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Neoadjuvant chemotherapy is the cornerstone treatment for locally advanced breast cancer. Balancing toxicity and efficacy are a common concern of patients treated with chemotherapy.The objective of this study was to determine the impact of dose intensity on pathologic complete response (pCR) at the time of surgery in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer.A retrospective, single-center review was conducted on patients with HER2+ breast cancer who received neoadjuvant docetaxel, carboplatin, trastuzumab and pertuzumab (TCHP) followed by definitive surgery.A total of 159 patients were included in the analysis; pCR was obtained in 66 patients (42%). There was no statistically significant difference between the mean dose intensity of each of the individual agents in TCHP and pCR rates. The mean overall dose intensity of docetaxel, carboplatin, trastuzumab and pertuzumab was 90.5%, 90.9%, 97.5%, and 93.9%, respectively. Although higher chemotherapy dose intensity ( 85%) was associated with higher pCR rates, no statistically significant difference was found compared with chemotherapy dose intensity 85%. The TCHP regimen was difficult to tolerate; 104 patients (65%) required a dose reduction or dose delay during treatment due to toxicity.The TCHP regimen, which combines chemotherapy and HER2-directed therapy is effective at obtaining pCR in patients with locally advanced HER2+ breast cancer. These results suggest that the dose intensity of the individual agents did not have a significant impact on pCR rates. Given these findings, providers may be more comfortable allowing dose reductions for greater patient tolerability without sacrificing efficacy.

Objective The primary objective of this study was to delineate differences in management, overall and distant disease-free survival in males diagnosed with breast cancer and treated at The Ohio State University Comprehensive Cancer Center as compared to comprehensively matched female subjects. Secondary objectives included assessment of clinical and histopathologic features and recurrence score, as measured by Oncotype DX and the modified Magee equation #2. Materials and methods This single institution retrospective study compared male and comprehensively matched female patients (1:2) with stage I-III breast cancer between 1994 and 2014. Recurrence risk was estimated using a modified Magee equation. Overall survival and distant disease-free survival were estimated and compared using Kaplan-Meier and Log-rank methods. Results Forty-five male breast cancer patients were included (stage I: 26.7%; stage II: 53.3%; stage III: 20.0%; hormone receptor positive: 97.8%; human epidermal growth factor receptor 2 negative: 84.4%) with a median age of 63.8 (43.0-79.4) years at diagnosis. Intermediate and low recurrence scores were most common in male and female patients respectively; mean score was similar between groups (20.3 vs. 19.8). The proportion of male breast cancer patients treated with adjuvant chemotherapy and post-mastectomy radiation was lower compared to female patients (42.2% vs. 65.3%, p=0.013; 22.7% vs. 44.4%, p=0.030, respectively). Overall survival and distant disease-free survival between male and female patients were similar. Conclusion Male breast cancer patient outcomes were similar compared to well-matched female patients suggesting that breast cancer specific factors are more prognostic than gender.

The goal of chemotherapy for metastatic breast cancer (MBC) is palliation of symptoms while minimizing treatment-related toxicities. It remains unclear whether use of granulocyte colony-stimulating factor (G-CSF) to maintain relative dose intensity of chemotherapy for MBC is associated with improved clinical outcomes. The medical records of MBC patients treated with chemotherapy in 1st–3rd-line settings between May 2010 and April 2014 were reviewed. Time to progression (TTP), progression-free survival (PFS), and overall survival (OS) were compared between patients who received G-CSF and those who did not. Antibiotic use, total clinic visits, and pre- and post-treatment Eastern Cooperative Oncology Group (ECOG) performance status were also compared between the groups. Of the 169 patients included, 55 (32.5%) received > 1 G-CSF dose and 114 (67.5%) did not receive any G-CSF. The median TTP was similar between the two groups (5.0 months (95% CI 3.4–7.1) vs. 5.2 months (95% CI 4.8–6.2) respectively; p = 0.998). The median PFS (p = 0.955; 5.0 months (95% CI 3.4–5.9) vs. 5.2 months (95% CI 4.7–6.0), respectively) and OS (14.6 (95% CI 9.0–26.6) vs. 18.5 months (95% CI 15.2–22.0) in G-CSF and non-G-CSF groups, respectively; p = 0.628) were also similar between groups. No significant between-group differences were noted in rate of decline in ECOG performance status, antibiotic use, and number of clinic visits and hospitalizations. This retrospective analysis did not find any evidence that the use of G-CSF to maintain chemotherapy dose intensity for the treatment of MBC improves TTP, PFS, and OS or results in improved ECOG performance status compared with lack of G-CSF use in patients with MBC treated in 1st to 3rd-line settings.

Mucopolysaccharidoses (MPSs) are a group of rare lysosomal storage diseases with multisystem manifestations, including carpal tunnel syndrome (CTS). This study comprised a systematic review of literature and hospital guidelines addressing the method and frequency of screening for carpal tunnel syndrome in mucopolysaccharidosis patients and a review of carpal tunnel syndrome in patients seen in the multidisciplinary mucopolysaccharidosis clinic of a pediatric hospital, in order to develop screening recommendations. The literature reported the importance of routine carpal tunnel syndrome screening from early childhood in patients with mucopolysaccharidosis I, II, IV, and VI. Screening methods included physical examination, nerve conduction studies, electromyography, and ultrasonography. Ten of 20 mucopolysaccharidosis patients in our series underwent carpal tunnel syndrome surgery. Given the high incidence of carpal tunnel syndrome at a young age in mucopolysaccharidosis, the authors recommend performing physical examination and obtaining patient and caregiver history for carpal tunnel syndrome every 6 months from the time of mucopolysaccharidosis diagnosis, supplemented by annual nerve conduction studies in cases with poor history or equivocal examination.

Background: Little is known regarding the effect of somatic tumor genomic testing on patient perceptions and psychological well-being. We previously demonstrated that patient perceptions of care can be negatively affected if their next cancer treatment is not supported by the genomic test. To further understand this, we investigated psychological effects of genomic testing, as well as sociodemographic and genomic comprehension factors that may attenuate these effects. Methods: In a prospective, single institution, single-arm trial, patients with metastatic breast cancer underwent next-generation sequencing (NGS) using Foundation Medicine at study entry, with sequencing results released to providers at time of next disease progression. We evaluated patient survey data before and after NGS, including questions about psychosocial characteristics, genetic comprehension, and perceived risks and expectations of the genomic testing. We evaluated psychosocial characteristics using 4 validated psychology measures: the Center for Epidemiologic Studies Depression Scale (CES-D), the Beck Anxiety Inventory (BAI), the Trust in Physician Scale (TPS), and the Communication and Attitudinal Self-Efficacy scale for Cancer (CASE-cancer). CASE-cancer measures self-efficacy, how confident patients are in their ability to navigate their cancer care. Genetic comprehension was assessed with a 7-question objective measure and a 6-question subjective measure. No formal genetic education was provided, but the informed consent process included an introduction to NGS. We included exploratory questions on perceived risks and expectations of NGS. Results: Among the 58 patients who completed the pre-NGS survey, we found high rates of depression (38%) and anxiety (47%) using validated metrics. Depression and anxiety were positively correlated (Pearson’s r=0.61; p Citation Format: Elizabeth J Adams, Sarah Asad, Mahmoud Abdel-Rasoul, Raquel E Reinbolt, Robert Wesolowski, Kaitlyn Tolliver, Susan Gillespie, Katherine A Collier, Anne Noonan, Sargar Sardesai, Jeffrey VanDeusen, Nicole Williams, Charles L Shapiro, Erin R Macre, Bhuvaneswari Ramaswamy, Clara N Lee, Maryam B Lustberg, Daniel G Stover. Perceptions of somatic genomic testing in patients with metastatic breast cancer: Psychosocial factors, emotional well-being, and genetic comprehension [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-10-03.

