bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peripheral neuropathy after breast cancer: An analysis of data from the Women’s Health Initiative Life and Longevity After Cancer cohort.
Authors: Kamgar Mandana , Assad Hadeel , Hastert Theresa A. , McLaughlin Eric , Reding Kerryn , Paskett Electra D. , Bea Jennifer W. , Shadyab Aladdin H. , Neuhouser Marian L. , Nassir Rami , Crane Tracy E , Sreeram Kalyan , Greenwald Mark K. , Simon Michael S. 
Published: May 2020

e24093 Background: There are over 3.8 million breast cancer survivors in the United States, and many experience long-term side effects from chemotherapy. Factors associated with peripheral neuropathy (PN), one troubling side effect, following breast cancer among women are unknown. Methods: We included 2,420 women enrolled in the Women’s Health Initiative and diagnosed prospectively with local or regional stage breast cancer and followed in the Life and Longevity After Cancer (LILAC) study. PN was assessed by response to the baseline LILAC questionnaire regarding the presence of “nerve problems, tingling sensations” after treatment. Data were collected on initial course of therapy (surgery, radiation, and chemotherapy) through Medicare linkage or the LILAC staging and treatment form. Chi-square and Wilcoxon rank-sum tests were used for univariate comparison of socio-demographics, clinical and diagnosis characteristics associated with the presence or absence of PN. Results: The sample included 1,913 women (79%) with local and 507 women (21%) with regional stage disease. Initial course of therapy included either surgery alone (21%), surgery and radiation (53%), or surgery and chemotherapy (+/- radiation) (26%). Seventeen percent of women reported experiencing PN days (30%), months (46%) or years (24%) following treatment. Three-quarters (74%) reported ongoing symptoms at the time of the LILAC survey. PN was reported by 33% of chemotherapy recipients, compared to 12% in the surgery alone group, and 11% in the group that received surgery and radiation (p<0.0001). The prevalence of PN was higher among women receiving regimens containing paclitaxel (52%) and docetaxel (39%), compared to those receiving other chemotherapy (17%) (p<0.0001). Conclusions: PN is an important complication of taxane-based chemotherapy. Further analysis will explore the relationship between socio-demographic, clinical and treatment on the development, timing of, and severity of PN after cancer directed therapy.
The chemo-brain effect in colorectal cancer patients.
Authors: Lee Matilda , Chong Wan Qin , Tan Hon Lyn , Chan Gloria , Ho Jingshan , Sundar Raghav , Chee Cheng Ean , Nasrallah Fatima , Koo Edward H , Yong Wei-Peng 
Published: May 2020

e24095 Background: The chemo-brain effect associated with systemic chemotherapy results in cognitive disturbances impacting the capacity to engage in tasks and quality of life (QOL). Patients with colorectal cancer (CRC) who receive adjuvant chemotherapy generally have long survival times. The long-term effect of chemotherapy on cognition is uncertain. We aimed to ascertain the frequency of long-term cognitive impairment using neuropsychological assessments and correlating with neuroimaging. Methods: In this prospective pilot study, patients (n=22) with stage II to III CRC between 45 to 75 years old, who were planned to receive adjuvant chemotherapy, were recruited. 3 visits were scheduled for each subject – pre-chemotherapy (V1), at 1 month post chemotherapy (V2), and at 6 months post chemotherapy (V3). Serial tests were performed – the Cambridge Neuropsychological Test Automated Battery (CANTAB), QOL questionnaires (Hospital Anxiety and Depression Scale (HADS), Perceived Deficits Questionnaire (PDQ), EORTC QLQ-C30, FACT-ES), 3 item pocket smell test, functional PET/MRI brain imaging, and blood biomarker studies. Results: 18/22 subjects (13 male, 5 female) had completed tests at all 3 visits; the median age was 62 years (range 51 – 69). 9/18 had an initial decline (median -0.033) of Rapid Visual Information processing (RVP) at V2; 3/9 showed improvement to baseline at V3. 8/18 had a persistent decline in RVP scores at V3 (median -0.054). This was associated with increased HADS depression scores (mean 3.63 at V2 vs 4.63 at V1), worsening attention scores (mean 4.38 at V3 and 3.63 at V1), prospective memory scores (mean 3.75 at V3 vs 3.38 at V1), and total scores (mean 14.63 at V3 vs 13.75 at V1) on the PDQ. 7/18 had an increase in Paired Associates Learning (PAL) errors (median +6) at V2. 3/7 improved to baseline at V3, while 4/7 continued to have a persistent decline. PAL scores were not associated with worsening retrospective or prospective PDQ memory scores, changes in HADS depression or EORTC QLQ-C30 scores. There was no difference in baseline CANTAB scores for patients reporting declining vs stable QLQ-C30 scores. Conclusions: Only half of patients with initial RVP A and PAL decline improved at 6 months post chemotherapy. Further efforts should be placed to identify those at risk of poor recovery, and develop strategies to manage the chemo-brain effect. The correlation of cognitive decline with neuroimaging will be presented in the final analysis.
A retrospective single-center evaluation of the safety and efficacy of direct oral anticoagulants versus low molecular weight heparin in patients with cancer-associated thrombosis.
Authors: McShane Melissa , Senchak Jordan , Stack Anthony , Frimpong Justina , Hellerslia Van T , Zhao Huaqing 
Published: May 2020

