tbuckley/cabot-search huggingface dataset:
Second Cancers in Patients With Chronic Lymphocytic Leukemia2
Authors: James W. Davis, Noel S. Weiss, Bruce K. Armstrong
Journal: JNCI Journal of the National Cancer Institute (1987)

Among 419 persons diagnosed as having chronic lymphocytic leukemia (CLL) in western Washington State between 1974 and 1983 and followed through January 1985, 9 subsequently developed other lymphoid cancers and 48 developed nonlymphoid cancers. Only 2 lymphoid and 21 nonlymphoid cancers were expected based on the rates of the western Washington population as a whole. Lung cancer accounted for about one-third of the excess rate observed. Three of the nonlymphoid tumors that occurred in the patients with CLL were classified as malignant fibrous histiocytomas, which represents an exceptionally high relative incidence for this histologic type. The excess risk of nonlymphoid cancers was present in both sexes, across all age categories, and in every length-of-follow-up interval. These results, taken together with those obtained from earlier investigations, suggest that persons with CLL are at increased risk of developing a second tumor, particularly in the lung. The reasons for this increased risk remain to be elucidated.
11C-Methionine positron emission tomography as an early predictor of outcome in bone and soft tissue sarcomas treated by carbon ion radiotherapy
Authors: H. Zhang, K. Yoshikawa, M. Tian, K. Tamura, S. Tanada, H. Tsujii
Journal: Journal of Clinical Oncology (2004)

3098 Background: The development of the novel carbon ion radiotherapy (CIRT) in the treatment of refractory cancers has resulted in the need for a way to accurately evaluate patients' prognosis. Amino acid metabolism of cancer is associated with numerous catabolic processes favoring tumor growth. As an essential amino acid, L-methionine plays a central role in the altered metabolism of cancer cells. We initially evaluated whether MET uptake and its change measured by PET after carbon ion radiotherapy were the early survival predicators in patients with bone and soft tissue sarcomas. Methods: MET PET was prospectively performed in 62 patients with bone and soft tissue sarcomas before and within one month after CIRT. Tumor MET uptake was measured with the semiquantitative tumor-to-nontumor ratio (T/N ratio). The MET uptake in the tumor and relevant clinical parameters were entered into univariate and multivariate survival analysis. Results: The overall median survival time was 20 months. Patients with a baseline T/N ratio of ≤ 6 had a significant better survival than patients with a baseline T/N ratio > 6 (2-year survival rate: 69.4% versus 32.3%, P=0.01). Patients with a post CIRT ratio of ≤ 4.4 had a better survival than that with a post CIRT ratio > 4.4 (2-year survival rate: 63.7% versus 41.3%, P=0.01). A significant higher survival rate was observed in patients with posttherapeutic MET uptake change of > 30% than patients in lower change group (2-year survival rate: 74.6% versus 41.6%, P=0.049). The multivariate analysis showed that both baseline and postCIRT T/N ratio were statistically significant independent predictors of patient survival. Tumors with larger T/N ratio had a significantly poorer prognosis. Conclusions: MET uptake, as measured by either baseline or postCIRT T/N ratio was an independent predictor of survival in patients with bone and soft tissue sarcomas treated by CIRT, while posttherapeutic MET uptake change might have potential value for the same purpose. No significant financial relationships to disclose.
The Cancer Risk of Protracted Use of Steroid Hormones
Authors: Roy Hertz
Journal: CA A Cancer Journal for Clinicians (1968)

When questioned about the carcinogenic hazard of protracted steroid hormone use, the Chief of the Reproduction Branch of the National Institute of Child Health and Human Development replied that such a concern has existed since the beginning of modern endocrinology when cornification of vaginal epithelium in mice occurred when they were administered ovarian extracts. Today, he states, we know that estrogens, when given in large does over prolonged periods, induce tumors of the breast, cervix, endometrium, pituitary, testicle, kidney, and bone marrow in mice, rats, rabbits, hamsters, and dogs (the most recent study cited being the development of breast cancer in beagle dogs after ingestion of an estrogen-progesterone combination). The applicability of these animals studies to humans is defended. Prescription of estrogens, which is extensive, is based on the negative animal study findings, the Chief states, and since chronicity of exposure to any carcinogen is the essential factor, dosage and duration of therapy must be carefully considered. Synergistic and antagonistic relationships between estrogen and progesterone components of combination steroid preparations are noted. Treatments of cancers based on estrogen and/or progesterone administration (e.g., endometrial carcinoma and cervical cancer) are discounted because of lack of evidence. In summary, women who use steroid contraception for prolonged periods run a risk of eventually developing cancer, though the extent of this risk remains undetermined.
Superior lung preservation with a polyethylene glycol based solution in a porcine lung transplant model
Authors: Anne Olland, Arne Neyrinck, Malika Benhamed, Thomas Boogmans, Alessia Stanzi, Karim Elbayed, Shana Wauters, Geert Verleden, Izzie Namer, Dirk Van Raemdonck
Journal: European Respiratory Journal (2012)

