tbuckley/cabot-search huggingface dataset:
Survival outcome of African American versus non-African American patients with advanced non-small cell lung cancer in first-line treatment studies by the Eastern Cooperative Oncology Group (ECOG)
Authors: T. L. Evans, W. Wang, J. Schiller
Journal: Journal of Clinical Oncology (2005)

7154 Background: African American (AA) patients diagnosed with malignancy generally have lower survival rates than non-AAs. The reasons for this are likely multifactorial and may include differential therapies, socio-demographic factors, or differential biology. Analyses of patients on clinical trials should eliminate differential therapy as a variable. The Cancer and Leukemia Group B (CALGB) previously analyzed 504 patients enrolled on first-line treatment trials of advanced non-small cell lung cancer (NSCLC) between 1989 and 1998 and found that AAs did have statistically worse survival relative to non-AAs, but the effect of ethnicity on survival disappeared after adjustment for performance status (PS) and weight loss (Blackstock, et al JNCI 2002,94:284–290). We attempted to confirm this finding through a larger analysis of ECOG studies conducted during a more recent time period. Methods: We retrospectively reviewed data from eight phase II/III ECOG studies evaluating first-line treatment of advanced NSCLC initiated between 1985 and 1999 (E1585, E1587, E1589, E2588, E5592, E1594, E2598, and E1599). All patients were ECOG PS 0–2. Results: Data on both ethnicity and survival were available on 2245 patients of whom 194 were AA (8.6%). There was no difference in survival between AA and non-AA patients (median survival 8.3 months versus 7.8 months, p=0.69 by log-rank.) There was a statistically significant correlation between AA ethnicity and poor performance status (PS 2 patients 17% vs. 6%, p<0.001 by chi-square) and between AA ethnicity and increased weight loss (>10% weight loss 18% vs. 10%, p=0.001). Conclusions: AA patients with advanced NSCLC enrolled on first-line ECOG studies had similar survival to non-AA patients. However, AA ethnicity was associated with worse performance status and a higher percentage of weight loss at diagnosis. This suggests that AA patients may present later in their disease course, though in the ECOG data set, this did not significantly impact upon survival. Our analysis does not address potential barriers to participation in clinical trials based upon ethnicity. No significant financial relationships to disclose.
2D-DIGE As a Tool to Analyze Lot-to-Lot Consistency of Complex Therapeutic Products Such As BAX 855, a PEGylated Recombinant FVIII
Authors: Hanspeter Rottensteiner, Christina Monetti, Herbert Gritsch, Alfred Weber, Hartmut J. Ehrlich, Friedrich Scheiflinger, Peter L Turecek
Journal: Blood (2011)
Phase II study of irinotecan and bevacizumab plus alternate day S-1 as second-line treatment in patients with metastatic colorectal cancer.
Authors: Chihiro Tanaka, Chu Matsuda, Ken Kondo, Yukihiko Tokunaga, Takao Takahashi, Chihiro Kosugi, Hiroyoshi Takemoto, Shigeyoshi Iwamoto, Koji Oba, Junichi Sakamoto, Hideyuki Mishima
Journal: Journal of Clinical Oncology (2016)

749 Background: The recommended dose of combination chemotherapy of irinotecan, bevacizumab and oral S-1 is 100mg/m 2 , 5mg/kg and 80-120mg/body respectively. To evaluate whether the dose of irinotecan could be raised to 150mg/m 2 with modified administration of S-1, we have conducted a phase II study of irinotecan and bevacizumab plus alternate day S-1 in patients with metastatic colorectal cancer (UMIN000008947). Methods: Patients with metastatic colorectal cancer after failure with first-line treatment of oxaliplatine and fluoropyrimidine were enrolled. Irinotecan (150 mg/m 2 ) and bevacizumab (5mg/kg) were given intravenously on day 1. Oral S-1was administered on alternate days at a dose of 40-60mg twice a day. Cycles were repeated every two weeks. Results: A total of 51 patients were evaluated in the first fouur cycles. Grade 3 and 4 neutropenia were 10% (10/51) and 13.7%(7/10), grade 3 and 4 thrombocytopenia were 0%(0/51) and 2.0% (1/51). Grade 2 and 3 mucositis were 13.7% (7/51) and 3.9% (2/51). Grade 2 and 3 nausea were 11.8% (6/51) and 2.0% (1/51). Grade 2 and 3 diarrhea were 17.6% (9/51) and 15.7% (8/51). The relative dose intensities were 84.8% for irinotecan, 87.5% for bevacizumab, and 84.8% for S-1 respectively in the first four cycles. Conclusions: Our data suggest that irinotecan (150 mg/m 2 ) and bevacizumab was administered safely with alternate day S-1 as second-line tratment in patients with metastatic colorectal cancer. Clinical trial information: 000008947.
Influence of tumor infiltrating Foxp3<sup>+</sup> regulatory T cells on prognosis in resectable gastric cancer.
Authors: J. M. Kwon, M. S. Cho, E. M. Nam, J. Y. Jo, S. Lee
Journal: Journal of Clinical Oncology (2011)

