Deniz Kahraman

Akinetic‐rigid and tremor‐dominant Parkinson's disease patients show different patterns of FP‐CIT Single photon emission computed tomography

To elucidate whether Parkinsons disease subtypes show a different pattern of Iodine‐123 fluoropropyl–;carbomethoxy‐3 β‐(FP‐CIT) single photon emission computed tomography (SPECT) binding in accordance with neuropathological findings.

Quantitative analysis of response to treatment with Erlotinib in advanced non–small cell lung cancer using 18F-FDG and 39-deoxy-39-18F-fluorothymidine PET

The purpose of this study was to evaluate the relevance for the prediction of clinical benefit of first-line treatment with erlotinib using different quantitative parameters for PET with both 18F-FDG and 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) in patients with advanced non–small cell lung cancer. Methods: Data were used from a prospective trial involving patients with untreated stage IV non–small cell lung cancer. 18F-FDG PET and 18F-FLT PET were performed before and 1 (early) and 6 (late) weeks after erlotinib treatment. Several quantitative standardized uptake values (SUVs) using different definitions of volumes of interest with varying isocontours (maximum SUV [SUVmax], 2-dimensional peak SUV [SUV2Dpeak], 3-dimensional [3D] peak SUV [SUV3Dpeak], 3D isocontour at 50% of the maximum pixel value [SUV50], 3D isocontour at 50% adapted for background [SUVA50], 3D isocontour at 41% of the maximum pixel value adapted for background [SUVA41], 3D isocontour at 70% of the maximum pixel value [SUV70], 3D isocontour at 70% adapted for background [SUVA70], and relative SUV threshold level [SUVRTL]) and metabolically active volume measurements were obtained in the hottest single tumor lesion and in the sum of up to 5 lesions per scan in 30 patients. Metabolic response was defined as a minimum reduction of 30% in each of the different SUVs and as a minimum reduction of 45% in metabolically active volume. Progression-free survival (PFS) was compared between patients with and without metabolic response measured with each of the different parameters, using Kaplan–Meier statistics and a log-rank test. Results: Patients with a metabolic response on early 18F-FDG PET and 18F-FLT PET in the hottest single tumor lesion as well as in the sum of up to 5 lesions per scan had a significantly longer PFS, regardless of the method used to calculate SUV. However, the highest significance was obtained for SUVmax, SUV50, SUVA50, and SUVA41. Patients with a metabolic response measured by SUVmax and SUV3Dpeak on late 18F-FDG PET in the hottest single tumor lesion had a significantly longer PFS. Furthermore, Kaplan–Meier analyses showed a strong association between PFS and response seen by metabolically active volume, measured either in early 18F-FLT or in late 18F-FDG. Conclusion: Early 18F-FDG PET and 18F-FLT PET can predict PFS regardless of the method used for SUV calculation. However, SUVmax, SUV50, SUVA50, and SUVA41 measured with 18F-FDG might be the best robust SUV to use for early response prediction. Metabolically active volume measurement in early 18F-FLT PET and late 18F-FDG PET may have an additional predictive value in monitoring response in patients with advanced non–small cell lung cancer treated with erlotinib.

Parkinson Subtypes Progress Differently in Clinical Course and Imaging Pattern

Objective To elucidate whether Parkinson’s disease (PD) subtypes show a differential pattern of FP-CIT-SPECT binding during the disease course. Methods We examined 27 patients (10 female, 17 male, mean age 61.68±11.24 years, 14 tremordominant, 13 akinetic-rigid) with [123I]FP-CIT-SPECT and clinical ratings including UPDRS III after at baseline and after a mean period of 2.47 years. Patients had been classified at baseline as tremordominant or akinetic-rigid according to a “tremor score” and “non-tremor score”. These subgroups were compared for differences in disease progression. Means of clinical ratings and the quantitative analyses of FP-CIT-SPECT for ipsi- and contralateral putamen and caudate nucleus were calculated and compared between baseline and follow-up. Results There were no statistical differences concerning age, disease duration, L-Dopa equivalent dose, disease severity (UPDRS III) or dopaminergic uptake in FP-CIT-SPECT at baseline between both subgroups. At follow-up, akinetic-rigid patients showed a distinct and statistically significant reduction of the dopaminergic uptake associated with significant progression of the clinical symptoms (UPDRS III). In contrast, in tremor patients the aggravation of clinical symptoms and dopaminergic deficit was less pronounced without statistical significance among assessments. Conclusions This study shows for the first time a considerable progression of clinical symptoms and in-vivo dopaminergic deficit of akinetic-rigid compared to tremordominant PD patients over time. Our data may help to improve strategic planning of further therapeutic trials and to provide a clearer prognosis for patients regarding the perspective of their disease.

