bluuebunny/crossref_metadata_2025_split huggingface dataset:
Birth and maternal characteristics, and childhood cancer in the United States: An ecological study.
Authors: Pereira Guilherme Abreu , Rodriguez-Galindo Carlos , Frazier A. Lindsay , Boffetta Paolo , Ribeiro Karina Braga 
Published: March 2020

10061 Background: Childhood cancer is rare, yet it represents a major cause of mortality in this age group. Its etiology is largely unknown. The aim of this study was to identify associations between pre- and perinatal characteristics and cancer development in children below age 5. Methods: We developed an ecological study correlating birth information and childhood cancer incidence in 0-4 year old at the State level. The following variables were analyzed: birth weight (BW), preterm birth, maternal age, plurality, maternal smoking, chronic hypertension (CH), diabetes mellitus (DM), pregnancy associated hypertension (PH) and eclampsia. Birth characteristics were obtained from Centers for Disease Control and Prevention (CDC) database (1995-2009), and childhood cancer incidence data from the National Program of Cancer Registries (NPCR) and the Surveillance, Epidemiology and End Results (SEER) program (1999-2009). Spearman correlation coefficients were calculated with SAS 9.2 (Cary, NC). Bonferroni correction was applied for multiple comparisons, ie, only results with p£0.01 were considered significant. Results: Acute lymphoid leukemia (ALL) (r=0.47, p <0.001), astrocytoma (AST) (r=0.59, p <0.001), neuroblastoma (NB) (r=0.48, p <0.001) and rhabdomyosarcoma (RMS) (r=0.51, p=0.003) were positively correlated with high BW (>4000g). ALL (r=0.46, p <0.001) was also positively correlated with advanced maternal age (40+ years). Moreover, a positive correlation was found between plurality and NB (r=0.50, p <0.001). Regarding maternal conditions, the following positive correlations were identified: DM with AST (r=0.40, p=0.009), NB (r=0.38, p=0.01) and WT (r=0.38, p=0.01). Conclusions: Well established correlations were replicated and new associations were suggested (e.g., AST and DM). In spite of the limitation of an ecological approach, this study provided new hypotheses to be explored in further analytical studies based on individual data.
Depression and anxiety (DA) in children within one year of a cancer diagnosis.
Authors: Leavey Patrick , Germann Julie N , Leonard David , Stuenzi Thomas , LeVieux Jane , Stewart Sunita 
Published: March 2020

10064 Background: While 10% of children were treated with anti-depressants within 1 year of a cancer diagnosis in a previous study, neither the prevalence nor time course of DA were studied. The American Association of Pediatrics advocates for the use of screening for DA, yet data are lacking regarding timing, frequency, or predictive success of screening in children concurrently receiving therapy for cancer. Methods: We evaluated 87 prospectively diagnosed children at a single institution for DA at 5 time points during the first year of a cancer diagnosis. 55 children completed all screening, 70 missed at most one visit. Starting within 1 month of cancer diagnosis, patients completed the Childhood Depression Inventory (CDI) and the Speilberger State/Trait Anxiety Inventory (STAI) and again at 3, 6, 9, and 12 months. Those patients who scored ≥ 11 on the CDI or ≥ one standard deviation above the mean for age on the STAI were referred for psychiatric consultation the same day. Results: Overall 33 patients (39%) indicated symptoms suggestive of either depression or anxiety during their first year of cancer therapy; n=29 (35%) depression, n=17 (20%) state and n=10 (12%) trait anxiety. Fifty-six consultations resulted in 33 psychiatry diagnoses confirmed in 21 patients (23 depression, 3 anxiety and 7 other). Half of the patients received a diagnosis of DA at least twice over the course of the study, suggesting persistent, significant symptoms. Conclusions: We conclude that screening for DA is effective in children with cancer and that prevalence for symptoms is high. The highest risk for symptoms of DA is within 1 month of diagnosis but during the 1st year of therapy children continue to suffer symptoms of DA highlighting the importance of continued screening. [Table: see text]
Neo-tAnGo science: A translational study of PAM 50 sub-typing in sequential fresh tissue samples during neoadjuvant chemotherapy.
