tbuckley/cabot-search huggingface dataset:
Cancer and heart disease, burden of disease, Puerto Rico 2000-2010.
Authors: Vivian S Green, Felipe Arbelaez, Cecile Marques-Goyco, Juan C. Orengo
Journal: Journal of Clinical Oncology (2015)

e12643 Background: The burden of disease can be estimated quantifying the mortality, the Years of Potential Life Lost (YPLL), the economic cost associated with YPLL and the Potentially Productive Years of Life Lost (PPYLL). The objectives were: a) estimate both YPLL and PPYLL for all causes, cancer and heart disease (HD) in Puerto Rico (2000-2010); b) estimate the cost associated with YPLL. Methods: Puerto Rico published mortality data (2000-2010) were analyzed. An upper limit of 80 years was established for the YPLL. The YPLL was divided by the total deaths in each year to calculate the Average Years of Life Lost (AYLL). The PPYLL was calculated by setting an interval: 16 – 65 years. The method of willingness to pay, using three times the GDP per capita in 2010, with a discount rate of 3% and an annual increase of 1%, was used to calculate the economic cost. Results: The YPLL for cancer represented in 2000 (56,178 years), 13.7% of YPLL for all causes and in 2010 (55,648 years), 16.2% of YPLL for all causes. The YPLL for HD in 2000 accounted for (51,498 years) and in 2010 for (39,625 years), 12.5% and 11.6% of the total YPLL respectively. The YPLL decreased 1% for cancer and 23% for HD from 2000-2010. The AYLL for cancer in 2000 and 2010 was 11.8 and 10.7 respectively, and for HD 8.2 and 7.6. The PPYLL in 2000 was 17,632 years for cancer and 14,206 years for HD; PPYLL in 2010 was 16,128 years for cancer and 10,811 years for HD. The cost associated with cancer for 2000 and 2010 was $ 3.6 billion and for HD $ 3.3 billion for 2000 and $ 2.6 billion for 2010. Conclusions: a) cancer mortality has increased from 2000 to 2010; b) YPLL has remained stable for cancer but still higher than HD (mortality for HD is greater); c) cancer deaths occur in younger people than in HD; d) The financial burden associated with cancer is higher than that for HD, but it has remained stable while for HD it has decreased.
A phase II study of radiation therapy (RT), paclitaxel poliglumex (PPX), and cetuximab (C) in locally advanced head and neck cancer (LA-HNC).
Authors: Seung Shin Hahn, Jeffrey Bogart, Chung Taik Chung, Jack Hsu, Robert Kellman, Michael Andrew Lacombe, Jung-AH Kim, Stephen L. Graziano, Dena Martin, Ajeet Gajra
Journal: Journal of Clinical Oncology (2013)

6059 Background: RT + cisplatin in LA-HNC showed a survival benefit over RT alone, but with significant toxicity. Addition of C to RT demonstrated survival benefit without increased RT-related toxicity. PPX consists of paclitaxel linked to a biodegradable, water-soluble polymer of glutamic acid. PPX has a radiation enhancement factor of ≈8 in a radiocurability murine model. This study addresses the combined use of intensity modulated RT (IMRT), PPX, and C in patients with LA-HNC. Methods: Eligible patients had untreated stage III/ IV squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, larynx, or unknown primary, ECOG PS 0-1, and adequate bone marrow function. Patients received C 400 mg/m 2 day 1 and 250 mg/m 2 weekly for 7 weeks. PPX was administered at 40 mg/m² weekly for 7 weeks. IMRT began on day 8 consisting of 69.96 Gy delivered in 2.12 Gy daily. Results: 38 patients with LA-HNC are included in this report and evaluable for response. 24 (63%) had CR and 14 (37%) had PR. HPV status is 21+, 11- and 8 unknown. Pre-therapy, 36 patients had nodal disease, 9 underwent neck dissection post-treatment and 1/ 9 patients had microscopic involvement by cancer. Locoregional tumor control occurred in 36/38 (95%) patients with two patients developing locoregional recurrence after completion of therapy. Two patients have died from metastatic disease and two patients are alive with distant metastases. Two additional deaths were unrelated to therapy (sudden cardiac death and COPD exacerbation with respiratory failure). The majority of adverse events (AEs) were grade 1/2 and consistent with known toxicities of individual agents. The most common grade 3 AEs were mucositis (n=28), radiation dermatitis (n=15), dehydration (n=8) and cetuximab rash (n=9). The median overall survival and progression free survival have not been reached. Updated numbers will be presented. Overall survival rate is 34/38 (89%) by intent-to-treat analysis, with a median follow up of 13 months. Conclusions: The combination of IMRT, PPX, and C is tolerable and shows promising clinical activity in patients with LA-HNC. An expansion cohort of HPV negative patients on this protocol is in progress. Clinical trial information: NCT00660218.
Fulfillment of the uncertainty principle in cancer clinical trials
Authors: S. Joffe, D. P. Harrington, S. L. George, E. J. Emanuel, L. Budzinski, J. C. Weeks
Journal: Journal of Clinical Oncology (2004)

