bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mortality and survival rates in children and adolescents enrolled in early phase trials with a dose-finding/dose-confirmation component: An innovative therapies for children with cancer (ITCC) study.
Authors: Carceller Fernando , Bautista Francisco , Castañeda Alicia , Surun Aurore , Wasti Ajla , Revon-Riviere Gabriel , Cortes Marta , Bergamaschi Luca , Juan Ribelles Antonio , Millen Gerard , Campbell Hewson Quentin , Amoroso Loredana , Van der Lugt Jasper , Fagioli Franca , Zwaan Michel , Marshall Lynley V , Vassal Gilles , Pearson Andrew DJ , Geoerger Birgit , Moreno Lucas 
Published: March 2020

e21509 Background: Participation of children with advanced solid cancers in phase I trials raises ethical and logistic dilemmas. Life-expectancy beyond 8-12 weeks is a common inclusion criterion, but it can be difficult to gauge. This multicentric European study assessed the mortality and survival rates in pediatric phase I trials. Methods: Retrospective study of patients aged < 18 years with solid tumors enrolled in phase I trials in ITCC centres between 2015-2017. Outcome variables were described and prognostic factors analysed. Results: 256 patients across 12 centres in 5 countries were eligible. Median age 11.8 years (range, 0.5-17.9). Female:Male ratio 1:1.9. Tumor location: central nervous system (CNS) 66% vs extra-CNS 34%. Main diagnoses: 22% soft tissue sarcomas, 13% high grade gliomas, 11% osteosarcomas. Most frequent therapy: single targeted agent (63%). Ten cases (4%) were not evaluable for response and 128 (50%) had progressive disease at first evaluation. Best responses were complete in 12 cases (5%), partial in 29 (11%) and stable disease in 77 (30%). Median follow-up 7 months (range, 0.5-42.4). Median Time On Study (TOS) 2.1 months (range, 0.2-38.1). The 30 and 90-day mortality on trial were 3% (8/256) and 21% (54/256), respectively. The 90-day survival (95%CI) for patients with CNS vs extra-CNS tumors was 88% (78-93) vs 76% (68-82), respectively. One-year Overall Survival (95%CI) for the whole sample was 40% (33-46). No toxic deaths on trial were reported. Twenty-five cases (10%) survived ≥365 days on trial. Median TOS 21.5 months (range, 12.3-38.1). Compared to patients who died within 365 days from Cycle1-Day1, those on trial ≥365 days had lower rates of metastatic disease (74% vs 28%, respectively, p < 0.001), higher objective response rates (13% vs 44%, respectively, p < 0.001) and higher disease stabilization (27% vs 56%, respectively, p < 0.001). Conclusions: Currently few patients die within the first cycle of treatment. However a fifth of all patients died within 3 months from trial initiation. Patients with CNS tumors have comparable survival rates to those with extra-CNS and should not be excluded from phase I trials solely because of their diagnosis. The survival rates beyond one year remain modest.
The evaluation of long term follow-up (LTFU) of children with osteosarcoma: The first report from a center in a developing country.
Authors: Tacyildiz Nurdan , Unal Emel Cabi , Dincaslan Handan , cakmak Tokuc Mine , Oktay Tanyildiz Gulsah , Kartal Omer , Yildiz Yusuf , Basarir Kerem , Yavuz Gulsan 
Published: March 2020