Objectives:  Scot15® is a low-K+ preservation solution including polyethylene glycol (PEG) as a colloid for protection of vascular endothelium during cold ischemia. PEG was previously demonstrated to have “immunocamouflage” properties. The aim of this study was to assess whether these properties would be beneficial in a pig lung transplant model.   Material:  Domestic pig donor lungs were flushed either with Scot15®[S;n=6] or Perfadex®[P;n=6] and stored on ice for 22 hours. The left lung was transplanted in a recipient animal observed during 6 hours after reperfusion. Pulmonary vascular resistance (PVR) and partial arterial oxygen tension (PaO 2 ) were measured hourly. Lung biopsies were taken for HRMAS detection of the respective colloid in the lungs. Bronchoalveolar lavage (BAL) was taken to assess neutrophilic alveolar recruitment. At the end of reperfusion, wet to dry weight ratio (W/D) was measured as a marker of lung edema.   Results:  HRMAS showed presence of PEG in the lungs in [S] before and during the reperfusion. Dextran was not detected in [P]. After 6 hours of reperfusion, PaO 2  was significantly better in [S](310±51mmHg versus 198±71mmHg in [P];p=0.03). PVR remained lower in [S] but the difference did not reach significance. Differential cell count of BAL showed lower neutrophilic cell count in [S](89±67neutrophils in [S] versus 139±53neutrophils in [P];p=0.001). There was no difference in W/D weight ratio (p=0.9).   Conclusion:  After 22 hours of cold ischemia, oxygenation capacity was superior with less inflammatory reaction in lung grafts preserved with Scot15®. Further experiments to study the “immunocamouflage” properties of PEG based solutions in lungs are warranted.
Abstract 19366: First-in-Human Dual Manganese- and Gadolinium-Enhanced Cardiac MRI Delineates the Peri-Infarct Region in Patients with Severe Ischemic Cardiomyopathy
Authors: Rajesh Dash, Yuka Matsuura, Paul J Kim, Hadas Shiran, Phillip Harnish, Michael V McConnell, Phillip C Yang
Journal: Circulation (2014)

Background:  Delayed Gadolinium (Gd) Enhancement MRI (DEMRI) overestimates infarct size. Manganese enters only live, active cells, and its T1 signal is  specific to live cardiomyocytes . We combined DEMRI and Manganese-enhanced MRI (MEMRI) in humans with ischemic cardiomyopathy to test if MEMRI provides unique infarct characterization.   Methods:  5 patients with ejection fraction (EF)  3 standard deviations (SDs) above mean (DEMRI) and >2 SDs below mean (MEMRI signal defect = scar). % Infarct to total LV mass was calculated.   Results:  LV EF=32±4% (mean±SD). DEMRI volumes (39±11%* of LV) were significantly (*p   Conclusion:  The DEMRI-MEMRI infarct size discrepancy may delineate a peri-infarct region, or “at-risk myocardium” that DEMRI does not detect.
Randomized multinational phase 3 trial of dacarbazine (DTIC) with or without Bcl-2 antisense (oblimersen sodium) in patients (pts) with advanced malignant melanoma (MM): Analysis of long-term survival
Authors: M. J. Millward, A. Y. Bedikian, R. M. Conry, M. E. Gore, H. E. Pehamberger, W. Sterry, A. C. Pavlick, R. C. De Conti, D. Gordon, L. M. Itri
Journal: Journal of Clinical Oncology (2004)

