tbuckley/cabot-search huggingface dataset:
Cytokine and angiogenic factor (CAF) profiling for identification of markers associated with response to cediranib in metastatic renal cell carcinoma (mRCC).
Authors: A. J. Zurita, M. Khajavi, P. Mulders, S. Yan, K. S. McKee, H. T. Tran, L. Pike, B. Mookerjee, J. Jurgensmeier, J. Heymach
Journal: Journal of Clinical Oncology (2011)

362 Background: Cediranib is a highly potent and selective signaling inhibitor of vascular endothelial growth factor (VEGF) receptors−1, −2, −3 and c-Kit. In a phase II trial, patients (pts) with mRCC were randomized 3:1 to treatment with cediranib or placebo to primarily assess the difference in change in tumor size at 12 weeks. Cediranib resulted in a significant reduction in tumor size vs. placebo (Mulders et al. ESMO. 2009). Here we investigated soluble biomarkers in serum and concentration changes during treatment. Methods: Pts received cediranib 45 mg/day PO or placebo for the first 12 weeks on treatment. At that time (or upon progression if earlier), treatment was unblinded and pts on placebo were given the option of receiving cediranib. Serum was collected from 61 pts at baseline (BL; cediranib 46, placebo 15), from 50 pts on day (D) 28, and from 45 pts on D84. Multiplex bead suspension arrays and ELISA were used to measure CAF concentrations including VEGF, placental growth factor (PlGF), sVEGFR-2, PDGFbb, HGF, MMP-9, multiple chemokines and interleukins (IL). The objectives of this exploratory analysis were to assess whether baseline CAFs were associated with changes in tumor size after 12 weeks of treatment and whether CAF levels changed while on treatment. Results: Of 39 CAFs available at BL, lower than median (‘low') concentrations of IL-10, VEGF, PlGF, stem cell factor (SCF), and monokine-induced by interferon-gamma (MIG) were associated with larger decreases in tumor size than high concentrations (independent of treatment arm), whereas the opposite trend was observed for IL-5 and TRAIL. Consistent with inhibition of VEGF signaling, cediranib treatment resulted in changes over time in VEGF (increase), sVEGFR-2 (decrease) and PlGF (increase) concentrations. In addition, SCF, a c-Kit ligand and M-CSF decreased, while VCAM-1 and TRAIL increased during cediranib treatment. Conclusions: Candidate CAFs associated with response to cediranib in mRCC such as IL-10 and VEGF were identified. Patients treated with cediranib showed distinct CAF changes compared with placebo. These results require independent validation in a larger trial. [Table: see text]
Early experience with robotic radiosurgery for local control of liver metastasis.
Authors: Michael Kwiatt, Francis R. Spitz, Tamara A. LaCouture
Journal: Journal of Clinical Oncology (2012)

295 Background: Liver toxicity limits radiation therapy for liver metastasis; however, robotic radiosurgery delivers effective doses with limited toxicities. Robotic radiosurgery may be an effective treatment for liver metastases in patients with lesions not amenable to surgical resection. Methods: We conducted a retrospective study of patients treated with robotic radiosurgery for liver metastasis at our institution from June 2008 and June 2010. Medical records were reviewed and all cases discussed in multi-disciplinary conference. Preradiosurgery and follow-up abdominal computed tomography (CT) scans reviewed for treatment response. Our primary endpoint was local recurrence, defined as increased enhancement or tumor progression within the treatment field on follow-up CT scan. Results: Thirty-three patients had 37 liver metastasis treated with robotic radiosurgery (17 colorectal, 4 ovarian, 4 breast, 3 melanoma, 2 liver, 2 lung, 1 gastric, 1 cholangiocarcinoma, 1 pancreas, 1 anal, 1 bladder). Eighteen of 33 patients (54.5%) had isolated liver metastasis. Prior to radiosurgery 27 of 33 patients (81.8%) had undergone surgical resection of primary tumor, 26 of 33 patients (78.8%) were treated with chemotherapy for metastatic disease, and 15 of 33 patients (45.5%) had non-liver radiation therapy. Median time from primary diagnosis to radiosurgery treatment was 33.3 months (5.7 to 320 months). Patients received median radiation dose of 30 Gy (22.5 to 42) over 3 to 5 fractions. Median follow up was 8.1 months (1.2 to 23.5). There were no cases of liver failure. Sixteen patients had disease progression outside the treatment field (15 liver, 6 systemic) with a median time to progression of 4.6 months (0.9 to 17.6). Five lesions (13.5%) had in field progression with a median time to progression of 10 months (2.6 to 13.1). Seventeen patients (51.5%) died during follow-up. Conclusions: Robotic radiosurgery offers a potential local therapy for patients with metastatic liver disease with limited toxicity. Longer follow-up and more patients are required to better assess its safety. Robotic radiosurgery may fill a role for patients with lesions not amenable to traditional ablative and surgical techniques.
NHS to fund large trial of pre-exposure prophylaxis for HIV prevention
Authors: Susan Mayor
Journal: BMJ (2016)

