tbuckley/cabot-search huggingface dataset:
Use of amplification of the 8q24 and 20q11–13 loci to predict progression-free survival of advanced epithelial ovarian cancer patients receiving standard therapy
Authors: E. Tominaga, H. Tsuda, T. Arao, S. Nishimura, T. Chiyoda, H. Nomura, F. Kataoka, N. Susumu, D. Aoki, K. Nishio
Journal: Journal of Clinical Oncology (2009)

e16526 Background: The purpose of this study was to identify genes that predict the progression free survival (PFS) of advanced epithelial ovarian cancer (aEOC) receiving standard therapy. Methods: We performed expression analysis using GeneChip (Human Genome U133 plus 2.0 Array) in aEOC cells produced by laser-based microdissection. Thirty three aEOC patients (stage IIc: 4, III: 19, IV: 10; serous adenocarcinoma: 21, endometrioid adenocarcinoma: 5, undifferentiated: 7) were included in this array study. All cases received staging laparotomy, cytoreductive surgery, and adjuvant chemotherapy (carboplatin + paclitaxel) as primary therapy. Results: Class comparison analysis between groups of NED (no evidence of disease) and non-NED identified 46 genes that exhibited significant differences (p &lt; 0.001). Among them, 6 (13%) genes are located in 8q24 and 9 (19.6%) genes are located in 20q11–13. Finally, we focused on 8q24 and 20q11–13 loci, and confirmed array data using real-time quantitative PCR in 94 validation sets. The validation showed that ZNF7, MAF1, ADRM1, and GNAS amplification was related with PFS (p &lt; 0.05, respectively). Conclusions: The amplification of 8q24 and 20q11–13 can predict the PFS of aEOC and these genes may be new biomarkers for aEOC. No significant financial relationships to disclose.
Improving quality at university based hematology/oncology fellowship continuity clinic with the quality oncology practice initiative (QOPI)
Authors: A. M. Coscio, A. Anguiano, N. M. Kuderer, M. Kelley
Journal: Journal of Clinical Oncology (2008)

6578 Background: Quality imporvement is an important component of improving cancer care and is now an ACGME requirement of fellowship training. The feasibility of integrating QI activities into fellowship training is not known. Methods: The Hematology/Oncology fellowship program at Duke University voluntarily participated in QOPI in Spring and Fall of 2007 in an effort to evaluate this quality improvement tool for compliance with ACGME requirements. For each round of chart abstractions, all patients seen in this clinic with lung cancer and colorectal cancer (charts identified by ICD-9 codes) within two years were screened for inclusion by the VA chief attending and 1–2 fellows; this screening process required approximately 6 hours.. EMR's of eligible patients were abstracted using the QOPI online tool by attending and fellow physicians. Each attending and fellow physician was assigned 6 to 8 patient charts to abstract data, and each chart required an average of 15 minutes. Results: During the Spring 2007 survey, there were multiple areas identified for improvement. A template was created within the electronic medical record based on this data to improve documentation. A specific hem/onc treatment note was implemented for all patients who are to receive chemotherapy or biotherapy (oral and IV) for their cancers. The template addressed areas for improvement including chemotherapy cycles, pain assessment and consent. Comparison of surveys revealed improvement in documentation of pain assessment (78% increase to 87%), chemotherapy intent discussion (72% increase to 86.5%) and number of chemotherapy cycles documented (54% increase to 90%). Conclusions: QOPI participation is viable option to comply with ACGME requirements. Participation may improve performance through increased awareness of quality measures. Implementation of required template into electronic medical record improves documentation. No significant financial relationships to disclose.
Analysis of prognostic (prog) Web-based models for stage II and III colon cancer (CC): A population-based validation of <i>Numeracy</i> (NUM) and <i>ADJUVANT! Online</i> (ADJ!)
Authors: S. Gill, C. Loprinzi, H. Kennecke, A. Grothey, G. Nelson, R. Woods, C. Speers, S. Alberts, A. Bardia, D. Sargent
Journal: Journal of Clinical Oncology (2009)

