tbuckley/cabot-search huggingface dataset:
Significance of necrosis and gene expression profiling in high-grade myxoid/round cell liposarcoma (MRLS) of the extremity
Authors: J. J. Yeh, C. A. Antonescu, N. D. Socci, S. R. Grobmyer, C. Sander, M. F. Brennan, S. Singer
Journal: Journal of Clinical Oncology (2005)

9015 Background: Myxoid liposarcoma represents a morphologic continuum, with histologic grade determined by the extent of the round cell (RC) component. For this study, MRLS was defined as having a ≥5% RC component. Our objectives were to determine factors that associate with recurrence and identify global gene expression profiles that correlate with prognostic factors predictive of outcome. Methods: A prospective database identified 57 consecutive patients with localized primary MRLS of the extremity treated between 1982 and 2003. Histology was reviewed for percent of necrosis and RC component. Microarray data from 6 tumors was analyzed using hierarchical and supervised clustering. A t-test was performed, using a false discovery rate of <0.05, to determine genes associated with necrosis. Results: Median age was 46 years (23–76) and median tumor size was 12 cm (1.7–38). Local recurrence developed in 10.5% (6/51) and distant metastasis in 40% (23/57) of patients. Five-year disease-specific survival was 81% and recurrence-free survival (RFS) was 58% with a median follow-up of 51.5 months (0–200). Patients with tumors without necrosis had a 5-year RFS of 72% compared to 46% for those with tumors with necrosis (p=0.02) by log-rank analysis. Age (p=0.03) and size (p=0.03) were significant by univariate Cox-regression analysis. Necrosis was the only independent adverse predictor of RFS with a hazard ratio of 2.7 (CI 1.1, 6.6, p=0.03). Hierarchical analysis demonstrated distinct gene expression profiles that correlated with the extent of necrosis. When tumors with and without necrosis were compared, 91 significant genes with greater than 2-fold differential expression were identified, including 6 that are involved in transcriptional regulation and apoptosis. Conclusion: Tumor necrosis is an important determinant of RFS in patients with MRLS of the extremity. Unsupervised learning methods were able to cluster MRLS by the extent of necrosis. Genes that are differentially expressed in MRLS with necrosis may be used to identify patients at risk for metastasis and serve as potential novel therapeutic targets. No significant financial relationships to disclose.
The impact of active smoking on survival outcome in metastatic renal cell carcinoma patients treated with targeted therapy.
Authors: Haoran Li, Nils Kroeger, Guillermo de Velasco, Frede Donskov, Hao-Wen Sim, Connor Wells, Igor Stukalin, Neeraj Agarwal, Hiral D. Parekh, Brian I. Rini, Jennifer J. Knox, Allan J. Pantuck, Toni K. Choueiri, Daniel Yick Chin Heng
Journal: Journal of Clinical Oncology (2016)

552 Background: Smoking increases the risk of developing renal cell carcinoma (RCC). The prognosis of active smokers compared with non-smokers with metastatic RCC (mRCC) has not been well characterized. Methods: Smoking data from 1,842 patients with mRCC treated with targeted therapy were collected through the International mRCC Database Consortium (IMDC) from 8 Cancer Centers. Patients were categorized as current, former and non-smokers at the time of starting targeted therapy, and analyzed for differences in IMDC risk criteria, response rate (RR), progression- free-, (PFS) and overall survival (OS). Results: Overall, 292 (15.9%), 755 (41.0%), and 795 (43.1%) were current, former, and non-smokers. There were no differences in sarcomatoid features, number of metastatic sites or non-clear cell histology in either former or current smokers when compared with non-smokers. Likewise, former smokers had statistically similar IMDC risk groups compared to non-smokers. However, current smokers were more likely to have hypercalcemia (p=0.004), neutrophilia (p=0.038), thrombophilia (p=0.002), and more patients had higher numbers of IMDC risk features (p=0.014) when compared with non-smokers. The RR at first-line targeted therapy of former (p=0.89) and current smokers (p=0.13) were similar to non-smokers. No differences in PFS were noted: 7.7 vs. 7.6 vs. 6.2 months (mo) in non-, former (p=0.92), and current smokers (p=0.66). Interestingly, while former- and non-smokers had comparable OS times (23.7 vs. 23.1 mo; p=0.71), current smokers had significantly shorter OS (15.8 mo; p=0.001) than non-smokers. Current but not former smoking status was an independent poor prognosis factor (HR=1.28; p=0.006) when adjusted for the IMDC risk criteria. Moreover, each pack year increased the risk of death 1% (HR=1.01; p=0.039). Conclusions: Active smoking is associated with more advanced IMDC risk criteria and diminished OS in mRCC patients treated with targeted therapy agents. On the other hand, patients who quit smoking returned to a similar risk of death compared to patients who never smoked. Smoking cessation should be a counselling priority among mRCC patients receiving targeted agents.
Satisfaction with breast cancer care in women treated within and outside a clinical trial: prospective assessment through a multi-center survey
Authors: C. Julian-Reynier, J. Genève, F. Dalenc, P. Viens, A. Monnier, P. Kerbrat, M. Namer, D. Serin, M. Rios, D. Maraninchi
Journal: Journal of Clinical Oncology (2005)

