bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychiatric Diagnosis in a Transcultural Setting: The Importance of Lexical Categories
Authors: Morice Rodney 
Published: May 2019

SummaryIn a transcultural setting, psychiatric diagnosis is often impeded by language and cultural barriers. A greater reliance on observed or reported behaviour than on the self-reporting of subjective discomfort may thus be expected, and this could result in the low prevalence of reported anxiety and depression in many transcultural psychiatric surveys. The language of the Pintupi Aborigines of Central Australia, until recently palaeolithic hunter-gatherers, is seen to contain lexical categories for anxiety and depression. This attests not only to their capacity to experience such affects, but also to their ability to express them verbally. The implications of this finding for psychiatric diagnosis are discussed.
Temozolomide versus irinotecan-temozolomide for children with relapsed and refractory high risk neuroblastoma (RR-HRNB): Results of the BEACON-Neuroblastoma randomized phase 2 trial—A European Innovative Therapies for Children with Cancer (ITCC) - International Society of Pediatric Oncology Europe Neuroblastoma Group (SIOPEN) trial.
Authors: Moreno Lucas , Moroz Veronica , Owens Cormac , Laidler Jennifer , Valteau-Couanet Dominique , Gambart Marion , Castel Victoria , Van Eijkelenburg Natasha , Castellano Aurora , Nysom Karsten , Gerber Nicolas U. , Laureys Genevieve , Ladenstein Ruth Lydia , Makin Guy , Vaidya Sucheta , Thebaud Estelle , Kearns Pamela , Pearson Andrew DJ , Wheatley Keith 
Published: May 2019

10001 Background: BEACON-Neuroblastoma is a randomized Phase II trial to assess the activity of backbone chemotherapy regimens for children with RR-HRNB and to determine if inhibiting angiogenesis with bevacizumab adds to the activity of this chemotherapy. Methods: Patients aged 1-21 years with RR-HRNB with adequate organ function and performance status were randomized in a 2x2 factorial design to: temozolomide (T) versus irinotecan-temozolomide (IT), with or without bevacizumab. Here we report the results of the irinotecan randomization (T vs. IT), which had a probability-based Bayesian design. Primary endpoint was best overall response (complete or partial) during the first 6 courses, by RECIST for measurable disease patients and International Neuroblastoma Response Criteria for evaluable disease patients for which overall response rate (ORR) was calculated. Results: From 2013 to 2018, 61 patients were randomized to treatment with T and 60 to IT. Median age was 5.8 years. 85 and 36 had measurable and evaluable disease respectively; 55 and 66 had refractory and relapsed disease; 22 had MYCN amplification. Baseline characteristics were balanced between the arms. Response data was not yet available for 2 patients on T. Response was not assessable for 17 patients (did not have treatment or stopped early) who were considered non-responders. The ORR was 24% for T and 17% for IT (risk ratio (RR) = 0.70, 95% credible interval 0.32 to 1.44). The probability that the RR for ORR was >1.0 was 17%, meaning that IT did not show greater activity than T. There was no interaction between treatment with/without bevacizumab (heterogeneity test, p=0.7). 27 (44%) T and 35 (58%) IT patients had grade ≥3 toxicities as per CTCAE v4.0. Diarrhea occurred in no patients on T and 7 (12%) on IT; hematological toxicities included anemia (6 T, 4 IT), neutropenia (14 T, 22 IT) and thrombocytopenia (14 T, 11 IT). Conclusions: Irinotecan does not improve the response rate when added to temozolomide in RR-HRNB, but does increase diarrhea. Longer follow-up is needed before assessing whether it impacts progression-free or overall survival. Number of responses by treatment arm. Clinical trial information: NCT02308527. [Table: see text]
Prognostic factors for survival after relapsed acute lymphoblastic leukemia (ALL): A Children’s Oncology Group (COG) study.
