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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 6_suppl ( 2020-02-20), p. 327-327
    Abstract: 327 Background: Though Black men with prostate cancer are more likely to have aggressive disease features than White men, race-specific differences in initial treatment responses in localized disease remains unknown. Methods: Individual patient data were obtained for 9259 patients (including 1674 [18.1%] Black men and 7585 [81.9%] White men) enrolled on eight randomized controlled trials evaluating definitive radiotherapy (RT) ± short-term or long-term androgen deprivation therapy (STADT and LTADT). The primary endpoints were biochemical recurrence (BCR), distant metastasis (DM), and prostate cancer-specific mortality (PCSM). Fine-Gray subdistribution HR (sHR) models were developed to evaluate the cumulative incidences of all endpoints after stratification by National Comprehensive Cancer Network risk grouping. A meta-analysis was done to estimate pair-wise comparisons of treatments within and between Black and White men, after adjusting for age, Gleason score, clinical T stage, and initial PSA. Results: Black men were more likely to have NCCN high-risk disease at enrollment (656/1674 [39.2%] vs 2506/7585 [33%] , p 〈 0.001). However, within the high-risk stratum Black men had lower 10-year rates of BCR (46.1% vs. 50.4%, p=0.02), DM (14% vs. 21.6%, p 〈 0.001), and PCSM (4.9% vs. 9.8%, p 〈 0.001). After adjusting for age and disease characteristics, Black men with high-risk prostate receiving RT+STADT had lower rates of BCR (sHR 0.73, 95% CI 0.62-0.86, p 〈 0.001), DM (sHR 0.64, 95% CI 0.49-0.84, p=0.001) and PCSM (sHR 0.49, 95% CI 0.25-0.95, p=0.04). There were no differences in BCR, DM, or PCSM among men receiving RT+LTADT. The interaction between race and the impact of adding STADT to RT alone on BCR was statistically significant (p=0.003). Conclusions: Black men enrolled on randomized trials with long-term follow-up have higher risk disease at enrollment, but have better BCR, DM, and PCSM outcomes with RT-based therapy compared with White men, particularly with the addition of STADT.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 4 ( 2023-02-01), p. 881-892
    Abstract: The sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT). MATERIALS AND METHODS Individual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer–specific mortality. RESULTS Overall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points ( P interaction 〈 .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P 〈 .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer–specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P 〈 .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT. CONCLUSION ADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 3
    Online Resource
    Online Resource
    Georg Thieme Verlag KG ; 2021
    In:  American Journal of Perinatology Vol. 38, No. S 01 ( 2021-08), p. e33-e38
    In: American Journal of Perinatology, Georg Thieme Verlag KG, Vol. 38, No. S 01 ( 2021-08), p. e33-e38
    Abstract: Objective This study aimed to investigate growth among neonates with gastrointestinal disorders. Study Design Inclusion criteria included neonates with gastroschisis, omphalocele, intestinal atresia, tracheoesophageal fistula, Hirschsprung's disease, malabsorption disorders, congenital diaphragmatic hernia, and imperforate anus born between 2010 and 2018. Anthropometrics were collected for the first 30 months, and a subgroup analysis was performed for gastroschisis infants. Results In 61 subjects, 13% developed severe growth failure within the first month. One-, four-, and nine-month weight and length z-scores were less than birth weight in all infants (p  〈  0.05). In infants with gastroschisis, a similar pattern was observed for weight z-scores only (p  〈  0.05). From birth to 15 months, head circumference z-score increased over time in all infants (p = 0.001), while in gastroschisis infants, weight, length, and head circumference z-scores increased over time (p  〈  0.05). Conclusion In a cohort of infants with gastrointestinal disorders, growth failure was followed by catch-up growth.
    Type of Medium: Online Resource
    ISSN: 0735-1631 , 1098-8785
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2021
    detail.hit.zdb_id: 2042426-7
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  • 4
    In: Prostate Cancer and Prostatic Diseases, Springer Science and Business Media LLC, Vol. 26, No. 1 ( 2023-03), p. 207-209
    Abstract: Radiotherapy impacts the local immune response to cancers. Prostate Stereotactic Body Radiotherapy (SBRT) is a highly focused method to deliver radiotherapy often used to treat prostate cancer. This is the first direct comparison of immune cells within prostate cancers before and after SBRT in patients. Methods Prostate cancers before and 2 weeks after SBRT are interrogated by multiplex immune fluorescence targeting various T cells and macrophages markers and analyzed by cell and pixel density, as part of a clinical trial of SBRT neoadjuvant to radical prostatectomy. Results Two weeks after SBRT, CD68, and CD163 macrophages are significantly increased while CD8 T cells are decreased. SBRT markedly alters the immune environment within prostate cancers.
