tbuckley/cabot-search huggingface dataset:
A randomized phase II, open-label study of sipuleucel-T with concurrent or sequential abiraterone acetate (AA) in metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Eric Jay Small, Raymond Lance, Thomas A. Gardner, Lawrence Ivan Karsh, Andrew Stubbs, Candice McCoy, Todd DeVries, Charles H. Redfern, Neal D. Shore
Journal: Journal of Clinical Oncology (2013)

114 Background: Sipuleucel-T and AA are both FDA approved for mCRPC. Given that androgen deprivation therapy is immunostimulatory, increased suppression of the androgen axis with AA could provide synergy in combination with sipuleucel-T; however, AA is given with prednisone (P), which may be immunosuppressive. In order to evaluate the impact of concurrent AA + P on product characteristics, a study of sipuleucel-T with concurrent or sequential AA + P was undertaken. Methods: Pts aged ≥18 yrs with asymptomatic or minimally symptomatic mCRPC, and ECOG PS 0/1 were randomized (1:1) to sipuleucel-T (3 infusions at approx 2-week intervals) with up to 26 weeks of AA + P (AA 1000mg QD + P 5mg BID) starting 1 day after the first sipuleucel-T infusion (concurrent arm) or at week 10 (sequential arm). The primary endpoint was cumulative CD54 upregulation (measure of antigen presenting cell activation); secondary and tertiary endpoints included CD54 + cell and total nucleated cell (TNC) counts (measures of product potency), safety and efficacy. Results: 29 pts have been enrolled. 16 pts in the concurrent arm (A) and 13 pts in the sequential arm (B) have completed sipuleucel-T treatment at the time of this interim analysis (7 Sept 2012). 27/29 pts received all 3 infusions of sipuleucel-T; 2 pts (both arm A) received only 1 infusion due to insufficient TNC count (n=1) and disease progression 8 days after randomization (n=1). No significant differences in median cumulative CD54 upregulation (31.6 vs 36.6) and CD54 + count (1.9 vs 2.1 x10 9 ) were observed between arms A and B, respectively. Increased CD54 upregulation with the 2 nd and 3 rd treatments were indicative of a prime boost effect in both arms. Similarly, the TNC profile over time was similar for both arms. The overall incidence of adverse events (AEs) was similar in arms A (81%) and B (77%). Common all-grade AEs included muscle spasms (31% vs 23%), oral paresthesia (19% vs 31%), chills (31% vs 8%) and cough (19% vs 15%). Conclusions: These data suggest that sipuleucel-T can be manufactured during treatment with AA + P with product potency and prime boost similar to that of sipuleucel-T alone. Clinical trial information: NCT01487863.
Identifying patients at increased cancer risk: Validation of the Health Heritage risk assessment and decision support tool.
Authors: Leigh A Baumgart, Kristen J Postula, Peter J Hulick, William A Knaus
Journal: Journal of Clinical Oncology (2014)

277 Background: Family history is critical to assess risk for cancer and inherited cancer syndromes. National Comprehensive Cancer Network (NCCN) guidelines are available to aid in identification and management of at-risk patients, but the guidelines are complex and ever-changing, hindering optimal use. This leads to under-recognition and mismanagement of high-risk patients. To address this need, we have developed and have fully implemented Health Heritage (HH), a web-based risk assessment and decision support tool. HH combines clinical data automatically extracted from a patient’s EHR with information entered by patients and shared between family members to provide personalized risk assessment and recommendations related to common cancers. This study aims to validate HH’s ability to properly identify patients who meet NCCN guidelines for a genetics evaluation and to stratify cancer risk. Methods: We performed a retrospective chart review of 100 patients seen at an adult genetics clinic in 2012. Relevant personal and family medical history and genetic test results were entered into HH. Independent of the HH assessment, each patient’s information was reviewed by a genetic counselor to assess fulfillment of NCCN guidelines for a genetics evaluation. A subset of records was reviewed to compare cancer risk stratification between HH and a medical geneticist. Results: 87 patients met NCCN guidelines for a genetics evaluation for breast/ovarian cancer, 2 for colorectal cancer, and 3 for multiple cancers; 8 patients did not meet guidelines. HH had a sensitivity of 98% and specificity of 88% in identifying patients who met these guidelines. For patients at increased risk for breast, ovarian, or colorectal cancer as determined by a medical geneticist, HH agreed 83%, 86%, and 75% of the time, respectively. Discordances were the result of both complex clinical situations better handled by the geneticist and also HH’s strict adherence to incorporating all information. Conclusions: Health Heritage is a highly sensitive tool for identifying at-risk patients appropriate for a genetics evaluation and its risk stratification is complementary in high risk settings requiring management recommendations.
Oncology comanagement agreements (CMA) and quality improvement.
Authors: David Haggstrom, Malaz Boustani, Jose Maroun Azar, Andrew Greenspan, Holly Goe, Larry Dean Cripe
Journal: Journal of Clinical Oncology (2014)

