Retrospective study evaluating dental side effects of radiotherapy in patients treated for head and neck cancer.

INTRODUCTION: Head and neck cancer squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide with around 600,000 new diagnosis each year. Nowadays, in locally advanced disease, radiotherapy (RT) play an important role, this with or without chemotherapy in organ preservation strategies. More specific for early stage localized disease, RT (or surgery) seems to give similar results on locoregional control (LRC) and choice is made according to the organ preservation issue. Despite the fact that technical improvements have been made to optimize the radiation dose delivery and minimize the normal tissue toxicity, RT is associated with potential early and late toxicities. Osteoradionecrosis of the jaw (ORNJ), especially seen after teeth extraction, is one of the associated toxicities and can significantly impair the patient's quality of life. Because of the fear of developing ORNJ, one is very reluctant to extract or place a dental implant post-radiotherapy, especially in high irradiation dose zones (>40 Gy). Hence, it is important to define teeth at risk of future extraction before initiating RT and to handle those in high-risk irradiation zones. In order to optimise extractions, we created a predictive model of the expected irradiation dose, and thus the need for extraction, to the teeth bearing bones. The aim of this study is to validate our model and to define the potential relationship between the radiation dose received by each tooth and the dental complications observed. MATERIAL AND METHODS: Between March 2012 and March 2018, patients with HNSCC treated by intensity modulated RT were retrospectively analysed. The mean irradiation dose for each tooth was generated on the administered treatment plan by contouring each tooth separately on each dosimetric scan section using dedicated software (Eclipse, Varian). In order to validate our predictive model, we compared the actual generated/administered teeth irradiation doses with the irradiation doses predicted by our model. RESULTS: Our predictive model was accurate in 69.6% of the cases. In 12.5% of cases the predicted dose was higher than the calculated dose and lower in 17,8% of the cases. A correct- or over-estimation (is the latter being clinically less worrying than an underestimated dose) was achieved in 82% of cases. For the 18% of cases underfitting, the mean margin of error was 5.7 Gy. No statistically significant association was found between the development of caries and doses to the teeth, doses to the parotid glands or dental hygiene. However, a significant association between dental irradiation at more than 40 Gy and the occurrence of dental fractures (p = 0.0002) were demonstrated. CONCLUSIONS: Our predictive model seems to be 82% accurate for dose prediction, hence might be helpful for optimizing/minimizing prophylactic extractions. Indeed, following our model, professionals could decide not to extract damaged teeth in areas not at risk of ORNJ, lowering morbidity during and after RT. Contrary to the literature, no relationship was found between the occurrence of dental caries and parotid irradiation and the patient's oral hygiene. However, for the first time, a highly significant correlation between the occurrence of dental fracture and dental irradiation at more than 40 Gy was observed.

Risk factors for imminent fractures: a substudy of the FRISBEE cohort.

Multiple factors increase the risk of an imminent fracture, including a recent fracture, older age, osteoporosis, comorbidities, and the fracture site. These findings could be a first step in the development of a model to predict an imminent fracture and select patients most at need of immediate treatment. INTRODUCTION: The risk of a recurrent fragility fracture is maximal during the first 2 years following an incident fracture. In this prospective cohort study, we looked at the incidence of recurrent fractures within 2 years after a first incident fracture and we assessed independent clinical risk factors (CRFs) increasing this imminent fracture risk. METHODS: A total of 3560 postmenopausal women recruited from 2007 to 2013 were surveyed yearly for the occurrence of fragility fractures. We identified patients who sustained a fracture during the first 2 years following a first incident fragility fracture. We quantified the risk of a new fracture and assessed independent CRFs, associated with an imminent fracture at various sites. RESULTS: A recent fracture was a significant CRF for an imminent fracture (OR (95% CI): 3.7 (2.4-5.7) [p < 0.0001]). The incidence of an imminent fracture was higher in subjects above 80 years (p < 0.001). Other CRFs highly predictive in a multivariate analysis were osteoporosis diagnosis (p < 0.01), a central fracture as the index fracture (p < 0.01), and the presence of comorbidities (p < 0.05), with likelihood ratios of 1.9, 1.9, and 2.2, respectively. An imminent fracture was better predicted by a central fracture (p < 0.01) than by a major osteoporotic fracture. The hazard ratio was the highest for a central fracture. CONCLUSION: In patients with a recent fracture, older age, osteoporosis, comorbidities, and fracture site were associated with an imminent fracture risk. These findings could be a first step in the development of a model to predict an imminent fracture and select patients most at need of immediate and most appropriate treatment.

Discriminating value of HR-pQCT for fractures in women with similar FRAX scores: A substudy of the FRISBEE cohort.

