bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of recurrence risk by subtype in ≤1 cm breast tumors.
Authors: Colonna Sarah V. , Higgins Ashantice K. , Alvarez JoAnn , Saville Benjamin R. , Lawrence Julia , Abramson Vandana Gupta 
Published: March 2020

1034 Background: Triple-negative breast cancers (TNBC) comprise 15% of breast cancers and lack ER, PR, and HER2 expression. TNBC is biologically aggressive with high rates of recurrence, but little is known about the prognosis of small (≤1cm) TNBCs compared to similarly sized breast cancers with other receptor profiles. The role of adjuvant chemotherapy for TNBC that is ≤1cm remains unclear. Methods: Electronic medical records of all women aged ≥ 18 years with ≤1 cm, node negative, invasive breast cancer from 1997-2007 diagnosed or treated at Vanderbilt or Wake Forest were reviewed. Tumor grade, receptor status, treatment details, and follow up and recurrence information were tabulated. Rates of local and distant recurrence among three different receptor subtype categories, ER+ or PR+, HER2 negative; ER-/PR-, HER2 negative; or any ER/PR, HER2 positive were compared using chi-square tests. Results: 437 women with ≤1cm breast tumors were identified. Women with TNBC not given chemotherapy were more likely to have distant recurrence at 9% compared to 2% for ER+ or PR+, HER2 negative and 4% for any ER/PR, HER2 positive. There were no recurrences among the 14 women with ≤1cm TNBC who received chemotherapy. Conclusions: Based on our two institution review, women with ≤1 cm TNBC are at an increased risk for distant recurrence compared to other subtypes when not treated with adjuvant chemotherapy. Further studies to determine the benefit of adjuvant chemotherapy in this population are needed. [Table: see text]
A multicenter phase I-II trial of weekly paclitaxel and carboplatin plus bevacizumab in women with triple-negative metastatic breast cancer.
Authors: Saloustros Emmanouil S. , Polyzos Aristidis , Christophyllakis Charalampos , Kentepozidis Nikolaos K. , Vamvakas Lampros , Kalbakis Kostas , Agelaki Sofia , Georgoulias Vassilis , Mavroudis Dimitrios 
Published: March 2020

1045 Background: Triple-negative breast cancer cells are unable to repair double stranded DNA breaks and hence have sensitivity to platinum agents. The combination of carboplatin and paclitaxel administered weekly is active and well tolerated. Bevacizumab when added to paclitaxel prolonged progression-free survival in metastatic breast cancer (MBC). We investigated the activity and toxicity of paclitaxel plus carboplatin and bevacizumab in triple-negative MBC. Methods: The study’s primary objective was to estimate the objective response rate [complete (CR) + partial remission (PR)] and toxicity of the combination in women with triple negative MBC who had no prior chemotherapy for metastatic disease. The study followed the Simon's two-stage optimal design with 16 patients initially evaluated for response and toxicity and then expanding to a total of 46 patients. The null hypothesis that the objective response rate is ≤40% could be rejected if the number of CR/PR was ≥23. Paclitaxel 90mg/m2and Carboplatin AUC 2 were administered on days 1, 8, and 15 every 4 weeks, preceded by bevacizumab 10 mg/kg on days 1 and 15. Results: 45 women with triple negative MBC have been recruited thus far. Of them, 12 were premenopausal and 27 had prior (neo-)adjuvant chemotherapy. The median cycles administered were 5 (range 1-8). Of 38 evaluable patients we observed 7 CR, 22 PR’s for an objective response rate 76%. Seven patients achieved stable disease, while two had disease progression. Median duration of response was 8.1 months with median time to progression 9.2 months. Neutropenia grade 3 and 4 was experienced by 13 and 6 patients, respectively, with one toxic death due to febrile neutropenia. Other grade 3 toxicities included anemia/neurotoxicity (n=2), thrombocytopenia/diarrhea (n=1). Conclusions: Although still ongoingthe study has achieved the primary objective of demonstrating clinical activity for weekly carboplatin and paclitaxel in combination with bevacizumab in triple negative MBC. We believe that this triplet combination merits further evaluation in this patient population for whom there is no standard treatment. Clinical trial information: NCT00691379.
A randomized phase II trial comparing docetaxel plus cyclophosphamide with epirubicin plus cyclophosphamide followed by docetaxel as neoadjuvant chemotherapy for hormone receptor-negative breast cancer: Kanagawa Breast Oncology Croup (KBOG) 1101 study.
Authors: Ishikawa Takashi , Shimizu Daisuke , Tanabe Mikiko , S.Oba Mari , Sasaki Takeshi , Morita Satoshi , Kida Kumiko , Nawata Shuichi , Mogaki Masatoshi , Doi Takako , Tsugawa Koichiro , Ogata Haruki , Kosaka Yoshimasa , Sengoku Norihiko , Suzuki Yasuhiro , Suto Akihiko , Chishima Takashi , Ichikawa Yasushi , Endo Itaru , Tokuda Yutaka ,   KBOG Study Group
Published: March 2020

