bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in lung cancer patients receiving carboplatin-based therapies.
Authors: Weinstein Cindy , Jordan Karin , Green Stuart , Khanani Saleem A. , Beckford-Brathwaite Elizabeth , Vallejos Waldimir , Pong Annpey , Noga Stephen Joseph , Rapoport Bernardo 
Published: September 2018

e21685 Background: Chemotherapy-induced nausea and vomiting (CINV) is a distressing symptom of cancer treatment; in lung cancer, carboplatin is commonly used. In a post hoc analysis, we explored prevention of CINV in lung cancer patients with a single-day triple-antiemetic fosaprepitant (FA) regimen compared with a standard 3-day control regimen. Methods: This was a phase 3, global, randomized, double-blind, parallel-group study in adults scheduled to receive an intravenous (IV) dose of ≥1 moderately emetogenic chemotherapy (MEC) on treatment day 1 (NCT01594749). Subjects were randomly assigned 1:1 to a control or FA regimen. The control regimen consisted of 8 mg oral ondansetron, 20 mg dexamethasone, and IV saline as placebo before the first dose of MEC on day 1, and 8 mg oral ondansetron 8 hours after the first dose and every 12 hours on days 2 and 3. The FA regimen consisted of the same dose of oral ondansetron on day 1, along with 12 mg dexamethasone and a single dose of 150 mg IV FA before the first dose of MEC on day 1, with no additional prophylactic antiemetic beyond day 1. The primary end point was complete response (CR; no vomiting or rescue medication) in the delayed phase (25-120 hours). Results: Overall, 1000 subjects were included in the intention-to-treat population (FA: n = 502; control: n = 498). The primary end point was met ( P < 0.001; FA vs control). In a subset of 254 subjects with lung cancer (71% male), 129 in FA regimen and 125 in control regimen, most (98%) received carboplatin-based chemotherapy. CR in the delayed phase was achieved by 80.6% in the FA group and 74.4% in the control group (difference, 6.2%). More subjects had no vomiting episodes in the FA (85.3%) vs control (78.4%) groups within the delayed phase (difference, 6.9%), and overall time-to-first vomiting episode was longer for subjects in the FA group. Adverse events (AEs) were similar between groups: overall AEs occurred in 57.7% and 54.8%, and serious AEs occurred in 12.3% and 12.1% in the FA and control groups, respectively. No serious AEs were considered related to study medication. Conclusions: A single-day IV FA regimen is effective for preventing CINV in patients with lung cancer receiving carboplatin. Clinical trial information: NCT01594749.
Systematic review and individual patient data based meta-analysis of palonosetron trials for chemotherapy induced nausea and vomiting.
Authors: Okada Yuki , Oba Koji , Furukawa Naoto , Komatsu Yoshito , Kosaka Yoshimasa , Okita Kenji , Yuki Satoshi , Celio Luigi , Aapro Matti S. 
Published: September 2018

e21688 Background: Several clinical trials have evaluated the need for corticosteroid-containing antiemetic regimens on the days after the first 24 hours to control delayed chemotherapy-induced nausea and vomiting (CINV) during moderate emetogenic chemotherapy (MEC) or anthracycline and/or cyclophosphamide (AC)-containing chemotherapy. Methods:We conducted systematic review using research databases and trial registries for any randomized controlled trials reporting CINV outcomes for a single 1-day-dexamethasone (D1 group) containing antiemetic regimen in chemotherapy-naive adult patients scheduled to receive a MEC or AC-containing chemotherapy, compared with additional dexamethasone on days 2 and 3 (D3 group). We also gathered the individual patient data (IPD) from each study investigator. The primary endpoint was complete response (CR: no vomiting and no rescue antiemetics) in the 5-day study period. Secondary efficacy end points were CR rates in 0–24 h and CR rates in 24–120 h; complete control in the overall, acute, delayed periods. An IPD meta-analysis was conducted to quantify the pooled risk differences between D1 group and D3 group and its interaction with patient characteristics using a fixed effect model. Results: Of 887 articles screened, 5 eligible studies were identified comprising 1194 patients, all enrolled in the meta-analysis. Overall, D1 group was not significantly inferior to D3 group in CR rate as well as CC rate [pooled risk difference in CR rate -1.5%, 95% confidence interval (CI) -7.1–4.0%; in delayed CR rate -2.4%, 95% CI -7.7–2.9%]. There was no significant interaction between dexamethasone regimen and patient characteristics (sex, age category ( < 60 or 60 years), and alcohol consumption). Conclusions: These results strongly suggest that the dexamethasone-sparing regimen is not associated with a significant loss in overall antiemetic control in an adult patient undergoing MEC or AC-containing chemotherapy, irrespective of patient baseline characteristics. These data contribute to simplify antiemetic regimens and spare many patients from the potential side-effects of multiple-day corticosteroids.
Randomized, single-blind, crossover study to assess the pharmacokinetic and pharmacodynamic bioequivalence of CHS-1701 to pegfilgrastim in healthy subjects.
Authors: Glaspy John A. , O'Connor Paula G. , Tang Hong , Finck Barbara 
Published: September 2018