Background Leptomeningeal carcinomatosis (LMC) is a complication of advanced malignancies wherein metastatic disease invades the meninges of the central nervous system via contiguous spread from bone or brain metastases or hematogenous spread from systemic disease. Breast cancer is the most common solid tumor etiology of LMC. Approximately 5% of patients (pts) with breast cancer develop LMC. LMC has a median survival of 4 weeks when untreated and 8-16 weeks with treatment. The diagnosis of LMC remains challenging with only 60% of pts having cerebrospinal fluid (CSF) positive for malignant cells. There is no generally accepted standard of care for treatment of LMC but it may involve intrathecal or systemic chemotherapy, whole brain or spinal radiotherapy, or a combination of modalities. We aimed to assess detection and treatment strategies of LMC in pts with breast cancer treated at the Ohio State University Comprehensive Cancer Center-James (OSUCCC-James) to better characterize the disease and guide clinical care. Methods An IRB-approved single-institution retrospective protocol was developed. Medical records of 469 pts who had undergone a procedure related to LMC diagnosis or treatment were identified and reviewed to determine study eligibility. Comprehensive data was obtained through information warehouse and chart review was performed for the eligible 69 pts with breast cancer diagnosed with LMC and treated at the OSUCCC-James between January 1, 2005 and December 31, 2015. Descriptive statistics were used to summarize demographic and clinical characteristics. Overall survival (OS) was defined as time from LMC diagnosis to death or last known follow-up, and was generated using Kaplan Meier methods. Comparisons in OS between groups were analyzed using Log-rank tests. Results Sixty-nine female pts were included in the analysis with the following characteristics: median age 55.7 years (range: 48-60.6 years), Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (86%; N=59), and Caucasian (78%; N=54). They had the following subtypes hormone receptor positive (HR +), and human epidermal growth factor receptor (HER2) negative (61%, N=42), triple negative (25%, N=17) and HER2 positive (10%, N=7). The most common sites of metastases included bone (42%), brain (28%), and lung (12%). The median time between the diagnosis of first metastasis and LMC was 0.9 years (range: 0-3.2 years). Of the 40 (58%) pts who underwent lumbar puncture, 21 (52%) pts had positive CSF cytology. Sixty-eight pts (99%) had MRI findings suggestive of LMC. The most common treatment modalities were systemic chemotherapy (N=14, 41%), radiotherapy (N=12, 35%), and intrathecal chemotherapy (N=14, 35%). Fifty-six pts (81%) had a change in systemic chemotherapy agent after diagnosis. The median OS of all pts was 2.4 months (95% confidence interval: 1.2-4.4). Pts with ER+/PR+/HER2- had a better OS (4.4 months, 95%CI 1.5, 6.1)) compared to those with HER2+ (1.3 months, 95%CI 0.2, 1.9) or ER-/PR-/HER2- (0.6 months, 95%CI 0.0, 15.8) subtypes (p-value=0.004). Pts with negative CSF cytology had a greater OS compared to those with positive CSF cytology (9.8 vs. 0.7 months, p=0.026) and pts who had a change in systemic treatment had a greater OS compared with patients who had no new treatment (2.5 months vs. 1.2 months, p =0.039). No significant difference was seen in OS between ECOG performance status groups. Conclusions LMC is a relatively rare yet devastating complication of breast cancer. Based on our institutional experience, LMC remains a clinical challenge and is associated with poor OS. Pts with triple negative and HER2 positive disease and those with high disease burden fare worse. Pts who had change in systemic therapy fare better. Dedicated clinical trials are urgently needed to improve outcomes. Citation Format: Hannah Rinehardt, Nicole Williams, Evan Morgan, Mahmooud Kassem, Marilly Palettas, Abdul Miah, Iyad Alnahhas, Pilar Guillermo Prieto Eibl, Anupama Suresh, Vinay Puduvalli, Pierre Giglio, Maryam Lustberg, Robert Wesolowski, Sagar Sardesai, Daniel Stover, Jeffrey VanDeusen, Jose Bazan, Bhuvaneswari Ramswamy, Anne Noonan. Assessment of leptomeningeal carcinomatosis management and outcomes in patients with advanced breast cancer from 2005 to 2015: A single institution experience [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-20-07.

Introduction: Adults age ≥65y constitute the majority of patients (pts) diagnosed with cancer. There is a gap in knowledge about the safest and most effect cancer treatments for older pts. At The Ohio State University, we have a longitudinal multidisciplinary geriatric clinic for adults ≥ 65 years of age diagnosed with breast cancer (BC). The clinic team consists of a physician, nurse practitioner, dietician, physical therapist, social worker nurse, and pharmacist. We evaluate the unique needs of older pts with breast cancer by completing a comprehensive geriatric assessment (CGA). Eligible patients are enrolled into OSU-16153 which is a is prospective cohort study of pts ≥65y with new diagnosis of BC to better understand complex health issues of this population, and to collect data to support future studies. Methods: Forty eight pts have completed the baseline questionnaires including demographics, lifestyle and health history and CGA. Summary statistics were used to describe the baseline characteristics. Results: The median age of patients enrolled in the study was 77 years (range 67-94), the mean BMI was 28, 50% (24/48) were Caucasian and 6% (3/48) were African American. Mobility was assessed mobility with the time get up and go (TGUG), mean 9.8 (SD=6.2) and grip strength, mean of 31. Cognitive limitations were screened with the blessed orientation memory concentration test, mean 3.9 (SD=5.0) and mini-cog, mean 3.6 (SD=1), malnutrition, mean 12.3 (SD=12.2) and depression, mean 1.6 (SD=2.4). Functional limitations were measured with Katz, mean 5.9 (SD=0.2), and Lawson, mean 7.8 (SD=0.8). Disease characteristics included 18% (9/48) Tis, 54% (26/48) T1, 21% (10/48) T2, 2%(1/48) T3, and 4% (2/48) T4 tumors, 65% (31/48) lymph node negative and 81% (39/48) estrogen positive (ER+),17% (8/48) ER negative and 4% (2/48) HER2 positive. Oncotype score was 25 in 4% (2/48). Twelve percent (6/48) received adjuvant chemotherapy for triple negative or ER+ breast cancer with high oncotype with docetaxel/cytoxan and 4% received trastuzumab based therapy and they were able to complete all planned cycles. Two pts received chemotherapy based on results of CGA. Forty-two pts were eligible to receive endocrine therapy (ET); 3 pts with ductal carcinoma in-situ (DCIS) and 2 pts with invasive BC declined, 1 did not follow up after her initial visit. Five pts switched ET due to side effects. The 7 patients with invasive BC who declined or switched ET due to side effects all had an abnormal TGUG, 43% (3/7) had an impaired min-cog and 57% (4/7) had impaired hand grip. Conclusions: The majority of older adults have no functional deficits in ADL/IADL, have adequate mobility and grip strength and did not screen positive for cognitive limitations, depression or, malnutrition. Our data shows that the mobility and cognitive assessment of a CGA may serve as a predictor of toxicity from ET therapy and identify patients who are at risk for side effects and who may benefit from additional interventions. The majority of pts who received adjuvant chemotherapy and ET tolerated well. Our pilot data shows a CGA is feasible and that a CGA helped direct appropriate therapy. Citation Format: Nicole Williams, Julie Stephens, Elizabeth Kress, Erin Frey, Susan Fugett, Paige Erdeljac, Stephanie Yager, Erin Holley, Cari Utendorf, Nikki Ford, Caitln Ubbing, Jeanie Overcash, Bhuvaneswari Ramaswamy, Anne Noonan. Feasibility of comprehensive geriatric assessment in an academic breast oncology clinic [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-16-01.

