Telehealth Preferences Among Patients With Advanced Cancer in the Post COVID-19 Vaccine Era.

BACKGROUND: Few studies have examined patient preferences for telehealth in palliative care after the availability of COVID-19 vaccines. We examined patient preferences for video versus in-person visits and factors contributing to preferences in the postvaccine era. METHODS: This is a cross-sectional survey of patients who were seen at our palliative care clinic between April 2021 and March 2022. Patients were surveyed directly their preference for either video or in-person visits for outpatient palliative care (primary outcome). We also surveyed preferences including convenience, cost, wait time, and perceptions of COVID-19 safety regarding their palliative virtual-video visit. We examined clinical factors associated with preferences with multivariate logistic regression. RESULTS: About 200 patients completed the survey. 132 (67%, 95% confidence interval [CI]: 60%, 74%) preferred virtual-video, while 16 (8%) preferred in-person visits during the COVID-19 pandemic. About 120 (61%, 95%CI: 54%, 68%) preferred virtual-video after the pandemic. Patients perceived virtual-video favorably regarding travel and related costs (179 [91%]), convenience (175 [88%]), and wait time (136 [69%]). Multivariable analysis showed concerns for catching COVID-19 from healthcare providers (odds ratio [OR]: 4.20; 95%CI: 1.24-14.25; P = 0.02) and feeling comfortable with computers or mobile devices (OR: 4.59; 95%CI: 1.02, 20.60; P = 0.047) were significantly associated with preferring virtual-video. Patients who were of Hispanic or Latino ethnicity (OR: 0.25; 95%CI: 0.09, 0.71) and had increased dypsnea (OR: 0.74; 95%CI: 0.59, 0.93) were less likely to prefer video over in-person. CONCLUSION: Patients expressed strong preference for video over in-person visits in the outpatient palliative care setting.

Impact of Dosing and Duration of Dexamethasone on Serious Corticosteroid-Related Adverse Events.

CONTEXT: Corticosteroids are commonly prescribed in oncology, but few studies have examined its adverse events (AEs) compared to placebo control. OBJECTIVES: Using data from a double-blind, placebo-controlled randomized trial, we evaluated the association between the dose and duration of dexamethasone and serious AEs. METHODS: This is a pre-planned secondary analysis of the Alleviating Breathlessness in Cancer Patients with Dexamethasone (ABCD) trial in which patients were randomized to dexamethasone 8 mg BID x1 week, then 4 mg BID x1 week or placebo, followed by an optional open-label phase with 4 mg BID x1 week, then 2 mg BID x1 week. The primary outcome was Grade 3+ AEs (CTCAE v4.03). We evaluated the association between AEs and dexamethasone exposure using multivariable logistic regression. RESULTS: Among 119 cancer patients, 32 received intervention followed by open label (mean exposure 243 mg over 27 days), 47 received intervention with no open label, 20 received placebo followed by open label, and 20 received no dexamethasone. The most common AEs included insomnia (31%), dyspepsia (21%), neuropsychiatric symptoms (18%), and infections (17%). Overall, 38 (32%) had Grade 3+ AEs and 27 (23%) were hospitalized. Patients with the greatest exposure to dexamethasone experienced more Grade 3+ AEs compared to those with no exposure (65% vs. 15%); odds ratio of 15.1 (95% CI 1.4-160.8, P = 0.01). CONCLUSION: Greater dexamethasone exposure, even at moderate doses, was associated with more serious AEs. Prescribers should cautiously weigh the risks and benefits of dexamethasone use, especially when considering for palliation of symptoms.

Postvaccine Era COVID-19 Pandemic-Related Distress in Palliative Care Patients With Advanced Cancer.

