tbuckley/cabot-search huggingface dataset:
A randomized, double-blind, placebo-controlled, phase III study in patients (Pts) with metastatic adenocarcinoma of the colon or rectum receiving first-line chemotherapy with oxaliplatin/5-fluorouracil/leucovorin and PTK787/ZK 222584 or placebo (CONFIRM-1)
Authors: J. R. Hecht, T. Trarbach, E. Jaeger, J. Hainsworth, R. Wolff, K. Lloyd, G. Bodoky, M. Borner, D. Laurent, C. Jacques
Journal: Journal of Clinical Oncology (2005)

LBA3 Background: PTK787/ZK 222584 (PTK/ZK) is a novel, oral, small molecule, anti-angiogenesis compound that blocks tyrosine kinase signaling from all known vascular endothelial growth factor (VEGF) receptors. Phase I/II studies of PTK/ZK as a single agent showed that it is safe and well tolerated. Dose response was observed by DCE-MRI. An expanded phase I/II study evaluating escalating doses of PTK/ZK in combination with oxaliplatin/5-FU/LV as first-line therapy of metastatic colorectal cancer (CRC) demonstrated that chemotherapy and PTK/ZK could be safely administered as combination therapy. An overall response rate of 49% was observed; an additional 44% of Pts achieved stable disease. Methods: A multinational, randomized double-blind, placebo controlled phase III study has recently been completed to evaluate PTK/ZK in combination with the FOLFOX-4 regimen (oxaliplatin/5-FU/LV) in Pts with metastatic adenocarcinoma of the colon or rectum. Pts were included if they had histologically documented metastatic CRC, the presence of measurable disease, WHO Performance Status of 0–2 and adequate organ and bone marrow function. Pts were stratified in a 1:1 randomization scheme to receive oxaliplatin/5-FU/LV every 2 weeks according to the FOLFOX-4 regimen (de Gramont 2000) with either placebo or PTK/ZK given at a dose of 1250 mg, administered on a once-daily continuous schedule. Adjuvant therapy for primary CRC was acceptable providing that at least 6 months had elapsed from the conclusion of therapy to the time disease recurrence was documented. The primary endpoint was progression free survival (PFS). The study was designed to have at least 90% power to detect an increase in median PFS from approximately 9 months to 12 months at 5% significance level (two-sided). PFS data for the two treatment arms will be compared using a stratified log-rank test. Results: A total of 1168 Pts were randomized. Data for the primary endpoint (PFS) and secondary endpoints (overall response rate, time to progression, safety) will be presented for both treatment groups. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis, Schering AG Novartis
Pre-admission escalation rate of daily opioid consumption (PERDOC), and total morphine equivalent daily dose on the first complete day of admission (D1-MEDD) to a tertiary-level palliative care unit (TPCU): Correlates and predictors in patients with advan
Authors: P. G. Lawlor, C. L. Nekolaichuk, S. S. Lowe, A. Kelly, R. L. Fainsinger, S. Watanabe, E. D. Bruera
Journal: Journal of Clinical Oncology (2007)