Background: Many individuals diagnosed with MBC and their loved ones struggle to find tailored disease specific resources and support (Mayer 2010). Due to a variety of constraints, oncologists are often challenged to adequately address MBC patients’ needs and concerns within the space of a standard medical visit. Managing expectations and emotions, as well as providing education on the complexities of the MBC journey, is daunting. Moreover, survivorship care to date has not addressed the unique needs of the rapidly growing population of individuals living with MBC. The Living Well with Advanced Breast Cancer Clinic (LWABC) was created to address these gaps in care and to offer comprehensive and personalized consultations for MBC patients. Methods: MBC-specific support services are provided in one multidisciplinary setting, providing a comprehensive experience that incorporates expert medical oncology and symptom education, integrative medicine, palliative medicine, dietetics, and a personalized check out experience with LWABC nurses. MBC patients are referred by their primary medical oncologists for a one-time visit to this clinic. Second opinions are not provided in LWABC; the visit is strictly focused on education for the patient and their caregivers. Each patient receives multidisciplinary one-on-one education from a medical oncologist using audio-visual aides, mind-body interaction by an integrative medicine physician, personalized dietary recommendations by an experienced dietician, and an introduction to the role of palliative care in improving quality of life while living with cancer. Services also include personalized care planning for supportive care, future trials, and referrals for other resources during their 2.5 hour visit. Results: Between October 2017-February 2019, 73 patients were scheduled twice a month in the half day LWABC clinic; 44 completed consultations. All patients had MBC with all subtypes represented: ER+PR+HER2- (28, 38%), HER2+ (6, 8%) and ER-PR-HER2- (6, 8%). Median age was 60 years (range 36-75). Median time from time of MBC diagnosis to clinic visit was 2 years (range 1-7 years). Referrals placed at the completion of the visit included: social work (5, 11%), psychosocial oncology (9, 20%), physical therapy (12, 27%), occupational therapy (4, 9%), and palliative medicine (3, 6%). Of the 28 patients (63%) who completed satisfaction surveys regarding their experience at the LWABC, 14 (63%) reported a 5/5 experience in every section reviewed. On average, overall experience was evaluated as a 4.82/5 [SD 0.42]. Comments from participants included: “I feel less fearful and more empowered. Knowledge is power. I am now armed with accurate and useful information and am less uncertain”; “I appreciated the relaxed setting that encouraged conversation. I may have received brochures in the past regarding different options but this setting changes how receptive I am to different treatments.” Many patients reported wanting additional follow up visits in the future. Barriers included provider availability, financial reimbursement, and time for patient travel/additional medical appointments. Conclusion: The LWABC consultative model is an innovative adjunct to the traditional medical oncology visit and provides critically needed education and exposure of MBC patients to supportive care services within a relaxed and intimate setting while screening for unmet needs. Feasibility and satisfaction with this model of care was high; patients felt empowered by the knowledge delivered during the sessions. Additional expansion opportunities, including an introduction to physical therapy and psychosocial oncology, are planned. To our knowledge, this is a unique and first-of a kind resource offered to patients with MBC. Citation Format: Bhuvaneswari Ramaswamy, Raquel R Reinbolt, Heidi Basinger, Lindsey Radcliff, Brittany Unthank, Kathy Hauck, Kelly Hoffman, Neil A. Borja, Sandra Pedraza, Erin E. Holley, Lanny O. Ntukidem, Mathew Cherian, Anne Noonan, Sagar Sardesai, Daniel G Stover, Jeffrey VanDeusen, Nicole Williams, Robert Wesolowski, Maryam B. Lustberg. Living well with advanced breast cancer: A unique multidisciplinary clinic designed to empower and educate patients with metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-13-06.

Purpose: TomoBreast compared normofractionated conventional radiotherapy (CR) with hypofractionated tomotherapy (TT), on the hypothesis that normal-tissue sparing by tomotherapy should reduce lung-heart toxicity. Quality of life (QOL) outcomes at 8-12 years are presented herein. Materials-Methods: The trial enrolled 123 women in 2007-2011, 64 were randomized to CR, 59 to TT. CR delivered 50 Gy in 25 fractions/5 weeks to the breast/chest wall and regional nodes if node-positive, 16 Gy/8 fractions/1.6 weeks sequential-boost in patients who underwent lumpectomy. TT delivered 42 Gy/15 fractions/3 weeks to the breast/chest wall and regional nodes if node-positive, concurrently with chemotherapy by institution's practice, 51 Gy simultaneous-integrated-boost in patients with lumpectomy. QOL assessments used the EORTC questionnaires QLQ-C30 and QLQ-BR23. Intent-to-treat analyses used the linear mixed-effect model (LMM), and survival analysis applied to time to >10% deterioration (TTD) in QOL-measures. A cardiorespiratory composite TTD event was defined as deterioration in any of the dyspnea, fatigue, physical functioning, or pain measures. Results: On survival and tumor control, there were no differences in overall and disease-free survival. On QOL analysis by LMM, TT in late >2 years period was associated with poorer nausea-scores (modeled deterioration 21.2%, P Linear mixed model by Time and Tomotherapy. Coef: %change from baselineEarly (≤2 years) assessmentLate (>2 years) assessmentTime Early effect coef/yearP- Tomotherapy Early effectP- Time Late effect coef/yearP- Tomotherapy Late effectP- Global health status11.3*-7.4*-0.6-4.7C30 summary5.8**-1.2-0.62.2Physical functioning5.30.3-0.5-1.0Role functioning25.0***-4.5-1.32.1Emotional functioning2.20.7-0.75.2Cognitive functioning3.63.1-1.5*15.7***Social functioning13.4**-2.1-1.0-8.4Fatigue free13.7**-1.6-0.62.3Appetence12.2**-0.70.52.1Nausea vomiting free9.3-12.1*-0.6-21.2***Constipation free-0.50.5-1.07.3Diarhea free3.1-3.3-0.7-3.6Pain free10.8-4.7-0.1-2.3Dyspnea free4.90.8-0.89.4*Sleep loss free3.2-2.80.3-1.4Financial stress free1.03.1-0.213.3***Good body image24.3**1.7-0.99.5Sexual functioning13.10.5-3.3-3.3Sexual enjoyment-1.6-4.31.8-2.1Future worry-free18.0**-5.6-1.0-13.3Systemic symptom free3.30.30.14.3Breast symptom free12.1**-0.50.65.2Arm symptom free-0.80.2-0.53.8Hair loss free23.40.5-0.3-20.6 Citation Format: Hilde Van Parijs, Vincent Vinh-Hung, Christel Fontaine, Guy A Storme, Nele Adriaenssens, Shane Hanon, Marian Vanhoeij, Maryam B Lustberg, Nicole Williams, Dung M Nguyen, Nam P Nguyen, Claire Verschraegen, Mark De Ridder. Quality of life in survivors of stage I-II breast cancer, 10 years outcome of a randomized clinical trial comparing post-operative hypofractionation with Tomotherapy versus conventional radiation treatment (TomoBreast) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-13-01.

Kingella kingae, a pathogen often responsible for musculoskeletal infections in children is the most common cause of septic arthritis and osteomyelitis in children 6 to 36 months of age. The aim of this study was to perform a systematic review of previous studies to determine the proportion of K. kingae in bacteriologically proven musculoskeletal infections among the pediatric population. A secondary objective was to describe the diagnostic strategies and outcome of patients with musculoskeletal infections caused by K. kingae. A systematic review was conducted to identify publications that report on musculoskeletal infections caused by K. kingae in the pediatric population (patients 0 to

Background Relative to other metastatic breast cancer subtypes, metastatic triple-negative breast cancer (mTNBC) has a shorter duration of response to therapy and worse overall survival. Among patients with mTNBC, it is hypothesized that inflammatory breast cancer (IBC) and young women have particularly aggressive phenotypes. We investigated clinical and cell-free DNA (cfDNA) characteristics of inflammatory-mTNBC and young-mTNBC. Patients and Methods We evaluated 158 patients with mTNBC who were stratified into 3 groups: (1) IBC; (2) patients aged 45 years or younger at primary diagnosis without IBC (non-IBC young); and (3) patients over age 45 at diagnosis without IBC. We evaluated clinicopathologic characteristics, sites of metastasis, survival outcomes, and the fraction of DNA in circulation derived from tumor (TFx). Results Analysis of metastatic sites revealed that young patients without IBC had the most frequent lung metastases (P = .002). cfDNA analyses of first sample showed that TFx was highest in the non-IBC young group but not elevated in the IBC group (analysis of variance P = .056 for first TFx). Individually, median overall survival from metastatic diagnosis for the IBC group was 15.2 months; for the non-IBC young group, 21.2 months, and for the non-IBC over 45 group, 31.2 months. Patients with IBC and young patients without IBC had worse prognosis relative to patients over 45 without IBC (log-rank P = .023). Conclusions Among patients with mTNBC in this single-institution cohort, patients with IBC and young patients without IBC had significantly worse overall survival compared with patients over 45 without IBC. Young patients without IBC had significantly higher cfDNA TFx, whereas patients with IBC did not have elevated TFx despite a poor prognosis. These findings demonstrate that further analyses of mTNBC subsets are warranted.

