tbuckley/cabot-search huggingface dataset:
The dose-effect relationship in preoperative chemoradiation of locally advanced rectal cancer: Preliminary results of a phase III trial.
Authors: A. K. M. Jakobsen, A. L. Appelt, J. Lindebjerg, J. Ploeen, S. R. Rafaelsen, T. Vuong
Journal: Journal of Clinical Oncology (2011)

3512 Background: Locally advanced rectal cancer represents a major therapeutic challenge. Preoperative chemoradiation is considered standard in many centers, but little is known about the dose-effect relationship in the clinical setting. The present study represents a phase III trial comparing two different doses of radiation. Methods: The inclusion criteria were resectable T3 and T4 tumors with a distance of ≤ 10 cm from the anal verge, histopathological verification of adenocarcinoma with a circumferential margin (CRM) ≤ 5 mm on MRI. Disease limited to the pelvis and performance status ≤ 2. The patients were randomized to receive 50.4 Gy/28 fractions to the tumor and pelvic lymph nodes based on 3D conformal radiotherapy (arm A) or the same treatment supplemented with an endorectal boost given as high dose rate brachytherapy in 2 fractions, each with a dose of 5 Gy, 1 cm from the applicator surface (arm B). Concomitant chemotherapy UFT (uftoral) 300 mg/m2 and and L-leucovorin 22.5 mg daily was added to both arms on treatment days. The primary endpoint was complete pathological remission (CPR). Secondary endpoints included response according to T-category based on the Mandard classification (TRG), rate of complete resection (R0), local recurrence, disease free survival and overall survival together with toxicity and surgical complications. Results: The study included 248 patients from Canada (24) and Denmark (224). Based on intention to treat there was no significant difference in the rate of CPR between the two arms (20% and 22%, respectively). The rate of R0 resection was different in T3 tumors (90% and 99%, respectively, p=0.03). The same applied to the rate of major response (TRG+2), 29% and 44%, respectively (p=0.04). There was no significant difference in toxicity or surgical complications (25% and 19%, respectively). Further results are awaited. Conclusions: This first randomized trial comparing two doses of radiation indicated that the higher dose increased the rate of major response by 50% in T3 tumors. The endorectal boost is feasible with no significant increase in toxicity or surgical complications.
The “old drug” DTIC as a second/third line chemotherapy in advanced soft tissue sarcomas (STS)
Authors: P. A. Zucali, A. Bertuzzi, H. J. Soto Parra, E. Campagnoli, R. Cavina, V. Quagliuolo, A. Santoro
Journal: Journal of Clinical Oncology (2004)

9032 Background: There is not a standard second line chemotherapy in advanced STS. DTIC is one of the most active drugs in the treatment of STS with a response rate (RR) of 17%. As a second line chemotherapy the data available confirm these interesting results. Therefore we conducted a retrospective analysis about 44 patients (pts) treated in our Institute with DTIC as second/third line therapy between May 1997 and October 2003. The aim of our analysis was to evaluate the RR, the progression free survival (PFS) and the median duration of response. Methods: About 44 pts anlysed, 36 were evaluable; 8 pts, after first cycle, were treated elsewhere. The median age was 55,5 (range 24–75). The 75% of pts (27/36) were metastatic and the 72% (26/36) had a disease grading 2–3. DTIC was done as second line chemotherapy in 70% of pts(25/36). The 75% of pts (27/36) and the 25% (9/36) had respectively progressive and relapsed disease before to start the treatment. DTIC was given every 21 days with three different schedules: DTIC 800 mg/sqm day 1 (20 pts); DTIC 400 mg/sqm days 1 and 2 (6 pts); DTIC 300 mg/sqm days 1, 2 and 3 (10 pts). Results: Among 36 evaluable pts, 3 (8%) achieved partial response (PR) and 7 (19%) stable disease (SD), with an overall disease control of 28%. No complete response was observed. As second line therapy DTIC achieved 2/25 PR and 5/25 SD. The median PFS and the median duration of response were respectively 2 and 8 months. The progression free rate at 3 and 6 months was respectively 33% (SE 7.86%) and 25% (SE 7.2%). No grade 3–4 hematologic and non-hematologic toxicity according to W.H.O. was observed. Conclusions: Our results suggest that DTIC as a second/third line therapy yields a satisfactory disease control in progressive STS; its activity seems to be comparable to other treatments, such as the high dose of ifosfamide or ET-743, but with a lower toxicity profile. The increse of dose-intensity to obtain a better RR is questionable considering cost-benefit ratio in terms of toxicities and overall survival. No significant financial relationships to disclose.
ECOG 1503: A phase II trial of triapine (NSC#663249) with gemcitabine (T/G) as 2<sup>nd</sup> line treatment of non-small cell lung cancer (NSCLC)
Authors: A. M. Traynor, D. E. Levy, G. K. Bayer, J. M. Tate, S. P. Thomas, M. A. Mazurczak, D. L. Graham, J. M. Kolesar, J. H. Schiller
Journal: Journal of Clinical Oncology (2006)