e21693 Background: CHS-1701 is a proposed biosimilar of pegfilgrastim, a pegylated form of recombinant human granulocyte colony stimulating factor approved for decreasing infection in patients receiving myelosuppressive anticancer drugs associated with febrile neutropenia. This multi-center, randomized, single-blind, 3-sequence, crossover study in healthy subjects assessed bioequivalence of CHS-1701 to pegfilgrastim with regard to pharmacokinetics (PK) and pharmacodynamics (PD). Methods: Subjects were randomized to 1 of 3 treatment sequences; each included 1 dose of CHS-1701 (6-mg) and 2 doses of pegfilgrastim (6-mg) separated by ≥28 days. Primary PK endpoints were area under the curve from 0 to infinity (AUC0-∞) and maximum concentration (Cmax). PD endpoints were maximum absolute neutrophil count (ANCmax) and ANC area under the curve (ANC AUCs). Bioequivalence was demonstrated if the 90% confidence interval (CI) for the geometric mean ratio (GMR) of CHS-1701 to pegfilgrastim was within 80-125% for the endpoints. Results: 122 subjects were randomized and treated. Baseline characteristics were comparable between treatment groups. Median age was 29.5 (range 18-45). PK bioequivalence criteria were met for Cmax (GMR = 105.0; 90% CI 95.5, 115.4) and AUC0–∞ (GMR = 97.5; 90% CI 88.6, 107.2). PD bioequivalence criteria were met for ANCmax (GMR = 99.6; 90% CI: 96.2, 103.2), ANC AUC0–last (GMR = 96.7; 90% CI: 92.2, 101.4), and ANC AUC0–480 (GMR = 99.8; 90% CI: 97.7, 102.0). Adverse events (AEs) occurred in 76.0%, 76.6%, and 73.1% of subjects during the CHS-1701, first pegfilgrastim, and second pegfilgrastim dosing periods across treatment sequences, respectively. Investigator-designated treatment-related AEs occurred in 71.9%, 71.2%, and 62.8% of subjects, respectively, and most commonly included back pain (47.9%, 42.3%, 33.3%) and headache (33.3%, 41.4%, 34.6%). There were no treatment-related serious AEs. Conclusions: This study established the bioequivalence of CHS-1701 to pegfilgrastim with respect to PK and PD. There were no unexpected safety findings, and the two treatments displayed similar safety profiles. Clinical trial information: NCT02650973.
Patient and physician satisfaction with analgesic treatment in Southeast Asia (SEA): Findings from the analgesic treatment for cancer pain in Southeast Asia (ACE) study.
Authors: Moon Hanlim , Thinh Dang Huy Quoc , Sriraj Wimonrat , Mansor Marzida Binti , Tan Kian Hian , Yusak Suhana , Kurnianda Johan , Nguyen Yen Phi , Ong-Cornel Annielyn Beryl , Hadjiat Yacine , Javier Francis 
Published: September 2018

