Benefits of cardiopulmonary resuscitation in cancer patients.

PURPOSE: According to meta-analytic data, the prognosis of a cancer patient post-cardiopulmonary resuscitation (CPR) is relatively similar to the general population. However, preselection of patients, the details of CPR, patient-specific characteristics, and post-CPR care are poorly described. The aim of this study is to identify prognostic factors in order to recognize cancer patient profiles more likely to benefit from CPR. METHODS: This is a retrospective study on a series of patients with solid or hematological malignancies who received CPR between January 2010 and December 2020 in a cancer institute. RESULTS: Sixty-eight patients were included. The ratio of solid to hematological malignancy was 44/24, of which 32 were metastatic solid tumors. Median age was 61 years. Hypoxemia (29%) was the primary factor for cardiac arrest, followed by septic shock (21%). ICU mortality and hospital mortality were 87% and 88% respectively. Younger age, the presence of hematological malignancy, or a metastatic solid tumor were poor predictors for in-hospital mortality. Similarly, cardiac arrest in the ICU, as the final consequence of a pathological process, and a resuscitation time of more than 10 min have a negative influence on prognosis. CONCLUSIONS: This study shows that CPR is a useful intervention in cancer patients, even in the elderly patient, especially in non-metastatic solid tumors where cardiac arrest is the consequence of an acute event and not a terminal process.

Impact of female obesity and assisted reproduction on uncomplicated pregnancies and healthy births: a study of 428 336 births in Flanders.

STUDY QUESTION: What is the impact of BMI on uncomplicated pregnancies and healthy births in women who did or did not have medically assisted reproduction (MAR, i.e. ART or hormonal stimulation without manipulation of eggs or embryos) in the Flanders region (Belgium)? SUMMARY ANSWER: Women with a higher BMI who use MAR are at the highest risk of pregnancy and birth complications. WHAT WE KNOW ALREADY: Medically assisted reproduction (MAR) is used increasingly worldwide and is associated with increased risk of adverse perinatal outcomes. Obesity is also increasing globally and obese women are more likely to seek MAR since obesity is associated with infertility. When obese women undergo MAR, the risk of adverse outcomes may be enhanced but it is not clear to what extent. STUDY DESIGN, SIZE, DURATION: We conducted a registry-based study using the data from the Study Centre for Perinatal epidemiology database for years 2009-2015, region of Flanders, Belgium. This included 428 336 women. PARTICIPANTS/MATERIALS, SETTING, METHODS: The average age was 30.0 years (SD 4.78), 194 061 (45.31%) were nulliparous, and 6.3% (n = 26 971) conceived with MAR. We examined the association of BMI and MAR with the following composite primary outcomes: 'uncomplicated pregnancy and birth' and 'healthy baby'. We conducted Poisson regression and adjusted for maternal age, parity, gestational weight gain, smoking and previous caesarean section. MAIN RESULTS AND THE ROLE OF CHANCE: In our study, 36.80% (n = 157 623) of women had an uncomplicated pregnancy and birth according to the definition used. The predicted probability of having an uncomplicated pregnancy and birth for women with a BMI of 25 kg/m2 who conceived spontaneously was 0.33 (0.32 to 0.35), while it was 0.28 (0.24 to 0.32) for women who used hormonal stimulation and 0.26 (0.22 to 0.29) for women who used IVF/ICSI. This probability reduced with increasing BMI category for both MAR and non-MAR users. For women with a BMI of 30 kg/m2, the predicted probability of having an uncomplicated pregnancy and birth was 0.28 (0.26 to 0.30) for women who conceived spontaneously, and 0.22 (0.16 to 0.29) and 0.20 (0.14 to 0.26) for women who used hormonal stimulation only or IVF/ICSI, respectively. The predicted probability of having a healthy baby for women with a BMI of 25 kg/m2 who conceived spontaneously was 0.92 (0.91 to 0.93), 0.89 (0.87 to 0.92) for women who used hormonal stimulation only and 0.85 (0.84 to 0.87) for women who used IVF/ICSI. LIMITATIONS, REASONS FOR CAUTION: The database did not include data on socio-economic status, pre-pregnancy morbidities and paternal BMI. Subsequently, we could not adjust for these factors in the analysis. WIDER IMPLICATIONS OF THE FINDINGS: Obese women who use MAR are at the highest risk of pregnancy and birth complications. This increase in interventions also has cost and resource implications which is relevant for funding policies. Weight loss interventions prior to MAR seem plausible but their (cost-) effectiveness needs urgent investigation. STUDY FUNDING/COMPETING INTEREST(S): F.W. received an Erasmus Plus training grant to visit A.B., L.A. and R.D. and conducted this study during this visit. The authors have no competing interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Safety of assisted reproductive techniques in young women harboring germline pathogenic variants in BRCA1/2 with a pregnancy after prior history of breast cancer.