NHS England has announced that it will fund a large clinical trial of pre-exposure prophylaxis (PrEP) to prevent HIV in at least 10 000 people over the next three years.

The initiative follows a legal battle over who should fund PrEP. NHS England initially took the position that local councils should commission preventative services such as PrEP1 and reiterated this in May after taking legal advice.2 But the High Court ruled in August that NHS England had responsibility.3

NHS England appealed against this decision …
Evaluation of recurrence score and traditional clinicopathologic metrics in a large ER-positive, lymph node–negative patient cohort.
Authors: F. L. Baehner, N. Liebermann, S. Shak, S. Klang, C. Yoshizawa, s. Lior, N. Siegelmann-Danieli
Journal: Journal of Clinical Oncology (2011)

30 Background: The 21 gene Recurrence Score (RS) assay provides prognostic and predictive info for ER+ breast cancer. In a large cohort of ER+, HER2 normal, lymph node negative (LN-) patients, the distribution of RS and RS groups, within categories of patient age, tumor size, grade, and joint categories (e.g., tumor size versus patient age), were examined. Methods: 2,097 pts from Clalit Health Services (CHS) and 484 from Maccabi Health Services (MHS) in Israel, had the RS ordered between 1/08-6/10. 1864 were LN-, ER+ and HER2 nrml (LN- grade 3 tumors of MHS pts were required to be &lt;2 cm). Pt age, tumor size and grade were obtained for 100%, 99% and 82%. Distributions of RS were compared among categories of the traditional factors and Spearman correlation coefficients (and 95% CI) were calculated to assess the association between the RS and them. Results: 99.3% were female. Standard distributions by age were: 23-40 yo, 3.2%; 40-49 , 16.5%; 50-59, 30.4%; 60-69, 32.8%; 70-85, 17.1%. By tumor size: &lt;1 cm, 12.5%; 1-2cm, 65.8%; &gt;2-3cm, 17.3%; &gt;3cm, 4.5%. By grade: 1, 18.1%; 2, 63%; 3, 18.9%. 79.7% were ductal &amp; 12.5% lobular. 81.9% were IHC PR+. Spearman correlation coefficients (and 95% CI) for continuous RS with standard metrics: age, -0.09 (-0.13, -0.04); tumor size (cm), 0.07 (0.02,0.12); grade, 0.33 (0.28, 0.37). Pts &lt;50 yo, 14.2% had high RS disease (dz); ≥50 yo 10.3% had high RS dz. In tumors ≤2 cm, 16% had high RS dz; &gt; 2 cm 30.7% had high RS dz. Of grade 1 tumors 1.4% had high RS dz and 30.7% had intermediate RS while 22.8% of grade 3 tumors had low RS dz. 7.5% of PR+ tumors had high RS dz and 20.1% of PR- tumors had low RS dz. Joint categories will be presented. Conclusions: There is a range of RS biology across patient age, tumor size and grade. The RS cannot be predicted by clinicopathologic variables. [Table: see text]
Nipple-sparing mastectomy: Evaluation of oncologic safety and aesthetic outcomes in 94 patients.
Authors: E. C. Millen, R. R. Pinto, L. Menezes, F. C. O. Almeida, G. Novita, A. L. Frasson, B. h. Paula, M. R. D. S. Cruz
Journal: Journal of Clinical Oncology (2011)

