tbuckley/cabot-search huggingface dataset:
Phase I study of imatinib mesylate (IM) and sorafenib (S) in patients (pts) with refractory castration-resistant prostate cancer (CRPC).
Authors: Chadi Nabhan, Dana Villines, Tina V. Valdez, Kathy Tolzien, Timothy M. Lestingi, Jacob D. Bitran, Christner M. Susan, Merrill J. Egorin, Jan H. Beumer
Journal: Journal of Clinical Oncology (2012)

146 Background: IM is an inhibitor of protein-tyrosine kinases including those that are over-expressed in bone metastases and primary prostatic adenocarcinoma. S is a potent inhibitor of wild-type and mutant BRAF, C-RAF, VEGFR2, VEGFR3, FLT3, and PDGFR-beta with modest activity in CRPC. We combined IM+S to determine the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) in CRPC pts. Methods: CRPC pts with measurable disease and adequate organ function who failed chemotherapy were eligible. Dose escalation followed a 3+3 study design. Toxicity was scored following CTCAEv3. Responses were defined by RECIST1.0. IM pharmacokinetics (PK) were determined on day 15, 4 h post-dose with a validated LC-MS assay. Results: Seventeen pts were enrolled; 10 were evaluable. At dose level 0 (DL0), 6 pts received S at 400 mg S with 300 mg of IM both given daily. At DL1, 4 pts received 400 mg S twice/day with 300 mg IM daily; inevaluable pts received &lt;1 cycle (5 withdrew consent, 1 rapid early progression, 1 non-compliant). Median age was 73 (57-89) and median PSA was 284 ng/ml (11.7–9027). Median number of prior non-hormonal therapies was 3 (1–12) and 12 pts had Gleason score ≥7 while 15 pts had bone as the major site of metastases. On DL0, 1/6 pts had DLT (gr 3 hand/foot). On DL1, 2/4 pts had DLT (1 gr 3 hand/foot, 1 gr 3 diarrhea). MTD was 300 mg IM and 400 mg S both qd. No biochemical responses were observed. Two pts on DL1 had stable disease radiographically by RECIST (overall clinical benefit for the entire cohort 20%). Median time to progression was 2 months (1-5) while median OS was 6 months (1-30+) with 3/17 patients (17%) remaining alive at a median follow-up of 21 months. Of patients enrolled, 10 had PK data, which suggested that S reduced IM clearance by 40%, resulting in 60% increased exposure (P = 0.009; two-tailed t-test on log-transformed values, compared to historic data). Conclusions: To our knowledge, this is the first report to show that IM+S can be safely combined in CRPC. The phase II recommended dose for future trials is 300 mg IM and 400 mg S, both given daily. The PK interaction might be of questionable clinical relevance because IM concentrations are within the commonly observed range.
IL-21 and IL-6 Mediate Interactions Between T Cells and Malignant B Cells in the Bone Marrow Microenvironment in Waldenstrom's Macroglobulinemia
Authors: Lucy S. Hodge, Steve Ziesmer, Frank J Secreto, Zhi-Zhang Yang, Anne Novak, Morie Abraham A Gertz, Stephen M Ansell
Journal: Blood (2012)
Pharmacological Inhibition Of The SIRT1 Deacetylase With The Small Molecule Inhibitor Tenovin-6 Enhances Ablation Of FLT3-ITD+ LSC In Combination With TKI Treatment
Authors: Ling Li, Tereza Osdal, YinWei Ho, Tinisha McDonald, Sookhee Chun, Su Chu, Allen Lin, Cedric Dos Santos, Mihaela Lucia Popa, Bjorn T Gjertsen, Wenyong Chen, Sonia Lain, Emmet McCormack, Ravi Bhatia
Journal: Blood (2013)
Locoregional lymphatic recurrence following axillary dissection for breast cancer.
Authors: S. M. L. Lim, F. L. Lam, S. J. N. Remulla
Journal: Journal of Clinical Oncology (2011)

