tbuckley/cabot-search huggingface dataset:
Dose and schedule selection for the anti-CTLA4 monoclonal antibody ticilimumab in patients (pts) with metastatic melanoma
Authors: J. Gomez-Navarro, A. Sharma, V. Bozon, C. Bulanhagui, D. Pavlov, S. Eck, A. Ribas, L. H. Camacho
Journal: Journal of Clinical Oncology (2006)

8032 Background: Ticilimumab therapy has demonstrated anti-tumor activity in pts with metastatic melanoma. Its indirect, immune-mediated antitumor effects pose unique challenges for dose/regimen selection. Methods: It was our original intention to select the clinical dose/regimen of ticilimumab based on (1) clinical safety and tolerability and (2) attainment of target plasma concentrations derived from pre-clinical work using an ex vivo assay of ticilimumab-induced enhancement of cytotoxic T-cell function. Because numerous pts with metastatic melanoma experienced clinical benefit (i.e., durable objective responses [OR] and/or long-term survival) in early clinical trials of ticilimumab, we are using (1) safety and tolerability and (2) clinical benefit to guide dose/regimen selection. Data for evaluating these criteria come from a single-dose Phase 1 trial (0.01, 0.1, 1, 3, 6, 10 and 15 mg/kg) and an ongoing multiple-dose Phase 1/2 trial in pts with melanoma (Phase 1 portion: 3, 6 and 10 mg/kg Q1M; Phase 2 portion: 10 mg/kg Q1M and 15 mg/kg Q3M). Results: In the single-dose Phase 1 trial, 10 mg/kg was the Protocol-defined MTD but a high rate of clinical benefit was seen in the 15 mg/kg dose cohort (6/6 pts). Because the DLTs seen at 15 mg/kg (Gr 3 diarrhea, Gr 3 rash) were moderate and resolved completely within 3 months of dosing, 15 mg/kg Q3M was proposed as a safe and tolerable dose and is being studied in the Phase 2 portion of the multiple-dose Phase 1/2 trial. The Phase 1 portion of the multiple-dose Phase 1/2 trial revealed that 10 mg/kg is safe and tolerable with monthly dosing so 10 mg/kg Q1M is also being studied in the Phase 2 portion of the trial. At the end of the Simon Optimum-defined Stage 1 of the Phase 2 portion of the ongoing trial, the OR rate (3/18 pts) is the same for both dosing regimens. However, with 15 mg/kg Q3M, Gr 3/4 adverse events were less frequent (6% versus 34%). Conclusions: 15 mg/kg Q3M is proposed as the clinical dose/regimen for ticilimumab in metastatic melanoma. This dose/regimen appears to have anti-tumor activity approximately equal to 10 mg/kg Q1M but it appears to have a superior safety profile. [Table: see text]
Short-term survival of ovarian cancer patients waiting more than six weeks after surgery before chemotherapy is given
Authors: T. Paulsen, J. Kærn, K. Kjærheim, T. Haldorsen, C. Tropé
Journal: Journal of Clinical Oncology (2006)