9065 Background: Although animal laboratory studies attest to opioid tolerance (OT), it can be difficult in clinical practice to determine whether substantive escalation in opioid dose (average of &gt;5% per day between initial daily dose and maximum daily dose to date) is due to disease progression (DP) or decreased opioid responsiveness, which in turn may be due to OT or other factors. Our study aims were to determine (1) the frequency of PERDOC&gt;5%, (2) the correlates and predictors of PERDOC&gt;5% and D1-MEDD. Methods: We retrospectively examined TPCU patient database records for demographics, physician rating of PERDOC in the Edmonton Staging System (ESS) for cancer pain classification, Edmonton Symptom Assessment System (ESAS) scores, and D1-MEDD. Consecutive 1st admission data on patients surviving &gt;3 days were included in the initial analysis. Using complete data, logistic regression and multiple regression models were created with PERDOC&gt;5% and log n D1-MEDD, respectively, as dependent variables. Results: From 1,351 patients who met the initial descriptive analysis eligibility criteria, 1212 (90%) had an ESS rating for PERDOC. The prevalence of PERDOC&gt;5% was 274/1212 (19.3%). Bivariate analysis (N=969, complete data) showed that PERDOC&gt;5% was positively associated (p&lt;0.05) with younger age, neuropathic pain component (NPC), a pathological level of psychological distress (PLPD), substance abuse, higher D1-MEDD, and higher ESAS pain score (ESAS-P). In the multivariate analysis, NPC (Odds ratio: 2.1, 95% confidence interval: 1.5–2.9), PLPD (1.7, 1.2–2.6), and higher D1-MEDD (2.2, 1.03–4.7) were the strongest independent positive predictors, and ESAS-P (1.01, 1.003–1.02) remained as a weaker predictor. In the D1-MEDD regression model, positive predictors (p&lt;0.05) were younger age, NPC, incident pain, PERDOC&gt;5%, PLPD, ESAS-P and ESAS anxiety scores. Conclusions: Aside from OT and DP, the multiple predictors identified for PERDOC&gt;5% and D1-MEDD underscore the need for a systematic multidimensional assessment of cancer pain that incorporates psychological and physical characteristics. No significant financial relationships to disclose.
Intraoperative identification of sentinel lymph node guided by near-infrared fluorescence imaging for breast cancer patients
Authors: N. Tagaya
Journal: Journal of Clinical Oncology (2007)

615 Background: Recently, radioactive tracer, a vital dye, or a combination of both has been applied intraoperatively to detect sentinel lymph nodes (SLN) for patients with early breast cancers. We present a novel method of SLN identification using near-infrared fluorescence imaging that provides with high detection and low false-negative rates. Materials and Methods: This study enrolled 52 patients with a tumor less than 3 cm in diameter. Their mean age was 54.7 years. Preoperative TNM stage was I in 35 cases, IIa in 12, and IIb in 5, respectively. Initially the combination dye of indocyanine green and indigocarmine was injected subdermally in the areola. Fluorescence imaging (photodynamic eye: Hamamatsu Photonics Co.) was obtained using a charge coupled device camera with a cut filter as the detector, and light emitting diodes at 760 nm as the light source. Subcutaneous lymphatic channels draining from the areola to the axilla or other directions were visible by fluorescence imagings immediately. After incising the axillary skin 1 cm cranial side from the disappeared point of fluorescence image, SLN was then dissected under the guidance of fluorescence. Results: In all but one patient, lymphatic channels and SLN were successfully visualized (identification rate: 98.1%). SLN was observed before skin incision in two patients. The number of fluorescence SLN ranged from 0 to 11 (mean: 4.7) and blue dyed SLN ranged from o to 6 (mean: 2.0). SLN was not identified in one patient in the former and 7 patients in the latter. Twelve patients had lymph node metastases pathologically. All of them were recognized by fluorescence imaging, however, three patients with metastatic LN were not identified by a vital dye. Conclusions: This method is feasible and safe to detect SLN intraoperatively with less invasive, real-time observation and no requirement of training. We are convinced that this method will provide with high detection and low false-negative rates in SLN navigation surgery. No significant financial relationships to disclose.
High expression of the transcription factor ERG predicts unfavorable outcome in acute T-lymphoblastic leukemia (T-ALL) in adults
Authors: C. D. Baldus, T. Burmeister, P. Martus, S. Schwartz, N. Goekbuget, C. D. Bloomfield, D. Hoelzer, W. K. Hofmann, E. Thiel
Journal: Journal of Clinical Oncology (2006)

