Interpregnancy maternal weight change is not associated with offspring weight and obesity at age 2 years.

BACKGROUND: Weight retention between pregnancies is associated with increased risk of perinatal complications, but it is unclear whether there is an association with offspring weight status. This study aimed to determine whether maternal interpregnancy weight change is associated with offspring overweight/obesity, controlling for confounding variables. SUBJECTS/METHODS: Routinely collected linked data from perinatal and child datasets, in Flanders, Belgium were used. Women having their first and second live births between 2009-2018 were included. The association between maternal interpregnancy weight change and overweight/obesity in the second child at 2 years was examined by logistical regression models. RESULTS: A total of 33,172 women were included. 52.7% (n = 17478) had a stable interpregnancy BMI, 24.1% (n = 8024) and 8.5% (n = 2821) had moderate and substantial BMI increases respectively. At 2 years, 91.6% (n = 30383) of the second offspring had a healthy weight, 0.6% (n = 210), 7.0% (n = 2312) and 0.8% (n = 267) were in the underweight, overweight and obesity BMI categories respectively. Multivariate analysis showed no statistical evidence that maternal interpregnancy BMI change is independently associated with overweight/obesity in the second child. The strongest independent factors were the first child (sibling) being in the obesity category at 2 years (odds ratio [OR] 7.2, [95% CI, 5.49-9.45] and being born Large for Gestational Age (LGA) (2.13 [1.92-2.37]). The following variables were also independently associated with the outcome measure: maternal African origin (1.90 [1.59-2.26]), maternal obesity at start of first pregnancy (1.33 [1.16-1.53]), excessive gestational weight gain in the second pregnancy (1.15 [1.04-1.28]), being born after a < 1-year interpregnancy time interval (1.17 [1.05-1.30]) and not being exclusively breastfed at 12 weeks old (1.29 [1.10-1.52]). CONCLUSION: Sibling obesity and being born LGA were most strongly independently associated with overweight/obesity at 2 years. This supports the need for family interventions and to address risk factors for development of LGA infants. There was no independent association with interpregnancy weight gain, contrary to what was hypothesised.

Empiric vs Preemptive Antifungal Strategy in High-Risk Neutropenic Patients on Fluconazole Prophylaxis: A Randomized Trial of the European Organization for Research and Treatment of Cancer.

BACKGROUND: Empiric antifungal therapy is considered the standard of care for high-risk neutropenic patients with persistent fever. The impact of a preemptive, diagnostic-driven approach based on galactomannan screening and chest computed tomography scan on demand on survival and on the risk of invasive fungal disease (IFD) during the first weeks of high-risk neutropenia is unknown. METHODS: Patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and allogeneic hematopoietic cell transplant recipients were randomly assigned to receive caspofungin empirically (arm A) or preemptively (arm B), while receiving fluconazole 400 mg daily prophylactically. The primary end point of this noninferiority study was overall survival (OS) 42 days after randomization. RESULTS: Of 556 patients recruited, 549 were eligible: 275 in arm A and 274 in arm B. Eighty percent of the patients had AML or MDS requiring high-dose chemotherapy, and 93% of them were in the first induction phase. At day 42, the OS was not inferior in arm B (96.7%; 95% confidence interval [CI], 93.8%-98.3%) when compared with arm A (93.1%; 95% CI, 89.3%-95.5%). The rates of IFDs at day 84 were not significantly different, 7.7% (95% CI, 4.5%-10.8%) in arm B vs 6.6% (95% CI, 3.6%-9.5%) in arm A. The rate of patients who received caspofungin was significantly lower in arm B (27%) than in arm A (63%; P < .001). CONCLUSIONS: The preemptive antifungal strategy was safe for high-risk neutropenic patients given fluconazole as prophylaxis, halving the number of patients receiving antifungals without excess mortality or IFDs. Clinical Trials Registration. NCT01288378; EudraCT 2010-020814-27.

Effect of the e-health supported INTER-ACT lifestyle intervention on postpartum weight retention and body composition, and associations with lifestyle behavior: A randomized controlled trial.