6003 Background: For randomized controlled trials to be ethical, the relative benefits of the study treatments must be uncertain. Therefore, the prior probability that either treatment is actually better should not be too high. Concerns about violation of this uncertainty constraint adversely affect accrual and other aspects of trial conduct. Methods: To estimate the prior probability that an adult cancer trial will favor the experimental or control treatment, we studied trials conducted by two cooperative groups that closed between 1981 and 1995. We abstracted design features from original protocols. We coded study results using statisticians' reports, published articles, or abstracts. The unit of analysis was the randomization. Using protocol-specified primary endpoints, we categorised each randomization as favoring control, showing no significant difference, or favoring the experimental treatment. We also calculated an effect size for each randomization. Results: 107 randomizations were eligible. Results were available for 103 (96%), from 93 trials. Of these, three (3%) favored the control treatment, 70 (68%) found no statistically significant difference between the treatments, and 30 (29%) favored the experimental treatment. The mean effect size was 1.19 (95% confidence interval 1.12–1.27), reflecting an advantage for the experimental treatment. Conclusions: We observed a measurable average improvement in disease control associated with assignment to the experimental rather than the control arm of an adult cancer cooperative-group trial. Nevertheless, the small magnitude of the advantage and the heterogeneity of the results suggest that as a group these trials satisfy the uncertainty principle. No significant financial relationships to disclose.
Prostate cancer incidence in a large cohort of Peruvian men affiliated to a prepaid system.
Authors: Alfredo Aguilar, Jorge Iberico, Silvia P Neciosup, Claudio J. Flores, Priscila I. Valdiviezo, Joseph A. Pinto, Juan F. Suazo, Ivan Carlos Aguilar Marin, Carlos S. Vallejos
Journal: Journal of Clinical Oncology (2013)

e12566 Background: Prostate cancer (PC) is the most common malignancy and the leading cause of death by cancer in Peruvian men (age-standardized rate [ASR] of 37 new cases/100,000 men estimated by GLOBOCAN 2008). The purpose of this study was to assess the incidence of PC in a cohort of men at Oncosalud, an oncologic pre-paid system that currently has 600,000 affiliates. Methods: We evaluated a dynamic cohort (period 1989 to 2011) of men affiliated to Oncosalud – Auna, an oncologic prepaid system.The crude incidence rate per year (number of new cases/men at risk), the specific rate according to age (number of new cases / persons-year), and cumulative risk were calculated. Results: Overall, during the assessment period, the PC incidence rate per year was 183.7 and the ASR incidence was 145 per 100,000 affiliates respectively. In our cohort of affiliates there were no PC cases before 1995 (with 3061 men at risk for that year). The highest incidence rate was 160.5 registered in 1999 (12,461men at risk). Incidence rates showed a decreasing tendency since 2008 (159.7 with a population at risk of 86,408 men), reaching its lowest value in 2011(92.3 with 213,531men at risk). According to age-groups, there were no PC cases under 35 years old except for the 20-24 year old group (incidence rate 2.3). Specific incidence rates per age-group increases from the 40 year old-group (38.5). The peak of PC incidence was between 75 to 79 years old (1506.05). In the same way, the cumulative risk increases after 40 years old. Conclusions: In our cohort of affiliates, the incidence of PC is greater than the general population, it could be due to the process of negative selection; on the other hand, specific incidence rates per age-group and cumulative risk are increased after 40 years, as seen in the general population.
Home-Based Hypnotherapy Self-exercises vs Individual Hypnotherapy With a Therapist for Treatment of Pediatric Irritable Bowel Syndrome, Functional Abdominal Pain, or Functional Abdominal Pain Syndrome
Authors: Juliette M. T. M. Rutten, Arine M. Vlieger, Carla Frankenhuis, Elvira K. George, Michael Groeneweg, Obbe F. Norbruis, Walther Tjon a Ten, Herbert M. van Wering, Marcel G. W. Dijkgraaf, Maruschka P. Merkus, Marc A. Benninga
Journal: JAMA Pediatrics (2017)

