tbuckley/cabot-search huggingface dataset:
Post-operative concomitant radiochemotherapy in the treatment of primitive CNS high grade gliomas. A retrospective analysis
Authors: P. Costa, F. Braga, C. Sottomayor, M. Honavar, M. Resende, H. Romaõ, J. Teixeira
Journal: Journal of Clinical Oncology (2006)

11528 Background: The authors analyse retrospectively the impact on tumour control and toxicity of concomitant radiotherapy (RT) and Temozolomide (TMZ) in high grade gliomas (HGG) of the CNS, in patients treated in the Clínica de Radioterapia do Porto - Portugal. Methods: This cohort represents all patients with HGG treated between January 2002 and January 2006, with concomitant RT a median total dose of 60 Gy, 2 Gy per treatment given once daily 5-days/week and TMZ 75mg/m 2 for 42 days, followed by adjuvant treatment with TMZ 5-days schedule every 28 days (150 mg/m 2 for the first cycle increased to 200mg/m 2 ). The cohort was retrospectively analyzed for gender distribution, age, extent of surgical resection, initial KPS, median overall survival (OS) and haematological toxicity. Results: 23 with HGG (6 females, 17 males) were treated with concomitant RT (44–72 Gy) and TMZ followed by adjuvant TMZ; median age was 58 (ranging from 17–72); median KPS was 80 (ranging from 40–90); 3 patients had complete resection, 17 partial resection and 3 biopsy. All patients except one, who had treatment interruption for thrombocytopenia, completed the concomitant phase of treatment; 19 patients continued to received adjuvant treatment with TMZ (median number of cycles was 5 (ranging from 1–20). Median OS (measured from the date of diagnosis to the date of death) was 20.4 month and 1 yr OS was 54%. During concomitant phase, one patient had grade 3–4 thrombocytopenia. During the adjuvant TMZ therapy 4 patients had grade 3–4 haematological toxicity (anaemia: 1; thrombocytopenia: 1; leucopoenia and thrombocytopenia: 2). Conclusions: The results of concomitant RT+TMZ followed by TMZ in these patients with HGG showed values in accordance with the latest data published on literature for this association. Differences observed might be due to the small sample size.RT+TMZ followed by adjuvant TMZ is a well tolerated treatment with better results in median OS comparatively with previous results of RT only treatment in HGG. Treatment related toxicity was within acceptable levels, and this approach became routine practice in this set of patients. No significant financial relationships to disclose.
Circulating endothelial cells, microparticles, and markers of inflammation and coagulation in glioblastoma patients before and after protracted temozolomide and radiotherapy.
Authors: G. Reynes, V. Martinez-Sales, V. Vila, T. Fleitas, M. Martin, E. Reganon
Journal: Journal of Clinical Oncology (2010)

2086 Background: Circulating endothelial cells (CECs) have prognostic and predictive value in breast cancer patients treated with metronomic chemotherapy. High levels of microparticles (MPs) are associated to shorter survival in prostate cancer. We investigated the pre- and posttreatment levels of CECs, MPs and several inflammation and coagulation markers in patients with newly diagnosed glioblastoma (GB) who received protracted temozolomide (PTMZ) and radiotherapy (RT). Methods: Peripheral blood was obtained from 14 patients with GB before and 4-5 weeks after beginning of treatment. Healthy subjects (n = 22) were used as controls. Isolation and quantification of CECs were determined by an immunomagnetic technique