Citations

Abstract Background: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype. Methods: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer–specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype. Results: There was no evidence of heterogeneous associations between risk factors and mortality by subtype (Padj > 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5–25 kg/m2 [HR (95% confidence interval (CI), 1.19 (1.06–1.34)]; current versus never smoking [1.37 (1.27–1.47)], high versus low physical activity [0.43 (0.21–0.86)], age ≥30 years versus <20 years at first pregnancy [0.79 (0.72–0.86)]; >0–<5 years versus ≥10 years since last full-term birth [1.31 (1.11–1.55)]; ever versus never use of oral contraceptives [0.91 (0.87–0.96)]; ever versus never use of menopausal hormone therapy, including current estrogen–progestin therapy [0.61 (0.54–0.69)]. Similar associations with breast cancer mortality were weaker; for example, 1.11 (1.02–1.21) for current versus never smoking. Conclusions: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype. Impact: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.

TPS264 Background: Trastuzumab (T), a monoclonal antibody (mAb) targeting HER2, is standard of care 1st-line therapy for advanced HER2+ GEJ/GC patients. M, an investigational Fc-engineered anti-HER2 mAb, targets the same HER2 epitope but with higher affinity for both 158V (high binding) and 158F (low binding) alleles of activating Fc receptor CD16A. Data suggest margetuximab coordinately enhances both innate and adaptive immunity, including antigen-specific T-cell responses to HER2. PD-1 and LAG-3 are T-cell checkpoint molecules that suppress T-cell function. Retifanlimab (also known as MGA012 or INCMGA00012) is a humanized, hinge-stabilized, IgG4 Κ anti-PD-1 mAb blocking binding of PD-L1 or PD-L2 to PD-1. Tebotelimab (also known as MGD013) is a humanized Fc-bearing bispecific tetravalent DART® protein that binds to both PD-1 and LAG-3, inhibiting their respective ligand binding. We previously reported that a CTX-free regimen of M+PD-1 blockade was well tolerated in GEJ/GC patients, and induced a 44% objective response rate (ORR) in a double-positive biomarker population. This was 2- to 3-fold greater than in historical controls with checkpoint inhibitors alone. This registration-directed trial assesses efficacy, safety, and tolerability of M+checkpoint inhibition ± CTX in metastatic/locally advanced, treatment-naïve, HER2+ GEJ/GC patients. Methods: This is a 2-cohort, adaptive open-label phase 2/3 study (NCT04082364). The first single arm, CTX-free cohort A, evaluates M+retifanlimab in HER2+ (immunohistochemistry [IHC] 3+) and PD-L1+ (excluding microsatellite instability high) patients. After 40 patients are evaluated for response/safety, additional patients will be enrolled if the threshold for continuation is met. In randomized cohort B, HER2+ (IHC 3+ or 2+/fluorescent in situ hybridization+) patients are enrolled irrespective of PD-L1 status. Part 1 of cohort B randomizes patients to 1 of 4 arms (50 patients each): control arm (T+CTX) or 1 of 3 experimental arms (M+CTX; M+CTX+retifanlimab; M+CTX+tebotelimab). CTX is investigator’s choice XELOX or mFOLFOX-6. Part 2 of cohort B consists of control (T+CTX) vs 1 experimental arm (M+CTX) + either retifanlimab or tebotelimab, depending on results from part 1; with 250 patients each. The primary efficacy endpoint for cohort A (both parts) is ORR per RECIST 1.1; for cohort B part 2 it is overall survival. Clinical trial information: NCT04082364.

Abstract Within COVID-19 there is an urgent unmet need to predict at the time of hospital admission which COVID-19 patients will recover from the disease, and how fast they recover to deliver personalized treatments and to properly allocate hospital resources so that healthcare systems do not become overwhelmed. To this end, we have combined clinically salient CT imaging data synergistically with laboratory testing data in an integrative machine learning model to predict organ-specific recovery of patients from COVID-19. We trained and validated our model in 285 patients on each separate major organ system impacted by COVID-19 including the renal, pulmonary, immune, cardiac, and hepatic systems. To greatly enhance the speed and utility of our model, we applied an artificial intelligence method to segment and classify regions on CT imaging, from which interpretable data could be directly fed into the predictive machine learning model for overall recovery. Across all organ systems we achieved validation set area under the receiver operator characteristic curve (AUC) values for organ-specific recovery ranging from 0.80 to 0.89, and significant overall recovery prediction in Kaplan-Meier analyses. This demonstrates that the synergistic use of an artificial intelligence (AI) framework applied to CT lung imaging and a machine learning model that integrates laboratory test data with imaging data can accurately predict the overall recovery of COVID-19 patients from baseline characteristics.