BACKGROUND: Knowledge is growing on the safety of assisted reproductive techniques (ART) in cancer survivors. No data exist, however, for the specific population of breast cancer patients harboring germline BRCA1/2 pathogenic variants. PATIENTS AND METHODS: This is a multicenter retrospective cohort study across 30 centers worldwide including women diagnosed at ≤40 years with stage I-III breast cancer, between January 2000 and December 2012, harboring known germline BRCA1/2 pathogenic variants. Patients included in this analysis had a post-treatment pregnancy either achieved through use of ART (ART group) or naturally (non-ART group). ART procedures included ovulation induction, ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection, and embryo transfer under hormonal replacement therapy. RESULTS: Among the 1424 patients registered in the study, 168 were eligible for inclusion in the present analysis, of whom 22 were in the ART group and 146 in the non-ART group. Survivors in the ART group conceived at an older age compared with those in the non-ART group (median age: 39.7 versus 35.4 years, respectively). Women in the ART group experienced more delivery complications compared with those in the non-ART group (22.1% versus 4.1%, respectively). No other apparent differences in obstetrical outcomes were observed between cohorts. The median follow-up from pregnancy was 3.4 years (range: 0.8-8.6 years) in the ART group and 5.0 years (range: 0.8-17.6 years) in the non-ART group. Two patients (9.1%) in the ART group experienced a disease-free survival event (specifically, a locoregional recurrence) compared with 40 patients (27.4%) in the non-ART group. In the ART group, no patients deceased compared with 10 patients (6.9%) in the non-ART group. CONCLUSION: This study provides encouraging safety data on the use of ART in breast cancer survivors harboring germline pathogenic variants in BRCA1/2, when natural conception fails or when they opt for ART in order to carry out preimplantation genetic testing.

Vessel morphology depicted by three-dimensional power Doppler ultrasound as second-stage test in adnexal tumors that are difficult to classify: prospective diagnostic accuracy study.

OBJECTIVES: To assess whether vessel morphology depicted by three-dimensional (3D) power Doppler ultrasound improves discrimination between benignity and malignancy if used as a second-stage test in adnexal masses that are difficult to classify. METHODS: This was a prospective observational international multicenter diagnostic accuracy study. Consecutive patients with an adnexal mass underwent standardized transvaginal two-dimensional (2D) grayscale and color or power Doppler and 3D power Doppler ultrasound examination by an experienced examiner, and those with a 'difficult' tumor were included in the current analysis. A difficult tumor was defined as one in which the International Ovarian Tumor Analysis (IOTA) logistic regression model-1 (LR-1) yielded an ambiguous result (risk of malignancy, 8.3% to 25.5%), or as one in which the ultrasound examiner was uncertain regarding classification as benign or malignant when using subjective assessment. Even when the ultrasound examiner was uncertain, he/she was obliged to classify the tumor as most probably benign or most probably malignant. For each difficult tumor, one researcher created a 360° rotating 3D power Doppler image of the vessel tree in the whole tumor and another of the vessel tree in a 5-cm3 spherical volume selected from the most vascularized part of the tumor. Two other researchers, blinded to the patient's history, 2D ultrasound findings and histological diagnosis, independently described the vessel tree using predetermined vessel features. Their agreed classification was used. The reference standard was the histological diagnosis of the mass. The sensitivity of each test for discriminating between benign and malignant difficult tumors was plotted against 1 - specificity on a receiver-operating-characteristics diagram, and the test with the point furthest from the reference line was considered to have the best diagnostic ability. RESULTS: Of 2403 women with an adnexal mass, 376 (16%) had a difficult mass. Ultrasound volumes were available for 138 of these cases. In 79/138 masses, the ultrasound examiner was uncertain about the diagnosis based on subjective assessment, in 87/138, IOTA LR-1 yielded an ambiguous result and, in 28/138, both methods gave an uncertain result. Of the masses, 38/138 (28%) were malignant. Among tumors that were difficult to classify as benign or malignant by subjective assessment, the vessel feature 'densely packed vessels' had the best discriminative ability (sensitivity 67% (18/27), specificity 83% (43/52)) and was slightly superior to subjective assessment (sensitivity 74% (20/27), specificity 60% (31/52)). In tumors in which IOTA LR-1 yielded an ambiguous result, subjective assessment (sensitivity 82% (14/17), specificity 79% (55/70)) was superior to the best vascular feature, i.e. changes in the diameter of vessels in the whole tumor volume (sensitivity 71% (12/17), specificity 69% (48/70)). CONCLUSION: Vessel morphology depicted by 3D power Doppler ultrasound may slightly improve discrimination between benign and malignant adnexal tumors that are difficult to classify by subjective ultrasound assessment. For tumors in which the IOTA LR-1 model yields an ambiguous result, subjective assessment is superior to vessel morphology as a second-stage test. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

