bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison among three predictive models for cancer-associated thromboembolism in a Hispanic population.
Authors: Ramos-Esquivel Allan , Hernández-Romero Gabriel , Marenco-Flores Ana , Umaña Carlos , Céspedes-Calvo Ana , Mora-Hidalgo Raquel 
Published: June 2023

e24074 Background: Several predictive scores have been developed to assess the risk of venous thromboembolism (VTE) among cancer patients. Although their use is currently recommended by several guidelines, it is unknown if these scores can accurately predict the risk of VTE in Hispanic patients that are at different risk for thrombosis. Methods: We retrospectively evaluated all outpatients with newly diagnosed solid tumors receiving systemic chemotherapy in Hospital San Juan Dios, San José, Costa Rica, from January to December 2021. For each patient, the Khorana, PROTECHT, and CONKO scores were calculated at the beginning of treatment. The sixth-month cumulative incidence of VTE was estimated using the Fine & Gray competing risk model for the overall population and stratified according to each risk category. A Kaplan-Meier analysis was used to compare the cumulative VTE incidences between high- and low-risk categories of the three predictive scores. The Cox regression analysis was used to calculate the hazard ratio (HR) and its corresponding 95% confidence interval (CI). The receiver operating characteristic (ROC) curve was used to assess the performance of each predictive tool through the analysis of the c-statistic, sensitivity, and specificity. Results: 708 patients were included in the analysis. After a median follow-up of 8.13 months, the cumulative VTE incidence at six months was 4.45% (95%CI: 3.25-6.91%). At the conventional positivity threshold of 3 points, these scores classified from 17.7 to 27.5% of all patients as high-risk for VTE. The 6-month incidence of VTE among high-risk patients ranged from 7.6% for the Khorana score to 9.3% for the CONKO score. Patients belonging to the high-risk category of the Khorana, PROTECHT, and CONKO scores had significantly higher risk of VTE in comparison to low-risk patients (Khorana score: HR: 2.66; 95%CI:1.20-5.89; p = 0.042; PROTECHT score: HR: 3.44; 95%CI:1.63-7.21; p = 0.001; CONKO score HR: 3.68; 95%CI:1.72-7.85; p = 0.001). Table 1 resumes the performance of the studied scores. Table 1. Performance of the Khorana, PROTECHT, and CONKO scores for the prediction of venous thromboembolism. Conclusions: The Khorana, PROTECHT, and CONKO scores accurately predict the risk of VTE in Hispanic patients with solid tumors with similar performance among them. However, their sensitivity and specificity remain poor for identifying all patients at risk for thromboembolic events.[Table: see text]
Incidence of second primary malignancies (SPMs) in patients with multiple myeloma (MM) receiving anti-CD38 monoclonal antibodies (mAbs): A systematic review and meta-analysis.
