bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of uni- or bilateral retinoblastoma with radiologic optic nerve invasion at diagnosis.
Authors: Choucair Marie-Louise , Brisse Herve , Freneaux Paul , Lumbroso Livia , Chevrier Marion , Doz Francois P. , Aerts Isabelle 
Published: September 2018

10551 Background: To evaluate treatment and outcome of patients with uni- or bilateral retinoblastoma (RB) with radiologic optic nerve invasion (RONI) at diagnosis. Methods: Retrospective clinical, radiological and histological review of patients with uni- or bilateral RB with RONI at diagnosis treated in the Institut Curie. Results: Between 1997 and 2014, 936 patients with RB were treated in the Institut Curie. Eleven patients had detectable RONI confirmed by Computed Tomography and/or Magnetic Resonance Imaging. RB was unilateral in 10/11 patients, bilateral in 1. Median age at diagnosis was 29 months (range 12-96). The patient with the bilateral RB had a unilateral RONI. Nine patients had ON enhancement and 3 had meningeal sheath enhancement. Nine received neoadjuvant chemotherapy (CT) and 2 had a primary enucleation. Partial response to neoadjuvant CT was obtained for all the patients. Enucleation was performed in 10/11 patients, by anterior approach in 3 patients, by anterior and subfrontal approach in 7 patients. Three patients had positive ON margin and among them, 2 were primary enucleated. All enucleated patients received adjuvant treatment (conventional CT: 10, High Dose CT: 7 and radiotherapy: 5). Three patients died of meningeal progression (2 during treatment and 1 during the first year after treatment). The patient with the bilateral RB was lost to follow up just after a meningeal progression during treatment. Seven are still alive (median follow up: 8 years, range : 1.5-17.5). Conclusions: Neoadjuvant CT has an important place in the management of unilateral RB with RONI at diagnosis. Pretreatment accurate staging by orbital and brain MRI is mandatory, as well as preoperative reassessment. Surgery should be performed by experienced ophthalmologists and if necessary neurosurgical team in order to obtain the best conditions for a tumor-free resection margin in patients with RONI.
Long-term growth and development in 268 bevacizumab (BEV)-treated and 135 control pediatric/adolescent patients (pts): An integrated analysis.
Authors: Müller Hermann L. , Merks Johannes H.M. , Geoerger Birgit , Grill Jacques , Hargrave Darren , Glade Bender Julia Lynne , Gururangan Sridharan , Navid Fariba , Johnston Michael , Bachir Jeanette , Hilton Magalie , Fürst-Recktenwald Sabine 
Published: September 2018

10554 Background: BEV has an established safety profile in adults, but long-term data in children are limited. This analysis examined the effects of BEV on growth/development in pediatric/adolescent pts. Methods: Data (height, weight, body mass index [BMI], bone age data) were pooled (5 trials): NCT00643565 (Ph2/soft tissue sarcoma); NCT01390948 (Ph2/high-grade glioma); NCT00085111 (Ph1/refractory solid tumors); NCT00667342 (Ph2/osteosarcoma); NCT00381797 (Ph2/glioma, medulloblastoma, ependymoma). Pts (<18 yrs old) received ≥1 dose of BEV + chemotherapy (CT) (n=268) or CT alone (n=135). Analyses were exploratory/descriptive. Reference growth data: WHO (<2 yrs); Centres for Disease Control (≥2 yrs). Results: Across the trials, mean number of BEV administrations per pt ranged 5.6–19.9 (dose 5–15mg/kg every 2/3 weeks). Median follow-up time, months (range): BEV+CT, 37.9 (2.4–64.2); CT, 22.9 (2.8–69.2). At baseline, median height, weight, and BMI were close to that of the reference population (mean standard deviation scores [SDS] close to 0). Over 60 months, a slight decline was observed in the mean SDS for height and weight in both arms in this cohort with different tumors/treatments (Table), but remained within normal range of healthy children. Trends were similar for BMI. No delay in growth velocity or bone age in BEV-treated pts vs CT only was observed up to 3 yrs, regardless of age/gender. A subgroup analysis of pts in the growth hormone-dependent development phase was consistent with the overall results. Conclusions: In this analysis, BEV inclusion in the treatment regimen did not have a negative impact on pediatric growth/development beyond that of CT alone. [Table: see text]
Human papillomavirus (HPV)-associated malignancies as subsequent malignant neoplasms (SMN) in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS).
Authors: Henderson Tara O. , Nathan Paul C. , Whitton John , Leisenring Wendy M. , Neglia Joseph Philip , Fowler Brynn , Arnold Michael A. , Howell Rebecca M. , Robison Leslie L. , Armstrong Gregory T. , Alexander Kenneth 
Published: September 2018