CONTEXT: The COVID-19 pandemic represents a source of distress in patients with advanced cancer; however, few studies have examined the extent of pandemic-related distress in the postvaccine era. OBJECTIVES: We conducted a cross-sectional survey to examine pandemic-related distress among patients seen by palliative care after vaccine availability. METHODS: Patients at our palliative care clinic were surveyed from April 2021 to March 2022 regarding 1) pandemic-related distress level, 2) potential contributors to pandemic-related distress, 3) coping strategies, 4) demographic factors and symptom burden. Univariate and multivariate analyses identified factors associated with pandemic-related distress. RESULTS: A total of 200 patients completed the survey. Of 79 (40%, 95% confidence interval [CI]: 33%, 46%) reported worse pandemic-related distress. Patients who reported greater distress were more likely to report worse social isolation (67 [86%] vs. 52 [43%]), staying home more often (75 [95%] vs. 95 [79%]), more negative experience staying at home (26 [33%] vs. 11 [9%]), worse stress with child-care duties (14 [19%] vs. 4 [3%]), less seeing family/friends (63 [81%] vs. 72 [60%]), and more difficulty traveling to medical appointments (27 [35%] vs. 20 [17%]). Thirty-seven patients (19%) reported more difficulty getting medical appointments. In multivariable analysis, younger age (odds ratio [OR], 0.97; 95% CI, 0.92-0.99; P = 0.01), worse isolation status (OR, 6.87; 95% CI, 2.76-17.12; P < 0.001), and more negative attitude towards staying home (OR, 4.49; 95% CI, 1.6-12.57; P = 0.004) were associated with pandemic-related distress. CONCLUSIONS: Patients with advanced cancer continued to experience pandemic-related distress in the postvaccine era. Our findings highlight potential opportunities to support patients.

Endometrial cancer patients understanding and interest in weight loss surgery.

OBJECTIVE: Obesity is a risk factor for endometrial hyperplasia (EH), endometrial intraepithelial neoplasia (EIN), and early type 1 endometrial cancer (EC) in 70%-90% of patients and is often a significant contributor to overall morbidity and mortality due to comorbidities. In 2011, bariatric surgery (BS) with lifestyle modification was identified as an intervention for reduction in overall mortality as well as risk for gynecologic cancers (Tsui et al., 2021). Our aim was to assess awareness of obesity as a risk factor and understanding of BS in an underinsured obese patient population with EC or EH. METHOD: This IRB-approved survey was distributed to patients with type I EC or EH within the past 5 years and a BMI >30. Questions addressed demographics, health habits, cancer and obesity awareness, as well as benefits and concerns about undergoing BS. Information was provided about dietary requirements after BS, and then interest in BS was surveyed. RESULTS: 61.2% of surveyed patients were interested in bariatric surgery for weight loss after receiving education about the procedure. Interest in bariatric surgery was correlated with higher BMI, higher ideal and comfortable weight loss in pounds and higher estimated weight loss that could be obtained with bariatric surgery. Additionally, patients who were interested in BS had better understanding of the risks of obesity with cancer overall. CONCLUSION: Obese patients with history of EC/EIN/EH are aware of hazards associated with excess weight and understand the relationship between EC/EIN/EH diagnosis and obesity, and overall are very interested in BS as a modality to improve their health.

Attitudes of Palliative Care Specialists Toward Assessing Sexual Dysfunction in Patients With Cancer.

CONTEXT: The sexual health of patients is frequently neglected. OBJECTIVES: To evaluate the attitudes and beliefs of palliative care providers toward discussing the presence of sexual dysfunction (SD) in patients with cancer METHODS: In this pilot study, an anonymous survey was conducted among palliative care professionals about their attitudes toward discussing SD RESULTS: Forty-nine (89%) palliative care providers completed the survey. Thirty-four (69%) responded that they rarely or never discussed sexuality with their patients and most believed it is the oncologist's responsibility. The top reasons for not discussing SD were that the patient did not raise the issue, lack of time and the presence of a third party. The majority acknowledged the need of more training and that printed materials would be helpful. CONCLUSION: Palliative care providers infrequently address the presence of SD among patients with cancer. Additional training and routine screening for SD might help addressing this problem.

Characterization of industry relationships in oncology.

BACKGROUND: Collaborative relationships between academic oncology and industry (pharmaceutical, biotechnology, "omic," and medical device companies) are essential for therapeutic development in oncology; however, limited research on engagement in and perceptions of these relationships has been done. METHODS: Survey questions were developed to evaluate relationships between academic oncology and industry. An electronic survey was delivered to 1000 randomly selected members of the American Society of Clinical Oncology, a professional organization for oncologists, eliciting respondents' views around oncology-industry collaborations. The responses were analyzed according to prespecified plans. RESULTS: There were 225 survey respondents. Most were from the United States (70.0%), worked at an academic institution (60.1%), worked in medical oncology (81.2%), and had an active relationship with industry (85.8%). One quarter (26.7%) of respondents reported difficulty establishing a relationship with industry collaborators, and most respondents (75%) did not report having had mentorship in developing these relationships. The majority (85.3%) of respondents considered these collaborations important to their careers. Respondents generally thought that scientific integrity was preserved (92%), and most respondents (95%) had little concern over the quality of the collaborative product. Many (60%) shared concerns over potential conflict of interest if an individual with a compensated relationship promoted an industry product for clinical care/research, yet most respondents (67%) stated these relationships did not shape their interactions with patients. CONCLUSIONS: This study provides novel data characterizing the nature of collaborative relationships between clinicians, researchers, and industry in oncology. Although respondents considered these collaborations an important part of clinical and academic oncology, formal education or mentorship around these relationships was rare. Conflicting findings around conflict of interest highlight the importance of more dedicated research in this area. PLAIN LANGUAGE SUMMARY: Business enterprises in health care play a central role in cancer research and care, driving the development of new medical testing, drugs, and devices. Effective working relationships among clinicians, researchers, and these industry partners can promote innovative research and enhance patient care. Study of these collaborations has been limited to date. Through distribution of a questionnaire to cancer clinicians and researchers, we found that most participants consider these relationships valuable, though they find establishing such relationships challenging partly because of gaps in educational programs in this area. Our findings also highlight the need for further policy around the potential bias these relationships can introduce.

