient of gene expression ( MORF4L2) and SUV. These observations provide the basis for further exploration of strategies that combine imaging parameters and disease-specific molecular data for the improvement of NET management. [ABSTRACT FROM AUTHOR]

The background induced by the high penetration power of the γ radiation is the main limiting factor of the current radio-guided surgery (RGS). To partially mitigate it, a RGS with β+-emitting radio-tracers has been suggested in literature. Here we propose the use of β--emitting radio-tracers and β- probes and discuss the advantage of this method with respect to the previously explored ones: the electron low penetration power allows for simple and versatile probes and could extend RGS to tumours for which background originating from nearby healthy tissue makes γ probes less effective. We developed a β- probe prototype and studied its performances on phantoms. By means of a detailed simulation we have also extrapolated the results to estimate the performances in a realistic case of meningioma, pathology which is going to be our first in-vivo test case. A good sensitivity to residuals down to 0.1 ml can be reached within 1 s with an administered activity smaller than those for PET-scans thus making the radiation exposure to medical personnel negligible. [ABSTRACT FROM AUTHOR]

Patient-specific absorbed dose calculation for nuclear medicine therapy is a topic of increasing interest. 3D dosimetry at the voxel level is one of the major improvements for the development of more accurate calculation techniques, as compared to the standard dosimetry at the organ level. This study aims to use the FLUKA Monte Carlo code to perform patient-specific 3D dosimetry through direct Monte Carlo simulation on PET-CT and SPECT-CT images. To this aim, dedicated routines were developed in the FLUKA environment. Two sets of simulations were performed on model and phantom images. Firstly, the correct handling of PET and SPECT images was tested under the assumption of homogeneous water medium by comparing FLUKA results with those obtained with the voxel kernel convolution method and with other Monte Carlo-based tools developed to the same purpose (the EGS-based 3D-RD software and the MCNP5-based MCID). Afterwards, the correct integration of the PET/SPECT and CT information was tested, performing direct simulations on PET/CT images for both homogeneous (water) and non-homogeneous (water with air, lung and bone inserts) phantoms. Comparison was performed with the other Monte Carlo tools performing direct simulation as well. The absorbed dose maps were compared at the voxel level. In the case of homogeneous water, by simulating 108 primary particles a 2% average difference with respect to the kernel convolution method was achieved; such difference was lower than the statistical uncertainty affecting the FLUKA results. The agreement with the other tools was within 3–4%, partially ascribable to the differences among the simulation algorithms. Including the CT-based density map, the average difference was always within 4% irrespective of the medium (water, air, bone), except for a maximum 6% value when comparing FLUKA and 3D-RD in air. The results confirmed that the routines were properly developed, opening the way for the use of FLUKA for patient-specific, image-based dosimetry in nuclear medicine. [ABSTRACT FROM AUTHOR]

Kidney dosimetry in 177Lu and 90Y PRRT requires 3 to 6 whole-body/SPECT scans to extrapolate the peptide kinetics, and it is considered time and resource consuming. We investigated the most adequate timing for imaging and time-activity interpolating curve, as well as the performance of a simplified dosimetry, by means of just 1-2 scans. Finally the influence of risk factors and of the peptide (DOTATOC versus DOTATATE) is considered. 28 patients treated at first cycle with 177Lu DOTATATE and 30 with 177Lu DOTATOC underwent SPECT scans at 2 and 6 hours, 1,2, and 3 days after the radiopharmaceutical injection. Dose was calculated with our simplified method, as well as the ones most used in the clinic, that is, trapezoids, monoexponential, and biexponential functions. The same was done skipping the 6 h and the 3 d points. We found that data should be collected until 100 h for 177Lu therapy and 70h for 90Y therapy, otherwise the dose calculation is strongly influenced by the curve interpolating the data and should be carefully chosen. Risk factors (hypertension, diabetes) cause a rather statistically significant 20% increase in dose (t-test, P < 0.10), with DOTATATE affecting an increase of 25% compared to DOTATOC (t-test, P < 0.05). [ABSTRACT FROM AUTHOR]