<h3>Importance</h3> Individual gut-directed hypnotherapy (HT) is effective in pediatric irritable bowel syndrome (IBS) and functional abdominal pain or functional abdominal pain syndrome (FAP[S]). It is, however, unavailable to many children. <h3>Objective</h3> To compare the effectiveness of HT by means of home-based self-exercises using a CD with that of individual HT (iHT) performed by qualified therapists. <h3>Design, Setting, and Participants</h3> This noninferiority randomized clinical trial with a follow-up of 1 year after the end of treatment was conducted from July 15, 2011, through June 24, 2013, at 9 secondary and tertiary care centers throughout the Netherlands. A total of 303 children were eligible to participate. Of those, 260 children (aged 8-18 years) with IBS or FAP(S) were included in this study. Children were randomized (1:1 ratio) to home-based HT with a CD (CD group) or iHT performed by qualified therapists (iHT group). No children withdrew from the study because of adverse effects. <h3>Interventions</h3> The CD group was instructed to perform exercises 5 times per week or more for 3 months. The iHT group consisted of 6 sessions during 3 months. <h3>Main Outcomes and Measures</h3> Primary outcomes were treatment success directly after treatment and after 1-year follow-up. Treatment success was defined as a 50% or greater reduction in pain frequency and intensity scores. The noninferiority limit was set at 50% treatment success in the CD group, with a maximum of 25% difference in treatment success with the iHT group after 1-year follow-up. Modified intention-to-treat analyses were performed. <h3>Results</h3> A total of 132 children were assigned to the CD group and 128 to the iHT group; 250 children were analyzed (126 in the CD group and 124 in the iHT group) (mean [SD] age, 13.4 [2.9] years in the CD group and 13.3 [2.8] years in the iHT group; 94 female [74.6%] in the CD group and 85 [68.5%] in the iHT group). Directly after treatment, 46 children (36.8%) in the CD group and 62 (50.1%) in the iHT group were successfully treated. After 1-year follow-up, the 62.1% treatment success in the CD group was noninferior to the 71.0% in the iHT group (difference, −8.9%; 90% CI, −18.9% to 0.7%;<i>P</i> = .002). <h3>Conclusions and Relevance</h3> Long-term effectiveness of home-based HT with a CD is noninferior to iHT performed by therapists in pediatric IBS or FAP(S). Treatment with hypnosis using a CD provides an attractive treatment option for these children. <h3>Trial Registration</h3> trialregister.nl Identifier:NTR2725
A prospective multicenter observational study of surgical palliation examining postoperative quality of life in patients treated for malignant gastric outlet obstruction caused by incurable advanced gastric cancer.
Authors: Kazumasa Fujitani, Masahiko Ando, Kentaro Sakamaki, Masanori Terashima, Ryohei Kawabata, Yuichi Ito, Takaki Yoshikawa, Masato Kondo, Yasuhiro Kodera, Masahide Kaji, Yoshio Oka, Hiroshi Imamura, Junji Kawada, Akinori Takagane, Hideaki Shimada, Yutaka Tanizawa, Takeharu Yamanaka, Satoshi Morita, Motoki Ninomiya, Kazuhiro Yoshida
Journal: Journal of Clinical Oncology (2017)