Background Additional use of cyclin-dependent kinase 4/6 inhibitors with endocrine therapy improves progression-free survival (PFS) in advanced hormone receptor (HR)-positive HER2-negative breast cancer. However, neutropenia is a common reason for dose reductions, leading to concerns about palbociclib efficacy at lower doses. A safety analysis confirmed no PFS differences between palbociclib doses in the second-line setting, but to our knowledge, this has not been evaluated for first-line treatment. Patients and Methods In this retrospective, single-center cohort study we evaluated real-world use of first-line palbociclib with aromatase inhibitor (AI) treatment in HR-positive, HER2-negative metastatic breast cancer patients who received treatment between February 2015 and July 2017. The primary objective was to determine PFS of treatment with palbociclib and an AI in a real-world first-line setting. Secondary objectives included determining the PFS for patients treated with palbociclib on the basis of final doses, time to first dose reduction, time to treatment failure (TTF), and safety. Results Seventy patients were included in the final analysis. Median PFS was 26.4 months. No significant differences in PFS were observed on the basis of final doses of palbociclib (P = .77). Time to first dose reduction was 2.3 months. Median TTF was 26.1 months. Dose delays, reductions, and Grade 3/4 neutropenia were common (63%, n = 44; 57%, n = 40; and 62%, n = 43, respectively). Conclusion Real-world first-line palbociclib treatment produced outcomes similar to those in PALOMA-2 (Palbociclib and Letrozole in Advanced Breast Cancer) (median PFS 26.4 months vs. 24.8 months) despite more dose reductions (57%, n = 40 vs. 36%, n = 160) and shorter time to first dose reduction (2.3 vs. 3.0 months). No significant differences in PFS were observed for the varying palbociclib doses. Palbociclib dose reductions might not significantly affect PFS in the first-line setting.

Purpose Capecitabine is widely used as a single agent on a 21-day cycle in the management of metastatic breast cancer (MBC). Our primary objective was to compare the standard dosing of capecitabine (Arm A: days 1–14 on 21-day cycle) to biweekly dosing (Arm B: days 1–7 and 15–21 on 28-day cycle) using retrospective data analysis. Methods 166 patients with MBC treated with single agent capecitabine at The Ohio State University from 2002 to 2014 were considered eligible. Median time to treatment failure (TTF) and overall survival (OS) were estimated using Kaplan-Meier (KM) methods. KM curves were compared using log-rank tests with Holm’s correction for multiplicity. Results Patients were grouped by dose schedule into one of three arms: Arm A (21-day cycle; capecitabine given at 1000 mg/m2 orally, twice daily on days 1–14 of 21-day cycle); Arm B (28-day cycle; capecitabine given at 1000 mg/m2 orally, twice daily on days 1–7 and 15–21 of 28-day cycle); and Arm C (changeover regimen where patients started on the 21-day cycle, but changed to a 28-day cycle for tolerability). No difference was found in TTF or OS for patients with MBC between those who received capecitabine on either standard dosing (Arm A) and those on a biweekly cycle (Arm B or C). Overall, 41% of patients required dose reduction. Conclusions Our single institution experience showed that alternate dosing of capecitabine (biweekly, 28-day cycle) may be a reasonable alternative to standard 21-day cycle with similar efficacy and fewer dose reductions.

PURPOSE: Proton pump inhibitors (PPIs) are used in cancer patients to manage treatment-related gastrointestinal symptoms and to prevent damage to the gastric mucosal lining during treatment. However, PPI use may contribute to cognitive problems. To compare PPI-users and non-users, breast cancer survivors reported cognitive problems in three studies. METHODS: In Study 1, breast cancer survivors (N=209; n=173 non-users, n=36 PPI-users; stages 0-IIIC) rated their cognitive function on the Kohli scale prior to cancer treatment, as well as one and two years later. In Study 2, women (N=200; n=169 non-users, n=31 PPI-users, stages 0-IIIa, M=11 months post-treatment) rated their cognitive function on the Kohli scale and BCPT checklist at three visits over a six-month period. In Study 3, participants (N=142; n=121 non-users, n=21 PPI-users; stages I-IIIa, M=4 years post-treatment) rated their cognitive function on the Kohli scale, BCPT checklist, and Functional Assessment of Cancer Therapy cognitive scale (FACT-cog). RESULTS: In Study 1, PPI-users reported more severe concentration problems (p=0.039) but not memory problems (p=0.17) than non-users. In Study 2, PPI-users reported more severe concentration problems (p=0.022) than non-users, but not memory problems or symptoms on the BCPT (ps=0.11). Study 3’s PPI-users reported more severe memory problems (p=0.002), poorer overall cognitive function (p=0.006), lower quality of life related to cognitive problems (p=0.005), greater perceived cognitive impairment (p=0.013), and poorer cognitive abilities (p=0.046), but not more severe concentration problems (p=0.16), compared to non-users. CONCLUSIONS/IMPLICATIONS: PPI use may impair breast cancer survivors’ memory, concentration, and quality of life.

Older age is associated with poorer outcomes of SARS-CoV-2 infection, although the heterogeneity of ageing results in some older adults being at greater risk than others. The objective of this study was to quantify the association of a novel geriatric risk index, comprising age, modified Charlson comorbidity index, and Eastern Cooperative Oncology Group performance status, with COVID-19 severity and 30-day mortality among older adults with cancer.In this cohort study, we enrolled patients aged 60 years and older with a current or previous cancer diagnosis (excluding those with non-invasive cancers and premalignant or non-malignant conditions) and a current or previous laboratory-confirmed COVID-19 diagnosis who reported to the COVID-19 and Cancer Consortium (CCC19) multinational, multicentre, registry between March 17, 2020, and June 6, 2021. Patients were also excluded for unknown age, missing data resulting in unknown geriatric risk measure, inadequate data quality, or incomplete follow-up resulting in unknown COVID-19 severity. The exposure of interest was the CCC19 geriatric risk index. The primary outcome was COVID-19 severity and the secondary outcome was 30-day all-cause mortality; both were assessed in the full dataset. Adjusted odds ratios (ORs) and 95% CIs were estimated from ordinal and binary logistic regression models.5671 patients with cancer and COVID-19 were included in the analysis. Median follow-up time was 56 days (IQR 22-120), and median age was 72 years (IQR 66-79). The CCC19 geriatric risk index identified 2365 (41·7%) patients as standard risk, 2217 (39·1%) patients as intermediate risk, and 1089 (19·2%) as high risk. 36 (0·6%) patients were excluded due to non-calculable geriatric risk index. Compared with standard-risk patients, high-risk patients had significantly higher COVID-19 severity (adjusted OR 7·24; 95% CI 6·20-8·45). 920 (16·2%) of 5671 patients died within 30 days of a COVID-19 diagnosis, including 161 (6·8%) of 2365 standard-risk patients, 409 (18·5%) of 2217 intermediate-risk patients, and 350 (32·1%) of 1089 high-risk patients. High-risk patients had higher adjusted odds of 30-day mortality (adjusted OR 10·7; 95% CI 8·54-13·5) than standard-risk patients.The CCC19 geriatric risk index was strongly associated with COVID-19 severity and 30-day mortality. Our CCC19 geriatric risk index, based on readily available clinical factors, might provide clinicians with an easy-to-use risk stratification method to identify older adults most at risk for severe COVID-19 as well as mortality.US National Institutes of Health National Cancer Institute Cancer Center.

Background There is increasing interest in better understanding the biology and clinical presentation of invasive lobular cancer (ILC), which is the most common special histological subtype of breast cancer. Limited large contemporary data sets are available allowing comparison of clinicopathologic features between ILC and invasive ductal cancer (IDC). Methods The Great Lakes Breast Cancer Consortium was formed to compare clinical behavior of ILC (n = 3617) and IDC (n = 30 045) from 33 662 patients treated between 1990 and 2017 at 3 large clinical centers. We used Kaplan-Meier analysis, Cox proportional hazards modeling, and propensity score matching to evaluate treatment differences and outcomes. All statistical testing used 2-sided P values. Results Compared with IDC, patients with ILC were more frequently diagnosed at later stages and with more lymph node involvement (corrected P Conclusions This large, retrospective, collaborative analysis with 3 clinical centers identified meaningful differences in clinicopathological features between ILC and IDC, providing further evidence that these are 2 different entities requiring different clinical management.