17151 Background: Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone) is a novel chelator of the ribonucleotide reductase (RR) subunit M2. Triapine was shown to enhance cellular uptake and DNA incorporation of gemcitabine in tumor cell lines. Preclinical evidence suggested that cells with the wild-type (wT) MDR1 gene may have lower intratumoral concentrations of Triapine. Objectives: Primary objective was response rate (RR). Secondary objectives included rate of stable disease (SD), progression free survival (PFS), overall survival (OS), and safety of T/G in the 2 nd line treatment of advanced NSCLC. Correlative objectives were to examine the effects of MDR1 polymorphisms, RRM1, RRM2, and p53R2 protein and gene expression, and germline and tumor mutations of p53 on clinical outcomes. Methods: Pts with relapsed NSCLC who failed one prior cytotoxic regimen were eligible; prior gemcitabine was excluded. Treatment: Triapine 105 mg/m 2 IV on days 1, 8, and 15 and gemcitabine 1000 mg/m 2 on days 1, 8, and 15, of a 28 day cycle. Results: 18 pts enrolled from 11/04–1/05. Stage: IIIB (1 pt); IV (17 pts). PS: 0 (4 pts); 1 (14 pts). Median number of cycles administered: 2. No objective antitumor responses were seen. 5 pts experienced SD (range 7–135 days). Median OS: 5.4 mo (95%CI 3.98, not yet reached); median PFS: 3.2 mo (95%CI 1.7, 6.4); estimated 1 yr OS: 39% (SE 13%). Worst Gr 3/4 toxicities: leucopenia (Gr 3–8 pts; Gr 4–1 pt), neutropenia (Gr 3–8 pts; Gr 4–2 pts), hypoxia (Gr 3–4 pts), vomiting (Gr 3–2 pts). Genotyping for MDR1 polymorphisms C1236T, G2677T, and C3435T was performed on all pts. None of the 5 pts with SD were wTs. Pts with wT MDR1 had increased GI and pulmonary toxicity. Additional correlative data will be available for the meeting. Conclusions: T/G did not demonstrate clinically relevant activity in relapsed NSCLC. Genotyping for MDR1 polymorphisms may predict both efficacy and toxicity. [Table: see text]
PTCT-02STEREOTACTIC LASER INTERSTITIAL ABLATION THERAPY FOR PEDIATRIC LOW-GRADE GLIAL NEOPLASMS
Authors: Jeffrey Murray, Mark Halverson, Hayden Head, David Donahue, John Honeycutt
Journal: Neuro-Oncology (2015)

