FDG-PET/CT after two cycles of R-CHOP in DLBCL predicts complete remission but has limited value in identifying patients with poor outcome - final result of a UK National Cancer Research Institute prospective study.

The UK National Cancer Research Institute initiated a prospective study (UKCRN-ID 1760) to assess the prognostic value of early fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in diffuse large B-cell lymphoma (DLBCL). In total, 189 patients with DLBCL treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) had baseline and post-cycle-2 PET (PET2) within a quality assurance framework. Treatment decisions were based on CT; PET2 was archived for central blinded reporting after treatment completion. The association of PET2 response with end-of-treatment CT, progression-free (PFS) and overall survival (OS) was explored. The end-of-treatment complete response rate on CT was 83·9%, 75·0%, 70·5%, 40·4% and 36·4% for Deauville score (DS) 1 (n = 34), 2 (n = 39), 3 (n = 46), 4 (n = 56) and 5 (n = 14) (P < 0·001); and 64·1% and 50·0% for the maximum standardised uptake value (∆SUVmax ) of ≥66% (n = 168) and <66% (n = 21), respectively (P = 0·25). After a median 5·4 years of follow-up, the 5-year PFS was 69·4%, 72·8%, 76·7%, 71·2% and 47·6% by DS 1-5 (P = 0·01); and 72·6% and 57·1% by ∆SUVmax of ≥66% and <66% (P = 0·03), respectively. The association with DS remained in multivariable analyses, and was consistent for OS. Early complete metabolic response (DS 1-3) at interim PET/CT after two cycles of R-CHOP in DLBCL was associated with a higher end-of-treatment complete and overall response rate; however, only DS-5 patients had inferior PFS and OS.

Adapted Treatment Guided by Interim PET-CT Scan in Advanced Hodgkin's Lymphoma.

BACKGROUND: We tested interim positron-emission tomography-computed tomography (PET-CT) as a measure of early response to chemotherapy in order to guide treatment for patients with advanced Hodgkin's lymphoma. METHODS: Patients with newly diagnosed advanced classic Hodgkin's lymphoma underwent a baseline PET-CT scan, received two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy, and then underwent an interim PET-CT scan. Images were centrally reviewed with the use of a 5-point scale for PET findings. Patients with negative PET findings after two cycles were randomly assigned to continue ABVD (ABVD group) or omit bleomycin (AVD group) in cycles 3 through 6. Those with positive PET findings after two cycles received BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone). Radiotherapy was not recommended for patients with negative findings on interim scans. The primary outcome was the difference in the 3-year progression-free survival rate between randomized groups, a noninferiority comparison to exclude a difference of 5 or more percentage points. RESULTS: A total of 1214 patients were registered; 937 of the 1119 patients (83.7%) who underwent an interim PET-CT scan according to protocol had negative findings. With a median follow-up of 41 months, the 3-year progression-free survival rate and overall survival rate in the ABVD group were 85.7% (95% confidence interval [CI], 82.1 to 88.6) and 97.2% (95% CI, 95.1 to 98.4), respectively; the corresponding rates in the AVD group were 84.4% (95% CI, 80.7 to 87.5) and 97.6% (95% CI, 95.6 to 98.7). The absolute difference in the 3-year progression-free survival rate (ABVD minus AVD) was 1.6 percentage points (95% CI, -3.2 to 5.3). Respiratory adverse events were more severe in the ABVD group than in the AVD group. BEACOPP was given to the 172 patients with positive findings on the interim scan, and 74.4% had negative findings on a third PET-CT scan; the 3-year progression-free survival rate was 67.5% and the overall survival rate 87.8%. A total of 62 patients died during the trial (24 from Hodgkin's lymphoma), for a 3-year progression-free survival rate of 82.6% and an overall survival rate of 95.8%. CONCLUSIONS: Although the results fall just short of the specified noninferiority margin, the omission of bleomycin from the ABVD regimen after negative findings on interim PET resulted in a lower incidence of pulmonary toxic effects than with continued ABVD but not significantly lower efficacy. (Funded by Cancer Research UK and Others; ClinicalTrials.gov number, NCT00678327.).

Results of a trial of PET-directed therapy for early-stage Hodgkin's lymphoma.

