bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of a non-peptidic mimic of host defense proteins, PMX30063, in an animal model of oral mucositis.
Authors: Scott Richard W , Korczak Bozena , Watkins Brynmor A , Sonis Stephen T. 
Published: March 2020

9119 Background: Oral ulcerative mucositis (OM) is a common, painful, dose-limiting toxicity of cancer therapy. The care for OM is largely palliative and there is an urgent need for new and effective therapies. Host defense proteins (HDPs) are amphiphilic components of the innate immune system that serve as a primary response to infection. Exclusive of their direct antimicrobial activity, HDPs have been shown to possess immune modulatory and anti-inflammatory activities. We are developing non-peptidic mimics of HDPs, capturing the structural and biological properties of HDPs within a framework of smaller fully synthetic oligomers. The lead compound, PMX30063, is in Phase 2 clinical trials for iv treatment of systemic staphylococcal infections. Recently, we observed that HDP mimics attenuate anti-inflammatory pathways and reasoned that these activities could be leveraged into a mucositis intervention. Methods: In an acute radiation hamster model, PMX30063 was applied as a topical rinse, 3 times daily at 1, 3 or 10 mg/ml over a 28 day treatment regimen ( n = 10), following a single radiation dose to the buccal cheek pouch (40 Gy). In a fractionated radiation model, radiation (7.5 Gy/dose) was administered on days 0, 1, 2, 3, 6, 7, 8 and 9, targeting the left buccal pouch mucosa. PMX30063 was given topically 3 times daily at 3 mg/ml over a 35 day regimen beginning on day 0 (n = 10). OM was scored using an established blinded method. Results: In the acute model, PMX30063 reduced the number of animal days with ulceration from 43% in vehicle-treated hamsters to < 5% in all 3 PMX30063 dose groups (χ2 test; p<0.001). In the fractionated model, PMX30063 significantly reduced the daily mucositis scores prior to peak mucositis and throughout the remaining course of treatment (Mann-Whitney Rank-sum analysis; p<0.001). PMX30063 reduced the number of animal days with ulceration from 55% in vehicle-treated hamsters to 3.3% (χ2 test; p<0.001). The time courses of efficacy argue that direct antimicrobial action is not the primary driver of efficacy. Conclusions: The safe and highly efficacious activity of PMX30063 in animals supports its further development as a topical therapeutic to prevent OM in cancer patients.
Efficacy and safety of balugrastim compared with pegfilgrastim in patients with breast cancer who are receiving chemotherapy.
Authors: Volovat Constantin D. , Gladkov Oleg , Bondarenko Igor , Barash Steven , Buchner Anton , Avisar Noa , Bias Peter 
Published: March 2020

9125 Background: Patients receiving cancer chemotherapy are at an increased risk of neutropenia. Recombinant granulocyte colony stimulating factors (G-CSFs) have been developed to stimulate proliferation and differentiation of neutrophils. Pegfilgrastim is a pegylated recombinant G-CSF that allows for once-per-cycle dosing. Balugrastim is a long-acting G-CSF composed of a genetic fusion between recombinant human serum albumin and G-CSF. The objective of this study was to compare the efficacy and safety of balugrastim and pegfilgrastim in patients with histologically or cytologically confirmed breast cancer who were scheduled to receive doxorubicin and docetaxel. Methods: In this double-blind, randomized, active-comparator, noninferiority trial, patients with ≥1.5x109 neutrophils/L, and ≥100x109 platelets/L were randomly assigned to subcutaneous injections of balugrastim 40 mg (n=153) or pegfilgrastim 6 mg (n=151) with stratifications for weight, prior chemotherapy exposure, and global location. The primary efficacy endpoint was the duration of severe neutropenia (days with an absolute neutrophil count <0.5x109 cells/L) during the cycle 1 for the population of patients who did not have major protocol violations. Results: Mean duration of severe neutropenia in cycle 1 was 1.1 days in the balugrastim group and 1.0 days in the pegfilgrastim group (95% CI for difference between groups -0.13 to 0.37). Fifty-eight percent of patients in the balugrastim group and 59% in the pegfilgrastim group had severe neutropenia during cycle 1 (95% CI for difference between groups -11.98% to 10.41%). Two and 4 patients, respectively, had febrile neutropenia during cycle 1; no patients in either group had febrile neutropenia during cycles 2-4. Twenty percent of patients in the balugrastim group and 19% in the pegfilgrastim group had adverse events that the investigator considered to be related to study medication. Six and 7 patients, respectively, had serious adverse events. Conclusions: The results of this study support the noninferiority of balugrastim versus pegfilgrastim, demonstrating that both compounds have comparable efficacy. There were no unexpected safety events.
A prospective study of family conferences (FCs) in a palliative care unit (PCU) at a comprehensive cancer center.
Authors: Dev Rony , Coulson Luke C , Pulivarthi Kalyan , Del Fabbro Egidio , Palla Shana L. , Yennurajalingam Sriram , Bruera Eduardo 
Published: March 2020