8127 Background: The assumption has been made that patients within clinical trials have a better information and follow-up that patients outside clinical trials. They could therefore have a higher satisfaction with care. We assessed prospectively satisfaction with care in women with breast cancer treated by the same adjuvant treatment within and outside a clinical trial. Methods: A dynamic cohort of women (N=524) affected by non metastatic breast cancer included or not in a standard group of a clinical trial or in a same standard adjuvant treatment outside a trial (6 FEC 100) has been contacted (16 French centers); 398 consented to participate (76%). Self administered questionnaires were completed by 378 of these women (95%) at the beginning of chemotherapy. A second and third assessment points are scheduled at 7 and 12 months The Comprehensive Assessment of Satisfaction with Care Scale (Brédart et al. 2001) was used as a main outcome. This scale has 9 dimensions (4 for doctors, 3 for nurses, 1 for care organization, 1 for general satisfaction). Results: After multivariate adjustment, the answer rate was significantly lower when the center included more cases in the study (p<0.001) and when the initial consultation was shorter (p<0.001). Satisfaction with doctors’ availability was higher for women belonging to the trial (n=191; average score 3.6) compared to women in the non-trial group (n=187; average score 3.4) (p=0.01). The frequency of doctors’ visits (p<0.01), the coordination between doctors (p<0.01) and the coordination between nurses and doctors (p=0.02) were more satisfactory for the trial group compared to the non-trial one. After multivariate adjustment on depression and educational level, the trial effect on satisfaction for doctors’ availability remained significant (p<0.01). The other 8 dimensions of satisfaction did not differ significantly between the two groups. Conclusions: Satisfaction about the availability of doctors appeared to be higher in the context of clinical trial compared to standard treatment. No significant financial relationships to disclose.
High-Throughput RNA Interference Screening Identifies Synthetic Lethality Between Oncogenic KRAS Dependency and Suppression of STK33
Authors: Claudia Scholl, Stefan Frohling, Ian F. Dunn, David A. Barbie, Anna C. Schinzel, So Young Kim, Serena J. Silver, Lars Bullinger, Peter Sandy, Jesse S. Boehm, David E. Root, Tyler Jacks, William C. Hahn, D. Gary Gilliland
Journal: Blood (2008)
Prognostic Value of Bone Marrow Angiogenesis in Patients with Multiple Myeloma Undergoing High-Dose Therapy and Autologous Stem Cell Transplantation.
Authors: Olga Pokrovskaya, Larisa Mendeleeva, Irina Kaplanskaya, Elena Parovichnikova, Sergei Kulikov, Valeryi Savchenko
Journal: Blood (2008)
Quantification of hypoxia-inducible factor-1α, vascular endothelial growth factor, and angiopoietin-2 expression in hepatocellular carcinoma using a real-time quantitative reverse transcription polymerase chain reaction.
Authors: B. Sharma, R. Srinivasan, Y. K. Chawla, A. Chakraborty, S. Kapil, B. Singla, A. Duseja, R. K. Dhiman, N. Kalra
Journal: Journal of Clinical Oncology (2011)