4044 Background: To aid in decisions regarding adjuvant therapy (AT) for resected high-risk CC, two prog models are in common use: the Mayo Clinic NUM calculator developed from a pooled data analysis of 7 randomized 5FU-based AT trials, and ADJ! developed using SEER data. This study examines the accuracy of NUM and ADJ! utilizing a cohort of patients (pts) referred to the BC Cancer Agency (BCCA). Methods: Demographic, disease and treatment data for pts with stage II/III CC referred to the BCCA from 1995–1996 + 1999–2003 were collected. Observed (obs) 5-year relapse free survival (RFS) and overall survival (OS) were compared to predicted estimates (pred) using NUM and ADJ!, both overall and for all prog subgroups with ≥ 10pts, as stratified by T stage, N stage, tumor grade and age. Data are presented in a descriptive manner and using confidence intervals. Results: Median follow-up was 5.6 yrs for 2,033 pts - 53% male, median age 68y, 40% N0. The mean percentages of 5 year pred outcomes for each of the two models and the actual Kaplan Meier mean survivals are presented in the table . The percentage correct predictions of 5 y status is also presented, with correctness deemed accurate if the pt was alive and predicted to be alive by ≥ 50% as determined by each model or dead while the respective tool predicted &lt; 50% possibility of being alive. For surgery alone pts, ADJ!pred were more often closer to what was observed, as compared to NUMpred, in the prog subgroups (for RFS 56%, OS 88%). For surgery + 5-FU pts, within these subgroups, NUMpred were more often closer to what was observed, as compared to ADJ!pred, for RFS (62%) and for OS (55%). Conclusions: In this independent population-based validation, NUM and ADJ! have acceptable and similar reliability with modest over-estimations of 5y RFS and OS. Both models thus appear to be useful adjuvant decision-aids. [Table: see text] No significant financial relationships to disclose.
Pathologic response rate for high-risk operable breast cancer after TNCF semi-intensive neoadjuvant chemotherapy: Updated data with long-term results.
Authors: X. Durando, H. Cure, C. Abrial, E. Goldschmidt, F. Penault-Llorca, I. Van Praagh-Doreau, C. Pomel, D. Machover, P. J. Chollet, M. Mouret-Reynier
Journal: Journal of Clinical Oncology (2010)

683 Background: We report an extended experience of TNCF protocol as semi-intensive primary chemotherapy for high risk operable breast cancer (Eur J Cancer. 1997;33:862-866). Methods: Between 04-91 and 06-98, 72 patients (pts) received 4-6 cycles every 3 weeks of THP-doxorubicin 20 mg/m2 D1 to D3, vinorelbine 25 mg/m2 D1 and D4, cyclophosphamide 300 mg/m2 and fluorouracil 400 mg/m2 D1 to D4. Results: Patients' characteristics were: 44 years median age (25-69), 61 premenopausal (85%), 57 ductal (83%), 7 lobular and 5 unspecified invasive carcinomas. After chemotherapy, all underwent surgery: 51 conservative (71%), 21 radical (29%). 14 stage IIa, 34 IIb, 21 IIIa and 3 IIIb patients were included in this high risk group for at least 3 of the following: age, tumor size > 3 cm (72), lymph node involvement (47 N1, 6 N2), SBR grade III (32), high S phase (39), negative hormonal receptors (39). Median number of cycles was 5 with an actual dose-intensity per drug of 81%-88%. Despite G or GM-CSF use (57/72 pts), constant WHO grade 3 or 4 neutropenia avoided toxic death, and all recovered rapidly normal counts (91% had at least one febrile episode of 2 days median duration). No clinical cardiac toxicity was observed (LVEF not systematic). The objective response rate was high: clinically (86%), on mammography (80%) and on echography (84%). After pathological review, 17 pts (24%) were devoid of any tumor in both breast and nodes, 7 others (10%) had only in situ carcinoma without invasive tumor. With a median follow-up of 186 months, 34 patients relapsed: 17 locally and 25 distantly. Median OS and DFS were respectively 200 and 165 months as of December 1, 2009, but were not reached for the 25 pCR patients versus 52 with residual disease (p > 0.016). PCR patients have not relapsed beyond 60 months with a plateau appearance. OS and DFS were 44.9% and 47% (91% and 63% for pCR patients). Conclusions: In conclusion, this semi-intensive regimen induced a severe, but not life-threatening hematologic toxicity, and resulted in a high pathologic complete response rate (34%) and 71% conservative surgery with a good late survival. No significant financial relationships to disclose.
Gemcitabine and irinotecan in patients with previously treated carcinoma of unknown primary site: A Minnie Pearl Cancer Research Network phase II trial
Authors: H. H. Doss, J. D. Hainsworth, D. R. Spigel, M. Kommor, M. Zakem, E. L. Raefsky, S. Litchy, F. A. Greco
Journal: Journal of Clinical Oncology (2004)

