tbuckley/cabot-search huggingface dataset:
Chemoradiation using 5-fluorouracil given every other day 24hours continuous iv infusion and cisplatin combination for the patients with esophageal cancer
Authors: K. Aiba, T. Kobayashi, N. Omura, Y. Suzuki, Y. Ishibashi, K. Nakada, N. Mitsumori, N. Hanyuh, K. Yanaga, M. Kobayashi, C. Kanehira
Journal: Journal of Clinical Oncology (2005)

4217 Background: 5-fluorouracil(5-FU) and cisplatin(CDDP) are key drugs for esophageal cancer. We performed a single institution chemoradiation study using every other day dosing of 5-FU to improve dose intensity(DI) and evaluated the efficacy and tolerance data. Methods: : Aim of study: Evaluating feasibility, efficacy and safety. Inclusion criteria: age<80, ECOG PS 0–2, disease-stages II,III,IV assessed by CT scan and EUS. Treatment scheme: Radiation:40Gy over 4 weeks(2Gy/fr/day Monday through Friday). Chemotherapy:5-FU 750 mg/m2 24hours continuous iv infusion day(D)1,3,5,8,10,12,15,17,19,22,24,26 and CDDP4mg/m2 iv D1–5,8–12,15–19,22–26 were given concurrently over the 4 weeks resulting in more than twice in terms of 5-FU DI compared with the other commonly used chemoradiation regimens. Responded tumors were resected, while additional 20Gy and the same chemotherapy were also given over 2 weeks to rest of the patients and stage IV patients. Results: : 28 patients with locally advanced esophageal cancer were treated between 2002 May and 2004 November. 27 patients were evaluable. 3 female, 24 male, median age 65(range 40–78) All patients had ECOG PS2 or better and squamous cell cancer. Stage II:4,III:12,IV:11. Primary tumor site:Upper: 2, Middle: 17, Lower: 8, Tumor length: median 70mm(35–160). Compliance with radiation, doses and timing: almost 100%. CR: 21% at the completion of scheduled chemoradiation regimen. 1-year survival was 60%, 2years 38%. Pathological CR was 30%(3/10) among patients undergone surgery. Grade 3/4 toxicity: Neutropenia 44%, Esophagitis 11%, Nausea 11%, Anorexia 33%. Conclusions: Chemotherapy employing dose intensified 5-FU regimen is a safe and well tolerated regimen for concurrent chemoradiation of locally advanced esophageal cancer. Since active drugs are limited for this disease, explorative study searching for improved outcome and sustaining safety is further warranted. No significant financial relationships to disclose.
Mortality and morbidity in long-term surviving patients treated with chemotherapy with or without irradiation for small-cell lung cancer.
Authors: K Osterlind, H H Hansen, M Hansen, P Dombernowsky
Journal: Journal of Clinical Oncology (1986)

Mortality and morbidity was investigated in a consecutive series of 72 patients with small-cell lung cancer (SCLC) who were found to be disease-free at restaging after 18 months of treatment. These patients were all the long-term survivors among 874 patients included in one of six trials between 1973 and 1981. All studies used combination chemotherapy with or without irradiation. Follow-up of the patients varied between 4 and 11 years. The estimated 5-year survival rate subsequent to discontinuation of therapy was 0.24, corresponding to a death rate of 0.25 per year or ten times greater than the expected mortality for persons of the same age group. This high mortality was primarily related to recurrent SCLC, the estimated cumulative risk of relapse reaching 46% at the time of the latest recurrence 5 years from diagnosis. The risk of relapse was generally independent of the pretreatment disease stage although it was reduced in patients with resectable disease and was greater in those with pretreatment liver or bone marrow metastases. Equal risks of relapse were related to the use of regimens with and without radiotherapy. The cumulative risk of relapse in patients surviving 3 years from initiation of the treatment was less than 15% and accordingly, 3 years of follow-up seems sufficient for comparison of long-term results obtained in different trials. The second factor resulting in death or disease was second cancer, for which the cumulated risk increased to 32%, the latest occurring 5.4 years from the diagnosis of SCLC. Five of these cases were non-small-cell lung cancers and three were secondary leukemias. The estimated mortality related to non-neoplastic conditions was just significantly greater than expected. In spite of the increased mortality in this series, 38 of 54 2-year disease-free survivors and 20 of 22 5-year survivors resumed a lifestyle similar to that before diagnosis of SCLC.
Prevention of Tumor Growth After Intradermal Iniection of BeG Extracts: A Comparison of Results in Strain-2 Guinea Pigs From the National Institutes of Health and From the National Jewish Hospital and Research Center2
Authors: B. Zbar, P. Minden, J.K. McClatchy, H.J. Rapp
Journal: JNCI Journal of the National Cancer Institute (1976)

