Jennifer R. Sadler

In the US, <20% of cancers are diagnosed by standard-of-care (SoC) screening. Multicancer early detection (MCED) tests offer the opportunity to expand cancer screening. Understanding the characteristics and clinical outcomes of MCED-detected cancers is critical to clarifying MCED tests’ potential impact. DETECT-A is the first prospective interventional trial of an MCED blood test (CancerSEEK). CancerSEEK, coupled with diagnostic PET-CT, identified cancers including those not detected by SoC screening, the majority of which were localized or regional. We report multiyear outcomes in patients with cancers diagnosed following a positive CancerSEEK test. Nine cancer types were diagnosed in 26 participants whose cancers were first detected by CancerSEEK. Information on cancer diagnoses, treatments, and clinical outcomes was extracted from medical records through November 2022. Data collection occurred at a median of 4.4 years (IQR: 4.1–4.6) following study enrollment. Thirteen of 26 (50%) participants were alive and cancer-free [ovarian (4), thyroid (1), uterine (2), breast (1), colorectal (2), and lung (3)]; 7/13 (54%) had cancers without recommended SoC screening modalities. All eight treated stage I or II participants (8/8, 100%) and 12/14 (86%) surgically treated participants were alive and cancer-free. Eligibility for surgical treatment was associated with favorable multiyear outcomes (P = 0.0002). Half of participants with MCED-detected cancers were alive and cancer-free after 4.4 years median follow-up. Most were diagnosed with early-stage cancers and were treated surgically. These results suggest that early cancer detection by CancerSEEK may have facilitated curative-intent treatments and associated positive clinical outcomes in some DETECT-A participants. Prevention Relevance: This study provides preliminary evidence of the potential of multicancer early detection testing as an effective screening tool for detecting cancers without standard-of-care (SoC) screening modalities and complementing SoC cancer screening.

Guideline recommended standard of care screening is available for four cancer types; most cancer-related deaths are caused by cancers without standard of care screening. DETECT-A is the first prospective interventional trial evaluating a multi-cancer early detection (MCED) blood test (CancerSEEK) in women without a history of cancer, providing the first opportunity to assess the long-term outcomes of individuals with false-positive (FP) MCED results. This prospective analysis of DETECT-A participants with FP results evaluates the performance of an imaging-based diagnostic workflow and examines cancer risk following a FP result. This analysis included all DETECT-A participants with a positive CancerSEEK test and subsequent flourine-18 fluorodeoxyglucose positron emission tomography-IV contrast-enhanced computed tomography (18-F-FDG PET-CT) imaging and clinical workup indicating no evidence of cancer within 1 year of enrollment (n = 98). Medical records, study interactions, and study surveys were used to assess cancer incidence, treatments, and clinical outcomes through August 2023. Ninety-five of 98 participants with a FP result remained cancer-free with a median follow-up of 3.6 years (IQR: 2.5–4.1) from determination of FP status. Three incident cancers were observed over the follow-up period. One bilateral stage IIIC ovarian cancer was diagnosed 1.9 years after determination of FP status; two stage I breast cancers were diagnosed 0.1 and 1.6 years from determination of FP status. The annual incidence rate of cancer during follow-up from FP determination was 1.0% (95% confidence interval, 0.2%–2.8%). Participants with a positive CancerSEEK test who underwent 18-F-FDG PET-CT and clinical workup without cancer findings had low risk for cancer over the following several years. Prevention Relevance: This study provides multiyear clinical outcomes data following a false-positive multi-cancer early detection test for individuals participating in a prospective interventional trial. It provides a preliminary performance assessment of an imaging-based diagnostic workflow following a false-positive multi-cancer early detection test.

