tbuckley/cabot-search huggingface dataset:
Efficacy and safety of PF-00299804 (PF299) in patients (pt) with advanced NSCLC after failure of at least one prior chemotherapy regimen and prior treatment with erlotinib (E): A two-arm, phase II trial
Authors: P. A. Janne, K. Reckamp, M. Koczywas, J. A. Engelman, D. R. Camidge, A. Rajan, F. Khuri, J. Q. Liang, J. O'Connell, G. Giaccone
Journal: Journal of Clinical Oncology (2009)

8063 Background: Options are limited for pts with NSCLC following chemotherapy and E. PF299 is an oral irreversible small molecule inhibitor of the HER-1,-2, and -4 tyrosine kinases. Based on non-clinical and phase I NSCLC data, this ongoing phase II U.S. trial evaluates PF299 in pts with NSCLC (KRAS wild-type) who have progressive disease after at least 1 prior chemotherapy regimen and after E. Methods: Pts were enrolled by histology: adenocarcinoma (Arm A) and non-adenocarcinoma (Arm B), and received PF299 45 mg QD. Endpoints include objective response rate, duration of response, progression-free survival, survival, safety/tolerability, and pharmacokinetics. Pharmacodynamic endpoints include assessment of serum levels of HER2 and EGFR extracellular domains. Tissue and blood KRAS assays, and EGFR studies on available tissue, are also being performed. Forty-four and 22 response-evaluable pts were planned to be enrolled into Arms A and B respectively. Results: Thirty-four pts with progressive NSCLC (25 female, 14 smoker) have enrolled to date (Arm A: 30; Arm B: 4): median duration of prior E: 11.5 months; median time since E: 2.5 months. Among 20 response-evaluable pts, stable disease (SD) was observed in 9/18 pts in Arm A, and 1/2 pts in Arm B: median duration of SD: 11.5 weeks [range 6+, 32+ weeks]. Observation of disease control included pts who had recently (≤8 weeks) discontinued E; and also pts whose tumor had known EGFR T790M mutations. At time of data cutoff, confirmation per RECIST of 2 partial responses is pending. The most common treatment-related AEs were skin and gastrointestinal disorders, with grade 3 AEs in 19% and 13% of pts, respectively. Two pts experienced grade 4 pulmonary embolus/dyspnea deemed possibly treatment-related, both in the setting of progressive disease. Conclusions: PF299 shows encouraging activity in NSCLC pts after failure of prior chemotherapy and E. The AE profile was predictable and consistent with the prior phase I trial. At submission, enrollment in the adenocarcinoma arm is complete and enrollment in the non-adenocarcinoma arm continues; updated efficacy data and tumor characterization will be presented. [Table: see text]
The Oncology Symptom Control and Information Resource (OSCIR): Using information technology to improve the management of cancer treatment-related side effects
Authors: C. DeAngelis, A. Giotis, L. F. Charbonneau, S. Zannella
Journal: Journal of Clinical Oncology (2007)

17031 Background: Management of treatment related side effects remains a challenge despite availability of effective therapies and management guidelines. The main reasons include ineffective assessment of the patient's experience, inability to access prevention and management guidelines in a timely manner, poor documentation and inefficient communication within the patient's care team. We postulate treatment related side effects could be more effectively managed using software designed to assist assessment and improve communication of the patient's experience. Methods: Software specifications included internet-based wireless capability, linking to existing electronic databases and facilitated data entry (drop down menus, check boxes, pop up windows, etc.). Oncology literature was reviewed to identify appropriate symptom assessment questionnaires, prevention and treatment strategies. The National Cancer Institute Common Terminology Criteria for Adverse Events v.3.0 was adapted. An iterative process was used for software development; content and functionality was discussed with programmers on an ongoing basis. This process is aimed at providing software that more completely meets the needs of users. Feedback from oncology pharmacists was sought regularly. Results: OSCIR has been developed to facilitate the assessment and management of nausea, vomiting, diarrhea, constipation, mucositis, and palmar-plantar erythrodysesthesia. Each side effect module includes onset and resolution, signs and symptoms, automated grading, non- and pharmacological management. Program features include downloading of electronic demographic information, chemotherapy regimen, laboratory results, call back roster, and communication tools. Conclusions: Using the iterative process we have created a program that addresses the needs of pharmacists involved in the assessment and management of treatment-related side effects. Further development will incorporate feedback from other members of the patient's care team and will include additional side effects and features. No significant financial relationships to disclose.
Randomized phase II/III trial of paclitaxel (P) plus carboplatin (C) with or without bevacizumab (NSC #704865) in patients with advanced non-squamous non-small cell lung cancer (NSCLC): An Eastern Cooperative Oncology Group (ECOG) Trial - E4599
Authors: A. B. Sandler, R. Gray, J. Brahmer, A. Dowlati, J. H. Schiller, M. C. Perry, D. H. Johnson
Journal: Journal of Clinical Oncology (2005)

