tbuckley/cabot-search huggingface dataset:
Feasibility and safety of combining nimotuzumab with temozolomide and radiotherapy in adult patients with glioblastoma: An Indian clinical experience.
Authors: P. K. Julka, S. Mallick, T. Puri, S. Goyal, N. Joshi, N. Gupta, G. K. Rath
Journal: Journal of Clinical Oncology (2010)

e12509 Background: Approximately 63% of glioblastomas (GBMs) are characterized by overexpression of the epidermal growth factor receptor (EGFR). This study was planned to assess the feasibility and safety of combining EGFR Inhibitor humanized MAb-nimotuzumab with temozolomide and Radiotherapy in adult patients with glioblastoma (GBM). Methods: Eighteen patients with GBM were enrolled (15 male; 3 females; median age 50 years, range, 28 to 60 years; median Karnofsky status, 90%; range, 70% to 90%;); 7 patients had undergone complete resection and 11 patients surgical decompression. Adjuvant therapy, which commenced 4 weeks following surgery, consisted of partial brain radiotherapy (60 gray in 30 fractions over 6 weeks), and concurrent temozolomide (75 mg/m2 daily for 42 days) and nimotuzumab (200 mg IV infusion for 60 minutes once weekly for 6 weeks). Following concurrent therapy, patients received temozolomide (150-200 mg/m2 PO D1-D5 q4 weeks for 6 cycles) with maintenance nimotuzumab (200 mg IV D1 q3 weeks) till progression. Results: All patients completed concurrent and adjuvant phase of treatment; 3 patients completed 6 cycles of maintenance treatment with nimotuzumab. Two patients were in complete remission at 25 and 19 months of follow up and one patient experienced stable disease for at least 19 months. Out of 8 evaluable patients the 6 month progression-free survival rate was 62%. The combination was well tolerated except one grade IV adverse event of thrombocytopenia that recovered on conservative therapy. Conclusions: Preliminary results suggest that the combination of nimotuzumab with temozolomide and radiotherapy in treatment of GBM is feasible and safe and can lead to improved survival outcomes in these patients. Future studies with large number of patients are warranted in similar setting. No significant financial relationships to disclose.
Ganglioside Profiles of Metastases and of Metastasizing and Nonmetastasizing Rat Primary Mammary Carcinomas&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn4"&gt;4&lt;/xref&gt;
Authors: V P Skipski, S P Carter, O I Terebus-Kekish, F J Podlaski, R H Peterson, C C Stock
Journal: JNCI Journal of the National Cancer Institute (1981)

The possible relationship between ganglioside levels and ganglioside profiles in malignant tumors and the formation of metastasis was investigated by the analysis of gangliosides in metastasizing SMT-2A and nonmetastasizing MT-W9a mammary carcinomas as well as in metastases formed from SMT-2A tumors. The extracted lipid of SMT-2A tumors contained 3.3-fold more lipid-bound sialic acid than did that of MT-W9a tumors. THe differences were also substantial in the ganglioside profiles in these 2 tumors. Plasma membranes isolated from SMT-2A tumors also contained 1.8-fold more lipid-bound sialic acid than did plasma membranes from MT-W9a tumors. Ganglioside profiles in two types of SMT-2A secondary tumors were investigated. The lipid-bound sialic acid content was 1.5-fold higher in tumor nodules in the lung and 1.9-fold higher in axillary lymph node tumors than it was in primary SMT-2A tumors. The ganglioside pattern in these 2 secondary tumors generally reflected that found in SMT-2A: high levels of gangliosides containing three or four sialic acid molecules. The lung nodule retained its specificity with respect to lipid-bound sialic acid content and ganglioside pattern after the lung nodule was sequentially transplanted three times to the site of the original SMT-2A tumor growth.
Correspondence
Authors: None Unknown
Journal: Cardiovascular Research (1997)

