bluuebunny/crossref_metadata_2025 huggingface dataset:
Breast cancer, placing drug interactions in the spotlight: Is polypharmacy the cause of everything?
Authors: Domínguez-Alonso José Alberto , Conde-Estévez David , Pi-Figueras Maria , Servitja Sonia , Digón Ana , Albanell Joan , Tusquets Ignacio
Published: May 2020

e24027

Background: Breast cancer is the most prevalent and lethal cancer among women. Forty one percent of cases occur in people ≥ 65 years. Decision on cancer treatment is particularly challenging among this group of age given its comorbidities and polypharmacy (PP). The main objectives are the analysis of potential drug-drug interactions (PDDI) in elderly breast cancer patients between daily medications and oncospecific therapy and their probable associations with age, BMI, Mini Nutritional Assessment (MNA), frailty and PP and the adverse effects during oncospecific treatment. Methods: A cohort of 77 patients ≥ 70 years with breast cancer underwent a Comprehensive Geriatric Assessment (CGA) by a Geriatrist at a university hospital. Baseline characteristics of the patients, demographical data, cancer stage, and oncospecific and daily treatments, as well as the complications and derived adverse effects were retrospectively collected using electronic medical records. Moreover, frailty categorization, daily medication number, comorbidities, Lawton and Barthel Index, malnutrition, MNA, BMI were prospectively collected using CGA report. PDDI between daily and oncospecific treatments were analyzed. Results: The median age of patients was 85 years (range 72-95). The median number of daily medications at CGA was 6 drugs (range 0-22) and most of the patients had PP at CGA and during oncospecific treatment (73% and 91%, respectively). Out of 719 PDDI, 530 (74%) were moderate ( r2= 0.72) and the median number of drugs during oncospecific treatment ( r2= 0.73) was 9 (range 3-26). Overall, by using Kruskal Wallis, 59 patients (77%) had any adverse effects statistically associated with frailty categorization and MNA ( p < 0.05). Furthermore, there was a tendency with oncospecific treatment, BMI and age ( p = 0.098, 0.089 and 0.062, respectively). The distribution of major, moderate and minor as well as total PDDI was statistically associated with PP at CGA and during oncospecific treatment ( p < 0.05). Conclusions: CGA should be applied in oncology elderly patients not only to assess clinical outcomes and categorize them in each frailty group but also to analyze PDDI by using specific web databases, thereby improving PP, PDDI and economic costs.
Integrating touchscreen-based geriatric assessment and frailty screening for adults with acute myelogenous leukemia to drive personalized treatment decisions.
Authors: Wujcik Debra , Papadantonakis Nikolaos , Wall Sarah Allison , Kasner Margaret T. , JAMY OMER HASSAN , Dudley William , Ingram Stacey A. , Lawhon Valerie , Son UI , Dudley Matthew
Published: May 2020

e24030

Background: AML is a disease of older adults, with median age of 68 years at presentation. NCCN guidelines suggest comprehensive geriatric assessments (GA) be included in clinical practice to guide treatment decisions. Utility of GA in older AML patients in a real-world environment is not yet established. We tested the feasibility of using a modified GA (mGA), administered by patient self-report on a touchscreen computer, real-time use and utility by clinicians and the correlation of mGA results on treatment decision-making. Methods: Sixty-two patients were recruited from three sites to complete a tablet-based mGA screening at a treatment decision-making time point. The mGA consists of the Frailty Index (FI) that includes four domains: age, activities of daily living, instrumental ADLs, and comorbidities. Falls within the past 6 months and patient reported health interference with function are also assessed. Results are displayed for the clinician to inform the treatment discussion. Results: Participants were mean age 73 years (range 61-88), 63% male, and 90% white. Frailty Index result was 32% fit, 40% intermediate, and 28% frail. Providers were asked the fit/frailty status prior to seeing the results of the mGA. Of 53 provider responses, there was 57% (n=30) provider concordance with the mGA result; 9% (n=5) said fit when mGA said intermediate and 17% (n=9) said intermediate when mGA said frail. When asked their goals of care, nearly all (n=60, 97%) patients agreed with the statement “my cancer is curable”, yet 30% (n=19) disagreed the treatment goal was to get rid of all the cancer. Nearly half (n=30) indicated they want to make treatment decisions together with the provider rather than provider or patient making decision alone. 73% (45/62) of patients were satisfied with the ease of using the survey and took an average 16.3 minutes to complete. Patient self-reported presence/severity of eight symptoms at baseline (see Table). Conclusions: A simple electronic tool may provide valuable insight into patient understanding of disease to better tailor patient-provider discussion and treatment decision-making. Providers overestimated fitness 26% of the time. Final results will be presented to include the outcome at 3 months by Frailty Index. [Table: see text]
Perspectives on healthcare providers’ role in health promotion among cancer survivors.
Authors: Halilova Karina I. , Ivankova Nataliya V. , Rogers Laura Q. , Pisu Maria , Kevin Fontaine R. , Martin Michelle Y. , Herbey Ivan I. , Thompson Lieu , Anusiewicz Colleen V. , Pekmezi Dorothy , Oster Robert A. , Schoenberger-Godwin Yu-Mei M. , Demark-Wahnefried Wendy
Published: May 2020

