bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene scoring model to predict recurrence in low- and intermediate-risk uterine endometrial cancer: Establishment of uterine print.
Authors: Chiyoda Tatsuyuki , Ito Yoichi M , Kataoka Fumio , Yamagami Wataru , Nomura Hiroyuki , Tsuda Hiroshi , Tanaka Hideo , Takano Masashi , Nishimura Sadako , Iguchi Yoko , Hashimoto Shiho , Yoshihama Tomoko , Susumu Nobuyuki , Aoki Daisuke 
Published: March 2020

5590 Background: Endometrial cancers (ECs) classified as low-, intermediate-, and high-risk, based on clinical and pathological features (CPF: Lurain, 2007) associated with 5%, 15%, and 25% risk of recurrence, respectively. The need for adjuvant chemotherapy in intermediate-risk patients is controversial. We examined whether gene expression profiling can more accurately predict the prognosis of ECs, excluding the CPF-based high-risk group. Methods: Tumor specimens were obtained from 136 ECs including 14 recurrences, excluding high-risk cases. Gene expression profiles were achieved using a custom array consisting of 85 genes associated with EC recurrence and 20 internal controls that were previously screened. We established the gene scoring model (GSM) for recurrence by the logistic regression model in randomly selected 68 ECs including 7 recurrences, and evaluated the accuracy of GSM in other 68 ECs including 7 recurrences. This process was repeated 100 times. We calculated the mean accuracy of GSM and compared it with the accuracy of CPF. We also compared GSM and CPF with respect to progression-free survival (PFS) by use of the log-rank test. Results: Median age of all cases was 58 (29-86) years, and stage, histologic grade, and risk classification based on CPF were as follows: (I, 107; II, 15; III, 14), (G1, 69; G2, 57; G3, 10), and (low, 67; intermediate, 69). The median follow-up period was 1830 (1626-3444) days. The GSM was established based on the expression of 4 genes (PRCC, SPC25, PXDN, and LBXCOR1) and 10 internal controls. The area under the receiver operating characteristic curve of GSM to predict recurrence was 0.87 in 68 test cases. Based on the CPF, 68 cases were classified as 30 low-risk and 38 intermediate-risk, and the sensitivity and specificity of CPF was 86% and 48% each in the 68 test cases. When sensitivity of GSM was fixed at 86%, specificity of 67% was achieved, and 68 cases were classified as 42 risk (-) and 26 risk (+). PFS was significantly related with GSM (p = 0.006); however, it was not related with CPF (p = 0.09). Conclusions: GSM can predict the prognosis of ECs (low- and intermediate-risk) more precisely than CPF.
Ethnic differences in tumor proliferation in women with early-stage breast cancer.
Authors: Kalinsky Kevin , Lim Emerson A. , Andreopoulou Eleni , Desai Avni Mukund , Wang Antai , Maurer Matthew A. , Crew Katherine D. , Greenlee Heather , Hibshoosh Hanina , Sparano Joseph A. , Hershman Dawn L. 
Published: March 2020

560 Background: Hispanic women have a higher mortality rate and lower incidence of breast cancer (BC) compared to Caucasian women. Studies report higher tumor proliferation in African American (AA) women compared to Caucasian women. The 21-gene assay (OncotypeDX) Recurrence Score (Score) is based on the expression of 16 cancer related genes, including 5 proliferation genes that are grouped to provide the proliferation axis score (PAS). We evaluated the differences in the Score and PAS between Hispanic and Caucasian women with early-stage BC in a matched cohort analysis. Methods: Women with early-stage BC who had a Score obtained from 2005- 2011 were identified. Hispanic women were matched to Caucasians in a 1:2 ratio, based on age (+/- 10 years), stage, and nodal status. Lymphovascular invasion (LVI) and grade were collected. The Score result, 10-year distant recurrence, ER/PR/HER2 expression, and PAS were obtained from the OncotypeDX assay. Assuming equal variances, we expected > 90% power to detect a difference in the mean PAS between Hispanic and Caucasian women Results: We identified 219 women who had OncotypeDX testing (74 Hispanic: 145 Caucasian). Of the 74 Hispanic women, 84% were from the Dominican Republic or Puerto Rico. Mean age was similar between groups (56.3 and 56.8). All but 8 patients were node(-). Mean PAS was higher in Hispanic (5.53, range: 3.9-7.8) vs Caucasian women (5.26, 3.7-7.3) (p=0.03, 95% CI: 0.03-0.51). The mean Score was 18.3 (0-54) and 16.3 (1-50) for Hispanic vs Caucasian women. There was no statistical difference in Score (p= 0.17) or 10-year distant recurrence (p=0.13) between groups. No differences were observed in median ER (9.8% vs 9.9%: Hispanic vs Caucasian), PR (7.3% vs 7.6%), or HER2 (9.1% vs 9.0%) by RT-PCR. Rates of LVI and grade 3 tumors were also not statistically different. Conclusions: Similar to higher PAS in AA women, Hispanic women with ER/PR(+), HER2(-) early-stage BC have higher tumor proliferation markers, measured by RT-PCR in the Oncotype DX assay, than Caucasian women. This may contribute to ethnic differences in BC mortality. We plan to evaluate ethnic differences in the 5 single PAS genes (CCNB1, MKI17, MYBL2, BIRC5, AURKA) to determine which are driving proliferation differences.
Neoadjuvant chemotherapy followed by chemoradiation in selected locally advanced squamous cervical cancer.
Authors: Cueva Juan Fernando , Martinez Lago Nieves , Vieito Maria , Gonzalez Patino Ezequiel , Curiel Garcia Maria Teresa , salvador Garrido Nuria , Palacios Ozores Patricia , Candamio Sonia , López López Rafael 
Published: March 2020

