tbuckley/cabot-search huggingface dataset:
Intensity-modulated radiation therapy (IMRT) in patients with locally advanced pancreatic cancer (LAPC).
Authors: Carla Hajj, Florence Huguet, Abraham Jing-Ching Wu, Eileen Mary O'Reilly, Corinne Winston, Diane Lauren Reidy, Peter J. Allen, Karyn A. Goodman
Journal: Journal of Clinical Oncology (2015)

377 Background: To assess IMRT safety and evaluate local control and resectability among patients with LAPC treated with induction CT followed by IMRT. Methods: We reviewed records of 134 LAPC patients treated with CT (median duration 3.2 months) followed by IMRT (median dose 56 Gy) between 11/2006 and 11/2012. Patients had LAPC based on T4 disease or unreconstructable involvement of portal vein/hepatic artery on imaging (n=102) or were found to be unresectable after an attempted resection (n=32). Induction CT was gemcitabine-based (n=98) or FOLFIRINOX (n=32); concurrent CT was gemcitabine in 88 patients, continuous 5-FU or capecitabine in 37 patients. IMRT was given after induction CT in the absence of evidence of disease progression. After IMRT, 81 patients received maintenance CT. Results: Acute grade 3 GI and hematologic toxicity were seen in 4 (2.9%) and 33 (24.6%) patients, respectively. Acute grade 4 GI and hematologic toxicity were seen in 0 and 5 (3.7%) patients, respectively. Ten patients (7.4%) developed late grade 1 GI toxicity and 2 patients (0.7%) developed compression fractures. Twenty-six (19.4%) patients underwent resection 4.1 months (mean) after IMRT; 22 (84.6%) had negative margins, one of whom had a pathologic complete response and 4 had a microscopically positive margin. With 20.1 months median f-up, median local progression-free survival (LPFS) was 17.6 months. One- and 2-year LPFS were 90% and 55% respectively. Median distant metastasis free survival (DMFS) was 15.2 months. One- and 2-year DMFS were 69.5% and 30.7% respectively. Median OS was 19.7 months for the whole population (24.8 months for surgical patients and 19.7 months for the non-surgical patients). One- and 2-year OS for all patients were 85% and 47% respectively; one- and 2-year OS for the surgical patients were 96% and 72% respectively. Conclusions: In this large cohort of patients treated with IMRT for LAPC, acute and late toxicity was minimal. Patients with non-progressive LAPC after induction CT who received IMRT had high rates of local control which could translate into a better quality of life. In selected patients, induction CT followed by IMRT can downstage tumors allowing for R0 resections and improved overall survival.
Expression of GHRH-R in primary and metastatic mammary carcinomas.
Authors: Norman L. Block, Mehrdad Nadji, Andrew V. Schally, Jonathan F. Lara, Richard Alan Michaelson, Suhail M. Ali, Kim Leitzel, Allan Lipton
Journal: Journal of Clinical Oncology (2014)

19 Background: In addition to its nominative function, as a neurohormone acting on the pituitary, Growth Hormone Releasing Hormone (GHRH) has been shown to modify the growth behavior of numerous cancers, including breast. GHRH is produced by tumor cells, acts in an autocrine/paracrine manner, and requires the presence of GHRH receptor (GHRH-R) on the tumor cells to exert its effects. As this work has been done predominantly on tumor cell lines and xenografts, we set out to examine the clinical analog. Methods: Matched primary and metachronous metastases from 50 breast cancers were included in this study of GHRH-R in breast cancer. Immunohistochemistry for GHRH-R (AbCam) was performed on paraffin sections and the staining results were assessed semi quantitatively from 0 (negative) to 3+ (strongly positive). A section from normal pituitary was use as positive control. Results: Forty-three of the primary breast cancers (86%) that ultimately relapsed or metastasized showed moderate to strong immunohistochemical expression of GHRH-R. Tumors from the metastatic foci also showed strong immunoreactivity in 78%, 71%, and 44% of liver, brain, and bone foci, respectively. The lower intensity of staining in bone samples may be due to the effect of the decalcification process routinely performed before staining. Whenever present, the non-neoplastic glands adjacent to breast tumors showed either negative or 1+ reaction for GHRH-R. The study population will be expanded to 100 patients, and the GHRH-R IHC results will be correlated with HER2, ER status, and clinical outcome. Conclusions: We conclude that the great majority of mammary carcinomas at primary and metastatic sites express GHRH-R. This finding could potentially serve as a basis for therapeutic approaches using peptide receptor antagonists. By receptor blockage using receptor antagonists, with minimal pharmacologic side effects, we have been able to control the growth in a number of tumor cell lines (HCC1806, MDAMB468, MDAMB435S, MCF7, T47D, HCC1937, BT474, and MX1s). Based on the presence of GHRH receptors in these clinical tumors, we conclude that clinical trials evaluating GHRH recpeptor antagonists are indicated.
Iron Chelation Therapy and Mobilization of Hematopoietic Peripheral Progenitors in Patients with β-Thalassemia Major
Authors: Gian Luca Forni, Marina Podestà, Marco Musso, Giovanna Piaggio, Khaled M Musallam, Manuela Balocco, Sarah Pozzi, Francesco Frassoni
Journal: Blood (2012)
Evaluation of the Prognostic Value of CD45RO+ and FOXP3+ Cells of the Micro-Environment In Classical Hodgkin Lymphomas Using Tissue Micro Array
Authors: Claire Benet, Emmanuelle Ferrant, Tony Petrella, Emilie Degrolard, Jean-Noel M. Bastie, Bernard Bonnotte, Rene-Olivier Casasnovas, Laurent Martin
Journal: Blood (2010)
Familial risk and heritability of genitourinary cancers in the Nordic Twin Cohorts.
Authors: Lorelei A. Mucci, Jacob Hjelmborg, Kathryn Penney, Axel Skytthe, Jennifer Harris, Hans-Olov Adami, Jaakko Kaprio
Journal: Journal of Clinical Oncology (2015)

