tbuckley/cabot-search huggingface dataset:
Outcomes after noncurative locoregional treatment in patients with unresectable metastatic colorectal carcinoma.
Authors: Qiong Yang, Fangxin Liao, Shousheng Liu, Chang Jiang, Wen-zhuo He, Liang-ping Xia
Journal: Journal of Clinical Oncology (2016)

654 Background: A curative hepatic or pulmonary metastasectomy for colorectal carcer is a generally accepted procedure. However, the value of noncurative locoregional therapy for unresectable metastatic colorectal carcer was not well defined. Methods: Of 1,174 patients with unresectable colorectal cancer from 2003 to 2014 retrospectively reviewed, 62 patients received curative regional treatment, 290 patients received locoregional therapy, and 822 patients received standard chemotherapy. Propensity score matching was used to adjust the balance of baseline data between locoregional therapy arm and chemotherapy arm. Kaplan-Meier survival analyses were based on data after propensity score matching. Factors possibly influencing survival were evaluated by univariate and subsequently by multivariate analyses. Results: After propensity score matching, 544 patients were included in this study, 272 in locoregional therapy arm and 272 in chemotherapy arm, respectively. Locoregional therapy included metastasectomy, radiofrequency ablation, percutaneous microwave coagulation therapy and radioactive particle implantation. The addition of locoregional therapy to chemotherapy significantly improved the overall survival with median overall survival 38.73 months (95%CI 34.93-42.54 months) in locoregional therapy arm versus 19.8 months (95%CI 18.06-21.54 months) in chemotherapy arm, respectively, p&lt;0.001. 9 factors were associated with overall survival by univariate analysis, which include primary tumor site, initial stage at first diagnosis, pathological grading, target organ of regional treatment, CA199 and LDH at diagnosis of advanced disease, CEA, CA199 and LDH before regional treatment. Furthermore, CEA (&gt;5ng/ml) and LDH (&gt;245U/L) before regional treatment were identified as independent poor prognostic factors by multivariate analysis. Median overall survival according to the presence of 0, 1, or 2 factors was 49.4 months, 35.7 months, and 27 months. Conclusions: Unresectable metastatic colorectal cancer also benefited from locoregional therapy. Two pre-locoregional treatment risk factors could select the patients most likely to benefit from this strategy.
An alternative method to detect peritoneal recurrence of gastric cancer: Clinical application of CT colonography.
Authors: Kenichi Iwasaki, Haruhiko Cho, Takafumi Watanabe, Hiroshi Kuwabara, Tsutomu Hayashi, Junya Shirai, Hirohito Fujikawa, Tetsuo Yoshida, Takaki Yoshikawa, Akira Tsuburaya
Journal: Journal of Clinical Oncology (2013)

19 Background: Peritoneal metastasis (PM) is among the most frequent patterns of recurrence of gastric cancer: however, it cannot be detected by general axial CT or even by PET until it develops to massive ascites or an overt peritoneal mass. CT colonography (CTC) is used to screen for colon cancer, with the advantage that it can provide both colonic and extracolonic information at the same time. Methods: CTC was applied for patients that were suspected to have PM based on their clinical symptoms and general CT findings, without sufficient information to confirm the diagnosis, to detect signs of peritoneal metastasis earlier. PM diagnosis in CTC was defined as the finding of an abnormal deformity of the colonic wall without intraluminal tumor by both the attending doctors and radiologists. Results: Twelve patients suspected of having PM were enrolled in the study. Nine of those patients (75%) were positive for PM by CTC. Abnormal colonic deformities were also identified in other locations other than the lesions detected by general CT in 6 patients. All of the nine patients with positive PM were clinically confirmed to have PM, and had a poorer prognosis (median survival: 252 days). The three patients with negative PM are all alive without recurrence. Conclusions: CTC is thus considered to be a candidate for the early detection of PM. Further study with more patients is therefore warranted.
Effect of combined consideration of distinct signatures of VEGF and soluble VEGFR2 on prognostic implication in gastric cancer.
Authors: Chan-Young Ock, Ah-Rong Nam, Ju-Hee Bang, Tae-Yong Kim, Kyung-Hun Lee, Sae-Won Han, Seock-Ah Im, Tae-You Kim, Yung-Jue Bang, Do-Youn Oh
Journal: Journal of Clinical Oncology (2016)

