tbuckley/cabot-search huggingface dataset:
Appropriateness of adjuvant systemic therapy for axillary node-negative breast cancer: a physician opinion survey.
Authors: C A Sawka, A M O'Connor, H A Llewellyn-Thomas, T To, S P Pinfold, D Harrison-Woermke
Journal: Journal of Clinical Oncology (1995)

PURPOSE To examine variations in physicians' recommendations for systemic adjuvant therapy in the treatment of women with node-negative breast cancer (NNBC) and to determine factors used in making specific recommendations. MATERIALS AND METHODS A questionnaire was sent by mail to all 149 Ontario physicians who actively treated breast cancer in 1993. The questionnaire described 48 clinical scenarios of women with NNBC, which included all possible combinations of the following factors: menopausal status, tumor size, hormone receptor status, histologic and nuclear grade, and lymphatic and/or vascular invasion. Respondents rated the appropriateness of administering tamoxifen, combination chemotherapy, or both tamoxifen and combination chemotherapy on a nine-point scale from extremely inappropriate to extremely appropriate. Respondent agreement and disagreement were tabulated for each scenario, and factors associated with specific treatment ratings were analyzed by logistic regression. RESULTS The response rate was 87%. Agreement for the appropriateness of specific therapies was most evident where clinical trials have demonstrated efficacy, whereas disagreement was observed in scenarios in which support for a specific treatment is not available in the current literature. Relevant tumor- and patient-specific factors were used in decision-making; personal characteristics of the respondents had no statistically significant impact on appropriateness ratings. CONCLUSION The physicians surveyed had good knowledge of NNBC prognostic factors, but had a range of opinion on optimal therapy for many clinical scenarios, which reflects current knowledge of the benefits of adjuvant therapy for NNBC.
Changing patterns in presentation and therapy of esophagogastric junction cancers in the United States.
Authors: Roderich Schwarz, David D. Smith, Rebecca A. Nelson
Journal: Journal of Clinical Oncology (2014)

22 Background: Esophagogastric junction cancer (EGJC) has recently been included within the esophageal cancer (EC) AJCC TNM staging criteria. Trends in clinical presentation, therapeutic approach and outcomes are of interest. Methods: We identified EGJCs from the U.S. population SEER database and examined incidence, demographic, therapeutic and outcomes information. Siewert classification-related EGJC subtype-associated findings were also examined. Results: EGJC age-adjusted incidence rates (x10 -5 ) have increased from 3.3 in 1973 to 7.5 in 2009. While the incidence rate for females has remained around 2, rates in males have increased from 6 to 13. Among 30,710 EGJC patients diagnosed between 1992 and 2009, potentially curative resection increased from 31% to 36% and radiation increased from 32% to 41% (p&lt;0.0001). For resected EGJCs, significant trends over time include: increased total LN count (mean: 15.5 vs. 12.3), fewer positive LNs (3.1 vs. 4), smaller tumor size (29% vs. 36% &gt;5 cm), lower T category (39% vs. 29% T1/2), lower N category (42% vs. 35% N0), lower stage group (29% vs. 38% stage 3/4), increased preoperative radiation (26% vs. 3%), decreased 90-day mortality (6.5 vs. 14.1%), longer overall survival (OS, median: 2.9 vs. 1.7 years) and longer disease-specific survival (median: 3.9 vs. 2.0 years) (all at p&lt;0.0001). Multivariate predictors of OS include TNM categories, age, ethnicity, radiation, and total LN count (all at p&lt;0.0001). There were significant differences in stage-for-stage OS between EC subtypes based on histology and primary tumor location, and in DSS between EGJC subtypes (Siewert I, II or III) as well. Conclusions: EGJC incidence rates, diagnosis and treatment have undergone significant changes within the U.S. population. The regional dissection extent remains an area of importance as it is associated with OS. Comparisons of various survival outcomes do not support using the same staging criteria for EGJC as for EC.
Gap Gene Regulatory Dynamics Evolve along a Genotype Network
Authors: Anton Crombach, Karl R. Wotton, Eva Jiménez-Guri, Johannes Jaeger
Journal: Molecular Biology and Evolution (2016)

