Federico Fallanca

Early chemotherapy intensification with BEACOPP in advanced-stage Hodgkin lymphoma patients with a interim-PET positive after two ABVD courses

Interim 2‐[18F]Fluoro‐2‐deoxy‐D‐glucose Positron Emission Tomography performed after two chemotherapy cycles (PET‐2) is the most reliable predictor of treatment outcome in ABVD‐treated Hodgkin Lymphoma (HL) patients. We retrospectively analysed the treatment outcome of a therapeutic strategy based on PET‐2 results: positive patients switched to BEACOPP, while negative patients continued with ABVD. Between January 2006 and December 2007, 219 newly diagnosed HL patients admitted to nine centres were enrolled; 54 patients, unfit to receive this treatment were excluded from the analysis. PET‐2 scans were reviewed by a central panel of nuclear medicine experts, according to the Deauville score ( Meignan, 2009 ). After a median follow up of 34 months (12–52) the 2‐year failure free survival (FFS) and overall survival for the entire cohort of 165 patients were 88% and 98%; the FFS was 65% for PET‐2 positive and 92% for PET‐2 negative patients. For 154 patients in which treatment was correctly given according to PET‐2 review, the 2‐year FFS was 91%: 62% for PET‐2 positive and 95% for PET‐2 negative patients. Conclusions: this strategy, with BEACOPP intensification only in PET‐2 positive patients, showed better results than ABVD‐treated historic controls, sparing BEACOPP toxicity to the majority of patients (Clinical Trials.gov Identifier NCT00877747).

Validation of an optimized SPM procedure for FDG-PET in dementia diagnosis in a clinical setting

Diagnostic accuracy in FDG-PET imaging highly depends on the operating procedures. In this clinical study on dementia, we compared the diagnostic accuracy at a single-subject level of a) Clinical Scenarios, b) Standard FDG Images and c) Statistical Parametrical (SPM) Maps generated via a new optimized SPM procedure. We evaluated the added value of FDG-PET, either Standard FDG Images or SPM Maps, to Clinical Scenarios. In 88 patients with neurodegenerative diseases (Alzheimers Disease—AD, Frontotemporal Lobar Degeneration—FTLD, Dementia with Lewy bodies—DLB and Mild Cognitive Impairment—MCI), 9 neuroimaging experts made a forced diagnostic decision on the basis of the evaluation of the three types of information. There was also the possibility of a decision of normality on the FDG-PET images. The clinical diagnosis confirmed at a long-term follow-up was used as the gold standard. SPM Maps showed higher sensitivity and specificity (96% and 84%), and better diagnostic positive (6.8) and negative (0.05) likelihood ratios compared to Clinical Scenarios and Standard FDG Images. SPM Maps increased diagnostic accuracy for differential diagnosis (AD vs. FTD; beta 1.414, p = 0.019). The AUC of the ROC curve was 0.67 for SPM Maps, 0.57 for Clinical Scenarios and 0.50 for Standard FDG Images. In the MCI group, SPM Maps showed the highest predictive prognostic value (mean LOC = 2.46), by identifying either normal brain metabolism (exclusionary role) or hypometabolic patterns typical of different neurodegenerative conditions.

C-11 choline versus F-18 fluorodeoxyglucose for imaging meningiomas: an initial experience.

Purpose: Positron emission tomography/computed tomography (PET/CT) with C-11 choline has been used for staging, restaging, and follow-up of various tumors, whereas its role for imaging meningiomas has only been preliminarily explored. The aim of this study was to compare C-11 choline and F-18 fluorodeoxyglucose (F-18 FDG) uptake in meningiomas and relate these findings to the histopathological analysis. Methods: Two sequential three-dimensional PET/CT scans with 370 MBq (10 mCi) of C-11 choline and 370 MBq (10 mCi) of F-18 FDG were performed 2 hours apart in 7 patients with histologically confirmed meningiomas. Five patients had WHO grade I and 2 had WHO grade II meningioma. For each scan, two-dimensional regions of interest were drawn on tumor boundaries and on the contralateral side on CT images and copied to the corresponding PET images. SUVmax and tumor-to-background ratio were calculated. Results: Relative to the contralateral side, C-11 choline uptake was increased in all meningiomas, whereas F-18 FDG uptake was decreased in 6 patients and increased in 1 of the 2 patients with grade II meningiomas. In the whole group, SUVmax of C-11 choline and F-18 FDG were 3.6 ± 1.3 and 5.7 ± 1.3, respectively. The tumor-to-background ratio for C-11 choline was much higher than that for F-18 FDG (5.3 ± 0.8 vs. 0.9 ± 0.2, respectively) (P < 0.001). The uptake of C-11 choline was higher in patients with grade II than in grade I meningiomas. Conclusions: These preliminary results suggest that C-11 choline may better image meningiomas in comparison with F-18 FDG. Clinical applications of C-11 choline PET/CT for grading and follow-up of meningiomas need to be assessed in further studies.

