tbuckley/cabot-search huggingface dataset:
The relationship between preoperative c-reactive protein and Fuhrman nuclear grade in stage T1 renal cell carcinoma.
Authors: Rishi Robert Sekar, Dattatraya Patil, Jeff Pearl, Yoram Baum, Mehrdad Alemozaffar, Christopher Paul Filson, Kenneth Ogan, Viraj A. Master
Journal: Journal of Clinical Oncology (2016)

593 Background: In an era of active surveillance for small renal masses (SRMs), non-invasive predictors of tumor aggressiveness may be helpful in identifying high-risk patients for surgical intervention. In this study, we evaluate the predictive value of preoperative C-reactive protein (CRP) on Furhman Nuclear Grade (FNG) in patients with stage T1 renal cell carcinoma (RCC). Methods: Patients who underwent nephrectomy for stage T1 RCC with documented preoperative CRP within 15 days of surgery were included in the study. Surgical pathology reports were used to determine TNM stage and FNG. Receiver operating characteristic (ROC) analysis, sensitivity-specificity analysis, and Youden index were used to determine the optimal threshold of preoperative CRP in predicting FNG 4 disease versus FNG 1-3 disease. Logistic regression analysis was then performed to assess the significance and independence of preoperative CRP in predicting FNG 4 disease. Results: 351 patients were included in the study. On ROC analysis, area under the curve (AUC) was 0.7576. The optimal threshold of preoperative CRP was determined to be 4.8 mg/dL. On univariate and multivariate analysis, CRP ≥ 4.8 mg/dL was found to be a significant and independent predictor of FNG 4 disease (log-rank, p=0.014, p=0.006, respectively). Conclusions: Our data show that preoperative CRP ≥ 4.8 mg/dL is a significant and independent predictor of FNG 4 disease in patients with stage T1 RCC. These findings suggest that a standardized and cost-effective preoperative laboratory value can provide crucial prognostic information in patients undergoing active surveillance for SRMs, allowing for improved patient selection for definitive surgical therapy. [Table: see text]
Voice of Cancer Patients: Analysis of patient concerns regarding cognitive deficits associated with treatment for breast cancer.
Authors: Sangeeta Aggarwal, Mingfeng Liu, Rishi Sharma, Fred Yang, Ankit Gupta, Divjot Singh, Rahul Sharma, Anirban Basak, Alok Aggarwal
Journal: Journal of Clinical Oncology (2015)

82 Background: Patients undergoing breast cancer treatment often report Symptoms of Cognitive Deficit (SCD). Many of them share their experiences on online forums, which contain millions of freely shared messages that can be used to analyze these SCD. Unfortunately, this data is unstructured, making it difficult to analyze. In this project we organize this data using methods from Big Data Science (BDS) and analyze it by creating a Decision Support System (DSS): an interface that can be used by patients and providers to understand how SCD are associated with specific types – hormonal only (HT), chemo only (CT), or both (CT/HT) – of breast cancer therapies. Methods: We collected 3.5 million unique messages from 20 unrestricted breast cancer forums that provide clinically relevant information. We next built custom ontologies for breast cancer treatments, SCD, and supportive therapies. Then, we created a DSS using methods from BDS, including topic modeling, information retrieval, and natural language processing to extract the relevant data from these messages. We also used token windows and co-occurrence-based algorithms to associate treatment with SCD and supportive therapies. To use this system, a user provides disease-related parameters and the treatment. The DSS then gives the percentage of messages discussing SCD for a similar cohort of patients and the percentage of messages that discuss supportive therapies for each of these SCD. Results: We found 15719 messages that had strong association of SCD with treatments. 3355 messages were from HT patients, 5740 messages were from CT patients, and 9095 messages were from CT/HT patients. Among HT, 28.18% patients taking aromatase inhibitors and 19.20% taking tamoxifen associated SCD to HT. Among CT, 35.26% patient receiving taxane containing chemo associated SCD to CT. SCD worsened during HT for CT/HT patients. Suggestive therapy: 80 messages found Vitamin B12 and B6 useful, 65 suggested Acetyle-L-Carnitine, and 50 suggested playing word games. Conclusions: Using methods from BDS, our DSS reliably associates SCD with HT, CT and CT/CT, and suggests supportive therapies. More research is needed to evaluate the role of supportive therapy for SCD.
The nucleoside diphosphate kinase-A as a migration suppressor in gastric lymphoma.
Authors: Jae J. Kim, Jin Il Kim
Journal: Journal of Clinical Oncology (2015)

