tbuckley/cabot-search huggingface dataset:
Clinical Significance of Chromosomal Abnormalities in Patients with Aplastic Anemia and Refractory Anemia Deduced From the Prevalence of PNH-Type Cells.
Authors: Naomi Sugimori, Hirohito Yamazaki, Chiharu Sugimori, Ken Ishiyama, Takamasa Katagiri, Shinji Nakao
Journal: Blood (2009)
Demography and treatment outcomes of triple-negative breast cancer: A single institution study.
Authors: S. E. James, P. Vos, T. Biswas
Journal: Journal of Clinical Oncology (2011)

179 Background: Triple negative breast cancer (TNBC) constitutes about 11-20% of all cases of breast cancer. TNBC has particularly aggressive clinical course and worse prognosis especially in African American (AA) women compared to white women. This retrospective study aims to investigate TNBC in the eastern North Carolina (NC) population, report treatment outcomes and determine the rate of recurrence. Methods: 202 TNBC patients treated at our institution between 1/01 and 11/09 were included in this analysis. Eastern NC has an AA population higher than the national average (30.2% vs. 12.4%) which is reflected in our patient demographics with 111 (55%) AA, 84 (41.6%) White, 5 (2.5%) Hispanic and 2 (1%) Chinese patients. Stage distribution was 41 (20%) stage I, 97 (48%) stage II, 37 (18%) stage III, 16 (8%) stage IV disease. Six patients (3%) had a diagnosis of DCIS and 5 (3%) were unknown. Majority was (79%) poorly differentiated carcinoma followed by moderately differentiated (13%) carcinoma. Variables were compared between groups using two-sample t-tests. Kaplan Meier curves were generated for overall survival (OS). Group was compared by log rank test. Results: The median FU time was 4.73 years (1.2–10.2). Median age at diagnosis was 53 (22-88) years overall, 51 years for AA and 57 years for White (p=0.01) patients. The overall median survival was 32.18 months with no difference between AA (32.39 months) and white (29.7 months) patients (p=0.785). 160 patients with stage I-III disease received chemotherapy with 96 patients (60%) receiving adjuvant and 64 (40%) receiving neoadjuvant therapy. The median survival for adjuvant patients was 37.08 months (6.87–113) vs 26.48 months (1.51–87.49) for neoadjuvant patients (p=0.001). 27 (14%) patients with stage I-III diseases experienced a local recurrence, 31 patients (15%) experienced distal recurrence with a median time to failure of 25.6 months. Conclusions: This study demonstrated no significant difference in median survival between AA and white patients; however, AA women were diagnosed at a younger age compared to white women. Patients treated with adjuvant chemotherapy had a significantly greater median survival when compared to patients receiving neoadjuvant treatment.
MLN9708, a Novel, Investigational Oral Proteasome Inhibitor, in Patients with Relapsed or Refractory Light-Chain Amyloidosis (AL): Results of a Phase 1 Study
Authors: Giampaolo Merlini, Vaishali Sanchorawala, Jeffrey A. Zonder, Vishal Kukreti, Stefan O Schonland, Arnaud Jaccard, Angela Dispenzieri, Adam D. Cohen, Deborah Berg, Guohui Liu, Alessandra Di Bacco, Neeraj Gupta, Ai-Min Hui, Giovanni Palladini, Raymond L. Comenzo
Journal: Blood (2012)
Computations Underlying Social Hierarchy Learning: Distinct Neural Mechanisms for Updating and Representing Self-Relevant Information
Authors: Dharshan Kumaran, Andrea Banino, Charles Blundell, Demis Hassabis, Peter Dayan
Journal: Neuron (2016)

Knowledge about social hierarchies organizes human behavior, yet we understand little about the underlying computations. Here we show that a Bayesian inference scheme, which tracks the power of individuals, better captures behavioral and neural data compared with a reinforcement learning model inspired by rating systems used in games such as chess. We provide evidence that the medial prefrontal cortex (MPFC) selectively mediates the updating of knowledge about one's own hierarchy, as opposed to that of another individual, a process that underpinned successful performance and involved functional interactions with the amygdala and hippocampus. In contrast, we observed domain-general coding of rank in the amygdala and hippocampus, even when the task did not require it. Our findings reveal the computations underlying a core aspect of social cognition and provide new evidence that self-relevant information may indeed be afforded a unique representational status in the brain.
