tbuckley/cabot-search huggingface dataset:
A multicenter, phase IV study of the effectiveness of palliative gemcitabine in patients with advanced pancreatic cancer.
Authors: David Wallace, Jina Zhang-Salomons, Christopher M. Booth, William J. Mackillop
Journal: Journal of Clinical Oncology (2012)

46 Background: Randomized controlled trials (RCTs) have shown that palliative gemcitabine provides clinical benefit and prolongs survival in patients with advanced pancreatic cancer. The purpose of this study was to determine if the efficacy of palliative gemcitabine demonstrated in RCTs has translated into effectiveness in routine clinical practice in Ontario. Methods: This was a retrospective cohort study of all patients with exocrine cancer of the pancreas treated with first line, single agent, palliative gemcitabine at all 13 provincial cancer centres in Ontario between 2008 and 2011. These patients were identified by linking electronic records of treatment from all cancer centres and hospitals in Ontario to the Ontario Cancer Registry. Patient-reported well-being and symptoms were captured by the Edmonton Symptom Assessment System, which has been in routine use at these centres since 2008. The effectiveness of gemcitabine was measured in terms of clinical benefit at two months and overall survival. Patients were classified as having achieved clinical benefit if they had not discontinued gemcitabine and their self-reported well-being was stable or improved at two months. Results: The study population included 423 patients. Their median age was 65 and 50% were women. Fifty-seven percent had stage IV disease, 17% had stage III disease, and 10% had recurrence after earlier treatment for stage I or II disease. Patients included in this study were older than, but otherwise similar to, patients enrolled in four relevant RCTs that used gemcitabine in the experimental or control arm. At two months, 36.9% (95% CI 29.6-44.2%) of patients in this study achieved clinical benefit, which was within the range of 24% to 56% observed in patients in these trials. Median overall survival was 5.7 months (95% CI 4.7-6.1), which was within the range of 5.4 to 6.9 months reported in the trials. Conclusions: The efficacy of gemcitabine demonstrated in RCTs has translated into effectiveness in routine clinical practice in Ontario. The approach described above could readily be used to study the effectiveness of other palliative interventions.
Randomized trial of first-line docetaxel + capecitabine (XT) versus docetaxel + epirubicin (ET) for metastatic breast cancer (MBC): Efficacy results of ERASME-4/CAPEDOC-EPIDOC
Authors: T. Bachelot, E. Luporsi, A. Bajard, J. Provencal, D. Coefic, C. Platini, D. Dramais, C. Oprea, R. Ferri-Dessens, D. Pérol
Journal: Journal of Clinical Oncology (2008)

1049 Background: In MBC, XT improves time to progression and overall survival (OS) vs docetaxel alone (O'Shaughnessy, 2002) and first-line capecitabine + paclitaxel shows similar efficacy to epirubicin + paclitaxel (Lück, 2007). The ERASME-4 and CAPEDOC- EPIDOC trials were designed to assess the efficacy of XT vs ET as first-line therapy for MBC. Methods: Patients (pts) with MBC and no prior chemotherapy (adjuvant therapy permitted) were randomized to 3-weekly cycles of either XT (docetaxel 75 mg/m², d1 + capecitabine 1,000 mg/m² twice daily, d1–14) or ET (docetaxel 75 mg/m², epirubicin 75 mg/m², both d1). In the ET arm, primary prevention of febrile neutropenia with hematopoietic growth factor was recommended; ET pts received capecitabine at progression. The primary endpoint was progression-free rate 6 months after randomization. The planned sample size of 106 pts (Simon 1985), gave 95% power to test a progression-free rate of 75% (XT) vs 60% (ET). Secondary endpoints included progression-free survival (PFS) and OS. Results: From Mar 2003 to Jan 2007, 92 pts were randomized (45 XT, 47 ET). Slow accrual led to premature study termination. The actual sample size allowed to effectively selecting the best arm for response rate with a power of 90%. Pt characteristics were well balanced between treatment arms; most had received adjuvant anthracycline. Toxicity was generally mild or moderate with only one episode of febrile neutropenia. Grade 3 hand-foot syndrome occurred in 17% of XT pts vs 0% of ET pts. The 6-month progression-free rate was 78% (CI95% 63 to 89%) with XT vs 74% (CI95% 60 to 86%) with ET (p=0.81). After a 15 months median follow-up, median PFS was 12 and 9 months, respectively (p=0.08). Median OS was 28 months in both arms (p=0.92). Conclusions: Despite low accrual, XT produces a 6-month progression-free rate equivalent to ET and may prolong PFS. XT is a highly active, non-anthracycline-containing, first-line treatment option for MBC patients previously exposed to adjuvant anthracycline therapy. No significant financial relationships to disclose.
Outcome according to metastatic site in patients with <i>KRAS</i> wild-type tumors: Analysis from the CRYSTAL and OPUS studies.
Authors: E. Van Cutsem, C. Bokemeyer, S. Heeger, U. Sartorius, P. Rougier, C. Kohne
Journal: Journal of Clinical Oncology (2011)

