Pierpaolo Alongi

Radiation Treatment of Lymph Node Recurrence from Prostate Cancer: Is 11C-Choline PET/CT Predictive of Survival Outcomes?

PET/CT is a valuable tool to detect lymph node (LN) metastases in patients with biochemical failure after primary treatment for prostate cancer (PCa). The aim was to assess the predictive role of imaging parameters derived by 11C-choline PET/CT on survival outcomes—overall survival, locoregional relapse-free survival, clinical relapse-free survival (cRFS), and biochemical relapse-free survival (bRFS)—in patients treated with helical tomotherapy (HTT) for LN recurrence. Methods: This retrospective study included 68 patients affected by PCa (mean age, 68 y; age range, 51–81 y) with biochemical recurrence after primary treatment (median prostate-specific antigen values obtained at the time of PET/CT scan, 2.42 ng/mL; range, 0.61–27.56 ng/mL) who underwent 11C-choline PET/CT from January 2005 to January 2013 and were treated with HTT in correspondence of the pathologic choline LN uptake. PET-derived parameters, including maximum/mean standardized uptake value (SUVmax and SUVmean, respectively) and metabolic tumor volume (MTV) with a threshold of 40%, 50%, and 60% were calculated. The best cutoff values of PET-derived parameters discriminating between patients with and without relapse, after treatment guided by PET, were assessed by receiver-operating-characteristic (ROC) curve analysis. Univariate and multivariate Cox regression analysis including the most predictive PET-derived parameters and survival outcomes were performed. Results: The median follow-up was 20 mo (mean, 26 mo; range, 3–97 mo). 11C-choline PET/CT showed pathologic LN uptake in 4 patients at the pelvic level, in 5 at the abdominal level, in 13 at both the pelvic and the abdominal level, and in 46 at the abdominal or pelvic or other sites. The 2-y overall survival, locoregional relapse-free survival, cRFS, and bRFS were 87%, 91%, 51%, and 40%, respectively. On the basis of ROC curves, the most discriminative cutoff value for MTV values was an MTV threshold of 60% (MTV60) of greater than 0.64 cm3. No significant cutoff values were found for SUVmax or SUVmean at univariate analysis, whereas MTV60 was confirmed as an independent predictor in multivariate analysis and significantly correlated with bRFS and cRFS. MTV60 and extrapelvic disease well predict the risk of cRFS. Conclusion: 11C-choline PET/CT performed as a guide for HTT on LN recurrence is predictive of survival. In particular, MTV60 and extrapelvic disease were the best predictors of tumor response for bRFS and cRFS in PCa patients with LN recurrence after primary treatment. This information may be useful in emerging treatment strategies.

18F-fluoroethylcholine (18F-Cho) PET/MRI functional parameters in pediatric astrocytic brain tumors.

Purpose To examine the feasibility of simultaneous acquisition of 18F-fluoroethylcholine (18F-choline) PET and functional MRI (standardized uptake value [SUV]max/mean and apparent diffusion coefficient [ADC]mean), using a hybrid PET/MRI scanner, for diagnosis and response assessment in a cohort of children with astrocytic brain tumors. Methods 18F-choline PET/MRI scans were performed in 12 patients with proven astrocytic tumors. Eight patients simultaneously underwent 18F-choline PET/MR follow-up scans after treatment. Uptake in the lesion above the normal brain activity was considered indicative of a positive scan. Maximum and mean SUVs (SUVmax and SUVmean) and mean ADC (ADCmean) of the whole tumor region of interest were assessed. Lesion size and contrast enhancement were recorded. For all tumors, the association between ADCmean and SUVmean/SUVmax values were assessed using the Spearman correlation coefficient. Results At baseline, the areas of 18F-choline uptake matched areas of contrast enhancement and restricted diffusion. There was a negative correlation trend between SUVmax and ADCmean and a positive correlation trend between SUVmax and tumor size. There was concordance between reduction in tumor size and reductions in SUVmax and SUVmean in 4 children, in three of whom ADCmean values were increased. In 2 patients, tumor size remained stable whereas SUVmax and SUVmean values were increased with reduction in the ADCmean values. Additionally, in 2 children, cross-sectional MRI showed an increase both in tumor size and SUVmax but a reduction in ADC values. Conclusions Simultaneous 18F-choline PET/MRI is a promising and reliable imaging tool for children with astrocytic tumors, as it permits monitoring of morphological and metabolic response and changes during therapy.

