tbuckley/cabot-search huggingface dataset:
Concordance of local pathology interpretation (LR) with central pathology review (CR) in primary tumor specimens from patients with renal cancer (RCC)
Authors: E. Carloss, M. Regan, M. Upton, A. Youmans, D. McDermott, A. Polivy, M. Atkins
Journal: Journal of Clinical Oncology (2004)

4548 Background: Histologic interpretations of RCC specimens are increasingly being used to develop prognostic models and guide Rx decisions. In order to assess the accuracy and completeness of pathology data contributed to large databases we collected H & E stained pathology slides and outside pathology reports of RCC primary tumors from pts with stage IV RCC. Methods: Central review (CR) was performed according to pre-set criteria by a single pathologist blinded to the outside pathology reading (LR). Findings were compared to LR and degree of concordance determined. Results: 165 specimens were obtained from bx or resection performed on independent pts between 1986 and 2001 (83% after 1994). CR classified specimens as either clear cell (148/90%), papillary (12/ 8%), chromophobe (2/1%), or indeterminate (3/ 2%). 59 (35%) were not subclassified by LR; 52 of the 59 (88%) were classified as clear cell by CR. 99% of those classified as clear cell by LR were confirmed to be by CR. 55 (33%) of LR did not include Fuhrman grade (FG). Of the 110 LRs specifying overall FG, 60 (55%) were concordant while 46 (42%) underestimated the grade. Predominant FG was more concordant (72% match) with balanced over/underestimation by LR. Features noted by CR included sarcomatoid 25%, papillary 13%, granular 60%, and alveolar 85%. Only 85 (52%) of LRs noted any RCC features. LR features mentioned among these 85 included sarcomatoid 16%, papillary 31%, granular 35%, and alveolar 9%. Concordance between CR and LR was seen in 76% sarcomatoid (k = 0.45), 84% papillary (k = 0.59), 49% granular (k = 0.07), and 29% alveolar (k = 0.12). Discordance was related predominantly to failure to note features in LR, except with papillary where 10/13 (77%) discrepancies were related failure to confirm this feature at CR. Conclusions: This analysis revealed an underestimation of overall FG and underreporting of pathologic subtype and most RCC features, excepting papillary, in LR relative to CR. This degree of discordance suggests that some Rx decisions based on LR or prognostic models derived from databases that rely on LR may be incorrectly or incompletely founded. No significant financial relationships to disclose.
Analysis of dose intensity in doxorubicin-containing adjuvant chemotherapy in stage II and III breast carcinoma.
Authors: P T Ang, A U Buzdar, T L Smith, S Kau, G N Hortobagyi
Journal: Journal of Clinical Oncology (1989)

Three hundred thirty-six patients with stage II or stage III breast cancer were treated on an adjuvant protocol containing fluorouracil, doxorubicin, cyclophosphamide, vincristine, and prednisone (FACVP). Depending on the estrogen-receptor (ER) status, the patients were subdivided to receive maintenance chemotherapy with or without tamoxifen. The administered dose intensity of fluorouracil, doxorubicin, and cyclophosphamide (FAC) (mg/m2/wk) relative to the projected dose intensity (based on planned dose) was computed for each patient. The relative dose intensity of the first six cycles of chemotherapy (RDI6) was compared with disease-free survival (DFS). Of the 299 patients who completed at least six cycles of therapy, 83% received dose intensities within 20% of standard intensity (.8 less than or equal to RDI6 less than or equal to 1.2). The group with the highest dose intensity (RDI6 greater than or equal to 1.13) had the longest DFS, though there was not a clear trend of linear association between dose intensity and DFS after adjustment for prognostic factors (P = .16). The patients who received at least standard dose intensity (RDI6 greater than or equal to 1.0) had longer DFS than those whose therapy did not reach standard intensity (RDI6 less than 1.0). This difference was significant in patients with stage III disease (P = .01). The 37 patients who completed fewer than six cycles of chemotherapy had the shortest DFS (5-year DFS of 48% v 65% in the others). This retrospective analysis, in a heterogeneously treated group of patients, did not show the differences in outcome associated with dose intensity as demonstrated in the earlier studies comparing projected dose intensity of various cyclophosphamide, methotrexate-, and fluorouracil (CMF)-containing adjuvant trials. Improved DFS was noted in the stage III patients receiving higher dose intensity. Our failure to demonstrate the differences in stage II patients may be due to the narrow range of dose intensity in this study or to a difference in the dose-response curves depending on the stage of disease.
Guidelines to reduce x ray examinations in accident departments
Authors: R D Hardern, D W Harmer
Journal: BMJ (1995)