e24037

Background: To further integrate health promotion into cancer survivorship care, we explored multilevel perspectives on potential roles healthcare providers could have in promoting uptake of web-based healthy lifestyle programs among cancer survivors. Methods: In developing the Aim, Plan, and Act on Lifestyles (AMPLIFY) Survivor Health diet and exercise web-based program, we conducted 10 focus groups with 57 cancer survivors and 27 individual semi-structured interviews with stakeholders representing advocacy groups (e.g., cancer survivorship support foundations; n = 8), cancer organizations (e.g., industry, health system; n = 11), and survivors’ supportive partners (n = 8). Verbatim transcripts were analyzed by multiple coders using inductive thematic analysis with NVivo 12. Results: Survivors (49% female; 40% African-American, mean age 63.7 years) and stakeholders (60% female) stated that healthcare provider and health system recommendation and support are vital for ensuring acceptance and use of web-based healthy lifestyle programs by cancer survivors. Survivors expressed that physician’s (e.g., oncologist, other physician) recommendation and support would motivate them to join and participate. Supportive partners also endorsed the importance of provider recommendations and the key role of health system support (e.g., reminders in doctor’s office, hospitals, web-based portal, and endorsement from cancer centers). Advocacy group representatives underscored the importance of data-driven support for the effects of such programs as critical for promotion. Moreover, technology supported continuous cancer care (e.g., physician communication and feedback) were seen as critical for sustained participation. Stakeholders from cancer organizations suggested survivors in need could be identified and referred during assessments in various cancer care clinics. This group also emphasized the need to integrate evidence-based healthy lifestyle recommendations into continuing medical education, medical board certifications, support and referrals into existing standard of cancer care, and to involve other key stakeholders and larger scale health systems in promotion. Conclusions: Healthcare providers and health systems have important roles in promoting and sustaining participation in web-based healthy lifestyle programs among cancer survivors. Further work developing, testing, and refining strategies to enhance their role in promoting the acceptability and uptake of healthy lifestyle programs by cancer survivors are needed.
Gender disparity on cigarette smoking among cancer survivors: Results from the National Health Interview Survey.
Authors: Jiang Changchuan , Wang Haowei , Deng Lei , Wang Qian , Han Xuesong , Shapiro Charles L.
Published: May 2020

e24040

Background: The smoking rate has been declining in the United States. Smoking cessation is a critical part of cancer survivorship care. Males have higher smoking rate than females in the general population. However, it remains unclear if cancer status modified the effect of gender on smoking rates. Methods: To evaluate the long-term pattern of smoking prevalence among female cancer survivors, we used the National Health Interview Survey 2000-2017 to estimate the age-adjusted current smoking rates among cancer survivors and participants without a history of cancer for men and women separately. Multivariable linear regression was used to estimate age-adjusted smoking rate in each group, using the US 2010 Census as the standardization population. We also used multivariable logistic regression to examine the whether cancer history modified the influence of gender on current smoking rate. All statistical analyses were performed with SAS 9.4 and accounted for NHIS survey design. Results: Of 526,547 participants, we identified 32,091 cancer survivors, including 11,642 male and 20,449 female cancer survivors. Male cancer survivors had a slightly lower smoking rates than non-cancer male participants (cancer survivors: 16.2%-29.7% vs non-cancer participants: 16.8%-24.4%; OR = 0.94, 95%CI 0.88-1.00, p = 0.05) after adjusting age and year of survey. However, female cancer survivors had a significant higher prevalence of smoking compared with non-cancer female participants (cancer survivors: 20.1-32.6% vs non-cancer participants: women: 12.8%-20.4%; OR = 1.45, 95%CI 1.38-1.52, p < 0.001) during the same period. The gaps in smoking prevalence between female cancer survivors and male cancer survivors were more significant than the gaps between male non-cancer participants and female non-cancer participants from 2000 to 2017 (p interaction < 0.001). Conclusions: Although more men smoke among people without a history of cancer, female survivors had a higher age-adjusted smoking rate than their male counterparts. Effective smoking cessation interventions need to target female survivors as well as male survivors. A gender-sensitive approach is required to address their specific needs in smoking cessation. [Table: see text]
Family building preferences among young women with invasive breast cancer.
Authors: Crown Angelena , Abdo Nadia , Noy Ariela , Chang Cassandra , Gemignani Mary , Goldfarb Shari Beth
Published: May 2020

e24057

Background: The American Society of Clinical Oncology guidelines recommend discussing the possibility of infertility in cancer patients of childbearing age being treated with gonadotoxic therapies. This prospective study examines the reproductive history and future family building preferences of young women with breast cancer. Methods: This is an Institutional Review Board approved prospective study of women < 45 years of age with non-metastatic invasive breast cancer who completed a questionnaire on reproductive history and family building preferences between April 2013 and December 2019. Questionnaires were administered at initial diagnosis and then annually. Results: Baseline questionnaires were completed by 164 women with a median age of 39 years old (range 20-45); 110 (59%) completed the 1 year follow up survey. Clinicopathologic features and treatment are shown in the table. The majority of women (n = 90, 55%) were parous and many had previous infertility (n = 60, 37%) at time of diagnosis. Most women (n = 87, 53%) wanted additional children or were unsure. Interest in embryo and/or oocyte cryopreservation was common (n = 51, 31%) as was interest in adoption (n = 52, 32%). Of the 110 women who completed the one year follow-up, 39 (35%) saw a reproductive endocrinologist, including 22 (20%) who elected embryo (n = 14) or oocyte (n = 8) cryopreservation. Overall, 88 (80%) women declined fertility preservation. The most common reasons included worrying about delay in cancer treatment (n = 10, 9%), fear of hormonal exposure (n = 7, 6%), and feeling rushed into making a decision (n = 6, 6%). Of 92 women with available data regarding satisfaction with their decision to pursue fertility preservation or not, 84% (n = 77) reported satisfaction whereas 14% (n = 15) reported mixed feelings or regret. Conclusions: Young women with breast cancer expressed a significant interest in family building options. However, pursuit of fertility preservation was uncommon despite a high rate of prior infertility in this cohort of mostly parous women. Decisional satisfaction was common. Further study of factors contributing to patient decision-making regarding fertility preservation and alternative family building options is warranted. Clinical trial information: NCT01788839 . [Table: see text]
Resilience and cognitive symptoms in cancer: An exploratory study.
Authors: Parsons Michael W. , Traeger Lara , Perez Giselle Katiria , Hirschberg April , Park Elyse R.
Published: May 2020

