tbuckley/cabot-search huggingface dataset:
Impact of absence of in-house radiation facilities for patients (pts) treated with concurrent chemoradiotherapy (CCRT) for locally advanced head and cancer (LAHNC): A 3-year public hospital (PH) experience at Louisiana State University (LSU) in New Orleans.
Authors: Shravan Kumar Narmala, Sumalatha Puligothram, Saima Jahangir, Troy Scroggins, Cruz Velasco-Gonzales, Brian C. Boulmay
Journal: Journal of Clinical Oncology (2014)

e17523 Background: CCRT is a standard of care for treatment of LAHNC. CCRT programs for LAHNC requires detailed coordination and delivery of supportive care. LAHNC pts treated at the public hospital (PH) in New Orleans receive daily XRT at a private facility (PF) remote from the site of CTX treatment. The underserved and under- or unisured population served by the PH system are often unable to secure reliable travel for supportive care required to treat LAHNC. There is paucity of data evaluating outcomes of LAHNC PH- based pts treated with CCRT. Methods: Pts treated for LAHNC from 1/2008 to 12/2011 at LSU were retrospectively reviewed. Data collected included: age, ethnicity, mean cumulative cisplatin dose (CCD), mean total radiation dose (TRD), and renal insufficiency (RI). The same variables were collected for the same time period from the private facility administering XRT from an insured patient cohort also receiving CTX at PF. Unbalance of cohorts and non-randomization were accounted for using propensity scores as a covariate. Endpoints evaluated were PFS (PFS) at 2 years and overall survival (OS) at 3 years. Results: Median age was 57 years old (yrs) at PH and 62 yrs at PF (p=0.000); 50% of pts at the PH were African American (AA), 34% at PF were AA, (p=.0094). CCD for pts who received cisplatin was 221mg/m^2 at PH and 217 mg/m^2 at PF. The TRD were 66.7 Gy at PH and 66.27 Gy at PF. 23% of pts receiving concurrent CTX/XRT at PH developed RI based on RIFLE criteria and 21% at PF developed RI. Overall survival (OS) at 36 months in pts treated at PH was 34.18% and 53.3% at PF, (p=0.1077). At 24 months 44.26% and 62.82% pts were progression free at PH and PF respectively (p=0.1565). Conclusions: Despite the potential safety and logisitical issues presented by administration of CTX and XRT at separate facilities, these data would suggest that outcomes for a medically underserved population are not adversely affected. Patient OS and PFS, while numerically different, are not statistically different when matched to an insured patient cohort treated with both CTX and XRT at a PF.
Usefulness of oncology time lines to multiple care providers.
Authors: John C. Krauss, Pamela Christine Fisher
Journal: Journal of Clinical Oncology (2014)

e17625 Background: Clinicians need summaries of complex medical histories to efficiently provide care to patients. Cancer patients have systemic treatments that span over years. Uniform presentation of the history has the competing priorities of being either complete, with every captured data point, or succinct, which may leave out information deemed necessary at a later point. We have constructed oncology time lines for every patient seen in our clinic. The timelines serve as a flow sheet of adjuvant and palliative treatments, and encompass systemic treatments, surgery, and radiation therapy. Methods: Timelines were constructed on every patient seen in clinic since Aug 2012. Charts for a 2 week period were reviewed 9 months later, and use of the timeline was noted. Results: In the two week period, 106 unique timelines were generated or curated, and 73 of these patients were seen by another provider in the following 9 months. There were 16 instances where the timeline was directly copied into another providers note, a 22% reuse rate. 49 of the 73 patients were being treated with palliative intent, whereas 14 of 16 patients with reused timelines were being treated with palliative intent. Hospitalists were the most common physician group to reuse a timeline. Conclusions: We believe that timelines can be extended into other medical specialties to succinctly present providers with meaningful histories. While challenges exist in determining the level of detail of a timeline, ongoing refinements may allow for physicians to better communicate the status of a patient with each other and with the patient. Sample time line. 2009 T2 1.2 cm adenocarcinoma of colon, 0/12 LN positive, no further therapy 2010 L breast cancer, 1.6 cm, 1/21 LN positive, ER positive, her-2 neu neg, stage II, lumpectomy 2010 4 doses AC, 3 doses paclitaxel (last dose held due to neuropathy) 2011 Jan XRT to L breast/chest wall competed 2011 Jan Anastrazole 1 mg/day start 2012 Nov Liver and lung mets, biopsy of liver mets shows colon cancer, CEA 25, stop anastrazole 2012 Dec Start FOLFOX, add in bevacizumab dose 3 2013 Jan 31 FOLFOX bev at 75% 2013 April 11 FOLFOX bev #9 2013 May 9 ,Progression, FOLFIRI -cetuximab, 75% doses FOLFIRI (previous tx)
Multicenter Prospective Phase II Study of Venetoclax in Patients with Previously Treated Waldenstrom Macroglobulinemia
Authors: Jorge J. Castillo, Joshua Gustine, Kirsten Meid, Toni Dubeau, Andrew Keezer, John N. Allan, Richard R. Furman, Tanya Siddiqi, Ranjana Advani, Jessica Lam, Zachary R Hunter, Guang Yang, Lian Xu, Matthew S Davids, Steven P Treon
Journal: Blood (2018)
Effect of body mass index on outcomes of autologous hematopoietic stem cell transplantation.
Authors: Sherilyn Alvaran Tuazon, Neil David Palmisiano, Scott W. Keith, Irina Kakhniashvili, Joanne E. Filicko-O'Hara
Journal: Journal of Clinical Oncology (2014)