The skeletal manifestations of lysosomal storage diseases (LSDs) are largely refractory to available therapeutic modalities. Consequently, there is an increasing need to manage their spinal deformities. The aim was to perform a systematic review to answer the questions, "What are the reported indications for surgery for spinal deformity in patients with LSDs?" and "what are the published surgical management strategies?".Articles that made reference to at least one LSD, a spinal abnormality and surgical management were included. Extracted study data included: study type, sample size, methodology and year of publication. The following clinical information was collected: demographics, spinal abnormalities, and surgical indications, details and outcomes.Thirty-seven articles were included, with 23 describing surgical management of craniocervical manifestations seen in mucopolysaccharidosis. Radiological evidence of myelopathy at the craniocervical junction and/or progressive clinical neurological compromise were accepted as surgical indications. Prophylactic surgery was proposed by some authors. The recommended surgical technique and whether to stabilise and/or decompress varied between articles and LSD types. Twenty-one articles discussed thoracolumbar pathology, including thoracolumbar kyphosis and scoliosis. Radiological severity, progression of deformity, and presence of neurological deterioration were discussed as surgical indications. Most papers recommended circumferential arthrodesis via combined anterior and posterior approaches.The surgical management of spinal disorders in LSDs remains controversial. Centres managing these patients should be encouraged to have a standardised system of reporting outcomes, to facilitate recommendations for management of the spinal manifestations.

Objectives To evaluate self-reported and performance-based functional status (FS) in older women with breast cancer according to stage and time of visit during treatment. Sample & setting 72 women with breast cancer aged 78 years or older and receiving any type of treatment at a midwestern outpatient clinic. Methods & variables FS was evaluated using grip strength, the Index of Activities of Daily Living (ADLs), the instrumental ADLs (IADLs) scale, and the Timed Up and Go Test (TUGT). Mixed models were fit for grip strength and the TUGT, and generalized estimating equations were used to fit binary logistic regressions for the Index of ADLs and the IADLs scale. Continuous FS outcomes were evaluated using means and standard deviations. Results Cancer stage and time of visit did not affect self-reported or performance-based FS scores. Most participants were considered independent on the Index of ADLs, the IADLs scale, and the TUGT, which did not change significantly between visits. Self-reported measures revealed less impairment. Implications for nursing Monitoring FS using self-reported and performance-based measures can ensure that older patients receive timely support.

Introduction Individuals with alopecia areata (AA) may experience significant impacts on their health-related quality of life. The novel Alopecia Areata Patient Priority Outcomes (AAPPO) questionnaire has been developed to assess hair loss signs, emotional symptoms, and activity limitations associated with AA. The objective of this study was to evaluate psychometric properties and establish scoring of the AAPPO in adults and adolescents with AA. Methods Scoring and measurement properties of the AAPPO were examined using baseline and 2-week follow-up data from a prospective, noninterventional, web-based study of 121 patients with AA (85 adults aged ≥ 18 years, 36 adolescents aged 12–17 years) with Severity of Alopecia Tool (SALT) ≥ 25% scalp hair loss. Results Exploratory and confirmatory factor analysis supported four single Hair Loss (HL) items, an Emotional Symptoms domain (ES; 4 items), and an Activity Limitations domain (AL; 3 items). Among all patients, the multi-item ES and AL domains had strong internal consistency (α ≥ 0.87); all HL items and domain scores had strong test-retest reliability (weighted kappa or intraclass correlation coefficients ≥ 0.78). All HL item scores demonstrated strong construct validity (r ≥ 0.52) compared with the patient-reported Alopecia Areata Symptom and Impact Scale (AASIS) hair loss subscale score; ES and AL domain scores exhibited strong construct validity (r ≥ 0.66) compared with the SF-36 Mental Component Summary (MCS) score. Using SALT scores, HL mean item scores were better (lower) in the 25–49% SALT subgroup versus those with highest SALT scores (76–100%); however, ES mean domain scores were better in the SALT 76–100% subgroup in the same comparison (p

PURPOSE: Adjuvant ovarian function suppression (OFS) in premenopausal hormone receptor (HR) positive breast cancer (BC) improves survival. Adherence to adjuvant gonadotropin-releasing hormone analogs (GnRHa) remains a challenge and is associated with toxicities and inconvenient parenteral administration. The goal of this study was to describe real-world adherence patterns and patient preferences surrounding adjuvant GnRHa. METHODS: We analyzed the medical records of premenopausal women with non-metastatic HR positive BC from January 2000 to December 2017; participants received adjuvant monthly goserelin or leuprolide at The Ohio State University. Data collected included demographics, clinicopathologic characteristics, and OFS adherence/side effects. We defined non-adherence as discontinuation of GnRHa within 3 years for a reason other than switching to an alternate OFS, delay > 7 days from a dose, or a missed dose. Chi-square tests assessed associations between clinical characteristics and outcomes. RESULTS: A total of 325 patients met eligibility. Of these, 119 (37%) patients were non-adherent to GnRHa; 137 (42%) underwent elective bilateral salpingo-oophorectomy after initial GnRHa. Those opting for surgery reported significantly more hot flashes (74% vs 48%, p < 0.001), arthralgias (46% vs 30%, p = 0.003), and vaginal dryness (37% vs 21%, p = 0.001) compared with patients remaining on GnRHa. CONCLUSION: Non-adherence to adjuvant GnRHa occurred in over a third of patients and almost half the patients initiating GnRHa underwent subsequent surgical ablation. These high frequencies highlight real-world patterns of OFS. Additionally, treatment toxicities may impact personal preference of OFS modality. Personalized practices to target predictors of adjuvant GnRHa non-adherence are critical to optimize symptoms, adherence, and survivorship.

IntroductionProximal humerus fractures (PHFs) comprise Methods and analysisWe will conduct a retrospective cohort study to evaluate the outcomes of patients who were diagnosed with a paediatric PHF at the Women’s and Children’s Hospital (WCH) in South Australia. The primary outcome will be each participant’s pain and quality-of-life outcome, determined by use of the Quick Disabilities of the Arm, Shoulder and Hand, Shoulder Pain and Disability Index and Paediatric Outcomes Data Collection Instrument. Secondary outcomes will include rates of non-union, persistent deformity and complications. The information for these variables will be acquired during a brief clinic appointment, and from the medical records and WCH radiology database. Multivariable logistic regression will be performed to determine the clinical variables associated with a worse clinical outcome.Ethics and disseminationThe study has been approved by the Women’s and Children’s Health Network Human Research Ethics Committee (protocol number: 2021/HRE00250). The study findings will be submitted to peer-reviewed scientific journals for publication and disseminated at conference presentations.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN12622000176763).

OBJECTIVE The objective of this review was to synthesize the best available evidence for the diagnostic test accuracy serum procalcitonin compared with serum C-reactive protein for suspected osteomyelitis and septic arthritis in hospitalized children and adolescents. INTRODUCTION Measurement of serum C-reactive protein remains a routine investigation for the diagnosis of osteoarticular infection in children and adolescents. Measurement of serum procalcitonin has been shown to outperform C-reactive protein in adults with osteomyelitis and septic arthritis. Before procalcitonin can be considered as a potential replacement or add-on test in children and adolescents, a systematic review and meta-analysis targeting this population should be conducted. INCLUSION CRITERIA Original studies reporting the diagnostic accuracy of procalcitonin and/or C-reactive protein in children and adolescents between one month and 18 years of age admitted to hospital with suspected osteoarticular infection were included. Studies must have compared the index test to at least one reference test. Reference test was defined as positive culture or polymerase chain reaction confirmation of a pathogen from blood, bone biopsy, or joint fluid aspirate in combination with at least two of the following: i) purulent material from sterile site, ii) positive radiological findings consistent with osteoarticular infection, and ii) symptoms and signs consistent with osteomyelitis and/or septic arthritis. METHODS The JBI methodology for systematic reviews of diagnostic test accuracy was followed. Information was sourced from four databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science) and four gray literature sources (MedNar, OpenGrey, Google Scholar, and ProQuest Dissertations and Theses). Only studies published in English were considered. The methodological quality of selected studies was formally evaluated, sensitivity and specificity data were extracted, and 95% confidence intervals determined. Meta-analysis was performed to estimate summary points using a bivariate model and to generate a hierarchical summary receiver operating characteristic (HSROC) curve with global measures of test accuracy performance, such as likelihood ratio and diagnostic odds ratio. A narrative was provided where meta-analysis was not appropriate. RESULTS Eight studies were included in the final analysis. Four of these studies used a common C-reactive protein test threshold of 20 mg/L. At this threshold, the estimated pooled sensitivity of C-reactive protein was 0.86 (0.68-0.96) and the pooled specificity was 0.9 (0.83-0.94). Using a hierarchical summary receiver operating characteristic model from six studies, the diagnostic odds ratio for C-reactive protein was estimated to be 39.4 (14.8-104.9) with a positive likelihood ratio 5.3 (2.3-11.9) and a negative likelihood ratio 0.1 (0.07-0.2). There were insufficient studies from this review to statistically evaluate the diagnostic accuracy of procalcitonin. CONCLUSION Clinicians should continue to measure serum C-reactive protein as the preferred inflammatory marker in hospitalized children and adolescents with suspected osteomyelitis or septic arthritis. More evidence is needed before incorporating procalcitonin routinely into clinicians' diagnostic test strategy. Improvements with the design, quality, and reporting of procalcitonin diagnostic test assays in children and adolescents with osteoarticular infection is needed. SYSTEMATIC REVIEW REGISTRATION NUMBER PROSPERO CRD42019140276.