11 Background: Twin studies estimate familial risk and heritability by leveraging the unique genetic relatedness of twins. We analyzed data from the Nordic Twin Study to investigate the genetic underpinnings of risk of genitourinary cancers. Methods: The cohort included 202,868 monozygotic (MZ) and same-sex dizygotic (DZ) twins from nationwide registries with follow-up via cancer registries. We examined cancers of the prostate, bladder, kidney and testes, and estimated familial risk, risk of a specific cancer in a twin, given that his co-twin was diagnosed with the same cancer, and heritability, the proportion of variation in cancer risk due to genetic differences. Statistical models used time-to-event analyses and accounted for censoring and competing risk of death. Results: During 32 years of follow-up, 5,041 cases of genitourinary cancer were diagnosed. The cumulative incidences in the cohort overall were 10.5% for prostate, 2.2% for bladder, 0.8% for kidney and 0.5% for testes. The strongest familial effects were found for testicular cancer. The familial risks of testicular cancer were 6% for DZ and 14% for MZ twins, i.e. a 12-fold and 28-fold higher risk for DZ and MZ twins, respectively, when their twin was also diagnosed with testicular cancer. Familial risk was also elevated for prostate, bladder, and kidney cancer and showed higher estimates among MZ than DZ twins. Statistically significant estimates of heritability were observed for prostate (57%) and kidney (38%) cancer, while testicular cancer showed evidence of both genetic (37%) and shared environmental (24%) effects. Conclusions: Familial risk estimates provide evidence of significant excess risks for individuals whose siblings develop genitourinary cancers. The higher concordance in MZ vs. DZ twins translated to strong heritability estimates for these malignancies. Results from this study have the potential to be directly translated to clinical practice and genetic counseling, and provide a context for the findings from genome wide association studies.
Teaching clergy about cancer alleviates their increased anxiety in counseling and visiting their congregants and, in their mind, makes them better religious leaders
Authors: K. R. Hoffman
Journal: Journal of Clinical Oncology (2008)

