tbuckley/cabot-search huggingface dataset:
Smoking in Relation to Mortality and Morbidity. Findings in First Thirty-Four Months of Follow-Up in a Prospective Study Started in 1959&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: E. Cuyler Hammond, Sc.D.
Journal: JNCI Journal of the National Cancer Institute (1964)

1) After answering detailed questionnaires, 442,094 men, aged 40–89, were traced for an average of 34.3 months. 2) Death rates were far higher in cigarette smokers than in nonsmokers, higher in those who started cigarette smoking at a young age than in those who started at an older age, and higher in current cigarette smokers than in excigarette smokers who had quit for a year or longer. Death rates increased with amount of cigarette smoking and degree of inhalation. 3) Death rates from the following diseases were much higher in cigarette smokers than in nonsmokers: cancer of the lung, buccal cavity, pharynx, larynx, esophagus, bladder, and pancreas; gastric ulcer; emphysema; and aortic aneurysm. Coronary artery disease death rates were highly related to cigarette smoking among men in the middle-age groups but less highly related among men in the old-age groups. In age group 40–59, the coronary artery disease death rate was 1.95 times as high among light cigarette smokers as among nonsmokers and 3.00 times as high among heavy cigarette smokers as among nonsmokers. 4) Death rates of cigarette smokers and nonsmokers were studied in relation to many other factors, such as longevity of parents and grandparents, cancer in parents and siblings, height, exercise, sleep, race, religion, education, marital status, nervous tension, and prior history of certain diseases. Within every group studied, the death rate of men who smoked 20 or more cigarettes a day was considerably higher than that of nonsmokers. 5) Nonsmokers were matched individually with men who smoked 20 or more cigarettes per day, the 2 men in each matched pair being similar in age, height, race, nativity, religion, marital status, residence (urban or rural), certain occupational exposures, education, drinking habits, nervous tension, use of tranquilizers, sleep, exercise, health at time of enrollment, and past history of cancer, heart disease, stroke, and high blood pressure. Altogether 36,975 such pairs were found. During the study, 1,385 of the 36,975 cigarette smokers died, while only 662 of the nonsmokers died. Of the cigarette smokers, 110 died with lung cancer and 654 with coronary artery disease, while, of the nonsmokers, 12 died with lung cancer and 304 with coronary artery disease. Emphysema caused the death of 15 cigarette smokers but only 2 nonsmokers. 6) The proportion of men hospitalized during the first 2 years of the study was considerably higher among cigarette smokers than among nonsmokers and increased with amount of cigarette smoking and degree of inhalation.
Second interim analysis of Global Investigation of Therapeutic Decisions in Unresectable HCC and of its Treatment with Sorafenib (GIDEON): U.S. versus global perspective on patient and disease characteristics, treatment history, and sorafenib use.
