tbuckley/cabot-search huggingface dataset:
Baseline differences in characteristics of a racially diverse group of men electing active surveillance.
Authors: Allison H. Feibus, Nora M. Haney, James Liu, Jason H Chiang, Elisa M. Ledet, John Boxberger, Justin Levy, Krishnarao Moparty, Brian E. Lewis, Raju Thomas, Oliver Sartor, Jonathan L. Silberstein
Journal: Journal of Clinical Oncology (2017)

103 Background: To date, large populations of men from European ancestry have been prospectively evaluated on Active Surveillance (AS), a strategy reserved for low risk prostate cancer (PCa). African Americans (AA) deemed to be candidates for AS have yet to be fully characterized. We sought to determine the similarities and differences of our AS cohort stratified by race. Methods: We identified 308 men from our multi-institutional, prospective AS database were analyzed. Inclusion criteria was PSA &lt; 20ng/mL, Gleason score ≤ 7, and clinical stage ≤ T2a. Men who sought treatment for their PCa or refused subsequent imaging and biopsy were excluded. Univariate analysis was done to analyze racial differences in demographic, clinical and pathologic variables. Results: We identified 308 men, 131 (43%) AA and 177 nonAA (57%). The groups were not significantly different with respect to age; 65 years, BMI 28.4, family history of PCa (22%), prior negative biopsy (21%) and clinical staging (87% T1c). Median follow-up is 25 months (IQR 12-44). Significant differences between the AA and nonAA cohorts did exist at baseline with respect to overall health, suggesting AA having worse overall health. More AA had diabetes (29 vs 14%; p = .03), were smokers (55 vs 29%; p &lt; .01), cardiovascular disease (21 vs 9%) and erectile dysfunction (43 vs 18%; p &lt; .01). Social characteristics also differed within the groups, with AA less likely to be married (47 vs 51%; p = .01). Despite a lack of difference with respect to biopsy Gleason score, AA had higher PSA (5.7 vs 5.0 ng/mL; p = 0.02), lower testosterone levels (250 vs 334 ng/dL; p = 0.05), greater PSA density (0.15 vs 0.12; p &lt; 0.01), and greater linear length of cancer per biopsy core (16 vs 13mm; p &lt; 0.01) at time of diagnosis and initiation of AS. Conclusions: Within our AS cohort, AA have worse overall health and more aggressive PCa features despite meeting inclusion criteria and selecting AS. Further prospective study is needed to determine how these competing factors may impact long term outcomes.
Randomized trial of exercise on quality of life and fatigue in women diagnosed with ovarian cancer: The Women’s Activity and Lifestyle Study in Connecticut (WALC).
Authors: Yang Zhou, Linda Gottlieb, Brenda Cartmel, Fangyong Li, Elizabeth A Ercolano, Maura Harrigan, Ruth McCorkle, Jennifer A. Ligibel, Vivian E. Von Gruenigen, Radhika Gogoi, Peter E. Schwartz, Harvey A Risch, Melinda L Irwin
Journal: Journal of Clinical Oncology (2015)

9505 Background: Ovarian cancer survivors experience a wide range of treatment side effects that can affect health-related quality of life (HRQOL). Physical activity has been shown to improve HRQOL for other cancer survivors; however, prior to our study, no large randomized exercise trial (RCT) has been conducted in ovarian cancer. We examined the effect of exercise vs. attention control on HRQOL and fatigue in ovarian cancer survivors. Methods: We randomized 144 physically inactive ovarian cancer survivors who had completed initial chemotherapy into a 6 month RCT of exercise vs. attention control. Women in the exercise arm received weekly phone calls from a certified exercise trainer and were counseled on increasing their physical activity to 150 min/wk of aerobic exercise. Women in the attention control arm also received weekly phone calls to discuss a relevant health topic. HRQOL and fatigue were measured via SF-36 and FACT-F questionnaires. Generalized linear models were used to compare baseline to 6-month changes in HRQOL and fatigue between the two arms. Results: At baseline, participants were, on average (mean + SD), 1.7 ± 1.0 years post-diagnosis, 54% stage III-IV, 57.3 ± 8.6 years of age, and exercised 31.0 ± 45.8 mins/wk. Baseline physical HRQOL (Physical component summary (PCS) score of the SF-36) (mean = 46.0 ± 9.0) and fatigue scores (mean = 36.3 ± 10.9) were similar for both arms.At 6 months, women in the exercise arm increased exercise by 132.8 ± 108.8 min/wk compared to 59.0 ± 90.4 min/wk in the attention control arm (P < 0.001). Women in the exercise arm improved physical HRQOL compared to a decreased physical HRQOL in women in the attention control arm (SF-36 PCS change score of 1.7 ± 1.1 vs. -1.9 ± 1.2, mean ± SE, P = 0.02). Borderline significant improvements in fatigue were observed for women randomized to exercise (FACT-F change score of 4.0 ± 1.1) vs. a 1.2 ± 1.2 increase for controls at six months, P = 0.06). Conclusions: Our results show that ovarian cancer survivors are interested in and able to exercise at recommended levels, with exercise improving physical HRQOL. Exercise programs for ovarian cancer survivors should be implemented in an effort to improve HRQOL. Clinical trial information: NCT02107066.