Developmental gene networks implement the dynamic regulatory mechanisms that pattern and shape the organism. Over evolutionary time, the wiring of these networks changes, yet the patterning outcome is often preserved, a phenomenon known as "system drift." System drift is illustrated by the gap gene network—involved in segmental patterning—in dipteran insects. In the classic model organism Drosophila melanogaster and the nonmodel scuttle fly Megaselia abdita, early activation and placement of gap gene expression domains show significant quantitative differences, yet the final patterning output of the system is essentially identical in both species. In this detailed modeling analysis of system drift, we use gene circuits which are fit to quantitative gap gene expression data in M. abdita and compare them with an equivalent set of models from D. melanogaster. The results of this comparative analysis show precisely how compensatory regulatory mechanisms achieve equivalent final patterns in both species. We discuss the larger implications of the work in terms of "genotype networks" and the ways in which the structure of regulatory networks can influence patterns of evolutionary change (evolvability).
MDR1 Gene Expression and Outcome in Osteosarcoma: A Prospective, Multicenter Study
Authors: Jay S. Wunder, Shelley B. Bull, Vicky Aneliunas, Peter D. Lee, Aileen M. Davis, Chris P. Beauchamp, Ernest U. Conrad, Robert J. Grimer, John H. Healey, Michael J. Rock, Robert S. Bell, Irene L. Andrulis
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Increased expression of the multidrug resistance gene (MDR1) has been implicated in osteosarcoma prognosis. This study represents the first prospective assessment of the prognostic value of MDR1 mRNA expression in patients with newly diagnosed extremity osteosarcoma. PATIENTS AND METHODS: A series of patients with high-grade, nonmetastatic extremity osteosarcoma were enrolled from six tertiary care institutions and observed prospectively for tumor recurrence (median follow-up duration, 30 months). All patients were treated with (neo)adjuvant chemotherapy and surgery. Tumors from 123 patients were analyzed for MDR1 mRNA expression. The association of the level of MDR1 expression with the risk of systemic recurrence was examined using survival analyses with traditional and histologic markers as prognostic factors. RESULTS: Using the highest MDR1 value for each patient, a dose-response relationship was not identified between the level of MDR1 expression and systemic relapse (relative risk, 1.15; P = .44). Analyses based on biopsy or resection values alone gave similar results (P = .11 and .41, respectively, log rank test). In multivariate analysis, large tumor size (&gt; 9 cm) was the only significant independent predictor of systemic outcome (relative risk, 2.8; P = .002). CONCLUSION: We did not identify any correlation between MDR1 mRNA expression and disease progression in patients with osteosarcoma. It is likely that alterations in other genes are involved in resistance to chemotherapy in osteosarcoma and that they play a more critical role than MDR1 in this disease.
Microcirculatory Studies in Rat Mammary Carcinoma. I. Transparent Chamber Method, Development of Microvasculature, and Pressures in Tumor Vessels<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>
Authors: W Peters, M Teixeira, M Intaglietta, J F Gross
Journal: JNCI Journal of the National Cancer Institute (1980)

Fragments of a mammary adenocarcinoma were implanted into transparent tissue chambers in the dorsal skin flaps of female inbred F344 rats. A chamber modification permitted repeated access to the tissue without infection, vessel disruption, or impairment of tumor growth. Tumors completely filled the chambers after 26–30 days. Development of tumor microvasculature was characterized by increase in number, length, and diameter of vessels. These changes were much more pronounced in capillaries and venules than in arterioles. Direct blood pressure measurements were performed in microvessels throughout the tumor during the first 3 weeks of growth as well as in micro-vessels of tumor-free control preparations containing subcutaneous tissue. Average pressures in arterioles of 40- to 11-μm diameter were between 23.0 and 17.3 cm H2O in tumors versus 25.5 and 16.2 cm H2O in controls. Average pressures in venous capillaries, venules, and veins up to 150-μm diameter were between 9.1 and 8.1 cm H2O in tumors and between 13.4 and 11.0 cm H2O in controls.
Phenothiazine Inhibition of Intestinal and Urinary Bladder Tumors Induced in Rats by Bracken Fern&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A M Pamukcu, L W Wattenberg, J M Price, G T Bryan
Journal: JNCI Journal of the National Cancer Institute (1971)

