tbuckley/cabot-search huggingface dataset:
Japanese breast cancer patients prefer detailed consent forms: A comparative study of detailed forms vs standard forms
Authors: K. Sato, T. Watanabe, N. Katsumata, Y. Ohashi
Journal: Journal of Clinical Oncology (2005)

6046 Background: The consent forms (CF) should be simple and readable to make the process of informed consent meaningful. However, Japanese people have higher education and achieve high proportion of literacy. We tested if the use of detailed CF, when compared with standard CF, would result in higher comprehension and satisfaction. Methods: Four versions of CFs, detailed CF with 4 instructional graphics, detailed CF, standard CF with graphics and standard CF, were developed. Readability of CFs corresponded to newspapers. Breast cancer patients (n=85) eligible for a randomized trial comparing the effects of adjuvant chemotherapy (UFT vs CMF) were randomized to receive each CF out of 4 versions after oral consultation with physicians. We conducted semi-structured interviews of patients to assess patients’ understanding of the parent study and satisfaction with CF. Results: Mean age of patients was 54 years and average term in school was 13.1 years. Mean score of correct responses to 17-item questions about the elements of the parent study was high (88%, 89%, 90%, 90%), no significant difference was noted in patients’ comprehension among 4 CFs arms. The proportion of patients who rated the provided CF was useful to understand the parent study were 57%, 36%, 23% and 20% (p=0.01). The proportion of patients who evaluated the CF was helpful to decide to participate in the parent study were 52%, 23%, 23% and 5% (p=0.003). Most patients preferred detailed CF with graphics, no significant difference was noted in the proportion of patients who answered CF caused anxiety among 4 CFs. Conclusions: The detailed CF does not improve patients comprehension, however, affects their satisfaction. Patients with standard literacy skills seek full information and evaluate that the detailed CF is useful to decision-making process. These findings suggest that information should be provided adequately according to patients’ need and education level. No significant financial relationships to disclose.
Breast cancer metastasis gene signature: The search for the holy grail.
Authors: R. E. Ellsworth, L. A. Field, B. Love, J. L. Kane, J. A. Hooke, C. D. Shriver
Journal: Journal of Clinical Oncology (2010)

1075 Background: Lymph node status remains one of the most useful prognostic indicators in breast cancer, however, current methods to assess nodal status disrupt the lymphatic system, lead to secondary complications, and 10-33% of women diagnosed with negative lymph nodes will develop metastases. Identification of molecular signatures discriminating primary tumors from patients with the propensity to metastasize from those without would allow for stratification of patients requiring surgical assessment of lymph node status and identification of node negative patients at high-risk of developing metastatic disease. Methods: Frozen breast specimens were collected from women with negative (n=39) and positive (n=35) lymph node status. Patients with positive BRCA1/BRCA2 status, neoadjuvant therapy or negative lymph node status who later developed distant metastasis were not included in this study. RNA was isolated from pure tumor cell populations after laser microdissection and gene expression data generated using HG U133A 2.0 arrays (Affymetrix). Data was randomly split into a training set (29 negative and 25 positive) and a validation set (10 negative and 10 positive) and a classifier was built using a forward-building Bayesian naïve classifier. Results: Neither age at diagnosis nor pathological characteristics including ER, PR, or HER2 status differed significantly between the two groups. A median prediction probability >95% was achieved with the Bayesian classifier using 17 markers (mean probability 94.31%, median 95.05%, min 74.62%, and max 99.91%) in the training set. The 17 marker panel was, however, only able to correctly classify 9/20 samples in validation set, resulting in approximately random classification. Conclusions: The inability to derive molecular profiles of metastasis may reflect tumor heterogeneity (e.g., different methods of metastasis for each tumor subtype), the presence of only a few cells within the primary tumor that have metastatic potential, or an inherited host susceptibility to metastasis, rather than molecular properties of the tumor itself. Together, these data suggest that a molecular signature that can discriminate between primary breast tumors with and without lymph node metastases does not exist. No significant financial relationships to disclose.
Azacytidine mitigates experimental sclerodermic chronic graft-versus-host disease
Authors: Gilles Fransolet, Grégory Ehx, Joan Somja, Loïc Delens, Muriel Hannon, Joséphine Muller, Sophie Dubois, Pierre Drion, Jo Caers, Stéphanie Humblet-Baron, Philippe Delvenne, Yves Beguin, Giuseppina Conteduca, Frédéric Baron
Journal: Journal of Hematology & Oncology (2016)