55 Background: At Indiana University Health, an integrated health care delivery system, an Oncology CMA was implemented in 2013 to provide a framework for engagement between administrators and physicians to improve the value of oncology care. Methods: A collaborative process was used to establish shared goals, measures for performance, and set target goals. For efficiency goals, a system redesign approach was taken. Project teams were organized to develop and implement strategies to achieve goals. Experts in implementation science consulted with individual project teams. Financial incentives were distributed across projects. Final performance measures were assessed across the oncology service line. Results: See Table. Conclusions: Overall, the Oncology CMA positively affected the value of care provided by medical oncologists. The level of physician engagement was variable, although clinical and financial benefits accrued to all members of the practice. Based upon the positive contribution of implementation scientists the CMA in 2014 was modified to create greater support for the design, implementation, and assessment of project goals and plans, It is anticipated that future years will include an institutionalized core of implementation scientists and a steering committee to oversee an ongoing discussion of goals and resource allocation. [Table: see text]
Retrospective review of extrapulmonary small cell carcinoma and prognostic factors.
Authors: J. E. Brammer, P. D. Lulla, M. A. Bilen, G. R. Lynch
Journal: Journal of Clinical Oncology (2011)

7075 Background: Extrapulmonary small cell carcinoma (EPSCC) is a rare cause of malignancy, with an incidence of approximately 1,000 cases per year. Overall survival (OS) in EPSCC is poor with median survival of 9.8 months in extensive disease (ED) and 34 months in limited disease (LD). Further characterization of EPSCC, prognostic factors, and response to treatment is critical for future management of this tumor type in a more heterogeneous population such as in the Texas Medical Center. Methods: Charts of 53 cases of EPSCC between 2000-2010 within the 3 affiliated hospitals of Baylor College of Medicine were reviewed. Univariate survival analysis was perfomed on dichotomized clinical and demographic data and represented as Kaplan-Meier curves. Multivariate analysis was performed utilizing Cox proportional-hazards regression model. Results: Cases of EPSCC were stratified based on organ system and stage, and were computed as shown in the table. ED (p=0.001), sodium <138 (p=0.02), and nongenitourinary (GU) EPSCC (p=0.04) were all significant predictors of OS on a univariate analysis. In a multivariate analysis, ED was statistically significant in predicting OS (p=0.014). Non-GU EPSCC was more likely to be ED at diagnosis than GU EPSCC (p=0.027). Conclusions: Unique to our study, GU EPSCC was more common than in previous reviews. Additionally, non-GU EPSCC was noted to be a poor predictor of OS and had worse survival than in previous series. Disease stage also negatively predicted OS. In our population, hyponatremia was associated with poor prognosis; which is intriguing given that it has been associated with poorer prognosis in small cell lung cancer. Prospective data is needed to further evaluate these trends. Disease location No. of patients (%) Limited disease (%) Extensive disease (%) Median survival (months) GU 14 (26) 13.1 Kidney 1 1 0 Bladder 11 9 2 Prostate 2 0 2 GI 8 (15) 1.7 Esophagus 2 1 1 Stomach 1 0 1 Pancreas 3 0 3 Gallbladder 1 0 1 Colon 1 0 1 Head and Neck 6 (11) 4 Larynx 2 1 1 Pharynx 1 0 1 Thyroid 1 1 0 Salivary glands 2 1 1 CUP 21 (40) 1.5 Liver 5 3 2 Lymph nodes 1 0 1 Other 15 3 12 Breast 1 (2) 1 0 73 Gyn 3 (6) 12.8 Cervix 3 2 1 Total 53 (100) 23 (43) 30 (57) 4.7 (0.3-99) Median survival p=0.001 14.5 3.7 Abbreviation: CUP, carcinoma of unknown primary.
Patients with metastatic papillary renal cell carcinoma (RCC) who may benefit from sunitinib therapy (tx): Results from an international metastatic RCC database.
Authors: Daniel Kejzman, Maya Gottfried, Natalie Maimon, Hans J. Hammers, Mario A. Eisenberger, Michael Anthony Carducci, Victoria J. Sinibaldi, Victoria Neiman, Eli Rosenbaum, David Sarid, Eliahu Gez, Avivit Peer, Avishay Sella, Wilmosh Mermershtain, Keren Rouvinov, Raanan Berger, Jae-Lyun Lee
Journal: Journal of Clinical Oncology (2014)