Authors: Earl Helena Margaret , Chin Suet-Feung , Dunning Mark , Iddawela Mahesh , Rueda Oscar , Russell Roslin , Jones Linda , Vallier A-L , Hughes-Davies Luke , Abraham Jean , Chan Steve , Skene Anthony , Benstead Kim , Gallagher Christopher J. , Murray Nicholas , Ritchie Diana , Dunn Janet A. , Hiller Louise , Provenzano Elena , Caldas Carlos ,   Neo-tAnGo Investigators
Published: March 2020

1015 Background: Neo-tAnGo was an NCRI UK neoadjuvant breast cancer study testing the addition of gemcitabine to anthracycline and taxane-based treatment and also the sequencing of chemotherapy. In a translational substudy, sequential fresh tissue was analysed for PAM 50 subgroups. Methods: Neo-tAnGo recruited 831 patients. 162 patients were consented for Neo-tAnGo Science, for 3 additional fresh tissue samples to be taken at diagnosis (diag), mid-chemotherapy (CT) and end-CT. Standard methodology was used for PAM 50 subtyping. Results: Fresh tissue samples at diag were received from 123 patients (pts). 45 pts (37%) had 2 additional samples provided (at mid- and end-CT). 57 pts (46%) had 1 additional sample provided (34 at mid-CT, 23 at end-CT). PAM 50 subtyping at diag was as follows: 31 (25%) BASAL; 30 (24%) HER2; 39 (32%) LUM B; 13 (11%) LUM A; 10 (8%) NORMAL-like. Pathological complete response rates (pCR: no disease in breast or axillary nodes, n = 121 pts) differed between PAM 50 subtype at diag (p = 0.04): BASAL 11/31 (35%); HER2 8/30 (27%); LUM B 3/37 (8%); LUM A 1/13 (8%); NORMAL-like 3/10 (30%). Of the 94 pts who were not PAM50 NORMAL-like at diag and had 2+ samples, 42 (45%) ‘shifted to NORMAL-like’. This was associated with slightly higher pCR rates (24% vs 15% who didn’t ‘shift to NORMAL-like’, p = 0.44) and borderline significantly higher rates of pCR or minimal residual disease (MRD: <10% residual scattered tumour cells) (48% vs. 27% who didn’t ‘shift to NORMAL-like’, p = 0.06). In the 102 pts with 2+ samples, 58 pts (57%) showed a shift to a better prognosis PAM 50 subtype after CT (Group (Gp) 1), 37 (36%) showed no change (Gp 2) and 7 (7%) a shift to a worse prognosis subtype (Gp 3). pCR rates were 26% Gp1, 14% Gp2 and 0% Gp3 (p = 0.05). pCR/MRD rates were 48% Gp1, 22% Gp2 and 0% Gp3 (p = 0.001). Conclusions: PAM 50 subtype at diagnosis correlates with pCR to neoadjuvant chemotherapy. Shift to a better prognosis PAM 50 group during neoadjuvant chemotherapy was demonstrated in 57% of pts and was significantly correlated with higher pCR and pCR/MRD rates. Clinical trial information: 78234870.
Efficacy of the combination of ABT-888 (veliparib) and carboplatin in patients with BRCA-associated breast cancer.
Authors: Somlo George , Frankel Paul Henry , Luu Thehang H. , Ma Cynthia , Arun Banu , Garcia Agustin , Cigler Tessa , Fleming Gini F. , Harvey Harold A. , Sparano Joseph A. , Nanda Rita , Chew Helen K. , Moynihan Timothy Jerome , Vahdat Linda T. , Goetz Matthew P. , Hurria Arti , Mortimer Joanne E. , Gandara David R. , Chen Alice P. , Weitzel Jeffrey N. 
