tbuckley/cabot-search huggingface dataset:
ATCT-33RESULTS FROM EARLY CLINICAL TRIALS FOR 4-DEMETHYL-4-CHOLESTERYLOXYCARBONYLPENCLOMEDINE (DM-CHOC-PEN)
Authors: Marcus Ware, Roy Weiner, Paul Friedlander, Tallat Mahmood, Adilia Hormigo, Craig Gordon, Yvonne Saenger, Venu Thirukonda, Thomas Cosgriff, Vijay Patel, Andrew Rogers, Gerard Bastian, Jay Jiguang Zhu, Sigmund Hsu, Lee Roy Morgan
Journal: Neuro-Oncology (2015)
Carboplatin and fluoropyrimidine-based treatment for metastatic gastric and gastroesophageal junction cancer: A retrospective review of the Stanford experience
Authors: P. L. Kunz, M. A. de Bruin, R. R. Balise, G. A. Fisher, J. M. Ford
Journal: Journal of Clinical Oncology (2009)

e15686 Background: There is no single standard chemotherapy regimen for the treatment of metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. At Stanford Cancer Center (SCC) we regularly use a regimen of carboplatin and 5- fluorouracil (CF) or carboplatin and capecitabine (CX) for the treatment of these patients. Methods: A single institution retrospective review of patients with metastatic gastric and GEJ adenocarcinoma treated with CF or CX was conducted. Patients received carboplatin AUC 6 on day 1 and either 5-FU at 200 mg/m2/day (via continuous IV infusion) or capecitabine at 1,000 mg/m2 po BID for 14 days, repeated every 21 days. Only patients treated at SCC who received ≥ 2 cycles of chemotherapy were included. Results: Fourty-five patients were identified. The majority (62%) were male. Median age at diagnosis was 66 years. Twenty-nine (64%) had gastric and 16 (36%) had GEJ cancers. Thirty-six patients (80%) were chemotherapy-naïve. Twenty-nine (64%) had poorly differentiated and 10 (22%) had moderately differentiated adenocarcinomas; 13 (29%) had signet ring features. The average number of cycles administered was 5.4; one possible treatment-related death (2%) was identified. Median time to progression was 4.9 months and median overall survival was 7.3 months. Conclusions: CF and CX are well tolerated and yield acceptable outcomes in high-risk metastatic gastric and gastroesophageal junction cancers. The tolerability allows for the addition of novel targeted agents in future studies. No significant financial relationships to disclose.
Case records of the Massachusetts General Hospital: case 18-1969
Authors: Castleman B, McNeely Bu
Journal: New England Journal of Medicine (1969)

Disscusion of a case concerning a 22 year old women admitted first to the hospital because of fever and pain in the joints.  After a 22 day hospital stay she was discharged.  The main treatment was aspirin.  The second and final admission a year and a half later was for general malaise and a low grade fever.  The patient 10 days before admission had gained 15 lbs. and edema of the ankles developed along with swelling and tenderness of the elbows.  5 months before entry the patient began to take an oral contraceptive C-Quens.  On the 22nd day of hospitalization the patient developed hypotension with a series of cardiac arrests and died.  The differential diagnosis and pathology are discussed and the clinical diagnosis was systemic lupus erythematesus fulminant.  As far as the role of the oral contraceptive in the clinical deterieration was concerned there was no evidence that a thrombogemic effect was implicated.  Despite extensive vasculitis none of the involved vessels had thrombi in their lumens.
Survey amongst health care professionals—Willingness to pay for novel therapies
Authors: W. K. Chia, S. W. Hee, H. C. Toh
Journal: Journal of Clinical Oncology (2006)

