tbuckley/cabot-search huggingface dataset:
TOPO1 expression in primary and metastatic GI cancers.
Authors: Michael Castro, Rebecca Feldman, Sandeep K. Reddy
Journal: Journal of Clinical Oncology (2016)

643 Background: Irinotecan failed in Stage III colon cancer, but succeeds in Stage IV, to prolong survival. We propose that TOPO1 over-expression is a phenomenon of metastatic disease, and perhaps part of the epithelial-mesenchymal-transition (EMT) associated with metastatic phenotypes. Methods: 5029 colorectal (CRC), 3016 pancreatic, 848 gastric and 309 small bowel adenocarcinoma (SBA) patients were included in the study and tested centrally at a CLIA laboratory (Caris Life Sciences, Phoenix, AZ). A threshold of ≥ 2+ and ≥ 30% (intensity and percent staining) and TOPO1 (1D6) clone was utilized. TOPO1 was examined in primary and metastatic specimens. Two-tailed Fisher’s exact test was performed to test where proportions of positive results were different by subgroup (p ≤ 0.05). Results: See table below. Conclusions: The EMT associated with the transition from primary to invasive metastatic disease appears to include upregulation of TOPO1, in some GI cancers, including CRC, pancreatic and gastric cancer. The paradoxical failure of adjuvant irinotecan in stage III, the epithelial phase of the cancer, may be due to a smaller fraction of patient's whose cancers express this biomarker of response in that setting. A re-examination of irinotecan makes sense for a portion of stage III patients whose cancer expresses high levels of TOPO1 in the primary lesion. The recent superiority with regard to response rate and survival or FOLFOXIRI over FOLFOX alone in the stage IV setting raises renewed interest in whether patients with non-metastatic disease could derive a superior cure rate if suitably selected for FOLFOXIRI with a biomarker approach. At the same time, a large number of patients fail to express TOPO1 in the metastatic setting and perhaps should be spared irinotecan-based approaches including the use of FOLFOXIRI. [Table: see text]
Integrating nursing into oral chemotherapy education.
Authors: Meghan Shea, Nancy Weinstein, Jessica A. Zerillo
Journal: Journal of Clinical Oncology (2016)

81 Background:The shift of chemotherapy administration from the oncology infusion suite to the home has unwound systems and left patients vulnerable to errors. Many of the safeguards for parenteral chemotherapy, including education by an oncology nurse, are absent for oral chemotherapy. The 2013 American Society of Clinical Oncology/Oncology Nursing Society Standards served as the framework for improving the initiation of oral chemotherapy at Beth Israel Deaconess Medical Center. Methods: Clinicians caring for patients with melanoma and renal cell cancer were surveyed. A team of clinicians, nurses and pharmacist delineated a process map from writing an oral chemotherapy prescription to first follow-up appointment. A retrospective chart review of baseline data provided by a specialty pharmacy revealed 33 patients who initiated oral chemotherapy between July 2014 to July 2015, were not on a clinical trial and had at least two follow-up appointments. The team’s aim is by February 1, 2016 patients initiating oral chemotherapy receive nursing education by the first follow-up visit and at least 50% have documentation of a comprehensive education, including administration, safe handling and side effects. Results: The survey response rate was 9 of 9 (100%). The clinicians ranked patient education as the top priority. Second to time, lack of nursing involvement was identified as the most common contributing factor to patients not receiving a comprehensive education. At baseline, 1 of 33 (3%) patients initiated on oral chemotherapy received education from a nurse. Side effect education was documented in 21 of 33 (64%) clinicians’ notes, though education on safe handling only in 7 of 33 (15%), and education on administration was never documented. Plan-Do-Study-Act cycles are ongoing to implement varied approaches of nursing involvement, including telephone and in-person consultations. Conclusions: Lack of nursing involvement was identified as a missing element in oral chemotherapy care. Because clinicians were engaged, a survey to evaluate the current process succeeded with a high response rate. At baseline, there are significant gaps and variability in current practice, and interventions to provide patients with a comprehensive education are underway.
Improved collaboration and clinical trial enrollment in adolescent and young adult (AYA) oncology patients after the establishment of an AYA program.
Authors: P. H. Shaw
Journal: Journal of Clinical Oncology (2010)

