tbuckley/cabot-search huggingface dataset:
DNA Image cytometry as a prognostic tool in stage II and stage III colorectal cancer
Authors: A. Buhmeida, A. Ålgars, R. Ristamäki, Y. Collan, K. Syrjänen, S. Pyrhönen
Journal: Journal of Clinical Oncology (2006)

13565 Background: We assessed the prognostic value of nuclear DNA content measured in the primary tumors of 123 patients with stage II or stage III colorectal cancer (CRC). Methods: Isolated nuclei from paraffin sections were stained with Feulgen and DNA was measured using a computer-assisted image analysis cytometry system (Ahrens ACAS). We applied 4 different approaches in analysis of DNA histograms: ABCDE approach, histogram range, peak evaluation, and DNA cut-off values. Results: Using the histogram range, narrow range was rare (3.7%) in patients who died of disease as compared with 16.4% among those alive (p=0.017). Modal peak evaluation was a significant predictor of disease free survival (DFS) (Kaplan-Meier log-rank p=0.0235). In the range evaluation, the first set (low-start gates) was a significant predictor of DFS (log-rank p=0.0121), where disease recurrence was closely associated the widest range (1.8c-&gt;10c) gates. Recurrence-free survival was markedly better among patients with narrow gate histograms than wide range histograms than among patients with wide range histograms (p&lt;0.03). The first set also proved to be significant predictor of disease specific survival (DSS) (log-rank p=0.0045), being markedly better (78–90.0%) among the patients with the narrow-gate histograms. Grading of the histogram range into two categories (with 6.0c as cut-off for low and wide range), was a powerful predictor of both DSS (log-rank p= 0.0092) and 5-year DFS (p=0.0106) in the whole series, and separately in Stage III (but not Stage II) disease; p=0.0131 and p=0.0201, respectively. Conclusions: The DNA image cytometry with careful analysis of the histograms may provide valuable prognostic information in CRC, with potential clinical implications in patient management, particularly in predicting the patients at high risk for recurrence who should be considered as candidates for adjuvant therapy. No significant financial relationships to disclose.
Combined EGFR targeted therapy in a novel in vivo pancreas cancer model
Authors: A. Jimeno, A. Chan, B. Rubio-Viqueira, X. Zhang, G. Cusatis, J. Wheelhouse, M. Varella-Garcia, F. R. Hirsch, P. Kulesza, M. Hidalgo
Journal: Journal of Clinical Oncology (2007)

14063 Background: EGFR inhibitors have a definite but limited activity in pancreatic cancer (PaCa). We have reported enhanced activity of dual EGFR therapy with a small molecule inhibitor (erlotinib) plus a monoclonal antibody (cetuximab) in head and neck cancer models. Human xenografted tumors recapitulate better the pathobiology of cancer than existing cell lines. Here we explored a dual EGFR targeting approach using a direct PaCa xenograft model, and sought after markers predicting efficacy. Methods: PaCa specimens obtained at the time surgery were implanted in nude mice and expanded to develop cohorts of tumor bearing mice suitable for drug evaluation. Ten cases were expanded, and within each case 4 groups of 6–8 mice each were treated with vehicle, erlotinib, cetuximab, and the combination of both for 28 days. Gene mutation analysis, gene amplification by fluorescence-in-situ hybridization, and immunohistochemistry (IHC) were done with untreated samples. Results: Two cases were sensitive to both single agents, but the combination did not induce higher efficacy in those. Two additional cases that were resistant to both single agents became sensitive with the combination. No egfr mutations were detected. Three and four cases carried low and high egfr polysomy (defined as [[Unsupported Character - ]] 4 copies in 10–40% and [[Unsupported Character - ]] 40% of the cells, respectively). No correlation was found between egfr copy number and efficacy. By IHC sensitive cases had a lower Ki67 proliferation index, and higher EGFR and nuclear pMAPK staining than resistant cases. The degree of Ki67 decrease after therapy correlated with efficacy. In cases resistant to the single agents but sensitive to the combination nuclear pMAPK only decreased with the dual targeting. Cases with high egfr polysomy were more labile to pharmacodynamic effects after treatment (such as EGFR or pMAPK decreases). Conclusions: EGFR inhibitors showed modest single agent antitumor effect that was enhanced with dual EGFR therapy in PaCa. No genomic markers predicted efficacy, although high egfr polysomy was associated with deeper pharmacodynamic inhibition, conceivably suggesting a phenomenon of pathway addiction. Higher pathway activation by IHC was linked with higher activity. No significant financial relationships to disclose.
Radiation Therapy Modalities in Prostate Cancer
Authors: Thomas J. Pugh, Bao-Ngoc Nguyen, James E. Kanke, Jennifer L. Johnson, Karen E. Hoffman
Journal: Journal of the National Comprehensive Cancer Network (2013)

