tbuckley/cabot-search huggingface dataset:
Final analysis of a safety and efficacy trial of preoperative sequential chemoradiation therapy for the nonsurgical treatment (NST) in early breast cancer (EBC): Japan Clinical Oncology Group Trial (JCOG0306).
Authors: H. Mukai, T. Watanabe, M. Mitsumori, H. Tsuda, S. Nakamura, N. Masuda, N. Yamamoto, T. Shibata, A. Sato, K. Aogi
Journal: Journal of Clinical Oncology (2010)

552 Background: The combination of preoperative anthracycline-containing regimen and taxane can obtain a good pathologic complete response (pCR) rate for patients (pts) with EBC. To pursue higher pCR rate with maintaining good systemic control may lead to the NST in the future. The objective of this trial is to determine whether the addition of radiation therapy (RT) to chemotherapy (CT) can surpass the pCR rate of 50% as the first step of turning the NST into reality. Methods: We conducted a safety and efficacy trial of CT (4 courses of doxorubicin and cyclophosphamide [60/600mg/m2] followed by 12 courses of weekly paclitaxel [80mg/m2]) and RT (whole breast 45Gy + boost 10Gy) sequentially as a primary therapy in pts with stage I-IIIA (5.0cm ≥ tumor size ≥ 2.0cm) breast cancer (BC). All pts received mastectomy or lumpectomy 12-16 weeks after completion of RT to maximize the effect of RT. Primary endpoint was pCR rate. pCR was assessed by the central pathological review board. Results: Between June 2004 and April 2005, 108 pts were enrolled. Median age was 50 years (range 23-69). 62% (67/108) were hormone receptor (HR) +, and 31% (34/108) had HER2+. 36% of the entire population achieved a pCR. The pCR rate was 57% in pts with HR-/HER2+, and 52% in triple-negative pts, respectively. While 7% of HR–/HER2+ pts recurred, higher incidence of recurrence (24%) was observed in triple-negative pts in follow-up of 4.5 years. The rate of breast- conserving surgery was 91% (96/106). One pt received debridement for radiation associated necrosis 3 months after lumpectomy. Other toxicities were mild to moderate. Conclusions: Preoperative sequential chemoradiation therapy did not increase the risk of operative complications and could achieve high rate of breast-conserving surgery, even though expected % pCR was not achieved. Choosing the subgroup of EBC can be necessary to realize NST in the next step. Characteristics No. of pts pCR rate No. of recurrence events HR+/HER2- 46 24% 10 (22%) HR+/HER2+ 20 40% 3 (15%) HR-/HER2- 25 52% 6 (24%) HR-/HER2+ 14 57% 1 (7%) No significant financial relationships to disclose.
The effect of food on the oral absorption of 9-nitrocamptothecin (9NC) in patients with relapsed solid tumors
Authors: S. Goel, S. Mani, T. Iqbal, K. Desai, R. A. Parise, R. Afroze, M. J. Egorin, W. C. Zamboni
Journal: Journal of Clinical Oncology (2004)