We read with great interest the review by Mubagwa and w x co-workers 1 on the effects of adenosine on the cardiovascular system. In this review the diagnostic effects of adenosine in arrhythmias were discussed. We would like to present some additional, clinically important effects and adverse effects of adenosine, focusing on arrhythmias. 1. Adenosine can not only unmask pre-excitation but in some cases can abolish pre-excitation due to the direct inhibitory effect on decremental pathway conduction conw x taining AV node-like structure 2 . 2. The therapeutic and diagnostic role of adenosine in wide-complex tachycardia was described in the review, but it may also be added that it could cause life-threatening conditions by precipitating atrial fibrillation in the Wolffw x Parkinson-White syndrome 3 . 3. Adenosine is a very useful drug in distinguishing between ventricular and supraventricular tachycardias and among the different forms of supraventricular tachycardias. In addition, adenosine may provoke potentially dangerous arrhythmias by accelerating the heart rate due to enhanced w x Ž . sympathetic tone in atrial flutter 4 Fig. 1 . 4. Another possibly important clinical value of adenosine is help in distinguishing between ventricular extrasystole and parasystole by causing temporary SA or AV w x Ž . block, or by terminating parasystolic activity 5 Fig. 2 .
Routine preventive care and cancer surveillance in long-term survivors (LTS) of colorectal cancer: Results from NSABP Protocol LTS-01
Authors: H. Kunitake, P. Zheng, G. Yothers, S. Land, L. Fehrenbacher, J. K. Giguere, D. L. Wickerham, P. A. Ganz, C. Y. Ko
Journal: Journal of Clinical Oncology (2009)

6500 Background: Little is known about the use of routine preventive care and cancer surveillance in long-term colorectal cancer survivors. NSABP LTS-01 is a study that examines the use of such services in long-term colorectal cancer survivors previously treated in NSABP adjuvant trials. Methods: Long-term colorectal cancer survivors (≥ 5 years) were recruited from five completed NSABP treatment trials (Protocols C-05, C-06, C-07, R-02, R-03) at 65 study sites. A survey battery for long-term survivors of colorectal cancer (LTS-01) was developed. A 1:4 comparison cohort case-matched by age, gender, race, and education was created from the 2005 National Health Interview Survey. Contingency tables and multivariate models were used to compare cohorts and determine predictors of preventive care and cancer surveillance. Results: 649 LTS-01 patients (625 colon, 24 rectal) completed the interview; 57% male, mean age 66.1yr (SD 10.5), median survival 8 yrs. LTS-01 patients were more likely to have a usual source of healthcare than the NHIS cohort (98% vs. 93%, p &lt; 0.0001). The number of ER visits in the previous 12 months was not significantly different between the two groups. LTS-01 patients were more likely to have received a flu shot in the past 12 months (68% vs. 42%, p &lt; 0.0001) and were also more likely to have undergone cancer screening by Pap smear (67% vs. 54%, p &lt; 0.001), mammogram (85% vs. 71%, p &lt; 0.001), and PSA test (84% vs. 75%, p &lt; 0.001). For CRC surveillance, 3% did not have a colonoscopy, 13% had not had a CEA test, and 34% did not have a CT scan in the last 5 years. The best predictor of the receipt of these cancer screening tests was the presence of health insurance (OR 2.6–4.5). No factor was uniformly associated with colorectal cancer surveillance. Conclusions: Long-term survivors of colorectal cancer achieve better routine preventive care including cancer screening than the general population. However in these stage II and stage III cancer patients cancer surveillance is variably performed. No significant financial relationships to disclose.
Breast cancers negative for estrogen receptor but positive for progesterone receptor, a true entity?
Authors: D T Kiang, R Kollander
Journal: Journal of Clinical Oncology (1987)