The expression of EGFR by immunohistochemical staining to predict the response of nimotuzumab in esophageal squamous cell carcinoma.
Authors: Xiaodong Zhang, Yan Cui, Jun Jia, Ming Lu, Jing Gao, Xicheng Wang, Jie Li, Yan Li, Xiaotian Zhang, Zhihao Lu, Jing Yu, Lin Shen
Journal: Journal of Clinical Oncology (2014)

e15046 Background: It has been demonstrated that epithelial growth factor receptor (EGFR) is overexpressed in 30-80% of esophageal cancer (EC). Therefore, the selection of potential population who could benefit from this treatment is of great importance. We analyzed the EGFR expression by immunohistochemical staining in advanced or metastatic esophageal squamous cell carcinoma (ESCC) patients who received combination treatment of nimotuzumab with chemotherapy to explore the correlation of the EGFR protein expression with the clinical response. Methods: The patients enrolled in this study were from a prospective phase II clinical trial of “Nimotuzumab plus paclitaxel and cisplatin as 1st line treatment for esophageal squamous cell cancer: a single centre prospective clinical trial” (NCT01336049). The tumor tissues were obtained from either gastroscopic biopsy or surgical removed mass. The expression of EGFR was detected by standard immunohistochemical stain methods. The high EGFR expression was defined as strong and continuous membrane staining in more than 50% cells. Results: Totally 55 tumor tissues of ESCC patients were analyzed. 18 of 55 (32.7%) were with high EGFR expression while the other 37 cases were with low to moderate EGFR expression. The expression of EGFR had no relation with the sex, age, tumor location, and tumor differentiation. The objective response rate in EGFR high expression group was 55.6% while that in EGFR low to moderate was 54.1% (p=0.6). The median progression-free survival in EGFR high expression group was much shorter than that in EGFR low to moderate expression group (5.9±1.3 months vs 11.0±3.1 months, P=0.047). The median overall survival in EGFR high expression group was also shorter than that in the EGFR low to moderate expression group (9.7±0.5 months vs 21.5±1.5 months, P=0.037). Conclusions: The overexpression of EGFR could not predict the ORR of the combination of nimotuzumab with chemotherapy. But the high expression of EGFR was associated with poor PFS and OS. It implied that EGFR expression might be a predictor of disease prognosis but not a predictor of the outcome of anti-EGFR agent, nimotuzumab, teatment.
Economic burden of adverse events in patients with metastatic renal cell carcinoma (mRCC).