Role of [18F]-fluoro-2-deoxy-D-glucose positron emission tomography in early and late therapy assessment of patients with advanced Hodgkin lymphoma treated with bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine and prednisone.

Abstract The prognostic value of positron emission tomography (PET) in early therapy response assessment, after completion of chemotherapy and 3 months after the end of treatment in advanced Hodgkin lymphoma (HL) remains to be defined. We report the results of 69 patients with first presentation of advanced HL. [18F]-fluoro-2-deoxy-d-glucose (FDG)-PET scan was performed after four cycles (PET-4), on completion of chemotherapy after 6/8 cycles (PET-6/8) and 3 months after the completion of chemotherapy (PET 3-months). Median follow-up was 55 months. The negative predictive value (NPV) for PET-4, PET-6/8 and PET 3-months was 98%, 95% and 97%, respectively. The 4-year progression-free survival (PFS) for PET-4 negative (n = 51) and PET-4 positive (n = 18) patients was 96% and 78%, respectively (p = 0.016). The 4-year PFS for PET-6/8 negative (n = 59) and PET-6/8 positive (n = 9) patients was 95% and 78%, respectively (p = 0.046). Patients with a large mediastinal mass constituted nearly all of the PET-4 positive (16/18) and PET-6/8 positive (8/9) patients. After radiotherapy of PET-6/8 positive patients, PET 3-months was negative in 64 (97%) and positive in two (3%) patients. PET 3-months after the end of chemotherapy was of limited value when the interim PET-4 was negative. Interim PET after four cycles of bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine and prednisone (BEACOPP) is a strong prognostic marker for PFS in advanced HL.

Assessment of Tumor Size Reduction Improves Outcome Prediction of Positron Emission Tomography/Computed Tomography After Chemotherapy in Advanced-Stage Hodgkin Lymphoma

PURPOSE Positron emission tomography (PET) after chemotherapy can guide consolidating radiotherapy in advanced-stage Hodgkin lymphoma (HL). This analysis aims to improve outcome prediction by integrating additional criteria derived by computed tomography (CT). PATIENTS AND METHODS The analysis set consisted of 739 patients with residues≥2.5 cm after chemotherapy from a total of 2,126 patients treated in the HD15 trial (HD15 for advanced stage Hodgkins disease: Quality assurance protocol for reduction of toxicity and the prognostic relevance of fluorodeoxyglucose-positron-emission tomography [FDG-PET] in the first-line treatment of advanced-stage Hodgkins disease) performed by the German Hodgkin Study Group. A central panel performed image analysis and interpretation of CT scans before and after chemotherapy as well as PET scans after chemotherapy. Prognosis was evaluated by using progression-free survival (PFS); groups were compared with the log-rank test. Potential prognostic factors were investigated by using receiver operating characteristic analysis and logistic regression. RESULTS In all, 548 (74%) of 739 patients had PET-negative residues after chemotherapy; these patients did not receive additional radiotherapy and showed a 4-year PFS of 91.5%. The 191 PET-positive patients (26%) receiving additional radiotherapy had a 4-year PFS of 86.1% (P=.022). CT alone did not allow further separation of patients in partial remission by risk of recurrence (P=.9). In the subgroup of the 54 PET-positive patients with a relative reduction of less than 40%, the risk of progression or relapse within the first year was 23.1% compared with 5.3% for patients with a larger reduction (difference, 17.9%; 95% CI, 5.8% to 30%). CONCLUSION Patients with HL who have PET-positive residual disease after chemotherapy and poor tumor shrinkage are at high risk of progression or relapse.

