bluuebunny/crossref_metadata_2025_split huggingface dataset:
Navigation-assisted surgery for bone and soft tissue tumors with bony extension.
Authors: Ieguchi Makoto , Hoshi Manabu , Takada Jun , Hidaka Noriaki , Shigeoka Yasushi , Nakamura Hiroaki 
Published: March 2020

10073 Background: In recent times,minimally invasive surgery, such as endoscopic surgery, has gained a lot of popularity.The navigation system was introduced to orthopedic surgery in the 1990s. These days, computed tomography (CT)-based navigation systems are commonly used in spine and joint replacement surgery because of their precision. The aim of our study was to evaluate the accuracy and efficacy of navigation-assisted excision of bone and soft tissue tumors. Methods: From January 2006 to December 2009, we performed navigation-assisted surgery in 16 patients (11 men and 5 women; mean age, 39 years; range, 13-70 years). We diagnosed 9 benign bone tumors and 7 malignant bone and soft tissue tumors. In 2 patients, the malignant soft tissue tumors infiltrated the adjacent bones. We performed excisional biopsies for the benign tumors and en bloc excisions for the malignant tumors. In all the cases, the point registration method was used with 10 skin markers that were placed around the tumor. Each excisional difference between the preoperative and postoperative plans was evaluated histologically or by postoperative CT. Results: The mean preoperative registration matching time was 12.8 min (range, 8-25 min). The total mean preparation time was 24 min (range, 16-35 min). The mean accuracy of this system, which was determined using the skin markers, was 0.93 mm (range, 0.6-1.5 mm). All biopsied and excised specimens were evaluated by pathologic examination and postoperative CT imaging. The mean difference between the planned margin and postoperative CT or the excised histological specimen was 0 to 4 mm. The mean follow-up period was 53.2 months (range, 10-70 months). There were no local recurrences, except for a case of chordoma that required excision of skip metastases and a case of extraskeletal osteosarcoma, in which the patient died from the disease. Conclusions: We report our experience with navigation-assisted surgery for bone and soft tissue tumors performed using skin markers. Navigation-assisted surgery was indicated in the case of sufficiently reliable, accurate, and minimally invasive resections.
Relationship of CUL4A gene underexpression and prognosis in localized high-risk soft tissue sarcoma (STS) patients of limbs or trunk wall.
Authors: Martin Broto Javier , Lopez-Pousa Antonio , Ramos Rafael , Gronchi Alessandro , Casali Paolo Giovanni , Gutierrez Antonio , Picci Piero , Ferrari Stefano , Cruz Josefina , Luna Fra Pablo , Casado Antonio , Cubedo Ricardo , Lasso Roberto , Poveda Andres , De Juan Ana , Balana Carmen , Calabuig Silvia , Obrador Antonia , Lopez-Guerrero Jose Antonio 
Published: March 2020

10079 Background: Genes involved in cell cycle checkpoints and chromosome stability seem to be relevant in distant metastases appearance in STS. CUL4A is an E3 ubiquitin ligase that has been related to both p16 activation and maintenance of genomic stability. Expression of CUL4A has been scarcely described in some tumors with divergent outcome and there are no publications regarding its expression in STS patients. We previously showed that protein underexpression of CUL4A in metastatic STS was related to poor survival. Methods: The expression level of CUL4A was determined by quantitative qPCR and was retrospectively performed in a subset of 39 high-risk (grade 3, deep tumours and > than 5 cm) localized STS of limbs or trunk wall patients for which histological material and clinical data were available. Patients of this series were enrolled prospectively into a randomized clinical trial conducted by the Italian and Spanish sarcoma groups (ISG-GEIS 0101) comparing 3 vs 5 cycles of epirrubicin and ifosfamide. Differences in PFS, RFS, and OS were calculated using log-rank test Results: The median age was 51 years with a median follow-up of 52 months. The pathologic subtypes were undifferentiated pleomorphic sarcoma (35.3%), synovial sarcoma (23.5%) and mixed subtypes (41.2%). Location was distributed as inferior limbs (66.6%), upper limbs (25.5%) and trunk wall (7.9%). No relationship was seen between CUL4A expression and clinical variables (histologic types, location, size or response to neoadjuvant treatment). The expression level of CUL4A was significantly associated with events of progression, 65% vs 32%, p =0.037, for expression values under and over the median respectively. Regarding 4 y actuarial survival, there was a significant worse PFS and RFS for patients underexpressing CUL4A (p=0.041 and 0.009 respectively) and a trend towards worse OS (p=0.056). Conclusions: Expression of CUL4A gene shows a prognostic role in sarcomas within this high risk localized subset of STS patients. The outcome of this exploratory analysis is aligned with our hypothesis that genes implicated in cell cycle regulation and chromosome stability could play a relevant prognostic role in STS.
Phase I, open-label study of olaparib plus cisplatin in patients with advanced solid tumors.
Authors: Balmaña Judith , Tung Nadine M. , Isakoff Steven J. , Graña Begoña , Ryan Paula D. , Rafi Rezvan , Tracy Michael , Winer Eric , Baselga José , Garber Judy Ellen 
Published: March 2020

