bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of insulin resistance on CAC scores in cancer survivors.
Authors: Jacobi Nicole , Ortman Syndal Ann , Buda Lea , Duprez Daniel 
Published: June 2023

e24056 Background: Many cancer (ca) survivors exhibit signs of insulin resistance (IR), an important risk factor for the development of coronary artery disease (CAD). Paramount in survivorship care is prevention of cardiovascular disease. Coronary artery calcium (CAC) scans offer a risk assessment of cardiovascular (CV) disease before cardiac damage has occurred. We investigated how IR affects CAC scores in cancer survivors. We hypothesized that CAC scores differ significantly between insulin-sensitive- and -resistant cancer survivors. Methods: We enrolled 90 cancer survivors of a large community hospital from March 2021 to January 2022 into this pilot study. Patients were subdivided into three groups: insulin-sensitive (IS), insulin-resistant/prediabetic and insulin-resistant/diabetic. Patients were tested for fasting insulin, -glucose, HgbA1c and lipids. Patients without evidence for prediabetes or diabetes also underwent an oral glucose tolerance test (oGTT). All patients received a CAC scan. Results: 32 patients were IS, 29 patients were IR/prediabetic and 29 patients were IR/diabetic. 17 CAC scans in the IS group, 6 CAC scans in the IR/prediabetic group and 5 CAC scans in the IR/diabetic group showed an Agatston score of 0. The p-value between the three groups was statistically significant ( p=0.005) where as the IR/prediabetic- and the IR/diabetic group did not differ statistically from each other. The mean MESA 10-year CHD risk with CAC was 7.8. There was a highly significant difference between the 3 groups: the IS group had a mean of 5.3, the IR/prediabetic group had a mean of 7.3, and the IR/diabetic group had a mean of 11.0 ( p < 0.001). The two IR groups did not differ statistically (p=0.076). Conclusions: Our study showed that IR including prediabetes significantly increases the MESA 10-yr. CHD Risk with CAC in cancer survivors. Survivors with IR also have less frequent zero CAC scores than insulin-sensitive survivors. Survivors disproportionately exhibit insulin resistance, partly due to the association of certain types of cancer with IR. This trial highlights the importance of screening survivors for IR. Survivors diagnosed with IR should be screened for CAD more frequently than the general population. CAC scans are an inexpensive and efficient way of screening asymptomatic cancer survivors for CAD.
Factors associated with long-term gastrointestinal toxicity in colorectal cancer survivors in the women’s health initiatives (WHI) study.
Authors: Han Claire , Reding Kerryn , Kalady Matthew , Yung Rachel Lynn , Paskett Electra 
Published: June 2023

e24057 Background: Colorectal cancer (CRC) survivors often experience long-term symptom toxicity after cancer treatments. We described persistent gastrointestinal (GI) toxicity related to cancer and treatments in long-term CRC survivors and assessed the risk and life impact factors of GI toxicity. Methods: A cross-sectional study utilized data from the Women’s Health Initiative (WHI) Life and Longevity After Cancer (LILAC) study that recruited postmenopausal women. CRC survivors after cancer treatments were included (N = 413). Pearson correlations/A Chi-square test and multivariable linear regression models were used to identify risk and impact factors of GI toxicity. Results: 81% of CRC survivors experienced persistent GI toxicity. Bloating/gas was the most prevalent (54.2%) and severe, followed by constipation (34.1%), diarrhea (33.4%), and abdominal/pelvic pain (28.6%). Time since cancer diagnosis (< 5 years), advanced cancer stage, low income, high psychological distress, poor dietary habits and physical activity, and impaired life impact measures (health-related quality of life, daily life interferences, and body image) were significantly associated with several GI toxicities. Fatigue and sleep disturbance were the most significantly associated with long-term GI toxicity (Table 1). Abdominal/pelvic pain significantly influenced life impact measures. Conclusions: GI toxicities are highly prevalent among CRC survivors, specifically in patients with high psychological distress. A better understanding of the long-term GI toxicity in CRC survivors and identifying those more vulnerable may inform future directions for managing CRC survivorship. An individualized, multifaceted intervention is warranted to consider psychosocial support, lifestyle intervention, and physical rehabilitation. [Table: see text]
The safety, tolerability and efficacy of LP-10 in subjects with refractory moderate to severe hemorrhagic cystitis: Phase 2a multicenter dose escalation clinical trial.
Authors: Chancellor Michael , Breyer Benjamin , Joshi Shreyas S. , Smith Christopher , Kaufman Melissa , Okonski Janet , Hafron Jason 
Published: June 2023

