tbuckley/cabot-search huggingface dataset:
Characteristics of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN): Male predominance, propensity for extramedullary involvement, and poor outcomes.
Authors: Naveen Pemmaraju, Deborah A. Thomas, Hagop M. Kantarjian, Jorge E. Cortes, Joseph Khoury, John T Manning, L Jeffrey Medeiros, Susan Mary O'Brien, Naval Guastad Daver, Sherry Pierce, Guillermo Garcia-Manero, Elias Jabbour, Nitin Jain, Muzaffar H. Qazilbash, Stefan Faderl, Arthur E. Frankel, Marina Konopleva
Journal: Journal of Clinical Oncology (2014)

7118 Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy. Little is known about characteristics and outcomes of patients (pts) with BPDCN. Methods: We performed an updated retrospective review of pts age ≥ 18 years with a pathological diagnosis of BPDCN. Results: 26 pts were evaluated at our institution (Oct 1998-Dec 2013). Median age was 58 years (range 20-86). 23 (88%) were male. Bone marrow (BM) was involved in 17 (65%), skin in 13 (50%), lymph nodes in 7 (27%), CSF in 3 (12%) and 1 (4%) pt each had disease involving the brain, uterus/ovary, elbow/soft tissue, and pleural fluid. Tumor immunophenotype: CD4+ (23/23), CD56+ (21/23), TCL-1+ (14/15), CD 123+ (13/14). CD22 was expressed in 2/5 pts. Cytogenetics in 14 pts showed: diploid (8), complex karyotype (5), and del (12p13) (1pt). Median CBC was: WBC 5.6 x 109/L (1.7-76.5), Hb 12.3 g/dL (8.3-14.6), and platelet count 160 x 109/L (44-294). Median BM blasts: 19% (0-94). Therapies given: 16 (62%) first-line therapy with Hyper-CVAD, 4 (15%) CHOP, 2 (8%) bortezomib-based, 1 clinical trial (DT-IL3), 1 daunorubicin+ARAC, 1 oral MTX, 1 interferon-based therapy. Five (19%) pts received radiation (XRT) as part of their therapy. Median follow-up time: 24 months (5-59 mo). Median number of chemotherapy regimens: 2 (1-6). CR was achieved in 14 pts. The median CR1: 18 mo (4-39 mo). Median overall survival (OS) was 29 mo (1-59 mo). 8 pts (31%) received stem cell transplant (SCT) (3 autologous, 3 allogeneic, 2 cord). Median OS for pts receiving SCT was 31 mo (13-40 mo) versus a median OS for non-SCT group (n=18) of 29 mo (1-59), p= 0.98. Conclusions: We observed a large male predominance, propensity for extra-medullary disease involvement, and overall poor outcomes despite intensive multi-agent chemotherapy and SCT for pts with BPDCN. A better understanding of the biologic basis of this disease and novel, targeted treatment approaches are urgently needed. Among novel therapies available, targeting cell surface CD123 appears to be most promising (DT-IL3) and investigation is ongoing (5/5 (100%) evaluable patients with major responses; Frankel,AE et al. ASH 2013).
Differential Expression of VEGFA Isoforms Regulates Metastasis and Response to Anti-VEGFA Therapy in Sarcoma
Authors: William R. English, Sarah Jane Lunt, Matthew Fisher, Diane V. Lefley, Mohit Dhingra, Yu-Chin Lee, Karina Bingham, Jack E. Hurrell, Scott K. Lyons, Chryso Kanthou, Gillian M. Tozer
Journal: Cancer Research (2017)