By the conventional steroid-binding assay method for receptor, 3% of 1,095 primary breast cancers (or 10.6% of 263 premenopausal tumors) were classified as negative for estrogen receptor (ER), but positive for progesterone receptor (PR). The true ER status in this rare group of tumors was further investigated by the enzyme-immunoassay (EIA) or immunocytochemical (ICA) staining method using monoclonal antibodies H222 and D547. Immunoreactive ER was present in nine ER-/PR+ tumors studied, whereas it was not detectable in nine age-matched ER-/PR- tumors. Immunoreactive ER was also present in 24 ER+ breast cancers studied, and was particularly higher in tumors that were PR+. Measurement of immunoreactive ER by monoclonal antibody method provides certain advantages over the conventional dextran-coated charcoal (DCC) method, especially in ER-/PR+ tumors.
Time dependence of prognostic values of gene-expression signatures for breast cancer
Authors: K. F. Lau
Journal: Journal of Clinical Oncology (2009)

11085 Background: Gene-expression signatures were shown to be prognostic and predictive for breast cancer but their performances over time have not been investigated. Methods: Recurrence score (RS) of oncotype, 70-gene profile (SGP) of Mammaprint, intrinsic subtype (IS) and wound signature (WS) were analyzed using a single dataset of 295 samples from Fan et al. (Fan et al. N Engl J of Med 2006; 355:560–9). Time-varying coefficient Cox models were used to estimate the time-dependent hazard ratios (HR) for relapse-free survival (RFS). Annualized RFS hazard rates were estimated using cubic splines. Concordance between RS and SGP was calculated for different intrinsic subtypes in all 295 samples and was evaluated in a subset of 173 ER+ samples not in the training set of SGP for unbiased comparison. Results: For the high risk groups of RS, SGP, IS and WS, hazard rates peaked around the 2 nd year from surgery and decreased rapidly over time. For the low risk groups, hazard rates also peaked around the 2 nd yr but remained fairly constant over time. Hazard ratios of high vs. low risk groups of RS at yr 2, 5 and 10 were 17.0 (8.4–34.0), 4.0 (2.0–8.0), 1.7 (0.83–3.4). For intermediate vs. low risk groups of RS, the corresponding HRs were 2.7 (1.1–7.0), 5.0 (1.1–7.4), 1.6 (0.63–4.2). Poor vs. good groups of SVP had HRs of 7.4 (4.5–12.1), 3.6 (2.2–5.9), 2.0 (1.2–3.3) at yr 2, 5, 10. HRs of Luminal B (LB), Basal-like (BL), HER2/ER- (HER2), Normal-like (NL) vs. Luminal A (LA) of Intrinsic Subtypes were 6.8 (4.0–11.5), 5.7 (3.2–10.0), 7.6 (4.0–14.1) and 1.7 (0.9–3.3) at yr 2. HRs at yr 5 were 4.0 (2.3–6.8), 0.7 (0.4–1.2), 1.1 (0.6–2.0) and 2.3 (1.2–4.4) respectively. For WS, HRs at yr 2, 5, 10 were 6.3 (3.3–11.9), 2.9 (1.6–5.6) and 2.2 (1.2–4.1) respectively. Concordance rates of RS and SVP were 1.0, 0.91, 0.86, 0.72 and 0.62 for BL, HER2, LB, LA, NL of Intrinsic Subtypes. In 173 ER+ samples not present in the SGP training set, concordance rate between RS and SVP was 0.77 (Cramer's V = 0.56); the same as in the whole set of 225 ER+ patients (Fan et al. N Engl J of Med 2006; 355:560–9). Conclusions: Prognostic values of gene-expression signatures decrease over time. They can best predict breast cancer relapse during the first 5 years. Concordance between RS and SPV is highest in the basal-like tumors and lowest in the Luminal B and Normal-like subtypes. No significant financial relationships to disclose.
Evaluation of relation of RAD51 and the effect of chemoradiation therapy for advanced rectal cancer.
Authors: T. Iwata
Journal: Journal of Clinical Oncology (2010)