Line 10, a transplantable hepatocellular carcinoma, was obtained originally from an NIH strain-2 male guinea pig fed diethylnitrosamine. The antitumor activity of BCG and BCG extracts was evaluated in strain-2 guinea pigs obtained both from NIH and the National Jewish Hospital and Research Center (NJH). Animals were immunized with these materials and then tested for their capacity to resist the growth of intradermally injected line-10 tumor cells. Tumor growth was not prevented in 18 NIH animals immunized with living BeG. No tumor growth occurred in 1 of 22 NIH animals immunized with a residue that remained after exhaustive methanol extraction of BCG and in 1 of. 44 NIH guinea pigs immunized with BCG extracts. In contrast, tumor growth was prevented in 13 of 22 similarly immunized NJH guinea pigs.
Brain metastasis of advanced gastric cancer is not hopeless: A retrospective, single-institutional study of long term follow-up in Korea
Authors: S. Lee, S. Rha, Y. Kim, S. Noh, H. Jung, H. Jeung, J. Jung
Journal: Journal of Clinical Oncology (2008)

15668 Background: Metastasis of advanced gastric adenocarcinoma to the brain is very rare and its incidence is low. However, little has been known regarding proper evaluation and treatment of these patients. Therefore, we reviewed our experience with brain metastasis of gastric adenocarcinoma to evaluate the efficacy of the treatment used. Methods: We analyzed 67 patients with brain metastasis of advanced gastric adenocarcinoma who were treated at the Severance Hospital Yonsei University College of Medicine between 1987 and 2006. The clinicopathological characteristics of 67 patients were assessed by medical record review retrospectively. Results: The median age was 59 years and the male-to-female ratio was 3.3:1. The most common cell types and the site included poorly differentiated (35.8%), and the distal body of the stomach (47.8%), respectively. The median interval between the diagnosis of advanced gastric cancer and the diagnosis of brain metastasis was 425 days. The median survival after brain metastasis was 105 days. When the patient had leptomeningeal seeding, the survival was 24 days which was shorter than 112 days of the peranchymal metastasis. Twelve patients treated with an operation or gamma knife surgery lived 186 days. Thirty five patients treated with whole brain radiation lived 112 days. Contrast with these patients, 136 patients received only supportive care showed the median survival of 26 days. The predicted probability of the survival correlated positively with only ECOG performance status and the treatment (P < 0.01). Conclusion: The outcome of the treated group was much better than that of the nontreatment group. ECOG performance status at the diagnosis of brain metastasis is a determinant of the survival.When the patient performance is favorable, early intervention is the only hope to prolong the survival in such patients. No significant financial relationships to disclose.
Abstract 18404: Current Status of Clinical Background of Hemodialysis Patients with Atrial Fibrillation in Japan: From the Fushimi Af Registry
Authors: Masaharu Akao, Yeong-Hwa Chun, Hiromichi Wada, Masahiro Esato, Tetsuo Hashimoto, Mitsuru Abe, Koji Hasegawa, Hikari Tsuji, Keizo Furuke, None The Fushimi AF Registry Investigators
Journal: Circulation (2012)