Published: March 2020

1024 Background: The combination of platinum agents and PARP inhibitors may benefit patients (pts) with BRCA-associated metastatic breast cancer (MBC). We report on the response and clinical benefit rates when combining the PARP inhibitor veliparib (V) and carboplatin (carb) in a phase I trial. Methods: BRCA carriers with MBC were eligible. Carb starting at an AUC of 6 was given IV in 21-day cycles (C) and V was given orally twice daily (BID) at dose levels (L) L1 through L5. Results: Twenty-eight pts (26 eligible) carrying BRCA1 (12) or BRCA2 (15), or both (1) mutations were accrued between June 2010 and June 2012. The median age (32-66) was 45 years. The number (#) of prior chemotherapy regimens given for MBC was 1 (0-5); 70% of BCs were ER+, and 7% were HER2+. The schema, dose limiting toxicities (DLT) during C 1, median # of Cs on trial, and maximum tolerated dose (MTD) are shown. There were 3 (12%) complete and 9 (35%) partial responses (PR). Unconfirmed PR or stable MBC (median duration: 8 months [6-10+]) were seen in 7 pts (27%); the clinical benefit rate was74%. The median progression-free survival (PFS) is 7.8 months (95% CI 7.3-9.5). The pt with Fallopian tube cancer had a CR. DLTs with C 1 were seen in 2/6 evaluable pts at L1 (1 pt w/grade 3 hyponatremia and dehydration, and 1pt w/grade 4 thrombocytopenia [PLT]), leading to de-escalation of carb. At L2, 1 pt had grade 4 PLT. At L5, 1 pt had grade 4 PLT, and 2 pts grade 3 PLT (1 pt also experienced grade 4 granulocytopenia [ANC]), defining the MTD at carb AUC 5 and V 150 mg BID (L4). Dose delays and/or dose adjustments due to grade ≥ 2 toxicities for ANC or PLT were seen during the first 3 Cs at L1 (100%), L2 (50 %), L3 (67%), L4 (83 %), and at L5 (67%). Conclusions: The combination of carb and V is active, and is associated with substantial clinical benefit rate and managable hematologic toxicities in BRCA carriers with MBC. Further definition of the role of V is warranted. [Table: see text]
NEOZOTAC: Efficacy results from a phase III randomized trial with neoadjuvant chemotherapy (TAC) with or without zoledronic acid for patients with HER2-negative large resectable or stage II or III breast cancer (BC)—A Dutch Breast Cancer Trialists’ Group (BOOG) study.
Authors: Charehbili Ayoub , van de Ven Saskia , Liefers Gerrit-Jan , Smit Vincent T. H. B. M. , Putter Hein , Heijns Joan Barbara , van Warmerdam Laurens , Kessels Lonneke , Dercksen Wouter , Pepels Manon J. , Maartense Eduard , Van Laarhoven Hanneke W. M. , Vriens Birgit , Wasser Martin N. , Hamdy Neveen A.T. , Meershoek – Klein Kranenbarg Elma , van Leeuwen-Stok Elise , Van De Velde Cornelis J. H. , Kroep Judith R. , Nortier J. W. R. 
Published: March 2020

1028 Background: The role of bisphosphonates when added to the neoadjuvant treatment of BC in enhancing the efficacy of therapy is still unknown. Methods: NEOZOTAC is a national, multicenter, randomized study comparing the efficacy of TAC (docetaxel, Adriamycin and cyclophosphamide i.v.) CT followed by G-CSF on day 2 with or without ZA 4 mg i.v. ,q 3 weeks in patients (pts) with stage II/III, measurable, HER2-negative BC and absence of prior bisphosphonate usage. The primary endpoint is the pathologic complete response (pCR) rate in the resection specimen and positive lymph nodes. 228 pts are needed to show an improvement of the pCR rates from 17% to 34% in the experimental arm using a 5% significance level based on the two-sided Fisher’s exact test with a power of 80%. Randomization was done by using the Pocock’s minimisation technique stratified by cT, cN and estrogen receptor status. pCR rate was analyzed using the Cochran-Mantel-Haenszel test, adjusting for the stratification factors. Analysis was based on intent-to-treat. An unplanned subgroup analysis of postmenopausal women (PMW; FSH >20 and estradiol <110) and baseline vitamin D levels was performed. Results: From July 2010 to April 2012, 250 patients from 25 participating sites were randomized. Pathologic response data of 228 patients are currently available. pCR rate did not differ between the two study arms (17% vs 16%, p = 0.81). However, a trend in benefit in favor of ZA was observed in PMW (18% vs 11%, OR 1.90, 95% C.I. 0.52 – 6.88). Patients with severe vitamin D insufficiency (<25 nmol/L) seemed to respond worse to CT numerically (6% vs. 18%). At ASCO pCR and clinical response data of all patients will be reported. Conclusions: Previously, we have shown that adding ZA to neoadjuvant CT is safe with good compliance.In this study, treatment with ZA did not result in a pCR benefit in the total study population. However our findings suggest that addition of ZA to neoadjuvant CT might be effective for enhancing response in PMW with BC. Clinical trial information: NCT01099436.