20691 Background: Clergy are an essential part of patient care. However they have their own anxieties when dealing with the cancer patient, particularly in trying to understand the diagnosis, treatment, resulting toxicities and results of therapy.This uncertainty makes it difficult for them to give the appropriate spiritual care to their congregant with cancer. Methods: Initially, six clergy recognized a need to improve their spiritual care of the cancer patient. A class was developed to teach an introduction to cancer. This included its diagnosis, staging and treatment in the curative and palliative setting. Initially the clergy were most interesed in understanding the terms used by their congregants when discussing their own illness. However, after the first session, the course expanded into an eight week, two hours per week course. Curriculum included hospital visits and patient contacts in the out-patient, in-patient, home and hospice-settings. Guest speakers covered surgery, radiation therapy, nursing, nutrition and rehabilitation services. No fee is charged for the class and all speakers and facilities donate their time. Patients volunteer to be seen by the clergy. Following the completion of this first effort, two further classes have been held with eight and twelve participants. Clergy from nine different faiths are participating in our third class. A take-home syllabus has been created and is updated with each class. Results: Initially no formal evaluation was done to judge the success of the program. With the start of the third session, the State-Trait Anxiety Inventory for adults (STAI Form Y) is being used as a pre-test and will be retaken six months after the completion of the class. Similarly, the ‘distress thermometer‘ is being used in an attempt to judge our participants’ ‘comfort zone‘ with these patients. Results from our third class will be available in June. Conclusions: Our clergy have recognized that learning about cancer makes their job of counseling their members with this disease much easier.The coursework used and the evaluation of our particular atttempt is continuing to evolve towards a goal of total success. No significant financial relationships to disclose.
Development of a question prompt sheet for cancer patients receiving outpatient palliative care.
Authors: Joseph Anthony Arthur, Sriram Yennu, Janet L. Williams, Kimberson Cochien Tanco, Diane D Liu, Eduardo Bruera
Journal: Journal of Clinical Oncology (2015)

25 Background: An effective communication strategy is the fundamental backbone in the delivery of an impeccable palliative care intervention. Different communication tools are sometimes utilized to enhance discussions between patients and their physicians. An example is a question prompt sheet (QPS) which is a structured list of potential questions available for the patient to ask their doctor during a clinical encounter. Although it has been shown to improve physician-patient interaction during clinical consultations, there is paucity of data on its use in the palliative care setting. The objective of this study was to develop a QPS that is feasible and applicable in palliative care clinical practice. Methods: An expert group of experienced physicians and mid-level providers were invited to participate in the study. The process was conducted in 3 Delphi rounds. In the last round, the top 25 questions with the highest level of endorsement were chosen and used towards the development of the QPS. Results: One hundred percent of the 22 experts invited to participate in the study accepted the invitation and completed all the 3 Delphi rounds. They consisted of 82% physicians and 18% mid-level providers. Participants were mostly males (59%), had a median age of 42 years, and a median of 8 years’ experience in palliative care. 98% of the top 25 questions for the QPS were endorsed by at least 50% of the expert panel in round 3. Twenty-eight percent of the questions were about symptoms, treatment and lifestyle, 24% were about commonly asked questions by caregivers, 20% were regarding end-of-life issues, 16% were regarding the nature of palliative care service, and 12% were regarding the type of available support. The question which had the highest number of endorsements among the panel members was “Is there someone I can talk to about my fears, concerns, spiritual or religious needs?” Conclusions: A 25-item, single page QPS containing some of the most relevant questions in diverse aspects of advanced cancer care and feasible for use in clinical practice was developed in this study. Further studies are needed to determine the clinical effectiveness of the QPS in assisting patient physician communication.
The Effect of Phenylhexyl Isothiocyanate on Drug Resistance of K562/A02 Cell Line
Authors: Bao-An Chen, Peng Yuan, Jian Cheng, Feng Gao, Jia-Hua Ding, Chong Gao, Yun-Yu Sun, Jun Wang, Gang Zhao, Hui-hui Song, Wen Bao, Ze-ye Shao, Guo-hua Xia, Quan-yi Lu, Xu-dong Ma, De-long Liu, Jue-qiong Wang, Xiao-ping Pei, Ning-na Chen
Journal: Blood (2008)
ERG protein expression in prostate and vascular tumors: A potential for ERG-based stratification.
Authors: G. Petrovics, S. Tan, A. Dobi, D. Young, Z. Wang, A. Paetau, Y. Chen, T. Sreenath, S. A. Brassell, M. Miettinen, I. Sesterhenn, D. G. McLeod, S. Srivastava
Journal: Journal of Clinical Oncology (2011)

