The impact of self-monitoring physical and mental health via an mHealth application on postpartum weight retention: Data from the INTER-ACT RCT.

Background: Postpartum weight retention (PPWR) has many health risks. Digital self-monitoring of weight can potentially make postpartum weight management easier. We aim to test to what extent the self-monitoring of weight, steps and mental health through an mHealth application increases postpartum weight loss and reduces the odds of substantial PPWR (≥5 kg). Methods: Participants were mothers in the intervention arm of the INTER-ACT multicenter randomized controlled trial (RCT), an inter-pregnancy lifestyle intervention among mothers with excessive gestational weight gain. Participants (n=288) had access to an mHealth application to log their weight, steps and mental health between 6 weeks and 6 months postpartum. A linear multiple regression model and a logistic regression model were run to test to what extent self-monitoring via the app increases postpartum weight loss and reduces the risk of substantial PPWR. Results: Women who logged their weight more often lost more weight (B=0.03, ß=0.26, CIB =[0.01,0.05], P<0.01), and had reduced odds of substantive PPWR (OR=0.99, CIOR =[0.98, 0.999], P<.05). Mental health logging reduced the odds of substantive PPWR (OR=0.98, CIOR =[0.97, 1.00], P<0.05), but was unrelated to the amount of weight loss. Steps logging was unrelated to either weight loss or substantive PPWR. Conclusion: Mothers with excessive gestational weight gain can benefit from app-based lifestyle interventions to reduce PPWR by self-monitoring their weight. More attention to mental health in PPWR interventions is needed.

Prediction of 177Lu-DOTATATE PRRT Outcome Using Multimodality Imaging in Patients with Gastroenteropancreatic Neuroendocrine Tumors: Results from a Prospective Phase II LUMEN Study.

Our objective was to predict the outcome of peptide receptor radionuclide therapy (PRRT) using multimodality imaging and tumor dosimetry on gastroenteropancreatic neuroendocrine tumor (GEP-NET) lesions and patients. Methods: This prospective study included patients with progressive GEP-NETs. Treatment consisted of 4 cycles of 7.4 GBq of 177Lu-DOTATATE. Imaging parameters were measured on 68Ga-DOTATATE PET/CT (SUVmax/mean, somatostatin receptor [SSTR] tumor volume [TV], total lesion SSTR expression, and tumor-to-blood and tumor-to-spleen ratios), 18F-FDG PET/CT (SUVmax/mean, metabolically active TV, and total lesion glycolysis), and diffusion-weighted MRI (apparent diffusion coefficient) in a maximum of 5 target lesions per patient at approximately 10 wk after each injection. Tumor dosimetry was performed using SPECT/CT at 3 time points for every cycle. Baseline imaging parameters, their relative changes after PRRT cycle 1 (C1), and the tumor-absorbed dose at C1 were correlated with lesion morphologic outcome. The average values of the imaging parameters and the minimal, maximal, and mean C1 tumor-absorbed dose in each patient were tested for association with progression-free survival (PFS) and best objective response (RECIST 1.1). Results: In the 37 patients, the median PFS was 28 mo. Eleven of the 37 (30%) achieved a partial response (RECIST 1.1). After a median follow-up of 57 mo, the median time to lesion progression had not been reached in 84 morphologically evaluable lesions, with only 12 (14%) progressing (size increase ≥ 20% from baseline). Patients receiving a minimal C1 dose of 35 Gy in all target lesions exhibited a significantly longer PFS (48.1 vs. 26.2 mo; hazard ratio, 0.37; 95% CI, 0.17-0.82; P = 0.02). Volumetric 68Ga-DOTATATE PET parameters correlated with lesion and patient outcome: patients with an SSTR TV decrease of more than 10% after C1 had a longer PFS (51.3 vs. 22.8 mo; hazard ratio, 0.35; 95% CI, 0.16-0.75; P = 0.003). There was no statistical evidence of an association between other dosimetric or imaging parameters and the lesion or patient outcome. Conclusion: Minimal tumor-absorbed dose at C1 is predictive of outcome in patients with GEP-NETs treated with PRRT, providing a basis for personalized dosimetry-guided treatment strategies. An SSTR TV decrease after C1 could be used for early therapy response assessment as a predictor of PRRT outcome.