Authors: Rheingold Susan R. , Ji Lingyun , Xu Xinxin , Devidas Meenakshi , Brown Patrick A. , Gore Lia , Winick Naomi J. , Carroll William L. , Hunger Stephen , Raetz Elizabeth A. , Loh Mignon L. , Bhojwani Deepa 
Published: May 2019

10008 Background: Survival of pediatric ALL patients (pts) now approaches 90%, but is historically poor for those who relapse. Methods: In the largest cohort assembled to date we analyzed overall survival (OS) rate post relapse, defined as duration between date of relapse and death, among pts diagnosed from 1996-2014 treated on 10 contemporary COG frontline trials. Comparisons of post-relapse OS were based on logrank tests, with two-sided p values reported. Results: Of 15,874 pts enrolled on frontline trials, 1,967(12%) relapsed. Relapse rates ranged from 35% in infant ALL to 9.7% in pts with NCI standard risk B-ALL. Rates were similar for T and B-ALL, 11% vs. 12%. Relapse patterns differed by phenotype: almost half of non-infant B-ALL relapses occurred late (≥36 mos), and at all time periods bone marrow (BM) relapse predominated. Conversely 65% of T-ALL relapses were early ( < 18 mos) with similar number of isolated CNS (iCNS) and isolated BM (iBM) relapses. Median time to relapse was shorter for infant ALL and T-ALL (both 13.8 mos) compared to B-ALL (34.4 mos). The 5yr OS rates (±SE) after relapse for B, T, and infant ALL were 52±1%, 33±3% and 19±4%, respectively, with greater variability in OS by site in T vs. B-ALL. 5yr OS rates for pts with early BM relapse was similar for both B and T-ALL (28%), but pts with B-ALL who relapsed between 18-36 mos fared better than pts with T-ALL (OS 50±2% vs 34±8%, p = 0.014). The 5yr OS rates for pts with late relapses were 65±2% for B-ALL and 50±12% for T-ALL. In multivariable analysis, time to relapse, site of relapse, age < 1 or > 10 yrs at diagnosis, initial WBC > 100K, and T-cell phenotype were associated with worse outcomes post relapse (all p < 0.01). Sex, CNS status at diagnosis, or prior therapy on POG versus CCG/COG backbone did not influence OS. Compared to pts treated from 1988-2002 (Nguyen et al. Leukemia 2008), 5yr OS rate post relapse has improved over time for B-ALL from 37±2% to 52±1% (p < 0.001) and T-ALL from 23±4% to 33±3% (p < 0.05). 5-yr OS rates improved significantly for pts with iBM from 24±2% to 45±2% (p < 0.001) and marginally for pts with iCNS from 59±3% to 65±3% (p = 0.15). Conclusions: In the modern era there are fewer relapses for B and T-ALL, however sites of recurrence and outcomes differ by phenotype. Infants continue to do poorly. Compared to prior analyses, survival after relapse is significantly improved.
Pyrotinib combined with capecitabine in women with HER2+ metastatic breast cancer previously treated with trastuzumab and taxanes: A randomized phase III study.
Authors: Jiang Zefei , Yan Min , Hu Xichun , Zhang Qingyuan , Ouyang Quchang , Feng Jifeng , Yin Yongmei , Sun Tao , Tong Zhongsheng , Wang Xiaojia , Yao Herui , Zou Jianjun , Zhu Xiaoyu ,   for the PHENIX Study Group
Published: May 2019

1001 Background: Pyrotinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor, showed promising anti-tumour activity and acceptable tolerability in patients with HER2+ metastatic breast cancer (MBC) in phase 1/2 trials. Methods: This double-blinded, multicentre, randomised phase 3 trial was conducted in Chinese patients with HER2+ MBC previously treated with taxanes and trastuzumab. Patients were randomly assigned (2:1) to receive 400 mg pyrotinib or placebo orally once daily for 21-day cycles in combination with capecitabine (1000 mg/m2 orally twice daily on days 1–14). The primary endpoint (IRC-assessed progression free survival [PFS]) was assessed in patients who received ≥1 dose of study treatment. Patients whose disease progressed on placebo plus capecitabine received subsequent single agent pyrotinib. Results: Between July, 2016 and November, 2017, 279 patients were randomised to pyrotinib plus capecitabine (n = 185) or placebo plus capecitabine (n = 94) arms. The median PFS was 11.1 months (95% CI 9.66, 16.53) in the pyrotinib plus capecitabine arm and 4.1 months (95% CI 2.79, 4.17) in the placebo plus capecitabine arm. seventy-one patients in placebo plus capecitabine arm received subsequent pyrotinib, showing single-agent response rate of 38.0% (95%CI 26.7%, 49.3%) and median PFS of 5.5 months (95% CI 4.07, 6.90). The most frequent (≥5%) treatment-related ≥ grade 3 adverse events were diarrhoea (30.8% vs 12.8% ) and hand-foot syndrome (15.7% vs 5.3%). Conclusions: In women with HER2+ MBC previously treated with taxanes and trastuzumab, pyrotinib plus capecitabine yield statistically significant better PFS. Pyrotinib monotherapy showed anti-tumour activity. Clinical trial information: NCT02973737. [Table: see text]
Upfront azacitidine (AZA) in juvenile myelomonocytic leukemia (JMML): Interim analysis of the prospective AZA-JMML-001 study.