223 Background: Hepatocellular carcinoma (HCC) is characteristically a hypervascular tumor and its progression is closely related to angiogenesis. Hypoxia inducible factor-1α (HIF-1 α), vascular endothelial growth factor (VEGF), and angiopioetin-2 (Ang-2) are key angiogenic factors in HCC. In this study, expression of HIF-1α, VEGF, and Ang-2 were analyzed and correlated with clinicopathologic features of HCC. Methods: Expression of HIF-1α, VEGF, and Ang-2 were analyzed by real-time quantitative reverse transcription polymerase chain reaction in 67 HCC patients (23HBV, 22HCV, 22NBNC) with mean age 59.09 ± 11.13 years (60 M: 7 F), 9 cirrhosis patients (2HBV, 2HCV, 5ALD) with mean age 48.33 ± 11.31 years (8 M:1 F), and 14 chronic hepatitis patients (7HBV, 7HCV) with mean age 48.33 ± 7.17 years (10 M: 4 F), respectively. HCC was diagnosed on the basis of EASL (European Association for the Study of the Liver) criteria. Results: Expression of HIF-1α and VEGF were found to be significantly higher in patients with HCC compared with cirrhosis and chronic hepatitis. Although Ang-2 expression was higher in HCC compared to cirrhosis and chronic hepatitis but the difference was not statistically significant. The difference in the expression of HIF-1α, VEGF, and Ang-2 in cirrhosis and chronic hepatitis were not significant. Tumor size was positively correlated with HIF-1 α(p = 0.268, p = 0.030)and VEGF (p = 0.546, p = 0.0001). A positive correlation was also seen between the HIF-1α and VEGF expression (p = 0.347, p = 0.0001). However no correlation of HIF-1α, VEGF and Ang-2 was seen with portal vein thrombosis, cirrhosis, etiology, AST, ALT, and platelets. Conclusions: HIF-1α and VEGF were highly expressed in HCC patients and may be responsible for the HCC growth. Further studies with a larger number of patients need to be done. No significant financial relationships to disclose.
Is elevated preoperative CEA level a significant predictor for decreased overall survival in patients with stage I to III rectal cancer?
Authors: Ulrich Guller, Dieter Koeberle, Rene Warschkow, Bruno Schmied, Thomas Cerny, Ignazio Tarantino
Journal: Journal of Clinical Oncology (2012)

403 Background: The objective of the present investigation was to assess whether elevated pre-operative CEA level represents a significant predictor for decreased overall survival in stage I-III rectal cancer patients. Methods: The present study is based on the colorectal database of the authors` hospital, one of the largest tertiary care centers of Switzerland. All patients undergoing a resection for stage I - III rectal cancer were consecutively included between 1991 and 2008. Average follow-up time was 50.3 months. The impact of pre-operative CEA on overall survival was assessed in Cox proportional hazard regression analyses after risk-adjusting for age, gender, body mass index, performance status, tumor stage, tumor distance from the anal verge, and neoadjuvant treatment. Pre-operative CEA levels were classified as normal (&lt; 5 µg/liter) versus elevated (&gt;5 µg/liter). All tests were two-sided, the level of statistical significance was set at 0.05. Results: Overall, 534 consecutive patients undergoing resection for stage I - III rectal cancer were included. Median age was 65 years (range 24 to 91 years), 62% of patients were male, median ASA was II (range I – IV), median body mass index 25.3 kg/m 2 (range 15.4 to 44.9 kg/m 2 ). Pre-operative CEA levels were elevated in 21.7% of all patients. After risk-adjusting in Cox proportional hazard regression analyses pre-operative CEA level (p&lt;0.001; odds ratio: 2.020), distance from the anal verge &lt;5cm (p&lt;0.001, odds ratio: 2.434), older age (p&lt;0.001; odds ratio: 1.069) and higher tumor stage (p=0.004, odds ratio: 2.003) were all significant predictors for poor overall survival. Forward- and backward variable selection including bootstrap analyses confirmed these results. Conclusions: The present investigation based on a large cohort of consecutive stage I – III rectal cancer patients provides compelling evidence that elevated pre-operative CEA level is a strong predictor of decreased overall survival even after risk-adjusting in Cox proportional hazard regression analyses. Therefore, it is crucial that pre-operative CEA is used as a prognostic factor in the pre-operative assessment of stage I-III rectal cancer patients.
Effects of an mTOR inhibitor RAD001 on human breast cancer stem cells in vitro and in vivo.
Authors: J. Zhang, X. b. Zhang, Y. Liu, J. j. Liu, Y. Ma, S. Zhang
Journal: Journal of Clinical Oncology (2011)