4167 Background: Three sequential phase II trials done by the Minnie Pearl Cancer Research Network of taxane, platinum, and etoposide combinations for carcinoma of unknown primary site (CUP) have produced median survivals of about 10 months, and 1, 2, 3, 5, and 8-year survivals of 42%, 22%, 18%, 12%, and 10%, respectively. In an effort to improve efficacy, we evaluated second-line treatment with a new combination regimen of gemcitabine and irinotecan. Methods: The primary objective was to evaluate the toxicity and response rate in CUP as second-line therapy. Eligible patients (pts) had adenocarcinoma, poorly differentiated adenocarcinoma, poorly differentiated carcinoma, or poorly differentiated neuroendocrine carcinoma (PDNE); one prior chemotherapy regimen, not including recent irinotecan and/or gemcitabine; absence of brain metastasis; and adequate organ function. Gemcitabine 1000 mg/m2 IV days 1, 8 and irinotecan 100 mg/m2 IV days 1, 8 were given every 21 days. Pts with objective responses or stable tumor after 2 cycles (6 weeks) continued additional 3-week cycles for a recommended 6 cycles. Results: 31 pts were treated and 27 were evaluable for response; median age 50 years (range 24–74); performance status (0=1, 1=28, 2=2); men - 15; women - 16. The response rate was 15% with 3 (11%) partial responses, 1 (4%) complete response. 11 pts had stable disease and 12 progressive disease. Of the 2 pts with PDNE, both had stable disease. The median time-to-progression, median survival, and 1-year survival were 3.5 months, 4 months, and 15%, respectively. Grade 3/4 toxicities included: neutropenia (30%), thromobcytopenia (8%), diarrhea (8%), anemia (9%), neutropenic fever (3%), nausea/vomiting (8%), and fatigue (8%). Conclusions: Gemcitabine/irinotecan is an active and well-tolerated second-line treatment for pts with CUP. A randomized prospective phase III study of gemcitabine/irinotecan compared to paclitaxel/carboplatin/etoposide in the first-line setting is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly; Pfizer-Pharmacia
Immunodetection of androgen and estrogen a,b receptors in human urinary bladder cancer
Authors: A. Gómez Pinillos, G. Bueno Serrano, S. Sacristán López, R. García González, C. Varona Crespo, E. Fernández Fernández, A. Moyano Jato, M. Arenas Jiménez, M. Toledo Lobo
Journal: Journal of Clinical Oncology (2007)

15616 Background: Bladder cancer predominates in males. Loss of androgen receptor (AR) has been associated with invasive and undifferentiated tumors but little is known about the role of hormonal receptors in this type of cancer. Methods: We evaluated samples from 41 nonconsecutive patients treated for bladder transitional cell carcinoma between 2001–2003. Immunohistochemistry was performed using anti-AR and anti-ER a,b antibodies on paraffin-embedded tumors from transurethral resections, nuclear expression was assessed. Western blotting for AR and pAKT were performed in 22 transurethral resections from nonconsecutive bladder cancer patients treated between 2004–2006. Chi-square and U Mann-Witney tests were performed. Results: Immunohistochemistry study: the male/female ratio was 9/1; 61% were noninvasive tumors (pTa, is,1) and 32% were invasive (pT2,3); 22% were G1 and 75% were G2,3. 95% were AR(+), 40% ERa(+) and 94% ERb(+). Significant differences in AR expression were observed between G1 78% and G2,3 tumors 100%, with a high grade tumor prevalence in the AR(+) tumors 81.6% p=0.046. No differences between ERa,b and differentiation were found. G2,3 tumors were predominantly ERb(+). AR was found in 92% noninvasive and in 100% invasive tumors p=0.53. No significant differences were found between invasiveness and ERa,b. Noninvasive tumors showed higher ERa,b expresión (54%, 95% respectively) than invasive tumors (20%, 91% respectively). Western blotting group: 54.5% were primary tumors and 45.5% were recidives. The noninvasive/invasive rate was 59/32%, the G1/G2,3 rate was 4.5/95.5%. 112, 250 and 160 kDa bands were found. AR/pAKT rate was 86.4/100%. 100% of invasive tumors and 86% G2,3 tumors were AR(+). No differences between pAKT, invasiveness, differentiation or AR expression were observed but recidivated tumors had a slight higher median expression level. Conclusions: AR is positively related to tumor grade and might be involved in bladder cancer progression. The profile of AR bands suggest covalent modifications, due to ubiquitin-mediated degradation or to activation mechanisms mediated by SUMO. Nuclear AR and the absence of bands under 90kDa suggest that activated protein is present in bladder cancer. pAKT/AR inhibitors could play a role for bladder cancer therapy. No significant financial relationships to disclose.
Accuracy of risk perceptions of women with ductal carcinoma in situ
Authors: K. O. Adloff, A. Partridge, E. Blood, C. Dees, C. Kaelin, J. Weeks, K. Emmons, E. Winer
Journal: Journal of Clinical Oncology (2004)

