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Background: Several narrative reports document long-term responses to regorafenib treatment in patients with metastatic colorectal cancer (mCRC). However, no large-scale study has assessed long-term responses and there are no established predictors of potential long-term benefit. We carried out an observational study of characteristics of patients treated in real-world clinical practice in the USA using duration of treatment (DoT) as a surrogate for treatment response. Patients and Methods: This retrospective cohort study used a de-identified electronic health record-derived database and included patients aged ≥18 years with mCRC who initiated regorafenib monotherapy between 1 July 2013 and 30 June 2023. Patient cohorts were defined by DoT ≥4 months (LTR4), ≥5 months (LTR5), or ≥6 months (LTR6) and are not mutually exclusive. Results: Of 2444 patients who initiated regorafenib monotherapy during the study, those with long-term response were analyzed: 544 had LTR4 (22%), 367 had LTR5 (15%), and 250 had LTR6 (10%). Most patients with long-term responses had left-sided tumors (65–70%), Eastern Cooperative Oncology Group performance status of 0/1 (67–68%), and liver metastases (55–61%) and had received prior bevacizumab treatment (60–67%). The median age in each group was 66 years, and patients most frequently initiated regorafenib as third-line treatment (31–33%). Median time to regorafenib discontinuation was 6.0–9.3 months among long-term responders. Conclusions: Most patients with long-term responses to regorafenib had favorable performance status at treatment initiation, left-sided tumors, and liver metastases and had received prior bevacizumab treatment. The study highlights that patients in the real-world setting were able to tolerate and maintain long-term responses to regorafenib treatment.

Background The randomized, dose-optimization, open-label ReDOS study in US patients with metastatic colorectal cancer (CRC) showed that, compared with a standard dosing approach, initiating regorafenib at 80 mg/day and escalating to 160 mg/day depending on tolerability increased the proportion of patients reaching their third treatment cycle and reduced the incidence of adverse events without compromising efficacy. Subsequently, the ReDOS dose-escalation strategy was included as an alternative regorafenib dosing option in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines. A retrospective analysis was conducted using a US claims database to assess whether inclusion of this dose-escalation strategy in NCCN Guidelines has influenced the use of flexible dosing in routine US clinical practice, and to describe clinical outcomes pre- and post-inclusion in NCCN Guidelines. Methods Patients with CRC in the Optum’s de-identified Clinformatics® Data Mart database initiating regorafenib for the first time between January 2016 and June 2020 were stratified based on whether they initiated regorafenib pre- or post-inclusion of ReDOS in NCCN Guidelines, and in two groups: flexible dosing (< 160 mg/day; < 84 tablets in the first treatment cycle) and standard dosing (160 mg/day; ≥ 84 tablets in the first treatment cycle). The primary endpoints were the proportion of patients who initiated their third treatment cycle and the mean number of treatment cycles per group. Results 703 patients initiated regorafenib during the study period, of whom 310 (44%) initiated before and 393 (56%) initiated after inclusion of ReDOS in NCCN Guidelines. After inclusion in the guidelines, the proportion of patients who received flexible dosing increased from 21% ( n  = 66/310) to 45% ( n  = 178/393), the proportion who received standard dosing decreased from 79% ( n  = 244/310) to 55% ( n  = 215/393), the proportion who initiated their third treatment cycle increased from 36% ( n  = 113/310) to 46% ( n  = 179/393), and the mean (standard deviation) number of treatment cycles increased from 2.6 (2.9) to 3.2 (3.1). Conclusions Following inclusion of ReDOS in NCCN Guidelines, real-world data suggest that US clinicians have markedly increased use of flexible dosing in clinical practice, potentially maximizing clinical benefits and safety outcomes for patients with metastatic CRC receiving regorafenib.

BackgroundPoverty may pose risks to child and adolescent mental health, but few studies have reported on this association among children and adolescents in low-income families in Norway.MethodsBased on a sample participating in an intervention for low-income families in Norway, we report data from the survey administered at the start of the intervention. Mental health problems were measured using the Strengths and Difficulties Questionnaire (SDQ; self-report (SR) n = 148; parent/proxy-report (PR) n = 153, mean age = 10.8). Demographic and family characteristics were obtained from parent reported data. Results are presented by gender and migration background. Regression analysis was used to investigate the relative contribution of background factors to mental health symptoms. The distribution of scores is compared to UK norms.ResultsParticipants reported relatively high scores on the Strengths and Difficulties Questionnaire (SDQ) Total Difficulties Scale (parent/proxy-report, PR mean=10.7; self-report, SR mean=10.1). Participants with non-immigrant backgrounds scored considerably higher on the Total Difficulties Scale (PR mean difference=2.9; SR 5.3) and on most other domains measured with the SDQ compared with their peers with immigration backgrounds. Participants generally scored higher than or equal to UK norms.ConclusionParticipants in the current study had many symptoms of mental health problems, with large differences between those with and without a migrant background. Interventions for low-income families should be based on detailed knowledge about differences in family risks, resources and needs.