LBA4 Background: The results of a randomized phase II trial of PC +/- bevacizumab (A) suggested improved activity for the combination of PCA when compared to PC alone (Johnson DH, et al JCO 2004). Grade 5 hemoptysis was seen in the PCA arms & multivariate analysis suggested squamous cell histology to be a significant risk factor. Methods: The primary endpoint of this randomized trial was to compare the effects of the addition of A to PC on overall survival in patients (pts) with previously untreated non-squamous NSCLC. Secondary endpoints included response rate, time to progression, and tolerability. Correlative studies consisted of pre & post-treatment circulating VEGF, VCAM, E-selectin & bFGF as prognostic & predictive markers. Other eligibility criteria included ECOG PS 0 or 1, & adequate hematologic, renal, & hepatic function. Pts with brain metastases were excluded. Pts were randomized to receive P 200 mg/m2 + C AUC=6 on day 1 every 3 wks or PC + A 15mg/kg day 1 (PCA) every 3 weeks. Pts on PCA continued bevacizumab after 6 cycles until progressive disease or intolerable toxicity. With at least 842 pts entered & a total information of 650 deaths, this study was designed to have 91% (80.5%) power to detect a 30% (25%) improvement in median survival from 8 months on PC to 10.4 (10.0) months on PCA with an overall one-sided type I error of 2.5%. Interim analyses were planned. Results: This study opened in 7/01, was suspended for a planned toxicity evaluation from 2–8/02. Accrual was completed in 4/04 with 444 pts assigned to PC & 434 to PCA. 10% were stratified as non-measurable, 11% having prior RT, 75% as prior weight loss < 5%, and 14% as stage IIIB. The 1st interim analysis was conducted at 48% information using data available as of 9/7/04. The independent DMC did not recommend release of Results: The 2nd interim analysis of overall survival will take place in 3/05. If the criteria for early stopping are met (+/-), then the interim study results will be released for presentation. Conclusions: To be reached if the data is available in 1st quarter of 2005. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Genentech Bristol-Myers Squibb, Genentech Bristol-Myers Squibb, Genentech
Low Foxp3 cells infiltrate is a marker of pathological complete response to neoadjuvant chemotherapy in breast carcinoma
Authors: S. Ladoire, L. Arnould, L. Apetoh, B. Coudert, F. Martin, B. Chauffert, P. Fumoleau, F. Ghiringhelli
Journal: Journal of Clinical Oncology (2007)

