tbuckley/cabot-search huggingface dataset:
Prognostic factors after pancreaticoduodenectomy for duodenal adenocarcinoma: Results from a dual center analysis.
Authors: Jin He, Wooil Kwon, Wenchuan Wu, John L. Cameron, Ralph H. Hruban, Matthew Weiss, Nita Ahuja, Timothy M. Pawlik, Jin-Young Jang, Christopher Lee Wolfgang
Journal: Journal of Clinical Oncology (2014)

e15181 Background: Duodenal adenocarcinoma (DA) represents approximately 1% of all gastrointestinal malignancies and has a dismal prognosis. The prognostic significance of the current AJCC staging system remains debated. Herein, we examine prognostic factors in patients who underwent pancreaticoduodenectomy (PD) of DA. Methods: A retrospective review of the prospective database was conducted to identify patients with DA who underwent PD between 1984 and 2010. Demographics, operative variables, pathologic findings, and survival data were analyzed. Univariate and multivariate analyses were performed to identify factors associated with survival. Results: There were 221 patients with 109 (49%) having classic PD and others having pylorus preserving PD. The median age was 65 (range, 24-103) and 131 (59%) are male. 208 (94%) had R0 resection. Lymph node (LN) metastasis was identified in 133 patients (60%). Median number of LN examined was 15. Thirty eight percent had N1 disease (less than or equal to 3 nodes) and 21% had N2 disease (more than 3 nodes). The AJCC stage distribution was classified as following: stage I (22, 10%), stage II (65, 29%), stage III (122, 55%), and stage IV (11, 5%). Median follow-up is 42 months. 59 (27%) patients received adjuvant chemotherapy. The median overall survival (OS) for the cohort was 49 months (95% CI 29-69 months). OS after resection was 48% at 5 years and 37% at 10 years. In univariate analysis, the LN metastasis and N staging predict worse survival (p<0.001). However, the N staging is the only independent predictor of worse survival in multivariate analysis (HR=2, 95% CI 1.4-2.9, p<0.001) (Table). Conclusions: N staging was identified as the only independent predictor of survival, which emphasizes the need for adequate lymphadenectomy to accurately stage DA. AJCC staging system cannot predict the survival in multivariate analysis. Multivariate analysis of factors predicting OS after PD for DA. Variables in the equation HR 95% CI for HR P Lower Upper Vein resection 3.7 0.5 26.9 0.19 Margin 1.6 0.8 3.2 0.19 POPF 1.3 0.8 2.1 0.33 DGE 0.9 0.5 1.5 0.62 Wound complications 0.6 0.4 1.0 0.05 N staging 2.0 1.4 2.9 <0.001 Staging 0.7 0.5 1.1 0.12
Randomized controlled trial on the skin toxicity of panitumumab in third-line treatment of KRAS wild-type metastatic colorectal cancer: HGSG1001 (Japanese Skin Toxicity Evaluation Protocol with Panitumumab: J-STEPP)—Additional analysis of antitumor efficacy.
