bluuebunny/crossref_metadata_2025 huggingface dataset:
Disparities in end-of-life inpatient care received by patients with metastatic cancer, 2010 to 2017.
Authors: Deeb Stephanie , Chino Fumiko , Diamond Lisa , Tao Anna , Aragones Abraham , Shahrokni Armin , Yerramilli Divya , Gillespie Erin F. , Tsai C. Jillian
Published: June 2021

12008

Background: Many patients with metastatic cancer receive high-cost, low-value care near the end of life. We examined interventions during terminal hospitalizations for patients with metastatic cancer to identify those with high likelihood of receiving futile care. Methods: A retrospective population-based cohort analysis of encounter-level data from the National Inpatient Sample was conducted, including records from 2010-2017 for patients ages ≥18 with metastatic cancer who died during hospitalization. We fit multivariable binomial logistic regression models to examine associations between exposures, including patient demographics, and the main outcome of aggressive, low-value, and high-cost medical care (Table). Results: Out of 321,898 hospitalizations among patients with metastatic cancer, 21,335 (6.6%) were terminal. Of these, 65.9% were white, 14.1% Black, 7.5% Hispanic, 58.2% were insured by Medicare or Medicaid, and 33.2% were privately insured. Overall, 63.2% were admitted from the Emergency Department (ED), 4.6% received systemic therapy, and 19.2% received invasive ventilation. Median total charges were $43,681. Black patients and publicly insured patients had higher likelihoods of admission from the ED and receiving ventilation, as well as higher total charges; similar trends emerged among patients of Asian race and Hispanic ethnicity. Patients hospitalized at urban teaching hospitals had higher likelihoods of receiving systemic therapy, ventilation, and incurring higher total charges (Table). Conclusions: Metastatic cancer patients of racial and ethnic minority groups and those with Medicare or Medicaid were more likely to receive low-value, aggressive interventions at the end of life. Further studies are needed to determine the underlying causes of these disparities in order to implement prospective interventions and advance appropriate end-of-life care.[Table: see text]
Predicting dying from lung cancer: Urine metabolites predict the last weeks and days of life.
Authors: Coyle Seamus , Chapman Elinor , Baker James , Coleman Hannah , Norman Brendan , Hughes David , Davison Andrew , Mason Stephen , Boyd Mark , Ellershaw John E , Probert Chris
Published: June 2021

12030

Background: Recognising dying is difficult. We believe there is a predictable biological process to dying and previously demonstrated that urinary volatile organic compounds change in the last weeks and days of life of patients with lung cancer. We further analysed our urine samples using a different metabolomic platform, Liquid Chromatography QTOF Mass Spectrometry (LC-QTOF-MS). Methods: We prospectively collected urine samples from people with lung cancer many of whom were in the last 4 weeks of life. The samples were analysed using a LC-QTOF-MS. Volcano plots identified metabolites that changed 2 fold for different time periods (0-28 days, 0-14 days, 0-7days, 0-5 days and 0-3 days). All metabolites were also grouped into weeks. A One-way ANOVA between the groups identified metabolites that changed significantly. Cox regression with Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression was used to analyse the data and create a statistical model. Results: 234 urine samples from 112 patients were analysed by LC-QTOF-MS. 90 metabolites were identified that increase or decrease in the last weeks or days. Pathway Analysis using MetaboAnalyst demonstrated a number of biochemical pathways affected during different time intervals; 0-2 weeks and 0-3 days before death. Cox LASSO regression analysis was performed for the last 28 days. A model using 21 metabolites, prognosticates for each day in the last 28 days with high AUC values (88-90%). Patients can be categorized into high, medium and low risk of death. A Kaplan-Meier survival analysis demonstrated the groups were well separated. Conclusions: The results confirm urine metabolites predict when people with lung cancer are in the last weeks and days of life. Our model, using 21 metabolites, prognosticates for each of the last 28 days of life and is approximately 88% -90% accurate. This is the only model able to prognosticate for the last week or days of life.
Incidence and risk factors for euthanasia or physician-assisted suicide in oncology patients: A systematic review.
Authors: Liu Wei , Liu Luke , Liu Alissa , Jia Sang , Liu Tony , Boldt Gabriel , Qu Melody , Ball Ian
Published: June 2021

12034

Background: In a growing number of jurisdictions, oncology patients may choose euthanasia or physician-assisted suicide (EPAS). A 2016 systematic review reported that 75% of U.S. and over 70% of Dutch and Belgian EPAS cases involved oncology patients. In the Netherlands and Belgium, the percentage of deaths among oncology patients via EPAS has been increasing. We investigated the incidence and risk factors for EPAS and EPAS requests in oncology patients. Methods: A systematic review was performed following PRISMA guidelines. PubMed, Embase and Cochrane databases were searched for articles from January 2000 to April 2020. Search terms were related to suicide, euthanasia, assisted dying, assisted death, right to die, mercy killing, and cancer. Eligible studies reported incidence and/or risk factors for EPAS/EPAS request based on at least 50 oncology patients. Eligibility for inclusion was independently reviewed by two authors, with discrepancies adjudicated by a third. Data obtained included: study type, country, cancer diagnosis, number of eligible patients, inclusion criteria, follow-up length, incidence of EPAS or EPAS request, and odds ratios (OR) for risk factors for EPAS and EPAS request. ORs and p values were extracted from studies whenever possible and were otherwise calculated based on the data provided using chi-squared test. Results: The search strategy identified 6519 results. 25 abstracts were selected for full-text review and 10 studies were included for analysis. All studies reported incidence of EPAS/EPAS request and 6 studies reported risk factors for EPAS/EPAS request. Six studies were from the Netherlands, 3 from Belgium, and 1 from Canada. Inclusion period for studies spanned from 1996 to 2018. Half of the included studies were prospectively conducted. Incidence of EPAS in cancer patients ranged from 7% to 15% and EPAS requests ranged from 8% to 27%. Factors significantly associated (p<0.05) with EPAS or EPAS request in any study are shown in the Table. Conclusions: Up to 15% of oncology patients choose euthanasia or physician-assisted suicide. Potentially modifiable symptoms including severe nausea, vomiting, and pain are significantly associated with EPAS in oncology patients.[Table: see text]
Inequity in location and quality of death of advanced cancer patients by immigrant status.
Authors: Tergas Ana Isabel , Shen Megan Johnson , Prigerson Holly Gwen , Dinicu Andreea , Neugut Alfred I. , Wright Jason Dennis , Hershman Dawn L. , Maciejewski Paul K.
Published: June 2021