BACKGROUND: It is unclear whether patients with early-stage Hodgkin's lymphoma and negative findings on positron-emission tomography (PET) after three cycles of chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) require radiotherapy. METHODS: Patients with newly diagnosed stage IA or stage IIA Hodgkin's lymphoma received three cycles of ABVD and then underwent PET scanning. Patients with negative PET findings were randomly assigned to receive involved-field radiotherapy or no further treatment; patients with positive PET findings received a fourth cycle of ABVD and radiotherapy. This trial assessing the noninferiority of no further treatment was designed to exclude a difference in the 3-year progression-free survival rate of 7 or more percentage points from the assumed 95% progression-free survival rate in the radiotherapy group. RESULTS: A total of 602 patients (53.3% male; median age, 34 years) were recruited, and 571 patients underwent PET scanning. The PET findings were negative in 426 of these patients (74.6%), 420 of whom were randomly assigned to a study group (209 to the radiotherapy group and 211 to no further therapy). At a median of 60 months of follow-up, there had been 8 instances of disease progression in the radiotherapy group, and 8 patients had died (3 with disease progression, 1 of whom died from Hodgkin's lymphoma); there had been 20 instances of disease progression in the group with no further therapy, and 4 patients had died (2 with disease progression and none from Hodgkin's lymphoma). In the radiotherapy group, 5 of the deaths occurred in patients who received no radiotherapy. The 3-year progression-free survival rate was 94.6% (95% confidence interval [CI], 91.5 to 97.7) in the radiotherapy group and 90.8% (95% CI, 86.9 to 94.8) in the group that received no further therapy, with an absolute risk difference of -3.8 percentage points (95% CI, -8.8 to 1.3). CONCLUSIONS: The results of this study did not show the noninferiority of the strategy of no further treatment after chemotherapy with regard to progression-free survival. Nevertheless, patients in this study with early-stage Hodgkin's lymphoma and negative PET findings after three cycles of ABVD had a very good prognosis either with or without consolidation radiotherapy. (Funded by Leukaemia and Lymphoma Research and others; RAPID ClinicalTrials.gov number, NCT00943423.).

PET-CT for staging and early response: results from the Response-Adapted Therapy in Advanced Hodgkin Lymphoma study.

International guidelines recommend that positron emission tomography-computed tomography (PET-CT) should replace CT in Hodgkin lymphoma (HL). The aims of this study were to compare PET-CT with CT for staging and measure agreement between expert and local readers, using a 5-point scale (Deauville criteria), to adapt treatment in a clinical trial: Response-Adapted Therapy in Advanced Hodgkin Lymphoma (RATHL). Patients were staged using clinical assessment, CT, and bone marrow biopsy (RATHL stage). PET-CT was performed at baseline (PET0) and after 2 chemotherapy cycles (PET2) in a response-adapted design. PET-CT was reported centrally by experts at 5 national core laboratories. Local readers optionally scored PET2 scans. The RATHL and PET-CT stages were compared. Agreement among experts and between expert and local readers was measured. RATHL and PET0 stage were concordant in 938 (80%) patients. PET-CT upstaged 159 (14%) and downstaged 74 (6%) patients. Upstaging by extranodal disease in bone marrow (92), lung (11), or multiple sites (12) on PET-CT accounted for most discrepancies. Follow-up of discrepant findings confirmed the PET characterization of lesions in the vast majority. Five patients were upstaged by marrow biopsy and 7 by contrast-enhanced CT in the bowel and/or liver or spleen. PET2 agreement among experts (140 scans) with a κ (95% confidence interval) of 0.84 (0.76-0.91) was very good and between experts and local readers (300 scans) at 0.77 (0.68-0.86) was good. These results confirm PET-CT as the modern standard for staging HL and that response assessment using Deauville criteria is robust, enabling translation of RATHL results into clinical practice.

Real-time differential tracking of human neutrophil and eosinophil migration in vivo.