e21698 Background: Adequate dosing of analgesics is important for optimum cancer pain control & quality of life (QoL). To understand current attitudes toward analgesic treatment for cancer pain in SEA, the ACE study explored patient & physician satisfaction with pain control in 6 SEA countries. Methods: This cross-sectional observational study included 465 adult outpatients prescribed analgesics for cancer pain for ≥1 month in Indonesia, Malaysia, Philippines, Singapore, Thailand, & Vietnam. Pain intensity, sleep disturbance, QoL, satisfaction with pain control, & physicians’ assessment of adequacy of analgesics were recorded via questionnaires. Current analgesic doses prescribed were extracted from medical records. Results: Most patients (84%) had stage 3 or 4 cancer. While 91% were prescribed opioids, mean reported pain intensity was 4.1 (0/no pain, 10/worst possible pain) & most had problems with sleep (55%) & QoL (problems with pain/discomfort [82%], usual activities [66%] & anxiety/depression [56%]). 60% of patients were satisfied with their pain control status & 30% found it acceptable. Physicians more often reported dissatisfaction with patients’ pain control status compared with patients (21% vs 10%). Patient-physician concordance in satisfaction with pain control was low (weighted Kappa 0.36; 95% CI 0.30-0.43). More than 1 in 4 physicians (29%) assessed prescribed analgesics to be “inadequate” for pain control. Median daily dose prescribed in oral morphine equivalents was 30 mg for both morphine & tramadol. Of the SEA countries included, prescribed doses of opioids were generally lower in Indonesia & higher in Vietnam. Conclusions: The results highlight the complexity of managing cancer pain in SEA. Despite unrelieved pain, sleep disturbance & QoL issues, many patients still reported satisfaction with pain control. Notably, physicians expressed dissatisfaction more frequently than patients. These findings suggest a need for all-round pain status assessment (including pain intensity, sleep disturbance, QoL) & improved patient-physician communication about analgesic treatment expectations, pain control & adverse effects.
A randomized, double-blind, placebo-controlled study of the safety and efficacy of olanzapine for the prevention of chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy.
Authors: Jeon So Yeon , Han Hye Sook , Bae Woo Kyun , Park Moo-Rim , Lee Sang-Cheol , Go Se-Il , Yun Hwan Jung , Ryu Hyewon , Im Yong-Jin , Song Eun-Kee 
Published: September 2018

e21699 Background: Olanzapine was found to be effective for preventing acute and delayed emesis in patients receiving highly emetogenic chemotherapy by randomized phase 3 study. However, there is limited data for the efficacy of olanzapine combined with palonosetron and dexamethasone in patients receiving moderately emetogenic chemotherapy (MEC). Methods: We conducted randomized, double-blind, placebo-controlled study to determine whether olanzapine could reduce the frequency of CINV and improve quality of life (QOL) in patients receiving palonosetron and dexamethasone for the prophylaxis of MEC induced nausea and vomiting. Two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4. The primary end point was the complete response (no emesis and no use of rescue medication) for the acute phase (0-24 hours after chemotherapy). Secondary end points included the complete responses for the delayed (24-120 hours) and overall phase (0-120 hours), proportion of significant emesis (VAS ≥ 25 mm) for overall phase, use of rescue medications, and effect on QOL by Functional Living Index-Emesis (FLIE) questionnaire. Results: Fifty-six patients were randomized and fifty-four patients were evaluable (29 assigned to olanzapine, and 25 to placebo). The complete response rate was not significant between olanzapine and placebo group in the acute (96.5% vs. 88.0%, P = 0.326), delayed (69.0% vs. 48.0%, P = 0.118), and overall phase (69.0% vs. 48.0%, P = 0.118). However, the percentage of patients with significant emesis (17.2% vs. 44.0%, P = 0.032) and the use of rescue medications (0.03±0.19 vs. 1.88±2.88, P = 0.002) were significantly lower with olanzapine than with placebo in the overall phase. Furthermore, olanzapine group experienced a better QOL than the placebo group, as reported on the FLIE questionnaire (P = 0.015). Conclusions: Olanzapine in addition to palonosetron and dexamethasone significantly improved the management of emesis and QOL among previously untreated patients receiving MEC, although the efficacy was limited to reduce the frequency of CINV. Clinical trial information: NCT02400866.
Integrating a touchscreen-based brief geriatric assessment in older adults with multiple myeloma.
Authors: Nathwani Nitya , Mohile Supriya Gupta , Lipe Brea , Carig Karen , DiGiovanni Laura , Davis Agnes , Wujcik Debra , Hurria Arti , Wildes Tanya Marya 
Published: September 2018