Effect of salvage radiofrequency ablation on local control of recurrent renal cell carcinoma.
Authors: S. P. Psutka, A. Daha, D. Gervais, A. S. Feldman
Journal: Journal of Clinical Oncology (2011)

355 Background: Radiofrequency ablation (RFA) has emerged as a safe and efficacious option to manage small renal cell carcinoma (RCC) in patients for whom comorbidities preclude surgical treatment. Salvage surgical excision of disease recurrence after ablative therapy is often complicated by extensive perinephric fibrosis. There are no reports in the literature which assess salvage RFA (sRFA) of recurrent disease (RD). The aim of this study was to assess the overall efficacy, complications, and safety of sRFA. Methods: Between 1998 and 2008, 313 patients underwent RFA for RCC. RD was defined as detectable new enhancing tissue in the prior RFA-cavitation site after a documented complete response. We retrospectively compared patients who developed RD (RD+, n = 15, 5.1%) with patients who remained disease free after a complete response (RD−, n = 296, 95%), assessing tumor characteristics (size, location, biopsy pathology), complications, and disease-free survival. Mean follow-up was 3 years (SD 2.1). Results: RD+ and RD− groups did not differ significantly in age, gender, or tumor type. In tumors &lt; 4cm, 3.3% were RD+. In tumors &gt;= 4cm, 9.6% were RD+ (p&lt;0.0001). RD+ groups were more likely to have central tumors (20% vs. 5.7%, p = 0.04). Mean time to disease recurrence was 1.47 years (SD 0.75, 0.5-3.5 yrs). Of the 15 patients with RD, 7 patients underwent sRFA, 6 patients elected observation due to comorbidities precluding further treatment, one patient received chemotherapy for widespread metastases and one patient underwent salvage partial nephrectomy, which was aborted due to extensive tumor burden and perirenal fibrosis. There were no complications related to sRFA. Of those who underwent sRFA, local recurrences were successfully ablated in 100% of cases with a single salvage RFA treatment. None of these sRFA cases developed locally recurrent disease at an average of 3 years follow-up. Conclusions: RD after RFA remains challenging to treat due to the significant comorbidities of the patients who are candidates for ablative treatment of RCC. RD was more likely to occur in centrally located tumors, &gt; 4cm in size. Salvage RFA successfully can achieve local control in these patients without increased rates of complications. No significant financial relationships to disclose.
Generation of Monoclonal TCR-Expressing Human T-Lineage Lymphocytes From Induced Pluripotent Stem Cells of Single Peripheral T-Lymphocyte Origin
Authors: Toshinobu Nishimura, Shin Kaneko, Haruo Gotoh, Naoya Takayama, Takafumi Shimizu, Shoichi Iriguchi, Yoko Tajima, Yutaka Yasui, Nobukazu Watanabe, Satoshi Takahashi, Koji Eto, Hiromitsu Nakauchi
Journal: Blood (2010)
A phase I/II study of adenovirus-mediated interleukin-12 gene therapy for hormone refractory prostate cancer: An interim report.