Authors: Niemeyer Charlotte M. , Flotho Christian , Lipka Daniel B. , Starý Jan , Rössig Claudia , Baruchel Andre , Klingebiel Thomas , Micalizzi Concetta , Michel Gérard , Nysom Karsten , Rives Susana , Schmugge Liner Markus , Zecca Marco , Baumann Irith , Benettaib Bouchra , Poon Jennifer , Simcock Mathew , Patturajan Meera , Van Den Heuvel-Eibrink Marry M. , Locatelli Franco 
Published: May 2019

10031 Background: Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for JMML patients (pts). Novel therapies controlling the disorder prior to HSCT are urgently needed. A phase 2, multicenter, open-label study was conducted to evaluate safety and anti-leukemia activity of AZA monotherapy prior to HSCT in pts with newly diagnosed (ND) JMML. Methods: AZA (75 mg/m2 IV) was administered once daily on days 1–7 of each 28-day cycle (C). Primary endpoint was number of pts with clinical complete remission or clinical partial remission (cPR) at C3 day (D) 28 (C3D28). Results: 18 JMML pts (13 PTPN11-, 3 NRAS-, 1 KRAS-, 1 NF1-mutated) were enrolled from 09/2015 to 11/2017. Median (range) white blood cell and platelet (Plt) counts were 19.7 (4.3–59.0) × 109/L and 28 (7–85) × 109/L, respectively. DNA methylation class (MC) was high, intermediate (int), or low in 11, 5, and 2 pts, respectively. 16 pts completed C3 and 5 pts C6. 2 pts discontinued treatment (Tx) pre-C3D28 due to disease progression (PD). 6 pts (33%) had ≥ 1 grade (Gr) 3–4 manageable adverse event (AE) related to AZA. Most common Gr 3–4 AEs related to AZA were neutropenia (2) and anemia (2). 11 pts (61%) were in cPR at C3D28; 7 had PD at C3D28 or prior. All 7 pts of the int/low MC and 4/11 in high MC achieved cPR. 17 pts received HSCT at median of 58 days (37–518) from last AZA dose; 14 were leukemia-free at a median follow-up of 15.7 months (0.1–31.7) after HSCT. 2 pts (high MC) given HSCT relapsed after allograft. 16/18 pts were alive at a median follow-up of 19.8 months (2.6–37.3) from diagnosis. 1 pt discontinuing Tx prior to C3 died from PD; 1 non-responder died from transplant-related causes. Plt response in pts with cPR prompted retrospective comparison of Plt counts at time of HSCT with a historical registry control cohort. Pts with NF1-mutated JMML with higher Plt counts versus other genetic subtypes were excluded. While 7/16 (44%) study pts had Plt counts ≥ 100 × 109/L at HSCT, only 10/58 (17%) historical cohort pts reached this cutoff ( P < 0.01). Conclusions: This study shows that AZA monotherapy was well tolerated in pts with ND JMML. Although the long-term advantage of AZA Tx remains to be fully assessed, responses show it was effective in JMML and provided clinical benefit to pts in this study. Clinical trial information: NCT02447666.