INTRODUCTION: Slowly growing deeply situated brain tumors in children pose a unique management dilemma. Considerations of watchful waiting, resection, chemotherapy and radiation therapy must be weighed carefully. With concerns over neurosurgical resection morbidity, the typical long-term ineffectiveness of chemotherapy and the feared sequelae of radiation therapy, our institution has chosen to manage select tumors using laser interstitial ablation via the stereotactic Visualase® system. METHODS: Five patients, ages 7, 8, 12, 15, 16 years had clinicoradiographic histories of slowly enlarging deep brain lesions characteristic of low-grade glial tumors. Locations included deep thalamus (2), cerebellar vermis (1), parieto-occiptal region (1) and a SEGA near a foramen of Monro (1). Options for management were discussed with each family, and laser ablation was decided upon. RESULTS: The patients were taken to the intraoperative MRI operating room for stereotactic needle biopsy and laser interstitial ablation during the same operation. Frozen section tissue analysis in all cases showed a low-grade glial tumor. Each patient underwent standard post-operative scanning, all showing evidence of lesional/peri-lesional signal change, a sign suggestive of desired zonal ablation injury to the tumor. Four patients had no evidence of post-procedure complications and were discharged several days post-procedure. One patient (cerebellar vermis) had significant post-ablation procedure ataxia and had evidence of incomplete ablation by virtue of tumor progression 16 months later, requiring a second ablation. None had evidence of concerning hemorrhage. All tumors were finalized as being low-grade glial (pilocytic) tumors. CONCLUSIONS: Stereotactic laser ablation therapy should be considered as an option in the management of select patients with deeply-situated glial tumors, in order to avoid potential serious neurosurgical morbidity via resection, or the dangers of irradiation. Continued long-term patient follow up will be needed in order to determine whether ablation therapy was successful. Further reporting on this technique by other investigators is suggested.
Human Thymus-Leukemia-Associated Antigen: Isolation and Partial Characterization 2
Authors: Boris E. Chechik, Maire E. Percy, Erwin W. Gelfand
Journal: JNCI Journal of the National Cancer Institute (1978)

Human thymus-leukemia-associated antigen (HThy-L), a saline-soluble antigen, was previously detected by immunodiffusion (but not on the cell surface) in significant quantity in extracts of normal thymocytes, cells from cultured T-cell lines, and erythrocyte-rosette-positive leukemia blasts. Two species of HThy-L were identified and isolated from normal human thymus tissue after extraction in tris buffer, ammonium sulfate fractionation, acid precipitation of inactive fractions, DEAE-cellulose (DE-52) chromatography, Sephadex G-100 gel filtration, and carboxymethyl-cellulose (CM-52) chromatography; On Sephadex G-100, both HThy-L species had a similar molecular weight (40,000--50,000), but they eluted in different positions on DE-52 and CM-52. Analysis by sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that each of the 2 HThy-L species contained 2 components with molecular weights of approximately 43,000 and 23,000. Further purification of HThy-L on Sephadex G-50 showed that the 43,000-dalton component possessed HThy-L activity.
Some Factors Influencing Prenatal Care
Authors: Avedis Donabedian, Leonard S. Rosenfeld
Journal: New England Journal of Medicine (1961)

TO achieve the full values of medical care, the patient and the physician should be brought together promptly whenever there is need for such service. Need occurs whenever, in the light of current medical knowledge, medical care would prevent illness, disability or death, would shorten or ameliorate the effects of illness or injury or would restore function when, because of illness, injury or congenital defect, capacity is reduced below the maximum achievable by the patient. This concept provides for accommodation to advances in understanding in the basic and clinical sciences.There are relatively few areas of medical practice in which . . .
P113 Clinical use of Adaptive Servo-Ventilation across the UK: results of a postal survey: Abstract P113 Table 1
Authors: CJ Murphy, D Gosh, S West
Journal: Thorax (2015)

