bluuebunny/crossref_metadata_2025_split huggingface dataset:
Entering a Clinical Trial: Is It Right For You?–A randomized study of the Clinical Trials Video and its impact on the informed consent process
Authors: Hitchcock-Bryan S. , Hoffner B. , Joffe S. , Powell M. , Parker C. , Wolanski A. , Eder J. P. , Shapiro G. I. , Bauer-Wu S. 
Published: March 2020

9072 Background: In an effort to improve the informed consent process for subjects considering participation in a clinical trial, we created an educational video: “Entering a Clinical Trial: Is it Right for You?” In this randomized study, we assessed the effect of the video on patients’ understanding and perceptions of clinical trials. We also assessed patient satisfaction with the video and how the video impacted decision-making and patient-provider communication. Methods: We recruited 90 adults considering cancer clinical trials of whom 77 participated. After discussing the trial with the physician and reading the trial consent form, patients were randomized to receive (n=38) or not receive (n=39) the study video. Using a validated questionnaire, we interviewed subjects to assess objective understanding of the trial, our primary endpoint, and self-reported understanding of clinical trials. All subjects completed a second interview assessing secondary endpoints, including patient-provider communication, satisfaction with video, and decision-making. We used linear regression (two-sided tests) to conduct the primary analysis and the Wilcoxon rank-sum test and descriptive statistics to analyze the secondary aims. Results: Neither objective nor self-reported understanding of clinical trials differed between the two groups (Mean 86.5 vs. 87, p=0.75). 85% (61/72) indicated the video was an important source of information about clinical trials; 89% of those who watched the video with their family/friends (n=37) said the video helped loved ones better understand clinical trials; 73% indicated it helped their family accept their decision about participation. 81% (58/72) felt better prepared to discuss the trial with their physician after watching the video. Of those who found the video helpful with decision- making, 80% (21/26) were considering a trial for the first time compared with 19% (5/26) veterans who had previously participated in a clinical trial. Conclusions: The video did not measurably improve subjects’ understanding of their clinical trials. However, subjects reported that the video was an important source of information, helped them educate their families, and enhanced patient-provider communication. No significant financial relationships to disclose.
Barriers to phase I clinical trial protocol IRB approval at KCI
Authors: Wang D. , Heath E. , Powell A. , Chaperon T. , LaGrone F. , LoRusso P. 
Published: March 2020

9080 Phase I oncology clinical trials are critical in the oncology drug development process. To protect human subjects, every phase 1 protocol must be approved by an institutional review board (IRB) to assure safety before patient accrual. As the volume and complexity of phase 1 trials have increased, the amount of time spent on IRB protocol reviews have also increased for various reasons. Objectives: 1) Determine the average time spent on protocol approval by IRB at KCI/WSU; 2) Identify potential issues raised by IRB resulting in approval delays; 3) Identify the redundancies for which “standard language” implementation could facilitate future IRB applications thereby expediting approval. Methods: 96 Phase 1 research IRB applications at KCI/WSU between 8/1/2005 and 10/31/2006 were reviewed. These applications were stratified based on submission (new protocol versus amendment) and IRB approval (tabled, provisional or approved) status. Concerns frequently brought up by the IRB were identified. Results: The average and median time spent from initial submission to final approval of all 96 applications were 41.4 days and 43 days, respectively. Forty eight of 96 applications (50%) were provisionally approved from the initial review. Average and median time of obtaining final approval were 52.5 days and 52 days. Nine of 96 (9.4%) protocols were tabled with their average approval 83 days. The most common concerns raised by IRB were risks/benefit issues. These concerns were an even greater approval barrier when protocols involved specialized technologies of molecular therapeutics or complicated study designs. Regulatory policy changes issued by oversight organizations also required “real-time” updates into protocols and consent form amendments. Areas of “standard language” for future IRB applications are being compiled and will be discussed upon presentation. Conclusion: Phase 1 clinical trials are essential to anti-cancer drug development. The complicated ethical issues and science warrant an ongoing constructive collaboration of both parties. Identification of commonalities that delay IRB approval will lead to more expeditious IRB approval not only at our institution, but could also benefit other institutions. No significant financial relationships to disclose.
Effect of pretreatment distress on daily fatigue after chemotherapy for breast cancer
Authors: Higgins S. C. , Montgomery G. H. , Bovbjerg D. H. 
Published: March 2020