e24102 Background: Over the past decade, there has been an increase in the use of direct oral anticoagulants (DOACs) in the cancer population despite limited data comparing its use against low molecular weight heparin (LMWH), the standard of care in cancer patients. Increasing data supporting DOACs in cancer-associated thrombosis has emerged over the past few years. Nonetheless, this study will evaluate the relative safety and efficacy of DOACs versus LMWH in cancer-associated thrombosis within an urban setting associated with low socioeconomic status. Methods: This is a retrospective chart review of medical records from patients treated at an urban academic medical center from October 2010 through October 2018. Patients met study inclusion if they had a diagnosis of venous thromboembolism occurring after the date of diagnosis of active cancer and were prescribed a direct oral anticoagulant (rivaroxaban, apixaban, dabigatran, edoxaban) or a low molecular weight heparin (dalteparin, enoxaparin, or fondaparinux) as monotherapy for the treatment of venous thromboembolic disease. Patients were excluded if they had less than 6 months of follow up data for reasons other than death. The primary outcomes were recurrent venous thromboembolism, major bleeding and death. Results: Of the 914 patients who met inclusion criteria, 286 were excluded due to lack of follow up data. The remaining patients included 472 in the LMWH arm and 156 in the DOAC arm. At 6 months, recurrent thromboembolism occurred in 5 of the 472 patients (1.1%) in the LMWH group as compared with 4 of the 156 patients (2.6%) in the DOAC group (p = 0.170). Major bleeding occurred in 36 patients (7.6%) in the LMWH group and 11 patients (7.0%) in the DOAC group (p = 0.813). Death within 6 months of starting anticoagulation occurred in 76 patients (16.1%) in the LMWH group and 16 patients (9.6%) in the DOAC group (p = 0.046). Discontinuation before 6 months of treatment occurred in 241 patients (51.2%) in the LMWH group and 46 patients (29.5%) in the DOAC group. Conclusions: The LMWH and DOAC groups had similar rates of recurrent thromboembolism and major bleeding. The mortality rate within 6 months of starting anticoagulation was significantly higher in the LMWH group and this difference requires further evaluation. These results help support the continued use of DOACs for the treatment of cancer-associated thrombosis and demonstrate that DOACs are as safe and effective as LMWH in this patient population.
PDGFC signaling is a potential therapeutic target for radiation proctopathy.
Authors: Fang Lekun , Xie Yunling , Zou Shaomin , Yang Ziqing 
Published: May 2020