Serum lactate dehydrogenase (LDH) is a potential prognostic biomarker of outcomes in patients with metastatic colorectal cancer (mCRC). This retrospective, observational study assessed real-world LDH testing patterns and LDH as a prognostic factor for overall survival (OS) in US patients receiving chemotherapy for mCRC.Patients and methods: Patients with mCRC who initiated first-line chemotherapy between January 1, 2016, and November 30, 2022, were selected from a nationwide de-identified Electronic Health Record-derived database. LDH value was categorized based on laboratory reference ranges. The prognostic relationship between pretreatment LDH value and OS was assessed using Kaplan-Meier and multivariate Cox proportional-hazards models.BACKGROUNDSerum lactate dehydrogenase (LDH) is a potential prognostic biomarker of outcomes in patients with metastatic colorectal cancer (mCRC). This retrospective, observational study assessed real-world LDH testing patterns and LDH as a prognostic factor for overall survival (OS) in US patients receiving chemotherapy for mCRC.Patients and methods: Patients with mCRC who initiated first-line chemotherapy between January 1, 2016, and November 30, 2022, were selected from a nationwide de-identified Electronic Health Record-derived database. LDH value was categorized based on laboratory reference ranges. The prognostic relationship between pretreatment LDH value and OS was assessed using Kaplan-Meier and multivariate Cox proportional-hazards models.Of 15 329 adult patients (median age 64 years), 3379 (22%) had LDH testing at or post-index; 21% had abnormal baseline values, while 40% had normal values. Patients with abnormal LDH levels were more likely to be female (47% abnormal LDH vs 41% normal LDH), age ≥65 years (52% vs 49%), African American or Black (12% vs 7%), or reside in the Northeast (30% vs 21%). The median OS (95% CI) in patients with normal baseline LDH was 29.9 (28.3-31.7) vs 16.8 (14.8-18.2) months for those with abnormal LDH. In a multivariate Cox proportional-hazards model, patients with abnormal baseline LDH had higher risk of death (HR 1.91, P < .0001) after adjustment for demographic/clinical characteristics.RESULTSOf 15 329 adult patients (median age 64 years), 3379 (22%) had LDH testing at or post-index; 21% had abnormal baseline values, while 40% had normal values. Patients with abnormal LDH levels were more likely to be female (47% abnormal LDH vs 41% normal LDH), age ≥65 years (52% vs 49%), African American or Black (12% vs 7%), or reside in the Northeast (30% vs 21%). The median OS (95% CI) in patients with normal baseline LDH was 29.9 (28.3-31.7) vs 16.8 (14.8-18.2) months for those with abnormal LDH. In a multivariate Cox proportional-hazards model, patients with abnormal baseline LDH had higher risk of death (HR 1.91, P < .0001) after adjustment for demographic/clinical characteristics.Abnormal baseline LDH levels were associated with shorter OS; however, only one-fifth of patients receiving chemotherapy underwent LDH testing. Efforts to increase LDH testing could be valuable in helping guide treatment decisions.CONCLUSIONAbnormal baseline LDH levels were associated with shorter OS; however, only one-fifth of patients receiving chemotherapy underwent LDH testing. Efforts to increase LDH testing could be valuable in helping guide treatment decisions.

Abstract Background Serum lactate dehydrogenase (LDH) is a potential prognostic biomarker of outcomes in patients with metastatic colorectal cancer (mCRC). This retrospective, observational study assessed real-world LDH testing patterns and LDH as a prognostic factor for overall survival (OS) in US patients receiving chemotherapy for mCRC. Methods Patients with mCRC who initiated first-line chemotherapy between January 1, 2016, and November 30, 2022, were selected from a nationwide de-identified Electronic Health Record-derived database. LDH value was categorized based on laboratory reference ranges. The prognostic relationship between pretreatment LDH value and OS was assessed using Kaplan–Meier and multivariate Cox proportional-hazards models. Results Of 15 329 adult patients (median age 64 years), 3379 (22%) had LDH testing at or postindex; 21% had abnormal baseline values, while 40% had normal values. Patients with abnormal LDH levels were more likely to be female (47% abnormal LDH vs 41% normal LDH), ≥ 65 years of age (52% vs 49%), Black or African American (12% vs 7%), or reside in the Northeast (30% vs 21%). The median OS (95% CI) in patients with normal baseline LDH was 29.9 (28.3-31.7) vs 16.8 (14.8-18.2) months for those with abnormal LDH. In a multivariate Cox proportional-hazards model, patients with abnormal baseline LDH had higher risk of death (HR 1.91, P < .0001) after adjustment for demographic/clinical characteristics. Conclusions Abnormal baseline LDH levels were associated with shorter OS; however, only one-fifth of patients receiving chemotherapy underwent LDH testing. Efforts to increase LDH testing could be valuable in helping guide treatment decisions.

