tbuckley/cabot-search huggingface dataset:
Stereotactic body radiation therapy for pancreatic cancer: Single institutional experience.
Authors: Shalini Moningi, Siva P. Raman, Avani Satish Dholakia, Amy Hacker-Prietz, Timothy M. Pawlik, Lei Zheng, Matthew Weiss, Daniel A. Laheru, Christopher Lee Wolfgang, Joseph M. Herman
Journal: Journal of Clinical Oncology (2014)

328 Background: Stereotactic Body Radiation Therapy (SBRT) is emerging as a possible standard treatment for pancreatic cancer; however, there is limited data to support its efficacy. This study reviews our institution’s experience using SBRT in the treatment of pancreatic cancer (PCA). Methods: Charts of all PCA patients receiving SBRT from January 2010 to June 2013 were retrospectively reviewed. The primary end points were overall survival (OS) and tumor response assessed by RECIST criteria. 95% of the PTV (GTV + 2-3 mm) received a total dose of 20-33 Gy in five fractions (4-6.6 Gy/fraction), with up to 20% heterogeneity allowed. Pre- and post-SBRT chemotherapy regimens included gemcitabine, cisplatin, FOLFIRINOX, 5-FU or paclitaxel. Results: 84 patients received SBRT, with a median follow-up time of 15.3 months. Median age was 66.5 years, 57.1% were male and 65.5% had head tumors. 66 patients received definitive SBRT for locally advanced or borderline resectable PCA, 4 patients were treated with adjuvant SBRT, and 14 received SBRT for treatment of recurrent disease. Median OS from the date of diagnosis for patients receiving definitive radiation was 17.8 mos (95% CI 14.9-20.9).For recurrent patients the median OS from first day of SBRT was 11.8 mos (95%CI 8.3-15.3). In the definitive SBRT group, among patients who were alive and had follow-up scans, the 6 and 12 month local control rate (stable or partial response) based on RECIST criteria was 84.6% and 81.8%, respectively. Five patients underwent surgery following SBRT and all had negative resection margins. Acute toxicity was minimal with most experiencing grade 1 or 2 fatigue and no grade 3/4 acute toxicity. Late grade 3/4 GI toxicity was seen in 5% (4/84) and 1 patient had a grade 5 GI bleed due to direct tumor invasion into the duodenum. Conclusions: Our early results using SBRT in the definitive and recurrent settings show favorable local control, toxicity, and survival when compared to historical outcomes using chemoradiation. Acute and late toxicity was minimal however the optimal dose and fractionation as well as normal tissue dose constraints need to be determined. Integration of SBRT with more aggressive chemotherapy may result in improved outcomes in patients with PCA.
Ongoing phase I studies of ABT-263: Mitigating Bcl-X<sub>L</sub> induced thrombocytopenia with lead-in and continuous dosing
Authors: A. W. Roberts, W. Wilson, L. Gandhi, O. A. O'Connor, C. M. Rudin, J. R. Brown, H. Xiong, Y. Chiu, S. Enschede, A. P. Krivoshik
Journal: Journal of Clinical Oncology (2009)