Role of 18FDG-PET/CT in detecting relapse during follow-up of patients with Hodgkin’s lymphoma

The role of 18FDG-PET/CT during follow-up of patients affected by Hodgkin’s lymphoma (HL) in complete remission after treatment is not fully elucidated, since a wide use of 18F fluorodeoxyglucose positron emission tomography/computed tomography (18FDG-PET/CT) in this setting could be limited by a relative high rate of false-positive results. Herein, we summarize a retrospective analysis of 27 patients with Hodgkin’s lymphoma in complete remission after the first-line (n = 20) or salvage (n = 7) therapy receiving serial 18FDG-PET/CT scans during follow-up. Out of 165 scans, 13 were suspected for relapse, which was confirmed in seven patients. All relapses were correctly identified by 18FDG-PET/CT positivity, with a 100% sensitivity; false-positive rate was 46% and negative predictive value was 100%. True-positive findings were mostly associated with multiple sites, subdiaphragmatic involvement, and/or previous sites of disease. According to our results, we conclude that performing routine PET/CT scan during follow-up of those patients who are at high risk of relapse would be advisable, although caution must be adopted when interpreting PET/CT results due to the relatively high rate of false-positive findings. If FDG abnormal uptake is present at multiple nodal sites, subdiaphragmatic lymph nodes, or previous sites of disease, histological verification of PET abnormal findings is warranted.

Pretransplantation [18-F]fluorodeoxyglucose positron emission tomography scan predicts outcome in patients with recurrent Hodgkin lymphoma or aggressive non-Hodgkin lymphoma undergoing reduced-intensity conditioning followed by allogeneic stem cell transplantation.

The use of positron emission tomography (PET) scanning in Hodgkin lymphoma (HL) and aggressive non‐Hodgkin lymphoma (HG‐NHL) has recognized prognostic value in patients who are receiving chemotherapy or undergoing autologous stem cell transplantation (SCT). In contrast, the role of PET before reduced‐intensity conditioning (RIC) and followed by allogeneic SCT has not been investigated to date.

Treating Pulmonary Silicosis by Blocking Interleukin 1

with favorable neurologic outcome and with no or slight disabilities after 1 year for three of them. Interestingly, not all patients had hemostasis disorders that could have precipitated the neurological injury. Moreover, vv-ECMO is not a risk factor for cerebral embolism as the extracorporeal circuit is only on the right side. Brain microbleeds are a well-recognized condition that can be diagnosed either on T2* or susceptibility-weighted imaging MRI sequences. They can be related either to an arteriolopathy (cerebral small vessel disease, amyloid angiopathy) or to diffuse emboli (endocarditis, fat emboli) (5). In our four cases, we observed a remarkably similar pattern of diffuse, symmetrical brain microbleeds in the white matter, predominating both in the subcortical white matter (U-fibers) and in the deep white matter (internal and external capsules). This pattern is strikingly similar to what has been reported in patients with fat emboli (5). However, none of our patients had any bone injury that could have caused this condition. Brain microbleeds can also occur in patients with endocarditis, but they appear to be scarcer (6), and none of our patients had endocarditis. Thus, our patients most likely underwent another mechanism of diffuse microemboli that was specifically related to ECMO. Because this complication remains exceptional in patients under ECMO, it should be promoted by another cofactor. Although we did not identify such a common cofactor in our patients, one can notice that two of them (cases 1 and 2) had chronic alcoholism, and one of them (case 4) had a history of multiple sclerosis: both are long-lasting proinflammatory conditions that may have fostered distal microhemorrhages in cerebral small vessels. In our patients, the demonstration on MRI of diffuse, innumerable brain microbleeds would have suggested a poor neurological outcome. However, quite unexpectedly, all four patients had a long-term favorable cognitive outcome. The absence of ischemic lesions on diffusion-weighted imaging (see the online supplement) in all four patients at the acute phase suggests that if microemboli have occurred, they were microscopic enough not to cause ischemic damage in the brain. Areas of edema were present in three patients at the acute phase (cases 1–3); they were associated with elevated apparent diffusion coefficient (see the online supplement), suggesting potentially reversible edema, which was demonstrated by follow-up MRI in case 2. Neurologists and intensivists should be aware of this rare complication of ECMO support and of its potentially favorable outcome. Our series strongly suggests that the occurrence of diffuse brain microbleeds in patients receiving ECMO should not motivate any limitation in active patient care. n