Abstract Elevated plasma concentrations of soluble VEGFA isoforms are associated with poor prognosis in parallel with improved response to treatment with the anti-VEGFA antibody bevacizumab. To uncover the underlying mechanism to these observations, we administered anti-VEGFA therapy to mice bearing luminescent mouse fibrosarcomas expressing single VEGFA isoforms or their wild-type counterparts expressing all isoforms (fs120, fs164, fs188, or fsWT). Expression of the more soluble isoforms conferred an advantage for lung metastasis from subcutaneous tumors (fs120/164 vs. fs188/WT); fs120 cells also produced more lung colonies than fs188 cells when injected intravenously. Metastasis from subcutaneous fs120 tumors was more sensitive than fs188 to treatment with the anti-VEGFA antibody B20-4.1.1. Despite elevated plasma levels of VEGFA in fs120 tumor-bearing mice and a dependence on VEGF receptor 1 activity for metastasis to the lung, B20-4.1.1 did not affect survival in the lung on intravenous injection. B20-4.1.1 inhibited subcutaneous tumor growth and decreased vascular density in both fs120 and fs188 tumors. However, migration of fs120, but not fs188 cells, in vitro was inhibited by B20-4.1.1. The greater survival of fs120 cells in the lung was associated with VEGFR1-dependent accumulation of CD11b-positive myeloid cells and higher expression of the VEGFR1 ligand, PlGF2, by the fs120 cells in vitro and in the plasma and lungs of fs120 tumor-bearing mice. We conclude that soluble VEGFA isoform expression increases fibrosarcoma metastasis through multiple mechanisms that vary in their sensitivity to anti-VEGF/VEGFR inhibition, with VEGFA-targeted therapy suppressing metastasis through effects on the primary tumor rather than the metastatic site. Cancer Res; 77(10); 2633–46. ©2017 AACR.
Patient-reported outcomes (PROs) in testicular cancer survivors (TCS): Do unmet needs resolve with routine care?
Authors: Steven C Palmer, David J. Vaughn, Abigail N. Blauch, Donna A. Pucci, Linda A. Jacobs
Journal: Journal of Clinical Oncology (2017)

56 Background: Unmet needs for intervention are common among cancer survivors, but may go unidentified and unaddressed in routine care, leading to poorer outcomes. PROs are becoming the standard of care at many treatment facilities and have been shown to be feasible and to potentially improve outcomes. However, communication of PROs to providers may be a necessary step in this process. We examined the prevalence and stability of unmet needs over a one-year time period in a sample of TCS to determine whether these resolve over time in routine care. As well, we examined the relationship of unmet needs to symptoms of anxiety and depression. Methods: Ninety-nine consecutive TCS were recruited from an ongoing survivorship clinic. Participants completed assessments of demographics, unmet needs, and anxiety and depression (HADS) prior to their visit and at a one year interval. To ensure routine care, providers were unaware of the results of unmet need screening. Results: Participants were primarily white (94%), early middle aged (M = 40 yrs), married (71%), and college educated (79%). Most participants were diagnosed with Stage I disease (73%) an average of 7 years previously. The number of unmet needs was generally low (M &lt; 0.89) at both time points, but varied from 0-10 (SD = 1.8 over both time points). The number of unmet needs was significantly associated over the one year time period (r = 0.65), and unmet need for specific symptoms at time one was associated with unmet need at time two for fatigue, pain, insomnia, numbness, aching joints, difficulty with concentration, memory, anxiety, decreased sexual interest, and weight gain (all X 2 &gt; 8.12, all p &lt; 0.05). Only muscle aches, depression, and body image were unstable over the one year period (all p &gt; 0.05). Number of unmet needs was associated with increased symptoms of depression and anxiety at both time points (all r &gt; 0.23 and &lt; 0.50, all p &lt; 05). Conclusions: Although unmet needs were fairly low, most failed to resolve over the one year time period in routine care, and greater unmet need was associated with more symptoms of depression and anxiety at both time points. The use of PROs may improve outcomes, but only if communicated to providers and acted upon in enhanced care.
Adjuvant radiochemotherapy in resectable stage II, III rectal cancer: Results of the FOGT-2 trial
Authors: L. Staib, M. Kornmann, E. Roettinger, S. Sander, W. Gaus, M. P. Lutz, K. H. Link
Journal: Journal of Clinical Oncology (2004)