using CD146 and lectin-1 of Ulex Europaeus combined with fluorescein. Flow cytometry of plasma was used for detection of total phosphatidylserine-positive MPs, labeled with FITC-Annexin V. Endogen thrombin generation (ETG) was measured by the calibrated automated thrombogram method (CAT). Prothrombin fragment 1+2 (F1+2) and interleukin-6 (IL-6) were measured by ELISA. Results: Mean number of CECs was significantly increased in patients before (112 ± 65 cells/mL) and after treatment (122 ± 80 cell/mL) as compared to controls (10 ± 5 cell/mL; p < 0.0001). Mean number of MPs was significantly increased in patients before (794 ± 573 MPs/μ L) and after treatment (408 ± 207 MPs/μ L) as compared to controls (234 ± 174 MPs/μ L; p < 0.05). Levels of IL-6 were significantly higher in patients before and after treatment (IL6, 8.3 ± 14.3 pg/mL; 3.2 ± 3.1 pg/mL) than in controls (0.9 ± 0.8 pg/mL). Levels of coagulation markers were significantly higher in patients before treatment (F1+2, 0.33 ± 0.18 pmol/mL; ETG, 234 ± 106 nM). However, levels of both markers decreased near normal values (F1+2, 0.22 ± 0.07 vs. 0.17 ± 0.04 pmol/mL; ETG, 169 ± 146 vs. 162 ± 72 nM) after treatment. Conclusions: CECs and MPs, as well as a set of markers of inflammation and coagulation, are strongly elevated in patients with GB. Coagulation markers decrease after treatment with PTMZ+RT. The influence of treatment on CEC and MP levels is unclear and needs further study. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering-Plough Schering-Plough
Divide and Conquer to Treat Lung Cancer
Authors: Bruce E. Johnson
Journal: New England Journal of Medicine (2016)

The tactic of divide and conquer, which has been attributed to Philip of Macedonia and Julius Caesar in warfare, is transforming the treatment of lung cancer. Biomarkers are being used to identify subsets of patients with lung cancer who can receive initial treatment with a checkpoint inhibitor or a targeted agent. The results of the KEYNOTE-024 trial, now reported in the Journal by Reck and colleagues,1 show therapeutic benefits for the checkpoint inhibitor pembrolizumab for the subset of patients with non–small-cell lung cancer (NSCLC) who have a high level of programmed death ligand 1 (PD-L1) expression, which is defined by . . .
Diagnosing Sporadic Creutzfeldt-Jakob Disease by the Detection of Abnormal Prion Protein in Patient Urine
Authors: Connie Luk, Samantha Jones, Claire Thomas, Nick C. Fox, Tze H. Mok, Simon Mead, John Collinge, Graham S. Jackson
Journal: JAMA Neurology (2016)

Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disorder associated with the accumulation of infectious abnormal prion protein through a mechanism of templated misfolding. A recent report has described the detection of abnormal prion protein in the urine of patients with variant CJD (vCJD) using protein misfolding by cyclic amplification, which was apparently absent in the more common sporadic form of CJD (sCJD). A noninvasive diagnostic test could improve early diagnosis of sCJD and, by screening donations, mitigate the potential risks of prion transmission through human urine-derived pharmaceuticals. Here, we describe the adaptation of the direct detection assay, developed originally as a blood test for vCJD, for the detection of disease-associated prion protein in urine samples from patients with sCJD.
A phase II trial of regorafenib as a single agent in patients with advanced and metastatic biliary tract carcinoma and first-line chemotherapy failure.