87 Background: The nm23-H1 gene encodes the NDPK-A (nucleoside diphosphate kinase A) that contributes variably to the migration of cancer cell. To investigate the role of the NDPK-A in gastric lymphoma, we examined the expression of NDPK-A in two different cancer cell lines of the same gastric lymphoma patient. Methods: The primary cell line of gastric lymphoma, RF-1, was cultured from the primary gastric lymphoma site, and the other cell line RF-48 was metastasized to the peritoneum of the same patient after 6 months. We have generated stable gastric lymphoma transfectants, pIRES-NDPKA-GFP-neo, that constitutively over-express transfected and vector form of NDPK-A, in addition to a reporter, green fluorescent protein(GFP). The transfected gastric lymphoma cell migration assay was performed 24-well modified chemotaxis chambers with FluroBloc membrane. Results: In regard to the migration rate of the gastric lymphoma cell lines, RF-1 vector was 75.8±7.5%, RF-1 transfected was 54.4±12.3%, RF-48 vector was 84.7±15.4%, RF-48 transfected type was 62.3±9.2%, RF-48 migrated better than RF-1, and the vector type migrated better than the transfected type. NDPK-A was presented more in RF-1 than RF-48, and presented more in the transfected type than the vector type, and concerning the migration rate, RF-48 migrated better than RF-1, and the vector type migrated better than the transfected type. Conclusions: In regard to the migration rate of the gastric lymphoma cell lines, RF-1 vector was 75.8±7.5%, RF-1 transfected was 54.4±12.3%, RF-48 vector was 84.7±15.4%, RF-48 transfected type was 62.3±9.2%, RF-48 migrated better than RF-1, and the vector type migrated better than the transfected type. NDPK-A was presented more in RF-1 than RF-48, and presented more in the transfected type than the vector type, and concerning the migration rate, RF-48 migrated better than RF-1, and the vector type migrated better than the transfected type.
Adjuvant chemoradiation (CRT) for high-risk gastric cancer (GC): Single-center experience using infusional 5-fluorouracil (5FU) and radiotherapy (RT).
Authors: K. Papademetriou, V. Vasiliou, P. Kountourakis, A. Bagatzounis, D. Papamichael
Journal: Journal of Clinical Oncology (2011)