9090 Background: Fatigue is one of the most frequently reported and aversive side effects of cancer chemotherapy. Prospective research has found that cancer patients’ levels of emotional distress prior to treatment are predictive of other side effects (e.g., nausea), but studies of such effects on fatigue are lacking. The present study prospectively tested the hypothesis that patients’ levels of emotional distress in the clinic prior to their first treatment infusion would predict the severity of their post-infusion fatigue. Methods: Sixty Stage I (32.6%) and II (67.4%) breast cancer patients (mean age=44.5 yrs), receiving standard outpatient chemotherapy (e.g., CMF), participated. The independent variable, emotional distress, was assessed (0–100) with a visual analog scale (VAS). The dependent variable, post treatment fatigue (PTF) was assessed (0–100) over each of the subsequent 6 days using end-of-day diaries, which also included assessment of distress (0–100). To explore temporal specificity, pretreatment distress was assessed for “last night”, “this morning” and “right now.” Results: Consistent with previous reports, PTF levels peaked at day 2 and began to decline after day 3, although they remained elevated across the period (p<.026). Repeated measures analysis indicated a significant main effect of pretreatment distress “right now” on PTF (p<.009); prior distress levels were less predictive. Additional regression analyses, controlling for pretreatment fatigue and daily distress, revealed a strongly selective effect of pretreatment distress on post peak PTF on days 5 (p<.002) and 6 (p<.026). Conclusions: This study is the first to demonstrate time-specific effects of pretreatment distress on PTF. Possible mechanisms of these effects now warrant investigation, as do possible benefits of brief interventions to reduce distress immediately prior to treatment. No significant financial relationships to disclose.
A phase III randomized controlled study comparing iron sucrose intravenously (IV) to no iron treatment of anemia in cancer patients undergoing chemotherapy and erythropoietin stimulating agent (ESA) therapy
Authors: Bellet R. E. , Ghazal H. , Flam M. , Drelichman A. , Gabrail N. , Woytowitz D. , Loesch D. , Niforos D. , Mangione A. , Anthony L. ,   Iron Sucrose Study Group
Published: March 2020

9109 Background: The effect of using IV iron sucrose in managing cancer chemotherapy-related anemia has not been previously reported. To investigate this issue, we conducted a randomized study of IV iron sucrose in patients (pts) with cancer chemotherapy-related anemia who completed 8 prior wks of ESA therapy. Methods: This prospective, multicenter, randomized, open label, Phase III clinical trial enrolled 375 pts with chemotherapy induced anemia (Hgb levels = 10.0 g/dL) and was conducted in 2 stages. During Stage I (8-wk duration), pts received treatment with fixed ESA doses (100-mcg of darbepoetin or 40,000 units epoetin wkly or 200 mcg of darbepoetin every other wk). Pts were classified as either ESA responders (= 1 g/dL increase in Hgb) or ESA non-responders with each group randomized (Stage 2) separately to receive either 12 wks of fixed doses of ESA plus up to 1,500 mg of iron sucrose (given in 3 divided doses of up to 500mg) or 12 wks of fixed doses of ESA alone. Laboratories (including iron indices and acute phase reactants), quality of life and adverse events were assessed at baseline and throughout. Results: Iron sucrose plus ESA compared to ESA alone resulted in greater mean maximum Hgb levels and greater number of pts who achieved Hgb increases = 2.0 and ≥ 3.0 g/dl in both prior ESA responders and non-responders. There was also a statistically significant improvement in fatigue and iron stores in the iron sucrose treated pts. Baseline iron status did not predict responsiveness to iron sucrose therapy. Three serious but non-life threatening iron sucrose related adverse events were observed including one case of significant, transient hypotension in a female weighing 50 kg. Conclusions: IV iron sucrose increased Hgb levels and iron stores significantly and is well tolerated in doses up to 500 mg increments in ESA treated patients with cancer chemotherapy- related anemia. IV iron sucrose should be considered in combination with erythropoietic therapy in anemic cancer patients receiving chemotherapy. [Table: see text]
Relations between psychotherapy and survival, coping strategies and quality of life (QOL) in patients with malignant gliomas: A randomized study
Authors: Jouniaux-Delbez N. , Andronikof A. , Delattre J. , Medioni J. 
Published: March 2020