Authors: Yoshimitsu Kobayashi, Yoshito Komatsu, Satoshi Yuki, Hiroshi Nakatsumi, Hiraku Fukushima, Takuto Miyagishima, Nobuyuki Ehira, Ichiro Iwanaga, Hiroyuki Okuda, Takaya Kusumi, Miki Tateyama, Yasushi Tsuji, Kazuteru Hatanaka, Michio Nakamura, Mineo Kudo, Tomofumi Takagi, Hiroyuki Hisai, Riichiro Abe, Koji Oba, Yuh Sakata
Journal: Journal of Clinical Oncology (2014)

3587 Background: Panitumumab (Pmab) has demonstrated efficacy in patients with KRAS wild-type metastatic colorectal cancer (mCRC). Although the STEPP study (Lacouture M. E. et al. J Clin Oncol. 2010; 28: 1351-7.) showed that pre-emptive skin treatment reduced skin toxicities compared with reactive treatment among patients receiving Pmab, data for Asians has not been reported. We planned a randomized, open-label trial to verify the differences between pre-emptive and reactive treatment for skin toxicities in Japanese patients. Methods: Patients receiving third-line Pmab-containing regimens for mCRC were randomly assigned 1:1 to pre-emptive (skin moisturizers, sunscreen, topical steroid, and minocycline) or reactive (only skin moisturizers) skin treatment. The primary endpoint was the cumulative incidence of ≥grade 2 skin toxicities during the 6-week treatment period. Retrospectively, a dermatologist reviewed skin toxicities, in a blinded manner, using photographs. Results: Of 95 enrolled patients, 47 were assigned to pre-emptive, and 48 to reactive treatment. The incidence of ≥grade 2 skin toxicities during the 6-week treatment period (investigators’ assessment) was 21.3% and 62.5% (risk ratio [RR], 0.34; 95% CI, 0.19 to 0.62; P < 0.001) for the pre-emptive and reactive treatment groups, respectively. A similar trend was observed in central review (18.6% and 50.0%, respectively [RR, 0.37; 95% CI, 0.19 to 0.74; P = 0.002]). There were no statistical differences in progression free survival (3.6 vs 4.0 months; hazard ratio [HR], 1.20; 95% CI, 0.78 to 1.84; P = 0.413), time to treatment failure (3.0 vs 3.5 months, [HR, 1.23; 95% CI, 0.80 to 1.89; P = 0.343]), and overall response rate (13.3% vs 18.2%; P = 0.530) between pre-emptive and reactive treatment groups. Conclusions: Pre-emptive skin treatment could reduce the severity of skin toxicities during Pmab treatment, and did not affect the anti-tumor efficacy of Pmab. Our data clearly validate that pre-emptive treatment can also be recommended in Japanese patients. Clinical trial information: 000004883.
Potential Barriers to Clinical Trials of New Therapeutics for Myelodysplastic Syndromes: Wide Variation in Risk Definitions and Trial Enrollment Criteria
Authors: Andrew M. Brunner, Jacqueline S. Garcia, R. Coleman Lindsley, Gregory A. Abel, Donna S Neuberg, Richard M. Stone, Timothy A. Graubert, David P. Steensma
Journal: Blood (2018)
Abstract 13203: Gender Difference in Clinical Characteristics and Outcomes of Japanese Patients Undergoing Coronary Revascularization Therapy in Drug Eluting Stent Era
Authors: Toshiaki Toyota, Natsuhiko Ehara, Shuichiro Kaji, Makoto Kinoshita, Atsushi Yamamuro, Takeshi Kitai, Kitae Kim, Atsushi Kobori, Tomoko Tani, Toru Kita, Yutaka Furukawa, Shunsuke Funakoshi, Ryuzo Sakata, Takeshi Morimoto, Takeshi Kimura
Journal: Circulation (2011)

Background: Limited data are available for sex-based differences in patients undergoing coronary revascularization in the drug-eluting stent (DES) era. Purpose: To identify sex-based differences in risk factor profiles and outcomes among Japanese patients undergoing first coronary revascularization in the DES era. Methods: The CREDO-Kyoto PCI/CABG registry cohort-2 is a multi-center registry enrolling consecutive patients undergoing first percutaneous coronary intervention or coronary artery bypass grafting in 2005-2007 at 26 hospitals in Japan. The study subjects consisted of 2640 women and 6675 men enrolled in the registry. Patients with malignant disease were not included. The outcome measures were all-cause death (AD), cardiovascular death (CVD), any coronary revascularization procedure (ACR) and major adverse cardiovascular events (MACE) as the composite of CVD, myocardial infarction and stroke. Results: A mean follow-up period was 1087 days. Women were older than men and more frequently had historie...
A phase I study to assess the safety, tolerability, and PK of dovitinib (D) in combination with gemcitabine (G) and capecitabine (C) in patients with advanced solid tumors.