4117 Background: Host immune reactions against cancers are often characterized by the presence of tumor infiltrating lymphocytes (TILs). Among TILs, Foxp3+ regulatory T cells (Tregs) are thought to decrease the immune response. However, the prognostic value of Tregs in cancer is not clear. Gastric cancer is the most common cancer in Korea and many patients with gastric cancer relapse despite surgical resection. The aim of this study was to determine the influence of Foxp3+ Tregs on prognosis in resectable gastric cancer. Methods: Tissues from 179 gastric cancer patients who underwent surgical resection were analyzed immunohistochemically for CD3+, CD8+, and Foxp3+ in relation to clinical outcome. The cases with stage IA were excluded. The number of positively stained lymphocytes was counted. Results: The high Foxp3+ Tregs group was associated with negative regional node metastasis (P=0.02) and early stage at diagnosis (P=0.01). There was a positive correlation between the number of Foxp3+ Tregs and CD8+ T cells (r=0.43, and P<0.01). The high CD8+ T cells group was also associated with negative regional node metastasis (P<0.01) and early stage (P=0.02). The disease-free survival was better in the high Foxp3+ Tregs group (P=0.01) and the high CD8+ T cells group (P=0.01). The Foxp3+ Tregs/CD3+ T cell ratios did not have any influence on the outcomes. But there were significant differences in nodal involvement (P=0.01) and stage(P=0.02) according to CD8+ T cells/CD3+ T cells ratios, and disease-free survival was longer in high CD8+ T cells/CD3+ T cells (P=0.02). On multivariate analysis for disease-free survival, the number of Foxp3+ Tregs (P<0.01) and TNM stage (P<0.01) were statistically significant variables. Conclusions: These results showed that a high number of intratumoral Foxp3+ Tregsis related to longer disease-free survival and is an independent prognostic factor for a favorable outcome. As a result, the level of Foxp3+ Tregsmight be a prognostic indicator for high risk of relapse and, thus, a need for more aggressive adjuvant therapy.
A retrospective study analyzing the association between tumor response (TR) according to Mcdonald criteria (MC) on MRI and survival (OS) in patients (PTS) with glioblastoma (GBM) treated with antiangiogenic drugs (AD).
Authors: G. Lombardi, F. Zustovich, A. Della Puppa, M. P. Gardiman, P. Farina, C. Carollo, L. Landi, D. Cecchin, R. Bertorelle, F. Berti, P. Fiduccia, D. D'Avella, V. Zagonel
Journal: Journal of Clinical Oncology (2011)

e12514 Background: In high-grade gliomas, MC using two-dimensional measurement is the most widely used method for assessing TR to treatment on MRI. With the recent introduction of AD that affect the permeability of tumor vasculature there are many doubts about the validity of MC mainly due to the probability of having a pseudo-response. We analyzed PTS treated with AD to evaluate the association between TR according to MC and survival (OS) (from antiangiogenic treatment to death). Methods: Retrospectively, we examined 48 consecutive PTS with GBM treated with AD: bevacizumab (20 PTS), sorafenib (27 PTS) and cilengitide (1 PT). All patients underwent MRI assessments according to MC every two months or when clinically indicated. Univariate and multivariate analyses of patient, disease and therapy characteristics were used to identify factors predicting OS. Results:13 (27.1%) and 35 PTS (72.9%) performed an AD as third or second line chemotherapy, respectively. 5 PTS performed a subsequent therapy after progression during antiangiogenic treatment. Median age was 55.1, ECOG performance status (PS) was 0 in 8 PTS, 1 in 19 PTS, 2 in 18 PTS and 3 in 3 PTS. After two months of treatment 25 PTS (52.1%) obtained a disease control (DC): stable disease (22 PTS) or partial response (3 PTS). 23 PTS (47.9%) obtained a progression disease. The median OS for all PTS was 6.2 months (CI 95% 4.9 – 7.6); the median time-to-progression from AD was 2.5 months. According to univariate analysis, good PS and DC were related to a longer OS (p=0.006 and 0.01, respectively). On multivariate analysis the same variables were found to be independent favourable predictors for OS: good PS (p=0.05; HR=0.08, CI 95% 0.01-0.5) and DC (p=0.02; HR=0.4, CI 95% 0.2-0.8). Conclusions: PTS with a good PS and DC on MRI according to MC after two months of antiangiogenic treatment have a better chance of prolonged OS. MC might be a valid method to assess the effectiveness of AD, especially in clinical trials.
Assessment of association between BRAF mutation status in melanoma tumors and response to ipilimumab.
Authors: J. Jackson, G. Whitney, O. Hamid, H. Schmidt, S. D. Chasalow, S. Alaparthy, Y. Bao, V. Shahabi
Journal: Journal of Clinical Oncology (2011)