Areal bone mineral density (aBMD) has a low sensitivity to identify women at high fracture risk. The FRAX algorithm, by combining several clinical risk factors, might improve fracture prediction compared to aBMD alone. Several micro-architectural and biomechanical parameters which can be measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) are associated with fracture risk. HR-pQCT in combination or not with finite element analysis (FEA) may be used to improve bone strength prediction. Our aim was to assess whether HR-pQCT measurements (densities, cortical and trabecular microarchitecture, biomechanical proprieties assessed by FEA) had an added value in predicting fractures in a subgroup of women belonging to the Belgian FRISBEE cohort. One hundred nineteen women who sustained a fracture (aged 60 to 85 years) during the initial follow-up of our cohort had a radius and tibia examination by HR-pQCT and were compared with controls matched for their FRAX score at baseline. We found that low distal radius total (OR = 1.41 [1.07-1.86] per SD, p < 0.05) and trabecular densities (OR = 1.45 [1.10-1.90], p < 0.01), trabecular number (OR = 1.32 [1.01-1.72], p < 0.05), intra individual distribution of separation (OR = 0.73 [0.54-0.99], p < 0.05) as several FEA parameters were significantly associated with fractures. At the distal tibia, impaired cortical density (OR = 1.32 [1.03-1.70] per SD, p < 0.05) and thickness (OR = 1.29 [1.01-1.63], p < 0.05) and apparent modulus (OR = 1.30 [1.01-1.66], p < 0.05) were significantly correlated with fractures. A low ultra distal radial aBMD (UDR) measured at the time of HR-pQCT was significantly associated with fractures (OR = 1.67 [1.22-2.28], p < 0.01). Women from both groups were followed further after the realization of the HR-pQCT and 46 new fractures were registered. In this second part of the study, low UDR aBMD (OR = 1.66 [1.18-2.35], p < 0.01), total (OR = 1.48 [1.08-2.03], p < 0.05), cortical (OR = 1.40 [1.04-1.87], p < 0.05) and trabecular (OR = 1.37 [1.01-1.85], p < 0.05) densities or apparent modulus (OR = 1.49 [1.07-2.05], p < 0.05) at the radius were associated with a significant increase of fracture risk. At the tibia, only the cortical density was significantly associated with the fracture risk (OR = 1.34 [1.02-2.76], p < 0.05). These results confirm the interest of HR-pQCT measurements for the evaluation of fracture risk, also in women matched for their baseline FRAX score. They also highlight that UDR aBMD contains pertinent information.

Regorafenib after failure of gemcitabine and platinum-based chemotherapy for locally advanced/metastatic biliary tumors: REACHIN, a randomized, double-blind, phase II trial.

BACKGROUND: There is a high unmet clinical need for treatments of advanced/metastatic biliary tract cancers after progression on first-line chemotherapy. Regorafenib has demonstrated efficacy in some gastrointestinal tumors that progress on standard therapies. PATIENTS AND METHODS: REACHIN was a multicenter, double-blind, placebo-controlled, randomized phase II study designed to evaluate the safety and efficacy of regorafenib in patients with nonresectable/metastatic biliary tract cancer that progressed after gemcitabine/platinum chemotherapy. Patients were randomly assigned 1 : 1 to best supportive care plus either regorafenib 160 mg once daily 3 weeks on/1 week off or placebo until progression or unacceptable toxicity. No crossover was allowed. The primary objective was progression-free survival (PFS). Secondary objectives were response rate, overall survival, and translational analysis. RESULTS: Sixty-six patients with intrahepatic (n = 42), perihilar (n = 6), or extrahepatic (n = 9) cholangiocarcinoma, or gallbladder carcinoma (n = 9) were randomized, 33 to each treatment group (33 per group). At a median follow-up of 24 months, all patients had progressed and six patients were alive. Median treatment duration was 11.0 weeks [95% confidence interval (CI): 6.0-15.9] in the regorafenib group and 6.3 weeks (95% CI: 3.9-7.0) in the placebo group (P = 0.002). Fourteen of 33 patients (42%) in the regorafenib group had a dose reduction. Stable disease rates were 74% (95% CI: 59-90) in the regorafenib group and 34% with placebo (95% CI: 18-51; P = 0.002). Median PFS in the regorafenib group was 3.0 months (95% CI: 2.3-4.9) and 1.5 months (95% CI: 1.2-2.0) in the placebo group (hazard ratio 0.49; 95% CI: 0.29-0.81; P = 0.004) and median overall survival was 5.3 months (95% CI: 2.7-10.5) and 5.1 months (95% CI: 3.0-6.4), respectively (P = 0.28). There were no unexpected/new safety signals. CONCLUSION: Regorafenib significantly improved PFS and tumor control in patients with previously treated metastatic/unresectable biliary tract cancer in the second- or third-line setting. CLINICAL TRIAL REGISTRATION: The trial is registered in the European Clinical Trials Register database (EudraCT 2012-005626-30) and at ClinicalTrials.gov (NCT02162914).