A phase II clinical study of pomalidomide (CC-4047) monotherapy for children and young adults with recurrent or progressive primary brain tumors.
Authors: Fangusaro Jason R. , Locatelli Franco , Garré Maria Luisa , Marshall Lynley V. , Massimino Maura , Benettaib Bouchra , Biserna Noha , Poon Jennifer , Quan Jackie , Conlin Erin , Lewandowski John , Simcock Mathew , Jeste Neelum , Hargrave Darren R , Doz Francois P. , Warren Katherine E. 
Published: May 2019

10035 Background: Central nervous system (CNS) tumors are the most common cause of pediatric cancer mortality and novel therapies are needed for refractory disease. Pomalidomide (pom) is an oral immunomodulatory agent with CNS penetration, anti-angiogenic, anti-inflammatory and cytotoxic activity. Methods: This Phase 2 study evaluated both safety and efficacy of pom in pediatric patients with recurrent/progressive CNS tumors. Using a Simon’s two-stage design, patients were stratified to high-grade glioma [HGG], ependymoma, medulloblastoma or diffuse intrinsic pontine glioma [DIPG] cohorts. Patients received pom 2.6 mg/m2 for 21 days of a 28-day cycle. The primary endpoint was objective response rate (complete response [CR], partial response [PR]) or prolonged stable disease [SD] (defined as ≥ 6 cycles, or ≥ 3 for DIPG). Stage 1 required ≥ 2/9 subjects, within each cohort, to have a response or prolonged SD to move into Stage 2, and ≥ 5/20 responders or patients with prolonged SD at the end of Stage 2 for pom to be deemed effective. Results: Of 52 treated patients (median age 11.5 y/o; range 4-18), 47 were evaluable for primary endpoint. Median treatment duration was 2 cycles (range 1-16). Only the HGG cohort met protocol-defined criteria to advance to Stage 2, with one PR and one prolonged SD in Stage 1. Forty-six of 47 evaluable patients discontinued pom, due to adverse event (n = 1; pneumonia), withdrawal by parent/guardian (n = 2), death (n = 4; 3 progressive disease, 1 sepsis), or progressive disease (n = 39). Nineteen of 52 treated patients experienced ≥ 1 grade 3–4 treatment-emergent adverse event (TEAE) related to pom, neutropenia (n = 15) being the most commonly reported. Twenty-six patients died on study. All deaths were attributed to either disease progression or complications from disease. Conclusions: Single agent pomalidomide failed to meet a clinically meaningful level of efficacy in children with recurrent/progressive HGG, DIPG, medulloblastoma or ependymoma. However, it should be noted that a sustained response was observed in a child with HGG, replicating the outcome observed in one child with HGG in the Phase 1 (PBTC-043) trial. Clinical trial information: NCT03257631.
Alfa-feto protein (AFP) as a predictor of outcome for children with germ cell tumors: A report from the malignant germ cell international consortium.