EDITOR,--Eugene McNally and colleagues report the effect of introducing guidelines on when to request radiographs for certain conditions presenting in an accident department.1 Two aspects of this paper merit discussion. Firstly, the outcome measured and the data presented do not seem to support the conclusions. Secondly, one should not infer that use of the posters containing the …
Phase I study of sunitinib in combination with carboplatin (C) plus paclitaxel (P) in patients (pts) with advanced solid tumors (STs)
Authors: E. I. Heath, G. R. Blumenschein, R. B. Cohen, P. M. LoRusso, N. K. LoConte, S. T. Kim, R. Chao, G. Wilding
Journal: Journal of Clinical Oncology (2008)

3565 Background: Sunitinib (SU) is an oral, multitargeted tyrosine kinase inhibitor of VEGFRs-1, -2, and -3, PDGFRs-α and -β, KIT, FLT3, CSF-1R and RET. SU is approved for the treatment of advanced RCC and imatinib-resistant/intolerant GIST and has demonstrated antitumor activity in patients with other advanced STs. This study evaluated the safety and efficacy of SU in combination with C/P. Methods: Pts with advanced STs for whom curative therapy was not available were enrolled. Serial pt cohorts received escalating daily doses of oral SU at 25, 37.5, or 50 mg for 2 wks of a repeated 3-wk cycle (2/1 schedule) or for continuous 3 wk cycles (CD schedule) in combination with C (AUC=6 mg·min/mL) plus P (175–225 mg/m2) given every 21 days. The maximum tolerated dose (MTD) of SU plus C/P was assessed based on observed dose limiting toxicities (DLTs) and adverse events (AEs). Results: As of Dec 2007, 15 pts were enrolled in the 2/1 schedule [25 mg (n=9) and 37.5 mg (n=6)] and 6 pts in the CD schedule [25 mg (n=3) and 37.5 mg (n=3)] both in combination with C/P (175 mg/m2). The median age for all enrolled pts was 59 yrs (range 37–76) and 43% of pts had received multiple prior systemic treatments. Pts enrolled had various STs, including pancreatic (n=4), NSCLC (n=3), SCLC (n=3), mesothelioma (n=3) and melanoma (n=3). Of the 15 pts enrolled in the 2/1 schedule, 4 pts were not evaluable for DLTs due to early discontinuation prior to start of C/P. There was one DLT observed at 25 mg in the 2/1 schedule (grade 4 ischemic optic neuropathy) and two DLTs at 37.5 mg (fatal GI hemorrhage and grade 3 neutropenic infection). The most commonly observed Grade 3/4 hematologic abnormalities (both schedules) included neutropenia (n=13) and lymphopenia (n=12). Other Grade 3/4 AEs included fatigue (n=2), thrombosis (n=1), ulcerative esophagitis (n=1) and syncope (n=1). Of the evaluable pts (both schedules), 1 pt with SCLC had a confirmed PR. Conclusions: These data suggest that the dose levels tested to date are tolerable in patients with advanced STs and may represent a clinically useful treatment option. The determination of MTD, safety, and efficacy of SU plus C/P are under further investigation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer AstraZeneca, Aventis, Genentech, GlaxoSmithKline, Pfizer, Takeda Pfizer AstraZeneca, Aventis, Genentech, GlaxoSmithKline, Pfizer, Takeda Amgen, Ariad, Array Biopharma, AstraZeneca, Boeringer Ingelheim, Bristol-Myers Squibb, Endocyte, Exelixis, Genentech, GlaxoSmithKline, ImClone, Merck, NCI, Nereus, Novartis, Pfizer, Roche, sanofi-aventis, Ziopharm
Characterization of the &lt;italic&gt;H-2&lt;/italic&gt; Antigens of L-M Mouse Cells Grown in Culture&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Sudha G. Gangal, D. J. Merchant, D. C. Shreffler
Journal: JNCI Journal of the National Cancer Institute (1966)

