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The prospective randomized Positron Emission Tomography (PET)-Guided Therapy of Aggressive Non-Hodgkin Lymphomas (PETAL) trial was designed to test the ability of interim PET (iPET) to direct therapy. As reported previously, outcome remained unaffected by iPET-based treatment changes. In this subgroup analysis, we studied the prognostic value of baseline total metabolic tumor volume (TMTV) and iPET response in 76 patients with T-cell lymphoma. TMTV was measured using the 41% maximum standardized uptake value (SUV41max ) and SUV4 thresholding methods. Interim PET was performed after two treatment cycles and evaluated using the ΔSUVmax approach and the Deauville scale. Because of significant differences in outcome, patients with anaplastic lymphoma kinase (ALK)-positive lymphoma were analyzed separately from patients with ALK-negative lymphoma. In the latter, TMTV was statistically significantly correlated with progression-free survival, with thresholds best dichotomizing the population, of 232 cm3 using SUV41max and 460 cm3 using SUV4 . For iPET response, the respective thresholds were 46.9% SUVmax reduction and Deauville score 1-4 vs 5. The proportion of poor prognosis patients was 46% and 29% for TMTV by SUV41max and SUV4 , and 29% and 25% for iPET response by ΔSUVmax and Deauville, respectively. At diagnosis, the hazard ratio (95% confidence interval) for poor prognosis vs good prognosis patients according to TMTV was 2.291 (1.135-4.624) for SUV41max and 3.206 (1.524-6.743) for SUV4 . At iPET, it was 3.910 (1.891-8.087) for ΔSUVmax and 4.371 (2.079-9.187) for Deauville. On multivariable analysis, only TMTV and iPET response independently predicted survival. Patients with high baseline TMTV and poor iPET response (22% of the population) invariably progressed or died within the first year (hazard ratio, 9.031 [3.651-22.336]). Due to small numbers and events, PET did not predict survival in ALK-positive lymphoma. Baseline TMTV and iPET response are promising tools to select patients with ALK-negative T-cell lymphoma for early allogeneic transplantation or innovative therapies. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the sites of metabolic changes with [18F]2-fluoro-2-desoxy-D-glucose (FDG) and positron emission tomography (PET) in patients with Creutzfeldt-Jakob disease and to correlate the findings with clinical symptoms. Static [18F]FDG-PET studies of eight patients with the diagnosis of confirmed or probable CJD were retrospectively analysed by two physicians from departments of nuclear medicine independently with a strong interrater agreement (κ=0,98). The clinical data of the patients, based on a standardized evaluation by physicians from the German Creutzfeldt-Jakob disease surveillance study, was correlated with the PET findings. [18F]FDG-PET shows widespread hypometabolism in CJD. All patients had a reduction of cerebral glucose metabolism in at least one temporal or parietal region. Additionally in 7 of our own 8 cases and 3 of 4 cases from the literature the occipital lobe, the cerebellum or the basal ganglia were involved. These findings differ from typical patterns of hypometabolism in Alzheimer's disease and other neurodegenerative disorders. In two thirds of the cases the distribution was markedly asymmetric. Myoclonus was present in five out of our eight own cases. Our data suggest that myoclonus might correlate with metabolic impairment of contralateral parietal and temporal lobes. In three of four patients with visual symptoms FDG uptake was reduced in the visual cortex bilaterally. Typical hyperintensities on MRI were only found in two of the eight cases at the time of PET-studies. Our results demonstrate that [18F]FDG-PET appears to be a sensitive investigation in CJD and could be useful to differentiate CJD from other neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Forty two examinations utilizing F-18 FDG-PET were performed in 23 patients with Hodgkin's disease to study for involved lymphoma regions and compared to conventional staging procedures. Twenty stagings were performed at diagnosis of untreated Hodgkin's disease or at first relapse, and 22 restagings during and after chemoradiotherapy. At diagnosis in 5 of 20 patients PET and other procedures revealed different extranodal manifestations and in 3 patients established different clinical staging. PET seemed to be accurate in the assessment of lymphoma involvement in nodal sites. During follow up, in 10 out of 22 investigations different results and discrepancy were recorded, mostly due to the different extent of F-18-FDG metabolism in residual masses in lymphatic tissues compared to CT, X-ray or ultrasonography. The results indicate that PET may have advantages in the assessment of remissions in nodal sites. Less conclusive results were observed with regard to extranodal involvement or inflammatory disease. In conclusion PET may be sufficient for the staging of the majority of patients with Hodgkin's disease and particularly for assessing remission status in nodal sites, but PET may have disadvantages in the evaluation of extranodal lymphoma and inflammatory disease. [ABSTRACT FROM AUTHOR]