1047 Background: Taxane-based regimens have been widely used to treat breast cancer. Accordingly, it has become important to identify subgroups in which anthracyclines are indispensable. Thus, we initiated a randomized phase II neoadjuvant chemotherapy (NAC) study to compare taxane with and without anthracycline in hormone-negative subtypes. Methods: Eligibility criteria were hormone-negative, an age younger than 80 years and ECOG PS0-1. According to HER2 status, patients were randomly assigned to TC (75/600 mg/m2) q3wks ×6 or FEC (500/100/500 mg/m2) q3wks ×3 followed by D (100 mg/m2) q3wks ×3. The primary endpoint was the rate of pathological complete response (pCR; Grade 3 and Quasi-pCR; Grade 3+2b). Secondary endpoints were safety, breast-conserving surgery ratio, disease-free survival, overall survival, and predictive factors (HER2, Ki-67, P-53, CK5/6, EGFR, and TOP2A by IHC and TOP2A by FISH) for each regimen. Results: 97 out of 103 patients were successfully analyzed (47 for TC6 and 50 for FEC-D). Severe adverse events (Grade ≥2) were frequently observed in FEC-D-treated patients with statistical significance (poor appetite, nausea/vomiting: p<0.001; febrile neutropenia: p=0.016). The pCR rate tended to be higher in FEC-D-treated patients compared with that of TC6-treated patients (pCR: 36.0 vs. 25.5%, n.s.; Quasi-pCR: 46.0 vs. 40.4%, n.s.). There was no significant difference of pCR rates in the HER2 and triple negative (TN) subtypes between each regimen. Among predictors, only positive markers CK5/6 and EGFR predicted the superiority of the FEC-D treatment (p=0.05). Conclusions: TC6 was safe and relatively active even in HER2 subtype patients. Therefore, the concurrent use of trastuzumab with TC could be a reasonable option for NAC in HER2 subtype patients. However, anthracyclines are required to treat basal-type TN cancer. Clinical trial information: UMIN000002215.
Imatinib failure-free survival (IFS) in patients with localized gastrointestinal stromal tumors (GIST) treated with adjuvant imatinib (IM): The EORTC/AGITG/FSG/GEIS/ISG randomized controlled phase III trial.
Authors: Casali Paolo Giovanni , Le Cesne Axel , Poveda Velasco Andres , Kotasek Dusan , Rutkowski Piotr , Hohenberger Peter , Fumagalli Elena , Judson Ian Robert , Italiano Antoine , Martin Broto Javier , Gronchi Alessandro , Dei Tos Angelo Paolo , Marreaud Sandrine , Van Der Graaf Winette T.A. , Zalcberg John Raymond , Litière Saskia , Blay Jean-Yves ,   EORTC Soft Tissue and Bone Sarcoma Group (EORTC STBSG), French Sarcoma Group (FSG), Italian Sarcoma Group (ISG), Grupo Español de Investigación en Sarcomas (GEIS), Australasian Gastro-Intestinal Trials Group (AGITG)
Published: March 2020