3505 Background: ABT-263, a novel, oral BH3 mimetic, potently inhibits multiple antiapoptotic Bcl-2 family proteins. Ongoing phase 1 studies of ABT-263 show anti-tumor activity in CLL and some lymphomas (Wilson W et al, ASH. 2008). However, thrombocytopenia (TCP) due to on-target Bcl-X L inhibition-induced platelet apoptosis is also observed. Platelet nadir occurred on days 3–5 on 14/21 d dosing with each exposure to drug, was proportional to starting platelet count and recovered during therapy due to compensatory increased megakaryopoiesis. TCP was a dose limiting toxicity (DLT) in 3 patients (pts) in CLL study M06–873 (N = 15) where starting platelet counts tend to be low. We tested 2 strategies to mitigate variability in circulating platelet levels and achieve higher cumulative exposure: introducing a lower lead-in dose and using a continuous dosing (CD) (21/21 d schedule). Methods: CD with a 7 d lead-in dose was explored (150, 150 or 100 mg lead-in doses) with dosing at 200 and 275 mg, 225 and 325 mg, or 125 and 250 mg in studies M06–814 (NHL), M06–822 (SCLC), and M06 873 (CLL), respectively. Results: 22 pts on 21/21 d dosing enrolled to date in the 3 studies. Cmax &amp; AUC at steady-state were comparable between pts at the same dose on 21/21 and 14/21 d schedules. Lead-in followed by CD appears to minimize platelet nadir and cycle variability. At 200 mg and grouping data from 200 and 225 mg doses, median platelet nadir in Cycle 1 was 46% and 42% of baseline on the CD schedule after lead-in vs 33% and 36% on the 14/21 schedule, respectively. For pts receiving 150 mg lead-in, nadir occurred during this phase, and platelet levels remained relatively stable on CD for doses up to 225 mg. 2 DLTs were observed for CD, 1 pt per study M06–814 (275 mg) and M06–873 (200 mg) experienced grade 4 (TCP). While CD enrollment and time on study is still limited, anti-tumor activity includes 1 unconfirmed partial response (68% CT regression) in a SLL pt at 275 mg and 3 CLL pts with ≥50% lymphocyte reduction for ≥2 months. Conclusions: Dosing schedule moderates early platelet nadir. Optimal dosing regimens may vary between tumor types especially where marrow infiltration is a feature. [Table: see text]
Isolation and characterization of an acute promyelocytic leukemia cell line selectively resistant to the novel antileukemic and apoptogenic retinoid 6-[3-adamantyl-4-hydroxyphenyl]-2-naphthalene carboxylic acid
Authors: Isabella Ponzanelli, Maurizio Giannı̀, Raffaella Giavazzi, Angela Garofalo, Ines Nicoletti, Uwe Reichert, Eugenio Erba, Alessandro Rambaldi, Mineko Terao, Enrico Garattini
Journal: Blood (2000)
Dihydropyrimidine dehydrogenase gene (DPYD) polymorphism among Caucasian patients (pts) with 5-FU and capecitabine (CAP)-related toxicity
Authors: N. A. Podoltsev, M. W. Saif
Journal: Journal of Clinical Oncology (2009)

e14588 Background: As many as 1 in 3 pts receiving 5-FU/CAP experience dose-limiting toxicity including diarrhea, hand-foot syndrome (HFS), mucositis and myelosupression. Deficiency of DPD, a rate limiting enzyme in 5-FU catabolism can lead to life- threatening complications. DPD deficiency was found to be related to &gt; 40 sequence variations in DPYD. Known deleterious mutations explain only a limited proportion of 5-FU's adverse events. Full sequence analysis of DPYD gene increases sensitivity by 20% vs. simple identification of two most common deleterious mutations (IVS14 +1 G&gt;A, D949V). Pretreatment detection could prevent serious, potentially lethal side effects. We present analysis of DPYD genotyping in untreated Caucasian pts (control group) and Caucasian pts with 5-FU/CAP-related grade 3/4 toxicities (toxicity group) who underwent TheraGuide 5-FU testing. Methods: Full sequencing of DPYD was performed by Myriad Genetic Laboratories, Inc. as part of TheraGuide 5-FU test. DNA was extracted and purified from white blood cells. Genetic variants within pt's DPYD were detected by comparison with a consensus wild-type DPYD sequence. Results: Among 227 pts from toxicity group 27 (12%) had deleterious mutations in DPYD: 12 (5%) had IVS14 +1 G&gt;A, 11 (5%) had D949V and 4 (2%) other mutations. Only 7/192 (4%) pts from control group had DPYD genotype abnormalities: 2 (1%) had IVS14 +1 G&gt;A, 4 (2%) had D949V and 1 (1%) other mutation. Genotype abnormalities were seen more frequently in toxicity group (p=0.001). Among 49 pts with HFS 9/49 (18%) had mutated DPYD. 9/46 (20%) pts with myelosupression were found to have a deleterious mutation. Mutations were more frequent in both subgroups when compared to control group: p=0.001 and 0.0007 respectively. Among 65 pts with toxicities due to CAP 9 (14%) had mutated DPYD which was more frequent than in control group (p=0.006). Conclusions: Mutated DPYD is frequently observed in Caucasian pts who experience toxicities while receiving 5-FU/CAP. Screening pts for DPYD mutations prior to administration of 5-FU/CAP using new pharmacogenetic testing methods may help to identify those pts who are at greatest risk for adverse effects, allowing a more individualized approach to their chemotherapy management. [Table: see text]
Cancer clinical trial accrual patterns among community cancer centers in the United States
Authors: J. A. Lee, M. A. Mathiason, C. A. Czeczok, J. K. Keller, R. S. Go
Journal: Journal of Clinical Oncology (2006)