Authors: Anuj Kishor Patel, Ronald G. Stoller, John C. Rhee, Barry C. Lembersky, James Ohr, James J. Lee, Nathan Bahary, Edward Chu, Weijing Sun
Journal: Journal of Clinical Oncology (2015)

TPS498 Background: Biliary tract cancers (including cholangiocarcinomas) are rare but aggressive malignancies with limited options for treatment. Currently, the combination of gemcitabine and cisplatin is considered the upfront systemic chemotherapy for patients with advanced and metastatic diseases. There is no ‘standard’ for second-line treatment. Several signaling pathways have been identified that might play a role in the development of biliary tract cancer and that may represent targets for directed therapies. Overexpression of VEGF and alterations of the Ras/Raf pathway have been identified in the majority of cholangiocarcinoma; some studies have shown these mutations to be associated with metastasis and poorer prognosis. Regorafenib is an oral multikinase inhibitor of multiple angiogenic and oncogenic kinases (VEGFR1-3, TIE2, PDGFR-β, FGFR1, KIT, RET, RAF) which has shown efficacy as a single agent in multiple solid tumors. This study evaluates the efficacy of regorafenib in patients with advanced/metastatic biliary tract cancer following the failure of first-line chemotherapy. Methods: Enrollment in this phase II, single-arm trial is ongoing. Eligible patients have unresectable advanced or metastatic biliary tract adenocarcinoma, and have failed first-line systemic chemotherapy. Patients receive regorafenib 120 mg orally daily in a 21 days on, 7 days off cycle. Tumor measurements take place every 3 cycles by CT or MRI imaging. Patients continue on therapy until disease progression or unacceptable toxicities. The primary end point of this study is median progression-free survival (PFS). To evaluate for evidence of activity, defined as a median PFS of 3.5 months or greater, with 83% power (one-sided test, α=0.10), target enrollment is 37 patients. Secondary endpoints include safety, overall response rate, disease control rate, median overall survival, and changes in biomarker levels. The correlation of these biomarkers and of tumor mutations with response to treatment is built into the study as well. As of September 2014, 9 patients had been enrolled. ClinicalTrials.gov Identifier: NCT02053376. Clinical trial information: NCT02053376.
Feasibility analysis of pathology and genetic yield from a prospective trial of tissue biopsies in metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Rafael E. Jimenez, Hugues Sicotte, Poulami Barman, Jason P. Sinnwell, Patrick W Eiken, Thomas D Atwell, Brendan P McMenomy, Winston Tan, Kevin Wu, Alan Haruo Bryce, Thai Huu Ho, Henry Clement Pitot, Fernando Quevedo, Brian Addis Costello, Roxana Stefania Dronca, Timothy J. Moynihan, Liewei Wang, Rui Qin, Rachel Carlson, Manish Kohli
Journal: Journal of Clinical Oncology (2015)

249 Background: Evaluating tumor specific pathologic and genetic profiles in mCRPC stage is difficult due to the limited availability of mCRPC tissue. We describe findings from a prospective cohort study performed to obtain concomitant histopathology and genetic information in mCRPC. Methods: Patients with mCRPC initiating abiraterone acetate therapy underwent 2 serial (3 months apart) metastatic (met) site needle core biopsies (NCB1/2). Bone lesions were biopsied using 11-13G core needles and 18G core biopsy devices were used for non-osseous masses. Up to 4 cores were obtained at each biopsy with the 1st core (S1) sent for DNA sequencing, the 2nd (S2) for RNA sequencing, and the 3rd/4th (X3, X4) submitted for xenograft implantation. From each, 1-2 mm segments were separated and formalin-fixed for histopathologic examination (HPE). Results: A total of 54 patients, enrolled between June 2013 and July 2014, underwent 94 NCB (54 NCB1, 40 NCB2), rendering a total of 259 samples (94 S1; 75 S2; 59 X3 and 31 X4) of which 85 (32%) were positive (pos) for tumor by HPE. Positivity for tumor in S1, S2, X3, and X4 cores was 42%, 33%, 22%, and 19%, respectively. At least one core pos for met tumor was observed in 62% NCB1 and 52% NCB2 (overall 52/94; 56%). Met sites biopsied include bone (71), lymph nodes (18), liver (3), penile (1) and pelvic (1) soft tissues. HPE revealed met adenocarcinoma in 44/52, and poorly differentiated carcinoma in 8/52. Gleason grade applied to the met ranged from 3+4 to 5+5. 45/85 pos samples (53%) had &gt; 50% tumor cellularity. Pos NCB in bone lesions was observed in 23/71 (32%), compared to 17/23 (73%) of non-bone sites (p=.0004). 85 S1 samples yielded DNA material, of which 66 (77%) had ≥10% tumoral DNA. 24 cases with negative HPE had ≥10% tumoral DNA; 7 cases with pos HPE had &lt;10 tumoral DNA. In all, 76/94 (81%) NCB yielded tumor material either by HPE or DNA analysis. Conclusions: NCB of mCRPC is feasible and provides adequate tissue for pursuing HPE and sequencing studies. HPE of extracted material correlates with DNA sequencing data and provides complementary information on tumor features. Bone lesions yield significantly less tumoral material than non-osseous sites.