10566 Background: It is not known whether childhood cancer survivors (CCS) develop human papillomavirus (HPV)-associated malignancies more frequently than the general population. Methods: We assessed the cumulative incidence of SMN in sites typically associated with HPV (HPV-SMN) and evaluated standardized incidence ratios (SIR) and absolute excess risks (AER) using age-, sex- and calendar-year specific rates from the Surveillance, Epidemiology and End Results (SEER) program. Multivariate Cox regression models identified associations between key risk factors and HPV-SMN development. Results: Among 27,620 CCS, 36 developed an HPV-SMN at a median age of 27 years (range: 8-42) and a median of 15 years (range: 5-29) after their primary cancer. The 30-year cumulative incidence of an HPV-SMN was 0.20% (95% confidence interval [CI]: 0.13%-0.28%). HPV-SMN locations included oral cavity/pharynx (N = 26, 72%), rectum (N = 4, 11%), cervix/uteri (N = 3, 8%), and vulva (N = 3, 8%). The incidence of HPV-SMN was almost 3-fold higher among CCS than the general population (SIR = 2.8, 95% CI 2.0-4.1) with an AER of 6.0/100,000 person-years. Rates were elevated in those exposed (SIR = 3.3, CI 2.1-5.2) and not exposed to radiotherapy (RT; SIR = 2.6, CI 1.4-4.8). Risk of oral cavity/pharynx SMN was elevated in both those exposed (SIR = 7.3, CI 3.9-13.6) and not exposed (SIR = 4.2, CI 2.2-8.1) to head or neck RT, whereas, risk in GU locations was elevated in those exposed (SIR = 4.1, CI 1.9-9.2) but not in those not exposed to pelvic RT (SIR = 0.8, CI 0.3-2.1). Male sex (HR = 2.9, CI 1.3-6.1), exposure to head/neck/pelvic RT (HR = 2.6, CI 1.2-6.1), and platinum chemotherapy (HR = 6.1, CI: 2.6-13.9) increased the risk. Among 15 deceased HPV-SMN cases, 10 (67%) died of their HPV-SMN. Conclusions: While the overall incidence is low, CCS are at increased risk of developing malignancies in locations commonly associated with HPV infection in the general population. Further research examining the role of HPV in the etiology of these SMNs is warranted. As HPV-SMNs are potentially preventable, promotion of HPV vaccination efforts should be considered in this population.
Second malignant neoplasms in a nationwide population-based cohort of childhood cancer survivors in Taiwan.
Authors: Yu Chu-Ling , Tonorezos Emily S. , Huang Chiung-Yu , Chiu Brian C-H , Chiang Chun-Ju , Ch'ang Hui-Ju , Liu Yen-Lin , Miser James S. , Chiou Hung-Yi , Yen Yun 
Published: September 2018

10569 Background: Childhood cancer survivors have excess risk of second malignant neoplasms, but data are limited in Asian populations. We established a nationwide retrospective cohort of childhood cancer survivors in Taiwan to study the risk of second malignant neoplasms in the population. Methods: Children and adolescents diagnosed with cancer before age 21 years between 1990 and 2011 were identified from the Taiwan Cancer Registry, the national cancer registry in Taiwan. One-year survivors of childhood cancer were ascertained through data linkage with the national death registry. Survivors were followed up through December 2012. Standardized incidence ratios (SIRs), absolute excess risks (AERs), and cumulative incidence of second malignant neoplasms were calculated. Results: A total of 186 second malignant neoplasms occurred among 15,263 1-year survivors of childhood cancer after a mean follow-up time of 8.0 years (SIR = 5.4, 95% confidence interval [CI] = 4.6-6.2; AER = 12.4 per 10,000 person-years). The most common types of second malignant neoplasms were gastrointestinal cancers (n = 37), leukemia (n = 28), endocrine cancers (n = 18), and brain cancer (n = 17). Cancers in the liver (n = 11, including 9 hepatocellular carcinoma) and colorectum (n = 16) accounted for 73% of second gastrointestinal malignant neoplasms in this population. The cumulative incidence of second malignant neoplasms at 10 and 20 years from follow-up was 1.0% (95% CI = 0.8-1.2%) and 3.0% (95% CI = 2.3-3.6%), respectively. Conclusions: Childhood cancer survivors in Taiwan experience excess risk of second malignant neoplasms, in particular gastrointestinal cancers, compared with the general population.
Accuracy of self-reported smoking status in adult survivors of childhood cancer: A report from St. Jude Lifetime Cohort study.
Authors: Huang I-Chan , Klosky James L. , Young Chelsea , Murphy Sharon , Srivastava Deo Kumar , Hudson Melissa M. , Robison Leslie L. 
Published: September 2018