What is the validity of self-reported fractures?

We assessed the validity of self-reported fractures, over a median follow-up period of 6.2 years, in a well characterized population-based cohort of 3560 postmenopausal women, aged 60-85 years, from the Fracture Risk Brussels Epidemiological Enquiry (FRISBEE) study. Incident low-traumatic (falls from a standing height or less) or non-traumatic fractures, including peripheral fractures, were registered during each annual follow-up telephone interview. A self-reported fracture was considered as a true positive if it was validated by written reliable medical reports (radiographs, CT scans or surgical report). False positives fractures were considered to be those for which the radiology report indicated that there was no fracture at the reported site. Among self-reported fractures, false positive rates were 14.4% for all fractures. The rate of false positives of 11.2% (n = 48/429) was not negligible for the four classical major osteoporotic fractures (MOFs: hip, clinical spine, forearm or shoulder fractures). In terms of fracture site, we found the lowest false positive rate (4.4%) at the hip, and the highest (16.8%) at the spine, with the proximal humerus and the wrist in between, at about 10% each. The global rates of false positives were 12.5% (n = 22/176) for other major fractures and 22.3% (n = 49/220) for minor fractures. Younger subjects, individuals with fractures at sites other than the hip, with a lower education level, or with a higher BMI were more likely to report false positive fractures. Our data indicate that the inaccuracy of self-reported fractures is clinically relevant for several major fractures, which could influence any fracture risk prediction model.

Osteoporosis treatment gap in a prospective cohort of volunteer women.

Despite the availability of efficient drugs to prevent osteoporotic fractures, only a minority of women receives osteoporosis therapy after a fracture. The high treatment gap in our cohort consisted of unselected volunteer patients highlights the urgent need of additional education, especially for the medical profession, regarding the risk-benefit balance of treatment. INTRODUCTION: Despite the availability of efficient drugs to prevent osteoporotic fractures, only a minority of women receives osteoporosis therapy after a fracture, with a treatment gap around 80%. This can have dramatic consequences for patients and the healthcare systems. METHODS: In this study based on longitudinal data from the FRISBEE (Fracture RIsk Brussels Epidemiological Enquiry) cohort of 3560 volunteer women aged 60 to 85 years, we evaluated the 1-year treatment gap after a first major incident fragility fracture. RESULTS: There were 386 first validated fragility fractures, 285 major osteoporotic fractures (MOF) and 101 "other major" fractures. The rate of untreated patients was 85.0% (82.8% for MOF versus 91.0 % for "other major" fracture sites) (p = 0.04), with a lower rate for spine (70.5%) and hip (72.5%) versus shoulder (91.6%) and wrist (94.1%) (p < 0.0001). More specifically, the treatment gap for patients with osteoporosis, defined by a T-score < - 2.5 SD was 74.6% versus 76.5% for patients with osteoporosis defined by the presence of hip, shoulder, or spine fractures, independently of DXA results. When considering age groups, the rate of untreated women was 87.9% for women 60-70 years old, 88.2% between 70 and 80 years and 77.8% above 80 years (p = 0.03), with a greater difference between women who were younger or older than 80 years at inclusion: 88.1% versus 77.8% (p = 0.009). A diagnosis of osteoporosis (p = 0.01) and age (p = 0.03) were the only clinical risk factors (CRFs) significantly associated with treatment initiation. CONCLUSIONS: This study highlights the urgent need of additional education, especially for the medical profession, regarding the risk-benefit balance of treatment.

Retrospective evaluation of the safety of low-level laser therapy/photobiomodulation in patients with head/neck cancer.