e14116 Background: In an attempt to improve local control and survival in patients with advanced rectal carcinoma, neoadjuvant chemoradiation therapy (CRT) has been increasingly used in patient management. However, a significant proportion of patients shows poor response to adjuvant CRT. Thus, the ability to predict CRT responsiveness in patients with rectal cancer would benefit effective management. Several molecular markers related to regulation of cell cycle, apoptosis, or DNA repair have been proposed as candidate predictors of therapeutic response to CRT, but, to date, none has been definitively proven to be predictive of CRT response. To evaluate the use of various molecular markers as predictors of the response to CRT in rectal carcinoma, we investigated immunohistochemical expressions of RAD51 in preoperative biopsy and resected specimen of 43 advanced rectal carcinomas. Methods: A total of 43 patients who were suffered from distal advanced rectal adenocarcinoma (clinical and radiological T3 or T4 stage) were investigated. All patients received preoperative CRT consisting of 4 cycles of S-1 (80 mg/m2 per day), concurrent with 40 Gy of pelvic irradiation. All patients completed neoadjuvant treatment and waited 6 weeks after completion of CRT before having curative radical resection. The relationship between pathological responses of the tumors after therapy and expression of RAD51 was investigated by immunostaining of preoperative biopsy and resected specimen. Results: Among 43 cases of rectal cancer patients with preoperative CRT, 18 cases were PR, 25 were SD in RECIST, and 18 were grade 1 (1a: 11, 1b: 7), grade 2: 19 and grade 3: 5 cases pathologically. Thirty nine cases (90.7%) were avoided from lateral lymph node dissection. RAD 51 expression showed in 23 cases of SD (92%), 2 cases of PR (11.1%) in RECIST, 16: 15 cases of grade 1 (biopsy: resected; 88.9: 83.3%), 8: 8 cases of grade 2 (both 49.5%) and 0: 1 case of grade 3 (0: 20.0%) pathologically. Two year survival was 90.2%. Conclusions: There is significantly reverse correlation between pathological evaluation of preoperative CRT and expression of RAD51. RAD51 could be one of predictive factor of preoperative CRT for advanced lower rectal cancer. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration The Research Support Foundation of The University of Tokushima and Taiho Pharmaceutical
Gene expression profiling (GEP) in multiple myeloma (MM): Distinguishing relapses with high-risk transformation from those with sustained low risk.
Authors: J. Sawyer, J. D. Shaughnessy, J. Haessler, A. Hoering, B. Barlogie
Journal: Journal of Clinical Oncology (2010)

8122 Background: GEP-defined high-risk identifies ∼15% of untreated patients with a dismal outcome. Among the 85% with low-risk MM, high-risk transformation can be observed at the time of relapse. The purpose of this investigation was to determine whether, among patients relapsing on Total Therapy 2 (TT2) and TT3, baseline features existed that could distinguish patients with sustained low-risk (LOLO) from those with high-risk progression (LOHI) versus those with HIHI. Methods: Of 351 TT2 and 510 TT3 patients with baseline (BL) GEP information, a total of 237 have relapsed with relapse GEP available in 127. We are reporting here on the frequency of LOHI transformation relevant to baseline characteristics and treatment details (TT2 control v thalidomide arm, TT3), timeliness of completion of therapy (CT), duration of disease control antedating relapse (DDC). Results: From our MM data base, we identified 60 LOLO, 26 LOHI and 34 HIHI. Distinguishing BL GEP features included higher median GEP risk score (RS) values in HIHI (1.136) v LOHI (0.289) v LOLO (-0.270) (p<0.001); delTP53 was more prevalent in HIHI (27%) v LOHI (8%) v LOLO (7%) (p=0.017); concomitancy of amp1q21/del1p was more frequent in HIHI (36%) than LOHI (17%) than LOLO (9%) (p=0.005). Among non-GEP BL parameters, CA-13/CA- hypo, high LDH (≥300 and ≥ 500 U/L), low albumin (<3.5 g/dL) and high B2M (> 5.5 mg/L) also were significantly more common in HIHI than LOHI and LOLO. Applying logistic regression, LOLO could be distinguished from LOHI by the presence metaphase cytogenetic abnormalities (CA) of the del13 variety (CA13; OR=0.37, p=0.055). Conclusions: Although HIHI is readily distinguishable from LOHI and LOLO by several baseline parameters, the absence of CA13 was the only baseline variable with near-significance in predicting, in low-risk myeloma, low- from high-risk relapse, attesting to the far- reaching power of metaphase karyotyping. No significant financial relationships to disclose.
Measuring clinical pathway compliance using a simulated patient approach with clinical performance and value (CPV) vignettes.
Authors: Karen K. Fields, Hatem Hussein Soliman, Eliot Lawrence Friedman, Rachel V. Lee, Maria Czarina Acelajado, Diana Tamondong-Lachica, John W. Peabody
Journal: Journal of Clinical Oncology (2013)