2106 Background: 9NC (Orathecin) is an orally administered camptothecin analogue that has completed phase III trials for pancreatic cancer. In biological solutions, camptothecin analogues occur in equilibrium between the active-lactone (LAC) and inactive-hydroxy acid (HA) forms. 9NC has been administered fasting, however it is unclear whether co-administration of 9NC with food alters absorption. Thus, we evaluated the disposition of 9NC and its 9-aminocamptothecin (9AC) metabolite under fasting conditions and after a standard meal. Methods: Patients (pt) were randomized to receive 9NC as a single oral dose at 1.5 mg/m2 with 500 mL of an acidic beverage under fasting conditions, or after a meal of 2 eggs, 8 oz of orange juice, buttered toast, 8 oz of milk, and 4 oz of hash brown potatoes. Following a 72-hour (h) washout period, 9NC was administered with the alternative condition (ie, with food or fasting). 9NC was then continued for five days of every week. Serial blood samples were obtained before and from 0.25 to 24 h after administration. 9NC and 9AC total (sum of LAC + HA) were measured by an LC-MS/MS assay. Area under the plasma concentration versus time curve (AUC) for 9NC and 9AC from 0 to 24 h was calculated by the log-trapezoidal method. Results: Sixteen pts with median (range) age 62 (47–83) years, with colorectal (6 pt), lung (2 pt) cancer, and others (8 pts), received 83 [median (range) 4 (2–9)] weeks of therapy. Overall, grade 3 or greater toxicities included diarrhea (1 pt), nausea (2 pt), vomiting (2 pt), fatigue (2 pt), anemia (3 pt), and neutropenia (3 pt). Three patients experienced stable disease for eight weeks. The pharmacokinetic data is tabulated. Mean (SD) ratio of 9NC AUCfood to AUCfasting was 0.67 (0.22). Mean (SD) ratio of 9AC AUCfood to AUCfasting was 0.87 (0.61). Conclusions: Co-administration of 9NC with food reduces its oral absorption. (Supported by SuperGen, Inc. and NCI 2P30 CA47904) Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Supergen Supergen
Experience with inhaled iloprost in paediatric pulmonary arterial hypertension
Authors: Alba Torrent Vernetta, Antonio Moreno Galdό, Inés Mir Messa, Sandra Rovira Amigό, Josep Girona Comas, Silvia Gartner, Maria Teresa Benabides Medina, Carlos Martin de Vicente
Journal: European Respiratory Journal (2011)

Background: Inhaled iloprost has been approved for the treatment of Pulmonary Arterial Hypertension (PAH) in adults, but there are few studies about its effects in children.

Objectives: To review long-term effects and outcomes of inhaled iloprost treatment in children with PAH.

Methods: Retrospective review of clinical and haemodynamic evolution in children with PAH after inhaled iloprost therapy.

Results: Between 2000-2010 25 patients with PAH were treated with inhaled iloprost (17 female; range 3 months to 12-years-old): 11 idiopathic, 1 pulmonary veno-occlusive disease, 4 associated with congenital heart disease, 7 lung disease, 1 schistosomiasis and 1 congenital metabolic disease. Clinical and haemodynamic parameters at baseline were: WHO class II in 3, III in 16, IV in 6, and median of mean pulmonary arterial pressure 56 mmHg (range 29-90 mmHg). Iloprost was started as initial therapy in 14 patients: 8 as monotherapy and 6 as combined treatment, and in 11 cases was added during the follow-up. Mean dose was 50 μg/day. Median follow-up was 3.6 years (range 1 month to 10 years). There were no serious side effects but facial flushing was often observed in those using a mask. During the follow-up iloprost was discontinued in 1 patient due to abdominal pain, 1 patient was lost, 12 patients improved their functional class, 3 remained stable, 3 received a lung transplant, 1 a heart-lung transplant and 4 died.

Conclusions: Inhaled iloprost is well tolerated in children, both as monotherapy and as a combined treatment, with minimal side effects. Although uncontrolled, data suggest long-term clinical benefit from continued therapy in 60% of patients.
Abstract 12345: QRS Duration and Radial Dyssynchrony Are Associated with Survival in Patients with Ischemic Cardiomyopathy Undergoing Cardiac Resynchronization Therapy
Authors: Phillip J Habib, Olusegun Oyenuga, Stephanie C Haberman, Hidekazu Tanaka, Evan Adelstein, John Gorcsan
Journal: Circulation (2010)
Evaluation of reduced intensity allogeneic hematopoietic stem cell transplantation (HSCT) using anti lymphocyte antibodies in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)
Authors: U. R. Popat, G. Carrum, R. Krance, M. Brenner, H. Heslop
Journal: Journal of Clinical Oncology (2004)