Authors: K. Sasaki, Y. Nasu, H. Kaku, M. Watanabe, H. Nose, D. Kanbara, T. Saika, H. Kumon
Journal: Journal of Clinical Oncology (2011)

148 Background: A phase I/II study of adenovirus-mediated interleukin-12 (IL–12) gene therapy for castration resistant prostate cancer has been initiated from May 2008 in Okayama University Hospital. Interim results of 10 cases including a positive clinical response are reported. Methods: Major inclusion criteria was a recurrence of prostate cancer following hormonal therapy with/without metastasis. Replication–defective adenovirus vector expressing IL–12 (Adv.IL–12) was injected directly into the prostate (or metastatic lesion in patients who received prostatectomy) in escalating doses from 1.0×10 10 to 5.0×10 12 viral particle (vp). GMP grade vector was produced at Center for Cell and Gene Therapy, Baylor College of Medicine (Director: Malcolm K. Brenner). Each patient received total of 3 times viral injections every 4 weeks. In addition to the safety profile, cancer control efficacy and immunological changes after viral injections were evaluated. Results: Ten patients received the gene therapy in doses of 1.0×10 10 to 5.0×10 11 vp from May 2008 to October 2010. 9 cases completed, and 1 patient dropped out the study because of rapid cancer progression. Major adverse effects are following: urinary retention (G1), trasaminase elevation (G3), fever up (G3). These adverse effects were rapidly disappeared after proper treatments. One patient with highest dose (5.0×10 11 vp) showed some clinical positive responses (PSA decrease, shrinkage of lymphnode metastasis), therefore received an additional viral injection. Temporal decreases just after each vector injections and gradual increases at the peak of 7-14 days after each vector injections in some immunocompetent cells (CD3+CD19–, CD3–CD19– CD16+CD56+, CD3+CD4–CD8–) were seen in relatively high dose group. Elevations of serum cytokines were observed in parallel with vector dose escalation. Conclusions: This interim report suggests the favorable safety profile and positive clinical responses in a clinical trial of Adv.IL–12 gene therapy for hormone refractory prostate cancer in higher doses of viral vectors. Further evaluations in the next higher vector doses are needed and in progress. No significant financial relationships to disclose.
Randomized phase II trial of gemcitabine plus S−1 combination therapy versus S−1 in advanced biliary tract cancer: Results of the Japan Clinical Oncology Group study (JCOG0805).
Authors: Makoto Ueno, Takuji Okusaka, Junki Mizusawa, Atsuo Takashima, Chigusa Morizane, Masafumi Ikeda, Yasuo Hamamoto, Hiroshi Ishii, Hiroki Hara, Akira Fukutomi, Masayuki Furukawa, Michitaka Nagase, Taketo Yamaguchi, Kenji Yamao, Shoji Nakamori, Tatsuya Ioka, Haruo Iguchi, Hiroyuki Miyakawa, Narikazu Boku, Junji Furuse
Journal: Journal of Clinical Oncology (2012)

4031 Background: Gemcitabine plus cisplatin combination (GC) therapy is the standard therapy for advanced biliary tract cancer (BTC). In previous trials, gemcitabine plus S-1 combination (GS) therapy and S-1 mono-therapy had shown considerable efficacy in patients with BTC. The aim of this trial is to evaluate the efficacy and safety of the two regimens and to determine which is more promising as a test arm regimen for a subsequent phase III trial. Methods: Chemotherapy-naive patients with recurrent or unresectable BTC (gallbladder [GB], intrahepatic biliary duct [IHBD], extrahepatic biliary duct [EHBD], ampulla of Vater [AV]), an ECOG PS of 0 - 1, and adequate organ function were randomly assigned to receive GS (gemcitabine: 1,000 mg/m 2 , iv, days 1 and 8; S-1: 60 mg/m 2 , p.o., days 1 - 14, every 3 weeks) or S-1 (80 mg/m 2 , p.o., days 1 - 28, every 6 weeks). We assumed that %1-year survival of one regimen is 30% and that of the other regimen is more than 40%. To ensure at least 85% probability of correct selection, 98 eligible pts are required. The decision rule was that the regimen with higher %1-year survival will be considered as more promising regimen. Results: From February 2009 to April 2010, 101 pts (GB, n=38; IHBD, n=35; EHBD, n=20; AV, n=8) were randomized (GS, n=51; S-1, n=50). For the GS arm and S-1 arm, %1-year survivals were 52.9% and 40.0%, the median survival time were 12.5 and 9.0 months (hazard ratio 0.86 [95%CI 0.54-1.36]; p=0.52), and the median progression-free survival time were 7.1 and 4.2 months (0.44 [0.29-0.67]; p&lt;0.0001). Grade 3/4 hematological toxicities were more frequent in the GS arm than in the S-1 arm, (percentage in GS/S-1 arms): neutropenia, 60.8/4.0; leukocytopenia, 29.4/2.0; hemoglobin, 11.8/4.0; and thrombocytopenia, 11.8/4.0; respectively. Although two treatment-related deaths occurred in the GS arm (pneumonitis, acute myocardial infarction), other grade 3/4 non-hematological toxicities were infrequent and reversible in both arms. Conclusions: The GS arm was superior in %1-year survival to S-1. Here we consider GS to be more promising as the test arm for a subsequent phase III trial comparing with GC.
