Citations

Abstract We used a rigorous PRoBE (prospective-specimen collection, retrospective-blinded-evaluation) study design to compare the ability of biomarkers of systemic inflammation and biomarkers of gastrointestinal (GI) tissue damage to predict response to corticosteroid treatment, the incidence of clinically severe disease, 6-month nonrelapse mortality (NRM), and overall survival in patients with acute graft-versus-host disease (GVHD). We prospectively collected serum samples of newly diagnosed GVHD patients (n = 730) from 19 centers, divided them into training (n = 352) and validation (n = 378) cohorts, and measured TNFR1, TIM3, IL6, ST2, and REG3α via enzyme-linked immunosorbent assay. Performances of the 4 strongest algorithms from the training cohort (TNFR1 + TIM3, TNFR1 + ST2, TNFR1 + REG3α, and ST2 + REG3α) were evaluated in the validation cohort. The algorithm that included only biomarkers of systemic inflammation (TNFR1 + TIM3) had a significantly smaller area under the curve (AUC; 0.57) than the AUCs of algorithms that contained ≥1 GI damage biomarker (TNFR1 + ST2, 0.70; TNFR1 + REG3α, 0.73; ST2 + REG3α, 0.79; all P < .001). All 4 algorithms were able to predict short-term outcomes such as response to systemic corticosteroids and severe GVHD, but the inclusion of a GI damage biomarker was needed to predict long-term outcomes such as 6-month NRM and survival. The algorithm that included 2 GI damage biomarkers was the most accurate of the 4 algorithms for all endpoints.

Objective Develop an online estimator that accurately predicts bronchopulmonary dysplasia (BPD) severity or death using readily-available demographic and clinical data. Design Retrospective analysis of data entered into a prospective registry. Setting Infants cared for at centres of the United States Neonatal Research Network between 2011 and 2017. Patients Infants 501–1250 g birth weight and 23 0/7–28 6/7 weeks’ gestation. Interventions None. Main outcome measures Separate multinomial regression models for postnatal days 1, 3, 7, 14 and 28 were developed to estimate the individual probabilities of death or BPD severity (no BPD, grade 1 BPD, grade 2 BPD, grade 3 BPD) defined according to the mode of respiratory support administered at 36 weeks’ postmenstrual age. Results Among 9181 included infants, birth weight was most predictive of death or BPD severity on postnatal day 1, while mode of respiratory support was the most predictive factor on days 3, 7, 14 and 28. The predictive accuracy of the models increased at each time period from postnatal day 1 (C-statistic: 0.674) to postnatal day 28 (C-statistic 0.741). We used these results to develop a web-based model that provides predicted estimates for BPD by postnatal day. Conclusion The probability of BPD or death in extremely preterm infants can be estimated with reasonable accuracy using a limited amount of readily available clinical information. This tool may aid clinical prognostication, future research, and center-specific quality improvement surrounding BPD prevention. Trial registration number NCT00063063

AbstractBackgroundReproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER)-positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear.MethodsAnalyses included up to 23 353 cases and 71 072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2–like, HER2-enriched–like, and triple-negative breast cancer) and by invasiveness. All statistical tests were 2-sided.ResultsCompared with nulliparous women, parous women had a lower risk of luminal A-like, luminal B-like, luminal B-HER2–like, and HER2-enriched–like disease. This association was apparent only after approximately 10 years since last birth and became stronger with increasing time (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.49 to 0.71; and OR = 0.36, 95% CI = 0.28 to 0.46 for multiparous women with luminal A-like tumors 20 to less than 25 years after last birth and 45 to less than 50 years after last birth, respectively). In contrast, parous women had a higher risk of triple-negative breast cancer right after their last birth (for multiparous women: OR = 3.12, 95% CI = 2.02 to 4.83) that was attenuated with time but persisted for decades (OR = 1.03, 95% CI = 0.79 to 1.34, for multiparous women 25 to less than 30 years after last birth). Older age at first birth (Pheterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) and breastfeeding (Pheterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) were associated with lower risk of triple-negative breast cancer but not with other disease subtypes. Younger age at menarche was associated with higher risk of all subtypes; older age at menopause was associated with higher risk of luminal A-like but not triple-negative breast cancer. Associations for in situ tumors were similar to luminal A-like.ConclusionsThis large and comprehensive study demonstrates a distinct reproductive risk factor profile for triple-negative breast cancer compared with other subtypes, with implications for the understanding of disease etiology and risk prediction.

The therapeutic options for patients with noninvasive or invasive breast cancer are complex and varied. These NCCN Clinical Practice Guidelines for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of ductal carcinoma in situ and the workup and locoregional management of early stage invasive breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org .

