bluuebunny/crossref_metadata_2025 huggingface dataset:
A prospective cohort study of stability in preference for place of death among patients with stage IV cancer.
Authors: Koh Ling En , Malhotra Chetna , Finkelstein Eric ,   COMPASS Study Group
Published: May 2020

e24148

Background: Advanced care planning (ACP) involves discussion and documentation of patients’ care preferences including their preference for place of death. This process assumes that patients’ preference will not change over time; yet evidence for this is inconclusive. The primary aim of this study was to test whether patient preference for place of death changes over time and to identify factors associated with this change. We also assessed whether patients who do not change their preference for place of death during the study duration have greater congruence between actual and baseline preference for place of death. Methods: As part of an ongoing cohort study, we surveyed 466 advanced cancer patients every 6 months in Singapore for a period of two years. We asked patients their preference for place of death (home/ institution/ unclear). We assessed proportion of patients who changed their preference from baseline and at every time point. We ran univariable and multivariable multinomial logistic regression models to assess the association between change in preference for place of death and patient socio-demographics (gender, race, education, housing, marital status) as well as time varying variables (quality of life (Functional Assessment of Cancer Therapy- General), pain severity (Brief Pain Inventory), psychological distress (Hospital Anxiety and Depression Scale), any intervening hospitalization). We used a logistic regression model to assess if no change in preference during the study period was associated with congruence between actual and baseline preference for place of death. Results: More than a quarter of patients changed their preference for place of death every 6 months with 55% changing their preference at least once within 2 years. There was no clear trend in direction of change in preference. Patients who were psychologically distressed at the time of survey had a greater relative risk of changing their preferred place of death to home (Relative Risk Ratio (RRR) 1.81; 95% Confidence Interval (CI): 1.16-2.82) and to institution (RRR 2.00; 95% CI: 1.17-3.42) relative to no change in preference. Having no change in preference for place of death during the study period was not associated with congruence between actual and baseline preference for place of death. Conclusions: The study provides evidence of instability in advanced cancer patients’ preference for place of death. It calls into question the validity of patient preference for place of death recorded on ACP documents and suggests that we should regularly re-evaluate these documents.
The benefits of an open art studio for patients with cancer: A mixed methods study.
Authors: Brondfield Sam , Perlis Cynthia
Published: May 2020

e24152

Background: Art therapy can improve quality of life (QOL) and symptoms in patients with cancer. However, prior studies have focused on time-limited interventions. At the University of California, San Francisco, the Art for Recovery Open Art Studio (OAS) allows patients with cancer to create art and discuss experiences as a group with an art therapist (C.P.) each week. Most patients participate weekly. Our research question was: What is the value of the OAS that keeps patients coming back? Methods: In April 2019, C.P. identified all 23 patients who had attended the OAS over the past three months. We excluded one due to cognitive impairment. We designed a one-time email survey with closed- and open-ended questions. We chose a survey rather than interviews to minimize burden to patients, minimize social desirability bias, and maximize time for reflection before responding. We drew upon S.B.’s formal training in survey design and C.P.’s decades of experience with the OAS for content validity. We conducted cognitive interviews with two patients for response process validity which did not result in changes. We reported closed-ended responses using descriptive statistics. We used a paired t-test to compare, retrospectively, mean QOL before attending the OAS to mean present QOL, on a five-point scale (poor to excellent). We felt a longer QOL survey could burden symptomatic patients. S.B. and C.P. independently coded open-ended responses and aligned codes through discussion. Results: Eighteen of 22 patients (82%) responded. Mean age was 54 (range 37-76). Mean duration of attendance was four years (range 10 months to 11 years), and median frequency was three times per month. All respondents found the OAS “very helpful,” and 17 of 18 (94%) felt the friendships from the OAS were “very valuable” (top of four-point scale). Mean QOL improved from 2.7 to 4.2 (p < 0.001). Coding revealed themes of self-reflection, emotional experience, artistic engagement, togetherness, and familiar surroundings as OAS benefits. Conclusions: Our study focuses on OAS elements that keep patients with cancer coming back for years. While our results align with prior studies showing improved QOL, our study additionally reveals the multifaceted benefits of experiencing the OAS longitudinally. Study limitations include small sample size, incomplete validity evidence for the survey, and social desirability bias in survey responses. Our study supports further exploration of longitudinal OAS experiences, which may provide benefits such as friendship and community that briefer art therapy interventions may lack.
Treatment in patients with cat receiving LMWH: Learnings from predicare, a non-interventional prospective cohort study.
Authors: Scotte Florian , Laporte Silvy , Chapelle Céline , Lamblin Anne , Meyer Guy
Published: May 2020

