bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome of clear cell sarcoma of the kidney (CCSK) treated on the National Wilms Tumor Study-5 (NWTS)
Authors: Seibel N. L. , Sun J. , Anderson J. R. , Breslow N. E. , Perlman E. J. , Ritchey M. L. , Thomas P. R. , Coppes M. J. , Grundy P. E. , Green D. M. 
Published: March 2020

9000 Background: CCSK was initially described by its bone metastasizing tendencies and propensity for late recurrences. Outcome for patients with CCSK has improved from NWTS 1–4. On NWTS 4 patients were randomized to treatment for 15 months vs 6 months. Their overall 8 year relapse free survival was 88% vs 61%, respectively. NWTS-5 was designed to improve the event free survival (EFS) and overall survival (S) for patients with CCSK by incorporating cyclophosphamide and etoposide. Methods: Prospective single-arm study conducted between August, 1995 and June, 2002. Patients less than 16 years of age with a centrally confirmed pathological diagnosis of CCSK were eligible. Staging consisted of CT scans of chest, abdomen, pelvis, bone scan, skeletal survey, and CT or MRI of head. Patients were treated with vincristine/doxorubicin/cyclophosphamide alternating with cyclophosphamide/etoposide for 24 weeks and XRT (10.8 cGy). Results: 110 eligible patients were enrolled on study. Median age was 22 months, 69% were males, and 63% white. Stage distribution was: stage I, 14; II, 41; III, 46; IV, 9 [metastatic sites: lung (3), bone (1), brain (1), liver (1), bone and bilateral lung (1) and other (2)] Median follow-up is 4.6 years. 5-year EFS and S were 79% (95% CI, 69% to 86%) and 89% (95% CI, 80% to 94%). All but one of 21 recurrences occurred within 3 years of initial treatment. The most common site of recurrence was brain (11/21). 5-year EFS for Stage I-IV was 100%, 87%, 74% and 36% respectively. Adverse prognostic factors for patients with Stage II/III disease were white race, and lymph node involvement. Conclusions: Outcome for patients with CCSK treated on NWTS-5 is similar to that seen on NWTS-4 and recent SIOP and UKCCSG trials. Stage is highly predictive of outcome. Brain recurrence was higher than that seen on NWTS-4; lung recurrences were lower. The next Childrens Oncology Group (COG) protocol will use the same treatment for patients with Stages I-III; therapy for patients with Stage IV disease will incorporate carboplatin. The role of XRT in CCSK needs to be evaluated. No significant financial relationships to disclose.
Site of metastases does not influence the clinical outcome of children with metastatic Germ Cell Tumors (GCT). A report from the Childrens Oncology Group (COG)
Authors: Malogolowkin M. H. , London W. B. , Cushing B. , Giller R. , Davis M. , Cullen J. , Olson T. A. 
Published: March 2020

9002 Background: To describe the clinical outcome of children with metastatic GCT (stage IV) at diagnosis according to the primary metastatic site(s). Methods: From March 1990 to February 1996, 299 children and adolescents with stage III/IV gonadal and stage I-IV extragonadal GCT were eligible for a Pediatric Intergroup high-risk (HR) GCT trial. Patients were randomized to receive 4–6 courses of cisplatin (P) standard dose [ 20 mg/m2/day (d) × 5] or high-dose (HDP) [40 mg/m2/d × 5] with etoposide (E) 100 mg/m2/d × 5 and bleomycin (B) 15 mg/m2 on d1. We retrospectively investigated the outcome of patients with stage IV and compared their outcome according to metastatic site(s). Results: There were 133 patients with stage IV disease. The median age was 2.6 years (y) [range, 3 d-19.3 y], 70 were female. Primary sites included: 43 testicular, 14 ovarian, 76 extragonadal (45 sacroccocygeal, 28 mediastinal, 3 other). Histologies included: 66 pure yolk sac tumors, 21 immature teratomas and yolk sac tumors, 26 mixed germ cell tumors, 7 pure germinoma/seminoma/dysgerminomas, 1 immature teratoma with a non-classic germ cell tumor, 2 mixed germ cell tumor admixed with a nonclassic germ cell tumor, 5 pure choriocarcinomas, and 5 patients with unknown histology. There were no statistically significant differences in the 5-year EFS or OS rates by site of metastases. Of the 19 patients with either bone or brain involvement, 17 patients had bone and 3 had brain metastases. Conclusion: The outcome for patients with metastatic GCT is excellent with contemporary cisplatin-based regimes and is independent of the site of metastatic disease. [Table: see text] No significant financial relationships to disclose.
A topotecan-containing induction regimen for treatment of high risk neuroblastoma
Authors: Park J. R. , Stewart C. F. , London W. B. , Santana V. M. , Shaw P. J. , Cohn S. L. , Matthay K. K. 
Published: March 2020

