ABSTRACT:A 78-year-old man with synchronous diagnosis of prostate cancer and lung adenocarcinoma was referred to our institute for prostate cancer staging with [ 18 F]F-prostate-specific membrane antigen (PSMA) 1007 PET/CT. In addition to the previously known lesion of the right lung, PSMA-targeted PET/CT highlighted 2 areas of abnormal uptake in the brain, in the left frontal and temporal lobes. A subsequent MRI confirmed the lesions observed on PET/CT. Because PSMA-targeting radiopharmaceuticals do not accumulate in healthy brain parenchyma, and recent literature reported promising performances of PSMA-targeted PET/CT in gliomas and metastases from tumors other than prostate cancer, this employment of PSMA radioligands needs to be further explored.

This retrospective study aims to establish 18F-fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) performance in finding hyperfunctioning parathyroid glands, analyze a potential role for semi-quantitative PET parameters and assess factors that may influence PET/CT outcome. Forty patients with suspect primary hyperparathyroidism (pHPT) and negative/equivocal conventional imaging underwent FCH-PET/CT in our Institution. For every lesion, visual and semi-quantitative analyses were performed on PET/CT images. In qualitative analysis, a lesion was considered positive if a clear focus of uptake, significantly higher than normal thyroid tissue, was identifiable. Ectopic focal uptake was also regarded as positive PET result. Lesion SUVMax was measured by assigning a spheric VOI to the suspect area of uptake. Thyroid SUVMean was assessed by placing a spheric VOI inside the contralateral thyroid lobe, and SUVratio was calculated using this background region. All patients were subsequently submitted to surgery and histopathologic workup. Sensitivity, positive predictive value (PPV) and accuracy were calculated based on histopathologic reports for every lesion. Pearson’s test was used to assess a correlation between laboratory and histopathologic features with SUVr. Four out of the 40 patients who underwent surgery for pHPT had more than one histologic proven unhealthy parathyroid and three had papillary thyroid cancer (PTC). A total of 48 lesions were analyzed. We found 42/48 lesions (87.5

Response assessment to definitive non-surgical treatment for head and neck squamous cell carcinoma (HNSCC) is centered on the role of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET-CT) 12 weeks after treatment. The 5-point Hopkins score is the only qualitative system available for standardized reporting, albeit limited by suboptimal positive predictive value (PPV). The aim of our study was to explore the feasibility and assess the diagnostic accuracy of an experimental 6-point scale (“Cuneo score”). We performed a retrospective, multicenter study on HNSCC patients who received a curatively-intended, radiation-based treatment. A centralized, independent qualitative evaluation of post-treatment FDG-PET/CT scans was undertaken by 3 experienced nuclear medicine physicians who were blinded to patients’ information, clinical data, and all other imaging examinations. Response to treatment was evaluated according to Hopkins, Cuneo, and Deauville criteria. The primary endpoint of the study was to evaluate the PPV of Cuneo score in assessing locoregional control (LRC). We also correlated semi-quantitative metabolic factors as included in PERCIST and EORTC criteria with disease outcome. Out of a total sample of 350 patients from 11 centers, 119 subjects (oropharynx, 57.1%; HPV negative, 73.1%) had baseline and post-treatment FDG-PET/CT scans fully compliant with EANM 1.0 guidelines and were therefore included in our analysis. At a median follow-up of 42 months (range 5-98), the median locoregional control was 35 months (95% CI, 32-43), with a 74.5% 3-year rate. Cuneo score had the highest diagnostic accuracy (76.5%), with a positive predictive value for primary tumor (Tref), nodal disease (Nref), and composite TNref of 42.9%, 100%, and 50%, respectively. A Cuneo score of 5-6 (indicative of residual disease) was associated with poor overall survival at multivariate analysis (HR 6.0; 95% CI, 1.88-19.18; p = 0.002). In addition, nodal progressive disease according to PERCIST criteria was associated with worse LRC (OR for LR failure, 5.65; 95% CI, 1.26-25.46; p = 0.024) and overall survival (OR for death, 4.81; 1.07-21.53; p = 0.04). In the frame of a strictly blinded methodology for response assessment, the feasibility of Cuneo score was preliminarily validated. Prospective investigations are warranted to further evaluate its reproducibility and diagnostic accuracy.