Background: Atrial fibrillation (AF) increases the risks of stroke and death, and the prevalence of AF is increasing significantly. Despite the remarkable effect of warfarin against embolic stroke, the use of warfarin in hemodialysis patients is controversial (or contraindicant), because of the high risk of bleeding in this patient population. The Fushimi AF Registry, a community-based prospective survey, was designed to enroll all of the AF patients living in Fushimi-ku, Kyoto, which is a typical urban district of Japan with a population of 283,000; rough estimate of 2,200 AF patients. The purpose of the study is to investigate the real-world current status of clinical backgrounds of Japanese AF patients, and to follow the clinical outcome in a long term. At present, we have enrolled 3,020 patients from March 2011 to March 2012. Methods and Results: We compared the clinical backgrounds of AF patients between those with hemodialysis (HD; n=87) and without it (NHD; n=2,933). Although the mean age was comparable between the two groups (HD vs. non-HD: 72.7 vs. 74.2; NS), HD group showed significantly higher rates of various co-morbidities (heart failure 40.2% vs. 27.9%; hypertension 80.5% vs. 60.5%; diabetes mellitus 55.2% vs. 23.3%). The rates of atherosclerotic vascular diseases were much higher in HD group (coronary artery disease 42.5% vs. 15.2%; myocardial infarction 21.8% vs. 6.4%; peripheral artery disease 19.5% vs. 4.4%), whereas the rate of stroke was comparable (21.9% vs. 19.4%; NS). HD group had higher risk profiles (CHADS2 score 2.72 vs. 2.07; p&lt;0.01), but received lower warfarin use (40.2% vs. 51.0 %; p=0.05). The rate of major bleeding was modestly higher in HD group (3.4% vs. 1.5%; p=0.15), but was much lower than previously reported (10-50%). Conclusion: The Fushimi AF registry represents the clinical profile of real-world Japanese AF patients. Hemodialysis patients with AF have higher risk profiles, but receive lower warfarin treatment for stroke prevention. The bleeding risk may be lower than reported under careful management, and therefore the use of warfarin could be considered in patients with particularly high risk for stroke in a case-by-case basis.
Adaptation to AI Therapy in Breast Cancer Can Induce Dynamic Alterations in ER Activity Resulting in Estrogen-Independent Metastatic Tumors
Authors: Damir Varešlija, Jean McBryan, Ailís Fagan, Aisling M. Redmond, Yuan Hao, Andrew H. Sims, Arran Turnbull, J.M. Dixon, Peadar Ó Gaora, Lance Hudson, Siobhan Purcell, Arnold D.K. Hill, Leonie S. Young
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Acquired resistance to aromatase inhibitor (AI) therapy is a major clinical problem in the treatment of breast cancer. The detailed mechanisms of how tumor cells develop this resistance remain unclear. Here, the adapted function of estrogen receptor (ER) to an estrogen-depleted environment following AI treatment is reported. Experimental Design: Global ER chromatin immuno-precipitation (ChIP)-seq analysis of AI-resistant cells identified steroid-independent ER target genes. Matched patient tumor samples, collected before and after AI treatment, were used to assess ER activity. Results: Maintained ER activity was observed in patient tumors following neoadjuvant AI therapy. Genome-wide ER–DNA-binding analysis in AI-resistant cell lines identified a subset of classic ligand-dependent ER target genes that develop steroid independence. The Kaplan–Meier analysis revealed a significant association between tumors, which fail to decrease this steroid-independent ER target gene set in response to neoadjuvant AI therapy, and poor disease-free survival and overall survival (n = 72 matched patient tumor samples, P = 0.00339 and 0.00155, respectively). The adaptive ER response to AI treatment was highlighted by the ER/AIB1 target gene, early growth response 3 (EGR3). Elevated levels of EGR3 were detected in endocrine-resistant local disease recurrent patient tumors in comparison with matched primary tissue. However, evidence from distant metastatic tumors demonstrates that the ER signaling network may undergo further adaptations with disease progression as estrogen-independent ER target gene expression is routinely lost in established metastatic tumors. Conclusions: Overall, these data provide evidence of a dynamic ER response to endocrine treatment that may provide vital clues for overcoming the clinical issue of therapy resistance. Clin Cancer Res; 22(11); 2765–77. ©2016 AACR.
Lack of significance for detecting bone marrow micrometastasis in patients with gastric cancer
Authors: M. Terashima, Y. Fujita, N. Kanzaki, S. Kashimura, M. Hoshino, S. Ohtani, S. Matsuyama, Y. Hoshino, M. Kogure, M. Gotoh
Journal: Journal of Clinical Oncology (2004)

