Right Atrium Mass Assessed with 18F-FDG PET/CT Scan Turns Out to Be an Uncommon Relapse of Testicular Diffuse Large B-cell Lymphoma: A Case Report.

We report the case of a 71-year-old man affected by testicular large B-cell lymphoma (DLBCL), treated with right orchiectomy and first-line chemotherapy (R-CHOP, 8 cycles). A complete remission was obtained after therapy. Twenty-two months after the primary diagnosis the patient suddenly presented dyspnoea and superior vena cava syndrome; thus, he underwent a CT scan that revealed a large mass in the right atrium, expanding to the superior vena cava. A differential diagnosis between a neoplastic mass and a clot was proposed. The subsequent MR did not clarify the nature of the mass; therefore, the patient underwent an 18F-FDG PET/CT scan (PET/CT), after a specific preparation to reduce fluoro-deoxyglucose (FDG) myocardial uptake. PET/CT revealed an intense FDG uptake involving the whole mass (SUVmax 9.4), suggestive for neoplasm and confirmed by the subsequent endocardiac biopsy. The patient was treated with 8 cycles of R-COMP, obtaining a complete remission, as indicated by the PET/CT performed after the seventh cycle of therapy. The case that we are reporting highlights that DLBCL can have an uncommon relapse presentation in the atrium. PET/CT, compared to conventional imaging, can be a valuable tool to detect early and better characterize cardiac lesions in order to improve the poor prognosis of these conditions.

Automated Synthesis of 68Ga-DOTA-TOC with a Cationic Purification System: Evaluation of Methodological and Technical Aspects in Routine Preparations.

BACKGROUND AND OBJECTIVE: Gallium-68 is a PET isotope available in each nuclear medicine departments, even those not equipped with a cyclotron, since it is easily obtained by eluting compact and transportable generator system. The preparation of Ga-68 DOTA-labeled compounds is performed by remotely controlled automated systems developed in order to ensure production efficiency, reproducibility of the results, fast reaction time, to facilitate the synthesis and minimize the radiation exposure. Many automatic synthesis systems are available on the radiopharmaceutical market, however, they requires some technical adaptations for routine use. We reported the [68Ga]Ga-DOTA-TOC production by automated cassette-based theranostic synthesizer system used in combination with a disposable GMP grade cassette system for cationic purification. METHODS: The synthesizer is integrated with the 68Ge/68Ga generator systems and it allows to perform elution, eluate purification and radiolabeling in about 38 minutes. We have performed in 2 year (January 2016 - January 2018) over 100 [68Ga]Ga-DOTA-TOC preparations. RESULTS: The average synthesis yield of radiopharmaceutical production was 54.4 ± 2.3 % and the radiochemical purity average was found 96.94 ± 0.74 %. Only three [68Ga]Ga-DOTA-TOC preparations have failed. CONCLUSION: The methodology and the adopted technical solutions allowed to obtain a high quality radiopharmaceutical product as required by the European Pharmacopoeia.

Multidisciplinary management improves survival at 1 year after surgical treatment for non-small-cell lung cancer: a propensity score-matched study.

OBJECTIVES: The management of patients affected by lung cancer requires the expertise of specialists from different disciplines. Although the advantages of multidisciplinary team discussions seem obvious, there are limited studies evaluating the influence of this approach on postoperative outcomes in non-small-cell lung cancer (NSCLC). The aim of this study is to examine the impact of a multidisciplinary approach on survival of patients undergoing surgery for NSCLC. METHODS: A retrospective analysis was performed on consecutive patients who underwent surgery for NSCLC between January 2008 and December 2015. Data were compared between patients treated before the implementation of a multidisciplinary tumour board (MTB), between 2008 and 2012, and those who received treatment after the implementation of the MTB, between 2012 and 2015. Patients were matched one to one according to the discussion of the MTB and on the basis of a propensity score built using several patient characteristics. A propensity score-matched analysis was performed to compare patient outcomes. RESULTS: A total of 246 patients were treated prior to the initiation of the MTB and 231 patients after the initiation of the MTB. Based on the propensity score, 2 well-matched groups of 170 patients were identified. Patients who were discussed at the MTB were noted to have better outcomes when compared with those who were not discussed at the MTB on different terms including complete staging evaluation, early tumour, node and metastasis (TNM) stages and 1-year survival rate. CONCLUSIONS: Implementation of a multidisciplinary thoracic malignancy conference increased the 1-year survival rate of patients who underwent a surgical resection for NSCLC.

Week one FLT-PET response predicts complete remission to R-CHOP and survival in DLBCL.

