bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacodynamic (PD) evaluation of soluble proteins from a phase I trial of lapatinib (L) in combination with sorafenib (S).
Authors: Simonelli Matteo , Zucali Paolo Andrea , Lorenzi Elena , Rubino Luca , De Vincenzo Fabio , Perrino Matteo , Rimassa Lorenza , Giordano Laura , Santoro Armando 
Published: March 2020

e21139 Background: At ASCO 2011 we presented safety and efficacy results from a phase I study of L in combination with S in patients with solid tumors refractory to standard therapy (NCT00984425). To investigate potential biomarkers of biological activity of this combination, we analyzed serum levels of a panel of soluble proteins characterizing the oncogenic signalling pathways targeted by L and S (VEGF, sVEGFR-2, EGF, sEGFR, sHER2/neu), and others mediators of angiogenesis such as sPDGFR, IL-8, IL-6, bFGF, PIGF, TGF-α e β, HGF. Methods: Serum samples from 22/30 patients enrolled in this trial were prospectively collected at baseline and then every two months until treatment discontinuation. Serum levels of VEGF, sVEGFR-2, EGF, sEGFR, sHER2/neu and sPDGFR were measured via enzyme-linked immunoadsorbent assays analysis (ELISA). Possible correlations between serum proteins levels and disease-control rate (SCR), PFS or OS were assessed by logistic and Cox regression model, respectively. Results: Analysis of baseline biomarkers as a function of demographic variables indicated that VEGF levels were inversely correlated with age (P= .018) and VEGFR-2 was significantly associated with tumor burden (P= .037). Risk of progression increased with high baseline sEGFR levels (HR 1.10; p= .0498). Overall, PD changes suggest that treatment with L and S increased VEGF and sHER2/neu levels, while decreased EGF, sEGFR, VEGFR-2 and sPDGFR. Mainly, sEGFR levels decreased by at least 75% at the first radiological assessment in half of patients, whereas at the end of treatment a reduction ≥80% was observed in 18 patients; a greater reduction of sEGFR levels was significantly associated with a higher risk of progression (HR 8.3; P <.01) and death (HR 3.6; P= .023). An increase of VEGF levels during treatment seemed to be associated with better SCR (OR: 6.33; P= .085). Conclusions: In this small subset of patients treated with L and S a significant modulation of serum biomarkers was observed. The clinical significance of these changes as potential surrogate markers requires further evaluation. Data concerning other angiogenic markers along with tissue analysis (IHC, FISH and mutation) will be presented at the meeting.
Positron emission tomography/computed tomography (PET/CT) as a biomarker of pathologic response to neoadjuvant chemotherapy in breast carcinoma.
Authors: Kelly Catherine M. , Smith Clare , Conlon Susan , Salman Reem , McCaffrey John , Jordan Emmet 
Published: March 2020

e21147 Background: Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast carcinoma is prognostic. Predictive biomarkers for pCR include early response to NAC, estrogen receptor (ER) negativity, HER2 positivity, and high Ki67. We assessed whether absence of fluoro-deoxy glucose (FDG) uptake measured by standardized uptake value (SUV) after NAC would predict pCR. Methods: We identified 23 patients (pts) who had PET/CT scanning pre and post NAC. We examined breast cancer subtype, chemotherapy (CT) regimen, number of cycles of CT given, clinical and pathological staging data and changes in SUV in the breasts and lymph nodes pre and post NAC. pCR was defined as no residual cancer in the breast or axillary lymph nodes. Results: Median age at diagnosis was 46 years (IQR; 37 to 56). Median tumor size at diagnosis was 30mm (IQR; 25 to 43) and 19 pts (83%) had node positive breast cancer. Most tumors were ductal (n=22) with 1 lobular cancer. Preoperatively 95% received all CT. All HER2+ pts received Trastuzumab. Anthracycline/taxane based regimens were most frequently given in 22 cases, 1 received lapatinib/trastuzumab. Five tumors (21.7%) were ER+/HER2+; 14 (60.9%) ER+/HER2-; 2 (8.7%) ER-/HER2+ and 2 (8.7%) were ER-/HER2-. All tumors were high (n=9, 39.1%) or intermediate grade (n=14, 61%). SUV was significantly lower post NAC (p=0.035). We observed no SUV uptake in breast or lymph nodes in 15 cases (65.2%) post NAC, these corresponded to; ER+HER2+ 4/5 (80%); ER+HER2- 7/15 (46.7%); ER-HER2- 2/2(100%), ER-HER2+ 2/2(100%). Absent SUV uptake post NAC was associated with a pCR (breast and lymph nodes) in 5/15 (33%) of pts (ER+HER2+ n=1, ER+HER2- n=1, ER-HER2- n=2, ER-HER2+ n=1). Ten of 15 tumors (67%) had no SUV uptake in the breast post NAC and 7 (47%) were associated with a pCR. There was a trend toward increased odds of pCR with no SUV uptake post NAC (OR 2.76; 95% CI 0.85 to 8.94: P= 0.09). Overall rate of pCR was 21.7% (n=5). Conclusions: A non-statistically significant trend toward increased odds of pCR with no SUV uptake post NAC was observed. Larger subtype-specific breast cancer cohorts will be required to determine the value of PET/CT as a predictive biomarker for pCR.
Expression of CK-19, galectin-3, and HBME-1 in the differentiation of thyroid lesions: Systematic review and DIAGNOSTIC meta-analysis.
Authors: Matos Leandro Luongo , Del Giglio Adriana Braz , Ogawa Carolina MATSUBAYASHI , Farah Michelle de lima , Pinhal Maria Aparecida Silva , Del Giglio Auro 
Published: March 2020