e24079

Background: One of the most common concerns of cancer survivors is cancer-related cognitive impairment (CRCI), which affects an individual’s ability to return to work, school, or other life activities. The etiology of CRCI is poorly understood. Numerous studies have demonstrated a relationship between emotional distress and cognitive dysfunction, though the core psychological construct underlying this relationship has been elusive. Resilience, defined as the ability to function well despite adversity, reflects individual capacity to manage stress and reduce allostatic load. We hypothesized that low resilience contributes to stress-related cognitive symptoms in cancer survivors, and that improvement in resilience through the Relaxation Response Resiliency Program (3RP), a psychotherapy group that reduces emotional distress, would reduce cognitive symptoms in cancer survivors. Methods: Consistent with prior protocols, adult cancer survivors participated in the 3RP program, a 9-week resiliency mind-body group treatment led by psychologists and/or psychiatrists. Survivors completed measures of cognitive symptoms (Patient Reported Outcome Measure Information System – Cognitive function; PROMIS-Cog) and resilience (Current Experiences Scale; CES) before and after treatment. Pearson correlations evaluated relationships between resilience and cognition. Results: 46 cancer survivors (mean age = 57, 85% female, 94% White, 4% Asian, 2% Black) completed \ CES and PROMIS-Cog at therapy intake, with 41% of subjects reporting significant cognitive impairment at baseline (defined as scores of < 1.0 SD on PROMIS-Cog). There was a significant correlation between these two scales prior to treatment (r = 0.33; p = 0.025), indicating that subjects with lower resilience reported poorer cognition. Thus far, 13 survivors have completed the 8-week therapy program, with 46% of these patients reporting significant cognitive difficulties. The post-treatment correlation between resilience and cognition was nonsignificant (r = 0.19;p = ns). Treatment effects were operationalized by change scores (follow up – baseline) for CES and PROMIS-Cog. The relationship between CES and PROMIS-Cog change scores was positive but not significant with the small sample size (r = 0.35; p = 0.028). Conclusions: This preliminary study suggests that there is a relationship between resilience and cognition in cancer survivors. Improvements in resilience through the 3RP treatment may reduce cognitive symptoms, though further work is needed to determine the significance of this effect.
With a little help from my friends: A multi-disciplinary approach to cancer survivorship.
Authors: Capozza Scott , Harrigan Maura , Brita Javin , Khairallah Angela , Sanft Tara B.
Published: May 2020

e24082

Background: Long term cancer survivorship care is an integral part of the overall arc of oncology care. There is currently no standard of care for survivorship care beyond dissemination of a Survivorship Care Plan and data evaluating current models is limited. Furthermore, the most current Commission on Cancer recommendations suggest that a multi-disciplinary approach to cancer survivorship will best address the late and long-term side effects that survivors experience1. Methods: A multi-disciplinary adult cancer survivorship clinic at Yale Cancer Center and Yale New Haven Hospital was established in October 2006. This clinic is overseen by a medical oncologist and features the medical expertise of four distinct providers: an advance practice practitioner (such as an APRN or PA), a licensed clinical social worker, an oncology board-certified registered dietitian and an oncology board-certified physical therapist. Survivors meet with each provider for 30 minutes. A follow-up visit is scheduled 2-3 months later to assess the interventions discussed at the first visit and make modifications as necessary. This comprehensive approach allows the providers to address a wide array of late and long-term side effects from cancer treatment, including fear of recurrence, cancer related fatigue and weight management. Beginning with evidence-based research in their respective fields, each provider can create an individualized plan to address these concerns. Results: The National Comprehensive Cancer Network's Distress Thermometer demonstrated an almost 75% decrease in distress in cancer survivors pre- to post initial visit (n = 1,116 patients). Additionally, cancer-related fatigue, as measured by the MD Anderson Brief Fatigue Inventory, decreased by almost 50% from first to second visit (n = 313 patients). Conclusions: This poster is the first to demonstrate the feasibility of implementing a multi-disciplinary cancer survivorship clinic to address the late and long-term side effects of cancer survivors. Further research evaluating the correlation between improved access to long term survivorship care, as well as the health care providers required to provide optimal care in this setting, is needed. 1. American College of Surgeons Comminssion on Cancer, https://www.facs.org/-/media/files/quality-programs/cancer/coc/optimal_resources_for_cancer_care_2020_standards.ashx . Accessed February 10th, 2020.
Cancer-related fatigue (CRF) in breast cancer survivors after treatment: A focus on physical condition.
Authors: Ruiz-Casado Ana , Maximiano Constanza , Mendez Miriam , Alvarez-Bustos Alejandro , De Pedro Cristina G , Mendez Marta , Romero-Elias María , Cebolla Hector , Ramos Javier , Osorio Pablo , Fiuza-Luces Carmen , Nuñez García Beatriz , Cantos Blanca
Published: May 2020