6505 Background: In adult T-ALL long-term survival remains limited to 32–46%. Transcription factors are frequently targeted by chromosomal translocations resulting in disruption of hematopoietic proliferation and differentiation. The oncogenic ETS transcription factor ERG is expressed during early T-cell development and shut off once T-cell commitment is complete. We hypothesized that due to its specific involvement in T-cell maturation and oncogenic potential, ERG might contribute to leukemogenesis. Thus we have determined the prognostic impact of ERG expression in T-ALL. Patients and Methods: ERG mRNA expression was analyzed by real-time RT-PCR in pretreatment marrow samples of 105 adults with T-ALL treated on German ALL protocols. Patients (pts) were dichotomized at ERG’s median expression into low (n=52) and high (n=53) expressers. HOX11 and HOX11L2 expression was determined by real-time RT-PCR. Immunophenotyping was performed differentiating T-ALL into 3 subtypes: pre-T (CD2-), thymic (CD1a+), and mature (sCD3+). Results: High ERG expression was associated with a higher relapse rate (45%) compared to pts with low ERG expression (20%; P=0.01). High ERG expressers compared to low ERG expressers had an inferior overall survival (OS, P=0.02; 5-year OS: high ERG 26% vs low ERG 58%) and relapse-free survival (RFS, P=0.003; 5-year RFS: high ERG 34% vs low ERG 72%). On multivariable analysis high ERG expression (P=0.005), immunophenotypic subgroups (pre-T vs mature vs thymic; overall P=0.04), HOX11L2 positivity (P=0.055) and absence of HOX11 expression (P=0.017) were independent adverse risk factors predicting RFS. Patients with high ERG expression had a hazard ratio (HR) for relapse of 3.2. Within the good prognostic subgroup of thymic T-ALL (n=57) high ERG (HR 4.1; P=0.02) and presence of HOX11L2 (HR 6.6; P=0.008) were independent adverse factors for RFS. Conclusion: High expression of the oncogene ERG is an adverse factor in adult T-ALL. Within thymic T-ALL otherwise classified as standard risk, high ERG expression identified pts that were more than four times likely to fail long-term RFS. The prognostic impact of ERG may assist treatment stratification and suggest the need of more intensive regimens for these high risk thymic T-ALL pts. No significant financial relationships to disclose.
High-Dose calcitriol, docetaxel, and estramustine in androgen-independent prostate cancer (AIPC): A phase I/II study
Authors: N. M. Tiffany, C. W. Ryan, M. Garzotto, E. M. Wersinger, T. M. Beer
Journal: Journal of Clinical Oncology (2004)

4678 Background: Phase II studies suggest that the clinical activity of docetaxel in AIPC may be increased by the addition of estramustine or high dose calcitriol. We sought to test the safety of a 3-drug regimen that combined docetaxel with estramustine and calcitriol. Methods: Patients with metastatic AIPC received calcitriol 60 mcg PO over 4 hours (15 mcg hourly for 4 doses) on day 1, dexamethasone 8 mg PO BID on days 1–3, estramustine 280 mg PO TID on days 1–5, and docetaxel 60 mg/m2 (70 mg/m2 starting in cycle 2 if no ≥ grade 3 toxicity during cycle 1) IV over 60 min on day 2. Treatment was repeated every 21 days for up to 12 cycles. Patients received aspirin 325 mg and warfarin 1 or 2 mg PO daily. Calcium supplements were prohibited within 7 days of calcitriol dosing and increased oral hydration on days 1–3 was recommended. A dose de-escalation scheme for calcitriol was planned if dose limiting toxicities were encountered during the first cycle of treatment in > 1/3 of patients. Results: 20 patients were enrolled between January and October 2003. 8 patients were chemotherapy-naïve and 12 had received prior docetaxel-based therapy (5 received more than 1 prior chemotherapy regimen). The regimen was generally well tolerated and criteria for dose de-escalation were not met. Treatment-related ≥ Grade 3 toxicity included: Hypophosphatemia- 4, Neutropenic fever - 2, perforated diverticulum - 1, edema - 1, vomiting - 1, ALT elevation - 1, anemia - 1, PTT elevation –1. 3 patients had thromboembolic complications and one patient had grade 3 hematuria thought to be due to tumor. Hypercalcemia was seen in 4 patients (1 grade 2, 3 grade 1). 17 patients are evaluable for PSA response at this time. 4 of 7 chemotherapy-naïve patients (57%) met criteria for PSA response (confirmed ≥ 50% decline). 1 of 7 patients (14%) treated with 1 prior docetaxel-containing regimen met these criteria. There were no responses among the 3 patients treated with more than 1 prior chemotherapy regimen. Conclusions: High-dose calcitriol may be safely added to docetaxel and estramustine administered on a 21-day schedule. Additional studies will further define the role of this regimen in AIPC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Pharmaceuticals
Memorial Sloan-Kettering Cancer Center program of cancer and aging. Experience of the 65+ Clinical Geriatric Program in the evaluation of older cancer patients
Authors: S. M. Lichtman, M. Boparai, K. Labzda, A. H. Martin, J. Giustino, J. G. Aquino, W. P. Tew, P. Hamlin, L. McEvoy, G. F. Bailey
Journal: Journal of Clinical Oncology (2008)

