tbuckley/cabot-search huggingface dataset:
Phase II study of neoadjuvant treatment with docetaxel, capecitabine, and trastuzumab in HER-2-positive locally advanced or inflammatory breast cancer: TXH trial
Authors: G. Perez Manga, P. Khosravi-Shahi, Y. Izarzugaza Peron, A. Soria Lovelle, R. Gonzalez del Val, M. Palomero Plaza, M. Riesco Martinez, Y. Jerez Gilarranz, J. Adeva Alfonso, A. Alonso
Journal: Journal of Clinical Oncology (2009)

e11581 Background: Preoperative chemotherapy(CT) with trastuzumab(H)improves pathologic complete responses(pCR) in patients(ps)with Her-2+locally advanced breast cancer(LABC). Methods: This is an unicenter phaseII trial of a new neoadjuvant CT with H(without anthracyclines)in Her-2+LABC.Primary end-point was pCR.Secondary endpoints were:clinical response rate(CRR);breast conservative surgery rate(BCSR);pathologic tumoral size(pTS);disease-free survival(DFS);overall survival(OS)and toxicity profile.Ps with histologically confirmed Her-2+LABC, PS ≤2, LVEF &gt;50%,and adequate bone marrow, renal and hepatic function were eligible.Treatment:docetaxel(T)36 mg/m 2 IV d1,8 and 22;capecitabine(X)750 mg/m 2 /12h PO d1- 14;and H 4mg/kgIV 1ºd,followed by weekly 2mg/kg in a 4-week course repeated for up to 4cycles,followed by surgery.Ps received a maximum of 6 cycles,according to investigator criteria.Radiotherapy(RT)and hormonetherapy(Ht) were allowed after surgery.Expression of markers was determined by immunohistochemistry(IHC)before CT. Results: The trial was closed due to poor accrual on March 2008.N=16ps:median age=47years(30–68); premenopausal=69%; ductal carcinoma=94%; left side=37,5%; clinical(c)stage:IIA=6.2%,IIB=43.8%;IIIA=31.2%;IIIB=18.8%;c node+=50%; median c tumoral size= 5cm(2- 10);grade:G2=53%and G3=47%;ER+ =75%;PgR+=62.5%;RP+/RE+ =62.5%;EGFR negative =87.5%;p53+=37.5;median KI67=22.5%(2- 79%);Her2+ by IHC+++ =87.5%and IHC++/FISH+ =12.5%;RT= 50%;median dose=50Gy;Ht=75%;and all ps received adjuvant H. 1º End Point: Three ps(18.8%) had pCR in breast and nodes;4ps(25%)had pCR in primary site,and among ps with c node+ 37.5%(3ps)had pCR in nodes. 2º End-Points: 1)CRR=81.2%(complete response=25%;partial=56.2%;no response=18.8%);2)BCSR=6.2%;3)Median pTS=2cm(0–5cm);4)Safety:TXH is very well tolerated:dose delays=14%;dose reductions=7%;no p had a decreased LVEF after neoadjuvant CT.Three ps had decreased LVEF during adjuvant H(median=43%).5)Only 2 events had occurred.Survival data will be reported in the meeting. Conclusions: Neoadjuvant TXH is a new active regimen in Her- 2+LABC with a manageable toxicity profile. No significant financial relationships to disclose.
Clofarabine plus cytarabine compared to cytarabine alone in older patients with relapsed or refractory (R/R) acute myelogenous leukemia (AML): Results from the phase III CLASSIC 1 trial.
Authors: S. Faderl, M. Wetzler, D. Rizzieri, G. J. Schiller, M. H. Jagasia, R. K. Stuart, S. Ganguly, D. Avigan, M. Craig, R. Collins, M. B. Maris, T. Kovacsovics, S. Goldberg, K. Seiter, P. Hari, F. Ravandi, E. S. Wang, S. Eckert, D. Huebner, H. Kantarjian
Journal: Journal of Clinical Oncology (2011)

6503^
Identification of pharmacogenomic markers for predicting sensitivity to BMS-354825, a SRC/ABL kinase inhibitor
Authors: E. Clark, K. A. Reeves, X. Han, P. M. Shaw, C. Fairchild, Q. Wu, S. Platero, T. W. Wong, F. Lee, F. Huang
Journal: Journal of Clinical Oncology (2005)

