Brain and whole-body FDG-PET in diagnosis, treatment monitoring and long-term follow-up of primary CNS lymphoma.

BACKGROUND: Positron emission tomography (PET) with F-18-labeled fluorodeoxyglucose (FDG) provides remarkable accuracy in detection, treatment monitoring and follow-up of systemic malignant lymphoma. Its value in the management of patients with primary central nervous system lymphoma (PCNSL) is less clear. PATIENTS AND METHODS: In a prospective trial, 42 FDG-PET examinations were performed in ten immunocompetent patients with newly diagnosed or recurrent PCNSL before and repeatedly during and after the treatment. Brain and whole body FDG-PET were compared to brain MRI and extra-cerebral CT, respectively. RESULTS: Before the treatment, 6 of 10 patients had congruent findings on FDG-PET and MRI of the brain. Three patients had lesions on brain MRI, not detected by FDG-PET. One patient had additional FDG-PET positive lesions inconspicuous in MRI. The follow-up suggested FDG-PET to be false positive in these lesions. After the treatment, brain PET was in agreement with MRI in 6 of 8 patients. In the remaining 2 patients there were persistent lesions in brain MRI whereas FDG-uptake was reduced to normal values. In the long-term follow-up of 5 patients (63-169 weeks), 3 patients retained normal in both PET and MRI. In 2 patients a new focal pathologic FDG-uptake was detected 69 and 52 weeks after the end of the treatment. In one of these patients, recurrence was confirmed by MRI not until 9 weeks after PET. CONCLUSIONS: Brain FDG-PET may contribute valuable information for the management of PCNSL, particularly in the assessment of the treatment response. Integration of FDG-PET into prospective interventional trials is warranted to investigate prognostic and therapeutic implications.

Takayasu arteritis is characterised by disturbances of B cell homeostasis and responds to B cell depletion therapy with rituximab.

UNLABELLED: Introduction Takayasu arteritis (TA) is a large vessel vasculitis involving the aorta and its major branches. T cell-mediated autoimmunity is thought to play a major role in its pathogenesis, while the role of B cells is still unclear. METHODS: B cell subsets in the peripheral blood of 17 patients with TA were analysed and compared with nine patients with active systemic lupus erythematosus (SLE) and nine healthy controls by flow cytometry. Based on these findings, three patients with active refractory TA were treated with B cell depletion therapy (BCDT) using monoclonal anti-CD20 antibodies (rituximab). RESULTS: The absolute number and frequency of peripheral blood CD19(+)/CD20(-)/CD27(high) antibody-secreting cells in patients with active TA was significantly higher than in healthy donors. As in active SLE, the majority of these cells are newly generated plasmablasts which significantly correlated with TA activity. Three patients with active refractory TA and expansion of plasmablasts were successfully treated with BCDT, which resulted in remission. CONCLUSION: Disturbances of B cell homeostasis may be critical in TA. Circulating plasmablasts could be a useful biomarker of disease activity and a tool for selecting appropriate candidates for BCDT. B cells and plasmablasts/plasma cells may therefore represent novel targets for effective therapies for TA.

First report on a prospective trial with yttrium-90-labeled ibritumomab tiuxetan (Zevalin) in primary CNS lymphoma.

Most patients with primary CNS lymphoma (PCNSL) relapse after primary therapy. Standard salvage treatment has not yet been established in PCNSL. Anti-CD20 immunotherapy has expanded treatment options in systemic B-cell lymphoma; however, its use is limited by reconstitution of the blood-brain barrier after tumor shrinkage. The aim of this phase II trial was to evaluate the therapeutic efficacy, toxicity, and biodistribution of yttrium-90 ((90)Y) ibritumomab tiuxetan in PCNSL. Ten patients with relapsed PCNSL were included in a phase II trial and treated with the (90)Y-labeled anti-CD20 antibody ibritumomab tiuxetan. Nine patients actually received the planned radioimmunotherapy. In six patients, biodistribution of the antibody was measured by indium-111 ((111)In) ibritumomab tiuxetan whole-body scans and single-photon-emission CT (SPECT) of the brain. All patients were evaluated for toxicity and response at least 4 weeks after therapy. Four patients responded: one patient had a complete response lasting 30+ months, and three patients had short-lived responses of

Yttrium-90 ibritumomab tiuxetan radioimmunotherapy in primary cutaneous B-cell lymphomas: first results of a prospective, monocentre study.

Radioimmunotherapy with Yttrium-90 ((90)Y) ibritumomab tiuxetan (IT) has been shown to be effective in systemic B-cell lymphomas. We conducted a pilot study to evaluate the outcome and assess complications of (90)Y IT therapy in patients with primary cutaneous B-cell lymphomas (PCBCL). Ten patients, all but one, with relapsed PCBCL were included and treated with rituximab (250 mg m(-2)/body surface) on days 1 and 8 followed by a single dose of (90)Y IT (11-15 MBq kg(-1)). The overall response rate was 100%. The complete response rate was 100%. The median time to relapse was 12 months. Ongoing remissions were achieved in four patients (median follow-up 19 months). Transient and reversible myelosuppression (grade 3-4) was the most frequent adverse event. Radioimmunotherapy with (90)Y IT is an effective treatment in relapsed primary cutaneous follicle centre lymphomas and diffuse large B-cell lymphoma leg-type. Further investigations in controlled randomised clinical trials evaluating the role of (90)Y IT versus rituximab in PCBCL are needed.