12036

Background: Most cancer patients prefer to die at home, a location associated with better quality of death (QoD) and caregiver outcomes. A number of studies demonstrate disparities in end-of-life (EoL) care among immigrant vs non-immigrant populations in the U.S. This study aims to evaluate how immigrant status affects location and QoD among patients with advanced cancer in the U.S. Methods: Data were derived from Coping with Cancer, a federally funded multi-site prospective study of advanced cancer patients and caregivers. The analytic sample of patients who died during the study observation period was weighted (Nw=308) to reduce statistically significant sociodemographic differences between immigrant (Nw=49) and non-immigrant (Nw=259) groups. Immigrant status was determined by patient self-report. Primary outcomes were location of death (intensive care unit, hospital, nursing home, inpatient hospice, home), death at preferred location (yes/no, as per caregiver report in post-mortem interview), and poor QoD (composite score of post-mortem caregiver ratings for patient psychological distress, physical distress, and quality of life in the last week of life). Results: As compared to non-immigrants, immigrants were more likely to die in a hospital as opposed to home [AOR 3.33; 95% CI (1.65-6.71); p=0.001] and less likely to die where they preferred [AOR 0.42, 95% CI (0.20-0.90); p=0.026]. As shown in Table, values-inconsistent aggressive EoL care mediated the effect of immigrant status on death at the patient s preferred location. Further, immigrants were more likely to have poor QoD [AOR 5.47; 95% CI (2.70-11.08); p<0.001]. In particular, among patients who preferred symptom-directed, comfort EoL care, immigrants as opposed to non-immigrants were more likely to have poor QoD [AOR 9.53, 95%CI (4.05-22.40); p<0.001]. Conclusions: Immigrants, as compared to non-immigrants, are more likely to die in hospital settings, less likely to die at their preferred location, and more likely to have poor QoD. These findings are consistent with previously described inequities in EoL care of immigrants and highlight the importance of determining the potential causes and solutions to ensure immigrants receive values-congruent care.[Table: see text]
Impact of the G8 score on the outcome of a cohort of elderly patients with solid or hematological malignancies.
Authors: Biello Federica , Mennitto Alessia , Mahmoud Abdurraouf , Platini Francesca , Ferrante Daniela , Bruna Riccardo , Patriarca Andrea , Nicolosi Maura , Ferrara Eleonora , Maggiora Paola maria , Rua Alessia , Deambrogi Clara , Pinato David James , Krengli Marco , Gaidano Gianluca , Gennari Alessandra
Published: June 2021

12038

Background: Elderly cancer patients may have important benefits from innovative treatments. However, they are often barred from clinical trials because of highly selective eligibility criteria, or due to biased and subjective physician standpoints including reluctance to invite elderly patients and fear of excessive toxicity. Indeed, geriatric assessment has been increasingly recognized as predictive and prognostic instrument to detect frailty in older adults with cancer. In this perspective, the G8 score is a simple and reproducible instrument to identify elderly patients who should undergo full geriatric evaluation. The aim of our study was to evaluate the impact of frailty assessment by the G8 screening tool on the outcome of onco-hematological patients. Methods: Between January 2017 and December 2020 the G8 screening tool was administered to patients, aged >65 years, referred to our center for solid and hematological malignancies. G8 score was assessed at the time of first access. The primary endpoint was overall survival. Multivariate analysis was performed according to G8 score, age, tumor type, stage and treatment. Results: In the observation period, 430 patients were screened for frailty by G8; median age was 77 years (65-92); of these, 331 (77%) had a G8 score <14. Pts with solid tumors were 310 (72%), 175 (57%) of whom had metastatic diseases; 227 (73%) had a G8 score <14. Pts with hematological malignancies were 120 (28%), 100 (83%) of whom had a G8 score <14. Systemic therapy was administered to 336 patients (78%). At a median follow up of 7.2 months (range 1 to 52) 101 pts (24%) were dead. Median overall survival (mOS) was 27 months (1-52+).Patients with solid tumors, classified as frail by a G8 score <14 had a 3-fold risk of death compared with those with G8 > 14 (OR 3.26, CI 95 1.5-7.2, p = 0.003). Conversely, this increased risk was not observed in hematological malignancies (OR 1.4, CI 95 0.4-4.6, p = 0.57). By multivariate analysis, G8 score was associated with a worse prognosis only in patients with solid tumors. Conclusions: Our analysis suggest that elderly frail patients with solid tumors have a significantly increased risk of death as compared to elderly fit patients. Conversely, no impact of frailty, as assessed by a G8 score < 14, was evident in elderly patients with hematological malignancies.
Brief relaxation training effects on long-term endocrine therapy adherence among women with breast cancer.
Authors: Ream Molly , Walsh Emily A , Jacobs Jamie M. , Schaefer Solle Natasha , Safren Steven A. , Antoni Michael
Published: June 2021

