bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serial assessment of regulatory T cells (Tregs) in pediatric AML: A prospective study.
Authors: Bansal Anuj Kumar , Sharawat Surender Kumar , Gupta Ritu , Sreenivas Vishnu kumar , Bakhshi Sameer 
Published: March 2020

9549 Background: Data of Tregs in pediatric AML is lacking. The study objectives were determining Tregs in pediatric AML at diagnosis and follow up; and correlating with outcome. Methods: From Nov 2010-May 2011, 30 consecutive AML patients ≤ 18 years were prospectively enrolled with 6 healthy controls. All patients received daunorubicin / cytarabine induction and 3 courses of cytarabine. Tregs (CD4+CD25+FoxP3+) were assessed at diagnosis, post-induction, post-consolidation, 3 and 6 months follow up and relapse. Results: 30 cases with median age 9.5 years; male/female ratio 14:16 had significantly higher baseline Tregs than healthy controls (12.36±4.65% vs 3.16±1.49%; p=0.0001). Patients with high Tregs frequency were females (p=0.044), WBC>50,000/mm3 (p=0.023), hypoalbuminemia (p=0.002), absence of lymphadenopathy (p=0.04) and linear correlation with peripheral blood blast% (r=0.55, p=0.0014). CR rate was 83.3% (25/30); EFS 38% and OS 73% at 14 months follow up. When Tregs were categorized as high and low based on median value, CR rate (86.6% vs 80%, p=NS), EFS [17% vs 60%, HR 1.46 (0.51-4.14) p=0.46] and OS (66% vs 80%, HR 0.58 (0.13-2.44) p=0.45) were not different. Amongst those who achieved CR, there were 7/13 relapses in those with high Tregs versus 3/12 in those with low Tregs (p=0.226).Tregs reduced post-induction (12.1±4.6 vs 6.32±2.8, p<0.000) from baseline. Using generalized estimating equation regression model, average Tregs reduction from post-induction till 3 month follow up was 0.785 units/visit (p<0.005) in those with continuous CR(n=15) and 1.25 units/visit (p<0.001) in those whom relapsed (n=10). Difference between these two groups was not significant. Tregs significantly increased at relapse as compared to post consolidation value (15.3±5.2 vs 4.5±1.9, p=0.003). Conclusions: This first study in pediatric AML demonstrates that Tregs is increased at diagnosis and is significantly associated with females, high WBC count, hypooalbuminemia, absence of lymphadenopathy and high peripheral blood blast%. Tregs significantly reduced post-induction on follow up; however, it increased at relapse. Baseline Tregs did not predict CR, EFS, or OS. However, there were more relapses in those with high baseline Tregs.
Minimal residual disease by flow cytometry at the end of chemotherapy for remission induction in pediatric patients with acute lymphoblastic leukemia: Experience from a center in a low-income country.
Authors: Perez Eloy , Cruz-Borja Primo , Chavez-Gallegos Silvia 
Published: March 2020

9554 Background: The presence of minimal residual disease (MDR) following therapy for acute lymphoblastic leukemia (ALL) has been shown to be an important prognostic marker in many studies. MRD is typically detected either by polymerase chain reaction amplification or by flow cytometry. Flow-based MRD assessment has the potential for rapidly identifying patients at increased risk of relapsed, allowing for prompt changes in therapy, including earlier intensification. There are not many information about the response by MRD in countries with limited resources. Methods: The patients included were 90 ALL patients treated at the Hospital Infantil de Morelia from June 1, 2009 to January 5, 2012. MRD positivity (+) was defined as >0.01% of the gated population. Results: MRD was obtained in 90 patients, 38 males and 36 females. The median age was 7 years (10 months to 15 years). The levels of MRD were: <0.01, 74 (82.2%), 0.01-1%, 9 (10%), ≥1%, 7 (7.7%). There was not a statistically significant association between the most important ALL prognostic factors (Gender, Age at diagnosis, White blood cell count at diagnosis, Central Nervous System disease, Prednisone response, DNA Index, Immunophenotype). Conclusions: The good response found is similar to that reported by international groups, a situation which suggests that the response to chemotherapy is appropriate. However, cure rates are still not equal making it necessary to review institutional treatment protocols and social characteristics of the population to achieve cure rates reported by international groups.
Effect of insulin-like growth factor 2 gene expression on pleuropulmonary blastoma and embryonal rhabdomyosarcoma.
Authors: Venkatramani Rajkumar , Triche Timothy J. , Larry Wang , Wai Daniel , Shimada Hiroyuki , Schaub Betty , Mascarenhas Leo 
Published: March 2020