The purpose of this study is to compare the performance of multidetector computed tomography (CT) and positron emission tomography/CT (PET/CT) with [18F]fluorodeoxyglucose in the diagnosis of multiple solitary lung nodules in 14 consecutive patients with suspicious lung cancer. CT and PET/CT findings were reviewed by a radiologist and nuclear medicine physician, respectively, blinded to the pathological diagnoses of lung cancer, considering nodule size, shape, and location (CT) and maximum standardized uptake value normalized to body weight (SUVbw max). Nodules were judged malignant or benign. The sensitivity, specificity, and accuracy of the two techniques were compared. CT had a sensitivity, specificity, and accuracy of 93.7, 86.7, and 90.3%, respectively, whereas PET/CT had a sensitivity, specificity, and accuracy of 75, 100, and 87.1%, respectively. Clinical management would have been erroneous in two patients by CT alone and in four patients by PET/CT alone. In one patient, the two techniques misdiagnosed the nodules (2 CT and 1 PET/CT). CT and PET/CT have complimentary roles in characterization of multiple solitary pulmonary nodules. Small nodules are poorly characterized by CT, and small-sized low-SUV malignant nodules are difficult to detect with PET/CT. [ABSTRACT FROM AUTHOR]

Neuroendocrine tumours (NET) are a heterogeneous group of neoplasms commonly occurring in the gastrointestinal tract or lungs but can occur in other regions. Primary ovarian NET account for 5% of all NET and 0.1% of all ovarian malignancies. In metastatic disease, the therapeutic goal is to extend survival and to improve quality of life. As these tumours express somatostatin receptors, somatostatin analogues are frequently used to control symptoms. Here we present a case of a pregnant woman with an ovarian NET with liver metastases and carcinoid syndrome who was treated with the somatostatin analogue, Octreotide LAR. We also summarize reported data of the use of somatostatin analogues during pregnancy. [ABSTRACT FROM AUTHOR]

Purpose: The calculation of patient-specific dose distribution can be achieved by Monte Carlo simulations or by analytical methods. In this study, fluka Monte Carlo code has been considered for use in nuclear medicine dosimetry. Up to now, fluka has mainly been dedicated to other fields, namely high energy physics, radiation protection, and hadrontherapy. When first employing a Monte Carlo code for nuclear medicine dosimetry, its results concerning electron transport at energies typical of nuclear medicine applications need to be verified. This is commonly achieved by means of calculation of a representative parameter and comparison with reference data. Dose point kernel (DPK), quantifying the energy deposition all around a point isotropic source, is often the one.Methods: fluka DPKs have been calculated in both water and compact bone for monoenergetic electrons (10-3 MeV) and for beta emitting isotopes commonly used for therapy (89Sr, 90Y, 131I, 153Sm, 177Lu, 186Re, and 188Re). Point isotropic sources have been simulated at the center of a water (bone) sphere, and deposed energy has been tallied in concentric shells. fluka outcomes have been compared to penelope v.2008 results, calculated in this study as well. Moreover, in case of monoenergetic electrons in water, comparison with the data from the literature (etran, geant4, mcnpx) has been done. Maximum percentage differences within 0.8·RCSDA and 0.9·RCSDA for monoenergetic electrons (RCSDA being the continuous slowing down approximation range) and within 0.8·X90 and 0.9·X90 for isotopes (X90 being the radius of the sphere in which 90% of the emitted energy is absorbed) have been computed, together with the average percentage difference within 0.9·RCSDA and 0.9·X90 for electrons and isotopes, respectively.Results: Concerning monoenergetic electrons, within 0.8·RCSDA (where 90%-97% of the particle energy is deposed), fluka and penelope agree mostly within 7%, except for 10 and 20 keV electrons (12% in water, 8.3% in bone). The discrepancies between fluka and the other codes are of the same order of magnitude than those observed when comparing the other codes among them, which can be referred to the different simulation algorithms. When considering the beta spectra, discrepancies notably reduce: within 0.9·X90, fluka and penelope differ for less than 1% in water and less than 2% in bone with any of the isotopes here considered. Complete data of fluka DPKs are given as Supplementary Material as a tool to perform dosimetry by analytical point kernel convolution.Conclusions: fluka provides reliable results when transporting electrons in the low energy range, proving to be an adequate tool for nuclear medicine dosimetry. [ABSTRACT FROM AUTHOR]

