Risk stratification in diffuse large B-cell lymphoma using lesion dissemination and metabolic tumor burden calculated from baseline PET/CT†.

BACKGROUND: We analyzed the prognostic value of a new baseline positron emission tomography (PET) parameter reflecting the spread of the disease, the largest distance between two lesions (Dmax). We tested its complementarity to metabolic tumor volume (MTV) in a large cohort of diffuse large B-cell lymphoma (DLBCL) patients from the REMARC trial (NCT01122472). PATIENTS AND METHODS: MTVs were defined using the 41% maximum standardized uptake value threshold. From the three-dimensional coordinates, the centroid of each lesion was automatically obtained and considered as the lesion location. The distances between all pairs were calculated. Dmax was obtained for each patient and normalized with the body surface area [standardized Dmax (SDmax)]. RESULTS: From the REMARC trial, 290 patients aged 60-80 years were included: 91% had an advanced stage and 71% International Prognostic Index (IPI) ≥3. High versus low SDmax significantly impacted progression-free survival (PFS) (P < 0.0001) and overall survival (OS) (P = 0.0027). Patients with SDmax > 0.32 m-1 (n = 82) had a 4-year PFS and OS of 46% and 71%, respectively, against 77% and 87%, respectively, for patients with low SDmax. High SDmax and high MTV were independent prognostic factors of PFS (P = 0.0001 and P = 0.0010, respectively) and OS (P = 0.0028 and P = 0.0004, respectively). Combining MTV and SDmax yielded three risk groups with no (n = 109), one (n = 122) or two (n = 59) factors (P < 0.0001 for both PFS and OS). The 4-year PFS were 90%, 63%, 41%, respectively, and the 4-year OS were 95%, 79%, 66%, respectively. In addition, patients with at least two of the three factors including high SDmax, high MTV, Eastern Cooperative Oncology Group (ECOG) ≥2 had a higher number of central nervous system relapse (P = 0.017). CONCLUSIONS: SDmax is a simple feature that captures lymphoma dissemination, independent from MTV. These two PET metrics, SDmax and MTV, are complementary to characterize the disease, reflecting the tumor burden and its spread. This score appeared promising for DLBCL baseline risk stratification.

Early metabolic response to chemoradiotherapy by interim FDG PET/CT is associated with better overall survival and histological response in esophageal cancers.

BACKGROUND: Early assessment of response to neoadjuvant chemoradiotherapy (CRT) is crucial in determining the most suitable treatment strategy in locally advanced oesophageal cancer (LAEC). AIMS: We evaluated the impact of early metabolic response during CRT on overall survival (OS) and histological response. METHODS: Patients with biopsy-proven oesophageal carcinoma underwent FDG PET/CT with evaluation of the standardized uptake value (SUV) before any treatment and during CRT after 20 Gy. RESULTS: 116 patients (Male: 66.4%, Median age: 63; squamous cell carcinomas (SCC): 70%) met inclusion criteria. Median OS was 21.7 months. There was a significant positive correlation between interim metabolic response and OS. In multivariate analysis, only metabolic response using the 50% cut-off value remained significantly associated with OS (IC95% = 0.28-0.73; p = 0.001). In this statistical analysis, surgery (p = 0.007) and T stage (p = 0.023) were also correlated with OS. There was a significant correlation between early metabolic response and local recurrence (Chi-squared test p = 0.0001). CONCLUSIONS: Early metabolic response using FDG PET/CT is associated with better OS, disease-free survival, local control and pathological response in patients treated by CRT for LAEC.

18F-FDG labelling of hematopoietic stem cells: Dynamic study of bone marrow homing by PET-CT imaging and impact on cell functionality.

PURPOSE OF THE STUDY: After transplantation, cord blood (CB) hematopoietic stem and progenitor cells (HSPCs) are able to home to the bone marrow niche and to reconstitute the hematopoietic system. PET-CT imaging may be a useful method to monitor this parameter in different conditions. The aim of our study was to set up an efficient method for HSPC radiolabelling with [18F] fluorodeoxyglucose (18F-FDG) and to follow early HSPC homing through PET-CT in mice. MATERIALS AND METHODS: Purified CB HSPCs were radiolabelled with 18F-FDG at 37° C with various conditions of cell concentration, incubation time and radioactivity concentration in order to define the in vitro condition that allows both sufficient 18F-FDG uptake to get high quality PET imaging, and preservation of HSPC viability and functional properties during 3h after radiolabelling. Then, 24h after 2.25Gy irradiation, eight NOD-scid/γc-/- mice were injected with 18F-FDG-labelled HSPCs, the biodistribution of which was followed using micro-PET-CT. RESULTS: The optimal incubation time was 45min with a stability of 48.3%±12.8% after 180min. The radio-uptake rate we obtained was 7.2%±1.7% with an activity of 5.6±2.1 MBq. Three hours after radiolabelling, viability was 96.7%±3.4%. Fifteen hours after radiolabelling, cell viability was 64.0%±2.3%, migration ability diminished from 51.0%±23.6% to 12.0%±9.1%, clonogenic capacity was null, and long-term engraftment in NSG mice also decreased compared to unlabelled cells. Micro-PET-CT experiments showed an accumulation of radiolabelled HSPCs for 2.5h after injection in the bone marrow and a slight elution of 18F-FDG. CONCLUSION: The activity of the obtained 18F-FDG-labelled HSPCs was sufficient to perform the micro-PET-CT imaging. Although the radiolabelling had a significant toxicity on HSPCs 15h after labelling, this technique allowed monitoring the beginning of HSPC homing into the bone marrow.

FDG PET-CT for solitary pulmonary nodule and lung cancer: Literature review.

