Superior vena cava syndrome in thoracic malignancies.

The superior vena cava syndrome (SVCS) comprises various symptoms due to occlusion of the SVC, which can be easily obstructed by pathological conditions (eg, lung cancer, due to the low internal venous pressure within rigid structures of the thorax [trachea, right bronchus, aorta]). The resulting increased venous pressure in the upper body may cause edema of the head, neck, and upper extremities, often associated with cyanosis, plethora, and distended subcutaneous vessels. Despite the often striking clinical presentation, SVCS itself is usually not a life-threatening condition. Currently, randomized controlled trials on many clinically important aspects of SVCS are lacking. This review gives an interdisciplinary overview of the pathophysiology, etiology, clinical manifestations, diagnosis, and treatment of malignant SVCS.

Intensity-modulated radiotherapy for a rendu-osler-weber disease patient with recurrent severe epistaxis: a case report.

We present a case of a Rendu-Osler-Weber disease patient with recurrent life threatening epistaxis demanding multiple blood transfusions despite of repetitive endoscopic laser and electrocoagulations, endovascular embolisation, septodermoplasty, and long-term intranasal dressings. As alternative treatment modalities repeatedly failed and the patient became almost permanently dependent on nasal dressing, we performed a highly conformal intensity-modulated radiotherapy of the nasal cavity; a total dose of 50 Gy in 2 Gy single fractions was applied. The therapy was very well tolerated, no acute toxicities occurred. Two weeks after the last radiation dose had been applied, the nasal dressing could be removed without problems. Endoscopical control revealed an almost avascular white mucosa without any trace of bleeding spots; previously existing hemangiomas and crusts had disappeared. After a 1-year-follow up, the patient had no significant recurrent epistaxis.

Quantitative analysis of extracapsular extension of metastatic lymph nodes and its significance in radiotherapy planning in head and neck squamous cell carcinoma.

PURPOSE: We performed a histopathologic analysis to assess the extent of the extracapsular extension (ECE) beyond the capsule of metastatic lymph nodes (LN) in head and neck cancer to determine appropriate clinical target volume (CTV) expansions. METHODS AND MATERIALS: All tumor-positive LN of 98 patients who underwent a neck dissection with evidence of ECE in at least one LN were analyzed by a single pathologist. The largest diameters of all LN, and in the case of ECE, the maximal linear distance, from the capsule to the farthest extent of tumor or tumoral reaction were recorded. RESULTS: A total of 231 LN with ECE and 200 tumor-positive LN without ECE were analyzed. The incidence of ECE was associated with larger LN size (p < 0.001). Of all tumor-positive LN with a diameter of < 10 mm or < 5 mm, 105/220 (48%) nodes or 17/59 (29%) nodes, respectively, showed evidence of ECE. The mean and median extent values of ECE were 2 and 1 mm (range, 1-10 mm) and the ECE was < or = 5 mm in 97% and < or = 3 mm in 91% of the LN, respectively. Overall, the extent of ECE was significantly correlated with larger LN size (Spearman's correlation coefficient = 0.21; p = 0.001). CONCLUSIONS: The incidence of ECE is associated with larger LN size. However, ECE is found in a substantial number of LN with a diameter of < 10 mm. The use of 10-mm CTV margins around the gross tumor volume seems appropriate to account for ECE in radiotherapy planning of head and neck cancer.

Short Communication: (18)F-immuno-PET: Determination of anti-CD66 biodistribution in a patient with high-risk leukemia.

The monoclonal antibody anti-CD66 labeled with (99m)Tc is widely used as Scintimun granulocyte for bone marrow immunoscintigraphy. Further, recently performed clinical radioimmunotherapy studies with [(90)Y]Y-anti-CD66 proved to be suitable for the treatment of hematologic malignancies. Before radioimmunotherapy with [(90)Y]Y-anti-CD66, dosimetric estimations are required to minimize radiotoxicity and determine individual applicable activities. Planar imaging, using gamma-emitting radionuclides, is conventionally carried out to estimate the absorbed organ doses. In contrast, immuno-PET (positron emission tomography) enables the quantification of anti-CD66 accumulation and provides better spatial and temporal resolution. Therefore, in this study, a semiautomated radiosynthesis of [(18)F]F-anti-CD66 was developed, using the (18)F-acylation agent, N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB). As a proof of concept, an intraindividual comparison between PET and conventional scintigraphy, using (18)F- and (99m)Tc-labeled anti-CD66 in 1 patient with high-risk leukemia, is presented. Both labeled antibodies displayed a similar distribution pattern with high preferential uptake in bone marrow. Urinary excretion of [(18)F]F-anti-CD66 was increased and bone marrow uptake reduced, in comparison to [(99m)Tc]Tc-anti-CD66. Nevertheless, PET-based dosimetry with [(18)F]F-anti-CD66 could provide additional information to support conventional scintigraphy. Moreover, [(18)F]F-anti-CD66 is ideally suited for bone marrow imaging using PET.