e24064 Background: Hemorrhagic Cystitis (HC), a rare but highly morbid disease for which there are currently no FDA approved treatments, can occur in cancer survivors including patients with prostate cancer, cervical/uterine cancer and colon cancer. Lipella Pharmaceuticals received orphan disease designation for HC, and recently completed a phase 2a clinical trial of LP-10 (intravesical tacrolimus) for the treatment of HC. Methods: The LP-10 Phase 2a clinical trial was a multi-center, dose-escalation study (clinicaltrials.gov: NCT01393223). The study recruited subjects with moderate to severe refractory HC. These subjects were treated with up to two courses of LP-10 intravesical bladder instillations (liposomal formulation of tacrolimus at 2 mg, 4 mg and 8 mg). Results: Fifteen subjects were screened (14 male and 1 female) and 13 enrolled. All enrolled subjects were male with mean age 67 (range 25-89 years old) with a history of prostate cancer (n = 9), bladder cancer (n = 2) and lymphoma (n = 2). Mean duration of HC was 4 years and ranged from 1-14 years. No subject discontinued treatment or were lost to follow-up. All subjects tolerated LP-10 instillations and completed the study without report of product related serious adverse events. 12 AEs were reported in 6 subjects. Pharmacokinetic analysis demonstrated short duration of low systemic uptake of tacrolimus. A dose response was noted with higher efficacy at both the 4mg and 8 mg dose groups. After LP-10 treatment, the number of cystoscopic bleeding sites and bladder ulcerations decreased and patients’ urinary symptoms improved. Conclusions: This first phase 2a study demonstrated safety and a signal of efficacy at intravesical tacrolimus (LP-10) doses of 4 mg and 8 mg for the treatment for HC, a rare and serious disease. Clinical trial information: NCT01393223 . [Table: see text]
Outcome of deep venous thrombosis and pulmonary embolism in COVID-19 cancer patients vs non-cancer patients.
Authors: Jones Can , Menchaca Kristina D. , Ostos Catherine , Elsheshtawi Mohamed , Velez-Quinones Virginia , Peles Shachar , Saeed Hayder 
Published: June 2023

e24066 Background: COVID-19 is associated with an increased incidence of venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE). Multiple mechanisms including COVID-19-induced endothelial dysfunction, cytokine storm, complement activation, and hypoxia lead to the activation of the coagulation cascade. Of note, VTE is the most common presentation of cancer-associated thrombosis. It is associated with worsened prognosis and mortality in both COVID-19 patients and cancer patients. Some studies indicated that comparing to COVID-19 non-cancer population, COVID-19 cancer patients have a higher risk of developing VTE. Methods: This retrospective cohort study identified 1,306 adult patients admitted to the tertiary medical center for COVID-19 treatment from 2020 to 2021, including 38 active cancer patients and 1268 non-cancer patients. Skin cancers were excluded. All patients received anticoagulant for VTE prophylaxis. The primary outcome of interest was the VTE incidence. Results: There was no significant difference in baseline demographics between groups. 35 non-cancer COVID-19 patients developed DVT (2.76%), while one patient had DVT in the cancer group (2.63%); for PE, 25 non-cancer patients were found to have PE (1.97%), while one cancer patient was diagnosed with PE (2.63%). There were no statistical differences in DVT and PE incidences between the COVID-19 cancer group and the non-cancer group during hospitalization. However, the cancer group was found to have older age (P < 0.001), higher D-dimer (P = 0.024) level, and more severe thrombocytopenia (P < 0.001). The COVID-19 cancer group revealed significantly higher in-hospital mortality (36.84%) comparing to the non-cancer group (14.98%) (P < 0.001). Conclusions: Our study revealed no differences in the incidence of PE and DVT between the COVID-19 cancer population and the COVID-19 non-cancer population; COVID-19 cancer patients experienced significantly higher mortality comparing to COVID-19 non-cancer patients. This highlights the importance of having larger-scale studies in the future to assess different outcomes in patients with malignancy and COVID-19.
Understanding cancer treatment decision making among cancer survivors.
Authors: Streck Brennan , Vo Jacqueline B. , Brandt Carolyn , Klein William , Han Paul , Ferrer Rebecca , Gillman Arielle Samantha 
Published: June 2023