Abstract Brain metastases are a challenging manifestation of renal cell carcinoma. We have a limited understanding of brain metastasis tumor and immune biology, drivers of resistance to systemic treatment, and their overall poor prognosis. Current data support a multimodal treatment strategy with radiation treatment and/or surgery. Nonetheless, the optimal approach for the management of brain metastases from renal cell carcinoma remains unclear. To improve patient care, the authors sought to standardize practical management strategies. They performed an unstructured literature review and elaborated on the current management strategies through an international group of experts from different disciplines assembled via the network of the International Kidney Cancer Coalition. Experts from different disciplines were administered a survey to answer questions related to current challenges and unmet patient needs. On the basis of the integrated approach of literature review and survey study results, the authors built algorithms for the management of single and multiple brain metastases in patients with renal cell carcinoma. The literature review, consensus statements, and algorithms presented in this report can serve as a framework guiding treatment decisions for patients. CA Cancer J Clin. 2022;72:454‐489.

Abstract Introduction: Patients at extremes of age may be particularly vulnerable to poor physical and mental health after treatment for breast cancer; we examined factors associated with poor health in older breast cancer survivors. Methods: The Mayo Clinic Breast Disease Registry (MCBDR) is a prospective longitudinal cohort study that enrolls Mayo Clinic Rochester patients diagnosed with stage 0-4 breast cancer (BC). In 2020, we mailed a survey to 1,273 MCBDR participants aged 77+. Three PROMIS-10 items were used to assess overall health, mental health, and physical function. Self-reported comorbidities were also collected. Multivariate logistic regression analysis was used to identify significant (p<0.05) predictors of overall health, mental health, and physical function. Independent variables included demographics, clinical characteristics, and comorbidities. Results: 848/1273 MCBDR participants (67%) responded, 842 reporting their overall health. Median age at survey return was 82 years (range 77-100), and the median time since cancer diagnosis was 12 years. Excellent or very good overall health, mental health, and physical function were reported by 48%, 63.5%, and 77.1%, respectively. Older age was associated with poorer self-reported overall health, as were heart disease, diabetes, and lung disease, reported by 18%, 14%, and 7%, respectively (p<0.05 for all; see Table). Only heart disease was statistically significantly associated with poorer mental health (p=0.03). Physical function was reportedly better in survivors without a history of diabetes, stroke, or lung disease (p<0.05 for all), and in those who were closer to their cancer diagnosis (p=0.03). Tumor characteristics were not associated with overall health, mental health, or physical function. Conclusions: Comorbidities are common and impact self-reported overall health, mental health, and physical function in older breast cancer survivors. Table: Multivariate logistic regression model for overall health Overall health self-reported as excellent or very good No Yes Total p-value (N=437) (N=405) (N=842) Age at survey (years) <.001 Mean (SD) 82.8 (4.22) 81.7 (3.85) 82.3 (4.08) Median (range) 82.0 (77.0, 96.0) 81.0 (77.0, 100.0) 82.0 (77.0, 100.0) Years from cancer diagnosis to survey 0.708 Mean (SD) 12.1 (5.16) 11.8 (5.47) 11.9 (5.31) Median (range) 12.2 (3.1, 36.9) 11.5 (3.1, 36.4) 12.0 (3.1, 36.9) T stage T2 or higher, n (%) 0.276 No 357 (81.7%) 337 (83.2%) 694 (82.4%) Yes 80 (18.3%) 68 (16.8%) 148 (17.6%) N stage N1 or higher, n (%) 0.185 No 376 (86.0%) 339 (83.7%) 715 (84.9%) Yes 61 (14.0%) 66 (16.3%) 127 (15.1%) M stage M1, n (%) 0.313 No 434 (99.3%) 404 (99.8%) 838 (99.5%) Yes 3 (0.7%) 1 (0.2%) 4 (0.5%) Race, n (%) 0.460 Non-White 13 (3.0%) 8 (2.0%) 21 (2.5%) White 424 (97.0%) 397 (98.0%) 821 (97.5%) Heart disease, n (%) <.001 No 334 (76.4%) 353 (87.2%) 687 (81.6%) Yes 103 (23.6%) 52 (12.8%) 155 (18.4%) High blood pressure, n (%) 0.376 No 168 (38.4%) 188 (46.4%) 356 (42.3%) Yes 269 (61.6%) 217 (53.6%) 486 (57.7%) Stroke, n (%) 0.195 No 407 (93.1%) 392 (96.8%) 799 (94.9%) Yes 30 (6.9%) 13 (3.2%) 43 (5.1%) Diabetes, n (%) <.001 No 355 (81.2%) 370 (91.4%) 725 (86.1%) Yes 82 (18.8%) 35 (8.6%) 117 (13.9%) Lung disease, n (%) 0.023 No 394 (90.2%) 386 (95.3%) 780 (92.6%) Yes 43 (9.8%) 19 (4.7%) 62 (7.4%) Liver disease, n (%) 0.345 No 425 (97.3%) 401 (99.0%) 826 (98.1%) Yes 12 (2.7%) 4 (1.0%) 16 (1.9%) Kidney disease, n (%) 0.240 No 408 (93.4%) 392 (96.8%) 800 (95.0%) Yes 29 (6.6%) 13 (3.2%) 42 (5.0%) Citation Format: Dhauna Karam, Robert A. Vierkant, Shawna Ehlers, Rachel A. Freedman, Nicole Larson, Charles L. Loprinzi, Fergus Couch, Janet Olson, Kathryn J. Ruddy. Physical function, mental health, and overall health of older breast cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5262.