e24087

Background: Fatigue is one of the most distressing symptoms among breast cancer survivors (BCS) after finishing their treatment. Besides cancer-related factors, fatigue may be influenced by socio-demographic, physical, medical, psychological and behavioural variables. Exercise is recommended to manage CRF. Methods: PH-UEM02 and PH-UEM06 were prospective observational studies in BCS after finishing their treatments. Fatigue was evaluated through the Perform Questionnaire (12-60, being 60 no fatigue). Anthropometry, physical condition (PC) and physical activity (PA) were objectively evaluated. One-mile walk test (MWT), handgrip and sit to stand were used to assess PC. PA was measured by using accelerometers. Clinical data (treatments) were obtained from the clinical record. Socio-economic, diet (PREDIMED questionnaire) and QoL (EORTC QLQ-C30) were reported by BCS. Results: 201 BCS were recruited (age 51±9, BMI 25.9±4, median time from diagnosis 22 months). 73% had been treated with chemo, 66% anthracyclines, 20% trastuzumab, 66% radiotherapy, 81% hormone (24% aromatase inhibitors). Mean PERFORM score (45.6/60). Adherence to Mediterranean diet (9.1/14). EORTC Global score (68.9/100). No association with age, socio-economic or marital status, previous chemo, anthracyclines or radiotherapy, WPA, estimated VO2max, handgrip, sit to stand or PREDIMED score was found. Weight, trastuzumab and MWT time were positively associated with fatigue (<.05). Time from diagnosis, basal and recovery heart rate, global QOL-EORTC were negatively associated. An interesting negative association with nut intake was found (<.05). 42% had a fatigue score (< 45) associated with QOL scores under the normative values for the Spanish population. Conclusions: 1. Prevalence of significant CRF in mid-term BCS is around 40%. Weight was a positive predictor. CRF diminishes along the time and has a strong impact on QoL. 2. Regarding PC/PA, only the time spent in MWT predicted fatigue. Neither WPA, estimated VO2MAX or muscular strength were associated with fatigue. 3. Regarding previous treatments, only trastuzumab was associated with CRF. 4. Interestingly heart rate (both basal and recovery) and nut intake were strongly associated with CRF. 5. More research is warranted in heart rate variability and potential related biomarkers. [Table: see text]
Trastuzumab-induced cardiotoxicity and hypertension among racially and ethnically diverse patients with HER2-positive early-stage breast cancer.
Authors: Chen Monica F. , Manson Daniel K. , Yuan Ariel , Crew Katherine D.
Published: May 2020

e24092

Background: Trastuzumab improves breast cancer survival but is associated with an increased risk of heart failure. Identifying risk factors associated with trastuzumab induced cardiotoxicity (TIC) would allow for more targeted and intensive screening for at-risk patients. Hypertension is one of the most consistent predictors of TIC. Racial/ethnic minorities are at higher risk of cardiovascular disease but are under-represented in studies of TIC. The objective of this study was to evaluate the relationship between race/ethnicity and risk of TIC among a diverse cohort of patients with HER2-positive early-stage breast cancer. Methods: We conducted a retrospective cohort study of patients treated at Columbia University between 2007 and 2016 for stage I-III breast cancer with adjuvant or neoadjuvant trastuzumab who had at least two echocardiograms. Mild TIC was defined as a ≥10% decline in left ventricular ejection fraction (LVEF); moderate TIC ≥15% decline; severe TIC ≥20% or decline in LVEF to < 50%. Diagnosis of hypertension, average systolic and diastolic blood pressure, and number of hypertension medications was assessed 1- year pre-treatment, during treatment, and 1-year post-treatment. We generated descriptive statistics and used multivariable logistic regression to evaluate demographic and clinical factors associated with TIC. Results: Of 279 patients evaluated, 36.6% were non-Hispanic white, 18.3% non-Hispanic black, 34.8% Hispanic, and 10.4% Asian. The average baseline LVEF was 60% and did not significantly differ between racial/ethnic groups. Mild TIC developed in 33.3% of patients, moderate TIC 18.6%, severe TIC 15.8%, and 14.7% with LVEF decline to < 50%. Patients with hypertension were at increased odds of developing TIC (OR = 2.41, 95% CI = 1.15-3.93; p = 0.02). Prevalence of hypertension was 53% among non-Hispanic white women, 69% non-Hispanic black, 53% Hispanic, and 39% Asian. Incidence of TIC did not differ significantly between racial/ethnic groups. Forty percent of patients with hypertension were not on any medications before initiating trastuzumab. Conclusions: There was no difference in TIC based upon race/ethnicity despite higher rates of hypertension among racial/ethnic minorities compared to non-Hispanic whites. However, a high portion of patients with hypertension were not on any medications before treatment. Increased screening and treatment of hypertension among patients receiving HER2-positive targeted therapy for early-stage breast cancer may be warranted.
The inadequacy of cardiovascular safety reporting in breast cancer clinical trials.
Authors: Hamid Arsalan , Oshunbade Adebamike A. , Kipchumba Rodney K. , Thigpen Samuel Calvin , Hall Michael E. , Butler Javed , Ruckdeschel John C.
Published: May 2020