6544 Background: AML and MDS are more frequent and have worse prognosis with increasing age. Although HSCT with fully ablative conditioning is curative in 30–50% of patients with AML, it is associated with 25–40% treatment related mortality and is therefore unsuited to most AML patients. HSCT using reduced intensity conditioning may be an alternative. Methods: Patients with high risk AML or MDS not eligible for conventional transplant because of age or co-morbidities were conditioned with a single fraction TBI 450 cGY, Fludarabine 120mg/m2, as well as ATG 40mg/kg or Campath 40 mg with or without CD45 monoclonal antibodies. Allogeneic bone marrow (7) or blood stem cells(16) from HLA identical (5 related and 13 unrelated). or one antigen mismatched (3 unrelated, 2 related) donors were infused. Results: 23 consecutive patients with AML (11), MDS (3), AML secondary to MDS (7) and therapy related MDS/AML (2) were enrolled. Median age was 55 (4–75) years with 13 males and 10 females. Cytogenetic studies showed complex karyotype(8), chromosome 7 abnormality (5), normal (5) and other abnormalities in 5 patients. 11 patients were in relapse with active disease and 12 were in complete remission (6 CR1, 6 CR2) at the time of transplant. At a median follow up of 385 days (46–1543), 14 patients are alive in remission with an actuarial disease free survival at one year of 58%. Of 5 patients (22%) who developed grade II-IV graft versus host disease (GvHD), 1 patient had severe (grade III-IV) GvHD which was fatal, 1 patient rejected the graft and died and 1 patient died of central line sepsis with a non relapse mortality of 13%(3/23). The remaining 6 patients died of progressive disease. Conclusions: Reduced intensity transplantation is a promising therapy for older patients with MDS and AML even when alternative donor cells are used No significant financial relationships to disclose.
Combination chemotherapy with or without thoracic radiotherapy in limited-stage small-cell lung cancer: a randomized trial of the Southeastern Cancer Study Group.
Authors: D H Johnson, D Bass, L H Einhorn, J Crawford, C A Perez, A Bartolucci, G A Omura, F A Greco
Journal: Journal of Clinical Oncology (1993)

PURPOSE The primary objective of this randomized prospective study was to compare the survival of limited-stage small-cell lung cancer (SCLC) patients treated with chemotherapy alone or chemotherapy plus thoracic radiotherapy (TRT). A secondary objective was to determine the effect of consolidation chemotherapy on survival. PATIENTS AND METHODS This multiinstitutional phase III study included 386 patients with limited-stage SCLC. All patients received cyclophosphamide 1,000 mg/m2, doxorubicin 40 mg/m2, and vincristine 1 mg/m2 (CAV) every 3 weeks for six cycles. Irradiated patients received 30 Gy in 10 fractions during weeks 1 and 2 of chemotherapy. Fifteen Gy in five fractions was administered during week 7 (total dose, 45 Gy). Following CAV, responding patients were randomized to receive two cycles of consolidation chemotherapy (cisplatin 20 mg/m2/d for 4 days plus etoposide 100 mg/m2/d for 4 days) or observation. RESULTS Complete (46% and 38%; P = .14) and overall response rates (67% and 64%; P = .58) were not statistically significantly different. Although not significantly different, median (14.4 v 12.8 months) and 2-year survival (33% v 23.5%) rates favored the irradiated patients. Grade 4 hematologic toxicity was greater in irradiated patients (60% and 39%; P &lt; .001). Patients given consolidation chemotherapy experienced superior median (21.1 v 13.2 months; P = .028) and 2-year survival (44% v 26%; P = .028) rates. CONCLUSION The concurrent use of TRT and CAV chemotherapy as administered in this study failed to improve the survival of limited-stage SCLC patients compared with CAV alone. Life-threatening hematologic toxicities were more frequent with combined-modality therapy. The survival of limited-stage patients treated with CAV (with or without TRT) was improved with two cycles of cisplatin and etoposide consolidation therapy. Whether similar survival results could be achieved with cisplatin and etoposide alone requires additional study.
Do sensitive patients have sensitive tumors?
Authors: M. Ozsahin, A. Zouhair, N. E. A. Crompton, R. Moeckli, L. Li, R. O. Mirimanoff, D. Azria
Journal: Journal of Clinical Oncology (2005)