2587 Background: Ipilimumab, a fully-human monoclonal antibody against CTLA-4, has demonstrated significant improvement in overall survival (OS) in previously treated advanced melanoma patients. The BRAF inhibitor, RG7204 (also known as PLX4032) has shown high objective response rates (up to 78%) in melanoma patients harbouring the BRAFV600E mutation but not in patients without the mutation (e.g. wild-type BRAF). As an immune potentiator, it is likely that ipilimumab acts independently of BRAF kinase mutations and similar activity in BRAF mutation positive and negative patients is expected. This retrospective analysis was carried out to assess if BRAF status affects the clinical activity of ipilimumab. Methods: CA184-004 was a randomized, double-blind, multicenter phase 2 trial of 82 previously treated or untreated patients with unresectable stage III or stage IV melanoma. Patients received ipilimumab 3 or 10 mg/kg every 3 weeks for 4 doses followed by maintenance dosing in eligible patients. The BRAFV600E mutation status for 80 patients was determined in tumor biopsies by PCR-based assays. Data on disease control were available for 69 patients with evaluated BRAFV600E mutation status. Analysis of the association of the BRAFV600E mutation status and safety of ipilimumab were not performed. Results: Rates of objective responses and stable disease in patients with BRAFV600E mutation positive tumors (0% CR, 10% PR, 20% SD) were comparable to those in patients with the wild-type gene (3.2% CR, 9.7% PR, 22.6% SD). Eleven patients displayed durable disease control (DDC: Complete response, partial response or stable disease lasting ≥ 24 weeks) of which 6 (55%) had BRAFV600E mutation positive tumors and 5 (45%) did not. In the 48 patients showing no DDC, the mutation frequency was 50%. Conclusions: In this study, no association between BRAFV600E mutation status of melanoma tumors and DDC after treatment with ipilimumab was detected at any dose.
Understanding patterns of genetic risk evaluation (GRE) referral and uptake in patients (pts) with epithelial ovarian cancer (EOC).
Authors: Yu Cao, Robert Morgan, Lucille A. Leong
Journal: Journal of Clinical Oncology (2016)

254 Background: EOC is the most common cause of gynecologic cancer death and fifth leading cause in women. ~20% cases are due to identifiable genetic risk (BRCA1/2 in 15%, Lynch syndrome 2%, other germline mutations 6%). Since 2013, National Comprehensive Cancer Network (NCCN) guidelines recommend all women with EOC be referred for GRE, to optimize risk stratification, genetic testing decisions, clinical management, with goal to reduce mortality. Yet physicians under-refer and pts under-utilize genetic services. Identifying clinically meaningful quality metrics and associated adherence is critical to improving cancer care. We aimed to characterize patterns of GRE referral and uptake in pts with EOC. Methods: Completed GRE was tracked in pts with EOC 2009-2015, using City of Hope (COH) cancer registry and genetics appointments system. Targeted chart review was done for pts identified as without GRE completion in 2014 (18 cases), 2015 (2 cases). Results: 91/191 (48%) analytic pts with EOC from 2009-15 registry data were identified with completed GRE. Targeted chart review of non-adherent cases: 2015: 1/2 pts did not complete GRE (at COH primarily for surgery). 2014: 7/18 pts documented with completed GRE; Pareto chart was constructed for 11 unaccounted non-adherent pts: see Table. Conclusions: 2014-15 GRE completion rate (68%) suggests a higher GRE referral rate, above that reported in literature (&lt;35%). In 2014, 75% pts seen by medical oncology had documented reasons for not completing GRE; 2/11 pts who did not complete GRE lacked a documented reason (see chart). Inability to track paper referrals (used prior to 2014) limited analysis. Promoting multidisciplinary educational interventions for specific audiences, collaboration between community and COH referring physicians, studying physician perceptions of GRE risks/benefits/barriers, EHR enhancements (e.g. creating a GRE check-off item, or documentation aids), and pt-centered assessment of GRE awareness and utilization may improve adherence with NCCN guidelines to 100% (CA33572). [Table: see text]
RAS mutations and their correlation with survival of patients with advanced pancreatic adenocarcinoma.
Authors: Thiago Lins Almeida, Jessica Ribeiro Gomes, Marcel Cerqueira Cesar Machado, Antonio C. Buzaid, Fernando C. Maluf
Journal: Journal of Clinical Oncology (2015)

