bluuebunny/crossref_metadata_2025 huggingface dataset:
Adherence to oral treatments in elderly patients with advanced prostate cancer: The ADHERE study, a prospective trial of the Meet-URO network.
Authors: Rescigno Pasquale , Maruzzo Marco , Rebuzzi Sara Elena , Murianni Veronica , Cinausero Marika , Lipari Helga , Fratino Lucia , Gamba Teresa , De Giorgi Ugo , Caffo Orazio , Bimbatti Davide , Dri Arianna , Mosca Alessandra , Giunta Emilio Francesco , Ermacora Paola , Di Maio Massimo , Basso Umberto , Fornarini Giuseppe , Banna Giuseppe Luigi L. ,   Meet-URO: Italian Network For Research in Urologic-Oncology
Published: June 2022

12044

Background: Novel anti-androgen hormonal therapies (NAHTs) for advanced prostate cancer (PC) are mainly oral with an overall good toxicity profile and offer the convenience of home administration and reduced hospital footfalls. This imposes the burden of self-administration, often unsupervised, on a population of elderly patients overwhelmed by the assumption of many other concomitant medications. Therefore, lack of treatment adherence is becoming an increasingly social and health issue. Methods: In a prospective observational cohort study, metastatic castration-resistant PC (mCRPC) patients aged ≥70 years receiving abiraterone (ABI) or enzalutamide (ENZ) were enrolled in six Italian centres of the Meet-Uro network and monitored for their treatment adherence. Monitoring included pill counting, self-assessment questionnaire and clinical diaries at each clinical visit. Non-adherence rates were based on proportions of missed/prescribed pills ratios by pill counting as an overall estimate or the median of individual values. Results: Overall, 234 pts were recruited (median age: 78 years [73-82], 86 were treated with ABI and 148 with ENZ; 69% of the pts received NAHT in the pre-chemotherapy setting, while 24% in the post-chemo and 6% had the two treatments consecutively. Pts were monitored for adherence for a median time of seven cycles [IQR:4-12]. The two arms were well balanced for all baseline characteristics, besides steroids use (100% vs 9%, p < 0.001), as ABI requires steroids, and Charlson score, whose range was higher for ENZ pts than ABI pts (range 10-12 vs 8-11, p = 0.028). Overall, the percentage of non-adherence was higher for ABI than ENZ (5.2 vs 4.2 missed/prescribed pills, p < 0.001). After Bonferroni correction, geriatric G8 score correlated with non-adherence (p = 0.004, r = 0.18). Pts on ENZ tended to report missing pills more frequently than ABI pts, and the reason for non-adherence was forgetfulness (42% vs 17%, p < 0.001). A third of pts never completed the clinical diary given at each cycle. Overall survival (OS) within the study was 48.8 months. However, patients on ABI had a longer progression-free survival (PFS) compared to pts treated with ENZ (median PFS 28.4 [24.2-32.5] vs 23.1 [18.2-28.1] months, p = 0.041). Conclusions: Physicians tend to treat elderly and frailer people with ENZ. mCRPC patients on ENZ are more adherent to treatment, with forgetfulness being a potential barrier. Nevertheless, OS and PFS were consistent with those from ABI and ENZ pre-chemo registration studies, with ABI conferring a longer PFS in our study population.
Using G8 and carg toxicity score to predict emergency room (ER) visits, hospitalizations, and mortality in older patients with newly diagnosed cancer.
Authors: Arora Amit , Sun Hongxin , Shaia John L. , Kolevska Tatjana , Kotak Dinesh , Belohlav Kate , Williams Grant Richard , Liu Raymond
Published: June 2022