The persistence of disseminated tumor cells after systemic therapy and their influence on prognosis in early breast cancer patients.
Authors: Hartkopf Andreas D. , Wallwiener Markus , Gruber Ines , Neubauer Hans , Hahn Markus , Wallwiener Diethelm , Taran Florin-Andrei , Fehm Tanja N. 
Published: March 2020

1030 Background: Detection of disseminated tumor cells (DTC) in the bone marrow (BM) of early breast cancer (EBC) patients before the administration of systemic therapy is associated with poor outcome. The aim of this study was to evaluate the impact of DTC on overall survival (OS) and disease free survival (DFS) in a large cohort of EBC patients after the administration of systemic therapy. Methods: EBC patients receiving systemic therapy (endocrine therapy and/or chemotherapy +/- HER2-directed treatment) either prior to surgery (neoadjuvant systemic therapy, NST) or after surgery (adjuvant systemic therapy, AST) at Tuebingen University Hospital, Germany between 01/2003 and 06/2012 were available for this analysis. BM aspirates were collected during surgery / one year after surgery in patients receiving NST / AST. DTC were identified by immunocytochemistry (pancytokeratin antibody A45/B3) and cytomorphology. Survival was analyzed using univariate (log-rank test) and multivariate analysis (cox regression). Results: DTC were detected in 201 of 608 (35%) patients. 175 of 419 (42%) patients treated with NST and 35 of 189 (19%) patients treated with AST were DTC-positive. Chemotherapy / endocrine therapy was administered prior to BM aspiration in 399 (96%) / 19 (5%) of the patients receiving NST and in 99 (52%) / 158 (84%) of the patients receiving AST. On univariate analysis, the detection of DTC was a significant predictor of poor DFS (HR: 2.27, 95% CI: 1.48 – 3.48, p<0.001) and poor OS (HR: 1.89, 95% CI: 1.19 – 3.00, p=0.007). On multivariate analysis (considering all clinicopathological factors and the DTC-status), independent factors for DFS were DTC-status (negative vs. positive), grading (G2-3 vs. G3), nodal-status (negative vs. positive), and the ER-status (negative vs. positive). Independent factors for OS were grading, PR-status (negative vs. positive) and nodal-status. Conclusions: The persistence of DTC in the BM of EBC patients after systemic treatment is a strong and independent marker of poor prognosis. Determination of the DTC-status is thus promising to monitor the effect of systemic therapy and to identify patients that are in need of additional adjuvant therapy.
The effect of obesity on prognosis in operable breast cancer patients treated with adjuvant anthracyclines and taxanes according to pathologic subtypes.
Authors: Pollán Marina , Pajares Bella , Martin Miguel , Mackey John Robert , Lluch Ana , Gavila Joaquin , Vogel Charles L. , Ruiz Borrego Manuel , Calvo Lourdes , Pienkowski Tadeusz , Rodriguez-Lescure Alvaro , Seguí Miquel Angel , Tredan Olivier , Anton Antonio , Ramos Vazquez Manuel , Camara M Carmen , Rodriguez-Martin Cesar , Carrasco Eva Maria , Alba Emilio ,   Spanish Breast Cancer Research Group (GEICAM)
Published: March 2020

1031 Background: According to observational studies, obesity is an unfavourable prognostic factor in breast cancer (BC), regardless of menopausal status and treatment received. Information collected in clinical trials should confirm this effect and serves to test its homogeneity by pathologic subtype. Methods: We retrospectively analysed 5,683 operable BC patients enrolled in four randomized clinical trials (GEICAM/9906, 9805, 2003–02, and BCIRG 001) evaluating adjuvant anthracyclines and taxanes. Our primary aim was to assess the prognostic effect of body mass index (BMI) on disease recurrence, breast cancer mortality (BCM), and overall mortality (OM). A secondary aim was to detect differences by BC subtypes (ER/PR-positive/HER2-negative, HER2-positive, triple-negative). Cox models were fitted for each end-point, adjusted by potential confounders. Results: Analyses adjusting for age, tumor size, nodal status, menopausal status, surgery, grade, hormone receptor and HER2 status, chemotherapy regimen, and undertreatment showed that obese patients (BMI 30.0–34.9) had similar prognoses to that of patients with a BMI<25 (reference group) in terms of recurrence (HR 1.08 [95% CI 0.9–1.3]; p=0.41), BCM (HR 1.02 [0.81–1.29]; p=0.85), and OM (HR 0.97 [0.78–1.19]; p=0.747). Patients with severe obesity (BMI≥35) had a significantly increased risk of recurrence (HR 1.26 [1.00–1.59]; p=0.05), BCM (HR 1.32 [1.00–1.74]; p=0.05), and OM (HR 1.35 [1.06–1.71]; p=0.02) compared to our reference group (Table). The prognostic effect of severe obesity did not vary by subtype. Conclusions: Severely obese patients treated with anthracyclines and taxanes present a worse prognosis regarding recurrence, BCM, and OM than patients with a BMI<25. The magnitude of the harmful effect of BMI was similar across subtypes. [Table: see text]
Increased expression of folate receptor-α (FRA) in triple-negative breast cancer: A potential therapeutic target.