472 Background: The randomized CRYSTAL and OPUS studies showed that adding cetuximab (cet) to first-line chemotherapy (CT) significantly improved clinical benefit in patients (pts) with KRAS wild-type (wt) metastatic colorectal cancer (mCRC). R0 resection of colorectal liver metastases is a potentially curative option in this setting. In this descriptive analysis of these trials the benefit of adding cet to CT according to metastatic site was investigated. Methods: KRAS wt pts were grouped according to liver-limited disease (LLD) and those with other metastatic sites (non-LLD). Treatment arms were compared for response rates (RR), R0 resection rates (R0R), progression-free (PFS) and overall survival (OS). Results: The proportion of patients with LLD was comparable in each study and treatment arm (21%-30%). For most efficacy endpoints, pts with LLD derived greater benefit from CT alone or cet + CT compared with pts with non-LLD (Table). The highest R0R were seen in pts with LLD receiving cet + CT; increasing 2.3 and 3.7 fold from CT alone in the CRYSTAL and OPUS studies respectively. In pts with non-LLD adding cet to CT increased median OS by 5.1 and 3.4 months in the CRYSTAL and OPUS studies respectively (Table). Conclusions: The addition of cet to standard CT increases the R0R, RR, PFS and prolongs OS in first-line mCRC in KRAS wt pts, regardless of LLD. In pts with non- LLD treated with cet and FOLFIRI median OS was prolonged by more than 5 months. [Table: see text] [Table: see text]
Early discharge of newborns [4] (multiple letters)
Authors: A. R. Cass, R. J. Volk, J. V. Cook, C. L. Woronick, H. W. Wetstone, P. Lariviere, D. Williams, W. L. Lupatkin, A. F. Jerant, T. D. Epperly, L. L. Liu, D. K. Shay, R. L. Davis, A. H. Novack, C. J. Clemens, M. B. Edmonson, J. J. Stoddard, S. Egerter, P. Braveman, J. Richmond, W. Kessel
Journal: JAMA (1997)
HIV-testing in a cancer center emergency department.
Authors: Bruno Palma Granwehr, Kelly W. Merriman, Zeena Shelal, Hadil Bazerbashi, Patricia A Brock, Carmen E. Gonzalez, Harrys A. Torres, Terry Rice
Journal: Journal of Clinical Oncology (2016)

225 Background: HIV is a cancer-associated virus classically associated with KS, NHL, and cervical cancer, but more recently with anal cancer, lung, and head and neck cancers. HIV testing and treatment are important for cancer patients for three reasons: 1) HIV treatment is associated with reduced transmission of a cancer-associated virus. 2) HIV treatment is associated with improved outcomes of cancer therapy in many cancers. 3) HIV testing optimizes quality of care, since testing is recommended by the Centers for Disease Control and Prevention (CDC) and the US Preventive Services Task Force (USPSTF)(A level recommendation) for patients between the ages of 15 and 65 years of age. Since emergency centers (EC’s) commonly provide immunizations and other preventive care, we implemented HIV testing at our cancer center EC. Methods: In our 44 bed cancer center EC with approximately 25,000 annual visits, routine implementation by physician order was implemented in July 2014. EC information technology (IT) assisted in modification of the order sets and facilitated documentation of specific consent for HIV. Educational materials were disseminated to patients and EC providers. A new consent form with integration of HIV consent, including a check box to refuse HIV testing, was implemented on June 19, 2015. Testing results are described through August 2015. Results: HIV testing increased significantly from July 2014 and August 2015. The impact on institutional testing was considerable, increasing from 1.2% of all HIV testing in 2013 to 15.1% to date in 2015. Between July 2014 and August 2015, 1.4% (0.4% incident) of 852 patients screened positive for HIV. Notably, 83% of patients agreed to HIV testing, but less than 20% of patients were actually tested. The highest refusal rate (18.8%) was in patients over age 70 and lowest (9.9%) in those 21-29 years of age. Conclusions: Routine HIV testing is feasible in a comprehensive cancer center ED, but increased awareness is necessary to optimize testing, given the high acceptance rate. Seroprevalence of HIV is comparable to non-cancer center EC’s (0.5-1.2%). These results demonstrate the acceptance by patients of testing for HIV, with implications in reduction of transmission of this cancer-associated virus.
Discriminant, identifiable plasma metabolites in pancreatic cancer–associated diabetes.
Authors: Shiro Urayama, Vladimir Tolstikov
Journal: Journal of Clinical Oncology (2014)