12061

Background: Despite life-saving potential, many women struggle to adhere to adjuvant endocrine therapy (AET) for their early-stage, hormone receptor-positive breast cancer. Prior research has demonstrated that emotional distress is a barrier to AET adherence. The current study aimed to test the long-term effects of two 5-week post-surgical group-based stress management interventions, cognitive behavioral therapy (CBT) and relaxation training (RT), versus an attention-matched health education (HE) control on AET adherence at long-term follow-up. Methods: We conducted long-term follow-up (median = 8 years, range = 7-11 years) of a cohort of women who enrolled in a randomized controlled trial of CBT vs. RT vs. HE shortly after surgery for stage 0-3 breast cancer.We measuredadherence with the Endocrine Therapy Medication Usage Questionnaire (ETMUQ) given at long-term follow-up. First, we established adherence factors on the ETMUQ via confirmatory factor analysis. We then used structural equation modeling to regress these factors on study arm, controlling for patient age, stage of disease, and treatments received (chemotherapy/radiation). Results: The sample was predominately middle-aged ( M= 54.81, SD= 10.19), White (41.5%) and Hispanic (42.2%), partnered (62.2%) with stage 1 (57.0%) or stage 2 (25.9%) disease. Of the women who completed long-term follow-up (N = 59, 44.7% of original sample); more than half (n = 30; 50.8%) reported having at least some problems with adherence. There was an effect of intervention group on adherence, such that women receiving RT (n = 15) had significantly better adherence than those receiving CBT (n = 20) on the factor measuring Forgetfulness/Inconsistency ( B(SE) =.57 (.34), p=.001), and marginally better adherence than those receiving CBT on the factor measuring Intentional Nonadherence ( B(SE) =.60 (.33), p =.062). There was no such effect when comparing RT or CBT to HE (n = 24). Conclusions: Women receiving RT were less likely to forget to take their AET and marginally less likely to intentionally miss doses of AET in the long-term compared to women receiving CBT. Future research could investigate the mechanism by which RT may improve adherence. For example, RT may reduce somatic symptoms related to AET or improve a patients’ self-efficacy to cope with these symptoms thereby reducing intentional non-adherence. In addition, RT may improve patients’ attention and awareness leading to less forgetfulness. Clinical trial information: NCT02103387.
Patient preferences for cancer survivorship care: Results of an online survey.
Authors: Attai Deanna J. , Katz Matthew S. , Streja Elani , Hsiung Jui-Ting , Zavaleta Beverly A , Nekhlyudov Larissa
Published: June 2021

12064

Background: Nearly 17 million cancer survivors live in the United States. Workforce shortages are projected to diminish the number of available medical oncologists (MOs) to care for newly diagnosed patients with cancer and for the growing number of cancer survivors. Models of survivorship care include oncologist-led, primary care-led, and shared care approaches. Recent proposals recommend a risk-stratified approach to care, guided by individual and cancer-specific factors, but there is little evidence regarding patient preferences for non-oncologist survivorship care. Methods: We developed a survey in partnership with patient advocates. The primary endpoints were patient-reported comfort with survivorship care by a primary care provider (PCP) or in a dedicated survivorship clinic. We distributed the survey to online, cancer-specific patient communities from June to August 2020. Logistic regression analyses were adjusted for patient age, race and ethnicity, insurance, and cancer type and stage. Results: Of 1166 responses, 975 surveys were complete and available for analysis. Respondents were primarily women (91%), white (92%), and US residents (73%); 78% had a college or graduate degree. Two-thirds had private insurance. Thirty-six different cancer types were reported; 61% of respondents had breast cancer, and 25% were treated for more than one type of cancer. Most respondents (83%) had nonmetastatic disease, 74% reported experiencing late effects of cancer therapy, and almost all (93%) had a PCP. Only 21% of respondents were comfortable seeing a PCP (versus MO) for survivorship care, including cancer follow-up, side effect management, and monitoring for recurrence or progression. About half (55%) were comfortable with follow-up in a survivorship clinic instead of with their MO. Multivariable analyses showed no significant associations between age, race or ethnicity, insurance, cancer type, or stage at diagnosis and comfort with follow-up care from a PCP or in a survivorship clinic. In analyses restricted to the 439 respondents with a history of early-stage breast cancer, the 239 (54%) who were within 1 to 5 years of diagnosis were less comfortable with PCP versus MO follow-up, compared with the 52 (12%) who were > 15 years from diagnosis (OR 0.40; 95% CI 0.20–0.75; p= 0.004). In this sub-analysis, time from diagnosis was not associated with comfort being seen in a survivorship clinic. Conclusions: In our study, most patients with a history of cancer were not comfortable receiving follow-up care from their PCP. It is often recommended that survivors of early-stage breast cancer transition to primary care for follow-up and surveillance, but our study revealed comfort with this approach only many years after diagnosis. While both PCP survivorship training and patient confidence in PCP follow up is needed, preferences of cancer survivors should be considered in designing new models of survivorship care.
Neuropsychiatric disorders in hospitalized patients undergoing chimeric antigen receptor T-cell therapy for aggressive lymphomas and acute lymphoblastic leukemia: A national study.
Authors: Emole Josephine , Lawal Odunayo Susan , Lupak Oleksandra , Udo Itoro
Published: June 2021