We investigated whether a postpartum lifestyle intervention reduced postpartum weight retention (PPWR) and improved body composition, and whether improved lifestyle was associated with less PPWR and improved body composition. A total of 1075 women with excessive gestational weight gain were randomized into the intervention (N = 551) or control (N = 524) group. A completion rate of 76% was reached. Anthropometrics and lifestyle data were collected at 6 weeks and 6 months postpartum. The e-health supported intervention consisted of 4 face-to-face coaching's, focusing on nutrition, exercise and mental wellbeing and using motivational interviewing and behavior change techniques. In the intervention group we observed; larger decrease in weight in women who reduced their energy intake (mean ± SD: 3.1 ± 4.2 kg vs. 2.2 ± 3.8 kg, P = 0.05) and decreased uncontrolled eating (3.5 ± 4.2 kg vs. 1.9 ± 3.7 kg, P ≤0.001) by the end of the intervention; larger decrease in fat percentage in women who reduced energy intake (2.3% ± 2.9 vs. 1.4% ± 2.7, P = 0.01), enhanced restrained eating (2.2% ± 3 vs. 1.4% ± 2.6, P = 0.02) and decreased uncontrolled eating (2.3% ± 2.9 vs. 1.5% ± 2.7, P = 0.01) and larger decrease in waist circumference in women who reduced energy intake (4.6 cm ± 4.8 vs. 3.3 cm ± 4.7, P = 0.01), enhanced restrained eating (4.5 cm ± 4.8 vs. 3.4 cm ± 4.8, P = 0.05) and decreased uncontrolled eating (4.7 cm ± 4.8 vs. 3.3 cm ± 4.8, P = 0.006), compared to those who did not. Improved energy intake, restrained eating and uncontrolled eating behavior were associated with more favorable outcomes in weight and body composition. ClinicalTrials.gov identifier:NCT02989142.

ROSALINE: a phase II, neoadjuvant study targeting ROS1 in combination with endocrine therapy in invasive lobular carcinoma of the breast.

Invasive lobular carcinoma (ILC) is the most common histologic subtype of breast cancer after invasive ductal carcinoma (i.e., no special type [NST]). ILC differs from NST in clinical presentation, site-specific metastases and response to conventional therapies. Loss of E-cadherin protein expression, due to alterations in its encoding gene CDH1, is the most frequent oncogenic event in ILC. Synthetic lethality approaches have shown promising antitumor effects of ROS1 inhibitors in models of E-cadherin-defective breast cancer in in vivo studies and provide the rationale for testing their clinical activity in patients with ILC. Entrectinib is a tyrosine kinase inhibitor targeting TRK, ROS1 and ALK tyrosine kinases. Here, the authors present ROSALINE (NCT04551495), a phase II study testing neoadjuvant entrectinib and endocrine therapy in women with estrogen receptor-positive, HER2-negative early ILC.

Breast cancer is the most common cancer among women worldwide. Breast cancer is not a unique disease, but rather a heterogeneous disease, with different subtypes. Lobular breast cancer is the second most common histologic subtype of breast cancer after ductal breast cancer. Lobular breast cancer has some peculiar characteristics that make it a distinct entity in the context of breast cancer. Nevertheless, few clinical studies so far have focused specifically on this subtype. ROSALINE is a clinical study aimed to test entrectinib, a new drug that showed promising activity in preliminary research studies, in combination with endocrine therapy in women with lobular breast cancer before surgery. Trial Registration Number: NCT04551495 (ClinicalTrials.gov).

PARIS score for evaluation of probability of SARS-CoV-2 infection in cancer patients.

Control of transmissible diseases as COVID-19 needs a testing and an isolation strategy. The PARIS score developed by Torjdman et al. was aimed at improving patient selection for testing and quarantining but was derived from a general population. We performed a retrospective analysis of the validity of the PARIS score in a cancer patient population. We included 164 patients counting for 181 visits at the emergency department of the Jules Bordet Institute between March 10th and May 18th which had a SARS-CoV-2 RT-PCR test at admission. Twenty-six cases (14.3%) were tested positive with a higher proportion of positive tests among hematological patients compared to those with solid tumors (26% vs 11% p = 0.02). No clinical symptoms were associated with a positive SARS-CoV-2 PCR. No association between anticancer treatment and SARS-CoV-2 infection was found. The PARIS score failed to differentiate SARS-CoV-2-positive and SARS-CoV-2-negative groups (AUC 0.61 95% CI 0.48-0.73). The negative predictive value of a low probability PARIS score was 0.89 but this concerned only 11% of the patients. A high probability PARIS score concerned 49% patients but the positive predictive value was 0.18. CT scan had a sensitivity of 0.77, specificity 0.51, a positive predictive value of 0.24, and a negative predictive value of 0.92. The performance of the PARIS score is thus very poor in this cancer population. A low-risk score can be of some utility but this concerns a minority of patients.