Single photon emission computed tomography: an alternative imaging modality in left ventricular evaluation.

Various diagnostic imaging modalities have been used for quantitative left ventricular (LV) parameters. Because of the suboptimal value of the most widely used technology, two-dimensional (2D) echocardiography, 3D ultrasonographic imaging has improved accuracy for LV volume and function. Single photon emission computed tomography (SPECT) is another diagnostic method where LV volumetric and functional parameters can be accurately provided by gated myocardial perfusion tomographic slices. First pass radionuclide venticulography is another imaging modality which has some practical limitations. Despite lower ejection fraction (EF) values compared with invasive approach, noninvasive techniques are accurate in determination of normal and depressed EF. Noninvasive techniques with 3D approach including gated SPECT are beneficial for not only global but also regional LV evaluation. It has been mentioned that the slight difference between echocardiography and SPECT could be caused by the diverse population studied. The results of diagnostic stress tests support that SPECT is feasible to use in evaluation of LV volume and functional analysis. Magnetic resonance imaging is an expensive modality to use routinely, but it preserves its importance in selected patients for providing precise LV geometric data.

Multimodal fusion imaging ensemble for targeted sentinel lymph node management: initial results of an innovative promising approach for anatomically difficult lymphatic drainage in different tumour entities.

PURPOSE: There are situations where exact identification and localisation of sentinel lymph nodes (SLNs) are very difficult using lymphoscintigraphy, a hand-held gamma probe and vital dye, either a priori or a posteriori. We developed a new method using a simultaneous injection of two lymphotropic agents for exact topographical tomographic localisation and biopsy of draining SLNs. The purpose of this prospective pilot study was to investigate the feasibility and efficacy of this method ensemble. METHODS: Fourteen patients with different tumour entities were enrolled. A mixture of (99m)Tc-nanocolloid and a dissolved superparamagnetic iron oxide was injected interstitially. Dynamic, sequential static lymphoscintigraphy and SPECT served as pathfinders. MR imaging was performed 2 h after injection. SPECT, contrast MRI and, if necessary, CT scan data sets were fused and evaluated with special regard to the topographical location of SLNs. The day after injection, nine patients underwent SLN biopsy and, in the presence of SLN metastasis, an elective lymph node dissection. RESULTS: Twenty-five SLNs were localised in the 14 patients examined. A 100% fusion correlation was achieved in all patients. The anatomical sites of SLNs detected during surgery showed 100% agreement with those localised on the multimodal fusion images. SLNs could be excised in 11/14 patients, six of whom had nodal metastasis. CONCLUSION: Our novel approach of multimodal fusion imaging for targeted SLN management in primary tumours with lymphatic drainage to anatomically difficult regions enables SLN biopsy even in patients with lymphatic drainage to obscure regions. Currently, we are testing its validity in larger patient groups and other tumour entities.

Impact of sentinel lymph node biopsy in patients with Merkel cell carcinoma: results of a prospective study and review of the literature.

PURPOSE: Merkel cell carcinoma (MCC) is the most aggressive of the cutaneous malignancies, showing a propensity to spread to regional lymph nodes (LNs). The aim of this prospective study was to examine the feasibility and clinical impact of sentinel lymph node biopsy (SLNB) in this cutaneous malignancy. METHODS: The study population comprised 23 patients with stage I MCC (median age 70 years, range 50-85 years). Lymphoscintigraphic mapping with( 99 m)Tc-nanocolloid was performed in all patients. Sentinel lymph nodes (SLNs) were identified, excised and analysed in serial sections by conventional histopathology and cytokeratin-20 immunohistochemistry. RESULTS: Metastatic disease was determined in the SLNs of 11 patients (47.8%). Elective lymph node dissection (ELND) was performed in eight of these 11 patients, four of whom had additional positive LNs. During follow-up (median 36.1 months, range 3-79 months), seven of the 23 patients (30%) relapsed: four had a local recurrence and three, in-transit metastases. Recurrence developed in two SLN-negative patients with local LN metastases and in one SLN-positive patient with distant metastases. This patient died, representing the only tumour-related death in our sample. Median survival was 49.1 and 35.5 months for SLN-negative and SLN-positive patients, respectively. This difference was not statistically significant (p=0.3452). CONCLUSION: SLNB allows for exact nodal staging in patients with MCC. Whether additional ELND is of further benefit remains unclear.

Subareolar injection of technetium-99m nanocolloid yields reliable data on the axillary lymph node tumour status in breast cancer patients with previous manipulations on the primary tumour: a prospective study of 117 patients.