e21703 Background: Multiple myeloma (MM) is a disease of older adults (OAs) with > 60% of diagnoses and nearly 75% of deaths occurring in patients > 65 years old (YO). Geriatric Assessment (GA) is associated with toxicity and survival in OAs with MM, but not routinely used in practice. This project pilot tests a tablet-based modified Geriatric Assessment (mGA) that presents compiled GA results, including (the Palumbo) frailty score, to clinicians at a treatment decision-making visit in a single screen dashboard. Methods: In this multisite ongoing study, 210 patients with MM ≥65 YO facing a decision point for care will complete a mGA that includes the Charlson Comorbidity Index (CCI), Katz Activity of Daily Living (ADL) Score, and Lawton Instrumental Activity of Daily Living (IADL) Score prior to meeting with a physician. mGA results, including composite frailty score, are provided to physicians at the start of a visit. Results: Thirty-six patients have been enrolled to date; enrollment continues. Participants are 69% (n = 25) white, 64% (n = 23) male, and mean age of 72 YO (range 65-87). Most (74%, n = 20) currently receive ≥1 therapy and have few co-morbidities (CCI median 1, SD 1.95, range 0-8); 57% require assistance with IADLs and 37% require assistance with ADLs. Based on Palumbo score, 36% of participants were frail (n = 13), 33% intermediate (n = 12), and 31% fit (n = 11). Providers report mGA results influenced treatment decision (54%, n = 28) and frailty score was the most frequently cited result to impact treatment decision-making (61%, n = 39). The most common way the mCGA influenced decision-making was to reduce dose/dose intensity (25%, N = 8). Clinicians on average spent 5 minutesreviewing the mGA results. Patients reported an average of 7 minutes to complete the survey, most independently (83%, n = 30), and were satisfied with the electronic program overall (80%, n = 29), including how easy it was to use (88%, n = 32). Conclusions: Preliminary data support feasibility, usability, and acceptability of the tablet-based mGA and that frailty score influences provider decision-making ≥50% of the time. Future analyses will explore the relationship of the mGA with toxicity, dose modification and/or treatment discontinuation in OAs with MM.
Differences in body composition between patients with early or metastatic breast cancer (BC).
Authors: Strulov Shachar Shlomit , Deal Allison Mary , Weinberg Marc , Williams Grant Richard , Nyrop Kirsten A , Choi Seul Ki , Benbow Julia M. , Muss Hyman B. 
Published: September 2018

e21707 Background: There is growing evidence in oncology that skeletal muscle (SM) loss, known as sarcopenia, can be identified from routine computed tomography (CT) imaging and used to predict increased chemotherapy toxicity, mortality, and other adverse clinical outcomes (Shachar-EJC, 2016, Shachar-CCR, 2016). The contributions of age-related and cancer-related loses in SM at diagnosis remains poorly understood. This study compares CT-derived measures of SM at the time of diagnosis in patients with early BC (EBC) versus metastatic BC (MBC) patients to investigate the impact of metastatic cancer on SM. Methods: Body composition measures were compared between patients with EBC receiving adjuvant chemotherapy and MBC initiating first line palliative chemotherapy. Measures were derived from analysis CT scans of L3 lumbar segments using radiological software (ABACS). Measures include: skeletal muscle area (SMA), density (SMD), index (SMI = SMA/height ^2), and integrated density (SMID = SMI x SMD). Sarcopenia was defined as SMI < 41(Martin-JCO, 2013). Lean body mass (LBM) was calculated (kg) = [(L3 Muscle measured by CT (cm2) × 0.3) + 6.06]) (Prado-CCR, 2009). Body surface area (BSA) was calculated using the Mosteller formula. T-tests (continuous) and Chi-squared tests (categorical) compared variables between groups; multivariable linear regression models controlled for age and body mass index (BMI). Results: MBC patients (n = 40) were older than EBC (n = 151) (56 vs 49 years, p < 0.001). Mean BMI and BSA were similar in both groups (29.0 vs 28.8, p = 0.84; 1.87 vs 1.86 m2, p = 0.55). After adjusting for age and BMI, SMI (41.3 vs 44.7 cm2/m2, p = 0.009), SMD (29.8 vs 36.4 Hounsfield Units, p < 0.0001), SMG (1250 vs 1612, p < 0.0001), and LBM (39.3 vs 41.9 kg, p = 0.024) were significantly lower in the MBC group. The MBC group included significantly more sarcopenic patients (58% vs 31%, p = 0.0016). Conclusions: Although BMI and BSA were similar in EBC and MBC patients, SM measures showed significant differences. MBCs had lower LBM, SMI, and SMD. More advanced BC was associated with higher proportions of sarcopenia. Further research is needed to explore interventions in sarcopenic patients in order improve outcomes in women with both EBC and MBC.
Factors impacting time to engraftment in patients with high-risk neuroblastoma following autologous stem cell transplant.
Authors: Hillier Kirsty , Krance Robert , Foster Jennifer Haunani 
Published: September 2018