The Impact of Weight on Quality of Life–Lite Clinical Trials Version (IWQOL-Lite-CT) was developed to assess weight-related physical and psychosocial functioning in the context of clinical trials. Data from two pivotal trials of once-weekly subcutaneous semaglutide for the purpose of weight management (NCT03548935 and NCT03552757) were analysed to confirm the structure, reliability, validity, and responsiveness of the IWQOL-Lite-CT and evaluate the magnitude of meaningful within-patient change in patients with overweight or obesity, with and without type 2 diabetes. Factor analyses and inter-item correlations confirmed the IWQOL-Lite-CT structure and scoring algorithm. Each composite score (physical, physical function, psychosocial, and total) demonstrated excellent internal consistency (Cronbach's alphas ≥ 0.82) and test–retest reliability (intraclass correlation coefficients ≥ 0.85) in both trials. Patterns of cross-sectional and longitudinal construct validity correlations were generally consistent with hypotheses. Each of the IWQOL-Lite-CT composites was able to discriminate between known groups. Effect sizes and paired t tests comparing IWQOL-Lite-CT scores at baseline and Week 68 were statistically significant for all composites in both trials (P

La Organización Mundial de la Salud (OMS) ha señalado que, a partir de 1990, hasta aproximadamente 2015 y luego, con cifras actualizadas, hasta 2020, las muertes maternas se han reducido en un 45% a nivel mundial, aunque todavía mueren 800 mujeres cada día por causas en gran parte prevenibles, antes, durante y después de un parto. Los datos del organismo internacional también indican que un 99% de las muertes maternas prevenibles ocurren en países de bajo y mediano ingreso.

ObjectivesThe need for palliative care (PC) will continue to increase in Canada with population aging. Many older adults prefer to “age in place” and receive care in their own homes. Currently, there is a lack of standardized quality indicators (QIs) for PC delivered in the community in Canada.MethodsA one-day workshop collected expert opinions on what should be measured to capture quality PC. Three brainstorming sessions were focused on addressing the following questions: (1) what is important to measure to support quality PC, regardless of setting? (2) Of the identified measures, are any of special importance to care provided in the home? (3) What are the challenges, barriers, and opportunities for creating these measures? The National Consensus Project (NCP) for Quality Palliative Care framework was used as a guide to group together important comments into key themes.ResultsThe experts identified four themes that are important for measuring quality, regardless of care setting, including access to care in the community by a multidisciplinary team, care for the individual with PC needs, support for the informal caregiver (e.g., family, friends), and symptom management for individuals with PC needs. Two additional themes were of special importance to measuring quality PC in the home, including spiritual care for individuals with PC needs and home as the preferred place of death. The challenges, barriers, and potential opportunities to these quality issues were also discussed.Significance of resultsPC experts, through this collaborative process, made a substantial contribution to the creation of a standardized set of QIs for community-based PC. Having a standardized set of QIs will enable health care professionals and decision makers to target areas for improvement, implement interventions to improve the quality of care, and ultimately, optimize the health and well-being of individuals with a serious illness.

In the United States, 13 million people identify as sexual and gender minorities. The purposes of this article were to (a) examine the associations among sexual orientation concealment and internalized homophobia with HIV knowledge, health literacy, and transactional sex through sexual identity; and (b) assess whether gender expression moderates those relationships in sexual minority men of color. A multigroup mediation path model examined the association between sexual orientation concealment and internalized homophobia on HIV knowledge, health literacy, and transactional sex through sexual identity by gender expression. Results suggest that, among those with a masculine gender expression, as sexual concealment increased, health literacy decreased. The association between sexual orientation concealment and transactional sex varied by participant's gender expression as did the association between internalized homophobia and HIV knowledge. Multiple intersecting identities, when faced with anticipated discrimination and homophobia, can negatively affect health outcomes and increase HIV risk in sexual minority men of color.

To discover DNA ligands against a predetermined receptor protein complex, we introduce a comprehensive version of ligand-guided selection (LIGS). LIGS is, itself, a variant of systematic evolution of ligands by exponential enrichment (SELEX). Herein, we have optimized LIGS to identify higher affinity aptamers with high specificity. In addition, we demonstrate the expandability of LIGS by performing specific aptamer elution at 25°C, utilizing multiple monoclonal antibodies (mAbs) against cultured cells and primary cells obtained from human donors expressing the same receptor. Eluted LIGS libraries obtained through Illumina high-throughput (HT) DNA sequencing were analyzed by bioinformatics tools to discover five DNA aptamers with apparent affinities ranging from 3.06 ± 0.485 nM to 325 ± 62.7 nM against the target, T cell receptor-cluster of differentiation epsilon (TCR-CD3ε) expressed on human T cells. The specificity of the aptamers was validated utilizing multiple strategies, including competitive binding analysis and a double-knockout Jurkat cell line generated by CRISPR technology. The cross-competition experiments using labeled and unlabeled aptamers revealed that all five aptamers compete for the same binding site. Collectively, the data in this report introduce a modified LIGS strategy as a universal platform to identify highly specific multiple aptamers toward multi-component receptor proteins in their native state without changing the cell-surface landscape. Keywords: Aptamers, SELEX, ligands, LIGS, CD3epsilon, T cells, nucleic acids

Background: Invasive lobular carcinoma (ILC) accounts for 5%–15% of all invasive breast cancer cases. ILC has the propensity for distant late recurrence with widespread metastatic disease. To our knowledge, there is limited data on the clinical outcomes and treatment strategies of metastatic ILC. This retrospective study evaluates the overall survival (OS) and progression-free survival (PFS) in the metastatic ILC population at a single institution, focusing on first line treatment received in the metastatic setting. Methods: A retrospective chart review was performed on patients (Pts) diagnosed with metastatic ILC diagnosed at The Ohio State University Comprehensive Cancer Center between January 1, 2004 and December 31, 2014 using an IRB approved protocol. Patient demographics, clinical characteristics, and treatment modalities were summarized with descriptive statistics. OS (time from metastasis to death or last known follow-up) and PFS (time from diagnosis of metastasis to progression) were compared between types of first-line treatment: endocrine therapy (ET), chemotherapy (chemo), chemo followed by ET, ET plus CDK 4/6 inhibitor, or other treatments. OS and PFS estimates were generated using Kaplan Meier methods and compared using Log-rank tests. Results: 60 female pts were included in this study. The median age was 59 years (24–78). 45 (75%) pts were postmenopausal, 44 (73%) ER+/PR+, 14 (23%) ER+/PR-, and 2 (3%) ER-PR-, 28 (47%) with only bone metastases, 19 (32%) with visceral and bone metastases, and 13 (22%) with liver metastases. Twenty-eight (47%) pts received first line ET therapy, 12 (20%) received ET + CDK 4/6 inhibitor, 7 (12%) received chemo alone, 4 (7%) received chemo followed by ET, and 9 (15%) received other types of first line therapy. The median OS was 3.0 years, and the median PFS was 1.4 years. No difference in the Kaplan-Meier curves was found between first-line treatment groups in OS or PFS (OS: P=.247; PFS: P=.436). Discussion: ILC is a histologically distinct disease from invasive ductal cancer. It has been previously shown that invasive lobular cancer may not be as sensitive to adjuvant chemotherapy. We showed that in the metastatic setting there was no difference in PFS and OS among first line treatment groups. ET remains preferred treatment option; however, based on our data, chemotherapy can be considered in patient with metastatic ILC in the appropriate clinical context such as visceral crisis.