We report the case of a 42-year-old woman being treated for an ovarian cancer who was diagnosed at the age of 40. A CT-positron emission tomography (PET) scan performed as follow-up documented abnormal uptake in the right breast. Mammograms were negative for malignancy, while a focal hyperechoic lesion was observed on ultrasonography in the same breast. Thus, she was referred to our institution for breast MRI, which showed a focal area of enhancement with atypical features. Percutaneous biopsy was performed, and a mammary hibernoma was diagnosed. Radiological and pathological correlation was provided. To our knowledge, this is the only report that describes the features of this rare tumour on four different imaging modalities (mammography, ultrasonography, MRI and CT-PET). [ABSTRACT FROM AUTHOR]

Intra-cardiac masses present an important problem in cardiology. The differential diagnoses includes tumours, which may be primary (benign or malignant) or metastatic, and infected mural thrombi. Myxomas, sarcomas, breast, lung and renal cancer represent the commonest causes of primary benign, malignant and metastatic intracardiac masses, respectively. Recent studies have shown that cardiac involvement in malignant lymphoma is common but under-investigated. Diagnostic imaging techniques for detection of cardiac masses include echocardiography, CT and MRI, with echocardiography having the highest sensitivity. We propose that 18-F-PET/CT may play an important role in the detection and evaluation of intra-cardiac masses. [ABSTRACT FROM AUTHOR]

Background: the characteristics of 90, suitable for therapy, are denoted by the lack of γ-emission. Alternative methods, using analogues labelled with 111In or 86Y, are generally applied to image 90Y-conjugates, with some inevitable drawbacks. New generation SPECT/CT image systems offer improved Bremsstrahlung images. The intent of this brief communication is to show that high quality 90Bremsstrahlung SPECT-CT images can be obtained, allowing the biodistribution of pure β-emitter therapeutical agents to be evaluated, also during the course of therapy. Methods: the hybrid system Siemens Symbia-T2 was used for the acquisition of images of a patient given 1.7 GBq of 90-DOTATATE. The following parameters were set for SPECT: 80 (50%) and 120 (30%) keV energy windows; medium energy collimators; 128 × 128 matrix, 64 projections (40s/step). Low-dose CT was acquired (80 mAs) for attenuation correction. Images were reconstructed with the OSEM 3D-Fast algorithm. Results: post-therapy SPECT-CT 90-Bremsstrahlung images of a patient undergoing receptor peptide radionuclide therapy are presented. 90-Bremsstrahlung images obtained are suitable for tumour and normal organ dosimetry, providing detailed information on biodistribution, comparable to 111In-diagnostic images. Conclusions: the improved Bremsstrahlung images means that the diagnostic examinations can be used for patient recruitment and that dosimetry evaluation can be restricted only to treated patients. This could avoid the need for a different radionuclide or isotope to mimic therapy. The clinical impact might be notable, as dosimetry and toxicity information are essential in radionuclide therapy, especially in patients with risk factors. [ABSTRACT FROM AUTHOR]