BACKGROUND: The standard therapeutic approach for locally advanced head and neck cancer is optimal use of radiation therapy with or without concomitant chemotherapy. The most common and distressing acute complication of such therapies is oral/pharyngeal mucositis that may be associated with severe morbidity and can interfere with the planned administration of therapy. METHODS: We have identified all patients diagnosed with head/neck cancer between 2005 and 2009, having received radiotherapy with or without cisplatin-based chemotherapy. Radiotherapy consisted of intensity-modulated radiation therapy (IMRT) in all patients. In patients with grade > 2 mucositis, photobiomodulation (PBM) consisted of three sessions of low-level laser irradiation weekly, in accordance with recently published recommendations for PBM. Patients who did not receive PBM were those for whom that approach was not requested by the radiotherapists and those who declined it. RESULTS: Two hundred twenty-two patients (62%) received PBM and 139 did not (39%). The patient's characteristics were equally distributed between the two groups. For overall survival, time to local recurrence, and progression-free survival, there was no statistical evidence for a difference in prognosis between patients with and without PBM. In a multivariate analysis, after adjusting for known prognostic factors, we found no statistical evidence that PBM was related to overall survival, progression-free survival, or local recurrence. CONCLUSIONS: Our results show evidence of no effect of PBM upon overall survival, time to local recurrences, and disease-free survival of patients with head and neck cancer treated with radiotherapy with/without chemotherapy.

Does the Prediction Accuracy of Osteoporotic Fractures by BMD and Clinical Risk Factors Vary With Fracture Site?

Several clinical risk factors (CRFs) have been shown to predict the risk of fragility fractures independently of BMD, but their accuracy in the prediction of a particular fracture site has not been extensively studied. In this study based on longitudinal data from the FRISBEE cohort (Fracture Risk Brussels Epidemiological Enquiry), we evaluated if CRFs are specific for sites of incident osteoporotic fractures during follow-up. We recruited 3560 postmenopausal women, aged 60 to 85 years, from 2007 to 2013, and surveyed yearly for the occurrence of fragility fractures during 6.2 years (median). We analyzed the association between CRFs included in the FRAX (fracture risk assessment tool) model or additional CRFs (falls, sedentary lifestyle, early untreated menopause, diabetes, use of selective serotonin reuptake inhibitors or proton pump inhibitors) and the first incident validated major osteoporotic fracture (MOF; n = 362; vertebra, hip, shoulder, and wrist) or other major fractures (n = 74; ankle, pelvis/sacrum, elbow, knee, long bones). Uni- and multivariate analyses using the Cox proportional hazards model were used. For MOFs considered together, the risk of fracture was highly associated in uni- and multivariate analyses (p<0.01) with osteoporosis (T-score < -2.5), prior fracture, age, BMD (assessed by DXA), and fall history (HR 2.34, 1.82,1.71, 1.38, and 1.32, respectively). For each site analyzed separately, prior OF, age, smoking, and total hip BMD remained independent predictors for hip fractures (HR 5.72, 3.98, 3.10, 2.32, and 1.92, respectively); osteoporosis, age, prior OF, glucocorticoids, and spine BMD for vertebral fracture (HR 2.08, 1.87, 1.78, 1.76, and 1.45, respectively); osteoporosis, prior OF, and femoral neck BMD (HR 1.83, 1.60, and 1.56, respectively) for wrist fracture; osteoporosis, prior OF, and spine BMD (HR 2.48, 1.78, and 1.31, respectively) for shoulder fracture; prior OF and diabetes (HR 2.62 and 2.03) for other major fractures. Thus, a prior fracture and BMD were the best predictors of fracture risk at any site. Other CRFs have a weaker predictive value, which is a function of the site of a future fracture. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

[Lung cancer: Prognosis in intensive care depends mainly on the acute complication]. / Cancer bronchique : le pronostic en soins intensifs dépendrait surtout de la complication.

INTRODUCTION: It has been demonstrated in unselected populations of cancer patients that prognosis in intensive care is essentially dependent on the extent of the acute physiological disturbance caused by the complication precipitating the admission. By contrast, the prognosis after hospital discharge remains dependent on the characteristics of the underlying neoplasm. The aim of our study was to confirm whether this general finding was the case in a specific population of lung cancer patients, since there are no data on this patient group in the literature. PATIENTS AND METHODS: We conducted a retrospective study including all patients with lung cancer admitted to our ICU between September 1, 2008 and December 31, 2013. RESULTS: During this period, 180 different patients with lung cancer were admitted into ICU. The simplified acute physiology score II (SAPS II) (OR 1.07 ; 95% CI 1.04-1.11), respiratory failure (OR 4.00; 95% CI 1.76-9.07) and the presence of therapeutic limitations were the 3 factors independently affecting hospital mortality in multivariate analysis. Considering only patients discharged alive from the hospital, the presence of metastases (HR 2.30; 95% CI 1.44-3.65) and limitations on therapy (HR 5,89; IC 95% 3,11-11,14) were the two statistically independent prognostic factors for overall survival. CONCLUSION: In this population of lung cancer patients admitted into ICU, independent predictors of hospital mortality are determined by the physiological perturbations induced by the acute presenting complication. After recovery from this, prognosis is again determined by the characteristics of the underlying cancer.