Efforts to Improve Naloxone Co-Prescription for Patients With Cancer Pain at Risk of Opioid Overdose.

Importance: Naloxone can be lifesaving in an opioid-related overdose (OD). However, the co-prescription of take-home naloxone (THN) is not widely adopted in routine clinical practice. We implemented a pilot program focused on increasing clinicians' awareness of THN and observed if this impacts THN prescriptions for our patients with cancer pain receiving opioids. Intervention: In January 2020, we initiated an educational program by twice-weekly video presentations and installed pamphlets in all clinic workstations highlighting the risk factors for ODs. We retrospectively reviewed electronic health records (EHR) of randomly selected patient visits, 200 each from eight weeks before intervention (BI) and eight weeks after the intervention (AI). Data on patient characteristics, risk factors for ODs, and THN prescriptions were collected. Results: In all, 380 unique patients were eligible for analysis. The median age was 60, 53% female, and 70% Caucasian. Eighty-two percent (152) BI and 73% (142) AI carried risk factors for ODs (p = 0.13). THN was prescribed to 21% (32/152) BI and 26% (37/142) AI (p = 0.53). Morphine-equivalent daily dose (MEDD) ≥100 mg (30%) and pulmonary disease (25%) were the most prevalent risk factors. The patient's likelihood of receiving a THN prescription increased by 0.9% for every 1-milligram increase in MEDD (p < 0.001, 95% confidence interval: 1.006-1.011). Conclusion: The educational intervention did not significantly increase the frequency of THN prescriptions. More direct interventions, including automatic EHR triggers, may need to be tested in future trials.

Differential Impact of a Multicomponent Goals-of-Care Program in Patients with Hematologic and Solid Malignancies.

We recently reported that an interdisciplinary multicomponent goals-of-care (myGOC) program was associated with an improvement in goals-of-care (GOC) documentation and hospital outcomes; however, it is unclear if the benefit was uniform between patients with hematologic malignancies and solid tumors. In this retrospective cohort study, we compared the change in hospital outcomes and GOC documentation before and after myGOC program implementation between patients with hematologic malignancies and solid tumors. We examined the change in outcomes in consecutive medical inpatients before (May 2019-December 2019) and after (May 2020-December 2020) implementation of the myGOC program. The primary outcome was intensive care unit (ICU) mortality. Secondary outcomes included GOC documentation. In total, 5036 (43.4%) patients with hematologic malignancies and 6563 (56.6%) with solid tumors were included. Patients with hematologic malignancies had no significant change in ICU mortality between 2019 and 2020 (26.4% vs. 28.3%), while patients with solid tumors had a significant reduction (32.6% vs. 18.8%) with a significant between-group difference (OR 2.29, 95% CI 1.35, 3.88; p = 0.004). GOC documentation improved significantly in both groups, with greater changes observed in the hematologic group. Despite greater GOC documentation in the hematologic group, ICU mortality only improved in patients with solid tumors.

Health Care Provider Attitudes and Beliefs Toward Nonmedical Opioid Use in Patients with Cancer Pain.

Background: Data on health care providers' (HCPs') perceptions about patients with cancer pain and nonmedical opioid use (NMOU) are lacking. We examined the perceptions and attitudes of HCPs and assessed the usefulness of an interdisciplinary opioid stewardship program (OSP) while caring for these patients. Methods: An anonymous cross-sectional survey was conducted among the supportive care HCPs between September and November 2021. Results: Of 85 HCPs, 64 responded (75%) to the survey. Participants perceived that NMOU is underdiagnosed (42/64; 67%), and caring for such patients is difficult (58/64, 91%) and time consuming (54/64, 87%). A majority (50/51, 98%) were aware of the OSP, and (48/51; 94%) found it helpful. Conclusion: HCPs reported that NMOU is underdiagnosed and is challenging to manage. They endorsed the utility of an OSP in managing patients with concurrent cancer pain and NMOU. Future research should identify ways to standardize care and integrate OSP in routine supportive oncology practice.