12055

Background: ASCO and NCCN guidelines recommends Geriatric Screening (G8) and CARG chemotherapy toxicity tool assessment for all older patient before receiving chemotherapy as high risk G8 (< 14) and CARG (≥10) are associated with increased chemotherapy toxicities. We conducted a pilot to understand predictors of high risk G8/CARG and if high risk G8/CARG can predict ER/hospitalization and mortality in community-based Oncology clinics in Kaiser Permanente Northern California. Methods: G8 and CARG were administered to all patients ≥65 years with newly diagnosed cancer from 5/1/21 to 12/31/21. Patients were followed for at least 30 days after assessment for ER/hospitalization and mortality. The median follow-up days from referral to ER/hospitalization was 96 days (range 0-273 days). Chi-Square tests were applied for G8/CARG risk category with demographic and utilization variables. Cox proportional-hazards models were performed to see the association between G8/CARG score and days from referral to ER/hospitalization, and days from referral to death, adjusted for age, sex, race, and cancer type. Results: During this pilot 1082 patients (52% female) completed G8, and 516 patients (57% female) completed CARG. Percentage of patients with high risk G8/CARG increased with each decade (G8: < 70 yrs (58%), 70-79 (63%), 80-89 (90%), ≥ 90 (100%); p < 0.001); (CARG: < 70 yrs (19%), 70-79 (43%), 80-89 (65%), 90 and above (81%); p < 0.001). More men than women had high risk CARG (48% vs. 39%, p = 0.012). Ethnicity was not associated with high risk G8 / CARG. Upper GI cancers (UGI) were associated with highest proportion of patients with high risk G8 (88%) and CARG (58%) whereas breast cancer (BC) had the lowest proportion of patients with high risk G8 (46%) and CARG (14%); p < 0.001. In the adjusted G8 model for ER/hospitalization, high risk G8 vs low risk (HR 1.58, CI 1.23-2.03, p = 0.0003) was related to ER/hospitalization. In the adjusted CARG model for ER/ hospitalization, high risk CARG vs low risk (HR 2.42, CI 1.37-4.29, p = 0.0024) and medium risk CARG vs low risk (HR 2.17, CI 1.23-3.83, p = 0.0074) were related to ER/hospitalization. In the adjusted G8 model for mortality, high risk G8 vs low risk (HR 4.52, CI 2.28-8.97, p < 0.0001) were related to mortality. In the adjusted CARG model for mortality, high risk CARG vs low risk (HR 3.92, CI 1.21-12.74, p = 0.023) and medium risk CARG vs low risk (HR 1.59, CI 0.48-5.33, p = 0.45) were related to mortality. Conclusions: This community-based pilot shows that increasing age is associated with high risk G8 / CARG. G8 and CARG assessment at the time of initial cancer diagnosis can predict early ER/hospitalization and mortality in older adults with cancer and should be included as a part of initial assessment.
Sacubitril-valsartan improves longitudinal strain and ejection fraction in preclinical models treated with anthracyclines through NLRP3, MyD88 pathways resulting in a reduction of myocardial IL-1β, IL-6, TNF-α and growth factors.
Authors: Maurea Nicola , Iovine Martina , Buccolo Simona , Caronna Antonietta , Maurea Carlo , Bonelli Annamaria , Paccone Andrea , Bisceglia Irma , Canale Maria Laura , Quagliariello Vincenzo
Published: June 2022

12063

Background: Doxorubicin-mediated adverse cardiovascular events are among the leading causes of morbidity and mortality in breast cancer patients. Sacubitril-valsartan (LCZ 696) is a combination drug, made up of neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan, used for the treatment of heart failure in patients with a reduced ejection fraction. We hypothesized that LCZ 696, administered during doxorubicin, could improve cardiac function and cardiac inflammation in preclinical models. Methods: Human fetal cardiomyocytes (HFC cell line) were exposed to subclinical concentration of doxorubicin (200 nM) alone or in combination with LCZ-696 (100 mM) for 72 h. After the incubation period, we performed the following tests: cell viability, apoptosis and necrosis; expression of malondialdehyde and 4-hydroxynonenal and concentration of intracellular Ca2+. Moreover, pro-inflammatory studied were also performed (activation of NLRP3 inflammasome; expression of TLR4/MyD88; mTORC1 Fox01/3a; NF-κB). C57Bl/6 mice were untreated (Sham, n = 6) or treated for 10 days with doxorubicin i.p at 2.17 mg/kg (DOXO, n = 6), LCZ-696 at 60 mg/kg (LCZ, n = 6) or doxorubicin combined to LCZ-696 (DOXO-LCZ, n = 6). Ejection fraction, radial and longitudinal strain were analyzed through transthoracic echocardiography (Vevo 2100). Cardiac tissue expression of NLRP3 inflammasome, Myd88, NF-kB and 13 chemokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF) were quantified. Results: LCZ-696 exerts cardioprotective effects, enhancing cell viability of 48-54.6% compared to only doxorubicin-treated cells (p < 0,001 for all); LCZ 696 decreased NLRP3, MyD88 and NF-kB expression in cardiac cells. In preclinical study, LCZ 696 improved significantly the EF and prevented the reduction of radial and longitudinal strain after 10 days of treatment with doxorubicin. A reduced expression of NLRP3, MyD88 and NF-kB in cardiac tissues was seen in DOXO-LCZ group compared to DOXO mice (p < 0.001). Cardiac expression of IL-1β, IL-6, TNF-α, G-CSF and GM-CSF were significantly reduced after treatment with LCZ-696 indicating anti-inflammatory properties. Conclusions: LCZ-696 exerts direct beneficial effects in cardiomyocytes exposed to doxorubicin. In preclinical models, LCZ-696 reduced inflammation and cytokine expression involved in doxorubicin-mediated cardiotoxicity.
Performance of the 2021 CKD-EPI equations without a race coefficient in a multi-racial population of adults with solid tumors: A prospective cross-sectional study.
Authors: Costa E Silva Veronica Torres , Gil-Jr Luiz A. , Inker Lesley , Caires Renato , Costalonga Elerson , Coura-Filho George , Estevez-Diz Maria Del Pilar , Castro Gilberto , Mathew Paul , Levey Andrew , Burdmann Emmanuel de Almeida
Published: June 2022