BACKGROUND: Hitherto, in vivo studies of human granulocyte migration have been based on indiscriminate labeling of total granulocyte populations. We hypothesized that the kinetics of isolated human neutrophil and eosinophil migration through major organs in vivo are fundamentally different, with the corollary that studying unseparated populations distorts measurement of both. METHODS: Blood neutrophils and eosinophils were isolated on 2 separate occasions from human volunteers by using Current Good Manufacturing Practice CD16 CliniMACS isolation, labeled with technetium 99m-hexamethylpropyleneamine oxime, and then reinfused intravenously. The kinetics of cellular efflux were imaged over 4 hours. RESULTS: Neutrophils and eosinophils were isolated to a mean purity of greater than 97% and greater than 95%, respectively. Activation of neutrophils measured as an increase in their CD11b mean fluorescence intensity in whole blood and after isolation and radiolabeling was 25.98 ± 7.59 and 51.82 ± 17.44, respectively, and was not significant (P = .052), but the mean fluorescence intensity of CD69 increased significantly on eosinophils. Analysis of the scintigraphic profile of lung efflux revealed exponential clearance of eosinophils, with a mean half-life of 4.16 ± 0.11 minutes. Neutrophil efflux was at a significantly slower half-life of 13.72 ± 4.14 minutes (P = .009). The migration of neutrophils and eosinophils was significantly different in the spleen at all time points (P = .014), in the liver at 15 minutes (P = .001), and in the bone marrow at 4 hours (P = .003). CONCLUSIONS: The kinetics of migration of neutrophils and eosinophils through the lung, spleen, and bone marrow of human volunteers are significantly different. Study of mixed populations might be misleading.

¹8F-FDG PET/CT in HIV-related central nervous system pathology.

PURPOSE: To evaluate the utility of ¹8F-FDG PET/CT in suspected cerebral pathology in HIV-infected individuals. METHODS: ¹8F-FDG PET/CT scans from 29 HIV-infected individuals (29 brain scans, 22 whole-body scans) who presented with neurological symptoms and signs were retrospectively reviewed and compared with subsequent clinical investigations. RESULTS: The majority of patients (n=25) were referred to differentiate infection from malignant causes of cerebral pathology. Ten of the 11 patients with an eventual diagnosis of toxoplasmosis infection were correctly diagnosed by ¹8F-FDG PET/CT showing lesional uptake less than that of normal brain cortex (mean SUVmax 3.5, range 1.9 - 5.8). All five patients with a final diagnosis of primary central nervous system lymphoma (PCNSL) were correctly diagnosed by ¹8F-FDG PET/CT showing lesional uptake greater than that of normal brain cortex (mean SUVmax 18.8, range 12.4 - 29.9). Four of the five patients with ¹8F-FDG PET/CT features suggesting a vasculitic process had vasculitis confirmed as the final diagnosis. Three patients showed variable uptake in multiple cerebral lesions (including final diagnoses of tuberculosis and metastases from lung cancer in two patients) and there were four other miscellaneous diagnoses. In 12 patients biopsies were performed at sites guided by PET abnormality (7 brain, 5 lymph nodes) confirming or excluding significant disease in 11. CONCLUSION: ¹8F-FDG PET/CT is particularly useful for differentiating between infection and PCNSL in HIV-infected patients with a cerebral lesion on MRI or CT. ¹8F-FDG PET/CT was also a helpful tool in the diagnostic work-up of patients with other HIV-related cerebral pathology. Additional advantages of ¹8F-FDG PET/CT are the abilities to assess abnormally increased glucose metabolism in the body and to identify potential sites for biopsy.

Evolution and resolution of human brain perfusion responses to the stress of induced hypoglycemia.

The relationship between the human brain response to acute stress and subjective, behavioural and physiological responses is poorly understood. We have examined the human cerebral response to the intense interoceptive stressor of hypoglycemia, controlling plasma glucose at either normal fasting concentrations (5 mmol/l, n=7) or at hypoglycemia (2.7 mmol/l, n=10) for 1 h in healthy volunteers. Hypoglycemia was associated with symptomatic responses, counterregulatory neuroendocrine responses and a sequential pattern of brain regional engagement, mapped as changes in relative cerebral perfusion using [(15)O]-H(2)O water positron emission tomography. The early cerebral response comprised activation bilaterally in anterior cingulate cortex (ACC) and thalamic pulvinar, with deactivation in posterior parahippocampal gyrus. Later responses (>20 min) engaged bilateral anterior insula, ventral striatum and pituitary. Following resolution of hypoglycemia, the majority of responses returned to baseline, save persistent engagement of the ACC and sustained elevation of growth hormone and cortisol. Catecholamine responses correlated with increased perfusion in pulvinar and medial thalamus, ACC and pituitary, while growth hormone and cortisol responses showed no correlation with thalamic activation but did show additional correlation with the hypothalamus and ventral striatum bilaterally. These data demonstrate complex dynamic responses to the stressor of hypoglycemia that would be expected to drive physiological and behavioural changes to remedy the state. Further, these data show that sustained stress and its aftermath engage distinct sets of brain regions, providing a neural substrate for adaptive or 'allostasic' responses to stressors.