Authors: Gerald J. Fetterly, Laura Pitzonka, Yujie Zhao, Grace K. Dy, Renuka V. Iyer, Susan Taubes, Jose Ricardo Perez, Kenneth W. Culver, John Wilton, Krystin Mongiardo, Wei Tan, William E. Brady, Amy Whitworth, Alex A. Adjei, Wen Wee Ma
Journal: Journal of Clinical Oncology (2014)

2603 Background: Fibroblast growth factor receptor (FGFR) signaling is implicated in many cancer types. D is a potent multikinase inhibitor of FGFRs, VEGFRs and PDGFR. D’s preclinical anti-cancer effect was most pronounced in pancreatic cancer (PC) with enhanced FGFR signaling. The trial aimed to determine the MTD, toxicity and PK profile of D plus G/C. Methods: Patients (pts) with advanced solid tumors in whom G/C was appropriate and ECOG PS 0-1 were eligible. Dose escalation was conducted per a 3+3 design (Part A) with an expansion cohort (Part B; n=20) at the MTD with advanced PC and biliary cancers. Dose levels were D 300/400/500 mg oral daily on a ‘5-days-on/2-days-off’ schedule with G 1000 mg/m2 i.v. weekly x 2 and C 650 mg/m2twice-daily x 14 days (1 cycle = 21 days). Adverse events (AEs) were graded using CTCAE 4.0 while tumor response by RECIST 1.1. Plasma samples were collected up to 48 hr post-dose. D, G, and C concentrations were determined using LC/MS/MS, and PK analysis was performed. Results: 18 pts were enrolled in total. 6 of 9 pts enrolled to Part A were evaluable for DLT. One of 6 pts treated at D 300 mg level experienced dose-limiting Gr3 colitis; 2 pts experienced non dose-limiting Gr2 neuropathy (reversible) after multiple cycles requiring D dose reduction. Dose escalation was halted and D 300 mg level used for Part B, which enrolled 9 pts so far. D 300 mg level was tolerable when dosed over multiple cycles. Preliminary efficacy included PFS > 12 months in 2 PC pts (1st line and post-FOLFIRINOX respectively). Common (>15%) ≥Gr 2 AEs included asthenia, elevated LFTs, N/V, hypertension, neutropenia and thrombocytopenia. Median Cmax and AUC24 for D were similar after 3 weeks of dosing; 181 (Day 1) vs. 221 ng/ml (Day 19) and 3419 vs. 3854 ng*hr/mL, indicating no presence of autoinduction of D metabolism. Median T1/2 of D was 13.1 hr. G and C PK were similar to literature. Conclusions: D 300 mg level was determined to be the recommended phase II dose and tolerable when dosed over multiple cycles. The PK analysis showed no drug-drug interaction. A clinical trial of D/G/nab-paclitaxel in PC is currently underway. Full toxicity and PK profile will be presented at the conference. Clinical trial information: NCT01497392.
Use of Functional Magnetic Resonance Imaging to Identify Risk Factors for Relapse in Patients With Stimulant Use Disorders
Authors: Jay Nierenberg
Journal: JAMA Network Open (2018)

Kelly H. MacNiven, PhD; Emily L. S. Jensen, BA; Nicholas Borg, BA; Claudia B. Padula, PhD; Keith Humphreys, PhD; Brian Knutson, PhD
Predictive value of BRCA1 haplotype for trabectedin efficacy in patients with advanced soft-tissue sarcoma.