9127 Background: TheFC provides the family information and emotional support in the transition to end-of-life care. There are a few, mainly qualitative, studies of FCs in a palliative care setting. A retrospective report suggested increased emotional expression by family members when patients were not present in the FC. The purpose of our study was to determine the characteristics of FCs and the effect of patient participation on emotional expression by family members. Methods: A prospective study was conducted during 18-month period with140 consecutive FCs conducted by an interdisciplinary team (palliative care physician, social worker, and others). Data collected included demographics, discharge disposition, number of participants, caregiver characteristics, expressions of emotional distress, conflict with healthcare providers, and topics discussed. Descriptive statistics and frequencies were calculated. Analysis was performed using a chi-square test. Results: 70 patients (50%) were female, 64 (46%) white, 127 (91%) with solid tumors and a median age of 59. In 68/140 family meetings (49%), patients actively participated. The primary caregivers were predominantly female (66%), white (49%), and either the spouse or partner (59%). A median number of 4 family members and 4 healthcare providers attended the FCs with median duration of 1 hour and median of 2 days prior to discharge. Questions concerning advanced directives, symptoms anticipated at death and caregiver well-being were infrequent. Patients verbalized distress frequently, (73.1%). Primary caregivers emotional expression of verbal distress were high but not significantly affected by patient presence (82% vs 82%, P:NS); however, verbal expressions of emotional distress by family were more common when patients were absent (87%) than when present (73%), p = 0.037. Conclusions: There was a high frequency of expression of emotional distress by patients and family members. Patient participation was associated with decreased verbal emotional expression by family members but not the primary caregiver. Further studies are needed on the benefits of allocating additional time to meet with family members without patient presence during a FC.
Palonosetron (PALO) plus 1-day versus 3-day dexamethasone (DEX) with or without aprepitant against delayed nausea (DN): Pooled analysis for 554 women receiving highly emetogenic chemotherapy (HEC).
Authors: Celio Luigi , Longo Flavia , Mansueto Giovanni , Lapadula Vittoria , Agustoni Francesco , Aapro Matti S. 
Published: March 2020

9133 Background: Nausea is more difficult to control than vomiting, because the incidence of the symptom continues to rise over the days after chemotherapy. This post-hoc analysis addressed two questions: 1) Does PALO plus single-dose DEX result in suboptimal control of DN when compared to the same regimen with additional DEX doses? 2) Is the combination of PALO, DEX, and aprepitant a more effective coverage against DN? Methods: The analysis was based upon outcomes in chemo-naïve women (median age =52) with solid tumors (89% breast) enrolled in two Phase III and two Phase II trials of HEC (AC combination or cisplatin). Patients received the following regimens: 1) PALO 0.25 mg plus DEX 8 mg IV on day 1 of chemotherapy (1-day regimen, n=243); 2) the same regimen on the day 1 followed by DEX 8 mg orally on days 2 and 3 (3-day regimen, n=207); or PALO plus DEX plus aprepitant 125 mg on day 1 followed by aprepitant 80 mg on days 2 and 3 (triple regimen, n=104). The pre-specified primary endpoint was the proportion of patients with no DN (days 2-5 after the first cycle of chemotherapy). The two primary comparisons were 1-day vs. 3-day regimen, and triple vs. 3-day regimen, with statistical significance set to the 0.025 level. Results: The 1-day to 3-day regimen comparison was not statistically significant (44% vs. 47.8%; risk difference (RD) = -3.8%, 95% CI (-5.4 to 12.9%), P=0.421 (two-sided chi-square test). The triple to 3-day regimen comparison was also not significant (57.7% vs. 47.8%), RD= +9.9%, 95% CI (-1.9 to 21.3%), P=0.101. More patients receiving triple regimen experienced no acute-onset nausea compared with those administered only DEX (97.1% vs. 51.2%, P<0.0001). Conclusions: This analysis provides evidence that PALO plus 1-day or 3-day DEX yield similar prevention of DN. The addition of aprepitant does not improve the control of DN. Complete results utilizing a multivariable model accounting for risk factors and trial heterogeneity will also be presented.
Outpatient chemotherapy supportive care: Trial of an IT-integrated, NP-delivered system for unrelieved symptoms.
Authors: Mooney Kathi , Beck Susan L. , Wong Bob , Dunson William A. , Wujcik Debra 
Published: March 2020