7505 Background: Chemotherapy resistance of MM has been linked to Bcl-2, an anti-apoptotic protein over-expressed in > 80% of pts. Oblimersen sodium (Genasense™; GNS) targets bcl-2 mRNA and increases apoptosis when added to chemotherapy. A prior study showed GNS down-regulates Bcl-2 in MM, and, when combined with DTIC, produced encouraging survival. We conducted a randomized trial of DTIC alone compared with DTIC plus GNS in pts with advanced MM. Methods: Eligibility: Stage 4 or unresectable stage 3; ECOG PS ≤ 2; adequate hematologic and organ function. Exclusions: brain metastases; prior chemotherapy. Pre-randomization strata: Liver metastases (Y/N); other visceral metastases or elevated serum LDH (Y/N); PS (0 vs. 1–2). Pts received DTIC 1,000 mg/m2 Q3 weeks. Patients randomized to GNS received 7 mg/kg/d for 5 days by continuous IV infusion prior to DTIC. Primary endpoint: overall survival (OS). Secondary endpoints: progression-free survival (PFS); response rate (RR, RECIST criteria). Results: Intent-to-treat (ITT) analysis for all 771 randomized pts showed estimated median survival of 9.1 mos for GNS/DTIC pts vs. 7.9 mos for DTIC alone (P=0.18). Although survival differences at 15 and 18 mo. landmarks were significant (P <0.05), the short follow-up of ITT pts (median=7 mos) precluded OS determination. For pts followed ≥ 12 mos, OS was superior for GNS/DTIC vs. DTIC alone (ITT [n=520]: 10.1 vs. 7.9 mos, P=0.067; Per-Protocol [n=480] 10.1 vs. 8.1, P=0.035; landmarks at 12, 15 and 18 mos, P<0.05). For the 771 ITT patients, GNS treatment increased both median PFS and TTP (74 vs. 49 days for both, P=0.0003). GNS also significantly increased ITT RR (CR+PR): 11.7% vs. 6.8%; P = 0.019. Fever, rigors, headache, neutropenia, thrombocytopenia, nausea, vomiting and anorexia were greater in GNS/DTIC pts. Therapy related deaths, discontinuations, and DTIC doses delivered in each group were not significantly different. Conclusions: GNS can enhance the antitumor effectiveness of DTIC. Follow-up analyses and long-term benefit in pts on extended GNS/DTIC will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genta, Inc. Genta, Inc. Genta, Inc. Aventis Genta, Inc .
Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) evaluation in glioblastoma (GBM) patients treated with bevacizumab (BEV) and irinotecan (CPT-11)
Authors: A. Desjardins, D. P. Barboriak, J. E. Herndon, D. A. Reardon, J. A. Quinn, J. N. Rich, S. Sathornsumetee, S. Gururangan, H. S. Friedman, J. J. Vredenburgh
Journal: Journal of Clinical Oncology (2007)

2029 Background: Significant responses seen in GBM patients treated with BEV and CPT-11 generated the need to develop ways to predict clinical benefit. DCE-MRI can be used to evaluate the microvasculature within tumors. DCE-MRI uses K trans, a volume transfer constant of contrast agent between blood plasma and the extravascular extracellular space, to determine vascular permeability. A 50% reduction in K trans is clinically meaningful. We report a phase II trial to determine the correlation between vascular permeability and radiographic response in GBM patients treated with the combination. Methods: Eligibility included patients with recurrent GBM. Both agents were given every 14 days. All patients received BEV at 10 mg/kg IV. CPT-11 was dosed at 340 mg/m 2 for patients on enzyme inducing antiepileptic drugs (EIAED) and 125 mg/m 2 for patients not on EIAED. Radiographic responses were assessed every 6 weeks. DCE-MRIs were performed before administration of chemotherapy, one day after treatment and after the first cycle. The primary endpoint was to examine the effect of BEV and CPT-11 treatment on vascular permeability as measured by percent change from baseline in K trans . Results: Twenty patients were enrolled, with a median age of 49.5 years. Fifteen patients are assessable for response. Best responses include one patient with complete response, 8 with partial response (response rate=60%), six patients with stable disease, and one with disease progression. K trans values are available for 13 patients; data are not available for seven patients (too early: 4, technical difficulty: 3). A reduction in K trans by 50% was observed in 6 patients one day after treatment and in 12 patients at the end of cycle 1. Changes in K trans value were highly correlated with the percentage decline in tumor volume from baseline to end of cycle one (Pearson correlation = 0.82; p=0.0006). Fifteen patients are still on study. Five patients came off due to disease progression. Conclusions: The utilization of DCE-MRI to determine a reduction in vascular permeability following a combination of BEV and CPT-11 is feasible and correlates significantly with the degree of tumor volume decrease. No significant financial relationships to disclose.
Phase III randomized trial to evaluate the use of gabapentin alone vs with continuing an antidepressant in women failing an antidepressant for the treatment of hot flashes: North Central Cancer Treatment Group Study N00C3
Authors: C. L. Loprinzi, J. W. Kugler, D. L. Barton, A. C. Dueck, L. K. Tschetter, R. A. Nelimark, E. P. Balcueva, M. D. Carlson, S. F. Duane, S. W. Corso
Journal: Journal of Clinical Oncology (2006)