Authors: Alec Goldenberg, Anthony B. El-Khoueiry, Robert C. G. Martin, Alan Paul Venook, Parvez Mantry, Pierre Michel Gholam, Brendan McGuire, Arun Sanyal, Jean-Francois Geschwind, Jorge A. Marrero
Journal: Journal of Clinical Oncology (2012)

e14581 Background: GIDEON is a global, prospective, noninterventional study of patients (pts) treated with sorafenib (SOR) for unresectable hepatocellular carcinoma (uHCC). Regions evaluated included US, Europe, Japan, Asia Pacific, and Latin America. Using data from the second interim analysis, we compare safety and efficacy of sorafenib in US pts with the entire (global) study population. Methods: Eligible pts had uHCC and were treated with SOR. Demographics, disease etiology, treatment history, and SOR dosing were compared in a descriptive, preplanned subgroup analysis. Results: The safety population comprised 1571 pts. In the 313 US pts, hepatitis B was less common (18% vs 37% global), but hepatitis C was more frequent (53% vs 32% global) (Table). Rate of alcoholic liver disease was higher in US pts (41% vs 29% global). At start of SOR, fewer US pts had BCLC stage C-D disease (49% vs 60% global), but more US pts were Child-Pugh (CP) B or C status (38% vs 25% global) (Table). Rates of prior surgery and locoregional treatment (LRT) were similar in US (11% and 49%, respectively) and global pts (19% and 55%, respectively). US pts received fewer TACE procedures (≥3 treatments: 13.8% vs 38.9% global); most (59%) TACE-treated pts in the US received 1 treatment. In US vs global pts, median time from prior surgery to start of SOR was 10 months (range 1-61) vs 14 months (range 1-181) and median time from last TACE to start of SOR was 3.2 months vs 3.1 months. Conclusions: Disease characteristics and treatment patterns differ in the US and global GIDEON populations. Although its limitations as an observational study must be considered, GIDEON is a valuable repository of data reflecting real-world practices in a variety of regions and pt types. [Table: see text]
Inhibition of P-Glycoprotein and Recovery of Drug Sensitivity of Human Acute Leukemic Blast Cells by Multidrug Resistance Gene (mdr1) Antisense Oligonucleotides
Authors: Sayuri Motomura, Toshiko Motoji, Minoko Takanashi, Yan-Hua Wang, Hiroko Shiozaki, Isamu Sugawara, Eizou Aikawa, Akihiro Tomida, Takashi Tsuruo, Naotoshi Kanda, Hideaki Mizoguchi
Journal: Blood (1998)
Is early detection of basal cell carcinoma worthwhile? Systematic review based on the WHO criteria for screening
Authors: I. Hoorens, K. Vossaert, K. Ongenae, L. Brochez
Journal: British Journal of Dermatology (2016)

The incidence of basal cell carcinoma (BCC) has risen three- to fourfold over the last 30 years and is expected to continue to increase with ageing of the population. Although BCC has a good prognosis, it causes significant morbidity and has an important impact on the public health budget due to direct treatment costs. Based on the existing evidence, a systematic evaluation of the World Health Organization criteria was performed to determine whether earlier detection of BCC could reduce morbidity and cost. BCC slowly increases in size, with a median increase in diameter of 0·5 mm over 10 weeks. There is an important delay in diagnosis ranging from 19 to 25 months. In several studies BCC size was the main determinant of treatment cost, surgical complexity, reconstruction technique and the specific surgical procedure performed, such as Mohs micrographic surgery or surgical excision. One study showed that size also seems to affect the cost per treatment for other nonsurgical options. The use of vismodegib, an inhibitor of the hedgehog pathway, is confined to locally advanced or metastatic BCC. Delays in diagnosis and appropriate treatment are the most important underlying causes in the occurrence of giant BCC and/or BCC with metastasis. Although the latter represent only a very small fraction of all BCCs, the majority of them are located in the facial region. The available data point to a slow increase in the size of BCCs over time. Size is one of the major determinants in choice of treatment and the associated cost, especially for facial BCC. Therefore we conclude that current data support early detection and adequate management of BCCs on the face.
