tbuckley/cabot-search huggingface dataset:
Apoptotic and anti-vascular activity of imatinib in GIST patients
Authors: J. C. Trent, H. Choi, K. Hunt, H. Macapinlac, D. McConkey, C. Charnsangravej, J. Abbruzzese, R. S. Benjamin, D. Davis
Journal: Journal of Clinical Oncology (2005)

9001 Imatinib mesylate (IM) is a potent inhibitor of the Kit/platelet-derived growth factor receptor(PDGFR) tyrosine kinases. We are investigating the early mechanisms of anti-tumor activity of IM in GIST patients(pts) as measured by 18-fluorodeoxyglucose(FDG) positron emission tomography(PET) imaging. We hypothesize that early reductions in GIST FDG avidity after IM therapy are due to induction of tumor cell apoptosis and anti-vascular activity. Pts with planned resection of their GIST were treated with IM(600 mg/day) preoperatively. Perfusion computed tomography(CT) and FDG PET scans were performed before and after IM therapy for 3, 5, or 7 days. All pts underwent pre-IM biopsy followed by resection no more than 6 hours after completion of IM therapy. CT perfusion parameters included blood flow(BF) and blood volume(BV) of the whole tumor. PET imaging was used to assess the maximum standardized uptake value(SUV) of FDG. Paired tumor biopsies and resected tumors were examined using immunofluorescent laser scanning cytometry to quantify endothelial and tumor cell apoptosis, microvessel density(MVD), phospho-Kit and phospho-PDGFR. 10 GIST pts underwent PET, 7 had a decrease in SUV of greater than 30% while 3 had no decrease or no baseline FDG avidity. The PET responders had a decrease while non-responders had an increase in BF (-37.8% vs. +38.5%, P=.02). PET responders had a decrease in BV compared to the increase seen in non-responders (-29.5% vs +24%, P=.04). 4 responders to IM had a decrease in phospho-Kit in the tumor-associated endothelium(avg. -45%, P=.07) and tumor cell compartment(avg -52%, P=.13). These tumors displayed a 7-fold (P=.08) and 2.8 fold (P=.23) increase in endothelial and tumor cell death, respectively, and a 36% reduction in MVD after IM. The tumor with reduction in BF(-74%) and BV(-61%) displayed the greatest increase in endothelial cell death(.05% to 11%, p<0.05). The most significant reduction in MVD(-78%, P<.05) was observed in the tumor with the greatest reduction in FDG uptake(-85%). IM induces tumor cell apoptosis after brief IM therapy and may have anti-vascular effects on GISTs. We believe that inhibition of Kit activation in the tumor-associated endothelium by IM is a novel finding. No significant financial relationships to disclose.
Adjuvant treatment strategy and results in small breast cancer tumors (pT1) with HER2 overexpression.
Authors: A. Hinke, P. Dall, G. Lenzen, C. Schumacher, D. Rezek, N. Gazawi, A. Ammon, F. G. Foerster, F. Beldermann, U. Cirrincione, J. Wilke
Journal: Journal of Clinical Oncology (2011)

607 Background: Trastuzumab (T) was registered in 2006 for the treatment of early, HER2+ breast cancer (BC), after surgery, adjuvant chemotherapy (aCT) and/or radiotherapy, without specific tumor size restrictions. In a prospective observation study the routine practice of HER2 antibody treatment in this setting was examined, with a special focus on the pT1 subgroup. Methods: At present, 2,677 patients (pts) have been enrolled in this ongoing non-interventional study from 270 German centres. After exclusion of pts who were non-eligible due to M1 disease, negative HER2 status, pTis stage, unknown pT, or insufficient documentation at present, 2138 pts remained for this analysis. Results: The proportion of pT1 in the total group of pT1-4 primaries was 926/2138 (43%). Median age was similar in the pT1 and pT2-4 groups with 56 and 56.5 years (y), respectively. The mean number of involved nodes was 1.5±3.6/3.4±5.7 (pT1/pT2-4), p<0.0001, with >10 nodes in 4%/12%. G3 tumors were only slightly less frequent in the pT1 group (49%/55%), as were hormone receptor negative cases (34%/39%). Interestingly, no difference was detected in the proportion receiving aCT in addition to T (92%/93%). However, while the rate of aCT with anthracyclines was similar (91%/90%), only 54% of pT1 pts received taxanes, compared to 66% in the pT2-4 group (p<0.0001). 46%/58% of pts were treated with a taxane/anthracycline combination. Platin derivatives were administered in 6%/7% only. Adjuvant radiotherapy was slightly less common in pT1 tumors (76%/79%). No differences were observed in T dosing, median number of cycles (18/18) and mean duration (50.1/50.4 weeks). After a follow-up of up to 6 years, 161 relapses were hitherto reported. As expected the risk of recurrence in pT1 treated with T is considerably lower, indicated by a hazard ratio for relapse (pT2-4 as reference) of 0.44 (95% confidence interval: 0.30-0.63), with Kaplan-Meier estimations for relapse-free survival of 95%/87% after 3 y and 82%/71% after 5 y. Conclusions: These results from a large community-based study confirm the favorable findings on adjuvant T+aCT from the randomized trials, independent of tumor size. Patients with pT1 tumors treated accordingly had an excellent prognosis.