19 Background: The risk of locoregional recurrence is of concern for women following breast cancer surgery. We report a single surgeon’s experience of locoregional lymphatic recurrence following axillary dissection (AD) in women with breast cancer. Methods: The aim of this study is to identify risk factors for locoregional lymphatic recurrence in women who have undergone breast surgery and AD for T1, T2 tumours. 14 women were identified over 10 years with documented recurrence in the regional lymphatic basin; ipsilateral, contralateral, supraclavicular and internal mammary lymph nodes. One patient presented with bilateral breast cancer. Patient characteristics as well as the tumour grade, ER, PR, HER2 reactivity and presence of lymphovascular invasion (LVI) were analysed. Results: Between 1996 and 2006, 756 women underwent primary surgery for breast cancer in our practice. We identified 14 women who relapsed with locoregional lymphatic recurrence and underwent further surgical management after a median follow-up of 4.5 years. 13/14 had undergone primary breast surgery at our centre, of which 73% underwent total mastectomy and AD. The median age was 48 years, 14% were nulliparous, and 50% were premenopausal. The mean tumour size was 2.48 cm and 7% had a contralateral cancer. The median axillary lymph node (LN) yield was 11.5 of which 57% (8/14) were node negative at primary surgery. In those 8 patients with negative AD, 50% recurred in the ipsilateral axillary LNs, 37.5% recurred in the ipsilateral supraclavicular LNs in the absence of axillary relapse, and 12.5% recurred in the contralateral axillary LNs in the absence of ipsilateral axillary relapse. Of the primary tumour characteristics, 13% were low grade, 43% had LVI, 57% were ER+, 64% PR+, 43% HER2+, and 14% triple negative. None of the patients had distant metastases at the time of relapse in the locoregional lymphatic basin. Conclusions: An axillary dissection did not prevent locoregional lymphatic recurrence in 14 women in our small series. On retrospective analysis, there was no dominant risk factor which could help to identify this group at high risk of relapse, although at least 50% who relapsed locoregionally were less than 50 years, premenopausal with a high tumour grade.
A Phase II Study of Consolidation Treatment with Iodione-131 Tositumomab (Bexxar™) in Multiple Myeloma (MM)
Authors: Daniel Lebovic, Mark S. Kaminski, Tara B. Anderson, Kristen Detweiler-Short, Kent A. Griffith, Terri L. Jobkar, Malathi Kandarpa, Andrzej Jakubowiak
Journal: Blood (2012)
Clinical outcomes of adult patients with relapsed Ewing sarcoma: A 30-year single institution experience.
Authors: S. I. Robinson, S. K. Ahmed, N. N. Laack, P. S. Rose, S. H. Okuno
Journal: Journal of Clinical Oncology (2011)

10041 Background: There is a paucity of information in the literature on adult patients with Ewing sarcoma (ES). This single institution retrospective study specifically aims to determine the prognostic factors that influence the outcome of adult patients who relapse following treatment for localized ES. Methods: The records of 69 patients 18 years and older with localized ES seen at the Mayo Clinic from 1977-2007 who relapsed following initial treatment were studied retrospectively. Early and late relapse were defined as prior to or greater than 2 years from initial diagnosis. Factors relevant to prognosis and survival were analyzed by statistical methods. Results: The median age at initial diagnosis was 28 years (range 18-60). Median follow up was 38 months (range 3.8-293). The 5-year post relapse (PRS) survival for the total group was 22.3%. Gender, site of primary tumor, local control modality, tumor size and age had no influence on outcome. The only statistically significant prognostic markers were site of initial relapse and time to first relapse, using the 2 year cut-off. The probability of 5-year PRS for patients who relapsed locally only was 50.2% versus 13.3% for distant relapse versus 16.67% who relapsed initially at both local and distant sites (p= 0.0209). Similarly, time of relapse ≤2 years versus >2 years from original diagnosis correlated with outcome: 7.6% versus 50.2% 5-year PRS respectively (p= <.0001). These prognostic factors remained significant on multivariate analysis. Conclusions: Adult patients with localized Ewing sarcoma who relapse locally or greater than 2 years following initial diagnosis have a better survival than patients who relapse distantly or prior to the 2-year time point. Aggressive salvage therapy may be warranted in this population.
Effect of neutropenia with adjuvant epirubicin-CMF on survival in patients with node-negative or 1 to 3 node-positive rapidly proliferating breast cancer.
Authors: B. Kopf, E. Scarpi, O. Nanni, M. Faedi, L. Gianni, A. Rocca, W. Zoli, D. Amadori, U. De Giorgi
Journal: Journal of Clinical Oncology (2011)