1009 Background: Olaparib (AZD2281) is an oral PARP inhibitor active in advanced ovarian and breast cancers. We conducted a multicenter, dose-finding study assessing safety/ tolerability of olaparib capsules plus cisplatin in patients (pts) with advanced solid tumors (NCT00782574), for potential use in the neoadjuvant setting. Methods: Pts received 21-day(d) cycles of olaparib, continuously (Cont) or intermittently (Int), plus cisplatin on d1 of each cycle.Each cohort recruited ≥3 evaluable pts with expansion to ≥6 pts if ≥1 had a dose-limiting toxicity. The last cohort was expanded to ensure ≥6 pts completed 4 treatment cycles. Pts who completed 6 combined therapy cycles or who stopped cisplatin due to cisplatin-related toxicity could enter the monotherapy phase (up to 400 mg BID olaparib). Primary objective: safety/ tolerability of ≥4 combined cycles; secondary objectives: pharmacokinetics, antitumor activity. Results: 54 pts received treatment; pts had breast (n=42), ovarian (n=10), pancreatic (n=1) or peritoneal (n=1) cancer. Median number of prior regimens = 4 (1–13). C2, C4 and C6 enrolled >6 pts. Most common grade (G) 3/4 AEs: neutropenia (n=9; 16.7%), leukopenia (n=4; 7.4%), anemia (n=3; 5.6%), vomiting (n=3; 5.6%). In C1–C5, 3 pts had AEs leading to discontinuation: 1 in C2 (thrombocytopenia); 2 in C3 (fatigue; complex migraine, dyspnea). In C6, all pts have ended combination phase and no G3/4 hematologic AEs were seen. Overall, 46% of pts had a dose reduction; 32% due to hematologic AEs. There were no drug-related deaths. 35 pts (65%) completed ≥4 combined cycles (C6, n=8). 18/54 evaluable pts (33%) had an objective response (complete, n=1; partial, n=17); 23 (43%) achieved stable disease. 7 pts (13%) had durable responses on monotherapy for ≥1 year. PK and BRCA1/2 data will be presented. Conclusions: Hematologic AEs led to dose reductions + schedule changes of olaparib with cisplatin 75 mg/m2. Tolerability improved with cisplatin 60 mg/m2. Antitumor activity was seen during combination and olaparib monotherapy phases, with some long responders. [Table: see text]
DNA repair metagene signature as a prognostic and predictive factor in molecular breast cancer subtypes.
Authors: Santarpia Libero , Iwamoto Takayuki , Di Leo Angelo , Hayashi Naoki , Stampfer Martha , Guarducci Cristina , Symmans William Fraser , Hortobagyi Gabriel N. , Pusztai Lajos , Giampaolo Bianchini 
Published: March 2020