12118

Background: Chimeric antigen receptor T cell therapy (CART) has shown efficacy in acute lymphoblastic leukemia (ALL), diffuse large B cell lymphoma (DLBCL), and primary mediastinal B cell lymphoma (PMBCL). While neurological toxicities of CART are known, neuropsychiatric disorders (NPD) in patients undergoing CART has not been well described. Our study assessed the prevalence of NPD in hospitalized patients (pts) undergoing CART, and explored association of NPD with clinical variables. Methods: Using the National Inpatient Sample database, we conducted a retrospective study of pts with ALL, DLBCL and PMLCL aged ≥ 18 years who underwent CART in 2018. Hospitalizations were selected using International Classification of Disease, Tenth Revision (ICD-10) codes. NPD of interest included anxiety, depression, adjustment disorder, insomnia, psychosis, dementia, bipolar disorder. Delirium was not included in the inventory of NPD since delirium is a neurotoxicity of CART, and inclusion of delirium as NPD would confound results. Patient, disease, and CART complications were extracted from hospitalization records. Regression analyses were used to assess association of NPD with clinical variables. Results: 945 CART procedures met the inclusion criteria (56 % males and 60% Caucasians). Majority of CART (88%) were performed for DLBCL and PMBCL. NPD was diagnosed in 31 % of pts. Anxiety was the most common NPD, followed by insomnia and depression. ALL pts were more likely to have NPD compared to pts with lymphoma (52% versus 28%, p<0.05). More females had NPD compared to males (40% versus 25%, p<0.05). Univariable analysis showed association of NPD with female gender [Odds ratio (OR)=2.03, 95% CI = 1.05-3.93] and ALL (OR=2.76, 95% CI = 1.03-7.43). In a multivariable model, NPD was associated with ALL (OR =3.57, 95% CI= 1.01-12.55), while the association of NPD with female gender was less certain (OR =1.41, 95% CI=0.73 - 2.74). There was no association between NPD and mortality, neurotoxicity, systemic inflammatory response syndrome or hemophagocytic lymphohistiocytosis. Conclusions: One in every 3 pts who underwent in-hospital CART for ALL or aggressive B cell lymphoma in 2018 had comorbid NPD. Females and ALL pts were at higher risk for NPD. As CART pts transition into longer follow up and survivorship, ours and similar results should inform the planning and allocation of psychosocial services.
Association of use of remote patient monitoring (RPM) with reduced hospitalizations in cancer patients with COVID-19.
Authors: Pritchett Joshua , Desai Aakash , Borah Bijan J , Xie Zhuoer , Saliba Antoine N , Leventakos Konstantinos , Coffey Jordan , Pearson Kristin , Speicher Leigh , Orenstein Robert , Virk Abinash , Ganesh Ravindra , Paludo Jonas , Haddad Tufia C.
Published: June 2021

1503

Background: Patients with cancer and COVID-19 are at risk for poor clinical outcomes. An established multi-site remote patient monitoring (RPM) service was rapidly adapted to support a novel, interdisciplinary COVID-19 program for outpatient management of patients at high-risk for severe illness. The goal of this study was to assess the impact of the RPM program on clinical outcomes and acute care utilization in cancer patients diagnosed with COVID-19. Methods: This is a cross-sectional analysis following a multi-site prospective observational study performed at Mayo Clinic Cancer Center (MCCC). All adult patients with active cancer – defined as currently receiving cancer-directed therapy or in recent remission on active surveillance – and PCR-confirmed SARS-CoV-2 infection between March 18 and July 31, 2020 were included. RPM was comprised of in-home technology to assess symptoms and physiologic data with centralized nurse and physician oversight. Results: During the study timeframe 224 cancer patients were diagnosed with COVID-19 at MCCC. Initial management included urgent hospitalization (within 48 hours of diagnosis) in 34 patients (15%). Of the remaining 190 patients (85%) initially managed in the outpatient setting, those who did not receive RPM were significantly more likely to experience hospitalization than those receiving RPM (OR 3.6, 95% CI 1.036 to 12.01, P = 0.044). Following balancing of patient characteristics by inverse propensity weighting, rates of hospital admission for RPM and non-RPM patients were 3.1% and 11% respectively, implying that RPM was associated with an 8% reduction in hospital admission rate (-0.077; 95% CI: -0.315 to -0.019, P = 0.009). Use of RPM was also associated with lower rates of prolonged hospitalization, ICU admission, and mortality, though these trends did not reach statistical significance. Conclusions: In the midst of a global pandemic associated with inpatient bed, ventilator, and PPE shortages, the RPM program provided an effective strategy for outpatient clinical management and was associated with decreased rates of hospitalization, ICU admission, and mortality in cancer patients with COVID-19. This care model enabled simultaneous opportunity to mitigate the increased risks of exposure, transmission, and resource utilization associated with conventional care.
Augmenting machine learning algorithms to predict mortality using patient-reported outcomes in oncology.
Authors: Parikh Ravi Bharat , Schnall Jill , Liu Manqing , Gabriel Peter Edward , Chivers Corey , Draugelis Michael , Ferrell Will , Lerman Caryn , Bekelman Justin E. , Chen Jinbo
Published: June 2021