Predictors of survival in refractory anemia with ring sideroblasts and thrombocytosis (RARS‐T) and the role of next‐generation sequencing
Authors: Mrinal M. Patnaik, Terra L. Lasho, Christy M. Finke, Curtis A. Hanson, Rebecca L. King, Rhett P. Ketterling, Naseema Gangat, Ayalew Tefferi
Journal: American Journal of Hematology (2016)

Refractory anemia with ring sideroblasts and thrombocytosis (RARS-T) shares overlapping features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). RARS-T is characterized by SF3B1 and JAK2 mutations and prognosis is considered to be better than MDS but not as good as MPN. The objective of the study was to identify predictors of survival in RARS-T. We analyzed clinical and laboratory variables in 82 patients and applied a 27-gene NGS assay to 48 marrow samples obtained at diagnosis. 94% of patients had ≥1 mutations; common mutations being: SF3B1 85%, JAK2V617F 33%, ASXL1 29%, DNMT3A 13%, SETBP1 13% and TET2 10%. In a multivariable survival analysis (n = 82), anemia (P = 0.02) [HB< 10 gm/dl: HR 2.3, 95% CI 1.2-4.6] and abnormal karyotype (P =.01) [HR 6.1, 95% CI 2.7-13.8] were independently prognostic for inferior survival. In patients with NGS information (n = 48), univariate analysis showed association between poor survival and presence of SETBP1 (P = 0.04) or ASXL1 (P = 0.08) mutations whereas the absence of these mutations (ASXL1wt/SETBP1wt) was favorable (P = 0.04); the number of concurrent mutations did not provide additional prognostication (P = 0.3). We developed a HR-weighted prognostic model, with 2 points for an abnormal karyotype, 1 point for either ASXL1 and/or SETBP1 mutations, and 1 point for a HB level < 10 gm/dl, which effectively stratified patients into three risk categories; low (0 points), intermediate (1 point) and high (≥2 points), with median survivals of 80, 42 and 11 months respectively (P = 0.01). In summary, we confirm the unique mutational landscape in RARS-T and provide a novel mutation-enhanced prognostic model.
Combined modality therapy of lung cancer and lung tolerance.
Authors: R P Abratt
Journal: Journal of Clinical Oncology (1996)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1996.14.4.1402 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8648399 Combined modality therapy of lung cancer and lung tolerance. R P AbrattxR P AbrattSearch for articles by this author https://doi.org/10.1200/JCO.1996.14.4.1402 PDF "Combined modality therapy of lung cancer and lung tolerance.." Journal of Clinical Oncology, 14(4), pp. 1402–1403© 1996 by American Society of Clinical Oncology
A comparison of carboplatin plus methotrexate versus methotrexate alone in patients with recurrent and metastatic head and neck cancer.
Authors: M Eisenberger, S Krasnow, S Ellenberg, H Silva, J Abrams, V Sinibaldi, D Van Echo, J Aisner
Journal: Journal of Clinical Oncology (1989)

Patients with recurrent and metastatic squamous cell carcinoma of the head and neck (SCCHN) were stratified by performance status, extent of disease, and prior radiotherapy and subsequently randomized to receive carboplatin (CBDCA; Bristol-Myers, Wallingford, CT) administered intravenously (IV) monthly, initially at doses of 400 mg/m2 in combination with methotrexate (MTX) given IV weekly at doses of 40 mg/m2 or MTX alone at the same dose/schedule. Significant dose-limiting myelosuppression required CBDCA dose reductions to 300 mg/m2 and, subsequently, 200 mg/m2. Nonhematological toxicities were not significant. Our study objective was to determine whether CBDCA plus MTX produce a substantial improvement in response rate over single-agent MTX. A response rate of 50% (complete [CR] plus partial response [PR]) for CBDCA plus MTX compared with 25% for MTX was specified as the difference to be detected. We employed a two-stage study design for randomized trials that allowed for early termination of studies involving relatively ineffective treatment regimens. With this design, the study could be closed after the first stage (20 patients entered onto each treatment arm) if the number of responders to CBDCA plus MTX were not superior to MTX. Five of 20 patients responded to treatment in each arm, and we were able to conclude that the addition of CBDCA to MTX is unlikely to result in a twofold increase in response rate compared with MTX alone in this group of patients. This two-stage design represents a simple and efficient method of testing the relative efficacy of new combinations containing at least one active agent against a suitable control arm in this disease. It addresses scientific and ethical issues of continuing testing with relatively ineffective treatments, and at the same time provides a reliable method for identifying very active regimens likely to represent significant therapeutic advances.