Despite improved survival in the Rituximab (R) era, a considerable number of patients with diffuse large B-cell lymphoma (DLBCL) ultimately die from the disease. Functional imaging using [18F]fluorodeoxyglucose-PET is suggested for assessment of residual viable tumor very early during treatment but is compromised by non-specific tracer retention in inflammatory lesions. The PET tracer [18F]fluorodeoxythymidine (FLT) as surrogate marker of tumor proliferation may overcome this limitation. We present results of a prospective clinical study testing FLT-PET as superior and early predictor of response to chemotherapy and outcome in DLBCL. 54 patients underwent FLT-PET prior to and one week after the start of R-CHOP chemotherapy. Repetitive FLT-PET imaging was readily implemented into the diagnostic work-up. Our data demonstrate that the reduction of FLT standard uptake valuemean (SUVmean) and SUVmax one week after chemotherapy was significantly higher in patients achieving complete response (CR, n=48; non-CR, n=6; p<0.006). Martingale-residual and Cox proportional hazard analyses showed a significant monotonous decrease of mortality risk with increasing change in SUV. Consistent with these results, early FLT-PET response showed relevant discriminative ability in predicting CR. In conclusion, very early FLT-PET in the course of R-CHOP chemotherapy is feasible and enables identification of patients at risk for treatment failure.

FDG PET/CT predictive role in follicular lymphoma.

PURPOSE: We present findings concerning (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) at end-treatment evaluation in follicular lymphoma (FL) in order to establish possible predictive factors for progression-free survival (PFS) and patient outcome. METHODS: We retrospectively analysed data from 91 consecutive FL patients (M:F = 51:40, mean age 61) referred to our PET Unit at therapy completion: 38 with an indolent form (grade 1-2) and 53 with an aggressive FL (grade 3a and b) according to the World Health Organization (WHO) classification. A total of 148 FDG PET/CT scans were analysed and findings reported as positive or negative for disease. The overall response to treatment was assessed according to the revised International Workshop Criteria (IWC). The final outcome was defined as remission or disease by taking clinical, instrumental and histological data as standards of reference, with a mean follow-up period of 3 years (range 1-8). A statistical analysis was performed with respect to PFS and patient outcome for FDG PET result, tumour grading, Follicular Lymphoma International Prognostic Index (FLIPI), disease stage and number of relapses, on uni- and multivariate analyses, with p < 0.05 considered as significant. RESULTS: Overall patients presented a mean PFS of 35 months (range 3-86), with a relapse rate of 42%. At final outcome, remission was achieved in 67 of 91 patients (74%). Of the different predictive factors, only FDG PET result significantly correlated with patient outcome (p = 0.0002). PET/CT performance at the end of treatment was as follows: 100% sensitivity, 99% specificity, 89% positive predictive value and 100% negative predictive value. The Kaplan-Meier analysis demonstrated a statistically significant correlation with PFS for FDG PET (p < 0.0001), FLIPI score (0-1 versus ≥ 2) (p = 0.0451) and number of relapses (none versus ≥ 1) (p = 0.0058). These findings were confirmed at the univariate analysis, whereas at the multivariate analysis only FDG PET (p = 0.0006892) and number of relapses (p = 0.01947) were independent predictive factors for PFS. CONCLUSION: End-treatment PET/CT in FL has high accuracy and appears to be a good predictor of PFS and patient outcome, irrespective of grading. As expected, patients facing more than one relapse seem to have significantly shorter PFS in the presence of a positive FDG PET.

Value of a Dixon-based MR/PET attenuation correction sequence for the localization and evaluation of PET-positive lesions.

PURPOSE: In this study, the potential contribution of Dixon-based MR imaging with a rapid low-resolution breath-hold sequence, which is a technique used for MR-based attenuation correction (AC) for MR/positron emission tomography (PET), was evaluated for anatomical correlation of PET-positive lesions on a 3T clinical scanner compared to low-dose CT. This technique is also used in a recently installed fully integrated whole-body MR/PET system. METHODS: Thirty-five patients routinely scheduled for oncological staging underwent (18)F-fluorodeoxyglucose (FDG) PET/CT and a 2-point Dixon 3-D volumetric interpolated breath-hold examination (VIBE) T1-weighted MR sequence on the same day. Two PET data sets reconstructed using attenuation maps from low-dose CT (PET(AC_CT)) or simulated MR-based segmentation (PET(AC_MR)) were evaluated for focal PET-positive lesions. The certainty for the correlation with anatomical structures was judged in the low-dose CT and Dixon-based MRI on a 4-point scale (0-3). In addition, the standardized uptake values (SUVs) for PET(AC_CT) and PET(AC_MR) were compared. RESULTS: Statistically, no significant difference could be found concerning anatomical localization for all 81 PET-positive lesions in low-dose CT compared to Dixon-based MR (mean 2.51 ± 0.85 and 2.37 ± 0.87, respectively; p = 0.1909). CT tended to be superior for small lymph nodes, bone metastases and pulmonary nodules, while Dixon-based MR proved advantageous for soft tissue pathologies like head/neck tumours and liver metastases. For the PET(AC_CT)- and PET(AC_MR)-based SUVs (mean 6.36 ± 4.47 and 6.31 ± 4.52, respectively) a nearly complete concordance with a highly significant correlation was found (r = 0.9975, p < 0.0001). CONCLUSION: Dixon-based MR imaging for MR AC allows for anatomical allocation of PET-positive lesions similar to low-dose CT in conventional PET/CT. Thus, this approach appears to be useful for future MR/PET for body regions not fully covered by diagnostic MRI due to potential time constraints.