Inflammatory pseudotumor of mediastinum treated with tomotherapy and monitored with FDG-PET/CT: case report and literature review

Mediastinal inflammatory pseudotumor is a rare disease with reactive pseudoneo-plastic features and a proven capacity for local invasion. The radiographic appearance of inflammatory pseudotumor is quite non-specific and the definitive diagnosis is based on the histological evaluation of tissue specimens. Resection of the lesion is the treatment of choice. However, nonsurgical treatments such as radiotherapy and steroids have been employed in the setting of incomplete surgical resection, tumor recurrence, and patients being unfit for surgery. The case described here is being reported because of the rare mediastinal location and atypical treatment approach including salvage irradiation and monitoring with FDG-PET/CT. Because of the irregular target volume inside the mediastinum as defined by FDG-PET/CT and the significant pulmonary comorbidity, it was deemed necessary to optimize dose delivery with intensity-modulated radiation therapy (IMRT). A possible gain by means of daily control of patient setup with image-guided radiation therapy was also hypothesized and we used tomotherapy to irradiate the lesion. The first FDG-PET/CT after treatment confirmed further reduction of the metabolic activity followed by stable disease in the mediastinum, with no new occurrence of disease 16, 24 and 30 months after tomotherapy.

A Cross-Validation of FDG- and Amyloid-PET Biomarkers in Mild Cognitive Impairment for the Risk Prediction to Dementia due to Alzheimer’s Disease in a Clinical Setting

Assessments of brain glucose metabolism (18F-FDG-PET) and cerebral amyloid burden (11C-PiB-PET) in mild cognitive impairment (MCI) have shown highly variable performances when adopted to predict progression to dementia due to Alzheimers disease (ADD). This study investigates, in a clinical setting, the separate and combined values of 18F-FDG-PET and 11C-PiB-PET in ADD conversion prediction with optimized data analysis procedures. Respectively, we investigate the accuracy of an optimized SPM analysis for 18F-FDG-PET and of standardized uptake value ratio semiquantification for 11C-PiB-PET in predicting ADD conversion in 30 MCI subjects (age 63.57±7.78 years). Fourteen subjects converted to ADD during the follow-up (median 26.5 months, inter-quartile range 30 months). Receiver operating characteristic analyses showed an area under the curve (AUC) of 0.89 and of 0.81 for, respectively, 18F-FDG-PET and 11C-PiB-PET. 18F-FDG-PET, compared to 11C-PiB-PET, showed higher specificity (1.00 versus 0.62, respectively), but lower sensitivity (0.79 versus 1.00). Combining the biomarkers improved classification accuracy (AUC = 0.96). During the follow-up time, all the MCI subjects positive for both PET biomarkers converted to ADD, whereas all the subjects negative for both remained stable. The difference in survival distributions was confirmed by a log-rank test (p = 0.002). These results indicate a very high accuracy in predicting MCI to ADD conversion of both 18F-FDG-PET and 11C-PiB-PET imaging, the former showing optimal performance based on the SPM optimized parametric assessment. Measures of brain glucose metabolism and amyloid load represent extremely powerful diagnostic and prognostic biomarkers with complementary roles in prodromal dementia phase, particularly when tailored to individual cases in clinical settings.

[11C]choline-PET-guided helical tomotherapy and estramustine in a patient with pelvic-recurrent prostate cancer: local control and toxicity profile after 24 months.

[11C]choline positron emission tomograhy can be useful to detect metastatic disease and to localize isolated lymph node relapse after primary treatment in case of prostate-specific antigen failure. In case of lymph node failure in prostate cancer patients, surgery or radiotherapy can be proposed with a curative intent. Some reports have suggested that radiotherapy could have a role in local control of oligometastatic lymph node disease. This is the first reported case of [11C]choline positron emission tomography-guided helical tomotherapy concomitant with estramustine for the treatment of pelvic-recurrent prostate cancer. At 24 months after the end of helical tomotherapy, prostate-specific antigen was undetectable and no late toxicities were recorded. A disease-free survival of 24 months, in the absence of any type of systemic therapy, is uncommon in metastatic prostate cancer. The therapeutic approach of the case report is discussed and a literature review on the issue is presented.

PET Neuroimaging: Insights on Dystonia and Tourette Syndrome and Potential Applications

Primary dystonia (pD) is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Gilles de la Tourette syndrome (GTS) is a childhood-onset neuropsychiatric developmental disorder characterized by motor and phonic tics, which could progress to behavioral changes. GTS and obsessive–compulsive disorders are often seen in comorbidity, also suggesting that a possible overlap in the pathophysiological bases of these two conditions. PET techniques are of considerable value in detecting functional and molecular abnormalities in vivo, according to the adopted radioligands. For example, PET is the unique technique that allows in vivo investigation of neurotransmitter systems, providing evidence of changes in GTS or pD. For example, presynaptic and post-synaptic dopaminergic studies with PET have shown alterations compatible with dysfunction or loss of D2-receptors bearing neurons, increased synaptic dopamine levels, or both. Measures of cerebral glucose metabolism with 18F-fluorodeoxyglucose PET (18F-FDG PET) are very sensitive in showing brain functional alterations as well. 18F-FDG PET data have shown metabolic changes within the cortico-striato-pallido-thalamo-cortical and cerebello-thalamo-cortical networks, revealing possible involvement of brain circuits not limited to basal ganglia in pD and GTS. The aim of this work is to overview PET consistent neuroimaging literature on pD and GTS that has provided functional and molecular knowledge of the underlying neural dysfunction. Furthermore, we suggest potential applications of these techniques in monitoring treatments.

