bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic medical conditions in adult survivors of retinoblastoma.
Authors: Friedman Danielle Novetsky , Chou Joanne F. , Oeffinger Kevin C. , Ford Jennifer , Sklar Charles A. , Li Yuelin , McCabe Mary S. , Robison Leslie L. , Kleinerman Ruth , Marr Brian , Abramson David H. , Dunkel Ira J. 
Published: March 2020

10019 Background: Increased risk of second malignant neoplasms (SMN) in retinoblastoma survivors (RBS) is well documented, but little is known about their long-term burden of chronic non-visual morbidity. Methods: RBS treated in NYC were asked to complete a comprehensive questionnaire, adapted from the Childhood Cancer Survivor Study (CCSS) surveys; frequencies of chronic conditions, excluding SMN, in 470 RBS and 2,377 CCSS siblings were calculated. A severity score, based on the NCI CTCAE v4 (ranging from grade 1 [mild] to grade 4 [disabling/life-threatening]) was assigned to each condition. Logistic regression was used to estimateodds ratios of chronic condition risk in RBS vs CCSS siblings, adjusted for age, sex, and race/ethnicity, reported as relative risks (RR) and 95% confidence intervals (CIs). Results: RBS and CCSS siblings were mean ages of 43 years (SD 11) and 38 years (SD 9), respectively, at the time of questionnaire completion. 53.6% of RBS had bilateral disease. After excluding SMN, 70.2% of RBS had at least one non-visual chronic condition while 14% had a grade 3-4 condition. The adjusted RR of a non-visual chronic condition in a survivor compared to siblings was 1.5 (95% CI, 1.2-1.8); for a grade 3-4 condition, the risk was 1.5 (95% CI, 1.1-2.1). The most common grade 3-4 non-visual conditions in RBS were hearing loss (3.6%; bilateral 5.6%, unilateral 1.3%, p=0.023) and thyroid nodules requiring partial or full thyroidectomy (3.4%; bilateral 5.6%, unilateral 0.9%, p=0.008). Rates of grade 3-4 thyroid nodules and hearing loss did not differ significantly when stratified by treatment received. Rates of all conditions in RBS are reported in the Table. Conclusions: RBS have a modestly increased risk of non-visual chronic conditions when compared to individuals of comparable age, sex and race/ethnicity. [Table: see text]
Role of IGF-1R inhibition on an Src-family kinase bypass resistance pathway: A rational basis for cotargeting IGF-1R and Src kinase in pediatric sarcomas?
Authors: Wan Xiaolin , Yeung Choh L , Heske Christine , Mendoza Arnulfo , Helman Lee J. 
Published: March 2020

10025 Background: Dysregulation of IGF signaling plays a fundamental role in oncogenesis in pediatric sarcomas. We recently completed a Phase II study targeting the IGFI receptor signaling pathway in refractory Ewing’s and other sarcomas. We demonstrated an objective response rate of 16 percent, but most responses were transient lasting less than 18 weeks. The majority of patients, even those with initial responses, do not have long term benefit from IGFIR blockade, indicating the presence of an innately resistant tumor mass or the recruitment of compensatory pathways allowing for continued growth. To improve on these responses, we have been probing these tumors to identify other critical pathways that might allow combined targeting approaches. Methods: Multiple RMS and ES cell lines were treated with IGF1R kinase inhibitors and assayed for up-regulation of various signaling pathways. Combination treatment with IGF1R inhibitors and inhibitors of additional signaling pathways were then tested in vitro and in vivo using standard techniques. For in vivo xenograft studies, treatments began 11 days following orthotopic injection of tumor cells. Results: We have identified repid up-regulation of Src family kinase (SFK) signaling within 4 hours of IGF1R blockade in both RMS and ES cell lines. Of note, combined treatment with IGF1R Ab plus IGF1R kinase inhibitors most potently upregulated SFK signaling. Based on these findings, we tested combined IGF1R blockade with SFK inhibition using the commercially available drug, dasatinib. We show that dual blockade of IGF1R and SFK pathways were synergistic in vitro. Furthermore, in xenograft models of RMS, the combination IGF1R and SFK inhibition led to long-term disease free status for at least 90 days in some mice, never seen in our hands previously using these models. Conclusions: This work identified that IGF-1R inhibition induced activation of Src kinase that may act as a by-pass pathway. Synergistic activity of IGF-1R and SFK kinase inhibitors was observed in vitro and in vivo. Dual IGFI and SFK kinase inhibition may lead to improved therapeutic outcomes.
Socioeconomic status and incidence of pediatric embryonal tumors in the United States.
Authors: Silva Raquel Ataide Peres , Pace-Emerson Tamara P. , Rodriguez-Galindo Carlos , Frazier A. Lindsay , Ribeiro Karina Braga 
Published: March 2020