180 Background: Pancreatic cancer has been associated with development of glucose intolerance and dysregulation. Based on our previous report of strong potential for existence of metabolite biomarkers for PDAC detection, in this study, we have pursued initial characterization of plasma metabolites for discriminating PDAC cases among diabetic patients. Methods: IRB-approved prospectively collected database and corresponding plasma from UC Davis Pancreas Registry was searched for appropriate cases: PDAC patients with recent-onset diabetes (≤3yrs prior to the index PDAC diagnosis) (Grp 1) and non-PDAC patients with long history of diabetes mellitus (&gt;3 yrs) (Grp 2). The plasma was processed and non-targeted GC/MS and targeted LC/MS were performed to assay for identifiable plasma metabolites. The data was processed and the peak intensity levels were normalized, scaled and identifiable metabolites were processed via metabolomics specific multivariate analysis and bootstrap methods as well as ROC evaluation (Metaboanalyst and ROCCET) for visualization and biomarker development. Results: We have identified 36 patients in Grp 1 and 22 patients for Grp 2. The metabolite specific multivariate and ROC analyses revealed specific features such as elaidic acid, uric acid, 2,3-propanediol, arachidonic acid, docosahexanoic acid, 5-oxo-EET, lysine, LysoPC(18:2), 9(10)-EpOME, LysoPC(16:0), sphingosine-1-phosphate and others as strong discriminators for recent-onset diabetic patients with pancreatic cancer. Such set yielded AUC of 0.964 with 15 features [CI=0.876-1]. Conclusions: We have demonstrated that an identifiable set of plasma metabolite biomarkers exists for discriminating diabetic patients with developing pancreatic cancer. These features could be utilized in a larger set of new-onset diabetic population for further validation in near-future study.
Assessing cardiac risk using heart rate variability in a phase II study of androgen-deprivation therapy and bevacizumab in noncastrate metastatic prostate cancer patients.
Authors: G. Gibney, A. Elfiky, C. J. Hoimes, A. Burns, E. Rowen, J. A. McDonough, R. Lampert, C. Gross, W. K. Kelly
Journal: Journal of Clinical Oncology (2010)

TPS244 Background: Androgen-deprivation therapy (ADT) is standard treatment in noncastrate patients with metastatic or recurrent prostate cancer (PC) with a median duration of response of 12-18 months. Preclinical data shows castration is correlated to decreased vascular endothelial growth factor (VEGF) expression and a synergistic effect with ADT and VEGF inhibition on tumor growth. This may lead to increased PC cell death and prolonged therapeutic effects of medical castration. Safety and biological effects of combination therapy need to be established. SEER database and other studies show PC patients treated with ADT were at increased risk of diabetes, myocardial infarction (MI) and sudden cardiac arrest. Cardiovascular events are more prevalent in anti-VEGF antibody (bevacizumab; BEV) treated patients. This study will assess autonomic dysregulation as a predictor for cardiovascular outcomes, which can be achieved via heart rate variability (HRV) monitoring where depressed HRV is associated with poor cardiac outcomes after MI and in the general population. HRV monitoring is a novel approach in cancer patients. Methods: Patients with prostatic adenocarcinoma, rising PSA after primary local therapy or surgery, and a PSA doubling time of < 6 months or evidence of metastatic disease are eligible. All patients must have adequate cardiac function and a Karnofsky PS ≥ 70%. Exclusions include MI, thromboembolic, or major hemorrhagic event within 6 months. 60 patients are planned for enrollment. Patients receive BEV 15 mg/kg every 3 weeks and ADT (leuprolide or goserelin) every 3 months for 3 cycles (1 cycle = 12 weeks; total 36 weeks). Patients receive bicalutamide 50 mg PO daily for the first 4 weeks. Cardiovascular status is assessed by serial cardiac biomarkers, echocardiogram (week 0 and 37) and 24-hour Holter monitor testing (week 0, 15, and 37) for HRV. The primary endpoint is cardiovascular outcome and adverse events. The secondary endpoint is PSA kinetics and duration of PSA response. Correlative studies to assess cytokine, circulating endothelial cell, and cell signaling protein levels are planned. Six patients have been enrolled to date. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech
Relationship of 4F2hc expression and grade of malignancy in renal cell cancer (RCC).
Authors: M. Pöttler, R. Novotny, A. Haitel, C. Zielinski, G. W. Prager
Journal: Journal of Clinical Oncology (2011)