5516 Background: The concept of expecting radiosensitive tumors in patients genetically hypersensitive to radiation is not widely accepted. Here, we aim to assess whether the tumors of patients with increased lymphocyte apoptotic response with head and neck cancer have a better outcome than their normoresponsive counterparts. Methods: Seventy-five patients with head and neck cancer treated with curative radiation therapy (RT) were included in the KFS 00539–9-1997/SKL 00778–2-1999 prospective study aiming at assessing the value of CD8 T-lymphocyte apoptosis in predicting intrinsic radiosensitivity. Male to female ratio was 60/15, and median age was 59 years (35–85). Median radiation dose was 66 Gy (60–74.4) administered in median 41 days (37–58). Dose per fraction was 2 Gy in the majority of the patients (n = 70). Prior to RT, all patients were tested using a rapid (48 h) apoptosis assay where fresh blood samples were irradiated with 8-Gy X rays. Lymphocytes were collected and prepared for flow cytometric analysis. Apoptosis was assessed by gradual degradation of DNA (sub-G1 peak on the DNA histogram). Acute (CTC v2.0) and late (RTOG/EORTC) toxicities were graded in all patients. Median follow-up period was 31 months (23–43). Results: Following in vitro 8-Gy irradiation, median radiation-induced CD8 apoptosis was 20.88% (5.69–57.00%). Radiation-induced CD8 apoptosis significantly predicted grade 2 and 3 late effects. The area under the curve of the receiver-operated characteristic curve (sensitivity versus 1-specificity) of CD8 apoptosis was 0.83. Median time to locoregional relapse was 30 months (1–43 months). There were 13 locoregional relapses among the 37 patients showing CD8 apoptosis below the median compared to 5 of 38 who were above (p = 0.02). Two-year estimated locoregional relapse rate was 31% (95% CI: 17–45%) versus 14% (95% CI: 3–25%), respectively (p = 0.03). Conclusions: In patients with head and neck cancer treated with definitive or postoperative RT, in vivo apoptotic response of CD8 lymphocytes depends on genetic radiosensitivity, and the tumor follows the same genetic radiosensitivity of normal tissues. However, these findings should be confirmed prospectively, and future dose escalation studies could be stratified using the apoptosis assay. No significant financial relationships to disclose.
Sonoporation enhances liposome accumulation and penetration in tumors with low EPR
Authors: Benjamin Theek, Maike Baues, Tarun Ojha, Diana Möckel, Seena Koyadan Veettil, Julia Steitz, Louis van Bloois, Gert Storm, Fabian Kiessling, Twan Lammers
Journal: Journal of Controlled Release (2016)
Abstract 17162: Early and Late Stent Thrombosis are Associated with Long-Term Cardiac Mortality: Results from Pooled PROTECT Trials
Authors: Eric A Secemsky, P. Gabriel Steg, Edoardo Camenzind, William Wijns, Eugene McFadden, Laura Mauri
Journal: Circulation (2014)