9137 Background: We tested an automated computer based remote monitoring system paired with nurse practitioner (NP) follow up using a case management system to address unrelieved symptoms. Methods: Prospectively 336 patients beginning a course of chemotherapy were randomized to the Telephone Care NP (TC) intervention (n 174) or usual care (UC) (n 162). All called daily reporting presence, severity, and distress (0-10 scale) for 11 common symptoms. Those in the TC intervention also received automated tailored symptom self-care messages and, based on automated alerts for unrelieved symptoms at moderate or higher levels, NP calls to further treat symptoms utilizing national guidelines. Results: There were no differences between groups on any demographics: 84% White, 56 years old, female (77%), breast (45%) or lung (17%) cancer. Average study days were 73 with 87% call completion. Prevalence of participants reporting moderate to severe symptoms were fatigue (86%), pain (80%), sleep (78%), nausea (60%), depressed mood (52%), anxious (49%), trouble thinking (48%), numbness (43%), sore mouth (38%), diarrhea (38%), and appearance concerns (35%). Mixed modeling with intention to treat was used to compare overall symptom scores by treatment condition (TC/UC) while accounting for individuals. Results indicate the TC group mean symptom score was significantly lower than UC (mean difference = .30, p < .001). Also, each symptom was significantly lower for the TC group except for diarrhea. Poisson regression showed TC had lower Severe days than UC (est. means and SE) 3.16 (0.44) vs 10.24 (1.84), p < .001; and lower Moderate days 8.91 (1.04) vs 19.06 (2.22), p < .001. TC had somewhat higher Mild days than UC 19.85 (2.81) vs 13.75 (1.85), p = .06; and more No symptom days 66.06 (3.82) vs 52.02 (4.15), p = .01. Mixed modeling was used to explore TC intervention impact following NP calls for alerts. TC reduced symptom scores compared to UC over a 4 day period (mean difference = 1.28, p< .001). Conclusions: Remote telephone monitoring of symptoms after chemotherapy with nurse practitioner follow up on moderate and severe symptoms results in decreased symptom severity, distress, fewer severe and moderate days and more no symptom days.
Relationship of divergent ancestral genetic variation on chromosome 6p22 and racial disparities in survival in neuroblastoma.
Authors: Pinto Navin R. , Gamazon Eric R , Konkashbaev Anuar , Im Hae Kyung , Diskin Sharon , London Wendy B. , Maris John M. , Dolan M. Eileen , Cox Nancy J , Cohn Susan Lerner 
Published: March 2020