Progression-free survival assessment by local investigators versus blinded independent central review in randomized clinical trials in metastatic breast cancer: A systematic review and meta-analysis.

INTRODUCTION: In randomized clinical trials (RCTs), blinded independent central review (BICR) is used to minimize heterogeneity and bias associated with radiological response evaluation by local investigators. However, BICR adds costs and complexity to the trial management. We assessed the discrepancy index between progression-free survival (PFS) assessment by local investigators and by BICR in RCTs conducted in patients with metastatic breast cancer (MBC). METHODS: A systematic search of PubMed, Embase, Cochrane databases and conference proceedings (ASCO, SABCS, ESMO) was performed up to January 4, 2023 (PROSPERO: CRD42021229865). All RCTs published from 2000 to 2022, including MBC patients treated in first- or second-line, and reporting PFS assessed by local investigators and BICR were included. A discrepancy index between BICR-assessed and investigator-assessed HR was calculated for each trial and an overall combined DI was obtained using a fixed-effects model. The agreement between hazard ratios (HR) of PFS assessed by local investigators and BICR was measured using intraclass correlation coefficient (ICC). RESULTS: We analyzed 24 studies including 13,168 patients. Among them, 19 (79%) were in first-line, 18 (75%) were phase III trials and 23 (96%) had PFS as primary endpoint. The overall combined discrepancy index was 0.97 (95%CI 0.85-1.10; ICC 0.831, p < 0.001) suggesting no statistically significant difference in PFS assessment between local investigators and BICR. This result was consistent across all analyzed subgroups. CONCLUSIONS: The good concordance between local investigator and BICR assessments supports the reliability of local investigator-assessed PFS as primary endpoint for RCTs in MBC and questions the practical utility of implementing BICR in all RCTs.

Ki-67 index after neoadjuvant endocrine therapy as a prognostic biomarker in patients with ER-positive/HER2-negative early breast cancer: a systematic review and meta-analysis.

BACKGROUND: Neoadjuvant treatment discriminates responders, but pathologic complete response is uncommon in oestrogen receptor (ER)-positive/HER2-negative early breast cancer. We aimed to assess the prognostic value of Ki-67 index after neoadjuvant endocrine therapy (NET). METHODS: We conducted a systematic literature search of PubMed, Embase, CENTRAL, and conference proceedings up to 22nd August 2023 to identify studies reporting the association of Ki-67 index after NET with recurrence-free survival (RFS) and/or overall survival (OS) in women with ER-positive/HER2-negative early breast cancer. We combined RFS and OS hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Twelve studies including 7897 patients were analysed. Most studies were clinical trials (n = 7547) including only postmenopausal women (n = 3953) treated with aromatase inhibitor (n = 3359). Three studies evaluated Ki-67 in a preplanned core biopsy at 2-4 weeks of NET (n = 3348), while nine evaluated Ki-67 in the surgical specimen (n = 4549) after 2-24 weeks of NET. Median follow-up ranged between 37 and 95 months for RFS and 62-84 months for OS. High Ki-67 index after NET was significantly associated with worse RFS (HR 2.48, 95% CI 1.86-3.30) and OS (HR 2.66, 95% CI 1.65-4.28). A sensitivity analysis including three studies that measured Ki-67 in a preplanned core biopsy showed similar association with RFS (HR 2.41, 95% CI 1.77-3.30). CONCLUSIONS: High Ki-67 after NET is associated with worse survival outcomes, even after a short course of NET, emphasising the prognostic value of this biomarker in women with ER-positive/HER2-negative early breast cancer.

Mental Health during the Interpregnancy Period and the Association with Pre-Pregnancy Body Mass Index and Body Composition: Data from the INTER-ACT Randomized Controlled Trial.