According to recently published guidelines, histological clarification by interventional techniques should be undertaken before planning the surgical management of patients with breast carcinoma. In patients with previous manipulations on the primary tumour, peritumoural injection in the context of preoperative scintigraphic detection of the sentinel lymph nodes is not possible. The aim of this prospective study was to clarify whether subareolar injection of nanocolloid can yield reliable data on the axillary lymph node tumour status in breast cancer patients with previous manipulations on the primary tumour. To date, 117 women (age 31-80 years) with breast carcinoma have been enrolled. All of these patients had undergone a biopsy (n=88) or surgery on the primary tumour (n=29) and were without clinical suspicion of lymph node metastases. Subareolar injection of 40 MBq technetium-99m nanocolloid was carried out in at least eight deposits around the areolar margin [one deposit in the middle of each quadrant and one deposit at each quadrant intersection (0.05 ml/deposit)]. Immediately after injection, dynamic and static lymphoscintigraphy of the axillary, thoracic and cervical areas was performed in various views with a gamma camera (LEAP collimator, 256x256 matrix). Lymphatic drainage was directed exclusively to the ipsilateral axilla. Sentinel lymph node biopsy and elective dissection of axillary lymph nodes were performed in all patients. All lymph nodes removed were examined by histology and immunohistochemistry. In 26 patients, lymph node metastases were found in the sentinel lymph nodes. In six of them, non-sentinel lymph nodes also showed tumour involvement. In the remaining 91 patients, lymph node metastases could be found neither in sentinel lymph nodes nor in non-sentinel lymph nodes. In conclusion, subareolar nanocolloid injection can yield reliable information on the axillary lymph node tumour status in patients with previous manipulations on the primary tumour in the breast.

Peritumoural versus subareolar administration of technetium-99m nanocolloid for sentinel lymph node detection in breast cancer: preliminary results of a prospective intra-individual comparative study.

The scintigraphic detection of sentinel lymph nodes (SNs) in early-stage breast cancer is a widely accepted diagnostic method. However, which radiotracer administration mode should be used is still controversial. This prospective study aimed to intra-individually compare the detection rates obtained after peritumoural versus subareolar injection with regard to SN number and localisation. Fifty-one women (age, 32-76 years) with breast cancer were investigated on two consecutive days. On day 1, 140-400 MBq technetium-99m nanocolloid was injected along the peripheral tumour margins. Static lymphoscintigrams of the axilla, thorax and neck were taken in various views 1 and 19 h p.i. On day 2, 10 MBq (99m)Tc-nanocolloid was injected subareolarly in the clock position of the tumour and dynamic and static scans were performed immediately. Thereafter, 30 MBq (99m)Tc-nanocolloid was administered peri-subareolarly and lymphoscintigrams were acquired in a dynamic and static manner. In 49/51 women, the different injection techniques disclosed the identical number and location of SNs in the axilla. In seven patients, the peritumoural injection detected additional SNs in the parasternal group. Axillary SNs were detected as early as 2-15 min following subareolar injection, both in the clock position and peri-subareolarly, as compared with about 1 h after peritumoural administration. Sixteen patients showed at least one tumour-positive SN, and nine also had tumour-positive non-SNs. One patient with a tumour-negative SN, visualised concordantly by both subareolar and peritumoural administration, demonstrated two metastatic non-SNs, yielding a false-negative rate of 5.9%. In conclusion, a simple subareolar injection in the clock position is sufficient for SN detection in breast cancer, if it is accepted that parasternal lymph node detection has no therapeutic consequences.

Influence of fast lymphatic drainage on metastatic spread in cutaneous malignant melanoma: a prospective feasibility study.

The concept of sentinel lymph node biopsy in cutaneous malignant melanoma is widely established. Preoperative cutaneous lymphoscintigraphic mapping is a reliable method for identifying the nodal basins at risk of metastases in melanomas. In this prospective study we investigated the correlation between the scintigraphic appearance time and the metastatic involvement of sentinel lymph nodes. In 276 malignant melanoma patients (137 women, 139 men; age 16-93 years), dynamic and static lymphoscintigraphy was performed after strict intracutaneous application of technetium-99m nanocolloid (40-150 MBq; 0.05 ml/deposit) around the tumour or biopsy scar. Analysis of dynamic scans primarily focussed on the appearance time of sentinel lymph nodes. Sentinel lymph node visualisation 20 min as slow drainage. Fast lymphatic drainage was found in 236 patients, of whom 34 (14.4%) had sentinel lymph node metastases. Twenty-two patients showed hybrid (fast and slow) lymphatic drainage, and eight (36.4%) of them had sentinel lymph node metastases. Seven of the latter demonstrated fast lymphatic drainage, while one showed one positive sentinel lymph node with fast and another with slow drainage. The melanomas of 18 patients demonstrated exclusively slow lymphatic drainage, in all cases without sentinel lymph node metastases. This prospective study indicates that the scintigraphic appearance time of sentinel lymph nodes seems to be a clinically relevant factor for prediction of metastatic spread of cutaneous malignant melanoma. Larger numbers of patients need to be examined to truly assess the benefit of the scintigraphic appearance time compared with other predictors of sentinel lymph node tumour positivity.