Is there a role for ¹¹C-choline PET/CT in the early detection of metastatic disease in surgically treated prostate cancer patients with a mild PSA increase <1.5 ng/ml?

PURPOSE: The aim of this study was to evaluate the potential usefulness of whole-body (11)C-choline PET/CT in the re-staging of prostate cancer (PC) patients previously treated with radical prostatectomy (RP), who presented a mild increase of prostate-specific antigen (PSA) <1.5 ng/ml (early biochemical relapse) during follow-up (FU). METHODS: We evaluated 102 consecutive patients (mean age = 68 years, range = 54-82 years) previously treated with RP and who presented during FU a mild increase of trigger PSA serum levels <1.5 ng/ml: mean 0.86 ± 0.40 ng/ml (range 0.2-1.5) and median 0.93 ng/ml (range 0.67-1.10). In this patient series (11)C-choline PET/CT was used as the first imaging examination at the time of the detection of a mild serum PSA increase <1.5 ng/ml. (11)C-Choline PET/CT was performed following standard procedures in our centre. At the time of PET/CT, 86 patients were not receiving any pharmacologic treatment, while 16 were under anti-androgenic therapy. Positive PET findings were validated by: (a) transrectal ultrasound (TRUS)-guided biopsy in cases of local recurrence, (b) surgical lymphadenectomy, (c) other imaging procedures or (d) FU lasting for at least 12 months. Univariate and multivariate analyses were used to evaluate the following variables: age, TNM staging, Gleason score, time from RP to the biochemical relapse, anti-androgen therapy at the time of (11)C-choline PET/CT scan, trigger PSA value and PSA kinetics, i.e. PSA doubling time (PSAdt) and PSA velocity (PSAvel), in order to assess the significant predictive factors related to the findings of a positive (11)C-choline PET/CT scan. RESULTS: Overall, (11)C-choline PET/CT showed positive findings in 29 of 102 patients (28% of cases). In detail, (11)C-choline PET/CT detected: local relapse in 7 patients, bone metastases in 13 patients (4 single and 9 multiple) and lymph node metastases in 9 patients (6 single and 3 multiple). Positive PET findings were validated by: (a) TRUS-guided biopsy in 7 patients with local recurrence, (b) surgery and lymphadenectomy in 3 patients, (c) other targeted imaging procedures (MR or bone scan) in 5 patients and (d) clinical FU lasting a minimum of 12 months and including also a contrast-enhanced CT (CECT), an MR, a bone scan and a repeated (11)C-choline PET/CT in 14 patients. Age, time to biochemical relapse (TTR), initial T staging, Gleason score and trigger PSA were not statistically significant in predicting a positive (11)C-choline PET/CT scan both at univariate and multivariate analysis. Instead, PSA kinetics (PSAdt and PSAvel), N status and anti-androgenic therapy at the time of PET scan were statistically significant predictive factors at univariate analysis. Of note, only PSAdt and initial N status were found to be significant and independent predictive factors at multivariate analysis. The mean PSAdt in PET-positive patients was 4.34 months (SD 2.82) while in PET-negative patients it was 13.30 months (SD 9.75) (p = 0.0001). The optimal threshold for PSAdt established by receiver-operating characteristic (ROC) analysis was 7.25 months (AUC 0.85; 95% confidence interval 0.77-0.91) providing 93% sensitivity, 74% specificity, 60% positive predictive value and 96% negative predictive value. CONCLUSION: In our study, (11)C-choline PET/CT was able to detect recurrent disease in 28% of the patients with mild biochemical relapse characterized by very low trigger PSA levels (PSA <1.5 ng/ml). Very interestingly (11)C-choline PET/CT detected distant unexpected metastases in 21% of the patients. At multivariate statistical analysis only PSAdt and node status were shown to be significant and independent predictive factors for positive (11)C-choline PET/CT. Therefore, (11)C-choline could be suggested to be performed early during initial biochemical relapse in patients presenting with fast PSA kinetics. The early detection of the site of recurrence could lead to a prompt instauration of the most appropriate treatment, i.e. local surgery or radiation treatment vs systemic treatment. In this view, one of the main advantages should be the avoidance of unnecessary local radiotherapy in those patients showing distant metastasis at (11)C-choline PET/CT.