Mental health problems and obesity are two common complications during pregnancy and postpartum. The preconception period is considered an appropriate period for prevention. Therefore, insights into interpregnancy mental health and the impact on weight and body composition are of interest to developing effective weight management strategies. The primary aim of this study is to assess the difference in women's mental health during the interpregnancy period and the association with pre-pregnancy body mass index (BMI) and body composition. The secondary aim is to study whether this association is affected by socio-demographic factors, interpregnancy interval and sleep. The study is a secondary analysis of the INTER-ACT e-health-supported lifestyle trial. Women were eligible if they had a subsequent pregnancy and mental health measurements at 6 weeks after childbirth and at the start of the next pregnancy (n = 276). We used univariate analyses to assess differences in mental health and performed regression analysis to assess their association with pre-pregnancy BMI and body composition at the start of the next pregnancy. Our results show a statistically significant increase in anxiety and depressive symptoms between 6 weeks after childbirth and the start of the next pregnancy (sSTAI-6 ≥ 40: +13%, p =≤ 0.001; GMDS ≥ 13: +9%, p = 0.01). Of the women who were not anxious at 6 weeks after childbirth (sSTAI < 40), more than one-third (39%) developed anxiety at the start of the next pregnancy (p =≤ 0.001). Regression analysis showed that sense of coherence (SOC-13) at the start of the next pregnancy was independently associated with women's pre-pregnancy BMI and fat percentage. We believe that the development of preconception lifestyle interventions that focus on both weight reduction and support in understanding, managing and giving meaning to stressful events (sense of coherence) may be of added value in optimizing women's preconception health.

Effect of the INTER-ACT lifestyle intervention on maternal mental health during the first year after childbirth: A randomized controlled trial.

We assess whether the INTER-ACT postpartum lifestyle intervention influences symptoms of depression and anxiety, sense of coherence and quality of life during the first year after childbirth. A total of 1047 women of the INTER-ACT RCT were randomized into the intervention (n = 542) or control arm (n = 505). The lifestyle intervention consisted of 4 face-to-face coaching sessions, supported by an e-health app. Anthropometric and mental health data were collected at baseline, end of intervention and 6-months follow-up. We applied mixed models to assess whether the evolution over time of depressive symptoms, anxiety, sense of coherence and quality of life differed between the intervention and control arm, taking into account the women's pre-pregnancy BMI. There was no statistical evidence for a difference in evolution in anxiety or quality of life between intervention and control arm. But an improvement in symptoms of depression and sense of coherence was observed in women who received the intervention, depending on the mother's pre-pregnancy BMI. Women with normal/overweight pre-pregnancy BMI, reported a decrease in EPDS between baseline and end of intervention, and the decrease was larger in the intervention arm (control arm: -0.42 (95% CI, -0.76 to -0.08); intervention arm: -0.71 (95% CI, -1.07 to -0.35)). Women with pre-pregnancy obesity showed an increase in EPDS between baseline and end of intervention, but the increase was less pronounced in the intervention arm (control arm: +0.71 (95% CI, -0.12 to 1.54); intervention arm: +0.42 (95% CI -0.42 to 1.25)). Women with a normal or obese pre-pregnancy BMI in the intervention arm showed a decrease in sense of coherence between baseline and end of intervention (-0.36) (95% CI, -1.60 to 0.88), while women with overweight pre-pregnancy showed an increase in sense of coherence (+1.53) (95% CI, -0.08 to 3.15) between baseline and end of intervention. Receiving the INTER-ACT postpartum lifestyle intervention showed improvement in depressive symptoms, in normal weight or overweight women on the short run, as well as improvement in sense of coherence in women with pre-pregnancy overweight only. Trial registration: ClinicalTrials.gov;NCT02989142.