e18004 Background: Obesity is increasingly common in patients undergoing hematopoietic stem cell transplantation (HSCT). Obese patients are thought to have poorer outcomes after HSCT due to excess inflammation, comorbidities, and lack of standard chemotherapy dosing, resulting in excess toxicity or decreased curative outcomes. We investigated the effect of Body Mass Index (BMI) on clinical outcomes in autologous HSCT patients. Methods: We retrospectively analyzed outcomes of 130 recipients of autologous HSCT for multiple myeloma (n=126) and amyloidosis (n=4) from 2006 to 2012. We categorized patients by BMI as normal, overweight, obese, or severely obese. We used linear regression for time to engraftment, maximum stool volume and number of stools per day, and logistic regression for acute kidney injury (AKI) and infections. Cox proportional hazards model was used to characterize the relationship between BMI groups and survival. Results: For conditioning regimen, 1 (0.8%) received melphalan (Mel) 100 mg/m2, 5 (3.8%) received Mel 140 mg/m2, 122 (93.9%) received Mel 200 mg/m2, and 2 (1.5%) received busulfan/cyclophosphamide. Two (1.5%) patients were underweight, 30 (23.1%) had normal weight, and 98 (75.4%) were overweight/obese. Compared to those with BMI < 25, the overweight had a 1.79-fold greater expected geometric mean maximum stool volume/day (p<0.01) and a 1.32-fold greater expected geometric mean maximum stool volume/day (p=0.04). Compared to those with normal BMI, patients with BMI >35 had 43-fold greater odds of AKI (p<0.01). No correlation was found between BMI and time to platelet engraftment (p=0.1), time to WBC engraftment (p=0.23), and occurrence of infections. No statistically significant differences were observed between BMI groups and overall survival. Conclusions: Overweight or obesity was not associated with worse overall survival in the setting of autologous HSCT. However, a BMI >25 was associated with more GI toxicity and a BMI >35 was associated with increased incidence of AKI. The reasons for this are unclear, but further research is necessary to optimize dosing of chemotherapy in obese/overweight patients to potentially reduce toxicity.
Comparison of Immunophenotypic Abnormalities in B-Lymphoblastic Leukemia (B-ALL) Minimal Residual Disease (MRD) of Adults and Children Utilizing the Children's Oncology Group (COG)-Validated Multiparameter Flow Cytometry (MFC)- MRD Approach: An Institutional Experience
Authors: Brooj Abro, Cara Lunn Shirai, Anjum Hassan, Yvette Kudlinski, Barbara Weddle, Friederike Kreisel
Journal: Blood (2018)
Molecular characterization of immunogenic cell death triggered by the high hydrostatic pressure in human tumor cells.
Authors: Irena Moserova, Iva Truxova, Pierre-Francois Cartron, Jirina Bartunkova, Radek Spisek, Jitka Fucikova
Journal: Journal of Clinical Oncology (2014)