e11514 Background: This study evaluated the antitumor effects of RAD001 alone or combined with docetaxel or herceptin respectively on CSCs of primary breast cancer cells and cell lines (MCF-7, MDA-MB-231, BT474) in vitro and vivo. Methods: In vitro studies, we sorted ESA+CD44+CD24-/low cells as breast CSCs by flow cytometry from primary cancer cells or cell lines. The inhibition of drugs on CSCs was quantified by MTT assay. Apoptosis and distribution of cell cycles were examined with flow cytometry. Test the tumorigenicities of CSCs after treatments by soft agar colony formation assay and human breast cancer xenograft assay. In vivo studies, the BALB/c mice were injected with MDA-MB-231 CSCs, given different treatments. After necroscopy, tumors were made into cell suspension in order to measure the percentage of CSCs. Expression of KI-67 and VEGF were analyzed by immunohistochemistry. Result: Treatment with RAD001 resulted in growth inhibition of all CSCs in a dose-dependent manner. There was an additive growth inhibitory effect of RAD001 combined with docetaxel or herceptin respectively on CSCs (P<0.001). The combination of RAD001 and Herceptin correlated with more profound effects on G1 progresson (P<0.001) and a significant decrease in cell viability defined as apoptosis (P<0.01), while RAD001 combined with docetaxel make an increase in G2-M cell cycle arrest (P<0.05). CSCs after combination treatment need 100- to 1000-fold more numbers to initiate a tumor than the untreated CSCs, and the ability of colony formation of CSCs were also reduced (P<0.001). In vivo studies, ESA+CD44+CD24-/low subpopulation in docetaxel or combination treatment xenografts were significantly enriched to 6-7%, which much more than 0.2-1% in untreated and RAD001 or Herceptin alone xenografts groups. Compared with the control group, the number of positive KI-67 cells and the content of VEGF were significantly reduced (P<0.001). Conclusion: We conclude that RAD001 has effective inhibitory effects on CSCs in vitro and vivo, and combination treatment with RAD001 and docetaxel or Herceptin may be effectful in refractory and metastatic breast cancer. But the drug interaction of three drugs in clinical study has to be evaluated in further studies.
Identification of quality improvement opportunities in kidney cancer surgery through a regional hospital-based urologic quality collaborative.
Authors: John L. Gore, Michael P Porter, Daniel W. Lin, Jonathan D. Harper, Zeila Schmidt, David R Flum
Journal: Journal of Clinical Oncology (2014)

413 Background: Patient selection for radical (RN) and partial nephrectomy (PN) for suspicion of kidney cancer may depend more on provider factors than patient characteristics. Observational data suggests that patients with small renal tumors have better overall survival when managed with PN rather than RN. We prospectively evaluated perioperative processes of care for patients undergoing kidney cancer surgery at Washington State hospitals participating in a surgical collaborative to identify quality improvement opportunities in kidney cancer care. Methods: We developed a chart abstraction tool that captures potential quality concerns in kidney cancer surgical care. The abstraction tool was implemented at nine regional hospitals with data consolidated for review quarterly. A sampling of PN and RN cases was abstracted. Hospital-specific feedback reports were blinded to hospital identity; data were analyzed as aggregate rates and hospital-specific rates using descriptive statistics. Presented results were not risk-adjusted. Results: We identified 75 patients undergoing RN or PN at 9 area hospitals from 2011-2013. Staging evaluations were uncommon (preoperative chest x-ray and chest CT in 41% and 20%, respectively). 13% percent of patients had a preoperative renal mass biopsy. For renal tumors ≤ 4 cm, 16/32 (50%) underwent PN. Hospital-specific utilization of PN for small renal masses exhibited variation: in 2 hospitals, 100% of tumors ≤ 4 cm were treated with PN, while 1 hospital performed RN in all cases, and the remaining hospitals ranged from 33%-67% utilization of PN. PN was less common for tumors 4-7 cm in size (4/26 cases [15%]). Venous thromboembolic events occurred in 4% of kidney cancer surgeries. Conclusions: We identified substantial variation in selection of surgical technique and postoperative outcomes following PN and RN for kidney cancer. Patients with small renal masses appear to have variable access to PN, which could impact their long-term health outcomes. Better understanding of provider knowledge and attitudes toward management of small renal masses could inform quality improvement initiatives to address the variations in care identified.
Predictors of choice of treatment in men with localized prostate cancer.
Authors: Ramdev Konijeti, Traci M. Blonquist, Barbara Halpenny, Fangxin Hong, Steven L. Chang, Quoc-Dien Trinh, Adam S. Kibel, Donna Lynn Berry
Journal: Journal of Clinical Oncology (2014)