6041 Background: Most cancer patients are diagnosed and treated in the community but clinical trial accrual rate is low. Published data on trial accrual from community-based cancer centers throughout the U.S. are limited. The Association of Community Cancer Centers (ACCC) is a national multidisciplinary education and advocacy organization that maintains a membership caring for over 60% of all patients with cancer in the U.S. In order to determine the clinical trial accrual patterns in the community across various geographic regions in the U.S., we performed a retrospective study utilizing the data from ACCC membership maintained at their web site. Methods: Data available from the most recent year (2003–2005) were obtained from 621 centers throughout the U.S., representing 49 states (no data for WY) and the DC. We investigated the number of patients (new and old) accrued into trials per year relative to the number of new analytical patients seen in the same year, a value we termed accrual ratio (AR). In addition, we studied the effects of geographic location, size of the cancer program, number of affiliations with National Cancer Institute sponsored cancer cooperative groups, and the number of medical/support/data management staffs on trial accrual. Results: A total of 670,215 new patients were seen across the ACCC membership with 43,743 patients accrued into trials for a median AR of 6.5% (range, 0.3–16.9). The top and bottom 5 accruing states were VT, MD, SD, LA, ID and KS, ND, VA, NH, AR, respectively. Regionally, the AR for Midwest, Middle Atlantic, West, South, Southwest, and New England were as follows: 7.4%, 7.0%, 6.2%, 6.0%, 5.7%, and 5.4% (p &lt; 0.001). One hundred (16.1%) centers representing 11.8% of all new patients were not affiliated with any of the cooperative groups. This group had the lowest AR (3.1%). AR increased when centers were affiliated with more cooperative groups (p &lt; 0.001) or cared for more new patients (p &lt; 0.001). The number of medical, support, and data management staffs did not influence accrual. Conclusions: Overall, clinical trial accrual in the U.S. community cancer centers is low. Accrual patterns differed significantly among various geographic locations. Better access to trials is needed in order to improve participation of cancer patients. No significant financial relationships to disclose.
Discordance in hormone receptor status in breast cancer during tumor progression.
Authors: E. Karlsson, L. S. Lindström, U. Wilking, L. Skoog, U. Johansson, J. Bergh
Journal: Journal of Clinical Oncology (2010)

1009 Background: In the metastatic situation therapy management is often based on primary tumor characteristics such as estrogen receptor (Er) and progesterone receptor (Pr) status. Discordance of those factors may lead to altered therapy management. Methods: Breast cancers from patients in the Stockholm health care region that relapsed during 1997 to 2007 were retrospectively compared for Er and Pr status. Monoclonal antibody based biochemical or immunohistochemical/immunocytochemical methods were used for determination of hormone receptor status. Histopathological or cytological information for primary and relapse tumors were collected from original pathology reports. The pathology laboratory at Karolinska University Hospital continuously participate in quality assurance programs for receptor analysis. Results: In 486 and 456 patients, Er and Pr information were available from the primary tumor and one or more recurrent sites, resulting in 679 and 630 pairs, respectively. For Er, 27% of patients changed from positive in primary tumor to negative in relapse tumor and 8% changed from negative to positive. Pr status changed in 38% of patients from positive to negative and 5% changed from negative to positive. In our univariate analysis the Er groups (concordantly positive/negative and two discordant), showed significantly different overall survival (log rank p<0.0001). The survival was worse for those with Er-negative relapse tumors compared to Er-positive, independent of primary Er tumor status. Conclusions: This study demonstrates that in nearly every third patient with breast cancer, the hormone receptor status changes during tumor progression. Thus, Er status of metastatic sites has impact on survival and therapy management of metastatic disease is not optimum when based on primary tumor characteristics. Altered management through tumor progression may improve survival, avoid over treatment, and support more frequent morphological confirmation of recurrent site. However, tumor heterogeneity, clonal selection by different adjuvant therapies, and methodological issues regarding receptor determinations may contribute to our findings and will be discussed further at presentation. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Affybodies, Amgen, AstraZeneca, GlaxoSmithKline, I3Innovus, Onyx/Bayer, Pfizer, sanofi-aventis, Tapestry Pharmaceuticals AstraZeneca, Pfizer, Roche Merck, Pfizer, Roche
Why did the gender difference influence survival in patients with completely resected stage I adenocarcinoma of the lung?
Authors: M. Tsuboi, H. Kato, Y. Ichinose, M. Ohta, E. Hata, N. Tsubota, H. Tada, H. Wada, N. Hamajima
Journal: Journal of Clinical Oncology (2007)