e24105 Background: Radiation proctopathy(RP), with acute or chronic rectal dysbiosis, arises as one of the most crucial complications of radiation therapy for pelvic malignancies. Common symptoms of RP patients include rectal breeding, incontinence and so on. However, its efficacy is disappointing due to lack of specific therapeutic drugs. Moreover, limitied scientific studies have been carried out to elucidate the mechanism of RP progression. Herein, we aim to study the underlying mechanism of RP with mouse model and clinical samples, and dig out its potential therapy. Methods: Firstly, chronic radiation proctopathy(CRP) mouse model is established by administering 25 Gy γ-irradiation in the pelvic region shielding the rest of bodies with lead blocks. Eight weeks later, the mice are harvested, and their colorectal tissues are used for RT-qPCR, western blot, immunostaining and transcriptome sequence analysis. Secondly, the outcomes of irradiated Pdgfc+/+ and Pdgfc−/− mice are compared and gene set enrichment analysis(GSEA) is used to further clarify the differences between these two groups. Lastly, crenolanib, a selective inhibitor of PDGFR, is subjected to mice before or after γ-irradiation to study its potential role in RP prevention and treatment. Results: In our RP mouse model, pdgfc and fibrosis markers are shown to highly express in the distal colorectal tissues after irradiation, Similarily, accumulation of PDGFC and fibrosis-related proteins is observed in RP patients’ tissues and serum. Besides, pdgfc appears in the list of cytokine and cytokine receptor interaction gene set which is the most enriched one in the radiation group. Furthermore, pdgfc knockout significantly alleviates radiation induced colorectal injuries in vivo, including mucosal lesions, submucosal thickening, and hyperplasia and edema of muscular layer. Moreover, GSEA reveals that pdgfc knockout may suppress RP progression through repression of pro-inflammatory cytokines and chemokines. Finally, crenolanib overcomes irradiation-induced injuries in the colorectal region of mice. Conclusions: PDGFC is an important regulator of RP progression, which may serve as a potentially therapeutic target for RP treatment.
Knowledge, attitude and practices regarding the use of medical cannabis: A national survey among Israeli oncologists.
Authors: Mirelman Dan , Waissengrin Barliz , Goldway Noam , Sharon Hagai , Brill Silviu , Wolf Ido 
Published: May 2020

e24125 Background: Despite lack of clinical trials reporting on beneficial effects of the cannabis plant for cancer-associated symptoms, its use is increasing worldwide. Approximately 10,000 Israeli cancer patients receive permits for the use of medical cannabis, making cannabis one of the most commonly prescribed oncology treatments in Israel and making the Israeli oncologists highly experienced with its use. The experience gained by the Israeli oncologists is therefore highly valuable. Methods: We conducted a web-based survey among all 238 Israeli oncologists, addressing personal experience; knowledge and attitudes toward the use of cannabis in oncology. Results: Response rate was 54% (n = 126), with the vast majority (87%) regularly prescribing cannabis to their patients. Anorexia, pain and nausea were the most common indications for cannabis use. While 90% of responders stated lack of sufficient knowledge regarding cannabis, its use was perceived as effective and safe. Interestingly, while most oncologists stated that opioids should be used as a first line treatment for cancer pain, most would prefer cannabis for pain relief if needed by a close relative. Oncologists who support cannabis legalization were more likely to prescribe it. Conclusions: Our findings indicate extensive use and perception of medical cannabis despite lack of knowledge, and support about efficacy and indicate a unique role for moral attitudes affecting clinical decisions. These data call for the implementation of an educational program and practical guidelines enabling more consistent and rational approach toward cannabis role in oncology.
Patient-reported and clinician-rated performance status and general health among women with gynecologic cancers on palliative chemotherapy.
Authors: Poort Hanneke , Thompson Embree , Lu Gang , Keating Nancy Lynn , Matulonis Ursula A. , Campos Susana M. , Horowitz Neil S. , Dinardo Margaret , Carlson Kenzie , Onnela Jukka-Pekka , Wright Alexi A. 
Published: May 2020

