Thierry Vander Borght

Omitting Radiotherapy in Early Positron Emission Tomography–Negative Stage I/II Hodgkin Lymphoma Is Associated With an Increased Risk of Early Relapse: Clinical Results of the Preplanned Interim Analysis of the Randomized EORTC/LYSA/FIL H10 Trial

PURPOSE Combined-modality treatment is standard treatment for patients with clinical stage I/II Hodgkin lymphoma (HL). We hypothesized that an early positron emission tomography (PET) scan could be used to adapt treatment. Therefore, we started the randomized EORTC/LYSA/FIL Intergroup H10 trial evaluating whether involved-node radiotherapy (IN-RT) could be omitted without compromising progression-free survival in patients attaining a negative early PET scan after two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) as compared with standard combined-modality treatment. PATIENTS AND METHODS Patients age 15 to 70 years with untreated clinical stage I/II HL were eligible. Here we report the clinical outcome of the preplanned interim futility analysis scheduled to occur after documentation of 34 events in the early PET-negative group. Because testing for futility in this noninferiority trial corresponds to testing the hypothesis of no difference, a one-sided superiority test was conducted. RESULTS The analysis included 1,137 patients. In the favorable subgroup, 85.8% had a negative early PET scan (standard arm, one event v experimental arm, nine events). In the unfavorable subgroup, 74.8% had a negative early PET scan (standard arm, seven events v experimental arm, 16 events). The independent data monitoring committee concluded it was unlikely that we would show noninferiority in the final results for the experimental arm and advised stopping random assignment for early PET-negative patients. CONCLUSION On the basis of this analysis, combined-modality treatment resulted in fewer early progressions in clinical stage I/II HL, although early outcome was excellent in both arms. The final analysis will reveal whether this finding is maintained over time.

Impact of dopamine transporter SPECT using 123I-Ioflupane on diagnosis and management of patients with clinically uncertain parkinsonian syndromes†

Imaging with 123I‐Ioflupane single‐photon emission computed tomography (SPECT) is a marker of nigrostriatal neuronal integrity, allowing differentiation of parkinsonism with loss of dopaminergic terminals (presynaptic Parkinson syndrome [PS]) from parkinsonism without nigrostriatal degeneration. This study assessed SPECT imaging in 118 patients with clinically uncertain parkinsonian syndromes (CUPS). In 36% of patients with presynaptic PS and 54% with nonpresynaptic PS, imaging results were not consistent with the initial diagnosis. After imaging, diagnosis was changed in 52% of patients. All patients with a final diagnosis of presynaptic PS had an abnormal image, whereas 94% of patients with nonpresynaptic PS had a normal scan. Imaging increased confidence in diagnosis, leading to changes in clinical management in 72% of patients. Consequently, visual assessment of 123I‐Ioflupane SPECT may have a significant impact on the clinical management of CUPS patients.

EANM procedure guidelines for PET brain imaging using [ 18 F]FDG, version 2

These guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee (ENC). The purpose of the guidelines is to assist nuclear medicine practitioners in making recommendations, performing, interpreting, and reporting the results of fluorine-18 fluoro-2-deoxyglucose ([18F]FDG) PET imaging of the brain. The aim is to help achieve a high standard of FDG imaging, which will increase the diagnostic impact of this technique in neurological and psychiatric practice. The present document replaces a former version of the guidelines that were published in 2002 [1] and includes an update in the light of advances in PET technology, the introduction of hybrid PET/CT systems and the broadening clinical indications for FDG brain imaging. These guidelines are intended to present information specifically adapted for European practice. The information provided should be taken in the context of local conditions and regulations.

EANM procedure guidelines for brain neurotransmission SPECT using 123 I-labelled dopamine transporter ligands, version 2

These guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee (ENC). The aim of the guidelines is to assist nuclear medicine practitioners when making recommendations, performing, interpreting, and reporting the results of clinical dopamine transporter (DAT) single photon emission computed tomography (SPECT) studies using 123I-labelled radiopharmaceuticals. The aim is to achieve a high-quality standard of DAT SPECT imaging, which will increase the diagnostic impact of this technique in neurological practice. The present document is an update of the 2002 guidelines [1] and has been guided by the views of various national societies: the Task Group Neuro-Nuclear-Medicine of the German Society of Nuclear Medicine [2], a consensus statement of the imaging centres included in the “Kompetenznetz-Parkinson” sponsored by the German Federal Ministry of Education, and the Task Group of Neuro-Nuclear-Medicine of the French Society of Nuclear Medicine [3]. The guidelines reflect the individual experience of experts in European countries. The guidelines are intended to present information specifically adapted to European practice. The information provided should be taken in the context of local conditions and regulations.