10036 Background: Of the 13,000 children diagnosed with cancer each year in the United States (US), the embryonal solid tumors, neuroblastoma (NB), retinoblastoma (RB), Wilms tumors (WT), hepatoblastoma (HB), rhabdomyosarcomas (RMS) and germ cell tumors (GCT), account for over 30% of the cases. Social disparities in cancer are well studied for adults, but few studies have focused on children, mostly for leukemia. The aim of this study is to evaluate the differences in incidence of rare cancers according to socioeconomic status (SES). Methods: Cases aged 0-19 were identified from the Surveillance Epidemiology and End Results (SEER) cancer registries from 1992-2009. Using data from the US 2000 Census, the county of residence of the cases was categorized above or below the national average for SES measures including: % persons with< high school education, % persons below poverty, % persons unemployed and % households with > 1 person/room. Age standardized rates per million (ASR), rate ratios (RR) and 95% confidence intervals (CI) were obtained. The findings were validated using cases from the National Program of Cancer Registries (NPCR) from 1999-2009, analyzed with the same SES variables. Results: Among cases identified in SEER, rates of NB and WT are higher in counties with upper SES measures whereas RB and GCT occurred more frequently in counties with lower SES measures. No association was found between SES and rates of HB and RMS. The results were reproducible with NPCR cases. For instance, ASR of NB is lower (SEER: 5.86; NPCR: 7.48) in counties where >19.6% of the population had not completed high school and higher (SEER: 8.41; NPCR: 8.47) in counties where ≤19.6% had not achieved a high school degree. (SEER: RR=0.69; 95%CI=0.62-0.77; NPCR: RR=0.88; 95%CI=0.84-0.93). Analysis of NB rates according to poverty, unemployment and crowding showed consistent results, with higher rates in counties with higher SES. Conclusions: The findings are suggestive of a relation between SES and cancer susceptibility that may be connected to environment and lifestyle. Understanding the role of contributing causes demands further studies to evaluate why cancer rates vary across cultural and ethnic groups as well as the magnitude of specific SE aspects.
Outcome in congenital hepatoblastoma compared with previously reported data.
Authors: Trobaugh-Lotrario Angela D , Chaiyachati Barbara H , Meyers Rebecka , Haberle Beate , Tomlinson Gail Elizabeth , Katzenstein Howard M. , Malogolowkin Marcio H. , von Schweinitz Dietrich , Krailo Mark D. , Feusner James Henry 
Published: March 2020

10037 Background: Congenital hepatoblastoma, defined as diagnosis in the first month of life (Ammann RA, Plaschkes JLeibundgut K. Congenital hepatoblastoma: A distinct entity? Med Pediatr Oncol 1999:32:466-468.), has been reported to have a poor prognosis; however, a comprehensive evaluation of this entity is lacking. Methods: We performed a retrospective review including three patients from the senior authors’ personal series and 23 cases identified in the databases of several multicenter group studies (INT-0098, P9645, 881, P9346, HB 89, HB94 and HB 99). We then compared this series with the data of all cases of congenital hepatoblastoma previously published in the literature. Results: The overall 2-year survival in our case series was 86% (18/21) with a median followup of 85.5 months (range 44 to 230 months). Presentation and treatment were not substantially different from hepatoblastoma cohorts unselected for age. The infants in our study exhibited a comparable survival rate to the reported disease free survival for a similar cohort of hepatoblastoma patients unselected for age between 1986 and 2002 (82.5%) [Tiao GM, Bobey N, Allen S, et al. The current management of hepatoblastoma: A combination of chemotherapy, conventional resection, and liver transplantation. J Pediatr 2005:146:204-211.]. The overall 2-year survival rate of cases previously reported in the literature was 0% (0/11) for patients reported before 1992, and 47% (8/17) for those reported after 1992. The improved survival of our current series of patients, collected from the past 20 years of German and American multicenter trials and personal series, suggests that the outcome of HB at this young age is much better than has been historically reported. Conclusions: Congenital hepatoblastoma does not appear to confer a worse prognosis. The overall survival in our series does not appear to be worse than in older children; more rigorous analysis should be conducted in future multicenter trials. It is possible that congenital HB should be treated like all other patients with hepatoblastoma provided that the child is stable enough to proceed with surgery and chemotherapy and complete staging is performed.
Time trends in the use of adjuvant chemotherapy (CTX) and outcomes in women with T1N0 breast cancer (BC) in the National Comprehensive Cancer Network (NCCN).
Authors: Luis Ines Maria Vaz Duarte , Ottesen Rebecca A , Hughes Melissa E , Mamet Rizvan , Burstein Harold J. , Edge Stephen B. , Gonzalez-Angulo Ana M. , Javid Sara H. , Moy Beverly , Rugo Hope S. , Theriault Richard L. , Weeks Jane C. , Lin Nancy U. 
Published: March 2020