10570 Background: Although clinicians often evaluate smoking behavior in cancer survivors via self-report, the validity of this approach is unknown. We validated self-reported smoking status by serum cotinine data in clinically assessed adult survivors of childhood cancer and identified factors contributing to misclassification. Methods: The study sample consists of 287 randomly selected adult survivors of childhood cancers participating in the St. Jude Lifetime Cohort Study and undergoing a risk-based clinical assessment in a survivorship clinic. Self-reported smoking status was classified as never (N = 105), past (N = 111), and current (N = 71) smokers. Age, sex, and race/ethnicity were balanced among the three groups (p’s > 0.05). Blood samples were obtained and serum cotinine levels were quantified by liquid chromatography tandem mass spectrometry. Misclassification was determined by the discrepancies between self-reported smoking status and race/ethnicity-specific serum cotinine thresholds (Benowitz et al. Am J Epidemiol 2009). Multiple logistic regression model was used to identify factors related to misclassification. Results: Of the 287 survivors (mean age = 34 years [range = 19-61]; mean time from diagnosis = 24 years [range = 11-46]), 55.4% were male and 84.0% non-Hispanic white. Cotinine levels consistent with recent active smoking were present in 39.4% compared to 24.7% who self-reported as being a current smoker (X2= 14.1; p = 0.0002). Rates of misclassification were 36.9%, 8.4%, and 6.7% in survivors who reported themselves as past, current, and never smokers, respectively. Among self-reported past smokers, 18-30 years of age at survey, male, and current marijuana use increased the risk of misclassification: RR = 3.0 (95%CI = 1.2-7.6), 2.5 (95%CI = 1.1-5.4) and 3.2 (95%CI = 1.1-9.3), respectively. Conclusions: Within a clinical setting, reliance on self-report of smoking status by survivors results in a high misclassification rate. For research, serum cotinine levels should be utilized to assign smoking status. For clinical care and health promotion, clinicians need to be aware of the high rate of misclassification when relying upon self-reported smoking status.
Pharmacogenetics revisits bevacizumab in breast cancer patients: An ancillary analysis of the UCBG trial COMET—A French multicentric prospective study from R&D UNICANCER.
Authors: Milano Gerard A. , Pierga Jean-Yves , Gal Jocelyn , Llorca Laurence , Dubot Coraline , Romieu Gilles , Desmoulins Isabelle , Brain Etienne , Goncalves Anthony , Ferrero Jean-Marc , Cottu Paul H. , Debled Marc , Tredan Olivier , Chamorey Emmanuel , Merlano Marco Carlo , Lemonnier Jérôme , Etienne-Grimaldi Marie-Christine 
Published: September 2018

1079 Background: Bevacizumab (Beva) is no longer unanimously recommended in the management of breast cancer (BC). Given the absence of faithful predictors of Beva treatment outcome, we made the hypothesis that constitutional gene polymorphisms could play a role in this context. We report the pharmacogenetic ancillary study of the prospective COMET trial conducted in advanced BC patients (pts) receiving first-line Beva associated with paclitaxel. Methods: Relevant targeted gene polymorphisms were analyzed (blood) in 203 prospective pts (mean age 55.3, median follow-up 24 months). VEGFA at positions -2578C > A (rs699947), -1498T > C (rs833061), -634G > C (rs2010963), and 936C > T (rs3025039) were analyzed by PCR-RFLP. VEGFR1 319A > C (rs9582036), VEGFR2 at positions 604C > T (rs2071559), 1192C > T (rs2305948), 1416T > A (rs1870377), IL8 251T > A (rs4073), CYP2C8 139C > T (rs1572080), 399T > C (rs10509681) and ABCB1 at positions 1199 C > TA (rs2229109), 2677G > TAC (rs2032582) were analyzed by Mass-Array Agena. ABCB1 1236C > T (rs1128503) and 3435T > C (rs1045642) were analyzed by pyrosequencing. All fitted HWE. Results: Median progression-free survival (PFS) was 10.8 months. VEGFR1 319A allele was associated with longer PFS (p = 0.03). The VEGFA-1498T allele was significantly associated with both longer overall survival (OS) (p = 0.005) and PFS (p = 0.065). The VEGFA -2578C allele was associated with greater OS (p = 0.002) and PFS (p = 0.071). These two VEGFA polymorphisms were in linkage disequilibrium (p < 0.0001). Multivariate Cox analysis showed that VEGFA -2578 (p = 0.001) and VEGFR2 1416 (p = 0.025) were significant predictors of OS: the score of favorable alleles (VEGFA -2575C and VEGFR2 1416T) was highly associated with OS (p = 0.0003), with median survival at 24 months being 30% for score 0 (95%CI 15-61), 65% for score 1 (95%CI 55-75) and 90% for score 2 (95%CI 67-90). Conclusions: Application of an easy-to-perform low-cost genotyping test may identify strong predictors of Beva outcome in metastatic BC pts. In the current era of precision medicine, a pharmacogenetic-based personalized Beva therapy deserves to be prospectively validated in BC pts. Clinical trial information: 2012-A00244-39.
A phase II, multicenter, randomized trial of eribulin plus gemcitabine (EG) vs. paclitaxel plus gemcitabine (PG) in patients with HER2-negative metastatic breast cancer (MBC) as first-line chemotherapy (KCSG BR13-11, NCT02263495).
Authors: Jung Kyung Hae , Park Yeon Hee , Im Seock-Ah , Sohn Joohyuk , Lee Keun-Seok , Chae Yee Soo , Lee Ki Hyeong , Kim Jee Hyun , Im Young-Hyuck , Kim Ji-Yeon , Kim Tae-Yong , Lee Kyung-Hun , Kim Sung-Bae , Ahn Jin-Hee , Kim Gun Min , Park In Hae , Lee Soo Jung , Han Hye Sook , Kim Se Hyun 
Published: September 2018

