Paolo Castellucci

11C-Choline Positron Emission Tomography/Computerized Tomography for Preoperative Lymph-Node Staging in Intermediate-Risk and High-Risk Prostate Cancer: Comparison with Clinical Staging Nomograms

BACKGROUND Conventional imaging (CI) techniques are inadequate for lymph node (LN) staging in prostate cancer (PCa). OBJECTIVES To assess the accuracy of (11)C-Choline positron emission tomography/computerized tomography (PET/CT) for LN staging in intermediate-risk and high-risk PCa and to compare it with two currently used nomograms. DESIGN, SETTING, AND PARTICIPANTS From January 2007 to September 2007, 57 PCa patients at intermediate risk (n=27) or high risk (n=30) were enrolled at two academic centres. All patients underwent preoperative PET/CT and radical prostatectomy with extended pelvic LN dissection (PLND). Risk of LN metastasis (LNM) was assessed using available nomograms. MEASUREMENTS Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and number of correctly recognized cases for LNM detection at PET/CT were assessed. The accuracy of PET/CT for LNM detection was compared with the accuracy of nomograms for LNM prediction by using receiver operating characteristic (ROC) analysis. RESULTS AND LIMITATIONS Fifteen patients (26%) had LNMs, and a total of 41 LNMs were identified. On a patient analysis, sensitivity, specificity, PPV, NPV, and number of correctly recognized cases at PET/CT were 60.0%, 97.6%, 90.0%, 87.2%, and 87.7% while, on node analysis, these numbers were 41.4%, 99.8%, 94.4%, 97.2%, and 97.1%. The mean diameter (in mm) of the metastatic deposit of true-positive LNs was significantly higher than that of false-negative LNs (9.2 vs 4.2; p=0.001). PET/CT showed higher specificity and accuracy than the nomograms; however, in pairwise comparison, the areas under the curve (AUCs) were not statistically different (all p values >0.05). CONCLUSIONS In patients with intermediate-risk and high-risk PCa, (11)C-Choline PET/CT has quite a low sensitivity for LNM detection but performed better than clinical nomograms, with equal sensitivity and better specificity.

Influence of Trigger PSA and PSA Kinetics on 11C-Choline PET/CT Detection Rate in Patients with Biochemical Relapse After Radical Prostatectomy

The purpose of this study was to investigate the effect of total prostate-specific antigen (PSA) at the time of 11C-choline PET/CT (trigger PSA), PSA velocity (PSAvel), and PSA doubling time (PSAdt) on 11C-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 11C-choline PET/CT. Patients were grouped according to trigger PSA (PSA ≤ 1 ng/mL, 1 < PSA ≤ 2 ng/mL, 2 < PSA ≤ 5 ng/mL, and 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: 11C-choline PET/CT detected disease relapse in 74 of 190 patients (38.9%). The detection rate of 11C-choline PET/CT was 19%, 25%, 41%, and 67% in the 4 subgroups—PSA ≤ 1 ng/mL (51 patients), 1 < PSA ≤ 2 ng/mL (39 patients), 2 < PSA ≤ 5 ng/mL (51 patients), and 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 11C-choline PET/CT detection rate was 12%, 34%, 42%, and 70%, respectively, in patients with PSAvel < 1 ng/mL/y (33 patients), 1 < PSAvel ≤ 2 ng/mL/y (26 patients), 2 < PSAvel ≤ 5 ng/mL/y (19 patients), and PSAvel > 5 ng/mL/y (28 patients). The 11C-choline PET/CT detection rate was 20%, 40%, 48%, and 60%, respectively, in patients with PSAdt > 6 mo (45 patients), 4 < PSAdt ≤ 6 mo (20 patients), 2 < PSAdt ≤ 4 mo (31 patients), and PSAdt ≤ 2 mo (10 patients). There was no statistical difference between PET-positive and -negative scan detection rates according to the Gleason score, pT and N status, patient age, or duration between surgery and biochemical relapse. Trigger PSA and PSAvel were found to be independent predictive factors for a PET-positive result (P = 0.002; P = 0.04) and PSAdt was found to be an independent factor only in patients with trigger PSA less than 2 ng/mL (P = 0.05) using multivariate analysis. Conclusion: The 11C-choline PET/CT detection rate is influenced by trigger PSA, PSAdt, and PSAvel. This finding could be used to improve the selection of patients for scanning by reducing the number of false-negative scans and increasing the detection rate of disease in patients with early relapse and potentially curative disease.