e24100

Background: Although some cardiovascular (CV) toxicity is detected in early phase trials of therapeutic agents, most CV toxicities are not appreciated until later phase clinical trials or general clinical practice. The high prevalence of cardiovascular disease (CVD) in the general population warrants study of how later phase oncologic pharmacotherapy clinical trials address eligibility and assess for treatment-related cardiotoxicity. We focused our study on phase 2 and 3 breast cancer trials to limit disease-specific variations. Methods: A methodical Embase search was performed for phase 2 and 3 trials administering breast cancer pharmacotherapy and including > 50 participants. Firstly, we examined CVD as an exclusion criterion. Secondly, we identified what CV safety assessments were reported such as troponin, brain natriuretic peptide (BNP), lipid profile, electrocardiogram (ECG), or CV imaging. Thirdly, we examined whether trials reported adverse CV events. Fischer’s exact test was applied to compare reporting amongst trial characteristics (trial funding source and type of agent administered), and a 2 sided p-value of < 0.05 was considered significant. Results: 50 published articles from 46 separate clinical trials were included. Patients with prevalent CVD were excluded in 67.4% of trials, the most frequently excluded CVD was heart failure/NYHA class > 1 (65.2% of trials). At least one pre or post-treatment CV safety assessment was reported in only 58.7% of trials, most commonly an ECG (52.2% of trials). BNP or troponin assessments were not reported in any trial. Adverse CV events were reported in 82.6% of trials, the most frequently reported event was hypertension (43.5% of trials). CV Safety assessments were more frequently reported in pharmaceutically funded trials compared to non-pharmaceutically funded trials (86.4 vs 10.0%, p < 0.001), and in trials administering targeted/immunotherapy agents compared to those administering only traditional chemotherapy/hormonal therapy (85.2 vs 21.1%, p < 0.001). Conclusions: Later stage breast cancer clinical trials are conducted in populations under-representative of patients with prevalent CVD, a common comorbidity. Trial funding source and type of agent administered impact whether or not CV toxicity is monitored. Despite the frequent exclusion of patients with CVD and poor safety assessment reporting, adverse CV events are frequently encountered and reported. Thus, these trials may underestimate CV toxicity risks for the greater population receiving such agents in clinical practice.
Real-world implementation of serious illness care program (SICP) in cancer care.
Authors: Karim Safiya , Lupichuk Sasha M. , Tan Amy , Sinnarajah Aynharan , Simon Jessica
Published: May 2020

e24112

Background: The Serious Illness Care Program (SICP) is a system-based intervention, including a conversation guide, which facilitates improved advance care planning (ACP) conversations between clinicians and seriously ill patients. A recent randomized control trial found the program reduced symptoms of depression and anxiety amongst oncology out-patients and improved process outcomes. We implemented the SICP in our center to determine if the effects of this program could be translated into the real world. Methods: Two outpatient oncology clinics implemented the SICP, each over a 16-week period. Patients were identified based on an answer of “no” to the question “would I be surprised if this patient died within the next year?”, or any patient with a diagnosis of metastatic pancreatic cancer, or symptom scores of > 7 on more than three categories of the patient reported outcome dashboard. Physicians were trained on how to conduct the SICP conversation. One patient per week was identified and prepared to have the SICP conversation with the goal of at least 12 conversations in each 16-week period. Rates of SICP conversation documentation on our system’s “ACP and goals of care designation (GCD) Tracking Record” and GCD orders were recorded. Patient satisfaction after each conversation and physician comfort level over time were assessed. Results: 16 patients were identified (8 patients in each 16-week period). One patient was lost to follow-up. Of the remaining 15 patients who had the SICP conversation, 14 (93%) had documentation on the Tracking Record and 8 (53%) had a GCD order. This was a major improvement over baseline rates of documentation (e.g. < 1 % Tracking Record use and 16% GCD for patients with GI cancers). 14 patients completed satisfaction surveys, of which 12 (86%) felt “completely” or “quite a bit” more heard or understood. Physician comfort level increased from 3.6 to 4.8 and from 4.8 to 5 out of 5, respectively over each 16-week period. Conclusions: SICP implementation resulted in high rates of documentation of goals and preferences. Patients felt heard and understood by their healthcare team, and comfort in these conversations improved over time for physicians. The goal number of conversations was not met, but otherwise the SICP was feasible to implement in the real world. Further study is required to identify the appropriate triggers and barriers to routine SICP conversations.
Real-world myeloid growth factor (MGF) prophylaxis patterns in patients receiving chemotherapy at intermediate-risk for febrile neutropenia (FN): A systematic review.
Authors: Wang Weijia , Li Edward C. , Campbell Kim
Published: May 2020