e24154

Background: Venous thromboembolism (VTE) is a difficult to treat condition in cancer patients with a persisting risk of recurrent VTE (rVTE). We conducted a prospective multicenter observational cohort study in VTE cancer patients treated with tinzaparin for 6 months in order to validate the Ottawa score. The Ottawa score is composed of 5 items, female (+1), lung (+1), breast (-1), cancer stage I (-2) and previous VTE (+1). Methods: Adult cancer patients with recent diagnosis of documented VTE treated with tinzaparin for 6 months were included. The primary endpoint was the rVTE within the first 6 months. Other endpoints were symptomatic rVTE and major bleeding (MB). All events were adjudicated by a Central Adjudication Committee. To validate the Ottawa score, the area under the curve (AUC) and its 95% CI were calculated on receiver operating characteristic curve analysis. Results: 409 patients were included; median age: 68 years; pulmonary embolism: 60.4%; lung cancer: 31.3%; digestive cancer: 18.3%; stage IV cancers: 67.0%. According to Ottawa score, 58% were classified at high clinical probability of recurrence (score ≥ 1). Among all patients, during the 6 months treatment period, 7.3% and 3.7% had rVTE and MB, respectively. 9.1% had rVTE for patients with a score ≥ 1 compared to 5 % for other patients (score < 1). AUC of the Ottawa score was 0.60 (95% CI 0.55-0.65). Conclusions: This prospective cohort of patients with cancer receiving tinzaparin for VTE reported that the Ottawa score did not accurately predict rVTE. Clinical trial information: NCT03099031 .
The incidence, risk factors and outcomes of chemotherapy related acute kidney injury in China.
Authors: Li Lu , Nie Sheng , Ren Chen , Li Yanqin , Wu Dehua
Published: May 2020

e24161

Background: Nephrotoxicity of chemotherapeutic agents remains a significant complication limiting the efficacy of the treatment. However, comprehensive data on the epidemiology and outcomes of chemotherapy related acute kidney Injury in China is lacking. Methods: We conducted a nationwide cohort study of hospitalized patients from 25 general and children’s hospitals in China during 2013-2015. Patient-level data were obtained from the electronic hospitalization information system, prescription database and laboratory databases of all cancer patients who received chemotherapy and had at least two serum creatinine tests within any 7-day window during the hospitalization. AKI was defined and staged according to Kidney Disease Improving Global Outcomes criteria. The incidence of AKI in patients with various type of cancer and chemotherapeutic agents was examined. The outcomes of AKI, including in-hospital mortality, death after discharge, kidney recovery, and length of stay, were also assessed. Results: A total of 23,232 cancer patients, including 3,120 children ( < 18 years old), 16,310 adult (19-65 years old) and 3,802 elderly patients ( > 65 years old), were analyzed. Platinum compounds and pyrimidine analogues were the most common used chemotherapy agents for cancer patients. The overall incidence of AKI was 4.9%. Patients with urinary system malignancy (12.3%), hematological malignancy (10.2%) and nerve motor system malignancy (4.1%) have the highest incidence of HA-AKI. The top three types of chemotherapy drugs with the highest incidence of AKI were Purine analogues (30.1%), folic acid analogues (15.3%) and combinations of antineoplastic agents (14.1%). The nephrotoxicity of chemotherapy drugs was different among age groups. AKI is associated with a higher risk of in-hospital mortality and death after discharge. Conclusions: The risk of AKI in cancer patients varied in different age group, type of cancer and chemotherapeutic agents.
Health-related values of newly-diagnosed cancer patients: Qualitative analysis of oncology nurse-led discussions.
Authors: Shin Paul , Okpako Molly , Lynch Kathleen , Romano Danielle R. , Bernal Camila , Desai Anjali V. , Epstein Andrew S.
Published: May 2020

e24163

Background: A novel, patient-verified summary documenting nurse-led discussions assessing health-related values of newly-diagnosed cancer patients has been implemented in outpatient gastrointestinal (GI) oncology clinics, but the content of these discussions has not previously been analyzed. Methods: Three interdisciplinary coders met and reviewed values summaries for 40 patients. Phase One meetings consisted of identifying key domains to guide line-by-line coding with ATLAS.ti software, codebook generation, and quality assurance of codebook fidelity. Phase Two meetings consisted of independent review and code categorization, followed by three successive consensus meetings of coders to identify themes. Results: Content analysis of 40 patient values summary documents revealed 5 distinct themes: Family, friends, and faith as sources of strength; strong family ties predominate definitions of living well. Despite this, patients stated that communication with loved ones about values and goals was limited; 35% of patients had not discussed core values prior to nurse-led discussion. Patients emphasized information processing and communication preferences as important definitions of selfhood. Patients defined treatment goals as survival and maintenance or return to “normal life” for as long as possible. When asked about treatment preferences during potential future crisis, patients emphasized quality of life over survival. Conclusions: Early, nurse-led values discussions provide important and unique data that are informative and actionable by clinicians in the delivery of person-centered care. Thematic analysis reveals that while family and friends are important, patients often had not discussed core values or care preferences with them. Although patients desire to live longer, treatment preferences during crisis are also shaped by expected quality of life from interventions. Assessment and creation of patient values summaries captures nuanced data that can facilitate discussion with loved ones and play a key role in surrogate decision-making during moments of crisis. Further mixed-methods analysis of patient variables ( e.g., age, stage) modifying values and impact on patient-reported outcomes is warranted.
Effectiveness of brief-focused cognitive behavioral therapy in the reduction of cancer-related distress and emotive problems: A comparative study.
Authors: Rossi Alessandro , Marconi Maria , Mannarini Stefania , Minelli India , Bianchi Silvia , Verusio Claudio
Published: May 2020