1082 Background: PG chemotherapy is one of the preferred chemotherapeutic regimens for patients with MBC. Eribulin mesylate is a non-taxane inhibitor of microtubule dynamics of the halichondrin class. A recent pooled analysis with eribulin showed improved overall survival (OS) in various patient subgroups. Furthermore, eribulin may have rational benefit compared with paclitaxel in terms of neurotoxicity. Methods: This study was a prospective randomized phase 2, open-label, two-arm, multi-center study comparing EG with PG chemotherapy for patients with HER-2 negative MBC as first-line treatment. Histologically confirmed breast cancer patients, at least 19 years of age, with no prior history of chemotherapy for MBC with evaluable lesions were included. Prior hormonal therapy as a treatment of Hormone Receptor (HR)-positive MBC was allowed. This design was hypothesized that EG chemotherapy would not be inferior to PG chemotherapy. The primary endpoint was Progression-Free Survival (PFS). Estimated 6 mo. PFS rate for each arm was 70%. The secondary endpoints were: Time to Treatment Failure (TTF); OS; neuropathic scale; toxicity; clinical benefit rate. Results: A total of 118 patients (median age: 50, 24-66) were enrolled between 2015 and 2016, and were randomly assigned to PG (n = 59) or EG (n = 59) chemotherapy. Mean number of metastatic sites was 3 (1-8). Six month PFS rates for both arms were 72% for EG and 73% for PG arm (p = 0.457). PFS in PG arm tends to be longer than in EG group (median PFS 12.6 for PG vs. 9.6 months for EG) without statistical significance. In addition, there was no significant difference in OS between the two groups (not reached vs. 21.2 months, p = 0.223). The median numbers of chemotherapy cycles of both groups were 8 for EG and 10 for PG (range 2-32). CBRs were 44% for EG and 45% for PG arm. Major toxicities were neutropenia and neurotoxicity. Grade II or more neurotoxicity was more common in PG than in EG group (40% vs.25%). Conclusions: EG chemotherapy showed similar clinical benefit with PG chemotherapy in terms of PFS but, more favorable neurotoxicity than PG chemotherapy. Clinical trial information: NCT02263495.
Association between insulin-like growth factor-1 receptor (IGF1R) expression in circulating tumor cells (CTCs) and prognosis in patients with metastatic breast cancer (MBC).
Authors: Gennari Alessandra , Zamarchi Rita , Amadori Dino , De Censi Andrea , Nanni Oriana , Bologna Alessandra , Cavanna Luigi , Gianni Lorenzo , Scaltriti Laura , Rossi Elisabetta , Facchinetti Antonella , Corradengo Davide , Foca Flavia , Bruzzi Paolo 
Published: September 2018

