Evaluation of the capability and reproducibility of RECIST 1.1. measurements by technologists in breast cancer follow-up: a pilot study.

The evaluation of tumor follow-up according to RECIST 1.1 has become essential in clinical practice given its role in therapeutic decision making. At the same time, radiologists are facing an increase in activity while facing a shortage. Radiographic technologists could contribute to the follow-up of these measures, but no studies have evaluated their ability to perform them. Ninety breast cancer patients were performed three CT follow-ups between September 2017 and August 2021. 270 follow-up treatment CT scans were analyzed including 445 target lesions. The rate of agreement of classifications RECIST 1.1 between five technologists and radiologists yielded moderate (k value between 0.47 and 0.52) and substantial (k value = 0.62 and k = 0.67) agreement values. 112 CT were classified as progressive disease (PD) by the radiologists, and 414 new lesions were identified. The analysis showed a percentage of strict agreement of progressive disease classification between reader-technologists and radiologists ranging from substantial to almost perfect agreement (range 73-97%). Analysis of intra-observer agreement was strong at almost perfect (k > 0.78) for 3 technologists. These results are encouraging regarding the ability of selected technologists to perform measurements according to RECIST 1.1 criteria by CT scan with good identification of disease progression.

High prevalence of pre-existing sarcopenia in critically ill patients with hematologic malignancies admitted to the intensive care unit for sepsis or septic shock.

BACKGROUND & AIMS: We aimed to evaluate body composition (BC) by computed tomography (CT) in hematologic malignancy (HM) patients admitted to the intensive care unit (ICU) for sepsis or septic shock. METHODS: We retrospectively assessed BC and its impact on outcome of 186 patients at the 3rd lumbar (L3) and 12th thoracic vertebral levels (T12) using CT-scan performed before ICU admission. RESULTS: The median patient age was 58.0 [47; 69] years. Patients displayed adverse clinical characteristics at admission with median [q1; q3] SAPS II and SOFA scores of 52 [40; 66] and 8 [5; 12], respectively. The mortality rate in the ICU was 45.7%. Overall survival rates at 1 month after admission in the pre-existing sarcopenic vs. non pre-existing sarcopenic patients were 47.9% (95% CI [37.6; 61.0]) and 55.0% (95% CI [41.6; 72.8]), p = 0.99), respectively, at the L3 level and 48.4% (95% CI [40.4; 58.0]) vs. 66.7% (95% CI [51.1; 87.0]), p = 0.062), respectively, at the T12 level. CONCLUSIONS: Sarcopenia is assessable by CT scan at both the T12 and L3 levels and is highly prevalent in HM patients admitted to the ICU for severe infections. Sarcopenia may contribute to the high mortality rate in the ICU in this population.

Non-invasive monitoring of diffuse large B-cell lymphoma by cell-free DNA high-throughput targeted sequencing: analysis of a prospective cohort.

From a liquid biopsy, cell-free DNA (cfDNA) can provide information regarding basal tumoral genetic patterns and changes upon treatment. In a prospective cohort of 30 diffuse large B-cell lymphomas (DLBCL), we determined the clinical relevance of cfDNA using targeted next-generation sequencing and its correlation with PET scan imaging at the time of diagnosis and during treatment. Using a dedicated DLBCL panel, mutations were identified at baseline for 19 cfDNAs and profiles were consistent with expected DLBCL patterns. Tumor burden-related clinical and PET scan features (LDH, IPI, and metabolic tumor volume) were significantly correlated with the quantity of tumoral cfDNA. Among the four patients presenting additional mutations in their cfDNAs, three had high metabolic tumor volumes, suggesting that cfDNA more accurately reflects tumor heterogeneity than tissues biopsy itself. Mid-treatment, four patients still had basal mutations in their cfDNAs, including three in partial response according to their Deauville scores. Our study highlights the major interests in liquid biopsy, in particular in the context of bulky tumors where cfDNA allows capturing the entire tumoral mutation profile. Therefore, cfDNA analysis in DLBCL represents a complementary approach to PET scan imaging.

Metabolic oxidative cleavage of thioesters: evidence for the formation of sulfenic acid intermediates in the bioactivation of the antithrombotic prodrugs ticlopidine and clopidogrel.

Metabolic cleavage of the CO-S bond of some thioesters RCOSR' with the formation of RCOOH requires a monooxygenase-dependent oxidative activation of this bond. The nature of the S-containing product(s) resulting from this cleavage remains unclear in most cases. This communication provides the first evidence for the formation of sulfenic acid intermediates 4a and 4b during the oxidative cleavage of the CO-S bond of thiolactone metabolites 2a and 2b of antithrombotic prodrugs, ticlopidine and clopidogrel, by rat and human liver microsomes. These intermediates have been trapped by dimedone, and the corresponding adducts 5a and 5b have been characterized by mass spectrometry (MS) and (1)H and (13)C NMR spectroscopy. Their formation is monooxygenase-dependent and almost completely inhibited by microsomal cytochrome P450 inhibitors. Moreover, they were also formed upon incubation with microsomes containing recombinant human P450 3A4, 3A5, 2C8, 2C9, 2C19, 2D6, or 1A2. In the presence of thiols such as mercaptoethanol, N-acetylcysteine, or glutathione, microsomal incubations of 2a led to mixed disulfides that have been characterized by MS and should result from reaction of 4a with these thiols. At high thiol concentrations, one observed in HPLC-MS the formation of a product exhibiting the MS expected for the previously described thiol metabolite 3a, a reduction product of 4a that has been reported as the pharmacologically active metabolite of ticlopidine. These data provide the first evidence for the formation of sulfenic acid reactive metabolites upon P450-catalyzed oxidative cleavage of thioesters. They also provide a first detailed mechanism for the previously described formation of pharmacologically active thiols such as 3a upon oxidative metabolism of ticlopidine and clopidogrel.