bluuebunny/crossref_metadata_2025_split huggingface dataset:
Olanzapine with or without an NK-1 receptor antagonist for preventing chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy: A phase III randomized, double-blind, placebo-controlled trial (ALLIANCE A221602).
Authors: Navari Rudolph M. , Le-Rademacher Jennifer , Smieliauskas Fabrice , Ruddy Kathryn Jean , Saphner Thomas James , Liu Heshan , Harlos Beth , Onitilo Adedayo A. , Giridhar Karthik , Singh Preet Paul , Reddy Pavan S. , Kruter Flavio , Raptis George , Loprinzi Charles L. 
Published: June 2022

12107 Background: Chemotherapy-induced nausea and vomiting (CINV), a major adverse effect of cancer treatment, can attenuate life quality. Multiple international antiemetic guidelines have recommended a 4-drug regimen (corticosteroid, 5-HT3 receptor antagonist, NK-1 receptor antagonist, and the antipsychotic medication olanzapine) for decreasing highly emetogenic CINV. This raised a question regarding whether antiemetic therapy regimens for highly emetogenic chemotherapy could be de-intensified, decreasing cost and side effects from anti-emetogenic agents. Methods: Study A221602 was developed to compare two olanzapine-containing antiemetic regimens, one with the use of an NK-1 receptor antagonist (aprepitant or fosaprepitant) and one without. Patients (pts) received intravenous highly emetogenic chemotherapy as either 1) cisplatin, given on one day, at a dose of ≥ 70 mg/m2, with or without other chemotherapy agent(s) or 2) doxorubicin (60 mg/m2) plus cyclophosphamide (600 mg/m2) on one day. Pts in both arms received 1) a 5-HT3 receptor antagonist (palonosetron 0.25 mg IV or ondansetron 8-16 mg IV or 16-24 mg PO,) on day one, 2) dexamethasone (12 mg PO, day one followed by 8 mg PO, days 2-4), and 3) olanzapine (10 mg/day PO, days 1 to 4). On Day 1, all agents were given prior to chemotherapy, with the exception that olanzapine could be taken prior to chemotherapy or at bedtime. Additionally, pts were randomized to receive an NK-1 receptor antagonist (fosaprepitant 150 mg IV or aprepitant 130 mg IV; 346 pts) or a matching placebo (344 pts). The primary objective was to compare the proportion of patients with no nausea for 5 days following receipt of their chemotherapy between the two study arms. Results: While there was no suggestion of outcome differences on day 1 between the two study arms, fewer pts (7.4%; upper limit of the 95% confidence interval was 13.5%) without NK-1 receptor antagonists were without nausea for the complete 5-day study period. Conclusions: Per the study design, created to exclude a 10% benefit for NK-1 receptor antagonists, the results did not provide sufficient evidence to reject the hypothesis that the 4-drug regimen was superior to the protocol 3-drug regimen (p=0.24). Support: UG1CA189823; Clinical trial information: NCT03578081.
A single-arm feasibility trial of memantine to prevent chemotherapy-related cognitive decline in patients with early breast cancer.
Authors: Nakamura Zev , Deal Allison Mary , Park Eliza Myung , Stanton Kate , Lopez Yesy , Quillen Laura J. , Kelly Erin O'Hare , Heiling Hillary M , Nyrop Kirsten A. , Ray Emily Miller , Dees Elizabeth Claire , Reeder-Hayes Katherine Elizabeth , Jolly Trevor Augustus , Carey Lisa A. , Abdou Yara , Olajide Oludamilola A. , McNamara Megan Ann , Ahles Tim , Muss Hyman B. 