Bracken fern (Pteris aquilina), mixed with grain (1:3 by weight), was fed to 2 groups of male and female albino rats that also received 2 mg thiamine hydrochloride subcutaneously once weekly. In Group 1, fed this diet, 19 of 21 rats surviving more than 6 months developed intestinal neoplasms (adenomatous polyps or adenocarcinomas) and the same number developed urinary bladder tumors (papillomas or transitional cell carcinomas). In Group 2, of 28 rats fed the bracken-fern diet, to which phenothiazine (2 mg/g diet) was added, 11 had intestinal tumors and 10 had bladder tumors. The average survival of the rats in both groups was 11 months. Nine rats fed a grain diet containing no bracken fern developed neither intestinal nor bladder tumors. Rats receiving the phenothiazine-bracken fern diet had persistently increased levels of benzo[a]pyrene (BP) hydroxylase activity in the mucosa of the small intestine, liver, and kidney, whereas rats fed the bracken fern diet (Group 1) showed normal or only slightly elevated levels of this enzyme. The magnitude of induction, relative to untreated control rats, was highest in the kidney and similar for the mucosa of the small intestine and liver. BP hydroxylase activity of the small intestine progressively decreased in all groups of animals. These data are consistent with the possibility that phenothiazine-stimulated microsomal metabolism of the bracken fern partially inhibits the genesis of intestinal and bladder neoplasms. However, the possibilities of a direct chemical interaction between carcinogen and phenothiazine at some point before the active site, or of a competitive inhibition of the carcinogen by the drug at some critical binding site, cannot be excluded.
P-066 S-1 in combination with epirubicin and oxaliplatin (EOS) in Caucasian patients (pts) with advanced or metastatic gastric cancer (AGC): Results of a phase I study
Authors: M. Moehler, B. Melichar, R. Obermannova, A. Weinmann, P. Scigalla, E. Kubala, R. Mahlberg, V. Heinemann, M. Tesarova, P. Janda, F. Biville, W. Mansoor
Journal: Annals of Oncology (2015)
Impact of surgery and chemotherapy on survival in patients with advanced cholangiocarcinoma: A multivariate analysis in a cohort of 242 consecutive patients
Authors: C. Dreyer, C. Le Tourneau, S. Faivre, V. Paradis, Q. Zhan, F. Degos, O. Farges, P. Hammel, P. Ruszniewski, J. Belghiti, E. Raymond
Journal: Journal of Clinical Oncology (2006)

4133 Background: Cholangiocarcinoma remains an orphan disease for which prospective studies are missing to evaluate the impact of systemic chemotherapy on survival. Methods: Univariate and multivariate analysis of parameters that might impact survival were analyzed in a cohort of 242 consecutive patients with cholangiocarcinoma treated in a single institution between 2000 and 2004. Variables were WHO performance status (PS), age, symptoms, tumor size, extent of the disease, lymph node involvement, site of metastasis, tumor markers, pathology, and type of treatment including surgery, chemotherapy and radiotherapy. Results: Statistically significant prognostic factors of survival in univariate analysis are displayed in the table : In multivariate analysis, PS, tumor size and surgery were independent prognostic factors. Subgroup analysis demonstrated that in patients with advanced diseases (lymph node involvement, peritoneal carcinomatosis and/or distant metastasis), patients who had no surgery benefited of chemotherapy (median survival 13.1 versus 7.4 months in patients with/without chemotherapy, p = 0.006). Moreover, survival was further improved when patients could benefit of chemotherapy following total and/or partial resection (median survival 22.9 versus 13.0 months in patients with/without chemotherapy, p = 0.03). Conclusions: This study strongly suggests the positive impact on survival of multimodality approaches including surgery and chemotherapy in patients with advanced cholangiocarcinoma. [Table: see text] No significant financial relationships to disclose.
A phase II multicenter trial of neoadjuvant chemotherapy FOLFOX6 in combination with bevacizumab for patients with resectable synchronous liver metastases after R0-resections of primary colorectal cancers: The interim analysis.
Authors: K. Miura, Y. Katayose, M. Oikawa, J. Yamauchi, N. Sakurai, H. Musha, Y. Narushima, K. Nakagawa, S. Egawa, M. Unno
Journal: Journal of Clinical Oncology (2011)

322 Background: Therapeutic strategies for colorectal cancer (CRC) patients with synchronous liver metastases are still indeterminate; therefore, we conducted a phase II multicenter trial of neoadjuvant chemotherapy mFOLFOX6 combined with bevacizumab for resectable synchronous liver metastases after R0-resections of primary CRCs. This study was started in June 2008. This is the interim report. Purpose: The aim of this interim analysis is to evaluate the response rate (RR) and adverse events (AEs) of the enrolled patients. Methods: Eligibility criteria included CRC patients with 10 or less synchronous liver metastases that were preoperatively diagnosed as surgically resectable. 20 of the enrolled patients received 8 courses of mFOLFOX6 with bevacizumab, but bevacizumab was omitted at the initial and the final courses, to avoid the AEs at the operations. The primary endpoint was the RR. Results: Among the 20 patients, one patient was excluded from the study because the assumed metastasis was diagnosed to be hemangioma later with the MRI imaging. RR was analyzed for the 19 patients, and AEs were analyzed for the 20 patients. Complete response and partial response were achieved in 2 (10.5%) and 11 (57.9%), respectively (RR: 68.4%); 4 (21.1%) were stable disease, and 2 (10.5%) were progressive disease. The RR was higher than the prespecified boundary; therefore, this study was scheduled to be continued. AEs were the following: neutropenia, hypertension, anemia, leucopenia, nausea, appetite loss, stomatitis, bleeding and proteinuria. Grade 3 neutropenia occurred in 4 cases (20.0%), and sensory neuropathy, stomatitis, diarrhea, and cerebral infarctions occurred in each one (5.0%) of the patients. There was no AE of grade 4 or 5. Liver resections were performed in 17 cases, and R0-resection was achieved in all of the operable cases (R0 rate was 85%). Conclusions: Neoadjuvant chemotherapy mFOLFOX6 combined with bevacizumab appears to be effective and well tolerated. The study is continued as scheduled, to further evaluate the benefit of this regimen. No significant financial relationships to disclose.
Provision of specialized palliative care in a multiprofessional network.
Authors: Jens Hermann Papke
Journal: Journal of Clinical Oncology (2014)