1086 Background: CTCs are strongly associated with prognosis in MBC. In a recent metanalysis on 1944 patients, a CTC count > 5/7.5 ml was associated with a 2-fold increased risk of progression and death. Little evidence is available on the prognostic role of phenotypic CTC assessment, however. In this study, nested in a randomized clinical trial of Ist line chemotherapy ± metformin, we evaluated the prognostic role of IGF1R expression in CTCs, given its potential growth promoting effect. Methods: CTCs were isolated from blood samples of enrolled patients; an automated sample preparation and analysis system (CellSearch) was customized for detecting IGF1R positive CTCs. The prognostic role of total CTCs, IGF1R positive (+ve) and negative (-ve) CTCs was assessed by fitting different PFS and OS multivariate Cox’s models.Results: CTC evaluation at baseline was performed in 72 of 126 patients, of whom 30 (42%) had CTCs ≥5/7,5ml and 41 (57%) had at least one IGF1R+ve CTC. In univariate analysis the prognostic role of total CTCs was confirmed: PFS ( < 5 vs ≥5) HR = 1.69, 95%CI 1.01-2.69, p 0.042 and OS HR = 2.80, 95%CI 1.47-5.30, p 0.002).However, when total CTCs were split in IGF1R+ve and IGF1R–ve, a striking difference was seen in the prognostic effect of these cell types.While no association was detected between an increasing number of IGF1R+ve CTCs and PFS or OS (p = 0.56 and p = 0.99), the number of IGF1R-ve CTCs ( < 4 vs ≥4) was strongly associated with an increased risk of progression and death: HR 1.93 (95%CI 1.15-3.23, p 0.013) and 3.65 (95%CI 1.88-7.09, p 0.001). In multivariate analysis, adjusted for metformin, the prognostic role of the number of IGF1R-ve CTCs was confirmed, while no residual prognostic role of total CTCs or number of IGF1R+ve cells was found (p = 0.55 and p = 0.64 for PFS; p = 0.86 in both cases for OS). Conclusions: In our study, the loss of IGF1R expression in CTCs exhibited a significant adverse prognostic effect, whereas no significant effect of total CTCs and IGF1R+ve CTCs was observed. This finding supports the biological characterization of CTCs as a critical step for further definition of their prognostic significance.
Retinoblastoma (Rb) protein expression in triple-negative breast cancer.
Authors: Patel Jaymin M , Torous Vanda , Hacker Michele R , Nalven Tessa , Garber Judy Ellen , Alexander Brian Michael , Lee Larissa Janeen , Collins Laura C. , Schnitt Stuart J. , Tung Nadine M. 
Published: September 2018

1097 Background: Expression of Rb, the protein product of the RB tumor suppressor gene, is required for cyclin D kinase (CDK) 4/6 inhibition in luminal breast cancers. Triple negative breast cancers (TNBC) frequently exhibit Rb loss and are thus believed to be poor candidates for CDK4/6 inhibition. However, the features associated with Rb loss in TNBC are poorly-defined. We aimed to assess whether TNBC that express the androgen receptor (AR) and resemble a more luminal subtype retain Rb more often than other TNBC. Methods: To assess the frequency and correlates of Rb expression in TNBC, we stained tissue microarrays (TMAs) containing 180 Stage I-III TNBC, 71 with germline BRCA1 mutations ( BRCA1+) and 109 without BRCA1 mutation (sporadic), using a mouse monoclonal antibody to human Rb (clone G3-245, BD Biosciences). Assessment of tumor size, histologic type, grade, lymphovascular invasion and lymph node status were assessed on histologic review. The TMAs, containing three 0.6mm cores/tumor, had been previously stained for AR, CK5/6, CK14 and EGFR. Log-binomial regression was used to calculate risk ratios (RR). Results: Fifty percent of TNBC were Rb-positive (Rb+; ≥10% nuclei staining) of which 84.4% had > 50% nuclei staining. Among TNBC that were Rb-negative, 76.6% had < 1% nuclei staining for Rb. AR expression (≥10% nuclei staining) was more common in Rb+ than Rb-negative TNBC (16.7% vs 4.5%; p = 0.01). In addition, Rb expression was significantly more common among sporadic than BRCA1+ TNBC (59.6% vs 35.2%, p = 0.001). Compared with Rb-negative TNBC, Rb+ tumors were associated with older age (mean 48.7 vs 45.7 years; p = 0.06) and lower histologic grade (grade 1 or 2: 9.2% vs 2.2%; p = 0.05). No other clinical or pathologic features were significantly associated with Rb status. In a multivariable model, both AR expression (RR, 1.65; 95% CI, 1.31-2.08) and lack of BRCA1 mutation (RR, 1.63; 95% CI, 1.17-2.29) significantly predicted for Rb expression among TNBC. Conclusions: Sporadic TNBC is significantly more likely to be Rb+ than BRCA1+ TNBC. Among TNBC, AR expression significantly predicts for Rb expression. These results suggest clinically relevant biomarkers that may predict for Rb expression and potential targeted therapies in TNBC.