20728 The aging of the population and the increased incidence of cancer with age have resulted in a marked increase in older cancer patients. In addition to their cancer they have increased comorbidity making treatment decisions and their care more complicated. The older patients are at increased risk to suffer cancer treatment related toxicities. Therefore a coordinated approach is required to optimize care by giving the patients the opportunity to benefit from treatment and at the time minimize suffering from toxicities. The Memorial Sloan-Kettering Cancer Center as part of the Cancer and Aging program has organized the 65+ Clinical Geriatric Group to achieve this goal. The group consists of participants with expertise in geriatrics, finance, nutrition, occupational therapy, music therapy, pharmacy, physical therapy, psychiatry, social work, palliative care, medical and surgical oncology. The group meets on a monthly basis to plan on an ongoing basis the building of an infrastructure for multidisciplinary geriatric oncology care in the institution. A database has been organized to assess the group’s activity and evaluate outcomes. In the 3rd quarter of 2007 there were 1202 patient visits by team members with the majority visits in nutrition (22%), physical therapy (22%), occupational therapy (14%), psychiatry (16%) and social work (16%). In the period Oct-Dec 2007 69 geriatric pharmacy consultations were performed (mean 75.5; median age 76 years; male-55%; female-45%). A comprehensive medication review was conducted which included evaluation of drug compliance, and unnecessary prescription drug evaluation (using Beer’s Criteria). In the same period 305 geriatric nutritional consultations were provided (male-40%; female-60%; 71% over 70 years; 39.8% were overweight/obese based on BMI). The referral pattern for the nutrition consults was: physician referral-32%; referral administration-50%; patient self referral-17.6%. The activity of the group demonstrates that a geriatric evaluation and support program can be conducted in the setting of a Comprehensive Cancer Center. Future activities will include development of institutional guidelines for multidisciplinary geriatric care. No significant financial relationships to disclose.
Efficacy of cabozantinib (Cabo) in medullary thyroid cancer (MTC) patients with RAS or <i>RET</i> mutations: Results from a phase III study.
Authors: Steven I. Sherman, Ezra E.W. Cohen, Patrick Schoffski, Rossella Elisei, Martin Schlumberger, Lori J. Wirth, Milan Mangeshkar, Dana T. Aftab, Douglas O. Clary, Marcia S. Brose
Journal: Journal of Clinical Oncology (2013)