Authors: Mian Agrima , Naqvi Syed Arsalan Ahmed , Ayaz Ahsan , Husnain Muhammad , Aljama Mohammed A. , Mohyuddin Ghulam Reham , Koehn Kelly , Mohan Meera , Riaz Irbaz Bin , Chakraborty Rajshekhar 
Published: June 2023

e24078 Background: The addition of anti-CD38 mAbs, daratumumab and isatuximab, to standard anti-myeloma regimens have drawn scrutiny towards long-term safety concerns, including the risk of SPMs. ICARIA-MM study reported SPMs in 3.9% patients (pts.) in the Isatuximab, pomalidomide and dexamethasone (Isa-Pd) arm compared to 0.7% in the Pd arm. We hypothesized that exposure to anti-CD38 mAbs could potentially increase risk of SPMs due to prolonged immunosuppression. An assessment of this association is warranted, given the improved life expectancy and growing prevalence of pts. with MM. Methods: We performed a meta-analysis on data obtained from RCTs published between January 2005 and April 2022 that compared anti-CD38 mAb-based regimens to other standard anti-myeloma regimens (control) in pts. with newly diagnosed or relapsed/refractory (r/r) MM. Total number of SPMs (including categories) were extracted for pts. in both groups. Malignant melanomas were included under solid SPM category. Binary outcome data were analyzed using fixed-effect Peto method. Treatment effect estimates were expressed as odds ratio (OR) and 95% confidence interval (CI). I2 > 50% indicated substantial heterogeneity. Results: 10 RCTs involving 4980 pts. were included, with 2824 (57%) and 2156 (43%) pts. randomized to the anti-CD38 mAb and control arms, respectively (Table). Overall, 191 and 112 SPMs were reported in the anti-CD38 mAb and control arms, respectively. At a median follow-up of 35.3 months, anti-CD38 mAb exposure was associated with an increased risk of developing SPMs compared to control (6.8% vs. 5.2%; OR: 1.53 [95% CI: 1.20-1.95]; I2= 0%). Non-melanoma cutaneous cancers were the most common, and higher in the anti-CD38 mAb vs. control arms (92 versus 47; OR: 1.77 [95% CI: 1.25-2.51]; I2= 0%). The increase in solid cancers (including melanoma) (OR: 1.28 [95% CI: 0.85-1.95]) and hematologic SPMs (OR: 1.86; [95% CI: 0.81-4.27] was not significant. On sensitivity analysis, the total number of SPMs were higher in the anti-CD38 mAb arm vs. control arm, regardless of the presence of immunomodulatory drugs in combination regimen. Conclusions: This meta-analysis shows an increased risk of SPMs in pts. with MM exposed to daratumumab or isatuximab, particularly that of non-invasive cutaneous tumors. This association should be further investigated in real-world settings using large databases. [Table: see text]
Risk factors and early biomarkers of nephrotoxicity associated with the use of anti-VEGF drugs.
Authors: Grechukhina Katerina , Chebotareva Natalia , Krasnova Tatyana , Zhukova Lyudmila 
Published: June 2023

e24079 Background: Anti-angiogenic anticancer drugs that block VEGF can cause kidney damage (Fujii et al., 2019). Among the mechanisms of nephrotoxicity thrombotic microangiopathy (TMA) of renal vessels can be distinguished (Estrada et al., 2019). TMA can be accompanied the development of anemia, excessive schistocytes, as well as increased LDH levels and a low platelet count, which indicated the occurrence of endothelial dysfunction and microangiopathic processes (Hauser et al, 2009). The goal of this study was to assess the risk factors of early nephrotoxicity and the utility of NGAL, KIM-1, HIF-1α and nephrin levels in urine as early biomarkers of nephrotoxicity. Methods: The study included 50 patients who received anti-VEGF drugs (aflibercept, bevacizumab or ramucirumab). Nephrotoxicity was determined as a decrease in glomerular filtration rate (GFR) to < 60 ml/min/1.73m2 at 8 weeks from the initiation of therapy. The laboratory parameters and the levels of KIM-1, NGAL, HIF-1α and nephrin in urine samples were determined by ELISA before treatment and after 1, 2, 4 and 8 weeks of treatment. To assess risk factors for nephrotoxicity we analyzed primary clinical and laboratory parameters. Results: Nephrotoxicity at 8 weeks was achieved in 21 (42%) of patients. A statistically significant decrease in hemoglobin and platelet count by 20 and 26%, respectively, from the initial level was observed. An increase in the number of schistocytes and a slight increase in LDH levels were also observed. The increase in NGAL, KIM-1 and nephrin levels was statistically significant in 1 weeks and the increase of HIF-1α in 2 weeks after the start of therapy (p = 0.001). The unfavorable predictors of nephrotoxicity as well as the favorable predictors in terms of decreasing renal function are presented in Table. ROC analysis demonstrated high sensitivity and specificity: NGAL – AUC 0.7; KIM-1 – AUC 0.69; HIF-1α – 0.7; nephrin – AUC 0.7. Conclusions: We report a significant increase in the parameters of microangiopathic hemolysis and in urine biomarkers of tubular and podocytic damage as well as hypoxia by the 8th week of treatment. We suggest that the TMA process can take part in renal damage. Increased levels of NGAL, KIM-1, HIF-1α and nephrin in the urine reflect the renal damage processes and have higher sensitivity and specificity then serum creatitine. The independent risk factors for nephrotoxicity are determined. [Table: see text]
A novel risk assessment metric for antimyeloma therapies and drug interactions.
