tbuckley/cabot-search huggingface dataset:
Adjuvant trastuzumab for breast cancer outside of clinical trials: Cardiotoxicity and economic evaluation
Authors: S. Snow, C. Skedgel, D. Rayson, K. Thompson, M. Sellon, P. Barnes, A. Jeyakumar, T. Younis
Journal: Journal of Clinical Oncology (2009)

6585 Background: Clinical and economic evaluations of adjuvant trastuzumab (aTZ) in breast cancer (BC) are based on clinical trial outcomes. Population based studies however provide unique opportunities to examine outcomes in a real world setting. We previously examined aTZ uptake in all patients diagnosed with stage I-III BC over one year in Nova Scotia, Canada (Snow et al SABCS 2007). We now report cardiotoxic events (CE) and an economic evaluation based on our previous cohort. Methods: A retrospective chart review of all patients treated with aTZ was conducted to abstract clinical-pathological characteristics, treatment details, CEs/significant LVEF declines, and associated medical resource utilization (MRU). Cardiac risk scores (CRS) (Rastogi et al ASCO 2007) were also computed for all patients. Biserial correlation was performed to detect differences in CRS scores among subgroups. Costs associated with aTZ were based on MRU; unit costs were derived from the literature and local resources. A probabilistic model (Skedgel et al ASCO 2008) was utilized to examine the cost per quality adjusted life year gained (QALYG) at a 25-year horizon with budget impact calculated in 2009 Cdn $. Results: Of a total population of 630 patients with stage I-III BC, 37 (5.9%) received aTZ as per HERA trial treatment schedule; two (5.4%) had a CE (one death) and five (13.5%) experienced significant LVEF decline. CEs and LVEF declines were higher in patients with baseline LVEF 50–55% vs. &gt; 55% (10% vs. 4% and 20% vs. 11%, respectively). CRS accurately predicted the observed CE rate, and was also predictive of significant LVEF decline (p = 0.056). Compared to previous estimates, the mean cost per patient of $46,070 (95%CI: $38,541-$54,422) was lower and the cost-utility of $60,439/QALYG was more favourable. Based on the observed aTZ utilization rate, a budget impact of $59.9m (95%CI: 42.5 m-79.9 m) for 2009 in Canada is expected. Conclusions: CEs and significant LVEF declines in this population based cohort appear comparable to that reported in clinical trials. Based on the aTZ costs per patient in this study, the cost-utility of aTZ is more favourable than previous estimates although the associated budget impact remains substantial. No significant financial relationships to disclose.
Osteonecrosis of the jaw incidence and contributing risk factors in cancer patients treated with IV bisphosphonates: A Veterans Administration Healthcare study
Authors: L. C. Dickerson, N. Desai, E. Walden, M. Chang, Y. Jiang, T. J. George
Journal: Journal of Clinical Oncology (2008)

20511 Background: Intravenous bisphosphonates (IVB) can improve complications of bone metastases, but are associated with osteonecrosis of the jaw (ONJ). The incidence is speculated to be 3–13% with a variety of risk factors proposed. This study was designed to establish ONJ incidence (primary aim) and associated risk factors (secondary aim) in cancer patients treated with IVB. Methods: All cancer patients receiving at least one dose of IVB between January 1, 2001 and December 31, 2005 were eligible. ONJ was defined by high clinical suspicion and/or confirmatory radiography or jaw bone biopsy. Odds ratio (OR) were calculated using Fisher’s exact test. Spearman’s correlation coefficients (rs) were calculated by the Wilcoxon rank sum test. The distribution of time to ONJ development was estimated by the Kaplan-Meier method. Results: 260 of 263 eligible consecutive patients were available for analysis. Tumor types were diverse. Median age was 67 (range 41–94) and the majority were men. Median IVB dose per patient was 2 (range 1–80) with 69 receiving pamidronate, 152 zoledronic acid, and 39 receiving both during therapy. The overall incidence of ONJ was 4.2% (11/260). Patients with ONJ received more doses (median 22 vs 2;rs=0.23;p=0.0003) and had a longer duration of IVB treatment (median 805 vs 92 days;rs=0.26;p<0.0001) compared to those without ONJ. There was no difference between pamidronate or zoledronic acid (incidence 2.9% vs 2.6%;p=NS), but exposure to both agents increased the incidence (12.8%;p=0.03). IVB treatment beyond 24 months was associated with a significantly higher incidence (16.7% vs 2.2%;OR=7.85;p=0.002). ONJ development was also associated with dental trauma (OR=47.9;p<0.0001), but not with the use of chemotherapy (1.62;p=0.75), radiotherapy (0.85;p=0.77), hormonal therapy (1.23;p=0.75), corticosteroids (0.85;p=0.77), statins (0.29;p=0.13), or thrombophilia (2.02;p=0.39). Conclusions: ONJ is a rare, but serious complication of IVB use. Major risk factors for development include prolonged IVB treatment and dental trauma. Our findings support ASCO guideline recommendations to limit IVB therapy to 24 months. Further studies are needed to predict individual patient risk for ONJ. No significant financial relationships to disclose.
A randomised trial of radical radiotherapy in pT1G3 NXM0 bladder cancer (MRC BS06)
Authors: S. J. Harland
Journal: Journal of Clinical Oncology (2005)