Cell strain L-M, a subline of strain L, grown for 25 years in vitro was investigated for H-2 antigenic specificities. The cells were tested for specificities 1, 3, 5, 8, 11, and 32 (A, C, E, H, K, and Dk, respectively), as the line originated from subcutaneous tissue of a C3H mouse having the H-2k allele. Reagent H-2 antisera having known H-2 antibodies, prepared in inbred strains of mice, were exhaustively absorbed with L-M cells. The absorbed antisera were tested for agglutination of appropriate indicator red cells from specific mouse strains. The absorption of hemagglutinins indicated presence of the particular antigenic specificity on L-M cells. Presence of certain of these specificities also was confirmed by immunization with L-M cells. Presence of specificity 32 (Dk) was demonstrated by cytotoxic activity. With these methods, L-M cells were shown to have retained all the H-2 antigenic specificities characteristic of C3H. The possibility of the use of H-2 specificities as genetic markers for identification of the strains of origin of murine cultures is discussed.
The True NTH Prostate Cancer Survivorship Care programme: Development and evaluation of a model for delivering follow-up care to men with prostate cancer.
Authors: Alison Richardson, Jane Frankland, Hazel Brodie, Deborah Cooke, Ruth Pickering, Heather Gage, Rebecca Foster, Claire Foster
Journal: Journal of Clinical Oncology (2016)

42 Background: Increasing use of prostate specific antigen (PSA), improvements in treatment and aging population have led to the escalating incidence of prostate cancer. 5 year survival rate is relatively high and men who have completed treatment require long-term follow-up to detect recurrence or progression of disease, monitor adverse effects of treatment and identify and address psychosocial needs. Studies demonstrate men have a range of unmet physical and psychosocial needs, and health services are struggling to cope with the growing numbers. Changes is critical for long-term sustainability of the health system in many developed nations Methods: This presentation presents a model of follow up care centered on remote surveillance of PSA combined with promoting patient self-management. This initiative is part of the True NTH programme of developments initiated in the UK with funding from Movember Foundation and Prostate Cancer UK. Traditional face to face clinic follow up consultations are replaced with: patient directed individually tailored care and surveillance programme which involves: a 4 hour preparatory patient workshop, remote assessment of unmet needs and symptoms and surveillance of PSA, patient information resources, survivorship care plan, communication of treatment summary and management plan to primary care, and rapid recall system for assessment in secondary care should the need arise. The care programme is mediated through clinician and patient access to an IT portal enabling communication. Results: The second part of the presentation will describe the evaluation protocol. A historical cohort design is comparing a group of men receiving clinic follow up care (N = 300) with men enrolled on the care programme (N = 300) in 3 centers. Patient-reported outcomes are collected at baseline, 4 months and 8 months. Health economic evaluation will compare costs of clinic based follow up with those of the care programme from both a health service and patient perspective. Conclusions: The evaluation will generate data on impact, acceptability and cost of this model of follow-up care.
Assessment of cancer pain
Authors: A. F. Dugas, B. A. Murphy, N. Wells, M. S. Dietrich, K. Dwyer
Journal: Journal of Clinical Oncology (2007)