Neuropsychological and FDG-PET profiles in VGKC autoimmune limbic encephalitis.

BACKGROUND Limbic encephalitis (LE) is characterized by an acute or subacute onset with memory impairments, confusional state, behavioral disorders, variably associated with seizures and dystonic movements. It is due to inflammatory processes that selectively affect the medial temporal lobe structures. Voltage-gate potassium channel (VGKC) autoantibodies are frequently observed. In this study, we assessed at the individual level FDG-PET brain metabolic dysfunctions and neuropsychological profiles in three autoimmune LE cases seropositive for neuronal VGKC-complex autoantibodies. MATERIALS AND METHODS LGI1 and CASPR2 potassium channel complex autoantibody subtyping was performed. Cognitive abilities were evaluated with an in-depth neuropsychological battery focused on episodic memory and affective recognition/processing skills. FDG-PET data were analyzed at single-subject level according to a standardized and validated voxel-based Statistical Parametric Mapping (SPM) method. RESULTS Patients showed severe episodic memory and fear recognition deficits at the neuropsychological assessment. No disorder of mentalizing processing was present. Variable patterns of increases and decreases of brain glucose metabolism emerged in the limbic structures, highlighting the pathology-driven selective vulnerability of this system. Additional involvement of cortical and subcortical regions, particularly in the sensorimotor system and basal ganglia, was found. CONCLUSIONS Episodic memory and fear recognition deficits characterize the cognitive profile of LE. Commonalities and differences may occur in the brain metabolic patterns. Single-subject voxel-based analysis of FDG-PET imaging could be useful in the early detection of the metabolic correlates of cognitive and non-cognitive deficits characterizing LE condition.

Megavoltage CT images of helical tomotherapy unit for radiation treatment simulation: impact on feasibility of treatment planning in a prostate cancer patient with bilateral femoral prostheses.

Metal prosthesis artefacts on CT images can be a significant problem in the definition of volumes of interest, dose calculation and patient setup in modern radiotherapy. We experienced considerable difficulties in defining the organs at risk and treatment volumes on kVCT images of standard CT simulation in a prostate cancer patient due to the presence of bilateral femoral prostheses causing artefacts. As shown in the current case, MVCT images of the patient in the treatment position obtained using a helical tomotherapy unit can provide sufficient morphological information to define the pelvic anatomic structures for radical prostate treatment planning. The patient completed the planned treatment and at 90 days after the end of treatment no severe side effects were recorded. Since there have been few reports on the use of MVCT images to overcome the problem of hip prosthesis artefacts, a brief literature review was also carried out.

Prefrontal Cortical Stimulation in Tourette Disorder: Proof-of-concept Clinical and Neuroimaging Study: FDG-PET Study and Cortical Stimulation in Tourette

The benefits of neurosurgery in Tourette Syndrome (TS) are still incompletely understood. Prefrontal cortical electrical stimulation offers a less invasive alternative to deep brain stimulation.

PET Evaluation of Late Cerebral Effect in Advanced Radiation Therapy Techniques for Cranial Base Tumors

BACKGROUND AND OBJECTIVE Even though the benefits of radiation therapy are well established, it is important to recognize the broad spectrum of radiation-induced changes, particularly in the central nervous system. The possible damage to the brain parenchyma may have clinical consequences and in particular cognitive impairment might be one of the major complications of radiotherapy. To date, no studies have investigated the effects of focal radiation therapy on brain structure and function together with the assessment of their clinical outcomes at a long follow-up. METHODS In this prospective study, we evaluated in six patients the possible brain late effects after radiation therapy, using a standardized neuropsychological battery, MRI and 18F-FDG PET using SPM and semi-quantitative methods, in patients affected by cranial base tumors who underwent gamma knife or tomotherapy. RESULTS Neuropsychological examinations showed no cognitive impairment after the treatment. In all patients, both MRI assessment and 18F-FDG-PET did not reveal any local or distant anatomical and metabolic late effects. CONCLUSION The present study support the safety of advanced radiation therapy techniques. 18F-FDGPET, using SPM and semi-quantitative methods, might be a valuable tool to evaluate the cerebral radiotoxicity in patients treated for brain neoplasms.