Pathological complete response (pCR) following neoadjuvant chemoradiotherapy or radiotherapy in locally advanced rectal cancer (LARC) is reached in approximately 15–30% of cases, therefore it would be useful to assess if pretreatment of 18F-FDG PET/CT and/or MRI texture features can reliably predict response to neoadjuvant therapy in LARC. Fifty-two patients were dichotomized as responder (pR+) or non-responder (pR-) according to their pathological tumor regression grade (TRG) as follows: 22 as pR+ (nine with TRG = 1, 13 with TRG = 2) and 30 as pR- (16 with TRG = 3, 13 with TRG = 4 and 1 with TRG = 5). First-order parameters and 21 second-order texture parameters derived from the Gray-Level Co-Occurrence matrix were extracted from semi-automatically segmented tumors on T2w MRI, ADC maps, and PET/CT acquisitions. The role of each texture feature in predicting pR+ was assessed with monoparametric and multiparametric models. In the mono-parametric approach, PET homogeneity reached the maximum AUC (0.77; sensitivity = 72.7% and specificity = 76.7%), while PET glycolytic volume and ADC dissimilarity reached the highest sensitivity (both 90.9%). In the multiparametric analysis, a logistic regression model containing six second-order texture features (five from PET and one from T2w MRI) yields the highest predictivity in distinguish between pR+ and pR- patients (AUC = 0.86; sensitivity = 86%, and specificity = 83% at the Youden index). If preliminary results of this study are confirmed, pretreatment PET and MRI could be useful to personalize patient treatment, e.g., avoiding toxicity of neoadjuvant therapy in patients predicted pR-.