Synthesis and biological evaluation of [(18)F]tetrafluoroborate: a PET imaging agent for thyroid disease and reporter gene imaging of the sodium/iodide symporter.

PURPOSE: The human sodium/iodide symporter (hNIS) is a well-established target in thyroid disease and reporter gene imaging using gamma emitters (123)I-iodide, (131)I-iodide and (99m)Tc-pertechnetate. However, no PET imaging agent is routinely available. The aim of this study was to prepare and evaluate (18)F-labelled tetrafluoroborate ([(18)F]TFB) for PET imaging of hNIS. METHODS: [(18)F]TFB was prepared by isotopic exchange of BF (4) (-) with [(18)F]fluoride in hot hydrochloric acid and purified using an alumina column. Its identity, purity and stability in serum were determined by HPLC, thin-layer chromatography (TLC) and mass spectrometry. Its interaction with NIS was assessed in vitro using FRTL-5 rat thyroid cells, with and without stimulation by thyroid-stimulating hormone (TSH), in the presence and absence of perchlorate. Biodistribution and PET imaging studies were performed using BALB/c mice, with and without perchlorate inhibition. RESULTS: [(18)F]TFB was readily prepared with specific activity of 10 GBq/mg. It showed rapid accumulation in FRTL-5 cells that was stimulated by TSH and inhibited by perchlorate, and rapid specific accumulation in vivo in thyroid (SUV = 72 after 1 h) and stomach that was inhibited 95% by perchlorate. CONCLUSION: [(18)F]TFB is an easily prepared PET imaging agent for rodent NIS and should be evaluated for hNIS PET imaging in humans.

Concordance between four European centres of PET reporting criteria designed for use in multicentre trials in Hodgkin lymphoma.

PURPOSE: To determine if PET reporting criteria for the Response Adapted Treatment in Hodgkin Lymphoma (RATHL) trial could enable satisfactory agreement to be reached between 'core' laboratories operating in different countries. METHODS: Four centres reported scans from 50 patients with stage II-IV HL, acquired before and after two cycles of Adriamycin/bleomycin/vinblastine/dacarbazine. A five-point scale was used to score response scans using 'normal' mediastinum and liver as reference levels. Centres read scans independently of each other. The level of agreement between centres was determined assuming (1) that uptake in sites involved at diagnosis that was higher than liver uptake represented disease (conservative reading), and (2) that uptake in sites involved at diagnosis that was higher than mediastinal uptake represented disease (sensitive reading). RESULTS: There was agreement that the response scan was 'positive' or 'negative' for lymphoma in 44 patients with a conservative reading and in 41 patients with a sensitive reading. Kappa was 0.85 (95% CI 0.74-0.96) for conservative reading and 0.79 (95% CI 0.67-0.90) for sensitive reading. Agreement was reached in 46 and 44 patients after discussion for the conservative and sensitive readings, respectively. CONCLUSION: The criteria developed for reporting in the RATHL trial are sufficiently robust to be used in a multicentre setting.

[18F]FDG PET/CT in the diagnosis of malignant peripheral nerve sheath tumours in neurofibromatosis type-1.