4505 Background: It has been estimated that 10–20% of patients who present with superficial bladder cancer will go on to develop muscle-invasive disease which is usually fatal. Previous studies have shown that up to 50% of patients with pT1G3 at presentation develop progressive disease. The problem of knowing how best to manage these bladder tumours remains of real interest. Hitherto there has been no randomised trials to guide management of pT1G3 tumours. The primary aim of this trial was to determine the efficacy of radical radiotherapy in reducing the incidence of progression of pT1G3 transitional cell carcinoma of the bladder to muscle-invasive disease and subsequent disease fatality. Methods: Eligible patients were those with a recent diagnosis (within 6 months) of pT1G3 NXMO tumours; complete transurethral resection; no clinical, radiological or biochemical evidence of distant metastases; no prior therapy with intravesical chemotherapy or BCG; and a WHO performance status of 0–2. Patients with single tumours were randomised between surveillance cystoscopy and radiotherapy and patients with multiple tumours (or associated CIS) were randomised between radiotherapy and intravesical therapy (either Mitomycin C or BCG - clinician’s choice). The trial was designed to recruit 200 patients (and observe 52 events) so as to reliably detect a decrease in the 5-year progression rate (the primary endpoint) from 40% to 20% (80% power, 5% significance level). Results: A total of 210 patients have been randomised between September 1991 and February 2003. 178 patients (85%) were male, 159 (76%) had a WHO performance status of 0 and 91 (43%) were over the age of 70. 77 patients (38%) had a single tumour and no CIS and 133 patients (65%) had either multiple tumours or CIS. A total of 62 events (progression or death from disease or treatment) have been observed across the two arms of the trial in the 204 eligible patients (control versus radiotherapy). This results in a hazard ratio of 1.16 (0.70,1,92), p=0.552, in favour of the control group. Conclusions: This data suggests that radiotherapy does not reduce or delay progression or death in pT1G3 bladder cancer. No significant financial relationships to disclose.
Role of 18F-fluorodeoxyglucose positron emission tomography in mucocutaneous malignant melanoma
Authors: M. Santisteban, A. Viudez, E. Salgado, C. Garrán, V. Navarro, J. De La Cámara, O. Fernández-Hidalgo, M. J. García-Velloso, S. Martín-Algarra
Journal: Journal of Clinical Oncology (2004)

7535 Background: 18F-Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET) has been reported to be a sensitive method for detecting mucocutaneous malignant melanoma (MM) metastases. The aim of this study is to analyse retrospectively the role of 18FDG-PET to stage, re-stage and follow-up of MM patients. Methods: Two hundred and ninety-six patients (135 men and 161 women) with MM were evaluated with 18FDG-PET from June 1996 to June 2002. Median age was 46 years (range:12–87). Location of primary MM was: extremities in 54%, trunk in 29%, head and neck in 11%, unknown origin in 4% and mucosas in 2% of the patients. Median Breslow thickness was 2 mm (range:0.2–20). According to the AJCC staging system, the distribution in stages I,II,III and IV at first diagnosis was 39%, 42%, 17% and 2% respectively. The role of PET was staging in 157 (53%) patients, re-staging in 54 (18%) patients and follow-up in 85 (29%) patients. Results: The sensitivity (S), specificity (E), accuracy (A), positive and negative predictive value (PPV and NPV) for detecting regional lymph nodes and metastatic disease by PET are showed in Table 1. Conclusions: 18FDG-PET is a reliable diagnosis technique for staging and restaging patients with MM. Follow-up should be done with clinical examination, biochemistry and conventional imaging studies because PET scanning in follow-up has a higher false positive rate. No significant financial relationships to disclose.
Comparison of chemoradiotherapy (CRT) and chemotherapy (CT) in patients with a locally advanced pancreatic cancer (LAPC) controlled after 4 months of gemcitabine with or without erlotinib: Final results of the international phase III LAP 07 study.
Authors: Pascal Hammel, Florence Huguet, Jean-Luc Van Laethem, David Goldstein, Bengt Glimelius, Pascal Artru, Ivan Borbath, Olivier Bouche, Jenny Shannon, Thierry André, Laurent Mineur, Benoist Chibaudel, Franck Bonnetain, Christophe Louvet
Journal: Journal of Clinical Oncology (2013)