e24128 Background: Oncologists’ perceptions of patients’ performance status (PS) and general health are key determinants of eligibility for chemotherapy and clinical trials. We sought to examine correlations between patient-reported and clinician-rated Eastern Clinical Oncology Group PS (ECOG-PS) and general health status (EQ5D) in women with incurable recurrent gynecologic cancers, as well as step counts from accelerometry as a proxy for objective PS. Methods: We used baseline data from a randomized trial evaluating a mobile health intervention that collects patient-reported outcomes and passive smartphone data and provides tailored symptom management advice. Half of participants also received a wearable accelerometer. We calculated Pearson correlations to determine agreement between ECOG-PS and EQ-5D assessments in patient-clinician dyads. We also calculated the median (IQR) step counts among a subset of women with ≥7 days of ≥8 hours wear time. Results: Data from 78 patient-clinician dyads demonstrated a moderate correlation between patient-reported and clinician-rated ECOG-PS (r = .47; P< .000). Among dyads, 38 (49%) had perfect agreement; 36 (46%) had higher patient-reported ECOG-PS, indicating more patient-reported functional limitations, compared with clinician reports; and 4 (5%) had lower patient-reported ECOG-PS. Comparisons between patient-clinician ratings of EQ-5D subscales indicated moderate agreement for mobility (r = 0.44; P< .001), pain/discomfort (r = 0.45; P< .001), and usual activities (r = 0.36; P= .002); and weak or no agreement for anxiety/depression (r = 0.31; P= .007) and self-care (r = 0.02; P> .05). Participants’ daily step counts varied widely (median = 5,511 steps, IQR = 3,784, range 1,736-13,961) and were not associated with patients’ or clinicians’ ECOG-PS estimates (r = -.12; P= 0.44 and r = -0.03; P= 0.84) or patient-reported mobility (r = -0.10; P =0.51). Conclusions: Among women with incurable gynecologic cancers, patients’ and clinicians’ perceptions of patients’ ECOG-PS were moderately correlated, although 46% of clinician ratings were more optimistic than patients’ ratings. There was also moderate agreement between dyads for mobility and pain/discomfort. Patients’ step counts were not correlated with ECOG-PS or patient-reported mobility. Future studies should examine these measures longitudinally to determine which is the most sensitive predictor of clinical outcomes. Clinical trial information: NCT03022032 .
Cannabidiol: Assessing preclinical safety in ovarian and endometrial carcinoma cell lines.
Authors: Rush Shannon , Kapur Arvinder K , Patankar Manish S. , Barroilhet Lisa Marie 
Published: May 2020

e24130 Background: Cancer patients use cannabidiol (CBD) for chemotherapy and cancer symptoms, though research of CBD safety and efficacy for these conditions are ongoing and mixed. We sought to determine endometrial (ECC1) and epithelial ovarian cancer (Kuramochi) cell proliferation when exposed to different concentrations of CBD, for the broader goal to establish if CBD can safely be utilized to treat the symptoms of cancer, including those caused by chemotherapy. Methods: ECC1 and Kuramochi cells were kept in media (RPMI with 10% bovine serum and 1% penicillin/streptomycin). We passaged cells when > 90% confluent by adding tryspin-EDTA, incubating at 37C for 3 minutes, then spinning down with media to harvest the cell pellet. Cells were re-suspended in media, counted and apportioned to 96 well plates. Plates were incubated at 37C x 24 hours. CBD (from Cayman Chemical) was suspended in DMSO per manufacturer instruction then used to treat cells x72 hours at different concentrations (2.5-50uM). MTT was added to cells, cells incubated at 37C x 3 hours, media and MTT were removed and DMSO was added. Optical depth (OD) was calculated for plates using SoftMaxPro version 6.2.2. ODs were used to calculate inhibitory concentration for 50% cell death (IC50). Results: Kuramochi and ECC1 demonstrated decreased cell proliferation when exposed to CBD for 72hours. ECC1 IC50 fell between 2.5-5uM. Kuramochi IC50 fell between 15-20uM. Nearly all ECC1 growth was inhibited at concentrations 10uM or greater. Kuramochi proliferation was 15% that of controls at concentrations of 40 and 50uM CBD. Conclusions: ECC1 and Kuramochi cells demonstrated decreased proliferation in the presence of CBD. This bodes well for future studies of concurrent exposure to CBD and cytotoxic chemotherapy. Further preclinical research needed on CBD effects in endometrial and ovarian cancer, as patients turn to CBD for symptomatic relief from cancer and chemotherapy side effects. [Table: see text]
Moderate to vigorous physical activity effect on chemotherapy-induced peripheral neuropathy.
Authors: Kanzawa-Lee Grace , Krauss John C. , Ploutz-Snyder Robert , Larson Janet , Resnicow Ken , Lievense Athena , Kavanagh Lauren , Smith Ellen M. Lavoie 
Published: May 2020