12064

Background: We previously showed that estimated glomerular filtration rate (eGFR) based on serum creatinine (Scr)(eGFRcr) using the 2009 CKD-EPI equation performed better than Cockroft-Gault equation (CG) in solid tumor patients in Brazil (Onco-GFR Study). In that study, eGFR based on Scr and cystatin C (Scys)(eGFRcr-cys) using the 2012 CKD-EPI was the most accurate equation and suitable for use as a confirmatory test. The CKD-EPI 2009 eGFRcr and 2012 eGFRcr-cys equations include a term for race (Black vs. non-Black). The 2021 CKD-EPI eGFRcr and eGFRcr-cys equations do not include race and are now recommended in the US, but have not been assessed in a multi-racial population or in cancer patients. The aim of this study is to evaluate the performance of the 2021 CKD-EPI equations in the Onco-GFR Study. Methods: Measured GFR (mGFR) was determined using the plasma clearance of 51Cr-EDTA. Scr and Scys assays were traceable to international standards. Results: A group of 1,200 patients recruited between April 2015 and September 2017 were included for analysis. Patients were 58.8±13.2 years, 50.8% male. Race distribution was Black participants 12.8% and non-Black participants 81.2%. Mean (SD) mGFR was 78.5±21.7 ml/min/1.73 m2. For eGFRcr, the overestimation of mGFR was larger for the 2021 vs. 2009 equation -10.0 vs. 8.1 ml/min/1.73m2, resulting in lesser accuracy 1-P30 of 22.3 vs. 19.1, but still more accurate than CG equation (1-P30 of 24.9, P = 0.05). For eGFRcr-cys, the overestimation of mGFR was larger for the 2021 vs. 2012 equation (-4.1 vs. -2.0 ml/min/1.73m2). eGFRcr-cys using the 2021 equation was more accurate than eGFRcr using the 2021 equation and eGFRcys using the 2012 equation (1-P30 9.8 vs. 22.3 and 12.3, p-values < 0.001 and 0.01, respectively) (Table). Conclusions: 2021 CKD-EPI eGFRcr equation race performed better than CG. 2021 CKD-EPI eGFRcr-cys performed better than 2021 eGFRcr and 2012 eGFRcys equations. Removing race from eGFR equations represents an advance and should be incorporated in cancer care. [Table: see text]
Randomized trial of atorvastatin during and following receipt of doxorubicin for breast cancer and lymphoma (WF-98213).
Authors: Hundley William Gregory , D'Agostino Ralph , Crotts Teresa , Hackney Mary Helen , Jordan Jennifer , Ky Bonnie , Wagner Lynne I. , Herrington David , Yeboah Joseph , Reding Kerryn , Ladd Amy , Rapp Steve , Russo Sandra , O'Connell Nathaniel S. , Weaver Kathryn E. , Dressler Emily Van Meter , Ge Yaorong , Melin Susan Anitra , Gudena Vinay K. , Lesser Glenn Jay
Published: June 2022