6000 Background: Cabo extends progression-free survival (PFS) in patients (pts) with progressive, metastatic MTC (Schöffski, J Clin Oncol 30, 2012). Mutations in the RET oncogene are associated with most hereditary cases and ~half of sporadic cases of MTC. RAS gene mutations have recently been identified in subsets of RET wild type (wt) cases. Therefore, we investigated the association of RET (a prospectively defined endpoint) and RAS mutations (a post hoc analysis) with efficacy outcomes in the phase 3 study of cabo in MTC. Methods: Pts enrolled into the double-blind, placebo-controlled phase III trial were evaluated for the presence of somatic and germline RET mutations using Sanger and next generation methods. A subset of pts determined to be RET wt (44 pts) or RET unknown (41 pts) were then evaluated for tumor-associated mutations in KRAS, NRAS, and HRAS in codons 12, 13, and 61 by next generation sequencing. Impact of RET and RAS gene mutation status was evaluated with respect to PFS and tumor response rate (RR) according to RECIST. Results: RET status was determined in 65% of the study pts (215/330), of which 79% harbored an activating mutation, and 21% were RET wt. All RET mutational subgroups (RET mutated, RET wt, and RET unknown) showed hazard ratios indicating PFS benefit from cabo treatment, and demonstrated RRs between 22% and 32%. However pts harboring a RET mutation had longer median PFS on cabo (60 wks) than pts with wt RET (25 wks, PFS difference p=0.0001). Also, pts with the poor prognosis mutation RET M918T showed a longer median PFS on cabo treatment (61 wks) than pts with any other RET mutation (36 wks, PFS difference p=0.009). Patients with hereditary MTC had similar PFS to those with sporadic disease, and the presence of the common RET polymorphism G691S had no effect on either PFS or RR. Sixteen of 85 tested pts (5% of total study pts) with wt or unknown RET status were found to harbor a RAS gene mutation. The RAS-mutated pts showed a similar RR (31%) and PFS (47 wks) as RET mutated pts (32% and 60 wks). Conclusions: While hazard ratios indicate PFS improvement for all RET subgroups on cabo, the extent of benefit may depend in part on RET genotype. Cabo treatment benefit is also seen in pts harboring a RAS mutation. Clinical trial information: NCT00704730.
CDC report confirms "Hispanic paradox"
Authors: M. McCarthy
Journal: BMJ (2015)

Despite having lower incomes and less access to health services, Hispanic people in the United States have lower overall mortality rates and a longer life expectancy than white people, a new report by the US Centers for Disease Control and Prevention has found.

The term “Hispanic paradox” is used to describe the projected longer life expectancy (by an estimated two years) and lower overall mortality rate of this ethnic group, “despite potential barriers to good health such as higher rates of being uninsured and worse profiles for some social determinants of health,” the report said.1

The Hispanic population is currently the largest ethnic group in the US, totalling almost 57 million people (or about one in six of the US population). By 2033 the Hispanic population is …
Left Ventricular Hypertrophy With Strain is Associated With Increased Myocardial Injury and Fibrosis in Patients With Aortic Stenosis
Authors: Calvin W. Chin, Mhairi Doris, Anoon S. Shah, Nicholas L. Mills, T'ng-Choong Kwok, Audrey White, Scott Semple, Sanjay Prasad, Marc R. Dweck, David E. Newby
Journal: Circulation (2013)
A phase I trial of the novel oral taxane BMS-275183 in patients with advanced solid tumors
Authors: L. E. Broker, F. Y. De Vos, H. Gall, J. A. Gietema, M. Voi, M. B. Cohen, E. G. De Vries, G. Giaccone
Journal: Journal of Clinical Oncology (2004)

