bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bianca: Phase II, single-arm, global trial to determine efficacy and safety of tisagenlecleucel in pediatric/young adult (YA) patients (Pts) with relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL).
Authors: Minard Veronique , Maude Shannon L. , Buechner Jochen , Krueger Joerg , Locatelli Franco , Attarbaschi Andishe , Laetsch Theodore Willis , González Martínez Berta , Diaz de Heredia Rubio Cristina , Awasthi Rakesh , Newsome Simon , Davis Jaclyn , Bubuteishvili-Pacaud Lida , Burkhardt Birgit 
Published: May 2020

e22504 Background: Pediatric/YA pts with r/r B-NHL are rare and have heterogenous, aggressive histology and poor prognosis. We report early results for tisagenlecleucel (anti-CD19 CAR-T cell therapy) in pediatric/YA pts with r/r B-NHL. Methods: BIANCA (NCT03610724) is a phase 2, single-arm, global, open-label trial of tisagenlecleucel in pediatric/YA pts with CD19+ r/r B-NHL. Pts must have confirmed mature B-NHL r/r to ≥1 prior lines of therapy and no active CNS involvement. Primary endpoint is ORR. Secondary outcomes include DOR, EFS, safety and pharmacokinetics. Results: As of Nov 4, 2019, 8 pts were enrolled, of whom 4 had large B-cell lymphoma (LBCL), 3 Burkitt lymphoma (BL), and 1 gray zone lymphoma (GZL) (Table). Five pts had ≥2 lines of prior therapy. Suitable apheresis product was harvested in all 8 pts. Five pts were infused and 3 were pending infusion at data cut off. Product was successfully manufactured within specifications for all infused pts. Median time from enrollment to infusion was 33 days (range 30-67). All 5 pts have ≥28 days follow up; 2 pts have ≥3 months follow up (median [range] 85 days [69-97]). All 8 pts received bridging chemotherapy (including 1 pt who also had surgery and 1 who also had radiotherapy). Tisagenlecleucel dose range was 0.3-1.1 × 108 CAR+ viable T cells (weight-based: 0.9-1.7 × 106 CAR+ viable T cells/kg). Cmax (range: Cmax= 8520-14,200 copies/µg; time to Cmax= 2-21 days; n = 4) was within range of expansion observed in pediatric/YA acute lymphoblastic leukemia and adult diffuse LBCL. All 5 pts had CRS; no grade ≥3 CRS was recorded. Three pts had neurologic events, including 2 grade 3/4 events. One pt died due to disease progression. Conclusions: Pediatric/YA pts with r/r B-NHL (including BL) were successfully infused with tisagenlecleucel in the BIANCA trial with a manageable safety profile. Apheresis/manufacturing were feasible in this cohort of rapidly progressing disorders. Tisagenlecleucel was shown to expand in vivo. BIANCA provides the first systematic data on CAR-T cell therapy in highly aggressive, pediatric/YA B-NHL. Planned enrollment is 35 pts (26 infused and evaluable). Clinical trial information: NCT03610724. [Table: see text]
Pediatric cancer registry in Turkey 2009-2019 (TPOG & TPHD).
Authors: Kutluk M. Tezer , Yeşilipek Akif 
Published: May 2020