486 Background: The VEGFR inhibitor sunitinib is a standard tx for metastatic clear cell RCC. Data on the activity of sunitinib in metastatic non clear cell RCC, is limited by small or heterogeneous (mixed histology or targeted therapies) studies, that revealed a lower antitumor activity than in patients with clear cell histology. We aimed to analyze the activity of sunitinib in a large international cohort of patients with metastatic papillary RCC, and to characterize patients who may benefit for this therapy. Methods: Records from metastatic papillary RCC patients treated with sunitinib in 10 centers across 3 countries were retrospectively reviewed. Univariate and multivariate analyses of association between clinicopathologic factors and clinical outcome were performed using Cox regression. Results: Between 2004-2013, 74 patients (median age 60, 68% male) with metastatic papillary RCC were treated with sunitinib. 78% had a prior nephrectomy. HENG risk was good 11%, intermediate 56%, and poor 33%. 21% were active smokers, and 31% users of angiotensin system inhibitors. 24% and 41% had liver and bone metastases, respectively. 55% had a pre-treatment neutrophil to lymphocyte ratio (NLR) &gt;3. 40% had dose reduction/treatment interruption. Sunitinib induced hypothyroidism and hypertension (HTN) occurred in 30% and 43%, respectively. 70% achieved a clinical benefit (partial response + stable disease), while 30% had disease progression within the first 3 months of therapy. Median progression free survival (PFS) and overall survival (OS) were 5 and 12 months, respectively. 27% had a PFS ≥ 1 year, and 26% survived ≥ 2 years. Factors associated with PFS were sunitinib induced HTN (HR 0.31, p=0.002), pre-treatment NLR &gt;3 (HR 5.3, p=0.001), and active smoking (HR 2.5, p=0.01). Factors associated with OS were sunitinib induced hypothyroidism (HR 0.4, p=0.024), past nephrectomy (HR 0.41, p=0.02), pre-treatment NLR &gt;3 (HR 2.25, p=0.036), and active smoking (HR 2.3, p=0.027). Conclusions: Clinicopathologic factors may be used to identify patients with metastatic papillary RCC who may benefit from sunitinib tx. A prolonged PFS and OS were noted in 26-27% of patients.
Association of RecQ1 A159C polymorphism with overall survival of patients with resected pancreatic cancer: A replication study in RTOG 9704.
Authors: D. Li, J. Moughan, C. H. Crane, J. P. Hoffman, W. Regine, R. A. Abrams, H. Safran, G. M. Freedman, C. Guha, J. L. Abbruzzese
Journal: Journal of Clinical Oncology (2011)

156 Background: To confirm whether a previously observed association between a DNA repair gene and clinical outcome of resectable pancreatic cancer patients treated with preoperative chemoradiation is reproducible in another patient population. Methods: We evaluated the RecQ1 A159C variant (rs13035) in patients with resected pancreatic cancer who were enrolled on the RTOG 9704 trial of 5FU-based chemoradiation preceded and followed by 5-FU or gemcitabine. DNA was extracted from paraffin-embedded tissue sections and genotype was determined using the Taqman method. A multivariate Cox proportional hazards model was used to determine if there is a correlation between genotype and overall survival (OS). Models were built using the stepwise selection procedure. The following variables were included in the model: genotype, treatment arm, age, gender, race, nodal involvement, tumor diameter, and surgical margin status. Results: A total of 154 out of 451 eligible patients were evaluated for the RecQ1genotype. There was no significant difference in baseline characteristics and overall survival time between patients who were and were not evaluated for the RecQ1genotype. In the 154 evaluated patients, the genotype distribution followed the Hardy-Weinberg Equilibrium, i.e. 37% had genotype AA, 43% AC, and 20% CC. The RecQ1 variant AC/CC genotype carriers were more likely to be node positive compared to the AA carrier (p=0.03). The median survival times (95% C.I.) for AA, AC, and CC carriers were 1.72 (1.36, 2.17), 1.57 (1.18, 1.80), and 1.18 (0.86, 1.75) years, respectively. On multivariate analysis, patients with the AC/CC genotypes were more likely to die than patients with AA genotype (HR=1.54, 95% C.I. = [1.07, 2.23], p=0.022). This effect is more definitive for patients on the 5-FU arm (n=82) (HR=1.64, 95% C.I. = [0.99, 2.70], p=0.055) than for patients on the gemcitabine arm (n=72, HR=1.46, 95% C.I. = [0.81, 2.63], p=0.21). Conclusions: Results of this study suggest that the RecQ1 A159C genotype is a prognostic or predictive factor for resectable pancreatic cancer patients who are treated with adjuvant chemoradiation. No significant financial relationships to disclose.
Secondary nonbreast malignancies (SNBM) after primary breast cancer (BC).
Authors: Joyce Georges Habib, Janet L. Espirito, Robyn K. Harrell, Brian Turnwald, Joyce O'Shaughnessy, Debra A. Patt
Journal: Journal of Clinical Oncology (2014)