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.

[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.

[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.

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.

Differences in ultrasound features of papillations in unilocular-solid adnexal cysts: a retrospective international multicenter study.

OBJECTIVES: To identify ultrasound features of papillations or of the cyst wall that can discriminate between benign and malignant unilocular-solid cysts with papillations but no other solid components. METHODS: From the International Ovarian Tumor Analysis (IOTA) database derived from seven ultrasound centers, we identified patients with an adnexal lesion described at ultrasonography as unilocular-solid with papillations but no other solid components. All patients had undergone transvaginal ultrasound between 1999 and 2007 or 2009 and 2012, by an experienced examiner following the IOTA research protocol. Information on four ultrasound features of papillations had been collected prospectively. Information on a further seven ultrasound features was collected retrospectively from electronic or paper ultrasound images of good quality. The histological diagnosis of the surgically removed adnexal lesion was considered the gold standard. RESULTS: Of 204 masses included, 131 (64.2%) were benign, 42 (20.6%) were borderline tumors, 30 (14.7%) were primary invasive tumors and one (0.5%) was a metastasis. Multivariate logistic regression analysis showed the following ultrasound features to be associated independently with malignancy: height of the largest papillation, presence of blood flow in papillations, papillation confluence or dissemination, and shadows behind papillations. Shadows decreased the odds of malignancy, while the other features increased them. CONCLUSION: We have identified ultrasound features that can help to discriminate between benign and malignant unilocular-solid cysts with papillations but no other solid components. Our results need to be confirmed in prospective studies. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Surgical treatment for periacetabular metastatic lesions.

INTRODUCTION: Periacetabular bone metastasis present with severe pain and functional loss leading to a poor quality of life. Surgical treatment remains challenging. MATERIAL AND METHODS: We reviewed all cases operated at our institution. We analyzed pain scores and functional status as well as complications and their risk factors. RESULTS: Thirty-five patients underwent curettage and cemented reconstruction. Mean surgical time was 168 min. Mean surgical blood losses were 3150 ml. Major complications were encountered in 23% and minor complications in 29% of cases. We found a significant pain relief (p < 0.0001) and improvement in functional status in the postoperative period (p < 0.0001). A Harrington grade 4 lesion was correlated with a higher complication rate (p-value = 0.002). CONCLUSIONS: In this series we were able to show that surgical management is an effective option in the treatment of metastatic bone disease to the pelvis. However, this treatment is very complex and associated with very high complication rates. Therefore, adequate patient selection and preoperative management is advocated.

[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.

[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.

Molecular imaging as a tool to investigate heterogeneity of advanced HER2-positive breast cancer and to predict patient outcome under trastuzumab emtansine (T-DM1): the ZEPHIR trial.