Authors: Audrey Laroche, Delphine Garbay, Vanessa Chaire, Valerie Le Morvan, Agnes Neuville, François Bertucci, Sébastien Salas, Roberta Sanfilippo, Philippe Pourquier, Antoine Italiano
Journal: Journal of Clinical Oncology (2014)

10598 Background: Trabectedin (T) has shown objective response and disease stabilisation in 5%–10% and 30-40% of unselected patients with advanced soft tissue sarcoma (STS) failing prior anthracyclines and/or ifosfamide chemotherapy. Although the precise mechanism of action of T is not elucidated, this drug has been found to be more active in tumor cells with a deficient homologous recombination (HR) repair system. BRCA1 is a key player of the HER system. Our aim was to determine whether the BRCA1 single nucleotide polymorphims status was associated with clinical activity of T in advanced STS patients. Methods: We have analyzed single nucleotide polymorphisms of BRCA1 in a cohort of 135 patients with advanced STS from nine major referral European centres for STS. All patients were treated between 1999 and 2011 in phase I-II clinical trials or in the context of a compassionate-use programme. T was given at different doses (0.5-3 mg/m2) with the use of two different schedules: a 3-h infusion or a 24-h continuous infusion. BRCA1 haplotype was also assessed in two independent cohorts of patients: (i) localized STS (n=85); (ii) advanced STS managed with doxorubicin (n=44). Results: 734 cycles of T were administered, with a median of 3 cycles per patient (range 1–23). One complete response, 16 partial responses, and 29 disease stabilizations that lasted for >6 months were observed. The 6-months non-progression rate was 40.5% for patients who had at least 1 allele of the most frequent BRCA1 AAAG haplotype vs 16.5% for patients with a different haplotype; P = .01). This was also associated with a significant difference in terms of overall survival (P = .009). BRCA1 haplotype was not associated with outcome in the two independents cohorts of patients with localized STS or advanced STS treated with doxorubicin. Conclusions: BRCA1 haplotype may represent a predictive DNA-based biomarker for T efficacy in advanced STS patients. In particular, sarcoma patients without AAAG allele (26.5% of patients in our study) are not likely to have sustained benefit from T. Such a biomarker assessable form paraffin-embedded tumor material could be easily integrable into routine practice provided it is validated in a prospective setting.
Hematopoietic Cell Transplant-Composite Risk (HCT-CR) — a Novel Prognostic Model to Predict Transplant Outcomes
Authors: Piyanuch Kongtim, Simrit Parmar, Denái R. Milton, Jorge M. Ramos Perez, Gabriela Rondon, Julianne Chen, Abhishek R Chilkulwar, Gheath Alatrash, Amin M. Alousi, Borje S Andersson, Jin S Im, Chitra Hosing, Qaiser Bashir, Issa F. Khouri, Partow Kebriaei, Betul Oran, Uday Popat, Richard E Champlin, Stefan O. Ciurea
Journal: Blood (2018)
MDM2 and Aurora Kinase a Contribute to SETD2 Loss of Function in Advanced Systemic Mastocytosis: Implications for Pathogenesis and Treatment
Authors: Manuela Mancini, Cecilia Monaldi, Sara De Santis, Cristina Papayannidis, Michela Rondoni, Luana Bavaro, Margherita Martelli, Abbenante Maria Chiara, Antonio Curti, Elisa Ficarra, Giulia Paciello, Maria Chiara Fontana, Roberta Zanotti, Massimiliano Bonifacio, Luigi Scaffidi, Livio Pagano, Marianna Criscuolo, Francesco Albano, Fabio Ciceri, Chiara Elena, Patrizia Tosi, Massimo Delledonne, Carla Avanzato, Luciano Xumerle, Peter Valent, Giovanni Martinelli, Michele Cavo, Simona Soverini
Journal: Blood (2018)
Cellular source of peritoneal free cancer cells during a reconstructive surgery after gastrectomy for gastric cancer.