e24116

Background: Many patients receiving myelosuppressive chemotherapy are at an intermediate risk (10-20%) of developing FN. In this setting, clinical practice guidelines recommend an individualized approach towards MGF prophylaxis based on regimen and patient-specific FN risk factors. The purpose of this review is to summarize and describe the real-world MGF prophylaxis patterns, patient-specific risk factors, and FN outcomes in patients receiving chemotherapy at intermediate risk of FN. Methods: We searched the MEDLINE database (PubMed) for peer-reviewed published articles using the keywords “primary prophylaxis,” “febrile neutropenia,” and “intermediate risk” from 2000-2020. Articles were included if they were cohort or case control studies, and excluded if the data were derived from clinical trials. Studies from outside the United States or where the methods cannot be verified were also excluded. Results: Out of 131 studies identified, 7 met the inclusion/exclusion criteria after review. Most studies included adult cancer patients diagnosed with breast, lung or colorectal cancer receiving chemotherapy identified using public/private insurance claims or electronic medical records. In the 2000s, MGF prophylaxis rates were around 17-22% in patients receiving intermediate-risk regimens; while in 2010s, the prophylaxis rate increased to > 50%. Patient-specific FN risk factors were prevalent, but MGF primary prophylaxis rates among those receiving intermediate risk regimens were generally low (around 24-28%); approximately 25% of patients with > 1 FN risk factor received primary prophylaxis. Primary prophylaxis rates differed by tumor type; breast cancer had the highest rate (~46%), followed by non-small cell lung (~24%), and colorectal (~8%). FN incidence varied among patients with FN risk factors (~7 to 29%) across intermediate risk regimens, and the relative risk of FN (vs. those without risk factors) ranged from 1.1 to 2.2. Conclusions: Although historically low, MGF prophylaxis in patients receiving intermediate risk regimens has been increasing. Patient FN risk factors were widespread and associated with increased FN incidence. Since appropriate primary prophylaxis in patients at intermediate-risk could potentially improve population-based FN-related outcomes, future studies should focus on whether biosimilar MGFs as primary prophylaxis are cost-effective and could better optimize the care reflected in current MGF practice guidelines.
The long and winding road in drug development: Learnings from on-going development of IEPA for chemotherapy-induced myelosuppression.
Authors: Pleimes Dirk , Meyer Michael , Czajkowski Maciej
Published: May 2020

e24134

Background: An orally bioavailable small molecule IEPA (Imidazolyl Ethanamide Pentandioic Acid) is under development as treatment for chemotherapy-induced myelosuppression (CIM) since 2013. A clinical phase 2a study in epirubicin and cyclophosphamide (CP) treated breast cancer patients demonstrated efficacy of prophylactic (5d pre-CTX) IEPA (100 mg ≈ 1.7 mg/kg/d) in the first but not the second batch of the drug product. After causality due to manufacturing was systematically excluded, the R&D team reassessed the development path and reinitiated non-clinical in vivo studies for efficacy optimization investigating a) the mode of action under different challenge (chemotherapy (CTX); radiation (RX)) b) treatment starting point c) dose d) frequency and e) route of administration to improve reproducibility of efficacy. Methods: The first study assessed hematological recovery over 19 days in mice receiving CTX and treated prophylactically (5 d pre-CTX) or therapeutically (1 h pre-CTX or 24 h post-CTX) with oral IEPA (100 mg/kg, Human Equivalent Dose (HED): 8 mg/kg) either once or twice daily. The second study investigated survival (LD25/30 and 50/30) and hematology in mice exposed to RX in prophylactically (3 d pre-RX) or therapeutically (24 h post-RX) IEPA (50 mg/kg/d) once vs. twice daily, oral vs. intraperitoneal (IP). Results: In mice exposed to CTX (200 mg/kg CP), both prophylactic and therapeutic IEPA treatment accelerated recovery of neutrophils, lymphocytes, and thrombocytes. The time to recovery of white blood cells to the baseline was reduced from 16.8 days to 5.5 days after therapeutic use of IEPA. Dose, treatment start and frequency showed comparable efficacy. In mice exposed to RX (6 Gy, LD50/30), therapeutic IEPA treatment improved survival by 30% (86% IEPA vs. 56% in control). Additionally, accelerated recovery of bone marrow cellularity and reduced body weight loss was observed. Higher doses increased efficacy, while frequency and route of administration of IEPA had limited impact. Conclusions: Two in vivo studies in mice reconfirmed IEPA’s safety and efficacy against both RX-induced mortality and CTX- and RX-induced myelosuppression. While once vs. twice daily and oral vs. IP produced no or only minor improvements, higher doses and therapeutics treatment starting 24 h post-exposure demonstrated reproducible efficacy. Results indicate that increasing the dose to up to 8 mg/kg (based on HED conversion) and starting treatment 24 h post-CTX may improve efficacy in future clinical trials.
Aggregated n-of-1 randomized controlled trial of nebulized fentanyl or nebulized furosemide in palliative care patients with refractory breathlessness.
Authors: Pimsa Pongput , Kawamatawong Theerasuk , Nagviroj Kittiphon , Muntham Dittapol , Konmun Jitprapa , Kongsuphon Noppadon , Laorchan Ruamporn , Koomwong Yupawadee , Chansriwong Phichai
Published: May 2020