21011 Background: T cell infiltration is associated with tumor prognosis in many cancer types. To assess the capacity of neoadjuvant chemotherapy to impact on T cell infiltration in breast cancer, we investigated if pathological complete response (pCR) to neoadjuvant chemotherapy correlated with T cell infiltration Methods: CD3, CD8 and Foxp3 positive cells were detected by immunohistochemistry in a series of 56 breast cancer patients treated by neoadjuvant chemotherapy. Infiltrates were analysed before and after the end of the treatment. Cytotoxic cells were stained using anti-Granzyme b and TiA1 antibodies Results: Poor prognosis factors (negative hormonal receptors, high tumor grade and nodal involvement) correlated with a significant higher number of CD3, CD8 and Foxp3 cells infiltrates before chemotherapy. Chemotherapy only induced a decrease in the number of Foxp3 cells (p&lt;0.01) while the level of CD8 and CD3 cells were maintained (p=0.8). pCR were observed in 12 patients who had a drastic decrease of Foxp3 positive cells (mean:1.6±1.4 versus 0.08 ± 0.2; p&lt;0.001) while these cells remained elevated in non responders (mean: 1.5±1 versus 1 ± 1 p=0.2). Furthermore, using a cutoff criterion that combined high CD8 infiltration and no Foxp3 cell infiltration on surgical specimens we could predict pCR with a sensitivity of 75% and a specificity of 93%. Cytotoxic effector cells infiltrate was only enhanced in pCR. In multivariate analysis, only high tumor grade and low Foxp3 cell infiltration on final histological specimens were independent predictors of a pCR (HR (95% CI): 17,7394 (1,1 to 272,5) p=0.04 and 0,0132 (0,0002 to 0,9) p=0.04 respectively). The Kaplan Meier estimate of metastasis-free survival indicated a trend toward higher percentage of metastases-free patients in pCR and combined immunological criterion (Log rank test, p=0.1 and p = 0.12 respectively) Conclusions: These findings indicate that pathological complete response to neoadjuvant chemotherapy is associated with an immunological profile consisting in absence of immunosuppressive Foxp3 cells, presence of high number of CD8 T cells, and an increased number of cytotoxic cells. These results argue for the induction of an antitumor immune response by chemotherapy in this group of patients No significant financial relationships to disclose.
The conversion ratio for opioid rotation from hydrocodone to other strong opioids in cancer patients.
Authors: Akhila Sunkepally Reddy, Sriram Yennu, Jimin Wu, Diane Liu, Suresh K. Reddy, Maxine De la Cruz, Eduardo Bruera
Journal: Journal of Clinical Oncology (2014)

164 Background: Cancer pain is initially treated with intermediate strength analgesics such as hydrocodone and subsequently escalated to stronger opioids. There are no studies on the process of opioid rotation (OR) from hydrocodone to strong opioids in cancer patients. Our aim was to determine the conversion ratio (CR) for OR from hydrocodone to morphine equivalent daily dose (MEDD) in cancer outpatients. Methods: We reviewed records of 3,144 consecutive patient visits at our Supportive Care Center in 2011-12 for OR from hydrocodone to stronger opioids. Data regarding demographics, Edmonton Symptom Assessment Scale (ESAS), and MEDD were collected in patients who returned for follow up within 6 weeks. Linear regression analysis was used to estimate the CR between hydrocodone and MEDD. Successful OR was defined as 2-point or 30% reduction in the pain score and continuation of the new opioid at follow up. Results: 170/3,144 patients underwent OR from hydrocodone to stronger opioid. 72% were white, 56% male, and 81% had advanced cancer. The median time between OR and follow up was 21 days. 53% had a successful OR with significant improvement in the ESAS pain and symptom distress scores. In 100 patients with complete OR and no worsening of pain at follow up, the median CR (Q1-Q3) from hydrocodone to MEDD was 1.5 (0.9-2) and hydrocodone dose to MEDD correlation was.52 (P&lt;0.0001). The correlation of CR with hydrocodone dose was -0.52 (P&lt;0.0001). The median CR of hydrocodone to MEDD was 2 in patients receiving &lt; 40mg of hydrocodone/day and 1 in patients receiving ≥ 40mg of hydrocodone/day (P&lt;0.0001). The median conversion ratio of hydrocodone to morphine was 1.5 (n=44) and hydrocodone to oxycodone was 0.9 (n=24). Conclusions: Hydrocodone is 1.5-fold stronger than Morphine. The median conversion ratio from hydrocodone to MEDD varied according to hydrocodone dose/day. [Table: see text]
Gradient between north and south remains
Authors: M J Hacking
Journal: BMJ (1994)