Immune response to anti-SARS-CoV-2 prime-vaccination in patients with cancer: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to evaluate the immune response to anti-SARS-CoV-2 prime-vaccination in patients with cancer. METHODS: We performed a systematic literature search using PubMed, Embase, and Cochrane Library until 28/09/2021, and conference proceedings from ASCO and ESMO 2021 annual meetings. We screened for observational or interventional studies including subjects ≥ 16 years old with cancer diagnosis who were vaccinated against SARS-CoV-2. Prime-vaccination was defined as one dose of Ad26.COV2-S vaccine or two doses of BNT162b2, mRNA-1273, ChAdOx1-S or inactivated SARS-CoV-2 vaccine. The outcomes were humoral and adaptive immune responses (proportion of subjects with positive titers of antibody anti-SARS-CoV-2 spike protein and anti-SARS-CoV-2 cellular responses, respectively). RESULTS: We included 89 records reporting data from 30,183 subjects. The overall seropositive rate within the first month after complete anti-SARS-CoV-2 prime-vaccination was 80% [95% confidence interval (CI), 72-86%], 60% (95%CI, 53-67%) in patients with hematological malignancies (HM) versus 94% (95%CI, 88-97%) in patients with solid malignancies (SM). The diagnosis of HM was significantly associated with a lower seropositive rate on multivariate meta-regression (odds ratio 0.35, 95% CI 0.18-0.69, HM versus both, p = 0.002). The overall humoral response was 49% (95% CI, 42-56%) after incomplete prime-vaccination and 79% (95% CI, 70-86%) at 2 months after complete prime-vaccination. These responses were also lower in patients with HM at these time points. The overall cellular response rate at any time after vaccination was 61% (95% CI, 44-76%). CONCLUSION: This meta-analysis provides compelling evidence of humoral and adaptive immune responses against SARS-CoV-2 in patients with cancer, which last for at least 2 months following complete prime-vaccination.

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.

Patient-reported outcomes in terms of swallowing and quality of life after prophylactic versus reactive percutaneous endoscopic gastrostomy tube placement in advanced oropharyngeal cancer patients treated with definitive chemo-radiotherapy: Swall PEG study.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is often used to provide nutritional support in locally advanced head and neck cancer patients undergoing multimodality treatment. However, there is little published data on the impact of prophylactic versus reactive PEG. PEG placement may affect swallowing-related physiology, function, and quality of life. The Swall PEG study is a randomized controlled phase III trial testing the impact of prophylactic versus reactive PEG on patient-reported outcomes in terms of swallowing and quality of life in oropharyngeal cancer patients. METHODS: Patients with locally advanced oropharyngeal cancer receiving chemo-radiotherapy will be randomized to either the prophylactic or reactive PEG tube group. Randomization will be stratified by human papillomavirus (HPV) status and unilateral versus bilateral positive neck lymph nodes. The primary objective of the study is the patient's reported outcome in terms of swallowing (MD Anderson Dysphagia Inventory (MDADI)) at 6 months. Secondary objectives include health-related quality of life, dosimetric parameters associated with patient-reported outcomes, chemo-radiation toxicities, PEG tube placement complications, the impact of nutritional status on survival and toxicity outcomes, loco-regional control, overall survival, the impact of HPV and tobacco smoking on survival outcomes and toxicities, and the cost-effectiveness of each treatment strategy. DISCUSSION: Findings from this study will enhance clinical evidence regarding nutritional management in oropharyngeal cancer patients treated by concurrent chemo-radiation. TRIAL REGISTRATION: ClinicalTrials.gov NCT04019548, study protocol version 2.0_08/08/2019. Registered on 15 July 2019.

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.

Mental health after childbirth and the impact on postpartum weight retention and body composition. Data from the INTER-ACT randomized controlled trial.

OBJECTIVE: To study the evolution of maternal mental health during the first year after childbirth in women with previous excessive gestational weight gain, and the relationship with postpartum weight retention and body composition. METHODS: Anthropometric and mental health data of 505 women of the INTER-ACT RCT control group were collected and assessed using descriptive statistics and mixed model analyses. RESULTS: At 6 weeks postpartum 28% of women reported depressive symptoms, 46% anxiety, 47% low sense of coherence and 48% low quality of life. From 6 weeks to 12 months postpartum there was a monthly increase (+0.38, p = .003) in anxiety and a monthly decrease (-0.39, p = .008) in quality of life. High levels of depressive symptoms at 6 weeks postpartum predicted higher body fat (+0.9%, p = .01) and higher waist circumference (+1.3 cm, p = .02) in the first year postpartum. High sense of coherence at 6 weeks postpartum predicted lower body fat (-0.8%, p = .01) the first year postpartum. CONCLUSIONS: In women with a history of excessive gestational weight gain, the first year after childbirth is characterized by a high prevalence of mental health problems in which levels of anxiety and quality of life deteriorate over time. Moreover, high levels of depressive symptoms and low sense of coherence in the first weeks postpartum predict unfavourable body composition outcomes in the year after childbirth.