1012 Background: We aimed to assess the prognostic and predictive role of DNA repair genes in breast cancer (bc) molecular subtypes. Methods: We evaluated Affymetrix gene expression profiling from untreated N- patients (N = 684), neoadjuvant treated tumors with taxanes- (N = 320), anthracyclines- (N = 211), and cisplatin- (N = 22) containing regimens. We assessed within 3 BC molecular subgroups (ER+/HER2-, HER2+, and ER-/HER2-) bimodality distribution, prognosis by association with distant relapse (N = 454, N = 105, and N = 125) and predictive value for likelihood of pathological complete response (pCR) (N = 208, N = 105, and N = 240). Moreover, we explored the function of relevant genes in BC cell lines. Results: Three genes (ERCC2, XRCC3, and RECQL4) showed bimodality in each bc subtype. Eight genes were associated with poor prognosis (including RECQL4) and 1 gene with good prognosis (ATM) [P < .0001] only in ER+/HER2- tumors. Our results suggest a subtype and treatment specific association with pCR although they did not satisfy stringent criteria for false discovery correction. In ER-/HER2- mismatch repair (MR) (MSH2 and MSH6) and MTMR15 genes were associated with response and resistance to taxane-containing regimens, respectively. TOP2A was the only gene associated with response to anthracycline but not taxanes in HER2+ tumors. RECQL4 had a positive trend with higher pCR in both ER+ and ER-/HER2- tumors. In in vitro studies we found that RECQL4 interacts with PARP1 and that the expression of these genes was correlated with sensitivity to chemotherapy and PARP inhibitors. Conclusions: We identified MR genes as potential predictive markers of response to taxanes-based regimens in ER-/HER2-. A novel gene RECQL4 showed bimodal distribution, prognostic value, and a trend for predictive association with response to taxanes-based chemotherapy, which was also confirmed by in vitro analysis. ATM deserves further evaluation as prognostic marker in ER+/HER2-.
Cancer gene profile of metastatic breast cancer.
Authors: Meric-Bernstam Funda , Frampton Garrett , Ferrer-Lozano Jaime , Yelensky Roman , Palmer Gary A. , Cronin Maureen T. , Stephens Philip J , Hale Katherine Stemke , Barrera Juan , Burgues Octavio , Lluch Ana , Mills Gordon B. , Gonzalez-Angulo Ana M. 
Published: March 2020

1015 Background: There is great interest in using genomic information to guide therapy selection in cancer patients. The aim of this study was to determine the spectrum of genomic alterations identified in MBC patients, and evaluate the concordance of alterations between primary and recurrent tumors. Methods: We performed comprehensive profiling on formalin-fixed paraffin embedded samples from 42 patients with MBC using a targeted next generation sequencing (NGS) assay in a CLIA laboratory (Foundation Medicine). Genomic libraries were captured for 3,230 exons in 182 cancer related genes plus 37 introns from 14 genes often rearranged in cancer and sequenced to an average depth of 390X with 99% of bases covered >100X. In total 30 primary and 37 recurrent tumors were profiled, including 3 separate recurrences in 1 patient and matched primary-recurrences in 22 patients. Point mutations, indels, copy number alterations and rearrangements were assessed. Alterations that are targetable with established or investigational therapeutics were considered “actionable”. Results: At least 1 genomic alteration was identified in all but 2 breast samples (both primary tumors). Point mutations were identified in several cancer-related genes including PIK3CA, TP53, PTEN, CDH1, ARID1A, AKT1, NF1, FBXW7 and FGFR3. Amplification was observed in HER2; 11 of 12 HER2 IHC positive samples were found to have HER2 gains by NGS; in addition, a HER2 gain was identified by NGS in a HER2- (1+ IHC) sample. Amplification of PIK3CA, IGF1R, FGFR2, AKT2, MDM2, and MCL1 plus a CDKN2A homozygous deletion were also identified. While the majority of known driver alterations (85%) were concordant in the matched pairs of primary and recurrent tumors, in 11 of 22 sets there was at least 1 discordant driver alteration, and these included both gains and losses of potential therapeutic targets. Overall 32 of 42 patients (76%) had an actionable genomic alteration. Conclusions: Genomic profiling of breast cancer samples reveals genomic alterations in most metastatic breast cancer patients. Over three quarters of patients have actionable findings, suggesting that genomic profiling may assist in individualized pathway-directed therapy.
A gene expression signature of MEK pathway activation to predict survival in triple-negative breast cancer.
Authors: Balko Justin M. , Sanders Melinda , Kuba Maria Gabriela , Pinto Joseph A. , Doimi Franco F. , Gomez Henry Leonidas , Arteaga Carlos L. 
Published: March 2020