e24169

Background: In recent years, there was an increase of cognitive-behavioral therapy (CBT) oriented brief-focused psychological intervention protocols for the reduction of cancer-related emotive difficulties that oncological patients have to face almost every day and that could have a negative impact on medical treatment (Di Matteo, Lepper & Croghan, 2006; NCCN, 2015). Thus, this study aimed to determine the effectiveness of a 10-session brief CBT (B-CBT-P) compared with a control group (CG). Methods: Participants ( n = 67; mean age = 63.11, SD = 12.1, 35 female) enrolled at the Oncology Day Hospital at the “Presidio Ospedaliero” of Saronno, ASST Valle Olona, Italy who undertook (B-CBT-P: n = 34) or non-undertook (CG: n = 33) a psychotherapy intervention – with one of two different psychologists (authors MM and MI) to avoid potential biases. Participants were tested with the Distress Thermometer and the Problem List (DT&PL) at the baseline (T1; overall McDonald’s omega = .90), at the end of the 10-sessions B-CBT-P (T2; overall McDonald’s omega = .89). Results: A multilevel-multivariate repeated measure regression analysis was performed – controlling for age, type and localization of tumor, and therapist. In line with psychotherapy protocol, results showed no statistical significant changes for ‘practical problems’ ( p = 0.0497 ns), ‘spiritual problems’ ( p = 0.321 ns), and ‘physical problems’ ( p = 0.206). Results revealed a statistical significance reduction of ‘relationships problems’ ( p = 0.015; pooled Cohen’s d = 0.341), ‘emotive problems’ ( p = 0.012; pooled Cohen’s d = 0.349), and the distress thermometer ( p = 0.008; pooled Cohen’s d = 0.373). Conclusions: Considering that emotive and relational problems, as well as distress, occurs frequently among oncological patients, this study is into an important area. Results suggest that B-CBT-P is statistically and clinically effective to improve the emotive and relational sphere of oncological patients. However, the small effect sizes found suggest that these short protocols may not be sufficient to bring important changes in the patient's life. This study opens up to the idea of improving these protocols so that the cancer patient can improve his quality of life – even with a few psychotherapy sessions.
Factors influencing patients’ decision to undergo scalp cooling in breast and gynecological cancer.
Authors: Elliott Elizabeth , Fracci Sarah , Lee Mary , Ferris Morgan , Rychlik Karen , Potkul Ronald , Lo Shelly S. , Thilges Sarah
Published: May 2020

e24175

Background: Chemotherapy-induced alopecia is a common and distressing side effect associated with the treatment of breast cancer (BC) and gynecological cancer (GC). Scalp cooling (SC) during chemotherapy decreases hair loss; why patients opt in or out of SC is unknown. A pilot study was conducted to determine reasons for opting in or out of SC. Methods: Patients at Loyola University's Cardinal Bernardin Cancer Center with BC and GC who were offered SC from 4/11/18 to 6/26/19 were asked to complete a survey ranking the importance of pre-specified factors behind their decision to (or not) pursue SC. The study was approved by the IRB. Chi-squared and Fisher’s exact tests were used on categorical variables; Wilcoxon rank sum test was used on continuous variables to determine any difference between those who opted in or out of SC. Results: 23/31 patients who were offered SC completed the survey (n = 12 [52.2%] opted to pursue SC, n = 11 [47.8%] opted out of SC). The average patient age was 51. Among patients who opted to pursue SC, maintenance of a sense of “normalcy” ranked as the most important factor behind their decision, followed by the impact of hair loss on children and family. Among the patients who opted not to pursue SC, patients ranked the cost of SC as the most important factor behind their decision. There were no statistically significant differences between patients who opted to pursue SC and those who did not in age, cancer type, relationship status, income, ethnicity, employment status away from the home, or presence of children or partners living in the home. Conclusions: Maintenance of a sense of “normalcy” and cost of treatment were the most important reasons behind patients’ decision to undergo or not undergo SC. Data from this pilot study will be used in a larger prospective study to inform how reasons for and expectations of SC impact distress and QOL.
Use of artificial intelligence for analyzing emotion vs patient global impression of change of melanoma treatments.
Authors: Su Ashley , Dupuis Léonie , Jueng Jeremy , Kunadia Anuj , Brooks Ian , Sinha Ritika , Siddiqui Fahad , Maner Brittany , Harding Tanner , Burton Vernon , Dellavalle Robert , Seyffert Jennifer , Solomon James A.
Published: May 2020

e24177

Background: The link between melanoma patients’ emotions and their impressions of treatments response are poorly understood. With the rise of social media, patients use online platforms to communicate their concerns related to melanoma treatments. In this study, we utilize real-world data collected from social media with search terms focused on treatment-specific Patients’ Global Impression of Change (PGIC) compared with their emotions. We aim to identify and focus melanoma patient perspective trends to improve patient-centered care. Methods: Social media data mining of search terms were extracted from millions of publicly available interactions on Twitter and other online platforms from May/2008 to January/2020 using Crimson Hexagon (database of real-time social media posts). Results: For chemotherapy posts, the top three emotions by volume were negative alongside negative PGIC “worse” (Worse/Sadness 700, Worse/Fear 596, Worse/Disgust 403, and “decline” (Decline/Sadness 262, Decline/Fear 186, Decline/Disgust 57). Interestingly, Sadness, Fear, and Disgust were as prevalent alongside positive PGIC “well” and “cured” (Well/Sadness 3577, Well/Fear 2545, and Well/Disgust 1770; Cured/Sadness 518, Cured/Disgust 275, and Cured/Fear 167). For Keytruda treatment posts, emotions in negative PGIC “worse” were (Worse/Fear 117, Worse/Anger 68, Worse/Sadness 6). In positive PGIC “well”, results were (Well/Fear 880, Well/Sadness 366, Well/Anger 186). Further analysis will compare these emotional sentiments with a spectrum of PGIC terms and specific types of melanoma treatments. Conclusions: To our knowledge, this is the first investigation of online patient melanoma treatments associated with PGIC terms. The findings indicate a trend of negative emotions even when patients have reported wellness or being cured by treatment. While treatments may be effective, patients are not necessarily satisfied. Correlating changes in emotions with perceived changes in disease severity can provide insight into patient perspectives, which has implications in translating clinical response and a need for continued emotional support in patients with treatment response.
Use of a patient-preferences shared-decision-making encounter tool in clinical practice for patients with non-Hodgkin’s lymphoma.
Authors: Wujcik Debra , Mehta Amitkumar N. , Corona Rachel , Cook Felice , Dudley Matthew , Dudley William
Published: May 2020