56 Background: Anti-angiogenic strategy in gastric cancer (GC) has been highlighted again due to the recent success of ramucirumab and apatinib. Therefore, the comprehensive network of VEGF, soluble VEGF receptor-2 (sVEGFR2) and cytokines and other angiogenic factors (CAF) in GC and their prognostic impact would be of importance, although they have been poorly understood. We aimed to find out the CAF signature associated with VEGF and sVEGFR2, and to explore their prognostic implication in GC. Methods: We measured pretreatment serum levels of 52 CAFs, including VEGF and sVEGFR2, using multiplex bead immunoassays and ELISA, in 70 patients who were diagnosed with GC in Seoul National University Hospital, and treated with palliative chemotherapy. Linear regression analysis for correlating CAFs with VEGF and sVEGFR2, and survival analysis by log rank test and Cox regression analysis were performed. Results: The VEGF signature was shown to be associated with seven CAFs (interluekin [IL]-7, IL-12p70, IL-2Ra, IL-10, stem cell factor, Fibroblast growth factor-basic, IL-3). The sVEGFR2 signature was associated with IL-4 and platelet-derived growth factor beta, but VEGF and sVEGFR2 showed no association with each other. Patients with high VEGF had a tendency to have worse overall survival (OS) than those with low VEGF (11.2 months versus 16.7 months; P = 0.061). However, among patients with high-sVEGFR2, OS was not different according to VEGF (12.1 months, high-VEGF versus 15.1 months, low-VEGF; P = 0.546). Interestingly, the poor prognostic impact of high-VEGF was far significant in patients with low-sVEGFR2 (10.9 months versus 16.8 months; P = 0.036). With this perspective, VEGF/sVEGFR2 ratio was significantly correlated with worse OS in univariate as well as multivariate analysis (HR 1.78 [95% CI 1.08-2.94], P= 0.024). Conclusions: Based on the comprehensive network analysis of CAF, VEGF and sVEGFR2 had distinct CAF signatures in GC. Consideration of both VEGF and sVEGFR2 confers more accurate prognostic implication compared with VEGF alone in GC. Regarding the angiogenic aspect, VEGF/sVEGFR2 ratio is significantly correlated with survival outcome in GC.
Increasing disparities in age-related incidence of colon and rectal cancer in the United States, 1975-2010.
Authors: Christina Edwards Bailey, Chung-Yuan Hu, Y. Nancy You, George J. Chang
Journal: Journal of Clinical Oncology (2014)

392 Background: The overall incidence of colorectal cancer (CRC) has been decreasing since 1998, but there has been an apparent rise in the incidence of CRC in young adults. The primary aim of this study was to evaluate age-related disparities in secular trends in CRC incidence in the United States. Methods: A retrospective cohort study was performed using the Surveillance, Epidemiology, and End Results (SEER) registry. All patients diagnosed with colon or rectal cancer from 1975 to 2010 was queried. SEER*Stat (version 8.04, National Cancer Institute) was used to obtain the annual cancer incidence rates, annual percent change (APC), and corresponding p values for the secular trends. Results: Overall age-adjusted CRC incidence decreased by 0.92% between 1975 and 2010. There has been a steady decline in the incidence of CRC in patients age 50 years or older, but the opposite trend has been observed in patients 20 to 34 years of age. The APC for patients with localized, regional, and distant colon cancer at diagnosis in the 20 to 34 year age group was 1.10 (95% CI 0.28 to 1.93; p=0.01), 0.91 (95% CI 0.23 to 1.61; p=0.01) and 1.81 (95% CI 0.88 to 2.75; p&lt;0.001). The APC for patients with localized, regional ,and distant rectal cancer in the 20 to 34 year age group was 4.03 (95% CI 3.02 to 5.05; p&lt;0.001), 3.05 (95% CI 1.95 to 4.17; p&lt;0.001) and 2.66 (95% CI 1.33 to 3.99; p&lt;0.001). Based on current trends, in 2030 the incidence rate for colon and rectal cancer will increase by 90% and 124.2% respectively for patients 20 to 34 years of age while decreasing by 37.8% and 34.3% for patients 50 to 75 years of age. Conclusions: There has been a significant increase in the incidence of CRC diagnosed in patients age 20 to 34, with a decline in older patients. Further studies are needed to determine the cause for these trends and identify potential preventive and early detection strategies. [Table: see text]
The prognostic value of semi-quantitative <sup>123</sup>I mIBG scintigraphy at diagnosis in high-risk neuroblastoma: Validation of the SIOPEN score method.
Authors: V. Lewington, U. Poetschger, A. Boubaker, Z. Bar-Sever, B. Drake, A. Staudenherz, M. R. Castellani, B. Lambert, K. Grange, P. Brock, A. Garaventa, I. Yaniv, D. Valteau Couanet, V. Castel, A. Forjaz De Lacerda, J. Malis, H. Schroeder, R. Luksch, K. Beiske, R. L. Ladenstein
Journal: Journal of Clinical Oncology (2011)