e14008 Background: Immunogenic cell death (ICD) is a form of cell death caused by certain chemicals or physical modalities: cytostatic agents such as anthracyclines, oxaliplatin and bortezomib, or radiotherapy and photodynamic therapy. Typical molecular events characteristic for ICD are surface exposure of calreticulin, HSP70, HSP90, release of intranuclear HMGB1 and the secretion of ATP from dying cells. We investigated the potential of high hydrostatic pressure (HHP) to induce ICD in human tumor cells and analyzed the key components of apoptotic pathways. Methods: We treated wide spectrum of primary human tumor cells and human cancer cell lines (acute lymphoblastic leukemia, ovarian and prostate cancer) by HHP in the custom made device and analyzed the expression of ICD markers, signaling pathways triggered by the treatment and capacity of HHP treated tumor cells to induce tumor specific immune responses. Results: HHP induced rapid expression of HSP70, HSP90 and calreticulin on the cell surface of early apoptotic cells. Cells treated by HHP produced high levels of reactive oxygen species (ROS). Pretreatment of cells with ROS inhibitors, N-acetyl-L-cysteine or L-glutathione, inhibited ROS production and calreticulin expression, indicating the importance of ROS pathway in HHP-mediated ICD. The other key components of the ER stress mediated apoptotic pathway, such as phosphorylation of eIF2α, the activation of caspase-8 and caspase-8-mediated cleavage of the ER protein BAP31 were also detected. The interaction of dendritic cells (DCs) with HHP-treated tumor cells led to faster rate of phagocytosis, upregulation of CD83, CD86 and HLA-DR and release of IL-6, IL-12p70 and TNFα. DCs pulsed with tumor cells killed by HHP induced high numbers of tumor-specific T cells. DCs pulsed with HHP-treated tumor cells also induced the lowest number of regulatory T cells. Conclusions: HHP is a reliable and potent inducer of ICD in human tumor cells. HHP activates the key components of ER stress mediated pathway. HHP treatment can be used for the induction of ICD in GMP settings in compliance with the regulatory requirement. This allows for the testing of HHP killed immunogenic tumor cells in cancer immunotherapy trials.
Multipotent mesenchymal stromal cells play critical roles in hepatocellular carcinoma initiation, progression and therapy
Authors: Zeli Yin, Keqiu Jiang, Rui Li, Chengyong Dong, Liming Wang
Journal: Molecular Cancer (2018)

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, with high morbidity, relapse and mortality rates. Multipotent mesenchymal stromal cells (MSCs) can be recruited to and become integral components of the HCC microenvironment and can influence tumor progression. This review discusses MSC migration to liver fibrosis and the HCC microenvironment, MSC involvement in HCC initiation and progression and the widespread application of MSCs in HCC-targeted therapy, thus clarifying the critical roles of MSCs in HCC.
Clinical significance of CD169-positive lymph node macrophages in human malignant tumors.
Authors: Koji Ohnishi, Yoichi Saito, Yoshihiro Komohara, Yuji Miyamoto, Satoshi Fukushima, Munekage Yamaguchi, Hideo Baba, Hironobu Ihn, Hidetaka Katabuchi, Motohiro Takeya
Journal: Journal of Clinical Oncology (2014)

11118 Background: CD169 (sialoadhesin) is a sialic acid receptor that is expressed on specific macrophages such as lymph node sinus macrophages. Animal studies have suggested that CD169+ macrophages have tumor-preventing activities, however, the role of these cells in human diseases has not been clarified. Methods: To examine the role of CD169 in anti-tumor immunity, we examined the expression of CD169 in regional lymph nodes (RLNs) and their relations with overall survival and clinicopathological factors in colorectal carcinoma (83 cases), melanoma (93 cases) and endometrial carcinoma (77 cases) by immunohistochemistry. To clarify the mechanism of CD169 expression in human macrophages, culture experiments were performed. Results: High density of CD169+ cells was significantly associated with longer overall survival in these tumors (p = 0.009, p = 0.001 or p = 0.007, respectively). In colorectal carcinoma and melanoma, multivariate analysis showed that the density of CD169+ cells was an independent prognostic factor. We also found that the density of CD169+ macrophage was positively correlated with the number of CD8+ cytotoxic T cells infiltrating into tumor tissues. The majority of CD169+ macrophages were in direct contact with CD8+ T cells expressing CD43, a major ligand of CD169, and many interferon (IFN) α-producing cells were detected surrounding the CD169+ cells. Furthermore, in our in vitro experiments with human macrophages, IFNα induced strong expression of CD169. These data suggest that CD169+ macrophages in RLNs promote CD8+ T-cell-mediated anti-tumor immunity and are associated with a better prognosis for cancer patients. Conclusions: CD169+ macrophages in RLNs may thus be a useful marker for assessing clinical prognosis and monitoring anti-tumor immunity in patients with colorectal carcinoma, melanoma and endometrial carcinoma.
Challenges to optimal care in colorectal cancer: An international study of oncologists’ needs.
Authors: Sean Hayes, John Marshall, Patrice Lazure
Journal: Journal of Clinical Oncology (2014)