3608 Background: In this phase III trial (FOGT-2) we studied whether one of the 5-FU modulations with either folinic acid (FA) or Interferon alpha-2a (IFNa) increased overall survival compared to the standard treatment in R0-resected rectal cancer, 5-fluorouracil (5-FU) plus levamisole (LEV) for 12 months, plus postoperative radiotherapy (RT). Methods: From 7/92 to 5/03 793 patients with resected rectal cancer stages UICC II (267 pts.) and UICC III (526 pts.) were randomized into three arms and stratified (N-stage, centers). After a postoperative loading course with 5-FU [450mg/ m2 d1–5 (arms A and C)] or 5-FU [450mg/m2 plus folinic acid (Rescuvolin, medac, Hamburg, Germany), 200 mg/ m2 d1–5 (arm B)], LEV was administered orally at 150 mg/d d1–3, q every 2 weeks. 4wks later treatment was continued weekly for up to 52 wks. RT was given over a 6-wks postoperative period in a 3-field technique up to a dose of 45–50,4 Gy in 1,8 Gy fractions 5x/wk with a 20% dose reduction of 5-FU. Arm A (280 pts.) was treated with 5-FU i.v. (450 mg/ m2 at d 1, q 1 w) plus LEV. 5-FU plus LEV was modulated in arm B (291 pts.) with FA (200mg/ m2 d1, q 1 w), and in arm C (222 pts.) with IFNa at 6 million units 3x/week, q 1 w. Arm C was closed early due to toxicity. Results: Toxic events WHO3,4, mainly diarrhea, leukopenia, occurred in 36% of all pts. (A, 31%, B,27%, C, 55%). Discontinuance rates were 34% (all), 33% (A), 31% (B), 39% (C). 80% of all pts. received treatment for at least 6 months. Overall relapse rates were 37% (all), 39% (A), 35% (B) and 37% (C). Tumors relapsed either locally (all: 6%; A, C:6%, B:5%) or distant (all: 26%; A: 27%, B, C: 26%) or both locally and distant (all: 5%; A: 6%, B, C: 5%). Death rates were 32% (all), 33% (A), 28% (B), and 34% (C), with no significant difference among arms in Kaplan-Meier analysis. There were 2 toxic deaths (A, C). Conclusions: Adjuvant postoperative radio-/chemotherapy with 5-FU +/- FA plus LEV for 12 months in more than 700 patients is safe, well tolerated and shows low local recurrence rates. IFNa-modulation of 5-FU (plus LEV) adds toxicity without therapeutic benefit. No significant financial relationships to disclose.
糖尿病ラットにおけるin vivo微小血管障害の発現を調節するプラスミノゲンアクチベーター(イルソグラジン)の新規阻害薬
Authors: Sakuma I, Hattori Y, Kao M, Koyama T, Yamada Y, Sato A, Tamada A, Akaishi Y, Fukao M, Kanno M, Woodcockmitchell J, Fujii S
Journal: Circulation (1996)
Delays in treatment for colorectal cancer patients in an NCI-designated cancer center serving a Hispanic majority community.
Authors: Tamna Wangjam, Sherri L. Rauenzahn, Praveena Iruku, Stephanie Purkat Lindauer, Matthew James Butler, Annie Hung, Kinan Yarta, Jessica Trevino Jones, Brandon Konkel, Andrew McCracken, Sukeshi R. Patel
Journal: Journal of Clinical Oncology (2017)

178 Background: Timeliness of cancer treatment is an important aspect of health care quality. Colorectal cancer (CRC) care requires the coordinated multidisciplinary effort of various aspects of the health care system, which can lead to delays between initial diagnoses to definitive therapy. Little is known about the time from diagnosis to cancer-directed treatment, neither about the factors that cause delays or its effect on patient outcomes. Delays to curative surgery beyond 12 weeks are associated with increased mortality in CRC. Longer time to adjuvant chemotherapy is associated with worse survival among patients with resected CRC. The objective of our study is to identify delays in initiation of CRC treatment and its causative factors. Methods: We retrospectively reviewed the medical records of colorectal cancer patients who were either initially diagnosed or had initial surgical resection at University Hospital and had further treatment at Cancer Therapy and Research Center, between 7/1/2010 and 12/22/2014. Data were collected on patient and disease characteristics, treatment timelines and outcomes, till pre-specified data cut-off date of 8/1/16. Results: Of 256 patients treated for CRC, 59 % were males, 59 % Hispanic, and 34 % were uninsured. Most had non-metastatic disease (70%). 72 % were still alive at the time of data cut-off. The median time from diagnosis to treatment (TDT) was 21 days, with 60 % between 0-30 days and 59 % between 31-89 days. Median time from first treatment to first progression or recurrence was 12 months (range 0.9- 42 mos.). Median overall survival (OS) was 17 months (0.1- 51 months). There were no statistically significant difference between the progression or recurrence free survival and OS in patients with TDT &lt;30 days, 30-89 days and &gt;90 days. Compared to non-Hispanics, Hispanic patients were more likely to have a TDT of 31-89 days (31% vs 37%, p= 0.0003) and &gt;/= 90 days (3% vs 7%, p= 0.0001). Conclusions: Hispanic patients were more likely to have a longer time from diagnosis to treatment compared to non-Hispanic patients. The various factors for such disparities in health care quality and their effect on survival needs to be explored further.
Written care plan and patient enablement: Pre-implementation data from the 4R in Oncology Project.
Authors: Julia Rachel Trosman, Christine B. Weldon, Claudia B. Perez, Swati Kulkarni, Seema Ahsan Khan, Nora Hansen, Valerie Nelson, Jennifer Stein, Melissa A. Simon, Jonathan Blake Strauss, Sasa M. Espino, Mikele Bunce, Wayne Pan, Sarah M. Friedewald, William John Gradishar
Journal: Journal of Clinical Oncology (2017)