9511 Background: A semi-quantitative reporting method developed by an international expert panel (J Nucl Med 2009;50:1379) was used to evaluate the role ofI-123 meta-IodoBenzylGuanidine [123I mIBG] imaging in high risk neuroblastoma [HR-NBL]. Method: Patterns of skeletal 123I mIBG uptake were assignednumerical scores (Mscore) ranging from 0 (no metastasis) to 72 (diffuse metastases) within 12 body areas as described previously (J Nucl Med 2009;50:1379). 271 anonymised, paired image data sets acquired at diagnosis and on completion of Rapid COJEC induction chemotherapy were reviewed, constituting a representative sample of 1602 children treated prospectively within the HR-NBL1/SIOPEN trial. Pre-and post-treatment Mscores were compared with bone marrow cytology (BM) and 3 year event free survival (EFS). Results: 224/271 patients showed skeletal mIBG uptake at diagnosis and were evaluable for mIBG response. Complete skeletal mIBG response (CR) to Rapid COJEC induction was achieved by 66%, 34% and 15% of patients who had pre-treatment Mscores of <18 (n=65, 29%), 18-44 (n=95,42%) and ≥45 (n=64, 28.5%) respectively (p<.0001). Mscore at diagnosis correlated with post treatment score (p<0.001) and with BM involvement (p<0.0001). The 3 year EFS in 47 children with Mscore 0 at diagnosis was 0.68 (±0.07), by comparison with 0.42 (±0.06), 0.35 (±0.05) and 0.25 (±0.06) for patients in pre-treatment Mscore groups <18, 18-44 and ≥45, respectively (p<0.001). An Mscore threshold of ≥45 at diagnosis was associated with significantly worse outcome by comparison with all other Mscore groups (p=0.029). Patients who achieved metastatic CR (mIBG and BM) after Rapid COJEC had a significantly longer 3 year EFS of 0.53 (±0.07) compared with 0.24 (±0.04) observed in children who did not reach CR (p=0.005). Conclusions: SIOPEN scoring of 123I mIBG imaging at diagnosis in children with HR-NBL predicts response to induction chemotherapy and outcome. (1) Lewington V et al. Development of a semi-quantitative I -123 mIBG reporting method in HR-NBL.
Implication of PARP-1 expression in prostate cancer progression.
Authors: E. Thomas, P. O. Gannon, I. H. Koumakpayi, M. Latour, A. Mes-Masson, F. Saad
Journal: Journal of Clinical Oncology (2011)

e15025 Background: Prostate cancer (PCa) is the leading cancer diagnosed in men, with one out of seven developing PCa and a quarter of those progressing to an advanced stage of the disease. Intense research is ongoing to be able to predict the probability of disease progression. As current nomograms are solely composed of clinico-pathological factors, the inclusion of molecular markers may potentially increase their precision. The over-expression of poly(ADP-ribosyl) polymerase-1 (PARP-1) is associated with colorectal cancer progression as well as a poor prognosis in ovarian and breast cancers. We hypothesized that the proportion of PARP-1 positive (+) nuclei would increase with PCa progression. The present study evaluated the value of PARP-1 in predicting biochemical recurrence (BCR) in PCa patients. Methods: We analyzed the nuclear localization of PARP-1 in prostate tissues by immunohistochemistry on tissue microarrays. Our cohort consisted of radical prostatectomy tissues from 62 patients with long follow-up operated at the Centre Hospitalier de l’Université de Montréal (CHUM). We analyzed the percentage of PARP-1+ nuclei using the Aperio software and the IHC Nuclear algorithm (v8.001) in both malignant and non-malignant (normal adjacent to the tumor, prostatic intra-epithelial neoplasia) tissues. Statistical analyses were performed using SPSS software (v.11). Results: We observed increased PARP-1+ nuclei in malignant tissues compared to non-malignant tissues (Wilcoxon, p=0.001). We found that the percentage of PARP-1+ nuclei in malignant tissues correlated with BCR (Spearman correlation, r=0.389, p=0.002). In a univariate COX regression model, the percentage of PARP-1+ nuclei predicted BCR (p=0.001). A multivariate COX regression determined that the percentage of PARP-1+ nuclei was a predictor independent of the clinico-pathological factors used in Kattan’s nomogram (p=0.048). Conclusions: Our analysis suggests that the percentage of PARP-1+ nuclei increases with PCa progression and that it can predict BCR independently of current clinico-pathological factors. Considering the predictive potential of PARP-1 in this cohort, we are expanding this analysis to a larger cohort to fully assess the predictive value of PARP-1 in PCa.
Effect of socioeconomic status and race on outcome after radical prostatectomy for localized prostate cancer
Authors: T. M. Koppie, A. S. Robbins, P. K. Mills, R. W. deVere White
Journal: Journal of Clinical Oncology (2008)