10500 Background: In 2004 we launched an open-label randomized trial with adjuvant IM for 2 yrs in localized, surgically resected, high/intermediate-risk GIST. Methods: Pts were randomized between 2 yrs of IM, 400 mg daily, and no further therapy after surgery. The primary end-point was OS, while RFS, RFI and toxicity were secondary end-points. Main eligibility criteria were: age >18 yrs, PS 0-2, localized CD117-positive GIST, intermediate or high risk according to the 2002 Consensus classification, R0 or R1 surgical margins, no previous medical therapy. Pts were stratified by risk, tumor site and margins. An accrual of 400 pts was planned, then escalated to 900. Given the prognostic improvement of advanced GIST pts, in 2009 the study IDMC authorized to change the primary end-point into IFS, whose failure was defined as the time when a different tyrosine kinase inhibitor (TKI) is started. We report on a planned interim analysis carried out after 115 events according to the new primary end-point, with a significance level of 1.5%. Hazard ratios (HR) and p-values were adjusted for stratification factors. Results: 908 pts were randomized between 2005 and 2008, 454 to IM and 454 to observation arm; 835 pts were eligible. 17% of pts treated with IM stopped early due to toxicity or refusal. With a median follow-up of 4.7 yrs, 5-yr IFS was 87% in the IM-arm vs 84% in the control arm (HR=0.80, 98.5% CI [0.51; 1.26], p=0.23); RFS was 84% vs 66% at 3 yrs, and 69% vs 63% at 5 yrs (p<0.001); 5-yr OS was 100% vs 99%. Among 528 pts with high-risk GIST by local pathology, 5-yr IFS was 79% vs 73% (p=0.11), and 77% vs 73% (p=0.44) amongst 336 high-risk GIST pts by centrally reviewed pathology. Conclusions: This study confirms that adjuvant IM has an overt impact on short-term freedom from relapse. In the high-risk subgroup, a non-statistically significant trend in favor of the adjuvant arm was observed in terms of IFS. This new end-point for the adjuvant setting, i.e. survival free from any failure of the first employed TKI, was designed to incorporate secondary resistance, i.e. the currently main factor adversely affecting prognosis of advanced GIST pts. Clinical trial information: NCT00103168.
SARC006: Phase II trial of chemotherapy in sporadic and neurofibromatosis type 1 (NF1)-associated high-grade malignant peripheral nerve sheath tumors (MPNSTs).
Authors: Widemann Brigitte C. , Reinke Denise K. , Helman Lee J. , Ludwig Joseph A. , Schuetze Scott , Staddon Arthur P. , Milhem Mohammed M. , Rushing Daniel A , Moertel Christopher L. , Goldman Stewart , Livingston Michael B. , Wagner Lars M. , Rodler Eve T. , Dombi Eva , Perry Arie , Annunziata Christina M. , Long Lauren , Viskochil David , Steinberg Seth M. , Baker Laurence H. 
Published: March 2020

10522 Background: MPNSTs occur in 10% of the NF1 population, and retrospective, pooled analyses have reported worse chemotherapy response for NF1 (9-18%) compared to sporadic MPNSTs (39-55%). Methods: We prospectively evaluated the objective response (OR) rate, [complete responses (CR) and partial responses (PR) WHO criteria] of children and adults with high-grade, unresectable or metastatic chemotherapy naive NF1 associated versus sporadic MPNST after 2 cycles of ifosfamide and doxorubicin (IA) followed by 2 cycles of ifosfamide and etoposide (IE) as primary endpoint. This was followed by surgery and/or radiation for local control and up to 2 more cycles of IA and IE each. Pathology was centrally confirmed. A Simon optimal two-stage design was used with a target response rate of 40% and 17 patients per stratum in the first stage. With 4+/17 ORs, enrollment was to be expanded to 37 patients per stratum, and 11+/37 ORs would be potentially consistent with a 40% OR rate. Results: Both initial stages met criteria for enrollment expansion with 4/17 PRs in NF1 and 4/12 PRs in sporadic MPNSTs, but only 1 additional PR was observed in the expanded NF1 stratum. Of the 9 PRs, 5 were first observed after 2 cycles IA, and additional 4 after 2 cycles IE. Enrollment was slower than expected and the trial was closed before full accrual. Conclusions: While the primary trial objective was not reached due to slow enrollment, with only 5/29 ORs in the NF1 stratum the desired OR rate of 11+/37 would have unlikely been met even if accrual had been completed. We observed a lower OR rate in NF1 compared to sporadic MPNSTs similar to retrospective literature reports. However, our trial was not powered to detect a difference in response rates between the two strata. In addition to PRs after both IA and IE, disease stabilization was achieved in most patients. Novel strategies including the evaluation of targeted agents in combination with chemotherapy should be considered. Clinical trial information: NCT00304083. [Table: see text]
Association of circulating VEGF-A levels with outcome in patients with vascular sarcomas receiving sorafenib (Sor): Exploratory analysis from AngioNext study.
Authors: Bal-Mahieu Christine , Fournier Charles , Ray-Coquard Isabelle , Chevreau Christine , Le Cesne Axel , Italiano Antoine , Bompas Emmanuelle , Robin Yves Marie , Bay Jacques-Olivier , Piperno-Neumann Sophie , Isambert Nicolas , Baldeyrou Brigitte , Lansiaux Amelie , Blay Jean-Yves , Clisant Stephanie , Penel Nicolas ,   French Sarcoma Group
Published: March 2020