3010 Background: BMS-354825 is a SRC/ABL kinase inhibitor currently in clinical trials for both CML and solid tumors patients. Molecular markers predictive of response to BMS-354825 could assist in clinical development by identifying patients most likely to derive clinical benefit. Methods: Gene expression profiling were performed in 23 breast and 23 lung cancer cell lines for which sensitivity (IC50) to BMS-354825 was pre-determined. Using the breast cell lines as a training set, 3 statistical analyses including: 1) KNN with a permutation test: 2) Pearson correlation between gene expression level and IC50 values; and 3) a t-test were performed to identify 137 genes whose expression levels are highly correlated with drug sensitivity. Then, a predictive model, consisting of the top 6 genes correlated with drug sensitivity, was built using a weighted-voting algorithm (Whitehead GeneCluster program) to predict sensitivity to BMS-354825 in an independent test set (23 lung cancer cell lines). Biological studies were also conducted to validate these markers. Results: From the 137 genes whose expression levels are highly correlated with drug sensitivity (p<0.05), we have identified 64 genes that are modulated by BMS-354825 treatment. Using the top 6 genes, we correctly predicted the sensitivity of 19 (83%) out of 23 testing samples across tissue types. Co-regulated expression patterns of these 137 genes were observed in primary breast tumors indicating their potential utility as response predictors. Subsequent biological studies to inhibit SRC-family kinase activity by treatment with BMS-354825 and siRNA have suggested that many of these genes are involved in SRC-family signaling pathways. Immunohistochemical analysis of several top candidate markers demonstrated that the protein level of the markers is also correlated with the sensitivity of cell lines to BMS-354825, indicating both RNA and proteins are candidate markers for predicting response to BMS-354825. Conclusions: This work has identified pharmacogenomic biomarkers with utility in predicting response to BMS-354825 in cell lines. These markers have clinical impact and will be used in planned clinical studies. No significant financial relationships to disclose.
The impact of pain reduction on other symptoms in patients with multiple myeloma-related painful vertebral fracture treated with kyphoplasty or vertebroplasty.
Authors: T. R. Mendoza, L. Koyyalagunta, A. W. Burton, S. K. Thomas, S. Giralt, J. J. Shah, J. Ting, M. R. Perez-Toro, C. S. Cleeland
Journal: Journal of Clinical Oncology (2010)

e19536 Background: Patients with cancer pain usually have associated symptoms. Generally, it is felt that a reduction in severity of pain will be associated with significant improvement in other symptoms as well. Patients with multiple myeloma (MM)-related painful vertebral compression fracture often show substantial reduction in pain after kyphoplasty (KP) or vertebroplasty (VP). We evaluated the association of changes in pain ratings with ratings of other cancer symptoms in this patient group. Methods: We retrospectively studied 79 patients with MM-related painful vertebral compression fracture who underwent KP or VP. The patients' ratings of pain and symptom severity using the Brief Pain Inventory (BPI) and the Edmonton Symptom Assessment Scale (ESAS), assessed both before and after undergoing KP or VP, were noted. Change scores and change score effect sizes were computed, and correlations were evaluated before and after treatment. Results: There were significant reductions in mean pain severity after treatment (1.8 on a 0-10 scale, p<.001). Effect-size reductions for the pain items ranged from 0.53 to 0.70. Also, significant reductions were noted (decreasing order) in anxiety (1.3, p<.001), drowsiness (1.3, p<.001), depression (0.80, p<.012), difficulty thinking clearly (0.79, p<.012), and fatigue (0.90, p<.028). Pain change scores were associated only with changes in anxiety. In contrast, depression change scores were related with all symptom change scores. Fatigue change scores were related to change scores in depression, anxiety, drowsiness, poor appetite, and insomnia. There were no significant differences between KP and VP in reducing pain. Conclusions: Most patients experienced pain reduction after KP or VP. Interestingly, while other symptoms were lower at follow up, pain reduction was significantly associated only with anxiety. The lack of a significant association between a reduction in pain with other symptoms suggests that simplistic views of symptom clusters need further evaluation and requires longitudinal examination. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Celgene, Millennium Celgene, Millennium Celgene, Medtronic, Inc., Millennium, Novartis
A population-based study of trastuzumab-mediated cardiotoxicity among early stage breast cancer patients treated with adjuvant trastuzumab
Authors: H. L. McArthur, J. Barnett, S. Chia
Journal: Journal of Clinical Oncology (2006)