5603 Background: Although there has not been a direct comparison between neoadjuvant chemotherapy followed by chemoradiation with chemoradiation alone, neoadjuvant chemotherapy is active in squamous cervical cancer. Methods: In this one arm phase II trial we accrued 25 patients from 2007 to 2012 diagnosed with squamous cervical cancer deemed poor candidates to initial chemoradiation (decided by a multidisciplinary committee). Patients had > 18 years of age, PS 0-1, adequate organ function an gave informed consent. They received neoadjuvant paclitaxel and cisplatin (80 and 33 mg/m2 respectively) on days 1,7, 15 of every 28 for two cycles and then external radiation in 1.8 Gy/ fraction with concurrent weekly cisplatin 40 mg/m2followed by brachytherapy in 5-6 applications. Dose intensity and toxicity was accrued, and both after neoadjuvant and chemoradiation patients were evaluated by RECIST 1.1 criteria for response with CT scan and pelvic MNR. Results: Baseline characteristics of the patients are listed in Table. 24 patients were evaluable for efficacy and safety. Response rate after neoadjuvant chemotherapy was 84 % (complete and partial responses in 24 and 60% of patients, respectively), without progression disease. Response rate after radiochemotherapy was 93 % (complete and partial responses in 52 and 41% of patients, respectively). After a mean of 29 months of follow up, 11 patients (45%) thus far have developed recurrent disease. Median progression-free survival and overall survival were 33 (23- 42) and 34+ m (29 – not reached). Treatment was well tolerated, without toxicities grade 3-4. Conclusions: Our weekly cisplatin-paclitaxel neoadjuvant regimen has been feasible and very effective in terms of dose delivery, tolerance and radiological responses without compromising definitive treatment with chemoradiation. If this approach is superior than the standard chemoradiation alone in this population should be explored in a randomized trial. [Table: see text]
Longitudinal quality of life (QOL) and sexual functioning in women undergoing pelvic exenteration for gynecologic malignancies.
Authors: Soliman Pamela T. , Sun Charlotte C. , Westin Shannon Neville , Ramondetta Lois M. , Bodurka Diane C. , Bradford Andrea 
Published: March 2020

5608 Background: Pelvic exenteration (PE) is en bloc resection of the pelvic organs including bladder, vagina, and rectum to treat central recurrence of a gynecologic malignancy. While this procedure has high morbidity, it is the only option for cure in some patients. The goal of this study was to assess QOL and sexual functioning in women who underwent PE with vaginal and/or bladder reconstruction. Methods: All patients were enrolled prior to PE. Surveys included the SF-12 (functional status), BIS (body image), SAQ (sexual functioning), SWD (satisfaction with decision), CES-D (depression), Stoma QOL, and DUFSS completed preoperatively (preop) and post-operatively at 4-6 wks, 6 mo, 1 yr, and 2 yrs. Descriptive statistics, chi-square, Mann-Whitney, and Kruskal Wallis tests were used to evaluate the data. Results: Between 2008 and 2012, 39 women participated. Median age was 56.7 yrs. Mean physical functional status scores (SF-12) declined through 6 mo postop, with improvements at 1 and 2 yrs (p=.002) but did not reach preop levels. SF-12 mental functioning scores declined immediately postop but returned to baseline by 6 mo. BIS was significantly worse at 1ys (p=0.02) and 2 yrs (p=0.025). Mean depression (CES-D) scores decrease but remained above the clinical cutoff of 17 at 6 mo. Poor sexual function was noted preop and did not improve. High scores for social support (DUFSS) remained constant. Stoma QOL improved in the first 2 yrs but not significantly. Pts reported high satisfaction with the decision to undergo PE, which did not change over time. Conclusions: While a majority of women remained satisfied with their decision to undergo PE, the procedure was associated with depression, worsening physical functioning and poor body image despite stable social support. Interventions are currently under development to improve QOL in this patient population. [Table: see text]
Competing risks of death in NCIC CTG MA.27 adjuvant exemestane versus anastrozole.
Authors: Chapman Judy-Anne W. , Shepherd Lois E. , Ingle James N. , Muss Hyman Bernard , Pritchard Kathleen I. , Gelmon Karen A. , Whelan Timothy Joseph , Elliott Catherine , Goss Paul E. 
Published: March 2020