e11566 Background: Patients who experience at least some degree of neutropenia whilst receiving adjuvant chemotherapy for breast cancer show improved survival. Tumor proliferation is a prognostic marker in breast cancer. We therefore hypothesized that patients with rapidly proliferating breast cancer and evidence of neutropenia whilst on adjuvant chemotherapy would have a better survival than that of similar patients in whom there was no evidence of myelotoxicity. Methods: We reviewed the case notes of 173 women treated in Wide Area of Romagna cancer centers with epirubicin followed by the intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) regimen or the inverse sequence for rapidly proliferating breast cancer, defined by thymidine labeling index (TLI) >3%, to identify patient- and treatment-related factors influencing outcome. Results: The actuarial 5-year overall survival for these women was 94%, with the anticipated poorer outcome for those with higher TLI (≥10% vs <10%, P=0.032). There was no evidence that ER-negative tumors, HER-2 positive disease or older age at presentation resulted in poorer survival. Of note, the absolute survival advantage was confined to the 47% of patients who had grade 3/4 neutropenia (P<0.001) with respect to those with grade 0-2 neutropenia (P=0.268). Conclusions: Our results suggest that neutropenia has a greater influence on outcome than age and tumor biological factors in patients with rapidly proliferating breast cancer.
Next Generation Flow (NGF): A High Sensitive Technique to Detect Circulating Peripheral Blood (PB) Clonal Plasma Cells (cPC) in Patients with Newly Diagnosed of Plasma Cell Neoplasms (PCN)
Authors: *Luzalba Sanoja-Flores, *Bruno Paiva, Juan A Flores-Montero, Noemi Puig, Leire Burgos, Omar García, Felipe Prosper, Juana Merino, Maria Belen Vidriales, Maria-Victoria Mateos, Ramon Garcia, Luis Palomera, Rafael Rios, María Consuelo Cañizo, Brian G M Durie, Jacques J.M. van Dongen, Jesus San Miguel, Alberto Orfao
Journal: Blood (2015)
Treatment of moderate-to-severe atopic eczema in adults within the U.K.: results of a national survey of dermatologists
Authors: K. Taylor, D.J. Swan, A. Affleck, C. Flohr, N.J. Reynolds
Journal: British Journal of Dermatology (2016)

Little is known about U.K. dermatologists' treatment approaches towards adult patients with recalcitrant moderate-to-severe atopic eczema.We wanted to learn about (i) treatment approaches used for this disease in the U.K.; (ii) factors that influence treatment decisions and (iii) perceived gaps in evidence on treatment safety and efficacy, and priorities for future trials.We conducted an online survey of consultant-level dermatologists in the U.K.Sixty-one respondents from over 30 centres reported on management of moderate-to-severe atopic eczema in adults, outwith the context of an acute flare. Phototherapy or psoralen-ultraviolet A was the most common therapeutic modality chosen first line (46%), and this was usually narrowband ultraviolet B. Systemic therapy was chosen as a first-line approach by 36% of dermatologists. Azathioprine was the commonest drug reported being used as first line followed by oral corticosteroids, ciclosporin and methotrexate. Methotrexate was the most common second-line treatment of respondents. The key factors that influenced decision making on the use of phototherapy and systemic agents were the respondent's clinical experience, results of baseline tests (systemic agents) and knowledge of both efficacy and acute and chronic side-effect profiles. The most important evidence gaps identified were the relative effectiveness of treatments, the alternatives to current approaches and the safety of long-term maintenance treatment. With regard to future trials, respondents suggested that priority should be given to studies involving methotrexate.While survey study designs have limitations, we found that phototherapy, in particular narrowband ultraviolet B, was respondents' preferred first-line treatment for adults with recalcitrant moderate-to-severe atopic eczema, perhaps reflecting access to, and clinical experience of, this approach. Azathioprine is widely used as a longer-term maintenance treatment.
Coexpression of PML/RARα and AML1/ETO Leads to ATRA Resistance In Vivo in Acute Promyelocytic Leukemia.
Authors: Rodrigo S. Abreu e Lima, Marcelo R. Baruffi, Ana Silvia G. Lima, Lorena L. Figueiredo, Roberto P. Falcao, Maria de Lourdes F. Chauffaille, Eduardo M. Rego
Journal: Blood (2004)
Detection and Characterization of Antigen-Driven CD8+ T Lymphocytes Specific for Wilms' Tumor Antigen in Patients with Non-Hodgkin Lymphoma
Authors: Ryotaro Nakamura, Anna Israyelyan, Corinna La Rosa, Weimin Tsai, Teodora Kaltcheva, Tumul Srivastava, Jessica Lo, Lia Aquino, Jianqiang Li, Young Kim, Joycelynne Palmer, David Senitzer, John Zaia, Stephen J. Forman, Don J. Diamond
Journal: Blood (2011)
MiR-132 and MiR-212 as Regulators of WT1 and GATA2 in Acute Myeloid Leukemia.
Authors: Maaike Luesink, Jeannet Nigten, Ruth H.J.N. Knops, Theo J.M. de Witte, Bert A. van der Reijden, Joop H. Jansen
Journal: Blood (2009)
When One Diagnosis Is Not Enough
Authors: Kym M. Boycott, A. Micheil Innes
Journal: New England Journal of Medicine (2016)