1006 Background: The role of adjuvant CTX in women with small BC is controversial. Here we analyze time trends of CTX use and outcomes in women with T1N0 BC treated at NCCN cancer centers. Methods: 8917 women were identified who received surgery or systemic therapy at an NCCN center with T1a, T1b or T1c N0 M0 BC between 2000-09. Tumors were grouped by biologic subgroups by hormone receptor (HR) and HER2 status and T subgroups (T1a, T1b, T1c). Primary endpoints were receipt of adjuvant CTX (± trastuzumab) and BC specific survival (BCSS). Chi-square, Cochran Armitage trend, Kaplan Meier estimates, log-rank test and Cox hazard proportional regression were used for analysis. In this report we focus on T1a/b results (N=4113). Results: Median follow up time was 5.5 years (range, 0.7-12.7). CTX use differed according to biologic and T subgroups, with significant changes over time (Table). In 2009, more than 50% of patients (pts) with HER2+ and HR-2- T1a/b breast cancers received CTX (± trastuzumab). The table lists use of CTX by year and subset and the 5 year BCSS for pts treated and not treated with CTX. Conclusions: A high proportion of pts with HER2+ and HR-HER2- T1N0 breast cancers received adjuvant CTX, with a sharp increase in use of CTX among HER2+ over the past decade. Use of CTX is higher in T1b compared to T1a tumors. In this study, women with T1a and T1b tumors have an excellent prognosis without CTX at 5 Yr. Careful examination of cutoffs for absolute benefit sufficient to recommend CTX is warranted. [Table: see text]
Surveillance and follow up of pediatric cancer from a developing country.
Authors: Nandy Argha , Mukhopadhyay Soma , Maity Debdatta , Bhattacharyya Gouri Shankar , Mukhopadhyay Ashis 
Published: March 2020

10069 Background: Childhood cancers, a leading cause of childhood deaths, affect more than 200,000 children worldwide, of which >80% are from developing nations. This demands for proper measurement of the incidence of various childhood cancers which led to a novel study in assessing the burden of childhood cancers in eastern India through analysis of hospital-based cancer registry data from our institute in between January 2001- December 2011. Methods: 3,200pediatriccancer patients between 0-15 yearsdiagnosed by means of histological and cytological examinations were included in this study. Based on histopathological classification, cancer cases were distributed into 3 different age groups. Their respective family functioning, mental health, self-esteem and social competence were examined. Details of disease, tobacco usage along with socio demographic data were collected through standard questionnaires. Comparative measures of disease incidence were also calculated. For measuring the tolerance, different drugs were administered to patients. Results: The incidence of different malignancies was recorded which were Leukemia (34.9%), Lymphoma (24.1%), Hodgkin’s disease (18.1%), NHL (6.0%), Ewing’s sarcoma (4.9%), Rhabdomyosarcoma (3.6%), Neuroblastoma (2.0%), Brain tumour (9.9%), Wilm’s tumour (6.0%), Lymphoid Leukemia (26.9%), Myeloid Leukemia (7.9%), Germ cell tumour (4.2%), Osteosarcoma (4.0%), Retinoblastoma (2.0%) and Soft tissue sarcoma (2.3%). The disease free survival (DFS) for ALL was 76%, NHL (84%), Soft tissue sarcoma (78%), CML (98%), AML (48%) and germ cell tumour (95%). Finally, 53.33% patients were subjected to post-therapy assessment, of which 98% showed no after effect of therapy on growth chart, heart and endocrine function. The toxicity of grade III and IV chemotherapy ranges from 10-20%. Conclusions: Based on our study, the most happening cancer was Leukemia (34.9%) followed by Lymphoma (24.1%) and soft tissue sarcoma (18%). The overall disease free survival for pediatric patients was 72% with acceptable toxicity. Our results are comparable with the studies of other developed countries.
Use of the FoundationOne next-generation sequencing (NGS) assay to detect actionable alterations leading to clinical benefit of targeted therapies for relapsed and refractory breast cancer.
Authors: Ross Jeffrey S. , Cristofanilli Massimo , Downing Sean , Yelensky Roman , Lipson Doron , Otto Geoff , Palmer Gary A. , Ali Siraj M. , Miller Vincent A. , Stephens Phil 
Published: March 2020