564 Background: Our group previously examined if baseline patient/tumor characteristics, or prior treatment affected cause of death in MA.17, a placebo controlled extended adjuvant trial of the aromatase inhibitor (AI) letrozole. We now examine factor effects on all cause mortality in MA.27. Methods: MA.27 was an adjuvant phase III superiority trial of 5 yrs of exemestane vs anastrozole, in ER+ postmenopausal breast cancer accrued between 2003 and 2008; event free survival was similar. We examined by intention-to-treat, the multivariate time-to-breast cancer-specific (BrCa), cardiovascular (Cardio), and other causes (OT) of death with log-normal survival analysis adjusted by treatment and stratification factors (lymph node status, adjuvant chemotherapy, celecoxib, aspirin, and trastuzumab). We tested whether factors were associated with 1) all cause mortality, and if so, 2) cause-specific mortality. We also fit step-wise forward cause-specific adjusted models. Results: 7,576 women (median age 64.1 years; 5417 (71.5%) <70 yrs and 2159 (28.5%) >70 yrs) were enrolled and followed for a median of 4.1 yrs. The 432 deaths comprised: 187 (43.3%) BrCa, 66 (15.3%) Cardiovascular, and 179 (41.4%) OT MA.27 therapy was not associated with mortality (p=0.84). Five baseline factors were differentially associated with cause of death. Older age was associated with greater BrCa (p=0.03), Cardio (p<0.001), and OT (p<0.001) mortality. Pre-existing cardiovascular history led to worse Cardio mortality (p<0.001). Worse ECOG performance status led to worse OT death (p<0.001). T1 tumors were associated with less BrCa mortality (p<0.001). PgR+ tumors were also associated with less BrCa mortality (p<0.001). There were fewer BrCa deaths with Node –ve disease (p<0.001), ER+ tumors (p=0.001) and without adjuvant chemotherapy (p=0.005); there was worse Cardio mortality (p=0.01) with receipt of trastuzumab; worse OT (p=0.03) for non-whites, and without adjuvant radiotherapy (p=0.003). Conclusions: 56.7% of deaths in MA.27 patients were non-breast cancer related. We showed baseline patient and tumor characteristics, and prior treatment differentially affected cause of death. Clinical trial information: NCT00066573.
Characteristics and clinical outcome of T1 breast cancer: A national multicenter retrospective cohort study.
Authors: Gonçalves Anthony , Classe Jean-Marc , Garbay Jean-Remy , Giard Sylvia , Helene Charytansky , Cohen Monique , Belichard Monique , Faure Christelle , Uzan Serge , Hudry Delphine , Azuar Pierre , Villet Richard , Gimbergues Pierre , Tunon de Lara Christine , Esterni Benjamin , Houvenaeghel Gilles 
Published: March 2020