Summary: Obesity and components of the metabolic syndrome (MetS) are associated with differences in brain structure and function and in general and food‐related cognition in adults. Here, we review evidence for similar phenomena in children and adolescents, with a focus on the implications of extant research for possible underlying mechanisms and potential interventions for obesity and MetS in youth. Current evidence is limited by a relative reliance on small cross‐sectional studies. However, we find that youth with obesity and MetS or MetS components show differences in brain structure, including alterations in grey matter volume and cortical thickness across brain regions subserving reward, cognitive control and other functions, as well as in white matter integrity and volume. Children with obesity and MetS components also show some evidence for hyperresponsivity of food reward regions and hyporesponsivity of cognitive control circuits during food‐related tasks, altered brain responses to food tastes, and altered resting‐state connectivity including between cognitive control and reward processing networks. Potential mechanisms for these findings include neuroinflammation, impaired vascular reactivity, and effects of diet and obesity on myelination and dopamine function. Future observational research using longitudinal measures, improved sampling strategies and study designs, and rigorous statistical methods, promises to further illuminate dynamic relationships and causal mechanisms. Intervention studies targeted at modifiable biological and behavioural factors associated with paediatric obesity and MetS can further inform mechanisms, as well as test whether brain and behaviour can be altered for beneficial outcomes.

Summary: Neuroimaging studies demonstrate associations of brain structure and function with children's eating behaviour and body weight, and the feasibility of integrating brain measures into obesity risk assessment and intervention is growing. However, little is known about lay perceptions of how the brain influences obesity. We investigated parent perceptions of brain contributions to obesity in three separate studies: 1) a study of mothers of adolescents recruited for neuroimaging research (n = 88), 2) a study of ethnically Chinese parents of 5–13 year olds participating in a parent feeding survey (n = 277), and 3) a study of parents of 3–15 year olds completing an online survey (n = 113). In general, parents believed that brain factors influence obesity, but considered them less influential than behaviours such as diet and exercise. Causal attributions for brain factors were correlated with attributions for genetic factors and biological factors (e.g., metabolism). Parents who perceived their child to be overweight or had a high concern about their child becoming overweight in the future rated brain factors as more important in determining their child's weight and more likely to lessen their child's ability to control their weight. Our results suggest that parents attribute obesity to the brain to a moderate degree, and that education or feedback regarding brain influences on obesity could be a promising obesity intervention component.

(1) Background: The coronavirus (COVID-19) pandemic has caused disruptions to what people eat, but the pandemic’s impact on diet varies between individuals. The goal of our study was to test whether pandemic-related stress was associated with food intake, and whether relationships between stress and intake were modified by appetitive and cognitive traits. (2) Methods: We cross-sectionally surveyed 428 adults to examine current intake frequency of various food types (sweets/desserts, savory snacks, fast food, fruits, and vegetables), changes to food intake during the pandemic, emotional overeating (EOE), cognitive flexibility (CF), and COVID-19-related stress. Models tested associations of stress, EOE, and CF with food intake frequency and changes to intake. (3) Results: Models demonstrated that the positive relationship between stress and intake of sweets/desserts was stronger with higher EOE, while the positive relationship between stress and intake of chips/savory snacks was weaker with higher CF. Higher EOE was associated with greater risk of increased intake of palatable foods. (4) Conclusions: Findings suggest that emotional overeating may escalate stress-associated intake of high-sugar foods, and cognitive flexibility may attenuate stress-associated intake of high-fat foods. Differences in appetitive and cognitive traits may explain changes to and variability in food intake during COVID-19, and efforts to decrease emotional overeating and encourage cognitive flexibility could help lessen the effect of COVID-19-related stress on energy dense food intake.

Identifying correlates of brain response to food cues and taste provides critical information on individual differences that may influence variability in eating behavior. However, a few studies examine how brain response changes over repeated exposures and the individual factors that are associated with these changes. Using functional magnetic resonance imaging, we examined how brain response to a palatable taste and proceeding cues changed over repeated exposures and how individual differences in weight, familial obesity risk, dietary restraint and reward responsiveness correlate with these changes. In healthy-weight adolescents (n = 154), caudate and posterior cingulate cortex (PCC) response increased with repeated cue presentations, and oral somatosensory cortex and insula response increased with repeated milkshake tastes. The magnitude of increase over exposures in the left PCC to cues was positively associated with body mass index percentile (r = 0.18, P = 0.026) and negatively associated with dietary restraint scores (r = −0.24, P = 0.003). Adolescents with familial obesity risk showed higher cue-evoked caudate response across time, compared to the low-risk group (r = 0.12, P = 0.035). Reward responsiveness positively correlated with right oral somatosensory cortex/insula response to milkshake over time (r = 0.19, P = 0.018). The results show that neural responses to food cues and taste change over time and that individual differences related to weight gain are correlated with these changes.