Reversed T Cell Receptor Docking on a Major Histocompatibility Class I Complex Limits Involvement in the Immune Response
Authors: Stephanie Gras, Jesseka Chadderton, Claudia M. Del Campo, Carine Farenc, Florian Wiede, Tracy M. Josephs, Xavier Y.X. Sng, Michiko Mirams, Katherine A. Watson, Tony Tiganis, Kylie M. Quinn, Jamie Rossjohn, Nicole L. La Gruta
Journal: Immunity (2016)
North American Leukemia, Intergroup Phase III Randomized Trial of Single Agent Clofarabine As Induction and Post-Remission Therapy, and Decitabine As Maintenance Therapy in Newly-Diagnosed Acute Myeloid Leukemia in Older Adults (Age ≥60 Years): A Trial of the ECOG-ACRIN Cancer Research Group (E2906)
Authors: James M. Foran, Zhuoxin Sun, David F. Claxton, Hillard M. Lazarus, Mary L. Thomas, Ari Melnick, Ross L. Levine, Elisabeth Paietta, Daniel Arber, Yangming Zhang, Jacob M. Rowe, John E. Godwin, Jessica K. Altman, Selina Luger, Aref Al-Kali, Hong Zheng, Keith Pratz, E. Randolph Broun, Bayard L. Powell, Kristen O'Dwyer, Mark R Litzow, Martin S Tallman
Journal: Blood (2015)
Plerixafor Improves Primary Tumor Response and Reduces Metastases in Cervical Cancer Treated with Radio-Chemotherapy
Authors: Naz Chaudary, Melania Pintilie, Salomeh Jelveh, Patricia Lindsay, Richard P. Hill, Michael Milosevic
Journal: Clinical Cancer Research (2016)

Abstract Purpose: There is an important need to improve the effectiveness of radio-chemotherapy (RTCT) for cervical cancer. The CXCL12/CXCR4 pathway can influence RT response by recruiting normal myeloid cells to the tumor microenvironment that in turn can exert radioprotective effects, and may promote metastases. The objective of this study was to explore the efficacy and toxicity of combining RTCT with CXCL12/CXCR4 inhibition in cervical cancer. Experimental Design: CXCR4 expression was measured in 115 patients with cervical cancer. Two primary orthotopic cervical cancer xenografts (OCICx) with different levels of CXCR4 expression were treated with RT (30 Gy: 15 daily fractions) and weekly cisplatin (4 mg/kg), with or without the CXCR4 inhibitor Plerixafor (5 mg/kg/day). The endpoints were tumor growth delay and lymph node metastases. Acute intestinal toxicity was assessed using a crypt cell assay. Results: There was a fivefold variation in CXCR4 mRNA expression in the patient samples, and good correlation between the expression in patients and in the xenografts. The combination of RTCT and Plerixafor produced substantial tumor growth delay and reduced lymph node metastases compared with RTCT alone in both of the xenograft models. There was a trend toward reduced acute intestinal toxicity with the addition of Plerixafor to RTCT. There were no changes in normal organ morphology to suggest increased late toxicity. Conclusions: This study demonstrates that the addition of Plerixafor to standard RTCT improves primary tumor response and reduces metastases in cervical cancer with no increase in toxicity. This combination warrants further investigation in phase I/II clinical trials. Clin Cancer Res; 23(5); 1242–9. ©2016 AACR.