6138 Background: Singapore’s state sponsored healthcare system provides subsidies for “standard” oncology drugs (patients co-pay). Patients pay full cost for access to newer therapies prior to Government assessment for subsidy eligibility. Methods: A questionnaire-based study was performed to determine willingness to pay (WTP) for newer anti-cancer therapies (Herceptin, Avastin, Iressa). In addition to absolute dollar cost, patients were asked to tradeoff material goods (cars, house, electronic goods) to purchase such drugs. Face to face interviews were conducted amongst HCP by a single interviewer at Singapore National Cancer Centre from 24 Nov to 16 Dec 06. The questionnaire provided didactic information of such drug benefits in either the appropriate adjuvant or palliative setting. Results: Population: 70 out of 76 HCP responded to the survey—36 doctors (radiation and medical oncologists) and 34 oncology nurses. 60% were female, 61% married and 48% had dependent children. 71% supported parents financially. Median length of practice for doctors(drs) was 10 years (range 2 to 35) and 9 years (range 2 to 29) for nurses(nrs). Median income bracket was USD 3000–5000/mth and USD 1200–3000/ mth respectively. Findings: 69% of respondents reported WTP for herceptin (97% for drs and 38% of nrs). Although drs were most able to afford herceptin, they also demonstrated the highest willingness to trade off material goods to pay for treatment. 57% would sell their houses and 71% sell their cars to pay for herceptin. Almost the entire cohort reported willingness to forego discretionary spending on restaurant dining, clothes and electronics. Only 20% of respondents were WTP for palliative avastin for advanced colon cancer. 53% were willing to pay for a trial of Iressa (for advanced non-small cell lung cancer). If response was favorable, 68% were willing to sell their house to pay to continue palliative treatment. This survey must be interpreted in the context of a relatively affluent Asian population. Conclusions: Government healthcare programs worldwide will find increasingly difficulty paying for expensive novel therapies. At an individual level, respondents demonstrate a high WTP and forego substantial material goods for access to such novel agents. No significant financial relationships to disclose.
Dose-dense chemotherapy (CT) with modified TCF regimen (TCF-DD) in metastatic gastric cancer (MGC): A Phase II study
Authors: M. Dalla Chiesa, G. Tomasello, S. Buti, F. Negri, M. Buononato, R. Longarini, R. Porzio, S. Lazzarelli, M. Brighenti, R. Passalacqua
Journal: Journal of Clinical Oncology (2007)

15068 Background: Previous studies reported that in lymphomas, early breast and bladder cancer, dose-dense CT is more effective than conventional treatment. We reported for the first time, in 2006 ASCO meeting, the feasibility of an intensified dose-dense TCF regimen (q2w) in MGC. This is the subsequent phase II study. Methods: patients (pts) with histologically confirmed measurable MGC, ECOG PS 0–3, received up to 6 cycles of Docetaxel 85 mg/m2 (75 mg/m2 after first 12 pts, 70 mg/m2 after the 28 th patient) day 1, Cisplatin 75 mg/m2 day 1 (60 mg/m2 after the 28 th patient) l-Folinic Acid 100 mg/m2 day 1 and 2, followed by 5-Fluorouracil 400 mg/m2 bolus day 1 and 2, and then 600 mg/m2 as a 22 hour continuous infusion day 1 and 2, every 14 days, plus Pegfilgrastim 6 mg on day 3. Pts with a PS &gt; 1 and/or age &gt; 65 years and/or pre-treated for the metastatic disease, received the same schedule with a dose reduction by 30%. Results: 31 consecutive pts were enrolled (81% male, 19% female; median age: 60, range 40–79; median ECOG PS: 1, range 0–3; 3 pts pre-treated). Primary end points were response rate and safety. A median of 4 cycles (range 1–6) per pts were administered. 15 pts (48%) required a dose reduction, mostly because of hematologic toxicity and severe asthenia. 10 pts (32%) were treated with full dose without any delay on at least the first 4 cycles. 25 pts were evaluated for response (3 too early, 1 early suspension because of severe allergic reaction to Docetaxel; 2 early deaths: 1 bowel perforation and 1 sepsis) and 30 for toxicity. 2 CR (multiple liver metastases), 12 PR, 4 SD and 7 PD were observed, for an ORR (RECIST criteria and intention-to-treat principle) of 50% (95% CI 30–65). At a median follow-up of 10 months (range 1–24), overall median survival was 6 months (range 1–20). Frequent grade 3 to 4 toxicities were: neutropenia (65%), thrombocytopenia (31%), anemia (14%) febrile neutropenia (31%), asthenia (62%), diarrhoea (21%) and stomatitis (14%). Conclusions: TCF-DD regimen in MGC is feasible and very active. The recommended dose (with reduction by 30% as above) for further randomised studies comparing TCF-DD with standard TCF is Cisplatin 60 mg/m2 and Docetaxel 70 mg/m2. No significant financial relationships to disclose.
Pharmacological Targeting of the Histone Chaperone Complex FACT Preferentially Eliminates Glioblastoma Stem Cells and Prolongs Survival in Preclinical Models
Authors: Josephine Kam Tai Dermawan, Masahiro Hitomi, Daniel J. Silver, Qiulian Wu, Poorva Sandlesh, Andrew E. Sloan, Andrei A. Purmal, Katerina V. Gurova, Jeremy N. Rich, Justin D. Lathia, George R. Stark, Monica Venere
Journal: Cancer Research (2016)