e15129 Background: The type II transmembrane protein 4F2hc (CD98hc, SLC3A2) has been shown to be essential in embryogenesis as well as in adolescence during cell proliferation, while in quiescent somatic cells 4F2 is not expressed. Overexpression of 4F2hc in somatic cells leads to malignant transformation. We were interested whether 4F2hc expression predicts malignant behavior of RCC. Methods: We analyzed 270 paraffin-embedded RCC tissue samples [219 from clear cell RCC (ccRCC) and 51 samples from papillary RCC (pRCC)] from a well characterized tissue bank of the Department of Clinical Patholgy, Medical University of Vienna. Tumors were classified according to recommendations of the WHO Classification 2004 and staged according to the TNM-System (Journal of Roentgenology, 2008), and graded according to Fuhrman et al (American Journal of Surgical Pathology, 1982). 4F2hc, cytocreatin 7 (CK7), CD10 as well as aquaporin-1 were detected via immunohistochemistry and semiquantitatively analyzed. By statistically analyses the Tukey test and students t- test was used and immunohistochemical scoring results, tumor type, grading and staging in carcinomas were compared. Results: We found that 4F2hc is highly expressed in papillary, as well as clear cell RCC, while no 4F2hc expression was found in benign oncocytomas. We found that 4F2 expression is mainly found in the more aggressive type II pRCC, whereby the less aggressive type I hardly showed any positive staining (type II 83.34%, type I 4.76% 4F2hc positive, p < 0.00001; n = 51). In ccRCC, we found a direct correlation between 4F2 expression and differentiation, whereby semiquantitative analysis showed the highest stain in less differentiated tumors. (grade 1: 31%, grade 2: 21%, grade 3: 67%, grade 4 - 96% 4F2hc positive, p<0.0003) Conclusions: We conclude that 4F2 expression reflects the more malignant phenotype in RCC and therefore represents a potential novel prognostic and diagnostic biomarker in renal cell cancer.
The Cell Surface NADH Oxidase ENOX2 Is Highly Expressed in Chronic Myeloid Leukemia (CML): a Redox Protein As a Secreted Surrogate Biomarker and Druggable Target
Authors: Seda Baykal, Maud Voldoire, Christophe Desterke, Nathalie Sorel, Hyacinthe Atchroue Johnson Ansah, Agnes Guerci-Bresler, Jean-Claude Chomel, Annelise Bennaceur-Griscelli, Ali G Turhan
Journal: Blood (2016)
The impact of gender on the outcome of malignant melanoma: Overview of seven EORTC phase III trials.
Authors: A. Joosse, S. Collette, S. Suciu, E. de Vries, T. Nijsten, P. Patel, U. R. Kleeberg, U. Keilholz, A. M. Eggermont, J. W. Coebergh
Journal: Journal of Clinical Oncology (2011)

8523 Background: Although underlying mechanisms are unknown, gender has a profound effect on cutaneous malignant melanoma prognosis. This analysis aims to assess the impact of gender on prognosis for patients with both localized and disseminated melanoma. Methods: Data from 7 phase III trials of the European Organization for Research and Treatment of Cancer (EORTC 18832, 18871, 18952, 18961, 18991, 18951, 18032) were retrieved. The impact of gender was assessed separately in localized (stage I/II), stage III and stage IV melanoma for 3 endpoints: overall survival (OS), relapse free survival (RFS)—or, in stage IV, progression free survival (PFS)— and time to distant metastasis (TTDM) from date of randomization in each trial. Cox regression models, stratified for trial, were fitted adjusting the gender effect on the outcome for all known prognostic factors and treatment. Similar methodology was used to perform subgroup analyses. Results: We included 2,672 local, 2,734 stage III and 1,306 stage IV melanoma patients. A highly consistent female advantage across all stages and different endpoints was observed (Table). Hazard ratios (95% confidence interval) for females compared to males adjusted for all known prognostic indicators. The female advantage in outcome was similar in pre- and postmenopausal age subgroups, and all other prognostic factor subgroups in stage I-III (e.g. tumor thickness, ulceration, primary site, age, nr of positive lymph nodes) or stage IV (performance status, LDH serum level and size of metastatic lesions). However, in patients with stage I-III head or neck melanoma, no gender difference in survival or progression was detected. Conclusions: Females exhibit a highly consistent and independent advantage in melanoma progression, metastasis and survival across all stages. Our results suggest a biological tumor-host interaction mechanism to explain this phenomenon, although hormonal status did not seem to explain the female advantage. Unraveling the melanoma gender mystery might reveal new therapeutic possibilities. Melanoma stage OS RFS/PFS TTDM I-II 0.70 (0.59-0.83) 0.69 (0.61-0.79) 0.69 (0.59-0.81) III 0.81 (0.73-0.91) 0.86 (0.77-0.95) 0.87 (0.78-0.97) IV 0.83 (0.73-0.94) 0.79 (0.70-0.88)
Does tumor grade affect the relationship between preoperative prostate-specific antigen (PSA) and biochemical recurrence (BCR)?
Authors: Alexander Sankin, Matthew Kent, Daniel Sjoberg, Peter T. Scardino
Journal: Journal of Clinical Oncology (2014)