Treatment modalities for resistant/relapsing gastric mucosa associated lymphoid tissue (MALT) non-Hodgkin's lymphoma (NHL) are not yet well standardized. In the past, most patients were treated surgically with a gastrectomy, while, more recently, radiotherapy and systemic approaches (chemotherapy and immunotherapy) have been used with improving results. Here, we report the case of a patient affected by MALT NHL resistant to antibiotics, chemotherapy and immunotherapy, who achieved a durable complete remission after radio-immunotherapy treatment with Zevalin (90Y ibritumomab-tiuxetan), administered in a singlestandard dose. This observation must be confirmed on a larger series but suggests that radio-immunotherapy may be a valid approach in treating relapsing MALT NHL patients, or those resistant to conventional therapies, so avoiding more aggressive and toxic approaches. [ABSTRACT FROM AUTHOR]

Background: An institutional task force on upper gastrointestinal tumours is active at the European Institute of Oncology (EIO). Members decided to collate the institutional guidelines on management of liver tumours (primary and metastatic) into a document. This article is aimed at presenting the current treatment guidelines as well as ongoing research protocols and trials in this field at the EIO. Methods: A steering committee convened to assign tasks to individual members. Contributions from experts in each treatment area were collated in a single document, in order to produce a draft for subsequent review from the aforementioned committee. Six drafts have been discussed and the final version approved. Results: Surgical, medical oncology, interventional radiology, nuclear medicine and radiation therapy approaches, their roles in management of liver tumours and ongoing research trials are presented and discussed in this article. Conclusions: At the EIO a multi-disciplinary integrated approach to liver tumours is standard and several ongoing research projects are currently active in this field. [ABSTRACT FROM AUTHOR]

Purpose: It was the aim of this study to assess the risk of lung cancer in postmenopausal women who received hormone replacement therapy (HRT). Experimental Design: This case-control study involves women who received medical services at Roswell Park Cancer Institute (RPCI) in Buffalo, New York, between 1982 and 1998, and who agreed to complete an epidemiological questionnaire. Participants with missing smoking data were excluded. The case group consisted of 595 women with primary lung cancer. Controls included 1,195 women, randomly selected from a pool of 5,845 eligible individuals, who received medical services at RPCI for non-neoplastic conditions; they had come to RPCI with a suspicion of neoplastic disease, but were diagnosed with neither benign nor malignant conditions. Controls were frequency matched 2:1 to cases on 5-year age intervals and exposure to smoking (ever/never). Cases and controls were comparable for age (means 61.3 and 61.0 years) and ever smoking (90%). Results: There were more former smokers among the cases (67 vs. 59% in controls); cases were less likely to be high school educated, were thinner, and were less likely to report HRT use compared with controls. Overall, hormone use was associated with a significant reduction in risk of lung cancer (adjusted odds ratio = 0.67; 95% confidence interval 0.53–0.85). Stratified analyses showed significant reductions in lung cancer risk in former smokers and women with normal to low body mass index. Conclusion: This study supports the hypotheses that there is a protective effect of HRT use on lung cancer risk in women. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: Cervical lymph node status is the most important pathological determinant of prognosis and decision making in head and neck squamous cell carcinoma (SCC). The aim of this study was to demonstrate that lymphoscintigraphy (LS) can supply a complete map of the lymphatic drainage before surgery, allowing planning of the type of intervention and serving to guide lymphadenectomy. Methods: The study population comprised 14 patients with T2-4 SCCs of the tongue and clinically negative lymph nodes in the neck (cN0) who were scheduled to undergo tumour resection and selective level I-IV neck dissection extended to level V. LS was performed in all patients following the injection of 99mTc-colloidal sulphide in three aliquots around the primary lesion. Dynamic, static and tomographic images of the head and neck were acquired. The operative specimens were subjected to lymphoscintigraphic evaluation. Preoperative and postoperative imaging results were compared with the pathological findings. All nodes were examined using haematoxylin-eosin staining. Results: Preoperative LS was successful in all patients. Preferential pathways of lymphatic drainage were identified: level II of the neck was the most common lymphatic drainage pattern, followed by levels IV and III. Contralateral drainage occurred in 11 patients and in two of them metastatic nodes were found on the contralateral side. Metastases were observed only in radioactive lymph nodes. Conclusion: LS is able to supply a complete map of the lymphatic drainage before surgery, making it possible to tailor selective neck dissection to each individual patient based on the results of preoperative mapping, thereby sparing healthy lymphatic tissue and reducing surgery-related morbidity. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the feasibility of sentinel node (SN) biopsy in occult breast lesions with different radiopharmaceuticals and to establish the optimal lymphoscintigraphic method to detect both occult lesions and SNs (SNOLL: sentinel node and occult lesion localisation). Two hundred and twenty- seven consecutive patients suspected to have clinically occult breast carcinoma were enrolled in the study. In addition to the radioguided occult lesion localisation (ROLL) procedure, using macroaggregates of techne- tium-99m labelled human serum albumin (MAA) injected directly into the lesion, lymphoscintigraphy was per- formed with nanocolloids (NC) injected in a peritumoral (group I) or a subdermal site (group II). In group III, a sole injection of NC was done into the lesion in order to perform both ROLL and SNOLL. Overall, axillary SNs were identified in 205 of the 227 patients (90.3%). In 12/62 (19.4%) patients of group I and 9/79 (11.4%) patients of group III, radioactive nodes were not visualised, whereas SNs were successfully localised in 85 of 86 patients of group II (P<0.001). Pathological findings revealed breast carcinoma in 148/227 patients (65.2%) and benign lesions in 79 (34.8%). A total of 131 axillary SNs were removed in 118 patients with breast carcinoma; intraoperative examination of the SNs revealed meta-static involvement in 16 out of 96 cases of invasive c arcinoma (16.7%). It is concluded that the combination of the ROLL procedure with direct injection of MAA into the lesion and lymphoscintigraphy performed with subdermal injection of radiocolloids represents the method of choice for accurate localisation of both non- palpable lesions and SNs. [ABSTRACT FROM AUTHOR]