e15171 Background: Frequent overexpression of ERG in prostate tumors is a result of prevalent gene fusions involving upstream sequences of androgen regulated genes (predominantly TMPRSS2) and downstream coding sequences of nuclear transcription factors within the ETS gene family (primarily ERG). Despite numerous reports of ERG alterations at the transcript and genome levels, the ERG oncoprotein remains to be defined. Using a highly specific ERG monoclonal antibody, we have recently developed a comprehensive insight into ERG expression in various cell types of benign and malignant prostate glands. Further, we have analyzed ERG protein expression in human tumors of diverse origins. Methods: Using whole-mount prostate sections from 150 prostatectomy specimens, ERG protein expression was analyzed in PIN, tumor foci, benign glands and other cell types in prostate. In randomly selected cases ERG protein expression was correlated with ERG fusion status. A broad range of vascular endothelial (n=250), other mesenchymal (n=973), and epithelial tumors (n=657) were examined. Results: CPDR ERG-MAb showed striking specificity for detecting prostate tumor cells (>99.9%). Specimens from 65% patients had one or more ERG positive tumor focus. Examination of ERG positive PINs and ERG positive tumors within the same whole-mount sections revealed a 97% concordance. In normal adult tissues, including human and mouse prostate, ERG was restricted to endothelial cells and a subset of bone marrow precursors. ERG was expressed in virtually all vascular tumors and absent in all epithelial tumors except prostate tumors. Conclusions: Taken together, the homogeneous and strong ERG expression in individual tumors and the remarkable correlation between ERG positive PIN lesions and tumors suggests a role for ERG in the pre-invasive to invasive transition of prostate cancer cells. The demonstrated high specificity of CPDR ERG-MAb has potential to provide new opportunities in prostate cancer diagnosis and stratification. Further, ERG is a highly specific new marker for benign and malignant vascular tumors.
Endoglin (CD105) driven selection of circulating mesenchymal cells in patients with metastatic adenocarcinomas.
Authors: S. Kaul, A. de Albuquerque, B. Hofmann, N. Fersis
Journal: Journal of Clinical Oncology (2011)

e13586 Background: CD105 is exclusively expressed in mesenchymal stromal and endothelial cells (MSE) of vascular and lymphatic vessels in several cancer tissues. In this study we have characterized these cells in peripheral blood by a new immunomagnetic isolation technique in combination with a multimarker gene analysis in parallel to the established detection of circulating adenocarcinoma cells (CTC). Methods: MUC1 (BM7) and EpCAM (VU1D9) antibodies were used for immunomagnetic tumor cell enrichment. The CD105 specific clone 266 (BD Pharmingen, UK) coupled to 4µm magnetic beads (Dynal, Invitrogen, UK) was used for the enrichment of endoglin positive cells in parallel blood samples. Separated cells were lysed and used for mRNA isolation and cDNA synthesis. A RT-qPCR approach using two multimarker primer sets for the markers CK19, MUC1, EpCAM, Survivin and CD105 (CTC-test) and CD105, CD44 and CD276 (MSE-test) were used for cell type specific identification and characterization. Results: Sensitivity of the MSE test was 2 cells as determined by spiking human endothelial cells and human stroma cells into 5ml blood of healthy volunteers. cDNA probes of CTC and MSE from 48 patients with metastatic adenocarcinomas were analysed with the overlapping gene panels. CTC positivity in this group was 64.6 % while the marker CD105 was not detectable in any of these samples. MSE positivity was recorded in 23 (47.9%) of these probes. In 21 of 31 CTC positive pts (68%) MSE positive cells were observed. In this group all MSE samples coexpressed CD44 and 7 probes were positive for the marker of malignant angiogenesis B7-H3 (CD276). Conclusions: CD105 driven immunomagnetic isolation of mesenchymal stromal and vascular endothelial cell types (MSE) in peripheral blood of patients with adenocarcinomas is feasible and this approach could be used in future to evaluate vascular toxicity of chemotherapy, early progression of metastasis and efficacy of antiangiogenic therapies
Retrospective review of leukemia cytogenetics and prior malignancies.
Authors: S. Sliesoraitis, B. Tawfik, L. R. Ellis, L. D. Case, J. Lawrence
Journal: Journal of Clinical Oncology (2011)