e21151 Background: The distinction between malignant and benign lesions of the thyroid gland often requires histological demonstration, once the fine-needle aspiration biopsy method applied pre-operatively has some limitations. In an attempt to improve diagnostic accuracy, markers have been studied by immunocyto- and immunohistochemistry techniques, mainly cytokeratin-19 (CK-19), galectin-3 (Gal-3) and Hector Battifora mesothelial-1 (HBME-1). However, current results remain controversial. The aim of the present article was to establish the diagnostic accuracy of CK-19, Gal-3 and HBME-1 markers, as well as their associations, in the differentiation of malignant and benign thyroid lesions. Methods: A systematic review of MEDLINE’s published articles was performed. After establishing the inclusion and exclusion criteria, 65 articles were selected. The technique of meta-analysis of diagnostic accuracy was employed, and global values of sensitivity, specificity, area under the ROC curve (AUC), and diagnostic odds ratio (dOR) were calculated. Results: The positivity ofCK-19 for the diagnosis of malignant thyroid lesions demonstrated sensitivity of 81% (IC95%: 79-83%), specificity of 73% (IC95%: 70-75%), AUC of 87,5% and dOR of 14,7 (IC95%: 8,2-26,4); for Gal-3, sensitivity of 82% (IC95%: 81-84%), specificity of 81% (IC95%: 79-82%), AUC of 90% and dOR of 23,4 (IC95%: 14,0-39,1); and for HBME-1, sensitivity of 77% (IC95%: 76-79%), specificity of 83% (IC95%: 82-85%), AUC of 92,8% and dOR of 41,0 (IC95%: 21,4-78,4). The association of the three markers determined sensitivity of 85% (IC95%: 78-90%), specificity of 97% (IC95%: 90-99%), AUC of 93,3% and dOR of 95,1 (IC95%: 25,2-359,1). Conclusions: The search for new molecular markers must continue in order to enhance the diagnostic accuracy of the differentiation between malignant and benign lesions of the thyroid gland, since the results found still show persistency of false-negative and false-positive tests.
NSABP B-38: Definitive analysis of a randomized adjuvant trial comparing dose-dense (DD) AC followed by paclitaxel (P) plus gemcitabine (G) with DD AC followed by P and with docetaxel, doxorubicin, and cyclophosphamide (TAC) in women with operable, node-positive breast cancer.
Authors: Swain Sandra M. , Tang Gong , Geyer Charles E. , Rastogi Priya , Atkins James Norman , Donnellan Paul P. , Fehrenbacher Louis , Azar Catherine A. , Robidoux Andre , Polikoff Jonathan , Brufsky Adam , Biggs David D. , Levine Edward A. , Zapas John L. , Provencher Louise , Perez Edith A. , Paik Soonmyung , Costantino Joseph P. , Mamounas Eleftherios P. , Wolmark Norman 
Published: March 2020