Previous studies have demonstrated that regulatory T cells (Tregs) play a protective role in the pathogenesis of chronic graft-versus-host disease (cGVHD). Tregs constitutively express the gene of the transcription factor Foxp3 whose CNS2 region is heavily methylated in conventional CD4+ T cells (CD4+Tconvs) but demethylated in Tregs. Here, we assessed the impact of azacytidine (AZA) on cGVHD in a well-established murine model of sclerodermic cGVHD (B10.D2 (H-2d) → BALB/cJ (H-2d)). The administration of AZA every 48 h from day +10 to day +30 at the dose of 0.5 mg/kg or 2 mg/kg mitigated chronic GVHD. Further, AZA-treated mice exhibited higher blood and thymic Treg frequencies on day +35, as well as higher demethylation levels of the Foxp3 enhancer and the IL-2 promoter in splenocytes at day +52. Interestingly, Tregs from AZA-treated mice expressed more frequently the activation marker CD103 on day +52. AZA-treated mice had also lower counts of CD4+Tconvs and CD8+ T cells from day +21 to day +35 after transplantation, as well as a lower proportion of CD4+Tconvs expressing the Ki67 antigen on day +21 demonstrating an anti-proliferating effect of the drug on T cells. Our results indicate that AZA prevented sclerodermic cGVHD in a well-established murine model of cGVHD. These data might serve as the basis for a pilot study of AZA administration for cGVHD prevention in patients at high risk for cGVHD.
Targeting BCR Activated STAT3 By Ibrutinib In Mantle Cell Lymphoma
Authors: Zhishuo Ou, Lan V Pham, Muychi T Vang, Liang Zhang, Jack Wang, Lauren M Strickland, Elyse R Lopez, Erin M Dominici, Alex Rollo, Archito T. Tamayo, Richard J. Ford, Michael Wang
Journal: Blood (2013)
Is the prophylactic use of colony stimulating factor and oral ciprofloxacin effective to prevent neutropenia in patients having docetaxel, doxorubicin, and cyclophosphamide for breast cancer as an adjuvant chemotherapy in Korea?
Authors: Y. Suh, C. Chun, S. Oh, S. Jung
Journal: Journal of Clinical Oncology (2006)

10736 Background: Recently, the combination chemotherapy including docetaxel (75 mg/m 2 ), doxorubicin (adriamycin) (50 mg/m 2 ), andcyclophosphamide (500 mg/m 2 ) has been reported to be effective as an adjuvant treatment for the early breast cancer patients. Though a few studies have been published to show preventive effect of the routine use of G-CSF and oral antibiotics on the severe neutropenia. We prosepctively tried to compare the possible role of this prophylactic measure on the prevention of high-grade neutropenia in breast cancer patients having this regimen in Korea. Methods: We prospectively compared prophylactic user group (100 patients) with non-use group (100 patients). Stage II breast cancer patients were enrolled for this study. We used three-day prescription of G-CSF (150 ug/day) and oral ciprofloxacin (500 mg/day) five days after the completion of each cycle for the user-group. Results: The percentage of febrile neutropenia was strikingly decreased in the user group (p &lt; .01). Number of patients showing grade II, III neutropenia didn’t show statistical difference between groups. Averge days required to recover from the neutropenia was 2.7days in two groups. The nadir of neutropenia was between 7–10 days after each cycle regardless of the prophylaxis. The duration of neutropenia seems to be dependent on the presence of the fever over 38’C after the chemotherapy. Once the fever developed, the neutropenia was becoming severer and more protracted. Conclusions: We think this combination chemotherapy effective to be used as an adjuvant treatment for the early breast cancer patients. But more care should be provided to prevent severe neutropenia after each cycle. Routine use of this prophylaxis failed to show significant differences in the rate of occurence of the severe neutropenia. But, we think that the prophylaxis seems to e effective to prevent febrile neutropenia. So, we suggest the routine prophylactic use of G-CSF and oral ciprofloxacin should be considered to be used in breast patients having docetaxel, adriamycin, and cyclophosphamide. No significant financial relationships to disclose.
Radiosensensitivity index prognostic for survival with adjuvant radiation in resectable pancreatic cancer.
Authors: Tobin Joel Crill Strom, Sarah E. Hoffe, Domenico Coppala, Gregory M. Springett, Mokenge Peter Malafa, Steven A. Eschrich, Javier Torres-Roca, Ravi Shridhar
Journal: Journal of Clinical Oncology (2015)