97 Background: The surgical treatment of breast cancer has evolved from radical mastectomy to breast conservation therapy. Today we have another therapeutic dilemma: how to manage the nipple-areolar complex (NAC) in mastectomy offering patients better aesthetic results with oncologic safety. Methods: We analyzed data on 125 consecutive nipple- or skin-sparing mastectomies (SSM) with immediate reconstruction with tissue expander, prosthesis or autologous tissue performed in 94 patients from 2003 to 2010 in a tertiary referral hospital. Nipple-sparing mastectomy (NSM) was performed for treatment disease (n= 94) and prophylaxis of contralateral breast or symmetrization in selected cases (n= 31). Results: Mean patients age was 46.8 years (range 27 to 69 years) and mean follow-up time was 27.2 months (range 2 weeks to 81 months). Twelve patients were stage 0, 41 stage I, 35 stage II A and B and 7 stage III. There were 125 nipple- or areola-sparing mastectomies (31 bilateral and 94 unilateral), including 112 NSM and 13 SSM. On pathologic review, 12 breasts had carcinoma in situ, 83 invasive carcinoma, and 31 breasts were cancer free. Thirteen nipples (13.8%) were compromised by tumor on subareolar biopsy and were removed. The location and type of incision was variable according to the tumor site and previous patient scar. Periareolar incision with prolongation along the inferior pole of breast was the preferred method. Patients with positive axillary node (27.5%) received adjuvant radiotherapy. There was no nipple necrosis. One patient presented local relapse in the skin-sparing group within 24 months. Conclusions: These data demonstrate that NSM is oncologically safe and can be performed with all types of breast reconstruction.
Value of prostate MRI in determining appropriate candidates for active surveillance.
Authors: Daniel Margolis, Nelly Tan, Shyam Natarajan, Karim Chamie, David Finley, Robert Evan Reiter, Jiaoti Huang, Steven Raman
Journal: Journal of Clinical Oncology (2012)

109 Background: The objective was to measure the added benefit of multi-parametric endorectal coil prostate MRI (eMRI) to traditional active (AS) criteria in delineating men with more advanced disease. Methods: We performed a retrospective study of 115 men who underwent robot-assisted laparoscopic prostatectomy (RALP) for their CaP with whole-mount pathological evaluation. All men underwent eMRI for surgical planning—including T2 weighted, diffusion-weighted (DWI), dynamic contrast-enhanced (DCE), and MR Spectroscopy—between July 2008 and March 2011. We examined the diagnostics of Epstein’s criteria (E-AS) for clinically insignificant CaP or in combination with MR parameters (eMRI-AS criteria) in predicting more advanced disease. E-AS criteria included Gleason score (GS) 3+3=6, &lt;3 biopsy cores positive, PSA &lt;10, ≤50% maximum % of cancer in any one core. The addition of apparent diffusion coefficient &gt;0.85x10-3 mm2/sec, Ktrans&lt;0.5 Hz, Kep&gt;1.5 Hz, and normal MRSI defined the eMRI-AS cohort. Outcomes were stratified into low vs. high surgical risk. Low-risk disease was defined as having pT2, GS &lt;3+4 with tumor size &lt;1.5 cm, and negative surgical margins (SM). Conversely, higher-risk disease included men with GS ≥4+3, positive SM, ≥pT3 or those with GS 3+4 with tumor size ≥1.5 cm. Results: We identified 104 who met our inclusion criteria. We excluded 11 (9%) men due to post-biopsy hemorrhage (n=4), failed DCE (n=4), poor DWI (n=2), and two-year delay between MRI and RALP (n=1). Mean age was 60.6 years. Thirty-seven men (35%) satisfied E-AS, while 25 men (24%) satisfied eMRI-AS. On whole-mount sectioning 49 (47%) men were low surgical risk. E-AS to detect low surgical risk revealed a sensitivity, specificity, false positive, false negative and AUC of 67%, 73%, 33%, 27%, and 70%, respectively. eMRI-AS performance parameters were: 62.8%, 94.4%, 37%, 5% and 78%—significantly different than E-AS (p=0.04). Conclusions: eMRI-AS outperformed Epstein-AS in identifying poor candidates from going onto AS. If patients were identified as AS candidates based on traditional criteria, we found that 27% actually had higher risk disease; whereas the addition of eMRI reduced this number to 5%.
Individualized vaccination of AML patients in remission is associated with induction of antileukemia immunity and prolonged remissions
Authors: Jacalyn Rosenblatt, Richard M. Stone, Lynne Uhl, Donna Neuberg, Robin Joyce, James D. Levine, Jon Arnason, Malgorzata McMasters, Katarina Luptakova, Salvia Jain, Jeffrey I. Zwicker, Ayad Hamdan, Vassiliki Boussiotis, David P. Steensma, Daniel J. DeAngelo, Ilene Galinsky, Poorvi Somaiya Dutt, Emma Logan, Mary Paty Bryant, Dina Stroopinsky, Lillian Werner, Kristen Palmer, Max Coll, Abigail Washington, Leandra Cole, Donald Kufe, David Avigan
Journal: Science Translational Medicine (2016)