Sepsis and Septic Shock Definitions in Patients With Cancer Admitted in ICU.

INTRODUCTION: In 2016, a new definition of sepsis and septic shock was adopted. Some studies based on the general population demonstrated that the Sequential Organ Failure Assessment (SOFA) score is more accurate than the systemic inflammatory response syndrome (SIRS) criteria to predict hospital mortality of infected patients requiring intensive care. PATIENTS AND METHOD: We have analyzed all the records of patients with cancer admitted for a suspected infection between January 1, 2013, and December 31, 2016, in our oncological intensive care unit (ICU). Sequential Organ Failure Assessment score and quick SOFA (qSOFA) score as well as SIRS criteria were calculated. We analyzed the accuracy of each score to predict hospital mortality in the setting of the new and old definitions of septic shock. RESULTS: Our study includes 241 patients with a solid tumor and 112 with a hematological malignancy. The hospital mortality rate is 37% (68% in patients with septic shock according to the new definition and 60% according to old definition) between 2013 and 2016. To predict hospital mortality, the SOFA score has an area under the receiver operating characteristic curve of 0.74 (95% confidence interval [CI], 0.68-0.79), the qSOFA of 0.65 (95% CI, 0.59-0.70), and the SIRS criteria of 0.58 (95% CI, 0.52-0.63). In multivariate analysis, a higher SOFA score or a higher qSOFA score indicates poor prognosis: odds ratio (OR) per 1-point increase by 1.28 (95% CI, 1.18-1.39) and 1.48 (95% CI, 1.04-2.11), respectively. Complete remission is a good prognostic factor for hospital mortality: OR 0.39 (95% CI, 0.22-0.67). CONCLUSION: The new definition of sepsis and septic shock is applicable in an ICU oncological population with the same reliability as in the general population. The SOFA score is more accurate than qSOFA and SIRS criteria to predict hospital mortality.

Reactive stroma and trastuzumab resistance in HER2-positive early breast cancer.

We investigated the value of reactive stroma as a predictor for trastuzumab resistance in patients with early HER2-positive breast cancer receiving adjuvant therapy. The pathological reactive stroma and the mRNA gene signatures that reflect reactive stroma in 209 HER2-positive breast cancer samples from the FinHer adjuvant trial were evaluated. Levels of stromal gene signatures were determined as a continuous parameter, and pathological reactive stromal findings were defined as stromal predominant breast cancer (SPBC; ≥50% stromal) and correlated with distant disease-free survival. Gene signatures associated with reactive stroma in HER2-positive early breast cancer (N = 209) were significantly associated with trastuzumab resistance in estrogen receptor (ER)-negative tumors (hazard ratio [HR] = 1.27 p interaction = 0.014 [DCN], HR = 1.58, p interaction = 0.027 [PLAU], HR = 1.71, p interaction = 0.019 [HER2STROMA, novel HER2 stromal signature]), but not in ER-positive tumors (HR = 0.73 p interaction = 0.47 [DCN], HR = 0.71, p interaction = 0.73 [PLAU], HR = 0.84; p interaction = 0.36 [HER2STROMA]). Pathological evaluation of HER2-positive/ER-negative tumors suggested an association between SPBC and trastuzumab resistance. Reactive stroma did not correlate with tumor-infiltrating lymphocytes (TILs), and the expected benefit from trastuzumab in patients with high levels of TILs was pronounced only in tumors with low stromal reactivity (SPBC <50%). In conclusion, reactive stroma in HER2-positive/ER-negative early breast cancer tumors may predict resistance to adjuvant trastuzumab therapy.

Personalised radioembolization improves outcomes in refractory intra-hepatic cholangiocarcinoma: a multicenter study.