PURPOSE: The detection of malignant peripheral nerve sheath tumours (MPNSTs) in patients with neurofibromatosis 1 (NF1) remains a clinical challenge. The purpose of this study was to evaluate the use of [(18)F]2-fluoro-2-deoxy-D-glucose PET/CT (FDG PET/CT with early and delayed imaging) in patients with symptomatic neurofibromas, to revalidate current cut-off values for identification of malignant change within neurofibromas and to examine the relationship between SUV and tumour grade. METHODS: Patients with symptomatic neurofibromas underwent FDG PET/CT imaging at 90 and 240 min. Semiquantitative analysis using maximum standardized uptake value (SUVmax) was performed and correlated with histology. RESULT: In 69 patients, 85 lesions were identified for analysis, including 10 atypical neurofibromas and 21 MPNSTs. Sensitivity of FDG PET/CT in diagnosing NF1-associated MPNST was 0.97 (95% CI 0.81-0.99) and the specificity was 0.87 (CI 0.74-0.95). There was a significant difference in SUVmax between early and delayed imaging and in SUVmax between tumours identified as benign and malignant on PET/CT. There was also a significant difference in SUVmax between tumour grades. CONCLUSION: FDG PET/CT is a highly sensitive and specific imaging modality for the diagnosis of MPNST in NF1 patients. We recommend performing early (90 min) and delayed imaging at 4 h for accurate lesion characterization and using a cut-off SUVmax of 3.5 on delayed imaging to achieve maximal sensitivity.

Observer variation in FDG PET-CT for staging of non-small-cell lung carcinoma.

PURPOSE: Error and variation in reporting remains one of the weakest features of clinical imaging despite enormous technological advances in nuclear medicine and radiology. The aim of this study was to evaluate agreement amongst experienced readers in staging non-small-cell lung cancer (NSCLC) with PET-CT. METHODS: A series of (18)F-FDG PET-CT scans from 100 consecutive patients were reviewed independently by three experienced readers, with two readers reviewing each scan series a second time. Individual mediastinal lymph node stations were assessed as benign/inflammatory, equivocal or malignant, and AJCC N and M stage were also assigned. Kappa (kappa) was used to compare ratings from two categories and weighted kappa (kappa(w)) for three or more categories, and kappa values were interpreted according to the Landis-Koch benchmarks. RESULTS: Both intra- and interobserver agreement for N and M staging were high. For M staging there was almost perfect intra- and interobserver agreement (kappa = 0.90-0.93). For N staging, agreement was either almost perfect or substantial (intraobserver kappa(w) = 0.79, 0.91; interobserver kappa(w) = 0.75-0.81). Importantly, there was almost perfect agreement for N0/1 vs N2/3 disease (kappa = 0.80-0.97). Agreement for inferior and superior mediastinal nodes (stations 1, 2, 3, 7, 8, 9) was either almost perfect or substantial (kappa(w) = 0.71-0.88), but lower for hilar nodes (10; kappa(w) = 0.56-0.71). Interreporter variability was greatest for aortopulmonary nodes (5, 6; kappa(w) = 0.48-0.55). CONCLUSION: Amongst experienced reporters in a single centre, there was a very high level of agreement for both mediastinal nodal stage and detection of distant metastases with PET-CT. This supports the use of PET-CT as a robust imaging modality for staging NSCLC.

FDG-PET/CT imaging in the management of HIV-associated multicentric Castleman's disease.

PURPOSE: To evaluate the role of FDG-PET/CT scanning in the management of HIV-associated multicentric Castleman's disease (MCD) a rare lymphoproliferative disorder associated with infection by human herpesvirus 8 (HHV8). MATERIALS AND METHODS: Nine patients with histologically confirmed MCD underwent fused FDG-PET/CT scans at initial MCD diagnosis (n = 3), at MCD relapse (n = 4), or during remission (n = 2). All seven patients with active MCD had markedly elevated plasma HHV8 viral loads, but the patients in remission had no HHV8 viraemia. The three patients with newly diagnosed MCD were not on antiretroviral therapy at the time of imaging, but the other six were all on fully suppressive antiretroviral regimens. RESULTS: In the seven patients with active MCD (newly diagnosed or relapse) 33/91 lymph node groups (36%) included radiologically enlarged nodes on the CT scan, whilst 57/91 lymph node groups (63%) showed enhanced FDG uptake on the PET scan. In scans from patients in remission, there were no enlarged lymph nodes on the CT scan but 3 lymph nodes (11%) demonstrated enhanced FDG uptake. The median SUV recorded for the seven patients with active MCD was 4.8 (range 2.6-9.3) which was significantly higher than the median value of 2.5 recorded for the patients in remission (Mann-Whitney U test, p = 0.011). CONCLUSION: Despite the small number of patients, in HIV-positive individuals with active MCD, FDG-PET scans more frequently detected abnormal uptake than CT scans detected enlarged lymph nodes. FDG-PET scanning has a useful role in the management of HIV-associated MCD in selecting appropriate sites for biopsy, and in staging and monitoring these lymphoproliferations.