Authors: O'Neill Allison Frances , Xia Caihong , Krailo Mark D. , Shaikh Furqan , Pashankar Farzana D. , Billmire Deborah F , Olson Thomas Arthur , Amatruda James F. , Villaluna Doojduen , Malogolowkin Marcio H. , Rodriguez-Galindo Carlos , Frazier A. Lindsay 
Published: May 2019

10036 Background: There are several studies describing the correlation between unsatisfactory tumor marker decline and poor prognosis in adult patients treated for germ cell tumors. In pediatric patients the data is limited. We therefore retrospectively analyzed data collected from pediatric patients treated on the Children’s Oncology Group (COG) Protocol AGCT0132 to determine whether a relationship exists between AFP decline and outcome. Methods: One hundred and thirty-one patients with germ cell tumors enrolled on Children’s Oncology Group Protocol AGCT0132 were eligible for analysis of AFP decline. Serum AFP half-life was calculated from levels collected post-operatively and after the start of chemotherapy, excluding values in the first 7 days of chemotherapy to accommodate unpredictable increases in the initial days of treatment. AFP decline was defined as automatically satisfactory (AFP normalized within the first two AFP measures following the start of chemotherapy), calculated satisfactory (AFP half-life ≤7 days following the start of chemotherapy), and unsatisfactory. Results: The 3-year event-free survival (EFS) was 87 % (95% confidence interval-CI: 79-92 %) for patients with a satisfactory decline and 62 % (95% CI: 31-82 %) for patients with an unsatisfactory decline (p = 0.006). In stratified analyses, this effect was limited to patients ≥11 years of age and with standard risk (SR2) disease ((p = 0.002 and p = 0.004, respectively). Three-year overall survival for patients with satisfactory versus unsatisfactory decline was not statistically significant. Conclusions: This study is the first to show an association between AFP decline and EFS in pediatric patients. Although there is no statistically significant association between tumor marker decline and overall survival, recognition of patients at high-risk of relapse may allow for early intensification of therapy and impact the rationale for future clinical trial design.
Randomized phase II study of eribulin mesylate (E) with or without pembrolizumab (P) for hormone receptor-positive (HR+) metastatic breast cancer (MBC).
Authors: Tolaney Sara M. , Barroso-Sousa Romualdo , Keenan Tanya , Trippa Lorenzo , Hu Jiani , Luis Ines Maria Vaz Duarte , Wulf Gerburg M. , Spring Laura , Sinclair Natalie Faye , Andrews Chelsea , Pittenger Jessica Demeo , Richardson Edward T. , Dillon Deborah , Lin Nancy U. , Overmoyer Beth , Partridge Ann H. , VanAllen Eliezer , Mittendorf Elizabeth A. , Winer Eric P. , Krop Ian E. 
Published: May 2019

1004 Background: Studies of checkpoint inhibitor monotherapy show only modest activity in HR+ MBC. We report data from the first randomized study comparing E plus P versus E alone in HR+/HER2- MBC. Methods: Eligible patients (pts) had HR+/HER2- MBC, ≥2 lines of hormonal therapies and 0-2 lines of chemotherapy for MBC. Pts were randomized 1:1 to E 1.4mg/m2 intravenously (IV) on d1 and d8 with P 200 mg/m2 IV on d1 of a 21-day cycle (Arm A) or E alone (Arm B). At time of progression, pts in arm B could crossover and receive P alone. Primary endpoint was progression-free survival (PFS). Key secondary endpoints were: objective response rate (ORR) and overall survival (OS). Exploratory analyses assessed the association between PFS and PD-L1 status, tumor-infiltrating lymphocytes (TILs), neutrophil-lymphocyte ratio (NLR), tumor mutation burden (TMB), and genomic alterations by next generation sequencing on archival tissue. Results: 88 pts initiated protocol therapy; the median age was 58, median prior lines of chemotherapy 1, prior lines of hormonal therapy 2. Median follow-up was 6.3 months. Median PFS and ORR were not different between Arms A and B (PFS 4.1 vs 4.2 months p = 0.38; ORR 25% and 34% respectively (p = 0.49). 14 patients initiated crossover treatment with pembrolizumab; 1 patient experienced a PR (ORR 7%). All-cause AEs occurred in 100% of pts (G3-4, 54.6%) including 2 treatment related deaths on Arm A, both from known AEs attributed to both drugs. PD-L1 assay was performed in 65 pts: 24 (36.9%) had PD-L1 positive ( > 1% with 22C3, centrally tested) tumors. PD-L1 status, TILs, NLR, TMB, and genomic alterations were not associated with PFS (Table). Updated data, including OS and genomic results, will be presented. Conclusions: Among pts with HR+/HER2- MBC, the combination of E and P was not associated with longer PFS than E alone in the ITT or PD-L1+ population, though the PD-L1+ subgroup had very limited power to assess P benefit. Clinical trial information: NCT03051659. [Table: see text]
Sponsorship of pediatric oncology interventional trials.
Authors: Neel Dylan , Shulman David Stephen , DuBois Steven G. 