1510

Background: Machine learning (ML) algorithms based on electronic health record (EHR) data have been shown to accurately predict mortality risk among patients with cancer, with areas under the curve (AUC) generally greater than 0.80. While patient-reported outcomes (PROs) may also predict mortality among patients with cancer, it is unclear whether routinely-collected PROs improve the predictive performance of EHR-based ML algorithms. Methods: This cohort study included 8600 patients with cancer who had an outpatient encounter at one of 18 medical oncology practices in a large academic health system between July 1st, 2019 and January 1st, 2020. 4692 (54.9%) patients completed assessments of symptoms, performance status, and quality of life from the PRO version of the Common Terminology Criteria for Adverse Events and the Patient-Reported Outcomes Measurement Information System Global v.1.2 scales. We hypothesized that ML models predicting 180-day all-cause mortality based on EHR + PRO data would improve AUC compared to ML models based on EHR data alone. We assessed univariate and adjusted associations between each PRO and 180-day mortality. To train the EHR-only model, we fit a Least Absolute Shrinkage and Selection Operator (LASSO) regression using 192 EHR demographic, comorbidity, and laboratory variables. To train the EHR + PRO model, we used a two-phase approach to fit a model using EHR data for all patients and PRO data for those who completed assessments. To test our hypothesis, we compared the bootstrapped AUC, area under the precision-recall curve (AUPRC), and sensitivity at a 20% risk threshold for both models. Results: 464 (5.4%) patients died within 180 days of the encounter. Decreased quality of life, functional status, and appetite were associated with greater 180-day mortality (Table). Compared to the EHR-only model, the EHR + PRO model significantly improved AUC (0.86 [95% CI 0.85-0.86] vs. 0.80 [95% CI 0.80-0.81]), AUPRC (0.40 [95% CI 0.37-0.42] vs. 0.30 [95% CI 0.28-0.32]), and sensitivity (0.45 [95% CI 0.42-0.48] vs. 0.33 [95% CI 0.30-0.35]). Conclusions: Routinely collected PROs augment EHR-based ML mortality risk algorithms. ML algorithms based on EHR and PRO data may facilitate earlier supportive care for patients with cancer. Association of PROs with 180-day mortality.[Table: see text]
Daily step counts to predict hospitalizations during chemoradiotherapy for head and neck cancer.
Authors: Izmailova Elena S. , Cohen Andrew , Kabarriti Rafi , Eichler Jeremy , Huang Chengrui , Ohri Nitin
Published: June 2021

1571

Background: Wearable activity trackers could provide useful data for managing cancer patients with respect to treatment selection, toxicity monitoring, and implementation of supportive care measures. Here, we seek to evaluate the association between daily step counts and hospitalizations in a cohort of patients with head and neck cancer (HNC). Methods: This analysis consists of patients enrolled in one of three prospective trials involving activity monitoring (NCT02649569, NCT03115398, NCT03102229) during chemoradiation. Study subjects were asked to wear a commercial fitness tracker continuously during the therapy. ECOG performance status (PS) was assessed at baseline, and quality of life (QoL) EORTC QLQ-C30 questionnaires were completed weekly. Multivariable Cox regression models with time-dependent covariates (average step count over the past 3 days, most recent QoL score) and time-fixed covariates (age, sex, baseline PS, study number, baseline tumor volume, and treatment setting [definitive versus postoperative]) were used to identify predictors of first hospital admission during the chemoradiotherapy course. In addition to the Cox regression models, linear mixed models were fitted with daily step count as the dependent variable to examine its relationship with certain independent variables including age, sex, weekend status, days after treatment initiation, and study number. Results: Sixty-six HNC patients who received chemoradiotherapy between 2015 and 2019 were included in the analysis. Median age was 60 (range: 27-88). 47% of patients had ECOG PS score 0, 47% ECOG score 1, and 6% ECOG score 2. 29% of patients had HPV-positive oropharyngeal tumors, and the most common other tumor subsites were larynx (27%), and nasopharynx (12%). The Cox regression survival model demonstrated a 26% reduction in the short-term hospitalization risk for every 1000 daily steps (averaged over the past 3 days, hazard ratio 0.74; 95% confidence interval (CI) 0.55-0.98, p = 0.0367). Hospitalizations were not significantly associated with most recent QoL or baseline ECOG PS. Additionally, according to the linear mixed model results, daily step count was not associated with age (p = 0.8048). Study subjects moved less on weekends (on average 245 fewer steps on weekends than weekdays, 95% CI 134-357, p < 0.0001). Also, an increase in most recently measured ECOG PS was associated with a decrease in daily step count (167 fewer steps for every increase in ECOG PS, 95% CI -289 to -45, p < 0.0072). Conclusions: Daily step counts are a dynamic predictor of hospitalizations in patients undergoing chemoradiotherapy for head and neck cancer. Interventional studies are needed to demonstrate feasibility of leveraging physical activity data to optimize supportive care during cancer therapy and enhance cancer care quality. Clinical trial information: NCT02649569, NCT03115398, NCT03102229.
Implementation of insurance marketplaces and changes in diagnosis stage in low-income cancer patients.
Authors: Kim Uriel , Koroukian Siran M. , Stange Kurt C , Spilsbury James , Rose Johnie
Published: June 2021