9110 Background: Cognitive and behavioral psychotherapies are able to modify reactions against stress. Whether psychotherapies can improve survival, coping strategies and QOL in situations such as cancer announcement is not known. Methods: Between September 2001 and October 2003, a single center two arms study was conducted. Voluntary patients with newly diagnosed malignant gliomas were prospectively and exhaustively randomized to have psychotherapy or not. Anti-cancer therapy was unchanged. Psychotherapy was performed monthly. Coping strategies and QOL using EORTC QLQ-C30 Questionnaire were evaluated every 6 months for one year. Results: 96 patients were randomized and 81 patients (50 men, 81%) completed the study. Mean age was 50 years (range: 22–67) and 79% had a performance status = 1, 70% had glioblastomas, 51% had at least partial surgical resection of the tumor, 95% received radiotherapy and 83% had at least 1 cycle of chemotherapy. After a median follow-up of 43 months, 68 deaths (84%) were noted and median survival time was 14.1 months. Despite a trend toward improved survival, psychotherapy was not a prognosis factor of survival (p = 0.19). Coping scores at 0, 6 and 12 months were similar in the two arms and no improvements between base line scores and later scores were noted. General QOL scores at 0, 6 and 12 months were similar in the two arms. More data will be presented at the meeting, notably in good responders to psychotherapy. Conclusions: In a large non selected population of patients with newly diagnosed malignant gliomas, psychotherapy does not improve coping score or QOL and doesn't significantly change survival. Further studies are required to determine which patients can benefit of psychotherapy. No significant financial relationships to disclose.
Patient-reported burden of mucosal injury (MUI): Comparison of clinician-rated MUI and patient-reported outcomes
Authors: Elting L. S. , Calais G. , Selva N. , Brachman D. , Kudrimoti M. , Spijkervet F. , Vera-Llonch M. , Oster G. , Keefe D. , Sonis S. T. ,   Triad BOI Head and Neck Group
Published: March 2020

9117 Background: Patient (pt) reported outcome (PROs) tools identify MUI and its impact on functional and subjective outcomes. Among outpts, PRO tools are attractive because opportunities for direct assessment are limited, but agreement between PRO tools and objective MUI measures has not been uniform. We prospectively compared an objective MUI score and 3 previously validated PRO tools. Method: The Triad Burden of Illness study is an international, 41-center, prospective study of the risk and outcomes of radiation and chemotherapy-induced MUI. At baseline and during chemoradiation therapy (CRT), pts with larynx (L), hypopharynx (H), or non-small cell lung cancers (NSCLC) completed a daily MUI symptom tool (OMDQ) and 2 weekly PRO tools (FACT-E quality of life, FACIT- Fatigue). Clinicians examined pts twice weekly and scored MUI (WHO scale). In this interim analysis, we used random effects linear regression to compare clinician and pt ratings and t-tests to compare PRO scores in pts with and without severe MUI. Result: To date, 29 pts have completed =2 paired assessments; 23 (79%) had L or H cancers. Ulcerative MUI (WHO = 2) was more common among L/H than NSCLC pts (39% vs 17%). Pt-rated MUI predicted clinician-rated MUI (p = 0.001). FACT-E and FACIT-F scores were significantly lower (worse) among pts with clinician-rated ulcerative MUI than pts without and among pts with pt-rated severe MUI symptoms (OMDQ= 2) than pts without. Differences were largest in the subscales for physical and functional wellbeing and esophageal symptom special concerns. Conclusion: PRO tools estimate the burden of CRT-induced MUI in outpts with L/H or NCSL cancers. MUI appears to be associated with significantly poorer quality of life, functional status, and symptom scores. 1- 9 p <0.01; 10p = 0.06. [Table: see text] [Table: see text]
Specific gene expression profiles and unique chromosomal abnormalities are associated with regressing tumors among infants with disseminated neuroblastoma
Authors: Lavarino C. , Cheung N. , de Torres C. , Domenech G. , Garcia I. , Alaminos M. , Ríos J. , Gerald W. , Kushner B. , LaQuaglia M. , Mora J. 
Published: March 2020