566 Background: T1N0M0 breast cancer (BC) are generally considered as carrying good prognosis and cancer-specific survival rates after 5 to 10 years are as high as 90 or 95% in many studies. However, they constitute a heterogeneous group and many studies identified biologically-defined at-risk patients within T1 BC. The objectives of our study were to describe the main characteristics of T1a, b, and c (11-15mm) BC and to identify prognostic factors for survival. Methods: We retrospectively collected the medical files of all patients diagnosed with BC who underwent sentinel lymph node biopsy (SLNB) between January 1999 and December 2008 in 13 French sites and examined overall survival (OS) and Relapse-free survival (RFS) in T1a, T1b and T1c 11-15 mm. Results: Among 8,100 women operated, 5,423 had T1 tumors (708 T1a, 2,208 T1b and 2,508 T1c 11-15mm). T1a differed significantly from T1b tumors with respect to several parameters : younger age, more frequent negative hormonal status and positive HER2 status, less frequent lymphovascular invasion (LVI), exhibiting a mix of favorable and poor prognosis factors. After a median follow-up of 60.5 months, OS rate was 97.6% (95CI: 97.1-98) at 60 months, 95.4%(94.5-96.4) at 84 months and 90.7% (85.2-96.4) at 120 months. No significant difference was observed between T1a, T1b and T1c tumors (p=0.335). RFS rates were 94% (95CI: 93.8-95.2), 92.1% [91.1-93.2] and 83.8% (77.6-90.5) at 60, 84 and 120 months respectively. RFS was significantly higher in T1b tumors (95.9%, 95CI: 95-96.9) as compared to T1a (93.2%, 91-95.4) or T1c tumors (93.8%, 92.8-94.9), p=0.0099. In multivariate analysis, SBR tumor grade, hormone therapy and LVI were independent prognostic factors for RFS, while hormone therapy and SBR grade were independently associated with OS. Conclusions: Relatively poor outcome of patients with T1a tumors might be explained by a high frequency of risk factors in this subgroup (frequent negative hormone receptors and HER2 overexpression) and by a less frequent administration of adjuvant systemic therapy (endocrine treatment and chemotherapy). Tumor size might not be the main determinant of prognosis in T1 breast cancer.
Aromatase inhibitor pain syndromes: Classification and determination of specific risk factors—A prospective multicenter cohort study.
Authors: Cottu Paul H. , Laroche Francoise , Pierga Jean-Yves , Coste J , Medkour T , Lotz Jean-Pierre , Beerblock Karine , Tournigand Christophe , Chauvenet Laure , Decleves Xavier , Boussahira D , Batteux F , Borderie F , Perrot Serge 
Published: March 2020

569 Background: Pain is frequent during Aromatase Inhibitors (AIs) treatment for breast cancer and several pain syndromes have been reported but not precisely defined. We developed a prospective multicentre study aiming at classifying AIs-related pain syndromes, comparing their impact on daily life, and identifying their specific determinants for a more targeted prevention approach. Methods: A one-year multicenter cohort prospective study, with 5 pre-scheduled visits, was carried out in early stage breast cancer women, free of pain, starting an AI treatment, recruited from 4 oncology centres. At baseline, clinical data (demography and psychosocial, cancer characteristics and treatments, pain, sleep, rheumatologic examination, cancer-related quality of life), biological data (sex hormones, vitamin D, bone biomarkers, oxidative stress, immunological and inflammatory markers), and genetic polymorphism for pain mechanisms (opioid and serotonin pathways) were recorded. Results: A cohort of 135 women was evaluated. Among them, 77 (57%) developed a pain syndrome along the study period, leading to AIs discontinuation in 12 cases. Five main different types of pain syndromes were identified: joint pain, in 48 women overall over the follow-up (36%), diffuse pain, in 30 women (22%), tendinitis, in 29 women (22%), and neuropathic pain, in 12 women (9%) and mixed types, which were frequent and often transient. Analyses demonstrated that risk factors for developing pain syndromes were baseline anxiety and impaired quality of life, while cancer features, genetic background, inflammation, immunological and sex hormone levels were not involved. Conclusions: In pain-free women with breast cancer starting an AI, risks for developing pain during the first year of treatment are slightly greater than 50%. We identified 5 main pain syndromes, joint and widespread pain being the most frequent. In all instances, initial psychological dimensions (personality, impaired quality of life and anxiety) are identified as major risk factors for pain development.
Randomized phase II placebo-controlled trial of fulvestrant plus vandetanib in postmenopausal women with bone only or bone predominant, hormone receptor-positive metastatic breast cancer (MBC): OCOG Zamboney study—NCT00811369.
Authors: Clemons Mark J. , Cochrane Brandy , Califaretti Nadia , Chia Stephen K. L. , Dent Rebecca Alexandra , Song Xinni , Robidoux Andre , Pond Gregory Russell , Parpia Sameer , Pritchard Kathleen I. , Levine Mark Norman 
Published: March 2020