5070 Background: To investigate the impact on short-term survival of time between surgery and start of first chemotherapy cycle in patients with advanced ovarian cancer. Methods: This prospective, population-based study comprised 371 patients with epithelial ovarian, tubal or peritoneal cancer diagnosed in 2002–2003. All patients underwent primary surgery, followed at different intervals by chemotherapy. The data were derived from notifications to the Norwegian Cancer Registry and included medical, surgical and histopathological records. Kaplan-Meier plots were used to show differences in survival, and Cox regression analysis was used to show the effect of prognostic factors on survival, expressed as hazard ratios (HRs). Results: No difference in survival between patient groups was seen when time between surgery and start of chemotherapy was divided into quartiles. The group of patients with interval between surgery and chemotherapy less than six weeks had inferior survival if they had residual disease after surgery. Adjusted HR = 2.36 (95% CI, 1.22–4.57). However, in the patient groups with interval more than six weeks, there was no significant difference in survival between patients without and with residual disease. Adjusted HR = 1.35 (0.51–3.56) versus HR = 1.64 (0.76–3.57). Conclusions: The interval between surgery and start of chemotherapy had no major impact on short-term survival after ovarian cancer. Patients might be included in chemotherapy trials when interval between surgery and start of chemotherapy is more than six weeks. [Table: see text] No significant financial relationships to disclose.
Synergistic Cytotoxicity Between Panobinostat and Ponatinib In Imatinib-Resistant Chronic Myeloid Leukemia Cells
Authors: Yasufumi Matsuda, Takahiro Yamauchi, Kanako Uzui, Eiju Negoro, Koji Morinaga, Hiroko Shigemi, Rie Nishi, Shinya Kimura, Taira Maekawa, Takanori Ueda
Journal: Blood (2013)
Adjuvant Endocrine Therapy for Women With Hormone Receptor–Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update on Ovarian Suppression
Authors: Harold J. Burstein, Christina Lacchetti, Holly Anderson, Thomas A. Buchholz, Nancy E. Davidson, Karen E. Gelmon, Sharon H. Giordano, Clifford A. Hudis, Alexander J. Solky, Vered Stearns, Eric P. Winer, Jennifer J. Griggs
Journal: Journal of Clinical Oncology (2016)

To update the ASCO adjuvant endocrine therapy guideline based on emerging data concerning the benefits and risks of ovarian suppression in addition to standard adjuvant therapy in premenopausal women with estrogen receptor-positive breast cancer.ASCO convened an Update Panel and conducted a systematic review of randomized clinical trials investigating ovarian suppression.Two trials investigating the addition of ovarian suppression to tamoxifen did not show an overall clinical benefit for ovarian suppression. Nonetheless, the addition of ovarian suppression to standard adjuvant therapy with tamoxifen or with an aromatase inhibitor improved disease-free survival and improved freedom from breast cancer and distant recurrence compared with tamoxifen alone among the subset of patients who were at sufficient risk for recurrence such that adjuvant chemotherapy was warranted. Compared with tamoxifen alone, ovarian suppression was associated with a substantial increase in menopausal symptoms, sexual dysfunction, and diminished quality of life.The Panel recommends that higher-risk patients should receive ovarian suppression in addition to adjuvant endocrine therapy, whereas lower-risk patients should not. Women with stage II or III breast cancers who would ordinarily be advised to receive adjuvant chemotherapy should receive ovarian suppression with endocrine therapy. The panel recommends that some women with stage I or II breast cancers at higher risk of recurrence who might consider chemotherapy may also be offered ovarian suppression with endocrine therapy. Women with stage I breast cancers not warranting chemotherapy should not receive ovarian suppression, nor should women with node-negative cancers 1 cm or less. Ovarian suppression may be administered with either tamoxifen or an aromatase inhibitor. Additional information is available at www.asco.org/guidelines/endocrinebreast and www.asco.org/guidelineswiki.
A Sensitive NanoString-Based Assay to Score STK11 (LKB1) Pathway Disruption in Lung Adenocarcinoma
Authors: Lu Chen, Brienne E. Engel, Eric A. Welsh, Sean J. Yoder, Stephen G. Brantley, Dung-Tsa Chen, Amer A. Beg, Chunxia Cao, Frederic J. Kaye, Eric B. Haura, Matthew B. Schabath, W. Douglas Cress
Journal: Journal of Thoracic Oncology (2016)
Waist size and mortality from prostate cancer
Authors: S. Marcella, G. G. Rhoads
Journal: Journal of Clinical Oncology (2005)