9564 Background: The sarcomatous element in pleuropulmonary blastoma (PPB) often cannot be differentiated from embryonal rhabdomyosarcoma (ERMS) by histology, particularly when characteristic elements like cartilage and respiratory mucosa are inapparent. The initial diagnosis is often ERMS. A diagnosis of PPB is based on a combination of clinical (age, location) and pathologic features. We hypothesized that the sarcomatous portions of PPB are a form of ERMS indistinguishable from typical ERMS. We reasoned that a detailed comparison of RNA expression could clarify this hypothesis. Methods: Samples from 7 PPB patients were obtained from the rhabdomyosarcomatous portion of the tumor by macro-dissection after pathologic review of all material. Representative ERMS tumor tissue was selected from 21 ERMS cases. FFPE tissue scrolls from each case were analyzed using Affymetrix Human Exon arrays after RNA extraction with Agincourt Formapure extraction kit and amplification using the NuGEN Ovation FFPE WTA kit and labeling with the Encore Biotin Module. Data analysis utilized Partek and Genetrix software. Results: All PPB cases and 7 of 21 ERMS cases were < 4 years old. 20 transcripts (10 annotated, 10 non-coding RNAs) were significantly differentially expressed in ERMS when compared to PPB patients. Insulin-like growth factor 2 (IGF2) was uniformly overexpressed in ERMS (19/21 > 200) but was expressed at low levels in PPB (p<0.001). 2 ERMS cases which had low level IGF2 expression were < 4 years of age. Expression in the other 5 ERMS aged <4 years was similar to ERMS overall (range, 500-2,000). No other differences between the two approached this degree of significance, despite a common rhabdomyogenic phenotype in the sarcomatous areas of PPB. Conclusions: We conclude that PPB is a distinct entity from most ERMS, and is not driven by IGF2 signaling. Rare cases of ERMS in the very young are more similar to PPB than common ERMS. This observation is highly significant, as IGF2 is known to drive growth in ERMS, generally related to demethylation secondary to LOH of 11p.
Do children, adolescents, and young adults with soft tissue sarcoma benefit from early detection of recurrences? Results of a population-based study.
Authors: Dantonello Tobias M. , Winkler Peter , Kube Stefanie , von Kalle Thekla , Kosztyla Daniel , Handgretinger Rupert , Veit-Friedrich Iris , Kaatsch Peter , Fengler Ruediger , Bielack Stefan S. , Leuschner Ivo , Niggli Felix , Ljungman Gustaf , Klingebiel Thomas , Koscielniak Ewa ,   Cooperative Weichteilsarkom Studiengruppe (CWS)
Published: March 2020