High ΔNp73/TAp73 ratio is associated with poor prognosis in acute promyelocytic leukemia
Authors: Antonio R. Lucena-Araujo, Haesook T. Kim, Carolina Thomé, Rafael H. Jacomo, Raul A. Melo, Rosane Bittencourt, Ricardo Pasquini, Katia Pagnano, Ana Beatriz F. Glória, Maria de Lourdes Chauffaille, Melina Athayde, Carlos S. Chiattone, Ingrid Mito, Rodrigo Bendlin, Carmino Souza, Cristina Bortolheiro, Juan L. Coelho-Silva, Stanley L. Schrier, Martin S. Tallman, David Grimwade, Arnold Ganser, Nancy Berliner, Raul C. Ribeiro, Francesco Lo-Coco, Bob Löwenberg, Miguel A. Sanz, Eduardo M. Rego
Journal: Blood (2015)
Three-month change in PSA as a surrogate endpoint for mortality in advanced hormone-refractory prostate cancer (HRPC): Data from Southwest Oncology Group Study S9916
Authors: E. D. Crawford, D. K. Pauler, C. M. Tangen, M. H. A. Hussain, E. J. Small, M. E. Taplin, P. A. Burch, G. F. Greene, P. Lara, D. P. Petrylak
Journal: Journal of Clinical Oncology (2004)

4505 Background: S9916 was designed to compare two regimens: mitoxantrone/prednisone (M+P) vs docetaxel/estramustine (D+E), in patients (pts) with HRPC. Stratification factors were: Progression type: inmeasurable/ evaluable disease vs increasing PSA only; NCI CTC Bone pain scale: Grade ≥ 2 vs < 2; and SWOG performance status 0–1 vs 2–3. The primary endpoint was survival. 770 pts were accrued. There were 406 deaths. Methods: Baseline, treatment and follow-up data were compiled for a subset of 499 pts who had a minimum of two PSAs recorded in the first 3 months on-study. 161 (32.3%) had a prior radical prostatectomy. We used Cox regression analysis to test whether PSA velocity was a prognostic factor for mortality independent of treatment (M+P vs D+E) received, adjusting for influential baseline variables. All statistical tests were 2-sided. Results: Initial PSA and prior prostatectomy were associated with mortality and included in all analyses. In an analysis without treatment, PSA velocity was correlated with survival (HR=3.67; 95% CI=(2.72,4.96), p<.0001), with odds of failing nearly quadrupling with a unit increase in PSA velocity. Without adjusting for PSA velocity, treatment was associated with mortality failure rate (HR = 1.39 for M+P vs. D+E, 95% confidence interval (CI)=(1.10,1.75), p=.006). After adjustment for PSA velocity, treatment was no longer associated with mortality (HR = 1.15 for M+P vs. D+E, 95% CI=(.91,1.46), p=.23), while PSA velocity was still significant (HR = 3.56, 95% CI=(2.62,4.83), p<.0001). Patients with a prior prostatectomy had a failure rate nearly half that for patients without prior prostatectomy (HR=.55, 95% CI=(.42,.72), p<.0001), and HR that less than doubled with a unit increase in PSA velocity (HR=1.69, 95% CI=(1.02,2.79), p=.0003). Conclusions: PSA velocity measured during the first 3 months of chemotherapy provides independent prognostic information to treatment and should be further investigated as a surrogate endpoint for mortality in future trials of chemotherapeutic regimens for HRPC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis National Institutes of Health; TAP Pharmaceutical Co.; Aventis Pharmaceutical Co.
Phase I evaluation of all-trans-retinoic acid in adults with solid tumors.