Authors: Xu Xuan , Jaberi-Douraki Majid , Anwer Faiz , Faiman Beth , Williams Louis , Mazzoni Sandra Ann , Khouri Jack , Valent Jason Neil , Ramachandran Remya Ampadi , Riviere Jim , Gadara Nuwan Millagaha , Golmohammadi Mobina , Wyckoff Gerald , Samaras Christy Joy , Samala Renato Verayo , Raza Shahzad 
Published: June 2023

e24082 Background: New treatments for multiple myeloma (MM) improved both the clinical course and survival. These differ in their mode of action, safety profile, and adverse events (AEs). The goal of this study is to establish the benchmark for an integrated systematic investigation to assess the toxicity of different anti-MM drug regimens (AMDR). Methods: We curated 342,213 MM patient information from 2016–2022 from the FDA Adverse Event Reporting System. A total of 71 AMDR were evaluated in 7 different system organ classes when mapped to MedDRA. Drug-associated genes and AEs were also quantified as genetic evidence of a drug-AE combination. Gene-gene associations were then explored using the STRING database. We then developed a novel risk assessment metric that combined historical data from MM patients with drug-AE scores regarding the AE occurrence, the number of reported AE, and the genetic evidence of drug-gene and gene-AE associations (GAA). This likelihood-based rating metric includes (vH): (very) high MDR risk–(very) frequent AEs and mortality with (very) significant GAA evidence; and similarly computed for M: medium risk; and L: low risk. Results: Our risk assessment findings revealed single agents (carfilzomib (K), bortezomib (V), daratumumab (D), lenalidomide (R), melphalan (Mel), thalidomide (T), ixazomib (Ix), elotuzumab (El), isatuximab (Is) or dexamethasone (d)) illustrated very low profile of toxicity compared to combination regimens. Overall, we found that AMDR profiles showed higher toxicities in 4 different SyOCs (hepatobiliary, cardiac, nervous, renal) with nominal issues in 3 SyOCs (vascular, neoplasm, GI). AMDR toxicity significantly increased when d was added to the treatment compared to AMDR without d. Cardiac and vascular AEs were higher with K-based combinations. Hepatobiliary toxicities were higher with V, K, or T-based combinations. Secondary neoplasms were seen more frequently in patients who received high dose Mel followed by R. Conclusions: Our analysis of large data shows the association of SyOCs and graded toxicity profiles with unique AMDR. The single drug or doublets without dexamethasone seemed to show an improved AE profile compared to those with dexamethasone used as doublets, triplets, or quadruplets. Secondary cancer risk was much higher with high dose Mel followed by R compared with other AMDR. Our assessment system provides a framework for AMDR comparison toward future precision MM therapeutics based on unique drug doses, combination regimens, patient phenotypic risk profiles, secondary cancer surveillance and interplay of genetics and comorbidities. [Table: see text]
Adverse events with the use of radiotherapy in patients with inflammatory arthritides and cancer: A systematic review and meta-analysis.
Authors: Lopez-Olivo Maria A. , Sharma Gaurav , Qureshi Sehrish , Hicklen Rachel S. , Tayar Jean H. , Suarez-Almazor Maria E. 