398 Background: Adjuvant radiation therapy (RT) for resectable pancreatic cancer remains controversial. We evaluated whether a previously validated molecular signature of tumor radiosensitivity (RSI) is prognostic for survival in pancreatic cancer. Methods: We identified patients treated with upfront surgery between 2006 and 2012. Briefly, RSI score is derived from the expression of 10 specific genes and a linear regression algorithm modeled on SF2 of 48 cancer cells (RSI, high index = radioresistant). We assessed the relative radiosensitivity of pancreatic cancers compared with other common cancers and then tested the association of RSI with overall survival (OS). Results: Compared with other common cancers such as lung, breast, and prostate, pancreatic cancers were more radioresistant as a group (p&lt;0.0001). We identified 80 patients who underwent upfront surgery with both RSI and clinical outcome available (49 RT, 31 no RT). Median follow-up among surviving patients was 4.1 years. Median OS for radiosensitive tumors (RS), defined by lower ½ RSI, was 2.7 years compared with 1.5 years for radioresistant (RR) tumors (p=0.35). Among the high-risk pancreatic cohort, (positive margins, positive lymph nodes, or a post-operative CA 19-9 &gt;90), irradiated patients with RS tumors had a trend toward improved OS (3y OS: 38% vs. 8%; p=0.07), while there was no difference in OS between RS and RR patients who weren’t treated with RT (p=0.79). When RSI was integrated, high-risk-RS patients had similar OS compared with low-risk-RR patients (3y OS: 38% vs. 50%; p=0.29). When low-risk-RR and high-risk-RS were combined into a single intermediate-risk group, RSI score added substantial prognostic value to OS outcomes on univariate (3 y OS: 78%, 42%, and 8%, for low-risk-RS, intermediate-risk group, and high-risk-RR, respectively; p=0.001) and multivariate analysis (intermediate-risk HR: 4.3, 1.0-18.6; p=0.053; high-risk HR: 9.9, 2.2-45.1; p=0.003). Conclusions: Patients with pancreatic tumors have relatively radioresistant tumors. Integrating RSI with standard prognostic variables refines the classification of resected pancreatic cancer patients.
Impact of young (Y) age on efficacy and safety in advanced colorectal cancer (aCRC): A pooled analysis examining 6,286 patients (pts) from nine first-line phase III chemotherapy (CT) trials.
Authors: C. D. Blanke, B. M. Bot, D. M. Thomas, A. Bleyer, C. Kohne, M. T. Seymour, A. De Gramont, R. M. Goldberg, D. J. Sargent
Journal: Journal of Clinical Oncology (2010)

3520 Background: CRC is primarily a disease of the elderly; however, the SEER database shows ∼10% of pts are age ≤50. Previous data suggested Y pts have worse outcomes. We sought to determine whether Y age is prognostic or influences efficacy or toxicity for aCRC pts treated with CT. Methods: We analyzed individual pt data on 6,286 subjects from 9 randomized phase III aCRC trials of 5FU-based single- agent and combination (comb) CT. Endpoints included progression-free survival (PFS), overall survival (OS), tumor response (RR), and grade ≥3 adverse events. Cox models stratified by study, and logistic-regression models adjusting for study, were used to test for age (<40 vs. ≥40; <50 vs. ≥50) effects and age-treatment interactions. Efficacy endpoints were explored in the full set of 9 trials and the subset of 5 studies comparing mono- to comb CT. Results: 793/6,286 (13%) were age <50, of which 188 pts (3% total) were <40. Comparing pts <50 to those ≥50: grade ≥3 nausea (N) (10% vs. 7%, p=0.01) was more common. However, rates of severe diarrhea (D) (11% vs. 14%, p=0.001) and neutropenia (NP) (23% vs. 26%, p<0.0001) were significantly lower in Y pts. Age was prognostic for PFS, with poorer outcomes in those <50 (median 6.0 vs. 7.5 months, HR=0.91, p=0.02), but it did not affect RR or OS. In the subset of mono- vs. comb CT trials, the relative PFS, OS, and ORR benefits of multi-agent CT were similar for Y and older pts (see Table). Results were comparable with the age 40 cutpoint. Conclusions: Based on a comparison with SEER, Y aCRC pts are proportionally represented on phase III studies. Y age is modestly associated with poorer PFS but not OS or RR in treated aCRC pts, and Y pts have more N but less D and NP with CT in general. Y vs. older pts derive the same benefits from comb CT. Based on these data, in the absence of a clinical trial, standard comb CT approaches are appropriate for Y aCRC pts. Age <50 Age ≥50 p value** Mono Comb HR/OR* Mono Comb HR/OR* Median PFS (months) 4.7 7.2 0.64 6.3 8.4 0.74 0.11 Median OS (months) 13.6 16.3 0.82 14.8 16.6 0.89 0.57 RR (%) 28 54 3.29 29 51 2.63 0.43 * HR of PFS/OS, OR for RR. ** p value testing for age by CT interaction. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, AstraZeneca, Bristol-Myers Squibb, Genentech, ImClone Systems, Novartis, Pfizer, Roche, sanofi-aventis Roche, sanofi-aventis Amgen, Genentech
A new prognostic index for systemic AIDS-related lymphoma
Authors: J. Stebbing, S. Mandalia, A.-M. Young, T. Dhillon, T. Newshom-Davis, C. Thirlwell, T. Powles, M. Nelson, B. Gazzard, M. Bower
Journal: Journal of Clinical Oncology (2005)