123 Background: It has been previously hypothesized that higher grade prostate tumors exhibit less predictable PSA secretion patterns as a consequence of cellular dedifferentiation. The purpose of this study is to investigate whether the relationship between PSA and BCR is different for high and low grade disease. Methods: We identified 6,616 patients who underwent radical prostatectomy (RP) from 1992-2012 for clinically localized prostate cancer without neoadjuvant treatment. We first created a Cox models to test for an interaction between PSA and both clinical and pathologic high grade cancer (Gleason grade (GG) &lt; 8 vs. GG 8-10). We then plotted five year risk of BCR as a function of PSA for patients with negative extracapsular extension (ECE), seminal vesical invasion (SVI), and lymph node invasion (LNI). Results: 6,125 (93%) patients in the cohort had GG &lt; 8, and 491 (7%) had GG 8-10. In total, 780 had BCR and 165 had distant metastasis. We found a significant interaction between PSA and pathologic high grade cancer (p=0.002). The risk of BCR increases at slightly different rates for low and high grade tumors as PSA increases. For example, an increase in PSA from 10 ng/ml to 20 ng/ml increases relative recurrence risk by 38% and 8% for low and high grade cancers, respectively. This interaction remained significant when patients with PSA &lt; 2.5 were excluded (P=0.006). There was no significant interaction between PSA and clinical high grade tumors (p=0.3). Conclusions: There appears to be a small statistically significant difference in relationship between preoperative PSA and BCR in high grade tumors when compared to lower grade tumors. This difference is not observed, however, when using biopsy GG rather than RP specimen GG.
A phase II study of combination therapy with liposomal doxorubicin and carboplatin (CBDCA) in patients (pts) with previously untreated small cell lung cancer (SCLC)
Authors: D. A. Vorobiof, B. L. Rapoport, C. F. Slabber, A. S. Alberts, A. Uys
Journal: Journal of Clinical Oncology (2005)

7279 Background: SCLC remains an aggressive disease with a poor survival. Combinations with doxorubicin and CBDCA are the standard chemotherapy regimen for the treatment of SCLC. A wide variety of dose and schedules have been employed when managing these patients. Pegylated liposomal doxorubicin, has shown anti-tumour activity and reduced toxicity compared with standard doxorubicin. Methods: The objective of this phase II study is to determine efficacy and toxicity of Caelyx at a dose of 50mg/m2 in combination with CBDCA (AUC = 5), in patients with chemo-naïve small cell lung cancer. A total of 6 - 8 cycles are repeated every 28 days. Results: Twenty-four patients have been entered to date. There are 17 males and 7 females. The median age is 63 years (range 42–73). The majority of patients (79%) presented with an ECOG PS of 0 - 1, despite the fact that more than 80% of patients presented with stage IV disease. A total of 108 cycles have been administered, with a median of 4 cycles (range 1–8). At this stage 21of the 24 patients are evaluable for response. One patient withdrew consent, one died due to pneumonia after 1 cycle and 1 patient is too early for evaluation. Documented responses include 4 (19%) complete and 8 (38%) partial responses. Four patients have stable disease and 5 patients progressed. Haematological toxicity includes anaemia (grade I-II: 8 patients; grade III: 6 patients), neutropenia (grade I-II: 15 patients; grade III-IV: 5 patients) and thrombocytopenia (grade I-II: 10 patients; grade III-IV: 4 patients). One patient developed febrile neutropenia. Non haematological toxicity includes PPE (grade I-II: 14 patients), nausea and vomiting (grade I - II in 7 patients), stomatitis (grade I-III: 8 patients; grade III-IV: 1 patient) and fatigue (grade I-III: 15 patients). No cardiac or renal toxicity have been observed. Conclusions: This phase II study combining CBDCA (AUC = 5) with Caelyx (50mg/m2), conducted in South Africa appears to be an active and very well tolerated first line chemotherapy regime for SCLC patients. The study is ongoing. No significant financial relationships to disclose.