Palliative chemotherapy: Does aggressive care beget aggressive care?
Authors: A. A. Wright, H. G. Prigerson
Journal: Journal of Clinical Oncology (2011)

6127 Background: The use of chemotherapy in patients with incurable cancers at the end-of-life (EOL) is increasing, despite growing concerns that it may be burdensome, expensive, and ineffective. This study sought to determine whether the receipt of palliative chemotherapy is associated with the intensity of EOL care received in a cohort of terminally-ill cancer patients. Methods: Coping with Cancer is an NCI/NIMH-funded, multi-site, prospective, longitudinal study of patients with advanced cancer. Baseline interviews with 358 patients assessed their sociodemographic characteristics, receipt of chemotherapy, and self-reported treatment preferences, terminal illness acknowledgement, and EOL discussions. Patients’ medical care in the last week of life was abstracted from medical charts, and place of death was assessed by caregiver report. Propensity-score weighted logistic regression models examined associations between the receipt of chemotherapy and patients’ EOL medical care, and place of death. Results: 190 of 358 (53.1%) advanced cancer patients who died a median of 4.5 months later received chemotherapy at baseline. Treated patients were more likely to prefer chemotherapy (AOR=2.03, 95% CI=1.27-3.24), compared with untreated patients, but not other life-extending measures (AOR=1.34, 95% CI=0.79-2.28). In propensity weighted models, that adjusted for observed differences between treated and untreated patients, patients who received chemotherapy at baseline had higher odds of undergoing mechanical ventilation (AOR=5.75, 95% CI 1.79-18.4), resuscitation (AOR=7.76, 95% CI 1.52-39.6), and death in an intensive care unit (AOR=2.69, 95% CI 1.21-5.98), compared with patients who did not receive chemotherapy at baseline, and lower odds of receiving more than one week of hospice services (AOR=0.64, 95% CI 0.45-0.92). Conclusions: The use of palliative chemotherapy in advanced cancer patients is associated with more intensive medical care near death and later hospice referrals, suggesting that aggressive care may beget aggressive care. Future studies should examine factors that influence chemotherapy decision-making at the EOL.
Evaluation of Lu-177 RM2 as a targeted radiopharmaceutical in a PC-3 xenograft model of androgen-independent prostate cancer.