4626 Background: Obesity has been hypothesized to be a risk factor for prostate cancer (CaP), but reports using body mass index (BMI) have been inconsistent. Some studies report a small increase in risk with elevated BMI while others have shown some protection. Measurements of visceral adiposity such as waist circumference have been less well studied but have also shown variation in the risk for CaP incidence. To our knowledge, no one has looked at the risk for CaP mortality. We hypothesized that central adiposity as measured by waist size is a risk factor for CaP mortality. Methods: We used data from a case-control study of PSA screening and CaP mortality for which we have information on BMI and waist size. 380 cases who died from CaP and the same number of controls were individually matched for age (55 - 79) and race. Controls were without evidence of advanced CaP. Conditional logistic regression was employed for univariate as well as multivariate associations. Results: The multivariate model with BMI, waist size, and socioeconomic status revealed that a girth of 40 inches was associated with 3.8 times the risk of death from CaP as compared to 32 inches or less. Girths of 32–36 and 36–40 inches were associated with ORs of 1.9 and 2.0 and p-values of .05 and .07 respectively. BMI above 25 independently protected from CaP (OR of 0.6, p = .02). A model with waist size only revealed a modest increase in risk for those with a girth greater than 40 inches but was not statistically significant (OR of 1.4, p=.38). Similarly, modeling BMI as a single, independent variable demonstrated a non-significant trend towards protection (OR of 0.7, p = .18 for a BMI of 30 and above compared to less than 25). Conclusions: Waist size, independent of BMI, may be a risk factor for CaP mortality. The finding that waist size increases risk while BMI decreases it suggests that these two measurements are describing distinctly different aspects of body habitus and that it is visceral adiposity that places a man at risk for death from prostate cancer. No significant financial relationships to disclose.
Real-Life Study on the Effect of Micronized Cellulose Powder As Add-on to Intranasal As-Needed Treatment of Subjects with Pollen Allergic Rhinitis
Authors: Todor A. Popov, Anna Valerieva, Martin K. Church, Maria Staevska, Tanya Kralimarkova, Elena Petkova, Elitsa Valerieva, Tsvetelina Lazarova, Vasil Dimitrov
Journal: Journal of Allergy and Clinical Immunology (2016)
Patients’ access to biological therapy in chronic inflammatory conditions; per capita GDP does not explain the intercountry differences
Authors: László Gulácsi, Fanni Rencz, Gyula Poór, Zoltán Szekanecz, Valentin Brodszky, Petra Baji, Márta Péntek
Journal: Annals of the Rheumatic Diseases (2016)

Biological agents revolutionised the treatment of chronic inflammatory diseases such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA) as well as Crohn's disease (CD), ulcerative colitis (UC) and psoriasis. RA studies highlighted that uptake of biologic drugs varies strongly across Europe and the income of a country is considered as a major determinant factor for usage.1–3 Putrik et al 4 ,5 found that access to biologics in RA—expressed as a composite score of availability, affordability and acceptability—showed a strong positive correlation with gross domestic product (GDP)/capita (r=0.86) in Europe. Much less is known on this topic in AS, PsA and the other three inflammatory diseases.

We analysed real-world biologic usage data and their relationships with GDP/capita in the six inflammatory conditions in Bulgaria, the Czech Republic, Hungary, Poland, Romania and Slovakia. According to our previous literature search, there is no precise and comparable country-specific prevalence data in this region.6–8 Therefore, we estimated the biologic treatment rates per 100 000 inhabitants.

Considering the total of six diagnoses, …
Vinylethylnitrosamine: A Potent Respiratory Carcinogen in Syrian Hamsters 2
Authors: Jürgen Althoff, Carter Grandjean, Liisa Russell, Paryiz Pour
Journal: JNCI Journal of the National Cancer Institute (1977)

Vinylethylnitrosamine (VEN), an alpha-beta unsaturated analogue of diethylnitrosamine (DEN), which may be formed by the enzymic conversion necessary for carcinogenesis, was synthesized and its biologic effect was examined by sc administration to Syrian hamsters. Distribution studies showed that the maximum amount of unaltered compound was found in various tissues 45 minutes after injection. The chemical was only partially excreted unchanged after 5 hours. Weekly treatment for life resulted in high incidence of malignant respiratory tract neoplasms with short latencies and in tumors of the upper digestive tract and pancreas. The effects of VEN were compared to those of the assumed parent compound, DEN.
Statutory approaches to limiting psychiatrists' liability for their patients' violent acts
Authors: P S Appelbaum, H Zonana, R Bonnie, L H Roth
Journal: American Journal of Psychiatry (1989)