    Type of Medium: Online Resource
    ISSN: 1365-7852 , 1476-5608
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2008886-3
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  • 5
    Online Resource
    Online Resource
    Informa UK Limited ; 2019
    In:  Journal of Asthma Vol. 56, No. 5 ( 2019-05-04), p. 512-521
    In: Journal of Asthma, Informa UK Limited, Vol. 56, No. 5 ( 2019-05-04), p. 512-521
    Type of Medium: Online Resource
    ISSN: 0277-0903 , 1532-4303
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2019
    detail.hit.zdb_id: 2043248-3
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  • 6
    Online Resource
    Online Resource
    Wiley ; 2023
    In:  Journal of Parenteral and Enteral Nutrition Vol. 47, No. 3 ( 2023-03), p. 354-363
    In: Journal of Parenteral and Enteral Nutrition, Wiley, Vol. 47, No. 3 ( 2023-03), p. 354-363
    Abstract: 100% soybean oil emulsions (SO100) are associated with poor docosahexaenoic acid (DHA) and arachidonic acid (ARA) status in extremely low birth weight (ELBW) infants. A multi‐oil emulsion with 15% fish oil (FO15) contains more DHA and ARA than SO100. This study compares clinical outcomes, namely growth and fatty acids, in ELBW infants who received S0100 or FO15. Methods This observational study included ELBW infants born between 2014 and 2019 who received SO100 or FO15 for 〉 7 days. Gas chromatography/mass spectrometry was used to measure erythrocyte fatty acids. Results The mean ± SD gestational age was 27 ± 3 and 26 ± 2 weeks for SO100 ( n  = 43) and FO15 ( n  = 43), respectively ( P  = 0.2). DHA (−0.3 ± 0.10% per week, P  = 0.026, for FO15 vs −0.2 ± 0.05% per week, P   〈  0.001, for SO100) and ARA (−0.8 ± 0.21% per week for FO15 vs −0.9 ± 0.17% per week for SO100; P   〈  0.001 for both) declined in both groups with no difference between groups ( P interaction 〉 0.7 for both). After controlling for days to reach full feeds, the mean difference in weight z score trajectories was similar (Est = −0.08; 95% CI, −0.82 to 0.04; P  = 0.2), and SO100 was associated with a nonsignificant increased odds for cholestasis (odds ratio, 3.1; 95% CI, 0.96–10.2; P  = 0.059). There was no difference in other clinical comorbidities. Conclusions In comparison with ELBW infants who received SO100, infants who received FO15 still demonstrated a decline in DHA and ARA. Growth and other clinical outcomes were unchanged.
    Type of Medium: Online Resource
    ISSN: 0148-6071 , 1941-2444
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2170060-6
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 6_suppl ( 2022-02-20), p. 277-277
    Abstract: 277 Background: The prognostic importance of local failure (LF) after definitive radiotherapy (RT) in patients with NCCN intermediate- (IRPCa) and high-risk prostate cancer (HRPCa) remains unclear, particularly given the likelihood that occult distant metastases (DMs) at presentation may be the true driver of natural history. Here, we leverage individual patient data (IPD) from 18 randomized control trials (RCTs) to evaluate the prognostic impact of LF and the kinetics of DM after RT. Methods: IPD for 18 RCTs were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) Consortium, comprising a total of 12533 patients (6288 HRPCa & 6245 IRPCa). Multivariable Cox proportional hazards (PH) models were developed to evaluate the relationship between overall survival (OS), PCa-specific survival (PCSS), DM-free survival (DMFS) & LF as a time-dependent covariate, adjusted for clinicodemographic parameters. Markov PH models, defined via transitions between 4 states, were developed to evaluate the aforementioned relationship. Proportional hazards assumption was imposed and examined for both models. Time is from randomization. Results: Median follow-up was 9.1 years. There were 795 (13%) LF & 1288 (21%) DM events for patients with HRPCa; these numbers were 449 (7%) & 451 (7%) for IRPCa. For HRPCa & IRPCa, 81% and 81% of DMs developed from a clinically relapse-free state (cRFS), with a median time of 46 and 60 months, respectively (p 〈 0.0001). 39% & 13% of DM events occurred within 2 years after RT for HRPCa & IRPCa, respectively. At later time points, DM events were more likely to emerge after an LF event for both HRPCa (9% vs. 34% between 0-2 vs. 8-10 years post-RT, p = 0.001) and IRPCa (10% vs. 34% between 0-2 vs. 8-10 years post-RT, p = 0.008). LF was significantly associated with OS (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.06–1.30), PCSS (HR 2.02, 95% CI 1.75-2.33) & DMFS (HR 1.94, 95% CI 1.75–2.15) (p 〈 0.01 for all) in patients with HRPCa. LF was also significantly associated with DMFS (HR 1.57, 95% CI 1.36–1.81) but not OS in patients with IRPCa. Patients who had not transitioned to the LF state had a significantly lower HR of transitioning to a PCa-specific death state than those who transitioned to the LF state (HR 0.32, 95% CI 0.21–0.50, p 〈 0.001). Conclusions: LF is an independent prognosticator of OS, PCSS & DMFS in HRPCa and of DMFS in IRPCa. The predominant mode of DM development is from the cRFS state, underscoring the importance of accurate upfront staging & systemic therapy. However, particularly at late time points, an increasing proportion of DM events originated after diagnosis of a LF, constituting a “second wave” of DM events. This suggests that optimizing local control is also important, though the majority of DM events appear prior to a clinically-detected LF.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 8