Authors: R. D. Breier, T. L. Rold, A. F. Szczodroski, T. J. Hoffman
Journal: Journal of Clinical Oncology (2011)

e13522 Background: Prostate cancer is the most common cancer in American men (after nonmelanoma skin cancers). In 2010 more than 200,000 cases were diagnosed and more than 30,000 men died of prostate cancer. One in six men will be diagnosed with prostate cancer during his lifetime and one in thirty six men will die of prostate cancer. Human prostate cancer has been shown to widely express the bombesin receptor (BB2R). Lutetium-177 (177 Lu) radiolabeled BB2r agonist analogs are currently being investigated preclinically for their utility as targeted radiation therapy agents. (Maddalena, J Nucl Med, 50:2017, 2009 and Johnson, Can Biother & Radiopharm, 21(2):155, 2006) Recently, Maecke and co-workers identified a high affinity BB2r antagonist (Ga-68 and In-111-RM2) for potential use as a PET/SPECT diagnostic imaging agent. (Mansi, Clin Can Res, 15(16):5240, 2009 and Mansi, Eur J Nucl Med Mol Imaging, May 2010) The purpose of this work was to investigate the biodistribution of Lu-177-RM2 for potential as a radiotherapeutic agent using a PC-3 xenografted SCID mouse model. Methods: Male SCID mice were inoculated subcutaneously with 5 million PC-3 cells/site in 100uL. At 4 weeks post-inoculation, pharmacokinetic studies of 177Lu-VA RM2 were conducted at 1, 4, 24, 48, 72, and 96 hours post-injection. Micro-SPECT/CT imaging studies were done at 24, 48, 72, and 96 hrs. Results: See table; shown in %ID/g. Conclusions: Our study demonstrates that Lu-177-RM2 shows promising pharmacokinetic properties with high affinity for the BB2 receptor and excellent tumor to blood and tumor to organ ratios. The prostate tumor uptake of Lu-177-RM2 is equal or greater than any previously identified BB2r targeting radiotherapeutic agent. Lu-177-RM2 exhibits rapid washout from the pancreas and other non-target organs making it an ideal candidate for tumor targeted therapy research. 1 HR 4 HRS 24 HRS 48 HRS 72 HRS 96 HRS Blood 0.36 +/- 0.15 0.02 +/- 0.01 0.00 +/- 0.00 0.00 +/- 0.00 0.00 +/- 0.00 0.00 +/- 0.00 Pancreas 17.53 +/- 1.97 1.59 +/- 0.7 0.26 +/- 0.03 0.18 +/- 0.04 0.19 +/- 0.03 0.03 +/- 0.00 Tumor 9.25 +/- 3.35 11.46 +/- 5.38 5.56 +/- 1.59 5.28 +/- 1.42 4.03 +/- 0.92 3.14 +/- 0.33
What is the benefit for patients suffering from metastatic colorectal cancer (mCRC) after bevacizumab-based regimen (BBR), cetuximab-based regimen (CBR), and panitumumab (P)?
Authors: J. Metges, J. Ramée, J. Raoul, A. Gourlaouen, M. Porneuf, O. Capitain, N. Achour, J. Egreteau, J. Douillard, F. Grude
Journal: Journal of Clinical Oncology (2011)

595 Background: Metastatic colorectal cancer (mCRC) management has been clearly improved by targeted therapies such as anti VEGF and /or anti-HER1 drugs. The evaluation of the use of targeted therapies in the real world is strategic to assess health politics. OMIT Bretagne-Pays de la Loire is a network of private and public cancer centers that has been leading cohort studies evaluating Folfiri-bevacizumab treatment, the cost of targeted therapies and the succession of targeted therapies. Methods: The purpose of this study is to evaluate the benefit and safety of three consecutive targeted therapies in patients with KRAS wild-type unresectable mCRC. Sex, age, localization of the primary tumor site, successive chemotherapeutic regimens, toxicities, response rates, progression free survival and overall survival have been studied. Results: 34 patients (22 men, 12 women, median age 63 years [43-82]) have been prospectively recruited between 2003 and 2010. All of them received bevacizumab specially in association with FOLFIRI, cetuximab in association with irinotecan, panitumumab as monotherapy and others chemotherapies than FOLFOX, FOLFIRI, XELOX. The primary tumor site was colon (71%), junction (5%), and rectum (24%). 22 patients had metastatic colorectal tumor, 28 were operated on their primary tumor and 12 underwent resection after one line of treatment. Patients received successively 3 to 8 different lines of treatment for progressive mCRC. Toxicities of targeted therapies were manageable. Objective responses were observed in 38% (13) of the patients treated with BBR, 37% (11) treated with CBR and 25% (6) treated with P. Disease stabilization was achieved in 32% (11) of the patients treated with BBR, in 10% (3) with CBR and in 8% (2) with P. PFS at 80 months is 15%. Median OS from first metastatic line at death was 47.43 months (24.23-70.84). PFS and OS curves will be shown during the meeting. Conclusions: Our study clearly shows that patients receiving successively the three schedules (BBR, CBR, P) have a high overall survival with manageable side effects. No significant financial relationships to disclose.