LBA1000 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Monday, June 4, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach (ITACA-S) trial: Comparison of a sequential treatment with irinotecan (CPT-11) plus 5-fluorouracil (5-FU)/folinic acid (LV) followed by docetaxel and cisplatin versus a 5-FU/LV regimen as postoperative treatment for radically resected gastric cancer.
Authors: Bajetta Emilio , Floriani Irene , Di Bartolomeo Maria , Labianca Roberto , Landi Lorenza , Santoro Armando , Casaretti Rossanna , Pasquini Enzo , Di Fabio Francesca , Rondini Ermanno , Pinotti Graziella , Bidoli Paolo , Rosati Gerado , Mambrini Andrea , Ciarlo Andrea , Cordio Stefano Sergio , Ricci Sergio , Frassineti Luca , Di Costanzo Francesco , Bochicchio Anna Maria ,   on behalf of ITACA-S Study Group
Published: March 2020

LBA4001 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Saturday, June 2, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
Evaluation of lapatinib as a component of neoadjuvant therapy for HER2+ operable breast cancer: NSABP protocol B-41.
Authors: Robidoux Andre , Tang Gong , Rastogi Priya , Geyer Charles E. , Azar Catherine A. , Atkins James Norman , Fehrenbacher Louis , Bear Harry Douglas , Baez-Diaz Luis , Kuebler J. Phillip , Margolese Richard G. , Farrar William Blair , Brufsky Adam , Shibata Henry R. , Bandos Hanna , Paik Soonmyung , Costantino Joseph P. , Swain Sandra M. , Mamounas Eleftherios P. , Wolmark Norman 
Published: March 2020

LBA506 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Sunday, June 3, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.
Randomized multicenter phase III trial of trabectedin (T) versus doxorubicin-based chemotherapy as first-line therapy in patients with translocation-related sarcoma (TRS).
Authors: Blay Jean-Yves , Leahy Michael Gordon , Bui Nguyen Binh , Patel Shreyaskumar , Santoro Armando , Hohenberger Peter , Demetri George D. , Lardelli Pilar , Perez Iratxe , Chawla Sant P. 
Published: March 2020

TPS10101 Background: One third of sarcoma histotypes have specific chromosomal translocations which result in abnormal transcription factors, integral to the change to a malignant phenotype. T is the first of a new class of anti-tumor agents with a transcription-targeted mechanism of action. In vitro evidence exists of the ability of T to interfere with the aberrant transcription factor’s binding to DNA promoters in TRS. Patients with TRS, such as myxoid/round cell liposarcomas (MRCL) have benefited from long-lasting tumor control in response to T. Methods: A randomized, phase III study of T (1.5 mg/m2 in 24-h intravenous infusion every 3 weeks [q3wk]) vs doxorubicin 75 mg/m2 q3wk, or doxorubicin 60 mg/m2 with ifosfamide 6-9 g/m2 q3wk) as first line treatment in patients with advanced TRS. Primary aim: to determine the efficacy of T vs doxorubicin-based therapy by comparing progression-free survival (PFS) in each arm. Secondary aims: comparison of PFS rates at six months, response rate (RR), PFS and RR by histological type (MRCL vs other subtypes), overall survival, safety, exploratory response evaluation by Choi criteria and pharmacogenomic analyses. Patients with confirmed TRS of the following subtypes: MRCL, alveolar soft part sarcoma,angiomatoid fibrous histiocytoma, clear cell sarcoma, desmoplastic small round cell tumor, low grade endometrial stromal sarcoma, low grade fibromyxoid sarcoma,myxoid chondrosarcoma and synovial sarcoma, are stratified by performance status (PS 0 vs 1-2) and sarcoma subtype (MRCL vs other subtypes) and randomized (1:1 ratio) to T or doxorubicin ± ifosfamide. Confirmation of the translocation by fluorescence in situ hybridization is compulsory for inclusion in the primary efficacy analysis. An adaptive design was chosen to test the reduction in relative risk of progression or death with T, an interim analysis will be conducted with 45 PFS events from 80 evaluable patients. To date 117 patients have been enrolled from six countries and 29 centers. An independent data monitoring committee met on 15 November 2011 and concluded that the trial should continue as planned.
Randomized multicenter double-blind phase II trial: The immunological adjuvant OPT-821 with or without a trivalent ganglioside vaccine in metastatic sarcoma patients following metastasectomy.
Authors: Carvajal Richard D. , Chugh Rashmi , Milhem Mohammed M. , Ryan Christopher W. , George Suzanne , Chmielowski Bartosz , Agulnik Mark , Rodler Eve T. , Elias Anthony D. , Budd G. Thomas , Tawbi Hussein , Movva Sujana , Van Tine Brian Andrew , Dickson Mark Andrew , Hensley Martee Leigh , Keohan Mary Louise , Tap William D. , Bennett Cathryn M. , Maki Robert G. , Schwartz Gary K. 
Published: March 2020