<h3>Introduction</h3> Adaptive Servo-Ventilation (ASV) is used to treat central sleep apnoea (CSA), but evidence for its use is limited. A large trial, SERVE-HF, randomised patients with CSA and left ventricular heart failure to ASV or control. Their results led to a field safety notice in May 2015, advising ASV is contraindicated in patients with symptomatic chronic heart failure and reduced ejection fraction. Sleep Centres therefore reviewed ASV in clinical practice; we sought information about ASV use in the UK. <h3>Methods</h3> A survey was sent to 187 UK sleep centres, asking about the use of ASV. <h3>Results</h3> Seventy-five surveys were returned (40% response rate). ASV was not used in 53% of centres. Of the 47% (n = 35) of sleep centres using ASV, the average number of patients on ASV per centre was 13 (range 1–69). For comparison, the average number on CPAP was 3368 (range 100–12000). Of the 454 patients using ASV, the reasons are shown in Table 1. Following the field safety notice, 66% of centres reviewed patients in clinic. Others contacted patients by phone (45%) or in writing (31%), or used a combination of these. Five centres did not contact their patients and five centres had to run between one and two additional clinics to review their ASV patients. Some repeated echocardiography. Seventy-two (48%) CSA-CSR patients were advised to stop using ASV. Fifteen chose to continue, 32 changed to CPAP/NIV, 14 stopped ASV, 11 were not specified. Clinicians rated ASV as <i>very</i><i>useful</i> (26%), <i>quite</i><i>useful</i> (23%) and <i>occasionally useful</i> (49%). <h3>Conclusions</h3> There is a wide range of clinical ASV use in sleep centres across the UK; many do not use it. Apart from SERVE-HF, there are few randomised clinical trials to inform who would benefit from ASV. Use may be determined by case series, expert opinion and individual response. This highlights the need for further research in this area.
Screening for alcoholism among college students
Authors: A R Favazza, B Cannell
Journal: American Journal of Psychiatry (1977)

When the Michigan Alcoholism Screening Test (MAST) was administered to 245 students on two midwestern college campuses, 29% of the students on the small, private college campus and 19% on the large state university campus scored more than 4 points, indicating possible alcoholism. The authors hope that this study will stimulate further research on alcoholism among college students.
Case 28-2012
Authors: Marc A. de Moya, Johnson T. Wong, Daniela Kroshinsky, Gregory K. Robbins, Anuradha S. Shenoy-Bhangle, Devon C. Gimbel
Journal: New England Journal of Medicine (2012)

Shock, abdominal-wall necrosis, and leukocytosis developed in a 30-year-old woman after a cesarean section and did not respond to antibiotics. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, and abdominal-wall débridement were performed.
Nutritional Benefits of Neonatal Screening for Cystic Fibrosis
Authors: Philip M. Farrell, Michael R. Kosorok, Anita Laxova, Guanghong Shen, Rebecca E. Koscik, W. Theodore Bruns, Mark Splaingard, Elaine H. Mischler
Journal: New England Journal of Medicine (1997)

