◥Purpose: We analyzed the utility of cell-free DNA (cfDNA) in a prospective population-based cohort to determine the mutational profile, assess tumor burden, and estimate its impact in response rate and outcome in patients with diffuse large B-cell lymphoma (DLBCL).Experimental Design: A total of 100 patients were diagnosed with DLBCL during the study period. Mutational status of 112 genes was studied in cfDNA by targeted next-generation sequencing. Paired formalin-fixed, paraffin-embedded samples and volumetric PET/CT were assessed when available.Results: Appropriate cfDNA to perform the analyses was obtained in 79 of 100 cases. At least one mutation could be detected in 69 of 79 cases (87%). The sensitivity of cfDNA to detect the mutations was 68% (95% confidence interval, 56.2-78.7). The mutational landscape found in cfDNA samples was highly consistent with that shown in the tissue and allowed genetic classification in 43% of the cases. A higher amount of circulating tumor DNA (ctDNA) significantly correlated with clinical parameters related to tumor burden (elevated lactate dehydrogenase and b2-microglobulin serum levels, advanced stage, and high-risk International Prognostic Index) and total metabolic tumor volume assessed by PET/CT. In patients treated with curative intent, high ctDNA levels (>2.5 log hGE/mL) were associated with lower complete response (65% vs. 96%; P < 0.004), shorter progression-free survival (65% vs. 85%; P ¼ 0.038), and overall survival (73% vs. 100%; P ¼ 0.007) at 2 years, although it did not maintain prognostic value in multivariate analyses.Conclusions: In a population-based prospective DLBCL series, cfDNA resulted as an alternative source to estimate tumor burden and to determine the tumor mutational profile and genetic classification, which have prognostic implications and may contribute to a future tailored treatment.

nAB concentrations remained high for the first 24 hours in BAL and for less time in BAS, with distribution of the drug being uniform in patients without BOS. Furthermore, lung-perfusion studies appear to be useful to ascertain nAB distribution in patients receiving lung transplantions.

Cell free circulating tumor DNA in cerebrospinal fluid detects and monitors central nervous system involvement of B-cell lymphomas. Abstract word count: 250 Text word count: 2898 Tables and figures: 5 Supplemental files: 2Acknowlegements: The authors would to thank the patients diagnosed at the Vall d'Hebron University Hospital that were enrolled in the study, as well as the Cellex Foundation for providing research facilities and equipment. ABSTRACTThe levels of cell free circulating tumor DNA (ctDNA) in plasma correlate with treatment response and outcome in systemic lymphomas. Notably, in brain tumors, the levels of ctDNA in the cerebrospinal fluid (CSF) are higher than in plasma. Nevertheless, their role in central nervous system (CNS) lymphomas remains elusive. We evaluated the CSF and plasma from 19 patients: 6 restricted CNS lymphomas, 1 systemic and CNS lymphoma, and 12 systemic lymphomas. We performed whole exome sequencing or targeted sequencing to identify somatic mutations of the primary tumor, then variantspecific droplet digital PCR was designed for each mutation. At time of enrolment, we found ctDNA in the CSF of all patients with restricted CNS lymphoma but not in patients with systemic lymphoma without CNS involvement. Conversely, plasma ctDNA was detected in only 2 out of 6 patients with restricted CNS lymphoma with lower variant allele frequencies than CSF ctDNA. Moreover, we detected CSF ctDNA in 1 patient with CNS lymphoma in complete remission and in 1 patient with systemic lymphoma, 3 and 8 months before CNS relapse was confirmed; indicating that CSF ctDNA might detect CNS relapse earlier than conventional methods. Finally, in 2 cases with CNS lymphoma, CSF ctDNA was still detected after treatment even though no tumoral cells were observed by flow cytometry (FC), indicating that CSF ctDNA better detected residual disease than FC. In conclusion, CSF ctDNA can better detect CNS lesions than plasma ctDNA and FC. In addition, CSF ctDNA predicted CNS relapse in CNS and systemic lymphomas.

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Our findings show a different pattern of regional cerebral glucose metabolism between AVH and physiological auditory activation. This feature does not support the hypothesis that AVH in acute schizophrenic patients reflects an abnormal activation of auditory-linguistic pathways. However, it does suggest that cortical regions implicated in the generation of inner speech could be involved.

This study aims to assess the influence of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) detection of recurrent disease on the management of patients with colorectal cancer and suspected recurrence. One hundred and twenty patients with suspected recurrence were studied with FDG-PET. Fifty-eight patients were referred for FDG-PET because of the elevation of serum tumour markers. Thirty-one patients were referred because of inconclusive results of conventional imaging modalities. Twenty-five patients had known recurrence and were referred for pre-surgical assessment. Six patients were referred because of abdominal pain. A major management change was considered when, as a consequence of FDG-PET results, medical treatment was changed to surgical, or surgical to medical or to no treatment. A minor management change was considered when changes were made within a treatment modality. Of the 58 patients with elevated serum carcinoembryonic antigen (CEA), FDG-PET detected recurrence and led to a major management change in 34 (58%). Eighteen underwent curative surgery and 16 were treated with systemic therapy. Of the 31 patients evaluated because of inconclusive results of conventional imaging modalities, FDG-PET was positive for recurrence in 24 and negative in seven. A major management change took place in 14 patients (45%). Of the 25 patients evaluated to rule out other sites of disease before surgery, FDG-PET did not show any other site of recurrence in 13 (52%) and showed more lesions in the remaining patients. Major management change took place in eight patients (32%). Overall, in the 120 patients studied, FDG-PET resulted in major management changes in 58 (48%), minor changes in four (3%) and no change in 54 (45%). It can be concluded that FDG-PET has a significant impact on the management of patients with suspected recurrence of colorectal cancer. FDG-PET detection of recurrence frequently allows curative surgical intervention. The early identification of distant metastases may also facilitate the implementation of systemic treatment.

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Whole-body FDG PET in RCC patients could help to diagnose cardiac metastasis, and allows the possibility of therapeutic surgery, due to the thrombus significance of heart involvement.