Abstract The nearly universal recurrence of glioblastoma (GBM) is driven in part by a treatment-resistant subpopulation of GBM stem cells (GSC). To identify improved therapeutic possibilities, we combined the EGFR/HER2 inhibitor lapatinib with a novel small molecule, CBL0137, which inhibits FACT (facilitates chromatin transcription), a histone chaperone complex predominantly expressed in undifferentiated cells. Lapatinib and CBL0137 synergistically inhibited the proliferation of patient-derived GBM cells. Compared with non–stem tumor cells (NSTC) enriched from the same specimens, the GSCs were extremely sensitive to CBL0137 monotherapy or FACT knockdown. FACT expression was elevated in GSCs compared with matched NSTCs and decreased in GSCs upon differentiation. Acute exposure of GSCs to CBL0137 increased asymmetric cell division, decreased GSC marker expression, and decreased the capacity of GSCs to form tumor spheres in vitro and to initiate tumors in vivo. Oral administration of CBL0137 to mice bearing orthotopic GBM prolonged their survival. Knockdown of FACT reduced the expression of genes encoding several core stem cell transcription factors (SOX2, OCT4, NANOG, and OLIG2), and FACT occupied the promoters of these genes. FACT expression was elevated in GBM tumors compared with non-neoplastic brain tissues, portended a worse prognosis, and positively correlated with GSC markers and stem cell gene expression signatures. Preferential targeting of GSCs by CBL0137 and synergy with EGFR inhibitors support the development of clinical trials combining these two agents in GBM. Cancer Res; 76(8); 2432–42. ©2016 AACR.
Prevalence of anxiety disorders in asthmatic patients
Authors: A Cappai, F Pinna, E Zaccheddu, S Floris, F Manunza, C Toscano Carruba, A Mancosu, S Palmieri, W Orru, F Argiolas, L Gambula, B Carpiniello, P Manconi, S Del Giacco
Journal: Allergy (2012)
Assessment of nutritional status and prognosis in advanced metastatic cancer (AMC) of gastrointestine (GI)
Authors: K. Choi, H. J. Kim, H. J. Cho, S. J. Oh, S. S. Lee
Journal: Journal of Clinical Oncology (2006)

18573 Background: Depletion of nutritional reserves and significant weight loss can lead to an increased risk of morbidity, reduced chemotherapy response, and shorter survival in patients (pts) with cancer. Numerous methodologies are used for the assessment of nutritional status. However, it remains unclear which of these tools is the most appropriate in the setting of cancer chemotherapy. The PINI (prognostic inflammatory nutritional index) is a simple scoring system that has been used to evaluate nutritional status and prognosis in critically ill pts. The aim of this study was designed to investigate the relationship between nutritional status after the palliative chemotherapy and prognosis in AMC of GI. Methods: This study included 130 pts with ECOG PS 1∼3 in AMC of GI following the palliative chemotherapy. ECOG PS, body mass index (BMI), alpha 1-acid glycoprotein (AGP), C-reactive protein (CRP), albumin (ALB), prealbumin (PALB), transferrin, protein, lactate dehydrogenase (LDH), PINI ratio [PINI = (AGP × CRP)/(ALB × PALB)], and survival time were evaluated. Results: In 130 patients, the median age was 57 years. The ECOG PS was 1: 68 patients, 2: 43 patients, 3: 19 patients. The mean value of PINI was PS 1: 16.0 ± 47.8, PS 2: 55.6 ± 106.9, PS 3: 106.3 ± 141.6. The mean survival was PS 1: 144.0 ± 71.8, PS 2: 68.9 ± 41.2, PS 3: 32.0 ± 6.9 days. In the PS 3 group, the mean values of AGP, CRP, and LDH were significantly higher than in the PS 1 group. In the PS 3 group, the mean values of ALB, PALB, and transferrin were significantly lower than in the PS 1 group. The survival time was correlated with the ECOG PS (r = −0.602, p &lt; 0.001,), PINI (r = −0.318, p &lt; 0.001,), AGP (r = −0.265, p = 0.002), CRP (r = −0.345, p &lt; 0.001), ALB (r = 0.324, p &lt; 0.001), PALB (r = 0.260, p = 0.003) and transferrin (r = 0.377, p = 0.001). Conclusions: The PINI should be considered nutritional status and prediction of prognosis in AMC of GI following palliative chemotherapy. [Table: see text] No significant financial relationships to disclose.
Elderly patients with hormone-sensitive breast cancer (HSBC): Are they receiving optimal treatment?
Authors: L. Balducci
Journal: Journal of Clinical Oncology (2008)