e22513 Background: The pediatric cancer registry is an essential element of pediatric cancer control. More than 200000 pediatric cancer cases annually are expected in children and adolescents aged 0-14 globally. The current efforts are focusing to improve the survival rates for children and adolescents in LMICs since the survival has already exceeded 80% in most of the high income countries. Here we present the most updated results of the pediatric cancer registry in Turkey. Methods: Pediatric cancer registry has been established by theTurkish Pediatric Oncology Group and Turkish Pediatric Hematology Association in 2002. The childhood cancer cases registered between 2009-2019 was included in this analysis. International Childhood Cancer Classification System was used for the classification. Essential demographic findings, ICD-O-3 morphology and topography codes were recorded for each case. Results: During the 11 years from 2009 to 2019, 17770 cases were registered. For all cases, median age was 6.8 year (0-17; M/F 9973/7789, 3 hermaphrodite, 5 unknown). Age distribution was 0-4 yrs, 40.3%; 5-9 yrs, 24.0%; 10-14 yrs, 23.6%; 15-19 yrs, 12.1%) The distribution of the tumor types were [number of cases, percentage of total, median age yrs, M/F]: Leukemia (4570, 25.7%, 5.5, 2633/1937); Lymphoma & other RES tumors (3477, 19.6%, 9.9, 2324/1150, 1 hermaphrodite & 2 unknown); CNS [brain & spinal] (2493, 14.0%, 6.9, 1363/1129, 1 unkown); Symphatetic system (1426, 8.0%, 2.4, 743/683); Retinoblastoma (348, 2.0%, 1.5, 204/144); Renal (905, 5.1%, 3.2, 435/469, 1 unknown); Liver (304, 1.7%, 1.8, 172/132); Malignant bone (1209, 6.8%, 12.6, 658/551); Soft tissue sarcomas (1221, 6.9%, 7.5, 703/518); Germ cell (1165, 6.6%, 8.8, 426/736, 2 hermaphrodite, 1 unknown); Carcinoma & other malignant epithelial (533, 3.0%, 13.8, 254/279); Other/non-specific malignant (119, 0.7%, 8.5, 58/61). Five year survival rate was found as 71.9%. Conclusions: The data is the most essential part of the cancer control.This registry has been used widely among professionals since its establishment in 2002. Survival rates for children and adolescents has been improved to 70%. This is at the acceptable level for the income level of Turkey which is classified as an upper middle income country. The registry is a useful source for investigators and decision makers at national and international level.
Modulation of radiation biomarkers in a randomized phase II study of 131I-MIBG with or without radiation sensitizers for resistant/relapsed neuroblastoma.
Authors: Campbell Kevin M. , Groshen Susan , Marachelian Araz , Pal Sharmistha , Haas-Kogan Daphne A. , Kellogg Mark , Evans Angela Clare , Coleman Matthew A. , Park Julie R. , Granger Meaghan , Matthay Katherine K. , DuBois Steven G. 
Published: May 2020

e22514 Background: 131I-metaiodobenzylguanidine (MIBG), a radiopharmaceutical agent, has demonstrated efficacy as a single agent for patients with neuroblastoma. Recently, trials have focused on MIBG combination strategies, though little is known about impact of combination agents on markers of radiation exposure. Methods: NANT11-01 (NCT02035137) was a multicenter, open label, randomized phase II clinical trial that evaluated MIBG therapy alone (Arm A) or in combination with vincristine/irinotecan (Arm B) or vorinostat (Arm C) for patients with resistant/relapsed neuroblastoma. We collected blood samples at baseline and 72 hours after MIBG infusion and determined plasma flt3 ligand, serum amylase, gamma-H2AX levels, and gene expression for key transcripts. We plotted relative change from baseline and evaluated association of marker modulation by treatment arm and clinical response using NANT response criteria. Results: The cohort included 65 patients who had at least one biomarker available for analysis (19 Arm A; 24 Arm B; 22 Arm C). Across all arms, plasma flt3 ligand and serum amylase were significantly positively modulated while BCLXL/BCL2L1 and BCL2 gene expression demonstrated significant negative modulation by 72 hours after MIBG infusion compared to baseline (p < 0.001 for all markers). For patients randomized to Arm B, we observed significantly greater positive modulation of Flt3 ligand (geometric mean fold change 4.21 for Arm B vs. 2.22 and 2.08 for Arms A and C, respectively; p < 0.001) and significantly greater negative modulation of BCLXL/BCL2L1 (geometric mean fold change 0.11 for Arm B vs. 0.55 and 0.43 for Arms A and C, respectively; p < 0.001). There were no statistically significant associations of differential modulation of a specific biomarker with higher likelihood of response (partial response or better), though there was a trend to suggest that responders had greater gamma-H2AX modulation (p = 0.053). Conclusions: Peripheral blood biomarkers relevant to radiation exposure demonstrate significant modulation after MIBG treatment, with differential modulation when chemotherapy is combined with MIBG. Analysis of additional markers and additional samples is ongoing. Clinical trial information: NCT02035137.
Female genital tract rhabdomyosarcoma in childhood and adolescence: A single center experience.
Authors: Yaman Bajin Inci , Kutluk Tezer , Yildiz Ferah , Karnak İbrahim , Oğuz Berna , Orhan Diclehan , Elmali Aysenur , Gultekin Melis , Aydin Burca , Yalcin Bilgehan , Kurucu Nilgun , Varan Ali , Akyüz Canan 
Published: May 2020