Role of 11C-choline PET/CT in the restaging of prostate cancer patients showing a single lesion on bone scintigraphy.

AIM: To assess the utility of (11)C-choline PET/CT in the restaging of prostate cancer (PC) patients who showed a single finding on bone scintigraphy (BS) that was classified as equivocal or suspected for metastatic lesion. MATERIALS AND METHODS: A total of 25 PC patients with biochemical failure (mean PSA value 11.1 ng/mL; median value 6.3 ng/mL; range 0.2-37.7 ng/mL) after primary treatment were included in this retrospective study. All of them showed a single lesion on BS reported as suspected for metastatic lesion or as equivocal finding. Patients underwent (11)C-choline PET/CT within 1-4 months from BS. Validation was established by follow-up for at least 6 months. RESULTS: On the basis of biopsy confirmation and/or 6-month follow-up, 22 of 25 patients were classified as positive for the presence of metastatic bone lesions: 13 with a single lesion and 9 with multiple lesions. (11)C-choline PET/CT was positive in 19/25 patients and, on a lesion basis, it showed 50 positive findings. BS results were confirmed in 8/25 (32%) patients. (11)C-choline PET/CT detected multiple sites of relapse in 11/25 (44%) patients: in 2/11, a single bone lesion associated with other extraosseous sites of relapse; in 6/11, multiple bone lesions; in 3/11, multiple bone lesions and other extraosseous localizations. Finally, 6/25 patients were negative on (11)C-choline PET/CT. In 3/6 patients, an osteoblastic lesion was seen on CT attenuation correction images (PET false negative; BS true positive), while in 3/6 patients only findings suggestive of the presence of degenerative disease were found (PET true negative; BS false positive). On a patient basis, (11)C-choline PET/CT showed a diagnostic sensitivity of 86% (19/22) and a specificity of 100% (19/19). CONCLUSIONS: In our study, (11)C-choline PET/CT detected unknown lesions in 11/25 patients. Patients with a single equivocal finding on BS could have important additional information from (11)C-choline PET/CT study, especially in the detection of additional metastases, to choose an appropriate treatment.

Influence of trigger PSA and PSA kinetics on 11C-Choline PET/CT detection rate in patients with biochemical relapse after radical prostatectomy.

UNLABELLED: The purpose of this study was to investigate the effect of total prostate-specific antigen (PSA) at the time of (11)C-choline PET/CT (trigger PSA), PSA velocity (PSAvel), and PSA doubling time (PSAdt) on (11)C-choline PET/CT detection rate in patients treated with radical prostatectomy for prostate cancer, who showed biochemical failure during follow-up. METHODS: A total of 190 patients treated with radical prostatectomy for prostate cancer who showed an increase in PSA (mean, 4.2; median, 2.1; range, 0.2-25.4 ng/mL) were retrospectively enrolled. All patients were studied with (11)C-choline PET/CT. Patients were grouped according to trigger PSA (PSA 5 ng/mL). In 106 patients, data were available for calculation of PSAvel and PSAdt. Logistic regression analysis was used to determine whether there was a relationship between PSA levels and PSA kinetics and the rate of detection of relapse using PET. RESULTS: (11)C-choline PET/CT detected disease relapse in 74 of 190 patients (38.9%). The detection rate of (11)C-choline PET/CT was 19%, 25%, 41%, and 67% in the 4 subgroups-PSA 5 ng/mL (49 patients)-respectively. Trigger PSA values were statistically different between PET-positive patients (median PSA, 4.0 ng/mL) and PET-negative patients (median PSA, 1.4 ng/mL) (P = 0.0001). Receiver-operating-characteristic analysis showed an optimal cutoff point for trigger PSA of 2.43 ng/mL (area under the curve, 0.76). In 106 patients, PSAdt and PSAvel values were statistically different between patients with PET-positive and -negative scan findings (P = 0.04 and P = 0.03). The (11)C-choline PET/CT detection rate was 12%, 34%, 42%, and 70%, respectively, in patients with PSAvel < 1 ng/mL/y (33 patients), 1 < PSAvel 5 ng/mL/y (28 patients). The (11)C-choline PET/CT detection rate was 20%, 40%, 48%, and 60%, respectively, in patients with PSAdt > 6 mo (45 patients), 4 < PSAdt