9013 Background: We assessed the toxicity and feasibility of adding dose-intensive topotecan and cyclophosphamide to a multi-agent chemotherapy induction regimen for treatment of newly diagnosed high-risk neuroblastoma. Methods: Patients received 2 cycles of topotecan (starting dose 1.2 mg/m2/day for 5 days) and cyclophosphamide (400 mg/m2/day for 5 days) (T/C) followed by an additional 4 cycles of chemotherapy; cisplatin, etoposide alternating with vincristine, doxorubicin, cyclophosphamide. Pharmacokinetically guided topotecan dosing (target systemic exposure of AUC 50 - 70 ng/ml*hr determined by single day topotecan lactone levels) was performed. Chemotherapy cycles were scheduled every 21 days, PBSC harvest occurred after T/C cycles and surgical resection of residual primary tumor after cycle 5. Results: Thirty-one patients, 3 with INSS Stage 3 and 28 with Stage 4, were enrolled between April 2004 and November 2005. Median age at diagnosis was 2.5 years (range 0.9 - 9.35 years). Ten of 25 patients had tumor cell MYCN amplification and 21 of 22 tumors were classified as unfavorable Shimada histology by central review. Targeted topotecan systemic exposure was achieved in 87% (27/31) of patients during T/C cycle 1 and in 85% (23/27) of patients during T/C cycle 2. PBSC collections occurred as intended in 95% of patients (21/22 patients), median harvest 30.8 × 106 CD34+cells cell/kg (range 2.24 - 542). No dose limiting toxicities occurred. All patients experienced Grade 3 or 4 hematopoietic toxicity. Febrile neutropenia occurred in 79% (19/24) of patients during T/C cycles and 78% (18/23) of patients during subsequent cycles of induction therapy. Documented infection occurred in 12.5% (3/24) patients during T/C cycles and 26% (6/23) during subsequent induction cycles. Dose intensity of all chemotherapy agents was maintained in 95.8% (23/24) of patients. Conclusions: This pilot induction regimen was well tolerated with expected and reversible toxicities. Dose intensity of standard induction chemotherapy agents was not limited by the addition of dose-intensive topotecan. These data support investigation of efficacy in a Phase III clinical trial for newly diagnosed high-risk neuroblastoma. [Table: see text]
Oral out-patient chemotherapy medication errors in children with acute lymphoblastic leukemia
Authors: Hawkins D. S. , Taylor J. , Winter L. , Geyer L. 
Published: March 2020

9028 Background: Oral out-patient chemotherapy medications (OOCMs) compromise the majority of therapy for children with acute lymphoblastic leukemia (ALL). OOCM are administered at the patient’s home, usually by parents with limited medical training. The frequency of errors in OOCM dose or schedule is unknown in children with ALL. Methods: We conducted a prospective case series. After providing informed consent, parents were interviewed during an ambulatory clinic visit to determine the dose and frequency of OOCMs administered since the last ambulatory clinic visit or hospitalization. Parents also completed a questionnaire regarding their understanding of the child’s OOCMs. Patient medical records were reviewed to determine the appropriate OOCM doses and schedules and then compared to the parent report. Pharmacy records were reviewed to determine how OOCMs were prescribed. OOCM errors included omission of any OOCM, use of an incorrect OOCM, > 10% deviation from the intended OOCM dose, or incorrect OOCM schedule. Results: 69 children (median age 6.4 years, range 1.3–17.9 years) participated, with a total of 171 OOCMs assessed. Fifteen (8.7%) OOCMs were given incorrectly, including 10 OOCMs administered incorrectly by parents, and five prescribed incorrectly. Eight errors involved under- or over-dosing within 10–20% of the intended OOCM dose. There were no errors in pharmacy dispensing. Errors were more common with glucocorticoids (9/60 OOCMs evaluated) than anti-metabolites (6/111 OOCMs evaluated). Conclusions: OOCM errors are unusual in children with ALL. Both administration and prescription errors were observed. Efforts to improve optimal use of OOCMs should include prevention of errors, potentially by identifying patients at higher risk for OOCM errors. No significant financial relationships to disclose.
Clinical outcome of pediatric Hodgkin’s disease in upper Egypt
Authors: Ebeid E. N. , Zaghloul M. , Khairy M. 
Published: March 2020