Comparison between 68Ga-DOTA-NOC and 18F-DOPA PET for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours

Purpose18F-FDG positron emission tomography (PET) value for the assessment of neuro-endocrine tumours (NET) is limited. Preliminary studies indicate that 18F-DOPA and 68Ga-DOTA-NOC are more accurate for disease assessment and 68Ga-DOTA peptides provide additional data on receptor status that are crucial for targeted radionuclide therapy. At present, there are no comparative studies investigating their role in NET.AimThe aim of this study was to compare 68Ga-DOTA-NOC and 18F-DOPA for the evaluation of gastro-entero-pancreatic and lung neuro-endocrine tumours.Materials and methodsThirteen patients with biopsy-proven NET (gastro-entero-pancreatic or pulmonary) were prospectively enrolled and scheduled for 18F-DOPA and 68Ga-DOTA-NOC PET. PET results obtained with both tracers were compared with each other, with other conventional diagnostic procedures (CT, ultrasound) and with follow-up (clinical, imaging).ResultsThe most common primary tumour site was the pancreas (8/13) followed by the ileum (2/13), the lung (2/13) and the duodenum (1/13). The carcinoma was well differentiated in 10/13 and poorly differentiated in 3/13 cases. 68Ga-DOTA-NOC PET was positive, showing at least one lesion, in 13/13 cases while 18F-DOPA PET was positive in 9/13. On a lesions basis, 68Ga-DOTA-NOC identified more lesions than 18F-DOPA (71 vs 45), especially at liver, lung and lymph node level. 68Ga-DOTA-NOC correctly identified the primary site in six of eight non-operated cases (in five cases, the primary was surgically removed before PET), while 18F-DOPA identified the primary only in two of eight cases.ConclusionsAlthough the patients studied are few and heterogeneous, our data show that 68Ga-DOTA-NOC is accurate for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours in either the primary or metastatic site and that it offers several advantages over 18F-DOPA.

68Ga-DOTANOC PET/CT clinical impact in patients with neuroendocrine tumors.

Several authors reported the superiority of 68Ga-DOTANOC PET/CT to conventional imaging (CI) for the assessment of neuroendocrine tumors (NET). However, the detection of a higher number of lesions is not necessarily followed by a modification of disease stage or therapeutic approach. The aim of this study was to assess the impact of 68Ga-DOTANOC PET/CT on the clinical management of NET patients. Methods: The study included 90 patients with pathologic confirmation of NET, CT performed within a month of 68Ga-DOTANOC PET/CT, and a follow-up period of at least 1 y. PET/CT results were compared with CI results. As a standard of reference to finally evaluate PET results, clinical and imaging follow-up data were used. To assess the clinical impact of PET findings, all referring physicians were contacted after PET and asked about how patients were managed. Stage or therapy modifications were independently recorded, and the overall impact was evaluated patient by patient if PET results either affected therapy or caused a change in disease stage. Results: Considering PET/CT and CI concordant cases (47/90 [52.2%]), PET findings affected the therapeutic management in 17 of 47 (36.2%) patients. Although PET did not result in modification of disease stage, 68Ga-DOTANOC detected a higher lesion number in most patients. PET/CT and CI findings were discordant in 42 of 90 (46.7%) patients: PET resulted in a modification of stage in 12 patients (28.6%) and affected the treatment plan in 32 patients (76.2%). PET and CT were both equivocal in 1 patient (1/90). Considering all cases, 68Ga-DOTANOC PET/CT affected either stage or therapy in 50 of 90 (55.5%) patients. The most frequent impact on management (27 patients) was the initiation or continuance of peptide receptor radionuclide therapy, followed by the initiation or continuance of somatostatin analog medical treatment (7 patients) and referral to surgery (6 patients). PET prevented unnecessary surgery in 6 patients and excluded from treatment with somatostatin analogs 2 patients with NET lesions that did not express somatostatin receptors. Less frequent impacts on management included the initiation of radiotherapy (1 patient), further diagnostic investigation (1 patient), and liver transplantation (1 patient). Conclusion: 68Ga-DOTANOC PET/CT either affected stage or caused a therapy modification in more than half the patients, thus confirming the clinical role of PET in the management of NET.