Oxytocin receptors (OTR) have been described in a number of tumours of different origin, and represent a new target for specific radiolabelled oxytocin (OT) analogues in cancer diagnosis and therapy. By linking the DOTA chelating agent to position 8 of the deamino derivative of Lys(8)-vasotocin (dLVT), we obtained a new compound (DOTA-dLVT) with the following characteristics: (1) it forms a monomeric and stable compound that binds to OTR with an affinity comparable to that of the endogenous OT ligand; (2) it is characterised by a very good selectivity profile for the human OTR, with a low affinity binding to the closely related V1a, V1b and V2 vasopressin receptor subtypes; (3) it induces rapid and persistent receptor internalisation and (4) when radiolabelled, [(111)In]-DOTA-dLVT is efficiently and selectively taken up by OTR-positive tumours grown in mice. These features makes radiolabelled DOTA-dLVT a very good candidate for the radiotargeting of OTR-expressing tumours. [ABSTRACT FROM AUTHOR]

The Pretargeted Antibody-Guided RadioImmunoTherapy (PAGRIT) method is based on intravenous, sequential administration of a biotinylated antibody, avidin/streptavidin and (90)Y-labelled biotin. The hybridoma clone producing the monoclonal antitenascin antibody BC4, previously used for clinical applications, was found not suitable for further development because of the production of an additional, nonfunctional light chain. In order to solve this problem, the new cST2146 hybridoma clone was generated. The monoclonal antibody ST2146, produced by this hybridoma, having the same specificity as BC4 but lacking the nonfunctional light chain, was characterised. ST2146 was found able to bind human tenascin at an epitope strictly related, if not identical, to the antigenic epitope of BC4. It showed, compared to BC4, higher affinity and immunoreactivity and similar selectivity by immunohistochemistry. Biodistribution studies of biotinylated ST2146 and three other monoclonal antitenascin antibodies showed for ST2146 the highest and more specific tumour localisation in HT29-grafted nude mice. On the overall, ST2146 appears to be a good alternative to BC4 for further clinical development of PAGRIT. [ABSTRACT FROM AUTHOR]