LBA4003 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June, 3, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Nsclc Patients with Brain Metastases Treated with Platinum-Based Doublets As First-Line Therapy: Analyses from the European Frame Observational Study
Authors: D. Moro-Sibilot, E.F. Smit, J.Castro De Carpeño, K. Lesniewski-Kmak, J.G. Aerts, R. Villatoro, K. Kraaij, K. Nacerddine, Y. Dyachkova, K. Smith, A. Girvan, C.M. Visseren-Grul, P.A. Schnabel
Journal: Annals of Oncology (2014)
The effect of hospital racial composition on obtaining surgery for non-metastatic small cell lung cancer (NSCLC)
Authors: C. S. Lathan, B. A. Neville, C. C. Earle
Journal: Journal of Clinical Oncology (2005)

6019 Background: We sought to assess the relationship between the percentage of Black patients at a hospital and the likelihood of obtaining cancer-directed surgery for Black and White patients with NSCLC. Methods: We examined claims data of Medicare-eligible patients with non-metastatic NSCLC living in areas monitored by the Surveillance, Epidemiology, and End Results (SEER) program between 1991–2001. Hospitals were categorized by the percentage of Black patients seen: <8%, 8–25% and >25%. Logistic regression was used to calculate the odds of having surgical resection. Results: Among 18,720 patients with NSCLC, 80% of White patients were seen at a hospital that had <8% Black patients, while 56% of Black patients were seen in hospitals that had >25% Black patients. In hospitals where Black patients were <8%, 50% of White patients obtained surgery vs. 41% of Black patients (p=0.001) In hospitals where Black patients were 8–25% of total patients, 49% of White patients had surgery vs. 36% of Black patients (p<0.001). Where Black patients were >25% of patients, White patients had lung cancer-directed surgery 48% of the time vs. 31% for Blacks (p<0.001). Multivariate logistic regression analysis revealed that racial composition of the hospital significantly predicted the likelihood of receiving surgery for Black patients (Odds Ratio (OR) 0.71 in a hospital with >25% Black patients, 95% Confidence Interval (CI) 0.52–0.96), but not for White patients. Conclusions: Black and White patients are generally treated at different hospitals. Hospitals that treat a larger number of Black patients are less likely to provide surgery to Black patients with non-metastatic NSCLC, but equally likely to perform surgery on White patients. These findings suggest that the racial segregation of medial care is likely a factor in the observed racial differences in lung cancer treatment and outcomes, but it doesn’t explain all of the disparity. Further examination of the role of hospital along with provider and patient attitudinal determinants is needed. No significant financial relationships to disclose.
Phase I trial of neoadjuvant dasatinib in patients with resectable malignant pleural mesothelioma
Authors: R. Mehran, J. Gil, D. Rice, S. Swisher, J. J. Lee, S. Lippman, K. Pisters, G. Blumenschein, W. K. Hong, A. S. Tsao
Journal: Journal of Clinical Oncology (2009)

