Plasma ceramide, a real-time predictive marker of pulmonary and hepatic metastases response to stereotactic body radiation therapy combined with irinotecan

AbstractBackground and purposesEarly biomarkers of tumour response are needed to discriminate between responders and non-responders to radiotherapy. We evaluated the ability of ceramide, a bioactive sphingolipid, to predict tumour sensitivity in patients treated by hypofractionated stereotactic body radiation therapy (SBRT) combined with irinotecan chemotherapy.Materials and methodsPlasma levels of total ceramide and of its subspecies were measured before and during treatment in 35 patients with liver and lung oligometastases of colorectal cancer included in a phase II trial. Cer levels were quantified by LC–ESI-MS/MS and compared to tumour volume response evaluated one year later by CT-scan.ResultsPretreatment plasma ceramide levels were not indicative of tumour response. Nevertheless, the levels of total ceramide and of its 4 main subspecies were significantly higher at days 3 and 10 of treatment in objective responders than in non-responders. According to Kaplan–Meier curves, almost complete tumour control was achieved at 1year in patients with increased total ceramide levels whereas 50% of patients with decreased levels experienced an increase in tumour volume.ConclusionsTotal plasma ceramide is a promising biomarker of tumour response to SBRT combined with irinotecan that should enable to segregate patients with high risk of tumour escape

Monocopper center embedded in a biomimetic cavity: From supramolecular control of copper coordination to redox regulation

International audienceThe electrochemical behavior of diversely substituted Cu-N-3-calix[6]arene, enzyme-like, "funnel" complexes is analyzed. The Cu(II)/Cu(I) redox process is regulated by the supramolecular organization of the Cu coordination. The presence of a "shoetree" alkyl nitrile guest molecule inside the host cavity is a prerequisite for a dynamic redox behavior. Combination of supramolecular CH-pi weak interactions with the calixarene cavity and electronic/steric effects from the N-3 substituting groups (pyridine, imidazole, pyrrolidine) enforces the preferential geometrical pattern adopted by Cu. This dictates the pathway of the electron-transfer process and, thus, the thermodynamics and kinetics of the redox reaction in the framework of a square-scheme mechanism. The present observations recall strongly the redox control exerted by the protein matrix on copper proteins through biological concepts such as induced fit mechanism, protein foldings, and entatic and allosteric effects

Prognostic value of FDG-PET indices for the assessment of histological response to neoadjuvant chemotherapy and outcome in pediatric patients with Ewing sarcoma and osteosarcoma.

The objective of this retrospective work was to evaluate the prognostic value on histological response and survival of quantitative indices derived from FDG-PET performed before and after chemotherapy (CHT), in a homogeneous pediatric Ewing sarcoma (EWS) and Osteosarcoma (OST) population.Thirty-one patients with EWS and 31 with OST were included. All patients were treated with neoadjuvant CHT, and underwent surgery for local control. All patients had FDG-PET at diagnosis and after CHT, prior to surgery. Several parameters were evaluated: SUVmax, SUVpeak, SUVmean, metabolic tumor volume, total lesion glycolysis, 7 textural features and 3 shape features (SF). The segmentation was performed using an adaptive approach. Results were compared to histopathological regression of the resected tumor and to clinical follow-up for survival evaluation.For EWS, univariate analysis did not highlight any prognostic value on histological response, or survival regardless of all the considered metrics. For OST, only one of the SF, namely elongation, was significantly associated with PFS and OS on both univariate and multivariate analysis (PFS: p = 0.019, HR = 5.583; OS: p = 0.0062, HR = 7.113).Only elongation determined on initial FDG-PET has a potential interest as a prognostic factor of PFS and OS in pediatric OST patients. Unlike recent studies of the literature realized in adult population, all the metrics reveal limited additional prognostic value in pediatric EWS patients. This seems to reinforce the question of whether children experience different subtypes of the same pathologies than older patients, with different outcomes

Survival Outcomes after Hyperthermic Intraperitoneal Chemotherapy for a First Ovarian Cancer Relapse: A Systematic Evidence-Based Review

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) is routinely used in the treatment of a first ovarian cancer relapse. Methods: This systematic review, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, aimed to assess the quality of scientific proof of the survival benefits of HIPEC, using Medline and Google Scholar. Qualitative analysis using the Oxford CEBM Levels of Evidence 2011 grading is reported. Results: Of 469 articles identified, 23 were included; 15 based on series of patients treated with HIPEC without a control group, and 8 case control series of patients treated with or without HIPEC. The series without a control group showed median overall survival (OS) ranged from 23.5 to 63 months, highlighting a broad standard deviation. Considering the case control series, OS was significantly better in the HIPEC group in 5 studies, and similar in 1. The current review showed considerable heterogeneity and biases, with an Oxford Level of Evidence grading of 4 for 22 selected series and 2 for one. Conclusions: There is no strong evidence to suggest efficacy of HIPEC in improving survival of patients treated for a first relapse of ovarian cancer due to the low quality of the data

Correlation between ERK1 and STAT3 expression and chemoresistance in patients with conventional osteosarcoma

BACKGROUND: The standard therapy regimen of conventional osteosarcoma includes neoadjuvant chemotherapy followed by surgical resection and postoperative chemotherapy. The percentage of necrotic tissue following induction chemotherapy is assessed by using the Huvos grading system, which classifies patients as “poor responders” (PR) and “good responders” (GR). The aim of this study was to identify molecular markers expressed differentially between good and poor responders to neoadjuvant chemotherapy in order to predict the response to chemotherapy in conventional osteosarcomas before beginning treatment. METHODS: Suppression Substractive Hybridization (SSH) was performed by using cDNA from frozen biopsy specimens. Expression of selected relevant genes identified by SSH was validated by using QRT-PCR. Immunohistochemistry (IHC) on tissue microarray (TMA) sections of 52 biopsies was performed to investigate protein expression in an independent cohort. RESULTS: ERK1 and STAT3 mRNA level were significantly different between PR and GR in an independent cohort. Phosphorylated STAT3 and ERK1 expressions by IHC on TMA were correlated with poor response to chemotherapy. CONCLUSIONS: Our results suggest that ERK1 and STAT3 expression are good predictive markers for chemotherapy response and that inhibitors might be used in combination with common chemotherapeutic drugs in conventional osteosarcomas

68 Ga‐PSMA PET/CT prospective study in prostate cancer patients with occult recurrence: Diagnostic performance and impact on therapeutic decision‐making and long-term benefits

International audienc

Various explorations conducted in a patient with osteosarcoma of the right tibia.

<p>FDG-PET scans acquired before (A) and after chemotherapy (B) in a patient with osteosarcoma of the right tibia. The maximum intensity projections of PET (first columns) and the coronal views of fused PET/CT images (third columns) showed evident significant reduction in MTV (second columns) using an adaptative threshold, after chemotherapy. The removed tumor specimen (C) was almost completely composed of necrotic tissue (99%).</p