EDITOR, - It is surprising that Margaret Eames and colleagues occasionally mentioned, but did not incorporate in their abstract or their section on the “implications for the Health of the Nation,” the overall geographical finding that premature mortality increases steeply from the south to the north of England.1 The differences in regional mortality have been fairly constant for at least the past 30 years2,3 and …
Long-term analysis of breast-conserving therapy (BCT) vs. mastectomy in early operable breast cancer
Authors: B. K. Rack, W. Janni, B. Strobl, M. Heinrigs, C. Schindlbeck, T. Blankenstein, D. Rjosk, G. Rammel, H. Sommer, K. Friese
Journal: Journal of Clinical Oncology (2005)

9612 Background BCT is the most frequently performed surgical treatment for primary breast cancer resulting in optimal cosmetic outcome. Aim of this study was to evaluate safety and outcome in comparison to mastectomy in a large population-based southern German breast cancer database with a long follow-up. Methods In a retrospective matched pair analysis on 1574 women with primary operable breast cancer, we compared local recurrence rates, DDFS and OAS after BCT and mastectomy. 787 pairs of pts with comparable tumor size, nodal status, grading, age and menopausal status were selected. The significance of various prognostic parameters at the time of primary diagnosis was evaluated, by multivariate analyses, with respect to locoregional recurrence, DDFS and OAS. The median follow-up was 58 months. Results Risk factors at primary diagnosis, such as tumor size and lymph node status, were comparable between both groups. Mastectomy resulted in a five-year survival rate of 93% compared to 94% with BCT (p=.29) and a DDFS rate of 89%, compared to 91% (p=.09), respectively. 92% of pts treated with mastectomy were free of loco-regional recurrence five years after primary diagnosis, while 93% of pts showed no sign of local recurrence after BCT (p=.13). However, node-negative pts showed an increased risk for loco-regional recurrence, when treated with BCT (p=.02). Multivariate analysis, allowing for type of surgery, tumor size, nodal status, grading, hormone receptor status and menopausal status showed that lymph node status (p<.001) and grading (p=.04) were the most significant single prognostic factors for survival, while DDFS was only predicted by nodal status (p<.001) and loco-regional recurrence by grading (p=.03), respectively. The primary surgical therapy was shown to be of no statistical influence (p=.17). Conclusions This analysis confirms previously published data which show equivalence of BCT and mastectomy in terms of OAS, DFS and local recurrence rate. These reassuring data are part of repeated regional quality assurance evaluations, monitoring adverse treatment effects. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, AstraZeneca, Aventis, Novartis, Pfizer
MicroRNA Regulation of Atherosclerosis
Authors: Mark W. Feinberg, Kathryn J. Moore
Journal: Circulation Research (2016)

Atherosclerosis and its attendant clinical complications, such as myocardial infarction, stroke, and peripheral artery disease, are the leading cause of morbidity and mortality in Western societies. In response to biochemical and biomechanical stimuli, atherosclerotic lesion formation occurs from the participation of a range of cell types, inflammatory mediators, and shear stress. Over the past decade, microRNAs (miRNAs) have emerged as evolutionarily conserved, noncoding small RNAs that serve as important regulators and fine-tuners of a range of pathophysiological cellular effects and molecular signaling pathways involved in atherosclerosis. Accumulating studies reveal the importance of miRNAs in regulating key signaling and lipid homeostasis pathways that alter the balance of atherosclerotic plaque progression and regression. In this review, we highlight current paradigms of miRNA-mediated effects in atherosclerosis progression and regression. We provide an update on the potential use of miRNAs diagnostically for detecting increasing severity of coronary disease and clinical events. Finally, we provide a perspective on therapeutic opportunities and challenges for miRNA delivery in the field.
Enzymatic Potential for Preformed Purine Metabolism in Hepatomas With Different Growth Rates 2
Authors: Allen R. Rhoads, Harold P. Morris
Journal: JNCI Journal of the National Cancer Institute (1977)