144 Background: In Germany specialised palliative care in outpatient setting is financed by health insurances since 2007. Home Care Sachsen e.V. is a specialised palliative care provider working with two palliative care teams including qualified nurses, physicians and social workers in closely cooperation with general practitioners and nursing services. We report about the results of our work in a rural area around Dresden in Saxony, Germany. Methods: Our data were collected prospectively with PalliDoc software. Results: Between 2011 – 2013 Home Care Sachsen e.V. served for 1,572 pts (888 m, 684 f); 93% with an oncologic disease. Median age was 71 y, Karnofsky index was 40%, median caring time 27 days. In this time, 25% of our pts had one stay in hospital, 8% two and 4% three and more. 63% had no stays in hospital. At least 1,271 pts. died: 65% at home; 9% in nursing homes and hospices; 15% in palliative care units and 11% in hospital. Conclusions: Mean home death rate of oncologic pts without intervention in Germany is about 44% (Papke J, Koch R: Places of Death from Cancer in a Rural Location. Onkologie (2007) 30, 105-08). This proportion could be enhanced considerably with outpatient palliative care. Providing of specialised palliative care with a multiprofessional team is effective to increase the rate of dying at home and to fulfill one of the strongest wishes of pts in a palliative situation.
90y Ibritumomab Tiuxetan as Initial Treatment for Follicular Lymphoma (ZEUS Protocol). An Italian Cooperative Study Group
Authors: A. M. Carella, S. Nati, G. Fraternali Orcioni, M. Petrini, S. Galimberti, U. Vitolo, N. Cascavilla, P.L. Zinzani
Journal: Blood (2008)
Concurrent paclitaxel/carboplatin/infusional 5-FU/radiation therapy (RT) with or without subsequent esophageal resection in patients with localized esophageal cancer: A Minnie Pearl Cancer Research Network trial
Authors: J. R. Gray, J. D. Hainsworth, A. A. Meluch, D. R. Spigel, S. H. Rosenoff, J. E. Bradof, R. C. Hermann, C. Meng, F. A. Greco
Journal: Journal of Clinical Oncology (2005)

4018 Background: Optimal treatment for patients (pts) with localized esophageal cancer is unclear. In various reported trials, results with concurrent chemotherapy/RT have been comparable to results with treatment programs containing surgical resection. We previously demonstrated the efficacy of preoperative concurrent paclitaxel/carboplatin/5FU/RT in a large phase II trial (41% 3-yr PFS). In this trial, we attempt to further define the role of surgical resection by randomizing pts to resection vs completion of full dose RT, following the same preop therapy. Methods: Eligibility: untreated esophageal/GE junction squamous or adenocarcinoma; clinical stage I-III; surgical candidate; ECOG PS 0–2; adequate organ function; informed consent. All pts received paclitaxel 200mg/m2 IV and carboplatin AUC 6.0 IV, days 1 & 22; 5-FU 225mg/m2/day, 24-h continuous infusion, days 1–42; radiation therapy 45 Gy (1.8 Gy single daily fractions). After completion of preop treatment, pts were randomized to either surgical resection (4–6 weeks after preop therapy) or continued RT (total dose 64.8 Gy) plus 1 additional course of paclitaxel/carboplatin. Overall survival and PFS were the major endpoints. Results: Between 10/99 and 10/04, 194 pts were treated: median age 60 years; male/female 81%/19%; adenocarcinoma 72%; distal or GE junction location 84%; clinical stage I vs II/III 9%/91%. Following chemotherapy/RT, 89 pts (46%) agreed to randomization, and 57 pts proceeded with the treatment to which they randomized. When all patients are considered, resected pts (N=91) and full dose RT pts (N=50) had similar median PFS (20 vs 15 mo; p=.92), OS (27 vs 24 mo; p=.74), and 3-yr survival (35% vs 31%). Comparisons were similar in the subset of randomized pts. 4 pts (2%) had treatment-related death during induction; 3 pts (3%) had postop death. Conclusions: Attempts to randomize pts to resection vs full dose RT were largely unsuccessful. However, in large parallel groups of pts, these treatments produced similar PFS and OS, suggesting resection may not be a required component of combined modality treatment. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb
Failure of 1H nuclear magnetic resonance spectroscopy of blood plasma to detect malignancy.
Authors: P Okunieff, M D Greenberg, A Zietman, J Kahn, S Westgate, L J Neuringer
Journal: Journal of Clinical Oncology (1990)