Performance of photodynamic therapy using multiple light sources in the rat R1 rhabdomyosarcoma tumor model
Authors: M. J. Winship, H. Xu, F. C. Zheng, M. A. Krouse, B. W. McIlroy, P. A. Mahoney
Journal: Journal of Clinical Oncology (2004)

3192 Background: Introducing photodynamic therapy (PDT) into routine clinical use will require a radical change in excitation source, and a better understanding of photosensitizer dosimetry and biological effect. Light Sciences Corporation (LSC) has designed a Light Infusion Therapy system (Litx), based on inexpensive light-emitting diode technology and the photosensitizer talaprofin sodium (LS11). One of the advantages to interstitial PDT with the system is the potential to treat patients with large tumors by simultaneous illumination using multiple light sources. Methods: WAG/Rij rat rhabdomyosarcomas were employed to assess the feasibility and safety of multiple light source (LS) treatments. Previous to the multiple LS studies, a series of single LS light dose escalation studies (5 to 40 mW/cm, 50 to 1000 J/cm) were performed using the same model. In the multiple LS studies, each tumor-bearing rat was given 5.0 mg/kg (iv) talaporfin sodium 90 minutes prior to illumination. Tumors were grown to a size sufficient for implantation of two or three 10 mm long LS. Treatments were performed at 40 mW/cm with two LS at a fluence of 400 J/cm, or three LS at 200 J/cm. The implantation geometry was chosen such that the effect zones would either overlap or abut each other, based on the tissue response from a single LS run at the same illumination parameters. The PDT effect was assessed 72 hours post-treatment, by Evans blue and TTC vital staining. Results: With a single LS in this WAG/Rij rat rhabdomyosarcoma model, the radius of Litx PDT effect zone is fluence-dependant; however, the effect zone length is related only to LS length. The kill zone radius from each LS in the two- and three- LS illuminations was equal to the radius from a single LS under the same treatment parameters. The effect zone lengths were also found to be the same as in the single LS illuminations. Conclusions: The feasibility and safety of simultaneous multiple LS illumination with the Litx system expands the treatable range to include larger tumors. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Light Sciences Corp. Light Sciences Corp. Light Sciences Corp.
Colony Stimulating Factors (Pegfilgrastim or Lenograstim) Use in Patients with Myeloma Undergoing Autologous Peripheral Blood Stem Cell Transplantation (APBSCT) Is Associated with Early Neutrophil Engraftment and Shorter Inpatient Stay with No Impact on Progression Free Survival (PFS) or Overall Survival (OS)
Authors: Georgina Mayer, Bhuvan Kishore, Richard Lovell, Emmanouil Nikolousis, Shankaranarayana Paneesha
Journal: Blood (2015)
Carbamylated Low-Density Lipoproteins Induce a Prothrombotic State Via LOX-1
Authors: Erik W. Holy, Alexander Akhmedov, Thimoteus Speer, Giovanni G. Camici, Stephen Zewinger, Nicole Bonetti, Jürg H. Beer, Thomas F. Lüscher, Felix C. Tanner
Journal: Journal of the American College of Cardiology (2016)
Phase 1a safety and pharmacokinetic study of oral NV-196 in patients with solid tumours
Authors: P. N. Mainwaring, L. West, A. J. Husband
Journal: Journal of Clinical Oncology (2008)

14615 Background: NV-196 antagonizes the anti-apoptotic factors that block the tumour necrosis factor-related apoptosis- inducing ligand (TRAIL) death receptors. NV-196 is broadly cytostatic and cytotoxic against most forms of human cancer cells in vitro, and is a potent chemo-sensitizer of most standard chemotoxic agents. Methods: Participants with a stable, solid malignancy, an estimated life-expectancy of at least 3 months, adequate renal, hepatic and haematological function and a Karnofsky PS ≥ 60% participated. Participants received a single oral dose of 100mg NV-196 on D1 with serial blood and urine samples collected for pharmacokinetic