Supplemental Digital Content is available in the text., Background: Closed reduction (CR) is a common treatment for infantile developmental dysplasia of the hip. The purpose of this observational, prospective, multicenter study was to determine the early outcomes following CR. Methods: Prospectively collected data from an international multicenter study group was analyzed for patients treated from 2010 to 2014. Baseline demographics, clinical exam, radiographic/ultrasonographic data, and history of previous orthotic treatment were assessed. At minimum 1-year follow-up, failure was defined as an IHDI grade 3 or 4 hip and/or need for open reduction. The incidence of avascular necrosis (AVN), residual dysplasia, and need for further surgery was assessed. Results: A total of 78 patients undergoing CR for 87 hips were evaluated with a median age at initial reduction of 8 months (range, 1 to 20 mo). Of these, 8 hips (9%) were unable to be closed reduced initially. At most recent follow-up (median 22 mo; range, 12 to 36 mo), 72/79 initially successful CRs (91%) remained stable. The likelihood of failure was unaffected by initial clinical reducibility of the hip (P=0.434), age at initial CR (P=0.897), or previous treatment in brace (P=0.222). Excluding those hips that failed initial CR, 18/72 hips (25%) developed AVN, and the risk of osteonecrosis was unaffected by prereduction reducibility of the hip (P=0.586), age at CR (P=0.745), presence of an ossific nucleus (P=0.496), or previous treatment in brace (P=0.662). Mean acetabular index on most recent radiographs was 25 degrees (±6 degrees), and was also unaffected by any of the above variables. During the follow-up period, 8/72 successfully closed reduced hips (11%) underwent acetabular and/or femoral osteotomy for residual dysplasia. Conclusions: Following an initially successful CR, 9% of hips failed reduction and 25% developed radiographic AVN at early-term follow-up. History of femoral head reducibility, previous orthotic bracing, and age at CR did not correlate with success or chances of developing AVN. Further follow-up of this prospective, multicenter cohort will be necessary to establish definitive success and complication rates following CR for infantile developmental dysplasia of the hip. Level of Evidence: Level II—prospective observational cohort.

BACKGROUND: Prior to treatment, breast cancer patients are less physically fit compared to peers; during cancer treatment, their fitness typically declines. Depressive symptoms are associated with reduced activity up to 5 years post-treatment, but research has not identified mechanisms linking depression and lower activity. The current study assessed relationships among breast cancer patients’ depression and perceived exertion during exercise as well as heart rate, an objective indicator of exertion. METHODS: Participants were 106 breast cancer patients, stages I–IIIA, who completed surgery but had not started adjuvant treatment. Heart rate and self-rated exertion, measured using the Borg Scale of Perceived Exertion, were assessed every 2 min during a graded exercise test. Depression was assessed using the CES-D and a structured clinical interview. RESULTS: Compared to women below the CES-D clinical cutoff, women with significant depressive symptoms reported steeper increases in exertion during the exercise test (p = .010) but had similar heart rates (p = .224) compared to women below the cutoff. Major depression history was unrelated to perceived exertion (ps > .224) and heart rate (ps > .200) during exercise. CONCLUSIONS: Women with currently elevated depressive symptoms experienced exercise as more difficult compared to women below the CES-D cutoff, but these self-perceptions did not reflect actual heart rate differences. Depression may make exercise feel more demanding, which could ultimately decrease patients’ likelihood of engaging in regular exercise. Results support the use of depression screening tools following breast cancer surgery to identify and intervene on individuals at risk for decreased physical activity during survivorship.

Background:Invasive lobular carcinoma (ILC) accounts for up to 15% of all breast cancers and is clinically and biologically distinct from invasive ductal carcinoma (IDC). Despite that, women with early stage ILC are often treated similarly to IDC. However, several retrospective studies suggest that patients (pts) with ILC may not derive survival benefit from the addition of chemotherapy to endocrine therapy relative to pts with IDC. The purpose of our study was to compare outcomes of pts with ILC treated with chemotherapy with those who received endocrine monotherapy. Methods: A retrospective review of pts with ILC or pleomorphic lobular carcinoma treated at the Ohio State University James Cancer Center from 2004-2014 was performed. Clinico-pathologic characteristics, treatment summary and clinical outcomes were collected. Distant disease-free survival (DDFS) was defined as time from diagnosis to the first distant metastases or death and overall survival (OS) was the time from diagnosis to death or last known follow up. DDFS and OS curves were created using Kaplan-Meier methods and compared using log-rank tests. Cox proportional hazard models were used to calculate univariate and multi variable hazard ratios (HR) for OS and DDFS. Results: We identified 379 pts with early stage ILC (stage I: 43% (162/379), stage II: 34% (127/379), stage III: 22% (84/379), unknown: 1% (6/379)). The majority of pts were post-menopausal (79%), Caucasian (92%) and ER+/PR+ (87%) and HER2 negative (96%). One hundred seventy six pts (46%) received chemotherapy and 189 (50%) pts received endocrine therapy alone. Pts who received chemotherapy had stage II or III disease, positive lymph nodes and grade 2 or 3 tumors; while pts who received endocrine monotherapy had stage I disease, negative lymph nodes and grade 1 or 2 tumors. We found a 51% decrease in chemotherapy (from 63% to 31%) and an increase in endocrine monotherapy use (from 34% to 65%) between 2004-2010 and 2011-2014. One hundred thirty two pts were evaluated with Oncotype DX, of which 76% (100/132) were node negative with the majority having a low recurrence score (low: 64%; intermediate: 33%; high: 3%). The use of Oncotype DX increased from 21.1% in 2004-2010 to 47.9% in 2011-2014. We found that 112 of 149 pts with at least 5 years follow up (75.2%) successfully completed five or more years of endocrine therapy. Univariate cox models showed worse DDFS HRs for type of therapy and node status (HR: 2.36, p=0.005, HR: 4.16, p Conclusion: We found no difference in DDFS between endocrine monotherapy and chemotherapy after adjusting for age, grade, and nodal involvement in pts with early stage ILC. This supports the hypothesis that ILC may not derive a significant benefit from the addition of chemotherapy. We need more prospective clinical trials considering histology to better understand how best to treat ILC. Citation Format: Williams N, Liu J, Stephens J, Palettas M, Boutrid H, Sardesai S, Reinbolt R, Stover D, VanDeusen J, Noonan A, Wesolowski R, Lustberg M, Ramaswamy B. Outcomes in hormone receptor positive, invasive lobular cancer in the era of endocrine monotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-14-12.

The compound SOP1812, a tetra-substituted naphthalene diimide (ND) derivative has been designed as a potent compound for targeting quadruplex sequences in cancer genes. It has been previously disclosed to have single-digit nM anti-proliferative activity in a panel of human cancer cell lines (Ahmed et al., ACS Med Chem Lett, 2020, 11, 1634-1644). It also has significant anti-tumor activity in several models for pancreatic cancer. We have also previously shown that two early-generation ND derivatives are active in both androgen-positive and negative prostate cancer cell lines (Mitchell et al, Biochemistry, 2013, 32, 1429-1436) and that these compounds down-regulate the transcription of quadruplex-containing genes such as c-MYC. We now report that this compound also shows significant anti-proliferative activity in several prostate cancer cell lines, notably with a GI50 value of 3 nM in the PC3 cell line. Abiraterone has a GI50 in this line of 4820 nM. By contrast SOP1812 has a GI50 of 247 nM in the LNCaP line, which is also derived from a patient with metastatic prostate cancer but is androgen positive. The PC3 line is derived from a metastatic carcinoma following androgen suppression therapy and is thus androgen independent and is a model for castration-resistant prostate cancer when hormone therapies are no longer effective. We have evaluated the activity of SOP1812 in the PC3 xenograft model using a twice-weekly 1 mg/kg dose regimen IV administered, against a saline control and abiraterone, at a daily dose of 200 mg/kg, administered by the PO route, both over a 28-day period. No weight loss was observed in treated animals with either drug. SOP1812 produced statistically significant tumor shrinkage (P value of 0.0008) relative to the controls, with a T/C value of 33.5% on day 28. Abiraterone treatment resulted in a T/C value of 61.6%, with a P value of 0.0382. SOP1812 is bio-available at therapeutic doses and is well tolerated at these levels in this animal model. It is currently being evaluated as a candidate for clinical development by Qualigen Therapeutics Inc. Citation Format: Nicole Williams, Jenny Worthington, Stephen Neidle, Ahmed Ahmed. The potent quadruplex-binding compound SOP1812 shows potent anti-proliferative activity in a prostate cancer cell panel and anti-tumor activity in an in vivo model of metastatic prostate cancer [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 4068.