Purpose To predict pathological response to neoadjuvant chemo-radiotherapy (CRT) in locally advanced rectal carcinoma (LARC), using a classifier based on texture features derived from MRI and PET acquisitions. Methods 47 patients with: (a) histologically diagnosis of LARC, (b) pre-treatment MRI and PET/CT, (c) neoadjuvant treatment consisting of 46–55 Gy in 23–30 RT fractions alone or in association with either infusional 5-FU or oral Capecitabine, and (d) total mesorectal excision were included in this study. Patients with complete (tumour regression grade, TRG = 1) or near complete (TRG = 2) regression were defined as responders (pR+), while patients with moderate (TRG = 3) to no regression (TRG = 5) were considered as non-responders (pR-) [ 1 Mandard A.M. Dalibard F. Mandard J.C. et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994; 73: 2680-2686 Crossref PubMed Scopus (1589) Google Scholar , 2 Santos M.D. Silva C. Rocha A. Matos E. Nogueira C. Lopes C. Tumor regression grades: can they influence rectal cancer therapy decision tree?. Int J Surg Oncol. 2013; 2013: 572149 Google Scholar ]. Before implementing texture analysis, tumours were semi-automatically segmented on T2-w MRI, ADC maps and PET/CT acquisitions. From the segmented tumours, the following quantitative features were extracted from T2-w, ADC and PET images: (a) first-order parameters: median, mean, percentiles (10th, 25th, and 75th), (b) SUV, metabolic volume and glycolytic volume only for PET images, and (c) 22 s-order texture parameters, derived from Haralick analysis [ [3] Haralick R.M. Shanmugam K. Dinstein I. Textural features for image classification. IEEE Trans Syst Man Cybern. 1973; SMC-3: 610-621 Crossref Scopus (17559) Google Scholar ]. Multivariate logistic regression was performed to identify features most correlated with TRG. Results Overall, 26 patients were classified as pR−, and 21 as pR+ after total mesorectal excision. Parameters included in the multivariate regression were “10th percentile PET”, “10th percentile T2-w”, “Homogeneity ADC”, “Homogeneity PET”, “Information measure of correlation T2-w” (p = 0.002). The area under the ROC curve was 0.83 (95% confidence interval = 0.69–0.93), sensitivity and specificity were 75% and 76%, respectively, in detecting responders. Conclusions Texture analysis could provide useful information in assessing response to neoadjuvant treatment in LARC patients. These preliminary results, if confirmed on larger dataset, could be useful to personalize the oncological pathway for patients, delaying or advancing surgery, according to the prediction of treatment response. To predict pathological response to neoadjuvant chemo-radiotherapy (CRT) in locally advanced rectal carcinoma (LARC), using a classifier based on texture features derived from MRI and PET acquisitions. 47 patients with: (a) histologically diagnosis of LARC, (b) pre-treatment MRI and PET/CT, (c) neoadjuvant treatment consisting of 46–55 Gy in 23–30 RT fractions alone or in association with either infusional 5-FU or oral Capecitabine, and (d) total mesorectal excision were included in this study. Patients with complete (tumour regression grade, TRG = 1) or near complete (TRG = 2) regression were defined as responders (pR+), while patients with moderate (TRG = 3) to no regression (TRG = 5) were considered as non-responders (pR-) [ 1 Mandard A.M. Dalibard F. Mandard J.C. et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994; 73: 2680-2686 Crossref PubMed Scopus (1589) Google Scholar , 2 Santos M.D. Silva C. Rocha A. Matos E. Nogueira C. Lopes C. Tumor regression grades: can they influence rectal cancer therapy decision tree?. Int J Surg Oncol. 2013; 2013: 572149 Google Scholar ]. Before implementing texture analysis, tumours were semi-automatically segmented on T2-w MRI, ADC maps and PET/CT acquisitions. From the segmented tumours, the following quantitative features were extracted from T2-w, ADC and PET images: (a) first-order parameters: median, mean, percentiles (10th, 25th, and 75th), (b) SUV, metabolic volume and glycolytic volume only for PET images, and (c) 22 s-order texture parameters, derived from Haralick analysis [ [3] Haralick R.M. Shanmugam K. Dinstein I. Textural features for image classification. IEEE Trans Syst Man Cybern. 1973; SMC-3: 610-621 Crossref Scopus (17559) Google Scholar ]. Multivariate logistic regression was performed to identify features most correlated with TRG. Overall, 26 patients were classified as pR−, and 21 as pR+ after total mesorectal excision. Parameters included in the multivariate regression were “10th percentile PET”, “10th percentile T2-w”, “Homogeneity ADC”, “Homogeneity PET”, “Information measure of correlation T2-w” (p = 0.002). The area under the ROC curve was 0.83 (95% confidence interval = 0.69–0.93), sensitivity and specificity were 75% and 76%, respectively, in detecting responders. Texture analysis could provide useful information in assessing response to neoadjuvant treatment in LARC patients. These preliminary results, if confirmed on larger dataset, could be useful to personalize the oncological pathway for patients, delaying or advancing surgery, according to the prediction of treatment response.