Authors: May Hagiwara, Rohit Borker, Gerry Oster
Journal: Journal of Clinical Oncology (2012)

e16573 Background: To estimate costs associated with adverse events (AEs) in patients receiving targeted therapies indicated for first-line treatment of mRCC. Methods: A retrospective study using a large US healthcare claims database (PharMetrics) from 1/2000 to 12/2009 was conducted. Study subjects were aged ≥18 years, had mRCC, and received first-line treatment with targeted therapies. AEs of interest comprised abdominal pain, back pain, diarrhea, dyspnea, extremity pain, fatigue/asthenia, hand-foot syndrome, hypertension, lymphopenia, nausea/vomiting, neutropenia, and proteinuria. Patients receiving care for these AEs were identified using ICD-9-CM diagnosis/procedure codes on healthcare claims. Costs were examined over a 30-day period, beginning with date of first mention of each AE; non-evented patients were assigned a “shadow” index date for comparison purposes. We estimated total costs over 30 days following the index date for patients with and without AEs, on both unadjusted basis and following adjustment for differences in baseline characteristics using a generalized linear model (GLM). Direct costs of targeted therapy were not considered. Results: Among patients receiving targeted therapy for mRCC, 64% had healthcare encounters for one or more AEs. AEs occurring with frequency &gt;20% included severe abdominal pain, back pain, fatigue/asthenia, and nausea/vomiting, respectively; 10-20% of patients had encounters for diarrhea, dyspnea, and extremity pain, respectively. Mean [SD] total costs of care during the 30-day, post-index period were substantially higher among patients with AEs ($12,177 [$19,621] vs $4070 [$8142] for those without AEs). Adjusting for differences in baseline characteristics, the estimated cost difference (95% CI) was $11,373 ($5286 - $21,419). Conclusions: Costs associated with AEs of first-line targeted therapies are substantial in patients with mRCC. Efforts to prevent and/or better manage these events may reduce healthcare costs.
Serum protein acidic and rich in cysteine (SPARC) as a prognostic marker in soft tissue sarcoma.
Authors: Sherif S. Morgan, Raymond B. Nagle, Lee D. Cranmer
Journal: Journal of Clinical Oncology (2013)

10581 Background: SPARC is a matricellular secreted glycoprotein that performs several functions, including modulating cellular adhesion and proliferation. It has been implicated in tumorigenesis and identified as an adverse prognostic factor in a number of cancers. The specific mechanisms involved have yet to be identified. Agents targeting SPARC-expressing tumors, such as nanoparticle albumin-bound-paclitaxel (NAB-P), have been developed. Soft tissue sarcomas (STS) represent a heterogeneous group of tumors with inadequate systemic therapies. Our objective was to explore the pattern of SPARC expression and its prognostic significance in STS. Methods: Formalin-fixed paraffin-embedded tissue sections were stained by immunohistochemistry using a mouse monoclonal antibody for SPARC (Abnova). Staining intensity was scored blindly. Patient survival was determined from patients’ medical records. Kaplan-Meier and log-rank analyses were used to compare survival by SPARC expression level. Results: 27 tissue specimens of various STS subtypes were investigated (Table). Elevated SPARC expression was observed in 56% of specimens, but did not correlate with underlying histology. Overall survival segregated into 2 groups based on SPARC levels. Patients who expressed low-to-moderate levels of SPARC exhibited median survival of 22.1 months, while the median survival of patients with moderate-to-high expression levels was 4.4 months (log rank; p=0.0016). Conclusions: A significant proportion of STS specimens exhibit elevated SPARC expression. Elevated SPARC does not correlate with underlying histology, although analysis of a greater number of specimens might reveal subtypes with more frequently elevated expression. Overall survival segregates strongly by degree of SPARC expression, with elevated expression being adverse. Our results suggest that analysis in STS of agents targeting SPARC, such as NAB-P, should be stratified by extent of SPARC expression. [Table: see text]
Prognostic value of tumor infiltrating lymphocytes in Epstein-Barr virus-associated gastric cancer.