e24192

Background: Non-Hodgkin lymphoma (NHL) is the fourth leading cause of cancer in the United States with 77,240 new cases and 19,940 deaths annually. Treatment options are numerous and driven by patient’s molecular profile, risk, preferences/goals, and ability to tolerate treatment. Aligning physician-patient goals of care and integrating patient preferences into a shared-decision making (SDM) model allows patients and providers to select treatment consistent with medical science and personalized to each patient. This project evaluates feasibility of a patient preferences (PP) SDM encounter tool using technology to facilitate SDM at treatment decision (TD) for patients with NHL. Methods: To date, 45 patients with NHL at a TD making point were recruited from two sites to complete a tablet-based PPSDM encounter tool. The tool includes questions about needs, decision making preferences, values and goals of care. Results are reviewed by the provider and used to facilitate SDM in treatment selection during the clinical encounter. Patients also completed measures to assess satisfaction with the TD, patient activation, and perceived achievement of desired role in SDM at 3 weeks and 3 months post TD. Results: Participants are mean age 66 years (range 23-86), 53% male, and 98% white. 47% (n = 45) preferred that their doctor share responsibility with them when deciding which treatment was best for them. 69% said they would like to make the TD together with family and close friends and 69% agreed that their spouse was the most important person in helping make a TD. 51% said spirituality did not play a part in their TD. When asked how they liked to get medical information, 67% said they wanted all the facts, but not the prognosis. 87% said they had identified a medical surrogate to make decisions, yet 31% had an advanced directive on file. 64% agreed their cancer was curable and 84% agreed that a treatment goal was to get rid of all cancer. 73% of providers used the PPSDM results in conversation with the patient and 53% indicated their patient management changed based on the PPSDM results. There was 24% concordance between patient and provider perception of how TD were made. Conclusions: Collecting patient preferences, values, and care goals prior to the clinical visit using technology is feasible in busy clinics. Although most providers used the PPSDM results and over half changed their management plan, there was low concordance between patient and provider perceptions. Final analysis will include 3 week and 3 month measures of patient activation and satisfaction.
Depression in cancer: An evaluation of patient education resources.
Authors: Li Jim (Zhang Hao) , Wang Mingyang , Ingledew Paris-Ann
Published: May 2020

e24194

Background: In recent years, there has been increasing awareness surrounding mental health and depression among cancer patients. Concurrently, the internet has cemented its role as a mainstay source of health information for the general public. However, little is known about the quality of online resources addressing depression specifically in cancer patients. Therefore, we aim to systematically evaluate the quality of such information. Methods: The term "depression in cancer patients" was searched online using the search engine Google and the meta-search engines Dogpile and Yippy. A set of predetermined inclusion and exclusion criteria was applied to all search results, which yielded 48 websites for inclusion. An evidence-based rating tool was then used to score the websites based on the six domains of Affiliation, Accountability, Interactivity, Structure & Organization, Readability, and Content Quality. The results were analyzed using descriptive statistics. Results: Of the 48 websites evaluated, 50% were commercial. In terms of accountability measures, 63% of websites disclosed authorship, 54% cited one or more reliable sources, and 38% were updated within the last two years. Although in-site search engines and video support were found in 94% and 52% of websites respectively, the presence of other interactive features were considerably lower. The average readability was at a grade 12.3 level using the Flesch-Kincaid scale and 11.3 using the SMOG Index, both of which were significantly higher than the traditionally recommended grade-six level ( p < 0.0001 for both). The most commonly covered topics were symptoms and treatment – found on 87% and 83% of websites respectively. Prevention and prognosis were not covered by any of the websites. Content accuracy was generally high among covered topics. Conclusions: Many websites addressing depression in cancer have poor authorship disclosure, attribution, and currency. Additional interactive features should be encouraged to facilitate user-friendliness. Poor readability may pose a barrier for patient comprehension, indicating a need for health care providers to proactively guide patients to suitable resources. Despite high content accuracy in other topics, prevention and prognosis are seldom covered. Our results could help guide the development of new patient education materials and better inform health care providers about the limitations of available online resources. Future research should aim to elucidate reasons contributing to difficult readability levels and identify topics that patients need additional information in.
Gender and time estimation as novel potent indicators of emotional concerns in cancer patients.
Authors: Yanchev Asen , Ivanova Martina , Donev Ivan , Dimitrova Eleonora , Conev Nikolay Vladimirov
Published: May 2020