96 Background: Although clinical pathways have the promise to improve the quality of care, they have had limited success changing practice or standardizing care. Moffitt Cancer Center (MCC) has &gt; 40 pathways incorporating interdisciplinary care strategies linked to evidence and decision support tools. Methods: To improve compliance with pathways we used an innovative measure to quantify quality of care, CPV vignettes. CPV vignettes are validated, simulated clinical scenarios constructed so that adherence to pathways is clear-cut. Providers care for identical cases so there is no need for case mix adjustment. After completing each case, providers are given personalized feedback. Twelve breast cancer (ca) vignettes were developed by MCC breast medical oncologists and surgeons and QURE, a healthcare measurement company. The cases were developed using MCC pathways, other evidence and core issues such as diagnostic work-up. The vignettes were randomized at the department level and given to all MCC providers who care for breast ca patients. A total of 18 providers took 34 CPVs: 7 medical oncologists, 6 advanced practitioners and 5 surgeons. QURE-trained physician abstractors blinded to the CPV-taker’s identity scored each vignette and provided confidential feedback. Results: Total scores for providers averaged 55.4%, s.d. 12.5%, a typical score for a CPV baseline study. Adherence to pathways varied by area with the highest concordance for radiation and hormonal therapy and the lowest for management of axillary lymph nodes (see Table). Conclusions: Adherence to pathways varied among providers and by clinical domain. Ongoing efforts will evaluate the impact of serial CPV measurement on pathway adherence. Simulations simplified the task of determining pathway adherence making pathway compliance at the physician level a reasonable expectation and standardization at the group level scientifically rigorous and feasible. [Table: see text]
Prognostic and predictive markers in recurrent high-grade glioma (HGG): Results from the BR12 randomized trial.
Authors: M. Brada, V. P. Collins, K. Ichimura, L. C. Thompson, R. Gabe, S. P. Stenning
Journal: Journal of Clinical Oncology (2010)