9573 Background: Most patients with pediatric soft tissue sarcoma (PSTS) achieve a 1st remission with primary therapy, but recurrences are frequent and drive mortality. Relapse detection (RD) is the foundation of post-treatment surveillance. The rationale for frequent follow-up investigations is RD in an early stage with better salvage options. There is however little evidence regarding the value of early asymptomatic RD and it was not investigated by any larger or population-based study in PSTS. We determined whether early radiographic RD in asymptomatic patients improves post-relapse outcome. Methods: Patients aged < 18 years at first reference-reviewed PSTS-diagnosis registered with CWS were enrolled if a 1st relapse occurred between 1/2003 and 7/2010. The methods of RD and their impact on outcome were evaluated. The data were correlated with the German Childhood Cancer Registry (GCCR), which receives all information about cancer patients < 18 years. Results: 235 patients from Germany (n = 212) and Sweden/Switzerland (n = 23) were eligible. In 2010 all German PSTS-patients were registered both with the GCCR and CWS. The most common PSTS-histiotypes were embryonal (n = 76) and alveolar (n = 74) rhabdomyosarcoma. 156 patients had primary nonmetastatic PSTS. The median time to relapse diagnosis (TTRD) was 1.4 years. 118 recurrences were locoregional, 38 combined and 79 metastatic. In 229 patients, the methods leading to RD could be evaluated. 139 recurrences were detected because of clinical signs and symptoms, primarily observed by patients and/or parents in 72%. 90 RDs were radiographic in asymptomatic patients. TTRD did not differ between symptomatic and asymptomatic patients. As of 12/2011, 77/235 patients are currently alive with a median follow-up of 5.4 years. Overall survival from primary surgery at 3-, 5-, and 10-years for all 235 patients was 49%, 34% and 22%. It was 43%, 29% and 23% for the symptomatic and 59%, 40% and 21% for the asymptomatic group (p = 0.05). Conclusions: In this series, early radiographic RD in asymptomatic PSTS-patients had no significant impact on TTRD or post-relapse survival, although asymptomatic patients tended to survive longer.
A multidisciplinary treatment comprising standard chemotherapy with vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide for Ewing sarcoma family of tumor (ESFT) in Japan: Results of the first Japan Ewing Sarcoma Study (JESS) 04.
Authors: Makimoto Atsushi , Chin Motoaki , Sumi Minako , Yokoyama Ryohei , Ishida Tsuyoshi , Okita Hajime , Matsuzaki Akinobu , Kikuta Atsushi , Watanabe Hiroyoshi , Ozaki Toshifumi , Isu Kazuo , Yano Michihiro , Hatori Masahito , Tsurusawa Masahito , Ohta Hideaki , Kawano Yoshifumi , Ishii Takeshi , Kawamoto Hiroshi , Morita Satoshi , Mugishima Hideo ,   Japan Ewing Sarcoma Study Group (JESS)
Published: March 2020

9574 Background: Survival rate of ESFT in Japan was reportedly less than 50% in 1990s. The JESS started in order to improve this condition by conducting clinical trials for ESFT in Japan. Methods: This is a phase II, non-randomized trial to test safety and efficacy of multidisciplinary treatment for non-metastatic ESFT. Age under 30 is eligible. Chemotherapy regimens are alternating vincristine 1.5 mg/m2 on day 1, doxorubicin 37.5 mg/m2 on days 1 and 2, cyclophosphamide 1200 mg/m2 on day 1 (VDC) and ifosfamide 1800 mg/m2 on days 1 through 5 and etoposide 100 mg/m2 on days 1 through 5 (IE) repeating every 21 days for 52 weeks. Local treatment includes surgical resection and/or radiation therapy, of which dosage varies from 0 to 55.8 Gy based on margin of the resection and pathological response. Primary endpoint is 3 year progression free survival (PFS). Statistical design was made to test whether the lower limit of 90% confidence interval (CI) of PFS will exceed the threshold of 60%. Planned sample size is 53 patients including 10% ineligible patients. Results: Fifty-three patients were registered from December 2004 to May 2008. Among the 53 patients, 7 patients were judged ineligible after the registration (metastatic disease 1, changed diagnoses 6). Forty six patients were considered as per protocol set and used for efficacy analyses. Three year PFS is 71.7% (90% CI: 0.59 – 0.81). Estimated 5 year PFS and OS are both 69.6%. Radiographic response rate (RR) in evaluable 38 patients is 71.1% and pathological RR in 25 is 52.0%. In safety data, hematological toxicities are significant such as grade 4 neutropenia observed in 98%. Although there is no previously unknown adverse event reported, there are three patients who experienced secondary malignancies (ALL 1, MDS 1, osteosarcoma 1). Conclusions: A multi-disciplinary treatment comprising standard multi-agent chemotherapy with vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide improved outcome of Ewing sarcoma family of tumor in Japan although statistical confirmation of absolute efficacy was not successful.
A phase II trial of docetaxel and irinotecan (DI) in children and young adults with recurrent or refractory Ewing sarcoma family of tumor (ESFT).
Authors: Yoon Jong Hyung , Park Hyeon Jin , Park Byung-Kiu 
Published: March 2020