Published: June 2022

12109 Background: Up to 75% of patients with breast cancer report cognitive decline following chemotherapy. There is no standard of care prevention or treatment of cognitive problems in these patients. This trial (NCT04033419) examines the feasibility of using memantine to prevent cognitive decline during chemotherapy for breast cancer. Methods: We enrolled patients with stage I-III breast cancer scheduled to receive neo/adjuvant chemotherapy. Participants completed a cognitive battery (4 traditional neuropsychological measures and 3 computerized tests) and surveys of self-reported cognition (PROMIS Cognitive Function Short Form 8a) and other neuropsychiatric symptoms at pre-treatment (baseline) and 4 weeks after the last cycle of chemotherapy (post-assessment). Memantine (10 mg BID) was initiated within 1 week of starting chemotherapy and continued until the post-assessment. Adherence and adverse event (AE) monitoring occurred every 2-3 weeks during chemotherapy infusion visits. We used descriptive statistics to evaluate recruitment, retention, and tolerability, adherence, and acceptability of memantine. To evaluate objective cognition, we standardized individual measures using population-based data and averaged them to calculate composite scores of 1) global cognition; 2) attention, working memory, and executive function; and 3) learning and memory. Improvement or decline was defined as ≥ 0.5 SD change between the two assessments. For self-reported cognition, established cutpoints were used to define clinically meaningful change. Results: Of 154 eligible patients approached, 56 (36%) enrolled. Of 51 who completed the baseline assessment and started memantine, 44 (86%) completed the post-assessment; 2 remain active. Among evaluable participants, 92% reported taking ≥ 90% of scheduled doses. Only 36% self-reported cognitive decline, while no change was reported in 57% and improvement in 7%. Decline in objective cognitive domains was observed in 7 - 14% (see Table). There were 7 ≥ grade 3 AEs 2 were possibly related to memantine (diarrhea and hypokalemia). Only 3 participants expressed worry about memantine and only 2 felt that taking memantine disrupted their lives. Conclusions: Our findings suggest that memantine is a safe and feasible intervention for chemotherapy-related cognitive decline and may ameliorate cognitive loss. Randomized controlled trials are needed to determine its preliminary efficacy. Clinical trial information: NCT04033419. [Table: see text]
Suicide risk among patients with cancer in the United States, 2000-2016.
Authors: Han Xuesong , Hu Xin , Ma Jiemin , Zhao Jingxuan , Nogueira Leticia M. , Ji Xu , Jemal Ahmedin , Yabroff K. Robin 
Published: June 2022

12119 Background: Individuals diagnosed with cancer have elevated suicide risk in the US, although little is known about risk associated with state of residence, health insurance coverage, or time since diagnosis by cancer types. This study used a recent national dataset to examine a wide range of patients’ sociodemographic and clinical factors that may be associated with suicide risks. Methods: We identified patients diagnosed with cancer from 43 population-based state cancer registries in 2000-2016 with follow-up through Dec 31, 2016. Standardized Mortality Ratios (SMR) and 95% confidence intervals (95CI) were calculated by state of residence, attained age group, sex, and race/ethnicity to compare suicide risks in the cohort vs. the general US population. Hazard Ratios (HR) and 95CI from multivariable Cox proportional hazard models were derived to identify cancer-specific risk factors of suicide among the cohort, controlling for competing risks from other causes of death. Results: Among 16,771,397 patients, 7,972,782 (47.5%) died during the study period, and 20,792 (0.3%) from suicide. The overall SMR for suicide was 1.26 (95CI = 1.24-1.28), decreasing from 1.67 (95CI 1.47-1.88) in 2000 to 1.16 (95CI 1.11-1.21) in 2016. Patients from Alaska, Colorado and Idaho, those aged 65-69 years (SMR = 1.44, 95CI = 1.39-1.50), Hispanic patients (SMR = 1.48, 95CI = 1.38-1.58), those uninsured (SMR = 1.66, 95CI = 1.53-1.80) or insured with Medicaid (SMR = 1.72, 95CI = 1.61-1.84) or ≤64 years of age with Medicare (SMR = 1.94, 95CI = 1.80-2.07) had the highest suicide risks compared to the general population. Moreover, the highest suicide risk occurred within two years of diagnosis (SMR [95CI] = 7.19 [6.97-7.41], 5.60 [5.35-5.84] and 4.18 [4.03-4.33] for ≤5 months, 6-11 months, and 12-23 months after cancer diagnosis, respectively). In the first two years following diagnosis, the risk of suicide was higher in patients diagnosed with distant-stage than early-stage diseases (HR = 1.29, 95CI = 1.21-1.37), and in patients with more cancer types with poor prognoses and high symptom burdens, such as cancers of oral cavity & pharynx, esophagus, stomach, brain, lung and pancreas (HRs ranged 1.23-2.10 vs. colorectal cancer, all P≤0.001). After two years, patients diagnosed with cancers subject to long-term quality of life impairment, such as cancers of oral cavity & pharynx, female breast, bladder, and leukemia (HRs ranged 1.17-1.54 vs. colorectal cancer, all P≤0.01), had higher suicide risks. Conclusions: Suicide risk among patients diagnosed with cancer decreased during the past two decades but remained elevated compared to the general population. Different geographic, racial/ethnic, socioeconomic, and clinical factors, some of which are modifiable, contribute to increased suicide risk among patients diagnosed with cancer. Tailored social and psych-oncological interventions are warranted for suicide prevention in this vulnerable population.