The investigation of solitary pulmonary nodule (SPN) and non-small cell lung cancer (NSCLC) has rapidly become one of the main indications for 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), currently combined with computed tomography (PET-CT). In this literature review, we first attempt to clarify how PET imaging contributes to investigating SPN, in conjunction with conventional CT. We highlight the prospects of research underway to improve our understanding of SPN. In the second part of this review, we analyze the current role of PET-CT in the overall care process for lung cancer. We review the indications for which consensus has been reached, for example initial staging, as well as new indications such as radiation therapy planning or prognostic assessment.

[Acid sphingomyelinase deficiency and spleen trauma: splenectomy or not splenectomy?]. / Déficit en sphingomyélinase acide et rupture splénique : splénectomie ou traitement conservateur ?

INTRODUCTION: Acid sphingomyelinase deficiency leads to a severe infantile disease (Niemann-Pick disease type A) or an attenuated form of the disease encountered in adults (Niemann-Pick type B), including pulmonary fibrosis and splenomegaly. CASE REPORT: A 52-year-old man with Niemann-Pick disease type B was admitted with splenic rupture. Embolization of the splenic artery was initially performed. Three months later, the splenic volume had increased and functional asplenia was diagnosed. Splenic scintigraphy showed 20% of functional splenic tissue. Splenectomy was finally performed because of complete necrosis of the spleen. CONCLUSION: Despite its theoretical contra-indication in Niemann-Pick disease due to a risk of respiratory insufficiency, splenectomy must sometimes be considered.

HER2-overexpressing breast cancer: FDG uptake after two cycles of chemotherapy predicts the outcome of neoadjuvant treatment.

BACKGROUND: Pathologic complete response (pCR) to neoadjuvant treatment (NAT) is associated with improved survival of patients with HER2+ breast cancer. We investigated the ability of interim positron emission tomography (PET) regarding early prediction of pathology outcomes. METHODS: During 61 months, consecutive patients with locally advanced or large HER2+ breast cancer patients without distant metastases were included. All patients received NAT with four cycles of epirubicin+cyclophosphamide, followed by four cycles of docetaxel+trastuzumab. ¹8F-fluorodeoxyglucose (¹8F-FDG)-PET/computed tomography (CT) was performed at baseline (PET1) and after two cycles of chemotherapy (PET2). Maximum standardised uptake values were measured in the primary tumour as well as in the axillary lymph nodes. The correlation between pathologic response and SUV parameters (SUVmax at PET1, PET2 and ΔSUVmax) was examined with the t-test. The predictive performance regarding the identification of non-responders was evaluated using receiver operating characteristics (ROC) analysis. RESULTS: Thirty women were prospectively included and 60 PET/CT examination performed. At baseline, 22 patients had PET+ axilla and in nine of them ¹8F-FDG uptake was higher than in the primary tumour. At surgery, 14 patients (47%) showed residual tumour (non-pCR), whereas 16 (53%) reached pCR. Best prediction was obtained when considering the absolute residual SUVmax value at PET2 (AUC=0.91) vs 0.67 for SUVmax at PET1 and 0.86 for ΔSUVmax. The risk of non-pCR was 92.3% in patients with any site of residual uptake >3 at PET2, no matter whether in breast or axilla, vs 11.8% in patients with uptake ≤3 (P=0.0001). The sensitivity, specificity, PPV, NPV and overall accuracy of this cutoff were, respectively: 85.7%, 93.8%, 92.3%, 88.2% and 90%. CONCLUSION: The level of residual ¹8F-FDG uptake after two cycles of chemotherapy predicts residual disease at completion of NAT with chemotherapy+trastuzumab with high accuracy. Because many innovative therapeutic strategies are now available (e.g., addition of a second HER2-directed therapy or an antiangiogenic), early prediction of poor response is critical.

[Extravasation of radiopharmaceuticals: preventive measures and management recommended by SoFRa (Société Française de Radiopharmacie)]. / Extravasation des médicaments radiopharmaceutiques : mesures préventives et prise en charge recommandées par la SoFRa (Société française de radiopharmacie).

Radiopharmaceuticals extravasation is rare but may have serious clinical issues. Because no specific recommendations are being proposed to date, the goals of our working group created within the French Society of Radiopharmacy are to determine preventive measures and to establish a pragmatic management of extravasation of these drugs. Our preventive measures are to recognize the symptoms (erythema, venous discoloration, swelling), to know the risk factors (which are related to radiopharmaceutical, patient, site of injection, injection technique) and severity (from erythema to skin necrosis, depending on the radionuclide) and how to avoid them (training and awareness of staff, choice of injection site, route of drug administration test, use of a catheter for administration of therapeutic radiopharmaceuticals). Management should be immediate. It can be facilitated by a specific emergency kit. General measures recommended are the immediate cessation of injection, aspiration of fluid extravasation, delimitation of the extravasated area with an indelible pen, informing the doctor. Specific measures taking into account the radiotoxicity of the radionuclide and the type of radiopharmaceutical were also established. The patient should be informed by the doctor about the risks and how to take care of. Traceability of the incident must be ensured. A multidisciplinary reflexion is essential to manage the extravasation as early and effectively as possible.

[Experiences in the decentralization of the medical welfare activities in the Turin commune]. / Esperienze di decentramento territoriale di attività sociosanitarie nel comune di Torino.

The welfare and medical activities in the town of Turin which have been decentralized in the quarters or in grouped quarters in order to answer better to the demands of the users, are analysed and explained here. Also a sample of building structure realized in Turin too, as a standard sample of social and medical centre and of basis services on its territory, is presented.