A personalized DC/AML fusion cell vaccine promotes the expansion of leukemia-specific T cells and prolonged remission in patients.
EphA3 as a target for antibody immunotherapy in acute lymphoblastic leukemia
Authors: S Charmsaz, F Al-Ejeh, T M Yeadon, K J Miller, F M Smith, B W Stringer, A S Moore, F-T Lee, L T Cooper, C Stylianou, G T Yarranton, J Woronicz, A M Scott, M Lackmann, A W Boyd
Journal: Leukemia (2016)

The human EphA3 gene was discovered in a pre-B acute lymphoblastic leukemia (pre-B-ALL) using the EphA3-specific monoclonal antibody (mAb), IIIA4, which binds and activates both human and mouse EphA3. We use two models of human pre-B-ALL to examine EphA3 function, demonstrating effects on pre-B-cell receptor signaling. In therapeutic targeting studies, we demonstrated antitumor effects of the IIIA4 mAb in EphA3-expressing leukemic xenografts and no antitumor effect in the xenografts with no EphA3 expression providing evidence that EphA3 is a functional therapeutic target in pre-B-ALL. Here we show that the therapeutic effect of the anti-EphA3 antibody was greatly enhanced by adding an α-particle-emitting 213Bismuth payload.
Bortezomib in Combination with Pegylated Liposomal Doxorubicin and Thalidomide (VDT), An Effective Steroid Independent Regimen for Previously Untreated Multiple Myeloma Patients: Final Result of a Phase II Study.
Authors: Taimur Sher, Kena C Miller, Sikander Ailawadhi, Debbie Manfredi, Margaret Wood, Wei Tan, Gregory Wilding, Hong Liu, Myron S Czuczman, Francisco Hernandez, Frederick Hong, Raman Sood, Saif Soniwalla, William Lawrence, Peter A. Kouides, Kelvin P. Lee, Asher Chanan-Khan
Journal: Blood (2009)
Comparison of Outcomes After Allogeneic Hematopoietic Cell Transplantation (Allo-HCT) In 73 Patients with Follicular Lymphoma (FL), Transformed Follicular Lymphoma (TL), or De Novo Diffuse Large B-Cell Lymphoma (DLBCL): Favorable Outcome for TL Similar to FL
Authors: Kohei Tada, Sung-Won Kim, Yoshitaka Asakura, Nobuhiro Hiramoto, Kimikazu Yakushijin, Saiko Kurosawa, Niina Ueno, Yutaro Kamiyama, Suguru Fukuhara, Shinichiro Mori, Yuji Heike, Ryuji Tanosaki, Kensei Tobinai, Yoichi Takaue, Takahiro Fukuda
Journal: Blood (2010)
Patient characteristics associated with the decision to undergo bilateral prophylactic mastectomy for lobular carcinoma in situ.
Authors: S. Muhsen, M. J. Junqueira, A. Park, J. S. Sung, S. Patil, S. Oskar, M. Morrogh, M. Morrow, T. A. King
Journal: Journal of Clinical Oncology (2011)