A consensus has developed among mental health professionals that the legal duty to protect potential victims of their patients' violent acts, as fashioned by the courts, requires modification. To date, 12 states have responded with legislation designed to clarify and limit clinicians' responsibilities. In addition, APA has distributed a model statute as a resource document to aid those psychiatrists interested in stimulating legislative action. This paper examines existing statutes and the APA resource document, considers the variety of ways in which the goals of reform can be achieved, and recommends approaches that balance desires for public safety with the legitimate needs and concerns of the mental health professions.
Hazards of small clinical trials.
Authors: S Piantadosi
Journal: Journal of Clinical Oncology (1990)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1990.8.1.1 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2295901 Hazards of small clinical trials. S PiantadosixS PiantadosiSearch for articles by this author Show More Johns Hopkins Oncology Center, Baltimore, MD. https://doi.org/10.1200/JCO.1990.8.1.1 First Page PDF © 1990 by American Society of Clinical Oncology
Inhalation Studies of Nickel Sulfide in Pulmonary Carcinogenesis of Rats2
Authors: A. D. Ottolenghi, J. K. Haseman, W. W. Payne, H. L. Falk, H. N. MacFarland
Journal: JNCI Journal of the National Cancer Institute (1975)

Journal Article Inhalation Studies of Nickel Sulfide in Pulmonary Carcinogenesis of Rats Get access A. D. Ottolenghi, A. D. Ottolenghi Search for other works by this author on: Oxford Academic PubMed Google Scholar J. K. Haseman, J. K. Haseman Search for other works by this author on: Oxford Academic PubMed Google Scholar W. W. Payne, W. W. Payne Search for other works by this author on: Oxford Academic PubMed Google Scholar H. L. Falk, H. L. Falk Search for other works by this author on: Oxford Academic PubMed Google Scholar H. N. MacFarland H. N. MacFarland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 54, Issue 5, May 1975, Pages 1165–1172, https://doi.org/10.1093/jnci/54.5.1165 Published: 01 May 1975 Article history Received: 04 October 1974 Accepted: 24 January 1975 Published: 01 May 1975
Use of health-related quality of life and clinical data as prognostic tools for survival prediction in a subgroup of metastatic cancer patients.
Authors: C. Quinten, F. Martinelli, J. Vercauteren, E. Greimel, B. B. Reeve, M. J. Taphoorn, C. S. Cleeland, J. Weis, J. Schmucker-Von Koch, A. Bottomley
Journal: Journal of Clinical Oncology (2010)

9146 Background: Health related quality of life (HRQOL) may provide added value alongside clinical data in predicting survival. The aim of this analysis was to construct a prognostic index (PI), including HRQOL and clinical data, to assess the accuracy of survival prognosis and to identify possible subgroups at increased risk of death in a cohort of patients with metastatic cancer. Methods: Baseline data were obtained from 17 closed European Organisation for Research and Treatment of Cancer (EORTC) randomized controlled trials in 7 cancer sites. A multivariate Cox regression model was constructed including clinical, socio-demographic and EORTC QLQ-C30 variables, that were retained as prognostic (p<0.05) after stepwise regression. A quantitative PI, representing a weighted combination of the bootstrapped parameter estimates of each prognostic variable, was constructed. The C-index was used to evaluate predictive accuracy of the PI; a log-rank test to identify significant separation between low and high survival risk subgroups. Results: HRQOL and clinical data were collected at baseline from 2,410 metastatic cancer patients. The final multivariate model included three clinical variables [age, gender (0=male;1=female), WHO performance status (PS)] and three QLQ-C30 parameters [physical functioning (pf), pain (pa) and appetite loss (ap)] (all p's<0.05). The bootstrapped estimates were used to create the PI as follows: PI=0.164*age - 0.239*gender [female] + 0.311*PS + 0.007*pf + 0.004*pa + 0.005*ap. Incorporating the HRQOL variables in the PI increased the relative predictive accuracy by 8.3% compared to clinical variables alone. A significant difference (HR=1.82; CI=1.57-2.11; p<0.001) in median survival (22 vs 11 months) in the studied population was identified based on the PI. Conclusions: This PI may be useful, after further validation, for health care professionals in predicting survival and identification of subgroups at increased risk of death. In addition, a PI can be used in clinical research as a key stratification factor in the design of clinical trials. However, additional research and external validation is needed to strengthen our results. No significant financial relationships to disclose.
Integrating cancer care: Patient and practice management processes among surgeons who treat breast cancer
Authors: S. J. Katz, S. T. Hawley, J. J. Griggs, M. Morrow, T. P. Hofer
Journal: Journal of Clinical Oncology (2009)