6 Background: Decision-making for surgical palliation remains one of the most challenging clinical scenarios since quality of life (QOL) is a key component of cancer care. We conducted this study to examine the impacts of surgical palliation on postoperative QOL in patients (pts) with malignant gastric outlet obstruction (GOO) caused by incurable primary gastric cancer (GC). Methods: Eligibility included (1) no oral intake or liquids only requiring parenteral nutrition (2) aged ≥20 (3) surgically fit (4) ECOG PS of 0-2 and (5) written IC. Patients underwent either palliative distal/total gastrectomy (DG/TG) or gastrojejunostomy (GJS). Treatment choice was left to the discretion of the physician. Validated QOL instruments (EORTC QLQ-STO22 and EuroQol-5D) assessed QOL at baseline, 2 weeks (wks), 1 month (m), and 3 months following the surgical palliation, and two observational outcomes (postoperative improvement of oral intake, and safety of surgical intervention) were evaluated. Results: 104 pts, 71 males and 33 females with a median age of 68 years, were enrolled. The types of surgery were DG in 23 pts, TG in 9 pts, GJS in 70 in pts, and exploratory laparotomy in 2 pts. Baseline QOL questionnaires were completed by 103 (99.0%) pts. Among the 104 pts, 98 (94.2%), 100 (96.1%), and 81 (77.9%) completed the 2-wk, 1-m, and 3-m follow-up survey, respectively. The mean baseline EQ-5D score was 0.74 (SD, 0.21). During the follow-up period, the mean scores remained consistent with the baseline scores; the change from baseline score was within ± 0.05 for the index. Many pts came to eat solid food at 2 wks postsurgery and remained tolerable thereafter (from 0 at baseline to 82, 85, 75 pts at 2 wks, 1 m, and 3 ms, respectively). Overall morbidity rate of ≥grade 3 on Clavien-Dindo classification and 30-day postoperative mortality rate was 9.6% (10 pts) and 2.0% (2 pts) with a median hospital stay of 13 days and re-operation rate of 3.9% (4 pts). Conclusions: In pts with malignant GOO caused by advanced GC, surgical palliation maintained patient QOL while improving solid food intake with an acceptable surgical safety. Clinical trial information: UMIN000023494.
A phase II clinical trial of HDACi (vorinostat) and AI therapy in breast cancer with molecular imaging correlates.
Authors: Hannah M. Linden, Brenda F. Kurland, Jeanne Link, Alena Novakova, Xiaoyu Chai, Jennifer M. Specht, Vijayakrishna K. Gadi, Julie Gralow, Erin K Schubert, Lanell Peterson, Janet F. Eary, Andrew Shields, David A. Mankoff, Kenneth A. Krohn
Journal: Journal of Clinical Oncology (2014)

556 Background: Histone deacetylase inhibitors (HDACi) have shown pre-clinical promise in estrogen receptor-modulation and restoring sensitivity to endocrine manipulation in ER+ breast cancer. Vorinostat is an FDA approved HDACi for CTCL, and could have a beneficial role in restoring ER-signaling in endocrine-resistant tumors. [F-18]fluoroestradiol (FES) PET imaging may be used to monitor regional ER expression in patients with breast cancer. Methods: Patients with metastatic breast cancer with prior clinical benefit from endocrine manipulation and who progressed on AI therapy were eligible. In part A patients cycled between vorinostat for 2 wks, and AI for 6 wks. In part B (reflecting results of HDACi trials) patients were given vorinostat 400mg po daily 5/7 days 3/4 wks while AI was given continuously. Paired FES and FDG PET were performed at baseline, wks 2 and 8; clinical/radiologic assessment of disease was also performed at wk 8. Patients with clinical benefit (response or stable disease) continued on treatment until progressive disease or study withdrawal. Lesion-level analysis of the association between baseline FES uptake (logged) and FES/FDG ratio used generalized estimating equations (GEE). Results: 16 of 20 planned patients have accrued and treatment is well tolerated; one withdrew for toxicity. The majority of patients have longstanding, bone/soft tissue dominant disease, and were previously treated with multiple endocrine and chemotherapy regimens. Six patients have had clinical benefit (4/8 evaluable on part B), remaining on study treatment for >40, 29, >21, and >8 wks. FES and FDG uptake was analyzed in 101 lesions in 16 patients. FES uptake in general remained stable during treatment and FDG declined in responding patients. Two responding patients showed increase in FES with clinical benefit and two patients with clinical benefit had negligible pre-therapy FES uptake. Conclusions: HDACi therapy can be effective in hormone-refractory breast cancer. Molecular imaging in parallel with early studies indicate a heterogeneity of response patterns, suggesting that some patients benefit from AI plus vorinostat, and some may benefit from the HDACi alone. Clinical trial information: NCT01153672.
Constitutive overexpression of the L-selectin gene in fresh leukemic cells of adult T-cell leukemia that can be transactivated by human T- cell lymphotropic virus type 1 Tax
Authors: M Tatewaki, K Yamaguchi, M Matsuoka, T Ishii, M Miyasaka, S Mori, K Takatsuki, T Watanabe
Journal: Blood (1995)
Comparative analysis of metabolic signature from malignant melanoma and uninvolved skin.
Authors: Friederike Egberts, Oliver von Kampen, Witigo von Schoenfels, Clemens Schafmayer, Katharina Balschun, Axel Hauschild, Alexander Arlt, Jochen Hampe
Journal: Journal of Clinical Oncology (2015)