10640 Background: Given the risk of cardiotoxicity demonstrated with trastuzumab (T) in the MBC literature, adjuvant T trials incorporated stringent cardiac monitoring. In 2005, several of these trials were reported with impressive DFS improvements. As a result of these trials, women in the province of British Columbia with HER-2 positive early stage breast cancer were offered T either concurrently or sequentially with their primary chemotherapy regimen. Given the paucity of data surrounding adjuvant T-mediated cardiotoxicity among the general population, we performed a retrospective review of cardiac toxicity among all patients receiving adjuvant T at the BCCA. Methods: Patients receiving adjuvant T between July 1, 2005 and December 31, 2005 either sequentially or concurrently with their primary chemotherapy regimen were identified by screening the BCCA pharmacy database. A chart review was conducted and the T start date; LVEF values at 0, 3 and 6 months; and patients with symptoms suggestive of congestive heart failure were identified. The mean LVEF values at 0, 3 and 6 months were calculated. Results: 133 patients received adjuvant T alone after completing their primary chemotherapy. The mean baseline LVEF was 60.5%. Of the 101 and 11 patients available for analysis at 3 and 6 months, the mean LVEF was 58.5% and 58.4%, respectively. 5 patients (3.8%) developed symptoms of CHF. 58 patients received adjuvant T concurrently with their primary chemotherapy (four cycles of AC followed by four cycles of concurrent paclitaxel and T). Of these, only 18 patients had an LVEF measured at 0 and 3 months, with a mean LVEF of 64.6% and 63.6%, respectively. Of the 7 patients who also had an LVEF measured at 6 months, the mean was 60.5% for an absolute decrease of 4.1% from baseline. One patient (1.7%) had symptomatic CHF. Conclusions: A clinically meaningful rate of cardiotoxicity is seen with both sequential and concurrent adjuvant T. In particular, we have demonstrated a higher rate of cardiotoxicity with adjuvant T alone than was observed in the HERA trial. These findings support ongoing stringent cardiac monitoring among the general population treated with adjuvant T. [Table: see text]
Abstract 15233: Hybrid Procedure for Hypoplastic Left Heart Syndrome Has Less Advantage on Ventricular Energetics Compared to the Norwood Procedure with Right Ventricle to Pulmonary Artery Shunt: An In-Silico Analysis
Authors: Shuji Shimizu, Toru Kawada, Toshiaki Shishido, Shunji Sano, Masaru Sugimachi
Journal: Circulation (2012)

Introduction: To reduce surgical invasions of the Norwood procedure, a hybrid procedure, bilateral pulmonary artery banding (PAB) combined with ductal stenting, has recently been conducted as a sta...
MRI of the breast before and after primary systemic therapy correlates with histopathological tumor size in patients with locally advanced breast cancer (LABC)
Authors: V. Russu, B. Lex, M. Popovich, K. Pfaffenberger, H. Volkholz, A. Tulusan
Journal: Journal of Clinical Oncology (2007)

507 Background: Primary systemic therapy (PST) is a widely accepted preoperative treatment for patients with locally advanced breast cancer (LABC). Different authors beside our study-group showed that MRI is a sensitive method in describing the remaining size of an invasive breast lesion after PST. The established methods for measuring the size of lesions and monitoring the tumour-response to chemotherapy are clinical palpation, mammography and ultrasound, but specificity of these methods is unsatisfactory. Our prospective data is to clarify the accuracy of MRI in monitoring the tumour-response to PST is presented. Methods: 207 female patients (range of age: 26a- 78a) with LABC (cT2 â€“ cT4) were examined with dynamic contrast enhanced MRI after PST. 173 (84%) patients have had MRI examination before and after PST. 145 (70%) patients had a ductal-invasive, 48 (23%) patients a lobular-invasive carcinoma. 70 (34%) patients were treated with sequential anthracyclin- and taxan-based chemotherapy and 137(66%) with only anthracyclin based chemotherapy. 51% patients were premenopausal. 70% had an ER-positive tumour. The measure of tumour-response to PST was graded in partial response (PR: &gt;50% of tumour reduction mm 2 ), no change (NC: &lt;50%) and complete response (CR: no evidence of residual tumour-cells). Results: Comparing tumour-size measured by MRI before and after PST 119 (69 %) of the patients had PR and 25 (14.5%) CR. The histological tumour- size after PST strongly correlated with the size measured by MRI r = 0,758 (pâ€ 1 0.001). Analyzing the tumour-types ductal-invasive carcinomas were significant (p&lt;0.001) better to monitor than lobular-invasive types (r=0.824/r=0.210). Conclusions: preoperative MRI seems to be a helpful tool in estimating the efficacy of the tumour-response to chemotherapy and for the operative planning in the patients with LABC after PST, especially for ductal-invasive tumours. No significant financial relationships to disclose.
The epipodophyllotoxins: both sides of the coin.
Authors: G K Rivera, C H Pui, W M Crist
Journal: Journal of Clinical Oncology (1993)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1993.11.8.1624 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8336199 The epipodophyllotoxins: both sides of the coin. G K RiveraxG K RiveraSearch for articles by this author , C H PuixC H PuiSearch for articles by this author , W M CristxW M CristSearch for articles by this author https://doi.org/10.1200/JCO.1993.11.8.1624 PDF "The epipodophyllotoxins: both sides of the coin.." Journal of Clinical Oncology, 11(8), pp. 1624–1625© 1993 by American Society of Clinical Oncology
Assessment and quantification of taxane-induced neurotoxicity in a phase III randomized trial of breast cancer (AC followed by PAC/DOC vs. PAC/DOC alone): N-SAS BC 02
Authors: K. Shimozuma, Y. Ohashi, A. Takeuchi, T. Aranishi, S. Morita, K. Kuroi, S. Ohsumi, H. Makino, T. Watanabe, F. H. Hausheer
Journal: Journal of Clinical Oncology (2006)