PURPOSE: Reported outcomes of patients with intra-hepatic cholangiocarcinoma (IH-CCA) treated with radioembolization are highly variable, which indicates differences in included patients' characteristics and/or procedure-related variables. This study aimed to identify patient- and treatment-related variables predictive for radioembolization outcome. METHODS: This retrospective multicenter study enrolled 58 patients with unresectable and chemorefractory IH-CCA treated with resin 90Y-microspheres. Clinicopathologic data were collected from patient records. Metabolic parameters of liver tumor(s) and presence of lymph node metastasis were measured on baseline 18F-FDG-PET/CT. 99mTc-MAA tumor to liver uptake ratio (TLRMAA) was computed for each lesion on the SPECT-CT. Activity prescription using body-surface-area (BSA) or more personalized partition-model was recorded. The study endpoint was overall survival (OS) starting from date of radioembolization. Statistical analysis was performed by the log-rank test and multivariate Cox's proportional hazards model. RESULTS: Median OS (mOS) post-radioembolization of the entire cohort was 10.3 months. Variables associated with significant differences in terms of OS were serum albumin (hazard ratio (HR) = 2.78, 95%CI:1.29-5.98, p = 0.002), total bilirubin (HR = 2.17, 95%CI:1.14-4.12, p = 0.009), aspartate aminotransferase (HR = 2.96, 95%CI:1.50-5.84, p < 0.001), alanine aminotransferase (HR = 2.02, 95%CI:1.05-3.90, p = 0.01) and γ-GT (HR = 2.61, 95%CI:1.31-5.22, p < 0.001). The presence of lymph node metastasis as well as a TLRMAA < 1.9 were associated with shorter mOS: HR = 2.35, 95%CI:1.08-5.11, p = 0.008 and HR = 2.92, 95%CI:1.01-8.44, p = 0.009, respectively. Finally, mOS was significantly shorter in patients treated according to the BSA method compared to the partition-model: mOS of 5.5 vs 14.9 months (HR = 2.52, 95%CI:1.23-5.16, p < 0.001). Multivariate analysis indicated that the only variable that increased outcome prediction above the clinical variables was the activity prescription method with HR of 2.26 (95%CI:1.09-4.70, p = 0.03). The average mean radiation dose to tumors was significantly higher with the partition-model (86Gy) versus BSA (38Gy). CONCLUSION: Radioembolization efficacy in patients with unresectable recurrent and/or chemorefractory IH-CCA strongly depends on the tumor radiation dose. Personalized activity prescription should be performed.

Prognostic value of adipose tissue and muscle mass in advanced colorectal cancer: a post hoc analysis of two non-randomized phase II trials.

BACKGROUND: The prognostic value of body composition in cancer patients has been widely studied during the last decade. The main finding of these studies is that sarcopenia, or skeletal muscle depletion, assessed by CT imaging correlates with a reduced overall survival (OS). By contrast, the prognostic value of fat mass remains ill-defined. This study aims to analyze the influence of body composition including both muscle mass and adipose tissue on OS in a homogeneous population of advanced colorectal cancer (CRC) patients. METHODS: Among 235 patients with chemorefractory advanced CRC included in the SoMore and RegARd-C trials, body composition was assessed in 217 patients on baseline CT images. The relationship between body composition (sarcopenia, muscle density, subcutaneous and visceral fat index and density), body mass index (BMI) and OS were evaluated. RESULTS: Patients with a higher BMI had a better OS (≥30 versus < 30, HR: 0.50; 0.33-0.76). Those with low muscle index and muscle density had an increased mortality (HR: 2.06; 1.45-2.93 and HR: 1.54; 1.09-2.18, respectively). Likewise, low subcutaneous and visceral fat index were associated with an increased risk of dying (HR: 1.63; 1.23-2.17 and 1.48; 1.09-2.02 respectively), as were a high subcutaneous and visceral adipose tissue density (HR: 1.93; 1.44-2.57 and 2.40; 1.79-3.20 respectively). In multivariate analysis, a high visceral fat density was the main predictor of poor survival. CONCLUSIONS: Our results confirm the protective role of obesity in CRC patients at an advanced stage, as well as the negative prognostic impact of muscle depletion on survival. More importantly, our data show for the first time that visceral adipose tissue density is an important prognostic factor in metastatic CRC. TRIAL REGISTRATION: NCT01290926 , 07/02/2011 and NCT01929616 , 28/08/2013.