Many patients with cystic fibrosis are malnourished at the time of diagnosis. Whether newborn screening and early treatment may prevent the development of a nutritional deficiency is not known.We compared the nutritional status of patients with cystic fibrosis identified by neonatal screening or by standard diagnostic methods. A total of 650,341 newborn infants were screened by measuring immunoreactive trypsinogen on dried blood spots (from April 1985 through June 1991) or by combining the trypsinogen test with DNA analysis (from July 1991 through June 1994). Of 325,171 infants assigned to an early-diagnosis group, cystic fibrosis was diagnosed in 74 infants, including 5 with negative screening tests. Excluding infants with meconium ileus, we evaluated nutritional status for up to 10 years by anthropometric and biochemical methods in 56 of the infants who received an early diagnosis and in 40 of the infants in whom the diagnosis was made by standard methods (the control group). Pancreatic insufficiency was managed with nutritional interventions that included high-calorie diets, pancreatic-enzyme therapy, and fat-soluble vitamin supplements.The diagnosis of cystic fibrosis was confirmed by a positive sweat test at a younger age in the early-diagnosis group than in the control group (mean age, 12 vs. 72 weeks). At the time of diagnosis, the early-diagnosis group had significantly higher height and weight percentiles and a higher head-circumference percentile (52nd, vs. 32nd in the control group; P=0.003). The early-diagnosis group also had significantly higher anthropometric indexes during the follow-up period, especially the children with pancreatic insufficiency and those who were homozygous for the deltaF508 mutation.Neonatal screening provides the opportunity to prevent malnutrition in infants with cystic fibrosis.
A Comparison of the Perioperative Neurologic Effects of Hypothermic Circulatory Arrest versus Low-Flow Cardiopulmonary Bypass in Infant Heart Surgery
Authors: Jane W. Newburger, Richard A. Jonas, Gil Wernovsky, David Wypij, Paul R. Hickey, Karl Kuban, David M. Farrell, Gregory L. Holmes, Sandra L. Helmers, Jules Constantinou, Enrique Carrazana, John K. Barlow, Amy Z. Walsh, Kristin C. Lucius, Jane C. Share, David L. Wessel, Frank L. Hanley, John E. Mayer, Aldo R. Castaneda, James H. Ware
Journal: New England Journal of Medicine (1993)

Hypothermic circulatory arrest is a widely used support technique during heart surgery in infants, but its effects on neurologic outcome have been controversial. An alternative method, low-flow cardiopulmonary bypass, maintains continuous cerebral circulation but may increase exposure to known pump-related sources of brain injury, such as embolism or inadequate cerebral perfusion.
Phase II trial of nab-paclitaxel as first-line therapy of hormone refractory metastatic prostate cancer (HRPC)
Authors: T. Kolevska, C. J. Ryan, V. Huey, L. Weisberg, S. Wang, D. Baer, A. Ghadialy, D. Goldstein, B. Fireman, L. Fehrenbacher
Journal: Journal of Clinical Oncology (2009)

5152 Background: Many patients with hormone refractory prostate cancer have poor tolerance to treatment. Docetaxel chemotherapy was shown to improve survival but has substantial toxicity, requires steroid administration, may cause poorly reversible neuropathy and requires long infusion times, all limiting its use. Nab-paclitaxel, an albumin-bound nanopaticle form of paclitaxel, delivers paclitaxel without steroids, requires only 30 minutes infusion time and has favorable toxicity profile that may be more tolerable but effective in patients with prostate cancer. The goal of this study was to evaluate the efficacy and toxicity of nab-paclitaxel in first line chemotherapy of men with castration resistant prostate cancer. Methods: nab-paclitaxel was given iv100 mg/m2 weekly x 3 of 4 weeks cycles. Main eligibility criteria include: hormone refractory metastatic prostate cancer, no prior chemotherapy, performance status 0–2. Primary endpoint was efficacy based on prostate-specific antigen (PSA) response. PSA response was PSA decrease of &gt;50%, progressive disease (PD) was PSA increase of &gt;25%, stable disease (SD) was &lt;25% PSA increase or &lt;50% decrease sustained longer that 8 weeks. Results: There are 38 patients enrolled, 35 were evaluable for response. Median age was 71 years old (range 57–86). One patient discontinued the treatment after 1 infusion due to toxicity (elevated ALT). PSA response was seen in 9 (25%) patients and SD in 15 patients (43%), with an overall response rate of 25% and clinical benefit of 68%. Seven patients received treatment for ≥ 6 months with minimal toxicity (range 6–10 months). Grade 3 related hematologic toxicity was reported in 7 (18%) patients (4 anemia, 4 neutropenia), grade 3 related non-hematologic toxicity was reported in 6 patients (1 hypokalemia, 1 muscle weakness, 2 fatigue, 1 fever, 1 neuropathy, 1 ALT elevation). Conclusions: Nab-paclitaxel has activity in patients with metastatic hormone refractory prostate cancer. This regimen was well tolerated, and may be useful in patients who are not suitable candidates for docetaxel based therapy. [Table: see text]
Pattern of breast diseases in Kuwait Cancer Control Center, Kuwait
Authors: S. A. Alawadi, M. D. Delvadiya
Journal: Journal of Clinical Oncology (2006)