Background: Trials of coronary stents have indicated high mortality risks associated with stent thrombosis (ST), but there have been few adequately powered studies with prospective late follow-up. Methods: The Patient-Related OuTcomes with Endeavor versus Cypher stenting Trial (PROTECT) randomized 8709 subjects to either Endeavor zotarolimus-eluting or Cypher sirolimus-eluting stents, and the PROTECT Continued Access Trial enrolled 1018 patients treated with Endeavor zotarolimus-eluting stents in the U.S. and Canada. Subjects in each were consented for 5 years of follow-up and completed 4 and 3 year follow-up to date respectively. The primary endpoint was ARC definite and probable ST. All potential ST events were stratified by time from index procedure: early (≤30 days), late (>30 and ≤360 days) and very late (>360 days). Baseline characteristics and rates of death and myocardial infarction (MI) were analyzed according to time of ST. Results: The median follow up was 4.1 years. There were 184 ST events: 6...
Humoral Immune Responses of Cats to Feline Leukemia Virus: Comparison of Responses to the Major Structural Protein p30 and to a Virus-Specific Cell Membrane Antigen (FOCMA)2
Authors: H. P. Charman, N. Kim, R. V. Gilden, W. D. Hardy, M. Essex
Journal: JNCI Journal of the National Cancer Institute (1976)

Radioimmunoprecipitation was used to test cat sera for ability to bind to the purified major internal protein p30 of feline leukemia viurs (FeLV), to the endogenous cat virus (RD-114), and to murine leukemia virus (MuLV). The data were compared with results of tests for antibody to the feline oncornavirus-associated cell membrane antigen FOCMA and for the presence of viremia. In contrast to the general lack of free antibody to FeLV p30 in a random sample of healthy cats, high levels of antibody to FeLV p30 and FOCMA were found in normal animals from high-leukemia-cluster households. Titers of greater than or equal to 200 for p30 and greater than or equal to 32 for FOCMA were found in nonviremic animals; a percentage of animals with high FOCMA titers and lower or no p30 binding activity were viremic. Animals with neoplasms were low or negative for FOCMA antibody and did not have high titers of free p30 antibody. The p30 binding activity could be divided into three main categories: high binding with FeLV p30 and much lower activity with RD-114 and MuLV p30's, as seen with hyperimmune sera; high binding with FeLV and RD-114 p30's and low activity with MuLV p30, possibly indicative of specific antibody to both of the aforementioned proteins; and low level binding to all three p30's.
Statins and superficial bladder cancer evolution after diagnosis: A population-based study
Authors: V. Fradet, O. Sheehy, F. Saad, J. LeLorier
Journal: Journal of Clinical Oncology (2008)

22047 Background: Statins are mostly associated with diminished incidence of many solid cancers. Our objective is to determine if statins reduce the risk of superficial bladder cancer [SBC] evolution after diagnosis. Methods: This study was based on administrative databases in Quebec, Canada, containing data on patient demography, prescription claims and physician services. Study patients were newly diagnosed with SBC and had a trans-urethral resection of tumor [TUR-BT] procedure between July 1, 1995 and January 1, 2002. We excluded patients with prior cancer diagnosis and those with immediate cystectomy, chemotherapy or radiation therapy. All eligible patients were grouped into cohorts of statin users and non-users. Cox regression models assessed time to recurrence, to progression to cystectomy and to death from all causes. Co-variables included were: sex, age, intravesical adjuvant therapy, chronic disease score, medical and emergency visits, and hospitalization days in the year prior to first TUR-BT. Models were adjusted for immortal time and used time dependent classification of exposure to statins. Results: Of the 4,834 cohort patients, 1,211 (25%) were statin users. Recurrence, progression of SBC, and death were observed in 2,340 (48%), 225 (5%), and 1,051 (22%) of patients, respectively. Baseline variables were similar in statin users and non users, except for intravesical adjuvant therapy, more frequent in unexposed patients (9.9% vs 7.8%). Statin use was associated with a Hazard Ratio [HR] (95% CI) of 0.97 (0.86–1.09) for recurrence, a HR of 0.58 (0.38–0.91) for SBC progression to cystectomy and a HR of 0.54 (0.44–0.66) for death from all causes. Conclusions: Statin use does not seem to have an impact of bladder cancer recurrence, but appears protective for superficial bladder cancer progression to muscle-invasive status leading to cystectomy, and for all-cause death. Its apparent efficacy suggests that further investigation in randomized trials may be warranted. No significant financial relationships to disclose.
Pseudoatrial Flutter Waves—When a Flutter Is Not a Flutter
Authors: Nathanial S. Nolan, Scott M. Koerber, Sudarshan Balla
Journal: JAMA Internal Medicine (2016)