In a previous study we applied a three-step avidin-biotin pretargeting approach to target 90Y-biotin to the tumour in patients with recurrent high grade glioma. The encouraging results obtained in this phase I-II study prompted us to apply the same approach in an adjuvant setting, to evaluate (i) time to relapse and (ii) overall survival. We enrolled 37 high grade glioma patients, 17 with grade III glioma and 20 with glioblastoma, in a controlled open non-randomized study. All patients received surgery and radiotherapy and were disease-free by neuroradiological examinations. Nineteen patients (treated) received adjuvant treatment with radioimmunotherapy. In the treated glioblastoma patients, median disease-free interval was 28 months (range=9-59); median survival was 33.5 months and one patient is still without evidence of disease. All 12 control glioblastoma patients died after a median survival from diagnosis of 8 months. In the treated grade III glioma patients median disease-free interval was 56 months (range=15-60) and survival cannot be calculated as only two, within this group, died. Three-step radioimmunotherapy promises to have an important role as adjuvant treatment in high grade gliomas, particularly in glioblastoma where it impedes progression, prolonging time to relapse and overall survival. A further randomized trial is justified. [ABSTRACT FROM AUTHOR]

The diagnosis of recurrent ovarian carcinoma is usually determined at surgical re-exploration since the main non-invasive diagnostic tests have low accuracy. It would be desirable to have a high accuracy non-invasive diagnostic procedure. With this aim, we have assessed the utility of three-step immunoscintigraphy. Thirty patients were intravenously injected with biotinylated monoclonal antibodies MOv18 and B72.3, followed by avidin-streptavidin injection and finally by 111In-biotin. Tumour recurrences were imaged 2 h post radioactivity injection. All patients underwent surgical re-exploration 3-4 days after immunoscintigraphy; the presence of tumour in the area of immunoscintigraphic uptake was evaluated in the biopsied material. Twenty-one patients studied were true-positive, five were true-negative, four were false-positive and none was false-negative. The diagnostic accuracy, positive predictive value and negative predictive value were 87%, 84% and 100% respectively. If these findings are confirmed in a larger number of patients, we expect immunoscintigraphy to be introduced as a cost-effective procedure in the follow-up of patients who have received surgery for ovarian carcinoma, since it promises to reliably identify patients who do not require surgical re-exploration, and guide biopsies when they are indicated. [ABSTRACT FROM AUTHOR]

Lymph node pathologic status is the most important prognostic factor in vulvar cancer; however, complete inguinofemoral node dissection is associated with significant morbidity. Lymphoscintigraphy associated with gamma-probe guided surgery reliably detects sentinel nodes in melanoma and breast cancer patients. This study evaluates the feasibility of the surgical identification of sentinel groin nodes using lymphoscintigraphy and a gamma-detecting probe in patients with early vulvar cancer. Technetium-99m-labelled colloid human albumin was administered perilesionally in 37 patients with invasive epidermoid vulvar cancer (T1-T2) and lymphoscintigraphy performed the day before surgery. An intraoperative gamma-detecting probe was used to identify sentinel nodes during surgery. A complete inguinofemoral node dissection was then performed. Sentinel nodes were submitted separately to pathologic evaluation. A total of 55 groins were dissected in 37 patients. Localization of the SN was successful in all cases. Eight cases had positive nodes: in all the sentinel node was positive; the sentinel node was the only positive node in five cases. Twenty-nine patients showed negative sentinel nodes: all of them were negative for lymph node metastases. Lymphoscintigraphy and sentinel-node biopsy under gamma-detecting probe guidance proved to be an easy and reliable method for the detection of sentinel node in early vulvar cancer. This technique may represent a true advance in the direction of less aggressive treatments in patients with vulvar cancer. [ABSTRACT FROM AUTHOR]