526 Background: Antidepressants do not adequately alleviate all HFs. Based on placebo-controlled data demonstrating that GABA is an alternative therapy for HFs, this trial was initiated to test whether the combination of an antidepressant and GABA was better than GABA alone in PTS with inadequate HF control on an antidepressant alone. Methods: Eligible PTS on antidepressants with bothersome HFs were randomized to two groups. PTS kept a daily HF diary during a baseline wk (while continuing their antidepressant). Following the baseline wk, all PTS were given GABA 300 mg at hs for 3 days, then BID for 3 days, and then TID for 22 days. One group continued their antidepressant while the other group was weaned off it over several days. PTS continued a daily HF diary during this 4-wk period. Efficacy was measured using the mean daily HF number and score; the latter measured by assigning points (1–4, for mild to very severe) to each HF and then adding the points for a given time. The study design provided 80% power to detect a difference in the changes from baseline at 4 wks between the two groups of 1.2 HFs/day, or 3 points/day in HF scores. Results: 115 PTS were randomized and given GABA. PTS continuing their antidepressant reported a 48% mean reduction in HF score after 4 wks, vs 49% for PTS stopping it (p=0.97). Mean HF numbers were reduced 50% and 47%, respectively (p=0.54). 16 other symptoms and quality of life items were measured by PT-completed weekly questionnaires, with the only suggestive changes from baseline between the two arms being more mood troubles after 2 wks of treatment (p=0.06) and more nervousness after 4 wks of treatment (p=0.01) in PTS stopping their antidepressant. Also, a mild temporary increase in dizziness after 1 wk of treatment was observed in the same group (p=0.08) suggestive of an antidepressant withdrawal reaction. Conclusion: This trial failed to provide any evidence that the combination of GABA and an antidepressant decreased HFs any more than did GABA alone in PTS who had inadequate HF control with an antidepressant alone. The 50% reduction in HFs in both arms is commensurate with the efficacy of GABA delineated in other published reports. No significant financial relationships to disclose.
FAC (fluorouracil, doxorubicin, cyclophosphamide) as second line chemotherapy in patients with metastatic breast cancer progressing under FEC (fluorouracil, epirubicin, cyclophosphamide) chemotherapy
Authors: G. Catimel, F. Chauvin, J.P. Guastalla, P. Rebattu, P. Biron, M. Clavelt
Journal: Annals of Oncology (1994)
1,25-Dihydroxyvitamin D3 Induces NAD(+)-Dependent 15-Hydroxyprostaglandin Dehydrogenase in Human Neonatal Monocytes
Authors: F. Pichaud, S. Roux, J.L. Frendo, R. Delage-Mourroux, J. Maclouf, M.C. de Vernejoul, M.S. Moukhtar, A. Jullienne
Journal: Blood (1997)
State of the research on breast cancer in young women.
Authors: Michelle Esser, Jean Rowe, Megan McCann, Stacy Lewis
Journal: Journal of Clinical Oncology (2014)