9516 Background: An increased prevalence of high-risk disease and worse outcome are observed in children with neuroblastoma who self-report as black versus white. We sought to determine whether genetic variation would explain this racial disparity. Methods: After quality control, we analyzed 511,836 germline genetic variants in 2,709 ethnically diverse children with neuroblastoma enrolled on Children’s Oncology Group study ANBL00B1 from 2001 to 2009. Genetic variation was summarized by conducting principal components analysis. The first principal component (PC1) separated patients with African ancestry from all others. PC1 was used as a continuous variable for ordinal regression with risk group and a Cox proportional hazard model of EFS. To identify genetic mechanisms for the observed disparities, we developed a method using genome-wide variation data applied to high-risk versus non-high risk samples. We identified a comprehensive list of loci with significant divergence between the ancestral populations. We then tested each such locus for association with high-risk phenotype using logistic regression with the proportion of African ancestry estimated by ADMIXTURE as covariate. Finally, top SNPs were added to multivariate models of both risk and event-free survival to determine if any top associations could abrogate observed disparities. Results: PC1 was associated with both risk (p = 0.007) and EFS (p = 0.037). We identified 72 population-divergent SNPs nominally associated with high-risk disease (p < 0.001). The risk allele for one of the top SNPs: rs9295536 (p = 9.2x10-8) was more common in the African ancestral population, was associated with high-risk phenotype and poor outcome in all patients and validated in a Caucasian-only subanalysis. In multivariate testing, this SNP abrogated the PC1 association with EFS (p = 0.18). Conclusions: A SNP with high divergence between ancestral populations on chromosome 6p22 accounts for the observed racial disparity in survival and is also a common genetic variant associated with survival in patients derived from either European or African ancestry (Bonferroni adjusted p < 0.05). Studies to elucidate the function of this SNP are underway.
Phase II study of temozolomide in combination with topotecan (TOTEM) in relapsed or refractory neuroblastoma and other pediatric solid malignancies: A European ITCC study.
Authors: Di Giannatale Angela , Mc Hugh Kieran , Dias Nathalie , Devos Annick , Geoerger Birgit , Jaspan Tim , Calmon Raphael , Courbon Frederic , Malekzadeh Katty , Aerts Isabelle , Verschuur Arnauld , Casanova Michela , Fouyssac Fanny , Rubie Herve , Corradini Nadege , Perel Yves , Zwaan Michel , Riccardi Riccardo , Le Deley Marie-Cécile , Caron Huib 
Published: March 2020

9517 Background: Temozolomide and topotecan have shown activity in several pediatric cancers, including neuroblastoma. Resistance to alkylating agents due to MGMT expression, MMR deficiency or microsatellite instability may be overcome through the combination with topoisomerase I inhibitors. The combination of temozolomide and topotecan (TOTEM) was well tolerated and showed preliminary activity in children with neuroblastoma and glioma (Rubie et al, 2010). Methods: This multicenter, non-randomized, multi-cohort Phase II study included children with neuroblastoma according to a 2-stage Simon design, and patients with central nervous system (CNS) and extra-cranial solid tumors in a descriptive design. Temozolomide was administered orally at 150 mg/m2 followed by topotecan at 0.75 mg/m2 intravenously for 5 consecutive days every 28 days. The main endpoint was objective response (OR), i.e., Complete or Partial Response (CR+PR), evaluated after 2 cycles according to WHO criteria, or INRC criteria for neuroblastoma patients with mIBG-positive lesions, by an independent radiological review. Independent review of mIBG imaging is pending. Results: 103 patients, median age 9.4 years (range 1-21), were treated between June 2009 and May 2011 in 18 centers: 38 neuroblastoma, 33 CNS tumors and 32 other solid tumors. Overall 420 cycles were administered (median 3 per patient; range 1-12). Grade 3 or 4 neutropenia was frequent (55% courses), though only 6% of patients developed febrile neutropenia. In the neuroblastoma cohort, 1 CR and 7 PR were observed, leading to an estimated OR rate of 21% (95%CI, 10-37%). Additionally 22 patients had disease stabilization (SD), leading to an overall tumor control (CR+PR+SD) of 79% (63-90%), and a 12-month progression-free survival rate of 47% (31-64%). Overall, 17/102 evaluable patients achieved an OR (17%, 10-25%), with 1 CR and 3 PR in 9 medulloblastoma (44%, 14-79%), 2 PR in 4 PNET, 1 PR in 12 malignant glioma, and 2 PR in 9 RMS. Conclusions: Temozolomide-topotecan combination results in significant tumor control in children with neuroblastoma and medulloblastoma/PNET with favorable toxicity profile.
Dietary intake and metabolic syndrome in adult survivors of childhood cancer.
Authors: Smith Webb A , Li Chenghong , Nottage Kerri , Srivastava Deokumar , Lanctot Jennifer , Green Daniel M. , Nolan Vikki G , Laver Joseph H. , Gurney James G. , Robison Leslie L. , Hudson Melissa M. , Ness Kirsten K. 
Published: March 2020