2009 EANM parathyroid guidelines.

The present guidelines were issued by the Parathyroid Task Group of the European Association of Nuclear Medicine. The main focus was imaging of primary hyperparathyroidism. Dual-tracer and single-tracer parathyroid scintigraphy protocols were discussed as well as the various modalities of image acquisition. Primary hyperparathyroidism is an endocrine disorder with high prevalence, typically caused by a solitary parathyroid adenoma, less frequently (about 15%) by multiple parathyroid gland disease (MGD) and rarely (1%) by parathyroid carcinoma. Patients with MGD may have a double adenoma or hyperplasia of three or all four parathyroid glands. Conventional surgery has consisted in routine bilateral neck exploration. The current trend is toward minimally invasive surgery. In this new era, the success of targeted parathyroid surgery depends not only on an experienced surgeon, but also on a sensitive and accurate imaging technique. Recognizing MGD is the major challenge for pre-operative imaging, in order to not direct a patient towards inappropriate minimal surgery. Scintigraphy should also report on thyroid nodules that may cause confusion with a parathyroid adenoma or require concurrent surgical resection. The two main reasons for failed surgery are ectopic glands and undetected MGD. Imaging is mandatory before re-operation, and scintigraphy results should be confirmed with a second imaging technique (usually US for a neck focus, CT or MRI for a mediastinal focus). Hybrid SPECT/CT instruments should be most helpful in this setting. SPECT/CT has a major role for obtaining anatomical details on ectopic foci. However, its use as a routine procedure before target surgery is still investigational. Preliminary data suggest that SPECT/CT has lower sensitivity in the neck area compared to pinhole imaging. Additional radiation to the patient should also be considered. The guidelines also discuss aspects related to radio-guided surgery of hyperparathyroidism and imaging of chronic kidney disease patients with secondary hyperparathyroidism.

Retrospective data-driven respiratory gating for PET/CT.

Respiratory motion can adversely affect both PET and CT acquisitions. Respiratory gating allows an acquisition to be divided into a series of motion-reduced bins according to the respiratory signal, which is typically hardware acquired. In order that the effects of motion can potentially be corrected for, we have developed a novel, automatic, data-driven gating method which retrospectively derives the respiratory signal from the acquired PET and CT data. PET data are acquired in listmode and analysed in sinogram space, and CT data are acquired in cine mode and analysed in image space. Spectral analysis is used to identify regions within the CT and PET data which are subject to respiratory motion, and the variation of counts within these regions is used to estimate the respiratory signal. Amplitude binning is then used to create motion-reduced PET and CT frames. The method was demonstrated with four patient datasets acquired on a 4-slice PET/CT system. To assess the accuracy of the data-derived respiratory signal, a hardware-based signal was acquired for comparison. Data-driven gating was successfully performed on PET and CT datasets for all four patients. Gated images demonstrated respiratory motion throughout the bin sequences for all PET and CT series, and image analysis and direct comparison of the traces derived from the data-driven method with the hardware-acquired traces indicated accurate recovery of the respiratory signal.

Positron Emission Tomography Score Has Greater Prognostic Significance Than Pretreatment Risk Stratification in Early-Stage Hodgkin Lymphoma in the UK RAPID Study.