1024 Background: Tumor cell proliferation measured by Ki67 in the surgically removed tumor after neoadjuvant chemotherapy (NAC) has been shown to predict patient outcome in breast cancer. It is unclear from these studies if breast cancer subtype may account in part for the predictive ability of Ki67. Thus, we tested whether Ki67 score in the surgically-resected residual tumor (RT) after NAC predicted outcome in a cohort of triple negative breast cancer (TNBC). Gene expression profiling was performed to identify molecular subtype and test the association with gene modules indicative of signaling pathway activation. Methods: Ki67 was scored in the RT of 89 patients with stage II-III TNBC (ER/PR/HER2 negative by IHC at diagnosis) that had been treated with NAC. Expression levels for 450 genes were quantified by Nanostring. Ki67, node and menopause status, age, therapy type (± taxanes), molecular subtype, and gene expression scores were tested for association to RFS and OS using univariate and multivariate CoxPH models. Results: Ki67 score in the post-NAC RT demonstrated a wide range (1.5-77.7%; median: 36.2%). Twenty seven % of RTs were 3+ HER2 by IHC. Molecular subtype in the RT was as follows: 64% Basal-like; 20% HER2-enriched; 6% LumA; 6% LumB; 4% Normal-like. In univariate analyses to respectively predict RFS and OS, node status (p=0.005 and p=0.02), number of nodes (p=0.003 and p<0.001), and the score of a gene expression module of MEK pathway activation (p=0.04 and p=0.01,) were significant. Basal-like subtype approached significance for RFS (p=0.1) and OS (p=0.05). In multivariate analyses, node status (p=0.002 for RFS and p<0.001 for OS) and MEK pathway activation score (p=0.04 and p=0.01) were significant predictors. Conclusions: Ki67 in the RT after NAC was not predictive of outcome in a cohort of TNBC. However, a gene expression signature of activated MEK was negatively associated with outcome. These data are consistent with the reported preclinical activity of MEK inhibitors against basal-like breast cancer cells and a possible role of this signaling pathway in chemotherapy resistance. They also support deep sequencing studies to identify genetic alterations in the RAS/MEK/MAPK pathway in TNBC.
Impact of surgery and radiation of the primary among women with de novo stage IV breast cancer.
Authors: Dawood Shaheenah S. , Dent Rebecca Alexandra , Gupta Sudeep , Litton Jennifer Keating , Mustafa Rashid , Cortes Javier , Mittendorf Elizabeth Ann , Gonzalez-Angulo Ana M. , Buchholz Thomas A. 
Published: March 2020

1032 Background: The aim of this retrospective study was to determine the impact of surgery(S) and radiation(R) therapy to the primary tumor among patients (pts) with stage IV denovo breast cancer. Methods: The SEER registry was used to identify pts with denovo stageIV breast cancer diagnosed between 1988 and 2008. Pts were divided into 4 groups based on type of treatment to primary tumor: both S+R, S alone, R alone, or no treatment of primary (no S/R). Breast cancer specific survival (BCS) was calculated from the date of diagnosis of breast cancer to the date of death from breast cancer or last follow up. Survival outcomes were estimated by the Kaplan-Meier method, and Cox models were fit to determine the association between treatment of primary and survival after adjusting for potential confounders (e.g age, grade, hormone receptor and race). Results: 25903 pts were identified; 4640 (17.9%) S+R, 6556 (25.3%) S, 4467 (17.2%) R, and 10240 (39.5%) no S/R. 1183 (4.6%) had surgery to sites other than the primary. Median age was 63 years. Median follow-up was 14 months. Median BCS was 23 months. Median BCS among pts who underwent S+R, S, R and no S/R was 36 months, 31 months, 18 months and 15 months respectively (p<0.0001). Among pts who underwent S+R, median BCS among pts who did and did not have surgery to sites other than primary was 50 months and 41 months respectively (p=0.029). Of the pts treated with S+R 10-year BCS was 18%. In the multivariable model compared to women who were in the no S/R group those who underwent S (HR= 0.59, 95%CI 0.55- 0.62,p<0.0001) and S+R (HR=0.51, 95%CI 0.47-0.55,p<0.0001) had decreased risk of death from breast cancer and those who underwent R (HR=1.13, 95% CI 1.04-1.21, p=0.002) had an increased risk of death from breast cancer. Pts who had surgery to sites other than the primary tumor had decreased risk of death from breast cancer compared to those who did not (HR=0.80, 95%CI 0.72-0.89,p<0.0001). Conclusions: Our results indicate that S+R of the primary breast tumor among pts with denovo stage IV breast cancer maybe associated with a decreased risk of death from breast cancer. A select subgroup of pts who undergo S+R may also benefit from surgery to sites other than the primary which may afford them maximum survival advantage.
Comprehensive investigation of adverse event (AE)-related costs in patients with metastatic breast cancer (MBC) treated with first- and second-line chemotherapies.
Authors: Hurvitz Sara A. , Guerin Annie , Brammer Melissa G. , Guardino Ellie , Zhou Zheng-Yi , Kaminsky Michael S , Wu Eric Q. , Lalla Deepa 
Published: March 2020