[11C]choline PET/CT imaging in occult local relapse of prostate cancer after radical prostatectomy.

PURPOSE: The aim of this study was to assess the accuracy and clinical impact of [(11)C]choline PET/CT for localizing occult relapse of prostate adenocarcinoma after radical prostatectomy. METHODS: Fourty-nine patients with prostate adenocarcinoma, radical prostatectomy, no evidence of metastatic disease, and occult relapse underwent [(11)C]choline PET/CT. Thirty-six of the patients had biochemical evidence and histological evaluation of local recurrence. Thirteen patients had PSA < 0.3 ng/ml and no evidence of active disease after 1 year follow-up. Focal nodular [(11)C]choline uptake in the prostatic fossa was visually assessed and graded on a five point scale. Maximum standardized radioactivity uptake value (SUV(max)) and the lesion size were measured. A receiver operating characteristic (ROC) analysis was performed and the clinical impact of the PET/CT study was determined. RESULTS: [(11)C]choline PET/CT was true positive in 23/33 patients and true negative in 12/13 controls. SUV(max) of local recurrence was 3.0 (median, range 0.6-7.4) and 1.1 (0.4-1.6) in controls (p = 0.0002). Lesion size was 1.7 cm (range 0.9-3.7). Area under the ROC curve for detecting relapse was 0.90 +/- 0.05 and 0.83 +/- 0.06 for visual evaluation and SUV(max), respectively. Sensitivity and specificity of [(11)C]choline PET/CT were 0.73 and 0.88, respectively. [(11)C]choline PET/CT identified 12/17 (71%) patients with a favourable biochemical response to local radiotherapy at 2 year (median, 0.8-3.2 range) follow-up. CONCLUSIONS: Focally increased [(11)C]choline uptake in the prostatic bed reliably predicted local low volume occult relapsing prostate adenocarcinoma after radical prostatectomy and identified 71% of patients with a favourable biochemical response to local radiotherapy.

Evaluation of [11C]-choline positron-emission/computed tomography in patients with increasing prostate-specific antigen levels after primary treatment for prostate cancer.

OBJECTIVE: To evaluate [(11)C]-choline positron-emission tomography (PET)/computed tomography (CT) for detecting clinical recurrence after primary treatment for prostate cancer. PATIENTS AND METHODS: In all, 50 patients with prostate cancer who had had initial therapy (radical prostatectomy in 40, external beam radiation in three and interstitial brachytherapy in seven) had PET/CT using [(11)C]-choline in the presence of an increased or increasing prostate-specific antigen (PSA) level. The mean (range) time to biochemical progression was 22 (2-136) months. Current PSA levels were determined in all patients at the time of examination. The results were correlated with the histopathology reports after targeted biopsy or surgery, and with the clinical follow-up. RESULTS: The mean (median, range) PSA level in patients with positive PET/CT was 3.62 (2.42, 0.5-13.1) ng/mL, and that in patients with a negative scan was 0.90 (0.95, 0.41-1.40) ng/mL. PET/CT was positive in seven of 13 patients with a PSA level of <1.5 ng/mL, and histology was positive in this group in nine. In 17 patients with PSA levels of 1.5-2.5 ng/mL PET/CT was positive in all and the histology was positive in 13; in 11 men with a PSA level of 2.5-5 ng/mL PET/CT was positive in all 11 and the histology was positive in 10; in nine men with PSA levels of >5 ng/mL PET/CT identified all as positive and the histology was positive in eight. The sensitivity at a PSA level of <2.5 ng/mL of PET/CT for detecting recurrence was 91% (95% confidence interval, 71-99%) with a specificity of 50% (16-84)%. CONCLUSION: [(11)C]-choline PET/CT seems to be useful for re-staging prostate cancer after curative therapy and with increasing PSA levels; this was verified by histological examination. We recommend this method at PSA levels of <2.5 ng/mL.

11C-choline positron-emission tomography/computed tomography and transrectal ultrasonography for staging localized prostate cancer.