9530 Background: The established International Prognostic Index (IPI) for lymphomas has not included patients with systemic AIDS-related non Hodgkin’s lymphoma (ARL). As this remains an important cause of morbidity and mortality in individuals infected with the human immunodeficiency virus (HIV), we wished to establish the most appropriate prognostic index for use in these patients. Methods: From a cohort of 9,621 HIV-positive individuals, univariate and multivariate analyses of 215 patients with ARL were used to examine standard and new criteria for survival following diagnosis. Cox’s proportional hazards regression analysis was used to determine the prognostic significance of clinico-pathological variables and prognostic risk scores were divided into quartiles. Results: Univariate analyses using the established IPI factors of age, stage, serum lactate dehydrogenase (LDH), performance status and extranodal sites were confirmed to be significant variables. In multivariate analyses of the entire cohort, the CD4 cell count at ARL diagnosis, a prior AIDS diagnosis, Burkitt’s lymphoma histology and IPI risk group were found to be significant. Regression modelling for patients diagnosed since 1996 (the era of highly active anti-retroviral therapy, HAART) reveals only two independent predictors of mortality: IPI risk group and CD4 cell count. These identified four risk strata with predicted one year survivals of 82%, 47%, 20% and 15%. The HAART era prognostic risk scores in the highest quartile derived a likelihood mortality ratio of 7.90 (hazard ratio 1) compared with a prognostic score of <1.0 (likelihood ratio of 0.23 (hazard ratio 0.15, 95% CI 0.06 to 0.33). Conclusions: For patients with ARL in the era of HAART, an accurate prognostic score can be established by combining the IPI with CD4 count. As patients presenting with ARL and a low CD4 count have a poor prognosis, this can be used to guide therapeutic options. No significant financial relationships to disclose.
The effect of tamoxifen (T) or exemestane (E) on bone mineral density (BMD) after 1 year of adjuvant treatment of postmenopausal women with early breast cancer
Authors: S. E. Jones, J. Cantrell, S. Vukelja, J. Pippen, J. O’Shaughnessy, J. L. Blum, R. Brooks, S. Mull, D. Ilegbodu, L. Asmar
Journal: Journal of Clinical Oncology (2005)

610 Background: Postmenopausal women are at risk for bone loss with the average anticipated loss of 1–2% per year. In this substudy of a larger ongoing adjuvant hormonal trial of T vs. E, we evaluated the effect of 1-year of adjuvant hormonal therapy on BMD. Methods: 625 women have entered this substudy. 182 women have now completed 1-year of blinded therapy with T or E at standard doses and have undergone baseline and 1-year BMD of the hip and spine measured by bone densitometry. No patient was receiving prescription bone agents. Mean differences between baseline and 1-year were tested within the treatment arms using paired t-tests. Results were reported as standardized T-scores to counteract the effect of underlying differences in the parameters of the 2 arms. Results: 103 women treated with T and 79 with E were evaluable with a median age of 64 years (range, 43–87). Initial BMD was similar for both arms. Baseline and 1-year data are shown in the table. Two fractures have been observed in the T arm, but no patient in either arm developed osteoporosis. Conclusions: At 1-year, based on changes in T-scores, tamoxifen was associated with no significant effect on BMD. Patients treated with exemestane experienced a decrease in BMD in the hip but not in the spine. No patient with a normal BMD became osteoporotic at 1-year. Supported by Pfizer, New York, NY Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer
Phase III study of tirapazamine, cisplatin and radiation versus cisplatin and radiation for advanced squamous cell carcinoma of the head and neck
Authors: D. Rischin, L. Peters, B. O'Sullivan, J. Giralt, K. Yuen, A. Trotti, J. Bernier, J. Bourhis, M. Henke, R. Fisher
Journal: Journal of Clinical Oncology (2008)