e21512 Background: The increased survival rate of childhood cancers resulted in long term side effects (LTSE). The aim was to investigate LTSE in our osteosarcoma survivors and compare the quality of life (QOL criteria with their own siblings as a developing country experience with no National LTFU guideline yet . Methods: At Ankara University Department of Pediatric Oncology 54 osteosarcoma pts have been followed between 2003- 2019 . Rate of heart, kidney disease, hearing difficulty, neurological problems, Life style parameters like; smoking, alcohol consumption, marital status, parenthood, education, the use of health care services and pain status of the 39 survivors were compared with their siblings (n = 77). Amputated and non-amputated groups were compared for QOL. Information obtained retrospectively from the patient charts, and phone calls. Kaplan-Meier, Chi-square, independent sample t-test were used. Results: The age and gender ratios were similar in the groups. The 16-year overall survival rate (OSR) was 72.4%. Patients with the poor risk criteria were in the Euramos MAP + IE regimen with 71.4% OSR ; 94.1%, in the low risk patients in Euramos MAP (p = 0.023) and 50.0% in the previous HDMTX regimens (p = 0.012). The rates of kidney (p = 0.045), heart disease (p < 0.001), neurological problems (p = 0.045), use of health care services (p < 0.001), limitations of physical function (p < 0.001) and pain (p = 0.002) were significantly higher in the survivors than siblings. The physical functions were normal in 76 siblings (98.7%) and in 14 of the survivors (35.9%) (p < 0.001). Being married (p = 0.001), having parenthood (p < 0.001), educated (p = 0.014) and employed (p < 0.001) were significantly higher in the siblings than in the survivors. The rates of hearing problems, smoking, alcohol consumption and psychiatric problems were similar in both groups. Secondary malignancy (1 leukemia, 1 bone tumor) was detected in two survivors while no cancer was found in the control group. The OS was 55.6% and 75.6% respectively in patients with amputation and with no amputation with no significant difference in the QOL (p = 0.424). Conclusions: Heart, neurological and kidney disease, physical dysfunction, and pain rates were significantly higher in survivors of osteosarcoma than their siblings in almost 2 decades. The social status (marriage, parenthood, education) of the survivors was also found to be markedly affected negatively. As we planned, development of risk-based LTFU guidelines are required to increase QOL during LTFU of these patients in our country.
Tumor molecular profiling in advanced pediatric brain tumors.
Authors: Basu Gargi D. , Natarajan Thanemozhi G , Szelinger Szabolcs , Bair Candyce M , White Tracey , LoBello Janine R , Garinger Nathan , Kurdoglu Ahmet , Royce Thomas 
Published: March 2020

e21516 Background: With the advent of high-throughput molecular profiling, clinical outcome in pediatric cancers has greatly improved due to our greater understanding of genetic origin of pediatric cancer, and availability of biomarker specific treatment options. However, pediatric brain tumors continue to be challenging in terms of therapy. The goal of this study was to evaluate the utility of integrative clinical sequencing in pediatric patients with brain tumors. Methods: Targeted exome sequencing of 562 genes in paired tumor-normal DNA was performed on 14 patients and tumor DNA and RNA was sequenced on additional 4 patients. Sequence analysis identified SNVs, indels, copy number events, fusions, alternate transcripts, breakpoints, TMB and MSI status. Clinically, actionable alterations were identified which could be targeted by FDA approved agents or clinical trials. Results: A total of 18 patients (1-17 y.o.) with low grade (n = 5) and high grade (n = 13) brain tumors were profiled. The cohort consisted of a spectrum of GBMs (45%), medulloblastomas (10%) astrocytomas (22%), and other brain tumors (23%). At least one targetable, driver alteration was identified in 83% of all patients, and 92% of high-grade patients had at least one targetable driver event. Targetable mutations were identified in histone and chromatin modifier genes like H3F3A in 3/18 cases (17%), SETD2, ARID1A, PBRM1 in 2/18 cases (11%), activation of PI3K/AKT/mTOR pathway genes in 6/18 cases (33%), DNA repair genes NBN, ATRX and BRCA2 in 3/18 cases (17%); BRAF V600E in 3 high-grade and a KIAA1549/BRAF fusion in a low-grade tumor, activation of cell cycle in 2/18 cases (11%), activation of FGFR pathway with FGFR1/TACC1 fusion and activating mutation in 2/18 cases (11%), activation of PDGFRA in 2/18 samples (11%), TP53 mutations in 4/18 cases (22%). A breakpoint translocation concurrent with LOH of PTCH1 locus was noted in a medulloblastoma patient. High TMB or MSI instability was not observed. Conclusions: Our results underline the importance of clinical sequencing in identifying targetable markers in high- risk brain tumors. Although limited by small sample size, our study highlights the need for ongoing clinical trials to integrate the genomic discoveries leading to better clinical outcomes.
Serum biomarkers for detection of cardiomyopathy in survivors of childhood cancer: A report from the St. Jude Lifetime Cohort.
Authors: Dixon Stephanie , Howell Carrie R. , Lu Lu , Ness Kirsten K. , Plana Juan , Joshi Vijaya , Luepker Russell V , Durand Jean-Bernard , Ky Bonnie , Lenihan Daniel John , Green Daniel M. , Partin, MS Robyn , Santucci Aimee , Howell Rebecca M. , Srivastava Deokumar , Hudson Melissa M. , Robison Leslie L. , Armstrong Gregory T. 
Published: March 2020