e22518 Background: Rhabdomyosarcoma is a rare tumor in children and adolescents, presenting 3% to 4% of all pediatric cancers. The female genital tract is considered as a favorable site of childhood RMS. The outcome has improved significantly during the last two decades, attributed to risk stratification and multimodality management of these challenging tumors. Here we present the clinical features and treatment results of girls with genital tract rhabdomyosarcoma to discuss. Methods: Fourteen girls with vaginal and uterine servical rhabdomyosarcoma younger than 18 years of age diagnosed and followed up between the years of 1995 and 2019 were included in this analysis. The clinical features and treatment results of patients were recorded from patient files and hospital information system retrospectively. Results: There were seven cases with vaginal and seven with uterin cervical carcinoma. All patients presented with polypoid masses protruding from the vagina. Median age of patients at diagnosis was 71 months (range 8-200 months). The IRS modified TNM staging was stage I for all the patients. All cases had embryonic type of RMS except one with alveolar type. All patients were treated with surgery and adjuvant chemotherapy, three received radiotherapy additionally. All achieved complete remission. Four patients experienced tumor relapse, 1 patient died with progressive disease. The median follow-up time was 75 months (7-271 months) for 13 patients who were alive with remission. Conclusions: Rhabdomyosarcoma is a rare sarcoma with a higher incidence in children and adolescents. With current treatment strategies, female genital tract rhabdomyosarcomas have a good prognosis. Favorable prognostic factors such as early stage at diagnosis and a favorable histology may contribute to the excellent observed survival. All parties who had involved on the care of these girls must be aware of the high survival with proper treatment to avoid treatment related morbidities and mortalities. Because of the rareness of the disease we wanted to share our experience.
Evaluation of the quality-of-life (QOL) and socio-demographic characteristics of patients with leukemia and lymphoma: Comparison with sibling and control group.
Authors: Tacyildiz Nurdan , Karakose Tugba , Unal Emel Cabi , Dincaslan Handan , Tanyildiz Gulsah , Çakmak Hatice Mine 
Published: May 2020

e22524 Background: Pediatric cancer patients have increased survival rates with intensive and effective treatment methods which causing some chronic health problems and lower quality of life in long term follow up. In our study, patients in their active treatment period compared to patients who have completed their treatment in recent 5 years and more than 5 years groups, besides compared with their own siblings and healthy control group,evaluated in terms of quality of life ( QOL). Methods: This study has been daone in the Department of Pediatric Hematology-Oncology, Ankara University School of Medicine. A total of 191 children were included in the study, including 36 sibling, 76 children with leukemia (n:31) and lymphoma (n:45) besides 79 healthy children. The Turkish translation of the PedsQL questionnaire was used to evaluate the patients' quality of life. IBM SPSS-25 package program was used for statistical analysis. Results: When the sociodemographic characteristics of the patient, sibling and control group were examined; we determined that the patients, siblings and control groups were similar in age, age and gender. However, we found that the education level for the patient group was statisticaly signicantly lower then the siblings and the control group. In addition, physical and mental functionning and friendship capasity scores were lower in patient group than the other two groups. According to timing of the treatment; patients and parents quality of life scores were significantly lower than the patients that finished their treatment in recent 5 years or more than 5 years. QOL scores were higest in survivors and parents group that were in more than 5 years after completed the treatment. The risk of lower QOL in patients under treatment was 7.48 times higher than the children who had ≥5 years of treatment (OR = 7,48; p < 0,05), and 2.64 times higher than those who were treated < 5 years (OR = 2,64; p > 0,05). In this study, there were no independent variables that had an impact on QOL of the sibling group. Conclusions: The QOLof patients diagnosed with leukemia and lymphoma is significantly lower than siblings and healthy group. No statistically significant difference was found between the sibling group and the healthy control group. After the end of active treatment, the QOL of the patients was reflecting important increase by the time .
Screening practices for late effects in pediatric patients on tyrosine kinase inhibitors.
Authors: Smith Stephanie M , Sabnis Himalee S. , Williamson Lewis Rebecca , Effinger Karen Elizabeth , Bergsagel Daniel John , Patterson Briana , Mertens Ann C. , Sakamoto Kathleen , Schapira Lidia , Castellino Sharon M. 
Published: May 2020