Authors: J S Lee, R A Newman, S M Lippman, M H Huber, T Minor, M N Raber, I H Krakoff, W K Hong
Journal: Journal of Clinical Oncology (1993)

PURPOSE Prompted by recent demonstrations that all-trans-retinoic acid (all-trans-RA) had efficacy in acute promyelocytic leukemia, a phase I trial of all-trans-RA was conducted to establish the maximum-tolerated dose (MTD) before phase II testing. PATIENTS AND METHODS Forty patients with a histologic or cytologic diagnosis of malignancy other than leukemia were treated with single daily oral doses of all-trans-RA ranging from 45 mg/m2 to 200 mg/m2. Doses of all-trans-RA were escalated in the next cohort of patients until the MTD was determined if the preceding dose level was not associated with significant toxicity. RESULTS Lung cancer was the most common type of tumor included in the study (26 cases) followed by head and neck squamous cell carcinomas (three cases), and squamous cell carcinoma of the skin (two cases); other miscellaneous solid tumors were also represented. Toxicities included cheilitis, skin reactions, headache, and nausea and vomiting, as well as transient elevations of liver enzymes and triglyceride levels. Skin toxicities, consisting of erythema with desquamation and paronychia, were considered to be the dose-limiting toxicity, and were observed in two of six patients who received 175 mg/m2/d, and in two of five patients who received 200 mg/m2/d. Of the 30 patients with assessable lesions, response was evaluated in 26 patients and no major objective tumor response was observed. Two patients were able to receive the drug for longer than 1 year without significant toxicities. There was considerable variation in individual patients' peak plasma all-trans-RA levels, and a decrease in the area under the curve of all-trans-RA plasma concentration was observed in all four patients evaluated. CONCLUSION For phase II study of adult patients, we recommend 150 mg/m2 of all-trans-RA administered orally once a day. However, for better optimization of drug administration schedules, further studies are needed.
Temozolomide phase II study in children with relapsing refractory high-risk neuroblastoma
Authors: H. Rubie, J. Chishlom, A. Defachelles, B. Morland, C. Munzer, D. Valteau Couanet, D. Hargrave, C. Bergeron, C. Coze, L. Djafari, G. Vassal
Journal: Journal of Clinical Oncology (2006)

9012 Background: To determine the response rate (RR) of neuroblastoma (NB) in children to temozolomide (TMZ), and evaluate the duration of response and tolerance of the drug in this patient population. Methods: A multicenter, phase II evaluation of an oral, daily schedule of TMZ (200 mg/m 2 on 5 consecutive days and repeated every 28 days) was undertaken in children with a refractory or relapsed high-risk NB (metastatic or localized with Myc-N amplification). Evidence of activity was defined by radiologic or MIBG scan evidence of sustained reduction in lesion size or activity whenever it occurs. Methodology included a two-step study using Fleming’s method with a first step of 15 patients and a second of 10 additional patients if 2 to 4 responses had been observed in the first cohort. All data were centrally reviewed by a panel. Results: Among 34 registered patients over a 14 month period in 14 centres, twenty five are finally evaluable and received 94 cycles of chemotherapy. Disease status was metastatic NB (n=23) either refractory (n=9) or in relapse (n=14). Grade ¾ thrombocytopenia was the most frequent toxic event (16% of the cycles). Myelosuppression resulted in significant treatment delays and dose reductions (24% and 21% of cycles respectively). Out of 25 patients, response (CR, VGPR or PR) was observed in 5 (RR=20 ± 8%) with a median duration of 6 months. Furthermore a mixed response or an objective effect was observed in respectively 2 and 3 additional patients. Conclusions: Temozolomide is effective in heavily pretreated patients with NB, and deserves further evaluation in combination with another drug No significant financial relationships to disclose.