e21526 Background: Childhood cancer survivors are at increased risk for cardiovascular morbidity and mortality. Little is known about the utility of cardiac biomarkers (NT-proBNP, cardiac troponin-T [TnT]) for long-term surveillance. Methods: Cross-sectional analyses of 1213 survivors ≥18 years of age and ≥10 years from cancer diagnosis (786 exposed to cardiotoxic therapy [174 radiation therapy (RT) alone, 366 anthracycline alone, 246 both] and 427 unexposed). TnT > 0.01 ng/ml and NT-proBNP levels > 97.5th percentile age- and sex-specific cutoffs were considered abnormal. Three-dimensional left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), diastolic function and cardiomyopathy (CM) according to the CTCAE v4.03 were evaluated. Generalized linear models estimated risk ratios (RR) and 95% confidence intervals (CI). Results: Among survivors (median 8.7 [range 0.0-23.6] years at diagnosis; 35.5 [range 19.1-62.2] years at evaluation), NT-proBNP and TnT were abnormal in 22.5% and 0.4%, respectively. A dose-dependent increased risk for abnormal NT-proBNP was seen with exposure to chest RT (referent no RT, 1- < 20 Gy RR 1.62 [CI 1.07-2.46], 20- < 30 Gy RR 1.68 [1.23-2.30], ≥30 Gy RR 3.66 [2.89-4.64]; p for trend < 0.0001) and anthracycline (referent no anthracycline, 1-200mg/m2 RR 1.39 [1.01-1.91], 201-350mg/m2 RR 2.28 [1.74-2.99], > 350mg/m2 RR 2.99 [2.27-3.95]; p for trend < 0.0001). Survivors with CM at the time of evaluation had abnormal NT-proBNP (grade 2 CM RR 1.46, CI 1.08-1.99; grade 3-4 CM 2.66, 2.02-2.39). However, among exposed survivors previously undiagnosed with clinical CM, NT-proBNP had poor sensitivity and moderate specificity in identifying those with new onset of abnormal LVEF ( < 53%), GLS or diastolic dysfunction: sensitivity (29%, 30%, 33%), specificity (75%, 77%, 76%). Also, 132 (20.2%) had abnormal NT-proBNP with normal LVEF (≥53%). Conclusions: Abnormal NT-proBNP levels were prevalent and associated with prior cardiotoxic therapy and established CM but were not sensitive for detection of new onset CM. Longitudinal follow-up is needed to determine whether abnormal NT-proBNP in the large number of survivors without CM is predictive of future CM.
A pilot study of sleep-related breathing disorders and hypersomnia in adult survivors of childhood Hodgkin lymphoma treated with thoracic radiation.
Authors: Mandrell Belinda Neal , Lewis William , Ogg Susan , Wise Merrill , Mulrooney Daniel A. , Robison Leslie L. , Hudson Melissa M. , Krull Kevin R. 
Published: March 2020

e21527 Background: Survivors of childhood Hodgkin lymphoma (HL) often report fatigue and daytime sleepiness. The presence of sleep disorders, such as obstructive sleep apnea (OSA), could further increase cardiovascular and cerebrovascular morbidity and mortality in these patients. The purpose of this pilot study was to assess for the presence of sleep-related breathing disorders and hypersomnia in adult survivors of childhood HL treated with thoracic radiation. Methods: Survivors, ≥18 years of age and ≥10 years from diagnosis, were randomly selected from the St. Jude Lifetime Cohort (SJLIFE) study and assessed with nocturnal polysomnography (PSG) and the multiple sleep latency test (MSLT). Enrollment was stratified by body mass index (BMI) to include an equal number of normal weight and overweight/obese survivors. Survivors with a history of neurotoxicity related to cancer therapies, and neurological, genetic, or neurodevelopmental conditions associated with neurocognitive impairment were excluded. Results: Thirty adult survivors of childhood HL (60% male; 73% white; mean age 35.8 years [range,19.9-52.8]; BMI 28.6 [range, 18.2-43.5]) enrolled, and 14 (47%) met PSG criteria for mild or moderate OSA (OSA; apnea-hypopnea index 5-30). Of those with OSA, 11 had concurrent hypersomnia using the MSLT criteria and 3 of these 11 met diagnostic criteria for narcolepsy. Twelve (40%) had hypersomnia without OSA and 3 of these 12 met diagnostic criteria for narcolepsy. Within the cohort, 86% had objective evidence of OSA and/or hypersomnia/narcolepsy. Conclusions: Findings suggest adult survivors of childhood HL may be at increased risk for OSA, which when concurrent with treatment-related cardiopulmonary and cerebrovascular risk may further increase morbidity and mortality. Future studies are warranted to compare the prevalence of OSA in this population with a matched community control group and examine whether and how the mechanism for OSA might differ from that in the general population.
Ultrasound versus physical exam to screen for secondary thyroid cancer among high-risk childhood cancer survivors.
Authors: Hess Jennifer , Walsh Alexandra Maria , Newbern Dorothee , Schafernak Kristian , Vern-Gross Tamara , Foote Janet 
Published: March 2020

