Semiquantitative analysis of interim 18F-FDG PET is superior in predicting outcome in Hodgkin lymphoma patients compared to visual analysis.

PURPOSE: To investigate the prognostic value of interim PET (PETi) in adult HL patients, comparing visual with semiquantitative analysis. MATERIAL AND METHODS: Retrospective analysis of Hodgkin's lymphoma (HL) patients diagnosed between 2012 and 2016 in the Onco-hematology Department of Instituto Português de Oncologia - Porto (median follow-up: 46.5 months [2.6-66.4]). Fifty-eight patients with available PET at diagnosis (PET0) and PETi data were included. PETi scans were analyzed according to Deauville 5-point scale (5-PS), and cut-off values for changes in maximum standardized uptake value [SUVmax], peak SUV [SUVpeak], metabolic tumour volume [MTV] and total lesion glycolysis index [TLG] between PETi and PET0 were computed using ROC analysis. Visual and semiquantitative data were compared with each other in the prediction of patient outcomes. RESULTS: Semiquantitative analysis obtained a higher sensitivity for persistent/relapsed disease compared to the 5-PS (70% vs. 10%, respectively), but lower specificity. It also demonstrated better predictive performance for response to first-line therapy (negative predictive value >92%). The positive predictive value was similar for all five measurements. At 60 months of follow-up, there was a significant difference between the progression free survival (PFS) curves of patients with positive and negative PETi according to ΔSUVmax (56.9% vs. 88.0%, p<0.05), ΔSUVpeak (55.9% vs. 88.1%, p<0.05), ΔMTV (35.3% vs. 88.7%, p<0.05), and ΔTLG (42.4% vs. 88.1%, p<0.05). Statistical significance was not reached when considering 5-PS results. DISCUSSION: PETi interpretation according to a semiquantitative approach appears to discriminate HL patients better than the visual 5-PS analysis. This could allow better detection of persistent or early relapsed disease, while a negative PETi result could support de-escalating therapy intensity.

Withdrawing and Withholding Life Support in Patients With Cancer in an ICU Setting: A 5-Year Experience at a European Cancer Center.

OBJECTIVE: This was an observational retrospective study aimed to examine the frequency and associated factors of withdrawing or withholding life support (WWLS) in the intensive care unit (ICU) of a comprehensive cancer center. METHODS: Medical records of adult patients with cancer admitted to the ICU between January 2010 and December 2014 were reviewed. Patients who died during that period were classified into 2 groups: full life support and withdrawing and withholding life support. The relative impact of demographic and clinical factors was assessed using logistic regression. RESULTS: A total of 247 patients died in our unit (mortality rate of 16.3%). Their median age was 62 (interquartile range [IQR] 51-73) years, there were 142 (57.5%) male patients, and they had predominantly solid malignancies (62.3%). The median Simplified Acute Physiology Score II and Acute Physiology and Chronic Health Evaluation scores were 67 (IQR 54-80) and 29 (IQR 23-55), respectively. Ninety-six (38.9%) patients died after WWLS with no statistically significant differences in decisions to limit therapy during the study period. Patients with advanced age, solid malignancies, nonneutropenic, and longer duration of mechanical ventilation were more likely to die after WWLS. In multivariate analysis, presenting with neutropenia was independently associated with a lower likelihood of dying after WWLS (odds ratio: 0.34, 95% confidence interval: 0.15-0.80). CONCLUSION: Limitation of therapy has been a common practice in oncologic ICUs over recent years. Neutropenia is an independent predictor of limitation of therapy.

SEPT2 is a new fusion partner of MLL in acute myeloid leukemia with t(2;11)(q37;q23).

We have identified a new mixed lineage leukemia (MLL) gene fusion partner in a patient with treatment-related acute myeloid leukemia (AML) presenting a t(2;11)(q37;q23) as the only cytogenetic abnormality. Fluorescence in situ hybridization demonstrated a rearrangement of the MLL gene and molecular genetic analyses identified a septin family gene, SEPT2, located on chromosome 2q37, as the fusion partner of MLL. RNA and DNA analyses showed the existence of an in-frame fusion of MLL exon 7 with SEPT2 exon 3, with the genomic breakpoints located in intron 7 and 2 of MLL and SEPT2, respectively. Search for DNA sequence motifs revealed the existence of two sequences with 94.4% homology with the topoisomerase II consensus cleavage site in MLL intron 7 and SEPT2 intron 2. SEPT2 is the fifth septin family gene fused with MLL, making this gene family the most frequently involved in MLL-related AML (about 10% of all known fusion partners). The protein encoded by SEPT2 is highly homologous to septins 1, 4 and 5 and is involved in the coordination of several key steps of mitosis. Further studies are warranted to understand why the septin protein family is particularly involved in the pathogenesis of MLL-associated leukemia.

Detection of prognostic significant translocations in childhood acute lymphoblastic leukaemia by one-step multiplex reverse transcription polymerase chain reaction.

The search for chromosomal translocations in de novo cases of childhood acute lymphoblastic leukaemia (ALL) is crucial for the selection of the appropriate therapeutic protocol. In this work, we describe a new method - one-step multiplex reverse transcription polymerase chain reaction (RT-PCR) - to screen for prognostic significant translocations in childhood ALL. Our approach involves a single PCR reaction for the simultaneous detection of the molecular rearrangements resulting from the t(9;22), t(12;21), t(4;11) and t(1;19), with a turnaround time of less than 24 h. This assay proved to be highly sensitive, specific, reproducible and easy to implement in a routine genetics laboratory.