e22008 Background: Neuroblastoma is the most common extra-cranial solid tumor of childhood, with overall survival for high-risk patients (HRNBL) near 50%. The outcomes of HRNBL have improved significantly with high dose chemotherapy followed by autologous stem cell rescue (ABMT). Data about factors influencing the rate of hematopoietic recovery following ABMT in HRNBL is lacking in the literature. Methods: This is a retrospective chart review of patients with HRNBL treated at Texas Children’s Hospital from October 2011 - November 2016. Neutrophil engraftment was considered the first of three consecutive days with post-transplant neutrophil count > 500 cells/uL. Red blood cell and platelet engraftment were considered at a hemoglobin > 8g/dL and platelets > 20,000/uL three days after the last transfusion. Race and conditioning regimen were analyzed using one-way ANOVA; amount of infused cells was analyzed using Pearson correlation coefficients; chemotherapy delay and bone marrow (BM) involvement after cycle 2 of induction chemotherapy were analyzed using independent sample t-tests. Results: The study included 17 males and 8 females with a median age at diagnosis of 3 years. 15 patients were Caucasian, 4 African-American, 5 Hispanic, and 1 Asian. The mean dose of infused CD34+ cells was 3.44x108cells/kg. 16 patients received conditioning therapy with carboplatin/etoposide/melphalan, 7 received busulfan/melphalan, and 2 received thiotepa/cyclophosphamide. Race was found to be significant for hemoglobin engraftment (p < 0.001). There were trends toward significance for conditioning regimen and neutrophil engraftment (p = 0.079), presence of delays in induction chemotherapy due to hematologic toxicity for platelet engraftment (p = 0.069) and BM involvement after cycle 2 of induction chemotherapy for hemoglobin engraftment (p = 0.12). Conclusions: Knowing the barriers for timely engraftment may help develop interventions for future patients. Race significantly impacted hemoglobin engraftment. Conditioning regimen, delays in induction chemotherapy, and BM involvement after cycle 2 of induction chemotherapy trended towards significance and need to be validated in a larger dataset.
SOX2 as a target for immunotherapy of pediatric gliomas.
Authors: Vasquez Juan , Huttner Anita , Zhang Lin , Marks Asher , Chan Amy , Baehring Joachim M. , Kahle Kristopher , Dhodapkar Kavita M. 
Published: September 2018

e22012 Background: New treatments are needed to improve outcomes for pediatric gliomas. Immune checkpoint inhibitors are effective therapies in tumors with a high mutation burden that express multiple neo-antigens. However, for pediatric tumors that carry few mutations, there is a need to identify new antigenic targets of anti-tumor immunity. SOX2 is an embryonal stem cell antigen implicated in the biology of glioma initiating cells. Expression of SOX2 by pediatric glial tumors, and the capacity of the immune system in these patients to recognize SOX2, has not been studied. Methods: We examined the expression of SOX2 on paraffin-embedded tissue from pediatric glial tumors (n = 30). The presence of T cell immunity to SOX2 was examined in both blood and tumor-infiltrating T cells using antigen-dependent cytokine and T cell proliferation assays (n = 15). The nature of tumor-infiltrating immune cells in glial tumors (n = 4) was analyzed using single cell mass cytometry. Results: SOX2 is expressed by tumor cells but not surrounding normal tissue in all low grade gliomas (n = 15), high grade gliomas (n = 7), ependymomas (n = 3) and in 60% of oligodendrogliomas (n = 5). T cells against SOX2 can be detected in blood and tumor tissue in 33% of patients. CD4 and CD8 tumor infiltrating T-cells display a higher proportion of PD-1 expression compared to circulating T cells (p < 0.05). Glial CD4 and CD8 T cells are enriched for tissue resident memory phenotype (TRM; CD45RO+, CD69+, CCR7-) and the expression of PD-1 is primarily on these TRM cells (p < 0.05). A subset of CD4 and CD8 TRM cells also co-express multiple inhibitory checkpoints including PD-L1 and TIGIT. Glial tumors also contain NK cells with reduced expression of lytic granzyme (p < 0.05). Conclusions: Our data demonstrate in vivo immunogenicity of SOX2, which is specifically overexpressed on pediatric glial tumor cells. Our data also suggest that the TRM subset of tumor-infiltrating T cells may be key targets for immune checkpoint blockade, and harnessing tumor immunity will likely require the combined targeting of multiple inhibitory checkpoints. Future efforts to target SOX2 with dendritic cell vaccines combined with immune checkpoint blockade could provide effective tumor immunity and improve outcomes in pediatric brain tumors.