Long-term follow-up of levonorgestrel intrauterine device for atypical hyperplasia and early endometrial cancer reveals relapse characterized by immune exhaustion.

BACKGROUND: Nonsurgical treatment options are increasingly needed for endometrial atypical hyperplasia (AH) and endometrioid endometrial cancer (EEC). Despite promising initial response rates, prospective long-term data and determinants for relapse are limited. METHODS: Follow-up data from patients in our prospective phase II trial of LIUD for AH/G1EEC were collected from medical records. Spatial transcriptomics (Nanostring GeoMX digital spatial profiling) with in silico cell type deconvolution and pathway analyses were employed on longitudinal biopsy samples from five patients across pre-treatment, on-treatment, and relapse. RESULTS: Of 43 participants exhibiting initial response to LIUD, 41 had follow-up data. Sixteen (39%) experienced relapse. Clinical factors associated with shorter response duration included younger age, initial diagnosis of G1EEC, lack of response at six months, premenopausal status, and Hispanic ethnicity (p<0.05), but only six-month response status remained a significant predictor in a multivariate model (p=0.023). LIUD increased abundance of NK cells (DMCP-counter score=46.13, FDR=0.004) and cytotoxic lymphocytes (DMCP-counter score=277.67, FDR=0.004), as well as lymphocyte cytotoxicity markers PRF1 (log2FC=1.62, FDR=0.025) and GZMA (log2FC=2.47, FDR=0.008). NK cells were reduced at relapse (DMCP-counter score=-55.96, FDR=0.02). Immune-related pathways (IFNα-response and TGFß-signaling) were enriched at relapse (FDR<0.05). IDO1 expression, reflecting immune exhaustion, was upregulated at relapse (FDR<0.05). CONCLUSIONS: Upfront resistance and relapse after initial response to LIUD for AH/G1EEC impacts nearly half of patients, remaining a major hurdle for non-surgical treatment of AH/G1EEC. Molecular studies evaluating longitudinal biopsies from a small cohort implicate immune mechanisms at relapse, including reversal of progestin-related immunomodulation and increased immune exhaustion.

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.

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.

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.

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.

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.

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.

Facilitated cascade testing (FaCT): a randomized controlled trial.

BACKGROUND: Identifying mutation-carrying relatives of patients with hereditary cancer syndromes via cascade testing is an underused first step in primary cancer prevention. A feasibility study of facilitated genetic testing of at-risk relatives of patients with a known pathogenic mutation demonstrated encouraging uptake of cascade testing. PRIMARY OBJECTIVE: Our primary objective is to compare the proportion of genetic testing of identified first-degree relatives of probands with a confirmed BRCA1/2 mutation randomized to a facilitated cascade testing strategy versus standard of care, proband-mediated, information sharing. STUDY HYPOTHESIS: We hypothesize that facilitated cascade testing will drive significantly higher uptake of genetic testing than the standard of care. TRIAL DESIGN: The FaCT (Facilitated Cascade Testing) trial is a prospective multi-institutional randomized study comparing the efficacy of a multicomponent facilitated cascade testing intervention with the standard of care. Patients with a known BRCA1/2 mutation (probands) cared for at participating sites will be randomized. Probands randomized to the standard of care group will be instructed to share a family letter with their first-degree relatives and encourage them to complete genetic testing. First-degree relatives of probands randomized to the intervention arm will receive engagement strategies with a patient navigator, an educational video, and accessible genetic testing services. MAJOR INCLUSION/EXCLUSION CRITERIA: Adult participants who are first-degree relatives of a patient with a BRCA1/2 mutation and have not had prior genetic testing will be included. PRIMARY ENDPOINT: Analyses will assess the proportion of first-degree relatives identified by the proband who complete genetic testing by 6 months in the intervention arm versus the control arm. SAMPLE SIZE: One hundred and fifty probands with a BRCA1/2 mutation will be randomized. Each proband is expected to provide an average of 3 relatives, for an expected 450 participants. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: January 2024. TRIAL REGISTRATION: NCT04613440.

Recommendations for Palliative and Hospice Care in NCCN Guidelines for Treatment of Cancer.