Evaluation of a Daily Nine-Item "Handbook for Self-Care at Work" for Palliative Care Clinicians.

Context: A daily nine-item "Handbook for Self-Care at Work" was created to increase the well-being and satisfaction of the staff at the department of palliative care of a tertiary oncological center in the United States. Objectives: To evaluate the perceived usefulness of and adherence to the Handbook. Design, Setting and Participants: An anonymous survey was conducted among the palliative care staff asking for the frequency of utilization and the perception of usefulness of the Handbook. Additional data collected included demographics, satisfaction with professional life, frequency of burnout, and frequency of callousness toward people. We also compared the use and perception of the Handbook before and during the COVID-19 pandemic. Results: Of 52 palliative care clinicians, 39 (75%) completed the survey. Most participants were women and were <49 years. Most respondents (59%) found the Handbook useful or very useful. Offer help, ask for help, and hydration were perceived as the most useful items. The items most frequently achieved were movement, hydration, and eat light. The least useful perceived item was nap time, which was rarely achieved. During the COVID-19 pandemic, 32 (82%) respondents found the Handbook to be as/somewhat more/much more useful, and 29 (75%) were able to adhere to the items as/somewhat more/much more often than before. Conclusion: Most respondents found the Handbook useful and were able to accomplish the items most of the days. During the COVID-19 pandemic, the staff felt that the Handbook was more useful.

Impact of an Interdisciplinary Goals-of-Care Program Among Medical Inpatients at a Comprehensive Cancer Center During the COVID-19 Pandemic: A Propensity Score Analysis.

PURPOSE: Many hospitals have established goals-of-care programs in response to the coronavirus disease 2019 pandemic; however, few have reported their outcomes. We examined the impact of a multicomponent interdisciplinary goals-of-care program on intensive care unit (ICU) mortality and hospital outcomes for medical inpatients with cancer. METHODS: This single-center study with a quasi-experimental design included consecutive adult patients with cancer admitted to medical units at the MD Anderson Cancer Center, TX, during the 8-month preimplementation (May 1, 2019-December 31, 2019) and postimplementation period (May 1, 2020-December 31, 2020). The primary outcome was ICU mortality. Secondary outcomes included ICU length of stay, hospital mortality, and proportion/timing of care plan documentation. Propensity score weighting was used to adjust for differences in potential covariates, including age, sex, cancer diagnosis, race/ethnicity, and Sequential Organ Failure Assessment score. RESULTS: This study involved 12,941 hospitalized patients with cancer (pre n = 6,977; post n = 5,964) including 1,365 ICU admissions (pre n = 727; post n = 638). After multicomponent goals-of-care program initiation, we observed a significant reduction in ICU mortality (28.2% v 21.9%; change -6.3%, 95% CI, -9.6 to -3.1; P = .0001). We also observed significant decreases in length of ICU stay (mean change -1.4 days, 95% CI, -2.0 to -0.7; P < .0001) and in-hospital mortality (7% v 6.1%, mean change -0.9%, 95% CI, -1.5 to -0.3; P = .004). The proportion of hospitalized patients with an in-hospital do-not-resuscitate order increased significantly from 14.7% to 19.6% after implementation (odds ratio, 1.4; 95% CI, 1.3 to 1.5; P < .0001), and do-not-resuscitate order was established earlier (mean difference -3.0 days, 95% CI, -3.9 to -2.1; P < .0001). CONCLUSION: This study showed improvement in hospital outcomes and care plan documentation after implementation of a system-wide, multicomponent goals-of-care intervention.

Perception of subjective lived experiences of individuals with anorexia-cachexia in patients with advanced lung cancer.