Tumor lesion glycolysis and tumor lesion proliferation for response prediction and prognostic differentiation in patients with advanced non-small cell lung cancer treated with erlotinib

Purpose The aim was to assess the value of tumor lesion glycolysis (TLG) and tumor lesion proliferation (TLP) determined by FDG and 3’-deoxy-3’-18F-fluorothymidine (FLT) PET for response prediction and prognostic differentiation in patients with advanced non–small cell lung cancer (NSCLC) treated with erlotinib. Patients and Methods FDG-PET and FLT-PET were performed in 30 patients with untreated Stage IV NSCLC before start of therapy, 1 (early) and 6 (late) weeks after erlotinib treatment. Functional tumor volume parameters including TLG in FDG-PET and TLP in FLT-PET were measured in the sum of up to 5 lesions per scan. Metabolic response was assessed using different cutoff values for percentage changes of TLG and TLP. Absolute baseline and residual levels of TLG and TLP were used for dichotomizing the patients into 2 groups. Kaplan-Meier analysis and the log-rank test were performed to analyze the association with progression-free survival (PFS). Results Patients with a metabolic response measured by early changes of TLP and late changes of TLG and TLP showed a significantly better PFS than metabolically nonresponding patients. A lower cutoff value of 20% or 30% for definition of metabolic response showed better differentiation between metabolically responding and nonresponding patients in cases where the 45% cutoff value revealed no significant results. Furthermore, patients with lower absolute early and late residual TLG and TLP levels had a significantly prolonged PFS. In contrast, absolute baseline TLG and TLP levels showed no significant association with PFS. Conclusions In patients with advanced NSCLC, percentage changes of TLG and TLP and absolute residual TLG and TLP levels under erlotinib treatment emerged as strong predictive factors for PFS. Our findings indicate that a cutoff value of 20% or 30% for definition of metabolic response measured by percentage changes of TLG and TLP provides suitable results for response prediction, which should be further validated.

Prognostic Impact of [18F]Fluorothymidine and [18F]Fluoro-D-Glucose Baseline Uptakes in Patients with Lung Cancer Treated First-Line with Erlotinib

3′-deoxy-3′-[18F]fluoro-L-thymidine (FLT) and 2′-deoxy-2′-[18F]fluoro-D-glucose (FDG) are used to visualize proliferative and metabolic activity of tumors. In this study we aimed at evaluating the prognostic value of FLT and FDG uptake measured by positron emission tomography (PET) in patients with metastatic non-small cell lung cancer (NSCLC) prior to systemic therapy with erlotinib. FLT and FDG maximum standardized uptake (SUVmax) values per patient were analyzed in 40 chemotherapy naive patients with advanced NSCLC (stage IV) before treatment with erlotinib. Prior therapy median SUVmax was 6.6 for FDG and 3.0 for FLT, respectively. In univariate analysis, patients with an FDG SUVmax <6.6 had a significantly better overall survival (16.3 months [95% confidence interval [CI] 7.1–25.4 months]) compared to patients with an FDG SUVmax ≥6.6 (3.1 months [95% CI 0.6–5.5 months]) (p<0.001, log rank). Similarly, low FLT uptake (SUVmax <3.0) was associated with significantly longer survival (10.3 months (0–23.3 months, 95% CI) compared to high FLT uptake (3.4 months (0–8.1 months, 95% CI) (p = 0.027). The independent prognostic value of baseline FDG uptake was demonstrated in multivariate analysis (p = 0.05, Cox regression). These data suggest that baseline SUVmax values for both FDG and FLT PET might be further developed as markers for prognostic stratification of patients in advanced NSCLC treated with tyrosine kinase inhibitors (TKI) directed against the epidermal growth factor receptor (EGFR). Trial Registration Clinicaltrials.gov, Identifier: NCT00568841

Are dopa-responsive dystonia and Parkinson’s disease related disorders? A case report