BACKGROUND: Integration of specialist palliative care into routine oncologic care improves patients' quality of life and survival. National Comprehensive Cancer Network (NCCN) cancer treatment guidelines are instrumental in standardizing cancer care, yet it is unclear how palliative and hospice care are integrated in these guidelines. In this study, we examined the frequency of occurrence of "palliative care" and "hospice care" in NCCN guidelines and compared between solid tumor and hematologic malignancy guidelines. MATERIALS AND METHODS: We reviewed all 53 updated NCCN Guidelines for Treatment of Cancer. We documented the frequency of occurrence of "palliative care" and "hospice care," the definitions for these terms if available, and the recommended timing for these services. RESULTS: We identified a total of 37 solid tumor and 16 hematologic malignancy guidelines. Palliative care was mentioned in 30 (57%) guidelines (24 solid tumor, 6 hematologic). Palliative care was mentioned more frequently in solid tumor than hematologic guidelines (median, 2 vs. 0; p = .04). Among the guidelines that included palliative care in the treatment recommendation, 25 (83%) only referred to NCCN palliative care guideline. Specialist palliative care referral was specifically mentioned in 5 of 30 (17%) guidelines. Only 14 of 24 (58%) solid tumor guidelines and 2 of 6 (33%) hematologic guidelines recommended palliative care in the front line setting for advanced malignancy. Few guidelines (n = 3/53, 6%) mentioned hospice care. CONCLUSION: "Palliative care" was absent in almost half of NCCN cancer treatment guidelines and was rarely discussed in guidelines for hematologic malignancies. Our findings underscored opportunities to standardize timely palliative care access across NCCN guidelines. IMPLICATIONS FOR PRACTICE: Integration of specialist palliative care into routine oncologic care is associated with improved patient outcomes. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology have an important role to standardize palliative care involvement for cancer patients. It is unclear how often palliative care referral is recommended in these guidelines. In this study involving 53 NCCN Guidelines for Treatment of Cancer, the researchers found that palliative care was not mentioned in over 40% of NCCN guidelines and was rarely discussed in guidelines for hematologic malignancies. These findings underscored opportunities to standardize timely palliative care access across NCCN guidelines.

Prospective phase II trial of levonorgestrel intrauterine device: nonsurgical approach for complex atypical hyperplasia and early-stage endometrial cancer.

BACKGROUND: The incidence of complex atypical hyperplasia and early-stage endometrioid endometrial cancer is increasing, in part owing to the epidemic of obesity, which is a risk factor tightly linked to the development of endometrial hyperplasia and cancer. The standard upfront treatment for complex atypical hyperplasia and early-stage endometrial cancer is hysterectomy. However, nonsurgical treatment of early-stage endometrial neoplasia may be necessary owing to medical comorbidities precluding surgery or desired future fertility. OBJECTIVE: This study aimed to evaluate the efficacy of the levonorgestrel intrauterine device to treat complex atypical hyperplasia and grade 1 endometrioid endometrial carcinoma. STUDY DESIGN: A single-institution, single-arm, phase II study of the levonorgestrel intrauterine device (52 mg levonorgestrel, Mirena) was conducted in patients with complex atypical hyperplasia or grade 1 endometrioid endometrial cancer. The primary endpoint was pathologic response rate at 12 months, including complete or partial response. Quality of life and toxicity were assessed. Molecular analyses for proliferation markers, hormone-regulated genes, and wingless-related integration site pathway activation were performed at baseline and 3 months. RESULTS: A total of 57 patients were treated (21 endometrial cancer, 36 complex atypical hyperplasia). The median age was 48.0 years, and the median body mass index was 45.5 kg/m2. Of the 47 evaluable patients, 12-month response rate was 83% (90% credible interval, 72.7-90.3)-37 were complete responders (8 endometrial cancer; 29 complex atypical hyperplasia), 2 were partial responders (2 endometrial cancer), 3 had stable disease (2 endometrial cancer; 1 complex atypical hyperplasia), and 5 had progressive disease (3 endometrial cancer; 2 complex atypical hyperplasia). After stratification for histology, the response rate was 90.6% for complex atypical hyperplasia and 66.7% for grade 1 endometrioid endometrial cancer. Notably, 4 patients (9.5%) experienced relapse after the initial response. Adverse events were mild, primarily irregular bleeding and cramping. Quality of life was not negatively affected. At 3 months, exogenous progesterone effect was present in 96.9% of responders (31 of 32) vs 25% of nonresponders (2 of 8) (P=.001). Nonresponders had higher baseline proliferation (Ki67) and lower dickkopf homolog 3 gene expression than responders (P=.023 and P=.030). Nonresponders had significantly different changes in secreted frizzled-related protein 1, frizzled class receptor 8, and retinaldehyde dehydrogenase 2 compared with responders. CONCLUSION: The levonorgestrel intrauterine device has a substantial activity in complex atypical hyperplasia and grade 1 endometrioid endometrial cancer, with a modest proportion demonstrating upfront progesterone resistance. Potential biomarkers were identified that may correlate with resistance to therapy; further exploration is warranted.