7647 Background: This study evaluates the influence of gender on survival and tumor recurrence in patients with completely resected stage IA and IB adenocarcinoma of the lung based on the analysis of the Japan Lung Cancer Research Group trial, which was a randomized prospective study of adjuvant chemotherapy with uracil-tegaful for stage I pulmonary adenocarcinoma. Methods: Patients were randomized to receive either oral uracil-tegaful (250 mg of tegaful/m 2 /day) for 2 years postoperatively or no adjuvant treatment. Survival was calculated from randomization until death. Survival estimated using the Kaplan-Meier method, and difference in survival between two groups was compares with the log-rank test. Results: The 5-year survival rate was 88.9% for the 502 women and 84.3% for the 477 men (median follow-up 72 months, p=0.0066). The relative risk of death for men vs women was 0.658 (95% C.I., 0.476–0.910, p=0.011), although the mean age of men was significantly less than that of women (p=0.041). There was no interaction between the gender differences and the efficacy of uracil-tegaful (p=0.657). However men presented with significantly more preoperative complications, more T2 diseases (p=0.0006), less non-papillary growth for histology (p=0.0078), less well differentiated subtype (p&lt;0.001), higher serum carcinoembryonic antigen (CEA) level (p=0.004), and more smoking history than women (p&lt;0.0001). Disease recurrence patterns were similar between the genders. The postoperative mortality showed a tendency to go up in men. Conclusions: Although longer life expectancy for women in Japan may in part explain, gender influences survival after complete resection for stage IA-B lung adenocarcinoma. The reasons for prolonged survival of women with this disease may be related to the several differences in the distribution of preoperative complications, smoking history and tumor biological behaviors such as T descriptor, histologic subtype, and serum CEA level. However cause- specific mortality was difficult to be explained. Further molecular epidemiologic and molecular profiling studies regarding gender as a prognostic and predictive factor for survival should be done. No significant financial relationships to disclose.
Abstract 20187: Type a Aortic Dissection in Bicuspid Aortic Valve and Marfan Syndrome Patients: Differences and Similarities
Authors: Marco Di Eusanio, Hasan Siddiqi, Eduardo Bossone, Linda Pape, Thomas G Gleason, Kevin M Harris, Truls Myrmel, Alan C Braverman, Thoralf M Sundt, Daniel G Montgomery, Eric M Isselbacher, Kim A Eagle, Christoph A Nienaber, Arturo Evangelista, Rossella Fattori
Journal: Circulation (2014)

Background:  Bicuspid aortic valve (BAV) and Marfan Syndrome (MFS) are associated with deleterious changes in the aortic media that predispose patients to Type A acute aortic dissection (TAAAD). Little comparison has been done regarding how TAAAD manifests itself in these different diseases.   Methods:  Type A patients enrolled in the International Registry of Acute Aortic Dissection with recorded history of either condition were compared (N=2320). BAV was noted in 93 patients (4.0%) and MFS in 84 (3.6%).   Results:  MFS patients presented younger (36.7±11.7 v 52.7±16.1, p  Patients with MFS were more likely to present with pain (96.4% v 86.8%, p=0.030); no other differences in presenting symptoms were noted. Annulus, root, sinotubular junction, arch, and descending aortic diameters were similar between groups. The ascending aorta was larger in BAV patients (median diameter 5.5 cm (4.8-6.4) v 4.8 (4.0-6.0), p=0.008). BAV patients were more likely to have periaortic hematoma at presentation (23.3% v 9.1%, p=0.024). Surgery was performed frequently in both groups (91.4% BAV v 90.5% MFS, p=NS) with BAV patients undergoing more aortic valve replacement (59.7% v 37.7%, p=0.008). In-hospital mortality was similar (16.1% BAV v 13.1% MFS, p=NS), and no other differences were seen in in-hospital complications or 5-year survival estimates. MFS patients were much more likely to require a subsequent aortic intervention on 5-year Kaplan-Meier analysis (0% in BAV v 51.4% MFS; p=0.003).   Conclusions:  Differences in patient history and ascending aortic size were noted between groups, while presentation, management and outcomes were similar. Notably, patients with MFS were much more likely to require an aortic operation 5 years post-discharge.
Leukemic burden in subpopulations of CD34+ cells isolated from the mobilized peripheral blood of alpha-interferon-resistant or -intolerant patients with chronic myeloid leukemia
Authors: D Van den Berg, M Wessman, L Murray, J Tong, B Chen, S Chen, D Simonetti, J King, G Yamasaki, R DiGiusto, D Gearing, C Reading
Journal: Blood (1996)
Cytokine levels in patients (pts) with colorectal cancer and breast cancer and their relationship to fatigue and cognitive function
Authors: J. L. Vardy, C. Booth, G. R. Pond, H. Zhang, J. Galica, H. Dhillon, S. J. Clarke, I. F. Tannock
Journal: Journal of Clinical Oncology (2007)