Role of [18F]Fluorodeoxyglucose Positron Emission Tomography Scan in the Follow-Up of Lymphoma

PURPOSE In lymphoma, [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) is routinely used for initial staging, early evaluation of treatment response, and identification of disease relapse. However, there are no prospective studies investigating the value of serial FDG-PET over time in patients in complete remission. PATIENTS AND METHODS All patients with lymphoma who achieved the first complete remission were prospectively enrolled onto the study and scheduled for serial FDG-PET scans at 6, 12, 18, and 24 months; further scans were then carried out on an annual basis. Overall, the population included 421 patients (160 patients with Hodgkins lymphoma [HL], 183 patients with aggressive non-Hodgkins lymphoma [NHL], and 78 patients with indolent follicular NHL). All patients had a regular follow-up evaluation, including complete clinical and laboratory evaluation, and final assessment of any suspect FDG-PET findings using other imaging procedures (computed tomography [CT] scan) and/or biopsy and/or clinical evolution. FDG-PET findings were reported as positive for relapse, inconclusive (when equivocal), or negative for relapse. RESULTS PET enabled documentation of lymphoma relapse in 41 cases at 6 months, in 30 cases at 12 months, in 26 cases at 18 months, in 10 cases at 24 months, and in 11 cases at more than 36 months. All 36 patients with inconclusive positive PET underwent biopsy; only 12 (33%) of 36 patients had a concomitant suggestion of positivity on CT. A lymphoma relapse was diagnosed in 24 (66%) of 36 patients. CONCLUSION Our results confirm FDG-PET as a valid tool for follow-up of patients with HL and NHL. In patients with inconclusive positive results, histologic confirmation plays an important role in identifying true relapse.

Predictive role of positron emission tomography (PET) in the outcome of lymphoma patients

An extensive analysis of the reliability of positron emission tomography (PET) after induction treatment in patients with Hodgkins disease (HD) or aggressive non-Hodgkins lymphoma (NHL). In all, 75 untreated patients with HD (n=41) or aggressive NHL (n=34) were studied with both PET and CT scans following standard chemotherapy induction therapy (ABVD or MACOP-B) with/without radiotherapy. Histopathological analysis was performed when considered necessary. After treatment, four out of five (80%) patients who were PET+/CT− relapsed, as compared with zero out of 29 patients in the PET−/CT− subset. Among the 41 CT+ patients, 10 out of 11 (91%) who were PET+ relapsed, as compared with 0 out of 30 who were PET−. The actuarial relapse-free survival (RFS) rates were 9 and 100% in the PET+ and PET− subsets, respectively (P=0.00001). All five patients who were PET+/CT− underwent a lymph node biopsy: in four (80%) cases, persistent lymphoma and was confirmed at histopathological examination. Two HD patients who were PET−/CT+ (with large residual masses in the mediastinum or lung) were submitted to biopsy, which in both cases revealed only fibrosis. In HD and aggressive NHL patients, PET positivity after induction treatment is highly predictive for the presence of residual disease, with significant differences being observable in terms of RFS. PET negativity at restaging strongly suggests the absence of active disease; histopathological verification is important in patients who show PET positivity.

A phase II trial of CHOP chemotherapy followed by yttrium 90 ibritumomab tiuxetan (Zevalin) for previously untreated elderly diffuse large B-cell lymphoma patients

BACKGROUND A prospective, single-arm, open-label, nonrandomized phase II combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus radioimmunotherapy trial was conducted to evaluate the efficacy and safety in untreated elderly diffuse large B-cell lymphoma (DLBCL) patients. PATIENTS AND METHODS From February 2005 to April 2006, in our institute we treated 20 eligible elderly (age > or =60 years) patients with previously untreated DLBCL using a novel regimen consisting of six cycles of CHOP chemotherapy followed 6-10 weeks later by (90)Y ibritumomab tiuxetan. RESULTS The overall response rate to the entire treatment regimen was 100%, including 95% complete remission (CR) and 5% partial remission. Four (80%) of the five patients who achieved less than a CR with CHOP improved their remission status after radioimmunotherapy. With a median follow-up of 15 months, the 2-year progression-free survival was estimated to be 75%, with a 2-year overall survival of 95%. The (90)Y ibritumomab tiuxetan toxicity included grade > or =3 hematologic toxicity in 12 of 20 patients; the most common grade > or =3 toxic effects were neutropenia (12 patients) and thrombocytopenia (7 patients). Transfusions of red blood cells and/or platelets were given to one patient. CONCLUSION This study has established the feasibility, tolerability, and efficacy of this regimen for elderly patients with DLBCL.