148 Background: Women at increased risk for breast cancer due to a diagnosis of lobular carcinoma in situ (LCIS) have three management options: high risk surveillance +/- chemoprevention (CP) or bilateral prophylactic mastectomy (BPM). Among a large cohort of women with LCIS, we previously reported there were no differences between women choosing CP compared to those choosing surveillance alone. The purpose of this study was to identify patient factors associated with the decision to pursue BPM for LCIS. Methods: We reviewed our prospectively maintained LCIS database to identify women choosing BPM (1995-2009). Comparisons were made between patients who chose BPM versus those who chose high risk surveillance +/- CP. Results: Among 995 pts with LCIS, 795 (80%) chose surveillance alone, 149 (15%) chose CP and 51 (5%) chose BPM. Compared to patients electing surveillance +/- CP patients who pursued BPM were younger at age of LCIS diagnosis (48 vs. 52 yrs, p &lt; 0.001), more likely to have bilateral biopsies with LCIS (14% vs. 3%, p = 0.002) and more likely to be premenopausal (82% vs. 57%, p &lt; 0.001). Patients choosing BPM were also more likely to have additional risk factors for breast cancer including: stronger family histories and extremely dense breasts (Table). Occult breast cancer was found in 4 (8%) BPM patients. At a median follow-up of 54 months (range 0-190 mos), 120/944 (13%) patients in the surveillance +/- CP group developed breast cancer. Conclusions: High-risk surveillance alone is the preferred management option for women with LCIS at our institution. Patients electing BPM are younger and more likely to have other associated risk factors for developing breast cancer. Further research to define how the increased risk imparted by LCIS is augmented by these factors may allow for better risk stratification and more informed discussions with patients. [Table: see text]
Absence of Chlamydial Infection in Japanese Patients with Ocular Adnexal MALT Lymphoma.
Authors: Yoshihiro Yakushijin, Toshio Kodama, Ikue Takaoka, Kazushi Tanimoto, Hiroko Bessho, Jun Yamanouchi, Taichi Azuma, Hiroshi Narumi, Takaaki Hato, Hitoshi Hasegawa, Masaki Yasukawa
Journal: Blood (2006)
Developmental Differences In the Let-7b/IMP-1/IGF-II Axis contribute to the High Proliferative Rate of Neonatal Megakaryocyte Progenitors.
Authors: Ravi K. Gutti, Hannes Sallmon, Zhi-Jian Liu, Francisca Ferrer-Marin, Alan Cantor, Matthew Bailey, Martha Sola-Visner
Journal: Blood (2010)
Outcome and Toxicities of Modified Augmented Berlin-Frankfurt-Muenster (ABFM) Therapy Used in the Treatment of Acute Lymphoblastic Leukemia in Adolescent and Young Adult Patients, Single Center Experience From Saudi Arabia
Authors: Suhaib Radi, Anas Merdad, Mona Al-Dabbagh, Ahmed Almohanad Absi, Ahmad Alsaeed, Ihab El-Hemaidi
Journal: Blood (2012)
Investigating the Nrf2 transcription factor as a regulator of cisplatin resistance in urothelial carcinoma (UC) cells.
Authors: S. J. Crabb, A. Hayden, K. Gould, L. Andrews, G. Packham
Journal: Journal of Clinical Oncology (2011)

256 Background: Nrf2 controls expression of multiple target genes, each containing an antioxidant response element (ARE). These targets mediate cellular protection through antioxidant response, cellular detoxification (including glutathione conjugation), and altered drug uptake/efflux. Some targets (e.g., metallothionein, glutathione reductase) are associated with UC characteristics, outcomes, and chemotherapy resistance. Nrf2 regulation is partially understood and includes negative regulation by Keap1 and phosphorylation. De-novo or acquired cisplatin resistance is a problem in UC. We hypothesised that it might be mediated by Nrf2. Methods: Nrf2 expression was assessed in UC clinical samples by immunohistochemistry. We then utilised a panel of UC cell lines, including a cisplatin resistant RT112 sub-line (RT112CP), to test Nrf2 axis expression and activation correlated to cisplatin sensitivity/resistance. Effects of AKT or HER2 kinase activity on Nrf2 activation were tested by chemical inhibition. Results: In UC clinical samples we detected Nrf2 over-expression in 64% of cancers compared to surrounding normal tissue. Varied Nrf2 expression levels were also detected in different UC cell lines whereas Keap1 demonstrated an inverse profile of both RNA and protein expression. Nrf2 expression was 4 fold greater in RT112CP cells which exhibited comparative cisplatin resistance (10 fold greater IC 50 in proliferation assays) compared to parental cells. Nrf2 over expression was functional in this model system as indicated by increased activity in ARE luciferase reporter assays, raised expression of Nrf2 transcriptional targets (metallothionein, glutathione reductase) and glutathione levels. Furthermore, depletion of Nrf2 in RT112CP cells by siRNA or transfection of a dominant negative Nrf2 construct partially restored cisplatin sensitivity. Finally chemical inhibition of AKT or HER2 reduced Nrf2 activation in ARE reporter assays. Conclusions: Nrf2 is overexpressed in a subset of UC. In cell line models it is functionally activated and contributes to cisplatin resistance, which is reversible. This might be amenable to detection and therapeutic reversal in the clinic. No significant financial relationships to disclose.
Intense dose-dense (idd) sequential chemotherapy with epirubicin (E), paclitaxel (T), and cyclophosphamide (C) (ETC) compared with conventionally scheduled chemotherapy in high-risk breast cancer patients (&gt; 3+LN): Eight-year follow-up analysis.
Authors: V. Moebus, C. Thomssen, H. Lueck, W. Kuhn, A. Junker-Stein, C. M. Kurbacher, U. Nitz, R. Kreienberg, M. Untch, C. Jackisch, J. B. Huober, A. Hinke, A. Du Bois, A. Schneeweiss
Journal: Journal of Clinical Oncology (2011)