9070 Background: Cytokines have been associated with fatigue and cognitive dysfunction. Here we evaluated plasma cytokine levels in pts with colorectal cancer (CRC) and breast cancer (BC) who were free of evident disease, and in healthy volunteers. Methods: Serum levels of 10 cytokines were measured using a LiquiChip assay on 251 subjects. CRC pts (n=136, ages 23–75) were evaluated at baseline (mean 8 weeks post-surgery [n=107] or before surgery [n=29]), with repeat measures at 6 months (56 post chemotherapy [CT], 14 without CT) and 12 months (32 post CT, 7 without CT). BC pts (n=51, ages 29–60) were within 5 years of diagnosis (33 after adjuvant CT). Healthy volunteers (n=64) had ages 20–62. Cancer pts completed questionnaires for fatigue &amp; QOL (FACT-F), anxiety/depression (GHQ), and perceived cognitive function (FACT-COG); they had neuropsychological assessment. Results: Cytokines were elevated in all cancer groups compared to healthy controls (p-values &lt;0.001; selected data in table ). Values were highest after surgery but remained significantly higher than healthy controls at 6–60 months after diagnosis, with a trend to being higher in cancer patients who had not received CT. There was a trend to elevated cytokines being associated with greater fatigue and cognitive impairment in both CRC and BC, but no association with QOL or anxiety &amp; depression. Conclusions: Cytokine levels were elevated in all cancer groups compared to healthy volunteers and remained elevated up to 5 years post diagnosis; they may be associated with cognitive dysfunction and fatigue. [Table: see text] No significant financial relationships to disclose.
Capecitabine (X) chemoradiation (CRT) in the preoperative treatment of patients (pts) with rectal adenocarcinomas: A phase II GERCOR trial
Authors: O. Dupuis, B. Vié, G. Lledo, C. Hennequin, M. Noirclerc, M. Bennamoun, J. M. Pavlovitch, J. H. Jacob
Journal: Journal of Clinical Oncology (2004)

3538
Interpreting in palliative care: A systematic review of the impact of interpreters on the delivery of palliative care services to cancer patients with limited English proficiency.
Authors: Milagros Silva, Margaux Genoff, Alexandra Zaballa, Stacy Marie Stabler, Francesca Gany, Lisa Diamond
Journal: Journal of Clinical Oncology (2014)

123 Background: According to the 2011 U.S. Census 60% of people living in the U.S. speak a language other than English at home, and of these approximately 40% have limited English proficiency (LEP). Language barriers can affect the health outcomes of LEP patients and the use of trained interpreters can improve patient-physician communication. Since effective communication is the cornerstone of delivering adequate palliative care, a systematic review was conducted to determine the impact of interpreters on the delivery of palliative care services to LEP patients with cancer. Methods: We conducted a systematic review of the literature search in all available languages of 6 databases from 1966 and 2013. Studies evaluated interpreter interventions for LEP patients receiving palliative care services. Of 38 references, 11 articles were found by multiple reviewers to meet inclusion criteria. Data were collected on the study design, size, comparison groups, outcomes, and interpreter characteristics. Results: A total of 6 qualitative and 5 quantitative studies assessed the use of interpreters. All studies found that the quality of care provided to LEP patients receiving palliative services is affected by communication. Most studies showed that when no trained interpreters were used, LEP patients and families had inadequate understanding about their diagnosis or prognosis during goals of care conversations, and worse symptom management at end of life including pain and anxiety. Half of the studies concluded that trained interpreters are not utilized adequately and several suggested that pre-meetings between clinicians and interpreters are important to discuss topics and terminology to be used during goals of care conversations. Conclusions: Published studies show worse outcomes during end of life care and goals of care discussions when trained interpreters are not used. Moreover, trained interpreters are not being used appropriately in the field. More clinically relevant studies are needed to improve the quality of care provided to LEP patients and families receiving palliative services.