6034 Background: DCIS is a complex clinical entity with a variable natural history, but a generally favorable prognosis. Limited previous data suggest that women with DCIS may overestimate their risks. Methods: Women diagnosed with DCIS in Eastern Massachusetts and North Carolina have been identified and asked to participate in a longitudinal study of psychosocial concerns, risk perceptions, and health behaviors. Questionnaires are mailed to women at baseline, 9, and 18 months. Data collection is completed via telephone. Results: 62% of eligible women have enrolled; 469 women have completed the baseline questionnaire of a planned 500. Preliminary data are available from 383 women. Median age of participants is 53 years (range 31–87); 86% are < 65 years old; 94% white; 85% at least high school graduates; 67% married; 44% working full-time. Only 5% of women recalled significant anxiety in the month prior to diagnosis, as measured by the Hospitalized Anxiety and Depression Scale (HADS); only 3% recalled significant depression. 73% saw an oncologist. When queried about their risk of future breast cancer events, 57% of women felt there was at least a moderate likelihood of developing DCIS again in the next 5 years; 70% reported at least a moderate likelihood of DCIS in their lifetime; 41% felt there was at least a moderate likelihood of developing invasive breast cancer in the next 5 years; 55% reported at least a moderate likelihood of invasive disease in their lifetime. Strikingly, 29% of respondents believed there was at least a moderate likelihood of DCIS spreading to other places in their body. A multivariate model revealed that depression in the month prior to diagnosis was the only factor associated with a belief that DCIS would spread. Non-significant covariates included age, race, education, marital status, employment, financial status, comorbidity, anxiety, and oncology consultation. Conclusions: A substantial proportion of women with newly diagnosed DCIS harbor inaccurate perceptions of breast cancer risks. Future research should assess the impact of altered risk perceptions on decision-making and psychosocial outcomes. (Supported by the Dana-Farber Harvard SPORE in Breast Cancer) No significant financial relationships to disclose.
A phase II trial of adjuvant UFT after sequential chemotherapy and radiotherapy in patients with stage IIIB non-small cell lung cancer and non-oriental ethnicity
Authors: A. C. Melo, D. S. Lima, I. A. Small, D. B. Olmedo, E. Toscano, P. de Biasi, R. Martins, C. G. Ferreira, M. Zukin
Journal: Journal of Clinical Oncology (2007)

18175 Background: The goals of chemoradiotherapy in non-small cell lung cancer (NSCLC) with stage III disease are to achieve local control, for which radiotherapy plays the main role, and eradicate occult distant metastases by chemotherapy. Systemic progression remains a significant cause of morbidity and mortality in these patients. Japanese trials showed that the combination of uracil and tegafur (UFT) improves survival in patients with early NSCLC. The Brazilian National Cancer Institute (INCA) conducted a phase II trial to evaluate the use of adjuvant UFT in patients with IIIB NSCLC treated with sequential chemoradiation. Methods: The eligibility requirements were stage IIIB NSCLC, an ECOG performance status 0 or 1 and normal end organ function. Patients were treated with induction chemotherapy with cisplatin (100 mg/m 2 - days 1 and 29) and vinblastine (5 mg/m 2 /week for 5 weeks) followed by 60 Gy of thoracic radiotherapy. Two weeks after the end of radiotherapy they started a fixed UFT oral dose (400 mg/day), administered continuously for one year if no progression was detected in this interval. Results: Between May 1999 and October 2003, 22 patients were enrolled; 15 were male (68.2%); 65% were white (no patients had oriental ethnicity); 11 were adenocarcinoma (50%), 9 squamous cell (40.9%); the median age was 55.5 years (range: 45–74 years). UFT’s toxicity was manageable with 13.6% of grades 3 and 4 toxicities (mainly fatigue, diarrhea, nausea and vomiting). Two patients discontinue UFT due to limiting toxicity (1 patient due to diarrhea and 1 due to nausea and fatigue). Median time on UFT was 5 months (range: 0.5–12 months). Median follow-up was 13.5 months (range: 6–77 months) and five patients are still alive. The median overall survival (OS) was 14 months (95% CI: 10.6–17.3) and the median progression-free survival was 8 months (95% CI: 3.4–12.5). Conclusions: UFT in this fixed dose schedule was well tolerated, but our results are almost identical to the Dillman′s original report with sequential chemotherapy and radiotherapy in stage IIIB NSCLC (13.7 months OS). Despite our limited sample size these data may suggest that adjuvant UFT do not add any benefit to sequential chemoradiation in this non-oriental population. No significant financial relationships to disclose.
Economic burden of relapsed/refractory diffuse large B-cell non-Hodgkin's lymphoma (DLBCL): A review of the literature.
Authors: K. A. Slawsky, T. F. Goss, R. Shinkle, X. Xu
Journal: Journal of Clinical Oncology (2010)