Eight carriers of the A3243G mutation of mitochondrial DNA without stroke-like episodes were monitored for up to 7 years in clinical and metabolic studies, by magnetic resonance imaging (MRI) and positron emission tomography (PET). None developed mitochondrial encephalopathy (MELAS), but 2 developed diabetes mellitus, 1 terminal kidney failure and 2 cardiomyopathy. One patient improved markedly under ubiquinone. Electroencephalography showed progressive slowing in 2 cases, but electrophysiological tests and MRI were otherwise noncontributary. PET showed widespread cortical and basal ganglion metabolic deficits in 6 cases. We conclude that internal medical complications are more common than MELAS in adult carriers of the mutation. PET findings, firstly reported in such patients, suggest that chronic subclinical encephalopathy is very frequent, and PET may play a role in monitoring in the future. [ABSTRACT FROM AUTHOR]

Objective: To connect a new family with early-onset Alzheimer disease (EOAD) in Germany to the American Volga German pedigrees. Design: Pedigree molecular genetic analysis. Setting: University Medical Centers in Fulda and Giessen, Germany, and in Seattle, Washington. Results: The families from Fulda, Germany, and the American Volga German families with EOAD share the same N141I PSEN2 mutation on an identical haplotypic background. This establishes that the N141I mutation occurred prior to emigration of the families from the Hesse region to Russia in the 1760s, and documents that relatives of the original immigrant families are presently living in Germany with the mutation and the disease. Conclusion: A family with the N141I mutation in PSEN2 that presently lives in Germany has been connected to the haplotype that carries the same mutation in pedigrees descended from the Volga Germans. This raises the possibility that the original patient with Alzheimer disease (Auguste D.), who had EOAD and lived in this same region of Germany, may also have had the PSEN2 N141I mutation. [ABSTRACT FROM AUTHOR]

The value of interim 18 F-FDG PET/CT (iPET)-guided treatment decisions in patients with diffuse large B-cell lymphoma (DLBCL) has been the subject of much debate. This investigation focuses on a comparison of the Deauville score and the change-in-SUV max (ΔSUV max ) approach-2 methods to assess early metabolic response to standard chemotherapy in DLBCL. Methods: Of 609 DLBCL patients participating in the PET-Guided Therapy of Aggressive Non-Hodgkin Lymphomas trial, iPET scans of 596 patients originally evaluated using the ΔSUV max method were available for post hoc assessment of the Deauville score. A commonly used definition of an unfavorable iPET result according to the Deauville score is an uptake greater than that of the liver, whereas an unfavorable iPET scan with regard to the ΔSUV max approach is characterized as a relative reduction of the SUV max between baseline and iPET staging of less than or equal to 66%. We investigated the 2 methods' correlation and concordance by Spearman rank correlation coefficient and the agreement in classification, respectively. We further used Kaplan-Meier curves and Cox regression to assess differences in survival between patient subgroups defined by the prespecified cutoffs. Time-dependent receiver-operating-characteristic curve analysis provided information on the methods' respective discrimination performance. Results: Deauville score and ΔSUV max approach differed in their iPET-based prognosis. The ΔSUV max approach outperformed the Deauville score in terms of discrimination performance-most likely because of a high number of false-positive decisions by the Deauville score. Cutoff-independent discrimination performance remained low for both methods, but cutoff-related analyses showed promising results. Both favored the ΔSUV max approach, for example, for the segregation by iPET response, where the event-free survival hazard ratio was 3.14 (95% confidence interval, 2.22-4.46) for ΔSUV max and 1.70 (95% confidence interval, 1.29-2.24) for the Deauville score. Conclusion: When considering treatment intensification, the currently used Deauville score cutoff of an uptake above that of the liver seems to be inappropriate and associated with potential harm for DLBCL patients. The ΔSUV max criterion of a relative reduction in SUV max of less than or equal to 66% should be considered as an alternative., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose Interim positron emission tomography (PET) using the tracer, [ 18 F]fluorodeoxyglucose, may predict outcomes in patients with aggressive non-Hodgkin lymphomas. We assessed whether PET can guide therapy in patients who are treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Patients and Methods Newly diagnosed patients received two cycles of CHOP-plus rituximab (R-CHOP) in CD20-positive lymphomas-followed by a PET scan that was evaluated using the ΔSUV max method. PET-positive patients were randomly assigned to receive six additional cycles of R-CHOP or six blocks of an intensive Burkitt's lymphoma protocol. PET-negative patients with CD20-positive lymphomas were randomly assigned or allocated to receive four additional cycles of R-CHOP or the same treatment with two additional doses rituximab. The primary end point was event-free survival time as assessed by log-rank test. Results Interim PET was positive in 108 (12.5%) and negative in 754 (87.5%) of 862 patients treated, with statistically significant differences in event-free survival and overall survival. Among PET-positive patients, 52 were randomly assigned to R-CHOP and 56 to the Burkitt protocol, with 2-year event-free survival rates of 42.0% (95% CI, 28.2% to 55.2%) and 31.6% (95% CI, 19.3% to 44.6%), respectively (hazard ratio, 1.501 [95% CI, 0.896 to 2.514]; P = .1229). The Burkitt protocol produced significantly more toxicity. Of 754 PET-negative patients, 255 underwent random assignment (129 to R-CHOP and 126 to R-CHOP with additional rituximab). Event-free survival rates were 76.4% (95% CI, 68.0% to 82.8%) and 73.5% (95% CI, 64.8% to 80.4%), respectively (hazard ratio, 1.048 [95% CI, 0.684 to 1.606]; P = .8305). Outcome prediction by PET was independent of the International Prognostic Index. Results in diffuse large B-cell lymphoma were similar to those in the total group. Conclusion Interim PET predicted survival in patients with aggressive lymphomas treated with R-CHOP. PET-based treatment intensification did not improve outcome.