e24076 Background: Nearly 20% of U.S. cancer survivors develop late cardiovascular disease (CVD) as a result of cardiotoxic cancer treatments. Patients and providers may consider alternative treatment options to lower cardiotoxicity risk, which may present a trade-off between reducing relatively near-term relapse/recurrence vs. preventing long-term CVD. Patients’ decision-making processes (e.g., delay discounting, risk perceptions for CVD vs. cancer) may affect such choices. However, these decision-making factors are not well understood in this context; nor is their association with treatment selection. Methods: In a cross-sectional survey using the online survey vendor Prolific, we recruited 443 U.S. cancer survivors (any type.) Using logistic regression, we assessed how survivors’ risk perceptions (deliberative, affective, and intuitive) for cancer vs. CVD were associated with decisions between two hypothetical cancer treatments involving different risk tradeoffs: Treatment 1: 5% chance of near-term cancer recurrence & 10% chance of CVD; Treatment 2: 10% chance of near-term cancer recurrence & 5% chance of CVD. We explored effects of delay discounting by randomizing participants to information describing immediate vs. delayed (10 years post-treatment) development of CVD. Results: Survivors ( Mage = 48, range 18-93) were, on average, 10.8 years from diagnosis. More survivors ( 72% v. 28%) chose Treatment 1 (lower cancer recurrence risk but higher risk of cardiotoxicity) than Treatment 2 (lower risk of cardiotoxicity but higher risk of cancer recurrence) . Immediacy of CVD development (immediate vs. delayed) was not associated with treatment selection (p = 0.12.) Modeling separately, higher levels of affective risk perception (“worry”) about cancer, but not worry about CVD, was associated with increased odds of choosing Treatment 1 ( OR= 1.25, p= 0.014.). Modeled together, cancer worry was associated with increased odds, whereas CVD worry was associated with decreased odds, of choosing Treatment 1 ( OR-cancer= 1.35, p= 0.002; OR-CVD= 0.76, p= 0.011). Neither deliberative nor experiential risk perceptions were significantly associated with treatment choice. Conclusions: Cancer survivors were more likely to select treatment that minimizes cancer recurrence rather than comparative CVD—regardless of the described immediacy of cardiotoxicity. Further, treatment decision also depended upon both cancer- and CVD-related worry but not deliberative or experiential risk perceptions. Comparatively to CVD, cancer is often more affectively-laden, especially among cancer survivors. These results suggest that in treatment discussions, clinicians may need to address not only the probabilities of treatment outcomes, but patients’ relative worries about cancer and cardiotoxicity.
External validation of biomechanical computed tomography for fracture risk classification in metastatic hormone sensitive prostate cancer.
Authors: Lin John Kent , Hearn Caleb , Getzen Emily , Long Qi , Drell Helayne , Lee David , Keaveny Tony M. , Jayadevappa Ravishankar , Robinson Kyle William , Wong Yu-Ning , Maxwell Kara Noelle , Narayan Vivek , Haas Naomi B. , Takvorian Samuel U. , Bikle Daniel , Chiang Janet M. , Khan Amna N. , Rajapakse Chamith S , Morgans Alicia K. , Parikh Ravi Bharat 
Published: June 2023

e24077 Background: For men with metastatic hormone-sensitive prostate cancer (mHSPC) on androgen deprivation therapy (ADT), guidelines recommend dual-energy X-ray absorptiometry (DXA) screening to identify fracture risk and benefit from antiresorptive therapy. However, only 8% of men with mHSPC receive routine DXA screening. Biomechanical computed tomography (BCT) is a radiomic technique that measures bone mineral density (BMD) and bone strength from routine staging and surveillance CT scans but has not been validated in mHSPC. Methods: This retrospective cohort study included 99 patients with incident mHSPC beginning ADT (2013-2020) at one academic (n = 70) and one tertiary VA medical center (n = 29) with CT abdomen/pelvis or PET/CT imaging at baseline (within 1 year prior to ADT initiation) and follow-up (1-2 years after ADT initiation). BCT-assessed BMD T-score and femoral strength were calculated from baseline and follow-up CT scans. We evaluated the association between BCT measures and subsequent pathologic and non-pathologic fractures within 3 years following mHSPC diagnosis. Results: Among 99 patients, mean age was 68 years, 48 (48.5%) were White, and 45 (45.4%) were Black. During median follow-up of 19 months, 23 (24%) developed a pathologic and 15 (15%) a non-pathologic fracture. BCT and DXA-assessed femoral-neck BMD T-score were strongly correlated (R2= 0.94, N = 23). Higher BCT-assessed baseline BMD (Odds Ratio [OR] 0.5, p = 0.03) and bone strength (OR 0.57, p = 0.02) were each associated with decreased pathologic fracture (Table). Neither BMD nor bone strength were significantly associated with non-pathologic fracture. BCT identified 10 (10%) men eligible for antiresorptive therapy by established BMD, strength, or FRAX criteria at ADT initiation, 4 (40%) of whom never received it by the end of follow-up. Between baseline and follow-up, both BMD (-0.27) and bone strength (-0.34) decreased among patients who did not receive antiresorptive therapy (n = 76), with no difference in longitudinal change between ADT alone vs with androgen receptor signaling inhibitors. Conclusions: In this diverse, multicenter cohort of men with mHSPC beginning ADT, BCT BMD assessed from routine CT scans strongly correlated with DXA-assessed BMD. BCT measurements predicted subsequent pathologic fracture and identified additional men who would benefit from antiresorptive therapy. BCT may provide a practical method to assess the role for anti-resorptive therapy in patients with mHSPC. [Table: see text]
NGAL and KIM-1 as early biomarkers of cisplatin-associated nephrotoxicity.
Authors: Chebotareva Natalia , Zhukova Lyudmila , Krasnova Tatyana , Grechukhina Katerina 
Published: June 2023