Bariatric Surgery Does Not Appear to Affect Women's Breast-Milk Composition.

Background: The breast-milk composition in the first 6 wk postpartum of women who have undergone bariatric surgery (BS) is unknown. Objective: The aim of this study was to examine 1) the breast-milk macronutrient and vitamin A composition in women who had and who had not undergone BS and 2) the impact of maternal diet on the breast-milk composition. We hypothesized that the milk of women who had undergone BS would be less energy dense and have a lower vitamin A concentration than that of other women. Methods: A multicenter prospective substudy was conducted at 2 university hospitals. Breast-milk samples were collected from 24 normal-weight [NW; mean ± SD body mass index (BMI; kg/m2): 21.5 ± 1.7; mean ± SD age: 29 ± 6 y], 39 overweight (OW; BMI: 26.9 ± 1.5; aged 29 ± 5 y), and 12 obese women (BMI: 35.0 ± 5.7; aged 29 ± 5 y) as well as from 11 women who had undergone BS (BMI: 28.0 ± 4.4; aged 30 ± 4 y) from day 3 until week 6 of lactation. Milk energy and macronutrients (Human Milk Analyzer; Miris) and vitamin A concentrations (iCheck Fluoro; BioAnalyt) were determined at the end of each week. Maternal diet (food-frequency questionnaire) and physical activity (Kaiser Physical Activity Survey) were measured during the third trimester of pregnancy and on day 3 or 4 and during week 6 of lactation. Statistical analyses include 1-factor ANOVA, Spearman and Pearson correlations, and multiple linear regression. Results: In all women, a weekly increase in milk energy, total fat, and total carbohydrates was seen, whereas a weekly decrease in proteins and vitamin A was found during the first 2 wk of lactation, followed by a stable concentration of all nutrients. At week 4, milk protein concentrations were higher in women who had undergone BS (14 g/L) compared with NW (8 g/L; P = 0.005) and OW (9 g/L; P = 0.019) women. At week 5, milk carbohydrate concentrations were higher in women who had undergone BS (74 g/L) compared with NW women (68 g/L; P = 0.042). Conclusions: Breast milk of women who have undergone BS appears to be adequate in energy, macronutrients, and vitamin A during the first 6 wk of lactation. This supports the conclusion that breast feeding should not be discouraged in this group of women. This trial was registered at http://www.clinicaltrials.gov as NCT02515214.

Increased live births after day 5 versus day 6 transfers of vitrified-warmed blastocysts.

PURPOSE: An investigation into the clinical implications of delayed blastulation (day 5 versus day 6) was carried out for cryo cycles, as heterogeneous results persist in the current literature. METHODS: We performed a retrospective study comparing clinical pregnancies and live births between 178 blastocysts vitrified and warmed on day 5 versus 149 on day 6. The stage of blastocyst development was taken into account and adjustment for confounding factors was performed. RESULTS: Our results demonstrate a significant difference in clinical pregnancy (43 versus 23% p value < 0.001) and live birth rates (34 versus 16% p value < 0.001) regarding the day of vitrification, in favour of day 5. This difference persisted after adjustment for confounding factors. The adjusted odds ratio for clinical pregnancies and deliveries for the day 5 group compared to that of the day 6 group was 2.83 (95%CI, 1.48 to 5.41) and 2.94 (95%CI, 1.39 to 6.22), respectively. When the stage of development of the blastocyst was taken into consideration, we still observed a significant advantage of day 5 versus day 6 vitrification. CONCLUSIONS: Day of vitrification (day 5 versus day 6) appears to be an independent predictor of clinical outcomes. Stratification of our cohort was carried out according to the developmental stage, and significant differences persisted. Although the transfer of day 6 cryopreserved embryos remains a viable option, giving priority to a day 5 embryo would reduce the time to pregnancy.

INTER-ACT: prevention of pregnancy complications through an e-health driven interpregnancy lifestyle intervention - study protocol of a multicentre randomised controlled trial.