Pooled Analysis of the Prognostic and Predictive Value of KRAS Mutation Status and Mutation Subtype in Patients with Non–Small Cell Lung Cancer Treated with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors
Authors: Alona Zer, Keyue Ding, Siow Ming Lee, Glenwood D. Goss, Lesley Seymour, Peter M. Ellis, Allan Hackshaw, Penelope A. Bradbury, Lei Han, Christopher J. O’Callaghan, Ming-Sound Tsao, Frances A. Shepherd
Journal: Journal of Thoracic Oncology (2015)
Estimation of Relative Risk From Vital Data: Smoking and Cancers of the Lung and Bladder&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R G Stevens, S H Moolgavkar
Journal: JNCI Journal of the National Cancer Institute (1979)

Mortality data from cancers of the lung and bladder in England and Wales were analyzed. With the use of detailed information on cigarette consumption, a nonlinear least-squares analysis showed that the differences between males and females in the rates of these cancers could be explained on the basis of differences in smoking habits. Furthermore, estimates of the relative risk due to smoking were obtained. The relative risks of smoking 146,000 cigarettes (equivalent to 20 cigarettes/day for 20 yr) were 4.3 for lung cancer and 2.9 for bladder cancer. These estimates agree with those obtained by other types of epidemiologic studies.
Arsenic Trioxide and Interferon- Synergize to Induce Cell Cycle Arrest and Apoptosis in Human T-Cell Lymphotropic Virus Type I–Transformed Cells
Authors: Ali Bazarbachi, Marwan E. El-Sabban, Rihab Nasr, Frédérique Quignon, Christian Awaraji, Joelle Kersual, Laurent Dianoux, Yael Zermati, Joud H. Haidar, Olivier Hermine, Hughes de Thé
Journal: Blood (1999)
A high density of tumor infiltrating CD3 and CD8 cells to predict recurrence free survival in patient with hepatocellular carcinoma.
Authors: Andrew Gabrielson, Yunan Wu, Bhaskar Kallakury, Jiji Jiang, Hongkun Wang, Lynt B. Johnson, Eddie Island, Thomas Fishbein, Rohits Satoskar, Reena Jha, Jaydeep Kachhela, Perry Feng, Tiger Zhang, Anteneh Tesfaye, Krithika Bhuvaneshwar, Yuriy Gusev, Petra Prins, John Marshall, Michael B. Atkins, Aiwu Ruth He
Journal: Journal of Clinical Oncology (2015)

280 Background: The ability to define risk of hepatocellular carcinoma (HCC) recurrence after resection could improve the clinical management of patients. The pathological factors currently indicative of tumor invasiveness, such as vascular invasion, elevated AFP and advanced pTNM stage, are the established risk factors for recurrence. It has been suggested that immune cells that infiltrate a tumor are a prognostic factor in predicting patient outcome. In this study, the prognostic significance of tumor immune infiltration, as defined by the Immunoscore methodology, was assessed in patients with HCC. Methods: The influence of immune infiltration on clinical outcome was evaluated in patients who had undergone resection of HCC. The density of intratumoral immune infiltrates were measured in the center of the tumor (CT) and in the invasive margin (IM) of 45 stage I to IV HCC tissue specimens from a single cohort. The density of total (CD3+) and cytotoxic (CD8+) T lymphocytes in the CT and IM were obtained by immunohistochemistry and quantified using a Nuance FX Multiplex Biomarker Imaging system in tandem with ImageJ image processing software. Immune cell density in the CT and IM was converted to a binary score (0 as Low, 1 as High), with a cutoff threshold determined by the median density of CD3+ and CD8+ cells (273 cells/mm² and 217.5 cells/mm², respectively). The Immunoscore values were correlated with tumor recurrence and recurrence-free survival. Results: High densities of both CD3+ and CD8+ T lymphocytes in the CT and IM, along with a corresponding Immunoscore of 3+ (on a scale from 0 to 4), were significantly correlated with a low rate of recurrence (p-value = 0.0004). High densities of CD3+ lymphocytes alone were correlated with a prolonged recurrence-free survival (p-value = 0.0005). High densities of CD8+ lymphocytes alone were also correlated with a prolonged recurrence-free survival (p-value = 0.0031). Conclusions: The Immunoscore is a useful prognostic marker in patients with HCC who have received primary tumor resection. To better characterize the immune landscape of HCC tumors, the correlation between the Immunoscore and additional immune biomarkers are being evaluated.