1576

Background: Millions of low-income Americans gained insurance coverage through Medicaid expansion and the “Marketplaces” of the Affordable Care Act (ACA). How Marketplaces have specifically improved cancer outcomes among these individuals is unclear. Thus, we examined changes in insurance status and diagnosis stage following the ACA among low-income (139-250% of the Federal Poverty Level [FPL]), non-elderly patients (ages 30-64). Methods: In Ohio’s cancer registry, we identified patients diagnosed with one of the top 16 cancers before (2011-2013, “Pre-ACA”) and after (Q3 of 2014-2016, “Post-ACA”) the implementation of the ACA’s insurance Marketplaces and either had private insurance or no insurance. Low-income patients were isolated using a novel, geographically-driven approach called probability weighting. Results: The uninsured percentage dropped from 12.9% to 4.9% between the Pre- and Post-ACA periods in the study sample (N = 10,747). An estimated 11.1% of individuals had Marketplace insurance Post-ACA. A significant but modest Post-ACA (versus Pre-ACA) shift toward non-metastatic disease was identified (Adjusted Odds Ratio [AOR]: 0.95, 95%CI: 0.90-0.99). The largest site-specific shifts were observed for thyroid (AOR: 0.50, 95%CI: 0.30-0.83) and ovarian (AOR: 0.74, 95%CI: 0.58-0.93) cancers. In a control analysis of wealthier (400%+ FPL), privately insured individuals, no significant shifts were identified (AOR: 0.97, 95%CI: 0.92-1.02). Conclusions: This is the first study to show an effect in cancer stage at diagnosis from the Affordable Care Act’s Insurance Marketplaces. We found that the Marketplaces greatly reduced the number of low-income, uninsured cancer patients, translating to significant improvements in cancer stage at diagnosis. As policy makers contemplate modifications to the ACA, they should carefully consider the impact of those changes on the highly vulnerable population of low-income cancer patients.
Patterns of telehealth utilization during the COVID-19 pandemic and preferences for post-pandemic telehealth use: A national survey of oncology clinicians.
Authors: Manz Christopher , Baxter Nancy N. , duPont Nefertiti C. , Markham Merry Jennifer , Drumheller Caitlin , Durakovic Lela , Kennedy Angela ,   ASCO Telehealth Disparities Taskforce
Published: June 2021

1580

Background: Rarely used in routine practice pre-pandemic, telehealth utilization for cancer care rose significantly during the COVID-19 pandemic. Increased familiarity with telehealth has led to calls to continue its use after the pandemic ends. Yet national patterns of oncology telehealth utilization by visit type, preferences for telehealth use post-pandemic and barriers to telehealth for patients with cancer have not been described. Methods: 9,336 survey invitations were emailed to US-based ASCO members who have agreed to receive communications. Survey distribution was equally divided over five US regions, and practice type (e.g., academic, community) was reflective of ASCO membership proportions. The survey was open and data collected from January 4-28, 2021. Non-respondents received two reminder emails at week intervals. Analysis is descriptive. Results: 200 respondents completed the survey (2%). Respondents were 72% medical oncologists, 66% urban, 64% academic-affiliated, and from 42 states. 99% currently offered telehealth. 63% used telehealth for <=30% of all patient visits in the last 30 days; 18% used telehealth for more than half of visits. Telehealth utilization varied by visit type (table). 64% reported that the care delivered in telehealth visits was similar quality to in-person visits (29% worse). Assuming no regulatory or financial barriers to telehealth use after the pandemic, 92% would like to use telehealth for at least some visit types; only 8% prefer not to use telehealth. 20% would like to use telehealth for all visits types, and 64%, 54%, 33% and 17% would like to use telehealth for survivorship, symptom management, evaluation of patients receiving treatment and new patient visits, respectively (multiple selections allowed). Major barriers to telehealth were lack of patient access to technology (reported by 81%), limited patient technological proficiency (80%), language barriers (45%), uncertainty about future reimbursement (41%) and lack of administrative resources to support clinicians (33%). 68% agreed that the barriers increase cancer care disparities. Conclusions: Telehealth utilization was widespread during the COVID pandemic and varied by visit type. Most respondents plan to use telehealth in the future, but report barriers to continued use that worsen disparities.[Table: see text]
Improving cancer patient care with a digital telemonitoring platform: The ConnectPatienToDoctor study.
Authors: Helissey Carole , Duverger Claire , Vanquaethem Hélène , Meghiref Yasmine , Parnot Charles
Published: June 2021

1581

Background: During COVID19 pandemic, clinicians have had to face two challenges in an unprecedented context: ensuring continuity of patient care for a disease that involves a life-threatening prognosis while reducing patients' vulnerability to this virus. The ConnectPatientToDoctor study aimed to evaluate a connected telemonitoring platform, Cureety, in cancer patient care. Patients and Methods: This prospective study was conducted at the Military Hospital Bégin. Each cancer patient was allowed to respond to a personalized symptomatology questionnaire based on CTCAE v.5.0, and personalized to their pathology and treatment. An algorithm evaluated the health status of the patient based on the reported adverse events and provided adapted recommendations. The calculated score allows to classify the patient into four different levels: (1) Correct State (green) (2) Compromised State (yellow) (3) State to be monitored (orange) (4) Critical State (red) In the case of orange or red classification, the patient was invited to call the hospital. In case of green or yellow classification, the patient received therapeutic advice set by the doctor, for each of the adverse events reported. The primary endpoint was to assess the feasibility of monitoring cancer patient with the connected platform. The secondary endpoint was to assess patient and caregivers’ satisfaction. Results: There were 108 patients included in the program between July 1st, 2020 and January 31st, 2021. The median age was 70 and 77% presented a metastatic stage. The most represented cancer was prostate (50%), followed by lung (24%) and breast (15%). Overall, 1864 questionnaires were completed by the patients, resulting in 543 yellow alerts and 133 orange or red alerts. More than 60% of the alerts was managed through outpatient care or with a rapid intervention to resolve the adverse events. On a satisfaction scale from 1 to 10, where 10 was the highest, 72% of the patients responded with a 9 or 10. And all caregivers were satisfied because they could offer a better care, prioritize care, and save time. Conclusions: Participants in ConnectPatientToDoctor study reported that they had a clear benefit from using a connected platform to monitor their treatment. Patients felt less isolated and felt that they benefited from personalized care. This solution makes it possible to streamline the patient care process.[Table: see text]
Changes in the blood-brain barrier properties in vitro after treatment with sera from breast cancer patients with primary cancer and visceral, bone or cerebral metastases.
Authors: Curtaz Carolin Julia , Constanze Schmitt , Meybohm Patrick , Wöckel Achim , Burek Malgorzata
Published: June 2021