Imaging of a thymoma incidentally detected by C-11 choline PET/CT

The integrated modality positron emission tomography/computed tomography (PET/CT) with C-11 choline is an established diagnostic tool for restaging prostate cancer patients with a biochemical failure after primary treatment. Thymoma is a rare tumor originating in thymus epithelial cells, asymptomatic in one-third to one-half of patients, and often occurring in the fourth and fifth decades of life. In the present case, C-11 choline PET/CT was performed in a prostate cancer patient with a biochemical relapse, to restage the disease. In addition to the detection of local recurrent disease in prostatic fossa, an abnormal C-11 choline increased uptake in mediastinum was reported. The mediastinal finding was initially wrongly interpreted by clinicians as a lymph nodal metastasis from prostate cancer. However, histopathological analysis confirmed the presence of a thymoma. Although rare, thymoma has to be considered as differential diagnosis in case of mediastinal masses presenting C-11 choline PET/CT positive findings, to avoid inappropriate patient management.

Early Chemotherapy Intensification With Escalated BEACOPP in Patients With Advanced-Stage Hodgkin Lymphoma With a Positive Interim Positron Emission Tomography/Computed Tomography Scan After Two ABVD Cycles: Long-Term Results of the GITIL/FIL HD 0607 Trial

Purpose To investigate the progression-free survival (PFS) of patients with advanced Hodgkin lymphoma (HL) after a risk-adapted treatment strategy that was based on a positive positron emission tomography scan performed after two doxorubicin, vinblastine, vincristine, and dacarbazine (ABVD) cycles (PET2). Patients and Methods Patients with advanced-stage (IIB to IVB) HL were consecutively enrolled. After two ABVD cycles, PET2 was performed and centrally reviewed according to the Deauville five-point scale. Patients with a positive PET2 were randomly assigned to four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) followed by four cycles of standard BEACOPP with or without rituximab. Patients with a negative PET2 continued ABVD, and those with a large nodal mass at diagnosis (≥ 5 cm) in complete remission with a negative PET at the end of chemotherapy were randomly assigned to radiotherapy or no further treatment. The primary end point was 3-year PFS. Results Of 782 enrolled patients, 150 (19%) had a positive and 630 (81%) a negative PET2. The 3-year PFS of all patients was 82%. The 3-year PFS of those with a positive and negative PET2 was 60% and 87%, respectively ( P < .001). The 3-year PFS of patients with a positive PET2 assigned to BEACOPP with or without rituximab was 63% versus 57% ( P = .53). In 296 patients with both interim and post-ABVD-negative PET who had a large nodal mass at diagnosis, radiotherapy was randomly added after chemotherapy without a significant PFS improvement (97% v 93%, respectively; P = .29). The 3-year overall survival of all 782 patients was 97% (99% and 89% for PET2 negative and positive, respectively). Conclusion The PET-driven switch from ABVD to escalated BEACOPP is feasible and effective in high-risk patients with advanced-stage HL.

Cervical thymic hyperplasia after chemotherapy in an adult patient with Hodgkin lymphoma: a potential cause of false-positivity on [18F]FDG PET/CT scanning