2029 Background: BMS-275183, a novel orally administered taxane, has been studied in this phase I trial to assess its safety, tolerability, pharmacokinetics (PK) and possible anti-tumor activity. Methods: BMS-275183 was given in a continuous, weekly schedule to adult patients (pts) with advanced solid tumors refractory to standard therapy. Plasma samples were collected on weeks 1 and 3 for 48 h after drug administration and analyzed using a LC/MS/MS assay. Results: To date, 31 pts have been treated at escalating dose levels of 5 mg (n=1) and 5 (n=2), 10 (n=1), 20 (n=1), 40 (n=1), 80 (n=1), 160 (n=1) and 320 mg/m2 (n=6), and at subsequent intermediate dose levels of 240 (n=2) and 200 mg/m2(n=15). Most common and dose limiting toxicity (DLT) consists of peripheral neuropathy, which was severe (CTC grade 3) in 1/6 pts at 320 and 2/2 pts at 240 mg/m2, and developed rapidly after the first dose but generally recovered to gr 1 after dose reduction or discontinuation. Severe hematological toxicity was infrequent with gr 3 - 4 neutropenia in 4/31 pts, all treated at doses ≥ 200 mg/m2. At the 200 mg/m2dose level (n=15), 5 DLTs were observed consisting of 3 cases of delayed recovery (> 1 week) from gr 2 neuropathy, 1 gr 4 malaise and 1 gr 3 diarrhea / gr 4 neutropenia. Other side effects included gr 1 - 2 arthralgia, myalgia, anemia, alopecia, gastrointestinal symptoms, fatigue, fever, epistaxis, skin rash and nail changes. PK analysis at the 200 mg/m2dose level (n=15) revealed a rapid uptake with a median Tmax of 1 h and a mean T½ of 20.3 h. The mean AUC is 4595 ng.h/mL with an interpatient variability of 56%. Interestingly, a correlation between the AUC and the severity of the side effects was observed, as most patients with a DLT or dose reduction, had an AUC > 5600 ng.h/mL following the first dose. Seven confirmed partial responses were observed in 23 evaluable pts, all treated at a dose ≥ 160 mg/m2: 4/8 evaluable NSCLC pts (duration 26, 28, 20 and 26+ weeks), 1/3 NSCLC pts with non-measurable disease (16 weeks), 1/1 sarcoma pt (50 weeks) and 1/1 prostate/NSCLC pt (19 weeks). Conclusions: BMS-275183 is a novel oral taxane with promising activity in NSCLC. The recommended dose for future phase II trials currently is 200 mg/m2. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb
Outcome following axillary staging in early breast cancer
Authors: M. R. Kell, J. Burke, M. Morrow
Journal: Journal of Clinical Oncology (2008)

543 Background: Sentinel lymph node biopsy (SLNB) has evolved as the standard of care for early-stage breast cancer. The benefits of SLNB are accurate staging with minimal morbidity when compared to axillary lymph node dissection (ALND). The aim of this study was to systematically appraise the outcome of SLNB when compared to conventional ALND. Methods: A comprehensive search for published trials which examined outcomes after SLNB for invasive breast cancer was performed using medline and cross referencing available data. Reviews of each study were conducted and data were extracted. Fixed and random effects methods were used to combine data. Primary outcomes were nodal positivity and surgery related morbidity. Results: Analysis of 2,659 patients from randomized trials demonstrates that the overall rate of positive axillary lymph nodes for those with clinically negative nodes was 27.1% for ALND and 30.9 % for SLNB (RR 1.09, CI 0.94–1.27, P>0.05). Patients who undergo SLNB are significantly less likely to suffer postoperative morbidity (RR 0.415, 95% CI= 0.28–0.62, p<0.05). The risk of postoperative wound infection (RR 0.61, 95% CI= 0.45–0.82, P=0.0011) and seroma (RR 0.5, 95% CI=0.35- 0.7, p<0.0001) are reduced in patients undergoing SLNB relative to ALND. The risk of arm swelling (RR 0.29, 95% CI= 0.21–0.39, P<0.0001) and paresthesia (RR 0.47, 95% CI=0.41–0.54, p<0.0001) at 6 months are also reduced in those undergoing SLNB. Conclusions: This meta-analysis confirms that SLNB is the optimum approach in terms of morbidity for the assessment of axillary metastasis in early, clinically node-negative breast cancer. These results confirm that SLNB is at least as good as ALND in detecting metastatic disease. No significant financial relationships to disclose.