7580 Background: The optimal multi-modality treatment for resectable malignant pleural mesothelioma (MPM) remains unknown. We designed a biomarker-based neoadjuvant trial from our preclinical studies showing that dasatinib, a multi-targeted Src kinase inhibitor, has activity against MPM and target specificity to Src Tyr419. Methods: Untreated MPM patients underwent extended surgical staging (ESS) with multiple biopsies to account for tumor heterogeneity, lymph node status and to rule out sarcomatoid features. If deemed a surgical candidate for either pleurectomy/decortication (P/D) or extrapleural pneumonectomy (EPP), patients received 4 weeks of oral dasatinib (70 mg BID) followed by P/D or EPP. If either a radiographic or molecular response (de-phosphorylation of Src Tyr419 in tumor) is achieved, an additional 2 years of dasatinib maintenance after adjuvant radiotherapy and systemic chemotherapy is given. The primary endpoint of this trial was biomarker modulation of Src Tyr419. Secondary endpoints included response, survival, safety/toxicity, and biomarker modulation in tumor/serum/platelets/pleural effusion. The total planned sample size is 24 to detect a 50% reduction in positive p-Src Tyr419 expression with 80% power, one-sided 10% type I error rate, and 10% inevaluable rate. Results: To date, ten patients have registered on the trial (4/08 - 12/08); six have successfully completed the ESS, neoadjuvant dasatinib, and P/D (n=3) or EPP (n=3). Two patients are still receiving neoadjuvant dasatinib; and 2 patients were deemed to not be surgical candidates due to a rapid decline in PS and one was found to have bilateral mesothelioma. The main side effects to dasatinib were grade 1–2: anemia, nausea, vomiting, anorexia, electrolyte abnormalities, fatigue, and anxiety. Grade 3 toxicities included hyperkalemia (1), infection - pneumonia (1), and hypoxia (1). There were no grade 4–5 toxicities. Post-surgical grade 3 toxicity included anemia, electrolyte abnormalities, arrhythmia, HTN, and pleural effusion; one grade 4 episode of hyperglycemia was seen. Conclusions: This study demonstrates that biomarker-based neoadjuvant MPM trials with novel agents are feasible. Updated clinical and translational correlative results will be presented. No significant financial relationships to disclose.
Venous thrombosis in breast cancer patients receiving tamoxifen and/or chemotherapy: A systematic review
Authors: L. K. Hicks, M. C. Cheung, M. Crump
Journal: Journal of Clinical Oncology (2004)

6145 Background: The association between breast cancer and venous thromboembolism (VTE) is well established. It is also generally accepted that antineoplastic therapy contributes to VTE-risk. However, the contribution of specific treatments has not been precisely determined. Methods: We systematically reviewed the literature on the association between VTE and chemohormonal therapy for breast cancer. Two authors independently selected articles from the PUBMED database. Inclusion criteria were studies of (1) breast cancer patients, (2) antineoplastic therapy, (3) VTE as a primary outcome, and (4) English language. Exclusion criteria were studies with (1) a sample size of less than 20, or (2) no control group. A grading scale for article quality was developed with guidance from Levine M et al, JAMA: 271(20), 1994. Two investigators independently graded all eligible reports. Results: The search strategy yielded 460 articles. Eight articles met all inclusion and exclusion criteria. The kappa statistic for article selection revealed excellent agreement between the two abstractors (K=0.87). Three studies addressed the association of adjuvant tamoxifen with VTE, 3 addressed the association of combined tamoxifen and chemotherapy with VTE, and 2 addressed the association of chemotherapy alone with VTE. The studies were heterogeneous with respect to design and quality. Seven studies reported a positive association between tamoxifen and/or chemotherapy and VTE. No studies achieved the highest possible quality score on our scale. No studies reported that their experimental and control arms were balanced with respect to major VTE risk factors. Only 2 studies ensured that the diagnosis of VTE was objectively determined in all cases. Conclusions: Current data suggests that both chemotherapy and tamoxifen contribute to the risk of VTE in breast cancer patients. However, there are few studies investigating VTE as a primary endpoint in breast cancer treatment. Moreover, the quality of existing studies is not high. To determine how much breast cancer treatment contributes to VTE-risk additional trials with VTE as a pre-specified, primary outcome are required. No significant financial relationships to disclose.
Induction of immune responses and clinical activity in a phase II trial of IDM-2101, a 10-epitope CTL vaccine, in metastatic NSCLC patients
Authors: M. Barve, J. Bender, B. Pappen, G. Ishioka, M. A. Morse, F. A. Greco, D. McCune, R. Steis, H. Khong, J. J. Nemunaitis
Journal: Journal of Clinical Oncology (2008)