Sapphyrins Exhibit Tumor Selectivity and Efficacy in Animal Models of Hematologic Malignancies.
Authors: Louie Naumovski, Mint Sirisawad, Philip Lecane, Jason Ramos, Darren Magda, Zhong Wang, Patti Thiemann, Garry Boswell, Dong-Gyu Cho, Jonathan Sessler, Richard A. Miller
Journal: Blood (2004)
Reduction of serum VEGF and IL-6 levels in patients with metastatic breast cancer: Results of a study of PTC299, an oral inhibitor of tumor VEGF synthesis, and aromatase inhibitors.
Authors: M. N. Dickler, B. P. Schneider, M. Volm, J. L. Speyer, Y. Novik, L. A. Callahan, C. H. Darby, J. Barth, G. L. Elfring, A. Ogden, A. Tiersten
Journal: Journal of Clinical Oncology (2011)

1100 Background: PTC299, an oral investigational drug, suppresses tumor growth by selective posttranscriptional inhibition of tumor VEGF and angiogenic cytokine synthesis. Alone, PTC299 shows antitumor activity and intratumoral reduction in VEGF synthesis in both hormone receptor-positive and -negative breast cancer (BC) xenografts. Alone or in combination with letrozole, PTC299 eliminates tumors in aromatase-overexpressing human BC xenografts. We report effects of PTC299 + aromatase inhibitors (AIs) on human serum VEGF (sVEGF) and IL-6 in patients (pts) with metastatic BC (mBC). Methods: Stage 2 of a Phase Ib study combining PTC299 + AI therapy is reported. Women with 1st or 2nd line HR+ mBC already receiving or newly initiating an AI receive concurrent PTC299 100 mg BID po until progressive disease (PD). sVEGF and IL-6 levels are obtained Days 1 (D1) and 42 (D42). Results: 24 women are enrolled; median age 57 years (range 26-82), ECOG PS 0 (n=15) or 1 (n=9). AI therapy is letrozole (n=11), anastrozole (n=6), or exemestane (n=7); median duration of therapy 16 weeks (range 3-65). Therapy is generally well tolerated; AEs have been predominantly Grade 1-2. The most frequent AEs are headache (25%) and hot flashes (25%) with no PTC299 dose reductions/ discontinuations due to AEs. Overall response rate 21% (5 pts: 2CR, 3PR); Stable Disease 38% (9 pts); PD 25% (6 pts); not evaluable 17% (4 pts). 19 patients had pre/post sVEGF and IL-6 samples. D1 sVEGF levels are elevated (normal ≤300 pg/mL) in 6/19 pts. Pts with elevated D1 sVEGF have median D42 reduction 237.5 pg/ml (range -27.4 to -408.6); Pts with normal D1 sVEGF are unchanged at D42. All pts have elevated D1 IL-6 levels. Pts with D1 IL-6 ≥10 pg/mL have a median D42 reduction 10 pg/mL (range -8.0 to -17.2); pts with D1 IL-6 ≤10 pg/mL are unchanged at D42. Conclusions: PTC299 + AIs is generally well tolerated, shows clinical activity, and reduces sVEGF and IL-6 in pts elevated at D1. These data provide preliminary support for the proposed mechanism of action that PTC299 inhibits production of tumor VEGF and other angiogenic cytokines with unchanged physiological VEGF production. Grant support from the DOD.
The NCCN-IPI Helps to Identify Very High-Risk Patients with DLBCL and Can be Improved By Other Independent Clinical Factors Including Bulky Disease and beta2-Microglobulin
Authors: Rita Coutinho, Joana Lobato, Susana Esteves, Susana Carvalho, Francesca Pierdomenico, Paulo Bernardo, Filipe Gonçalves, Joana Desterro, Soraia Martins, Carla Silva, Maria Gomes Silva
Journal: Blood (2015)
Adjuvant and neoadjuvant chemotherapy (NAC) with ifosfamide (IFO) and doxorubicin hydrochloride (ADM) for high-grade soft tissue sarcomas (STS) in the extremities: Japan Clinical Oncology Group study JCOG030404.