Objectives: This study was designed to compare the effectiveness of positron emission tomography (PET) and magnetic resonance imaging (MRI) in the pretherapeutic staging of squamous cell carcinoma (SCC) of the head and neck., Patients and Methods: The study included 34 consecutive patients (27 males, 7 females; mean age 61 years; range 42 to 82 years) with SCC of the head and neck. All the patients underwent whole body [18F]fluorodeoxyglucose (FDG)-PET and MRI scans for pretherapeutic evaluation. Diagnoses were confirmed by histopathologic examination of endoscopic biopsy specimens., Results: The sites of the primary tumors were the oropharynx (n=15, 44%), larynx (n=10, 29%), hypopharynx (n=8, 24%), and nasopharynx (n=1, 3%). Surgery was the treatment of choice in 20 patients (59%), including 23 neck dissections. Fourteen patients (41%) were treated with radiochemotherapy. Both PET and MRI were able to detect the primary tumor in 33 cases (97%). In two patients (6%), PET was able to detect distant metastases in the lung and iliac bone, all of which were confirmed by biopsies. Seven neck specimens (30%) showed lymph node metastasis. Sensitivity and specificity rates for detection of lymph node metastasis were 100% and 87.5% for PET, and 85.7% and 87.5% for MRI, respectively., Conclusion: Although PET seems to be superior to MRI in detecting nodal disease and distant metastases, it is still early to recommend it as a primary tool for pretherapeutic evaluation of head and neck cancers due to its limited availability and higher cost.

25 patients with cancer of unknown primary (CUP) were studied using PET-FDG. Whole-body-PET scans were performed based on previous morphological information. All patients underwent conventional diagnostic modalities prior to and after the PET-study. True positive results were obtained in 12/25 patients (48%) and the primary identified by PET was confirmed by further procedures. True negative results were obtained in 8/25 patients (32%) and no primary tumor was found by PET or other clinical investigations. False positive results were obtained in 5/25 patients (20%). No false negative results were obtained. In 11 patients having CT compared with PET the primary tumor was exclusively localized by PET in 8 patients (73%) and also by CT in 3 patients (27%); CT was unable to identify the tumor in 8/11 patients detected by PET. PET affected management and directed treatment in 11/25 patients (44%). The sensitivity of PET-FDG was 100%, specificity 61%. These observations demonstrate that PET-FDG is a highly sensitive method to detect CUP. Correctly classified patients in an early stage of disease may lead to benefit from a more targeted therapy with prolonged survival time. In cases of advanced disease PET might not decisively influence survival time.