1009 Background: Genomically-informed cancer therapy linking therapeutics targeting the molecular alterations driving the malignancy has the potential to transform the care of patients with metastatic breast cancer (MBC). Methods: DNA was isolated from 4 FFPE sections cut at 10 microns from 177 consecutive MBC that had relapsed after surgery, conventional hormonal/chemo and anti-HER2 targeted therapies received by our CLIA lab (Foundation Medicine). DNA sequencing was performed for 3,320 exons of 182 cancer-related genes to average depth of 1017X. Actionable Genomic alterations (GA) were defined as those linked to targeted anti-cancer therapies approved or being evaluated in active registered clinical trials. Results: Genomic profiles were generated from 169/177 (95%) BCs identifying 565 GA, averaging 3.34 GAs per tumor (range 0 to 10). 152 (90%) tumors harbored an actionable alteration mean 1.88 per tumor (range 0 to 6). In 124 (73%) tumors, ≥1.0 actionable GA was detected that would be missed by current “hotspot assays”. Notable GA involved PIK3CA (37%), ERBB2 (14%), FGFR1/2 (14%), PTEN (10%), MDM2 (7%), CCND1/CCNE1/CDK4 (7%), BRCA1 and BRCA2 (6% each) and ESR1 and EGFR (3% each). Of 23 ERBB2 GA, 74% were amplifications and 26% were mutation/gene fusion. The frequency of ERBB2 mutation/fusion was significantly enriched in CDH1 mutated ILC (~9% of total BC) with a frequency of 19.0% (4/21) compared to other histological types of BCs 1.4% (2/148) [p=0.002]. Significant clinical efficacy included patients with HER2 IHC/FISH negative tumors featuring HER2 and EGFR activating mutations benefitting from lapatinib/trastuzumab and erlotinib respectively. Conclusions: Comprehensive genomic profiling with a NGS assay identified actionable GAs in the majority of MBC patients including ERBB2 and EGFR mutations that initiated use of targeted therapies resulting in significant clinical benefit. These data provide a framework for the GAs expected in advanced BC and should facilitate the implementation of molecularly targeted trials supporting the efforts for a modern approach to precision medicine for the disease.
Sentinel node biopsy following neoadjuvant chemotherapy in biopsy proven node positive breast cancer: The SN FNAC study.
Authors: Boileau Jean-Francois , Poirier Brigitte , Basik Mark , Holloway Claire , Gaboury Louis , Sideris Lucas , Meterissian Sarkis H. , Arnaout Angel , Brackstone Muriel , McCready David R. , Karp Stephen Eric , Wright Frances Catriona , Younan Rami , Provencher Louise , Patocskai Erika , Omeroglu Atilla , Robidoux Andre 
Published: March 2020

1018 Background: A significant and increasing proportion of patients (>30%) with biopsy proven node positive breast cancer will obtain a pathological complete response (pCR) in the axilla after neoadjuvant chemotherapy (NAC). If sentinel node biopsy (SNB) can accurately identify these patients, they could potentially avoid the morbidity of an axillary node dissection. The primary aim of this study is to evaluate the identification rate (IR), false negative rate (FNR) and accuracy of SNB in this setting. The accuracy of post NAC axillary ultrasound and clinical examination are evaluated as secondary endpoints. Methods: Patients with biopsy proven node positive breast cancer (T0-3, N1-2, M0) treated with NAC were eligible to participate in this multi-centre prospective trial. Following NAC, axillary ultrasound and clinical examination results were obtained. At time of surgery, all participants underwent both a SNB and a completion node dissection. A SNB IR greater than 90% and a FNR of less than 10% were pre-determined as being optimal. Results: From September 2009 to December 2012, 153 patients were accrued to the study. 7 patients were not eligible and 5 patients had not yet undergone surgery at the time of analysis. Axillary pCR rate = 34.0% (48/141). SNB IR = 87.2% (123/141), 95% CI [81.7%-92.7%] and FNR = 9.9% (8/81), 95% CI [3.4%-16.4%]. If only one sentinel node was removed, FNR = 19.0%(4/21); if there were 2 or more sentinel nodes, FNR = 6.6% (4/61) (p < 0.0001). Accuracy of SNB, axillary ultrasound and clinical examination were 93.5%, 63.2%, and 45.5% respectively. Conclusions: SNB following NAC in biopsy proven node positive breast cancer is associated with a suboptimal IR. FNR (less than 10%) and accuracy of SNB in this study are comparable to that of patients that present with clinically negative nodes. The FNR decreases when more than one sentinel node is identified. However, in an era where regional nodal radiation is increasingly used, the relevance of leaving residual disease in the undissected axilla after NAC is unknown and remains to be investigated. Clinical trial information: NCT00909441.
Effect of margin width on local recurrence (LR) in triple-negative (TN) breast cancer treated with breast-conserving therapy (BCT).
Authors: Pilewskie Melissa Louise , Ho Alice Y. , Orell Emily , Stempel Michelle , Chen Yu , Eaton Anne , Patil Sujata , Morrow Monica 
Published: March 2020