e24080 Background: Cisplatin can cause renal injury in one-third of the patients. After the uptake by tubular renal cells cisplatin causes TNF-a immediate inflammation and death of tubular cell, ischemia and vascular damage on the kidney, which results in glomerular filtration rate (GFR) decrease (Toyuz et al, 2019). Serum creatinine is increased at the time of approximately 50% of nephrons are damaged. The identification of predictors and early markers of renal damage will make it possible to identify a high-risk group and monitor renal damage (Touyz, 2018). NGAL is activated immediately after ischemic or direct toxic damage to the kidneys in the distal segments of the nephron (Schmidt-Ott et al, 2007; Mishra). KIM-1 is an early marker of proximal tubule damage (Prasaja et al, 2015). Both NGAL and KIM-1 demonstrated their role of renal damage biomarkers in contrast-induced acute kidney injury. The goal of this study was to assess NGAL and KIM-1 as biomarkers of early nephrotoxicity induced by cisplatin and to assess their role as risk factors. Methods: The study included 50 patients who received cisplatin. Nephrotoxicity was determined as a decrease in GFR to < 60 ml/min/1.73 m2 at 8 weeks from the initiation of therapy. The levels of KIM-1 and NGAL 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, a logistic regression analysis was performed with the inclusion of primary clinical and laboratory parameters. ROC-analysis was used to assess sensitivity and specificity of markers. Results: The decrease of GFR less then < 60 ml/min/1.73 m2 at 8 weeks was observed in 11 (22%) of patients. There were no signs of increase of blood pressure in 8 weeks of observation. Serum creatinine increased clinically significant in 8 weeks after the start of therapy. The level of NGAL and KIM-1 rapidly increased in 1 week after the start of therapy (p < 0.001) which is shown in Table. The unfavorable predictor of nephrotoxicity was a 1-week increase of urine NGAL and KIM-1: OR 8.37; 95%CI 4.64-95.84; p = 0.001. Both NGAL and KIM-1 demonstrated high sensitivity, specificity and area under the curve (AUC) – both 0.69 as early biomarkers of nephrotoxicity assessed after 8 weeks from the start of therapy. Conclusions: An increase of KIM-1 and NGAL observed earlier then serum creatinine increase. Elevation in 1 week after the initiation of therapy can predict nephrotoxicity with high specificity and sensitivity. At the same time an early increase in the concentrations of KIM-1 and in the urine is the independent risk factors for cisplatin-induced nephrotoxicity. [Table: see text]
Immune checkpoint inhibitors (ICIs) with or without anti-angiogenic agents (AAAs) and cardiovascular toxicity: A meta-analysis.
Authors: Madonia Giorgio , Veccia Antonello , Berti Alvise , Caffo Orazio , Russo Antonio , Gori Stefania , Inno Alessandro 
Published: June 2023