Background: Regorafenib (R) and Trifluridine/Tipiracil ± bevacizumab (T) are approved for treating refractory metastatic colorectal cancer (mCRC) but their optimal sequence is unclear. This study describes the characteristics/clinical outcomes of patients with mCRC in U.S. clinical practice treated sequentially with R-T or T-R. Methods: A retrospective cohort study of 818 patients treated with R-T or T-R between January 2015 and November 2022 was conducted using an electronic health record-derived database. The primary objective was to describe the demographic/clinical characteristics and biomarker status of patients treated with R-T or T-R, stratified by treatment line/age. Secondary objectives were to evaluate/estimate the frequency of neutropenia and myelosuppression-related treatments, the number/type of subsequent therapies, time to treatment discontinuation (TTD), and overall survival (OS). Results: Baseline characteristics were similar among patients who received R-T (n = 393) or T-R (n = 425). Lower rates of moderate/severe neutropenia (26%/12% vs. 32%/16%) and granulocyte colony-stimulating factor/erythropoietin use (22% vs. 24%) were observed with R-T versus T-R. The median TTD was 8.7 months and 8.5 months with R-T versus 8.1 months and 7.9 months with T-R as third- and fourth-line treatment, respectively. The median OS was 13.1 months and 11.6 months with R-T versus 11.5 months and 10.3 months with T-R as third- and fourth-line treatment, respectively. Conclusions: This study did not show a statistically significant difference in OS with R-T versus T-R. Although limited by its retrospective nature, the study suggested R-T may be preferable to T-R given the observed reduction in neutropenia/myelosuppression-related treatments.

Breast cancer is the most frequently diagnosed cancer in females globally. However, we know relatively little about trends in males. This study describes United Kingdom (UK) secular trends in breast cancer from 2000 to 2021 for both sexes. We describe a population-based cohort study using UK primary care Clinical Practice Research Datalink (CPRD) GOLD and Aurum databases. There were 5,848,436 eligible females and 5,539,681 males aged 18+ years, with ≥ one year of prior data availability in the study period. We estimated crude breast cancer incidence rates (IR), prevalence and survival probability at one-, five- and 10-years after diagnosis using the Kaplan–Meier method. Analyses were further stratified by age. Crude IR of breast cancer from 2000 to 2021 was 194.4 per 100,000 person-years for females and 1.16 for males. Crude prevalence in 2021 was 2.1% for females and 0.009% for males. Both sexes have seen around a 2.5-fold increase in prevalence across time. Incidence increased with age for both sexes, peaking in females aged 60–69 years and males 90+ . There was a drop in incidence for females aged 70–79 years. From 2003–2019, incidence increased > twofold in younger females (aged 18–29: IR 2.12 in 2003 vs. 4.58 in 2018); decreased in females aged 50–69 years; and further declined from 2015 onwards in females aged 70–89 years. Survival probability for females after one-, five-, and ten-years after diagnosis was 95.1%, 80.2%, and 68.4%, and for males 92.9%, 69.0%, and 51.3%. Survival probability at one-year increased by 2.08% points, and survival at five years increased by 5.39% from 2000–2004 to 2015–2019 for females, particularly those aged 50–70 years. For males, there were no clear time-trends for short-term and long-term survival probability. Changes in incidence of breast cancer in females largely reflect the success of screening programmes, as rates rise and fall in synchronicity with ages of eligibility for such programmes. Overall survival from breast cancer for females has improved from 2000 to 2021, again reflecting the success of screening programmes, early diagnosis, and improvements in treatments. Male breast cancer patients have worse survival outcomes compared to females, highlighting the need to develop male-specific diagnosis and treatment strategies to improve long-term survival in line with females.

How neurovascular coupling develops in preterm-born neonates has been largely neglected in scientific research. We measured visually evoked (flicker light) hemodynamic responses (HRs) in preterm-born neonates (n  =  25, gestational age: 31.71  ±  3.37 weeks, postnatal age: 25.48  ±  23.94 days) at the visual cortex (VC) and left frontotemporal lobe (FTL) using functional near-infrared spectroscopy (fNIRS) neuroimaging. We found that the HR characteristics show a large intersubject variability but could be classified into three groups according to the changes of oxyhemoglobin concentration at the VC [(A) increase, (B) decrease, or (C) inconclusive]. In groups A and B, the HRs at the left FTL were correlated with those at the VC, indicating the presence of a frontotemporal–occipital functional connectivity. Neonates in group A had a higher weight at measurement compared to those in group B, and had the lowest baseline total hemoglobin concentration and hematocrit compared to group C. To the best of our knowledge, this is the first fNIRS study showing (1) that the HRs of preterm-born neonates need to be classified into subgroups, (2) that the subgroups differed in terms of weight at measurement, and (3) that HRs can be observed also at the FTL during visual stimulation. These findings add insights into how neurovascular coupling develops in preterm-born neonates.