Association between state Medicaid policies and accrual of Black participants to cancer clinical trials.
Authors: Takvorian Samuel U , Chatterjee Paula , Mamtani Ronac , Wu Yaxin , Guerra Carmen , Werner Rachel M. , Schpero William 
Published: June 2022

1501 Background: Black individuals remain underrepresented in U.S. cancer clinical trials, partly due to financial barriers to participation. While coverage of the routine costs of trial participation has long been mandatory for Medicare and the commercially insured, only 16 states have enacted similar mandates for Medicaid enrollees. Given the disproportionate representation of Black individuals in state Medicaid programs, we hypothesized that such mandates may have led to improved accrual of Black participants to cancer clinical trials. Methods: We conducted a retrospective, quasi-experimental study using de-identified data from the ECOG-ACRIN Cancer Research Group to evaluate changes in the accrual of Black participants to cancer clinical trials associated with state-mandated Medicaid coverage of routine trial costs. The study population included non-elderly adults enrolled in therapeutic clinical trials for breast, colorectal, lung, or prostate cancer from 2000-2019. We employed a difference-in-differences approach with event-study specification to compare outcomes in states that mandated Medicaid coverage of routine trial costs relative to states that did not, before and after mandates were enacted. Outcomes included the proportion of trial participants who had Medicaid insurance (vs. non-Medicaid) and the proportion who were Black (vs. non-Black). Models adjusted for age, sex, cancer type, cancer stage, study phase, and study site (community vs. academic). Results: Among 24,321 trial participants (mean age 52.0 [SD 8.2] years, 82.8% female), 7.2% had Medicaid coverage and 10.5% were Black. Compared to states without Medicaid coverage mandates, states with mandates had a statistically significant increase in the proportion of Black trial participants in the first year following the mandate (+6.4 percentage points [95%CI 1.8% to 11.0%]) but not in subsequent years. There was no association between state mandates and the proportion of trial participants enrolled in Medicaid (effects ranged from -0.7 percentage points [95%CI -4.6% to 3.3%] in the first year after mandates to -3.9% [95%CI -8.6% to 0.8%] in the third year). Conclusions: State-mandated Medicaid coverage of the routine costs of trial participation was associated with a short-term increase in the proportion of Black trial participants. These findings suggest that Medicaid policies have the potential to improve representation of racial minority groups in cancer clinical trials, and support recent federal legislation mandating state Medicaid programs to cover trial participation costs as of January 2022. Our study was limited by use of data from only one large cancer research group, focus on only four common cancers, and limited power to analyze the policy impact for other racial and ethnic minority groups. Additional work is needed to replicate these findings in larger cohorts of trial participants.
Impact of broadening trial eligibility criteria on the inclusion of patients with brain metastases in cancer clinical trials.
