90Y TOF-PET based EUD reunifies patient survival prediction in resin and glass microspheres radioembolization of HCC tumours.

Clinical studies reported a twofold ratio between the efficacies per Gy of resin versus glass spheres. Our aim is to investigate whether this difference could result from the different degrees of heterogeneity in sphere distribution between the two medical devices. The 90Y TOF-PET based equivalent uniform doses (EUD) was used for this purpose. 58 consecutive HCC radioembolizations were retrospectively analyzed. Absorbed doses D and Jones-Hoban EUD in lesions were computed. Radioembolization efficacy was assessed using Kaplan-Meier survival curves. In order to match together the glass and resin spheres survival curves using a 40 Gy-threshold, an efficacy factor of 0.73 and 0.36 has to be applied on their absorbed dose, respectively. Using EUD, a nice matching between glass and resin survival curves was obtained with a better separation of the responding and not responding survival curves. The results clearly support the fact that the activity heterogeneity observed in 90Y TOF-PET post radioembolization does not only result from statistical noise, but also reflects the actual heterogeneity of the spheres distribution. Use of EUD reunifies the efficacy of the two medical devices.

Activity and safety of afatinib in a window preoperative EORTC study in patients with squamous cell carcinoma of the head and neck (SCCHN).

Background: To investigate the activity and safety of afatinib in the preoperative treatment of squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: This study was an open-label, randomized, multicenter, phase II window of opportunity trial. Treatment-naïve SCCHN patients selected for primary curative surgery were randomized (5 : 1 ratio) to receive afatinib during 14 days (day -15 until day -1) before surgery (day 0) or no treatment. Tumor biopsies, 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET), and magnetic resonance imaging (MRI) were carried out at diagnosis and just before surgery. The primary end point was metabolic FDG-PET response (according to EORTC guidelines). Other end points included response assessment based on the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, dynamic contrast-enhanced (DCE)-MRI, diffusion weighted (DW)-MRI, safety, and translational research (TR). Results: Thirty patients were randomized: 25 to afatinib and 5 to control arm. Of the 23 eligible patients randomized to afatinib, 16 (70%; 95% CI: 47% to 87%) patients had a partial metabolic FDG-PET response (PMR). Five patients (22%; 95% CI: 8% to 44%) showed a partial response by RECISTv1.1. Responses assessed via DCE-MRI and DWI-MRI did not show a strong association with PMR or RECIST. One patient discontinued afatinib after 11 days for grade 3 diarrhea with subsequent renal failure and 24 days delay in surgery. No grade 4 toxicities or surgical comorbidities related to afatinib were reported. TR results indicated that PMR was more frequent in the tumors with high Cluster3-hypoxia score expression and with TP53 wild type. Conclusion: Afatinib given for 2 weeks to newly diagnosed SCCHN patients induces a high rate of FDG-PET partial metabolic response and partial response according to RECISTv1.1. Afatinib can be safely administered before surgery. Although exploratory, the hypoxic gene signature needs further investigations as a predictive biomarker of afatinib activity. Clinical trial registration: ClinicalTrials.gov: NCT01538381.

First Robinsoniella peoriensis aortic cross homograft mycotic pseudoaneurysm: A case report and review of the literature.

Mycotic aortic aneurysm is a rare and challenging complication of aortic homografts caused by an infection and is associated with high morbidity and mortality. We report the first case of an aortic cross homograft mycotic pseudoaneurysm caused by Robinsoniella peoriensis in a 70-year-old man. Our patient underwent surgery for a recurrence of aortic cross mycotic pseudoaneurysm at the level of the aortic homograft he had had 7 years before. A clot-removal of the pseudoaneurysm was surgically carried out and the homograft was completely removed. Anaerobic culture from tissue samples yielded pure growth of a spore-forming Gram-positive rod, identified later as Robinsoniella peoriensis by 16S rRNA gene sequencing. The patient was then discharged with oral clindamycin according to the in vitro susceptibility testing. Identification of R. peoriensis might be challenging in clinical laboratories with no access to molecular methods.

Tumour response and safety of cetuximab in a window pre-operative study in patients with squamous cell carcinoma of the head and neck.