e24084 Background: ICIs have extended survival across many tumor types at the cost of immune-related adverse events (irAEs) that can involve any organ or system, including cardiovascular system. Emerging evidence suggest that ICIs may have a role in promoting the atherosclerotic plaque progression, thus leading to acute vascular events (AVEs) This may represent a concern when combining ICIs with other anti-cancer agents burdened by cardiovascular toxicity, such as anti-angiogenic agents (AAAs), that are associated with increased risk of hypertension (HTN) and AVEs. In the present meta-analysis, we aimed to evaluate the odds of adverse events (AEs), irAEs, HTN and AVEs with ICI+AAAs, as compared with AAAs alone. Methods: Phase III randomized controlled trials were identified by searching the MEDLINE/PubMed, Cochrane Library and ASCO Meeting abstracts, from inception until June 2022. Systematic review and metanalysis were conducted according to PRISMA guidelines. AEs, irAEs, HTN and AVEs were collected (main outcomes of this metanalysis), objective response rate (ORR) and progression free survival (PFS) were also collected (secondary outcomes). AVEs were defined as stroke, myocardial infarction, thrombotic events, pulmonary embolism. Severe AEs, irAE, HTNs and AVEs were defined as grade ≥3 according to the National Cancer Institute Common Terminology for Adverse Events (CTCAE) version 4.0 or 4.03, as reported in each trial. Results: Twelve trials with a total of 8124 patients (4159 in the experimental arms and 3965 in the control arms) were included in the meta-analysis. The addition of ICIs to AAAs did not increase the rate of AEs (any grade, OR 1.15, 95%CI 0.71-1.85; severe, OR 1.18, 95% CI 0.96-1.44). In contrast, the incidence of irAE was significantly higher in the ICIs+AAA- group versus AAAs (any grade: OR 1.97, 95%CI 1.21-3.21, p = 0.007; severe: OR 3.20, 95%CI1.41-7.29, p = 0.006), as expected. There was no difference in terms of any grade HTN between the 2 groups (OR 1.17, 95%CI 0.91-1.50, p > 0.05), but severe HTN was higher among patients treated with ICIs+AAAs as compared with those receiving AAAs alone (OR 1.24, 95%CI 1.01-1.53, p = 0.04). AVEs rates were low in both groups (2.2% and 1.9% for ICI+AAA and AAA alone, respectively). A subset analysis of trials specifically reporting AVEs did not show any increase in ICIs+AAAs versus AAAs alone (any grade: OR 1.21, 95%CI 0.68-2.16, p > 0.05; severe: OR 1.14, 95%CI 0.61-2.15, p > 0.05). Overall, the ORR and PFS were higher in the ICIs+AAAs group as compared to AAAs alone (OR 2.25, 95%CI 1.70-2.97, p < 0.001; OR 4.37, 95%CI 2.91-5.83, p < 0.001, respectively). Conclusions: The addition of ICIs to AAAs significantly increased the risk for irAEs and severe HTN, but not the risk for AVEs.
Barriers to offering female fertility preservation to pediatric and young adult oncology patients: A national survey of pediatric hematology oncology providers in the United States and Canada.
Authors: Walker Amanda , Baskir Elan , Matthes Geoffrey , Pentakota Sri Ram , Bhatla Teena , Batra Surabhi 
Published: June 2023

e24088 Background: The American Society of Clinical Oncology (ASCO) recently updated its guidelines on fertility preservation based on similar rates of pregnancy from oocyte and embryo preservation. However, fertility preservation in female pediatric and young adults undergoing cancer treatment remains a challenge due to barriers in communication, lack of awareness and resources. Methods: A survey created using SurveyMonkey was sent electronically to all physicians who were Children’s Oncology Group (COG) members (2190), weekly for 4 weeks. Results: 304 physicians (13.8%) responded to the survey. While most providers discuss the possibility of infertility with all female patients (83%), only 43% offer fertility preservation irrespective of age. Cancer diagnosis is a key factor in the decision to offer fertility preservation to patients (63%). Ewing sarcoma (75%), osteosarcoma (69%), and bone marrow transplant candidacy (70%) are the most common diagnoses associated with physician offering of fertility preservation. It is typically offered prior to the first round of chemotherapy (53%). Seventy-five percent of providers report that insufficient time before starting chemotherapy is a major barrier to offering fertility preservation. Severity of patient illness (58%), insurance issues and high cost (19%), provider belief that it is not necessary in every patient (25%), and lack of data supporting female fertility preservation and experimental methods (16%) are other barriers which impact the decision to offer fertility preservation. Ovarian suppression (77%), cryopreservation (egg freezing) (85%), and ovarian tissue freezing (66%) are the most discussed fertility preservation options with only one out of four providers discussing freezing embryos. Only one out of five providers check Anti-Mullerian hormone (AMH) levels prior to starting cancer treatment; however, two out of five check AMH levels after completion of therapy. Most providers do not check AMH levels. Conclusions: Despite high risk for infertility among female cancer patients due to treatment and several advances that have been made in the field, the practice of offering fertility preservation is not universal due to various barriers at the physician and institutional level. Physician education and familiarity with ASCO’s newer guidelines is one way to promote a healthier dialogue and informed decision making. We also conclude that detailed guidelines and monitoring practices for diminished ovarian reserve are lacking and need further thought.[Table: see text]