PREDICT underestimates survival of patients with HER2-positive early-stage breast cancer.

The prognostic performance of PREDICT in patients with HER2-positive early breast cancer (EBC) treated in the modern era with effective chemotherapy and anti-HER2 targeted therapies is unclear. Therefore, we investigated its prognostic performance using data extracted from ALTTO, a phase III trial evaluating adjuvant lapatinib ± trastuzumab vs. trastuzumab alone in patients with HER2-positive EBC. Our analysis included 2794 patients. After a median follow-up of 6.0 years (IQR, 5.8-6.7), 182 deaths were observed. Overall, PREDICT underestimated 5-year OS by 6.7% (95% CI, 5.8-7.6): observed 5-year OS was 94.7% vs. predicted 88.0%. The underestimation was consistent across all subgroups, including those according to the type of anti HER2-therapy. The highest absolute differences were observed for patients with hormone receptor negative-disease, nodal involvement, and large tumor size (13.0%, 15.8%, and 15.3%, respectively). AUC under the ROC curve was 73.7% (95% CI 69.7-77.8) in the overall population, ranging between 61.7% and 77.7% across the analyzed subgroups. In conclusion, our analysis showed that PREDICT highly underestimated OS in HER2-positive EBC. Hence, it should be used with caution to give prognostic estimation to HER2-positive EBC patients treated in the modern era with effective chemotherapy and anti-HER2 targeted therapies.

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.

Combined Metabolically Active Tumor Volume and Early Metabolic Response Improve Outcome Prediction in Metastatic Colorectal Cancer.

Stratification of metastatic colorectal cancer (mCRC) patients is mostly based on clinical and biologic characteristics. This study aimed to validate the prognostic value of 18F-FDG PET/CT-based biomarkers such as baseline whole-body metabolically active tumor volume (WB-MATV) and early metabolic response (mR) in mCRC. Methods: The development cohort included chemorefractory mCRC patients enrolled in 2 prospective Belgian multicenter trials evaluating last-line treatments (multikinase inhibitors). The validation cohort included mCRC patients from an Italian center treated with chemotherapy and bevacizumab as first-line. Baseline WB-MATV was defined as the sum of metabolically active volumes of all target lesions identified on the baseline 18F-FDG PET/CT. Early mR assessment was performed following usual response criteria (response threshold of 30% [PERCIST-30%], response threshold of 15% [PERCIST-15%], European Organization for Research and Treatment of Cancer) and the so-called CONSIST method, which defines response as a decrease of SULmax ≥ 15% for all target lesions. Baseline WB-MATV and early mR assessment were investigated along with usual clinical factors and correlated with overall survival (OS) and progression-free survival (PFS). Results: Clinical factors, baseline WB-MATV, and early mR were evaluable in 192 of 239 and 94 of 125 patients of the development and validation cohorts, respectively. Except for PERCIST-30%, all response methods were equivalent in terms of outcome prediction, and CONSIST was found to be the most accurate. Baseline WB-MATV and early mR using the CONSIST method were independent prognostic parameters after adjustment for clinical factors in the development and validation sets for both OS (hazard ratio [HR] WB-MATV: 1.87 [95% CI, 1.17-2.97], P = 0.005, and HR early mR: 1.79 [95% CI, 1.08-2.95], P = 0.02 for the validation set) and PFS (HR WB-MATV: 1.94 [95% CI, 1.27-2.97], P = 0.002, and HR early mR: 1.69 [95% CI, 1.04-2.73], P = 0.03 for the validation set). Conclusion: Baseline WB-MATV and early mR are strong independent prognostic biomarkers for OS and PFS in mCRC, regardless of treatment received. Therefore, combining these biomarkers improves risk stratification for OS and PFS in mCRC.