6526 Background: The Institute of Medicine has called for cancer care models that parallel those underway to integrate the management of patients with chronic conditions. The objective of this study was to evaluate patterns and correlates of such initiatives in the practices of surgeons treating women with breast cancer. Methods: We developed 5 multi-item scales to describe breast cancer patient and practice management processes based on the Chronic Care Model (multidisciplinary clinician communication; availability of clinical information; patient decision support; access to information technology; and practice management initiatives). We then performed a survey among attending surgeons of a population-based sample of patients diagnosed with breast cancer during a period from June 2005-February 2007 in metropolitan Los Angeles and Detroit (N = 312, response rate 76.1%). We evaluated the distribution of management process measures across selected characteristics of providers and practices. Results: About half of the surgeons devoted 15% or less of their total practice to breast cancer; while 16.2% of surgeons devoted 50% or more. The deployment of management processes varied markedly with most surgeons reporting low use. For example, only about 10% of surgeons indicated that half or more of their patients were exposed to multidisciplinary physician communication; while only 5% indicated that half or more of their patients were provided decision and care support services such as attending a presentation or viewing a video about breast cancer prior to surgery or attended a patient support group. Management process measures were positively associated with greater levels of surgeon specialization and the presence of a teaching program. Cancer program status (NCI center, ACS cancer program, neither) was weakly associated with any of the management process measures. Conclusions: The low uptake of patient and practice management processes observed in this study suggests that breast surgeons are not convinced that these processes matter or that there are logistical and cost barriers to implementation. More research is needed to understand how variation in patient and practice management processes may affect the quality of care for patients with breast cancer. No significant financial relationships to disclose.
Reversal of advanced renal dysfunction on bortezomib treatment in multiple myeloma patients
Authors: A. Mohrbacher, A. M. Levine
Journal: Journal of Clinical Oncology (2005)

6714 Background: Bortezomib is a highly active agent in multiple myeloma. Advanced stages of multiple myeloma are freqeuntly associated with progressive renal failure. We report here 6 cases of acute advanced deterioration of renal function on prior renal insuficiency in chronic MM patients, with complete or near complete reversal of severe renal dysfunction after treatment with Velcade and Dexamethasone. Methods: Pts received Velcade 1.0 mg/m2/d IV d1,4,8,11 and Dexamethasone 20 mg IV d1,4,8,11. Results: Rapid reversal of acute deterioration of renal dysunction was demonstrated after treatment with Velcade and Dexamethasone in this retrospective review of patient cases. Improvement of renal function was generally evident quickly, often less than 2 weeks, earlier than expected from general myeloma tumor response. A review of a trial of treatment with Velcade where Dexamethasone was added in later cycles may address possible evidence of synergy of Velcade and dexamethasone in reversal of renal dysfunction. Animal models suggest NFkB, the target of Bortezomib, is upregulated in acute tubular injury from proteinuria and suggest further study of this drug’s possible role in protecting renal function. Conclusions: In summary, rapid and at times dramatic reversal of severe renal dysfunction is seen with Velcade and Dexamethasone, sparing the 6 patients above from imminent dialysis. Prevention of end stage renal failure is an important clinical goal given the prolonged survivals seen in myleoma patients in the current era, and the known impact of renal failure on their survival. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Millennium Millennium
The Relation of Ejection Fraction and Global Longitudinal Strain in Amyloidosis: Implications for Differential Diagnosis
Authors: Efstathios D. Pagourelias, Jürgen Duchenne, Oana Mirea, Georgios Vovas, Johan Van Cleemput, Michel Delforge, Tatyana Kuznetsova, Jan Bogaert, Jens-Uwe Voigt
Journal: JACC. Cardiovascular imaging (2016)