9558 Background: Over the past thirty years there has been significant improvement in the survival rates of pediatric and older cancer patients, but adolescent and young adult (AYA) patients aged 15-40 years old have not seen the same improvement. The reasons are multifactorial but data has shown a direct correlation between improving cure rates and clinical trial enrollment. We have published data showing inferior clinical trial enrollment when these patients are treated at an adult versus an affilaited pediatric oncology center. To address this deficit, we at the Children's Hospital of Pittsburgh (CHP) and University of Pittsburgh Cancer Institute (UPCI) established a joint AYA Oncology Program. The primary goal of this program was and is to improve outcomes by increasing clinical trial accrual in this population. Methods: We retrospectively analyzed patients referred to our AYA program from July, 2006 through December, 2009 to establish if referrals were improving and clinical trial enrollment was increasing versus historical controls from 2003-2006 at the same institutions. Patients outside of the AYA age range could be evaluated if they were diagnosed with a malignancy more common in this age group. Results: 46 patients were referred to our program from 9 different hospitals. In the year prior to program (2005), only 2 patients were referred which increased to 15 in 2006, followed by 11 in 2007, 13 in 2008 and 14 projected for 2009. The median age of all patients evaluated was 22 years-old (range 13-75 years). 18 of these patients were treated or followed at CHP with 5 (27%) enrolled on a clinical trial. 21 were treated at the UPCI with 5 (24%) on a clinical trial. There was no difference in enrollment rates in those patients treated at CHP after the program was established but there was superior trial participation compared to the previous three years at the UPCI (p<0.001). Conclusions: Our data demonstrate that establishing a unified AYA Oncology Program both leads to increased referrals and improved clinical trial enrollment in this population. It is too soon to conclude if more trial participation for these patients will translate into improved disease-free survival. No significant financial relationships to disclose.
Clinical significance of Fas, VEGF, and EGFR expression in advanced gastric carcinoma.
Authors: Sheng Ye, Jian Rong, Xiaohong Fu, Tongyu Lin
Journal: Journal of Clinical Oncology (2013)

58 Background: Researches had proved that apoptotic signal proteins Fas-mediated cellular apoptosis influenced development of gastric carcinoma and affected survival of gastric carcinoma patients. Epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) over expression had been associated with poor survival in several cancers including gastric carcinoma. Methods: Immunohisto-chemistry was performed to detect Fas, EGFR and VEGF protein expression in 60 newly diagnosed patients with gastric carcinoma in the First Affiliated Hospital of Sun Yat-sen University from November 1999 to June 2005. Clinical Data of these patients were reviewed. Time to progression (TTP) and overall survival (OS) were compared by log-rank test according to the expression status of Fas, EGFR and VEGF. Results: There were 40 males and 20 females, all patients were stage IV. All patients were treated with infused fluorouracil plus leucovorin and oxaliplatin or paclitaxel. The positive rate of Fas, EGFR and VEGF in gastric carcinoma was 73.3%, 35% and 40% respectively. TTP for patients with Fas positive was significantly superior to patients with Fas-negative (p&lt;0.05). EGFR and VEGF were not correlated with TTP (p&gt;0.05). Fas, EGFR and VEGF were not associated with overall survival(p&gt;0.05). Conclusions: Fas, EGFR and VEGF are often expressed in gastric carcinoma. Fas expression is correlated with longer TTP. EGFR and VEGF expression were not associated with TTP. Fas, EGFR and VEGF were not a prognostic factor for OS.
Venous thromboembolism in patients with pancreatic cancer: Incidence and effect on survival in east Asian ethnic groups.
Authors: Jong-Chan Lee, Junhyeon Cho, Yohan Park, Young Sun Ro, Hyejin Choi
Journal: Journal of Clinical Oncology (2013)