Definitive radiation therapy is the preferred treatment for many men with prostate cancer. Several modalities are used for radiation treatment delivery, including 3-dimensional conformal radiation therapy, intensity-modulated radiation therapy, proton beam therapy, stereotactic body radiation therapy, high-dose-rate prostate brachytherapy, and low-dose-rate prostate brachytherapy. This article reviews technologic advances that have enhanced radiation delivery and describes contemporary radiation treatment techniques for prostate cancer.
Induction chemotherapy with S-1 plus cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN)
Authors: J. Chung, Y. Choi, H. Shin, G. Choi, W. Lee, Y. Joo, C. Shon
Journal: Journal of Clinical Oncology (2006)

15501 Background: This study was to assess the efficacy and safety profiles of the combination treatment with S-1 and Cisplatin in patients with locally advanced SCCHN. Methods: Eligible patients were defined as histologically confirmed SCCHN, stage III or IV with no evidence of distant metastasis, evaluable lesions, adequate organ function, age of 20–80 years, and performance status 0,1 or 2. Cisplatin was infused over 1 hour on day 1 (75 mg/m 2 ) and S-1 was administered orally for 14 consecutive days (day 2–15). The dosages of S-1 were assigned according to the patients’ body surface area (BSA): 50 mg twice a day (BSA &lt; 1.5m 2 ), 60 mg twice a day (BSA &gt; 1.5m 2 ). Each course was repeated every 3 weeks. After 2 course, tumor response were evaluated by CT scan and laryngoscopy. If the patients achieved a response (complete response: CR, or partial response: PR), they received one more course of chemotherapy before undergoing the radiotherapy or operation as a definitive local treatment. Results: All 22 patients were assessable for response and toxicity. The overall response was 80.9% (CR: 3, PR: 14). The adverse reactions occurred 120 times in 54 courses of 22 cases. The most common grade 3/4 adverse events were neutropenia, which occurred in 8 patients. Non-hematological toxicity of grade 3 and 4 included nausea and vomiting in 4 patients, fever in one patient and, fatigue in one patient. Since the observation period is short, the analysis about survival rate is not obtained so far. Conclusions: S-1 plus Cisplatin combination chemotherapy is effective against locally advanced SCCHN with mild toxicity. No significant financial relationships to disclose.
Influence of independent review committees (IRC) on assessment of response rate and progression free survival in phase III clinical trials
Authors: E. X. Chen, G. R. Pond, P. Tang
Journal: Journal of Clinical Oncology (2008)

6567 Background: Determination of the effectiveness of anti-cancer therapy often depends on accurate assessment of changes in sizes of tumoral lesions. Investigators (INV) could potentially be biased in their assessment. Our objective was to determine the influence of IRC on assessment of response rate (RR) and progression free survival (PFS) in phase III clinical trials (RCTs). Methods: RCTs evaluating systemic therapy for advanced solid malignancies were identified through a systemic search of Medline from January 1995 to January 2007 and ASCO meeting abstracts from 2004 to 2007. Studies were included if both INV and IRC determined RR and/or PFS were reported and each arm of a study enrolled ≥ 100 patients. Results: Nineteen trials were included in the analysis: 16 reported RR and 8 reported PFS. The median trial size was 602 patients. The mean INV determined RR was 4.59% higher than that of IRC (95% CI 2.75% - 6.44%), as calculated across all 32 trial arms. In 12/16 trials, INV overestimated RR in both experimental and control trial arms. IRC determined RR was higher in both arms in only 1 trial. For median PFS, the estimated mean difference, was 0.19 months (95% CI 0.63 - 0.24) months in favor of INV assessment. There was a significant difference in INV determined RR in 3/16 trials, and PFS in 1/8 trials that was not apparent in IRC assessment. Conclusions: Investigators overestimate RR and PFS compared to IRC in RCTs. This overestimation could lead to the erroneous conclusion of significant treatment effects. An IRC should be utilized in RCTs in advanced solid malignancies if the primary endpoint requires assessment of changes in sizes of tumoral lesions. Both INV and IRC assessments should be included in publications. No significant financial relationships to disclose.
Retrospective analysis of pathologic response in colorectal cancer liver-only metastases following treatment with bevacizumab.
Authors: Ruth Vera, Joan Figueras, Maria Luisa Gomez Dorronsoro, S. Lopez-Ben, Antonio Viúdez, Bernardo Queralt, Irene Hernandez, R. Scalzone, Cruz Zazpe, R. Ortiz
Journal: Journal of Clinical Oncology (2012)