Authors: Crozier Jennifer A. , Necela Brian M. , Thompson E Aubrey , Geiger Xochiquetzal , Moreno-Aspitia Alvaro , McCullough Ann E. , Pockaj Barbara A. , Cunliffe Heather , Sun Zhifu , Kalari Krishna R. , Kachergus Jennifer M. , O'Shannessy Daniel J. , Maltzman Julia D. , Ballman Karla V. , Andorfer Cathy A. , Perez Edith A. 
Published: March 2020

1037 Background: Folate receptor alpha (FRA the product of the FOLR1 gene) has been identified as a potential prognostic and therapeutic target in a number of cancers. A correlation has been shown between intense expression of FRA in breast tumors and poor prognosis, yet little is known about FOLR1/FRA expression across clinically relevant breast cancer subtypes. Methods: 131 breast cancer tumors including 4 benign, 33 ER+, 26 HER2+, and 68 triple negative (TN) were constructed into tissue microarrays (TMAs). FRA expression was analyzed by immunohistochemistry (IHC) using a high affinity FRA antibody. Tumor membrane staining intensity was scored by a pathologist as negative (0), weak (1+), moderate (2+) and strong (3+). The percent of cells within each tissue core stained at each intensity was recorded to calculate an H-score. The H-score is a weighted score that captured both the proportion of positive staining and intensity for each tumor. H-score values can range from zero (no membrane staining) to a maximum of 300 (100% membrane staining at 3+). H-scores for each patient sample were averaged over 3 TMA cores. The mean H-scores for each tumor subtype and the percentage of 3+ staining in >30% of tumor cells were compared by a Mann-Whitney test. The distribution of FOLR1 mRNA was completed using a TCGA RNA-seq dataset from 691 breast tumors classified as ER+, HER2+ and TN. FOLR1 levels of TN versus ER+ and HER2+ were compared by a Mann-Whitney test. Results: The mean H-score for the benign tumors was 0, ER+ (13.31), HER2+ (39.36), TN (119.02). The median H-score for the benign tumors was 0, ER+ (0), HER2+ (7.5), TN (127.5). The TN tumors mean and median H scores were significantly higher than benign, ER+ or HER2+ (p<0.001). The largest percentage of 3+ staining in >30% of tumor cells was observed in TN tumors (36.7%) and lowest in ER+ tumors (0%) (p<0.001). TN tumors had significantly higher levels of FOLR1 mRNA compared to ER+ and HER2+ subtypes (p<0.0001). Conclusions: Our data indicate that expression of FRA is highly prevalent in TN tumors and is supported by FOLR1 mRNA levels. Anti-FRA therapy may represent an important therapeutic intervention in TNBC who to this point have no active targeted treatment options.
A phase III, open-label, randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes: Subgroup analyses.
