tbuckley/cabot-search huggingface dataset:
The role of metastasectomy in patients with renal cell carcinoma with sarcomatoid dedifferentiation: A matched controlled analysis.
Authors: Arun Z. Thomas, Mehrad Adibi, Rebecca Slack, Leonardo Daniel Borregales, Megan M. Merrill, Pheroze Tamboli, Kanishka Sircar, Eric Jonasch, Nizar M. Tannir, Surena F. Matin, Christopher G. Wood, Jose A. Karam
Journal: Journal of Clinical Oncology (2016)

565 Background: Renal cell carcinoma with sarcomatoid dedifferentiation (sRCC) is an aggressive tumor generally associated with a poor clinical course. Management of metastatic sRCC remains a therapeutic challenge with no standard treatment strategies. Our objective was to evaluate whether metastasectomy has any survival benefit in patients with synchronous or asynchronous metastatic sRCC treated with radical nephrectomy (RN). Methods: From an institutional database of 273 patients with sRCC treated with nephrectomy, we matched 80 patients with synchronous and asynchronous metastasis for age, ECOG performance status, histology and nodal status. Matched pairs were then retained only if patients who did not undergo metastasectomy were comparably alive at the time of metastasectomy in matched surgical patients to reduce the bias in survival outcomes. Overall survival (OS) from nephrectomy was studied using univariable and multivariable proportional hazards regression. Results: Median OS was 8.3 months (95%CI 6.5-10.5 months) and 18.5 months (95%CI 11.5-42.9 months) for patients with synchronous and asynchronous metastases, respectively. OS for patients undergoing metastasectomy for synchronous metastasis was comparable to non-surgical patients (8.4 and 8.0 months, respectively, p=0.35). Similarly, within the asynchronous cohort, median OS was 36.2 months (95%CI 7.6-Not Reached) in the metastasectomy group and 13.7 months (95%CI 8.8-41.6) in the non-metastasectomy group (p=0.29). On multivariable analysis, positive lymph node (LN) at nephrectomy was associated with increased risk of death in both synchronous and asynchronous patients groups; (HR=2.1 [95%CI 1.1-4.0] p=0.03) and (HR=3.3 [95%CI 1.2-9.2] p=0.02), respectively. Conclusions: Metastasectomy in patients with synchronous or asynchronous metastases after nephrectomy does not appear to confer significant survival benefit in patients with sRCC, particularly in patients with pathological LN positive disease at nephrectomy.
Angiogenic gene expression in primary neuroendocrine tumors and their metastases.
Authors: Tanja Milosavljevic, Michael Anthony Hall, Luis Del Valle, Elise Juge, Jovanny Zabaleta, J Philip Boudreaux, Yi-Zarn Wang, Catherine T. Anthony, Eugene Woltering
Journal: Journal of Clinical Oncology (2016)

200 Background: Neuroendocrine tumors (NETs) are neoplasms arising from the cells of the nervous, endocrine and hormonal systems. They most commonly originate in the small bowel (SB) and frequently metastasize to the lymph nodes (LNs) and/or liver (LV). Current treatment of metastatic NETs involves a variety of approaches including antiangiogenic therapies. Our group demonstrated that there are significant histologic and functional differences between the primary NETs and their nodal or organ metastases. We hypothesized that sampling of multiple tumor sites within the same individual will reveal differential expression profiles of angiogenesis-related genes. Methods: Tissue-matched normal and tumor tissue samples were obtained from patients with well differentiated NETs who underwent simultaneous removal of their primary tumor, nodal, and organ metastasis. High quality RNA was extracted from each tumor site using TRIzol and RNeasy Mini kit. Gene expression of 28 well-documented angiogenesis-related genes was assessed using Custom Quantitative RT-PCR array. These gene expression trends were validated by Illumina microarray and TaqMan analysis. Immunohistochemistry (IHC) staining was performed using Avidin-Biotin-Peroxidase complex, with the markers: SSTR2 and FGFR3. Results: Normal SB, LN, and LV gene expression of 28 genes was compared to that of the tumor sample at each tumor site [4-fold change, p ≤ 0.01]. A consistent up-regulation of SSTR2 and SSTR1 was seen in 18/24 (75%) samples. Up-regulation of FGFR3 and SSTR5 was observed in 13/24 (50%) of tumors. TGFA and IGF were consistently down-regulated in 12/24 (50%) and 10/24 (42%) of tumor samples, respectively. Six genes expression trends were validated by TaqMan analysis and Illumina microarray analysis. IHC staining revealed higher SSTR2 and FGFR3 protein expression in all three tumor sites compared to the control. Conclusions: Expression of angiogenesis-related genes varies between the primary tumor (SB) and metastatic sites (LV, LN) within the same individual. We found a positive correlation between SSTR2 and FGFR3 gene and protein expression levels in all three tumor sites.
Mind-body medicine epigenetic technique (MET) and EGR1 (zif268) gene expression.
Authors: Francisco Ventura Munoz
Journal: Journal of Clinical Oncology (2015)