e18564 Background: The addition of rituximab to standard CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) has been shown to be cost-effective. With demonstrated clinical efficacy, it is standard first-line treatment for DLBCL. Treatment for relapsed/refractory (R/R) DLBCL is less clear, and we sought to assess its economic impact. Methods: A structured literature review was performed to assess the economic, clinical, and patient burden of R/R DLBCL. English-language articles published between 01/1999 and 06/2009 were systematically reviewed in Medline PubMed and the Cochrane database. Articles were considered relevant to economic burden if they reported resource utilization and/or costs associated with treatment for R/R DLBCL. Results: Of 127 articles identified on NHL, 18 addressed economic outcomes. While articles focusing on first-line comparisons included aggregate estimates of additional treatment costs, detailed cost and resource utilization estimates were not identified in the R/R setting. While it is clear from the literature that the economic burden of DLBCL is substantial, rigorous economic analyses have not been reported in the R/R population and no economic analyses were identified that examined the treatment costs for R/R DLBCL. One retrospective analysis examining costs of aggressive NHL (not DLBCL specifically) associated with treatment from a US-perspective reported that treatment failure was the most costly outcome with a mean monthly cost of $14,174; however, costs were not specific to individual regimens. Two studies (from a Canadian and Netherlands perspective each) were identified that provided general (not treatment-specific) resource utilization and cost estimates for R/R treatment. Conclusions: As there is no clear standard treatment for R/R DLBCL, economic comparisons between treatment alternatives may provide selection guidance in situations in which clinical efficacy is considered equivalent. Published literature has not robustly examined treatment options and their relative cost-effectiveness, and more research is needed to define the economic burden associated with the treatment of R/R DLBCL. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MedImmune, LLC MedImmune, LLC AstraZeneca
Serum biomarkers as predictors of clinical outcome after cetuximab-based therapy in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN)
Authors: R. L. Ferris, T. Feinstein, J. Grandis, R. Johnson, B. Branstetter, W. Gooding, A. Argiris
Journal: Journal of Clinical Oncology (2009)

6035 Background: We correlated a panel of serum cytokines and growth factors with antitumor activity in patients (pts) with locally advanced SCCHN treated with cetuximab-based therapy. We have shown that similar biomarkers may be promising for the early detection of SCCHN (Linkov, Can Epi Biomarkers 2007). Methods: We used multi-analyte biomarker profiling for measurement of multiple serum biomarkers (Luminex Corp., Austin, TX). 39 pts with stage III-IVB SCCHN were treated with cisplatin, docetaxel, and cetuximab (TPE) for 3 cycles followed by radiotherapy, cisplatin, and cetuximab (XPE) and then maintenance cetuximab (Argiris, ASCO 2008, A6002). 31 cytokines and growth factors were measured before and after 3 cycles (9 weeks) of induction TPE. Clinical results were correlated with biomarkers, including 23 pts with PET response. Results: 31 pts had baseline biomarkers and 25 paired samples, pre- and post-TPE. Median follow-up was 22 months. Median age 54 years (21–74); male: 27; stage IV: 29; primary site: oropharynx, 16; larynx, 4; hypopharynx, 3, nasopharynx, 3; oral cavity, 3; and unknown, 2. Eight analytes changed significantly after induction. Adjusting p values for false discovery, the following analytes retain a p &lt;0.05: MCP1c, IP-10, Leptin, IL-5, Eotaxin, IL-6, GCSF, CXCL5. In 23 pts with PET response assessment, low vascular endothelial growth factor (VEGF) levels or low IL-6 levels at baseline may be associated with complete response: 4/5 pts with low baseline VEGF (&lt;20.9 pg/ml) had a complete response by PET vs 1/18 pts with high baseline VEGF. Of 31 pts, 9 have progressed. Among tests of association of the 31 analytes and progression-free survival (PFS), VEGF was the only one with a raw p value &lt;.05 (p = .027), although the adjusted p value was not significant. A decrease in VEGF with treatment had a weak but not statistically significant association with longer PFS. Conclusions: Baseline serum biomarkers and in particular, VEGF and IL-6, were identified as potentially useful predictive markers of cetuximab-based therapy. Due to the small sample size and multiple testing, these biomarkers need to be validated in a larger study in SCCHN specifically powered for biomarker associations. No significant financial relationships to disclose.