325 Background: The prognosis of pancreatic adenocarcinoma (PA) remains poor despite FOLFIRINOX and nab-paclitaxel-gemcitabine based chemotherapy. The epidermal growth factor receptor (EGFR) has a major role in pancreatic cancer carcinogenesis.The RAS status showed to be a predictive factor for response to anti-EGFR therapy in colon cancer. We aim to analyze the K-RAS and N-RAS status in PA and its prognostic impact. Methods: Retrospective analysis included 24 patients with metastatic (67%) or locally advanced (29%) PA at diagnosis (AEMOC, Brazil). K-RAS and N-RAS profile were performed by polymerase chain reaction and bidirectional sequencing (codons 12, 13, 61, 117, 146). The results were then analyzed in regards to overall survival (OS) and progression-free survival (PFS) in PA. Results: The sample showed: median age of 63 years (28-86), 62.5% male, 45.8% smoker, head site (67%), ductal (68%), and mild differentiation features (45%). The first-line therapy was FOLFIRINOX (62.5%) and gemcitabine (33.3%). The median PFS and OS were 6.5 and 13 months (mo), respectively. Nineteen patients (79.1%) presented mutation in K-RAS: four c.35G&gt;A (G12D), four c.34G&gt;C (G12R), four c.35G&gt;T (G12V), three c.35G&gt;C (G12A), one c.437C&gt;T (A146V), and one c.34G&gt;T (G12C). Mutation in N-RAS (c.38G&gt;A (G13D) was detected in only one patient (4%). The only independent factor for survival was K-RAS status: the c.35G&gt;A (G12D) polymorphism yielded worse PFS and OS when compared to non-c.35G&gt;A (G12D) mutation: 3 vs 7 mo [HR 0.25, 95% CI, (0.04–1.63)] for PFS (p&lt;0,0043) and 3.5 vs13 mo [HR 0.17, 95% CI, 0.01-1.58)] for OS (p&lt;0,0001), respectively. Conclusions: K-RAS was the only prognostic factor for PFS and OS, with the polymorphism c.35G&gt;A (G12D) being related to a worse prognostic. Further studies are necessary to better evaluate whether K-RAS and N-RAS status is prognostic and/or predictive factor.
Outcomes following involved field radiotherapy (IFRT) with or without rituximab in patients (Pts) with limited-stage low-grade non-Hodgkin lymphoma (NHL) staged with CT versus PET.
Authors: J. N. Lukens, S. Nasta, E. Glatstein, J. P. Plastaras
Journal: Journal of Clinical Oncology (2011)

8065 Background: To evaluate whether staging with PET translates into improved disease free survival (DFS) for pts with early stage FL, we performed an analysis of CT and PET staging for pts with early-stage, low-grade NHL treated with IFRT. A secondary objective was to evaluate whether the addition of Rituximab to IFRT improves DFS in this subset of pts. Methods: Pts with Stage I or II low-grade NHL treated with initial IFRT at our institution between 1992 and 2009 were identified. A retrospective analysis was undertaken to evaluate staging by CT versus PET. DFS was defined as time from initiation of IFRT to progression, death or last contact alive. Results: 44 pts were identified; 17 staged by CT, and 27 by PET. The CT-staged pts were more frequently Stage I (94% CT vs 70% PET, p=0.12). The groups were equally matched by FLIPI score, with most pts falling in the low-risk group. Median follow-up for those staged by CT was 12.4 years, compared to 4.9 years for those staged by PET. DFS was better for those staged with CT compared to PET, but this difference did not reach statistical significance (88% vs 68% at 5 years, respectively, p=0.14). Twelve pts received 4 doses of adjuvant Rituximab following IFRT; significantly more of these pts were Stage II compared to those who did not receive Rituximab (50% versus 9%, respectively, p=0.007). With a median follow-up of 5.2 years, DFS was significantly worse in Rituximab treated pts compared to those who did not receive Rituximab (5 year DFS of 45% vs 87%, respectively, p=0.04). Conclusions: In this retrospective analysis of low-grade early stage NHL pts treated with initial radiation, a significant difference in DFS based on staging by CT versus PET was not detected. However, a larger percentage of pts staged by PET were Stage II compared to those staged by CT, a potential confounder. The addition of Rituximab to IFRT in this group of pts yielded worse DFS, although this likely reflects a selection bias of higher stage patients in this retrospective study. A randomized controlled trial of IFRT with or without Rituximab, stratified by Stage, is needed to establish the role of Rituximab in this patient population.
Induction of immunogenicity after irradiation of renal carcinoma cell lines.
Authors: Gregory Janda, Mohammad Habiby, Jan Hoffmeyer, Michelle Romano, Graham Walter Warren, Thomas Schwaab
Journal: Journal of Clinical Oncology (2013)