Sorafenib Monotherapy Is Effective In Relapsed and RefractoryFlt3-ITD Positive Acute Myeloid Leukemia, Particularly After Allogenic Stem Cell Transplantation
Authors: Stephan Metzelder, Anemone Finck, Martin Fey, Sebastian Scholl, Matthias Kröger, Andreas Reiter, Helmut R. Salih, Katharina Götze, Ralf Georg Meyer, Aristoteles Giagounidis, Wolfram Brugger, Matthias Vöhringer, Lothar Müller, Linn Yeh Ching, Peter Dreger, Masanori Mori, Nadezda Basara, Kerstin Schaefer-Eckart, Beate Schultheis, Claudia Baldus, Andreas Neubauer, Andreas Burchert
Journal: Blood (2010)
Prognostic relevance of 46 clinical, “classical” laboratory and oncological parameters in patients with advanced non-small cell lung cancer
Authors: S. Holdenrieder, J. von Pawel, V. Heinemann, H. Raith, K. Feldmann, U.-H. Stenman, D. Nagel, P. Stieber
Journal: Journal of Clinical Oncology (2005)

7196 Background: Currently, conflicting data are available concerning the prognostic relevance of biochemical markers in lung cancer. Methods: In a prospective study on 300 patients with newly diagnosed, advanced non-small cell lung cancer (NSCLC) undergoing chemotherapy, we investigated 46 pretherapeutic parameters including clinical factors (age, gender, performance score (PS), weight loss (WL), T-, N-, M-stage, histology, grading, number and localisation of metastases, mode of therapy), “classical” laboratory markers (WBC, RBC, hemoglobin, platelets, CRP, sodium, potassium, chloride, calcium, creatinine, urea, glucose, uric acid, triglyceride, cholesterol, albumin, bilirubin, AST, ALT, GGT, AP, LDH), and oncological parameters (CEA, CYFRA 21–1, NSE, CA125, CA15–3, CA72–4, CA19–9, S100 all by Elecsys/Roche; SCC by Imx/Abbott; ProGRP by ELISA, βHCG by IFMA; Chromogranin A by RIA). In statistical analysis, first, all clinical parameters with independent prognostic relevance were selected by Cox regression analysis. Second, all biochemical markers in logarithmized manner and those clinical factors selected in step one were included in Cox regression analyses (backward selection) of 100 bootstrap replications of the data set. All markers which remained in the model >25% of the runs were, third, tested in Cox regression analyses using both forward and backward selection in parallel. Results: Median survival of 172 patients who died was 6.3 months (range 1 to 26). For 128 censored patients, the median observation time was 7.3 months (1 to 29). Concerning clinical factors, PS, WL, metastases other than lung (MOL), and mode of therapy showed prognostic relevance. In the bootstrap analyses, 22 biochemical and clinical markers remained >25% of the runs in the model. Finally, in both forward and backward selection, the resulting multivariate model constisted of PS, MOL, ln-CRP, ln-CYFRA 21–1, ln-NSE, ln-CA72–4, and ln-βHCG with hazard ratios of 2.6, 2.4, 1.5, 1.2, 0.6, 1.2, and 1.2, respectively. Conclusion: Standardized procedure for establishing prognosis in advanced NSCLC revealed PS, MOL, CRP, CYFRA 21–1, NSE, CA72–4, and βHCG as independent prognostic markers. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott, ALSI/IBL, Hoffmann-La Roche, Schering
A cross-sectional analysis of symptom burden among adult cancer patients in a Filipino tertiary care cancer center.