10754 Background: The aim of this case series study is to evaluate the outline and pattern of female breast cancers in Kuwait. Methods: Our study consisted of data from 300 cases of female breast cancer seen in our outpatient department. Data on profile of their disease at presentation and known risk factors was retrieved. The analysis indented to examine the pattern of the disease and risk factor profile of the patients. Results: Out of 300 patients, 52% were Kuwaiti citizens, 24% were Arabs from other countries, 23% were of Asian origin and 1% was of other nationality. Their median age ± SD (Standard Deviation) was 50 ± 9.7 years. Most patients were younger than 55 years (77.4%) and were predominantly premenopausals (63%). Only 18% had stage I disease at presentation, whilst 54 %, 24 %, and 4% had stage II, III and IV disease, respectively. Among patients with known axillary nodal status (298 patients) 44.3% were node-negative whilst 39.6% and 16.8% had N1 and N2 disease, respectively. History of benign breast disease was positive in 9% and only 1% had breast biopsy done before the biopsy which diagnosed cancer. In 20.7% there was family history of breast cancer. Among them 11.7% had first degree relative with breast cancer, 3.3%, 7.3% and 1% patients had either mother, sister or both with history of breast cancer. Whilst 12% patients had second degree relatives with breast cancer, 3% patients out of them had both first and second degree relatives with breast cancer. History of alcohol ingestion was rare, only 0.7% patients were taking alcohol. 9.7% patients were nulliparous, while 10.7% patients had their first child after the age of 30 years. Breast feeding was common, 80 % patients breast fed their children and 43.3 % did that for more than 6 months. Age at menarche was 12 years or less in 34 % patients and age at menopause was more than 55 years in only 6.3% patients. Oral contraceptives were used by 38.7% patients, 12%, 9.3% and 17.3% patients used them for 2 or less, 2 to 5 or more than 5 years, respectively. Only 3% patients took hormone replacement therapy, 7 of them took that fore more than 2 years. Only 6 % patients gave history of smoking and only half of them were currently smoking. Conclusions: This data analysis suggested that pattern of breast cancer in Kuwait is similar to other countries in this region. No significant financial relationships to disclose.
Evidence for Multiple Sites of Regulation of Heme Synthesis in Murine Erythroleukemia Cells
Authors: P S Ebert, H L Bonkowsky, A Deisseroth
Journal: JNCI Journal of the National Cancer Institute (1979)

Friend murine erythroleukemia (MEL) cells can be induced to differentiate along the erythroid pathway by such dissimilar agents as dimethyl sulfoxide (DMSO), butyrate, inhibitors of DNA synthesis, and certain highly polar agents. This study showed differential biochemical effects of the potent inducers DMSO and butyrate on the heme biosynthetic pathway in three clones of Friend MEL cells. When the cells were incubated with combinations of DMSO and butyrate, hemoglobin production was less than that amount produced when each inducer was incubated singly with the cells. Procaine, a local anesthetic that competes with Ca2+ and thus affects membrane permeability, slightly inhibited DMSO-mediated hemoglobin production but almost tripled the level stimulated by butyrate alone. Similarly, EDTA, which also can bind Ca2+ and which can modify the activity of heme biosynthetic enzymes, also inhibited hemoglobin production mediated by DMSO, whereas it stimulated hemoglobin production in cells exposed to butyrate. Total porphyrin accumulation was greater in DMSO-treated cells than in butyrate-treated cells, which suggests that butyrate induces the enzymes of the heme pathway more efficiently than does DMSO. DMSO and butyrate may affect the heme biosynthetic pathway by multiple mechanisms or, alternatively, they may affect the multistep pathway at various points, producing partial blocks or incomplete enzyme induction.