Background: Axillary lymph node dissection is an established component of the surgical treatment of breast cancer, and is an important procedure in cancer staging; however, it is associated with unpleasant side effects. We have investigated a radioactive tracer-guided procedure that facilitates identification, removal, and pathologic examination of the sentinel lymph node (i.e., the lymph node first receiving lymphatic fluid from the area of the breast containing the tumor) to predict the status of the axilla and to assess the safety of foregoing axillary dissection if the sentinel lymph node shows no involvement.Methods: We injected 5-10 MBq of 99mTc-labeled colloidal particles of human albumin peritumorally in 376 consecutive patients with breast cancer who were enrolled at the European Institute of Oncology during the period from March 1996 through March 1998. The sentinel lymph node in each case was visualized by lymphoscintigraphy, and its general location was marked on the overlying skin. During breast surgery, the sentinel lymph node was identified for removal by monitoring the acoustic signal from a hand-held gamma ray-detecting probe. Total axillary dissection was then carried out. The pathologic status of the sentinel lymph node was compared with that of the whole axilla.Results: The sentinel lymph node was identified in 371 (98.7%) of the 376 patients and accurately predicted the state of the axilla in 359 (95.5%) of the patients, with 12 false-negative findings (6.7%; 95% confidence interval = 3.5%-11.4%) among a total of 180 patients with positive axillary lymph nodes.Conclusions: Sentinel lymph node biopsy using a gamma ray-detecting probe allows staging of the axilla with high accuracy in patients with primary breast cancer. A randomized trial is necessary to determine whether axillary dissection may be avoided in those patients with an uninvolved sentinel lymph node. [ABSTRACT FROM AUTHOR]

Summary Background: Flavonoids are polyphenolic antioxidants occuring in vegetables and fruits as well as beverages such as tea and wine which have been thought to influence oxidative damage. Aim of the study: We wanted to verify whether a complex mixture of wine tannins (wine complex polyphenols and tannins, WCPT) prevent chemically-induced oxidative DNA damage in vivo. Methods: Oxidative DNA damage was evaluated by measuring the ratio of 8-hydroxy-2'-deoxyguanosine (80HdG)/ 2-deoxyguanosine (2dG) x 10-6 in hydrolyzed DNA using HPLC coupled with electrochemical and UV detectors. Results: We treated rats with WCPT (57 mg/kg p.o.) for 14 d, a dose 10-fold higher than what a moderate wine drinker would be ex posed to. WCPT administration significantly reduced the ratio of 80HdG/2dG x 10[sup -6] in liver DNA obtained from rats treated with 2nitropropane (2NP) relative to controls administered 2NP only (33.3 +/- 2.5 vs. 44.9 + 3.2 x 10[sup -6] 2dG; mu +/- SE; p<0.05). On the contrary, pretreatment with WCPT for 10 d did not protect the colon mucosa from oxidative DNA damage induced by 1,2-dimethylhydrazine (DMH). 2NP and DMH are hepatic and colon carcinogens, respectively, capable of inducing oxidative DNA damage. Conclusions: WCPT have protective action against some types of chemically-induced oxidative DNA damage in vivo. [ABSTRACT FROM AUTHOR]