674 Background: Recent reports have shown that pathological response predicts for better outcome (overall survival) following preoperative chemotherapy and surgical resection of colorectal cancer (CRC) liver-only metastases. The aim of this retrospective analysis was to evaluate the effect of adding bevacizumab to standard chemotherapy on pathological response in patients with CRC liver only metastases. Methods: Patients with stage IV CRC with liver metastases who received neoadjuvant chemotherapy (oxaliplatin-or irinotecan-based) at two Spanish centres were analysed retrospectively. Pathological response was evaluated as follows: complete pathological response (cPR), PR1 (25% of residual tumour), PR2 (25–50% of residual tumour), PR3 (&gt;50% of residual tumour). cPR or PR1 was considered to be a good response, and PR2 or PR3 a poor response. Results: A total of 81 patients were evaluated. Of these, 43 received chemotherapy alone and 38 received chemotherapy plus bevacizumab. Baseline characteristics were as follows: median age 61.0 years (range 43.0–80.0 years); male/female (67%/33%); tumour location – colon (69%) / rectum (31%); hepatic metastases – synchronous (74%) / metachronous (26%); In terms of pathological response, 58% of patients receiving bevacizumab had a good response (cPR + PR1) compared with 28% of those receiving chemotherapy alone. At the end of the analysis, 68% of patients were still alive. Conclusions: Adding bevacizumab to oxaliplatin-based chemotherapy in the neoadjuvant setting improves the pathological response of liver metastases in patients with stage IV CRC. These findings indicate that pathological response might be a good indicator of outcome for patients receiving bevacizumab in the neoadjuvant setting.
The yield of peripheral blood stem cells (PBSC) in hematological or solid tumour patients treated with high dose chemotherapy and hemopoietic growth factors
Authors: A. M. Liberati, M. Schippa, V. Festuccia, M. Albanesi, P. Ferrara, M. Gunnellini, V. Di Loreto, R. Pace, D. Siepi, L. Falchi
Journal: Journal of Clinical Oncology (2008)

22220 Background: Factors potentially relevant in the yield of PBSC (CFU-GM and CD34+ cells) were evaluated in solid tumors (breast cancer 45, other than breast cancer 9), multiple myeloma (MM 75), clinically indolent or aggressive non-Hodgkin lymphoma (I-NHL 20, A- NHL 84) or classical Hodgkin lymphoma (HL, 38) patients. Methods: These factors were divided into host (age, disease histology and stage), therapeutic history before mobilization (mobilizing therapy during first or salvage treatment, number of cycles and of drugs used and exposure to alkylating agents or radiotherapy) and mobilizing program-related (type of mobilizing chemotherapy and type and dose of hemopoietic growth factor). Intermediate-dose chemotherapy consisted of 3–4g/m2 cyclophosphamide (CTX) or 800mg/m2 carboplatin (CBDCA) or 8mg/m2 mithoxantrone, 3g/m2 cytarabine and 8mg/m2 dexamethasone days 1–2 (miniMAD) or 100mg/m2 cisplatinum day 1, 4g/m2 cytarabine day 2, 40mg dexamethasone days 1–4 (DHAP) or 120mg/m2 epirubicin. The combination of 8 mg/m2 mithoxantrone, 4 g/m2 cytarabine and 8 mg/m2 dexamethasone days 1–3 (MAD) or 7 g/m2 CTX or ifosfamide 4g/m2 were defined as high- dose chemotherapy. Results: Linear regression analysis indicated that recovery of CFU-GM/Kg and CD34+cells/Kg was affected by disease type (decreasing from solid tumors to I-NHL) and amount of chemotherapy expressed as number of drugs or chemotherapy cycles given before mobilization. However, the CFU-GM/Kg cells yield, but not that of CD34+ cells/Kg was higher when G-CSF rather than GM-CSF was employed. The number of CD34+ cells/Kg recovered was significantly superior in pts in complete remission at the time of mobilization and in those not previously exposed to radiation therapy. The mobilizing scheme employed affected the CFU-GM/CD34+ cell ratio indicating that large numbers of more immature precursors were obtained when 7g/CTX or MAD were employed. Conclusions: The yield of PBSC was mainly related to patient history, previous exposure to chemotherapy, state of disease at mobilization and mobilization scheme. No significant financial relationships to disclose.
Cancer patient (CP), health care professional (HCP), and layperson priorities between survival time (ST) and quality of life (QOL).
Authors: E. D. Saad, G. N. Marta, L. G. Del Nero, G. N. Marta, A. Mangabeira, G. Critchi, J. L. F. da Silva, P. M. Hoff
Journal: Journal of Clinical Oncology (2011)