Objective: Cancer cachexia (CC) is a frequent and debilitating syndrome in patients with cancer. It has serious implications for patients, extending beyond physical problems into psychological, and social domains. The objective of our study was to qualitatively understand the experiences related to CC in patients with advanced lung cancer. Methods: Patients with advanced lung cancer with anorexia (≤ 37 points on Functional Assessment of Anorexia/Cachexia Treatment-ACS) and weight loss were eligible. Patients participated in semi-structured interviews prior to study treatment (n = 19). Qualitative analysis was conducted using interpretative phenomenological approach. Results: Two super-ordinate themes emerged (anorexia and weight loss). Patients reported experiencing distress related to anorexia, weight loss, lack of social eating, worsening function, body image, and eating habits. The encouragement to eat by the family was often distressing to the patient. The treatment recommendations by their oncologist for anorexia and weight loss was felt inadequate. Patients felt that the treatment for CC should improve appetite and weight gain as well as their mood and be independent. Conclusions: The findings of the study suggests that anorexia and weight loss results in high levels of distress due to their effects on physical and psychosocial domains. Further studies are needed to better understand the experience of anorexia and weight loss to develop strategies to effectively treat CC. Trial registration: NCT03637816.

Changes in Apparent Diffusion Coefficient (ADC) in Serial Weekly MRI during Radiotherapy in Patients with Head and Neck Cancer: Results from the PREDICT-HN Study.

Background: The PREDICT-HN study aimed to systematically assess the kinetics of imaging MR biomarkers during head and neck radiotherapy. Methods: Patients with intact squamous cell carcinoma of the head and neck were enrolled. Pre-, during, and post-treatment MRI were obtained. Serial GTV and ADC measurements were recorded. The correlation between each feature and the GTV was calculated using Spearman's correlation coefficient. The linear mixed model was used to evaluate the change in GTV over time. Results: A total of 41 patients completed the study. The majority (76%) had oropharyngeal cancer. A total of 36 patients had intact primary tumours that can be assessed on MRI, and 31 patients had nodal disease with 46 nodes assessed. Median primary GTV (GTVp) size was 14.1cc. The rate of GTVp shrinkage was highest between pre-treatment and week 4. Patients with T3-T4 tumours had a 3.8-fold decrease in GTVp compared to T1-T2 tumours. The ADC values correlated with residual GTVp. The median nodal volume (GTVn) was 12.4cc. No clinical features were found to correlate with GTVn reduction. The overall change in ADC for GTVn from pre-treatment was significant for 35th−95th percentiles in weeks 1−4 (p < 0.001). Conclusion: A discrepancy in the trajectory of ADC between primary and nodal sites suggested that they exhibit different treatment responses and should be analysed separately in future studies.

Open-Label Placebo for the Treatment of Cancer-Related Fatigue in Patients with Advanced Cancer: A Randomized Controlled Trial.

BACKGROUND: The purpose of this study was to determine the effects of an open-labeled placebo (OLP) compared to a waitlist control (WL) in reducing cancer-related fatigue (CRF) in patients with advanced cancer using Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). MATERIALS AND METHODS: In this randomized controlled trial, patients with fatigue ≥4/10 on Edmonton Symptom Assessment Scale (ESAS) were randomized to OLP one tablet twice a day or WL for 7 days. On day 8, patients of both arms received a placebo for 3 weeks. Changes in FACIT-F from baseline to day 8 (primary outcome) and at day 29, were assessed. Secondary outcomes included FACT-G, Multidimensional Fatigue Symptom Inventory-SF, Fatigue cluster (defined as a composite of ESAS fatigue, pain, and depression), Center for epidemiologic studies-depression, Godin leisure-time physical activity questionnaire, and global symptom evaluation. RESULTS: A total of 84/90 (93%) patients were evaluable. The mean (SD) FACIT-F change at day 8 was 6.6 (7.6) after OLP, vs. 2.1 (9.4) after WL (P = .016). On days 15 and 29, when all patients received OLP, there was a significant improvement in CRF and no difference between arms. There was also a significant improvement in ESAS fatigue, and fatigue cluster score in the OLP arm on day 8 of the study (0.029, and 0.044, respectively). There were no significant differences in other secondary outcomes and adverse events between groups. CONCLUSIONS: Open-labeled placebo was efficacious in reducing CRF and fatigue clusters in fatigued advanced cancer patients at the end of 1 week. The improvement in fatigue was maintained for 4 weeks. Further studies are needed.

Effect of dexamethasone on dyspnoea in patients with cancer (ABCD): a parallel-group, double-blind, randomised, controlled trial.