e14571 Background: Postoperative CRT is a standard treatment option for fully resected high risk GC. Adjuvant CRT using bolus 5FU significantly improved overall (OS) and disease free survival (DFS) versus surgery alone. However, this regimen is associated with significant toxicity and poor tolerability. Methods: Sixty eight patients (pts) with high risk GC were referred following surgery for adjuvant CRT. The treatment comprised six cycles of the “modified de Gramont”regimen [leucovorin: 350 mg iv (d1) and 5-FU: 400 mg/m2 iv-bolus (d1), 2,800mg/m2 over 46 hours]; the third and fourth cycle of chemotherapy given concurrently with RT as follows: total dose of RT 4,500 cGy in 25 fractions of 180 cGy. Pts were evaluated retrospectively for toxicity, DFS and OS. Results: With a median follow-up period of 32 months (mo; range: 5–90), 68 patients (36 men, 32 women), median age 59 years (range: 30-76) were treated; stage IB: 4,4% (3/68 pts), IIA:7,35% (5/68 pts), IIB:13% (9/68 pts), IIIA: 11,7% (8/68 pts), IIIB: 30,8% (21/68 pts), IIIC: 32,3% (22/68 pts). The median DFS and OS were 25,2 and 32 mo, respectively. Three year DFS and OS were 24% and 29%. Grade III or higher myelotoxicity was: neutropenia 16% (11 pts); two pts grade IV neutropenia, thrombocytopenia 3% (2 pts). Grade III or higher non hematologic toxicity were: diarrhea 19% (13pts), vomiting 3% (2 pts), stomatitis/esophagitis 8% (6 pts) and constipation 3% (2 pts). There was no grade IV non hematologic toxicity. Fifty-three pts (78%) completed the treatment. Discontinuation was necessary in 5 pts due to diarrheas, 3 due to neutropenia, 3 due to performance status deterioration, 1 patient due to infection, 1 due to arythmia and 2 pts after informed consent withdrawal. Two pts died during treatment: one from possible/unconfirmed cardiovascular event and the other one due to sepsis. Conclusions: Despite a relatively short median follow-up and small sample size, our findings suggest that this regimen could be an alternative option, with favorable toxicity and tolerability in patients with fully resected high risk GC.
Conversion to resectability in unresectable metastatic colorectal cancer chemotherapy (mCRC) trials.
Authors: Sarah Chrabaszcz, Rahul Rajeev, Brittany Klooster, Ashley Chinn, T. Clark Gamblin, Fabian McCartney Johnston, Ben George, Anjishnu Banerjee, Kiran Turaga
Journal: Journal of Clinical Oncology (2016)

641 Background: Patients with mCRC undergoing surgical metastasectomy have been shown to derive significant survival benefit with a potential for cure. We hypothesized that conversion to resectability (c2r) is correlated with increased overall survival in patients with unresectable mCRC. Methods: Prospectively registered systematic review (PROSPERO CRD42015024104) was utilized to identify randomized clinical trials published after 2003. Exposure of interest was c2r from unresectable disease, while the outcome was overall survival (OS). Clinical trials were classified into three groups based on difference in c2r between the two study groups ( &lt; 2, 2-2.9, ≥ 3 %). Generalized estimating equations(GEE) were used to measure associations while adjusting for multiple observations from the same trial. The Cochrane risk of bias tool was used to evaluate the methodological quality. Results: Out of 2,902 studies reviewed, 30 satisfied selection criteria (n = 13,618 patients). All studies had two arms only (100%). Median c2r was 7.3% (Interquartile Range 5%-12.9%), with maximum c2r in FOLFOX/FOLFIRI+ cetuximab arm (28.6%). The median difference in c2r between two arms of the same study was 2.3% (IQR 1.3 – 3.4%) and the maximum difference was 15.4% seen in FOLFOX/FOLFIRI+ cetuximab vs. FOLFOX/FOLFIRI (Ye, 2013). Median OS for the entire cohort of patients was 20.7 months (IQR 18.9 – 22.7 months), with a between group difference of 1.3 (IQR -1.2 – 3.6 months). The maximum survival benefit between two study arms was 9.9 months. Median survival difference between the two study arms with a minimal c2r difference ( &lt; 2%) was 0.8 months, as compared to 1.6 months with higher c2r ( ≥ 3%). Incremental dose effect response was noted with an increasing c2r leading to improved overall survival in regression models (p = 0.021, r 2 = 0.16). Higher response rates also correlated with higher c2r rates (p = 0.003, r 2 = 0.25). Conclusions: Conversion to resectability is positively correlated with an improvement in survival in trials examining therapies for unresectable mCRC. Patient level data examining the contribution of metastasectomy to the overall survival benefit of systemic chemotherapy needs to be further examined.
Immune cell repertoire in patients with metastatic renal cell carcinoma: Data from prospective clinical trial.
Authors: Vijay Damarla, Paul Elson, Laura S. Wood, Sylvia Sybor, Pat A. Rayman, Yu Ning Wong, Elizabeth R. Plimack, James Finke, Brian I. Rini
Journal: Journal of Clinical Oncology (2015)