e24138

Background: Advance cancer patients frequently have breathlessness and worsening by refractory to conventional therapies, which need adjunctive therapy. Nebulized Fentanyl and nebulized furosemide have been identified as a novel symptoms approach. Individual patients with the same breathlessness conditions may respond differently to similar treatments, thus no standard adjunctive treatments. N-of -1 study is a within-patient randomized, double-blind, and crossover trials in 1 patient. This study aims to comparing the efficacy in relief breathlessness. Methods: N-of-1 study which enrolled patients at Ramathibodi hospital who have breathlessness with mMRC scored ≥ 3 from 1st Jan 2019 to 31st Jan 2020. Study was done as 1 cycle of 3-days of treatment that nebulized fentanyl or furosemide or sterile water (SW). Fentanyl 50 mcg or Furosemide 40 mg or SW that all diluted in SW to be in 6 ml. Jet nebulizer increased delivery of aerosol to lungs that all administered for 4 minutes. Main outcome measured breathlessness intensity Borg scale: 0-10, peripheral capillary O2 saturation, Visual cough score, satisfactions, and adverse events (AEs) that collected at baseline, 15, 30 and 60 minutes post treatment. Type of medication that patients preferred. Results: 19 patients were enrolled; 68.4% were ECOG status 4. All patient previously treated with systemic opioids with dose 29.8±20.9 mg/day. Majority were diagnosed with lung metastatic cancer. Baseline of mean Borg scale were not significant in all groups. All 3 medications significantly reduced Borg scale over time; Fentanyl -2.84 ± 0.17(95% CI -3.19 to -2.49); p = 0.0001, Furosemide -3.05±0.22 (95% CI -3.49 to -2.61); p = 0.0001, and SW -2.52±0.21 (95% CI -2.95 to -2.10); p = 0.0001. No significantly different in reduction of breathlessness, AEs and change in visual cough score in all medications. Most of AEs were mild grade. Majority of patients’ preference was furosemide (42.0%). Conclusions: Adjunctive treatment nebulizer drugs with fentanyl, furosemide and sterile water significantly improve breathlessness symptoms. No significant different in efficacy, adverse events in nebulized fentanyl, furosemide and sterile water. N-of-1 trials may provide a rational and effective method to best choose drugs for individuals with breathlessness.
Pain medication use in patients with HR+, HER2-neg advanced breast cancer treated with endocrine therapy and a CDK 4/6 inhibitor: A U.S. FDA pooled analysis.
Authors: Gao Jennifer J , King-Kallimanis Bellinda , Hodgdon Christine , Cheng Joyce , Fiero Mallorie , Bandaru Pradeep , Girvin Andrew , Osgood Christy , Ison Gwynn , Amiri-Kordestani Laleh , Pazdur Richard , Beaver Julia A.
Published: May 2020

e24145

Background: Pain medications (PMs) are commonly used to treat pain in patients (pts) with advanced/metastatic breast cancer (MBC). We examined PM usage patterns in pts receiving CDK 4/6 inhibitor (CDKI) based treatment. Methods: We pooled data from seven phase 3 randomized, controlled trials of CDKI + endocrine therapy in pts with hormone receptor positive, human epidermal growth factor receptor-2 negative MBC. PM were categorized as opioid (includes codeine-containing), NSAID, or other (i.e. bone-directed, antiepileptic, topical PMs). All analyzed pts received at least 1 dose of CDKI/placebo and had concomitant PM with a documented start date. Medications prescribed during hospitalizations were not included. We evaluated percent PM by demographic factors and pts with bone mets, and liver/lung mets. Results: 2416 pts met the inclusion criteria, of which 928 pts started a PM before the study and 1488 pts did not start PM before the study. Of the 1488 pts not on a PM before the study, 739 started a PM after study started, and 749 did not receive any PM at any time. Of the 739 pts who started a PM only after study start, overall, 59% were prescribed only an NSAID, 10% were prescribed only opioid, 17% were prescribed both an NSAID and opioid, and 14% were prescribed other PMs. The PM use by percent in demographic subgroups in the 1488 pts who took none or more PMs only after study start are presented in the table. Conclusions: To our knowledge, this is the first analysis of PM usage patterns in pts with MBC receiving CDKI or placebo with hormonal therapy on clinical trials. NSAID use was higher than opiates in all prespecified subgroups. Future analyses will examine the benefit of different classes of pain medications in treating symptoms of pain and whether there are differences between study treatment arms Percent PM Use by Class (Patients Who Took None or More PM Only After Study Start). [Table: see text]
Caregiver and patient distress in young adults with new cancer diagnoses.
Authors: Baum Laura Van Metre , Schremp Emma , Borinstein Scott C. , Friedman Debra L.
Published: May 2020

e24165

Background: A cancer diagnosis is stressful for both patients and caregivers, and there may be interdependence of mental health. Integration of caregivers into support for AYAO patients may improve outcomes. Methods: We enrolled dyads of AYAO patients (age 15-39) and their caregivers within the first month of treatment. Eligible patients were treated with curative intent or expected remission of at least 5 years. We assessed participants at baseline using validated self-reported survey methods, including the COmprehensive Score for financial Toxicity (COST), Impacts of Events Scale-Revised (IES-R), Adult Self-Report (ASR), NCCN Distress Thermometer and Problem List, and FACT-G and FACT-GP instruments. Results: We enrolled 13 dyads with patient age range 22 to 39 (median 29) years with 60% male patients and 30% male caregivers. Median scores for the NCCN Distress Thermometer were 5.0 for patients (sd 2.9) and caregivers (sd 2.4), with a score of 3 consistent with significant distress. On the Problem List, greater than half of both patients and caregivers reported “yes” to problems with “insurance/financial,” “work/school,” “treatment decisions,” “fears,” “sadness,” “worry,” and “fatigue,” and independently with “family health issues” and “work/school,” respectively. Median patient FACT-G summary score was 78, with median sub-scale scores (27.5 social, 19.5 functional, 17.5 emotional, 15.5 physical). Likewise, median caregiver FACT-GP score was 58 with sub-scale scores (20 physical, 20 functional, 15 social, 10 emotional), with higher scores indicating better quality of life. COST median scores were 12 for patients (sd 9) and caregivers (sd 7), where max score 44 indicates least financial toxicity. IES-R median patient and caregiver scores were 16 (sd 16) and 46 (sd 26), respectively, with scores >24 concerning for PTSS. In contrast, median patient and caregiver ASR depression and anxiety sub-scales were not in the range for concern. Conclusions: Diagnosis is a critical moment of distress for caregivers and patients alike. Effective interventions are needed to alleviate acute suffering and to improve short-term psychological and financial wellbeing for both caregivers and patients. Such outcomes may translate to longer-term benefit. As we continue to accrue dyads, we will follow them over 6 months to assess changes in distress pattern over time and identify the critical time periods for intervention.
An innovative, internet-based assessment of financial toxicity (FT), psychological distress, and quality of life (QOL) in ovarian cancer survivors (OCS).
Authors: Hlubocky Fay J. , Peppercorn Jeffery , Young Karen , Cord Sandra , Wroblewski Kristen , Yamada Seiko Diane , Cella David , Lee Nita Karnik , Daugherty Christopher
Published: May 2020