Initiation of a new anti-cancer medical treatment in ICU: a retrospective study.

PURPOSE: The purpose of our study is to evaluate the characteristics of patients whose medical anti-cancer treatment has been initiated at the ICU and to release prognostic factors for hospital mortality in these patients. MATERIAL AND METHODS: We analyzed retrospectively all the records of cancer patients admitted between 01/01/2007 and 31/12/2017 in our ICU and for whom a new anti-cancer medical treatment was initiated during their ICU stay. RESULTS: Our study includes 147 patients, 78 men (53%) and 69 women (47%), with a median age of 58 years. Eighty patients (54%) had a solid tumor and 67 (46%) a hematological malignancy. ICU mortality was 23% and hospital mortality 32%. The poor prognostic factors for hospital mortality were: higher SOFA, higher Charslon comorbidity index and the presence of a therapeutic limitation (introduced at the time of admission or within 24 hours of admission to the ICU). One-year survival for patients who survived hospital stay was 37% (17% for those with a solid tumor and 61% for the ones with a hematological malignancy). CONCLUSION: Initiation of an anti-cancer medical treatment is feasible and can lead to good 1 year survival rate, especially for those with a hematological tumor.

FDG positron emission tomography imaging and ctDNA detection as an early dynamic biomarker of everolimus efficacy in advanced luminal breast cancer.

Biomarkers to identify patients without benefit from adding everolimus to endocrine treatment in metastatic breast cancer (MBC) are needed. We report the results of the Pearl trial conducted in five Belgian centers assessing 18F-FDG-PET/CT non-response (n = 45) and ctDNA detection (n = 46) after 14 days of exemestane-everolimus (EXE-EVE) to identify MBC patients who will not benefit. The metabolic non-response rate was 66.6%. Median PFS in non-responding patients (using as cut-off 25% for SUVmax decrease) was 3.1 months compared to 6.0 months in those showing response (HR: 0.77, 95% CI: 0.40-1.50, p = 0.44). The difference was significant when using a "post-hoc" cut-off of 15% (PFS 2.2 months vs 6.4 months). ctDNA detection at D14 was associated with PFS: 2.1 months vs 5.0 months (HR-2.5, 95% CI: 1.3-5.0, p = 0.012). Detection of ctDNA and/or the absence of 18F-FDG-PET/CT response after 14 days of EXE-EVE identifies patients with a low probability of benefiting from treatment. Independent validation is needed.

Evolution of Postpartum Weight and Body Composition after Excessive Gestational Weight Gain: The Role of Lifestyle Behaviors-Data from the INTER-ACT Control Group.

Women with excessive gestational weight gain are at increased risk of postpartum weight retention and potentially also unfavorable body composition. Insight into the lifestyle behaviors that play a role in the evolution of postpartum weight and body composition among these women could aid identification of those at highest risk of long-term adverse outcomes. This secondary analysis of the INTER-ACT randomized controlled trial investigates control group data only (n = 524). The evolution of weight retention, percentage loss of gestational weight gain, fat percentage, waist circumference, and associated lifestyle behaviors between 6 weeks and 12 months postpartum were assessed using mixed model analyses. At six weeks postpartum, every sedentary hour was associated with 0.1% higher fat percentage (P = 0.01), and a higher emotional eating score was associated with 0.2% higher fat percentage (P < 0.001) and 0.3 cm higher waist circumference (P < 0.001). Increase in emotional eating score between 6 weeks and 6 months postpartum was associated with a 0.4 kg (P = 0.003) increase in postpartum weight retention from six months onwards. Among women with overweight, an increase in the uncontrolled eating score between 6 weeks and 6 months postpartum was associated with a 0.3 kg higher postpartum weight retention (P = 0.04), and 0.3% higher fat percentage (P = 0.006) from six months onwards. In conclusion, sedentary and eating behaviors play important roles in postpartum weight and body composition of women with excessive gestational weight gain and should therefore be incorporated as focal points in lifestyle interventions for this population.