OBJECTIVE L-Dopa-responsive dystonia (DRD) is a hereditary dystonia characterized by an excellent response to low dosages of levodopa. DRD patients may also develop Parkinsonism which resembles idiopathic Parkinsons disease. In classical DRD no changes in the dopaminergic uptake have been observed. METHODS A 65-year old woman presented with clinically remarkably slowly progressing Parkinsons disease (PD) without any dystonic signs and excellent response to dopaminergic medications. We obtained a [(123)I] FP-CIT-SPECT (DaTSCAN™) in order to elucidate a striatal dopaminergic deficit. RESULTS We found a reduced uptake in the [(123)I] FP-CIT-SPECT (DaTSCAN™) contralateral to the more affected body side. Additionally, the patient showed a heterozygous deletion of the GHC1 gene. CONCLUSIONS Patients with mild parkinsonian symptoms, excellent response to low dosages of dopaminergic drugs and a reduced dopamine-transporter uptake in [(123)I] FP-CIT-SPECT might more commonly be GCH1 mutation carriers than has previously been supposed. PD patients with a positive family history of DRD and combination of these clinical symptoms should be offered genetic counselling and testing for GCH1.

18-Fluorodeoxyglucose positron emission tomography/computed tomography for assessment of response to brentuximab vedotin treatment in relapsed and refractory Hodgkin lymphoma.

Abstract Brentuximab vedotin has emerged as a possible treatment option in patients suffering from relapsed and refractory Hodgkin lymphoma (HL). We investigated the role of 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for monitoring treatment response to brentuximab vedotin in patients with relapsed and refractory HL. Twelve consecutive, heavily pretreated patients with relapsed and refractory HL treated with brentuximab vedotin were available for analysis. FDG-PET/CT studies were performed early during treatment after a median of 3 cycles (range, 2–5 cycles), and were analyzed visually using a 5-point scale (5PS) and quantitatively using the maximum standardized uptake value (SUVmax) and the three-dimensional (3D) isocontour at 50% of the maximum pixel value (SUV50) in the hottest single lesion. The median follow-up in our study cohort was 16 months (range, 5–30 months). The median progression-free survival (PFS) was 12.5 months and PFS at 12 months was 58%. Patients treated with brentuximab vedotin and negative interim FDG-PET/CT assessed by visual or quantitative analysis demonstrated a significantly prolonged PFS compared to patients with positive interim FDG-PET/CT. The 1-year PFS was 100% in patients with negative interim FDG-PET/CT assessed by visual analysis, whereas patients with positive interim FDG-PET/CT had a worse outcome with a 1-year PFS of 38% (p = 0.033). The 1-year PFS was 75% in patients with negative interim FDG-PET/CT assessed by quantitative analysis using the SUV50, whereas patients with positive interim FDG-PET/CT had a worse outcome with a 1-year PFS of 25% (p = 0.017) Interim FDG-PET/CT might be a suitable diagnostic approach to predict response to brentuximab vedotin in relapsed and refractory HL.

11C-methionine positron emission tomographic imaging of biologic activity of a recurrent glioblastoma treated with stereotaxy-guided laser-induced interstitial Thermotherapy

In patients with recurrent glioblastoma multiforme (GBM), local minimally invasive treatment modalities have gained increasing interest recently because they are associated with fewer side effects than open surgery. For example, local tumor coagulation by laser-induced interstitial thermotherapy (LITT) is such a minimally invasive technique. We monitored the metabolic effects of stereotaxy-guided LITT in a patient with a recurrent GBM using amino acid positron emission tomography (PET). Serial 11C-methyl-L-methionine positron emission tomography (MET-PET) and contrast-enhanced computed tomography (CT) were performed using a hybrid PET/CT system in a patient with recurrent GBM before and after LITT. To monitor the biologic activity of the effects of stereotaxy-guided LITT, a threshold-based volume of interest analysis of the metabolically active tumor volume (MET uptake index of ≥ 1.3) was performed. A continuous decline in metabolically active tumor volume after LITT could be observed. MET-PET seems to be useful for monitoring the short-term therapeutic effects of LITT, especially when patients have been pretreated with a multistep therapeutic regimen. MET-PET seems to be an appropriate tool to monitor and guide experimental LITT regimens and should be studied in a larger patient group to confirm its clinical value.