19500 Background: This study investigates: 1) The concordance between patients and staffs’ standard use of the numerical rating scale (NRS) for pain, in which 1–4 is mild pain, 5–6 is moderate and 7 and above is severe; 2) The relative importance of functional impairment secondary to pain in patients’ pain ratings. Methods: Patients with cancer and current or previous pain (N=178) were asked to complete a fifteen minute interview with open-ended questions about their perception of pain. Results: When asked to define mild, moderate and severe pain according to the NRS, 65% of patients gave numbers that did not meet standard definitions as noted above. When asked to define mild, moderate and severe pain in general, 38% differentiated severity of pain based on its impact on their ability to fulfill activities of daily living (ADLs) and 39% differentiated it based on their emotional reactions. When asked to define tolerable pain, 28% described it in terms of its impact on ADLs, while 30% described it in terms of the NRS. For those patients who used a NRS, the mean value for tolerable pain was 4.9 (range 2–8) and the mean value for intolerable pain was 8.1 (range 5–10). 26% of patients defined satisfactory pain control based its impact on ADLs while only 2% defined it according to a NRS. 68% of patients reported that pain interfered with their ADLs, however only 33% reported that pain medication interfered. Conclusions: There is discordance between the standard definition of the NRS and patient perceptions of it, suggesting it should be supplemented by other types of pain assessment. Based on NRS, patients tolerate higher levels of pain than expected. Patient satisfaction with pain control is more dependent upon ability to complete ADLs than on a numerical rating of pain. Therefore, patients’ ability to function at an acceptable level should be part of the standard pain assessment. No significant financial relationships to disclose.
pH‐Activatable MnO‐Based Fluorescence and Magnetic Resonance Bimodal Nanoprobe for Cancer Imaging
Authors: Benedict You Wei Hsu, Michael Ng, Aaron Tan, John Connell, Thomas Roberts, Mark Lythgoe, Yu Zhang, Siew Yee Wong, Kishore Bhakoo, Alexander M. Seifalian, Xu Li, John Wang
Journal: Advanced Healthcare Materials (2016)

Stimuli‐responsive nanoprobes that combine both fluorescence and magnetic resonance imaging (MRI) are anticipated to be highly beneficial for tumor visualization with high imaging sensitivity. By employing an interfacial templating scheme, a pH‐activatable fluorescence/MRI dual‐modality imaging nanoprobe is successfully developed based on the coencapsulation of MnO nanoparticles and coumarin‐545T inside a hybrid silica nanoshell. To promote cancer cell targeting with high‐specificity, the nanoprobes are also conjugated with folic acid to establish a greater affinity for cancer cells that over‐express folate receptors on their cell membrane. In the new nanosystem, MnO nanoparticles are shown to function as an efficient fluorescence quencher of coumarin‐545T prior to cellular uptake. However, fluorescence recovery is achieved upon acidic dissolution of the MnO nanoparticles following receptor‐mediated endocytosis into the low pH compartments of the cancer cells. Meanwhile, the Mn 2+ ions thus released are also shown to exert a strong T 1 contrast enhancement in the cancer cells. Therefore, by demonstrating the dual‐activatable MRI and fluorescence imaging in response to the low pH conditions, it is envisioned that these nanoprobes would have tremendous potential for emerging cancer‐imaging modalities such as image‐guided cancer therapy.
Preparation and characterization of pelletized solid dispersion of resveratrol with mesoporous silica microparticles to improve dissolution by fluid-bed coating techniques
Authors: Jian Li, Xiaoqing Miao, Tongkai Chen, Defang Ouyang, Ying Zheng
Journal: Asian Journal of Pharmaceutical Sciences (2015)