2035 Background: BR12 randomised 447 chemo-naïve pts with recurrent HGG between PCV and TMZ, subrandomising TMZ between 200 mg/m2 for 5 days (TMZ5) and 100 mg/m2 for 21 days (TMZ21). Tumour samples were requested on all pts; 354 (79%) samples were obtained, 314 sufficient for molecular analysis of potential prognostic and predictive markers (mkrs). Methods: DNA was isolated from micro-dissected sections of tumour in paraffin blocks. Array- CGH data using a custom tiled path array of chromosome (chr) 1 and 19 incorporated into a 1 Mb genome-wide array determined locus copy number. IDH1 and IDH2 mutation was identified by pyrosequencing and MGMT methylation (meth) by bisulfite modification followed by PCR and pyrosequencing reporting % meth at each of 16 CpGs. The following mkrs were assessed: chr 1, 1p, 1p36, 7, 10, 19, 19q and 19q13 status; PTEN, MGMT and CDKN2A copy number; EGFR, MDM2, CDK4 and PDGFRA amplification; TP53, IDH1 and IDH2 mutation. Each was added to a Cox regression survival model including age, gender, tumour grade and WHO performance status. An initial exploratory analysis of MGMT meth status has been carried out using mean % meth across all 16 CpGs. Further analyses will examine individual CpG data. Results: MGMT pyrosequencing succeeded for 91% of pts on whom it was attempted, aCGH; 93% and 87% for TP53 and IDH1. Total loss of 1p was noted in 2%, (95% CI 0.5%, 4.7%); loss of 1p36 in 23%, (95% CI 18%, 28%). IDH1 mutation, PTEN copy number, EGFR amplification, chr 10 status and MGMT meth were individually prognostic but only IDH1 mutation (hazard ratio [HR] mutated vs. normal = 0.54, p = 0.008); and MGMT meth% (HR > 10% vs ≤ 10% = 0.57, p = 0.001) were independent of each other and the clinical factors. There was no evidence of a predictive effect for benefit of TMZ over PCV for any of these mrks or for TMZ5 over TMZ21 for MGMT meth. Conclusions: In this cohort IDH1 mutation and MGMT meth are strong, independent prognostic factors. Initial analysis suggests a prognostic but not predictive role for meth status in this setting with prolonged administration of TMZ21 failing to overcome the prognostic relevance of unmethylated MGMT. Further analysis and modeling of the overall and individual CpG data may provide further clarification. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Bristol-Myers Squibb, Roche Schering-Plough
Surgical Management of De Novo Stage IV Breast Cancer
Authors: Jilma Patrick, Seema Ahsan Khan
Journal: Journal of the National Comprehensive Cancer Network (2015)

Management of the intact primary tumor in women presenting with stage IV breast cancer has classically been determined by the presence or absence of symptoms. However, multiple retrospective reviews completed over the past decade suggest a survival advantage with resection of the intact, asymptomatic primary tumor in these women. These reviews are not without bias, and recently completed randomized trials do not support a significant survival benefit, although local control benefits may exist. Completion of ongoing trials is needed to reach a definitive conclusion regarding the merit of primary tumor resection for local control and survival. Until unbiased data are available, local therapy for the asymptomatic primary cannot be routinely recommended, but may be considered in selected individuals, with multidisciplinary input, when systemic disease is well controlled.
Abstract 11872: Receptor for Advanced Glycation End Products Silencing Suppress Arrhythmia and Improve Electrical Conduction by Increasing Connexin43 via Wnt1 Activation in Rat Model for Ischemia Reperfusion Injury
Authors: Hyelim Park, Hyewon Park, Jisoo Lim, Hui-Nam Pak, Moon-Hyoung Lee, Donghoon Choi, Sun Hwa Kim, Boyoung Joung
Journal: Circulation (2014)

Introduction:  Expression of receptor for advanced glycation end products (RAGE) plays a crucial role in mediating cardiac ischemia/reperfusion (I/R) injury. Although the detailed mechanisms are unknown, RAGE silencing has been suggested as a cardioprotective therapy. I/R injury is related to increased GSK 3β, and Wnt family of genes is one of the regulators of gap junction expression and function.   Hypothesis:  This study evaluated the effect of RAGE silencing on electrical conduction, arrhythmia, connexin43 (Cx43) and Wnt activation in rat I/R injury model.   Methods:  Sprague-Dawley rats underwent 1 hour of ligation of the left anterior descending artery, followed by reperfusion for 2 hours (I/R, n=11). RAGE-siRNA/PEI-DA nanocarriers were treated after I/R injury for RAGE silencing (I/R+RAGE, n=10), and scrambled RNA for the discrimination of RNA effect (I/R+scRNA, n=9). Hearts were perfused, optically mapped to analyze action potential durations (APD), intracellular Ca 2+  transients, and restitution kinetics (RK), and tested for VF vulnerability.   Results:  Compared with control (n=10), I/R rats had shorter APD, slower conduction velocity (CV; p   Conclusions:  RAGE silencing therapy suppressed VT/VF in I/R hearts by increasing CV from a combination of the inhibition of GSK 3β and enhancing Wnt1, β-catenin and Cx43 in rat model for I/R injury.