452 Background: Immune dysfunction is documented in renal cell carcinoma (RCC) patients and likely influences tumor progression. An ongoing prospective trial of observation in metastatic RCC patients prior to systemic therapy is investigating circulating immune cell populations. Methods: Asymptomatic patients with low volume metastatic disease were enrolled and followed until starting initial systemic treatment. Peripheral blood specimens were collected at baseline and again at 3, 6, 9, 12, 16, 20, and 24 months, and then every 6 months until initiating systemic therapy. Immune parameters measured included CD3+ and CD4+ INF-γ producing T cells (INF-γ+ T), CD4+CD25+FoxP3+ regulatory T-cells (Treg), CD33+HLADr-CD15+CD14- neutrophilic myeloid-derived suppressor cells (N-MDSC), monocytic M-MDSC, total MDSC, and lineage-negative MDSC. Similar immune parameters were recorded for treatment-naïve patients prior to immediate systemic therapy (sunitinib or pazopanib, n=34) and healthy volunteers (n=22) on separate IRB-approved protocols. The immune data was analyzed using Wilcoxon rank sum and signed rank tests and proportional hazards models. Results: Forty patients enrolled in the observation study had immunologic data. 25 patients (62%) started systemic therapy, and 15 (38%) continue observation. The observation group had lower baseline levels of MDSC, N-MDSC, M-MDSC, Tregs and higher levels of CD3+INF-γ+ T cells, CD4+ INF-γ+ T cells, and lineage negative MDSC compared to the immediate treatment group, although higher MDSCs and lower Tregs compared to healthy controls. The impact of baseline parameters on the duration of observation revealed that lower Tregs (p=0.003) were associated with a longer time on observation. There were no significant changes in immune parameters of observation patients over the length of observation. Conclusions: Metastatic RCC patients with indolent disease have low levels of Treg and MDSC, and a relatively preserved immune cell repertoire compared to patients requiring immediate therapy. Lower baseline Tregs may be associated with a longer length of observation.
Response to EGFR TKIs in never smokers with stage IV <i>EGFR</i> mutant squamous cell carcinoma of the lung (SQCC).
Authors: P. K. Paik, N. Rekhtman, G. J. Riely, V. A. Miller, M. Ladanyi, M. G. Kris
Journal: Journal of Clinical Oncology (2011)

e18020
Characteristics of emergency department visits among non-admitted oncology patients.
Authors: Belen Fraile, Stephen Schleicher, Christopher Baugh, Craig A. Bunnell, Robert Mersereau, Spyros Potiris, Joseph O. Jacobson
Journal: Journal of Clinical Oncology (2014)

37 Background: Use of costly emergency department (ED) resources is high amongst oncology patients. However, many oncology patients who visit the ED are discharged home without admission to an inpatient setting. A better understanding of why this group of patients presents to the ED can inform alternative interventions to shift care to less costly settings and reduce ED utilization. Methods: We conducted a review of administrative data at Brigham and Women’s Hospital (BWH) that serves as the ED for patients undergoing cancer treatment at the Dana Farber Cancer Institute. We identified oncology diagnosed patients that presented to the ED between 9/1/2011 and 9/30/2012 (n=6,035 unique visits). We focused our analysis in those patients ultimately discharged home, directly discharged (Home n=1647) or after an ED observation stay &lt; 24 hours (ED Obs n=379) to evaluate opportunities for improvement. We then reported charges, cancer type, primary ED discharge ICD-9 code, and tests ordered per ED visit by disposition status. Results: We found that 34% of the ED encounters (n=2,026) were ultimately discharged home (directly discharged or after an ED observation stay). Among them, the average charge per visit for these patients varied from $3,304 (SD= 2,734) for Home to $10,951 (SD= 6,540) for ED Obs. 73% (n=1,473) of these patients had solid tumor diagnoses. The five most common solid tumor diagnoses associated with these patients were gastrointestinal (16%), gynecologic (12%), genitourinary (10%), breast (10%), and thoracic (9%). The most common ICD-9 codes associated with these patients’ admissions were abdominal pain (9%), fever (5%), dyspnea (5%), chest pain (3%), and nausea (3%). Of these outpatients, 53% (n=1,066) had at least one radiologic test performed, the most common tests being chest x-ray in 41% and CT scans in 16%. Conclusions: About 1 in 3 cancer patients who present to the ED are not admitted to an inpatient setting, representing potentially avoidable costly ED visits. Most of these patients are represented by five solid tumor diseases. Improved alternative outpatient access and management strategies of symptoms such as abdominal pain, dyspnea, and nausea in these patients may reduce ED utilization in this patient population.
The predictive role of midtreatment changes in survivin, GSTP1, and topoisomerase 2 alpha expressions for pathologic complete response to neoadjuvant chemotherapy in patients with locally advanced breast cancer.
Authors: S. Keskin, Y. Eralp, E. Akisik, E. Akisik, A. Igci, M. Muslumanoglu, S. Yilmaz, M. Tunaci, H. Camlica, S. Tuzlali, P. Saip, N. Dalay, V. Ozmen, E. Topuz
Journal: Journal of Clinical Oncology (2011)