Predictive factors for cancer-associated thrombosis in a large retrospective single-center study.

BACKGROUND: The relationship between cancer and thrombosis has been studied for years, but reliable guidelines for thromboprophylaxis in that situation are still unclear. METHODS: We retrospectively reviewed the files of 3159 consecutive patients with newly diagnosed solid tumors at Jules Bordet Institute from January 2008 to December 2011. Among them, 99 developed a symptomatic thromboembolic episode and were matched with 2 controls (nested case control). The aim was to identify risk factors of thromboembolic events and to validate in our setting the Khorana score. RESULTS: In the cohort study, nodal status ≥ 2, presence of metastases, and primary tumor site were found to be the most significant predictive factors of a thromboembolic event (n = 99; 3.1%) in the multivariate analysis. In the nested study (n = 265), hemoglobin < 13 g/dL or treatment with a red cell growth factor, CRP ≥ 31.6 mg/L, creatinine level > 0.96 mg/dL, chronic inflammatory disease, and personal or familial history of thromboembolic events were found to be the most significant predictive factors of a thromboembolic event in the multivariate analysis. In our population, the sensitivity, specificity, positive predictive value, and negative predictive value of the Khorana score were respectively 29%, 93%, 15%, and 96%. CONCLUSION: We confirm the value of the risk factors identified in the literature with the additional presence of nodal involvement, elevated CRP, and creatinine levels, which may be helpful for patient risk stratification and should be considered in future clinical trials. Our results also suggest that the Khorana score might help to identify patients who can safely be spared of thromboprophylaxis.

[Diagnostic approach of an IgM monoclonal gammopathy and clinical importance of gene MYD88 L265P mutation]. / Approche diagnostique d'une gammapathie monoclonale à IgM et intérêt clinique de la recherche de la mutation L265P du gène MYD88.

INTRODUCTION: An IgM monoclonal gammopathy points to a diagnosis of Waldenstrom's Macroglobulinemia. Other B lymphoproliferatives disorders should be ruled out but the limits are sometimes difficult to define. The discovery of the L265P mutation of the MYD88 gene simplified potentially the situation. POPULATION AND METHODS: 383 patients of the Jules Bordet Institute with an IgM level above 2 g/L were reviewed. For the 49 who had a monoclonal peak, we analysed the underlying pathology in termes of general, clinical and biological characteristics. We checked if the MYD88 mutation had been detected. The overall survival rate was studied. RESULTS: 5 histological groups were identified: Waldenstrom's Macroglobulinemia (MW, N = 27), lymphoplasmacytic lymphoma (LLP, N = 10), marginal zone lymphoma (LMZ, N = 7), monoclonal gammopathy of unknown significance and multiple myeloma (MGUS/MM, N = 5). The MW group was compared to the other groups. Regarding biological characteristics, the IgM level upon diagnosis was statistically higher in the MW group with a median level at 19.5 g/L (2.3-101 g/L) (p-value = 0,0001). Concerning the clinical characteristics, a splenomegaly was more frequent in the LMZ group (p-value = 0,04). The L265P mutation of the MYD88 gene was found in 77 % of patients in the MW group, 60 % of patients in the LLP group and 67 % in the LMZ group (p-value = 0,38). For the 49 patients, the 10-yearoverall survival was 85 % (CI 95 %, 67 % to 94 %) and the 15-year-overall survival was 65 % (CI 95 %, 41 % to 81 %). CONCLUSION: A monoclonal IgM peak suggests a MW but other B lymphoproliferatives disorders should be excluded. Even if the L265P mutation is frequent in the LLP/MW, it is not specific. A precise diagnosis requires collating clinical, histological, immunophenotypical and genetical data.