Authors: Kaufman Peter Andrew , Cortes Javier , Awada Ahmad , Yelle Louise , Perez Edith A. , Wanders Jantien , Olivo Martin S. , He Yi , Dutcus Corina , Twelves Christopher 
Published: March 2020

1049^ Background: This phase III study, comparing eribulin versus capecitabine, showed a non-significant trend for superior overall survival (OS; hazard ratio [HR] 0.88 [95% confidence interval (CI) 0.77, 1.00]; p = 0.056) but not progression-free survival (PFS; HR 1.08 [95% CI 0.93, 1.25]; p = 0.31). Pre-specified exploratory subgroup analyses previously presented showed that patients with triple-negative, ER-negative or HER2-negative disease may have a greater benefit in OS with eribulin compared with capecitabine. Here we present further pre-specified exploratory analyses of OS and PFS. Methods: Patients (eribulin n=554; capecitabine n=548) with locally advanced or MBC had received ≤3 prior chemotherapy regimens (≤2 for advanced disease), including an anthracycline and a taxane. Patients were randomized (stratified for geographic region and HER2 status) 1:1 to 21-day cycles of eribulin mesylate 1.4 mg/m2 i.v. on days 1 and 8 or capecitabine 1.25 g/m2BID orally on days 1-14. Further pre-specified exploratory subgroups included: age; receptor status; number and setting of prior chemotherapy regimen(s); sites of disease; number of organs involved; and time to progression after last chemotherapy. Results: From analyses for OS, patients with only non-visceral disease (HR 0.51; 95% CI 0.33, 0.80), with >2 organs involved (HR 0.75; 95% CI 0.62, 0.90), who had progressed >6 months after last chemotherapy (HR 0.70; 95% CI 0.52, 0.95), or who had received an anthracycline and/or a taxane in the metastatic setting (HR 0.84; 95% CI 0.72, 0.98), appeared to benefit more from treatment with eribulin compared with capecitabine. For OS, in no subgroup was a trend favoring capecitabine seen. Data for other pre-specified subgroups for both OS and PFS will be presented. Conclusions: In addition to patients with triple-, ER-, or HER2-negative disease, further pre-specified exploratory analyses suggest that other patient subgroups may particularly benefit from treatment with eribulin; further studies are warranted to address these hypotheses. Clinical trial information: NCT00337103.
Phase III trial of nilotinib versus imatinib as first-line targeted therapy of advanced gastrointestinal stromal tumors (GIST).
Authors: Blay Jean-Yves , Shen Lin , Kang Yoon-Koo , Rutkowski Piotr , Qin Shukui , Nosov Dmitry , Novick Steven C. , Taningco Lilia , Mo Shuyuan , Reichardt Peter , Demetri George D. 
Published: March 2020

10501^ Background: Nilotinib (N) is a Bcr-Abl, KIT, and PDGFR tyrosine kinase inhibitor. This Phase III trial compared N and imatinib (I) as first-line therapy of advanced GIST. Accrual was stopped when a futility boundary was crossed at interim analysis (IA). This final analysis of the core study examined the effect of mutation on outcomes. Methods: Patients (pts) with unresectable and/or metastatic GIST who had no prior antineoplastic therapy or had recurrence ≥6 months (mos) after adjuvant I were randomized 1:1 to open-label N 400 mg bid or I 400 mg qd (400 mg bid for KIT exon 9 mutants). The primary endpoint was progression-free survival (PFS) per adjudicated central review. Enrollment targeted 736 pts to observe 375 events, yielding 90% power to detect a hazard ratio (HR) of 0.71 (median, 28 [N] and 20 [I] mos) with two-sided 5% type I error. Prior to IA, crossover was allowed only for pts with progressive disease (PD); after IA, pts on N with or without PD were offered I. Results: At IA, the PFS HR for N vs I of >1.111 suggested a low probability of N superiority to I. Final analysis was performed in 644 pts; both PFS and OS favored I. In subgroup analysis of 401 pts who had mutational data, there was a large PFS difference favoring I in KIT exon 9 mutants, but similar PFS in KIT exon 11 mutants (Table). Based on immature data, OS favored I in all mutants. Conclusions: The IA showed N could not be superior to I for PFS in the overall population as first-line targeted therapy for pts with advanced GIST. PFS of N and I differed according to molecular subtypes, with PFSfavoring Iin KIT exon 9 mutants but roughly similar in exon 11 mutants. Clinical trial information: NCT00785785. [Table: see text]