Authors: Shinkyo Yoon, Soo Jung Lee, Yee Soo Chae, Byung Wook Kang, Jong Gwang Kim, An Na Seo, Han Ik Bae, Wansik Yu, Ho Young Chung, Seung Soo Lee, Oh Kyung Kwon, Seong Woo Jeon, Hyun Seok Lee
Journal: Journal of Clinical Oncology (2015)

4062 Background: It is well known that lymphocytic infiltration around tumor can be considered as a host immune reaction against tumor cells, although prognostic implication of lymphocyte infiltration in gastric cancer are not certain. Therefore, we investigated prognostic impact of tumor-infiltrating lymphocytes (TILs) in Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC), which can be sub-classified into 3 histological subtypes according to the host immune response: lymphoepithelioma-like carcinoma (LELC), carcinoma with Crohn’s disease-like lymphoid reaction (CLR), and conventional-type adenocarcinoma (CA). Methods: In situ hybridization for EBV positivity was performed in 1318 cases that underwent surgery or endoscopic submucosal dissection at Kyungpook National University Hospital between January 2011 and November 2014. Histopathologic analysis of percentage of TILs was performed on hematoxylin and eosin–stained sections. TILs were defined as the percentage of tumor stroma containing infiltrating lymphocytes. A tissue with TILs over 20% was considered TILs-positive. EBVaGCs were also sub-classified into 3 histological subtypes: LELC, CLR, and CA . Results: EBVaGC was identified in 111 cases (8.4%) from a total of 1318 gastric cancer. The median age was 62 years (32-80), and 86 patients (77.5%) were male. The pathologic stages after resection were as follows: stage I (n = 69), stage II (n = 24), stage III (n = 16), and stage IV (n = 2). TILs-positive patients were 65 patients (58.6%). The number of histologic subtypes of EBVaGC was as follows: LELC (n = 35), CLR (n = 50), and CA (n = 26). In the univariate analysis, TILs score and EBVaGC sub-classification was significantly associated with disease-free survival (DFS), respectively (p = 0.016, p = 0.001). The LELC and CLR groups with TILs-positive showed an improved DFS compared to the CA group with TILs-negative (p = 0.002). This difference was also significant in the multivariate analysis (p = 0.018). Conclusions: TILs and sub-classification of EBVaGC may constitute prognostic factor in EBVaGC. As a result, this finding suggests that the host cellular immune response could be useful as a prognostic marker for EBVaGC.
Effect of a novel CDX2 splice variant on tumorigenicity in gastroesophageal junction adenocarcinoma xenografts.
Authors: Matthew Witek, Scott A Waldman, Adam Snook, Stephanie Schulz
Journal: Journal of Clinical Oncology (2012)

e14619 Background: Patients with locally advanced adenocarcinoma of the gastroesophageal junction (GEJ) that undergo aggressive neoadjuvant chemoradiation therapy followed by an extensive oncologic resection have a 25-50% risk of developing locoregional recurrences and/or distant metastases. There is an unmet need for biomarkers that predict tumor behavior following neoadjuvant therapy that can be used to direct future therapy. CDX2, an intestine-specific transcription factor that regulates proliferation and differentiation, is ectopically expressed by epithelial cells lining the GEJ during intestinal metasplasia and retained by adenocarcinomas. To date, CDX2 has not been shown to contribute to the tumorigenic potential of GEJ adenocarciomas limiting its use as a predictive or prognostic marker. Methods: CDX2 mRNA from GEJ tissues were sequenced. Wild type and splice variant transcripts and proteins were analyzed by Western blot, RT-PCR, luciferase assays, and fluorescent IHC. In vitro and in vivo proliferation assays were performed with OE19 cells retrovirally transduced to over-express either GFP or CDX2/AS. Results: We identified a novel splice variant of CDX2, CDX2/AS (alternative splicing) encompassing a protein in which the 85 carboxyl-terminal residues in CDX2 are replaced with a 45 residue domain enriched in arginine and serine. CDX2 and CDX2/AS were concomitantly expressed in adenocarcinomas arising from the GEJ. CDX2/AS localizes to nuclear matrix associated foci with splicing factors in contrast to CDX2 that exhibits a diffuse nuclear expression pattern. CDX2/AS did not activate promoters of putative CDX2-dependent genes but inhibited CDX2 transcriptional activity. Over-expression of CDX2/AS in the GEJ adenocarcinoma cell line OE19 did not impact its growth in vitro but did significantly increase its tumorigenicity in nude mice. Conclusions: We discovered a CDX2 splice variant with dominant-negative properties that increases the tumorigenic potential of GEJ adenocarcinoma xenografts. Further investigation examining the relationship between CDX2/AS expression and human tumor characteristics will determine its value as a prognostic and/or predictive biomarker.