e24195

Background: Psychological stress is frequent after a cancer diagnosis. Thus screening is crucial for detecting it. The emotion thermometers (ETs) are validated screening tools and have five dimensions (distress, anxiety, depression, anger, and need‐for‐help). Methods: Time estimation was assessed in 374 chemonaïve patients with solid tumors by evaluating each subject’s prospective estimation of how quickly one minute passed compared to the actual time. ETs were used at the beginning of treatment to evaluate level of psychological stress of each patient. A multivariate analyses of covariance was run for the ETs as dependent variables with the addition of the following covariates: age and time estimation and gender as a fixed factor. Results: There were significant negative correlations between values of ETs and time estimation except anger. Women exhibited significantly faster time estimation than men. Using Pillai’s Trace, we found that there was a significant effect of gender and fast time estimation on reported values of ETs (V = 0.06, F (5,366) = 4.96, p < .001; V = 0.05, F (5,366) = 3.84, p = .002, respectively). The covariate, time estimation, was significantly related to reported values of all ETs. There was also a significant effect of relationship on the gender and reported values of all ETs, except for depression and need-for-help after controlling for the effect of age and time estimation. Planned contrasts revealed that female are significantly more distressed, anxious and less angry when compared to males. Conclusions: Gender and time estimation are novel potent indicators of emotional concerns in cancer patients prior to starting chemotherapy.
The DISCO app: A pilot test of an electronic patient intervention to reduce the financial burden of cancer through improved cost communication.
Authors: Hamel Lauren M. , Dougherty David W. , Hastert Theresa A. , Seymour Erlene Kuizon , Kim Seongho , Assad Hadeel , Phalore Jasminder , Eggly Susan
Published: May 2020

e24197

Background: Financial toxicity, the burden of treatment cost, affects 30-50% of people with cancer in the United States. Although experts recommend patients and oncologists discuss treatment cost to identify patients who need assistance, cost discussions occur in fewer than half of cancer treatment discussions. We pilot-tested the feasibility and efficacy of the Discussions of Cost (DISCO) App, a patient communication intervention designed to improve cost discussions and other financial toxicity-related outcomes during and following oncology treatment consultations. The DISCO App provides an individualized list of cost-related questions patients can ask their oncologist, specific to a patient’s economic situation. Methods: While waiting to see their oncologist, newly diagnosed patients with breast or lung cancer (n=32) used the DISCO App on an iPad. Clinic visits were videorecorded and patients completed pre- and post-intervention measures of self-efficacy for managing treatment costs, self-efficacy for interacting with oncologists, cost-related distress, and perceptions of the DISCO App. A trained coder observed the recordings to determine the presence of a cost discussion, the cost-related topic, and any emergent factors. Results: Findings showed increases in patients’ self-efficacy for managing treatment costs (p=.02) and interacting with oncologists (p=.001). Cost-related distress decreased but not significantly (p=.20). Patients reported the DISCO App was understandable (M=4.5 out of 5), useful as they talked with their oncologist (M=4.0), and 84% of patients reported needing less than 15 minutes to use the DISCO App. Most (94%) interactions were videorecorded (in two cases technical difficulties prevented videos from being collected); all (100%) of the videorecorded interactions included a cost discussion. The most frequently discussed topics were: insurance, time off from work, and financial navigation. Frequently, the oncologist asked the patient for his/her question list and discussed/answered the questions. Conclusions: Findings suggest the DISCO App is feasible to implement in the clinic and effective in improving patient-oncologist cost discussions and financial toxicity-related outcomes. Patient acceptance of the DISCO App and oncologist engagement suggested the intervention prompted cost discussions. Next steps include conducting a longitudinal randomized controlled trial to determine the effectiveness of the DISCO App on financial toxicity, and other outcomes. Clinical trial information: NCT03676920 .
Video conferencing long distance caregivers during oncology appointments: Implications for clinical practice.
Authors: Blackstone Eric , Park Sumin , Krishnamurthi Smitha S. , Bajor David Lawrence , Mazanec Polly , Day Kim , Douglas Sara L
Published: May 2020

e24198

Background: Distance Caregivers (DCGs) – caregivers living > 1 hour away from the patient – face unique challenges regarding frustration at receiving second hand information about the patient’s condition and uncertainty regarding how to assist the patient. Videoconferencing allows DCGs to connect for the patient’s oncology appointments while avoiding costly travel expenses and time away from work and family. Methods: 441 patient-DCG dyads enrolled in a randomized controlled trial at a large, urban comprehensive cancer center. Patients of all cancer types were eligible if they had monthly oncologist appointments. DCGs were randomized to one of three arms. Arm 1 – received four monthly videoconference coaching sessions with a nurse or social worker, connected for the patient’s oncology appointments, and had access to a website designed for DCGs; Arm 2 – connected for the patient’s oncology appointments over four months and had access to the DCG website; Arm 3 – received access to the DCG website. To evaluate the impact on clinical practice, outpatient oncology appointments were timed. Helpfulness of the intervention was rated from 0-10 with higher scores representing greater amounts of helpfulness. Descriptive statistics, ANOVA, and Pearson’s correlation were conducted to describe features, determine group differences, and identify relationships among variables. Results: Mean helpfulness ratings were 9.06 (patients), 9.30 (local caregivers), 9.08 (DCGs), and 7.98 (oncologists). Average appointment times (in minutes) for Arm 1, Arm 2, and Arm 3 were 19.63 (SD = 7.69), 21.34 (SD = 9.95), and 17.80 (SD = 10.20), respectively. Arm 2 had significantly longer appointments than Arm 3 (mean difference: 3.54, p = .025). No relationships were found between length of appointment time and helpfulness ratings. Conclusions: The videoconferencing intervention was well-received by oncologists, patients, and DCGs. Appointments were longest in Arm 2, followed by Arm 1, then Arm 3 (control). It makes sense that connecting an additional person lengthened the meetings, but it was noteworthy that Arm 2 was longest. DCGs in Arm 2 (who did not have the coaching) likely had more unanswered questions that were discussed with the oncologist compared to Arm 1 DCGs. Cancer centers should consider this when implementing videoconferencing technology. Clinical trial information: NCT02666183 .
A phase III, randomized, double-blind study of adjuvant cemiplimab versus placebo post-surgery and radiation therapy (RT) in patients (pts) with high-risk cutaneous squamous cell carcinoma (CSCC).
Authors: Rischin Danny , Fury Matthew G. , Lowy Israel , Stankevich Elizabeth , Han Hyunsil , Porceddu Sandro
Published: May 2020