Using Continuous Glucose Monitoring to Motivate Physical Activity in Overweight and Obese Adults: A Pilot Study.

BACKGROUND: Regular physical activity (PA) is associated with a lower risk of several types of cancers. However, two-thirds of overweight/obese adults are not sufficiently active; this, in combination with the unfavorable effect of excess body weight, puts them at a greater risk for cancer. One reason that these individuals do not engage in enough PA may be their lack of motivation to change their current behavior due to the perception of putting in effort for possible future gain without obvious short-term benefits. There is a need for innovative ways to help individuals recognize the immediate health benefits of PA and thus increase their motivation. METHODS: This pilot intervention tested a PA education module that included a one-on-one counseling session highlighting the acute effects of PA on glucose patterns, followed by a 10-day self-monitoring period with a continuous glucose monitor (CGM) and a Fitbit tracker. Participants rated the acceptability of the education module on a 5-point Likert scale and completed surveys assessing stages of change for motivational readiness. RESULTS: Nineteen overweight/obese adults (84% female) completed the study. Participants gave high ratings to the counseling session for improving their PA-related knowledge (mean = 4.22), increasing motivation (mean = 4.29), and providing personally relevant information (mean = 4.35). The summary acceptability scores for the self-monitoring period were 4.46 for CGM and 4.51 for Fitbit. Participants reported a significant decrease in the precontemplation stage and an increase in the action stage (P < 0.05). CONCLUSIONS: CGM is a feasible tool for PA interventions. IMPACT: Information from CGM could be used as biological-based feedback to motivate PA.See all articles in this CEBP Focus section, "Modernizing Population Science."

Phase I study of the PARP inhibitor talazoparib with radiation therapy for locally recurrent gynecologic cancers.

PARP inhibitors have been shown to radiosensitize tumor cells in both in vitro and in vivo studies. This is a phase I study that aims to determine the safety, tolerability, and maximally tolerated dose of talazoparib, a PARP inhibitor, when delivered concurrently with radiotherapy in women with recurrent gynecologic cancers.

Knowledge matters and empowers: HPV vaccine advocacy among HPV-related cancer survivors.

PURPOSE: To describe knowledge about human papillomavirus (HPV), HPV-related care behavior, and advocacy intent (e.g., vaccine recommendation and willingness to become an advocate for vaccination) and to investigate associations between knowledge, HPV-related care behavior, and advocacy intent among HPV-related cancer survivors. METHODS: A cross-sectional online survey was offered through Qualtrics to HPV-related cancer survivors who were either volunteers at a cancer center or patients of survivorship clinics. RESULTS: A total of 200 survivors responded. Only 33.2% of respondents reported knowing their cancer was HPV-related and 56.8% reported HPV vaccine is safe. Participants who knew that their cancer was caused by HPV were more likely to have vaccinated their children (p < .001). Also, participants who knew that the vaccine is safe were more willing to recommend the vaccine (p < .001), to be a peer mentor for others with HPV-related cancers (43.2% vs. 14.0%, p < .001), and to act as an advocate for increasing vaccination rates (44.1% vs. 24.4%, p = 0.01). Finally, survivors who were aware of the vaccine's effectiveness in decreasing precancerous lesions were more likely to recommend the vaccine (45.7% vs. 12.0%, p = .002). CONCLUSIONS: Raising survivor awareness of the link between HPV and cancer and HPV vaccine safety may increase their willingness to serve as powerful opinion leaders and peer mentors to promote HPV vaccination. Providers may take the simple step of informing patients that their cancer is HPV-related and HPV vaccine is safe to increase the number of informed and empowered survivors.