9501 Background: Among human cancers, neuroblastoma (NB) has the highest incidence of spontaneous remission, especially among the subgroup of stage 4s NB affecting infants. Clinical distinction of stage 4s from lethal stage 4 can be difficult, but critical, since it is the basis for therapeutic decisions. The identification of biological markers that allow a precise distinction of these NB subgroups will aid accurate classification. Methods: Thirty-seven infants with NB were treated at MSKCC from 1987 to 2000. Ten stage 4s and 19 stage 4 were evaluated by allelic and gene expression analyses. Results: All stage 4s patients underwent spontaneous remission while only 69% of newly diagnosed, previously untreated stage 4 patients survived despite combined modality therapy. Among stage 4 tumors, 19/19 were near-diploid/tetraploid, 8/19 MYCN amplified, 50% had LOH at 1p36, 43% had LOH at 1p34-p31 and/or 14q and 37% had LOH at 11q and/or 1p22. Among stage 4s tumors, 7/8 were near-triploid, none MYCN-amplified and LOH was restricted to 11q. Gene expression profiling identified 233 differentially expressed genes between stage 4 and 4s tumors. 25% of these genes with increased expression in stage 4s NB mapped to 1pter-p13, with transcription level correlated with LOH and ploidy. Conclusions: These findings suggest that differential expression of subsets of genes located at specific chromosomal regions play a significant role in the biology of disseminated NB. Besides offering a biological definition of stage 4s, these expression profiles may provide new insights in the genetic control of spontaneous remission in neuroblastoma. No significant financial relationships to disclose.
Fecundity of males after treatment for childhood cancer. A report from the Childhood Cancer Survivor Study (CCSS)
Authors: Green D. M. , Kawashima T. , Leisenring W. , Stovall M. , Donaldson S. S. , Sklar C. A. , Byrne J. , Robison L. L. 
Published: March 2020

9516 Background: Determine the proportion of male (M) survivors with impaired fecundity (IF). Methods: 6,555 CCSS M participants and 1,606 M siblings (S) were classified as surgically sterile (SS) for contraceptive purpose, SS for non-contraceptive purpose, IF (ongoing attempts to become pregnant for a period of one year without success or use of medication to help achieve a pregnancy), or fecund (F). Odds ratios (OR) were estimated using logistic regression, controlling for education level, marital status, age at baseline questionnaire, race/ethnicity and smoking status. Results: M were 6–29 years from cancer diagnosis (mean-16.3 years) and 15–44 years of age at the time of study (mean-25.4 years). 331 (5.0%) M or their partners were SS, 487 (7.4%) had IF and 5,737 (87.5%) were F. The OR (95% confidence interval (CI)) for being F was 0.66 (95% CI, 0.54–0.80) (p<0.0001) compared to F MS. Among M, the OR for IF was 2.60 (95% CI, 1.97–3.42) (p<0.0001) compared to F MS. The OR for IF was increased among those with a testicular (T) radiation dose (RD) of 0.1–499 cGy (OR=1.42; 95% CI 1.07–1.89; p=0.015), 500–599 cGy (OR=3.16; 95% CI 1.48–6.72; p=0.0028), 600–1,499 cGy (OR=2.53; 95% CI 1.26–5.09; p=0.009) and ≥ 2,400 cGy (OR=3.04; 95% CI 1.39–6.64; p=0.0054), pituitary (P) RD of 0.1–499 cGy (OR=1.89; 95% CI 1.41–2.55; p<0.0001), CCNU (OR=2.14; 95% CI 1.25–3.66; p=0.0054), cyclophosphamide (OR=1.56;95% CI 1.23–1.97; p=0.0002), nitrogen mustard (OR=2.88;95% CI 2.08- 4.00; p<0.0001), procarbazine (OR=2.97; 95% CI 2.24–3.93; p<0.0001), vinblastine (OR=2.07;95% CI 1.41–3.04; p=0.00022), vincristine (OR=1.90; 95% CI 1.45–2.49; p<0.0001) and melphalan (OR=2.43; 95% CI 1.09–5.43; p=0.03). The OR for IF increased with increasing alkylating agent score (AAS) (1st tertile OR=1.70; 95% CI 1.19–2.43; p=0.0035; 2nd tertile OR=2.63; 95% CI 1.82–3.81; p<0.0001; 3rd tertile OR=3.42; 95% CI 2.41–4.86; p<0.0001). Multivariate analysis demonstrated that the combination of P ≥ 500 cGy and T ≥ 500 cGy (OR= 2.65; 95% CI 1.44–4.86; p=0.0017) and increasing AAS (1st tertile OR=1.56; 95% CI 1.04–2.34; p=0.031; 2nd tertile OR= 2.22; 95% CI 1.43–3.44; p=0.00036; 3rd tertile OR=2.72;95% CI 1.74–4.25; p<0.0001) were associated with IF. Conclusions: M have IF due in part to TRD and PRD and increasing AAS. No significant financial relationships to disclose.
Long-term cardiac outcomes following low-dose anthracycline exposure
Authors: Wright J. A. , Reimold S. , Turoff A. , Brooks S. , Huet B. , Eshelman D. , Winick N. , Oeffinger K. 
Published: March 2020