151 Background: Pancreatic cancer is known to be most frequently associated with venous thromboembolism (VTE), with the incidence of 10~20% in Western countries. As for the East Asian ethnic groups, just one small retrospective study showed lower incidence (5.3%) than other ethnic groups. However, there have been no large retrospective cohort studies of VTE in pancreatic cancer of East Asian ethnic group. Methods: We retrospectively reviewed the medical records of patients diagnosed with pancreatic adenocarcinoma in 2005~2010 at Severance Hospital, Seoul, Korea. Principal outcomes were incident VTE events and mortality. Cox proportional hazards models were used to analyze associations between specific risk factors and principal outcomes. Results: We investigated 1334 patients with pancreatic adenocarcinoma and 218 (16.3%) patients were excluded due to incomplete medical records and loss to follow-up. Among 1116 eligible patients, the overall and 1-year cumulative VTE incidence were 13.9% and 11.2% respectively. The incidence rate during the half year, 1-year and 2-years were 23.4, 17.7, 15.6 events per 100 person-years, respectively. Among total of 155 VTE patients, abdominal VTE was 52.9%, deep vein thrombosis was 21.3%, pulmonary thromboembolism was 19.4%, and head and neck VTE was 18.7%. In multivariable analyses, significant predictors of developing VTE included advanced metastatic stage (HR=2.08, 95% CI 1.37 to 3.17) and treatment of chemotherapy or radiotherapy, including CCRT (HR=1.52, 95% CI 16 to 1.99). VTE was a significant risk factor of 1-year and overall mortality (HR=1.44, 95% CI 1.15 to 1.79 and HR=1.45, 95% CI 1.21 to 1.73). Among 155 VTE patients, head and neck (H&amp;N) VTE revealed highest risk of overall mortality (HR=2.05, 95% CI 1.27 to 3.33, versus non-H&amp;N VTE). Conclusions: Approximately 13.9% of pancreatic adenocarcinoma patients developed VTE in East Asian ethnic group and this incidence was not significantly different from other ethnic groups. Advanced metastatic stage was the strongest predictor of VTE which would be a significant risk factor of 1-year mortality. Among VTE patients, head and neck VTE was 18.7% and showed the highest risk of overall death.
Prospective assessment of the adherent perinephric fat in partial nephrectomies: Predictors and impact on peri-operative outcomes.
Authors: Charles Dariane, Cecile Badoual, Joan Tordjman, Karine Clement, Thomas Le Guilchet, Sophie Hurel, Arnaud Mejean, Marc Olivier Timsit
Journal: Journal of Clinical Oncology (2016)

543 Background: The surgical complexity of partial nephrectomy (PN) can be partly anticipated using renal morphometric scores that do not consider patient related issues such as obesity or perirenal fat. Our primary objective was to prospectively assess the predictive factors for adherent perinephric fat (APF) and its impact on the onset of complications. The secondary objective was to correlate the surgical appraising with the histological reality of APF. Methods: Fifty consecutive patients undergoing robotic or open PN were prospectively included from November 2014 to March 2015. The previously published Mayo adhesive probability score (MAP score) was calculated and compared to the per-operative surgical assessment of APF using a 0 to 3 scale (APF being defined by a score ≥ 2). Fat was analyzed histologically for fibrosis (HES staining and picrosirius red) and inflammatory infiltrate of macrophages (immunohistochemistry using anti-CD68 antibody). Results: APF was present in 18 patients (36%), with no impact on surgical approach (31.3% vs 38.9 robotic way, without surgical conversion). APF was associated with longer operating time (169 min vs. 146 min, p = 0.036) and increased blood loss (469 mL vs 179 mL, p = 0.014). Duration of clamping, rate of positive margins, blood transfusion and the Clavien-Dindo score were not different (Table 1). In multivariate analysis, only male gender (p = 0.044), age (p = 0.014) and MAP score (p = 0.00057) were significant predictors of APF. Histologically, APF was characterized by a marked fibrosis but no macrophage infiltrate. Conclusions: APF can be accurately predicted using radio-clinical data as the MAP score, combined with age and gender. APF is associated with increased operative time and blood loss without impacting the rate of complications. Histological analysis of APF demonstrates significant fibrosis without inflammatory infiltrate. [Table: see text]
Novel MRI techniques as biomarkers of rapid response prediction in advanced cervical cancer
Authors: V. N. Harry, S. Semple, F. J. Gilbert, D. E. Parkin
Journal: Journal of Clinical Oncology (2008)