10539 Background: The aim of this study is to investigate the effect of change in expression levels of survivin, glutathione-S-transferase P1 (GSTP1) and topoisomerase 2 alpha (TOP2A) on response to NAC consisting of 4 cycles doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) followed by 4 cycles docetaxel (100 mg/m2) ± trastuzumab. Methods: Tumoral expression of markers obtained before CT, after 4 cycles of AC and completion of CT, were analyzed by real-time PCR. Survivin expressions were additionally analyzed in serial blood samples. Results: The median age of pts (n=32) was 48 (28-75) yrs and median follow-up was 36.3±12.5 months (9.4-53.6). The majority of pts had clinical stage T3-T4 (n=23, 72%), clinically lymph node positive (n=29, 91%), grade III (n=23, 72%), ER positive (n=17, 53%), PgR positive (n=21, 66%), and HER-2 negative (n=27, 84%) disease. 14 pts (43.8%) developed recurrence and 6 pts (18.8%) died during follow-up. The median PFS was 29.3±14.5 months. The table shows changes in serial expression levels of markers analyzed. Serial GSTP1 expression in pts with clinical partial and complete response (CR) decreased from 1.41 to 0.33 and to 0.19 (p:0.0001). In addition, expression levels in pts with a pathological CR in breast and axilla were 1.85, 0.33 and 0.28 (p:0.0001). Anthracycline-related decrease in GSTP1 expression was determined as the only independent prognostic variable for PFS (p=0.01). Nevertheless, there was not correlation between survivin and TOP2A expression and clinicopathologic parameters, response, and survival. Conclusions: Downregulation of GSTP1 is a significant predictor of pCR and improved PFS during anthracycline and taxane-based NAC for pts with LABC. Monitoring GSTP1 expression levels may be used as an early predictor for response to NAC in LABC pts. Expression levels of markers during treatment (median ± SD). Before CT After four cycles CT After eight cycles CT p GSTP1 2.30±59.7 0.34±25.2 0.24±2.9 0.014 TOP2A 0.27±1.3 0.27±3.8 0.14±0.8 NS Survivin 0.93±5 0.16±3.8 0.19±0.2 NS Survivin in blood 0.87±2.5 0.86±4.8 0.55±2.5 NS
Redefining CTCs: Detection of additional circulating tumor cells using an antibody capture cocktail and HER2 FISH.
Authors: F. Z. Bischoff, T. J. Pircher, T. Pham, K. Wong, S. Mikolajczyk, P. Cotter, J. A. Mayer
Journal: Journal of Clinical Oncology (2011)