With hydrophilic surface and high surface area, porous silica has been applied to load insoluble drugs. Compared to solvent equilibrium method, resveratrol (RES)–mesoporous silica microparticles (MSM) solid dispersion prepared by fluid bed demonstrated higher drug loading and more complete dissolution. Pore volume and diameter have more remarkable effects than surface area to the drug loading and in vitro dissolution profiles. RES–polyethylene glycol solid dispersion with high drug loading showed fast but incomplete dissolution due to the recrystallization. The combination of fluid bed and MSM was an effective strategy to improve drug loading as well as dissolution for poorly water-soluble drugs.
LS³: A Method for Improving Phylogenomic Inferences When Evolutionary Rates Are Heterogeneous among Taxa
Authors: Carlos J. Rivera-Rivera, Juan I. Montoya-Burgos
Journal: Molecular Biology and Evolution (2016)

Phylogenetic inference artifacts can occur when sequence evolution deviates from assumptions made by the models used to analyze them. The combination of strong model assumption violations and highly heterogeneous lineage evolutionary rates can become problematic in phylogenetic inference, and lead to the well-described long-branch attraction (LBA) artifact. Here, we define an objective criterion for assessing lineage evolutionary rate heterogeneity among predefined lineages: the result of a likelihood ratio test between a model in which the lineages evolve at the same rate (homogeneous model) and a model in which different lineage rates are allowed (heterogeneous model). We implement this criterion in the algorithm Locus Specific Sequence Subsampling (LS³), aimed at reducing the effects of LBA in multi-gene datasets. For each gene, LS³ sequentially removes the fastest-evolving taxon of the ingroup and tests for lineage rate homogeneity until all lineages have uniform evolutionary rates. The sequences excluded from the homogeneously evolving taxon subset are flagged as potentially problematic. The software implementation provides the user with the possibility to remove the flagged sequences for generating a new concatenated alignment. We tested LS³ with simulations and two real datasets containing LBA artifacts: a nucleotide dataset regarding the position of Glires within mammals and an amino-acid dataset concerning the position of nematodes within bilaterians. The initially incorrect phylogenies were corrected in all cases upon removing data flagged by LS³.
Comparison of the Radiotherapeutic Efficacy in Nsclc with Postoperative Mediastinal Lymph Nodes Recurrence and Stage Iii
Authors: Hisao Imai, Haruyasu Murakami, Reiko Yoshino, Akira Ono, Hiroaki Akamatsu, Tetsuhiko Taira, Hirotsugu Kenmotsu, Tateaki Naito, Yoshio Tomizawa, Toshiaki Takahashi
Journal: Annals of Oncology (2014)
Phase II trial of ixabepilone and carboplatin with or without bevacizumab in patients with previously untreated advanced non-small cell lung cancer.
Authors: D. Shipley, D. R. Spigel, H. A. Burris, D. M. Waterhouse, C. D. Webb, V. Gian, L. L. Hart, F. A. Greco, J. D. Hainsworth
Journal: Journal of Clinical Oncology (2010)