9035 Background: To assess clinical outcome of chemotherapy and involved field radiotherapy in all stages of pediatric Hodgkin’s Disease in rural areas of Egypt treated at Menya oncology centre which is located 300km south the capital. Methods: Between April 2000 and November 2005, 27 previously untreated patients were investigated, treated and analyzed for remission and survival. Results: There were 21 males and 6 girls with a median age of 11 years, 29.6% were less than 10 years, 70.3% had advanced stage disease (IIB-IV), bulky mediastinal mass in 19 cases spleen involvement in 6 cases, bone marrow aspirate was free in all cases, bone marrow biopsy was not done. patients with stage I and IIA received 2 courses of EOPA (etopsid, vincristine, prednisone and doxorubicin), patients with stage IIb and IIIa received 2 courses of EOPA and 2 courses of ECOP (etopsid, cyclophophamide, vincristine and prednisone), while patients with stage IIIb and IV received 2courses of EOPA and 4 courses of ECOP, All patients received involved field radiotherapy according to stage. Complete remission was achieved in 96.2%. Progressive disease in 1 (3.7%) which required change line of therapy. Out of the 27 patients 3 (11.1%) have relapsed (17, 22 and 25 months) post completion of chemotherapy and were treated with another line of chemotherapy. The 2 years DFS was 90.9% with 95% of CI (73%-100%). Treatment was given outpatient, with no supportive therapy or toxic deaths and no secondary malignancy from etopsid Conclusions: This regimen provides high rate of durable remission in rural areas of Egypt with limited resources (drugs availability and supportive measures). No significant financial relationships to disclose.
Identification of candidate tumor related genes using comprehensive gene expression analysis of neuroblastic tumors
Authors: Mora J. , Lavarino C. , Domenech G. , Rios J. , Gerald W. , De Torres C. , Cheung N. 
Published: March 2020

9051 Background: Neuroblastic tumors (NBTs) represent a heterogeneous and relatively well defined spectrum of neoplastic diseases. We performed gene expression analysis to molecularly characterize the distinct clinicobiological subtypes of NBTs. Methods: Gene expression analysis of 106 NBTs (10 ganglioneuromas, 10 stage 4s, 29 loco-regional (stages 1, 2, 3), and 57 stage 4) and 12 neuroblastoma cell lines was performed using Affymetrix Genechip Human Genome U95 Set Arrays. Differential expression between predefined groups of biological and clinical relevance was determined by differences >3 standard deviations between the means for groups, step-down permutation and false discovery rate methods. Results: Gene expression analysis of clinically defined groups including stage 4 infants versus children, metastatic versus non metastatic, and stroma poor loco-regional versus stage 4, revealed that many differentially expressed genes mapped to chromosomal regions with well described recurrent abnormalities in NBTs (chromosomes 1, 11, 17, 19 and X). Pairwise comparison analysis of biologically defined groups, including triploid versus diploid/tetraploid NBTs, identified significantly discriminating genes that map to the same chromosomal regions. Gene expression analysis of MYCN-amplified versus MYCN non amplified NBTs, confirmed a functional overrepresentation for genes involved in protein biosynthesis. Conclusions: Gene expression profile analysis of clinically and biologically relevant subgroups of NBTs revealed differential expression of genes at specific chromosomal regions known to have strong association between genetic alterations and NBT clinical features. The identification of altered expression helps to define critical chromosomal regions and identify tumor related candidate genes within each region. No significant financial relationships to disclose.
Gliomatosis Cerebri: A pediatric case series and review of the literature
Authors: Armstrong G. T. , Phillips P. C. , Rorke-Adams L. B. , Judkins A. , Localio A. R. , Fisher M. J. 
Published: March 2020