Role of 11C-choline PET/CT in the re-staging of prostate cancer patients with biochemical relapse and negative results at bone scintigraphy

AIM to evaluate the utility of (11)C-choline PET/CT in prostate cancer (PC) patients who have demonstrated a biochemical recurrence and a negative bone scintigraphy (BS). MATERIALS AND METHODS 123 consecutive PC patients (mean age 67.6 years; range 54-83) with a biochemical relapse (mean PSA value 3.3ng/mL; range 0.2-25.5) after radical prostatectomy (RP) were included in our retrospective study. Patients underwent a BS that resulted negative and a (11)C-choline PET/CT within 4 months from BS (range: 1 day to 4 months; mean: 2.5 months). Validation of results was established by: (1) a positive biopsy, (2) a positive subsequent BS, CT or MR and (3) a normalization of (11)C-choline uptake after systemic therapy or a progression of the disease. RESULTS (11)C-choline PET/CT was positive in 42/123 patients (34.1%). (11)C-choline PET/CT detected lesions in: bone (10 patients), lymph-nodes (20 patients), bone and lymph nodes (7 patients), bone and lung (1 patient), lymph-nodes and lung (1 patient), local relapse (3 patients). Overall, (11)C-choline PET/CT showed a total of 30 unknown bone lesions in 18/123 (14.6%) patients. CONCLUSION (11)C-choline PET/CT showed a better sensitivity than BS in patients with biochemical relapse after RP: (11)C-choline PET/CT detected unknown bone lesions in 18/123 (14.6%) patients.

COMBINED 18F-FDG-PET/CT IMAGING IN RADIOTHERAPY TARGET DELINEATION FOR HEAD-AND-NECK CANCER

PURPOSE To evaluate the effect of the use of (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in radiotherapy target delineation for head-and-neck cancer compared with CT alone. METHODS AND MATERIALS A total of 38 consecutive patients with head-and-neck cancer were included in this study. The primary tumor sites were as follow: 20 oropharyngeal tumors, 4 laryngeal tumors, 2 hypopharyngeal tumors, 2 paranasal sinuses tumors, 9 nasopharyngeal tumors, and 1 parotid gland tumor. The FDG-PET and CT scans were performed with a dedicated PET/CT scanner in one session and then fused. Subsequently, patients underwent treatment planning CT with intravenous contrast enhancement. The radiation oncologist defined all gross tumor volumes (GTVs) using both the PET/CT and CT scans. RESULTS In 35 (92%) of 38 cases, the CT-based GTVs were larger than the PET/CT-based GTVs. The average total GTV from the CT and PET/CT scans was 34.54 cm(3) (range, 3.56-109) and 29.38 cm(3) (range, 2.87-95.02), respectively (p < 0.05). Separate analyses of the difference between the CT- and PET/CT-based GTVs of the primary tumor compared with the GTVs of nodal disease were not statistically significant. The comparison between the PET/CT-based and CT-based boost planning target volumes did not show a statistically significant difference. All patients were alive at the end of the follow-up period (range, 3-38 months). CONCLUSION GTVs, but not planning target volumes, were significantly changed by the implementation of combined PET/CT. Large multicenter studies are needed to ascertain whether combined PET/CT in target delineation can influence the main clinical outcomes.

68ga-dota-noc: a new Pet tracer for evaluating patients with bronchial carcinoid

BackgroundConventional imaging techniques [computed tomography (CT), ultrasound, magnetic resonance] and somatostatin receptor scintigraphy are often insufficient to make a conclusive diagnosis of bronchial carcinoid (BC). PET is commonly used for the assessment of lung cancer but 18F-fluorodeoxyglucose, the most frequently used PET tracer, presents a low sensitivity for the detection of neuroendocrine tumours (NETs). New PET radiopharmaceuticals such as 68Ga-DOTA peptides, which directly bind to somatostatin receptors and are usually expressed on NET cell surfaces, have been reported to be superior to both morphological and somatostatin receptor scintigraphy imaging for gastroenteropancreatic NETs. However, their role in BC has never been evaluated. Our aim is to evaluate the role of 68Ga-DOTA-NOC (68Ga-labelled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-Nal3-octreotide) PET for the assessment of BC patients. MethodsTen patients with pathologically proven well-differentiated BC and one patient with highly suggestive CT images for BC were studied by 68Ga-DOTA-NOC PET/CT. PET findings were compared with clinical follow-up, pathology and contrast-enhanced CT findings. Results68Ga-DOTA-NOC PET/CT detected at least one lesion in nine of 11 patients and was negative in two. PET/CT and contrast-enhanced CT were discordant in eight of 11 patients, whereas in only three patients both provided similar results. PET/CT detected a higher number of lesions in five patients and excluded malignancy at sites considered positive on CT in three of 11; follow-up confirmed PET/CT findings in all patients. In PET/CT-positive patients, the mean maximal standardized uptake value was 25.9 [4.4–60.5]. On a clinical basis, PET/CT provided additional information in nine of 11 patients leading to the changes in the clinical management of three of nine patients. ConclusionPET/CT with 68Ga-DOTA-NOC was useful in BC patients because it led to a better evaluation of the extent of the disease.