7601 Background: The epothilones represent a new class of cytotoxic agents which are active in several solid tumor settings, including non-small-cell lung cancer (NSCLC). The purpose of this phase II trial was to evaluate the objective response rate (ORR) of a novel combination of ixabepilone (I) and carboplatin (C) (± bevacizumab) in advanced NSCLC. A prior phase I trial of I and C established the doses for this study (Plummer, CCR 2008). Methods: Eligible patients (pts) were aged ≥ 18 years, treatment naïve, with stage IIIB/IV NSCLC, ECOG PS 0-1, and adequate organ function. Pts received either I/C (Arm A) or I/C/bevacizumab (Arm B) per the treating physician's decision, following lead-in safety phases for both arms. Pts must have met standard bevacizumab eligibility criteria for enrollment on Arm B. Treatment: I 30 mg/m2 and C AUC = 6, both IV q21 days (Arms A and B); and bevacizumab 15 mg/kg IV q21 days (Arm B only). After 6 cycles, pts on Arm B could continue bevacizumab until progression. Results: 82 pts were enrolled from11/08-9/09. 66 pts (Arm A = 40; B = 26) are included in this analysis. Baseline characteristics were similar in each arm; except only nonsquamous histology was permitted on Arm B. The median age was 63 yrs (range 43-85); male, 50%; ECOG 0 = 45%; adenocarcinoma (A = 30%, B = 82%). The median follow-up was 7 months (range 3.6-12.5); and the median number of cycles for arms A and B were 2 and 3, respectively. 88% of pts are alive. The ORRs for arms A and B were: 28% (95% CI 15%-44%) and 46% (CI 27%-67%), respectively. 40% of pts (Arm A) and 28% (Arm B) had stable disease. Median PFS and OS have not been reached. Grade 3/4 toxicity: anemia (A-8%/B-8%), neutropenia (A-33%/B-27%), thrombocytopenia (A-17%/ B-3%), hypersensitivity reaction (A-2%/B-14%), diarrhea (A-8%/B-5%), dyspnea (A-10%/B-12%), and neuropathy (A-2%/B-0). Bevacizumab-specific toxicities included: G1/2 hypertension (17%) and proteinuria (17%), and G3 gastrointestinal perforation (appendiceal, diverticular, 1pt each). Conclusions: These ixabepilone-based regimens appear to be active in the first-line NSCLC treatment setting with expected and manageable toxicities. PFS and OS results will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech
Treatment Satisfaction, Symptom Control, and Quality of Life (Qol) with Lanreotide Autogel (Lan) in Neuroendocrine Tumour (Net) Patients with Carcinoid Syndrome (Cs): Results from the Symnet Study
Authors: P. Ruszniewski, M. Caplin, J.W. Valle, C. Lombard-Bohas, G. Poston, P. Perros, L. Holubec, G. Delle Fave, D. Smith, P. Niccoli, P. Maisonobe, P. Atlan
Journal: Annals of Oncology (2014)
Abstract 2477: Repetitive Apneic Events Augment Arterial Blood Pressure Fluctuation in Patients with Central and Obstructive Sleep Apnea Syndrome
Authors: Takeshi Takamura, Kaoru Dohi, Katsuya Onishi, Emiyo Ogawa, Hiroshi Nakajima, Masaki Tanabe, Hiroya Tamada, Masatoshi Miyahara, Mashio Nakamura, Masaaki Ito
Journal: Circulation (2008)

Background: Sleep apnea-hypopneas induce transient increases in arterial blood pressure (BP). We test the hypothesis that periodic nocturnal apneic events augment those hemodynamic responses in patients both with central and obstructive sleep apnea syndrome (SAS). Methods: Eleven patients with central SAS (CSAS: mean age 70 ± 10 years), 11 patients with obstructive SAS (OSAS: mean age 64 ± 12 years), and 8 normal controls (Control) were studied. Polysomnography was performed and BP was measured on a beat-by-beat basis by finger plethysmography all through the sleep. Severity of SAS was assessed by apnea-hypopnea index (AHI). The degree of BP fluctuation associated with periodic nocturnal apnea-hypopnea was assessed by spectral analysis of mean BP variability. Spectral plots of mean BP were calculated in 2-min segments using a maximum entropy method. Power spectrum of mean BP variability was quantified by measuring the area in the very-low-frequency band which coincides with frequency of apnea-hypopneas (sleep apnea band: 0.01– 0.03 Hz), and was normalized by dividing by the total power in the spectrum up to 0.4 Hz. Results: AHI was similar in CSAS and OSAS (38.3 ± 9.5* and 39.8 ± 11.3*, *p&lt;0.05 vs. Control: 2.5±1.6*). Repetitive fluctuations in BP coincided with periodic apnea-hypopneas were clearly observed in patients with SAS, and were more prominent in CSAS (Normalized spectral power of mean BP in sleep apnea band: 0.72 ± 0.10*† in CSAS, 0.62 ±0.13* in OSAS, and 0.46±0.07 in Control, * p&lt;0.05 vs. Control, and †p&lt;0.05 vs. OSAS). Conclusion: Periodic nocturnal apneic events augment blood pressure fluctuation in patients both with central and obstructive SAS.smoking.