Authors: Satoshi Murata, Katsushi Takebayashi, Hiroshi Yamamoto, Tsuyoshi Yamaguchi, Sachiko Kaida, Mitsuaki Ishida, Masatsugu Kojima, Eiji Mekata, Tomoharu Shimizu, Hisanori Shiomi, Shigeyuki Naka, Hiromichi Sonoda, Hiroyuki Ohta, Hiroya Akabori, Tsuyoshi Mori, Tomoko Umeda, Yoshihiro Kubota, Hidetoshi Okabe, Tohru Tani
Journal: Journal of Clinical Oncology (2014)

e15063 Background: We have recently shown that viable cancer cells spilled into peritoneal cavity during curative gastric cancer (GC) surgery more frequently in cases with advanced tumor invasion and lymph node metastasis. In addition, 2.8% of early GC without any vessel invasions showed viable cancer cells in the peritoneal cavity during surgery, suggesting the presence of other channels for the spilling of cancer cells. Laparoscopic distal gastrectomy (LDG) with intracorporeal reconstruction has been applied according to advances in surgical techniques. However, oncological evaluation of LDG may not be fully performed. In this study, we examined the possibility of spilling cancer cells into the peritoneal cavity during the surgery for alimentary reconstruction in GC. Methods: Patients with open distal gastrectomy (n=37) or laparoscopic assisted distal gastrectomy (n=73) for GC were prospectively evaluated cytological examination of remnant stomach just before alimentally tract reconstruction. Ki67 staining was examined for the proliferative activity of detected cells. Results: Cancer cells were detected in 25 (22.7%) of 110 remnant stomachs of the patients received gastrectomy just before reconstruction. According to the depth of tumor invasion, incidence of cancer cell detection in patients with mucosal (m), submucosal (sm), proper muscle (mp), subserosal (ss), or serosal (se) tumor invasion was 1/28 (3.6%), 4/23 (17.4%), 4/15 (26.7%), 8/17 (47.1%), or 8/27, (29.6%), respectively. Cancer cells detected formed clustering. All of cases with cancer cells showed positive for Ki67 staining, indicating having proliferative ability. Incidence of cancer cell detection in the remnant stomach was significantly more in differentiated type than in undifferentiated type (p < 0.05). Conclusions: Viable and proliferative cancer cells present in the remnant stomach at the reconstruction of alimentary tracts after gastrectomy for GC. The prevention from spilling out cancer cells into peritoneal cavity should be seriously considered. Complete laparoscopic intracorporeal reconstruction should be accessed carefully from the oncological points of view as well as minimally invasive view.
Monosomy 7 associated with juvenile myelomonocytic leukemia in an infant.
Authors: Adriana Carolina Bello
Journal: Journal of Clinical Oncology (2014)

e18007 Background: 14 months old boy started clinical symptoms ay ave 10 months, with pallor and severe progressive anemia (Hb 2g/dl) and high red blood transfusion requirements. No significant past medical history: one episode bronchiolytis at age 6 months. Uneventful neonatal and developmental milestones. No consanguineity or illness in family members. Methods: No siblings or early child deaths. Mother and father in good health. Healthy looking child, normal height and weight. Pallor, no jaundice or bleeding manifestations. No evident physical stigmata, only café-au-lait macular spots (total 35) over trunk, necck and extremities. No malformations at hands, head, feet, bones, internal organs, heart. initial CBC Hb 6.9; Hct 20.8%; MCV 87.2; Plt 126.000; WBC 13.600 (L68%, M 15%, N17%). Blood chemistry panel and coagulation, fibrinogen: Normal. LDH: 704 Uric acid: 3.3. Electrolytes: Normal. Alk Phos: Normal. T3- T4 –TSH: Normal. Immunoglobulins (E, G, M, A): Normal HPLC: HbA (HbF of patient and parents is Normal 0.3%). Bone survey: No malformations or osteolytic lesions. No mediastinal mass.Serologies (HIV, Hep A,B,C, CMV, EBV, HSV)Negative Parvo B19 (PCR) from bone marrow: Negative. A bone marrow showed Morphology and immunophenotype: Negative for leukemia or dysplasias. Absence of erythroid precursor elements. 2 y/o boy with very severe hyporregenerative anemia that required leukorreduced, antigen matched RBC transfusions every 3 weeks (total 12 transfusions). The other series remained mostly unaffected. Clinical symptoms mild comprising occasional diarrhea and mid respiratory infections.Results: First diagnosed as pure red cell aplasia. However, started to develop progressive splenomegaly (up to 8cm below LCM), despite regular RBC transfusions. No thrombocytopenia. high LDH and monocytosis started to appear, and peripheral smear started to show blasts of myeloid morphologic aspect, CD33, 117 positive. Conclusions: A suspect diagnosis of NF1, JMML was confirmed when bone marrow was sent for cytogenetics, that were consistent with monosomy -7 (14 out of 16 metaphases). The patient was transferred to a specialized center for further treatment, with hematopoietic stem cell transplantation.