BACKGROUND: Only human epidermal growth factor receptor (HER)2 status determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) has been validated to predict efficacy of HER2-targeting antibody-drug-conjugate trastuzumab emtansine (T-DM1). We propose molecular imaging to explore intra-/interpatient heterogeneity in HER2 mapping of metastatic disease and to identify patients unlikely to benefit from T-DM1. PATIENTS AND METHODS: HER2-positive mBC patients with IHC3+ or FISH ≥ 2.2 scheduled for T-DM1 underwent a pretreatment HER2-positron emission tomography (PET)/computed tomography (CT) with (89)Zr-trastuzumab. [(18)F]2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT was performed at baseline and before T-DM1 cycle 2. Patients were grouped into four HER2-PET/CT patterns according to the proportion of FDG-avid tumor load showing relevant (89)Zr-trastuzumab uptake (>blood pool activity): patterns A and B were considered positive (>50% or all of the tumor load 'positive'); patterns C and D were considered negative (>50% or all of the tumor load 'negative'). Early FDG-PET/CT was defined as nonresponding when >50% of the tumor load showed no significant reduction of FDG uptake (<15%). Negative (NPV) and positive predictive values (PPV) of HER2-PET/CT, early FDG response and their combination were assessed to predict morphological response (RECIST 1.1) after three T-DM1 cycles and time-to-treatment failure (TTF). RESULTS: In the 56 patients analyzed, 29% had negative HER2-PET/CT while intrapatient heterogeneity (patterns B and C) was found in 46% of patients. Compared with RECIST1.1, respective NPV/PPV for HER2-PET/CT were 88%/72% and 83%/96% for early FDG-PET/CT. Combining HER2-PET/CT and FDG-PET/CT accurately predicted morphological response (PPV and NPV: 100%) and discriminated patients with a median TTF of only 2.8 months [n = 12, 95% confidence interval (CI) 1.4-7.6] from those with a TTF of 15 months (n = 25, 95% CI 9.7-not calculable). CONCLUSIONS: Pretreatment imaging of HER2 targeting, combined with early metabolic response assessment holds great promise for improving the understanding of tumor heterogeneity in mBC and for selecting patients who will/will not benefit from T-DM1. CLINICALTRIALSGOV IDENTIFIER: NCT01565200.

Intra-cavitary uterine pathology in women with abnormal uterine bleeding: a prospective study of 1220 women.

OBJECTIVES: Our primary aim was to assess how patients' characteristics, bleeding pattern, sonographic endometrial thickness (ET) and additional features at unenhanced ultrasound examination (UTVS) and at fluid instillation sonography (FIS) contribute to the diagnosis of intracavitary uterine pathology in women presenting with abnormal uterine bleeding (AUB). We further aimed to report the prevalence of pathology in women presenting with AUB. METHODS: 1220 consecutive women presenting with AUB underwent UTVS, colour Doppler imaging (CDI) and FIS. Most women (n = 1042) had histological diagnosis. RESULTS: Mean age was 50 years and 37% were postmenopausal. Of 1220 women 54% were normal, polyps were diagnosed in 26%, intracavitary fibroids in 11%, hyperplasia without atypia in 4% and cancer in 3%. All cancers were diagnosed in postmenopausal (7%) or perimenopausal (1%) women. ET had a low predictive value in premenopausal women (LR+ and LR- of 1.34 and 0.74, respectively), while FIS had a LR+ and LR- of 6.20 and 0.24, respectively. After menopause, ET outperformed all patient characteristics for the prediction of endometrial pathology (LR+ and LR- of 3.13 and 0.24). The corresponding LR+ and LR- were 10.85 and 0.71 for CDI and 8.23 and 0.26 for FIS. CONCLUSION: About half of the women presenting to a bleeding clinic will have pathology. In premenopausal women, benign lesions are often the cause of AUB. For the prediction of intracavitary pathology ET is of little value in premenopausal women. CDI and FIS substantially improve the diagnostic accuracy.

Transvaginal ultrasound assessment of myometrial and cervical stromal invasion in women with endometrial cancer: interobserver reproducibility among ultrasound experts and gynecologists.

OBJECTIVES: To assess interobserver reproducibility among ultrasound experts and gynecologists in the prediction by transvaginal ultrasound of deep myometrial and cervical stromal invasion in women with endometrial cancer. METHODS: Sonographic videoclips of the uterine corpus and cervix of 53 women with endometrial cancer, examined preoperatively by the same ultrasound expert, were integrated into a digitalized survey. Nine ultrasound experts and nine gynecologists evaluated presence or absence of deep myometrial and cervical stromal invasion. Histopathology from hysterectomy specimens was used as the gold standard. RESULTS: Compared with gynecologists, ultrasound experts showed higher sensitivity, specificity and agreement with histopathology in the assessment of cervical stromal invasion (42% (95% CI, 31-53%) vs 57% (95% CI, 45-68%), P < 0.01; 83% (95% CI, 78-86%) vs 87% (95% CI, 83-90%), P = 0.02; and kappa, 0.45 (95% CI, 0.40-0.49) vs 0.58 (95% CI, 0.53-0.62), P < 0.001, respectively) but not of deep myometrial invasion (73% (95% CI, 66-79%) vs 73% (95% CI, 66-79%), P = 1.0; 70% (95% CI, 65-75%) vs 69% (95% CI, 63-74%), P = 0.68; and kappa, 0.48 (95% CI, 0.44-0.53) vs 0.52 (95% CI, 0.48-0.57), P = 0.11, respectively). Though interobserver reproducibility (in the context of test proportions 'good' and 'very good', according to kappa) regarding deep myometrial invasion did not differ between the groups (experts, 34% vs gynecologists, 22%, P = 0.13), ultrasound experts assessed cervical stromal invasion with significantly greater interobserver reproducibility than did gynecologists (53% vs 14%, P < 0.001). CONCLUSION: Preoperative ultrasound assessment of deep myometrial and cervical stromal invasion in endometrial cancer is best performed by ultrasound experts, as, compared with gynecologists, they showed a greater degree of agreement with histopathology and greater interobserver reproducibility in the assessment of cervical stromal invasion.