BACKGROUND: Systemic corticosteroids are commonly prescribed for palliation of dyspnoea in patients with cancer, despite scarce evidence to support their use. We aimed to assess the effect of high-dose dexamethasone versus placebo on cancer-related dyspnoea. METHODS: The parallel-group, double-blind, randomised, controlled ABCD (Alleviating Breathlessness in Cancer Patients with Dexamethasone) trial was done at the at the University of Texas MD Anderson Cancer Center and the general oncology clinic at Lyndon B Johnson General Hospital (both in Houston, TX, USA). Ambulatory patients with cancer, aged 18 years or older, and with an average dyspnoea intensity score on an 11-point numerical rating scale (NRS; 0=none, 10=worst) over the past week of 4 or higher were randomly assigned (2:1) to receive dexamethasone 8 mg orally every 12 h for 7 days followed by 4 mg orally every 12 h for 7 days, or matching placebo capsules for 14 days. Pharmacists did permuted block randomisation with a block size of six, and patients were stratified by baseline dyspnoea score (4-6 vs 7-10) and study site. Patients, research staff, and clinicians were masked to group assignment. The primary outcome was change in dyspnoea NRS intensity over the past 24 h from baseline to day 7 (±2 days). Analyses were done by modified intention-to-treat (ie, including all patients who were randomly assigned and started the study treatment, regardless of whether they completed the study). Enrolment was stopped after the second preplanned interim analysis, when the futility criterion was met. This study is registered with ClinicalTrials.gov (NCT03367156) and is now completed. FINDINGS: Between Jan 11, 2018, and April 23, 2021, we screened 2867 patients, enrolled 149 patients, and randomly assigned 128 to dexamethasone (n=85) or placebo (n=43). The mean change in dyspnoea NRS intensity from baseline to day 7 (±2 days) was -1·6 (95% CI -2·0 to -1·2) in the dexamethasone group and -1·6 (-2·3 to -0·9) in the placebo group, with no significant between-group difference (mean 0 [95% CI -0·8 to 0·7]; p=0·48). The most common all-cause grade 3-4 adverse events were infections (nine [11%] of 85 patients in the dexamethasone group vs three [7%] of 43 in the placebo group), insomnia (seven [8%] vs one [2%]), and neuropsychiatric symptoms (three [4%] vs none [0%]). Serious adverse events, all resulting in hospital admissions, were reported in 24 (28%) of 85 patients in the dexamethasone group and in three (7%) of 43 patients in the placebo group. No treatment-related deaths occurred in either group. INTERPRETATION: High-dose dexamethasone did not improve dyspnoea in patients with cancer more effectively than placebo and was associated with a higher frequency of adverse events. These data suggest that dexamethasone should not be routinely given to unselected patients with cancer for palliation of dyspnoea. FUNDING: US National Cancer Institute.

A Not So Perfect Score: Factors Associated with the Rate of Straight Line Scoring in Oncology Training Programs.

Straight line scoring (SLS), defined as trainee assessments with the same score for all evaluation items, is statistically improbable and potentially indicates inaccurate assessment. Factors contributing to higher SLS rates are unknown, and knowledge of SLS prevalence within oncologic training is lacking. SLS frequency was measured for evaluations from all Accreditation Council for Graduate Medical Education (ACGME)-accredited programs at a single cancer care institution between 2014 and 2018. SLS prevalence was estimated using hierarchical linear models (HLM) that considered characteristics of evaluator, trainee, and evaluation potentially related to SLS. Results were compared with national SLS rates. Six thousand one hundred sixty evaluations were included from 476 evaluators. Overall prevalence of SLS was 12.1% (95% CI 4.5-28.8). Residents (vs fellows) were less likely to have SLS evaluations (OR 0.5, 95% CI 0.4-0.8), though for all trainees increasing training year corresponded with increasing SLS frequency (OR 1.5, 95% CI 1.3-1.7). SLS was more common in procedural specialties compared with medical specialties (OR 2.1, 95% CI 1.1-3.8). Formative evaluations had lower SLS rates (OR 0.6, 95% CI 0.5-0.9) than summative evaluations, while milestone-based evaluations had higher rates than those that were not milestone-based (OR 1.5, 95% CI 1.03-2.2). Features of evaluators, such as subspecialty within oncology, and of trainees, such as seniority or trainee type, were related to SLS. Summative intent and milestone-based evaluations were more likely to be straight line scored. Specific evaluation scenarios at higher risk of SLS should be further examined.

Open vs minimally invasive radical trachelectomy in early-stage cervical cancer: International Radical Trachelectomy Assessment Study.