112 Background: BC survivors are at higher risk of developing SNBM due to treatment effects and shared behavioral and genetic factors. Associations between histologic subtypes of primary BC and secondary endometrial or ovarian cancer have been reported. Less is known about subtype-specific associations with other secondary solid tumors. We aimed to determine the prevalence of SNBM across US Oncology practices and what subtype-specific associations, if any, exist between primary BC and SNBM. Methods: We conducted a retrospective database analysis identifying BC patients (pts) diagnosed between 01/2007 and 05/2013. SNBM were ascertained from codified fields in pts electronic records. Age at BC diagnosis, BC stage, estrogen receptor (ER), progesterone receptor (PR), HER2 status, BMI and smoking history were collected. Chi-square tests were used to compare categorical variables. Logistic regression was used to predict likelihood of secondary malignancies in separate multivariate models. Results: 105,795 pts with stage 0-IV BC were identified. 2,237 (2.1%) were diagnosed with ≥ 1 SNBM. Mean age at diagnosis and follow-up were 59.5 and 2.6 years respectively. Pts with SNBM were more likely to have: older age, ≥ stage I, HER-2 negative disease, BMI ≥25 and past/current smoking history. SNBM were most commonly: Non-small cell lung cancer (NSCLC) (n=346), colorectal (CRC) (n=250), uterine (n=192), ovarian (n=130), thyroid (n=106) and kidney cancer (n=73). No associations were found between BC subtypes and ovarian, uterine, thyroid or NSCLC. Significant positive and negative associations between triple-negative breast cancer (TNBC) and secondary CRC and kidney cancer, respectively, were noted. In multivariate analysis, TNBC was predictive of secondary kidney cancer (OR 2.00, p=0.019). TNBC (OR 0.47, p=0.009), age ≤55 (OR 0.27, p&lt;0.0001) and BMI ≤30 (OR 0.64 for BMI 25-30, p=0.019) were negative predictors of secondary CRC. Conclusions: Our study is the first to report direct and inverse associations between primary TNBC and secondary kidney and CRC, respectively. The short follow-up precludes treatment-related effects. Results may potentially be attributed to genetic, environmental or lifestyle factors and warrant further research.
Steroid metabolism gene CYP17, CYP1A1*2B, CYP1A1*2C and risk of breast cancer in Mexican women
Authors: M. Moreno, E. Sarti, N. Herrera, J. Ramirez, V. Robles, R. Tapia
Journal: Journal of Clinical Oncology (2008)

1524 Background: Breast cancer is the 2nd cause of women mortality in Mexico, increasing this rate over the past ten years. Functional polymorphisms in genes encoding steroid metabolizing enzymes may contribute to this understanding by serving as surrogate markers for altered long-term hormone exposure and, thus, as biomarkers of individual breast cancer susceptibility. In order to determine the impact of CYP17 and CYP1A1 genotypes on the risk to develop breast cancer, we realized a case-control study of breast cancer patients and healthy controls among women invited to participate in this study from a Public Hospital in Mexico City. Methods: 90 breast cancer patients and 87 healthy controls, who had given their informed consent were included. All breast cancer patiens had pathologically confirmed as breast carcinoma, all were diagnosed and treated at the “1o de Octubre” hospital. Epidemiological questionnaire and genotyping data were obtained. CYP17 and CYP1A1 were genotyped using PCR/restriction fragment lenght polymorphism. For CYP17 a single nucleotide polymorphism at the 5‘untraslated region of the CYP 17 was done (MspA1 restriction sitie). Two polymorphism for CYP1A1 were analized: 2455 A>G (CYP1A1*2B) and 4889 A >G (CYP1A1 *2C). Results: We found an increased risk of breast cancer in women carrying the allele CYP1A1*2B. The odds ratio was 2.6 (CI95%= 1.08–6.4; p <0.032). In the stratified analysis, this risk was increased when CYP1A1*2B and CYP1A1*2C were presented together. The odds ratio was 3.4 (CI95%= 1.2- 9.3; p<0.017). Regarding the CYP17 genotype, it was not preliminary associated with breast cancer risk. Conclusions: These results suggest that CYP1A1*2B and CYP1A1*2C genotype could be a biomarker for breast cancer risk in our general Mexican population. It‘s necesary to increase the sample size and add others genes encoding steroid metabolizing enzymes. No significant financial relationships to disclose.
Epithelial Fli1 deficiency drives systemic autoimmunity and fibrosis: Possible roles in scleroderma
Authors: Takehiro Takahashi, Yoshihide Asano, Koji Sugawara, Takashi Yamashita, Kouki Nakamura, Ryosuke Saigusa, Yohei Ichimura, Tetsuo Toyama, Takashi Taniguchi, Kaname Akamata, Shinji Noda, Ayumi Yoshizaki, Daisuke Tsuruta, Maria Trojanowska, Shinichi Sato
Journal: The Journal of Experimental Medicine (2017)