A phase I trial of MK 2206 in children with refractory solid tumors: A Children’s Oncology Group study.
Authors: Christine L. Phillips, Maryam Fouladi, John Peter Perentesis, Sarah Leary, Renee M. McGovern, Joel M. Reid, Ashish M Ingle, Charlotte H Ahern, Matthew M. Ames, Peter Houghton, L. Austin Doyle, Brenda Weigel, Susan Blaney
Journal: Journal of Clinical Oncology (2012)

9581 Background: AKT, a serine threonine protein kinase, is activated downstream of phosphatidylinositol 3-kinase (PI3K) which transmits signals from cytokines, growth factors and oncoproteins to multiple targets. Activated AKT regulates survival, proliferation, and growth. The PI3K/AKT pathway is downstream of most of the common growth factor tyrosine kinase receptors in cancer, e.g., EGFR, HER2, IGFR, etc., and is a driver of tumor progression in many cancers. AKT protein kinase is activated in many pediatric solid tumors, including glioblastoma, malignant rhabdoid tumors, neuroblastoma, synovial sarcoma, rhabdomyosarcoma and medulloblastoma. MK2206, an oral allosteric AKT1, 2,3 inhibitor, has demonstrated antitumor activity in in vitro and in vivo cancer models.A phase I trial evaluating MK2206 was conducted in children with refractory solid tumors. Methods: Using a rolling-6 design, MK2206 was administered either once every 7 days (schedule 1), or once every other day (schedule 2) in a 28-day cycle. Serial PK studies were obtained on day 1, cycle 1 and trough samples were obtained on days 7, 14, 21 and 28. Biological studies included analysis of PI3K/PTEN/AKT-cell signaling pathway in pre and post-therapy in PBMC and in tumors at diagnosis or recurrence. Results: Forty-five patients [23 males, median age 13.6 years (range 3.1-21.9)] with malignant glioma (14), ependymoma (4), hepatocellular carcinoma (3), gliomatosis cereberi (2) or other tumors (22) were enrolled; 34 were fully evaluable for toxicity (schedule 1 n=17; schedule 2 n=17). Schedule 1 DLTs included: grade 3 dehydration in 1/6 patients at 28 mg/m 2 ; grade 4 hyperglycemia and neutropenia in 1/6 patients at 45 mg/m 2 . There were no DLTs at 35 mg/m 2 and dose level 4 (58 mg/m 2 ) is currently open for patient accrual with one enrollment. Schedule 2 DLTs included: grade 3 alkaline phosphatase in 1/6 patients at 90 mg/m 2 ; grade 3 rash in 1/6 patients at 120 mg/m 2 ), and grade 3 rash in 2/6 patients at 155 mg/m 2. Conclusions: The recommended pediatric phase II dose of weekly MK2206 is 120 mg/m 2 and the last cohort of patients to the every other day dosing schedule of MMK206 is enrolling. PK and PD data are currently being analyzed and will be presented.
Predictive testing for selection of patients for extended endocrine therapy: Clinical utilization of Breast Cancer Index (BCI) in early-stage, ER+, LN- breast cancer.