Authors: Unger Joseph M. , Xiao Hong , Hershman Dawn L. , Vaidya Riha 
Published: June 2022

1505 Background: On October 2, 2017, the American Society of Clinical Oncology, Friends of Cancer Research, and the U.S. Food and Drug Administration (ASCO/FoCR/FDA) issued a joint research statement recommending that certain eligibility criteria in cancer clinical trials, including those related to brain metastases, be broadened to make trials more inclusive. We examined whether patterns of exclusions regarding patients with brain metastases changed over time in relation to these recommendations. Methods: We used data from ClinicalTrials.gov to evaluate patterns of trial eligibility criteria in phase I-III U.S.-based interventional clinical trials for patients with advanced breast, colorectal, or lung cancers from January 2013 through October 2021. Trial inclusion and exclusion criteria were abstracted; to enhance validity, reviewers were blinded to the year of trial activation. For each trial, we determined whether patients with brain metastases were not excluded, conditionally excluded (i.e., excluded in some circumstances), or wholly excluded. Trial registrations between October 2, 2017-December 31, 2018 were excluded to allow 1 year for newly conceived trials to adopt the recommendations, plus 3 months to account for the lag time between loading trial records and trial activation dates; thus, the independent exposure variable was January 1, 2019. An interrupted time series analysis with multinomial logistic regression was used to assess whether the ASCO/FoCR/FDA recommendations were associated with changes in brain metastases eligibility criteria. Results: We evaluated N = 1998 trials. Patients with brain metastases were not excluded in 307 trials (15.4%); conditionally excluded in 1459 trials (74.8%); and wholly excluded in 196 trials (9.8%). In the post-recommendation period, we found a 92% increase in the odds of trials with brain metastases not excluded compared to conditionally excluded (OR = 1.92, 95% CI, 1.08-3.45, p =.03). The estimated proportion of trials in which patients with brain metastases were not excluded increased from 9.2% had the recommendations not been made to 15.6% (p =.04). Conversely, the proportion of trials in which patients with brain metastases were conditionally excluded (76.9%) was lower than expected (85.3%, p =.02). We found no difference in the proportion of trials in which patients with brain metastases were wholly excluded (7.5% vs. 5.4%, p =.28). Conclusions: The ASCO/FoCR/FDA recommendations were associated with a shift in patterns of brain metastases exclusion criteria from conditionally excluded to not excluded. To our knowledge, this is the first evidence that cancer clinical trials have become more inclusive of a broader set of patients in response to the ASCO/FoCR/FDA recommendations. More inclusive eligibility improves trial access and representativeness, increasing trial validity and the pace at which trials enroll.
Imaging and physician visits at cancer diagnosis: COVID-19 pandemic impact on cancer care.
Authors: Fu Rui , Sutradhar Rinku , Li Qing , Hanna Timothy , Chan Kelvin K. , Coburn Natalie , Hallet Julie , Eskander Antoine ,   Pandemic - Ontario Collaborative in Cancer Research (POCCR)
Published: June 2022

1522 Background: Understanding how cancer system responded to the first wave of the COVID-19 pandemic has crucial implications to de-escalation measures in future waves. Here we examined the pandemic impact on the provision of diagnostic imaging (MRI, CT, and ultrasound) and physician visits (virtual and in-person) at cancer diagnosis in Ontario, Canada. Methods: For each week of June 26, 2016–September 26, 2020, we identified cancer diagnoses whose time around diagnosis (91 days +/- the date of diagnosis) fell into this week and restricted those diagnoses to be one per person-day and to patients aged 18+ at the beginning of that week. For these cancer patients, we used physician claims database to identify diagnostic imaging and visits received around cancer diagnosis. In separate segmented negative binomial regression procedures, we assessed the trends in weekly volume of these services per thousand cancer patients in pre-pandemic (June 26, 2016 to March 14, 2020), the change in mean volume at the start of the pandemic, and the additional change in weekly volume in the pandemic (March 15, 2020 to September 26, 2020). Results: Among 403,561 cancer patients in the cohort, 41,476 (10.3%) were diagnosed in the pandemic. As COVID-19 arrived, mean diagnostic imaging volume decreased by 12.3% (95% CI: 6.4%-17.9%) where ultrasound decreased the most by 31.8% (95% CI: 23.9%-37.0%) and MRI did not change (p-value = 0.27). Afterwards, the volume of all scans increased further by 1.6% per week (95% CI: 1.3%-2.0%), where ultrasound increased the fastest by 2.4% for each week (95% CI: 1.8%-2.9%). Mean in-person visits dropped by 47.4% when COVID-19 started (95% CI: 41.6%-52.6%) while virtual visits rose by 5515% (95% CI: 4927%-6173%). In the pandemic era, in-person visits increased each week by 2.6% (95% CI: 2.0%-3.2%), but no change was observed for virtual visits (p-value = 0.10). Conclusions: Provision of diagnostic imaging and virtual visits at cancer diagnosis has been increasing since the start of COVID-19 and already exceeded pre-pandemic utilization levels. These findings imply the feasibility of combining virtual consultations with diagnostic imaging to manage new cancer patients and highlight the need to monitor the quality of these services.
FDA analysis of expanded access use in pediatric patients from 2015 to 2020.