8523 Background: Chemotherapy-induced peripheral neuropathy (CIPN) commonly occurs during taxane chemotherapy (Tx). There is no standardized approach used in the assessment of CIPN. Physician-based instruments (e.g., NCI-CTC) are widely used for this purpose, but are associated with several important limitations. As current medical evidence suggests that physician-based assessments under-report the incidence and severity of subjective symptoms, they cannot reliably or accurately assess symptoms of CIPN. We prospectively assessed CIPN during Tx in a phase III randomized trial to evaluate the reliability and sensitivity of these different approaches. Methods: Three hundred breast cancer (BC) patients entered the National Surgical Adjuvant Study of Breast Cancer 02 (N-SAS BC 02), a phase III randomized trial comparing 4 cycles of AC followed by 4 cycles of Tx (paclitaxel [PAC] or docetaxel [DOC]) vs. 8 cycles of Tx alone in N+ BC patients after surgery. CIPN and QOL were secondary endpoints. Patient-based PNQ and FACT-Ntx were compared to the clinician-based NCI-CTC. Assessments were conducted at baseline, 3rd, 5th, 7th cycles, 8 months, and one year after starting adjuvant treatments. A linear mixed effect model was used to compare data in the two treatment groups across repeated cycles of treatment. Results: Average response rate of the instruments was &gt; 90%. Sensory PNQ scores strongly correlated with sensory FACT-Ntx scores (r=0.70), while they weakly correlated (r=0.43) with NCI-CTC scores. NCI-CTC scores distributed between 0 and 2, while PNQ scores distributed between 0 and 4. Comparison of CIPN during the first 3 cycles showed that significantly higher overall incidence of sensory disturbance was observed in Tx compared with AC as assessed by both PNQ (PAC, P&lt;0.0001; DOC, P=0.0007) and NCI-CTC (PAC, P&lt;0.0001; DOC, P=0.0026). The PNQ appeared to detect more severe grades of sensory neuropathy compared to NCI-CTC. Conclusions: This study confirmed that physicians tended to underestimate CIPN, and patient-rated PNQ was a more reliable and valid instrument to assess CIPN. The development of new and reliable assessment methods would represent important medical advancements for cancer patients. [Table: see text]
Osteosarcoma pulmonary metastasis: Prognostic factors of 88 patients submitted to surgical resection
Authors: F. A. Schutz, R. N. Younes, J. A. Borges, J. L. Gross
Journal: Journal of Clinical Oncology (2007)