20638 Background: Breast cancer incidence, prevalence, and mortality increase with age. About 50% of women with breast cancer are older than 65, yet this population is often underrepresented in clinical trials. This study explores the benefits of adjuvant hormone treatment of breast cancer, including selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs), in older women. Methods: Trials evaluating tamoxifen (TAM) and AIs in postmenopausal women with HSBC were reviewed to examine their effects on elderly women (EBCTCG, ATAC, BIG 1–98, IES, MA.17, etc). Results: The EBCTCG analysis showed a similar reduction in recurrence risk with adjuvant TAM therapy for younger (<40 y) and older (≥70 y) women, but many older women discontinue TAM due to tolerability issues. Also, SSRIs are being prescribed more frequently to treat depression in elderly patients, and the concomitant use of SSRIs with TAM decreases TAM efficacy. In clinical trials comparing AIs and TAM (BIG-1, ATAC, IES), AIs were superior to TAM in patients of all ages. In the BIG 1–98 study, letrozole (LET) provided a 21% reduction in the risk of recurrence in patients >65 years old (n=2867) that reached statistical significance (HR=0.79; P=0.02). LET showed a significant benefit regardless of age in the extended adjuvant setting following 5 years of TAM in the MA.17 trial, and disease-free survival (DFS) and distant DFS were significantly improved in all patients receiving LET vs placebo. Conclusions: Many elderly women with HSBC may not receive optimal therapy. TAM offers less protection against relapse than the AIs and has diminished efficacy in women taking SSRIs. The AIs appear superior to SERMs in terms of DFS and safety for women of all ages and should be the adjuvant hormone treatment of choice in older women. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen, Novartis, Ortho, Pfizer, sanofi-aventis, Speaker Bureau
Pediatrician Sees Long Road Ahead for Flint After Lead Poisoning Crisis
Authors: Bridget M. Kuehn
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Obstructive and perforative colonic carcinoma: patterns of failure.
Authors: C Willett, J E Tepper, A Cohen, E Orlow, C Welch
Journal: Journal of Clinical Oncology (1985)

Carcinoma of the colon complicated by obstruction or perforation has been recognized as having a poorer prognosis than tumors without obstruction or perforation. To clarify the natural history, failure patterns, and implications for adjuvant treatment after resection with curative intent, a review of the recent Massachusetts General Hospital (MGH) experience was undertaken. From 1970 to 1977, 77 patients with obstructive colonic carcinoma and 34 patients with localized perforation at the tumor site were identified and compared with a control group of 400 patients without obstruction or perforation undergoing curative resection. All patients were observed for a minimum of five years or until the patient's death. The actuarial five-year survival and disease-free survival rates in patients with obstruction was 31% and 44%, respectively, in contrast to 59% and 75% in control patients. For patients with localized perforation, the five-year actuarial survival and disease-free survival rates were 44% and 35%, respectively. Of the 77 patients with obstructing tumors, 32 patients (42%) developed local failure--nine with local failure only and 23 patients with local failure and distant metastases. Thirty-four patients (44%) developed distant metastases. Fifteen (44%) patients of 34 with perforative colonic carcinoma had local failure. Distant metastases occurred in 15 patients (44%). The incidence of local failure and distant metastases in the control group was 14% and 21%, respectively. The rate of local failure and distant metastases increased with stage and was generally higher stage for stage than in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
Integration of specific copy number imbalances and prediction models of early-stage breast cancer recurrence.
Authors: P. Thompson, K. Do, A. M. Brewster, J. Shim, J. L. Murray, S. Tsachavidis, A. Sahin, G. B. Mills, M. Bondy
Journal: Journal of Clinical Oncology (2010)