BACKGROUND: Minimally invasive radical trachelectomy has emerged as an alternative to open radical hysterectomy for patients with early-stage cervical cancer desiring future fertility. Recent data suggest worse oncologic outcomes after minimally invasive radical hysterectomy than after open radical hysterectomy in stage I cervical cancer. OBJECTIVE: We aimed to compare 4.5-year disease-free survival after open vs minimally invasive radical trachelectomy. STUDY DESIGN: This was a collaborative, international retrospective study (International Radical Trachelectomy Assessment Study) of patients treated during 2005-2017 at 18 centers in 12 countries. Eligible patients had squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma; had a preoperative tumor size of ≤2 cm; and underwent open or minimally invasive (robotic or laparoscopic) radical trachelectomy with nodal assessment (pelvic lymphadenectomy and/or sentinel lymph node biopsy). The exclusion criteria included neoadjuvant chemotherapy or preoperative pelvic radiotherapy, previous lymphadenectomy or pelvic retroperitoneal surgery, pregnancy, stage IA1 disease with lymphovascular space invasion, aborted trachelectomy (conversion to radical hysterectomy), or vaginal approach. Surgical approach, indication, and adjuvant therapy regimen were at the discretion of the treating institution. A total of 715 patients were entered into the study database. However, 69 patients were excluded, leaving 646 in the analysis. Endpoints were the 4.5-year disease-free survival rate (primary), 4.5-year overall survival rate (secondary), and recurrence rate (secondary). Kaplan-Meier methods were used to estimate disease-free survival and overall survival. A post hoc weighted analysis was performed, comparing the recurrence rates between surgical approaches, with open surgery being considered as standard and minimally invasive surgery as experimental. RESULTS: Of 646 patients, 358 underwent open surgery, and 288 underwent minimally invasive surgery. The median (range) patient age was 32 (20-42) years for open surgery vs 31 (18-45) years for minimally invasive surgery (P=.11). Median (range) pathologic tumor size was 15 (0-31) mm for open surgery and 12 (0.8-40) mm for minimally invasive surgery (P=.33). The rates of pelvic nodal involvement were 5.3% (19 of 358 patients) for open surgery and 4.9% (14 of 288 patients) for minimally invasive surgery (P=.81). Median (range) follow-up time was 5.5 (0.20-16.70) years for open surgery and 3.1 years (0.02-11.10) years for minimally invasive surgery (P<.001). At 4.5 years, 17 of 358 patients (4.7%) with open surgery and 18 of 288 patients (6.2%) with minimally invasive surgery had recurrence (P=.40). The 4.5-year disease-free survival rates were 94.3% (95% confidence interval, 91.6-97.0) for open surgery and 91.5% (95% confidence interval, 87.6-95.6) for minimally invasive surgery (log-rank P=.37). Post hoc propensity score analysis of recurrence risk showed no difference between surgical approaches (P=.42). At 4.5 years, there were 6 disease-related deaths (open surgery, 3; minimally invasive surgery, 3) (log-rank P=.49). The 4.5-year overall survival rates were 99.2% (95% confidence interval, 97.6-99.7) for open surgery and 99.0% (95% confidence interval, 79.0-99.8) for minimally invasive surgery. CONCLUSION: The 4.5-year disease-free survival rates did not differ between open radical trachelectomy and minimally invasive radical trachelectomy. However, recurrence rates in each group were low. Ongoing prospective studies of conservative management of early-stage cervical cancer may help guide future management.

MEK inhibition overcomes resistance to EphA2-targeted therapy in uterine cancer.

BACKGROUND: Our pilot clinical study of EphA2 inhibitor (dasatinib) plus paclitaxel and carboplatin showed interesting clinical activity in endometrial cancer with manageable toxicity. However, the underlying mechanisms of dasatinib resistance in uterine cancer are unknown. Here, we investigated potential mechanisms underlying resistance to EphA2 inhibitors in uterine cancer and examined the anti-tumor activity of EphA2 inhibitors alone and in combination with a MEK inhibitor. METHODS: We evaluated the antitumor activity of EphA2 inhibitors plus a MEK inhibitor using in vitro and in vivo orthotopic models of uterine cancer. RESULTS: EphA2 inhibitor induced MAPK in dasatinib-resistant uterine cancer cells (HEC-1A and Ishikawa) and BRAF/CRAF heterodimerization in HEC-1A cells. EphA2 inhibitor and trametinib significantly increased apoptosis in cancer cells resistant to EphA2 inhibitors compared with controls (p < 0.01). An in vivo study with the orthotopic HEC-1A model showed significantly greater antitumor response to combination treatment compared with dasatinib alone (p < 0.01). Combination treatment increased EphrinA1 and BIM along with decreased pMAPK, Jagged 1, and c-MYC expression in dasatinib-resistant cells. In addition, Spearman analysis using the TCGA data revealed that upregulation of EphA2 was significantly correlated with JAG1, MYC, NOTCH1, NOTCH3 and HES1 expression (p < 0.001, r = 0.25-0.43). Specifically, MAP3K15 and the NOTCH family genes were significantly related to poor clinical outcome in patients with uterine cancer. CONCLUSIONS: These findings indicate that the MAPK pathway is activated in dasatinib-resistant uterine cancer cells and that EphrinA1-mediated MEK inhibition overcomes dasatinib resistance. Dual targeting of both EphA2 and MEK, combined with chemotherapy, should be considered for future clinical development.