55 Background: The IOM ’11 and ’13 reports recommend a written care plan (WCP) at cancer diagnosisto enable teamwork and patient (pt) engagement. Standardized multimodality WCP is a key part of the 4R model of care planning and pt engagement proposed under “NCI ASCO Teams” Project (Trosman JOP 2016). 4R (Right Information / Care / Patient / Time) is under implementation at three centers: academic, community and safety net. As current state assessment prior to implementing 4R and standard multimodality WCP, we surveyed pts not impacted by 4R on care planning, enablement and whether they received any WCP. Methods: Survey of breast cancer stage I-III pts who received care at the three sites Jan ’15 - Mar ’16, prior to 4R. We used simple frequencies and Fisher’s exact test in analysis. Results: Survey response rate: 48%, 197/410. Gaps of &gt; 30% were reported in 6 of 8 aspects of care planning and pt enablement - Table. A non standard WCP was received by 45% of pts. Receiving a WCP impacted whether pts were clear about care (90% with WCP vs 50% without, p &lt; .0001), able to manage own care (81% with WCP vs 59% without, p = .001) and overwhelmed (49% with WCP vs 68% without, p = .006). Care complexity was a significant factor for feeling overwhelmed by pts without WCP (60% of pts receiving &gt; 6 care services felt overwhelmed vs. 39% of pts receiving &lt; = 6 services, p = .04), but not a significant factor in pts with WCP (38% vs 44%, p = .7). More pts with WCP reported well managed care by providers than pts without WCP (78%, 64%, P = .04). Conclusions: Serious gaps found in care planning and pt enablement at our sites support the need for 4R implementation. Even pre-4R, non standard WCPs improve pt understanding of care and ability to manage it, and reduce the impact of care complexity on pts. Providers using WCP appear to also coordinate care, but WCP itself may be an important factor of patient enablement. [Table: see text]
A Bare-Bones Approach
Authors: Karen Lavery, Daniel J. Gilden, Sanjay Saint, Marc A. Judson, Gurpreet Dhaliwal
Journal: New England Journal of Medicine (2017)

A 60-year-old woman with type 1 diabetes mellitus, who was feeling well except for mild fatigue, was found to have abnormal levels of hemoglobin, creatinine, and serum calcium on laboratory testing before planned cataract surgery.
The depletion of PinX1 involved in the tumorigenesis of non-small cell lung cancer promotes cell proliferation via p15/cyclin D1 pathway
Authors: Xiao-Peng Tian, Xiao-Han Jin, Mei Li, Wei-Juan Huang, Dan Xie, Jia-Xing Zhang
Journal: Molecular Cancer (2017)

The telomerase/telomere interacting protein PinX1 has been suggested as a tumor suppressor. However, the clinical and biological significance of PinX1 in human non-small cell lung cancer (NSCLC) is unclear.PinX1 gene/expression pattern and its association with NSCLC patient survival were analyzed in cBioportal Web resource and two cohorts of NSCLC samples. A series of in vivo and in vitro assays were performed to elucidate the function of PinX1 on NSCLC cells proliferation and underlying mechanisms.More frequency of gene PinX1 homozygous deletion and heterozygote deficiency was first retrieved from cBioportal Web resource. Low expression of PinX1 correlated with smoking condition, histological type, T stage, N stage, M stage and TNM stage, and was an independent predictor for overall survival in a learning cohort (n = 93) and a validation cohort (n = 51) of NSCLC patients. Furthermore, knockdown of PinX1 dramatically accelerated NSCLC cell proliferation and G1/S transition, whereas ectopic overexpression of PinX1 substantially inhibited cell viability and cell cycle transition in vitro and in vivo. p15/cyclin D1 pathway and BMP5 might contribute to PinX1-associated cell proliferation and cell cycle transition.The cost-effective expression of PinX1 could constitute a novel molecular predictor/marker for NSCLC management.
Risk factors for ifosfamide-related encephalopathy (IRE) in sarcoma (S) patients (pts).
Authors: Natacha Stern, Cyril Lervat, Anne Sophie Defachelles, Thomas Ryckewaert, Guillaume Marliot, Ilyes Sakji, Charlotte Peugniez, Nicolas Penel
Journal: Journal of Clinical Oncology (2015)