10525 Background: We have carried out a stratified phase II study of Sor in pts with advanced angiosarcoma (AA, n=32), malignant solitary tumour (SFT, n=4) & epithelioid hemangioendothelioma (EE, n=13). We report here the correlative analysis of predictive value of circulating pro/anti-angiogenetic biomarkers. Methods: Using ELISA method (R&D SYSTEMS) Circulating biomarkers (VEGF-A [pg/mL], Thrombospondin-1 (TSP1) [µg/mL], Stem Cell Factor (SCF) [pg/mL], Placental growth factor (PlGF) [pg/mL], VEGF-C [pg/mL] & E-selectin [ng/mL]) have been measured before Sor treatment & after 7 days. We analyze the correlation with histological subtypes, presence of metastases, best response and occurrence of hemorrhage and Gr3-4 arterial hypertension. Results: VEGF-A (mean value 475 vs 541 pg/mL, p=0.002), TSP1 (16 vs 24 µg/mL, p=0.0002), PlGF (20.9 vs 40.7 pg/mL, p=0.0001) significantly increased during the treatment. Sor treatment did not affect the levels of SCF, VEGF-C & E-selectin. The distributions of all biomarkers were similar across the histological subtypes, whatever the presence of metastasis, the occurrence of hemorrhage or arterial hypertension. 2 biomarkers were associated with better outcome:VEGF-A & PlGF. Best objective response and non-progression at 180 days were associated with low level of VEGF-A at baseline (p=0.04 and p= 0,03 respectively). There was a correlation between circulating level of VEGF-A & time to progression (TTP) (r=-0.47, p=0.001). Best objective response and non-progression at 180 days were not associated with baseline level of PlIGF (p=0.34 and 0.07), but there was a correlation between circulating level of PlIGF at baseline and TTP (-0.31, p=0.02). Conclusions: In pts with vascular sarcomas receiving Sor, we have observed a significant decrease in circulating level of VEGF-A. Low level of VEGF-A at baseline (<500 pg/mL) was significantly associated with better outcome, especially best objective response rate, non-progression at 180 days and time to progression. Clinical trial information: 2007-004651-10.
Prognostic significance of Wnt signaling pathway molecules in nongastric GIST patients: A tissue microarray-based (TMA) analysis.
Authors: Martin Broto Javier , Ramos Rafael , Martinez-Trufero Javier , Calabuig Silvia , Horndler Carlos , Casado Antonio , Ortega Luis , Gonzalez de Sande Luis Miguel , Izquierdo Francisco , Gutierrez Antonio , Sala Angeles , Ugalde Aitziber , Valverde Claudia María , de Torres Ines , Losa Ferran , Blanco Remei , Gomez Rosa Maria Sanchez , Cubedo Ricardo , Carrasco Juan Antonio , Balañá Carmen ,   Spanish Group for Research on Sarcomas (GEIS)
Published: March 2020

10529 Background: Pathogenesis in GIST could be related to cancer stem cell hypothesis (highly chemo resistant, very uncommon complete responses, kit is stem cell marker) even though no stem cell component in GIST has been yet demonstrated. Wnt signaling regulates proliferation in some normal and cancer stem cells as it occurs with intestinal epithelium. We have explored the prognostic significance of several Wnt signaling pathway and related molecules. To investigate the prognostic significance of β-Catenin, CDC25A, ROR2, p53, CUL4A, AKT-p and VEGFR-3 by immunohistochemical (IHC) analysis in TMA specimens of 101 non-gastric GIST. Methods: Data of diagnostic, therapeutic and follow-up procedures stem from the GIST Registry of GEIS. Cytoplasmic and/or membrane staining was deemed positive for ROR-2, VEGFR-3 and p-AKT antibodies whereas nuclear staining was positive for β-Catenin, CDC25A, CUL4A and p53 antibodies. IHC positive cases were considered if they displayed staining in at least 10% of cells. Statistical analyses for correlation of protein expression with known prognostic variables (mitoses, size) were performed with Mann-Whitney U test. Results: A subset of 101 non-gastric localized GIST patients was selected (90 intestinal, 15 others: mainly rectum and omentum). The median age was 62 y with gender distribution of 59M/42F and the median of follow-up was 36 months. The positivity for each protein was distributed as follows: ROR-2 63%, p-AKT 55%, β-Catenin 53%, VEGFR-3 22%, CDC25A 20%, p53 8% and CUL4A 7%. A statistically significant correlation was found between mitoses and β-Catenin (median 5 if negative/ 10 if positive, p=0.028); VEGFR-3 (median 5 if negative/21 if positive, p=0.002); CUL4A (median 6 if negative/60 if positive, p= 0.027). Additionally, tumor size was statistically correlated with VEGFR-3 (median 7 if negative/11 if positive, p=0.007). Conclusions: VEGFR-3, β-Catenin and CUL4A are correlated with the highest proliferative non-gastric GIST. These findings deserve further analysis and lead to potential new molecular therapeutic targets in GIST. This study was partially granted by Buesa Grant of GEIS.
Switching chemotherapy in adult osteosarcoma patients with poor necrosis rates post neoadjuvant methotrexate, cisplatin, and doxorubicin (MAP).
Authors: O'Kane Grainne , Cadoo Karen Anne , Walsh Elaine , O'Keane Conor , O'Toole Gary , Dudney Sean , Carney Desmond 
Published: March 2020