20502 Background: Pulmonary metastasis from Osteosarcoma occurs in 30% to 40% of cases. Chemotherapy and surgical resection are the current preferred options for these patients, although overall outcome remains poor, with few patients achieving long term overall survival. Prognostic factors for better selecting these patients are needed. Methods: We reviewed the survival and the prognostic factors from 88 consecutive patients with pulmonary metastasis from osteosarcoma, submitted to metastasectomy at a single institution. Clinical and demographic variables, related to the primary tumor as well as to the pulmonary metastases and treatment procedures were registered. Univariate ( Log-rank and Breslow tests) and multivariate analysis (Cox-regression) were performed to identify significant prognostic factors related to overall survival. Results: Median follow-up time was 34 months, and 12.5% were alive without disease, 14.8% were alive with disease, 58% were dead of disease, 1,1% were dead from other causes, and 14.8% were lost to follow-up. The overall 5- year survival was 19%. Disease free interval (DFI), number of thoracotomies and complete resection at last thoracotomy were significant prognostic factors at univariate analysis. Median survival from first thoracotomy for patients with DFI = 12 months was 24.6 months, compared to 9.6 months for DFI &lt; 12 months (p= 0.0014). Complete resection at last thoracotomy significantly improved median overall survival (19.1 versus 9.6 months) (p=0.0117). Cox-regression analysis showed only disease free interval more than 12 months (p=0.014) and complete resection at last thoracotomy (p=0.003) to be independent significant prognostic factors. Sex, age, site and stage of primary tumor, number of lung nodules, bilateral nodules, and chemotherapy treatment for lung metastases did not significantly impact on survival. Conclusion: Disease free interval and complete resection at last thoracotomy are significant prognostic factors for patients with resected pulmonary metastasis from osteosarcoma. No significant financial relationships to disclose.
Abstract 16926: First Global Assessment of Circulating Plasma MicroRNAs as Potential Biomarkers for Pulmonary Arterial Hypertension
Authors: Kenny Schlosser, R. J White, Duncan J Stewart
Journal: Circulation (2012)

Background:  Circulating extracellular microRNAs (miRNAs) have been identified as possible biomarkers in cancer and some cardiovascular diseases, but as yet their levels have not been examined in the plasma of patients with pulmonary arterial hypertension (PAH).  Hypothesis:  Altered levels of circulating miRNAs will provide insight into underlying mechanisms of PAH and serve as disease-specific biomarkers.   Methods:  A global screen of 1066 different miRNAs was performed with a discovery cohort of 4 treatment-naive patients with idiopathic (I) PAH and 3 healthy controls (age and sex matched). Total RNA was extracted from plasma and profiled with a miRNA (RT)-qPCR array platform (Qiagen). A separate cohort of 13 healthy controls and 14 PAH patients (8 associated (A) and 6 IPAH) was used for validation purposes. MicroRNA expression levels were normalized with a mean-centering restricted method in the discovery cohort, and 2 novel internal reference genes were used in the validation cohort.   Results:  436±45 miRNAs were detectable (PCR Cq cutoff    Conclusion:  This first global assessment of circulating miRNAs in IPAH supports their utility as non-invasive biomarkers for disease activity.
Protein biosignature identified by LC-MS/MS in classifying breast cancer and predicting tumor response to neoadjuvant therapy.
Authors: H. R. Chang
Journal: Journal of Clinical Oncology (2010)

e21050 Background: In this study, we investigated proteomic biosignature by LC-MS/MS to classify tumor subtypes and to predict tumor response to neoadjuvant therapy. Methods: Baseline breast cancer specimens of 39 patients who were enrolled in an IRB-approved clinical trial including 28 HER2-positive and 11 triple negative (TNBC) tumors were studied. The protein extracts of all tumors were subjected to abundant protein depletion including albumin, hemoglobulin and immunoglobulin removal. Samples were digested by trypsin and analyzed by Orbitrap LC-MS/MS. Bioworks Software (Thermo-Fisher) was used to study the mass spectra against a human trypsin injected protein database. Positive protein identification was defined if the X corr was ≥ 2.0 for doubly charged ions and ≥ 2.5 for triply charged ions. Scaffold software was used to verify the proteins identified by SEQUEST. Results: In this study, we identified 20 proteins by LS-MS/MS that correctly classified all HER2 positive tumors and 7 of the 11 TNBC. We found that ALDH A1, galactin 3-binding protein, L-plastin and moesin were elevated in TNBC and CK19, transferin and transketolase were over-expressed in HER2 positive cancers. In HER2 positive breast cancer, heat shock proteins 10KD and 70 KD, annexin V and peroxiredoxin 5 were associated with poor tumor response to docetaxel, carboplatin ± trastuzumab (TC ± H). In TNBC annexin I, periostin precursor, tubulin α1/β5 and caldesmon were associated with drug resistance to neoadjuvant TC. Conclusions: Proteomic biosignatures may differentiate tumor types and predict tumor response to chemotherapy. When sufficiently validated, candidate biomarkers may be developed into diagnostic tools for cancer screening and for tailored therapy. No significant financial relationships to disclose.