9056 Background: Gliomatosis Cerebri (GC) is a rare and universally fatal glial neoplasm of the central nervous system. Although over 160 cases have been reported in the medical literature, the largest pediatric case series published to date includes only three patients. We describe the largest cohort to date of children with GC and explore relationships between potential prognostic factors, treatment, and survival. Methods: Imaging, pathologic, and outcome information were reviewed for this case series of thirteen patients diagnosed with GC and treated at the Children’s Hospital of Philadelphia (CHOP) between 1982 and 2005. All patients had GC confirmed by biopsy. Twelve patients were treated with cranial irradiation; eight of these received adjuvant chemotherapy as well. A single patient under one year of age was treated with chemotherapy alone. A review of the literature identified 51 reported cases of GC in the pediatric population. Results: The progression free survival (PFS) in the CHOP cohort was 13% (range: 1.5–22.5 months) and the overall survival rate (OS) was 64% (range: 6.5–27 months) at 2 years. Time to progression was significantly prolonged for those with no evidence of tumor enhancement on initial imaging (p = .03). OS was significantly shorter for patients who presented in the first decade of life (p = .04). When survival data from patients reported in the literature are combined with the CHOP cohort, treatment significantly prolonged OS (p = .003). Conclusions: Outcome in pediatric patients with GC is extremely poor, however treatment prolongs OS. Age less that 10 years and enhancement on MRI at diagnosis may be risk factors for shorter survival. No significant financial relationships to disclose.
Results of chemotherapy (CT) based protocol for treatment of retinoblastoma (RB)
Authors: Goyal L. , Banavali S. , Bhagwat R. , Arora B. , Muckaden M. , Laskar S. , Padhye B. , Nicholson A. , Kurkure P. , Parikh P. 
Published: March 2020

9068 Background: One the main reasons for delayed presentation of children with RB in India is non acceptance of enucleation. CT is being increasingly utilized as primary treatment of RB to reduce the tumor volume and thus avoid enucleation and/or external beam radiation (EBRT) in early stage disease and reduce the risk of relapse in advanced stage disease. Methods: This retrospective (from 1996 to 2001) study involved 62 Patients (pts) (30 were bilateral) who received CT consisting of monthly cycles of carboplatin, etoposide, vincristine and cyclophosphomide. Pts with stage I disease, were started on CT alone, whereas most of the other pts were also started on concurrent EBRT (50Gy). Where indicated, pts also received local therapy, usually cryotherapy & EBRT. Eyes which did not show response or had stable disease, were advised enucleation. Results: Majority of pts had Reese-Ellsworth groups IV-V (74.1%). 17 pts had Stg I, 22 Stg II, 17 Stg III & 6 Stg IV disease (St Jude’s). All pts received CT (median 12 cycles). Out of 92 eyes only 79 were evaluable (13 were already enucleated).The response rate was 73.2% (51.8% CR or near CR); 12.9% had progressive disease. 47 Pts (74%) received RT. Only 23 pts received focal treatment (Cryotherapy 15, laser 3, combination 5). Vision was present in 38 eyes (48.1%) at presentation. 26 eyes (68.4%) were finally saved with useful vision. 20 pts had recurrence. 18 have died (17 died of disease, 1 treatment related sepsis). In those following up in the clinic, survival is 77% for stage I; 78.5% for stage II; 41.6% for stage III. All stage IV pts have died except 1 with nodal disease. Conclusions: CT has a role in the management of RB, however unless it is coupled with good focal therapy the results are poor as shown here. Also longer follow-ups are required because of late recurrences. This data highlights that in developing countries the social reasons complicate patient treatment & compliance. Further efforts are needed to spread awareness of this disease so that patients are diagnosed and treated in earlier stages so as to improve the outcomes. No significant financial relationships to disclose.
Sunitinib (SU) response in imatinib-resistant (IM-R) GIST correlates with KIT and PDGFRA mutation status
Authors: Heinrich M. C. , Maki R. G. , Corless C. L. , Antonescu C. R. , Fletcher J. A. , Fletcher C. D. , Huang X. , Baum C. M. , Demetri G. D. 
Published: March 2020