5569 Background: The emergence of functional imaging techniques that can integrate pathophysiological and morphological changes offers great promise in providing early markers of tumour response. This would ultimately enable the development of customised regimes as well as facilitate clinical trials on targeted therapeutic agents. Diffusion weighted MRI (DWI) can characterise biological tissues based on their water diffusion properties and allows for the calculation of the apparent diffusion coefficient (ADC), a parameter which refers to the specific diffusion capacity of tissues. Similarly, dynamic contrast-enhanced imaging (DCE-MRI) can exploit tumour enhancement characteristics to assess vascularity changes and the antiangiogenic response of a tumour during therapy. We investigated DWI and DCE-MRI as early predictors of treatment outcome in women with advanced cervical cancer. Methods: Twenty women with cervical cancer FIGO stage 2b and above who received concurrent chemoradiation were included in a prospective cohort study. MR imaging was carried out before therapy and then repeated after 2 weeks of therapy using the phased array torso coil of a 1.5 T scanner. This included a diffusion weighted epi acquisition and dynamic T1 images using Gd-DTPA contrast. Change in ADC as well as change in peak and mean enhancement between these two examinations was tested for correlation with tumour response or non-response as determined by clinical assessment. A p value of < 0.05 was considered significant. Results: ADC change (p = 0.004, r = 0.62, Pearson correlation) as well as change in peak (ρ=.690, p=.004 Spearman's correlation) and mean (ρ=.677, p=.006 Spearman's correlation) tumour enhancement after 2 weeks of treatment all showed a significant correlation with clinical response. Conclusions: Diffusion and dynamic MRI parameters predicted treatment response as early as 2 weeks in women receiving concurrent chemoradiation for advanced cervical cancer. These techniques may ultimately prove to be useful biomarkers for predicting therapy response and so improve patient care by individualising therapy and allowing for early modifications to be made to the therapy regime. Reliable and rapid response prediction may also assist in the development of new targeted therapeutic agents. No significant financial relationships to disclose.
PDGFR-α/β expression correlates with the metastatic behavior of human colorectal cancer—A rationale for a molecular targeting strategy?
Authors: C. Schimanski, T. Wehler, P. Galle, I. Gockel, M. Moehler
Journal: Journal of Clinical Oncology (2008)

22019 Background: As new multi-target tyrosin kinase inhibitors are emerging in the therapy of various malignancies, our aim was to define the (co-)expression pattern of receptor-tyrosine-kinases PDGFRα/β in human colorectal cancer. Methods: The (co-)expression pattern of PDGFRα/ß was analyzed by RT-PCR in 99 histologically confirmed human colorectal carcinomas and five colorectal cancer cell lines. In addition, IHC staining was applied for confirmation of expression and analysis of RTK localisation. Results: Colorectal cancer cell lines revealed varying expression intensities of PDGFRα and PDGFRß. The majority of human colorectal cancer specimens revealed a PDGFRα (83%) or PDGFRß (60%) expression. While PDGFRα showed a predominantly cytoplasmatic staining in tumor cells as well as in stromal pericytes, PDGFRß was mainly restricted to stromal pericytes only. PDGFRα expression also significantly correlated with lymph node metastasis (P=0.0082) and advanced UICC stages III/IV (P=0.018) in older patients (P=0.043). PDGFRß expression only revealed a trend towards lymphatic dissemination (P=0.099) Co-expression of PDGFRα/β occurred in 57% of colorectal cancer samples whereas another 29% of samples depicted a mono-expression of PDGFRα or PDGFRß. Interestingly, PDGFRα/β expression significantly correlated with lymphatic metastasis (P=0.007) and advanced UICC stages III/IV (P=0,017) in older patients (P=0.03). Conclusion: Our results reveal, that PDGFR-α/β expression significantly correlates with lymphatic dissemination and therefore encourage an application of PDGFR-α/β RTK-inhibitors within a combination therapy. No significant financial relationships to disclose.
Overexpression of IL-32 as a novel prognostic factor in patients with clear cell renal cell carcinoma after a nephrectomy.
Authors: Hyo Jin Lee, Hyun-Jung Lee, Zhe Long Liang, Jae-Sung Lim, Jin Man Kim
Journal: Journal of Clinical Oncology (2012)