1037 Background: MBC is incurable and managed with ongoing therapy. This study examined the incremental costs of chemotherapy-associated AEs in MBC. Methods: The PharMetrics Integrated Database (2000-2010) was used to identify MBC pts treated either 1st or 2nd line with a taxane (T) (paclitaxel or docetaxel) or capecitabine (C)-based regimen for ≥30 days (defined as a treatment episode (TE)). Incremental costs attributable to AEs were assessed by comparing costs incurred during TEs with and without AEs. AEs were identified using medical claims with a diagnosis for ≥1 event of interest (e.g., infections, fatigue, anemia, neutropenia). Pt characteristics were balanced between comparison groups (with and w/o AEs) using inverse probability weighting method. Incremental monthly costs due to AEs were estimated during the TEs and included the following cost components: inpt (IP), outpt (OP), emergency room (ER), other medical service, pharmacy costs (chemotherapy and other drugs), and total healthcare costs. Statistical comparisons were conducted using Wilcoxon tests. Results: 3,222 women (mean age=57) received a T or C as 1st or 2nd-line therapy for MBC. Of the 2,678 1st-line pts, 69.7% received T and 30.3% with C; average monthly total costs ranged from $9,159 to $10,298. AEs were commonly seen in pts treated with 1st-line T and C (94.6% and 83.7%). On average, the total monthly incremental cost associated with AEs was 38% higher ($3,547) for T and 9% higher ($854) for C. IP and other drug costs accounted for a majority of these costs. Of 1,084 2nd-line pts, 66% received T and 34% C, with average monthly total costs ranging from $5,950 to $12,979. 94.4% of T pts and 84% of C pts in the 2nd-line had an AE. The average total monthly incremental cost associated with AEs for T was $5,320 and $4,933 for C (69.5% and 82.9% higher vs pts w/o AEs). Pharmacy costs accounted for a majority of increased costs seen in pts with AEs treated with T; IP and OP accounted for a majority of these costs in pts treated with C. Conclusions: This is the 1st study assessing costs associated with AEs for tx of mBC. AEs are associated with a substantial economic burden that is mainly explained by increased IP, OP, and pharmacy costs.
Association between vitamin D deficiency and breast cancer histology: A retrospective database review.
Authors: Bhargava Ranjana S. , Zhu Yue , Weinstock Chana , Hanna Nader , Tkaczuk Katherine Hanna , Bao Ting , Chumsri Saranya 
Published: March 2020

1039 Background: Vitamin D (Vit D) deficiency has been shown to be associated with a higher risk of developing breast cancer. Inverse association has also been shown between vit D level and tumor size. However, the association between vit D deficiency and breast cancer histology remains unclear. Preclinical data has suggested that vit D plays an essential role in the terminal differentiation of breast cells. Thus, we hypothesize that vit D deficiency would be associated with estrogen receptor-negative tumors, particularly triple-negative breast cancers (TNBC) which are associated with aggressive clinical course. Methods: We conducted a retrospective database review to obtain information including age, race, tumor histology, size, stage, and vit D levels in newly diagnosed breast cancer patients at University of Maryland Greenebaum Cancer Center. Results: 150 patients presented between July 2008 and August 2011 were included in this analysis. Average age at diagnosis was 57 (range 30-87), and 56% of patients were African American. Overall, 80% of the patients were vit D deficient at diagnosis, with levels < 30 ng/ml. African-American patients were more likely to be severely vit D deficient with levels < 10 ng/ml compared to Caucasians (33% vs. 7.5%, p= 0.0002). Patients with TNBC were more likely to be vit D deficient at diagnosis compared to hormone receptor-positive patients (93% vs. 76%, p =0.015). These patients also had the lowest mean (18) and median (16) of vit D levels compared to all other patients. This difference is also statistically significant in multivariate analysis when adjusted for age, race, and stage (OR 3.96; p=0.04). Regardless of the ER/PR status, Her 2 negative patients were more vit D deficient compared to Her 2 positive patients (86% vs. 61%, p=0.001). Unlike previous studies, no correlation was seen between tumor size and vit D levels. Furthermore, there is also no association between stage, nodal involvement, or Ki67 and vit D level. Conclusions: Vit D deficiency is common among patients with newly-diagnosed breast cancer, particularly African American patients. Patients with TNBC have a significantly higher likelihood of being vit D deficient than patients with other histological subtypes.