Accuracy of DaTSCAN (123I-Ioflupane) SPECT in diagnosis of patients with clinically uncertain parkinsonism: 2-year follow-up of an open-label study.

We previously reported on the role of dopamine transporter (DAT) SPECT in the workup of patients with clinically uncertain parkinsonian syndromes (CUPS). The findings of that study supported the use of SPECT imaging with DaTSCAN (123I‐Ioflupane) for accurate diagnosis in this population. We report here the 2‐year follow‐up of the CUPS study, which aimed to validate the results of DaTSCAN imaging and to ascertain whether a second scan could minimize any residual diagnostic uncertainty among those with an inconclusive diagnosis. Eighty‐five of 118 patients (72%) were available at follow‐up. In 8 of 85 patients the neurologist was unable to provide a definite diagnosis (named as inconclusive). At follow‐up, clinical diagnosis agreed with initial DaTSCAN SPECT results in 69 of 77 patients (90%) in whom a specific diagnosis was established. A second SPECT scan was performed if clinical diagnosis at follow‐up differed to that suggested by the initial scan (n = 8) or was inconclusive (n = 8). Among 8 patients whose clinical diagnosis differed to DaTSCAN images, a second scan was performed in 6 (2 refused) and the results supported the final clinical diagnosis in 4. Follow‐up DaTSCAN SPECT helped to establish a diagnosis in 7 of 8 patients (87.5%) with a previously inconclusive diagnosis. DaTSCAN imaging shows a high rate of agreement with clinical diagnosis after 2‐years follow‐up. A second scan at 2 years follow‐up can reduce remaining diagnostic uncertainty that is present even after a prolonged period of observation.

EANM procedure guideline for brain perfusion SPECT using (99m)Tc-labelled radiopharmaceuticals : version 2

These guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee (ENC). The purpose of the guidelines is to assist nuclear medicine practitioners when making recommendations, performing, interpreting, and reporting the results of brain perfusion single photon emission computed tomography (SPECT) studies using 99mTc-labelled radiopharmaceuticals. The aim is to achieve a high quality standard for brain perfusion SPECT imaging, which will increase the diagnostic impact of this technique in clinical practice. The present document replaces a former version of the guideline published in 2001 which was inspired by the Society of Nuclear Medicine Procedure Guideline for Brain Perfusion SPECT [1], the views of the Society of Nuclear Medicine Brain Imaging Council [2], and the individual experience of experts in European countries. The guidelines are intended to present information specifically adapted to European practice. The information provided should be taken in the context of local conditions and regulations.

Development and Application of a Real-Time On-Line Blinded Independent Central Review of Interim Pet Scans to Determine Treatment Allocation in Lymphoma Trials

We appreciate the interest shown in our report by Gemici and the opportunity to respond to his comments. He published an excellent review article on tumor lysis syndrome (TLS) in 2006. He suggested that our patient may not be the third reported instance of TLS caused by radiotherapy because three patients had already been cited in his report. However, as we mentioned, only adult patients were included in our report. If pediatric patients were to be included, there would be more than three instances before his review. He also pointed out the inappropriateness of urine alkalinization during treatment of our patient. It is true that routine use of urine alkalinization is not recommended in most instances because of the potential risk of worsening renal problems or neurologic manifestations of hypocalcemia, although it seems not to have affected the clinical course of our patient. Therefore, as he described, physicians should be aware of this controversial issue during management of TLS. He also added that increasing the urinary flow rate is a better alternative than urine alkalinization. However, vigorous hydration with diuretics is not a matter of alternative choice because it is the single most important measure to treat TLS. The only decision to be made would be whether to use additional urine alkalinization for management of TLS. Finally, he mentioned that the daily fractionated dose in addition to total dose should also be considered. We agree on his opinion in the aspect that all reported patients with TLS had received 3 Gy of daily dose. He also suggested that TLS might develop later and at higher total dose if lower daily dose ( 2 Gy) were to be used. However, it is uncertain whether lower daily dose can result in TLS because there has been no such report on the matter. The threshold of radiation dose leading to rapid cell destruction might exist even in radiosensitive tumor cells. For better understanding, more experiences regarding radiotherapy-induced TLS need to be accumulated.