1529 Background: DNA Copy number alterations (CNAs) are common in breast cancers. Their role as molecular predictors of disease recurrence risk is less clear. Methods: We conducted CN analyses using high- density molecular inversion probe (MIP) arrays in 971 tumors early stage breast cancers. A binning strategy and CoxBoost algorithm were used to reduce the CN data to chromosomal segments relevant to recurrence and applied to a multivariate model using a randomly selected training set (n = 728). A complete Cox proportional hazards risk prediction model was built including clinicopathological characteristics, intrinsic tumor subtype (approximated by immunohistochemistry methods) and CNA markers and validated independently in 243 cases. Validation in the independent sample set included comparisons to known clinical models of breast cancer recurrence that contained the intrinsic subtypes. Separate models for triple-negative and luminal breast cancers were also explored. Results: The dimensionality of the CNA data were reduced with circular binary segmentation and fusing of the segments across samples to 1593 common CNA segments across the genome. Following a step-wise model selection in training sample, age at diagnosis, tumor size, lymph node status, approximated tumor subtypes, and 19 CNA markers were retained in a full model for time to recurrence. The C-index for the full model (clinical + tumor subtype + 19 CNA segments) gave the strongest predictive estimate for recurrence (C-index = 0.71 ± 0.035) compared to the best clinical+ intrinsic subtype model (C-index = 0.62 ± 0.041). Models built for luminal and triple negative tumors incorporating CNAs significantly outperformed models with clinical characteristics alone. This was particularly true for triple negative tumors, where the combination of CNA markers + clinical co-variates yielded a strong predictive estimate for recurrence (C-Index = 0.79 ± 0.023) compared to the clinical model (C-Index = 0.64 ± 0.034). Conclusions: Measures of specific CNAs add significant additional predictive information for risk of recurrence and suggest additional opportunities to refine prognostication for early stage luminal and triple-negative breast cancers. No significant financial relationships to disclose.
Abstract 94: Closed Loop Compression Depth Optimization in a Pig Model
Authors: Paul Aelen, Simone Ordelman, Pierre Woerlee, Gerrit-Jan Noordergraaf
Journal: Circulation (2014)

Introduction: CPR success depends on blood flow generated by it, affected among others by compression depth. AHA guidelines advise the same small range of depths for all patients, while their individual optimum may vary widely. Therefore, an individual patient may have an increased chance of survival if CPR is performed at this optimum depth. We investigated the feasibility of an automated compression depth tuning algorithm. Methods: In five Yorkshire pigs (about 31 kg) aortic and right atrial pressure were measured with Millar catheters. CPP and aortic diastolic blood pressure (DBP) were calculated in real-time. DBP was used as CPR quality indicator (QI), i.e. as a surrogate for myocardial blood flow. After VF induction, CPR was performed at 100 cpm for 10 min with a proprietary automated CPR device. Compression depth was tuned automatically every 2 min by first decreasing depth by 0.5 cm, followed by increasing depth by 1 cm, both for 20 seconds. The depth at the highest QI was used as new depth in the next cycle (Fig. 1). It was determined whether the QI reflected CPP. Tuning step size (cm) and duration (s) were studied to see if these resulted in clinical relevant QI changes. Results: The mean correlation coefficient between the QI and the CPP was 0.7. The mean QI change per depth change was 2.3 mmHg (about 10% change). The algorithm had a bias towards lower depths as the depth increase first had to overcome the QI change of the preceding decrease which did not result in a steady state QI within 20 seconds. The algorithm tuned to a compression depth between 2.5 and 4.5 cm for these animals. Conclusion: DBP can be used as a CPR quality indicator as its correlation with CPP is high. A step size of 0.5 cm is a viable choice for a tuning algorithm as it resulted in clinical relevant changes of QI within 20 seconds. A bias to a certain compression depth should be prevented by either lengthening the duration of the depth change or by performing the increase and decrease at non-consecutive time intervals.