TPS10084

Background: CSCC is the second most common skin cancer. While the surgical cure rate for CSCC is > 95%, a proportion of pts are considered to have high risk for recurrence as assessed by immune status, primary disease stage, extent of nodal involvement, presence of extracapsular extension, and prior treatment. Post-operative RT is recommended for pts with high-risk features, but relapse with locoregional recurrence or distant metastases may still occur. This study evaluates the efficacy of cemiplimab, a human anti‒PD-1 monoclonal antibody, as an adjuvant therapy for pts with CSCC with high-risk features, after surgery and RT. Methods: This randomized, placebo-controlled, double-blind, multicenter, Phase 3 study will evaluate cemiplimab as an adjuvant treatment for pts with high-risk CSCC, based on surgical and clinicopathologic findings, who have completed surgery and post-operative RT (NCT03969004). Immunocompromised pts were excluded. The trial will enrol 412 pts from about 100 sites in North America, Europe, and Asia-Pacific regions. Pts with at least one of the following high-risk features are eligible: a) nodal disease with extracapsular extension b) in-transit metastases c) T4 lesion d) perineural invasion, and e) recurrent CSCC with at least one other risk factor. In Part 1 (blinded), pts will be randomized 1:1 to receive cemiplimab 350 mg or placebo intravenously every 3 weeks (Q3W) for up to 48 weeks. In optional Part 2 (unblinded), pts in the placebo arm who experience disease recurrence or pts in the cemiplimab arm who experience disease recurrence ≥3 months after completion of 48-week treatment in Part 1 will be eligible to receive open-label cemiplimab 350 mg Q3W for up to 96 weeks. Key objectives are to compare disease-free survival (primary) as well as overall survival, freedom from locoregional relapse, and distant relapse (secondary) of adjuvant cemiplimab vs placebo in pts with high-risk CSCC. This study is currently open for enrollment. Clinical trial information: NCT03969004.
A phase II study of anti-PD1 monoclonal antibody (Nivolumab) administered in combination with anti-LAG3 monoclonal antibody (Relatlimab) in patients with metastatic melanoma naive to prior immunotherapy in the metastatic setting.
Authors: Rohatgi Anjali , Massa Ryan Campbell , Gooding William E. , Bruno Tullia C. , Vignali Dario , Kirkwood John M.
Published: May 2020

TPS10085

Background: Novel checkpoint inhibitors are a promising treatment for advanced melanoma, as only a fraction of patients have durable responses to current FDA-approved immunotherapy. Lymphocyte activation gene 3 (LAG3) is an inhibitory checkpoint receptor on CD4+ and CD8+ T cells, where engagement results in suppression of T cell activation and proliferation. LAG3 and PD1 are co-expressed on T cells during T cell receptor signaling and are down-regulated after antigen clearance. Persistent stimulation leads to prolonged LAG3 and PD1 expression and to T cell exhaustion, a possible mechanism of resistance to immunotherapy. Both LAG3 and PD1 are expressed on tumor-infiltrating T cells in melanoma. Murine tumors treated with both anti-LAG3 and anti-PD1 have demonstrated increased tumor regression than tumors in mice treated with either single agent. Further, a phase I trial has demonstrated safety of combined anti-LAG3 monoclonal antibody, relatlimab and anti-PD1 monoclonal antibody, nivolumab. Methods: This phase II, single-center clinical trial is designed to enroll treatment naive patients with unresectable or metastatic melanoma to ultimately receive combined relatlimab and nivolumab after a lead-in arm where patients are randomized to receive relatlimab, nivolumab, or the combination for the first 4 week cycle. For the lead-in phase, patients will have baseline and post-treatment blood and tumor sampling. Disease assessment by imaging will occur after the lead-in phase at 4 weeks. After completion of the lead-in phase, all patients proceed to combination therapy with disease assessment at 12-week intervals. The primary endpoint for the lead-in phase is to evaluate changes in immune cell populations in peripheral blood and tumor with the single agents and combination treatment. The primary endpoint for the combination phase is best overall anti-tumor response. Secondary clinical endpoints include progression-free survival, overall survival, duration of response and toxicity. Exploratory endpoints are to determine the mechanistic effects of anti-LAG3 and anti-PD1 on the blood and tumor microenvironment, cytokine signatures, and correlation of these with clinical response. The study is currently accruing with enrollment of 9 out of 42 patients. Clinical trial information: NCT03743766.
Immunotherapy and chemotherapy combination for chest wall disease: TBCRC 044 trial.
Authors: Vidula Neelima , Nanda Rita , Miller Kathy , Pohlmann Paula Raffin , Abramson Vandana G , Emens Leisha A. , Park Ben Ho , Liu Minetta C. , Goga Andrei , Rugo Hope S.
Published: May 2020