Procalcitonin is a Predictor for High-Grade Vesicoureteral Reflux in Children: Meta-Analysis of Individual Patient Data

OBJECTIVE To assess the predictive value of procalcitonin, a serum inflammatory marker, in the identification of children with first urinary tract infection (UTI) who might have high-grade (≥3) vesicoureteral reflux (VUR). STUDY DESIGN We conducted a meta-analysis of individual data, including all series of children aged 1 month to 4 years with a first UTI, a procalcitonin (PCT) level measurement, cystograms, and an early dimercaptosuccinic acid scan. RESULTS Of the 152 relevant identified articles, 12 studies representing 526 patients (10% with VUR ≥3) were included. PCT level was associated with VUR ≥3 as a continuous (P = .001), and as a binary variable, with a 0.5 ng/mL preferred threshold (adjusted OR, 2.5; 95% CI, 1.1 to 5.4). The sensitivity of PCT ≥0.5 ng/mL was 83% (95% CI, 71 to 91) with 43% specificity rate (95% CI, 38 to 47). In the subgroup of children with a positive results on dimercaptosuccinic acid scan, PCT ≥0.5 ng/mL was also associated with high-grade VUR (adjusted OR, 4.8; 95% CI, 1.3 to 17.6). CONCLUSIONS We confirmed that PCT is a sensitive and validated predictor strongly associated with VUR ≥3, regardless of the presence of early renal parenchymal involvement in children with a first UTI.

Is procalcitonin a good marker of renal lesion in febrile urinary tract infection

Four recent prospective studies have suggested that procalcitonin (PCT), a polypeptide produced by the macrophage-monocyte system during severe bacterial infection, might be more specific than leukocyte count or C-reactive protein (CRP) in predicting acute renal involvement during an episode of febrile urinary tract infection (UTI) [1, 2, 3, 5]. The aim of our prospective study was to confirm such findings.

The cost effectiveness of 123I-FP-CIT SPECT imaging in patients with an uncertain clinical diagnosis of parkinsonism

Purpose123I-N-ω-fluoropropyl-2-β-carboxymethoxy-3β-(4-iodophenyl)nortropane (123I-FP-CIT) Single-photon emission computed tomography (SPECT) has been suggested to be a useful diagnostic adjunct in patients with clinically uncertain parkinsonism. We developed a pharmaco-economic (PE) model, evaluating the cost effectiveness of adding 123I-FP-CIT SPECT to the diagnostic workup. As the model was developed before application of the diagnostic technique in real practice, a predictive validity assessment was performed based on data from a large nationwide patient registry in these patients.MethodsA PE model, using a Markov state transition model, was created, based on literature-derived and clinical expert panel data. Effects were expressed as adequately treated years (ATY). Key input data were compared to the real-life patterns in a nationwide multi-centre clinical setting, based on a complete national registry of 1,701 consecutive patients. The change in initial diagnosis and alteration of management of the patient after SPECT were registered.ResultsIn the PE model, it was calculated that management would change in 48.5% of patients by SPECT and that, over a 5-year period, 1.2 ATYs could be gained at a yearly additional cost of €72. From the studied 1,701 patients, nigrostriatal degeneration was observed in 59.8%, the initial diagnosis was changed in 51.5%, management was altered in 49%, and cost effectiveness was increased to €358 per ATY.ConclusionGood correspondence between assumed and observed changes in patient management was found, indicating that 123I-FP-CIT SPECT is influential in diagnosis and management of patients with uncertain clinical diagnosis of parkinsonism. This can be achieved at a marginal added cost to the health insurance and leads to a significant gain in ATY.