e21528 Background: Thyroid cancer is a common secondary malignancy among childhood cancer survivors who have received radiation to the head, neck and/or upper thorax. The optimal strategy for surveillance for thyroid carcinoma in childhood cancer survivors remains controversial. Current Children’s Oncology Group recommendations are limited to physical exam. The objective of this study was to determine the sensitivity and specificity of thyroid ultrasound versus neck exam by a pediatric endocrinologist in the diagnoses of thyroid cancer in a cohort of high-risk childhood cancer survivors. Methods: Medical records of childhood cancer survivors who received radiotherapy to the head, neck and/or upper thorax were reviewed. These patients were seen in a comprehensive childhood cancer survivorship clinic from 01/01/2010 to 12/31/2017. Patient populations included oncology, bone marrow transplant and brain tumor patients. Results: 226 patients received radiation to the head, neck and/or upper thorax. Of those, 129 patients were male (57%). Sixteen (7.1%) of patients developed a secondary thyroid malignancy including 4 patients previously treated for an oncological malignancy, 9 patients treated with bone marrow transplantation, and 3 patients with a CNS malignancy. Median radiation dose was 1800 cGy (range 400-5940 cGy). Time to thyroid carcinoma diagnosis occurred at a median of 12 years (range 4-19 years) from treatment with radiation. Screening ultrasounds were obtained in 146 (65%) patients while 226 (100%) had a physical exam. Two cases were identified by abnormalities on physical exam. The sensitivity of US was 100% (CI 80.6-100) compared to a sensitivity of 12.5% (CI 3.5-36) using physical exam (P < 0.0001). Screening ultrasound had a specificity of 73% (CI 65.1-80.1) while physical exam yielded a specificity of 100% (CI 98.2-100). Conclusions: Regular screening with ultrasounds provide the greatest sensitivity for detection of secondary thyroid carcinomas after head, neck and upper thorax radiation in childhood cancer survivors. If screening ultrasounds were not routinely utilized in our clinic, 14 of the 16 patients (87.5%) would have had a delay in their diagnosis of a secondary thyroid malignancy. Screening ultrasounds may lead to earlier detection of thyroid carcinomas, with the potential to decrease the need for aggressive surgery, radioiodine therapy and, ultimately, to decrease recurrence risk.
Peripheral-blood stem cell transplantation in pediatric recipients in Peru: Experience of a reference center.
Authors: Maradiegue Essy , Sulca-Huamani Oliver Guillermo , Quincho-Lopez Alvaro Jesus , Meza Kelly Jasmin , Vasquez Liliana , Garcia Juan Luis , Chavez Sharon , Ugaz Cecilia , Montoya Jacqueline , Ordoñez Katy , Diaz Coronado Rosdali Yesenia , Zapata Arturo , Morales Roxana , Reaño Romulo , Hernandez Broncano Eddy 
Published: March 2020

e21530 Background: Stem cell transplantation (SCT) is a curative treatment for children with refractory/relapsed malignancies. However, data on pediatric transplantation in developing countries like Peru is still needed. The aim of this study was to describe and assess the survival and complications of children with neoplastic disease who have received peripheral-blood stem cell transplantation (PBSCT) at a reference center in Peru. Methods: A retrospective longitudinal study was performed by reviewing medical histories of 20 children (≤14 years) with neoplastic disease who underwent related allo- or auto-PBSCT from October 2014 to December 2017 of INEN (Instituto Nacional de Enfermedades Neoplásicas). In the cases of ALL > 3 years, radiotherapy was not part of the conditioning regimen. The Kaplan-Meier method was used to determine the overall survival (OS) and event-free survival (EFS). Data were analyzed using Stata/MP 14.0. Results: We found 13 males and 7 females with a median age of 9.5 years (1-14), of whom 18 received allo-SCT and 2 auto-SCT. Diagnosis: 14 ALL(66.6%), 1 AML(4.7%), 1 NHL(4.7%), 2 biphenotypic leukemia(9.5%), 1 juvenile chronic myelomonocytic leukemia(4.7%) and 1 germ cell tumor(4.7%) who performed two auto-transplants. Complete remission (CR) was achieved before transplantation in 19 cases: 8(38%) 1CR; 8(38%) 2CR and 3(14.2%) 3CR. A median of 7.14x106CD34+/kg (3.97-13.05) (auto- vs allo-; 6.35 vs 7.27) were collected and median time to myeloid engrafment: 11 days. At a median follow-up of 12 months (1-39) the 2-year OS and EFS were 75.7% (95% confidence interval [CI], 38-92%) and 51.6% (95% CI, 22-74%) respectively. Considering only ALL > 3 years, OS and EFS were 51.9% and 45.1%, respectively. Acute graft-versus-host disease (GVHD), chronic GVHD, transplantation-related mortality (TRM) and relapse were 27.7%, 11.1%, 4.7%, and 33.3%, respectively. Conclusions: We are encouraged by this first experience in our country. OS and EFS are comparable with results at the international level. However, survival of children with ALL > 3 years who did not receive radiotherapy is less than international standards. Studies with a higher number of cases and longer follow-up time are needed to reach definitive conclusions.
Current practices and attitudes in menstrual management in adolescents with cancer: A national survey of pediatric oncology providers.
Authors: Close Allison , Jones Kelley , Landowski Allison , Switzer Galen E , Miller Elizabeth , Friehling Erika 
Published: March 2020