PURPOSE: Accurate stratification of patients is an important goal in Hodgkin lymphoma (HL), but the role of pretreatment clinical risk stratification in the context of positron emission tomography (PET) -adapted treatment is unclear. We performed a subsidiary analysis of the RAPID trial to assess the prognostic value of pretreatment risk factors and PET score in determining outcomes. PATIENTS AND METHODS: Patients with stage IA to IIA HL and no mediastinal bulk underwent PET assessment after three cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine; 143 PET-positive patients (PET score, 3 to 5) received a fourth doxorubicin, bleomycin, vinblastine, and dacarbazine cycle and involved-field radiotherapy, and 419 patients in complete metabolic remission were randomly assigned to receive involved-field radiotherapy (n = 208) or no additional treatment (n = 211). Cox regression was used to investigate the association between PET score and pretreatment risk factors with HL-specific event-free survival (EFS). RESULTS: High PET score was associated with inferior EFS, before (P < .001) and after adjustment (P = .01) for baseline risk stratification. Only patients with a postchemotherapy PET score of 5 (uptake ≥ three times maximum liver uptake) had an increased risk of progression or HL-related death (hazard ratio, 9.4 v score of 3; 95% CI, 2.8 to 31.3 and hazard ratio, 6.7 v score of 4; 95% CI, 1.4 to 31.7). Patients with a PET score of 5 also had inferior progression-free and overall survival. There was no association between European Organisation for Research and Treatment of Cancer or German Hodgkin Study Group risk group and EFS, before or after adjusting for PET score (all P > .4). CONCLUSION: In RAPID, a positive PET scan did not carry uniform prognostic weight; only a PET score of 5 was associated with inferior outcomes. This suggests that in future trials involving patients without B symptoms or mediastinal bulk, a score of 5 rather than a positive PET result should be used to guide treatment escalation in early-stage HL.

Routine positron emission tomography and positron emission tomography/computed tomography in melanoma staging with positive sentinel node biopsy is of limited benefit.

Positron emission tomography (PET) is increasingly used for the staging and management of melanoma. The aim of this study was to evaluate the role of PET or PET/ computed tomography (CT) as a routine procedure in patients with positive sentinel node biopsy (SNB). Thirty patients with melanoma of Breslow thickness greater than 1 mm who had PET or PET/CT scans performed within 100 days after a positive SNB were reviewed retrospectively. Two patients (6%) had a positive PET scan, none of which were melanoma related. The first patient had a synchronous neuroendocrine thyroid tumour and the second patient had increased uptake in the chest wall, which proved to be old trauma. Lymph node dissection was positive in five cases (16%). With a median follow-up of 24 months, 21 patients remained disease free. In none of the 30 cases did the early PET scan after a positive SNB alter subsequent melanoma management. The role of PET scanning soon after a positive sentinel node biopsy seems to be of limited benefit. It is questionable whether any imaging is beneficial at this stage. The results of this review suggest that PET scanning might not be indicated for this group of patients.

Use of the CT component of PET-CT to improve PET-MR registration: demonstration in soft-tissue sarcoma.

We have investigated improvements to PET-MR image registration offered by PET-CT scanning. Ten subjects with suspected soft-tissue sarcomas were scanned with an in-line PET-CT and a clinical MR scanner. PET to CT, CT to MR and PET to MR image registrations were performed using a rigid-body external marker technique and rigid and non-rigid voxel-similarity algorithms. PET-MR registration was also performed using transformations derived from the registration of CT to MR. The external marker technique gave fiducial registration errors of 2.1 mm, 5.1 mm and 5.3 mm for PET-CT, PET-MR and CT-MR registration. Target registration errors were 3.9 mm, 9.0 mm and 9.3 mm, respectively. Voxel-based algorithms were evaluated by measuring the distance between corresponding fiducials after registration. Registration errors of 6.4 mm, 14.5 mm and 9.5 mm, respectively, for PET-CT, PET-MR and CT-MR were observed for rigid-body registration while non-rigid registration gave errors of 6.8 mm, 16.3 mm and 7.6 mm for the same modality combinations. The application of rigid and non-rigid CT to MR transformations to accompanying PET data gives significantly reduced PET-MR errors of 10.0 mm and 8.5 mm, respectively. Visual comparison by two independent observers confirmed the improvement over direct PET-MR registration. We conclude that PET-MR registration can be more accurately and reliably achieved using the hybrid technique described than through direct rigid-body registration of PET to MR.

Assessing response to chemotherapy in metastatic melanoma with FDG PET: Early experience.

OBJECTIVE: The management of metastatic melanoma remains challenging with only modest response rates to chemotherapy but the need to identify the best re-staging techniques remains paramount. This study evaluates our early experience in the use of FDG PET-CT in the assessment of early response to chemotherapy in metastatic melanoma. METHODS: FDG PET-CT was performed at baseline and following two or three cycles of combination or single agent chemotherapy in seven patients. Response was assessed visually as complete, partial metabolic response or progressive disease. RESULTS: There was intense FDG uptake in all metastases at baseline. Following two to three cycles of chemotherapy, there was a complete metabolic response (CMR) in one patient, partial metabolic response (PMR) in two patients and progressive metabolic disease (PMD) in the remaining three patients. Survival was 679 days in the single patient with a CMR, median of 206 and 129 days in the patients with PMR and PMD respectively. CONCLUSION: This pilot study demonstrates the potential use of FDG PET as a biomarker in early response assessment to chemotherapy in metastatic melanoma. PET-CT already plays in integral role in staging high risk melanoma patients and it may also have a promising role in assessing response to current and novel therapies. Further larger studies examining specific therapies and optimal timing are required.