Purpose or ObjectiveNeoadjuvant chemotherapy (CT) and chemoradiotherapy (CRT) have a survival benefit over surgery alone in oesophageal cancer.However, the rates of pathological complete response (pCR) are relatively low, ranging between 15-25% in clinical trials.Currently there is no established means of predicting, which patients will achieve a good pathological outcome following induction treatment.The aim of this study was to determine whether magnetic resonance imaging (MRI) biomarkers either at baseline or following neoadjuvant CT/CRT can predict pathological response. Material and MethodsFollowing IRB approval and informed consent, 25 prospective patients (median age 67 years (range 41-78), 20 male) with newly diagnosed oesophageal carcinoma (21 adenocarcinomas, 4 squamous cell carcinomas) underwent a 1.5T MRI before and after neoadjuvant CT/CRT, which included T2-weighted, dynamic contrast enhanced (DCE) T1-weighted and a diffusion weighted (DWI) sequence (b values: 50-900 s/mm).Tumour was outlined an all sequences generating corresponding 3D volumes of interest (VOI) from which the following values were derived: T2w voxel signal intensity histogram features (mean, skewness, kurtosis and entropy); DCE transfer constant (K trans ), DCE extravascular-extracellular space (Ve); DWI apparent diffusion coefficient (ADC).Primary outcome was good pathological response: pathCR or near-pathCR (Mandard tumor regression grade [TRG] 1 or 2).Predictive value was assessed using a linear regression model with Huber-M-estimation (to reduce the sensitivity to outliers given relatively small sample size), p values were adjusted for multiple comparison using Benjamin Hochberg correction (FDR<5%). Results22 patients received induction CT, 3 patients received CRT.6 patients (26%) had a good pathological response.Simple linear regression incorporating all 7 imaging variables at 2 timepoints (14 factors) identified post CT/CRT T2w entropy and kurtosis to be significantly associated with continuous Mandard TRG (FDR p-value 0.03, R 2 0.39 and FDR p value 0.03, R 2 0.25, respectively).Analysis of variance on dichotomized pathological outcome, confirmed good pathological Response (Mandard TRG 1-2) to be significantly associated with higher post CT/CRT T2 entropy and lower post CT/CRT T2 kurtosis (FDR p-value 0.006 and 0.02, respectively).In addition, good pathological response was significantly associated with an increase in T2w entropy post CT/CRT (median 11.2% versus 3.3%, p=0.02). ConclusionHigher post-treatment T2w intra-tumoural entropy (marker of lesional heterogeneity) and a greater increase in T2w entropy following CT/ CRT were associated with good pathologic response in our study.Greater heterogeneity may reflect cancer cell regression, development of fibrosis and influx of immune cells.

The aim of this study was the assessment of semi-quantified salivary gland dynamic scintigraphy (SGdS) parameters independently and in an integrated way in order to predict primary Sjögren’s syndrome (pSS).

________________________________________________________________________________administered in escalating doses to cohorts of three patients at each dose level.Phase II was then assessed at the selected maximum tolerated dose (MTD).The patients were monitored for acute toxicity using the Common Toxicity Criteria, version 3.0 and late toxicity using the RTOG/EORTC.tweenNovember 2008 and March 2015, a total of 36 patients with primary carcinoma of the cervix, FIGO stage IB1 to IIIB, confirmed by histology, negative para-aortic lymph nodes were enrolled into this phase I / II trial.Chemotherapy agents were administered in escalating doses to cohorts of three patients at each dose level.Phase II was then assessed at the selected maximum tolerated dose (MTD).The patients were monitored for acute toxicity using the Common Toxicity Criteria, version 3.0 and late toxicity using the RTOG/EORTC.

We hypothesized that the IL-1β-511 C>T polymorphism could be associated with the development of neurotoxicity and that it could be a possible biomarker to rate the risk of occurrence of neurotoxicity in cancer patients. Genomic DNA was extracted from 85 cancer patients: 49 received systemic chemotherapeutic treatment (CHT) and 36 patients did not receive it (No-CHT). All subjects were genotyped for the functionally active polymorphisms of IL-1β-511 C>T. We estimated neurotoxicity with the evaluation of neurological deficits. CHT patients showed erythrocytopenia, neurological deficit and a slight lowering of cognitive performance. The subgroup of patients carrying the CC genotype of the IL-1β-511 C>T gene showed lesser neurological deficits. In the context of cancer treatment, we suggested the potential value of IL-1β-511 C>T as genetic biomarkers to identify patients with higher risk to develop neurological deficits.