9579 Background: Patients with ESFT resistant to second-line therapy, such as topotecan plus cyclophosphamide, have a dismal prognosis and few therapeutic options. Docetaxel (D), a microtubule inhibitor, demonstrated activity in patients with ESFT (Zwerdling T et al. Cancer 2006:106:1821-1828). Irinotecan (I), a toposiomerase I inhibitor, is being evaluated in clinical trials for ESFT. Despite the different mechanisms of action of D and I, and their activities as a single-agent against ESFT, DI combination has not been previously evaluated in ESFT. Thus, we prospectively performed a single-arm, phase II trial of DI in a single center in Korea. Methods: Patients <30 years with ESFT, who failed second-line therapy, were eligible for the study. D was administered IV over 60 minutes at a dose of 100 mg/m2 on Day 1, and I at a dose of 80 mg/m2 over 90 minutes on Days 1 and 8 of a 21-day cycle until disease progression. The primary end-point was objective response assessed by RECIST; the secondary end-point was safety. All toxicities were graded according to the National Cancer Institute’s Common Toxicity Criteria (version 4.0). Results: Of seven eligible patients (4 males; median age, 17 years (range 5-21)), 4 were recurrent/refractory cases, and 3 refractory cases. Median number of previous regimens was 6 (range 3-6). One CR, 1 PR, and 5 PD were obtained by DI combination (median number of cycles, 2 (range 1-15)), with objective response (CR+PR) rate of 2/7 (28.6%). One patient with PR achieved CR with subsequent surgery. CR of these two patients lasted 8.9 months and 10.6 months. Of all seven patients fully evaluable for toxicity, grade 4 neutropenia occurred in 7 (100%); grade 3 and 4 thrombocytopenia in 1 (14%) and 6 (86%), respectively; grade 3 pericardial effusion, paresthesia, motor weakness, oral mucositis, each in one (14%). Two patients required ≥1 dose delay; 2 required ≥1 dose reduction due to adverse events, but no one experienced treatment-related mortality. Conclusions: DI combination demonstrated activity in children and young adults with ESFT who were heavily pre-treated, and was feasible.
Integration of genomic and proteomic data to identify MYCN-regulated genes, proteins, and interaction networks in neuroblastoma cells.
Authors: Kristjansdottir Kolbrun , Bontempo Kelly M. , Regan Kelly E. , Khan Saira , Volchenboum Samuel Louis 
Published: March 2020