e19576 Background: Late effects of cancer treatment are the occurrence of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The communication of potential risk will influence a patient’s decisions for treatment. However, a specific risk tailored to the individual is unavailable. Leukemia patients with a prior history of chemotherapy or radiation leads to attribution of cause to prior treatments received. The incidence of MDS and unfavorable AML cytogenetics increases with age. We sought to determine if advserse cytogenetics occurs more commonly in patients with a prior malignancy. Methods: We conducted a retrospective review of patients with MDS or AML between 2002 and 2009. Excluded were a prior hematologic malignancy; no cytogenetics; acute promyelocytic leukemia; and age less than 18 years old. Patients identified with a history of malignancy prior to MDS/AML were our study population, and those with MDS/AML without a preceding malignancy were controls. Cytogenetics, age, and gender were collected. The available records of prior therapy (radiation and chemotherapy) were limited. Results: 447 patients met study criteria: 88 in the prior malignancy group and 359 controls. The mean age was 64.7 years in the group with a prior malignancy and 57.7 years in the control group. The occurrence of abnormal cytogenetics was more common in the prior malignancy group. The 5q abnormality occurred 22.6% vs 13.9% (p=0.07), 7q abnormality occurred 20.5% vs 10.6% (p=0.01), chromosome 16 abnormalities occurred 9.5% vs 4.6% (p=0.14), and complex cytogenetics occurred 5.8% vs. 3.4% (p=0.36). In contrast normal cytogenetics occurred more frequently in the group without a prior malignancy 45.4% vs 36.4% (p=0.13). There were only 3 cases of 11q23 abnormalities. Conclusions: From a single institution review we found that patients with a diagnosis of MDS/AML and a history of a prior malignancy are significantly older and are more likely to have abnormal cytogenetics. The relative contribution of age and prior malignancy to cytogenetics cannot be determined. The occurrence of 7q abnormalities was significantly more common in those patients who develop MDS or AML with a prior solid malignancy.
Circulating Antibodies to ALK Inversely Correlat with Relapse Risk and Circulating Tumor Cells in Children and Adolescents with ALK-Positive Anaplastic Large Cell Lymphoma
Authors: Karen Pulford, Christine Damm-Welk, Birgit Burkhardt, Martin Zimmerman, Alfred Reiter, Kamel Ait-Tahar, Wilhelm Woessmann
Journal: Blood (2008)
Restoration of B Cell Development after Lentiviral Transduction of CD34+ Hematopoietic Cells from RAG-1 Deficient Patient.
Authors: Chantal Lagresle-Peyrou, Pierre Charneau, Christophe Hue, Karine Mollier, Isabelle Andre-Schmutz, Delphine Bonhomme, Salima Hacein-Bey-Abina, Jean-Pierre de Villartay, Alain Fischer, Marina Cavazzana-Calvo
Journal: Blood (2004)
Impact of health insurance (HI) on outcomes in patients with advanced (adv) NSCLC.
Authors: H. Khadim, J. Hussain, N. Newman, S. L. Graziano, A. Gajra
Journal: Journal of Clinical Oncology (2010)

e18048 Background: HI status has been shown to impact outcomes in breast and colon cancers as well as use of surgery and radiation in earlier stages of NSCLC. Information on impact of HI upon patterns of care in adv NSCLC is scant. We examined the relationship of HI with use of chemotherapy (CH), targeted therapy (TT), clinical trial enrollment (CTE) and overall survival (OS) in patients (pts) with adv NSCLC in a single institution retrospective cohort. Methods: Pts with diagnosis of stage IIIB/ IV (adv) NSCLC were identified from tumor registry after approval by the IRB. Information on HI status, age, sex, histology, stage, performance status (PS), wt loss, serum albumin level, use of CH, TT and dates of diagnosis and death were collected. Three HI categories were defined: Medicaid only (MD) includes uninsured pts; Medicare (MC) includes supplemental HI; and private insurance (PI). OS was estimated with Kaplan Meier method and compared with log rank test. Cox regression was used to determine simultaneously the associations between OS and potentially prognostic variables. Results: MC pts were older p<.001. PI pts had a better PS, received CH more often (p 0.04) and had higher CTE (p 0.05). On univariate analysis, factors associated with longer OS include female sex, PS of 0-1, <5% wt loss, use of CH and use of TT (Table). No significant difference in OS was noted between MD, MC and PI pts. On Cox regression analysis use of CH (OR 0.32 C.I. 0.23-0.45, p<0.001) and PS (OR 0.68 C.I. 0.48-0.96, p=0.03) were associated with decreased, and male sex (OR 1.37 C.I. 1.06-1.77, p 0.02) with increased risk of death. HI status was not associated with OS in this model. Conclusions: No major differences in OS were observed based on HI in pts with adv NSCLC. Limitations include small sample size, retrospective nature, and single institution review in NY state. This unusual trend, if confirmed in larger prospective series from other states in the United States would imply a favorable change solidifying the effectiveness of various HI models in the delivery of care to pts with adv NSCLC. Variable n = 255 OS (mos) p value Age 0.01 Sex M/F 4.3/5.6 0.03 PS 0-1/>1 7.8/2 <0.001 Weight loss <5%/> 6.3/3.9 0.001 CH Y/N 8.7/1.8 <0.001 TT Y/N 9.6/3.8 <0.001 MD/PI 3.9/5.8 0.12 MC/PI 5.1/5.8 0.82 MD/MC 3.9/5.1 0.31 No significant financial relationships to disclose.