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.

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.

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.

177 Lu-DOTATATE PRRT Safety and Organ-at-Risk Dosimetry in Patients With Gastroenteropancreatic Neuroendocrine Tumors : Data From the Prospective Phase 2 LUMEN Study.

PURPOSE: The aim of this study was to assess the association among toxicity, dosimetry of organs-at-risk, and disease progression in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with 177 Lu-DOTATATE. PATIENTS AND METHODS: Thirty-seven patients with GEP-NETs underwent 177 Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in a single-arm, prospective, phase 2 study, where patients were followed up with blood tests, isotopic glomerular filtration rate (iGFR), and imaging examinations (CT/MRI and PET) every 6 months until disease progression. Adverse events (AEs) graded per CTCAEv4.03 and occurring during treatment were collected and followed up until resolution. Dosimetry, including biologically effective doses (BEDs) to kidneys, BED to bone marrow, and absorbed dose (AD) to spleen, was performed after each PRRT cycle. Statistical analyses explored associations among dosimetry, toxicity, and patient progression free-survival. RESULTS: The most common AEs were anemia and lymphopenia (65%), followed by thrombocytopenia and fatigue (each 51%), alopecia (46%), and nausea (41%). The most common grade ≥3 AE was lymphopenia (43%). There was no grade ≥3 nephrotoxicity. The median iGFR % decrease was 11% ( P < 0.001), at a median follow-up of 23 months. iGFR %decrease and renal BED did not correlate (Spearman ρ = -0.09). Similarly, no significant association was found between bone marrow BED or spleen AD and the grades of hematological toxicities. We observed no association between progression free-survival and either the decline of renal function or the occurrence of hematological toxicities during PRRT. CONCLUSIONS: This study confirms the safety profile of 177 Lu-DOTATATE PRRT in patients with GEP-NETs irrespective of the dosimetry of organs at risk. Kidney, bone marrow, and spleen dosimetry measures were not associated with renal or hematological toxicity.

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.