TPS10103 Background: The gangliosides GM2, GD2, and GD3 are strongly expressed in sarcoma and represent novel antitumor targets. We have demonstrated the safety and immunogenicity of individual monovalent ganglioside conjugate vaccines when administered with OPT821, a synthetic saponin adjuvant that augments the T-cell response. Antitumor effects are observed with anti-ganglioside antibodies in preclinical models, with greatest benefit seen in the micrometastatic setting. Patients (pts) with metastatic sarcoma rendered disease-free by surgery are at high risk for disease recurrence, with no therapy demonstrated to improve outcomes. Therefore, this population is ideally suited to test the efficacy of vaccine induced anti-ganglioside antibodies. We thus initiated this randomized double-blind phase II study of OPT821 with or without a trivalent ganglioside vaccine composed of GM2, GD2 lactone and GD3 lactone conjugated to KLH, an immunogenic carrier protein. Methods: A total of 134 pts will be randomized on a 1:1 basis stratified by disease state (relapsed disease vs metastasis at time of diagnosis), disease-free interval and number of relapses. Key inclusion criteria include stage IV sarcoma (locoregional recurrence is not sufficient) rendered disease-free following surgery or multi-modality therapy, no more than 8 weeks since surgery, and no continuous use of anti-inflammatory medications. Pts with Ewings sarcoma, GIST and rhabdomyosarcoma (except pleomorphic/anaplastic) are ineligible. Eligible pts will receive 10 subcutaneous injections in the outpatient setting over 84 weeks. The primary endpoint is progression-free survival (PFS). Secondary objectives include overall survival (OS) and 1- and 3-year PFS rate. Exploratory objectives include correlation of serologic response to outcome, comparison of tumor ganglioside expression at baseline and at recurrence, and analysis of circulating tumor cells. Enrollment began in July 2010. As of January 1, 2012, 83 patients had been recruited from 12 participating sites. Clinicaltrials.gov#: NCT01141491. Funded by Mabvax Therapeutics and NIH (R21CA13386).
A phase III, randomized trial of docetaxel plus carboplatin (TP) versus epirubicin plus cyclophosphamide followed by docetaxel (EC-T) as adjuvant treatment for triple-negative, early-stage breast cancer in Chinese patients.
Authors: Yuan Peng , Xu Binghe 
Published: March 2020

TPS1135 Background: Triple-negative [estrogen receptor (ER)-/progesterone receptor (PR)-/HER2-] breast cancer (TNBC) accounts for about 15% of all breast cancers and is associated with very poor prognosis. A combination of anthracycline and taxanes represents the most commonly used adjuvant chemotherapy for TNBC patients. BRCA1, a protein responsible for repair upon DNA damage, is often dysfunctional in TNBC. As a result, TNBC is often sensitive to DNA-damaging agents (e.g., cisplatin and carboplatin). A phase II study of docetaxel plus carboplatin as neoadjuvant treatment for TNBC achieved promising response rate (Chang, CANCER, 2010). Encouraged by this important finding, we are currently conducting a phase III trial to examine docetaxel plus carboplatin as adjuvant chemotherapy in patients with early-stage TNBC (registration number at www.ClinicalTrials.gov: NCT 01150513). Methods: All participants received radical mastectomy or breast-conserving surgery for pT1-3N0-2 breast cancer. All cancers were negative for ER, PR, HER2/Neu. All participants had adequate organ function and performance status. The age ranged from 18 to 70 years. Patients randomly received a TP regimen (docetaxel 100 mg/m2 plus carboplatin AUC=6 on day 1, 21 days a cycle for 6 cycles) or a EC-T regimen (epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 on d1, 21 days a cycle for 4 cycles; followed by docetaxel 100 mg/m2 on d1, 21 days a cycle for 4 cycles). Adjuvant radiotherapy was permitted in both arms. The primary endpoint is disease-free survival (DFS). Secondary endpoints included adverse event and quality of life (QoL). The study planned to recruit 500 subjects over a period of 5 years, with 5-year follow-up (once every 6 months). Target hazard ratio is 0.86 (5 year DFS of 74.0% vs. 71.0%). The estimated power is 0.80; 1-sided type 1 error was set at 0.05). The study was activated in June 2010 with enrollment of 110 subjects.
ANZ1001 SORBET: Study of estrogen receptor beta and efficacy of tamoxifen, a single arm, phase II study of the efficacy of tamoxifen in triple-negative but estrogen receptor beta-positive metastatic breast cancer.
Authors: Phillips Kelly-Anne , Kiely Belinda E. , Francis Prudence A. , Boyle Frances M. , Fox Stephen B. , Murphy Leigh , Gebski Val , Lindsay Dianne Frances , Sutherland Robert L. , Badger Heath D. , Forbes John F. ,   Australia and New Zealand Breast Cancer Trials Group
Published: March 2020