9526 Background: Childhood cancer survivors (CCS) are at increased risk for metabolic syndrome (MetSyn) and increased morbidity and mortality from cardiovascular disease. Following a heart healthy diet may decrease this risk. The purpose of this investigation was to characterize dietary patterns and to evaluate the association between diet and MetSyn among CCS. Methods: CCS who were 10+ year survivors of childhood cancer, who were older than 18 years of age, and participating in the St. Jude Lifetime Cohort Study (SJLIFE). They completed a medical assessment based on Children’s Oncology Group screening guidelines, and a food frequency questionnaire (FFQ). Laboratory and physical measures were obtained to determine MetSyn status using the NCEP-ATPIII criteria. Participants were classified as having MetSyn if they met the criteria for ≥3 components of MetSyn. Data from the FFQ were used to score dietary patterns according to WCRF/AICR recommendations. Those who met ≥4 of the 7 recommendations were classified as following a “healthy diet.” A stratified analysis by sex using log-binomial regression models was undertaken to evaluate associations between diet and MetSyn, adjusted for age, age at diagnosis, cranial radiation, education, household income, and smoking status. Results: Among 1421 participating CCS (49.3% male, median age 33.0 years, range, 18.9-60.0 years), 31.5% met the criteria for MetSyn and 25.8 % followed a healthy diet according to the WCRF/AICR recommendations. In multiple regression models stratified by sex, females who followed a “healthy diet” were 2.1 (95% CI 1.5-2.9) times less likely and males who followed a “healthy diet” were 2.2 (95% CI 1.5-3.1) times less likely to have MetSyn than those who reported following a “healthy diet”. Conclusions: Heart healthy diets in CCS are associated with decreased risk for MetSyn. Dietary interventions may be warranted in CCS with MetSyn.
Effect of dexraoxane on impaired mitochondrial structure and function in doxorubicin-treated childhood ALL survivors.
Authors: Lipshultz Steven E. , Miller Tracie L. , Gerschenson Mariana , Neuberg Donna S. , Stevenson Kristen , Franco Vivian I , Anderson Lynn , LiButti Daniel , Silverman Lewis B. , Vrooman Lynda M. , Sallan Stephen E. ,   Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia Consortium
Published: March 2020

9530 Background: Cardiotoxicity in doxorubicin (DOX)-treated long-term childhood cancer survivors is characterized by impaired cardiac function which is partly mediated by mitochondrial (mt) energy production. Preclinical studies show irreversible DOX-associated cardiac mt dysfunction. A response to impaired mt function is to increase the mtDNA copies/cell (mtDNA). We examined mtDNA and function in peripheral blood mononuclear cells (PBMCs) in childhood survivors of high-risk ALL who received DOX alone or DOX plus dexrazoxane (DOX/DEX). Methods: Patients with HR ALL treated on DFCI Childhood ALL protocols from 1987-2005 were eligible for this study. PBMCs mtDNA and oxidative phosphorylation (OXPHOS) NADH dehydrogenase (CI) and cytochrome c oxidase (CIV) activities were measured by RT-PCR and immunoassays respectively. A Wilcoxon rank-sum test was used to compare continuous measures between groups. Models for mitochondrial parameters were based on maximum likelihood variance component estimation and were adjusted for patient characteristics. Results: 64 patients provided samples at a median follow-up of 7.8 (2.9-30.2) years. 58% received DOX/DEX. Median cumulative DOX dose was 300 mg/m2. A significant difference was detected between groups for mtDNA (p=0.001, adjusted p=0.015). MtDNA medians for the DOX and DOX/DEX groups were 1106.3 and 310.5. No significant differences were found between groups for CI or CIV activities. Conclusions: DOX-treated survivors have increased mtDNA consistent with impaired mt function, which is abrogated by concurrent use of DEX. The use of DOX/DEX is associated with lower mtDNA. Due to a compensatory increase in mtDNA to augment mt function, overall mt function is not different between groups. This compensatory mechanism in 7.8-year survivors at risk for cardiac dysfunction is concerning over their subsequent lifespan. [Table: see text]