e14532 Background: Oncologists involved in the care of patients with colorectal cancer (CRC) may experience various challenges that potentially hinder optimal care. An international, institutional review board (IRB)-approved needs assessment was conducted to determine gaps in the knowledge, skills, and competencies of oncologists caring for patients with CRC in seven countries. Methods: A mixed-methods approach was employed, combining qualitative data (semi-structured interviews) and quantitative data (online surveys). The sample consisted of 358 oncologists from China (n=68), France (n=44), Germany (n=44), Italy (n=45), Spain (n=44), UK (n=45), and US (n=68). ANOVAs and Tahmane’s T2 post-hoc tests were performed to investigate country differences in responses to the survey. Results: Ten practice gaps were identified internationally, across the continuum of care, from diagnosis to treatment and management. Among these was a gap in oncologists’ ability to individualize treatment. Elements of the patient and tumor profile creating the biggest challenge to the individualization of treatment differed by country. In Germany, liver/lung metastases was the co-morbidity most frequently reported as a significant challenge to treatment selection (p<0.001), while oncologists in the UK and Spain reported more difficulties adapting treatment in the presence of a cardiac co-morbidity (p=0.003). Individualization of treatment is further complicated by gaps from three additional domains: 1) sequential use of treatment options (59% reported needing improvement); 2) Adjustment of treatment plan to chemo-resistance (72% reported a significant challenge); and 3) mutation analysis (64% reported needing improvement in their skill to subsequently adapt treatment choices). Conclusions: Challenges hindering oncologists’ capability to individualize treatment were identified in seven countries. As new treatments become available and new tumor specific mutations are discovered, there is an increasing need to better support oncologists in their efforts to provide the best treatment for each patient. This study’s findings should help oncologists reflect on their own practice and select continuing education programs adapted to their needs.
A New Stromal Signature Applicable to Formalin-Fixed Paraffin-Embedded Tissues Identifies Patients at Risk in Prospective Clinical Trials of the German High-Grade Non-Hodgkin Lymphoma Study Group
Authors: Annette M. Staiger, Michael Altenbuchinger, Marita Ziepert, Christian Kohler, Heike Horn, Michael Huttner, Katrin Huettl, Wolfram Klapper, Monika Szczepanowski, Julia Richter, Andreas Rosenwald, Harald Stein, Alfred Feller, Peter Moeller, Martin-Leo Hansmann, Markus Loeffler, Viola Poeschel, Gerhard Held, Lorenz Truemper, German Ott, Rainer Spang
Journal: Blood (2018)
The orally bioavailable parthenolide analogue, DMAPT, has anti-cancer activity which is mediated by generation of reactive oxygen species (ROS) and inhibition of nuclear factor kappa B and has single agent in vivo activity
Authors: Praveen Kusumanchi, Rajasubramaniam Shanmugam, Peter Crooks, Craig Jordan, Harikrishna Nakshathri, Christopher Sweeney
Journal: Cancer Research (2008)

2318  Death from prostate cancer is due to hormonal and chemotherapy resistance. New therapies are needed. We have previously shown that the naturally occurring product, parthenolide, inhibits NFκB and cellular proliferation in vitro. However, it has no single agent activity in in vivo models although it augments the efficacy of the anti-androgen, bicalutamide, and the cytotoxic, docetaxel. Dimethylaminoparthenolide DMAPT is a bioavailable analogue and provides serum concentrations greater than 20µM in mice. Our recent in vitro studies using the androgen independent cell lines, PC-3 and CWR22Rv1, have shown that DMAPT inhibits NFκB DNA binding and proliferation of CWR22Rv1 and PC-3 with IC50’s between 5 and 10μM. Moreover, DMAPT reduces expression of the NFκB target gene TRAF2 in both cell lines as well as induces re-expression of p73 in PC-3 but not in CWR22Rv1. Further, DMAPT results in generation of reactive oxygen species (ROS) with resultant phosphorylation of JNK and cJun. N-acetylcysteine (NAC), blocks DMAPT induced generation of ROS and JNK/cJun activation as well as its anti-proliferative properties . Furthermore, the JNK inhibitor SP600125 blocks the ability of DMAPT to induce JNK activation and partially protects the cells from DMAPT’s anti-cancer activity. To determine whether DMAPT has single agent in vivo activity in prostate cancer cells, athymic nude mice were inoculated subcutaneously with CWR22Rv1 and PC-3 in the flank. Mice were treated by daily oral gavage with solvent (control) or DMAPT at doses ranging from 40 to 100 mg/kg/day as well as 100 mg/kg twice per day. Unlike parthenolide, DMAPT as a single agent decreased the volume of the subcutaneous tumors in a dose dependent manner. In conclusion, DMAPT has a complex mechanism of action that involves both the generation of ROS and inhibition of an oncogenic transcription factor, NF\#312;B. The improved water solubility has resulted in single agent in vivo activity in two androgen independent prostate cancer cell lines.
Persisting new nodules in incidence rounds of the NELSON CT lung cancer screening study
Authors: Joan E Walter, Marjolein A Heuvelmans, Kevin ten Haaf, Rozemarijn Vliegenthart, Carlijn M van der Aalst, Uraujh Yousaf-Khan, Peter M A van Ooijen, Kristiaan Nackaerts, Harry J M Groen, Geertruida H De Bock, Harry J de Koning, Matthijs Oudkerk
Journal: Thorax (2018)