e24151 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common intractable side effect of oxaliplatin treatment that presents with numbness, tingling, and nerve pain in both hands and feet; and sometimes, weakness and impaired balance and quality of life. Moderate-vigorous (MV) physical activity (PA) may reduce CIPN by improving blood circulation, chemotherapy distribution, inflammation, oxidative stress, and neuroplasticity. This dose-response analysis aimed to explore the effect of different MVPA and total PA doses on CIPN severity among oxaliplatin-receiving gastrointestinal cancer survivors. Methods: The original pilot RCT tested an 8-week home-based brisk walking intervention versus PA education alone to reduce CIPN. This analysis focuses on the intervention group ( n = 29), which received MVPA motivational supports (e.g., a Fitbit Charge 2, walking plan, motivational interviewing). Participants completed self-report CIPN severity surveys at baseline (2nd oxaliplatin infusion) and 8 weeks. Fitbit-classified minutes of weekly MV and daily total (light-vigorous) PA were averaged over the 8 weeks. MVPA was dichotomized: met 225 weekly MVPA minutes ( n = 17) or not ( n = 19). Linear regression was used to analyze the effect of MVPA/total PA changes and effects on 8-week CIPN severity, controlling for oxaliplatin dose received and baseline CIPN levels. Results: Increases over the 8 weeks were observed in patients’ MVPA (mean difference [ MD] = 17.39 min/week; 95% CI 1.38, 33.40; p = .03) and total PA ( MD = 7.80 min/week; 95% CI 2.31, 13.29; p = .01). Total PA had no effect on the outcomes. However, averaging at least 225 MVPA minutes per week led to less severe sensory CIPN ( MD = -7.28; 95% CI -13.53, -1.03; p = .03), particularly tingling in the hands ( MD = -26.35; 95% CI -44.03, -8.68; p = .01). The models accounted for 37% and 44% of the variance in sensory CIPN ( p = .02) and tingling at 8 weeks ( p = .01), respectively. Conclusions: This pilot study provides preliminary evidence that increasing weekly MVPA, specifically, may lead to reduced CIPN severity among gastrointestinal cancer survivors receiving oxaliplatin. A larger study that utilizes stronger MVPA measurement and biomarker evaluation is needed. Clinical trial information: NCT03515356 .
Effect of growth differentiation factor 15 (GDF-15) inhibition on energy balance in cancer cachexia and in lipopolysaccharide (LPS)-induced sepsis mouse models.
Authors: Breen Danna , Bennett Donald , Jagarlapudi Srinath , Joaquim Stephanie , Zou Chang , Patel Anita , Wu Zhidan , Seeley Randy , Zhang Bei Betty , Bezy Olivier 
Published: May 2020

e24153 Background: Growth differentiation factor 15 (GDF-15) is a cytokine that induces anorexia, weight loss and has been reported to be associated with cachexia and poor survival in illnesses characterized by inflammation such as cancer cachexia and heart failure. In preclinical cancer cachexia models, GDF-15 inhibition has been demonstrated to reverse cachexia and improve survival. Circulating GDF-15 is also elevated in patients with sepsis and is associated with increased complications and poor survival. However, the role of infection- and sepsis-induced GDF-15 in mouse models is controversial based on published reports. Methods: In this study, we examined the effect of GDF-15 inhibition on tumor and lipopolysaccharide (LPS)-induced anorexia, weight loss, and survival using a GDF-15 neutralizing antibody (mAB2) and GDF-15 knockout mice. Results: mAB2 efficacy was confirmed by reversing AAV-GDF-15-induced weight loss in wildtype mice. A cachectic (anorexia and weight loss) mouse tumor model was established with subcutaneous implantation of mouse renal cell carcinoma (RENCA) cells. The chemotherapy sorafenib was administered to slow tumor progression. Plasma GDF-15 was increased to ~2 ng/mL, similar to levels in cancer patients. Treatment with mAB2 rapidly reversed both anorexia and weight loss in the tumor-bearing mice. LPS injection (intraperitoneal, 5 mg/kg) increased circulating GDF-15 in wildtype mice reaching concentrations like that reported in septic patients within 90 minutes and remaining elevated after 48 hours (~1 ng/mL). LPS decreased food intake, body weight, and increased mortality (~20%). Different from the tumor model, GDF-15 neutralization with mAB2 did not prevent or exacerbate any of the effects of LPS. There were no observed detrimental effects of mAB2 treatment in either model. Similarly, in GDF-15 knockout mice the LPS effect on energy balance and survival was comparable to that observed in wildtype controls. Plasma GDF-15 was undetectable in the GDF-15 knockout mice. Conclusions: Taken together, these data suggest that GDF-15 is a critical regulator of energy balance and survival in selective pathophysiological states associated with weight loss.