12072

Background: Statins taken for cardiovascular (CV) indications by breast cancer (BC) and lymphoma survivors during doxorubicin (DOX) treatment may attenuate left ventricular ejection fraction (LVEF) decline, but statin impact among these survivors with no CV indications is unknown. Methods: In 279 patients from 31 cancer centers, we conducted a double blind, placebo-controlled, 24-month randomized trial of 40mg/day atorvastatin among those receiving DOX for BC or lymphoma. At pretreatment, six and 24 months after initiating DOX for BC or lymphoma, we assessed LV volumes, strain, mass, and LVEF (via cardiac magnetic resonance), cognitive function and serum markers of inflammation. Using a linear model adjusted for pretreatment measures, our primary analysis assessed change in LVEF over time by randomization group. Results: Participants were aged 49±12 years; 92% women, 83% white race. The mean pooled LVEF decline from pretreatment to 24 months was 62.2±6.0% to 57.6±6.3% (p < 0.001). Adjusting for pretreatment LVEF, 24-month declines in LVEF averaged 3.5±0.5% and 3.3±0.5% respectively for placebo vs statins (p = 0.83). Both randomized groups were similar for: incidence of > 10% change in LVEF, LV strain, LV mass, cognition and inflammation biomarkers, including among those > 90% study drug compliant (p > 0.05 for all). Conclusions: In BC and lymphoma survivors with no existing indication for statin therapy, prospective statin administration does not appear to impact LVEF declines two years after doxorubicin. Clinical trial information: NCT01988571. [Table: see text]
Quantification of methylation-specific cardiomyocyte cell-free DNA as an early marker of cardiotoxicity in patients with breast cancer receiving anthracyclines and trastuzumab.
Authors: Moore Zachary Ray , Yu Anthony Francis , Liu Jennifer , Dang Chau T. , Oeffinger Kevin C. , Steingart Richard , Schmitt Adam
Published: June 2022

12090

Background: There is currently no way to reliably predict which patients undergoing therapy for breast cancer will develop cardiotoxicity. An early biomarker of cardiotoxicity could provide opportunity for intervention prior to the appearance of gross abnormalities on echocardiogram (ECHO). A droplet digital PCR (ddPCR) assay for circulating cell-free DNA (cfDNA) can detect cfDNA released from dying cardiomyocytes with high sensitivity by differentiating cfDNA of cardiomyocyte origin based on the pattern of methylation specific to the cell type. Circulating cfDNA of cardiac origin was tested as an early biomarker of toxicity in patients who underwent breast cancer treatment while closely monitoring cardiac function in a prospective clinical trial. Methods: A cardiomyocyte methylation-specific quantitative ddPCR assay was tested in plasma samples from 29 patients who were part of a larger prospectively enrolled cohort of women who received anthracyclines and trastuzumab for HER2-positive breast cancer. Blood samples were tested from prior to doxorubicin and cyclophosphamide (AC) chemotherapy, two months later after completing AC and prior to trastuzumab, and every 3 months to 12 months post-treatment. Patients were assessed for clinical cardiotoxicity, defined as heart failure (NYHA class III/IV) or significant EF decline (> = 10% to below 53% or > = 16%) until completion of cancer therapy. The maximum detected level of cardiac cfDNA (copies per 500 µL plasma) was compared between those who experienced cardiotoxicity and those who did not by two-sided T-tests. Results are reported as mean +/- standard deviation. Results: At baseline, cardiac cfDNA levels were low (mean 1.1 +/- 2.4 copies). Of 29 patients, five developed clinical cardiotoxicity. The maximum number of cfDNA copies at any time point was elevated in patients who experienced cardiotoxicity compared to those who did not (mean of 20.6 +/- 7.3 copies versus 9.3 +/- 9.8 copies, p = 0.0216). Of the patients with cardiotoxicity, elevated cfDNA of greater than 10 copies was detected an average of 3.6 +/- 2.5 months prior to the onset of clinical cardiotoxicity. Conclusions: Methylation specific cardiac cfDNA shows promise as an early indicator of cardiotoxicity in patients treated with anthracyclines in this pilot study. A previously reported analysis in the levels of seven other biomarkers including high-sensitivity troponin I and NT-proBNP pre- versus post-treatment in the full cohort of 80 patients did not show any statistically significant associations with the development of cardiotoxicity, suggesting that cardiac cfDNA may be uniquely informative. Clinical trial information: NCT02177175.
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.
Impact of provider education on hepatitis B screening practices prior to patients receiving cancer treatment.
Authors: Adashek Michael , Culver Jacob , Carrera Carolyn Anne
Published: June 2022