TPS1114

Background: Immunotherapy combined with chemotherapy is being studied in metastatic breast cancer, and may have durable outcomes. Chest wall recurrence represents a difficult to treat subtype of breast cancer with a poor prognosis, with lymphovascular invasion in the primary tumor a significant risk factor. Given the inflammatory nature of this disease and the association of programmed cell death 1 (PD-1) expression with lymphovascular invasion, we hypothesized that the combination of pembrolizumab, an anti-PD-1 antibody, with carboplatin may be effective as treatment for breast cancer chest wall recurrences. Methods: This randomized phase II study is enrolling 84 patients with breast cancer involving the chest wall, who may also have distant metastases. Patients receive treatment with pembrolizumab 200 mg and carboplatin AUC 5 every 3 weeks for 6 cycles (Arm A, n = 56) followed by maintenance pembrolizumab +/- carboplatin (Arm Ax), or carboplatin AUC 5 every 3 weeks for 6 cycles (Arm B, n = 28) with an option to cross-over to pembrolizumab +/- carboplatin on progression (Arm Bx). Patients with all disease subtypes, triple-negative, hormone receptor positive/HER2- after 2 prior lines of hormone therapy, and HER2+ disease (with the option to continue trastuzumab) are eligible, with no limit on the number of prior therapies. Prior platinum chemotherapy is allowed in the absence of overt disease progression. Patients undergo clinical assessment with every cycle of treatment including chest wall photography, scans (CT chest, abdomen, and pelvis) every 2 cycles, and have peripheral blood and chest wall biopsies collected at baseline and the start of cycle 3 for correlative studies. The primary endpoint is the disease control rate in the chest wall and distant sites at 18 weeks of treatment based on RECIST 1.1. The study is powered to determine a 20% difference in disease control between arms (hazard ratio 0.52, α = 0.10, β = 0.20). Additional endpoints include response by tumor programmed death ligand 1 (PD-L1) status and irRECIST, progression-free survival, and toxicity. Chest wall tumor samples will be analyzed for changes in tumor immune composition, and PD-L1 and MYC oncogene expression, based on preclinical data to suggest that PD-L1 may be upregulated by MYC. Peripheral blood samples will be evaluated for changes in PD-L1 expression, cell-free DNA, and circulating tumor cells with treatment. The study is enrolling patients at 7 sites within the Translational Breast Cancer Research Consortium (TBCRC), with current enrollment of 38/84 patients. Clinical trial information: NCT03095352 .
A phase I/II clinical trial of the reversible LSD1 inhibitor, seclidemstat, in patients with relapsed/refractory Ewing sarcoma.
Authors: Reed Damon R. , Mascarenhas Leo , Meyers Paul A. , Chawla Sant P. , Harrison Douglas James , Setty Bhuvana , Metts Jonathan , Wages David S. , Stenehjem David D. , Santiesteban Daniela Y. , DuBois Steven G.
Published: May 2020

TPS11567

Background: Ewing sarcoma (ES) is a rare, aggressive bone and soft tissue cancer that predominantly afflicts adolescents and young adults. Novel therapeutic agents are needed as there are no approved targeted treatments for this disease. ES is characterized by a chromosomal translocation resulting in an EWS/ETS fusion oncoprotein, a transcription factor that results in aberrant gene expression leading to ES progression. Lysine specific demethylase 1 (LSD1) associates with EWS/ETS oncoproteins to alter gene expression and contribute to disease progression. Directly inhibiting EWS/ETS is challenging and little progress has been made, though targeting LSD1 presents a viable therapeutic strategy for ES. Seclidemstat (SP-2577, Salarius Pharmaceuticals) is a first-in-class, orally bioavailable, small molecule with reversible and noncompetitive selective inhibition of LSD1 at low nanomolar concentrations (IC50: 25-50 nM). Seclidemstat inhibits LSD1’s scaffolding functions and enzymatic activity to help reverse aberrant gene expression. In vitro data show that treatment with seclidemstat, or seclidemstat analog, modulates EWS/ETS transcriptional activity, down-regulating oncogene expression and up-regulating tumor-suppressor gene expression. In in vivo xenograft studies (e.g., SK-N-MC, A673), mice treated with seclidemstat show significant tumor growth inhibition/regression vs the control vehicle group. Methods: This phase 1/2 clinical study of seclidemstat is being conducted in relapsed or refractory ES (NCT03600649). The trial is an open-label, non-randomized dose-escalation/dose-expansion study designed to determine the maximum tolerated dose through single-patient dose escalation followed by traditional 3+3 design. The primary objective is to assess seclidemstat’s safety and tolerability while secondary objectives include pharmacokinetics, efficacy and exploratory pharmacodynamic markers. Patients must be ≥12 years old, have received at least 1 prior line of therapy including a prior camptothecin-based regimen, with a life expectancy > 4 months. All patients receive seclidemstat twice-daily (BID) as oral tablets until unacceptable toxicity or disease progression. Patients are followed for survival until the end of study. The trial is currently recruiting across 8 locations in the United States. Upon identification of the recommended phase 2 dose, that cohort will be expanded to enroll a total of 20 patients. Clinical trial information: NCT03600649 .
SPEARHEAD-1: A phase II trial of ADP-A2M4 SPEAR T cells in patients with advanced synovial sarcoma or myxoid/round cell liposarcoma.
Authors: Araujo Dejka M. , Druta Mihaela , Agulnik Mark , D'Angelo Sandra P. , Blay Jean-Yves , Strauss Sandra J , Valverde Claudia , Abdul Razak Albiruni Ryan , Van Winkle Erin , Trivedi Trupti , Biswas Swethajit , Williams Dennis , Norry Elliot
Published: May 2020