9584 Background: Neuroblastoma is the most common extracranial solid tumor found in children. The most common marker prognostic of poor outcome is amplification of the MYCN oncogene, yet the biological programs by which MYCN affects its aggressive phenotype are largely unknown. In order to identify biological pathways affected by MYCN amplification, we performed global analysis of genes and proteins in the Tet 21/N neuroblastoma cell line. Methods: MYCN expression in Tet21/N cells is regulated by tetracycline. Gene arrays were performed on MYCN-high and MYCN-low Tet21/N cells and SH-EP parental cells using Affymetrix GeneChip Human Exon 1.0 ST. For proteomic analysis, the cells were labeled with stable isotopes for relative quantitation, enriched for phosphoproteins to enhance detection of signaling proteins, and analyzed by GeLC-MS/MS analysis. Integrative pathway analysis was performed on the genomic and proteomic datasets using DAVE and GeneGo. Results: Integrating genomic and proteomic data in MYCN-high and MYCN-low expressing cells identified 88 proteins and 300 genes that change in abundance. We compare these results with previous studies and find both novel and previously identified genes and proteins. Integrating proteomic and genomic data identified over 50 gene products that are present in both analyses and are altered in abundance in response to modulating MYCN expression. The majority of these have discordant abundance changes, with protein levels more frequently altered with no change in gene expression. We have validated changes in protein levels using Western blots including NPM1 and MATR3. We present interaction networks and pathways that correlate with MYCN expression. Conclusions: We showed a significant discordance between gene and protein expression, underscoring the need for integrative genomic and proteomic analysis to describe complex systems. Our analysis identified previously reported and novel genes and proteins and networks regulated by MYCN expression that may provide new insights into the biology of MYCN-amplified tumors.
A national survey of general internists' preferences and knowledge gaps regarding the care of childhood cancer survivors.
Authors: Henderson Tara O. , Nathan Paul C. , Rasinski Kenneth , Suh Eugene , Kigin Mackenzie , Wroblewski Kristen , Ford Jennifer , Tonorezos Emily S. , Oeffinger Kevin C. , Daugherty Christopher 
Published: March 2020

9586 Background: Although most childhood cancer survivors (CCS) report obtaining health care in the community, primary care physicians’ views and knowledge regarding the long-term follow-up (LTFU) care of CCS are largely unknown. Methods: Surveys were mailed to a random sample of 1,907 general internists under age 65 years from the American Medical Association Physician Masterfile in November 2011. A second mailing to non-responders is ongoing. Results: 892 (47%) physicians have responded. Respondents have practiced a median of 10 years (range: 3-20), and see a median of 70 patients/week (range: 40-100). 46% are in solo/group practice, 17% in multi-specialty practice, and 14% in academic practice. In the last five years, 53% have seen at least one CCS, 71% of whom have never received a treatment summary. 85% prefer to care for CCS in consultation with a cancer center based physician. A vignette of a 29-year-old female treated for Hodgkin lymphoma with mantle radiation at age 16 was provided and participants were asked a series of questions regarding monitoring for late effects. The percentage of responses that were concordant with available LTFU Surveillance Guidelines were: breast cancer, 29%; cardiac, 15%; thyroid, 77%; and all three recommendations, only 5%. By logistic regression, greater likelihood of concordance with at least one surveillance recommendation was associated with being female (OR=2.0 95% CI 1.3-3.1), seeing more patients/week (OR=1.4 per SD increase, 95% CI 1.1-1.7) and more years in practice (OR=1.3 per SD increase, 95% CI 1.0-1.6). The two modalities felt to be most useful for independent care of CCS by internists were access to LTFU guidelines and receiving a patient-specific care plan from the cancer center. Conclusions: Although the majority of internists are willing to follow CCS, they appear unfamiliar with the available LTFU guidelines and prefer to care for patients in collaboration with a cancer center based physician.
Patient preference between pazopanib (Paz) and sunitinib (Sun): Results of a randomized double-blind, placebo-controlled, cross-over study in patients with metastatic renal cell carcinoma (mRCC)—PISCES study, NCT 01064310.
Authors: Escudier Bernard J. , Porta Camillo , Bono Petri , De Giorgi Ugo , Parikh Omi , Hawkins Robert E. , Sevin Emmanuel , Negrier Sylvie , Khan Sadya , McCann Lauren , Mehmud Faisal , Cella David 
Published: March 2020