Authors: K. Tanaka, J. Mizusawa, H. Fukuda, N. Araki, H. Chuuman, M. Takahashi, T. Ozaki, T. Hiruma, H. Tsuchiya, H. Morioka, T. Morita, T. Wada, M. Hatori, Y. Yoshida, J. Toguchida, S. Abe, A. Matsumine, R. Yokoyama, Y. Iwamoto
Journal: Journal of Clinical Oncology (2011)

10078 Background: STS are rare malignant tumors and relatively resistant against chemotherapy. The efficacy of systemic adjuvant chemotherapy for STS is still controversial and only a few prospective trials of NAC for STS in the extremities have been reported. We therefore carried out the multicenter phase II study of NAC for patients with STS in the extremities. Methods: Patients with operable, FNCLCC grade 2/3 non-round cell STS in the extremities, Stage III (T2bN0M0, AJCC 6th edition), ECOG performance status 0-1, and age 20-70 were eligible. The patients were initially treated with NAC consisted of ADM 60mg/m2 and IFO 10g/m2 for 3 courses with 3-week interval. After the completion of tumor resection, additional 2 courses of the same regimen as NAC were carried out. The primary endpoint was 2-year progression-free survival rate (PFS). Results: A total of 72 patients were enrolled and 70 patients were eligible. The median age of the patients was 49 years (21-66), 53% were male. The major pathological subtypes were synovial sarcoma 20, malignant fibrous histiocytoma 17 and leiomyosarcoma 11 patients. The protocol treatments were completed in 74 % of the eligible cases. Seventy patients underwent surgery as protocol treatment. Wide margin was achieved in 61 patients, whereas marginal margin and intralesional margin were in 8 and 1 patients, respectively. With median follow-up of 3.6-year for eligible cases, 2-year and 4-year PFS were 75.7% and 65.3%, respectively. Overall survival rates for 2-year and 4-year were 91.4% and 81.8%, respectively. There was no treatment related death. Grade 3 or 4 hematologic toxicities (leucopenia and neutropenia) were observed in most of the patients and the most frequent non-hematologic toxicities were nausea and appetite loss. Conclusions: Although the toxicities of the regimen were significant, NAC followed by post-operative chemotherapy using ADM and IFO was well tolerable. The outcome of the trial for the patients with operable, high-grade STS in the extremities was far better than expected, and this regimen is promising for further investigation by phase III trials.
Palliative transurethral resection in men with castration-resistant prostate cancer (CRPC): Minimally invasive procedure with minimal morbidity?
Authors: Charlotte Piper, Robin Epplen, Thomas van Erps, David J. K. P. Pfister, Daniel Porres, Axel Heidenreich
Journal: Journal of Clinical Oncology (2012)

233 Background: About 20 to 30% of men with CRPC with a prostate in situ will develop subvesical obstruction due to locally progressing prostate cancer with time. Treatment options include palliative TURP, urinary diversion by transurethral or suprapubic catheters. There are only few reports critically evaluating the outcome of palliative TURP and the development of associated symptoms of locally progressing CRPC. Methods: We retrospectively reviewed all patients who underwent palliative TURP for locally advanced CRPC with regard to the functional and oncological outcome. In addition, we analysed the frequency of complications associated with locally advanced (LA) CRPC. Patient with incidental prostate cancer were excluded from the analysis. Results: Between 2004–2010 a total of 83 patients were identified. The mean age of the patients was 76 (60–91) years. Mean PSA at time of TURP was 78 (1–253) ng/ml. Initial therapy included androgen deprivation monotherapy in 67.8%, radiation therapy in 28.6% and active surveillance in 3.4%.The mean size of the prostate was 40 (15–130) ml, the mean resected prostate weight was 18.6 (2–56) g. The mean Gleason score was 8.3 (6–10). The indication for palliative TURP was subvesical obstruction with a postvoid residual urine &gt; 100ml in 68.8 %, recurrent gross hematuria in 13.2% and acute urinary retention in 18.1%. 19 (2.9%) pts demonstrated uni- or bilateral upper urinary tract obstruction necessitating drainage by endoluminal stenting or percutaneous nephrostomy. The mean catheterization time was 3.4 (2–6) days; postoperative complications developed in 15 (18.1%) pts and included: urinary retention in 2 pts, intravesical blood clots in 3 pts, permanent suprapubic catheter in 3 pts, stress urinary incontinence in 2 pts and re-do TURP in 3 pts. Perioperative mortality was 0% and after a mean follow-up of 3.6 years, 27 (32.5%) pts had died due to prostate cancer. Conclusions: Palliative TURP in men with LA-CRPC is fairly safe, but side effects are higher compared to conventional TURP. Due to a high frequency of involvement, the upper urinary tract has to be screened prior to palliative TURP.