TPS1136 Background: Targeted therapies are needed for triple negative breast cancer (BC). ERβ is expressed in at least 20% of triple negative BCs. ERβ binds estrogen and tamoxifen with a similar affinity to ERα. ERβ has 5 isoforms but only ERβ1 is fully functional. ERβ expression has been shown to be significantly associated with improved distant disease free survival and better overall survival in tamoxifen treated ERα negative patients in retrospective studies. This “proof of principle” study will determine the efficacy of tamoxifen in patients with triple negative but ERβ positive metastatic BC. Methods: This single arm phase II study, being conducted by the Australia and New Zealand Breast Cancer Trials Group, has a Simon's 2 stage optimal design. The primary end-point is objective response rate (complete and partial responses). Progression free survival and clinical benefit rate will also be assessed. Eligibility criteria include histologically or cytologically confirmed metastatic triple negative BC (ER and PR absent, HER2 ISH negative or IHC 0 or 1) and measureable disease as per RECIST 1.1. Consenting patients undergo central ERβ testing and confirmation of triple negative status on a metastatic biopsy sample. ERβ positive patients (ERβ1 nuclear staining with Allred score >4) are offered trial participation. To date 12 potentially eligible patients have been screened for ERβ; 4 had Allred score >4 (although 2 of these subsequently proved to be ineligible for the trial), 7 had Allred scores <4 and 1 result is pending. Consenting patients receive tamoxifen 20mg per oral daily until disease progression, unacceptable toxicity or withdrawal of consent. If there are ≥2 responses in the first stage of 28 patients, an additional 38 patients will be accrued. Tamoxifen will be considered worthy of further research if there are ≥6 responses in the total 66 patients recruited. Current accrual is 1. Registered on ANZCTR (12610000506099).
Q-CROC-03: A prospective biopsy driven clinical trial to study the mechanisms of resistance to chemotherapy in triple-negative breast cancer patients.
Authors: Aguilar-Mahecha Adriana , Lafleur Josiane , Seguin Carole , Mihalcioiu Catalin Liviu Dragos , Roy Josee-Anne , Desbiens Christine , Robidoux Andre , Diaz Zuanel , Pelmus Manuela , Batist Gerald , Basik Mark ,   Quebec Clinical Research Organisation in Cancer
Published: March 2020

TPS1139 Background: Resistance to chemotherapy or targeted agents is the cause of death in most patients dying of breast cancer and one of the major challenges presently faced by oncologists. In triple negative breast cancers (TNBCs), drug resistance emerges quicker than in other breast cancer subtypes and contributes to the poor prognosis seen in these patients. The lack of targeted therapies to treat TNBC highlights the important need to better understand the molecular mechanisms contributing to chemotherapy resistance in order to develop new therapeutic strategies. However, the difficulty in obtaining tissue samples from drug resistant tumors has been one of the limiting factors in this field of study. Methods: We have designed a prospective phase II clinical trial where paired biopsies are collected from chemotherapy resistant TNBCs (NCT01276899). Four needle core biopsies are collected before the initiation of treatment and 2 weeks before surgery or at the time of progression in the neoadjuvant and metastatic settings respectively. Metastatic sites eligible for biopsy include liver, lung, skin and lymph nodes. This study is presently recruiting at 5 major health centers in Quebec and will soon open in the USA. We have currently enrolled 13 patients in the neoadjuvant setting and 2 metastatic patients. Major challenges in patient enrolment will be discussed. We have standardized the methods of collection and processing of tissue and blood specimens to ensure their molecular integrity and compatibility with different genomic and proteomic molecular platforms. Analysis of tumor cellularity has been incorporated into our quality control and we have optimized the extraction of nucleic acids to obtain high yields and optimal quality. Paired biopsies will undergo Next Gen Sequencing, flow sorted aCGH analysis, gene expression and miRNA profiling as well as phosphoproteomic profiling using reverse phase protein arrays. Collection of clinical data will allow molecular profiling data to be linked to clinical response data so as to determine DNA, RNA and protein factors correlated with tumor resistance to chemotherapy.