413 Background: Interleukin-32 (IL-32) is a proinflammatory cytokine, which acts as an important pathogenetic factor in various diseases and malignancies. However, the clinical significance of IL-32 expression in renal cell carcinoma has not been previously investigated. Methods: We examined 112 patients with localized clear cell renal cell carcinoma (CCRCC) who underwent nephrectomy. The clinicopathologic data were obtained by retrospective review and the expression levels of IL-32 were studied by immunohistochemistry. Tumors were classified into four scores based on the staining intensity (0, no staining intensity; 1, weak; 2, intermediate; 3, strong). The cases with staining intensities from 0 to 2 were included in the IL-32 low expression group (LEG); whereas, those with staining intensity of 3 were considered the IL-32 high expression group (HEG). Correlations between IL-32 expression and clinicopathologic features were determined. Results: Staining intensities were determined for all cases as follows: 26 cases (23.2%) (score 0), 43 cases (38.4%) (score 1), 31 cases (27.7%) (score 2), and 12 cases (10.7%) (score 3). IL-32 HEG showed a higher recurrence rate compared to the IL-32 LEG (50% vs. 13%, P=0.001). For survival rates, the 5-year recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) rates were lower in the IL-32 HEG compared with the IL-32 LEG (RFS, 87% vs. 50%, P = 0.001; DSS, 92% vs. 58.3%, P &lt; 0.001; OS, 84% vs. 58.3%, P = 0.026, respectively). Univariate analyses showed that Fuhrman nuclear grade and high IL-32 expression were significant prognostic factors for predicting RFS, DSS, and OS in CCRCC; while, multivariate analyses indicated Fuhrman nuclear grade and high IL-32 expression (RFS, HR, 4.932, P = 0.009; DSS, HR 6.736, P = 0.002; OS, HR, 2.992, P = 0.037, respectively) were still independent risk factors. Conclusions: IL-32 overexpression was associated with high recurrence rates and low RFS, DSS, and OS, suggesting that it could be a novel prognostic factor for predicting outcomes in patients with CCRCC after a nephrectomy.
NOD2/CARD15 Variants of Donor and Recipient as Critical Risk Factors for the Development of Bronchiolitis Obliterans Syndrome after Allogeneic Stem Cell Transplantation.
Authors: Gerhard Hildebrandt, Daniel Wolff, Bernd Hertenstein, Hildegard T. Greinix, Gerhard Rogler, Julia Brenmoehl, Christian Schulz, Anne M. Dickinson, Reinhard Andreesen, Ernst Holler
Journal: Blood (2005)
Collective analysis of efficacy and safety of patients with advanced hepatocellular carcinoma (HCC) enrolled into early-phase clinical trials.
Authors: Vinu Madhusudanannair, Brad H. Pollock, Norma Ketchum, Steven Weitman, John Sarantopoulos, Devalingam Mahalingam
Journal: Journal of Clinical Oncology (2014)

320 Background: Sorafenib is the only approved systemic therapy in HCC. Clinical trials in HCC often exclude patients with Child-Pugh Stage (CPS) B/C cirrhosis. Furthermore, limited information on outcomes specific to HCC population are reported from early clinical trials. We evaluated the efficacy and safety of early phase clinical trial agents used to treat HCC. Methods: 42 consecutive patients with advanced HCC enrolled in one of the 53 phase I trials at our institution between 2003- 2013 were analyzed. Median progression free survival (mPFS) and overall survival (mOS) were estimated from Kaplan-Meier curves along with medians and groups were compared with the log rank test. The magnitude of association and survival was estimated with the hazard ratio (HR). Results: Median age 63 (33–84), males 75 %, ECOG PS 0–1 92%, CPS A 19%, B 71.7% and C 9.4%. 41.5% subjects were treated with prior Sorafenib. Class of agents used included cytotoxics such as microtubule inhibitors (26.4%), anti-folates (5.7%), alkylators (1.9%), topoisomerase inhibitors (5.7%), and non-cytotoxic agents such as pro-apoptotic therapies (15.1%), anti-VEGF (17%) mTOR/ EGFR/ IGFR (22.6%), and HDAC inhibitors (5.7%). When evaluating for efficacy for all patients, the mPFS (95% CI) =2.3 (1.9, 3.9) months and 12 month OS ± SEM = 59% ± 15%. The mPFS was 3.7 months versus 2.1 months for CPS A subjects and CPS B/C subjects respectively (HR 1.5, CI: 0.7- 3.5, p= 0.31). The 12-month OS was 80 ± 18% among pts with CPS A vs 74 ± 8% in CPS B. Grade 3-4 toxicity included hematologic (13.2%) and hepatic (20.8%), with no significant difference in toxicity between the two CPS groups. Finally, cytotoxic agents had a mPFS of 3.1 months (95% CI: 2.1- 4.4) vs 1.9 months (95% CI: 1.1- 2.3) for non-cytotoxic therapy (HR 1.56, 95% CI: 0.8–3.07, p = 0.19). The 12 month OS was 46% vs 50% between these two groups (HR 6.2, CI: 1.3–29.3, p = 0.009). Conclusions: Patients with advanced HCC have a modest survival that is compounded further by poor liver function. Our data suggests that there are no significant differences in efficacy and safety between HCC patients with varying liver dysfunction based on CPS status.