• In bone mCRPC, each treatment has an effect on PCa cells and bone microenvironment. • Clinical trials have been performed to evaluate radium 223-based combination therapies. • Pretreated and un-pretreated patients have different morbidity and clinical outcomes. • Different bone metabolic status could justify the different clinical outcomes. • Associating bone protecting agents reduce treatment-related morbidity. Chemotherapeutic agents (docetaxel, cabazitaxel), hormonal therapies (abiraterone, enzalutamide) and radium-223 improve survival in patients with bone metastatic castration-resistant prostate cancer (mCRPC). Combinations of radium-223 with these agents or novel drugs have been investigated in order to improve survival and decrease bone-related morbidity. In mCRPC, clinical and preclinical data indicate that radium-223, abiraterone and enzalutamide have a direct effect on prostate cancer cells and bone microenvironment when administered as single agents. Initial results from studies of radium-223 and abiraterone, enzalutamide or docetaxel demonstrated efficacy without any safety concern in pre-treated mCRPC; however, this safety profile changed when radium-based combination therapies were administered in un-pretreated mCRPC. This review underline the biological rationale for combining radium strategies, investigating their effects on bone in terms of control of skeletal-related events and bone disease progression. The aim is to understand the possible reasons why different radium-based combination treatments can led to different clinical outcomes. [ABSTRACT FROM AUTHOR]

The management of aggressive fibromatosis (AF) is problematic, and few options are available to patients unsuitable for surgery and resistant to external-beam radiation therapy (EBRT). We report on two patients with fast-growing recurrences of AF resistant to EBRT who obtained protracted clinical benefits with (90)Y-DOTATOC. (90)Y-DOTATOC should be further investigated in this setting. [ABSTRACT FROM AUTHOR]

Introduction: Peptide receptor radionuclide therapy with 177Lu-DOTATATE (177Lu-PRRT) has shown activity against advanced well-differentiated pancreatic neuroendocrine tumors (P-NET) in previous phase I/II studies. Aim(s): We evaluated the efficacy and safety profile of 177Lu-PRRT administered at two different dosages (500 mCi and 750 mCi). Materials and methods: Fifty-two patients received a cumulative activity of 18.5-27.8 GBq in five cycles, administered on the basis of kidney function or bone marrow reserve. Results: Twenty-six patients with no risk factors received a mean full dosage (FD) of 25.53 GBq (range 21-28). The remaining 26 patients with risk factors received a reduced dosage (RD) with a mean total activity of 17.76 GBq (range 11-20). Both therapeutic dosages resulted in antitumor activity with 13% CR, 27% PR and 46% SD in the FD patients group and 4% CR, 15% PR and 58% SD in the RD patient groups. Progression-free survival has not yet been reached in the FD group and was 20 months in the latter RD group. No major acute or delayed hematological or renal toxicity occurred. Grade 3 renal toxicity occurred in only one patient who received the lower dosage. Conclusion: Hyper-fractionated therapy with 177Lu PRRT showed antitumor activity in P-NETs, with minimal toxicity. 27.8 GBq is safe and can be use in eligible patients with no risk factors. A lower total activity of 18.5 GBq also showed antiproliferative activity and can be offered to patients with reduced kidney and hematological function. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor on radioimmunotherapy.

Kidney dosimetry in (177)Lu and (90)Y PRRT requires 3 to 6 whole-body/SPECT scans to extrapolate the peptide kinetics, and it is considered time and resource consuming. We investigated the most adequate timing for imaging and time-activity interpolating curve, as well as the performance of a simplified dosimetry, by means of just 1-2 scans. Finally the influence of risk factors and of the peptide (DOTATOC versus DOTATATE) is considered. 28 patients treated at first cycle with (177)Lu DOTATATE and 30 with (177)Lu DOTATOC underwent SPECT scans at 2 and 6 hours, 1, 2, and 3 days after the radiopharmaceutical injection. Dose was calculated with our simplified method, as well as the ones most used in the clinic, that is, trapezoids, monoexponential, and biexponential functions. The same was done skipping the 6¿h and the 3¿d points. We found that data should be collected until 100¿h for (177)Lu therapy and 70¿h for (90)Y therapy, otherwise the dose calculation is strongly influenced by the curve interpolating the data and should be carefully chosen. Risk factors (hypertension, diabetes) cause a rather statistically significant 20% increase in dose (t-test, P < 0.10), with DOTATATE affecting an increase of 25% compared to DOTATOC (t-test, P < 0.05). [ABSTRACT FROM AUTHOR]