Published: June 2023

e24090 Background: Radiotherapy is a cornerstone for multi-modality cancer treatment. However, there have been concerns that in patients with inflammatory arthritides (i.e., rheumatoid arthritis, juvenile idiopathic arthritis ankylosing spondylitis, Still’s disease) radiotherapy could result in deleterious outcomes, and radiation oncologists may be hesitant to administer radiation therapy to these patients. Methods: We conducted a systematic review to determine the risk of developing adverse events (AEs) from radiotherapy in patients with cancer and inflammatory arthritides. We searched in 4 electronic databases from inception through October 2022. Study selection, data collection and risk of bias assessment were independently performed by two investigators. We performed random-effects meta-analysis to determine the incidence of acute (≤ 90 days) and late ( > 90 days) AEs and evaluated the risk of developing AEs in these patients compared with cancer patients without inflammatory arthritides. Results: Out of 9,723 records retrieved from our searches, we included 7 cohort studies (5 included a control group) and 14 case reports (describing 22 patients). The age of the included patients ranged from 16-72 years. The median follow-up ranged from 1.5 to 12.5 years. Median radiation doses ranged from less than 40 Grays (exact doses not provided) to more than 60 Grays. The pooled incidence of acute AEs for patients with inflammatory arthritides when considering controlled and uncontrolled studies was 32% (95%CI 14%, 53%). When compared with controls (cancer patients receiving radiotherapy without inflammatory arthritides) no statistical difference was observed (Relative risk [RR] using only controlled studies 1.3; 95%CI 0.67, 2.5). For late AEs, the pooled incidence for patients with inflammatory arthritides when considering controlled and uncontrolled studies was 20% (95%CI 8%, 34%). However, the AEs in patients with inflammatory arthritides was significantly higher than that of controls (RR using only controlled studies 2.3; 95%CI 1.3, 4.3). The most common acute AEs reported were radiation dermatitis, gastrointestinal or genitourinary toxicity, and flares of the autoimmune disease. The most common late AEs reported were fibrosis, lymphedema, and pneumonitis. Out of the case reports, 5 patients reported late AEs and the remaining patients did not report AEs. Conclusions: While there were no differences in the frequency of acute AEs, patients with inflammatory arthritides had a statistically significant increased rate of late AEs compared with people without arthritides. Our results can assist in providing evidence-based information to patients with inflammatory arthritides considering radiotherapy.
Building epigenetic clocks for estimating accelerating aging in patients with testicular cancer treated with cisplatin-based chemotherapy.
Authors: Wojewodzic Marcin W , Sydhagen K. Aurora , Rounge Trine B. 
Published: June 2023

e24099 Background: DNA methylation is highly correlated with chronological age. This is essential for constructing epigenetic clocks. Epigenetic clocks can shade light not only about the biological age, but also describe the functional state of the body after chemotherapy (CT). Patients with testicular cancer (TC) treated with CT are prone to develop metabolic syndrome (MetS) later in life, that may be also mediated through epigenetic changes (Bucher, Clin Epigenetics. 2019; 11:179). If age acceleration is also a mediator in the CT~MetS relationship remains unknown. We developed an epigenetic clock, and then analyzed differences in biological age acceleration between groups of TC patients 16 years after CT. TC patients had undergone one of two treatments: either surgery or a combination of CT or surgery only. Half of the patients in both treatment-groups had developed MetS. Methods: First, we used an elastic net to develop epigenetic clocks based on DNA methylation from publicly available data sets (EPIC array). We tested the differences in age accelerations (residual and intrinsic age acceleration) between groups of TC patients that received CT and orchiectomy with those TC patients with orchiectomy only. Also, the linear regression used treatment type and MetS diagnosis as independent variables. Results: Five epigenetic clocks were developed, of which one, performing best, was chosen to be used in further analyses. This clock, the Aurora’s clock, had a root mean square error of 3.1/3.8 and R2 of 0.95/0.9 shown in two different test sets. In addition to Aurora’s clock, eABEC and Levine DNAm PhenoAge were used (Lee, BMC Genomics. 2020, 21, 747; Levine, Aging. 2018, 2018,10:573-591). The linear regressions indicated a lower age acceleration for the group treated with both CT and surgery, compared to the group treated with surgery only. The significance level varied between the clocks, with a p-value ranging from 0.03 to 0.17. All three clocks estimated a higher age acceleration for patients diagnosed with MetS, but this was only significant when applying Levine DNAm PhenoAge (p = 0.03 for residual age acceleration, and p = 0.045 for intrinsic age acceleration). Conclusions: These findings indicate that CT does not lead to increased age acceleration 16 years after treatment. However, individuals diagnosed with MetS can have an elevated age acceleration. These findings can have clinical implications for managing patients' after TC diagnosis (i.e. MetS can be predicted from age acceleration). Testing the clocks in an independent cohort of TC is needed for validation of our results.