417 Background: Cellular vaccine therapy in RCC has shown disappointing clinical and immunologic results. Poor immunogenicity of tumor associated antigens (TAAs) and their restricted expression may account for a lack of antigen-specific T cell responses. Irradiation induces TAA expression and enhances the immunogenicity of tumor cells. We investigated the influence of irradiation on the immunogenicity of RCC tumor cells. Methods: Six (ACHN, 786-0, 769-P, Caki-1, A-498, A-704) commercially available RCC cell lines were cultured and subsequently exposed to 0, 12, or 16 Gy of ionizing radiation. Alive cells and supernatant were isolated at 2, 24, and 48 hours after irradiation. The TAA expression (CA9, 5T4, MUC-1, NY-ESO-1, HSP-70) was assessed using flow cytometry. Expression relative to control (ERC) was calculated. Cytokine analysis was performed using a 9-plex Luminex human cytokine assay and reported as the mean concentration of all cell lines. Results: CA9, 5T4, and NY-ESO-1 demonstrated a marked increase in expression in 4 of 6 cell lines while MUC-1 and HSP-70 had increased expression in all cell lines after irradiation. The range and mean ERC across all six cell lines at 48 hours after irradiation with 16 Gy are shown in the table. Il-2, Il-6, IFN-gamma and Il-4 increased in irradiated cells with peak concentrations vs. control of: 0.55 vs. 0.47, 1631 vs. 1358, 10.06 vs. 7.61, 1.07 vs. 0.77 pg/ml, respectively. Conclusions: Irradiation of RCC cell lines increased TAA expression in the majority of cell lines. Immunomodulatory cytokines were induced with radiation. These data suggest that RCC tumor irradiation may provide a novel means to increase the immunogenicity and subsequent efficacy of RCC-targeted immunotherapy. [Table: see text]
The metabolic risk profile of breast cancer survivors 2 to 6 months post-chemotherapy.
Authors: E. M. Guinan, J. M. Hussey, J. M. Walsh, M. J. Kennedy, E. M. Connolly
Journal: Journal of Clinical Oncology (2011)

e19612 Background: Overweight and obesity are associated with poor outcomes for patients with breast cancer. Physical inactivity coupled with weight gain during treatment place breast cancer survivors at risk of developing obesity related problems including the metabolic syndrome (MetSyn). We report baseline findings of an ancillary study to an ongoing randomised controlled trial (PEACH trial) (Walsh J.M. et al. 2010 Pragmatic Randomized Trial of Individually Prescribed Exercise versus Usual Care in Heterogeneous Cancer Survivor Population. A Feasibility Study. PEACH: Prescribed Exercise After Chemotherapy. BMC Cancer. 10[42]) examining the effect of exercise on the metabolic risk profile of breast cancer survivors, 2-6 months post chemotherapy. Methods: Breast cancer survivors who consented to partake in the PEACH trial were requested to participate. The five clinical features of the MetSyn were measured: waist circumference, resting blood pressure, triglycerides, high-density lipoprotein cholesterol and fasting glucose, along with a lipid profile and C – Reactive Protein (CRP). Insulin resistance was estimated by the homeostatic model assessment (HOMA) index. Subjects were classified with the MetSyn if they presented with three of the five clinical features. Results: Eighteen subjects (mean (±SD) age 46.17±7.93 years) have completed assessments, 44% were overweight and 28% obese. Four subjects were classified with the MetSyn and a further 7 presented with two clinical features. Fourteen subjects (77.8%) were centrally obese with a mean waist circumference of 87.6±9.89cm. The mean total cholesterol level was 5.37±1.02 mol/L, with 11 subjects (61.1%) presenting with measurements above 5.2mol/L. The mean HOMA score was 1.93±1.16. CRP levels were low at < 10.00mg/L. Conclusions: Results indicate that breast cancer survivors present with an unfavourable metabolic profile in the six months following chemotherapy. The high percentage of subjects presenting with an elevated waist circumference is concerning and may contribute to further development of MetSyn. Interventions to target this problem including diet and exercise are warranted in this population.