The objective of this study was to investigate the possible associations between the Distress Thermometer (DT) scores and the brain metabolism of structures involved in stress response. Twenty-one cancer patients were assessed using the DT, Problem Checklist and Hospital Anxiety and Depression Scale (HADS). The psychological measures were correlated with [18 F]PET-FDG brain glucose metabolism. Multiple and linear regression and binary logistic regression were run to analyse data. The DT and HADS scores illustrated that 48% of patients were distressed, 19% were depressed and 48% were anxious. Results showed that some subcortical areas activity, such as part of midbrain and of hypothalamus, was correlated with the DT scores. The Problem Checklist scores correlated with the activity of the same areas and included more regions in the limbic forebrain and brainstem. Compared with the DT and Problem Checklist, HADS-Depression scores showed a more extensive pattern of correlation with brain activity, including limbic and cortical areas. The results highlighted that the DT scores correlated with the activity of brain areas typically involved in stress response. Indeed, hypothalamus metabolism was found to be the best predictor of distressed patients.

AIM:A growing number of neuropsychological studies reported that chemotherapy may impair brain functions, inducing persistent cognitive changes in a subset of cancer survivors. The aim of this paper was to investigate the neural basis of the chemotherapy induced neurobehavioral changes by means of metabolic imaging and neuropsychological testing.METHODS:We studied the resting brain [¹⁸F]FDG-PET/CT images of 50 adult cancer patients with diagnosis of lymphoma: 18 patients were studied prior and 32 after to chemotherapy. All patients underwent to a neuropsychological examination assessing cognitive impairment (tests for shifting attention, verbal memory, phonemic fluency), depression, anxiety and distress.RESULTS:Compared to no chemotherapy patients, the treated group showed significant bilateral lower rate of glucose metabolism in prefrontal cortices, cerebellum, medial cortices and limbic brain areas. The metabolism of these regions negatively correlated with number of cycles and positively with post-chemotherapy time. The treated group showed a poorer performance in many frontal functions, but similar level of depression, anxiety and distress.CONCLUSIONS:Chemotherapy induced significant long-term changes in metabolism of multiple regions with a prevailing involvement of the prefrontal cortex. The observed cognitive dysfunctions could be explained by these changes. The recovery from chemotherapy is probably affected by treatment duration and by the time elapsed after its end. We speculated that the mechanism could be an accelerating ageing / oxidative stress that, in some patients at risk, could result in an early and persistent cognitive impairment.

Background: A growing number of studies reports that chemotherapy may impair brain functions inducing cognitive changes which can persist in a subset of cancer survivors.Aims: To investigate the neural basis of the chemotherapy-induced neurobehavioral changes by means of metabolic imaging and voxel-based statistical parametric mapping analyses. Methods: We studied the resting brain [18]FDG-PET/CT images of 43 adult cancer patients with solid (n=12, 28%) or hematologic malignancies (n=31, 72%); 12 patients were studied prior to chemotherapy (No chemotherapy) while treated patients were divided into two matched subgroups: Early High (<9 months after chemotherapy, >6 chemotherapy cycles, n=10), and Late Low (>9 months after chemotherapy, <6 chemotherapy cycles, n=21). Findings: Compared to No chemotherapy, the Early High subgroup showed a significant bilateral (p<0.05) lower regional cerebral metabolic rate of glucose metabolism in both the prefrontal cortices and white matter, cerebellum, posterior medial cortices and limbic regions. A similar pattern emerged in the Early High versus Low Late comparison, while no significant result was obtained in the Low Late versus No chemotherapy comparison. The number of cycles and the post-chemotherapy time were negatively and positively correlated, respectively, with a set of these same brain regions. Interpretation: The present study shows that chemotherapy induces significant transient changes in the glucose metabolism of multiple cerebral cortical and white matter regions with a prevailing involvement of the prefrontal cortex. The severity of these changes are significantly related with the number of chemotherapy cycles and a subset of brain regions seems to present longer lasting, but more subtle, metabolic changes.