9502 Background: IM resistance in advanced GIST represents a major clinical problem. SU (SU11248) is an oral multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activities related to KIT, PDGFRs, VEGFRs, RET and FLT3 inhibition. SU has demonstrated efficacy in clinical trials of pts with IM-R GIST. Methods: This study examined the relationship between tumor kinase genotypes and SU clinical activity in 97 pts with metastatic IM-R GIST treated as part of a phase I/II trial. Tumors were imaged by CT or MRI for RECIST-defined response assessment. Tumor specimens were obtained prior to (n=76) and following (n=64) IM therapy and analyzed for primary or secondary KIT and PDGFRA mutations, respectively. Results: Clinical benefit (CB; defined as PR or SD >6 months) with SU was observed for all major molecular GIST subtypes: KIT exon 11 (42 pts, CB 36%), KIT exon 9 (19 pts, CB 42%), PDGFRA (4 pts, CB 25%), no KIT or PDGFRA mutation (wild-type [WT]; 9 pts, CB 56%). Notably, the PR rate for GISTS with primary KIT exon 9 mutations was 37%, vs 5% for KIT exon 11 mutations (P=0.003). PFS and OS were significantly longer for pts with either a primary KIT exon 9 mutation or WT KIT/PDGFRA compared with pts with a KIT exon 11 mutation (exon 9 vs 11: PFS P=0.0007, OS P=0.005; WT vs exon 11: PFS P=0.03, OS P=0.01). Secondary KIT mutations (in exons 13, 14, 17 or 18) were found in 62% of GISTs with a primary KIT exon 11 mutation, but only in 16% with a primary KIT exon 9 mutation (P=0.002). No secondary mutations were found in GISTs lacking a primary KIT/PDGFRA mutation. Biochemical profiling of secondary kinase mutations revealed in-vitro sensitivity of KIT exon 13 and 14 mutations to SU, while secondary KIT exon 17 and 18 mutations were resistant to SU in vitro. These in-vitro results were consistent with clinical results: CB was observed in 65% of pts with secondary KIT mutations in exon 13 or 14 and in only 9% of pts with secondary KIT exon 17 or 18 mutations (P=0.006). Conclusions: Our findings suggest that, similar to prior results observed using imatinib, CB of SU following failure of IM treatment is significantly influenced by both primary and secondary mutations in the predominant pathogenic kinase, the uncontrolled activity of which is a critical etiologic factor for GIST. [Table: see text]
Sirolimus reduced tumor-related morbidity and resulted in biochemical and radiographic response in patients with progressive sarcoma
Authors: Schuetze S. M. , Baker L. H. , Maki R. G. 
Published: March 2020

9503 Background: Chemotherapy options for palliative treatment of advanced sarcomas are limited and studies are underway to identify new classes of active agents. Second generation inhibitors of the mammalian target of rapamycin (mTOR) are being tested in phase II trials. Objective responses of sarcomas to the mTOR inhibitor AP23573 have been reported. Sirolimus (rapamycin) is a macrocyclic triene antibiotic that inhibits activation of S6 kinase, the cdk2/cyclinE complex and phosphorylation of retinoblastoma protein and causes cell cycle arrest in G1-S phase. Methods: We report the cases of four (out of 20) patients (pts) with progressive, metastatic sarcoma failing 2–6 chemotherapies treated with sirolimus and followed for clinical benefit. Sirolimus was self-administered daily with (n=2) or without (n=2) daily oral cyclophosphamide 200 mg every other week. Patients were followed in clinic for disease and toxicity assessments every 2 weeks. Molecular analysis of mTOR targets will be performed. Results: Patients with MFH, leiomyosarcoma, angiosarcoma and osteosarcoma were treated using 4–8 mg sirolimus daily for a median of 16 weeks (range 8–28 wks). Three pts were symptomatic from disease and had reduced performance status prior to treatment. All 3 pts had subjective improvement in tumor-related symptoms and 2 had improvement in performance status. LDH and bilirubin fell from 1,712 u/L and 5.6 mg/dl to 388 u/L and 1.1 mg/dl, respectively, in the pt with angiosarcoma during 3 months of sirolimus and cyclophosphamide. Alkaline phosphatase fell from 791 u/L to 120 u/L in the pt with osteosarcoma over 6 weeks of simolimus and cyclophosphamide. Three pts had minor radiographic improvement in tumor and remain on treatment. One pt has died of disease progression. Treatment was well tolerated. Conclusions: Sirolimus treatment was associated with improvement in tumor-related symptoms, performance status and biochemical markers of disease activity and inhibited tumor growth in pts with advanced sarcoma failing multiple prior therapies. Phase I studies of sirolimus in advanced cancer are underway at the University of Chicago. Formal study of sirolimus in advanced sarcoma is contemplated. No significant financial relationships to disclose.