574 Background: Biomarkers of bone turnover, including urine N-telopeptide (uNTx) and serum C-telopeptide (sCTx) reflect tumor-related bone breakdown and have been used as surrogate measures of response to therapy in trials. Vascular endothelial growth factor (VEGF) levels correlate with extent of bone metastases (BM). We assessed whether vandetanib, an inhibitor of VEGF, epidermal growth factor receptor and RET signalling, improved uNTx response when added to fulvestrant (F) in patients with BM. Methods: Postmenopausal patients with bone only, or bone predominant, hormone receptor positive MBC were randomised to F (500mg IM day 1, 14, 28, then monthly) with either vandetanib (100mg PO OD) (FV) or placebo (FP) until progression. The primary objective was uNTx response (>30% reduction from baseline). uNTx was collected at baseline, weekly to wk 4, at wk 12 and then every 12 wks. Secondary objectives included PFS, OS, RECIST response, pain and toxicity. Results: 61 patients were allocated to FV and 68 to FP. Median age was 59. 18% had received 1 prior chemotherapy regime and 73% prior endocrine therapy for MBC. uNTx response (n=124 pts) was 64% for FV vs. 52% for FP (p=0.20). No difference was detected between groups for median PFS; 6 months for FV vs. 4.8 months for FP, HR=0.93 (95% CI: 0.64 to 1.36). 16 patients died in FV arm vs. 21 in the FP arm, HR=0.71 (95% CI: 0.37 to 1.36). For those patients with measurable disease, clinical benefit rates were 41% and 43%, respectively, p=1.00. Serious adverse events were similar, 3.3% for FV vs. 5.9% for FP. Elevated baseline uNTx (>65 nM BCE/mmol Cr) was prognostic for PFS, HR=1.62 (95% CI: 1.08 to 2.43 and for mortality, HR= 2.4 (95% CI: 1.2 to 4.6). In an exploratory analysis uNTx was predictive of responsiveness to FV for PFS, HR=0.60 when uNTx >65 vs. HR=1.37 when uNTx <65, P = 0.025 for interaction. Conclusions: The addition of vandetanib to F did not improve biomarker response, PFS or OS compared to F alone in patients with bone predominant disease. Exploratory analyses confirmed that baseline bone turnover markers are prognostic for PFS and OS. Clinical trial information: NCT00811369.
Evaluation of the prognostic significance of RACGAP1, Ki67, and TOP2A mRNA expression in high-risk early breast cancer.
Authors: Pliarchopoulou Kyriaki , Gogas Helen , Papadimitriou Christos A. , Wirtz Ralph M , Kouvatseas George , Timotheadou Eleni , Stavridi Flora , Christodoulou Christos , Koutras Angelos , Pisanidis Nikolaos , Pentheroudakis George E. , Bafaloukos Dimitris , Samantas Epaminontas , Kalogeras Konstantine T. , Dimopoulos Meletios A. , Pectasides Dimitrios G. , Fountzilas George 
Published: March 2020

582 Background: Proliferation is a major process in carcinogenesis. RACGAP1 is a protein involved in cell growth regulation and metastasis, Ki67 is a known proliferation marker and TOP2A has a key role in DNA replication and remodeling. The aim of the present study was to explore the prognostic significance of a signature of proliferation markers, such as RACGAP1, Ki67 and TOP2A on disease-free survival (DFS) and overall survival (OS) in high-risk early breast cancer patients. Methods: A total of 1681high-risk breast cancer patients, enrolled in two consecutive phase III trials, were treated with anthracycline-based adjuvant chemotherapy. Formalin-fixed paraffin-embedded tumor tissue samples from 963 of these patients were extracted using a standardized fully automated isolation method for total RNA based on silica-coated magnetic beads, followed by multiplex RT-qPCR for assessing RACGAP1, Ki67 and TOP2A mRNA expression. CALM2 was included in the same reaction, as a reference gene. Results: After a median follow-up of 107 months, 289 patients (30.0%) demonstrated disease progression and 261 (27.1%) patients died. Univariate analysis revealed that poor OS was associated with high RACGAP1 mRNA expression (p=0.0185, log-rank), high Ki67 (p=0.0219), as well as high TOP2A (p=0.0019) mRNA expression, while in multivariate analysis only TOP2A retained significance (Wald’s p=0.008). In an effort to improve prognostic significance, combinations of the expression of two or all three genes were tested, with low mRNA expression of the three genes being associated with improved DFS (HR=0.74, CI=0.56-0.98, p=0.035) and OS (HR=0.60, CI=0.42-0.85, p=0.004). However, in multivariate analysis, none of the combinations retained prognostic significance, except the combination of high RACGAP1 and TOP2A mRNA expression, which was found to be associated with decreased DFS (HR=1.26, CI=0.96-1.63, p=0.092) and OS (HR=1.49, CI=1.10-2.03, p=0.009). Conclusions: High RACGAP1 and TOP2A mRNA expression was found, in multivariate analysis, to be of adverse prognostic significance in high-risk early breast cancer patients treated with anthracycline-containing adjuvant chemotherapy.