Authors: Warren Ramos Bacorro, Jocelyn C Que, Teresa Tan Sy Ortin, Thomas W. Feeley, Cielito C. Reyes-Gibby
Journal: Journal of Clinical Oncology (2015)

98 Background: Palliative and supportive care has been shown to improve quality of life (QOL) and survival and reduce caregiver burden and costs, but remains poorly integrated into cancer care in the Philippines. Understanding symptom burden profile among patients will guide policy-making in a limited/moderate resource setting. Methods: This cross-sectional study was conducted among adult Filipino cancer patients. Demographic and clinical data were collected from medical records and patient interviews. Symptom severity and interference were assessed using the M.D. Anderson Symptom Inventory. Symptom prevalence and mean severity scores were determined. Pearson correlation analysis was used to examine relationships between symptom severity and interference. Results: Participants (n = 251)were aged 18-80 years; the majority were aged &lt; 60, females, or with good performance status (PS). Breast, head-and-neck and gastrointestinal primaries were most common; 45% had advanced disease. Moderate and severe symptoms were prevalent across stages. Fatigue (65%), pain (62%), sadness (62%), and anxiety/distress (58%) were the most prevalent, most severe and most interfering. In metastatic disease, sadness was most prevalent, and fatigue, most serious; among those with poor PS, disturbed sleep was most prevalent and most serious. Pain was more disabling among females, and fatigue and sadness, among the elderly. Conclusions: This is the first study to describe symptom burden among adult Filipino cancer patients. The clinical impact of symptoms is determined by their concurrence and the patient’s demographic and clinical profile. Symptom burden is highest for fatigue, pain, sadness, and anxiety/distress. Comprehensive symptom evaluation and tailored approach to care is necessary for optimal management. While a clinical practice guideline (CPG) has been adopted for use at our institute, effective CPGs for the screening, assessment and management of fatigue, depression and anxiety/distress have yet to be identified and implemented.
ESCMID dagger and ECMM double dagger joint clinical guidelines for the diagnosis and management of mucormycosis 2013
Authors: O. A. Cornely, S. Arikan-Akdagli, E. Dannaoui, A. H. Groll, K. Lagrou, A. Chakrabarti, F. Lanternier, L. Pagano, A. Skiada, M. Akova, M. C. Arendrup, T. Boekhout, A. Chowdhary, M. Cuenca-Estrella, T. Freiberger, J. Guinea, J. Guarro, S. de Hoog, W. Hope, E. Johnson, S. Kathuria, M. Lackner, C. Lass-Floerl, O. Lortholary, J. F. Meis, J. Meletiadis, P. Munoz, M. Richardson, E. Roilides, A. M. Tortorano, A. J. Ullmann, A. van Diepeningen, P. Verweij, G. Petrikkos
Journal: Clinical Microbiology and Infection (2014)
Presence of carcinoma in situ (CIS) in bladder cancer biopsies and its relationship to pathologic complete response (pCR) rates to neoadjuvant chemotherapy (neo-CTx).
Authors: Derek E. Thomas, Kevin Rice, Jose Alexandre Pedrosa, Paul Johnston, Marietta L. Moore, Angela D. Reed, Dylan M. Cregar, Cindy Franklin, Michael O. Koch, Richard Bihrle, Richard Foster, Timothy A. Masterson, Thomas A. Gardner, Chandru Sundaram, Charles R. Powell, Stephen Beck, David A. Grignon, Liang Cheng, Noah M. Hahn
Journal: Journal of Clinical Oncology (2013)

286 Background: Despite an improved overall survival with neo-CTx for muscle-invasive urothelial carcinoma (miUC) patients (pts) prior to cystectomy, the adoption of neo-CTx in suitable pts has been suboptimal. While associated with a more aggressive phenotype in early stage UC, the prognostic role of CIS in miUC is less clear. In particular, the effect of concurrent CIS in pts undergoing neo-CTx prior to cystectomy is unknown. Methods: A retrospective review of the Indiana University Simon Cancer Center urology and medical oncology clinical databases was performed spanning the years 1991 – 2012. Subjects with miUC, pathology reports available for both transurethral resection of bladder tumor (TURBT) and cystectomy procedures, and confirmed receipt of neo-CTx were included in this analysis. Pts with clinically positive lymph nodes (LN+) were included provided