INTRODUCTION: Une gammapathie monoclonale à IgM évoque généralement le diagnostic de maladie de Waldenström. D'autres syndromes lymphoprolifératifs B doivent être exclus mais les " frontières " entre les différentes entités sont parfois mal définies. La découverte de la mutation L265P du gène MYD88 a potentiellement simplifié cette situation. Population et méthodes : 383 patients de l'Institut Jules Bordet présentant un taux d'IgM supérieur à 2 g/L ont été étudiés. 49 d'entre eux présentaient un pic monoclonal pour lesquels nous avons réalisé l'analyse de la pathologie sous-jacente en terme de caractéristiques générales, cliniques et biologiques et avons identifié si une recherche de mutation MYD88 avait été réalisée. La survie globale a également été étudiée. Résultats : 5 groupes histologiques ont été identifiés : maladie de Waldenström (MW, N = 27), lymphome lymphoplasmocytaire (LLP, N = 10), lymphomes de la zone marginale (LMZ ; tous types confondus, N = 7), gammapathie monoclonale de signification indéterminée et myélome multiple (MGUS/MM, N = 5). Le groupe MW a été comparé aux autres groupes. En terme de caractéristiques biologiques, c'est le taux d'IgM au diagnostic qui est statistiquement plus élevé dans le groupe MW avec un taux médian de 19,5 g/L (2,3-101 g/L) (p-valeur = 0,001). Concernant les caractéristiques cliniques, une splénomégalie est plus souvent présente dans le groupe LMZ (p-valeur = 0,04). La mutation L265P du gène MYD88 est retrouvée chez 77 % des patients du groupe MW, 60 % des patients du groupe LLP et 67 % des patients du groupe LMZ (p-valeur = 0,38). La survie globale des 49 patients est de 85 % à 10 ans (IC 95 %, 67 % à 94 %) et de 65 % à 15 ans (IC 95 %, 41 % à 81 %). CONCLUSION: Un pic d'IgM monoclonal évoque généralement une MW, mais il faut toujours exclure d'autres syndromes lymphoprolifératifs B. Alors que la mutation L265P du gène MYD88 est fortement exprimée chez les patients porteurs d'un LLP/MW, elle n'en est pas pour autant spécifique. Un diagnostic précis nécessite aujourd'hui d'intégrer les données cliniques, histologiques, immunophénotypiques et génétiques.

Are concurrent systematic cores needed at the time of targeted biopsy in patients with prior negative prostate biopsies?

INTRODUCTION AND OBJECTIVES: MRI-guided targeted biopsies are advised in patients who have undergone an initial series of negative systematic biopsies, in whom prostate cancer (PCa) suspicion remains elevated. The aim of the study was to evaluate whether, in men with prior negative prostate biopsies, systematic cores are also warranted at the time of an MRI-targeted repeat biopsy. MATERIAL AND METHODS: We enrolled patients with prior negative biopsy undergoing real time MRI/TRUS fusion guided prostate biopsy at our institute between 2014 and 2016. Patients with at least one index lesion on multiparametric MRI were included. All eligible patients underwent both systematic random biopsies (12-14 cores) and targeted biopsies (2-4 cores). RESULTS: The study included 74 men with a median age of 65 years, PSA level of 9.27ng/mL, and prostatic volume of 45ml. The overall PCa detection rate and the clinically significant cancer detection rate were 56.7% and 39.2%, respectively. Targeted cores demonstrated similar clinically significant PCa detection rate compared to systematic cores (33.8% vs. 28.4%, P=0.38) with significantly less tissue sampling. Indeed, a combination approach was significantly superior to a targeted-only in overall PCa detection (+16.7% overall detection rate, P=0.007). Although differences in clinically significant PCa detection were statistically non-significant (P=0.13), a combination approach did allow detecting 7 extra clinically significant PCas (+13.8%). CONCLUSIONS: In patients with elevated PSA and prior negative biopsies, concurrent systematic sampling may be needed at the time of targeted biopsy in order to maximize PCa detection rate. Larger studies are needed to validate our findings. LEVEL OF EVIDENCE: 4.

Clinical significance of CD73 in triple-negative breast cancer: multiplex analysis of a phase III clinical trial.

Background: CD73 is an ecto-enzyme that promotes tumor immune escape through the production of immunosuppressive extracellular adenosine in the tumor microenvironment. Several CD73 inhibitors and adenosine receptor antagonists are being evaluated in phase I clinical trials. Patients and methods: Full-face sections from formalin-fixed paraffin-embedded primary breast tumors from 122 samples of triple-negative breast cancer (TNBC) from the BIG 02-98 adjuvant phase III clinical trial were included in our analysis. Using multiplex immunofluorescence and image analysis, we assessed CD73 protein expression on tumor cells, tumor-infiltrating leukocytes and stromal cells. We investigated the associations between CD73 protein expression with disease-free survival (DFS), overall survival (OS) and the extent of tumor immune infiltration. Results: Our results demonstrated that high levels of CD73 expression on epithelial tumor cells were significantly associated with reduced DFS, OS and negatively correlated with tumor immune infiltration (Spearman's R= -0.50, P < 0.0001). Patients with high levels of CD73 and low levels of tumor-infiltrating leukocytes had the worse clinical outcome. Conclusions: Taken together, our study provides further support that CD73 expression is associated with a poor prognosis and reduced anti-tumor immunity in human TNBC and that targeting CD73 could be a promising strategy to reprogram the tumor microenvironment in this BC subtype.

Distribution of clinical risk factors for fracture in a Brussels cohort of postmenopausal women: The FRISBEE study and comparison with other major cohort studies.