TPS11569

Background: ADP-A2M4 specific peptide enhanced affinity receptor (SPEAR) T-cells are genetically engineered to target MAGE-A4+ tumors in the context of HLA-A*02. MAGE-A4 has been described as having high expression in synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCLS) [1, 2]. This Phase 2 trial was initiated based on the favorable benefit:risk profile of ADP-A2M4 observed in a Phase 1 trial (NCT03132922) of ADP-A2M4 which demonstrated compelling clinical responses in patients with SS. Methods: This Phase 2, open-label trial (SPEARHEAD-1; NCT04044768) is designed to evaluate the efficacy, safety and tolerability of ADP-A2M4 in patients with advanced/metastatic SS or MRCLS who are HLA-A*02 positive and whose tumors express the MAGE-A4 protein. Enrolled patients are to undergo apheresis, and their isolated T-cells are then transduced with the MAGE-A4c1032 TCR, and expanded. Prior to ADP-A2M4 infusion, patients are to receive lymphodepleting chemotherapy consisting of fludarabine (30 mg/m2/day x 4 days) and cyclophosphamide (600 mg/m2/day x 3 days). Patients are to receive 1 – 10 × 109 transduced T-cells. An independent Data Safety Monitoring Board will review ongoing safety and benefit:risk during the interventional phase of the study. Disease will be assessed by independent review per RECIST v1.1 by CT/MRI at weeks 4, 8, 12, 16, 24, and every 2 months thereafter until confirmed disease progression. As of 24 Jan 2020, there were 17 clinical sites open in the US, one in Canada, and two in Spain. References: 1. Iura K, et al. Cancer-testis antigen expression in synovial sarcoma: NY-ESO-1, PRAME, MAGEA4, and MAGEA1. Human Pathology 2017; 61:130-139. 2. Iura K, et al. MAGEA4 expression in bone and soft tissue tumors: its utility as a target for immunotherapy and diagnostic marker combined with NY-ESO-1. Virchows Archiv 2017;471:383–392. Clinical trial information: NCT04044768 .
A phase Ib adaptive study of dasatinib for the prevention of oxaliplatin-induced neuropathy in patients with metastatic colorectal cancer receiving FOLFOX chemotherapy and bevacizumab.
Authors: Noonan Anne M. , Lustberg Maryam B. , Schnell Patrick , Hays John L. , Jin Ning , Abushahin Laith I. , Malalur Pannaga G. , Roychowdhury Sameek , Elkhatib Rifat T. , Chen Huizi , Al Mutar Salwan , Sparreboom Alex , Hu Shuiying
Published: May 2020

TPS12125

Background: Neurotoxicity is one of the most significant and disabling side effects of oxaliplatin and frequently limits the cumulative amount that can be used. The mechanism of oxaliplatin-induced neurotoxicity remains uncertain, although our preliminary studies suggest that oxaliplatin uptake by organic cation transporter 2 (OCT2) into mouse and rat dorsal root ganglion is a prerequisite for oxaliplatin-induced peripheral neuropathy. The activity of OCT2 is dependent on tyrosine phosphorylation by the SRC-kinase family member Yes1, which is highly sensitive to inhibition by several FDA-approved, small molecule kinase inhibitors such as dasatinib. We have previously shown that pre-treatment with oral dasatinib prevented acute and chronic oxaliplatin-induced peripheral neuropathy in mouse and rat models. Methods: This is a phase Ib dose-finding study of dasatinib given in combination with mFOLFOX6 with or without bevacizumab. The study explores the hypothesis that the addition of dasatinib prior to oxaliplatin will inhibit OCT2 activity and reduce oxaliplatin-induced neuropathy. This hypothesis will be tested in a Bayesian Phase 1b trial with adaptive dose selection using efficacy-toxicity trade-offs (modified toxicity-efficacy probability interval dose-finding design) in patients with confirmed stage IV colorectal cancer who are candidates for mFOLFOX6 with bevacizumab therapy. Patients who have documented peripheral neuropathy or prior exposure to oxaliplatin will be excluded. The primary objective is to determine the recommended Phase 2 dose which is defined as the lowest intermittent dose of dasatinib that affects serum biomarkers of OCT2, including methylnicotinamide and creatinine, by ≥2-fold without influencing the clearance of oxaliplatin by > 20%. The following doses will be used: oxaliplatin 85mg/m2 IV, 5FU bolus 400mg/m2 IV bolus with Leucovorin 400mg/m2, bevacizumab 5mg/kg, followed by infusional 5FU 2400mg/m2 IV over 46 hours given on a day 1 and 15 schedule every 28 days. Dasatinib will be administered at one of 2 dose levels – 100mg or 140mg po. Dasatinib will be given 24 hours and 30 mins prior to oxaliplatin on C1D14, C1D15 respectively and repeated on C1D28 and C2D1. Secondary objectives include evaluation of the influence of dasatinib on the pharmacokinetics of oxaliplatin and vice versa. Quality of life will be explored using the CIPN20 questionnaire. The trial opened to enrollment in Dec 2019 (NCT04164069) and is accepting patients. Clinical trial information: NCT04164069 .