117 Background: Young Survival Coalition (YSC) is the premier global organization dedicated to the critical issues unique to young women and breast cancer. In May, 2014, YSC released its Research Agenda which identified the most pressing research questions that must be answered in order to improve the quantity and quality of life for young women affected by breast cancer. Methods: This Research Agenda arose out of an almost two-year-long process created and facilitated by YSC, called the Research Think Tank (RTT). YSC assembled doctors, researchers and advocates to focus on six areas of particular importance to its young constituents: risk factors; treatment; metastasis; quality of life; fertility; and pregnancy. Results: Through the work of the RTT, YSC assessed the current state of knowledge as well as existing gaps in each of the six identified areas. While work is needed in all areas, there have been recent updates and progress regarding treatment and fertility. Additionally, quality of life studies examine the uniqueness of breast cancer in young women, although application of this knowledge through tested interventions, decision aids, or guidelines and tools for physicians are still lacking. Aspects of pregnancy during breast cancer and after breast cancer have been studied but many open questions remain. There has been little progress in understanding why so many breast cancers are diagnosed in the postpartum period, why they tend to be more aggressive, and what can be done to prevent or treat it. Research examining metastasis in young women is rare. Most research focuses on postmenopausal patients, and many studies set criteria that specifically exclude younger women. This is the topic area most in need of work and priority. Similarly, little research focuses on the specific risk factors for early onset breast cancer. These are likely distinct from the risk factors associated with postmenopausal breast cancer yet they are rarely separately examined. Conclusions: Compared to older women, young women generally face more aggressive cancers, lower survival rates, and unique psychosocial concerns. Breast cancer in young women is an area in need of additional work and clarification in order to increase their quantity and quality of life.
Effectiveness of angionten II receptor blocker (ARB), candesartan, in the treatment of hormone refractory prostate cancer (HRPC)
Authors: H. Uemura, Y. Miyoshi, H. Ishiguro, N. Nakaigawa, K. Noguchi, Y. Kubota
Journal: Journal of Clinical Oncology (2004)

4614 Background: Angiotensin II receptor (AT1 receptor) blockers (ARB) are a class of antihypertensive agent. Based on our preclinical study which demonstrated candesartan, one of ARB, can suppress signal transduction pathways mediated by growth factors, cytokines and angiotensin II through AT1 receptor in prostate cancer cells (Mol. Cancer Ther. 2:1139, 2003), a clinical trial of candesartan for HRPC was undertaken. Methods: Twenty-two patients with HRPC were enrolled in this study. Pts characteristics: median age=74 year (range 63–92), median on study PSA=28.2 ng/ml (range 0.65–684). Prior therapy included (n pts): maximum androgen blockade (22), radiotherapy (7), chemotherapy (3). Nine pts had bone-only disease, 9 pts had bone and soft tissue disease, and 2 had only soft tissue disease. Pts were instructed to take candesartan, daily p.o., started with 4 mg (up to 12 mg). Simultaneously all pts were treated with LH-RH analogue, although the antiandrogen was discontinued. The end point of this study was the assessment of changes in PSA. Decline in absolute PSA value was defined as a reduction compared with the maximum value in the treatment or the screening value. Pts underwent regular measurement of PSA monthly. Results: Five patients (22.7%) showed a decrease in PSA ≥ 50%, and 4 patients (18.2%) showed decrease in PSA < 50%. Overall 9/22 (40.9%) patients showed a PSA response despite the fact that all patients had androgen-independent cancers. The median interval before PSA decrease was 8 weeks (range 4–40 weeks). The mean time to progression of PSA was 7.8 months (range 2 to 24 months). Only one patient showed an objective response, indicating the size reduction of metastatic tumors in lung. Administration of candesartan was well tolerated, and its adverse event showed only hypotension in 3 patients. Conclusion: We believe that this agent has a novel ability to suppress the cell growth of androgen-independent cancer and prolong the prognosis of HRPC, although we do not think the dose of candesartan is enough to control HRPC completely. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ministry of Education, Science, and Culture of Japan
High-dose versus low-dose vinblastine in cisplatin-vinblastine-bleomycin combination chemotherapy of non-seminomatous testicular cancer: a randomized study of the EORTC Genitourinary Tract Cancer Cooperative Group.
Authors: G Stoter, D T Sleyfer, W W ten Bokkel Huinink, S B Kaye, W G Jones, A T van Oosterom, C P Vendrik, P Spaander, M de Pauw, R Sylvester
Journal: Journal of Clinical Oncology (1986)

Two hundred fourteen patients with disseminated non-seminomatous testicular cancer were randomized to receive induction chemotherapy with cisplatin, vinblastine, and bleomycin (PVB). The randomization was for vinblastine 0.4 mg/kg/cycle or 0.3 mg/kg/cycle. The complete response (CR) rates to both regimens were identical: 68% and 71%, respectively. In addition, there was no significant difference in disease-free and overall survival. There was a significant decrease in the incidence of WBC nadirs below 1,000/microL: 29% and 13%, respectively (P = .01). Of the non-hematologic toxicities, there was a significant reduction in the incidence of mucositis: 53% and 37%, respectively (P = .006). The major prognostic factor was tumor volume. This study confirms that vinblastine 0.3 mg/kg/cycle in PVB chemotherapy is as effective and less toxic than vinblastine 0.4 mg/kg/cycle.