1018 Background: Dose-dense chemotherapy has become one of the possible standards in breast cancer patients (pts). Both, CALGB C9741 and AGO-ETC have reported statistical significant benefit in 5-year DFS and OS. We now report long-term safety and efficacy after 8 years of follow-up. Methods: A multi-center phase-III trial of the German AGO Group recruited 1284 pts from 12/98 until 4/03. Pts below 65 years of age were eligible if they had at least 4 involved axillary lymph nodes. In the experimental arm, pts were assigned to receive three courses each of epirubicin (150 mg/m2), paclitaxel (225 mg/m2) and cyclophosphamide (2500 mg/m2) at 2-week intervals (q2wks) (iddETC) with G-CSF support (5µg/kg/SC day 3−10). In the standard arm 4 courses of conventional dosed epirubicin/cyclophosphamide (90/600 mg/m2) followed by 4 courses of paclitaxel (175 mg/m2) (q3wks) were given. Results: Median age was 51 years. Risk factors were well balanced in both arms. 58% and 42% of the pts had 4−9 and >9 infiltrated nodes. The median number of positive nodes was 8. No severe late cardiotoxicity was reported. 8 vs. 0 pts in the idd ETC-Arm developed AML or MDS. 4 of these 8 pts. received less than the planned 9 cycles. At a median follow-up of 8 years 231 pts in the idd ETC arm vs. 285 pts in the standard arm had relapsed. This difference was highly significant in the one-sided log-rank test (p<0.0001) with a HR of 0.71 (95% CI: 0.59 − 0.84). 8-year RFS is 62% in the idd ETC-arm vs. 51% in the standard arm. 172 pts. have died in the idd ETC arm vs. 205 in the standard arm (two-sided log-rank test: p=0.0086; HR: 0.76 (95% CI: 0.62−0.93). 8-year OS is 71% in the idd ETC-arm vs. 65% in the standard arm. The results are independent from hormone receptor, menopausal status, number of positive nodes (4−9; >9) or HER2-expression. Conclusions: Eight year follow-up analysis of the AGO-ETC trial confirmed that intense- dose-dense ETC significantly improves DFS and OS in high-risk breast cancer pts.
Prognostic Significance of VEGF, VEGF Receptors, and Microvessel Density in Diffuse Large B Cell Lymphoma Treated with Anthracycline-Based Chemotherapy.
Authors: Dita Gratzinger, Shuchun Zhao, Robert J. Tibshirani, Eric D. Hsi, Christine P. Hans, Brad Pohlman, Martin Bast, Abraham Avigdor, Ginette Schiby, Arnon Nagler, Gerald E. Byrne, Izidore S. Lossos, Yasodha Natkunam
Journal: Blood (2007)
Mast Cells Are Involved by the Malignant Process and Play An Important Role in the Pruritogenesis in Patients with Myeloproliferative Disorders
Authors: Takefumi Ishii, Jiapeng Wang, Wei Zhang, John Mascarenhas, Ying Dai, Vesna Najfeld, Ronald Hoffman, Nathaniel Wisch, Mingjiang Xu
Journal: Blood (2008)