An accurate diagnosis is essential for effective medical management; in the case of rare genetic disease, it also guides genetic counseling. Nevertheless, clinical assessments and conventional genetic testing lead to a diagnosis in less than half of patients.1 The introduction of whole-exome sequencing has substantially improved our ability to provide patients with a molecular diagnosis and is increasingly the approach of choice for patients with rare diseases. With the genes known for more than half of the predicted 7000 rare diseases,2 such hypothesis-free approaches to diagnosis are attractive and have the potential to end the "diagnostic odyssey."As clinicians, we . . .
Disease-specific survival outcomes in lymph node–positive patients with prostate cancer treated with radiotherapy.
Authors: G. Crehange, V. K. Weinberg, A. Izaguirre, C. C. Hsu, I. J. Hsu, A. R. Gottschalk, K. Shinohara, P. Carroll, M. Roach
Journal: Journal of Clinical Oncology (2011)

182 Background: Involvement of regional lymph nodes (LN+) at the time of prostate cancer (PCa) diagnosis is widely regarded as an adverse prognostic factor associated with poor outcome. No commonly utilized treatment, composed of any combination of androgen ablation, surgery and radiation, has proven to be superior for survival. This study will evaluate the clinical survival outcomes of patients (pts) with newly diagnosed LN+ PCa at the University of California San Francisco (UCSF). Methods: All newly diagnosed LN+ PCa pts treated with External Beam Radiation Therapy (EBRT) as primary therapy or after surgery, each with and without androgen ablation between 1987 and 2009 were included. All pts had confirmed pathologic or radiologic LN+ whereas none had evidence of metastases on the work up. Cause Specific Survival (CSS), Disease Free survival (DFS) and biochemical control were measured from the start of treatment. PSA failure was determined by the Phoenix definition after EBRT and by a confirmed PSA &gt;1 ng/mL following RP+EBRT. Results: A retrospective analysis identified 91 pts with LN+ at the time of diagnosis (75.8% high risk pts) with disease follow-up. Thirty-four (37%) were managed with exclusive EBRT alone (eRT), 18 pts (20%) with a combination of radical prostatectomy (RP) and adjuvant EBRT (RP+aRT) and 39 pts (43%) were treated with a combination of RP + salvage RT (RP+sRT). Overall 78% of patients also received hormone therapy (HT): 74.0% with eRT, 89% with RP+aRT and 79% with RP+sRT. The 10 years CSS estimates was 89% for eRT, 0% after RP+aRT and 88% after RP+sRT. The 10 years DFS estimates was 33% for eRT, 0% after RP+aRT and 75% after RP+sRT. Among pts remaining disease free the median follow-up is 38 mos for eRT, 26 mos for RP+aRT and 64 mos for RP+sRT. The last PSA for these patients was &lt;0.1 for 85% of all patients which included 47% following eRT, 100% after RP+aRT and 97% after RP+sRT. There were 7 deaths due to PCa occurring between 5 and 73 mos from the start of EBRT. Conclusions: The results of the current analysis indicate that some pts with LN+ from PCa have prolonged disease free outcomes; and for these men, aggressive treatment may be appropriate. No significant financial relationships to disclose.
Impact of Long-Term Sequelae Diagnosed after Hematopoietic Cell Transplantation (HCT) on Health-Related Quality of Life (HRQL): A Report from the Bone Marrow Transplant Survivor Study.
Authors: Can-Lan Sun, Liton Francisco, Andrea R. Carter, K. Scott Baker, Marcia Grant, Daniel J. Weisdorf, Stephen J. Forman, Smita Bhatia
Journal: Blood (2006)
The Current State of Epigenetic Research in Humans
Authors: John M. Greally, Amanda J. Drake
Journal: JAMA Pediatrics (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Primary osteosarcomas of the mandible: Joint study of the Groupe Sarcome Francais (GSF), Rare Cancer Network, and Groupe d’Etude des Tumeurs de la Tete et du Cou (GETTEC).
Authors: J. Thariat, I. L. Ray-Coquard, A. Thyss, A. Italiano, J. Sarini, R. C. Miller, E. Bompas, A. Brouchet, O. Dassonville, S. Salas, P. Maingon, J. Kurtz, H. Reychler, T. de La Motte Rouge, K. Aldabbagh, J. Usseglio, P. Kerbrat, J. Lotz, L. Chaigneau, M. Julieron
Journal: Journal of Clinical Oncology (2011)