Published: May 2019

10044 Background: The sponsor of a clinical trial is the single entity responsible for the overall conduct and oversight of the trial. Sponsors may be pharmaceutical/biotech companies (“industry”), government agencies (e.g. NIH), or other entities such as academic institutions. Trial sponsorship may have important regulatory and financial implications for the trial intervention under investigation. We sought to compare oncology trial sponsorship based upon age of eligibility. Methods: We used the clinicaltrials.gov database to evaluate all interventional trials from September 1, 2009 to December 1, 2018. We included all trials regardless of indication and then separately analyzed only oncology trials. We analyzed sponsor status as “industry”, “government”, or “other”. Results: Sponsorship data were available for 59,582 interventional trials across all disciplines (n = 15,564 oncology trials). Across all disciplines and ages of eligibility, lead trial sponsorship was 34% industry, 5% government, and 61% other. Across all oncology trials, sponsorship mix was similar: 31% industry; 6% government, and 62% other. Among adult oncology trials (age of eligibility starting at age 18 years), trial sponsorship was 33% industry, 6% government, and 61% other. Among pediatric-only oncology trials (age of eligibility capped < 18 years), trial sponsorship was 25% industry, 1% government, and 74% other. 5% of industry sponsored trials across all indications were pediatric-only compared to 0.63% of industry-sponsored trials in oncology. 95% of industry sponsored pediatric-only oncology trials were phase 1 or 2 trials, compared to 90% in adults. Conclusions: Pediatric-only interventional oncology trials are less likely to be industry sponsored compared to adult oncology trials or trials across all disciplines. Less than 1% of industry sponsored interventional trials in oncology focus on children < 18 years of age.
Male fertility preservation (FP) at pediatric cancer centers: A report from the Children’s Oncology Group (COG).
Authors: Levine Jennifer , Brackett Julienne , Cherven Brooke , Frederick Natasha , Klosky James L. , Ahmed-Winston Sameeya , Bryson Elyse , Kelvin Joanne Frankel , Quinn Gwendolyn P. , Meacham Lillian R. , Freyer David Robert , Dvorak Christopher C. , Chow Eric Jessen 
Published: May 2019

10050 Background: Preserved fertility after cancer is a priority for male survivors and their families. Sperm banking (SB) before initiation of treatment is standard of care for post-pubertal males. Experimental testicular tissue cryopreservation (TTC) is the only current option for pre-pubertal boys. ASCO recommends TTC be carried out under an experimental protocol. We surveyed COG sites about their FP infrastructure and practices. Methods: A REDcap survey was emailed to one individual previously identified as knowledgeable about FP or the Principal Investigator at each COG site. Site specific factors associated with outcomes were determined using logistic regression. All study procedures were IRB-approved. Results: Responses were received from 144 of 220 institutions (65%). Discussions about fertility were reported as routinely held with all post-pubertal males, all males “at risk” of infertility, and all males at 108 (75%), 100 (69%), and 55 (38%) institutions, respectively. SB was available at 135 (94%) sites; 105 (73%) offer SB inpatient and outpatient, 88 (64%) offer SB to all post-pubertal males, and 39 (28%) offer SB after chemotherapy has started. TTC was accessible at 37 (27%) sites and was independently associated with large (>120 new patients/year) size (odds ratio [OR] 3.3 95% confidence interval [CI] 1.2-9.3), and the presence of a FP navigator/team [OR 3.3 CI 1.4-7.8). Seventeen sites (12%) offered TTC by referring elsewhere, 14 (10%) under an IRB protocol and 6 (4%) as a clinical service. Conclusions: SB is widely available across participating COG sites, however only 2/3 of sites offer banking to all post-pubertal males. The availability of TTC at treating institutions is quite limited. This access may be modifiable given the association of an established FP navigator/team with the ability to offer and/or refer patients to outside institutions for TTC. There are practices, such as SB after the start of treatment and offering TTC as a clinical service, that do not align with guideline recommendations. These survey results suggest FP services remain inadequate in this patient population and highlight opportunities for research leading to interventions.