e21533 Background: Adolescents and young adult (AYA) females with cancer are at risk of heavy menstrual bleeding (HMB) due to thrombocytopenia, coagulopathy, and/or disruption of the hypothalamic-pituitary-gonadal axis. Options for temporary menstrual suppression (MS) include combined oral contraceptives (OCPs), progestin-only therapy, GnRH agonists, and intrauterine devices. Currently, little is known about current practices to help prevent and treat HMB in AYA women with cancer. Methods: We conducted a national cross-sectional internet-based survey of providers from 100 pediatric oncology centers. Institutions were randomly selected to allow for even representation by program size and geography. Face and content validity were assessed prior to distribution. Descriptive statistics were used to analyze respondent characteristics, attitudes, and practices for managing menstrual suppression. Chi-squared test or Fischer’s Exact test (for small cell sizes across groups) were used for analysis of categorical data. Kruskal-Wallis one-way ANOVA tests were used to compare means. Results: The majority of respondents (94%) have recommended preventative MS. MS in pediatric oncology patients is most often managed by oncology (61%) versus gynecology (22%) or adolescent medicine (12%). Greater than 50% of respondents agreed that patients with the following types of cancer should receive preventative MS: sarcomas, acute leukemias, lymphomas, and germ cell tumors. GnRH agonists were the most preferred method of MS (52%). Most respondents agreed that it is important to consider MS (94%), and that a formal guideline about initiation of MS would be helpful (95%). Less than half (46%) of participants felt comfortable personally managing MS. Conclusions: The vast majority of pediatric oncologists have used preventative MS, most commonly GnRH agonists, and feel that it is important to consider in the majority of AYA cancers. Although pediatric oncologists are most often managing MS, they do not feel comfortable doing so and desire guidelines to help with management.
Parental insights into phase I pediatric oncology clinical trials: Findings from a phenomenological study.
Authors: Crane Stacey , Croop James , Lee Jill Lunsford , Walski Jamie , Haase Joan 
Published: March 2020

e21534 Background: Phase I clinical trials (P1Ts) are an essential step in the validation of novel therapies to treat childhood cancer. Children with cancer participate in P1Ts when no known curative therapy remains for their cancer. It is important to understand the experiences of children with advanced cancer and their families in P1Ts to ensure that participation supports the participants well-being. Methods: An empirical phenomenology study, using an adapted Colaizzi method, was conducted of 11 parents lived experiences of their childs participation in pediatric oncology P1Ts. Parents were recruited from two pediatric academic medical centers in the Midwest United States and from national childhood cancer groups not affiliated with either medical center. Parents participated in individual interviews (mean length 59.1 minutes), with one broad data-generating question. Demographics and the childs clinical trial records provided additional context for understanding the experiences. This presentation describes the study themes identified that were specifically related to pediatric oncology P1T processes and logistics. Results: Parents experiences during the P1Ts were primarily positive. However, data analysis revealed five aspects of P1T participation that were problematic for parents to varying degrees. These aspects were: (1) Learning About Clinical Trials, (2) Being Referred to Another Institution, (3) Undergoing Research-Only Procedures, (4) Complying with the Trial Requirements, and (5) Taking Oral Medications. Conclusions: While overall experiences during P1T participation were positive, improvements can be made that could potentially enhance participants experiences. In particular, enhancing the education provided to participants during on-trial processes and minimizing the logistical burdens associated with P1T requirements may help to address problematic aspects of P1Ts.