Advanced hepatocellular carcinoma (HCC) treated with sunitinib (Su) and transarterial chemoembolization (TACE): Phase II trial final report.
Authors: Renuka V. Iyer, Garin Tomaszewski, Yuhsin V Wu, Boris W. Kuvshinoff, Adrienne E. Groman, Nikhil I. Khushalani, Catherine Grande, Patricia D. Zagst, Kimberly Clark, Gerald J. Fetterly
Journal: Journal of Clinical Oncology (2012)

275 Background: TACE and anti-angiogenic agents have individually been effective in inoperable HCC. In this prospective phase 2 study, the effects and PFS of Su+TACE was evaluated. Methods: Eligibility: ECOG PS 0, 1, inoperable HCC, Child Pugh (CP) A/B, platelets &gt;100K, bilirubin &lt; 2 and no contraindications to TACE. Treatment: Cycle (C) 1 -Su 37.5mg po days (d)1-7; - TACE with doxorubicin in lipodiol on d8;- Su 37.5mg po qd d15-36; - 2 wks off C2 onwards - Su 4 wks on (dose escalation to 50mg in pts without grade 3 toxicities);- 2 wks off DCE-MRI, sVEGFr, monocytes, and Su PK were assessed at d0, 8, 10, and 36. Results: Characteristics of the 16 pts were: median age 74 yr (range 40-86), all with CP A cirrhosis (etiology: hepB: 2, hepC: 6, ETOH: 1, unknown: 7), and PS 0: 12, PS 1: 4. 10 pts had liver only and 6 pts had extrahepatic disease. Median PFS was 8 mo (95% CI 4.3-9.3) and OS was 14.9 mo (95% CI 6.3-27.1) with a median follow up of 12.8 mo (5 pts still alive) receiving a median of 3 cycles (range 1-7). Responses by RECIST criteria were PR: 2, SD: 11 and PD: 3 for total clinical benefit of 81%. DCE-MRIs pts (8) showed median Ktrans change of -20% after d7 of Su and a further 7% after TACE+Su. There was concurrent decrease in viable tumor, 3% (d8) and 15% (d36) respectively. Steady-state Su concentration ranged from 20-150 ng/ml, which is above the IC 50 values of 4-30 ng/ml for VEGF inhibition. PK/PD modeling estimated a Su IC 50 values of 15 and 10 ng/ml to modulate Ktrans and AUC 90 . sVEGFR2 levels change with Ktrans and AUC 90 . Median monocyte counts of 0.4x10 9 /L decreased by 50% on d36 after TACE. 11 pts (69%) had grade 3/4 toxicities attributable to Su. Of a total of 57 events, the most frequent (n&gt;5) were thrombocytopenia (10), amylase/lipase increase (9), lymphopenia (7), and fatigue (6). Dose delays and dose reductions occurred in 13 and 3 pts respectively. Reasons for discontinuing therapy were toxicity (7), progression of disease (7), and withdrawal of consent (2). Conclusions: Improvement in PFS and OS was seen with acceptable toxicity in the first study of Su + TACE in HCC. In addition, it shows a relationship between Su concentration and Ktrans, AUC 90 , sVEGFR2 and monocytes; with additional decrease seen after TACE.