4200 Background: We had previously reported that peritoneal micrometastasis determined by CEA mRNA level in peritoneal washings using real-time quantitative RT-PCR (RQ-PCR) is a good predictor for peritoneal recurrence in gastric cancer. In addition, several investigators had reported that bone marrow micrometatstasis is frequently observed even in early gastric cancer and a predictor of hematological metastasis in gastric cancer. However, these investigators determined the expression level of CEA or CK19 mRNA by nested RT-PCR, which is thought to have high false positive results. In the present study, in order to determine the significance of bone marrow micrometastasis in gastric cancer more precisely, we investigated the mRNA expression level of CEA, CK19 and CK20 using RQ-PCR. Methods: Bone marrow samples were aspirated from the sternum at a time of surgery in 65 patients with respectable gastric cancer. Total RNA was extracted from bone marrow by AGPC methods. The expression level of CEA, CK19 and CK20 mRNA were determined by RQ-PCR using ABI PRISM 7000 and adjusted by GAPDH mRNA level. To determine the detection limit of these genes, gastric cancer cell line MKN-45 was serially diluted in peripheral blood mononuclear cells (PBMCs). Results: In basic experiment, one cancer cell by CEA and CK19 mRNA and ten cancer cells by CK20 mRNA were detectable in 1,000,000 PBMCs using this system. In clinical samples, only one patient, having Stage IV disease, out of 65 patients (1.5%) showed positive CEA, CK19 and CK20 mRNA. Positive expression of CEA, CK19 or CK20 mRNA was not detectable in the remaining patients. There was no significant correlation between bone marrow micrometastasis and clinicopathologic features including simultaneous or metachronous hepatic metastasis and patient survival. Conclusions: The incidence of bone marrow micrometastasis is not so high as had previously reported. The significance of bone marrow micrometastasis appeared to be quite low in gastric cancer. No significant financial relationships to disclose.
Attempts to ban DDT have had “tragic consequences”
Authors: Annabel Ferriman
Journal: BMJ (2001)

Pressures on poor countries to ban the insecticide DDT because of fears that its use would harm the environment have led to a resurgence of malaria in the world, yet the environmental impact of its use are “negligible,” a study published this week has said.

The study shows that after malaria was eradicated in wealthy countries and DDT was banned in those places, poor countries were pressured by health and donor agencies and environmental groups to stop using DDT spraying programmes. The agencies feared that they would harm the environment and adversely affect human health.

But these fears were unsubstantiated, the study's authors believe. “No scientific peer reviewed study has ever replicated any case of negative human …
The effect of nilotinib on major molecular responses (MMR) compared with imatinib in Japanese patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): Results from the Japanese subset of ENESTnd.
Authors: M. Hino, I. Matsumura, M. Kurokawa, T. Amagasaki, M. Yanada, N. J. Gallagher
Journal: Journal of Clinical Oncology (2010)