they underwent cystectomy with curative intent. Associations between pCR and pt baseline age, gender, race, clinical stage (T2N0 vs. T3/T4/N+), chemotherapy regimen received (cisplatin combination therapy (CisCTx) vs. non-cisplatin based), and presence of CIS on TURBT sample were tested by multinomial logistic regression analysis with statistical significance set at p&lt;0.05. Results: 72 miUC pts satisfying the inclusion criteria were identified. Cohort demographics included: median age – 59 yrs, 76% male, 93% Caucasian, 63% T2N0, 32% LN+, 81% CisCTx neo-CTx regimen, 32% CIS on TURBT, pCR for entire cohort 18%. The presence of CIS on TURBT was significantly associated with decreased rates of pCR (1/23 vs. 12/49) p=0.002. TURBT CIS was not associated with decreased rates of less than pT2N0 (12/23 vs. 18/49) p=0.562. Seven pts (30%) with CIS on TURBT sample achieved pTisN0 at cystectomy. Conclusions: The presence of CIS in TURBT specimens is associated with decreased rates of pCR at cystectomy in miUC pts treated with neo-CTx. The finding of pTisN0 at cystectomy is common after neo-CTx in pts with CIS in preop TURBT specimens. Validation of the prognostic significance of TURBT CIS on pCR rates and characterization of pTisN0 clinical course in TURBT CIS pts after neo-CTx is warranted.
Immunomodulatory switch maintenance therapy in metastatic colorectal carcinoma: The phase III IMPALA study.
Authors: David Cunningham, Werner Scheithauer, Alfredo Zurlo, Ramon Salazar, Michel Ducreux, Tom Samuel Waddell, Christophe Tournigand, Alberto F. Sobrero, Eric Van Cutsem, Dirk Arnold
Journal: Journal of Clinical Oncology (2016)

TPS785 Background: The Toll-like receptor 9 agonist MGN1703 was compared to placebo in 59 metastatic CRC (mCRC) patients with disease control after standard induction chemotherapy in the double-blind randomized phase 2 IMPACT study. MGN1703 showed a superior effect over placebo, with a hazard ratio (HR) for the primary endpoint “PFS on maintenance” of 0.55 (p = 0.041) by local assessment and 0.56 (p = 0.070) by independent radiological review. Exploratory PFS analyses identified patients with objective RECIST response, normalized CEA and presence of activated NKT cells at the end of induction treatment to benefit the most from MGN1703. The OS evaluation showed a HR of 0.40 (median 24.5 vs. 15.1 months) for patients with RECIST response after induction therapy. Furthermore, at time of IMPACT study closure, 4 MGN1703 patients were still without progressive disease and continued treatment in compassionate use. As of August 2015, 3 patients were still receiving MGN1703 treatment in excess of three years (47-55 months), with 2 objective responses ongoing over 46 months. Methods: The international, multicenter, open-label phase 3 IMPALA study is conducted in collaboration with the AIO, TTD and GERCOR cooperative groups. In IMPALA, mCRC patients having achieved an objective tumor response following any type of first line induction therapy are randomized to receive MGN1703 switch maintenance monotherapy in the experimental arm or local standard of care in the control arm. In case of relapse, patients will reintroduce induction treatment whenever feasible, with those in the experimental arm continuing to receive MGN1703 therapy in the weeks without infusional chemotherapy. The primary endpoint of the study will be OS. Secondary endpoints include PFS, response rates, safety, and QoL in selected centers. Induction treatment, CEA and activated NKT at baseline are stratification factors and will be prospectively assessed. All randomized patients take part in a comprehensive immune monitoring plan evaluating cytokines and chemokines in serum and the activation status of immune cell populations. Recruitment started in September 2014 and the study is expected to recruit 540 patients within 24 months in 8 European countries. Clinical trial information: NCT02077868.
The Use of Tetradenoylphorbol Acetate Stimulated Peripheral Blood Cells for Interphase Fluorescence In-Situ Hybridization Analysis May Enhance Its Prognostic Value for Patients with Chronic Lymphocytic Leukemia
Authors: Julio Delgado, Anna Aventin, Javier Briones, Jana Sanchez, Josep Nomdedeu, Jorge Sierra
Journal: Blood (2008)