LBA6008 Background: Promising results in a randomized phase II trial with the hypoxic cytotoxin, tirapazamine combined with cisplatin and radiation led to this phase III trial known as HeadSTART. Methods: Patients with previously untreated Stage III or IV (excluding T1–2N1 and M1) SCC of the oral cavity, oropharynx, hypopharynx or larynx, were randomized to receive definitive radiotherapy (70 Gy in 7 weeks) concurrently with either cisplatin (100 mg/m2) on day 1 weeks 1, 4 and 7 (CIS) or cisplatin (75 mg/m2) plus tirapazamine (290 mg/m2/day) on day 1 of weeks 1, 4 and 7 and tirapazamine alone (160 mg/m2/day) on days 1, 3 and 5 of weeks 2 and 3 (CIS/TPZ). The primary endpoint was overall survival (OS). Secondary endpoints included failure-free survival (FFS), time to locoregional failure (LRF), toxicity and quality of life. The planned sample size was 850, which provides 90% power to detect a difference in 2-year survival rates of 60% v 70% (HR = 0.69). A comprehensive prospective review of radiotherapy protocol compliance was conducted, blinded to treatment arm. Results: 861 patients were accrued from 89 sites in 16 countries. In an intention to treat analysis the 2-year OS rates were 65.7% CIS and 66.2% CIS/TPZ (95% CI: -5.9% to 6.9% CIS/TPZ-CIS). There were no significant differences in FFS or time to LRF. More hearing loss was observed with CIS, while more diarrhea and muscle cramps were observed with CIS/TPZ. No significant differences in acute radiation toxicities were observed. 20% patients were found to have major deviations in the radiotherapy plan with the potential for an adverse impact on tumor control. This was associated with an increased risk of death (HR=1.56; p=< 0.0001), any failure (HR=1.65; p< 0.0001), and locoregional failure (HR=1.82; p=0.0002).There was some evidence of a treatment effect in patients without major radiotherapy deviations, HR for risk of LRF (CIS/TPZ:CIS) 0.74, 95% CI: 0.53 to 1.04. Conclusions: We found no evidence that the addition of TPZ to chemoradiation, in patients with advanced head and neck cancer not selected for the presence of hypoxia, improves overall survival. Radiotherapy deviations had a major adverse impact on treatment outcome. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis sanofi-aventis
Adjuvant endocrine monotherapy with tamoxifen or aromatase inhibitors for postmenopausal women with breast cancer: What is the economic impact of CYP 2D6 testing?
Authors: T. Younis, D. Rayson, C. Skedgel
Journal: Journal of Clinical Oncology (2010)

6010 Background: The Early Breast Cancer Trialists' Collaborative Group (EBCTCG) has demonstrated significant improvements in breast cancer (BC) outcomes associated with adjuvant tamoxifen (TAM) and/or aromatase inhibitor (AI) therapy. Compared to TAM alone, upfront AI for 5-years has been associated with improved BC outcomes and favorable cost-effectiveness (CE). BC outcomes with adjuvant TAM may be dependent on CYP 2D6 metabolizer status (EM: extensive, IM: intermediate, PM: poor). This study examines the potential economic impact of utilizing CYP 2D6 testing as a decision aid to select treatment prior to adjuvant TAM or AI monotherapy. Methods: A generic state-transition model was developed to compute BC outcomes over a 25-year horizon in hypothetical cohorts of postmenopausal women receiving 5-years adjuvant TAM or AI monotherapy. We calculated disease-free survival (DFS) rates, cumulative life-years ( LYs), quality-adjusted life-years (QALYs) and costs (Cdn$) associated with adjuvant endocrine therapy according to CYP 2D6 status. A decision analysis was conducted to test the economic impact of CYP 2D6 testing. Efficacy outcomes were derived from the EBCTCG meta-analyses. Impact of impaired CYP 2D6 enzyme activity (PM ± IM) on BC outcomes, and its prevalence, was derived from studies reported to date (Goetz et al, SABCS 2008). Costs and outcomes were discounted at 3%. Sensitivity analyses were conducted. Results: In patients with non impaired CYP 2D6 activity, DFS rates and cumulative LYs/QALYs were comparable between TAM and AI monotherapy. For this subset, AI monotherapy was not CE relative to TAM. In a decision analysis, CYP 2D6 testing before adjuvant endocrine monotherapy was cost saving compared to no testing. The specific economic impact was dependent on predicted BC outcomes in patients with impaired CYP 2D6 activity treated with TAM alone. Conclusions: TAM alone appears to be the economically preferred adjuvant endocrine strategy compared to AI monotherapy in BC patients with non impaired CYP 2D6 activity. Overall, CYP 2D6 testing before adjuvant endocrine therapy with TAM or an AI monotherapy appears to be a cost-saving strategy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Novartis, Pfizer AstraZeneca, Novartis, Pfizer AstraZeneca, Novartis, Pfizer