2026

Background: The progression of brain metastases during breast cancer correlates with poor overall survival, but also with a reduced quality of life. During the metastatic progression of breast cancer, the key event for entry into the brain is the migration of cancer cells across the blood-brain barrier (BBB). To date, it is still controversial which serum factors play a role in cerebral expansion and what effects they have on the BBB. We hypothesize that sera from breast cancer patients with cerebral metastases contain unique factors that can affect BBB integrity. Methods: We used the CD34+ cells-derived human in vitro BBB model (brain-like endothelial cells, BLECs) in co-culture with brain pericytes, which was validated in our previous studies, to analyse the BBB properties after patient sera treatment. We used paracellular permeability measurements for fluorescein (400 Da), immunofluorescence staining, Western blot and mRNA analysis to examine the effects of patient sera on the properties of BBB in vitro. We collected serum samples from five patient cohorts (30 patient per group planned/150 in total/ current recruited patients 130): 1) healthy donors (current recruited patients- 23), 2) breast cancer patients with primary cancer (recruited patients- 30), 3) breast cancer patients with bone metastases (recruited patients- 29), 4) visceral metastases (recruited patients- 30), or 5) cerebral metastases (current recruited patients- 18). We then used 2% patient sera in cell culture medium to treat the cells for 24 hours. Results: Sera from breast cancer patients with cerebral and bone metastases led to a significant increase in the paracellular permeability for fluorescein. This could also be visualized by immunostaining cells with anti-claudin-5 antibody. Tight junction protein claudin-5 and occludin mRNA was reduced in BLECs, while mRNA of efflux pumps Breast cancer resistance protein (BCRP) and P-glycoprotein (P-GP) was induced in BLECs treated with serum from breast cancer patients with primary cancer, cerebral and visceral metastases. At the protein level, efflux pumps BCRP and P-GP were induced in cells treated with sera from breast cancer patients with cerebral metastases, while they were reduced in cells treated with sera from breast cancer patients with bone metastases. Conclusions: Sera from breast cancer patients with primary cancer and breast cancer metastases have an effect on the integrity of BBB in vitro. Reduced barrier properties of brain endothelial cells can contribute to the formation of cerebral metastases in advanced stages of breast cancer. Keywords: metastatic breast cancer, blood-brain barrier, in vitro models
PD-L1-R: A MR based surrogate for PD-L1 expression in Glioblastoma multiforme.
Authors: Sforazzini Francesco , Salome Patrick , Kudak Andreas , Ulrich Matthias , König Laila , Warta Rolf , Bougatf Nina , Debus Juergen , Herold-Mende Christel , Knoll Maximilian , Abdollahi Amir
Published: June 2021

2041

Background: Efficacy of PD-L1 immune checkpoint inhibitor therapy in Glioblastoma multiforme (GBM) is limited and the prognostic value of PD-L1 in GBM is an active field of research. We therefore sought to identify a MR based surrogate for PD-L1 expression in GBM. Methods: T1 post contrast images (T1ce) acquired immediately before surgery of 121 subjects with primary GBM (RTK I, II and mesenchymal subtype, as determined from Illumina Human Methylation array data) were analyzed. Following standard pre-processing (bias filed correction, brain extraction), 1150 radiomics features were calculated from gross tumor volumes (GTV). The cohort was then divided into training/validation (70%/30%). Cross-validation and model-selection were applied to identify features associated with PD-L1-M expression (estimated from methylation data and highly correlated with PD-L1 RNA-sequencing based measure, as recently reported). Features were used to identify two groups of tumors differing in PD-L1-M expression (PD-L1-R high and low), for which a logistic regression model was trained. Overall survival was assessed between PD-L1-R high/low. Results: PD-L1-R high and low groups showed significant differences in PD-L1-M values (training: p=0.002, validation: p=0.04, full cohort: p<0.001). The same model was used to split tumors into 2 groups, using features from non-T1ce sequences. All of the tested MR modalities showed at least a trend in PD-L1-M values in the two groups (T2w: p=0.037, T1w: p=0.089, FLAIR: p=0.091). Further investigations on the whole cohort (121 subjects) showed that PD-L1-R low group was enriched for RTK II sub-type (48%), while PD-L1-R high for mesenchymal sub-type (48%). Refer to Table 1 for more information. In addition, evaluation of survival data showed a difference in overall survival (likelihood ratio test p value 0.048, OR 0.52, 95% CI [0.27; 0.98]), with the PD-L1-R high group having a better prognosis. Conclusions: We presented a radiomics model PD-L1-R which allowed to identify GBM with low and high PD-L1-M expression from T1 post contrast agent images. Future work should validate these findings in independent cohorts.[Table: see text]
Improved risk stratification via integration of radiomics and dosiomics features in patients with recurrent high-grade glioma undergoing carbon ion radiotherapy (CIRT).
Authors: Salome Patrick , Sforazzini Francesco , Kudak Andreas , König Laila , Kickingereder Philipp , Bougatf Nina , Wick Wolfgang , Jäkel Oliver , Debus Juergen , Knoll Maximilian , Abdollahi Amir
Published: June 2021