Personalized sedation goal for agitated delirium in patients with cancer: Balancing comfort and communication.

BACKGROUND: Agitated delirium is common and highly distressing. Medications are often needed to reduce agitation, but it is unclear what the desired level of sedation is. This study assessed personalized sedation goals (PSGs) and their predictors for patients in a delirium clinical trial and in clinical vignettes. METHODS: This was a preplanned secondary analysis of a double-blind randomized clinical trial examining the sedative effect of chlorpromazine and/or haloperidol in patients with agitated delirium. At the baseline, caregivers and nurses were independently asked to select the PSG for the trial patient from 5 choices corresponding to Richmond Agitation Sedation Scale (RASS) scores of 0 or higher (no sedation), -1 to -2, -3, -4, and -5 (deep sedation). Respondents also selected a PSG for 6 vignettes that differed by the level of agitation, ability to communicate, and survival. RESULTS: Forty-two caregivers and 39 nurses answered questions regarding PSGs. For the trial patient, caregivers preferred RASS scores of -1 to -2 most often (36%), whereas nurses preferred an RASS score of -3 most often (51 %). Caregivers were significantly more likely than nurses to choose lighter sedation (odds ratio [OR], 4.8; P = .01) despite reporting greater delirium-related distress (P = .0006). Patients were undersedated 33% to 53% of the time and oversedated 0% to 15% of the time according to the PSG response criteria. In the case vignettes, deeper sedation was preferred by nurses (P < .0001) and for patients who were unable to communicate (OR, 3.1-4.4; P < .0001) and had a shorter life expectancy (OR, 1.7; P = .002). CONCLUSIONS: Caregivers often preferred lighter sedation than nurses. Many patients were undersedated in comparison with caregivers' PSGs, and this highlights room for improvement. LAY SUMMARY: In the last days of life, many patients with cancer develop delirium and become restless/agitated; this can be highly distressing. Caregivers and physicians alike are often concerned about the use of sedatives for agitated delirium and try to find a balance between maximizing comfort and maintaining communication. This study examined the concept of a personalized sedation goal for setting an individualized target for the level of sedation. Caregivers often preferred lighter sedation than nurses. Many patients were undersedated in comparison with caregivers' stated goals, and this highlights room for improvement.

Recommendations for supportive care and best supportive care in NCCN clinical practice guidelines for treatment of cancer: Differences between solid tumor and hematologic malignancy guidelines.

PURPOSE: It is unclear how NCCN guidelines recommend "supportive care" and "best supportive care" in oncology practice. We examined the usage of "supportive care" and "best supportive care" in NCCN guidelines and compared between solid tumor and hematologic malignancy guidelines. METHODS: We reviewed all updated NCCN Guidelines for Treatment of Cancer in October 2019. We documented the frequency of occurrence, definition, and timing of introduction of each term. We compared between solid tumor and hematologic malignancy guidelines. RESULTS: We identified a total of 37 solid tumor and 16 hematologic guidelines. Thirty-seven (70%) guidelines mentioned "supportive care" and 36 (68%) mentioned "best supportive care." Hematologic guidelines were significantly more likely than solid tumor guidelines to use the term "supportive care" (median occurrence 19 vs. 2; P = 0.001) and to describe "supportive care" as management of cancer-related complications (N = 11/15, 73% vs. N = 2/22, 9%; P < 0.001). Domains of specialist palliative care were infrequently mentioned (N = 10/37, 27%). In contrast, solid tumor guidelines were significantly more likely than hematologic guidelines to mention "best supportive care" (median occurrence 6 vs. 0; P = 0.016). This term was rarely defined and mostly used in the advanced disease setting. CONCLUSION: "Supportive care" and "best supportive care" were frequently used in NCCN guidelines, with significant variations in usage between solid tumor and hematologic oncologists. "Supportive care" was mostly limited to management of cancer-related complications and treatment adverse effects in NCCN guidelines, highlighting the need to go beyond the traditional biomedical model to more a patient-centered care model with greater integration of palliative care.