18F-Tetrafluoroborate, a PET Probe for Imaging Sodium/Iodide Symporter Expression: Whole-Body Biodistribution, Safety, and Radiation Dosimetry in Thyroid Cancer Patients.

We report the safety, biodistribution, and internal radiation dosimetry, in humans with thyroid cancer, of 18F-tetrafluoroborate (18F-TFB), a novel PET radioligand for imaging the human sodium/iodide symporter (hNIS). Methods: Serial whole-body PET scans of 5 subjects with recently diagnosed thyroid cancer were acquired before surgery for up to 4 h after injection of 184 ± 15 MBq of 18F-TFB. Activity was determined in whole blood, plasma, and urine. Mean organ-absorbed doses and effective doses were calculated via quantitative image analysis and using OLINDA/EXM software. Results: Images showed a high uptake of 18F-TFB in known areas of high hNIS expression (thyroid, salivary glands, and stomach). Excretion was predominantly renal. No adverse effects in relation to safety of the radiopharmaceutical were observed. The effective dose was 0.0326 ± 0.0018 mSv/MBq. The critical tissues/organs receiving the highest mean sex-averaged absorbed doses were the thyroid (0.135 ± 0.079 mSv/MBq), stomach (0.069 ± 0.022 mSv/MBq), and salivary glands (parotids, 0.031 ± 0.011 mSv/MBq; submandibular, 0.061 ± 0.031 mSv/MBq). Other organs of interest were the bladder (0.102 ± 0.046 mSv/MBq) and kidneys (0.029 ± 0.009 mSv/MBq). Conclusion: Imaging using 18F-TFB imparts a radiation exposure similar in magnitude to many other 18F-labeled radiotracers. 18F-TFB shows a biodistribution similar to 99mTc-pertechnetate, a known nonorganified hNIS tracer, and is pharmacologically and radiobiologically safe in humans. Phase 2 trials for 18F-TFB as an hNIS imaging agent are warranted.

Sentinel Node in Oral Cancer: The Nuclear Medicine Aspects. A Survey from the Sentinel European Node Trial.

PURPOSE: Nuclear imaging plays a crucial role in lymphatic mapping of oral cancer. This evaluation represents a subanalysis of the original multicenter SENT trial data set, involving 434 patients with T1-T2, N0, and M0 oral squamous cell carcinoma. The impact of acquisition techniques, tracer injection timing relative to surgery, and causes of false-negative rate were assessed. METHODS: Three to 24 hours before surgery, all patients received a dose of Tc-nanocolloid (10-175 MBq), followed by lymphoscintigraphy. According to institutional protocols, all patients underwent preoperative dynamic/static scan and/or SPECT/CT. RESULTS: Lymphoscintigraphy identified 723 lymphatic basins. 1398 sentinel lymph nodes (SNs) were biopsied (3.2 SN per patient; range, 1-10). Dynamic scan allowed the differentiation of sentinel nodes from second tier lymph nodes. SPECT/CT allowed more accurate anatomical localization and estimated SN depth more efficiently. After pathological examination, 9.9% of the SN excised (138 of 1398 SNs) showed metastases. The first neck level (NL) containing SN+ was NL I in 28.6%, NL IIa in 44.8%, NL IIb in 2.8%, NL III in 17.1%, and NL IV in 6.7% of positive patients. Approximately 96% of positive SNs were localized in the first and second lymphatic basin visualized using lymphoscintigraphy. After neck dissection, the SN+ was the only lymph node containing metastasis in approximately 80% of patients. CONCLUSIONS: Best results were observed using a dynamic scan in combination with SPECT/CT. A shorter interval between tracer injection, imaging, and surgery resulted in a lower false-negative rate. At least 2 NLs have to be harvested, as this may increase the detection of lymphatic metastases.