e17001 Background: Initial data from the global ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients) trial demonstrated superior efficacy of nilotinib compared with imatinib in pts with newly diagnosed Ph+ CML-CP. The purpose of this post-hoc sub-group analysis was to assess the efficacy of nilotinib compared to imatinib in the subset of Japanese patients in ENESTnd. Methods: 79 (9%) Japanese pts of 846 total pts were randomized to nilotinib 300 mg twice a day (bid) (n = 30), nilotinib 400 mg bid (n = 24), or imatinib 400 mg once a day (qd) (n = 25). Primary endpoint was rate of MMR at 12 months (mo). Results: Baseline demographics were similar to the overall study population with the exception that there were fewer Japanese pts with high Sokal risk scores (10%, 13%, and 8% for nilotinib 300 mg bid, 400 mg bid, and imatinib) compared with the overall study population (28% across arms). Median dose intensities of nilotinib were near planned dosing in all treatment arms and similar to the overall population. Rates of MMR at 12 mo were at least twice as high for nilotinib 300 mg bid (57%) and 400 mg bid (50%) compared with imatinib (24%). Kaplan-Meier estimated median time to MMR was faster for nilotinib 300 mg bid (5.8 mo) and 400 mg bid (8.4 mo) compared with imatinib (not yet reached). Rates of complete cytogenetic response (CCyR) by 12 mo were similar for all treatment arms (nilotinib 300 mg bid, 77%; 400 mg bid, 83%; imatinib, 76%). No pts on nilotinib progressed, while 1 pt progressed on imatinib. Both drugs were well-tolerated. Conclusions: Nilotinib at both doses led to twice the rate of MMR in Japanese CML pts compared with imatinib. These data suggest that MMR is a more suitable endpoint compared to CCyR for measuring deeper responses to nilotinib, regardless of Sokal risk. Molecular responses at 12 mo were higher in the Japanese subset compared with the overall ENESTnd population. The improved efficacy of nilotinib compared with imatinib support the use of nilotinib in the treatment of Japanese patients with newly diagnosed Ph+ CML- CP. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis
Subcutaneous interleukin-2, interferon alfa-2a, and continuous infusion of fluorouracil in metastatic renal cell carcinoma: a multicenter phase II trial. Groupe Français d'Immunothérapie.
Authors: A Ravaud, B Audhuy, F Gomez, B Escudier, T Lesimple, C Chevreau, J Y Douillard, A Caty, L Geoffrois, J M Ferrero, C Linassier, M Drevon, S Négrier
Journal: Journal of Clinical Oncology (1998)

A phase II trial was designed to determine the efficacy and the tolerance of interleukin-2 (IL-2), interferon alfa-2a (IFNalpha), and fluorouracil (5-FU) in patients with metastatic renal cell carcinoma.One hundred eleven patients were included. Patients received subcutaneous IL-2 9 x 10(6) IU daily for 6 days and IFNalpha 6 x 10(6) IU on days 1, 3, and 5 every other week for 8 weeks. 5-FU was administered through a continuous infusion at 600 mg/m2 for 5 consecutive days for 1 week every 4 weeks.The response rate was 1.8% (95% confidence interval [CI], 0% to 4.3%) with only two partial responses (PRs). Toxicity was moderate with 3.6% grade 4 events and two deaths related to treatment.This regimen of IL-2, IFNalpha, and 5-FU in patients with metastatic renal cell carcinoma was ineffective. The results raise the question of the dose and schedule of subcutaneous cytokines that must be used in metastatic renal carcinoma.
Use of targeted agents in elderly cancer patients (ECP) according to the Comprehensive Geriatric Assessment (CGA)
Authors: L. Fratino, A. Bearz, C. Simonelli, A. Giacalone, I. Sartor, A. M. Colussi, M. Berretta, E. Vaccher, M. Spina, U. Tirelli
Journal: Journal of Clinical Oncology (2008)

