bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modified CARG score using data from the electronic health record to predict chemotherapy toxicity in older adults.
Authors: Martin Jasmine L , Wu Kathie , Gupta Mudit , Johns Alicia M , Adonizio Christian S. 
Published: June 2022

12038 Background: Older adults starting chemotherapy are at greater risk of toxicity compared with younger patients. Additional tools are needed to aid in management decisions for this population. The Cancer and Aging Research Group (CARG) chemotherapy toxicity calculator is one such tool, which stratifies older adults into high, intermediate, or low risk for chemotherapy toxicity (Hurria, A., Mohile, S., Tew, W. P., & et al. (2016). Validation of a prediction tool for chemotherapy toxicity in older adults with cancer. Journal of Clinical Oncology, 34(20), 2366–2371. https://doi.org/10.1200/jco.2015.65.4327). This tool relies on a face-to-face encounter to ask questions, e.g. “How is your hearing?” or “Can you take your own medicines?” in addition to lab values such as hemoglobin and creatinine clearance. We modified the CARG chemo toxicity calculator to include data points which could be pulled from the electronic health record (EHR) without the need for a face-to-face encounter to assess for an association with emergency department (ED) visits and hospital admissions. Methods: Retrospective data analysis was conducted using the EHR of patients over age 65 diagnosed with a solid tumor from 1/1/2019 to 12/31/2020 who started chemotherapy. A modified CARG score was calculated using age, cancer type, number of drugs, hemoglobin, creatinine clearance, and falls within the past 6 months. The remaining items needed to calculate the complete CARG score were excluded since they were not accessible in the EHR. We assessed ED visits leading to admission, ED visits leading to discharge, direct admissions, and the total of all 3 visit types for all patients. Results: A modified CARG score was calculated for 763 patients. Multiple models were evaluated and negative binomial distribution was found to be the best fitted for our data. For every one unit increase in our calculated score the number of ED visits which lead to hospital admission increased by 6% (p-value = 0.0156). Additionally, there was a 5% increase in combined ED visits, ED visits leading to admission, and direct admissions for every one unit increase in risk score (p-value = 0.0063). ED visits that did not lead to admission were found not to have an association with the risk score (p-value= 0.1263). (Table) Conclusions: A modified CARG score using data obtained from patients’ EHR had a statistically significant association with increased ER visits that resulted in hospital admission and with the total of ED visits leading to admission, ED visits leading to discharge, direct admissions. Using these outcomes as a surrogate for toxicity, we deduce that a simple tool could be used to predict chemotherapy toxicity in older adults. [Table: see text]
Deficit Accumulation Frailty Index (DAFI) scores and acute myeloid leukemia outcomes.
Authors: Lai Catherine , Conway Olivia , Lee Minji , Le-Rademacher Jennifer , Mandelblatt Jeanne S. , Klepin Heidi D. 
Published: June 2022

12040 Background: Novel strategies are needed to assess frailty in the context of therapy decisions for older adults with acute myeloid leukemia (AML). Our objectives were to describe pre-treatment DAFI scores for older AML patients treated on clinical trials and explore their relationship with treatment outcomes. Methods: We conducted a exploratory analysis utilizing data from two clinical trials of adults aged ≥60 years with newly diagnosed AML (Alliance/CALGB 11001 [intensive therapy] and Alliance/CALGB 11002 [non-intensive therapy]). We included the subset of patients in each trial enrolled on geriatric assessment companion studies (Alliance/CALGB 361006, 361101). A DAFI score was calculated for each patient using 51 variables including demographic, geriatric assessment, and laboratory data derived from the geriatric assessment. Individuals with ≥90% items were included (consistent with other studies); DAFI scores ranged from 0 to 1 and were evaluated using established categories (0- <.2 [robust]; 0.2-<.35 [pre-frail]; 0.35+ [frail]) and as a continuous score. Associations between DAFI scores and toxicity and overall survival (OS) were evaluated with Fisher’s exact-testing and Kaplan Meier/cox proportional hazards, respectively. Results: The median age was 68 years (range 61, 82) and 72 years (range 61, 92) for those getting intensive (N=31) and less intensive therapy (N= 75), respectively. Individuals in the intensive study had a median pre-treatment DAFI score of 0.15 (range 0.05, 0.31) and were all categorized as robust (75%) or pre-frail (25%). There was no significant difference in median OS (14.6 vs. 14.7 months) or non-hematological grade 3+ adverse events (AEs; 85% vs. 89%) between robust vs. pre-frail individuals in this trial, respectively. However, pre-frail adults experienced a trend towards greater grade 4 non-hematological toxicity than robust individuals (67% vs 26%, p=0.05). In the non-intensive trial, the median DAFI score was 0.24 (range 0.04, 0.48) and most individuals were pre-frail (49.3%) or frail (17.3%). Non-hematologic grade 3+ AEs did not vary by DAFI group, 88% robust, 95% pre-frail, and 77% frail (p=0.15). Median OS was 7.4, 10.8, and 6.3 months for robust, pre-frail, and frail respectively (p=0.17). Adjusting for age, each 0.1 increase in DAFI score was associated with increased mortality hazard (HR 1.8, 95% CI 1.0-3.2). Conclusions: DAFI score calculation provides a potential novel strategy for categorization of frailty in AML. In our assessment, higher DAFI scores were associated with toxicity during intensive induction and mortality in the less intensive setting. This method should be studied in larger samples randomized by treatment intensity. Support: UG1CA189823; Bayer Healthcare/Berlex (CALGB 11001); NCT01253070 (CALGB 11001). Clinical trial information: NCT01253070, NCT01420926.
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.