AbstractThere is a lack of validated tools to measure fatigue in patients with inflammatory skin, neuropsychiatric, and medical disorders. The use of nonvalidated tools may compromise the quality of data. The purpose of this meta‐review was to evaluate existing fatigue scales commonly used to assess fatigue in other inflammatory conditions and to identify if there are scales that have been validated in dermatologic conditions. The PubMed/MEDLINE and SCOPUS databases were systematically searched from inception through March 10, 2020, in accordance with the PRISMA statement. Validated tools were identified and assessed according to their main measurement properties. The literature search identified 403 references, and eight studies were eligible and assessed in this review. The unidimensional fatigue scales included were the Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT‐F), Brief Fatigue Inventory, Fatigue Severity Scale, Numerical Rating Scale – Fatigue, and Visual Analog Scale – Fatigue. The multidimensional fatigue scales found were the Checklist Individual Strength, Chalder Fatigue Scale, Multidimensional Assessment of Fatigue, Multidimensional Fatigue Inventory Scale, and Piper Fatigue Scale. To measure fatigue, a brief scale with the ability to detect change is needed as there is a growing interest in evaluating this dimension of treatment response. In addition, a good content validity is also needed. From this systematic review, none of the selected scales have had content validation, even though the FACIT was validated in patients with psoriatic arthritis. Validation studies in specific disorders are urgently warranted.

Multiple myeloma is a malignant neoplasm of plasma cells that accumulate in bone marrow, leading to bone destruction and marrow failure. This manuscript discusses the management of patients with solitary plasmacytoma, smoldering multiple myeloma, and newly diagnosed multiple myeloma.

Introduction: Pectus excavatum is a common congenital anomaly in the pediatric population. During the postoperative period, pain control is one of the top priorities. As a result, multiple techniques for pain control have been developed, including thoracic epidural analgesia, multimodal analgesia (MM), and elastomeric pain pump (EPP) placement. The purpose of this study was to evaluate the effectiveness of pain control using EPP as an adjunct to MM after the minimally invasive repair of pectus excavatum (MIRPE). Methods: We identified all pediatric patients undergoing MIRPE from June 2017 to July 2018. MM was employed in all patients; some patients additionally received subpleural EPP as adjuncts to postoperative analgesia. We reviewed pain scores, length of stay, opioid use, and complications. Results: During the study period, a total of 62 patients were included. The study cohort was divided into 15 patients undergoing MM alone versus 47 patients undergoing subpleural EPP placement plus MM (EPP + MM). Median pain scores were lower in the EPP + MM group (2.9 versus 4.2, P < .05). There was a significant reduction of total inpatient opioid use in the EPP + MM group (357.6 mg versus 466.9 mg, P = .03). There was no difference in median length of stay or complications. We found no significant difference between subpleural versus subcutaneous placement of the infusion catheters. Conclusion: The use of subpleural EPP as an adjunct to MM is an effective way to reduce pain and opioid use after MIRPE without increased risk of complications. Type of Study: Retrospective study with comparison group.

Abstract Mutations in any of the genes encoding the four subunits of succinate dehydrogenase (SDH), a mitochondrial membrane‐bound enzyme complex that is involved in both the tricarboxylic acid cycle and the electron transport chain, can lead to a variety of disorders. Recognized conditions with such mutations include Leigh syndrome and hereditary tumors such as pheochromocytoma and paraganglioma (PPGL), renal cell carcinoma, and gastrointestinal stromal tumor. Tumors appear in SDH mutation carriers with dominant inheritance due to loss of heterozygosity in susceptible cells. Here, we describe a mouse model intended to reproduce hereditary PPGL through Cre‐mediated loss of SDHC in cells that express tyrosine hydroxylase (TH), a compartment where PPGL is known to originate. We report that while there is modest expansion of TH + glomus cells in the carotid body upon SDHC loss, PPGL is not observed in such mice, even in the presence of a conditional dominant negative p53 protein and chronic hypoxia. Instead, we report an unexpected phenotype of nondiabetic obesity beginning at about 20 weeks of age. We hypothesize that this obesity is caused by TH + cell loss or altered phenotype in key compartments of the central nervous system responsible for regulating feeding behavior, coupled with metabolic changes due to loss of peripheral catecholamine production.

Purpose This clinical focus article introduces primary and secondary muscle tension dysphagia (MTDg) as a functional idiopathic dysphagia that is often encountered in the otolaryngology clinic setting. Critical aspects of clinical assessment and treatment approaches will be discussed. The presented case study will describe a multidisciplinary evaluation and efficacy of therapy. Conclusions MTDg is a diagnosis of exclusion for a functional idiopathic swallowing disorder associated with abnormal laryngeal muscle tension. Abnormal laryngeal muscle tension is often associated with disorders of laryngeal hyperresponsiveness such as muscle tension dysphonia, chronic cough, globus pharyngeus, and paradoxical vocal fold motion. MTDg patients may exhibit concurrent disorders of laryngeal hyperresponsiveness. Proper dysphagia and gastroesophageal screening are critical in diagnosis of MTDg and must not be omitted. Our studies have shown high treatment efficacy with unloading of laryngeal muscle tension with the use of voice therapy technique utilized in treatment of muscle tension dysphonia.