The patient’s medical history was significant for chronic obstructive lung disease, obstructive sleep apnea, type II diabetes mellitus, hypertension, hyperlipidemia, and major depressive disorder. The patient denied palpitations or light-headedness in the postoperative period. The patient reported a history of intermittent dizziness and falls over the preceding months. A telemetry strip that prompted the referral is shown in Figure 1. On examination, the patient was in no apparent distress. Her heart rate was regular without murmurs or gallops. Auscultation of lungs revealed normal breath sounds. She had a resting tremor in her right hand. There was no rigidity in any extremities, and the rest of the physical examination findings were normal. She was admitted to the cardiology service for management of new-onset atrial flutter. Serum chemistries (including potassium and magnesium) and complete blood cell count were within normal limits. A 12-lead electrocardiogram (ECG) was performed on arrival to the telemetry unit. It was determined that the ECG demonstrated artifactual waves, most prominent in the limb leads (Figure 2). It was determined that she had pseudoatrial flutter waves and she was subsequently discharged with an event monitor to determine the underlying cause of her falls.
Stillbirths: progress and unfinished business
Authors: J Frederik Frøen, Ingrid K Friberg, Joy E Lawn, Zulfiqar A Bhutta, Robert C Pattinson, Emma R Allanson, Vicki Flenady, Elizabeth M McClure, Lynne Franco, Robert L Goldenberg, Mary V Kinney, Susannah Hopkins Leisher, Catherine Pitt, Monir Islam, Ajay Khera, Lakhbir Dhaliwal, Neelam Aggarwal, Neena Raina, Marleen Temmerman, Vicki Flenady, J Frederik Frøen, Mary V Kinney, Luc de Bernis, Joy E Lawn, Hannah Blencowe, Alexander Heazell, Susannah Hopkins Leisher
Journal: The Lancet (2016)
Structural Decoding of the Netrin-1/UNC5 Interaction and its Therapeutical Implications in Cancers
Authors: Mélodie Grandin, Markus Meier, Jean Guy Delcros, Denise Nikodemus, Raphael Reuten, Trushar R. Patel, David Goldschneider, George Orriss, Natalie Krahn, Amina Boussouar, Riad Abes, Yann Dean, David Neves, Agnes Bernet, Stephane Depil, Fiona Schneiders, Kate Poole, Robert Dante, Manuel Koch, Patrick Mehlen, Jörg Stetefeld
Journal: Cancer Cell (2016)
Cytologic evidence for gene amplification in methotrexate-resistant cells obtained from a patient with ovarian adenocarcinoma.
Authors: J M Trent, R N Buick, S Olson, R C Horns, R T Schimke
Journal: Journal of Clinical Oncology (1984)

To analyze if methotrexate (MTX) resistance arises from gene amplification in a patient treated clinically with MTX, the cytogenetic and drug sensitivity profile of the tumor colony forming units (TCFUs) from a 58-year-old woman with stage III well-differentiated ovarian serous adenocarcinoma was studied. This patient had not received treatment directed against her tumor for nine months before this study, but had received oral-dose MTX (2.5 mg, twice weekly) for three years for the treatment of psoriasis. Analysis of TCFUs grown in nucleoside-free media demonstrated MTX resistance at concentrations of up to 100 micrograms/mL (2.2 X 10(-4)M). Cytologic evidence for dihydrofolate reductase (DHFR) gene amplification in TCFUs was determined by in situ hybridization, using radiolabeled cDNA to DHFR mRNA. Results localized the DHFR sequences to an abnormally staining region present on chromosome 4q. This study supports the notion that alterations in gene dosage (that is, gene amplification) play a role in the development of drug resistance in spontaneous human cancers.