5061 Background: In the US, profound social disparities in cancer diagnosis, treatment and mortality have been demonstrated in various cancers. We sought to evaluate the impact of socioeconomic status (SES) on utilization and cancer specific survival (CSS) after radical prostatectomy (RP) for Gleason <7, localized prostate cancer. Methods: The California Cancer Registry (CCR) is a population-based registry that has collected cancer incidence data for the entire population of California since 1988. We evaluated the association between SES and CSS for men who underwent initial RP for localized, Gleason score <7 prostate cancer in California from 1996 to 2005. SES status was defined using a residential block group method and ranked into quintiles. Survival was analyzed using Cox proportional hazards models. Results: Between 1996 and 2005, 123,836 men were diagnosed with localized, Gleason score <7 prostate cancer. Of these men, 39,192 (32%) underwent RP as initial therapy. Men of lower SES were less likely to undergo RP for localized prostate cancer than men of higher SES. For men who underwent RP (n = 39,192), the risk of death from prostate cancer declined 51% from the lowest quartile of SES to the highest quartile of SES (P for linear trend = 0.0003). Adjustment for race produced nearly identical results. (see table) Conclusions: Men of lower SES are less likely to undergo RP in the management of localized prostate cancer. Even when RP is performed, men with lower SES still have an increased cancer specific mortality when compared to men of higher SES. Quintile of SES Percent of patients undergoing RP HR for death from prostate cancer HR for death from prostate cancer–adjusted for race 1 (lowest) 27.4 1.00 (referent) 1.00 (referent) 2 29.2 0.74(0.46–1.18) 0.67(0.42–1.08) 3 30.1 0.72(0.46–1.13) 0.63(0.40–0.99) 4 32.2 0.48(0.30–0.76) 0.40(0.25–0.66) 5 (highest) 35.3 0.49(0.32–0.76) 0.41(0.26- 0.65) No significant financial relationships to disclose.
CK13 expression in prostate tumors of patients with bone metastases at diagnosis.
Authors: Sandy Liu
Journal: Journal of Clinical Oncology (2016)

257 CK13 Expression in Prostate Tumors of Patients with Bone Metastases at Diagnosis Sandy T. Liu, Radu Cadaneanu, Kevin Lai, Bao Zhang, Haibo Liu, Lihong Huo, Colette Galet, William Aronson, Matthew Rettig, Michael Lewis, Isla P. Garraway; University of California Los Angeles, Los Angeles, CA Background: Biomarkers of lethal prostate cancer (PCa) are needed for appropriate clinical management. Benign stem/progenitor (S/P) cells reside in the basal layer of prostatic ducts/acini and function as cells of origin for PCa. Aggressive tumor cells may co-opt properties of S/P cells, such as mechanisms of resistance to castration. Distinct prostate epithelial populations, including stem-like tubule-initiating cells (TIC), basal cells (BC), and luminal cells (LC) can be isolated from benign prostate tissue. In this study, gene expression analysis was performed on benign prostate to identify TIC markers that may persist in cancer. Methods: Microarray analysis was performed on Epcam+CD44-CD49f Hi TIC, Epcam+CD44+CD49f Hi BC, and Epcam+CD44-CD49f Lo LC using Affymetrix Array. Data was analyzed using Partek Genomics and validated with RT-PCR. Immunohistochemistry (IHC) was performed on 1) prostate tissue microarray (TMA) from 332 prostatectomies 2) pretreatment tissue from stage M1 patients and 3) post-treatment prostate tissue. Results: Affymetrix identified increased cytokeratin 13 (CK13) expression in TIC relative to BC and LC. Rare CK13+ epithelia are seen in ducts/acini of benign prostate tissue. TMA IHC revealed CK13+ cancer cores in 9% of cases, and significantly correlated with recurrence (p = 0.031), progression to castration-resistance (p = 0.05), and metastases (p = 0.009). Biopsy tissue from hormone-naive patients with diffuse bone metastases displayed CK13+ tumors in primary and metastatic foci. Epithelial cells populating residual prostate glands following radiation and ADT also displayed CK13 expression. Conclusions: CK13+ tumors reflect a “stem-like” state, enabling survival in low-androgen conditions and interactions that support invasion/metastases. Further characterization of CK13+ PCa variants could lead to clinical trials investigating agents that may prevent/treat dissemination and progression.
Optimizing surgical instrument sets for cases involving breast and plastic surgeons.
Authors: Abigail Suzanne Caudle, Jason B. Fleming, Brian M Garcia, Marina Lozano, Darryl Rigby, Rita Manuel-Byrd, Lisa McMillian, Chris Avalos, Rachel Hodge, Charles E Butler, Kelly Hunt, Don Baumann
Journal: Journal of Clinical Oncology (2016)