2043

Background: Unique radiobiological and physical properties of carbon ion radiotherapy (CIRT) may be favorably utilized to improve outcome in recurrent High-Grade Glioma (rHGG). There are currently no standardized criteria for stratification of rHGG patients for re-irradiation (re-RT). This study evaluated the impact of morphological data (radiomics) and physical information (dosiomics) in stratifying rHGG patients for CIRT. Methods: Quantitative radiomics and dosiomics features were extracted from CIRT planning CTs with dose distribution (DD) and multiparametric MRIs (mpMRI, pre re-RT) of 141 patients (recurrent grade III: n=56 40%, grade IV: n=85 60%) treated with a median dose of 42 Gy (RBE) and a median fraction of 13. The MR sequences considered are T1 weighted pre-and post-contrast agent, fluid-attenuated inversion recovery (FLAIR) and apparent diffusion coefficient (ADC). Benefit of a re-RT risk score (RRRS), comprising the initial tumour grade, age and the Karnofsky Performance Score was shown to correlate with superior outcome in CIRT and conventional re-RT and was also studied here in parallel. Feature sets - a) RRRS, b) radiomics, c) dosiomics features - were evaluated both separately and combined. Multiple feature selection methods were used independently on the CT, DD and the MR sequences, followed by a stepwise Cox's Proportional Hazard model selection per modality or combination thereof. Multivariable models were ranked by 10-fold cross-validated concordance index (C-I). Results: Compared to the RRRS model (OS/PFS, C-I: 0.68/0.61), the multimodality model considering radiomics and dosiomics features (RD) allowed improved prognostic separation (OS/PFS, C-I: 0.77/0.70). The RD signature consisted of 12 and 10 textural features for the OS and PFS models. Combining the RD model with RRRS yielded the best performance (OS/PFS, C-I: 0.78/0.73). No significant correlation between the textural features and the prescribed dose, tumor grade and volume was found, with the Spearman's correlation coefficient ranging between -0.06 to 0.17. Conclusions: Integrating multimodal information outperforms unimodal prognostic separation of rHGG following CIRT, highlighting the importance to consider biological, physical and morphological data for patient stratification. Prospective validation studies of this multimodal stratifier is warranted.[Table: see text]
Cost-effectiveness of concomitant and adjuvant temozolomide for glioblastoma patients with unmethylated O6-methylguanine-DNA methyltransferase promoter regions in the United States.
Authors: Midha Manav Dev , Votruba Mark Edward
Published: June 2021

2058

Background: Promoter region methylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene has emerged as a predictive factor for longer overall (OS) and progression-free (PFS) survival response to concomitant and adjuvant temozolomide (TMZ) chemotherapy in glioblastoma. Recently, several investigators have suggested the small survival benefit of TMZ for unmethylated patients is insufficient to warrant the increased risk of adverse events and that these patients should instead be enrolled in clinical trials. This study informs the debate by estimating the incremental costs and benefits associated with TMZ use in methylated and unmethylated patients based on available published evidence. Methods: Published OS and PFS Kaplan-Meier curves were digitized, parameterized, and extrapolated to ten years. Partitioned Survival Analysis trees were constructed in TreeAge Pro 2020. Costs of TMZ, RT, and inpatient hospitalization were included, among others. It was assumed that all patients receive surgery prior to beginning radiation, and that RT and TMZ (six adjuvant cycles) dosing was standard. Published utilities associated with the progression-free and post-progression health states, subject to each treatment, were used. A 3% annual discount rate and a willingness-to-pay of $150,000/quality-adjusted life year (QALY) were assumed. Probabilistic sensitivity analysis (PSA) was conducted. Results: In methylated patients, RT + TMZ versus RT is associated with $67,622 in additional costs and 10.91 additional quality-adjusted life months (QALMs). In unmethylated patients, RT + TMZ versus RT is associated with $9,203 in additional costs and 2.24 additional QALMs. The implied incremental cost effectiveness ratios (ICERs) support TMZ use in both populations and suggest it is more favorable for unmethylated patients ($74,378/QALY and $49,302/QALY for methylated and unmethylated patients, respectively). However, the incremental net monetary benefit (INMB) associated with TMZ use is substantially smaller for unmethylated patients ($18,797 versus $68,753) due to the smaller survival gains for this population. PSA results indicate that TMZ is more likely to be cost-effective for methylated (89.3%) than unmethylated (77.4%) patients. Conclusions: Post-radiation clinical trial enrollment should be considered instead of TMZ for unmethylated glioblastoma patients. While the estimated ICER justifies the use of TMZ for unmethylated patients – in fact, does so more strongly than for methylated patients – the relatively small incremental health benefit is plausibly outweighed by the opportunity cost of not enrolling these patients in clinical trials that offer the possibility of more substantive gains to current and future glioblastoma patients.