e20016 Background: In a variety of malignancies, metabolites have been investigated in order to identify potential biomarkers and therapeutic targets. Current clinical strategy for staging and prognostication of malignant melanoma relies mainly upon the AJCC classification. However, this clinicopathological stage gives little insight into the biological characteristics of the tumor. We hypothesized that global metabolic profiling of malignant melanoma would define metabolic signatures that discriminate malignant from normal skin and may also distinguish clinicopathological and prognostical features. In this study we compared metabolic signatures from either primary melanoma or melanoma metastases with matched control non-neoplastic skin from the same patient. Methods: Human fresh (non-fixed) biopsied melanoma samples and matched controls from uninvolved skin were obtained from 40 melanoma patients (primary melanomas: n = 23, cutaneous melanoma metastases: n = 17) during surgery and subjected to a two-stage metabolomic screening experiment using gas chromatography/mass spectrometry (GC/MS). Results: In a set of 300 chemically defined metabolites, the metabolic profiles of primary melanoma and metastatic tissue suggested a key role for metabolic pathways of apoptosis, energy metabolism, and proliferation. Several metabolites including cyclopentenone, methylsalicylate, malonate, trimethyl-cis-aconitate, and dimethyluracil differed significantly between melanoma and normal tissue meeting the discovery (p < 2.0×10(-4)) and the replication thresholds (p < 3.5×10(-3)). Cyclopentenone prostaglandins have been shown to have a proapoptotoc effect on melanoma cells and to activate the nuclear factor E2-related factor 2 (Nrf2)- pathway, which, in turn, contributes to tumorigenesis via protection from tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis. Conclusions: Our results illustrate the potential of GC/MS to specify the metabolic signature of melanoma. We found clear differences between primary melanoma, metastatic tissue and uninvolved skin. Metabolomics may help to characterize novel pathways and potential new biomarkers in melanoma.
Clinical correlates of memory problems in middle-aged adult-onset cancer survivors in the United States: A national cross-sectional study.
Authors: Pascal Jean-Pierre, Michael Grandner, Ashley Jean-Pierre, Sheila N. Garland, Erin Richards, Gloria Maciorowski
Journal: Journal of Clinical Oncology (2014)

e20588 Background: Cancer and its treatments can deleteriously impact cognitive functioning in cancer patients and survivors. The etiology of cancer/treatment-related memory problems is generally attributed to various genetics, biological, and psychosocial factors. The present study assessed clinical predictors of self-reported memory problems (SRMP). Methods: We analyzed data from 160 adult cancer survivors, aged 41-64 years, who completed the 2007-2008 National Health and Nutrition Examination Survey. Participants with a history of brain tumor/stroke were excluded since these conditions generally cause direct brain insults/cognitive impairments. Clinical variables assessed obesity (body mass index evaluated [1] continuously or [2] dichotomized at 30kg/m2), hypertension ([1] previous diagnosis and/or current treatment for hypertension and [2] measured blood pressure >140/90mmHg), high cholesterol ([1] previous diagnosis and/or current treatment for high lipids and [2] serum cholesterol, assessed continuously), diabetes ([1] previous diagnosis and/or current treatment for diabetes and [2] log hba1c level), and inflammation ([1] log c-reactive protein). Population-weighted binomial logistic regression analyses, adjusted for age, sex, race/ethnicity, education and income, assessed clinical predictors of memory problems. Results: Obesity (assessed continually or binomially), history of hypertension, objectively determined blood pressure (>140/90mmHg), and history of diabetes were not associated with SRMP (p>0.05). Current hba1c levels (p<0.05), history of high cholesterol (p<0.01), serum cholesterol levels (p<0.01), and C-reactive protein levels (p<0.05) predicted SRMP. Conclusions: Elevated glucose and cholesterol levels, as well as inflammation were associated with SRMP. Strategies to alleviate SRMP burden need to more systematically assess and control these conditions for cancer patients and survivors.