33 Background: Processing operative instrumemt sets is a major cost for surgical cancer care. Optimizing standard sets requires availability of instruments reflecting varied surgeon preferences while minimizing unnecessary instruments. Additionally, increasing utilization of oncoplastic reconstruction after mastectomy and lumpectomy requiring breast and plastic surgery sets further expands the number of instruments required. The goal of our study was to optimize standard sets used for cases combining breast and plastic surgeons and to determine cost savings Methods: Baseline data was recorded over a 2 week period (13 cases) including number of instruments available and number unused for non- flap breast-plastics combo (BPC) cases. An independent observer timed instrument set-up times. 22 breast and 14 plastic surgeons were polled for their requested instruments for designated cases. A BPC set was designed based on this data and reviewed with surgeons to update preference cards. After a 6 week implamentation/education period, repeat data was recorded (18 cases). Cost of instrument processing was based on labor and supply cost of $0.22/instrument. Results: Two breast surgery sets (65 and 97 instruments) and one plastics set ( 93 instruments) were used at baseline. The median number of available instrumeets was 172.5/case, with median 126.5 instruments unused. A mean of 3.8 separately packaged instruments were required per case with mean set-up time of 4m46s. The new BPC set contains 103 instruments. A median of 106.5 instruments were available after implementation. The median number of unused was reduced by 53% to 59.5, with a drop in number of separately processed instruments to 2.5. Mean set-up time was reduced to 2m16s. Reducing the size of of standard sets reduced processing costs by $12.10 or $19.14/case (depending on the breast set used for comparison). Combining sets resulted in an additional cost savings of $6.56/case by reducing extra packaging costs. Conclusions: combining breast and plastic sets and eliminating unnecessary instruments resulted in cost savings of $18.66-$25.70/case. It also reduced OR instrument set-up time by 2.5 minutes/case which has significant impact at high volume centers.
<sup>1</sup>H NMR–based metabolic profiling of serum for the detection of pancreatic cancer.
Authors: K. Owusu-Sarfo, V. Asiago, N. Gowda, N. Shanaiah, B. Xi, E. G. Chiorean, D. Raftery
Journal: Journal of Clinical Oncology (2011)

193 Background: Pancreatic cancer (PC) is one of the leading causes of cancer deaths with a 5-yr mortality rate of 95%, and the lack of a suitable early detection method contributes to its poor prognosis. Metabolomics, the analysis of the metabolic profiles in biological samples such as serum and urine is emerging as an important tool to complement other “omic” techniques. In an effort to identify potential biomarkers for PC, we analyzed serum from PC patients (pts) focusing on altered metabolic profiles using 1 H nuclear magnetic resonance (NMR). Methods: The metabolite profiles from serum samples consisting of 55 PC pts and 32 healthy controls were analyzed using NMR combined with advanced supervised and unsupervised multivariate statistical methods such as partial least squares discriminant analysis (PLSDA) and principal component analysis (PCA). A number of metabolite markers selected based on p values and logistic regression rank the importance of each potential marker. Statistically significant metabolites between cancer and controls were used to build a prediction model. Results: Based on multivariate logistic regression analysis of 20 targeted metabolites, 10 metabolite markers were selected from the variable selection process and used to build a regression model with high accuracy (AUROC &gt;0.99), a sensitivity of 95% and specificity of 95% using a training set of samples. When the model was tested on an independent set of patient samples, it yielded a sensitivity of 95% and a specificity of 100% (AUROC &gt;0.98). Box and whisker plots for individual markers verified the high performance of all 10 markers. Conclusions: The high sensitivity of the metabolic profile that distinguishes PC pts from controls indicates the potential utility of 1 H NMR metabolic profiling for the early detection of PC. The investigation has identified perturbations in several pathways such as glycolysis and amino acid metabolism, highlighting their contribution to disease onset. This study demonstrates the potential of metabolite profiling as an important tool toward detecting PC development. Future studies will involve metabolite validation on high risk pts, and additional mass spectrometry based metabolic discovery efforts. No significant financial relationships to disclose.