Authors: Duke Elizabeth , Kormanik Natasha L. , Barone Amy , Singh Harpreet , Beaver Julia A. , Pazdur Richard , Reaman Gregory H. , Donoghue Martha Boeri 
Published: June 2022

1529 Background: Expanded Access is a regulatory mechanism that enables patients with a life-threatening condition or serious disease to receive treatment with an investigational drug outside of a clinical trial when no comparable or satisfactory alternative options are available. FDA has decades of experience with expanded access, but little has been reported about its use in pediatric cancer patients. Methods: FDA’s central electronic database was queried for single-patient investigational new drug (spIND) applications submitted to the Office of Oncologic Diseases between January 2015 through December 2020. Data collection included IND receipt date, IND type/status, drug name, and patient demographics. Duplicate or exempt INDs, those cancelled by the physician-sponsor before initiating therapy, and those requested for indications that occur almost exclusively in adults (e.g. lung cancer) or were missing patient age were excluded. Results: Of 2,901 unique spINDs granted, 534 (18%) were for patients less than 18 years of age. The pediatric population was 57% male, median age 6.0 years (range 0.1 to 17); race/ethnicity were reported in <1%. Patients were treated in 132 zip codes across 39 states; one-quarter of submissions were from 5 large academic hospitals. Central nervous system tumors were the most common indication (Table 1). A total of 98 unique drugs were requested, with 1 to 73 spINDs for each drug; approximately 50% were for tyrosine kinase inhibitors, 25% for other small molecules, and the remainder for immunotherapies and other drug types. Median time for FDA to grant was 1 day. Follow-up information was provided for 75% (annual report or withdrawal letter); 1/3 were withdrawn within 1 year. Over the last 2 years, utilization of the program increased by 120%. Conclusions: While approximately 1% of all cancers per year are diagnosed in children under 17 years of age, 18% of spINDs over the last five years were for pediatric patients. Although utilization of this program for children is robust, efforts are needed to assess its impact on patient outcomes and ensure its availability to patients, families, and institutions more widely. These data highlight interest within the pediatric oncology community in accessing innovative therapies, which supports early investigation of promising new drugs in children.[Table: see text]
Oncology hospital at home in rural communities: The Huntsman at Home rural experience.
Authors: Mooney Kathi , Dumas Kimberly , Fausett Angie , Littledike Marcene , Ulrich Cornelia M , Titchener Karen 
Published: June 2022

1535 Background: Oncology hospital at home programs have shown promise in decreasing unplanned health care utilization while improving quality of life. While most hospital at home programs serve local urban areas, we extended our oncology hospital at home program, Huntsman at Home, to provide equitable distribution of program services for cancer patients living in rural communities at a distance from our cancer center. Methods: Utilizing a community engagement approach we redesigned our urban Huntsman at Home program for 3 rural communities in Southeastern Utah, a 2 to 5 hour one-way drive from Huntsman Cancer Institute. We systematically collected patient data and program modifications required for rural community delivery during the program’s first 6 months. Care was delivered by on-ground and telehealth nurse practitioner visits and on-ground registered nurse and physical therapy visits. Cardiovascular remote monitoring was utilized during acute care episodes. Results: A total of 47 cancer patients (31 men; 16 women; mean age 69 years) were admitted to the rural program during the first 6 months. Seven patients had 9 acute illness episodes of care. The average length of acute episode care was 6.1 days for treatment of infection, respiratory distress/ hypoxia, cardiac instability (hypotension, tachycardia), and dehydration/electrolyte imbalance and uncontrolled vomiting. Forty patients received subacute management aimed to prevent acute episodes and escalation to the emergency department (ED) or hospitalization. Subacute patients were in the program an average of 15.8 days. There were 4 appropriate escalations (2 hospitalizations, 1 ED visit returned to home and 1 ED visit with hospitalization) for symptoms related to disease progression requiring imaging and hospital-based procedures and one for diagnosis of a post-surgical PE. We found geographic and social determinates of health impacted rural patients’ cancer burden, most notably transportation barriers (44.7%). Secondarily, we found food insecurity impacted nutritional status in 14.9% of patients. A significant number of patients experienced financial toxicity (29.8%) related to lost wages, co-pays and/or out of pocket expenses for care. Lack of health literacy impacted 48.9% of patients effectively navigating their health care and self-management at home. Robust communication and coordination between the hospital at home clinical team, local primary care providers, the rural hospital, community resources and the patients’ cancer center oncology team were keys to improving care pathways. Conclusions: Rural oncology hospital at home is feasible and addresses geographic disparities in equitable access to acute and subacute cancer care in local communities. It requires adaptation to rural needs and culture, coordinated escalation procedures and a focus on addressing geographic and social determinates of health that impact cancer burden.