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 4, No. Supplement_1 ( 2020-05-08)
    Abstract: Objectives: Estrogen receptors (ER-alpha, ER-beta) and aromatase (key enzyme for estrogen synthesis) are expressed in most human non-small cell lung cancers (NSCLCs). High intratumoral estrogens and elevated aromatase in NSCLC are reported to predict poor clinical outcome. In vitro, estrogen stimulates NSCLC gene expression and, tumor progression and diminishes tumor cell apoptosis. Furthermore, preclinical NSCLC models demonstrate that aromatase inhibitors (AIs) prevent these processes, and that cisplatin with AIs elicits dramatic growth inhibition. Additionally, depletion of autocrine/paracrine estrogen production hypersensitizes cells to DNA-damaging effects of platinum therapy, providing a rationale for this trial. This open-label, phase 1b, single-center study evaluated safety and tolerability of AI exemestane combined with carboplatin and pemetrexed in postmenopausal women with stage IV non-squamous, NSCLC. Materials/Methods: Exclusion criteria included untreated CNS metastasis, major surgery in prior 4-weeks to therapy, prior/concurrent investigational or standard therapy (except TKI and/or immunotherapy in prior 4-weeks). Trial patients received escalating doses of exemestane (starting 1-week before chemotherapy) at 25 mg PO daily (Cohort 1) or 50 mg PO daily (Cohort 2) with carboplatin (AUC 6 mg x min/mL) and pemetrexed (500 mg/m2) IV q3 weeks for 4 cycles. Thereafter, patients could continue therapy with exemestane and/or pemetrexed. Result: Ten patients consented for study and 2 patients screen-failed. Three patients completed therapy in Cohort 1, and five patients were treated in Cohort 2. The median number of cycles was 15 (range 1-54). The MTD was exemestane 50 mg PO daily with combination chemotherapy. Intention to treat analysis showed an overall response rate (ORR) of 62.5% [5 of 8 patients with partial remission (PR)] and clinical benefit rate was 87.5% (7 of 8 patients with stable disease or PR). ORR was significantly associated with tumor aromatase expression (p=0.02). There was no correlation between ORR and ER-alpha or progesterone receptor by IHC. Circulating estrogen levels decreased with exemestane, and quality of life measures did not significantly change. No patients left the study for adverse events. Conclusion: CCombination chemotherapy with exemestane in postmenopausal women with Stage IV non-squamous, NSCLC is safe and well-tolerated. Biomarker studies show that ORR correlates significantly with tumor aromatase expression. These findings support future clinical trials to confirm antitumor efficacy with this combination therapy.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2020
    detail.hit.zdb_id: 2881023-5
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  • 9
    Online Resource
    Online Resource
    Wiley ; 2021
    In:  Journal of the American Geriatrics Society Vol. 69, No. 2 ( 2021-02), p. 512-516
    In: Journal of the American Geriatrics Society, Wiley, Vol. 69, No. 2 ( 2021-02), p. 512-516
    Abstract: Briefer measures of symptoms and functional limitations may reduce assessment burden and facilitate monitoring populations of persons with dementia (PWD). DESIGN Prospective follow‐up study. SETTING University‐based dementia care management program. PARTICIPANTS 1,091 PWD. MEASUREMENTS We assessed cognition (Mini Mental State Examination (MMSE)—11 tasks), neuropsychiatric symptom severity (Neuropsychiatric Inventory Questionnaire Severity Scale (NPIQ‐S)—12 items), and functional ability (Activities of Daily Living (ADL)—6 items; Functional Activities Questionnaire (FAQ)—10 items). Item response theory was used to select subsets of items by identifying low item discrimination ( 〈 1.50), poor item fit ( χ 2 ), local dependence (LD), and with difficulty similar to other items. We estimated correlations between original and shorter scales and compared their associations with mortality. We added two symptoms (trouble swallowing, coughing when eating) reflecting late‐stage dementia complications, created a multi‐dimensional dementia assessment composite, and examined its association with mortality. RESULTS Five MMSE tasks were eliminated: two with low discrimination, two with difficulty similar to other items, and one with poor fit. The remaining tasks were correlated with the full MMSE at r = 0.82. We retained three ADLs that were correlated with the total ADL set at r = 0.95 and kept five FAQ items that were not LD (correlation with full FAQ, r = 0.97). Associations with mortality were similar between the longer and shorter scales. A higher score on the composite (range 0–100) indicates worse dementia impact and was associated with mortality (hazard ratio (HR) per scale point: 1.03 (1.02–1.04)). CONCLUSION These brief assessments and dementia composite may reduce administration time while preserving validity.
    Type of Medium: Online Resource
    ISSN: 0002-8614 , 1532-5415
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2040494-3
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  • 10
    In: JAMA Ophthalmology, American Medical Association (AMA), Vol. 140, No. 5 ( 2022-05-01), p. 496-
    Type of Medium: Online Resource
    ISSN: 2168-6165
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
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