analysis for NV-196 and its metabolite NV-143 over the following 2 days. Repeated dosing began on day 3 with 100 mg NV-196 administered 8- hourly for 5 days until the morning of the 8th day when patients received their last dose of NV-196. Physical examination, AE reporting, vital signs and clinical laboratory testing was conducted to determine the safety and tolerability of NV-196. Free and total (unconjugated plus conjugated) NV-196 and NV-143 concentrations were determined using liquid chromatography tandem mass spectrometry, with validated and non-validated methods, respectively. Results: Eight female and 5 male subjects consented to participation: 2 prostate, 1 fallopian, 2 breast, 2 ovarian, 1 gastric, 2 colorectal, 1 bladder, 1 melanoma and 1 adrenal. Mean Tmax, Cmax, t1/2, λt and AUC0–24h values for conjugated NV-196 and conjugated NV-143 in the single and repeat dose phases were obtained and will be presented. Steady state concentrations of conjugated NV-196 and NV-143 were reached within three days of dosing in the repeat dose phase. NV-196 was excreted predominantly in a conjugated state. There were two unrelated Serious Adverse Events - 1 abdominal pain and 1 bowel obstruction which both required hospitalization. There was one case of Grade 4 toxicity for anemia. Conclusions: The three times daily dosing regime was successful in achieving elevated plasma concentrations of NV- 196 and NV-143 in their conjugated forms. Recovery of NV-196 and its metabolites in the urine was low a result which may reflect the incomplete absorption of NV-196 and/or suggests the contribution of excretion via the bile duct without significant toxicity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novogen Novogen Novogen
Association of Borna disease virus infection with depression in cancer patients
Authors: C. Jehn, D. Kuehnhardt, C. Schulz, M. Krebs, B. Flath, K. Possinger, L. Bode, J. Eucker
Journal: Journal of Clinical Oncology (2008)

20514 Background: Borna disease virus (BDV) is a RNA virus which can persistently infect neurons of the limbic system. Several seroepidemio-logic data suggest an association of BDV with neuropsychiatric dis-orders, however inconsistent detectability has weakened a possible link-age. The objective of this cross-sectional study was to investigate, if an association exists between BDV infection and depression in patients with advanced cancer receiving chemotherapy. Methods: 55 inpatients (pts) with metastatic cancer (Stage IV) were assessed by the Hospital Anxiety and Depression Scale (HADS) for depressive symptoms and diagnoses of major depression (MD) was established according to the DSM-IV criteria. IL-6, BDV-specific circulating immune complexes (CIC), antibodies and plasma antigens were determined by enzyme immunoassays (EIAs). In the statistical analysis the Mann-Whitney test and Spearman-Rho correlations were applied. Results: 55 pts (age: 59,9 years; SD 10,2) had a mean Karnofsky-index (KI)of 66,5% (SD:12,1). 26 pts had MD. Pts with MD showed a significant increase in BDV-specific antigens (p=0,050) and antibodies (p=0,045) and IL-6 (p<0,001), compared to patients without MD. CIC were not increased in MD (p=0,53). Depressive symptoms were more closely correlated with level of BDV antibodies (r=-0,296; p=0,028) and IL- 6 (r=5,6; p<0,001), than symptoms of anxiety. Symptoms of anxiety showed a significant correlation to increased age(r=-0,28; p=0,042), whereas depressive symptoms correlated more closely with a decreased KI (r=-0,35; p=0,011). No correlations were found for level of symptoms vs. BDV-antigen or CIC. Conclusions: In pts with metastatic cancer, MD is associated with increased levels of BDV- specific antigen and antibody. Symptoms of depression and anxiety are only correlated with increased levels BDV-antibody. Symptoms of anxiety seem to be related to age, whereas symptoms of depression are related to decreased KI. No significant financial relationships to disclose.