The activities of five enzymes associated with purine reutilization and interconversion were determined in hepatomas with different growth rates. The activities of hypoxanthine and adenine phosphoribosyltransferases in this spectrum of hepatomas ranged from 50 to 170% of normal control liver. The ratio of activity of hypoxanthine phosphoribosyltransferase to adenine phosphoribosyltransferase was moderately reduced in hepatomas when compared to that in normal liver. No consistent alteration in the activity of guanine aminohydrolase was observed within the spectrum of these hepatomas. The activity of xanthine oxidase in hepatomas was either normal or significantly reduced when compared to the levels of activity exhibited by normal controlliver. Only purine nucleoside phosphorylase activity was consistently and significantly altered in ali hepatomas. This enzyme activity was reduced to levels of 9–42% of those in normal liver. Purine nucleoside phosphorylases from hepatoma and normal liver were similar, as judged by their behavior on DEAE-cellulose column, polyacrylamide gel electrophoresis, and kinetic analysis. Although several of the enzyme activities were markedly reduced in the most rapidly growing tumors, the enzymes did not exhibit any correlation with tumor growth rate, and their activity in host liver was not appreciably changed by the growing tumor.
Subtle neuropsychiatric sequelae of carbon monoxide intoxication: two case reports
Authors: J W Jefferson
Journal: American Journal of Psychiatry (1976)

Carbon monoxide intoxication may result in subtle neuropsychiatric abnormalities that can be overlooked, misdiagnosed, or not fully appreciated. The author describes two patients who developed subtle but troublesome emotional cognitive problems following carbon monoxide poisoning and stresses the value of sequential neuropsychological testing and judicious psychiatric counseling in such cases.
The Neoadjuvant Model and Complete Pathologic Response in Breast Cancer
Authors: Veerle Bossuyt, Christos Hatzis
Journal: JAMA Oncology (2016)

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Surgical management of carcinoma gall bladder: MCS experience
Authors: C. Khandelwal, V. P. Singh, J. K. Singh
Journal: Journal of Clinical Oncology (2005)

4272 Background: Carcinoma gall bladder is one of the most aggressive malignancies, with very poor outcome. At the time of presentation, most of the cases are either locally advanced or are metastatic. Surgery is the only modalitywith a curative and also a useful palliation.Patterns of presentation and management differ significantly in different regions of the world.In this era of laparascopic surgery, for gall stones.quite a few cases of incidently diagnosed carcinoma gall bladder present asymptomatically or with minimal symptoms. Majority of patients with symptomatic disease are in an advanced stage. Aim:To analyse the clinical presentation and surgical outcomeof gall bladder cancer in patients with or without prior surgery. Methods: A total of 496 patients of carcinoma gall bladder were seen in our out-patient department during the period Jan.2002 - Jan 2004.Disease profile and treatment outcomeof 27 patients operated at MCS were analysed retrospectively. Results: 17 patients (62%) presented as primary cases while 10 patients (37.03%) came after prior surgery. Among the patients with prior surgery, seven (70%) had laparoscopic cholecystectomy while in 3 (30%) open surgery was performed. Most patients were throughly worked up before being taken up for surgery. Radical surgery was possible in 17 patients (62.9%) while in 10 patients (37.03%) palliative surgery was done due to local advacment or advanced disease state. Nine patients (33.3%) without prior surgery could undergo radical surgery. In the prior surgery group, in all seven (100%) laparoscopic surgery patients, Curative resection was possiblewhile in oneof the three (33%) open surgery group, radical resection could be achieved. Reasons for their inoperability was probably local advancement or advanced disease with post operative dense fibrotic lesions. Conclusions: Incidentally diagnosed (asymptomatic ) gall bladder cancer has a better resectability rate as compared to compared to those with symptoms and radical surgery can be better achieved in patients with prior surgery. No significant financial relationships to disclose.