9519 Background: Pediatric cancer survivors treated with moderate-high dose (=250mg/m2) anthracycline therapy are known to be at risk for cardiac toxicity. It remains unclear what cardiac risk exists for survivors who received a low dose (<250mg/m2) therapy. Methods: Cardiac MRI and maximal VO2max testing were performed on young adult survivors of childhood acute lymphoblastic leukemia (ALL). MRI measurements included ejection fraction (EF), left ventricular (LV) mass, end diastolic volume (EDV), end systolic volume (ESV), and concentricity (LV mass/EDV). Survivors who were treated with low dose anthracycline (< 250mg/m2) were compared to those without anthracycline exposure. Spearman correlations and multivariable linear regression were used to examine the relationship between anthracycline dose and measures of cardiac function and cardiorespiratory fitness. Results: Sixty-seven survivors (mean age 23.9 ±5 years) participated, including 39 (58.2%) females. The mean interval from cancer diagnosis to study was 17.4 ± 6.6 years. The number of participants by cumulative anthracycline dose were 19 (28.4%) with no exposure, 28 (41.8%) with doses of 1–249mg/m2, and 20 (29.8%) with doses of =250mg/m2. When adjusted for age and race, there was not a significant difference in the cardiac MRI outcomes and VO2max levels between participants who received 1- 249mg/m2 of anthracycline versus those without anthracycline exposure. Conclusions: With continued use of anthracyclines at cumulative low doses, particularly in ALL standard risk trials, it is important to determine if there is a long-term cardiotoxicity. With a mean follow-up of 17 years, our data support the safety of low cumulative dose anthracycline. [Table: see text] No significant financial relationships to disclose.
Role of fractalkine (CX3CL1) rich neuroblastoma microenvironments for ganglioside GD2 directed immunotherapy
Authors: Lode H. N. , Zeng Y. , Fest S. , Gaedicke G. 
Published: March 2020

9521 Background: Fractalkine (FKN) is a unique CX3C chemokine (CX3CL1) known to induce adhesion and migration of leukocytes mediated by a membrane-bound and a soluble form. Methods: We found that FKN is expressed in >90% of 68 neuroblastoma (NB) samples as determined by cDNA microarray analysis. FKN expression was inversely correlated with MYCN amplification, suggesting a higher expression of FKN in MYCN non amplified tumors. We characterized the effect of FKN in the neuroblastoma microenvironment in a mouse model. We demonstrate that FKN released from NB cells mediate migration and adhesion of CD4+-, CD8+- and NK- cells and subsequent secretion of IFN-γ, in vitro and in vivo. However, the presence of FKN in NB microenvironments did not result in significant anti-NB activity. Results: Targeting of IL-2 into the NB microenvironment using anti-ganglioside GD2 antibody cytokine fusion proteins (ch14.18-IL-2) is currently under clinical evaluation. We investigated a the role of FKN in this context. For this purpose, IL-2 was targeted to GD2 positive NB microenvironments secreting FKN. Only mice bearing FKN and IL2 enriched NB microenvironments exhibited a reduction in primary tumor growth and a complete eradication of experimental liver metastases, in contrast to controls with only FKN or IL-2 enriched NB. This effect was specific since a non-specific antibody-IL-2 fusion protein ch225-IL-2 was ineffective. The mechanisms involved included NK-cell activation by targeted IL-2 into FKN rich NB as indicated by the enhancement of NK-cell mediated lysis using YAC-1 cells as targeted cells. The depletion of NK cells in vivo inhibited the therapeutic effect. Furthermore, co-culture of NXS2-FKN cells and NK cells in vitro induced the expression of IFN-γ by NK cells. However, the depletion of CD8+ T-cells in vivo abrogated the therapeutic effect, and these effector cells showed the highest cytolytic activity against NXS2 target cells in vitro. Finally, only the FKN and IL-2 enriched NB microenvironment resulted in T-cell activation and the release of proinflammatory cytokines. Conclusions: In conclusion our data suggest that targeted IL-2 therapy of FKN rich NB associated with MYCN non-amplified tumors may result in T-cell mediated immune responses. No significant financial relationships to disclose.