Change in quality of life of metastatic breast cancer patients seeking treatment at Komfo Anokye Teaching Hospital, Ghana.
Authors: Agbeko Anita Eseenam , Bekae Adelaide , Boakye-Yiadom Jonathan , Arthur Joshua 
Published: June 2023

e24111 Background: Despite developments in breast cancer screening for early diagnosis and treatment, 20-85% of women go on to develop distant metastasis, based on tumor biology, stage at presentation and treatment modalities received. The primary goal of treating metastatic breast cancer (MBC) is to improve quality of life (QoL). This study assessed the change in QoL for patients with MBC seeking treatment at Komfo Anokye Teaching Hospital (KATH). Methods: Women with MBC seen at KATH had QoL assessed using the Functional Assessment of Cancer Therapy Breast (FACT-B) questionnaire before, and 3 months after they were supposed to have received systemic treatment - chemotherapy, hormonal, target therapy. Data was analyzed using STATA v17 software. The higher the FACT scores, the better the QoL. Results: Fifty-six women with MBC were interviewed. Their mean age was 51.7 years. Only 27 (48%) of them received some systemic treatment – chemotherapy, hormonal, target therapy – over the study period. Baseline median QoL scores in the wellbeing domains were physical (PWB) = 17.5, social/family (SWB) = 16.0, emotional (EWB) = 12.0, functional (FWB) = 8.0, breast cancer subscale (BCS) = 22.0. Their median total QoL scores were FACT-B = 77.5; FACT-B TOI = 48.5 and FACT-G = 54.5. At follow up, 28 (50%) of participants were alive. About a third (9/28) of them received no systemic treatment. Of the remaining 19; 4, 1 and 14 received one, two and three cycles of systemic treatment respectively. Their median QoL scores were PWB = 20.5, SWB = 16.0, EWB = 16.0, FWB = 15.0, BCS = 22.5, FACT-G = 72.0, FACT-B = 94.5, and FACT-B TOI = 61.0. Fourteen had improved, and 14 had deteriorated QoL. The median minimally important difference (MID) for the improved QoL group was MID FACT-B = -22, MID FACT-B TOI = -10 and MID BCS = -4, and for the deteriorated QoL group was MID FACT-B = 26.9, MID FACT-B TOI = 18 and MID BCS = 5. Being dead at follow up was related to receiving no treatment (AOR = 6.97, CI: 1.91 – 25.47, p-value = 0.003) and having one metastatic site at baseline (AOR = 5.23, CI:1.43 – 19.12, p-value = 0.01). Conclusions: Mortality among women with MBC was high (50%), especially among those who did not receive any systemic treatment or had one metastatic site. Of the survivors, equal proportions had significantly improved and significantly deteriorated QoL scores albeit varying treatment courses received. Further studies are needed to explore how systemic treatment or not impact QoL changes and survival outcomes of MBC patients in KATH.
Nutrition assessment reports in oncology clinical trials.