10631 Background: Most circulating tumor cell (CTC) platforms rely on EpCAM for capture and cytokeratin (CK) for detection. However, an important population of cells that display an epithelial-mesenchymal transition (EMT) phenotype will be missed. We report a new strategy to efficiently isolate a more heterogeneous population of CTCs using an antibody cocktail. Methods: In the first prospective study, blood (20 mL) was collected from 23 patients diagnosed with various late stage metastatic/recurrent cancer (breast, CRC, lung, prostate) following IRB approval. PBMCs were incubated with either EpCAM alone or a mixture of 10 capture antibodies to target both epithelial and mesenchymal cells. CTCs were subsequently captured in the CEE channels and detected with cytokeratin (CK) and CD45. A second prospective IRB approved study involving 54 patients diagnosed with late stage metastatic/recurrent breast cancer was performed using similar detection strategies (CK cocktail mixture and anti-CD45) with the addition of HER2 FISH to determine amplification status among captured CK+/CD45- and CK-/CD45- cells (presumable EMT cells). Results: In the first study, overall detection of CK+ cells was 83% with EpCAM alone and 93% with antibody cocktail. In addition, a median of 0.4 CK+ cells/mL and 1.0 CK+ cells/mL was observed using EpCAM and antibody cocktail, respectively. In the second study, CK+/CD45- cells were detected in 43 of 54 cases (80%). Among the 43 cases in which CK+/CD45- cells were detected, high concordance (93%) in HER2 status between primary tumor and CTCs was observed with Her2 amplification noted in both CK+/CD45- (50%) and CK-/CD45- (50%) cells. Conclusions: We have developed a novel and robust method for CTC enumeration that utilizes a cocktail of antibodies for the detection of a heterogeneous population of CTCs in multiple cancer types. Our findings suggest an important population of CK- cells is being missed by current stain criteria. Data also demonstrate that recovery of CTCs from peripheral blood using the CEE platform is efficient and suitable for FISH-based testing.
Role of M402, a novel heparan sulfate mimetic, in pancreatic cancer cell invasion and metastasis: Inhibition of the Sonic Hedgehog pathway and heparanase activity.
Authors: Zoya Galcheva-Gargova, Chia Lin Chu, Alison Long, Jay Duffner, Kimberly Holte, Birgit Corinna Schultes
Journal: Journal of Clinical Oncology (2012)

25 Background: M402 is a novel heparin sulfate mimetic that binds to multiples growth factors, adhesion molecules, and cytokines to inhibit tumor angiogenesis, progression, and metastasis in nonclinical studies. We investigated if M402 could modulate tumor-stroma interactions in pancreatic cancer by inhibiting the Sonic Hedgehog (Shh) pathway as well as inhibit the activity of the extracellular matrix degrading enzyme, heparanase. Methods: Surface plasmon resonance (SPR) was used for analysis of M402 binding to Shh in vitro. A cell based Gli-1 reporter assay was implemented to assess the effect of M402 on Shh signaling. Immunohistochemistry and RT-qPCR were utilized to investigate M402’s effect on Shh activity in an orthotopic Capan-2 model in nude mice. The effect of M402 on heparanase activity in vitro and on Capan-2 tumor samples isolated from treated and untreated mice was measured using an HTRF-FRET assay. Results: There was specific binding of M402 to Shh in vitro. Additionally, Shh signaling was inhibited in the presence of M402. Immunohistochemistry and RT-qPCR of Capan-2 tumor samples from animals treated with M402 also demonstrated reduction of Shh signaling via Gli, its targeted transcription factor. The degree of inhibition of heparanase activity, as measured in the HTRF assay, was affected by the size, structure, and sulfation pattern of the different heparin sulfate mimetics evaluated. M402 was the most potent inhibitor of heparanse activity in vitro from all compounds tested. In addition, treatment with M402 inhibited heparanase activity in the pancreatic tumor lysates in a dose-dependent manner. Conclusions: M402 was shown in nonclinical studies to modulate tumor-stroma interactions involved in the metastatic, invasive, and desmoplastic pathways by simultaneously inhibiting two distinct pathways: Shh signaling and the activity of heparanase. M402 regulates a variety of polysaccharide-based binding proteins, which provides a rationale for the clinical investigation of M402 in a range of cancers.