Pain during Fallopian-tube patency testing by hysterosalpingo-foam sonography.

OBJECTIVES: To evaluate perception of pain during Fallopian-tube patency testing by hysterosalpingo-foam sonography (HyFoSy). METHODS: In this cross-sectional study, 216 consecutive women presenting at a university fertility clinic for HyFoSy examination were included. Patients were instructed to take ibuprofen 1 hour before the procedure. Immediately after the procedure, patients filled in a questionnaire concerning discomfort or pain experienced during the process, including a visual analog scale (VAS) score for perception of pain. RESULTS: The median VAS score for perception of pain during transvaginal ultrasound examination and during HyFoSy examination was 1.5 (95% CI, 1.2-1.7) and 3.6 (95% CI, 3.0-4.0), respectively. One-third of women reported that the level of discomfort or pain during HyFoSy examination was similar to that during the preceding transvaginal ultrasound examination and 48% of women considered HyFoSy examination to be neutral/unpleasant, but not painful. There was an inverse association between both patients' age and parity and the pain experienced. CONCLUSIONS: HyFoSy examination is tolerated well and allows for reliable tubal patency testing without exposing the patient to ionizing radiation in an outpatient setting with a low technical failure rate.

Rate and patterns of ICU admission among colorectal cancer patients: a single-center experience.

PURPOSE: The purposes of this study were to evaluate, in colorectal cancer patients, the cause of ICU admission and to find predictors of death during and after hospitalization. METHODS: This is a retrospective study including all patients with colorectal cancer admitted in the ICU of a cancer hospital from January 1st 2003 to December 31 2012. RESULTS: Among 3721 ICU admissions occurring during the study period, 119 (3.2 %) admissions dealt with colorectal cancer, of whom 89 were eligible and assessable. The main reasons for admission were of metabolic (24 %), hemodynamic (19 %), cardiovascular (18 %), gastrointestinal (16 %), respiratory (13 %), or neurologic (6 %) origin. These complications were due to cancer in 43 %, to the antineoplastic treatment in 25 %, or were unrelated to the cancer or its treatment in 33 %. A quarter of the patients died during hospitalization. Independent predictors of death were the Sequential Organ Failure Assessment (SOFA) score (with risk of dying increasing by 42 % per unit of SOFA score), fever (with risk of dying multiplied by three per °C), and high values of GOT (with risk of dying multiplied by 1 % per unit increase), while cancer control (i.e., stage progression or not), compliance to the initial cancer treatment plan, and LDH ≤ median levels had prognostic significance for further longer survival after hospital discharge. CONCLUSION: This is the first study looking at specific causes for unplanned ICU admission of patients with colorectal cancer. Hospital mortality was influenced by the characteristics of the complication that entailed the ICU admission while cancer characteristics retained their prognostic influence on survival after hospital discharge.

The landscape of medical oncology in Europe by 2020.