1021 Background: Positive lumpectomy margins are associated with increased rates of LR after BCT; however, the effect of increasing negative margin distance on LR is controversial. Rates of LR vary by breast cancer subtype, with the highest rates seen in TN cancers. The purpose of this study was to examine the rate of LR in relationship to margin width in TN breast cancers treated with BCT. Methods: All women with TN breast cancer who underwent BCT between 1999-2009 were identified from a prospectively maintained database. Margins were defined as positive (tumor on ink), close (≤2mm), or negative (>2mm) for either invasive or in situ cancer. Patients with positive margins (n=46) were excluded. Statistical comparisons were by t tests, Fisher’s exact test, and Wilcoxon rank sum test. Cumulative incidence of LR was compared using competing-risks methodology. Results: Characteristics of the 535 cancers (in 534 patients) with close (n=71) and negative (n=464) margins are compared in the Table. At median follow-up of 84 months (range, 8-165 months) there were 37 local, 18 regional, and 77 distant recurrences or deaths as first events. 10 patients had LR prior to planned radiation therapy (RT). The cumulative incidence of LR at 60 months for patients with close margins was 7.3% (95% CI, 1.1-13.6), and 5.1% (3.0-7.2) for negative margins. After controlling for use of chemotherapy, there was no significant difference in LR between the entire close and negative margin groups (p=.07) or after exclusion of recurrences prior to RT (p=.06). A difference in the risk of distant recurrence or death was not observed (p=.60). Conclusions: Margin width greater than 2mm was not associated with a clinically meaningful reduction in LR risk. This, coupled with reports of similar LR in TN cancers treated with BCT or mastectomy, suggests that larger surgical procedures do not improve outcomes in this high-risk patient subset. [Table: see text]
The prognostic implications of redox protein expression in stage I-III triple-negative breast cancer.
Authors: Lee Soohyeon , Kim Da Rae , Kim Min Whan 
Published: March 2020

1035 Background: It is well known that increased reactive oxidative stress (ROS) in cancer cells correlates with poor prognosis and aggressiveness of tumor cells. The aim of this study is to investigate the expression of redox proteins in triple-negative, early breast cancer (TNBC) which shows aggressive phenotype among breast cancer and to demonstrate relationships between expression of ROS markers and clinical outcomes. Methods: Tissues from 135 cases of TNBC from curative surgery at Severance Hospital, Seoul, Korea, from December 2005 to January 2008 were analyzed. Immnunochemical (IHC) staining for redox proteins including thioredoxin reductase, glutathione S-transferase (GST) α, catalase, vitamin D-up-regulated protein 1 (VUDP), and manganese superoxide dismutase (MnSOD) was performed to evaluate the difference between clinicopathological parameters. The mono-carboxylate transporter 4 (MCT4) in stroma was done by IHC staining, too. Results: The median age of 135 TNBC patients was 48 (range 27-76). TNM staging were as follows; T1 (n=52, 38.5%), T2 (n=81, 60%), T3 (n=2, 1.5%), N0 (n=88, 65.2%), N1 (n=35, 25.9%), N2 (n=8, 5.9%), N3(n=4, 3.0%). Median follow up was 59 months (range 12-99). Samples were divided into high or low ROS expression level semi-quantitatively. The catalase high expressed group was tend to have lower N stage (p=0.016), lower tumor recurrence (p=0.02) as well as longer overall survival rates (p=0.05). Higher expression of MTC4 in stroma was strongly associated with higher MnSOD expression group analysis (p=0.015) and had significantly longer overall survival (p=0.032). Conclusions: This study shows the expression of ROS proteins could contribute defining aggressiveness of TNBC as well as the prognosis. Considering the lack of targeted molecules as well as molecular heterogeneity of TNBC, ROS markers may provide clues to clinical outcomes in TNBC.