OBJECTIVES: The estimation of fracture risk using clinical risk factors (CRFs) is of primary concern in osteoporosis management, but only some risk factors have been thoroughly evaluated and incorporated in predictive models. We have launched a large prospective study, the 'Fracture Risk Brussels Epidemiological Enquiry' (FRISBEE), to develop a new predictive model for osteoporotic fractures. The aims of this report are to describe the methodology of the FRISBEE study and to compare the distribution of CRFs in our cohort with those reported in other large studies. STUDY DESIGN: FRISBEE is a new study that prospectively evaluates a cohort of 3560 post-menopausal women (aged 60-85 years) followed yearly for the occurrence of fragility fractures. Multiple validated CRFs, densitometry (DXA) values and intake of medication were systematically registered at baseline. The distribution of the FRISBEE CRFs has been compared with the distributions of CRFs in the cohorts used to develop the FRAX® model as well as in more recent cohorts. For these recent cohorts, we focused on CRFs not included in FRAX®. RESULTS: The most frequently encountered CRFs used in FRAX® were a prior fragility fracture (27.1%) and a parental history of hip fracture (13.4%). The prevalence of some CRFs not integrated in FRAX® was relatively high, such as the use of proton pump inhibitors (20.8%) and a history of fall(s) (19.7%). The prevalence of many CRFs was quite variable between cohorts; for example, the prevalence of 'personal prior fragility fracture' ranged from 9% to 51%. CONCLUSION: We found considerable heterogeneity in the prevalence of CRFs between cohort studies. The impact of these differences on the predictive value of a particular CRF is unknown. We will construct a predictive model calibrated to the Belgian population. More importantly, the FRISBEE study should allow us to determine the predictive value of newly recognized CRFs in addition to the FRAX® algorithm to reliably estimate fracture risk.

Intravenous iron therapy for anemic cancer patients: a review of recently published clinical studies.

Based on available literature and on the present review, IV iron administration to anemic cancer patients can increase significantly the level of Hb, probably independently from the precise mechanism of anemia itself. However, in future studies, the benefit should be evaluated taking into account whether the anemia is due to absolute or functional iron deficiency; therapeutic modalities might be different for these two conditions. Along the same lines, it appears important to further evaluate the respective roles of PO and IV iron therapies and the modalities of their use in clinical practice. Until the results of such studies are available, it appears reasonable to propose IV iron therapy to anemic cancer patients as the resulting rise of Hb level may increase their quality of life and performance status and reduce the need for erythropoietin-stimulating agents and/or blood transfusions.

First 200 consecutive transumbilical single-incision laparoscopic TEPs.

BACKGROUND: Endoscopic pre-peritoneal mesh repair (TEP) through single-incision laparoscopy (SIL) permits placement of a large mesh through a final millimetric umbilical scar. This prospective study evaluates the first 200 consecutive SILTEPs performed by a single surgeon. PATIENTS AND METHODS: Between November 2011 and September 2015, 200 consecutive SILTEPs were performed in 161 patients. The mean age was 49.8 ± 16.3 years and the mean BMI was 24.5 ± 3.4 kg/m2. The technique involved one 11-mm trocar, one 10-mm 0° scope and curved reusable instruments. A supplementary 1.8-mm straight trocarless grasping forceps was percutaneously inserted for perioperative complications or difficulties. RESULTS: A unilateral hernia repair was performed in 122 patients, and a bilateral repair in 39 patients. The total operative time was 57.4 ± 22.3 min, and pure laparoscopic time was 46.6 ± 21.6 min. There was no need for insertion of a supplementary 5-mm trocar, and the need for insertion of 1.8-mm trocarless grasper was 32.9%. Perioperative complications occurred in 73 patients. The mean final scar length was 15.3 ± 2.6 mm. The mean hospital stay was 1.0 ± 0.3 days. Postoperative complications at the access site affected 15 patients and at the hernia site 31 patients. After a mean follow-up of 25.4 ± 12.3 months, there was one asymptomatic, small incisional hernia at the access site as well as one reoperation for recurrent inguinal hernia at 16 months. No other late complications were registered. CONCLUSION: Transumbilical SILTEP permits placement of a large mesh through a final millimetric scar. Getting over the learning curve in conventional multitrocar TEP is mandatory. As per our institute's algorithm, the contraindications continue to be giant inguino-scrotal, incarcerated and recurrent inguinal hernias.

[The Glasgow inflammatory score and lung cancer: A predictor of admissions to emergency units]. / Score inflammatoire de Glasgow et cancer bronchique : une aide pour hospitaliser aux urgences.