e22527 Background: BCR-ABL tyrosine kinase inhibitors (TKIs) have revolutionized treatment of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) and chronic myeloid leukemia (CML). The off-target effects of long-term TKI use in children are poorly understood. We evaluated institutional screening practices for cardiac and endocrine late effects in those who had received TKIs at two large pediatric cancer centers. Methods: This retrospective cohort included patients diagnosed with Ph+ALL (post completion of frontline therapy) or CML at age < 21 years with ≥1 years of follow-up. Patients were censored at stem cell transplant, blast crisis, secondary neoplasm, death, or last contact. Demographics, clinical features, and incidence of screening echocardiogram (ECHO), electrocardiogram (EKG), dual-energy x-ray absorptiometry (DXA), bone age, and thyroid function (TSH) were abstracted. Descriptive statistics and incidence of screening are presented by diagnosis. Results: The cohort (n = 68) was 50% female, 28% non-Hispanic white, 24% non-Hispanic black, 24% Asian, and 19% Hispanic. CML: Patients were diagnosed at 12.9±4.6 years of age and had 6.3 (0.9-15.6) years of TKI exposure and 6.3 (0.9-15.6) years of follow-up. Imatinib was most commonly used (80%) followed by dasatinib (59%); 48% were exposed to > 1 TKI. Excluding tests at diagnosis, 48% had an ECHO and 48% had an EKG during the follow-up period. TSH, DXA and bone age were measured in 50%, 9% and 11% patients, respectively. Ph+ALL: Patients were diagnosed at 10.8±5.1 years of age and had 2.8 (0.6-11.6) years of TKI exposure and 5.7 (2.1-11.8) years of follow-up. Dasatinib was most commonly used (73%) followed by imatinib (64%); 36% were exposed to > 1 TKI. All received anthracyclines and steroids. Excluding tests at diagnosis, 91% had an ECHO and 77% had an EKG. TSH, DXA and bone age were measured in 82%, 68% and 36% patients, respectively. Conclusions: We note inconsistent cardiac and endocrine screening in patients receiving TKIs for CML and Ph+ALL. Evidence-based guidelines for long-term follow-up and structured monitoring for potential off-target effects are needed. A prospective screening study is in progress and may enhance our understanding of the prevalence of late effects of TKIs. [Table: see text]
The role of peer support in psychosocial outcomes among adolescent and young adult (AYA) cancer survivors.
Authors: Matsui Motohiro , Taku Kanako , Tsutsumi Rina , Ueno Midori , Seto Mayuri , Makimoto Atsushi , Yuza Yuki 
Published: May 2020

e22528 Background: Adolescents and young adults (AYA) who experienced cancer treatment sometimes show posttraumatic stress symptoms (PTSS) and yet report positive psychological changes, known as posttraumatic growth (PTG). Literature suggests PTSS and PTG are not on opposite ends of a single spectrum but rather coexist. It is expected to have distinct relationships with social support, and yet, the roles of peer support remain unknown. This study examines PTG and PTSS, and their correlates with peer support among AYA cancer survivors. Methods: A cross-sectional study was conducted using a questionnaire survey with AYA cancer survivors. A total of 212 AYA survivors were recruited from 11 cancer centers and 12 cancer patients’ communities. They completed a self-report measure of the PTG Inventory and the Impact of Event Scale revised (IES-R) to assess PTSS. Diagnosis, treatment, peer support (i.e., affiliation to AYA patients’ community and friendship with other AYA cancer patients), and social status information was also collected from questionnaires. A series of multiple regression analyses was used to identify significant correlates among peer support, PTG and PTSS. Results: PTG and PTSS were not significantly correlated with each other, being consistent with the previous studies. PTG was positively associated with male gender, years since diagnosis, good communication with others, and friendship with other AYA cancer patients. Friendship with other AYA cancer patients was positively associated with not just the overall PTG but all five domains of PTG. PTSS was associated with years since diagnosis, unemployed status, and symptom of late effects. PTSS was, however, unlike PTG, not related with friendship with other AYA cancer patients or affiliation to AYA patients’ community. Conclusions: Good communication and friendship with other AYA cancer patients is suggested to play an important role in PTG but not PTSS. Psychosocial intervention to facilitate peer support among AYA cancer patients would possibly contribute to revive their lives through PTG. Future studies should further investigate what factors would contribute to alleviation of PTSS and foster PTG. Clinical trial information: UMIN000035439.
Mutational analysis of radiation-induced subsequent thyroid cancers in pediatric patients.
Authors: Hess Jennifer , Walsh Alexandra Maria , Schafernak Kristian 
Published: May 2020