OBJECTIVE: To evaluate and compare the role of (11)C-choline positron emission tomography (PET) and transrectal ultrasonography (TRUS) in the preoperative staging of clinically localized prostate cancer. PATIENTS AND METHODS: Fifty-five consecutive patients with biopsy-confirmed prostate cancer had TRUS and (11)C-choline PET as a part of their clinical staging programme before radical retropubic prostatectomy (RP). The PET images were prospectively interpreted by a consensus decision of two nuclear medicine physicians and one radiologist with special expertise in the field. The TRUS was done by one experienced urologist. The criteria evaluated prospectively in each patient were extracapsular extension (ECE), seminal vesicle invasion (SVI) and bladder neck invasion (BNI). The results were compared with the histopathological findings after RP. RESULTS: At pathology, 32 patients were classified pT2, 16 as pT3a and three had pT3b lesions. In four patients the histopathological examination showed pT4 with BNI. The overall accuracy of PET in defining local tumour stage (pT2 and pT3a-4) was 70%; the overall accuracy by TRUS was 26%. PET was more sensitive than TRUS for detecting ECE (pT3a) and SVI (pT3b) in advanced stages, and in pT4 stages. The sensitivity and positive predictive value (PPV) (95% confidence interval) in stages pT3a-pT4 for PET were 36 (17-59)% and 73 (39-89)%. The sensitivity and PPV in stages pT3a-pT4 for TRUS were 14 (3-35)% and 100 (29-100)%. CONCLUSIONS: (11)C-choline PET and TRUS tended to understage prostate cancer. This series shows the current limited value of TRUS and PET for making treatment decisions in patients with clinically localized prostate cancer, especially if a nerve-sparing RP is considered. Treatment decisions should not be based on TRUS and (11)C-choline PET findings alone. In future studies, the combination of metabolic and anatomical information of PET and endorectal magnetic resonance imaging should be evaluated, as this might optimize the preoperative staging in prostate cancer.

Direct comparison of [18F]FDG PET/CT with PET alone and with side-by-side PET and CT in patients with malignant melanoma.

PURPOSE: The purpose of this retrospective, blinded study was to evaluate the additional value of [18F]FDG PET/CT in comparison with PET alone and with side-by-side PET and CT in patients with malignant melanoma (MM). METHODS: A total of 127 consecutive studies of patients with known MM referred for a whole-body PET/CT examination were included in this study. PET alone, side-by-side PET and CT and integrated PET/CT study were independently and separately interpreted without awareness of the clinical information. One score each was applied for certainty of lesion localisation and for certainty of lesion characterisation. Verification of the findings was subsequently performed using all available clinical, pathological (n=30) and follow-up information. RESULTS: The number of lesions with an uncertain localisation was significantly (p<0.001) reduced by PET/CT and side-by-side PET and CT (p<0.05) in comparison with PET alone. In line with this increase in certainty integrated PET/CT reading also improved certainty in characterisation of lesions, however, this did not reach significance (p=0.057) compared versus PET alone. Respectively, PET, side-by-side PET and CT and PET/CT showed a sensitivity of 86%, 89% and 91%, a specificity of 94%, 94% and 94%, a positive predictive value of 96%, 96% and 96% and a negative predictive value of 80%, 83% and 87%. CONCLUSION: Integrated PET/CT offers a significant benefit in lesion localisation and an improvement in lesion characterisation compared with PET alone or with side-by-side PET and CT. The benefit is not as great as that reported for other tumour entities, which may be due to the high avidity of MM for [18F]FDG.

Multiple Myeloma: Molecular Imaging with 11C-Methionine PET/CT--Initial Experience.