BACKGROUND: To investigate the safety and activity of cetuximab in the pre-operative treatment of squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Cetuximab was administered for 2 weeks before surgery to 33 treatment-naïve patients selected for primary surgical treatment. Tumour biopsies, 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography ((18)FDG-PET) and imaging were carried out at baseline and before surgery. The primary aim of the study was safety and the secondary aims included metabolical, radiological and pathological tumour response. Five untreated patients were included as controls. RESULTS: Cetuximab given 24 h before surgery was safe. Ninety percent of patients had (18)FDG-PET partial response (EORTC guideline) in the cetuximab group versus 0% in the control group. Delta maximal standardized uptake values (ΔSUVmax) were correlated with tumour cellularity on the surgical specimens (P < 0.0001). For patients with ΔSUVmax less than -25% or less than -50%, Ki67 was significantly decreased by cetuximab (P = 0.01 and 0.003). Cetuximab induced down-regulation of pEGFR (P = 0.0004) and pERK (P = 0.003). CONCLUSIONS: Short-course pre-operative administration of cetuximab is safe and shows a high rate of (18)FDG-PET response. (18)FDG-PET response was correlated with residual tumour cellularity suggesting that (18)FDG-PET deserves further investigation as a potential early marker of cetuximab activity in SCCHN.

MRI for response assessment in metastatic bone disease.

BACKGROUND: Beyond lesion detection and characterisation, and disease staging, the quantification of the tumour load and assessment of response to treatment are daily expectations in oncology. METHODS: Bone lesions have been considered "non-measurable" for years as opposed to lesions involving soft tissues and "solid" organs like the lungs or liver, for which response evaluation criteria are used in every day practice. This is due to the lack of sensitivity, specificity and measurement capabilities of imaging techniques available for bone assessment, i.e. skeletal scintigraphy (SS), radiographs and computed tomography (CT). RESULTS: This paper reviews the possibilities and limitations of these techniques and highlights the possibilities of positron emission tomography (PET), but mainly concentrates on magnetic resonance imaging (MRI). CONCLUSION: Practical morphological and quantitative approaches are proposed to evaluate the treatment response of bone marrow lesions using "anatomical" MRI. Recent developments of MRI, i.e. dynamic contrast-enhanced (DCE) imaging and diffusion-weighted imaging (DWI), are also covered. KEY POINTS: • MRI offers improved evaluation of skeletal metastases and their response to treatment. • This new indication for MRI has wide potential impact on radiological practice. • MRI helps meet the expectations of the oncological community. • We emphasise the practical aspects, with didactic cases and illustrations.

High FDG uptake on FDG-PET scan in HIV-1 infected patient with advanced disease.

UNLABELLED: We report the case of a 48-year-old Caucasian male positive for HIV-1 who was admitted in our clinic for a fever of unknown origin with weight loss. The CD4 cell count was 99/mm3 and the viral load (VL) was 836500 copies/ml. A first FDG-PET-CT showed abnormal hypermetabolism of multiple lymp nodes, of the bone marrow and of the spleen. Tuberculosis and lymphoma were excluded by a lymph node biopsy and a culture. Six months after the start of a highly active anti-retroviral therapy (HAART) containing lamuvidine, tenofovir, atazanavir boosted by ritonavir, a new FDG-PET-CT showed a complete normalisation of the metabolism in the regions previously described as having a high FDG uptake. The VL was < 37 copies/ml and his CD4 cell count was 399/mm3. IN CONCLUSION: in patients with advanced HIV infections presenting with FUO, high uptake in 18FDG-PET-CT can be the marker of advanced disease reflecting the areas of viral replication.

Myocardial revascularization for severe left ventricular dysfunction. Factors influencing early and late survival.

The results of coronary bypass surgery have been assessed in 102 patients with severe left ventricular dysfunction who had a preoperative left ventricular ejection fraction of < or = 0.35 (mean (s.e.m.) 0.29 (0.01)). Independent risk factors influencing operative mortality were obesity (P = 0.0290) and the need for preoperative intra-aortic balloon counterpulsation (P = 0.0010). Cox regression analysis using as its end-point 'cardiac-related death' demonstrated three variables; the need for preoperative intra-aortic balloon counterpulsation (P < 0.001), advanced age (P = 0.011), and obesity (P = 0.36). In a subset of 43 patients who did not have these risk factors, the 4-year cardiac-related death rate was 95.1 (3.4)%. The operative mortality and long-term survival can be expected to be satisfactory in patients with severe left ventricular dysfunction, provided they have a viable myocardium rather than myocardial fibrosis.