BACKGROUND: Excessive maternal pre-pregnancy and gestational weight gain are related to pregnancy- and birth outcomes. The interpregnancy time window offers a unique opportunity to intervene in order to acquire a healthy lifestyle before the start of a new pregnancy. METHODS: INTER-ACT is an e-health driven multicentre randomised controlled intervention trial targeting women at high risk of pregnancy- and birth related complications. Eligible women are recruited for the study at day 2 or 3 postpartum. At week 6 postpartum, participants are randomised into the intervention or control arm of the study. The intervention focuses on weight, diet, physical activity and mental well-being, and comprises face-to-face coaching, in which behavioural change techniques are central, and use of a mobile application, which is Bluetooth-connected to a weighing scale and activity tracker. The intervention is rolled out postpartum (4 coaching sessions between week 6 and month 6) and in a new pregnancy (3 coaching sessions, one in each trimester of pregnancy); the mobile app is used throughout the two intervention phases. Data collection includes data from the medical record of the participants (pregnancy outcomes and medical history), anthropometric data (height, weight, waist- and hip circumferences, skinfold thickness and body composition by bio-electrical impedance analysis), data from the mobile app (physical activity and weight; intervention group only) and questionnaires (socio-demographics, breastfeeding, food intake, physical activity, lifestyle, psychosocial factors and process evaluation). Medical record data are collected at inclusion and at delivery of the subsequent pregnancy. All other data are collected at week 6 and month 6 postpartum and every subsequent 6 months until a new pregnancy, and in every trimester in the new pregnancy. Primary outcome is the composite endpoint score of pregnancy-induced hypertension, gestational diabetes mellitus, caesarean section, and large-for-gestational-age infant in the subsequent pregnancy. DISCUSSION: INTER-ACT is a unique randomised controlled lifestyle intervention trial in its implementation between pregnancies and during the subsequent pregnancy, with an e-health driven approach. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02989142 . Registered August 2016.

In vitro fertilization for women infected by hepatitis C virus: a matched case-control study and a systematic literature review.

PURPOSE: The aim of this study was to investigate whether infection of women by the hepatitis C virus (HCV) reduces the chance of conceiving after in vitro fertilization (IVF). METHODS: We performed a retrospective blind matched case-control study where IVF outcomes for the first 37 cycles of HCV sero-positive women were compared to those of 107 cycles of an uninfected control group. Our results were included in a systematic literature review. RESULTS: Out of five eligible studies, ours included, three observed an impact of HCV infection, though at various levels including response to stimulation, fertilization, implantation, and pregnancy rates. Two studies differentiated results for patients with confirmed active viral replication. Matching criteria and populations studied varied between studies. CONCLUSIONS: More and larger studies with well-defined groups are needed to clarify the eventual impact of the HCV on IVF outcomes. Data concerning the infectious status of a patient as well as her health state should be systematically recorded. A multi-disciplinary approach as well as a thorough knowledge of the patient's general health state might prove useful in the management and counseling of these patients in terms of success in conceiving.

In vitro fertilization when men, women, or both partners are positive for HIV: a case-control study.

PURPOSE: The aim of this study was to compare the outcomes of in vitro fertilization (IVF) for couples where one or both partners were positive for the human immunodeficiency virus (HIV) to matched control couples. METHODS: A matched case-control retrospective study was performed. Data for 104 couples where the woman was HIV-positive; for 90 couples where the man was HIV-positive; and for 33 couples where both partners were HIV-positive were prospectively analyzed in comparison to matched controls treated in our center during the same period. The main outcomes were clinical pregnancy and live birth rates. RESULTS: For couples involving an HIV-positive man, clinical outcomes were comparable to controls and resulted in the birth of 18 healthy babies after 90 cycles. When the woman was affected, cycle cancelation, number of retrieved oocytes, and on-going clinical pregnancy rates per transfer were statistically reduced. Implantation rates were comparable to those of non-affected controls. Seven healthy babies for 104 cycles were obtained. For a couple in which both partners were HIV-positive, only one healthy birth occurred after 33 cycles. Pregnancy rates were systematically reduced though not significantly probably due to sample size. CONCLUSIONS: Our data suggest that IVF outcomes were similar to controls when men were HIV-positive and remain acceptable when women were HIV-positive. IVF outcomes were severely reduced in our sero-concordant couples; however, many patients had severe HIV disease previously, and therefore, these results should be reassessed in patients treated early in their disease.

The prognostic performance of Adjuvant! Online and Nottingham Prognostic Index in young breast cancer patients.