e19524 Background: Relatively little is known about societal priorities regarding treatment goals in medical oncology, and the choice between prioritizing ST or QOL might depend on having been diagnosed with cancer. Based on our clinical experience, we hypothesized that prioritizing ST would be more frequent, and QOL less frequent, among CP than in controls. Methods: We used a questionnaire with four case vignettes to interview CPs and two control groups chosen at our hospital: (1) HCPs working at the Oncology Department, and (2) laypersons, most of whom with administrative functions and no recent cancer cases in the close family. After informed consent, the questionnaire addressed issues regarding treatment choices and priorities, asking participants about what they felt appropriate for the fictitious cases. Results: A total of 214 individuals participated: 101 CPs, 44 HCPs, and 69 laypersons. Mean ages in the three groups were 56, 34, and 31 years, respectively. CPs had gastrointestinal (25%), breast (22%), hematologic (10%), lung (8%), and other tumors (36%), and TNM stages were I/II/III/IV in 22/13/34/31%, respectively. The table displays treatment priorities in the three groups for a fictitious patient with cancer (p=0.005). In the CP group, no significant differences in priorities were found between TNM stages I to III versus IV patients. Results for other issues of the questionnaire and further exploratory analysis will be presented. Conclusions: Both ST and QOL appear important to CPs, HCPs and laypersons, but ST seems to be of higher priority among people diagnosed with cancer, whereas laypersons appear more likely to prioritize QOL than CPs and HCPs. Further studies are needed to better understand these important societal issues. This work was supported in part by the Sao Paulo Medical Council (CREMESP). Priority CPs HCPs Laypersons ST, regardless of QOL 21.2% 2.3% 11.8% ST, as long as QOL not compromised 59.6% 72.7% 54.4% QOL, regardless of ST 15.2% 22.7% 33.8% Do not know or prefer not to choose 4.0% 2.3% 0%
Phase III, Randomized, Double-blind Trial of Sunitinib Versus Placebo in Patients With Progressive, Well-differentiated Pancreatic Islet Cell Tumours
Authors: E. Raymond, Ivan Borbath, J. Raoul, P. Niccoli, Y. Bang, C. Lombard-Bohas, P. Metrakos, D. Lu, C. Blanckmeister, A. Vinik
Journal: Annals of Oncology (2009)
Long-term central venous catheters and infections in older adults with cancer.
Authors: Allison Nicole Lipitz Snyderman, Kent Sepkowitz, Elena B. Elkin, Laura C. Pinheiro, Peter Bach
Journal: Journal of Clinical Oncology (2013)

125 Background: Long-term central venous catheters (CVCs) facilitate venous access to administer intravenous fluids and treatments such as chemotherapy. However, CVCs can also be a source of harmful bloodstream infections, a risk that may be underappreciated. Our objective was to assess the impact of long-term CVC use on the risk of infections in a population-based cohort of cancer patients. Methods: Retrospective analysis using the population-based SEER-Medicare dataset for patients over age 65, diagnosed from 2005 to 2007 with invasive colorectal cancer (n = 36,272), head and neck cancers (n = 8,459), lung cancer (n = 56,770), pancreatic cancer (n = 10,536), or non-Hodgkin lymphoma (n = 14,432), or invasive or non-invasive breast cancer (n = 42,271). Cox proportional hazards regression was used to examine the impact of CVC use on infection risk, with CVC exposure treated as a time-varying predictor. We used multivariable analysis and propensity score methods to control for patient characteristics. Results: Adjusting for demographic and disease characteristics, long-term CVCs significantly increased the risk of infection by at least 40%, across all cancer types (Table). The greatest effect of CVCs on infection risk was in patients with breast cancer. Conclusions: Long-term CVC use is associated with an increased risk of infections for older adults with cancer. Careful assessment of the need for long-term CVCs, and targeted strategies to reduce infections for patients requiring their use, are critical to improving cancer care quality. [Table: see text]
Abstract 15066: Erythrocyte-Rich Thrombi Aspirated from Patients with ST-Elevation Myocardial Infarction Influence Oxidative Stress and Predict Long-Term Mortality
Authors: Kei Yunoki, Takahiko Naruko, Ryushi Komatsu, Kenichi Sugioka, Masashi Nakagawa, Nobuyuki Shirai, Satoko Wada, Kengo F Kusano, Hiroshi Ito, Akira Itoh, Kazuo Haze, Makiko Ueda
Journal: Circulation (2010)
Survival analyses from the Women's Intervention Nutrition Study (WINS) evaluating dietary fat reduction and breast cancer outcome
Authors: R. T. Chlebowski, G. L. Blackburn, M. K. Hoy, C. A. Thomson, A. E. Giuliano, P. McAndrew, C. A. Hudis, J. Butler, A. Shapiro, R. M. Elashoff
Journal: Journal of Clinical Oncology (2008)