20619 Background: Epidermal Growth Factor Receptor (EGFR) inhibitors (Gefitinib and Erlotinib) increase the survival of NSCLC patients, while Sorafenib has clinical activity in advanced renal cell carcinoma (RCC). Safety and oral route administration of these drugs are noteworthy therapeutical peculiarities in ECP, but little is known about these topics in frail ECP. In this study, we describe the results obtained using oral targeted therapies in ECP assessed through the CGA. Methods: CGA is used as a screening tool to help decision making and to identify factors associated with toxicity among ECP at our Institute. According to CGA, ECP are classified in i) fit, ii) unfit and iii) frail patients. 53 ECP (median age: 74 yrs) with NSCLC (38) or RCC (15) represent this study population. Frails NSCLC ECP were treated with EGFR inhibitors as first line therapy, whereas in fit and unfit ones EGFR inhibitors were used as second line therapy. Among RCC, fit and unfit ECP were treated with Sorafenib: frail ECP underwent best supportive care. Results: Of these 53 ECP, 35.8% was fit, 37.7% unfit and 26.4% frail. Of 22 ECP with NSCLC treated with Gefitinib, 9 had clinical response (3 PR and 6 SD). The most common toxicities were gastrointestinal ( 3 G1 and 1 G2) and cutaneous ( 4 G2). 16 ECP with NSCLC were treated with Erlotinib: 7 (43.8%) showed clinical response (1 CR, 5 PR, 1 SD). Commonest toxicities were fatigue (2 G2), and cutaneous ( 4 G2). Among ECP with RCC, 11 were treated with Sorafenib (8 needed therapy discontinuation and/or dose reduction). Of them, 3 ECP showed PR, 2 SD, 4 PD and 2 were not evaluable; commonest toxicities were fatigue (G3), mucositis (G2) and hypertension (G1/2). Conclusions: Our experience seems to indicate that the oral use of targeted agents represents a treatment option in unfit ECP, even a feasible one in frail patients when Gefitinib or Erlotinib are used. This preliminary observation suggest that incorporation of CGA in oncology may help to better evaluate the usefulness of biological therapies among ECP. No significant financial relationships to disclose.
Abstract 13844: Quantitative Analysis of Pericardial Inflammation with Cardiac Magnetic Resonance Imaging (CMR) Predicts Outcome in Patients with Constrictive Pericarditis
Authors: Paul Cremer, Muhammed Tariq, Abhishek Karwa, Andres Schuster, Deborah Kwon, Allan L Klein
Journal: Circulation (2014)

Introduction:  Patients with constrictive pericarditis and intense pericardial inflammation may be more likely to respond to anti-inflammatories. We hypothesized that a quantitative assessment of pericardial inflammation with CMR would better discriminate which patients would improve with medical therapy.   Methods:  Consecutive symptomatic patients on anti-inflammatory therapy with echo and clinical evidence of constriction and CMR studies between January 2009 and September 2013 were included. The primary outcome was clinical resolution, defined as asymptomatic without pericardiectomy at follow-up. Inflammation was calculated as the volume of pericardium and epicardial fat on LGE that was 6 standard deviations above the signal intensity of normal myocardium. Nominal logistic regression was used to calculate the area under the receiver operating characteristic curves (AUC).   Results:  Our cohort had 39 patients (56.1 ± 14.0 years) with a median follow-up of 348 days (IQR 134,597). NYHA Class was 2 (IQR 2,3), and 22 patients had chest pain. All patients had a diastolic septal bounce and either a >15% expiratory increase in early mitral inflow (n=26) or a medial e’ velocity ≤9 cm/s (n=27). Decreased age (51.8 v. 60.7 years, p = 0.02), increased NYHA class (3 v. 2, p = 0.02), chest pain (68.2% v. 31.8%, p =0.02), increased ESR (33 v. 11, p=0.01), increased LGE pericardial thickness (5 v. 4 mm, p = 0.04), and increased pericardial LGE volume (82 v. 35 mL, p    Conclusions:  In patients with constrictive pericarditis, a quantitative assessment of pericardial LGE predicts clinical resolution and has incremental prognostic value when added to clinical factors and ESR.