Water-suppressed proton nuclear magnetic resonance (NMR) of plasma was proposed as a technique for detecting malignant tumors. In that analysis, bloods drawn from cancer patients at the Beth Israel Hospital (BIH; Boston, MA), were easily distinguished from normal subjects by measuring and averaging the proton NMR methyl and methylene line widths of plasma lipoproteins. We collected blood at the Massachusetts General Hospital (MGH), including from normal controls, patients with untreated and treated malignant tumors, and patients with nontumor diseases. The plasma NMR analyses were carried out blind. The code was not broken until all patient charts and pathology records were reviewed, plasma analyses were completed, and patients had been divided into appropriate clinical groups. Analysis of these data showed no differences between the means of the study groups (false-positive and false-negative frequencies 46% and 57%, respectively). An inverse correlation of methyl/methylene line widths with age (P less than .01), and a correlation with nitrate-requiring cardiovascular disease (P less than .05) was, however, evident. This test cannot be validly used to detect malignancy.
A Phase 1B Study of Pembrolizumab (Pembro; Mk-3475) in Patients (Pts) with Advanced Gastric Cancer
Authors: K. Muro, Y. Bang, V. Shankaran, R. Geva, D.V.T. Catenacci, S. Gupta, J.P. Eder, R. Berger, E.J. Gonzalez, J. Pulini, A.B. Ray, M. Dolled-Filhart, K. Emancipator, K. Pathiraja, X. Shu, M.R. Koshiji, J. Cheng, H.C. Chung
Journal: Annals of Oncology (2014)
Impact of interobserver variability in delineating clinical target volumes (CTV) for head and neck intensity modulated radiation therapy (IMRT): Potential for a geographical miss
Authors: S. Chilukuri, S. Surana, P. P. Mohanty, R. Kuppuswamy
Journal: Journal of Clinical Oncology (2009)

e17013 Background: Despite modern day imaging techniques and guidelines for delineation of the clinical target volume, there remains significant inter-observer variability in delineating the CTV. With the use of IMRT, the target volume receives a significant tumoricidal dose while the regions just outside the target receive unpredictable doses. In this report, the dose to the region just outside the planning target volume (PTV) (defined as volume of uncertainty [VOU]), presumed to represent the regions subject to maximum inter-observer variability, was studied. Methods: The IMRT plans of 12 patients with head and neck cancer were used to determine the dose just outside the high-risk CTV by growing volumes around CTV with 3 mm, 5 mm, and 7 mm margins. These volumes were edited at regions close to skin/air and bone. PTVs were subsequently grown using the same margins as used in the original plans. With the Boolean operations, each of these volumes was subtracted from the existing PTV to generate the volumes of uncertainty (VOU) in 3 dimensions. The dose to these VOUs was analyzed. D95, D90 and median dose which are the doses received by 95%, 90%, and 50% of the target volume respectively were studied. Results: The median prescribed dose was 68 Gy (60 Gy-72 Gy). The median percentage D95 for 3mm, 5mm and 7mm VOU was 82.5% ± 4.95, 77.25% ± 5.53, and 69% ± 6.93, respectively. The median percentage D90 for these VOU's was 87.7% ± 3.53, 83.2% ± 4.61, and 79% ± 4.5, respectively. The median dose to each of these VOU”s was 96% ± 1.6, 94.5% ± 1.95, and 92.5% ± 1.85 respectively. Conclusions: This study documents that the volumes of uncertainty surrounding the PTV, which could contain subclinical disease, in fact receive a significant amount of RT dose. Hence, despite a large amount of evidence for inter-observer variability in target delineation for head and neck cancer,the majority of locoregional recurrences are within the high dose region and not marginal failures. No significant financial relationships to disclose.