Background The US guidelines recommend low-dose CT (LDCT) lung cancer screening for high-risk individuals. New solid nodules after baseline screening are common and have a high lung cancer probability. Currently, no evidence exists concerning the risk stratification of non-resolving new solid nodules at first LDCT screening after initial detection. Methods In the Dutch-Belgian Randomized Lung Cancer Screening (NELSON) trial, 7295 participants underwent the second and 6922 participants the third screening round. We included participants with solid nodules that were registered as new or &lt;15 mm³ (study detection limit) at previous screens and received additional screening after initial detection, thereby excluding high-risk nodules according to the NELSON management protocol (nodules ≥500 mm 3 ). Results Overall, 680 participants with 1020 low-risk and intermediate-risk new solid nodules were included. A total of 562 (55%) new solid nodules were resolving, leaving 356 (52%) participants with a non-resolving new solid nodule, of whom 25 (7%) were diagnosed with lung cancer. At first screening after initial detection, volume doubling time (VDT), volume, and VDT combined with a predefined ≥200 mm 3 volume cut-off had high discrimination for lung cancer (VDT, area under the curve (AUC): 0.913; volume, AUC: 0.875; VDT and ≥200 mm 3 combination, AUC: 0.939). Classifying a new solid nodule with either ≤590 days VDT or ≥200 mm 3 volume positive provided 100% sensitivity, 84% specificity and 27% positive predictive value for lung cancer. Conclusions More than half of new low-risk and intermediate-risk solid nodules in LDCT lung cancer screening resolve. At follow-up, growth assessment potentially combined with a volume limit can be used for risk stratification. Trial registration number ISRCTN63545820 ; pre-results.
Drug-company–sponsored lectures and physicians' prescribing patterns.
Authors: Shin Ogita
Journal: Journal of Clinical Oncology (2014)

e17575 Background: Pharmaceutical companies frequently sponsor free lectures and/ or seminars for physicians. Although the contents (i.e. presentation slides) can be reviewed for their adequacy in advance, the actual presentations are not regulated. Moreover, the effect of those conferences on physician's practice pattern has not been well studied. Methods: “Bone modifying agent (BMA) conference” was held at St. Luke’s International Hospital on July 4, 2013. The conference was sponsored by Daiichi-Sankyo and AstraZeneca who sell denosumab, a newer BMA approved in Japan in January, 2012. Zoledronic acid was an older BMA and was considered as the competing product. Patients who started denosumab and/or zoledronic acid for metastatic bone disease from March 5, 2013 (4 months before the conference) to November 4, 2013 (4 months after the conference) were identified, and their ordering physicians were included in the analysis. The rate of denosumab and/or zoledronic acid use were compared between the two physician groups who attended the BMA conference and those who did not. Results: Fifteen physicians prescribed the BMAs newly on metastatic cancer patients during the study period. Five of them attended the conference and ten did not. Before the conference, 70% of non-attending and 60% of attending physicians had used zoledronic acid (p= 0.70). After the conference, 80% of non-attending physicians still prescribed zoledronic acid whereas only 20% of attending physician used zoledronic acid (p= 0.025). There was no difference in the denosumab use between the two physician groups before and after the conference. Conclusions: Physicians who attended the drug company sponsoring lecture were less likely to prescribe the competing product. The effect of pharmaceutical sponsored conference should be studied more rigorously in a prospective fashion, and the physicians should be aware of the potential risk of participating in such lectures.