10036 Background: Mandibular osteosarcoma (MOS) is a rare disease (dz) whose incidence is 1/10 million/year. The prognosis mainly depends on local control. Indications of radiotherapy (RT) for R1 disease (dz) or chemotherapy (chemo) vary among centers. This study focused on the impact of surgery and perioperative management toward outcome. Methods: Prognostic factors (age, histology, tumor size, margins, RT and chemo) for local control and survival were analyzed. Results: 93 patients (pts) treated between 1994 and 2004 were included; 63% were male. Median age was 37 years (14-79). Median tumor size at diagnosis was 4.5 cm. Nodal involvement occurred in 4%. Histology was conventional 32%, osteoblastic 23%, chondroblastic 20%, fibroblastic 5%, small cell 1%, low-grade 4% or unspecified 15%. Tumor size influenced the use of preoperative chemo (p .017) and there was a center effect for chemo and RT use (p .015). Preoperative chemo was performed in 71%, with various regimens containing adriamycin, cisplatin, and methotrexate, yielding a 30% favorable histological response rate. Adequate margins (≥ 0.5 cm) were obtained in 56% of pts. Preoperative chemo improved the rate of R0 margins (68% vs 37%) (p .045). Postoperative chemo was delivered in 58% and postoperative RT in 26% of pts: 42% / 58% with R0 / R1-2 dz, respectively. Neither in R0 nor R1 groups did RT (median 60 Gy) improve local control. Median follow-up for living pts was 52 months. Crude local control, metastatic failure, dz-free, survival rates were 71%, 26%, 63% and 65%, respectively. Metastatic rates were 24% / 32% with / without chemo (NS) and 44% / 19% with / without local relapse (p .01). On uni/multivariate analyses, margins (2 cm / 0.5-2 cm / R1 / R2) were prognostic factors for local control and dz-free survival (p .015); age and tumor size for overall survival (p .05). Conclusions: This largest series to date mostly included high grade MOS. Despite being non-randomized, the results suggest that preoperative chemo may increase the rate of adequate margins, which was a major prognostic factor for local control and dz-free survival. The subset of pts that might benefit from RT and the optimal dose remain to be identified.
Risk-adapted screening in bladder cancer using the open-access Internet-based questionnaire RiskCheck bladder cancer: First evaluation by the health services research foundation IQUO, Germany.
Authors: Gerson Luedecke, Goetz Geiges
Journal: Journal of Clinical Oncology (2012)

263 Background: Till this day urologists are waiting on symptomatic persons to initiate any diagnostic work-up to identify bladder cancer (BC) patients. In result we diagnose a quarter to a third of our patients as muscle-invasive cancers. The open-access questionnaire RiskCheck bladder cancer (RCBC) was proven in a pilot-study in daily routine from German urologists organized in the health services research foundation IQUO on asymptomatic patients. Methods: The open-access RCBC questionnaire was used in urological offices to check asymptomatic patients for their BC risk exposure (personal, smoking, occupation and medical induced). The tool delivers the classical risk stratification in low- intermediate- and high risk. All people with intermediate and high risk were checked for tumor presence by urine diagnostics and in case of suspect results controlled by cystoscopy. Statistical analysis was made by IBM-SPSS 19 for incidence distribution and correlation between risk stratification and tumor detection was proven by classification tree analysis, significance p &lt; 0.05. Results: Out of 196 checked asymptomatic persons 185 (93.4%) were negative for tumor and 11 had a detectable tumor. In the group of NED 125 (68.1%) persons were classified as low risk, 26 (15.7%) as intermediate and 30 (16.2%) as high risk. Out of the 11 detected tumors 9 were at intermediate or high risk (81.8%). This resulted in an over all detection rate of 5.6% and focused on the risk population of 13.2%. The association of tumor presence and increased risk was significant (p &lt; 0.01). Compared to the western incidence rates this is an increase in effectiveness of 377. Conclusions: Risk-adapted screening in bladder cancer delivers a reasonable approach to diagnose bladder cancer before emerging symptoms. The questionnaire RCBC integrates evidence based bladder cancer inductors, is easy in use and as a open-access tool available in 10 languages via the Internet ( www.riskcheck-bladder-cancer.info) .
Effective and Non-Cytotoxic p53 Independent Epigenetic-Differentiation Therapy In Xeno-Transplant Models of Human Acute Myeloid Leukemia
Authors: Kwok Peng Ng, Quteba Ebrahem, Soledad Negrotto, Reda Mahfouz, Kevin Link, Zhenbo Hu, Xiaorong Gu, Anjali Advani, Matt Kalaycio, Mikkael A. Sekeres, Edward A. Copelan, Jaroslaw P Maciejewski, James C. Mulloy, Yogenthiran Saunthararajah
Journal: Blood (2010)