e22531 Background: The genetic landscape of radiation induced pediatric thyroid cancers is unclear. Radiation (RT) induced thyroid cancers frequently demonstrate tumorigenesis driven by fusion oncogenes. However, data is limited to children exposed to radioactive contamination after the Chernobyl nuclear accident. Little is known about the genetic landscape of subsequent pediatric thyroid cancers after RT exposure for the treatment of a primary malignancy or conditioning regimens prior to bone marrow transplantation (BMT). The objective of this study was to assess the prevalence of different mutations in a small cohort of pediatric patients who developed a subsequent thyroid cancer after RT exposure for the treatment of a primary disease. Methods: This is a single-center retrospective study. Thyroid tissue blocks from 10 pediatric patients who underwent thyroidectomy between 2010 and 2019 for subsequent thyroid cancers after RT for treatment of a primary malignancy or BMT were analyzed for genetic alterations using targeted next-generation sequencing for alterations in 112 genes linked to thyroid cancer. Thyroid cancers included 7 papillary (PTC) and 3 follicular thyroid carcinomas (FTC). Results: Ten samples (6 females) were genotyped. The mean age at thyroid cancer diagnosis was 15.7 years (range 11–22 years) at a mean of 10.3 years (range 6 – 19 years) after RT exposure. The mean RT dose was 2618 cGy (range 400 – 10,080 cGy) delivered to the head, neck, and/or chest. Mutations were noted in 6/10 (60%) of patients. Mutations were detected in 6/7 (85.7%) of PTC cases: EMLA/NTRK in 2 cases, STRN/ALK in 2 cases, RET in 1 case, and CCDC30/ROS in 1 case. A DICER.1 c.5438A > C p.E1813A was also identified in a patient with an EMLA/NTRK fusion. Of 3 FTC patients, (2/3) 67% had copy number alterations, but no mutations were observed. BRAFV600E mutations were not present in any tissues analyzed. Conclusions: An exceedinlgy rare ROS fusion was identified. Multiple RT induced thyroid lesions were positive for classic therapeutic targets including NTRK3, ALK, ROS1, and RET fusions, demonstrating a potential role for tyrosine kinase inhibitor therapy for refractory, recurrent or metastatic disease. All cases were negative for mutant BRAFV600E consistent with the pathogenesis of RT induced thyroid cancers primarily activated by fusions rather than point mutations. Larger, pediatric cohorts with RT induced thyroid cancers followed long term will enable the genotypic variability, clinical presentation, and response to therapy to be better assessed.
Locally advanced GCTB recurrence after neoadjuvant denosumab use.
Authors: Taveira Gabriela Monte Tenorio , Marinho Felipe Da Silva , Souza Antonio Marcelo Gonçalves de , Carneiro Wagner cabral Gomes 
Published: May 2020

e23507 Background: Giant Cell Tumor of Bone is a RANK/RANK-ligand (RANKL) positive, aggressive, locally destructive tumor leading to pain and impairment of movement and limb function. Even though surgery remains the standard treatment, the use of denosumab, monoclonal antibody RANK-L inhibitor is associated with tumor response and surgical morbidity, with downstaging benefit. Methods: All GCTB patients from 2005 to 2020 from Pernambuco Cancer Center Hospital were included in the study and followed up. All patients received Denosumab 120mg on D1, D8 and D15 (attack phase), and maintenance phase of 120mg monthly. Results: A total of Fifty GCTB Patients were included in the study, being mostly women (62%), between 21-40 yrs. old (56%), Capanacci III (72%), with tumors located in femur (41%), tibia (23%), and more rarely in talus or orbit. Denosumab neoadjuvant was prescribed to 40 patients, being 28 locally advanced disease and 12 irresectable or metastatic disease, with a median of 10 doses received. Among resectable Patients, after neoadjuvant denosumab, 25 were submitted to intralesional surgery (curettage/bone cement) and 3 to en-bloc surgery/prothesis. Overall recurrence after neoadjuvant denosumab was observed in 22% (9/40) and 32% (8/25) among Patients that received neoadjuvant denosumab and intralesional surgery. Denosumab was approved for irresectable GCTB, or when surgery may render high morbidity. Neoadjuvant Denosumab use has been related to lower recurrence rate, as well as reduction in invasive procedures morbidity and sequelae in motricity. In the present study, recurrence rate of 22%, regardless of the therapeutic modality applied, corroborates recurrence rates in published data (16-30%). Among locally advanced patients, even though recurrence rates are expectedly higher, there were lower rates of aggressive surgery and joint preservation. Motor sequelae was observed in 12,5% (5/40) of patients, with quality of life improvement and pain reduction after treatment. Conclusions: Neoadjuvant denosumab for GCTB provides promising results, with acceptable recurrence rates, as well as a less aggressive approach, with lower risk of morbidity or sequelae and excellent safety profile.