CRA4502 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Saturday, June 2, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
Evaluation of variables that may impact the use of Oncotype DX testing.
Authors: Szabo Stephen , Gilmore James W. , Haislip Sally , Hassell Robert , Cooper Joseph , Richardson Steve , Fitzgerald Meghan , Feinberg Bruce A. 
Published: March 2020

e11002 Background: Cardinal Health Specialty Solutions (CHSS) partners with payers to manage clinical care pathways in oncology and rheumatology. Observations from one such pathway with CareFirst BlueCross Blue Shield revealed that in patients with estrogen receptor-positive early-stage breast cancer (ESBC), there was an underuse of Oncotype DX testing. To better understand physician behavior as it relates to Oncotype DX testing, CHSS examined patterns of Oncotype DX use in a large private practice oncology group with a robust electronic medical record (EMR), Georgia Cancer Specialists (GCS). We aimed to determine the variables that most impacted the use of Oncotype DX testing. Methods: Using the GCS EMR from 2009 to 2011, we retrospectively identified patients diagnosed with ESBC who were eligible for Oncotype DX testing (stage I-II, node-negative, estrogen receptor-positive, HER2-negative). The use of Oncotype DX testing was analyzed by patient age, tumor size, tumor grade, and physician prescribing patterns. Results: Of the 1908 patients identified with ESBC, 788 were eligible for Oncotype DX testing and 288 (37%) underwent testing. In an analysis by age, Oncotype DX was utilized in 34% of patients ≤ 45 years, 49% in patients 46-55 years, 37% in patients 56-65 years, 34% in patients 66-75 years, and 13% in patients > 75 years old. Oncotype DX use was 37% and 36% in patients with tumor sizes <2 cm and 2-5 cm, respectively; and, 45%, 43%, and 67% in patients with grade 1, 2, or 3 tumors, respectively. Of the 41 physicians who were evaluated, 10 (24%) used Oncotype DX <15% of the time, 13 (32%) used Oncotype DX 15-40%, 10 (24%) used ODX 41-60%, and 8 (20%) used Oncotype DX > 60% of the time. There were no significant differences in patterns of chemotherapy use. Conclusions: Based on this analysis, eligible patients with ESBC between 46-55 years of age, with small and intermediate sized tumors (<2-5 cm), and with grade 3 tumors were most likely to undergo Oncotype DX testing. Although some trends in use were observed with specific tumor characteristics, physician behavior (choice) was the most significant variable in Oncotype DX testing.
Loss of nuclear p27KIP1 (p27) expression as a predictor of lymph node spread in T1 breast cancer.
Authors: Ling Huichung Tina , Smith Julia Anne , Kwa Maryann , Dilawari Asma Ali , Cangiarella Joan , Goldberg Judith D. , Hochman Tsivia , Andreopoulou Eleni , Guth Amber Azniv , Roses Daniel F. , Formenti Silvia , Muggia Franco 
Published: March 2020

e11010 Background: We originally reported that p27 loss in T1a/b breast carcinomas was associated with lack of estrogen and progesterone (ER/PR) hormone receptors, but not in T1c node negative tumors (Mirchandani et al, Anticancer Research 2011). The current study explored the association of p27 expression with lymph node (N) status. Methods: 217 consecutive patients with T1 tumors were identified from 2001-2003. All patients underwent sentinel node biopsy (and complete lymphadenectomy when positive on frozen section): 111 were N0 and 106 were N+. Immunohistochemistry was performed for ER/PR, Her2, and nuclear p27 (low vs normal) and tumors were graded (well, moderate, and poorly differentiated). Analysis was conducted to define associations between standard variables and p27 expression among node positive and node negative tumor carriers (Table). Results: Low p27 expression was found in 21% of N0 and 36% of N+ T1 breast cancer patients (Chi-square=6.14, p-value=0.01). However from a series of multivariable analyses, only tumor size was significantly associated with node positivity. Conclusions: Poorly differentiated tumors, T1c tumors, and low p27 expression were associated with lymph node positivity, but only tumor size was significant in multivariable analysis. Contrary to our prior report, the relationship between low p27 and ER/PR- is strongest in the T1c subset (data not shown). Future studies will expand study cohorts to explore whether low p27 expression is a biomarker of poor outcome at 10 years in patients with T1 tumors treated with antiestrogens. [Table: see text]