e24168

Background: FT is recognized as a significant predictor of stress for OCS on treatment yet little is known about its impact during long-time survivorship. Using an innovative, internet-based design, we assessed the prevalence of FT, psychological distress, and QOL among OCS. Methods: OCS members from the National Ovarian Cancer Coalition (NOCC) completed this web-based assessment using the following measures: COmprehensive Score for Financial Toxicity (COST); Hospital Anxiety/Depression Scale (HADSA/D); and the Functional Assessment of Cancer Therapy-Ovarian (FACIT-O/QOL). Clinical/socio-demographic data were collected. COST-FT severity was categorized into low FT/high FT and the correlation (r) between COST scores and self-reported QOL and distress was conducted. Results: A total of 146/300 (49% ) NOCC subjects were approached for study participation and completed the FT, distress, QOL web-based assessment. Demographics include: median age 59y (range 32-83y); 92.5% Caucasian, 64.4% married/domestic partnership; 59.6% Stage III-IV cancer-diagnosis; median disease duration 6y (range < 1-34y); 50% employed full/part-time; 54.8% college/post-graduate education; and 71.9% completed treatment. Median COST score for the total population was 27 (range: 1–44). The median score in the low FT tertile was 16 (range: 1-22), while the high FT median score was 31 (range: 23-44). High FT respondents rated their HADS-anxiety (8.3 ± 4.9 v. 6.2 ± 3.5, p = 0.002); HADS-depression (5.3 ± 4.2 v. 3.1 ± 3.0, p = 0.004); and overall FACT-O/QOL (99.8 ± 23.6 v. 118.7 ± 19.5; p = 0.001) as significantly worse compared to low FT respondents. Significant moderate correlations between COST and FACT-O/QOL (r = -0.52; p < 0.001), HADS-anxiety (r = 0.4, p < 0.001), and HADS-depression (r = 0.44, p < 0.001) were identified. Older age was associated with less FT (r = -0.30, p < 0.001). Conclusions: Innovative methods of FT evaluation, e.g. using advocacy groups (NOCC) and internet-based assessment, is feasible, and may offer new ways to follow the distress of long term survivor cohorts. Our study data reveal that FT impacts OCS QOL and distress.
Can a brief multimedia intervention facilitate breast cancer patients’ communication about sexual health? Findings from a randomized controlled trial.
Authors: Reese Jennifer B. , Beach Mary Catherine , Sorice Kristen A. , Pollard Whitney , Daly Mary Beryl , Handorf Elizabeth A. , Porter Laura S , Tulsky James A. , Lepore Stephen J
Published: May 2020

e24179

Background: Many women with breast cancer (BC) lack the confidence to discuss sexual health with their clinicians. We evaluated, in a randomized controlled trial, a brief multimedia intervention designed to facilitate BC patients’ communication about sexual health. Methods: We randomly assigned BC patients to either a multimedia sexual/menopausal health communication skills intervention [ Starting the Conversation (STC), including a video, workbook, and pamphlet with local and web-based resources] or a control [resource guide only]. About 1-2 weeks after patients received materials, we audio recorded a clinic encounter with their BC provider, and subsequently coded the dialogue for patients raising the topic of sexual health or asking > 1 sexual health question. Self-report surveys administered at baseline, post-intervention, and 2-month follow-up assessed patients’ self-efficacy for discussing sexual health with their BC providers, sexual function, anxiety and depression, and quality of life. T-tests or mixed-effects logistic regression compared study arms; analyses of communication outcomes (patient raising the topic or asking a question during clinic encounter) were clustered by providers. Results: Study participants were 144 BC outpatients (82% acceptance rate; mean age = 56; 67% white; 15% metastatic; 31% active treatment). Women in the STC arm versus the control arm were more likely to raise the topic of sexual health [OR = 2.48 (1.11, 5.55), p= .03] and more likely to ask a sexual health question [OR = 2.93 (1.04, 8.26), p= .04]. Specifically, 51% of women in the STC arm raised the topic of sexual health versus 30% in the control arm and 40% of women in the STC arm asked a sexual health question versus 19% in the control arm. At 2-month follow-up, women in the STC arm showed greater improvements in self-efficacy ( p= .03) and anxiety, t(139) = 2.0, p= .04) compared to the control arm. Conclusions: STC, a brief multimedia intervention, was effective in facilitating BC patients’ communication about sexual health during routine clinic encounters and significantly reduced patients’ anxiety, possibly due to greater patient confidence in expressing their medical needs. Future studies should use longer-term follow-up and examine how sexual health communication can translate to improved patient sexual outcomes. Clinical trial information: NCT03624972 .