1539

Background: Hepatitis B virus (HBV) reactivation is a known side effect of CD20 targeted therapies with complications ranging from transient hepatitis to fulminant hepatic failure and death. In 2020 the American Society of Clinical Oncology (ASCO) expanded its provisional clinical opinion (PCO) to recommend HBV screening for all patients prior to receiving non-hormonal systemic anti-cancer therapies and if positive, offer viral prophylaxis or treatment. We assessed in a single-institution prospective study if a provider-led educational session on the 2020 ASCO PCO was effective in increasing HBV screening among patients receiving systemic non-hormonal anti-cancer therapies. Methods: An educational session for 30 minutes on the benefits outlined in the ASCO 2020 PCO discussing hepatitis B screening was held at a community-based hematology/oncology practice in Michigan. HBV screening panel was added to pre-chemotherapy lab order sets. Provider compliance with HBV screening recommendations was assessed monthly. Patients with positive HBV serology were identified and referred to Hepatology for monitoring and anti-viral treatment/prophylaxis as indicated. Data from 1,984 patient encounters for cancer treatment utilizing either chemotherapy or rituximab among 12 providers from March of 2020 to December 2021. Multivariate and logistic regression analysis was performed. Results: The educational intervention on the best practices of screening for Hepatitis B was effective in raising screening. Prior to intervention, 79.3% of all patients receiving rituximab (N = 140) and 15.7% of all patients receiving chemotherapy (N = 1277) had documentation for Hepatitis B before cancer treatment. Post-intervention hepatitis B testing increased both among patients receiving rituximab to 95.8% (N = 48) and chemotherapy to 29.9% (N = 519). In summary, prior to intervention, just 22.0% of 1,417 patient encounters had documentation for Hepatitis B screening before undergoing a treatment regimen. Post-intervention this level was raised to 35.45% (= 37.41,). In this study, 3 cases (0.5%) of acute and 12 cases (2.0%) of chronic HBV were identified from the 603 tested patients. A mixed effects logistic regression model controlling for treatment type and provider found patient encounters occurring post-intervention were 2.30 times more likely to be screened (OR = 2.30, 95% CI = [1.81, 2.93], p < 0.001). Conclusions: Our single educational session discussing the 2020 ASCO PCO and testing techniques for HBV was effective at increasing the odds of screening 2.3 times among patients receiving non-hormonal systemic anticancer therapies adjusting for therapy and provider. This may serve as a model for other implementations of PCOs. Further research will assess long-term oncologic outcomes of those identified with HBV and effects of anti-viral interventions.
Analysis of the likelihood of depression versus distress screening to identify need for intervention.
Authors: Csik Valerie Pracilio , Hannan Emma , Waldman Lauren , Garber Greg D. , Worster Brooke
Published: June 2022

1544

Background: Psychosocial assessments are increasingly used to evaluate a patient-centered approach to quality cancer care delivery. Value-based oncology programs endorse screening metrics at every encounter. To comply with expectations of these programs, our cancer center utilizes two standardized tools: Patient Health Questionnaire (PHQ) to screen for depression at every encounter; National Comprehensive Cancer Network Distress Thermometer (NCCNDT) to screen for acute distress at clinically meaningful intervals. In 2021, oncology patients completed, on average, 5 annual appointments at Sidney Kimmel Cancer Center (SKCC), with a median appointment frequency of once every 19 days. Given the high encounter-per-patient ratio, we aimed to assess utility of frequent screening leading to supportive intervention. Methods: A retrospective analysis was conducted of medical oncology patients seeking care at SKCC with a completed depression and/or distress screening, as recorded in the patient’s electronic health record, between 1/1/2021 and 12/31/2021. This analysis intended to evaluate the percentage of patients whose scores indicate need for intervention. Patients who received more than one screening were attributed the highest score recorded during the measurement period. Results: A total 13,342 patients were screened at least once for either depression (n = 7,433), distress (n = 1,325), or both (n = 4,584). 3% of all patients screened ever met the intervention threshold (IT) for depression; 33% met the IT for distress. Of the patients who received both types of screenings, 31% met the IT for distress without meeting the threshold for depression. Those 1,418 patients would not have been referred for intervention through depression screening alone. Conclusions: This analysis highlights routine depression screening among a cancer population with a high encounter-per-patient ratio may not be sensitive in identifying need for supportive intervention. It also suggests that distress screening is more likely to lead to a supportive intervention than depression screening alone. This analysis combined with the anecdotal assessment by social workers supports the value of distress at clinically meaningful intervals over depression screening at each encounter. [Table: see text]