10530 Background: Chemotherapy in the treatment of osteosarcoma has improved 5 year overall survival (OS) from 20% with surgery alone to 60-70%. However, poor tumor necrosis following neoadjuvant chemotherapy (NAC) is associated with decreased survival, therefore strategies to improve outcomes are required for these patients. Methods: Records from all adult patients diagnosed with osteosarcoma between 1986 and 2012 were retrospectively reviewed. Patients were stratified according to age at diagnosis (<40yrs and >40yrs), stage (localised or metastatic) and tumor necrosis post NAC (<90% and >90%). All patients received 2 cycles of methotrexate alternating with cisplatin/doxorubicin (MAP) preoperatively. Following surgery, patients with >90% tumor necrosis continued MAP whilst those with <90% necrosis switched to 4 cycles of ifosfamide and etoposide (IE). Results: 105 patients were identified and 98 who received systemic chemotherapy were included. Median age was 23yrs (Range 15-75yrs); 68% of patients were male. Limb sparing surgery was performed in 76% of applicable patients. Of the patients with localised disease (N=85), 5 year OS, with a median follow up of 8 years (1-26 yrs) was 68% (p=0.002). Patients <40 yrs with localised disease had a 5yr OS of 71% (N=73) compared to 40% in those >40 yrs (N=12) (p=0.05). 2/13 patients with metastatic disease at diagnosis are disease free >10 years post diagnosis. 65 of 73 patients with localised disease < 40 yrs had histology reviewed post neoadjuvant MAP. 34/65 (52%) had >90% tumor necrosis and continued on MAP, 5 yr OS 79%, 31 patients (48%) had <90% necrosis and received adjuvant IE, 5 yr OS 68% (P=0.10). Conclusions: Age and stage are important prognostic factors in patients with osteosarcoma treated with chemotherapy and surgery. Historically, patients with <90% tumor necrosis post NAC are considered to have a poorer prognosis. Switching from MAP to IE is an appropriate salvage regimen in such patients and appears to improve long term survival.
Ten-year prospective experience of gastrointestinal stromal tumors (GISTS) from the Cambridge GIST Study Group, United Kingdom.
Authors: Bulusu Venkata Ramesh , Hatcher Helen , Hardwick Richard , Carroll Nicholas , Pursglove Stephanie , Save Vicki , Safranek Peter , Earl Helena Margaret ,   Cambridge GIST Study Group
Published: March 2020

10541 Background: Cambridge GIST study group was formed in 2003. GIST specialist multidisciplinary team (MDT) and GIST clinic were established with central review of histology/pathology and management plans. We present our 10 year experience of a prospective database which formed the template for the United Kingdom national GIST registry. Methods: All patients (pts) who have been referred to the GIST MDT were included in the study. The following data was prospectively collected: patient demographics, presenting symptoms, site, size, histology including mutational data (where available) risk stratification of the GISTS, surgical interventions, systemic therapies, other tumours occurring in GIST pts. Results: 260 patients (pts) were reviewed in the GIST MDT. 29 pts had endoscopic/imaging diagnosis of a GIST and were not included in the final analysis. 41 pts had other tumours diagnosed when GIST was initially suspected. Histologically confirmed GISTS N=190. Male: Female 52%:48%. Median age 64 years (range 14-94), 4% <40years. 84% had surgical intervention (primary or metastatectomy), 9% had resections on imatinib/sunitinib. Tumour characteristics: Site: Stomach-73%, small bowel-16%, EGIST-4%, colorectal-3%, duodenum-3% and oesophagus-1%. Size 0.1-40 cm. Histology subtype: Spindle cell =84%, mixed=12% and epitheloid=4%. Miettinen risk stratification groups: High risk=27%, intermediate risk=16% and very low risk/low risk=57%. Mutational status results in 36 pts: exon 11=64%, PDGFRA= 14%, wild type=11%, exon 9=5.5%, exon 13=5.5%. 14% of GIST pts had other tumour either prior to diagnosis or during treatment/follow up of GISTS. Conclusions: This is the first prospective regional GIST registry data from UK. Our results mirror other large prospective series. GISTS should be managed by an experienced multidisciplinary specialist team to provide a high quality patient centred service.