Authors: Stephen C. Malamud, Brock Schroeder, Theresa N. Operana, Catherine A. Schnabel
Journal: Journal of Clinical Oncology (2015)

545 Background: Randomized trials have demonstrated significant but modest (3-5%) benefit from extended (10y) endocrine therapy (EET) vs 5y in pts with early stage ER+ breast cancer. Clinical practice guidelines have speculated on the risk vs benefit of EET in pts with a low clinicopathologic risk profile. Breast Cancer Index (BCI) is a gene expression-based test that that is prognostic for risk of late (> 5y) recurrence and predictive of EET benefit. This study examined the clinical utility and utilization of BCI in clinical practice, and its ability to identify pts likely to benefit from EET in an otherwise low risk population. Methods: Consecutive cases (N = 853) from LN- pts submitted for BCI prognostic and BCI predictive [HoxB13/IL17BR (H/I) ratio] analyses were investigated. Patient characteristics, clinician testing patterns, and clinical results were analyzed descriptively. Results: Patient characteristics are shown in the top table. BCI identified 54% and 46% as having low and high risk of late recurrence, respectively. Predictive testing identified 42% of pts with a high likelihood vs. 58% with a low likelihood of benefit from EET. The bottom table shows the integrated prognostic and predictive results. In the subset of pts with a low clinicopathologic risk profile (LN-, T1, Grade 1-2, HER2-neg; n = 321), BCI identified 23% of pts with both a high risk of late recurrence (mean, 7.1% DRR) and likely to benefit from EET. Physicians utilized BCI across a range of intervals from time of diagnosis: 11% < 2y; 14% ≥ 2 to < 4y; 57% ≥ 4 to < 6y; and 18% ≥ 6y. Conclusions: Data from this large retrospective analysis further define BCI clinical utility in selection of which early-stage, ER+ pts are at risk of late recurrence and likely to benefit from EET vs those that may be adequately treated with 5y of endocrine therapy. Characteristics (N = 853) Mean Age > 65y 57y 27% Size ≤ 1cm > 1 - ≤ 2cm > 2 - ≤ 5 cm >5 cm % 26 49 23 2% Grade 1 2 3 % 29 52 19 HER2 Neg Pos % 89 19 Stratification by BCI prognostic (risk of late recurrence) and BCI predictive (H/I) All pts (N=853) Likelihood of Benefit Risk Group Low High Low 43% 11% High 15% 31% LN-, T1, Grade 1-2, HER2- (n = 321) Low High Low 54% 12% High 11% 23%
Trends in utilization of chemotherapy and radiation for resectable gastric adenocarcinoma: An NCDB analysis.
Authors: Benjamin Mitchell Motz, Patrick Daniel Lorimer, Kendall K Walsh, I'sis N Perry, Yimei Han, Richard L. White, Jonathan C. Salo, Joshua S. Hill
Journal: Journal of Clinical Oncology (2017)

163 Background: Locally advanced gastric adenocarcinoma (GACa) is optimally treated with a combination of surgery, chemotherapy (CHEMO) and radiation (RT). Utilization of therapies can vary with institutional practices. Methods: The NCDB was queried for pts with GACa who had RO resection (2006-2012). Pts with metastatic disease, incomplete pathologic staging, and incomplete CHEMO or RT sequencing data were excluded. Pts were divided into groups by treatment regimen: G1: perioperative CHEMO; G2: adjuvant CHEMO±RT; G3: neoadjuvant CHEMORT; G4: other adjunctive regimens; G5: surgery only. Pts who received neoadjuvant therapy were staged using clinical TNM; those who did not or had incomplete clinical staging were staged using pathologic TNM. 3 subsets were created: LOCAL: T0-2N0, LOCALLY ADV: T3-4N0, REGIONAL: N+. Chi-square, univariate, multivariable with stepwise selection, and Cochran-Armitage time trend analyses were performed. Results: N = 12946: G1 = 1099, G2 = 4771, G3 = 180, G4 = 244 and G5 = 6652. The percentage of pts receiving adjunctive therapy was determined for each subset: LOCAL = 17.2%, LOCALLY ADV = 59.8%, and REGIONAL = 66.0%. Use of adjunctive therapy increased from 2006: 44% to 2012: 53% (p &lt; 0.01). Use of perioperative CHEMO increased from 2006: 4% to 2012: 18% (p &lt; 0.01). Factors affecting use of adjunctive therapy on multivariable analysis are: age (p &lt; 0.01), race (p &lt; 0.01), income (p &lt; 0.01), insurance (p &lt; 0.01), comorbidity score (p &lt; 0.01), and facility volume (p = 0.01). Conclusions: Though utilization of adjunctive therapy is increasing, a large proportion of pts with resectable GACa do not receive recommended adjunctive therapy. This study highlights disparities in utilization of optimal multimodality care. National efforts to expand access to care are necessary to improve outcomes in resectable GACa. [Table: see text]