Abstract #4283: Erythropoetin receptor (EpoR) was expressed at low to undetectable levels in tumor cell lines: Expression was not regulated by hypoxia and no epo-induced downstream signaling was detectable
Authors: Susan Swift, Steve Elliott, Leigh Busse, Ian McCaffery, John Rossi, Aaron Ellison, Yun Lin, Sean Yoder, Angus Sinclair, C. Begley
Journal: Cancer Research (2009)

EpoR mRNA and protein expression were surveyed in 67 tumor cell lines from ovary, breast, head and neck, lung, brain, prostate, cervix, liver, colon and blood. A sensitive and specific anti-EpoR monoclonal antibody (mAb), A82, was recently discovered allowing analysis of EpoR levels in human cells by immunoblotting. Total EpoR protein levels were estimated by comparing the amount of full length (59 kDa) EpoR protein in total cell lysates to a known amount of purified EpoR protein. The functional form of EpoR is a dimer, so total EpoR protein levels are reported as dimers/cell. The cell lines, UT-7/Epo and OCIM-1 cells were used as positive controls and in repeat experiments the total amount of EpoR varied 2-3-fold (30,000 -100,000 and 8,000 -16,000 EpoR/cell respectively). Primary human erythroid cells (generated from purified CD34+ cells after 4 days in-vitro culture) had 32,000-64,000 EpoR/cell. Scatchard analysis of UT-7/Epo and OCIM-1 cells demonstrated 10-20% of the total EpoR protein was detected on the cell surface, while COLO677 and 769-P cells showed no binding (and also had no detectable EpoR protein). In a survey of 61 solid tumor cell lines, 26 had no detectable EpoR protein (  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4283.
Abstract MP14: Long-chain Monounsaturated Fatty Acids and Incidence of Coronary Heart Disease: The Cardiovascular Health Study
Authors: Fumiaki Imamura, Rozenn N Lemaitre, Irena King, Xiaoling Song, David S Siscovick, Dariush Mozaffarian
Journal: Circulation (2013)

Background: Decades-old animal experiments demonstrated that consumption of large amounts of long-chain monounsaturated fatty acids (LCMUFA, 22:1 and 24:1 fatty acids) caused cardiotoxicity. We recently found that plasma phospholipid 22:1 and 24:1 were associated with higher incidence of congestive heart failure (CHF) in two independent cohorts: the Cardiovascular Health Study (CHS) and the Atherosclerosis Risk in Communities Study. However, their association with incident CHD is unknown. Aim: to investigate association of plasma phospholipid 22:1 and 24:1 levels with incident CHD. Methods: The study included 3,221 adults free of CHD (age=74.9±5.2) in CHS in whom plasma phospholipid LCMUFA were measured in 1992. Incident CHD events from 1992 to 2006 were centrally adjudicated, and we assessed total CHD, including fatal CHD (fatal MI and other CHD deaths) and non-fatal MI. We examined prospective associations of LCMUFA with incident CHD using Cox proportional hazards. We further evaluated potential confounding or mediation by baseline risk factors and incident CHF. Results: Mean±SD phospholipid levels of 22:1 and 24:1 were 0.03±0.01 and 1.96±0.44 percent of total fatty acids. During 34,776 person-years, 628 incident CHD events occurred, including 309 fatal CHD and 401 non-fatal MIs. After multivariable adjustment, higher levels of both 22:1 and 24:1 were associated with higher risk of total incident CHD. Hazard ratios (95% CI) for quintiles 5 vs. 1 of 22:1 and 24:1 levels were 1.48 (1.07-2.06, p trend=0.005) and 1.65 (1.16-2.34, p trend=0.001). The associations with CHD were largely specific to fatal CHD rather than non-fatal MI (Figure). These associations did not change after adjustment for incident CHF and baseline risk factors including circulating lipids, blood pressure, and inflammatory markers. Conclusions: Higher levels of circulating 22:1 and 24:1 LCMUFA were associated with higher incidence of CHD, in particular fatal CHD, supporting the possibility of cardiotoxicity by current levels of LCMUFA exposure.