82 Background: The Personal Patient Profile-Prostate (P3P) is an Internet-based decision support program for men with newly diagnosed prostate cancer (CaP), which significantly reduced decisional conflict in treatment selection in a multicenter trial (2007 to 2009). We performed an ad hoc analysis of data from the trial (including five sites in Washington, Pennsylvania, Georgia, and Texas) to determine factors associated with initial treatment selection (watchful waiting [WW], external radiation [XRT], brachytherapy, or surgery [RP]) in men with localized CaP. Methods: Baseline patient characteristics measured for 462 patients included age, income (less than $35,000 vs. more than $35,000), employment (working vs. not ), relationship status (married/partnered vs. not), state and trait anxiety, amount of confidence in a particular physician (a lot vs. less), and whether the patient was seen by a urologist only or both a urologist and radiation oncologist. Univariate and multivariable logistic regression were used to identify predictors of initial treatment choice within 6 months of diagnosis. Results: Common treatment choices were RP (48%), XRT (21%), and WW (15%). In both univariate and multivariable analyses, men seen by a urologist only were more likely to choose WW (p=0.03 and p=0.02, respectively); employed men were less likely to choose WW (p=0.01 and p=0.02, respectively). In multivariable analysis, married/partnered men were more likely to choose surgery (p=0.03); anxiety was not statistically significantly associated with any treatment choice. Conclusions: Our findings suggest that treatment choice is related to social infrastructure and type of specialist seen. These findings should guide counseling of patients with newly diagnosed localized CaP. Further studies related to the role of sociodemographic characteristics and access to specialty care in initial treatment choice are warranted.
Size-Tunable Gd<sub>2</sub>O<sub>3</sub>@Albumin Nanoparticles Conjugating Chlorin e6 for Magnetic Resonance Imaging-Guided Photo-Induced Therapy
Authors: Lijuan Zhou, Tao Yang, Junxing Wang, Qiaoli Wang, Xiaoyan Lv, Hengte Ke, Zhengqing Guo, Junkang Shen, Yong Wang, Chungen Xing, Huabing Chen
Journal: Theranostics (2017)

Protein nanoparticles as nanocarriers are of particular interest in the field of cancer therapy.Nevertheless, so far a facile fabrication of theranostic protein nanoparticles have been explored with limited success for cancer imaging and therapy.In this work, we demonstrate the controllable synthesis of size-tunable Gd2O3@albumin conjugating photosensitizer (PS) (GA-NPs) using hollow albumin as the nanoreactor for magnetic resonance imaging (MRI)-guided photo-induced therapy.The growth of Gd2O3 nanocrystals within the hollow nanoreactors is well regulated through reaction time, and a typical PS (e.g.chlorin e6) is further conjugated with the protein corona of the nanoreactor through facile chemical coupling, followed by the formation of theranostic GA-NPs.GA-NPs exhibit good longitudinal relaxivity, ideal photostability, enhanced cellular uptakes, and preferable size-dependent tumor accumulation.Moreover, GA-NPs effectively generate remarkable photothermal effect, intracellular reactive oxygen species from Ce6, and subsequent cytoplasmic drug translocation, thereby leading to severe synergistic photothermal and photodynamic cell damages.Consequently, GA-NPs exhibit an in vivo size-dependent MRI capacity with enhanced imaging contrast for effective tumor localization, and also generate a potent synergistic photodynamic therapy/photothermal therapy efficacy under irradiation owing to their enhanced tumor accumulation and strong photo-induced cytotoxicity.These results suggest that GA-NPs can act as a promising theranostic protein nanoplatform for cancer imaging and photo-induced therapy.
Dose intensity and survival outcomes with adjuvant FOLFOX for colon cancer.
Authors: Martin Smoragiewicz, Khodadad Rasool Javaheri, Yaling Yin, Sharlene Gill
Journal: Journal of Clinical Oncology (2014)

423 Background: Adjuvant FOLFOX chemotherapy for resected high-risk colon cancer is associated with a low risk of febrile neutropenia (FN). Nonetheless, neutropenia is a common cause of dose modification or delay with unknown consequences on outcomes. We examined the effect of neutropenia-related and other dose limiting toxicities (DLT), relative dose intensity (RDI) of oxaliplatin and 5-FU, on relapse-free (RFS) and overall survival (OS) in patients treated with FOLFOX chemotherapy for resected high-risk colon cancer. Methods: A chart review was conducted on patients treated at the British Columbia Cancer Agency with ≥ 1 cycle of FOLFOX chemotherapy for resected stage II or III colon cancer between January 1, 2006 and December 31, 2007. RFS and OS were analyzed by the Kaplan-Meier method and multivariate Cox proportional-hazards models. Results: 114 patients (median age 59.2 years, 43.8% male, 98% stage III, median follow-up 5.2 years) were included. 90% of patients experienced any DLT, while 58% of patients had a neutropenia related DLT. There were no documented episodes of FN. G-CSF was used in 9.6% of patients. Median RDI was 81% and 85% for oxaliplatin and 5-FU, respectively. Oxaliplatin and 5-FU RDI were not associated with RFS or OS when analyzed as continuous variable or categorically (Table). Conclusions: DLTs affect the majority of patients on adjuvant FOLFOX for high-risk colon cancer, but RFS and OS do not appear to be affected by the associated lower RDI of oxaliplatin and 5-FU. [Table: see text]