PurposeTo compare the performance of anchor-based and distribution-based methods for estimating thresholds of meaningful within-patient change of clinical outcome assessments in conditions reflecting data characteristics of small- to medium-sized clinical trials.MethodsData sets were generated from the joint distributions of the PROMIS PF 20a T-score changes and a seven-point global change anchor measure. The 108 simulation conditions (1,000 replications per condition) included combinations of three marginal distributions of T-score changes, three improvement percentages in the anchor measure, four levels of responsiveness correlations, and three sample sizes. Threshold estimation methods included mean change, median change, ROC curve, predictive modeling, half SD, and SEM. Relative bias, precision, accuracy, and measurement significance of the estimates were evaluated based on comparison with true thresholds and IRT-based individual reliable changes of PROMIS scores. Quantile regression models were applied to select and interpret effects of simulation conditions on estimation bias.ResultsWhen PROMIS T-score changes were distributed normally, the predictive modeling method performed best with 50% or more responders identified by the anchor; the mean and median methods were preferred with 30% responders. For skewed distributions, the median method and ROC method gained more advantages. Among the evaluated study conditions, the improvement percentage condition had the most obvious effects on estimation bias.ConclusionTo establish accurate and precise thresholds, clinical researchers are recommended to prioritize study designs with at least 50% anchor-defined responders and strongly responsive target endpoints with highly reliable scoring calibration and to select optimal anchor-based methods given the data characteristics.

PurposeLeptomeningeal carcinomatosis (LMC), a common complication of advanced malignancies, is associated with high morbidity and mortality, yet diagnosis and treatment decisions remain challenging. This study describes the diagnostic and treatment modalities for LMC and identifies factors associated with overall survival (OS). MethodsWe performed a single-institution retrospective study of 153 patients diagnosed with LMC treated at The Ohio State University between January 1, 2010 and December 31, 2015. ResultsMedian age at diagnosis was 55.7 years, and 61% had Eastern Cooperative Oncology Group baseline performance status ≤1. Most common primary tumors were breast (43%), lung (26%), and cutaneous melanoma (10%). At presentation, most patients were stage III-IV (71%) with higher grade tumors (grade III: 46%). Metastases to bone (36%), brain (33%), and lung (12%) were the most common sites with a median of 0.5 years (range, 0-14.9 years) between the diagnosis of first metastasis and of LMC. 153 (100%) patients had MRI evidence of LMC. Of the 67 (44%) who underwent lumbar puncture (LP), 33 (22%) had positive cerebrospinal fluid (CSF) cytology. Most patients received radiotherapy for LMC (60%) and chemotherapy (93%) for either the primary disease or LMC. 28 patients received intrathecal chemotherapy, 22 of whom had a primary diagnosis of breast cancer. 98% died with median OS of all patients was 1.9 months (95% CI: 1.3-2.5 months). ConclusionDespite improved treatments and targeted therapies, outcomes of LMC remain extremely poor. Positive CSF cytology was associated with lower OS in patients who had cytology assessed and specifically in patients with breast cancer. CSF cytology serves as an important indicator for prognosis and helps aid in developing individualized therapeutic strategies for patients with LMC.

Background Neoplasm-related pain is often suboptimally treated, contributing to avoidable suffering and increased medical resource use and costs. We hypothesized that dementia may contribute to increased resource use and costs in patients hospitalized for neoplasm-related pain in the United States. Aims To examine how persons with cancer and dementia use medical resources and expenditures in US hospitals compared to ondividuals without dementia. Design This study examined a retrospective cohort. Setting Admissions to US hospitals for neoplasm-related pain from 2012-2016 Participants/Subjects Methods Data were obtained from the 2012-2016 National Inpatient Sample (NIS). The sample included hospital admissions of individuals aged 60 or older with a primary diagnosis of neoplasm-related pain. Dementia was defined using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), and ICD-10-CM diagnosis codes. Primary outcomes were number of admissions, costs, and length of stay (LOS). Descriptive statistics and multivariable regression models were used to examine the relationships among dementia, costs, and LOS. Results Of 12,034 admissions for neoplasm-related pain, 136 (1.1%) included a diagnosis of dementia and 11,898 (98.9%) did not. Constipation was present in 13.2% and 24.5% of dementia and nondementia admissions, respectively. The median LOS was 4 days in persons with dementia and three in those without. Mean costs per admission were higher in persons without dementia ($10,736 vs. $9,022, p = .0304). In adjusted regression results, increased costs were associated with nonelective admissions and longer LOS, and decreased costs with age above the mean. In contrast, decreased LOS was associated with age above the mean and nonelective admissions. Dementia was associated with neither endpoint. Conclusion This study provides nurses and other health care professionals with data to further explore opportunities for improvement in cancer pain management in patients with and without dementia that may optimize use of medical resources.

The objective of this pilot study was to evaluate the change in sexual function following treatment with fractional CO2 laser therapy in breast cancer (BC) survivors with genitourinary syndrome of menopause (GSM).A single-arm feasibility study of BC survivors with symptoms of GSM, including dyspareunia and/or vaginal dryness, was conducted. Participants who received three treatments with fractional CO2 laser and 4-week follow-up were contacted for patient-reported outcomes and adverse events at 12 months. Sexual function was measured using the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale Revised (FSDS-R). Descriptive statistics were calculated for patient demographics and disease characteristics for the set of participants who agreed to long-term follow-up and those who were lost to follow-up. FSFI and FSDS-R scores were summarized at baseline, 4 weeks and 12 months, as well as the change from baseline, and were compared using a Wilcoxon signed rank test.A total of 67 BC survivors enrolled, 59 completed treatments and 4-week follow-up; 39 participated in the 12 month follow-up. The overall FSFI score improved from baseline to 4-week follow-up (median Δ 8.8 [Q1, Q3] (QS) (2.2, 16.7)], P 0.001). There were improvements at 4 weeks in all domains of the FSFI (P 0.001 for each) including desire (median Δ 1.2; QS [0.6, 1.8]), arousal (median Δ 1.2; QS [0.3, 2.7]), lubrication (median Δ 1.8 (0, 3.3), orgasm (median Δ 1.2; QS [0, 3.6]), satisfaction (median Δ 1.6 (0.4, 3.2)), and pain (median Δ 1.6 (0, 3.6). The FSDS-R score also improved from baseline to 4-week follow-up (median Δ -10.0; QS [-16, -5] P 0.001) indicating less sexually related distress. The scores of the FSFI and FSDS-R remained improved at 12 months and there were no serious adverse events reported.In BC survivors with GSM, the total and individual domain scores of the FSFI and the FSDS-R improved after fractional CO2 laser therapy.Video Summary:http://links.lww.com/MENO/A711.

Handedness is a significant behavioral asymmetry; however, there is debate surrounding the age at which hand preference develops, and little research has been conducted on handedness in older adults. The current study examined performance on the long pegboard, to identify similarities and differences in young children (ages 4-7 years), older children (ages 8-12 years), young adults (ages 18-25 years), and older adults (ages 70+ years). Average time per hole, number of hand switches, and errors were assessed with left- and right-hand starts. A left-right ratio was computed from the long pegboard, along with laterality quotients from the Waterloo Handedness Questionnaire (WHQ). Results revealed faster performance when participants started the task on the right side of the long pegboard with the right-hand, coupled with a later switch to the left-hand. There was a greater number of errors with left-hand starts, and an earlier switch to the right-hand. Age was a significant predictor of the average time per hole and number of errors. Long pegboard ratio and WHQ laterality quotient were only correlated for adults. Together, findings offer insight regarding age-related effects in handedness and support the long pegboard as a useful measure of handedness.

When the COVID-19 pandemic began, formal frameworks to collect data about affected patients were lacking. The COVID-19 and Cancer Consortium (CCC19) was formed to collect granular data on patients with cancer and COVID-19 at scale and as rapidly as possible. CCC19 has grown from five initial institutions to 125 institutions with >400 collaborators. More than 5,000 cases with complete baseline data have been accrued. Future directions include increased electronic health record integration for direct data ingestion, expansion to additional domestic and international sites, more intentional patient involvement, and granular analyses of still-unanswered questions related to cancer subtypes and treatments.