BACKGROUND: Limited data are available on the prognostic performance of Adjuvant! Online (AOL) and Nottingham Prognostic Index (NPI) in young breast cancer patients. METHODS: This multicentre hospital-based retrospective cohort study included young (⩽40 years) and older (55-60 years) breast cancer patients treated from January 2000 to December 2004 at four large Belgian and Italian institutions. Predicted 10-year overall survival (OS) and disease-free survival (DFS) using AOL and 10-year OS using NPI were calculated for every patient. Tools ability to predict outcomes (i.e., calibration) and their discriminatory accuracy was assessed. RESULTS: The study included 1283 patients, 376 young and 907 older women. Adjuvant! Online accurately predicted 10-year OS (absolute difference: 0.7%; P=0.37) in young cohort, but overestimated 10-year DFS by 7.7% (P=0.003). In older cohort, AOL significantly underestimated both 10-year OS and DFS by 7.2% (P<0.001) and 3.2% (P=0.04), respectively. Nottingham Prognostic Index significantly underestimated 10-year OS in both young (8.5%; P<0.001) and older (4.0%; P<0.001) cohorts. Adjuvant! Online and NPI had comparable discriminatory accuracy. CONCLUSIONS: In young breast cancer patients, AOL is a reliable tool in predicting OS at 10 years but not DFS, whereas the performance of NPI is sub-optimal.

Monitoring metabolic response using FDG PET-CT during targeted therapy for metastatic colorectal cancer.

INTRODUCTION: The introduction of targeted drugs has had a significant impact on the approach to assessing tumour response. These drugs often induce a rapid cytostatic effect associated with a less pronounced and slower tumoural volume reduction, thereby impairing the correlation between the absence of tumour shrinkage and the patient's unlikelihood of benefit. The aim of the study was to assess the predictive value of early metabolic response (mR) evaluation after one cycle, and its interlesional heterogeneity to a later metabolic and morphological response assessment performed after three cycles in metastatic colorectal cancer (mCRC) patients treated with combined sorafenib and capecitabine. METHODS: This substudy was performed within the framework of a wider prospective multicenter study on the predictive value of early FDG PET-CT response assessment (SoMore study). A lesion-based response analysis was performed, including all measurable lesions identified on the baseline PET. On a per-patient basis, a descriptive 4-class response categorization was applied based upon the presence and proportion of non-responding lesions. For dichotomic response comparison, all patients with at least one resistant lesion were classified as non-responding. RESULTS: On baseline FDG PET-CT, 124 measurable "target" lesions were identified in 38 patients. Early mR assessments showed 18 patients (47 %) without treatment resistant lesions and 12 patients (32 %) with interlesional response heterogeneity. The NPV and PPV of early mR were 85 % (35/41) and 84 % (70/83), respectively, on a per-lesion basis and 95 % (19/20) and 72 % (13/18), respectively, on a dichotomized per-patient basis. CONCLUSIONS: Early mR assessment performed after one cycle of sorafenib-capecitabine in mCRC is highly predictive of non-response at a standard response assessment time. The high NPV (95 %) of early mR could be useful as the basis for early treatment discontinuation or adaptation to spare patients from exposure to non-effective drugs.

AURORA: bariatric surgery registration in women of reproductive age - a multicenter prospective cohort study.

BACKGROUND: The expansion of the obesity epidemic is accompanied with an increase in bariatric procedures, in particular in women of reproductive age. The weight loss induced by the surgery is believed to reverse the negative impact of overweight and obesity on female reproduction, however, research is limited to in particular retrospective cohort studies and a growing number of small case-series and case-(control) studies. METHODS/DESIGN: AURORA is a multicenter prospective cohort study. The main objective is to collect long-term data on reproductive outcomes before and after bariatric surgery and in a subsequent pregnancy. Women aged 18-45 years are invited to participate at 4 possible inclusion moments: 1) before surgery, 2) after surgery, 3) before 15 weeks of pregnancy and 4) in the immediate postpartum period (day 3-4). Depending on the time of inclusion, data are collected before surgery (T1), 3 weeks and 3, 6, 12 or x months after surgery (T2-T5) and during the first, second and third trimester of pregnancy (T6-T8), at delivery (T9) and 6 weeks and 6 months after delivery (T10-T11). Online questionnaires are send on the different measuring moments. Data are collected on contraception, menstrual cycle, sexuality, intention of becoming pregnant, diet, physical activity, lifestyle, psycho-social characteristics and dietary supplement intake. Fasting blood samples determine levels of vitamin A, D, E, K, B-1, B-12 and folate, albumin, total protein, coagulation parameters, magnesium, calcium, zinc and glucose. Participants are weighted every measuring moment. Fetal ultrasounds and pregnancy course and complications are reported every trimester of pregnancy. Breastfeeding is recorded and breast milk composition in the postpartum period is studied. DISCUSSION: AURORA is a multicenter prospective cohort study extensively monitoring women before undergoing bariatric surgery until a subsequent pregnancy and postpartum period. TRIAL REGISTRATION: Retrospectively registered (July 2015 - NCT02515214 ).