PURPOSE: To prospectively assess molecular imaging of multiple myeloma (MM) by using the radiolabeled amino acid carbon 11 ((11)C) methionine and positron emission tomography (PET)/computed tomography (CT). MATERIALS AND METHODS: The study was approved by the institutional local ethics committee and the national radiation protection authorities. All patients with MM and control patients gave written informed consent. Nineteen patients with MM (11 women, eight men; age range, 42-64 years) and 10 control patients with hyperparathyroidism without hematologic diseases (six women, four men; age range, 43-75 years) underwent PET/CT 20 minutes after injection of a mean of 1.0 GBq +/- 0.2 (standard deviation) (11)C-methionine. Presence and extent of CT-assessed tumor manifestations and (11)C-methionine bone marrow (BM) uptake were determined on the basis of maximum standardized uptake value (SUV(max)). BM imaging patterns, normal BM, and maximal lesion (11)C-methionine uptake in patients with MM were compared with those in control patients. In two patients with MM, sulfur 35 ((35)S) methionine uptake in freshly isolated BM plasma cells was measured. Values for SUV(max) of groups were compared by using the Mann-Whitney test on a per-patient basis. RESULTS: (35)S-methionine uptake of plasma cells was five- to sixfold higher than in normal BM cells. (11)C-methionine BM uptake in control patients was homogeneous and low. All patients with MM except one with exclusively extramedullary myeloma had (11)C-methionine-positive lesions. Maximal lesion and normal BM (11)C-methionine mean SUV(max) were 10.2 +/- 3.5 and 4.3 +/- 2.0, respectively, and thus were significantly higher than that of BM in the control group (mean, 1.8 +/- 0.3; P < .001). Extramedullary MM was clearly visible in three patients (mean SUV(max), 7.2 +/- 2.4). Additional (11)C-methionine-positive lesions in normal cancellous bone were found in nearly all patients with MM. In pretreated patients with MM, a moderate fraction of osteolytic lesions had no (11)C-methionine uptake. CONCLUSION: On the basis of increased methionine uptake in plasma cells, active MM can be imaged with (11)C-methionine PET/CT.

Imaging prostate cancer with 11C-choline PET/CT.

UNLABELLED: The ability of 11C-choline and multimodality fusion imaging with integrated PET and contrast-enhanced CT (PET/CT) was investigated to delineate prostate carcinoma (PCa) within the prostate and to differentiate cancer tissue from normal prostate, benign prostate hyperplasia, and focal chronic prostatitis. METHODS: All patients with PCa gave written informed consent. Twenty-six patients with clinical stage T1, T2, or T3 and biopsy-proven PCa underwent 11C-choline PET/CT after intravenous injection of 1,112 +/- 131 MBq 11C-choline, radical retropubic prostatovesiculectomy, and standardized prostate tissue sampling. Maximal standardized uptake values (SUVs) of 11C-choline within 36 segments of the prostate were determined. PET/CT results were correlated with histopathologic results, prostate-specific antigen (PSA), Gleason score, and pT stage. RESULTS: The SUV of 11C-choline in PCa tissue was 3.5 +/- 1.3 (mean +/- SD) and significantly higher than that in prostate tissue with benign histopathologic lesions (2.0 +/- 0.6; P < 0.001 benign histopathology vs. cancer). Visual and quantitative analyses of segmental 11C-choline uptake of each patient unambiguously located PCa in 26 of 26 patients and 25 of 26 patients, respectively. A threshold SUV of 2.65 yielded an area under the receiver-operating-characteristic (ROC) curve of 0.89 +/- 0.01 for correctly locating PCa. The maximal 11C-choline SUV did not correlate significantly with PSA or Gleason score but did correlate with T stage (P = 0.01; Spearman r = 0.49). CONCLUSION: 11C-Choline PET/CT can accurately detect and locate major areas with PCa and differentiate segments with PCa from those with benign hyperplasia, chronic prostatitis, or normal prostate tissue. The maximal tumoral 11C-choline uptake is related to pT stage.

Anti-CD45 monoclonal antibody YAML568: A promising radioimmunoconjugate for targeted therapy of acute leukemia.

UNLABELLED: The outcome of hematopoietic cell transplantation for hematologic malignancies may be improved by delivering targeted radiation to hematopoietic organs while relatively sparing nontarget organs. We evaluated the biodistribution of 111In-labeled anti-CD45 antibody in humans using the rat IgG2a monoclonal antibody YAML568 that recognizes a common CD45 epitope present on all human leukocytes. METHODS: Eight patients undergoing bone marrow transplantation received YAML568 labeled with 122 +/- 16 MBq of 111In intravenously followed by serial blood sampling, urine collection, and conjugated view planar gamma-camera imaging up to 144 h after injection. Time-activity curves were obtained using region-of-interest analysis in the accumulating organs and residence times were calculated. An estimate for the radiation-absorbed doses for each organ per unit of administered activity of 90Y was calculated using software for internal dose assessment. The first patient received no unlabeled antibody preloading. The second 2 patients received a preloading dose of 10 mg (0.15 mg/kg). The last 5 patients received a preloading dose of 30-47 mg (0.5 mg/kg). RESULTS: No significant administration-related side effects were seen. The 3 patients receiving no antibody or low antibody preloading had an unfavorable biodistribution with a high initial accumulation of activity in the liver (37%) and the spleen (34%). For the patients receiving 0.5-mg/kg antibody preloading, the estimated radiation-absorbed doses for red bone marrow, spleen, liver, kidney, and total body were 6.4 +/- 1.2, 19 +/- 5, 3.9 +/- 1.4, 1.1 +/- 0.4, and 0.6 +/- 0.1 mGy/MBq, respectively, demonstrating preferential red marrow targeting. A linear regression model showed that the amount of unlabeled antibody preloading per body weight has a strong influence on the estimated red marrow absorbed dose (P = 0.003, R2 = 0.80). CONCLUSION: This study shows that the anti-CD45 monoclonal antibody YAML568 is suitable for delivering selectively radiation to hematopoietic tissues when labeled with 90Y provided that a preloading dose of about 0.5 mg/kg unlabeled antibody is given.