BACKGROUND: In the United States, there will be a shortage of medical oncologists (MO) by 2020. However, this information is not available for Europe. The aim of this study was to assess the current number of MO in the 27 European Union (27-EU) countries and to predict their availability by 2020. MATERIAL AND METHODS: Between June 2012 and January 2013, a survey was submitted to health authorities, medical oncology societies, and personal contacts in all 27-EU countries in order to gather annual data on the number of practicing MO. Data were collected by e-mail, telephone contact, or through research on official websites. Data regarding cancer incidence in 2008 and projections for 2015 and 2020 were obtained through Globocan. The mean annual increase in the number of MO was calculated for each country. The total number of MO by 2015 and 2020 was estimated, and the ratio of new cancer cases versus number of MO was calculated for 2008, 2015, and 2020. RESULTS: Twelve countries provided sufficient data. The average mean annual increase in the total number of MO was 5.3% (range 1.8%-8.7%), with Belgium being the lowest and UK the highest. The 2008 ratio of cancer cases versus MO was lowest in Hungary (113) and highest in UK (1067). A favorable decrease in this ratio was estimated in most countries. CONCLUSION: Our estimates, based on incidence and not on prevalence, indicate that MO availability will probably meet the projected need in most of the 12 countries analyzed, provided that: (i) these countries maintain their rate of annual increase in MO; and (ii) no unforeseen changes occur in cancer incidence. Unfortunately, minimal information is available for Eastern Europe. Our data call for the prospective surveillance of the cancer burden and MO availability to ensure adequate and equal care for cancer patients throughout Europe.

Systematic review about breast cancer incidence in relation to hormone replacement therapy use.

BACKGROUND: Several studies report a decrease in breast cancer incidence subsequent to the decrease in hormone replacement therapy (HRT) use. But its magnitude and the time-lag may vary between countries. This may reflect differences in populations, previous type and prevalence of HRT use and breast cancer screening. AIM: To review systematically studies assessing the relation between breast cancer incidence and change of HRT use. MATERIAL AND METHOD: Descriptive analysis of the methodology of the studies including design limitations and presence of confounding factors, data sources for breast cancer and HRT and regimens of HRT used. RESULTS AND DISCUSSION: Eighteen articles were selected. Most studies were ecological and confounding factors such as mammography screening and changes in reproductive and lifestyle habits could not be excluded. Sources of data on breast cancer and HRT were heterogeneous and only few data on HRT regimens used were available. Most studies concluded that the decrease in HRT use during the last decade was probably associated with a decrease in breast cancer incidence, especially for women aged 50 years or more. CONCLUSIONS: Data, mostly from epidemiological studies, suggest that the decrease in breast cancer incidence can be partly attributed to the drop in HRT use. Nevertheless, available studies are hampered by a number of limitations and it remains difficult to evaluate the exact impact of the drop in HRT use on the decrease in breast cancer incidence. Especially, the studies are seldom based on detailed individual data and do not provide information on regimens used, type of cancers and possible confounding factors.

Development and external validation of new ultrasound-based mathematical models for preoperative prediction of high-risk endometrial cancer.

OBJECTIVES: To develop and validate strategies, using new ultrasound-based mathematical models, for the prediction of high-risk endometrial cancer and compare them with strategies using previously developed models or the use of preoperative grading only. METHODS: Women with endometrial cancer were prospectively examined using two-dimensional (2D) and three-dimensional (3D) gray-scale and color Doppler ultrasound imaging. More than 25 ultrasound, demographic and histological variables were analyzed. Two logistic regression models were developed: one 'objective' model using mainly objective variables; and one 'subjective' model including subjective variables (i.e. subjective impression of myometrial and cervical invasion, preoperative grade and demographic variables). The following strategies were validated: a one-step strategy using only preoperative grading and two-step strategies using preoperative grading as the first step and one of the new models, subjective assessment or previously developed models as a second step. RESULTS: One-hundred and twenty-five patients were included in the development set and 211 were included in the validation set. The 'objective' model retained preoperative grade and minimal tumor-free myometrium as variables. The 'subjective' model retained preoperative grade and subjective assessment of myometrial invasion. On external validation, the performance of the new models was similar to that on the development set. Sensitivity for the two-step strategy with the 'objective' model was 78% (95% CI, 69-84%) at a cut-off of 0.50, 82% (95% CI, 74-88%) for the strategy with the 'subjective' model and 83% (95% CI, 75-88%) for that with subjective assessment. Specificity was 68% (95% CI, 58-77%), 72% (95% CI, 62-80%) and 71% (95% CI, 61-79%) respectively. The two-step strategies detected up to twice as many high-risk cases as preoperative grading only. The new models had a significantly higher sensitivity than did previously developed models, at the same specificity. CONCLUSION: Two-step strategies with 'new' ultrasound-based models predict high-risk endometrial cancers with good accuracy and do this better than do previously developed models.