e21523 Background: Ifosfamide is one of the major agent for S management, whatever the histology (osteo-S, Ewing S, Rhabdomyo-S …). IRE is a rare but severe adverse event. Methods: We have carried out a single-center retrospective study to assess the occurrence and the risk factors for IRE after the first cycle of ifosfamide-based CT in adult and juvenile S pts. We have collected the data describing pts (age, gender, BMI, albumin, baseline ASAT/ALAT) and tumors characteristics (histology, leptomeningeal met.), ifosfamide administration modalities (dose/day, cumulative dose/ cycle, fractionation, duration and volume of infusion), co-medications (cisplatin, doxorubicin, etoposide, opioids, benzodiazepine, aprepitant) and outcome. Results: From 09/2008 to 11/2013, 187 S pts have been treated with Ifosfamide. The median age was 27 (0-78). Histologies were Soft Tissue Sarcomas (78), OsteoS (48), Ewing S (41) and RMS (26). We have identified 8 IRE occurring after first cycle (4.2% [1.8-8.2]). Renal function was normal in all cases. Only 8 pts have received aprepitant, none of them experienced IRE. Under univariate analysis, the risk factors for IRE were: PS ≥ 2 (OR = 9.5 [2.4-38.8]), Albumin ≤ 36 g/L (9.8 [1.2-80.2]), leptomeningeal met (OR = 13.2 [2.7-63.2]), 4 or 5 successive days of ifosfamide administration (OR = 6.0 [1.4-25.6]). 3 factors remained statistically significant in logistic regression analysis: Albumin ≤ 36 g/L (OR = 11.2 [1.7-67.4]), leptomeningeal met (16.0 [3.3-45.6]) and 4 or 5 successive days of ifosfamide administration (8.1 [2.1-20.7]). Conclusions: Ifosfamide must given with caution in pts with hypoalbuminemia or with known leptomeningeal met. A 4 to 5 days fractioned ifosfamide seems associated with increased risk for IRE; this figures contrasts with published PK studies demonstrating that fractionation induces auto induction ifosfamide metabolism and increases ifosfamide clearance.
Induction chemotherapy before lung cancer resection: Experiences and perspectives
Authors: M. Pesek, V. Spidlen, P. Mukensnabl
Journal: Journal of Clinical Oncology (2004)

7329 Background: Surgical therapy can be offered only to approximately 10% of patients suffering from this disease in Czech Republic. Currently, attention is focused on treatment procedures aiming to cause a downstaging of lung cancer. We report on our experience with induction preoperative treatment of those patients in years from 1986 to 2003. Methods: The subjects of our analysis are all the patients, who were treated by preoperative oncological treatment, by chemotherapy or chemoradiotherapy followed by surgery. Also patients who underwent non-radical surgery are included. The first group (A) includes the patients, who were treated in the years from 1986 to 1999 by combinations of cytostatic agents of 1st and 2nd generations. Group B includes patients treated by combination of vinorelbine-iphosphamide-cisplatin, group C treated by combination of gemcitabine-cisplatin and group D s treated by combination of paclitaxel-carboplatin. Group E includes patients with small cell cancers. Each group was further analysed by sex, age, stage and type of tumour, extent of surgery, presence of perioperative morbidity and mortality, teatment effect on downstaging and overall survival. Number of chemotherapy cycles and possible consequential treatment administered because of residual disease or cancer relapse were also registered. Results: In groups A-D, most frequent cancer type was epidermoid, most frequent stages were IIIA/IIIB. Downstaging was found in group A in 43% of patients, in B in 46%, in C in 41%, in D in 62%. Pathologic CR was found in A in 17%, in B in 19%, in C in 25%, in D in 0%. Postoperative mortality in groups A – E was 5,3% of patients. Brain metastases in postoperative follow up were found in groups A and B in 10 patients, while in groups |C and D in none. 3-years survival was in A in 54%, in B in 40%, in C in 33%, in D in 37% and in E in 34% of patients. Out of a total of 13 patients with histological complete remission, currently 10 patients are alive; mean follow-up time being of 31 months, range 6.2 – 96.6 months. Three year survival rate is 46%, five year survival rate is 38% so far. Conclusions: Preoperative chemotherapy is of value in responders. It shares 20% in our resected patients. No significant financial relationships to disclose.
Local Therapy Improves Survival in Metastatic Prostate Cancer
Authors: Sami-Ramzi Leyh-Bannurah, Stéphanie Gazdovich, Lars Budäus, Emanuele Zaffuto, Alberto Briganti, Firas Abdollah, Francesco Montorsi, Jonas Schiffmann, Mani Menon, Shahrokh F. Shariat, Margit Fisch, Felix Chun, Thomas Steuber, Hartwig Huland, Markus Graefen, Pierre I. Karakiewicz
Journal: European Urology (2017)