Oocytes affected by smooth endoplasmic reticulum aggregates: to discard or not to discard?

PURPOSE: Oocytes containing smooth endoplasmic reticulum aggregates (SERa) have been associated with reduced fertilization and clinical pregnancy rates as well as compromised neonatal outcomes. It was therefore recommended by an Alpha-ESHRE Consensus to discard oocytes presenting this dysmorphism. The data in the literature are nevertheless conflicting and healthy babies have recently been obtained from affected oocytes. The objectives of this study were to compare clinical outcomes between ICSI cycles with and without oocytes affected by smooth endoplasmic reticulum aggregates and to confirm whether affected oocytes can produce healthy babies. METHODS: A prospective observational study was performed comparing 714 SERa- ICSI cycles to 112 SERa+ cycles. Among the SERa+ cycles, 518 SERa- oocytes and 213 SERa+ oocytes were analyzed. Fertilization, embryo quality, and pregnancy rates as well as neonatal outcomes were compared between SERa+ and SERa- cycles as well as between SERa+ and SERa- oocytes. RESULTS: The presence of SERa was not associated with an adverse effect on embryological, clinical or neonatal data for SERa+ cycles and oocytes. Seven healthy babies were born from embryos originating from SERa+ oocytes. CONCLUSIONS: These results are encouraging and might contribute in the future to a revision of the Alpha-ESHRE Consensus. Larger studies, including a correlation between frequency and size of SERa, clinical outcomes and malformation rates, as well as the follow-up of babies born are nevertheless necessary. In the meantime, the currently conflicting data requires caution when considering transfers of embryos affected by SERa.

Epidemiology and outcome of fungemia in a cancer Cohort of the Infectious Diseases Group (IDG) of the European Organization for Research and Treatment of Cancer (EORTC 65031).

BACKGROUND: Anti-cancer treatment and the cancer population have evolved since the last European Organisation for Research and Treatment of Cancer (EORTC) fungemia survey, and there are few recent large epidemiological studies. METHODS: This was a prospective cohort study including 145 030 admissions of patients with cancer from 13 EORTC centers. Incidence, clinical characteristics, and outcome of fungemia were analyzed. RESULTS: Fungemia occurred in 333 (0.23%; 95% confidence interval [CI], .21-.26) patients, ranging from 0.15% in patients with solid tumors to 1.55% in hematopoietic stem cell transplantation recipients. In 297 evaluable patients age ranged from 17 to 88 years (median 56 years), 144 (48%) patients were female, 165 (56%) had solid tumors, and 140 (47%) had hematological malignancies. Fungemia including polymicrobial infection was due to: Candida spp. in 267 (90%), C. albicans in 128 (48%), and other Candida spp. in 145 (54%) patients. Favorable overall response was achieved in 113 (46.5%) patients by week 2. After 4 weeks, the survival rate was 64% (95% CI, 59%-70%) and was not significantly different between Candida spp. Multivariable logistic regression identified baseline septic shock (odds ratio [OR] 3.04, 95% CI, 1.22-7.58) and tachypnoea as poor prognostic factors (OR 2.95, 95% CI, 1.66-5.24), while antifungal prophylaxis prior to fungemia (OR 0.20, 95% CI, .06-.62) and remission of underlying cancer (OR, 0.18; 95% CI, .06-.50) were protective. CONCLUSIONS: Fungemia, mostly due to Candida spp., was rare in cancer patients from EORTC centers but was associated with substantial mortality. Antifungal prophylaxis and remission of cancer predicted better survival.