INTRODUCTION: In a first study, we found predictive factors for hospital admission in lung cancer patients consulting at the emergency department. Knowing that systemic inflammation is a prognostic factor in cancer patients, the goal of our study was to determine whether systemic inflammation measured using the modified Glasgow prognostic score can improve the predictive value of our previous model. METHODS: We conducted a retrospective study including all patients with lung cancer consulting at the emergency department of an oncology hospital between January 1st 2008 and December 31st 2010. RESULTS: Of the 548 emergency department visits, C-reactive protein and albumin needed for calculating the Glasgow score, were available for 291 visits. Multivariate analysis identified three predictors of hospitalization subsequent to a visit at the emergency ward: the Modified Glasgow Prognostic Score (mGPS) (OR=2.72; P<0.0001), arrival by ambulance (odds ratio [OR]=21.38; P<0.0001) and the presence of physical signs associated with the complaint (OR=2.72; P<0.05). CONCLUSION: The mGPS is an independent predictor for hospitalization in patients with lung cancer consulting at the emergency department.

The current use and attitudes towards tumor genome sequencing in breast cancer.

There is increasing availability of technologies that can interrogate the genomic landscape of an individual tumor; however, their impact on daily practice remains uncertain. We conducted a 28-item survey to investigate the current attitudes towards the integration of tumor genome sequencing in breast cancer management. A link to the survey was communicated via newsletters of several oncological societies, and dedicated mailing by academic research groups. Multivariable logistic regression modeling was carried out to determine the relationship between predictors and outcomes. 215 physicians participated to the survey. The majority were medical oncologists (88%), practicing in Europe (70%) and working in academic institutions (66%). Tumor genome sequencing was requested by 82 participants (38%), of whom 21% reported low confidence in their genomic knowledge, and 56% considered tumor genome sequencing to be poorly accessible. In multivariable analysis, having time allocated to research (OR 3.37, 95% CI 1.84-6.15, p < 0.0001), working in Asia (OR 5.76, 95% CI 1.57 - 21.15, p = 0.01) and having institutional guidelines for molecular sequencing (OR 2.09, 95% 0.99-4.42, p = 0.05) were associated with a higher probability of use. In conclusion, our survey indicates that tumor genome sequencing is sometimes used, albeit not widely, in guiding management of breast cancer patients.

[Difficulties and limitations in conducting translational research in thoracic oncology. A practical example]. / Difficultés et limites dans la conduite d'une étude translationnelle en oncologie thoracique. Un exemple pratique.

INTRODUCTION: In a first study, we identified signatures of 3 mRNAs (semaphorin 3D [SEMA3D], cytokeratin 16 [KRT16] and UL16 binding protein 2 [ULBP2]) associated to response to a cisplatin-vinorelbin chemotherapy and to survival of advanced non-small cell lung cancers (NSCLC). MATERIAL AND METHODS: The aim of this study was to develop immunohistochemistry tests for KRT16, ULBP2 and SEMA3D and to test proteins expression for prediction of response and survival in biopsies of the same patients. RESULTS: We were not able to reproduce by the protein expression study the signature predicting response to chemotherapy in advanced NSCLC. CONCLUSION: We highlight the difficulties of translational research in thoracic oncology emphasizing the complexity in obtaining adequate tissue samples and the difficulties in conduction and transposing in routine practice high throughput technique for transcriptomic analyses.

[Implementation of an oncological care program in a multidisciplinary clinic]. / Implémentation d'un programme de soins oncologiques en consultation multidisciplinaire.

INTRODUCTION: A working group has highlighted guidelines in thoracic oncology in Europe without study of their implementation, due to a lack of data. METHODS: The records of 354 untreated lung cancer patients seen between January 2009 and December 2012 were reviewed. Any new treatment should have been proposed by a multidisciplinary consultation (MDC) in accordance with an oncology care program (OCP) based on the European Lung Cancer Working Party guidelines. RESULTS: For the 354 patients, there were 636 MDC (332, 176, 81 and 47 in 1st, 2nd, 3rd and subsequent lines). For the first line, the MDC rate was 88%, in accordance with the OCP, and 75% of treatments were in agreement with the guidelines. For the 2nd and 3rd lines, the rates were 93% and 92% respectively (MDC), 90 and 89% (OCP), 55 and 63% (guidelines). In the first line, the main causes of non-compliance with the OCP were patient's refusal or doctor's choice and with guidelines a lack of adequate recommendations for specific situations such as comorbidities or the appearance of new treatments. CONCLUSION: The vast majority of patients are the subject of a MDC with a high rate of application of OCP. Guidelines should be updated regularly to incorporate new treatments.