8057 Background: IDM-2101 is a 10-peptide vaccine designed to induce multi-specific CTL responses against MHC class I epitopes of CEA, p53, HER-2/neu and MAGE 2/3. Seven epitopes are modified for enhanced MHC binding or heteroclitic T-cell activation and 2 epitopes are native wild-type (WT) sequences. Also included is the class II helper epitope PADRE. We report here immune responses and clinical activity from a Phase 2 trial of IDM-2101. Methods: 68 HLA-A2+ good performance patients (pts) with Stage IIIB/IV or recurrent NSCLC were enrolled. Patients were required to have a tumor volume <125 cm2. Pts received 6 induction doses (0.5 mg/epitope) q3 wks followed by maintenance treatments at 2–3 month intervals. 63 pts were treated with one or more doses. 72 HLA-A2 negative pts who were otherwise eligible were retrospectively selected as relevant controls. Endpoints included survival, clinical responses and induction of immune responses. CTL responses in peripheral blood MNC were measured, at predefined time points, after a 10 day in vitro stimulation with peptide followed by an IFNγ ELISPOT assay. Results: 30 of 33 available pts (91%) that were monitored for CTL showed positive responses to 1 or more epitopes and 21 of 33 pts (64%) responded to at least 3 epitopes. All 9 vaccine epitopes were immunogenic in at least 1 patient. CTL responses were detected in 3 of 4 pts tested at 12 months. T helper-cell responses against PADRE measured with a direct IFNγ ELISPOT assay were observed in 18 of the 33 pts (55%) tested. Toxicities attributable to vaccine were mild and consisted mostly of injection site reactions. Clinical responses included 1 CR, 1 PR and SD of ≥3 months in 54 of 63 pts (86%). 14 pts completed 2 years of dosing and remain without evidence of progression. Interim analysis of one-year survival in IDM-2101 treated pts was 60%, compared to 49% in the HLA-A2 negative group and median survival for treated pts was 17.3 months compared to 12.0 months for pts in the HLA-A2 negative group. A trend toward longer survival was observed in pts who responded to more epitopes. Conclusions: IDM-2101 was well- tolerated, induced broadly-specific CTL responses and may provide a survival benefit in metastatic NSCLC patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration IDM Pharma, Inc, Pharmexa-Epimmune
Incidence and initial characterization of circulating tumor cells in different cancer entities.
Authors: Z. Liu, A. Fusi, I. Tinhofer, A. H. Schmittel, U. Keilholz
Journal: Journal of Clinical Oncology (2010)

e21083 Background: Circulating tumor cell (CTC) quantification has been approved for monitoring of blood from metastatic breast, colon and prostatic cancer patients. In other cancers little is known about the presence of CTCs. CTCs might represent a potential alternative to invasive biopsies and assessment of their receptor profile may be helpful in planning and monitoring treatment strategies. This study was undertaken to investigate prevalence and characteristics of CTCs in a variety of solid tumors. Methods: After informed consent, fifty consecutive 20 mL-peripheral blood samples were collected from 38 patients with different metastatic epithelial cancers (n = 30) or metastatic melanoma (n = 8). After lysis of erythrocytes, cells were enriched for tumor cells by CD45 depletion. Cells were stained for CD45 to exclude leukocytes from the analysis and for the epithelial markers EpCAM and Cytokeratin 7, 8 or the melanoma marker HMW-MAA/MCSP, respectively. In 16 samples from patients affected by epithelial cancers a co-staining for EGFR was carried out. Control tubes including appropriate isotypic controls were added. Cells were analysed on a FACSCanto II. CTCs were defined EpCAM+Cytokeratin+CD45- in case of epithelial cancers or as HMW-MAA/MCSP+CD45- in case of melanoma. Results: In blood from patients with epithelial cancers CTCs were detected in 20/40 samples (50%). The absolute number of CTCs ranged from 2 to 37 (median 3) per 10 mL of blood. Besides breast cancer (5/9) and colon cancer (3/11) samples, CTCs were also detected in ovarian (4/8), cervix (2/4), head and neck (3/3), gastric (2/3) and non-small cell lung cancer (1/2) samples. In ten out of 16 samples (62.5%) CTCs were positive for EGFR (4 breast cancer, 2 head and neck, 2 ovarian, 1 gastric and 1 cervix cancer sample). In blood from melanoma patients CTCs were detected in 6/10 samples (60%). The absolute number of CTCs ranged from 5 to 551 (median 19) per 10 mL of blood. Conclusions: CTCs can often be detected in blood from patients with metastatic epithelial cancer or melanoma. CTCs were more abundant in melanoma compared to epithelial cancers. Phenotypic characterization identified EGFR as potential target to eradicate the EGFR-positive pool of CTCs. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Serono Merck Serono Merck Serono
Guide to Medical Informatics, the Internet and Telemedicine, by Enrico Coiera Cybermedicine, by Warner Slack
Authors: P. Taylor
Journal: BMJ (1998)

Enrico Coiera Chapman and Hall Medical, £29.99, pp 376 ISBN 0 412 75710 9

Warner Slack Jossey-Bass Publishers, £15.95, pp 214 ISBN 0 7879 0343 4

In his Guide to Medical Informatics, the Internet and Telemedicine Enrico Coiera defines medical informatics as “the rational study of the way we think about patients, and the way that treatments are defined, selected and evolved. It is the study of how medical knowledge is created, shaped, shared and applied.” This definition is a great deal broader than just “computers in medicine,” and the vision implicit in Coiera's book is not merely of medical practice improved and assisted by computerised systems but of health care thoroughly transformed through the adoption of rational procedures. Importantly, these procedures are not necessarily the consequences of new technology but of …