Authors: Aung Ye Myint , Aktas Aynur , Shroff Vishal , Kadakia Kunal C. , Waldman Jake , Walsh Declan 
Published: June 2023

e24142 Background: Malnutrition is common in cancer and associated with greater treatment toxicity and poor clinical outcomes. Validated screening tools can identify individuals at risk; however, they are underutilized in clinical practice. It is also unclear how nutrition status is assessed and reported in oncology clinical trials. We analyzed nutrition assessment protocols in clinical trials published in major US oncology journals. Methods: Three researchers (YA, AA, VS) identified studies published in the Journal of Clinical Oncology, JAMA Oncology, and the New England Journal of Medicine under the “original reports”, “original articles”, or “’ research” categories, respectively (1/1/2022-12/31/2022). We selected studies that reported outcomes of systemic therapeutic interventions in any Phase clinical trial. This included chemotherapy, hormone therapy, and immunotherapy alone or combined with radiation therapy or surgical procedures. Systematic reviews, meta-analyses, commentaries, retrospective studies, and secondary analyses of pooled data from completed trials were excluded. Descriptive statistics summarized how malnutrition risk was assessed and nutrition data reported. Results: 521 articles were reviewed; 153 (29%) studies met eligibility criteria. Most were randomized trials (103/153, 67%) and Phase II or III (126/153, 82%). Malnutrition risk assessment was absent from all studies. Overall, 15/153 (10%) reported either baseline Body Mass Index or pre-treatment weight changes. These variables were included in the survival analysis of 5/15 studies. The primary cancer sites studied were breast (5/15), gynecologic (3/15), hematologic (3/15), multiple sites (2/15), prostate (1/15), and pancreatic (1/15). Conclusions: Most oncology clinical trials ignore and/or underreport nutrition status. Only 10% of the studies reported nutrition status data, and not all cancer sites were represented. There is a need to routinely assess nutrition status and (given the major prognostic value) investigate its potential uses for patient selection and stratification in clinical trials.
Therapeutic evaluation on Chinese calycosin decoction for chemoradiotherapy induced thrombocytopenia.
Authors: Lv Guangmei , Hu Meng , Wan Haijun Wan , Liang Wei , Ha Wentao , Zhao Sunyan , Gong Yongling 
Published: June 2023

e24153 Background: Chemotherapeutic thrombocytopenia is often accompanied with hospitalized cancer patients associated with anti-tumor therapy, so called CRIT (Chemoradiotherapy induced thrombocytopenia). In addition to the risk of thrombocytopenic hemorrhage, we also observed the implementation of the originally scheduled chemoradiotherapy with limits of dose and frequency. However, CRIT therapy administered with Chinese calycosin decoction may benefit those affected patients. Methods: Forty CRIT patients diagnosed in the Nanjing 1st Hospital,China, from 2019 to 2021, were enrolled and divided randomly into herbal group (n = 19) and control group (n = 21). Herbal group was treated with additional calycosin decoction, while control group received conventional treatment related to CRIT in the mean time. The primary endpoint of efficacy assessment was time to recovery (TTR) for CRIT. Secondary endpoints were delayed termination rate (DTR) of chemoradiotherapy, incidence of hospitalization (IH) and incidence of platelet transfusion (IPT). Results: The effective rate of herbal group (13/19, 68.4%) and control group (12/21, 57.1%), and no grade 3 or 4 adverse gastrointestinal reactions were observed during treatment. Compared with the control group, TTR of grade Ⅰ-Ⅲ CRIT patients in herbal treatment group was relatively shorter (11.1±1.8d vs 13.8±2.1d), DTR (3/15,20% vs 7/16, 44%), and IH (7/15,47% vs 11/16,69%) was significantly lower, difference was statistically significant (P < 0.01). TTR, DTR, IH and IPT of grade Ⅳ CRIT patients were not significantly different between the two groups (P > 0.05). Conclusions: Chinese herbal managing of CRIT with calycosin decoction might be an additional choose option, help to benefit stand dosage implementation of chemoradiotherapy and socioeconomic cost.