Systemic sclerosis (SSc), or scleroderma, is a multisystem autoimmune disorder characterized by vasculopathy and fibrosis in the skin and internal organs, most frequently in the esophagus and lungs. Hitherto, studies on SSc pathogenesis centered on immune cells, vascular cells, and fibroblasts. Although dysregulated keratinocytes in SSc have been recently reported, the contribution of epithelial cells to pathogenesis remains unexplored. In this study, we demonstrated the induction of SSc-like molecular phenotype in keratinocytes by gene silencing of transcription factor Friend leukemia virus integration 1 (Fli1), the deficiency of which is implicated in SSc pathogenesis. Keratin 14-expressing epithelial cell-specific Fli1 knockout mice spontaneously developed dermal and esophageal fibrosis with epithelial activation. Furthermore, they developed remarkable autoimmunity with interstitial lung disease derived from thymic defects with down-regulation of autoimmune regulator (Aire). Importantly, Fli1 directly regulated Aire expression in epithelial cells. Collectively, epithelial Fli1 deficiency might be involved in the systemic autoimmunity and selective organ fibrosis in SSc. This study uncovers unidentified roles of dysregulated epithelial cells in SSc pathogenesis.
Disease control and survival outcomes for rectal adenocarcinoma (RA) managed with neoadjuvant chemoradiotherapy (nCRT): Performance of serum CEA changes as a biomarker.
Authors: Tangel Chang, Sudershan Bhatia, Daniel James Berg, John Michael Buatti, John Watkins
Journal: Journal of Clinical Oncology (2016)

552 Background: nCRT is commonly employed in advanced or distal RA, with validated associations between tumor response and disease control; however, the identification of patients likely to respond remains elusive. The present investigation seeks to determine whether absolute CEA levels and changes during treatment are associated with pathologic complete response (pCR), freedom from failure (FFF), disease specific survival (DSS), and overall survival (OS). Methods: Retrospective analysis of clinicopathologic and treatment factor association with outcomes. Eligible patients underwent nCRT followed by mesorectal resection; patients with pre-nCRT evidence of metastasis or who did not undergo resection were excluded. CEA levels were recorded at 3 times: pre-nCRT (C1), post-nCRT/pre-op (C2), and post-op (C3; &lt; 45 days of surgery, or &lt; 225 days if post-op C given). Univariate analysis was performed to identify clinicopathologic factor association with pCR, FFF, DSS, and OS. The absolute and relative changes in interval CEA levels were computed and included as factors in the analysis. Results: From 2003-11, 71 patients were eligible. At median follow-up of 57 months (range, 5-124), 20 patients had RA recurrence and 25 had died (19 recurrent). nCRT resulted in pCR for 19 patients (27%), which was associated with DSS (p = 0.04). The estimated 5-year FFF, DSS, and OS for the entire population were 69%, 77%, and 72%, respectively. Clinical and pathologic N-stage, nodal ratio, ypTNM stage, and stage migration post-CRT were significantly associated with FFF, DSS, and OS. The relative change from C1 to C2 was significantly associated with pCR (exp(b); p = 0.031). Absolute C3 was associated with FFF (1.091; 0.001), DSS (1.183; 0.018), and OS (1.092; 0.002); however, absolute and relative changes at C2 and C3 as compared with C1 did not demonstrate associations with disease control or survival endpoints. Conclusions: Within the present study, changes in CEA levels following CRT were associated with pCR. Additionally, initial post-op CEA demonstrated associations with disease control and survival endpoints.