A 30-year-old woman was referred for a positron emission tomography/computed tomography (PET/CT) scan with [F]fluorodeoxyglucose ([F]FDG) for staging of Hodgkin lymphoma (HL), nodular sclerosis type, diagnosed by biopsy of a bulky mediastinal mass. The scan demonstrated tracer uptake in the cervical lymph nodes bilaterally, in the bulky mediastinal mass and in the lungs, spleen and some lumbar and sacral vertebral bodies (top left). A PET/CT scan performed 1 month after completion of treatment (doxorubicin, bleomycin, vinblastine, dacarbazine, six cycles) showed complete metabolic response (centre of top left image). This finding was confirmed by another PET/CT performed 3 months later. Seven months after the end of chemotherapy, a follow-up PET/CT showed an intense tracer uptake [standardized uptake value (SUV)max = 4AE1 g/ml] in the left supraclavicular region (black arrow, right of top left image), suspicious for lymph node recurrence of HL. A contrast enhanced CT performed 3 d after the PET/CT showed a 20 · 14 mm oval nodule located medially to the jugular vein, suspicious for malignant adenopathy (lower left). A fused PET/ CT axial image showed increased [F]FDG uptake in the solid component of the nodule (right of lower left image). The lesion was resected. Histopathological examination (right) showed well-represented thymic compartments, including cortical (white arrow) and medullary areas (white arrowhead). In addition, a well-formed Hassal’s corpuscle was recognizable (black arrow) (Haematoxylin and Eosin, 200·). Thymic hyperplasia after chemotherapy is a common phenomenon in children and can occasionally be observed in young adults. This phenomenon has seldom been described in older adults. A normal variant in which the thymus extends superiorly to the left brachiocephalic vein and anteriorly to the brachiocephalic artery or left common carotid artery can occur. This can be visualized on CT as a soft tissue nodule that can mimic superior mediastinal adenopathy. In paediatric patients, [F]FDG uptake in a superior mediastinal nodule can be correctly attributed to ectopic thymus whether the intensity of [F]FDG SUVmax or the morphological characteristics are similar to the thymus. In the present case, the lack of significant thymic activity, the absence of thymic enlargement in the anterior mediastinum, the cervical involvement at first diagnosis, and the CT appearance of the soft tissue nodule led to the erroneous suspicion of recurrence of lymphoma. This report shows that increased [F]FDG uptake in hyperplastic ectopic thymic tissue following chemotherapy can also occur in adult patients. This rare normal variant should be kept in mind in PET/CT studies in patients with HL.

18F-FDG PET/CT in gastric MALT lymphoma: a bicentric experience

PurposeThe role of 18F-FDG-PET/CT in evaluating gastric MALT lymphoma is still controversial. In the literature the detection rate of 18F-FDG-PET/CT in patients with gastric MALT lymphoma is variable, and the reason for this heterogeneity is not still clear. Our aim was to investigate the particular metabolic behavior of these lymphoma.Materials and methodsSixty-nine patients (26 female, 43 male) with histologically confirmed gastric MALT lymphoma who underwent a 18F-FDG-PET/CT for initial staging from two centers were included. The PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value (SUVmax), lesion-to-liver SUVmax ratio, and lesion-to-blood pool SUVmax ratio and compared with Ann Arbor stage, epidemiological (age, sex), histological (presence of gastritis, ulcer, H. pylori infection, plasmacytic differentiation, Ki-67 index), and morphological (tumor size, superficial lesions or mass-forming) characteristics.ResultsThirty-six patients (52 %) had positive PET/CT (average SUVmax was 9±6.7; lesion-to-liver SUVmax ratio 3.7±2.6, lesion-to-blood pool SUVmax ratio 4.8±3.3) at the corresponding gastric lesion; the remaining 33 were not 18F-FDG-avid. In the univariate analysis, 18F-FDG avidity was significantly associated with morphological features (mass forming p<0.001 and high maximum diameter p<0.001), Ann Arbor stage (p=0.010), and Ki67 index (p<0.001) and not correlated with age, sex, presence of gastritis, ulcer, Helicobacter pylori infection, and plasmacytic differentiation. In the multivariate analysis, the correlations with gross morphological appearance, Ann Arbor stage, and Ki-67 score were confirmed. SUVmax, lesion-to-liver SUVmax ratio, and lesion-to-blood pool SUVmax ratio correlated significantly only with Ki67 index (p=0.047; p=0.012; p=0.042).Conclusions18F-FDG avidity was noted in 52 % of gastric MALT lymphoma and this avidity is correlated with gross morphological characteristics, tumor stage, and Ki-67 index. SUVmax, lesion-to-liver SUVmax ratio, and lesion-to-blood pool SUVmax ratio are correlated only with Ki-67 index, and only lesion-to-liver SUVmax ratio was independently associated with Ki-67 score.