522 Background: We previously reported five year results with follow up through October, 2003 of a phase III randomized trial where a dietary intervention targeting fat intake reduction, associated with significant weight loss, improved relapse-free survival compared to control in women with resected, early stage breast cancer receiving conventional cancer management (RR 0.79, P=0.034) (JNCI 2006;98:1767- 76). After initiating the dietary intervention with 16 visits over 8 weeks, ongoing adherence was addressed by q 3 month nutritionist contacts. Active dietary intervention and contacts with nutritionists ended in May, 2004. We now report a protocol-mandated survival analysis update. Methods: Updated survival information was obtained through October, 2007 largely through national death registries and randomization group survival differences were examined using Cox proportional hazards models in intention-to-treat analyses. Exploratory analyses examined survival by hormone receptor subgroups and active dietary intervention status. Results: Although fewer deaths were seen in the intervention group (9.1% vs. 11.1% cumulative mortality, RR 0.83) the difference was not statistically significant (P=0.146). In the 362 women with ER- and PR- disease, a significant overall survival benefit was seen for intervention group participants (7.5% vs. 18.1%, cumulative mortality, RR 0.41, P=0.003). The influence of ongoing active dietary intervention was examined by analyses censored six months after contact with nutritionists ended (for survival before and after 12/31/04). Conclusions: A dietary intervention targeting fat intake reduction did not significantly increase overall survival of women with resected breast cancer receiving conventional cancer management. Exploratory analyses suggest dietary intervention influence on survival may be greater in hormone receptor negative subgroups and during the period of active dietary intervention. Dietary Intervention Effect on Survival By Receptor Status and Active Dietary Intervention Interval Patient Group # entered Entire Period During Intervention After Intervention Ended # Deaths RR P value # Death RR P Value # Death RR P value All 2437 251 0.83 0.146 208 0.78 0.068 43 1.15 0.217 ER + 1959 183 0.88 0.146 147 0.85 0.459 36 1.08 0.221 ER − 478 68 0.68 0.059 61 0.60 0.049 7 1.57 0.599 No significant financial relationships to disclose.
Long term survivors with glioblastoma multiforme (GBM) treated on RTOG protocols with irradiation and nitrosurea have higher initial expression of Ki-67
Authors: A. K. Choucair, W. Seiferheld, C. Ford, J. Hansen, B. Dabbas, C. Schultz, A. Schulsinger, M. Mehta, W. Curran
Journal: Journal of Clinical Oncology (2004)

9661 Background: Ki-67 is a nuclear antigen that is upregulated during cellular proliferation. Ki-67 expression has been both positively and negatively associated with survival in a number of tumor primaries. Similarly, in patients with GBM, prior studies of the prognostic value of initial Ki-67 expression for overall survival have reported conflicting results with some suggesting a positive, others a negative, and others no correlation. Methods: In this study we compared the nuclear expression of Ki-67 using Mib-1 antibody between 28 long term (>18 months) and 35 short term (< 6 months) GBM survivors receiving irradiation and BCNU who were selected from RTOG Tissue Bank and who met the following criteria: eligibility requirements for the RTOG study on which they were enrolled, received the BCNU arm, and had survival 18 months. Tumor cell expression was quantitated by performing immunohistochemistry on tumor array slides with determination of positively staining cells by use of the Chromovision automated cell imaging system. Results: *Multivariate logistic regression with Ki-67, age, KPS and extent of resection. Conclusions: In this patient population, long term GBM survivors have a higher percentage of tumor cells expressing Ki-67. This suggests that further investigation of factors that are altered during the cell cycle may be of value in identifying prognostic factors for long term GBM survivors. No significant financial relationships to disclose.