Internal radionuclide therapy: the ULMDOS software for treatment planning.

Before therapy with unsealed radionuclides, a dosimetry assessment must be performed for each patient. We present the interactive software tool ULMDOS, which facilitates dosimetric calculations, enhances traceability, and adequate documentation. ULMDOS is developed in IDL 6.1 (Interactive Data Language) under Windows XP/2000. First the patient data, the radiotracer data, and optionally urine and serum data are entered. After loading planar gamma camera images and drawing regions of interest, the residence times can be calculated using fits of the time activity data to exponential functions. Data can be saved in ASCII format for retrospective examination and further processing. ULMDOS allows one to process the dosimetric calculations within a standardized environment, spares the time-consuming transfer of data between different software tools, enables the documentation of ROI and raw data, and reduces intraindividual variability. ULMDOS satisfies the required conditions for traceability and documentation as a prerequisite to routine use in clinical settings.

Response assessment of aggressive non-Hodgkin's lymphoma by integrated International Workshop Criteria and fluorine-18-fluorodeoxyglucose positron emission tomography.

PURPOSE: To determine whether a response classification based on integration of fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) into the International Workshop Criteria (IWC) provides a more accurate response assessment than IWC alone in patients with non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Fifty-four patients with aggressive NHL who underwent FDG-PET and computed tomography 1 to 16 weeks after four to eight cycles of chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone were assessed for complete response (CR), unconfirmed CR (CRu), partial response (PR), stable disease (SD), and progressive disease (PD) by the IWC and by integrated IWC and FDG-PET (IWC+PET). Progression-free survival (PFS) was also compared between IWC- and IWC+PET-assigned response designations. RESULTS: By IWC, 17 patients had a CR, seven had a CRu, 19 had a PR, nine had SD, and two had PD. In comparison, by IWC+PET, 35 patients had a CR, 12 had a PR, six had SD, one had PD, and zero had a CRu. In separate multivariate models, PFS was significantly shorter in patients with PR than in those with a CR using IWC (hazard ratio [HR], 8.9; P = .021) or IWC+PET (HR, 29.7; P = .0003). However, when the two classifications were included in the same multivariate model, only IWC+PET was a statistically significant independent predictor for PFS (P = .008 v P = .72 for IWC). In addition, when patients with a PR by IWC and a CR by IWC+PET were compared with those with a CR by IWC and a CR by IWC+PET, there was no significant difference in PFS (HR, 1.6; P = .72), indicating that IWC+PET identified a subset of IWC-PR patients with a more favorable prognosis. CONCLUSION: Compared with IWC, the IWC+PET-based assessment provides a more accurate response classification in patients with aggressive NHL.

Internal radionuclide therapy: The ULMDOS software for treatment planning.

Before therapy with unsealed radionuclides, a dosimetry assessment must be performed for each patient. We present the interactive software tool ULMDOS, which facilitates dosimetric calculations, enhances traceability, and adequate documentation. ULMDOS is developed in IDL 6.1 (Interactive Data Language) under Windows XP/2000. First the patient data, the radiotracer data, and optionally urine and serum data are entered. After loading planar gamma camera images and drawing regions of interest, the residence times can be calculated using fits of the time activity data to exponential functions. Data can be saved in ASCII format for retrospective examination and further processing. ULMDOS allows one to process the dosimetric calculations within a standardized environment, spares the time-consuming transfer of data between different software tools, enables the documentation of ROI and raw data, and reduces intraindividual variability. ULMDOS satisfies the required conditions for traceability and documentation as a prerequisite to routine use in clinical settings.