4 Background: This is a pilot study update on the potential of MET to up-regulate EGR1 gene expression in patients diagnosed with breast cancer. EGR1 gene expression is associated with learning and memory. Methods: The selection process for the study participants was nonrandom. The following was the eligibility criteria. 1. Inclusion Criteria: Breast Cancer, Stages II, III 2. Exclusion Criteria: Cognitively impaired, weak or ill. The study utilized two groups. Each group was assigned two research participants. Group One received one session of MET. Group Two received two sessions of MET. Each MET session was approximately 25-35 minutes in duration. Blood samples were taken at baseline and post-MET sessions to provide evidence in gene expression changes. For Group Two, the post-MET session blood draw was done 7 days after baseline. 1. Primary Endpoint: To determine whether MET can up-regulate EGR1 gene expression. 2. Secondary Endpoint: To determine whether there is a correlation between up-regulated EGR1 gene expression with up-regulated TP53 and TP53AIP1 gene expression. The blood samples were sent to genomics labs at the Childrens Hospital of Los Angeles and the University of Nevada Las Vegas for mRNA extraction and microarray analysis. The gene expression was measured by DNA microarray results using the “PrimeView gene chip” and “Partek Genomics Suite” statistical software. Results: For two participants in Group 1 and one participant in Group 2, there was biologically significant up-regulation in EGR1 gene expression. However, only one participant from Group 1 evidenced a biologically significant up-regulation of EGR1 gene expression along with a biologically significant up-regulation of TP53 and TP53AIP1 gene expression. One major limitation of these findings is the statistical insignificance of the results due to the small number of participants. Conclusions: This pilot study evidenced the up-regulation of EGR1 gene expression potentially due to MET and provided evidence for potential correlation between EGR1, TP53 and TP53AIP1 gene expression. TP53 and TP53AIP1 gene expression are known to induce apoptosis. This study also provided a foundation for a larger study with more participants.
Validation of the AJCC staging system (7th edition) in Asian patients with localized prostate cancer undergoing radical radiotherapy.
Authors: M. Wong, C. Yip, X. Hou, P. Tan, H. Huang, B. Chowbay, W. Lau, T. Tan, M. Tan, F. Wong
Journal: Journal of Clinical Oncology (2011)

112 Background: The epidemiology of prostate cancer (PCa) varies widely internationally. Although prostate cancer is usually regarded as uncommon in Asia, dramatic rises in recent years have resulted in it being ranking third by incidence in Singapore. Conventional prognostic parameters derived from Western populations have been integrated into systems such as the new AJCC seventh edition staging system, the validity of which is unclear in Asia. We thus sought to validate its performance, alongside other prognostic factors in a large Asian series of radiotherapy patients. Methods: A retrospective review of 404 consecutive Singaporean patients receiving radical radiotherapy between 1997 and 2005 at the National Cancer Centre was performed. The primary outcome was biochemical relapse free survival (BRFS), defined by the Phoenix criteria. Prognostic risk groups were defined using AJCC seventh edition. Univariate analysis (UVA) and multivariate analysis (MVA) was performed for other putative risk factors: age, race, Gleason score, prognostic risk grouping, tumour classification, radiation delivery technique, radiotherapy dose, hormonal therapy (HT) and initial PSA. Results: Median age was 69; median BRFS was 55 months with 71 biochemical relapses. 4 risk factors showed univariate association with BRFS: AJCC risk groups (p=0.038), T-stage (p=0.018), RT dose (p=0.025) and initial PSA value (p=0.013) with AJCC risk groups and initial PSA value remaining significant after MVA ( Table ). Harrell's c-index for AJCC risk grouping was 0.56, with no significant difference seen in outcomes between AJCC risk group II and III. Conclusions: Our results validate the new AJCC seventh edition prostate cancer prognostic risk grouping in an Asian radiotherapy population for the first time; the actual association however is relatively weak possibly due to differences in biology, screening or epidemiology. [Table: see text] No significant financial relationships to disclose.
Implementation of survivorship care plans: Lessons learned at the Kaiser Permanente Oakland Medical Center.
Authors: Pamela Kim Washington, Yan Li, Dennis S Durzinsky, James Duffy, Veronica Shim, Nicole M Barnett, Nakeia Warren, Kay Stodd
Journal: Journal of Clinical Oncology (2016)

75 Background: Beginning in 2015, the Commission on Cancer (CoC) requires accredited facilities to provide eligible patients with a Survivorship Care Plan (SCP). While the benefits of SCPs in the quality and continuity of care are well documented in the literature, there is a dearth of information regarding best practices for implementation. Here we describe lessons learned in the development of a SCP at the Kaiser Permanente Oakland Medical Center (OMC). Methods: Adult patients with a diagnosis of stage 1-3 cancer who received curative treatment were identified by the Northern California Kaiser Permanente Cancer Registrar. Consistent with CoC guidelines for 2015, 10% of all eligible patients (n = 1160) are required to receive a SCP 3-6 months following active treatment. Thus, a total of 116 patients with a diagnosis of breast, colon, lung/bronchus, prostate, or melanoma of the skin at OMC were given a SCP. The implementation timeframe was July to December 2015. Use of a modified ASCO template was recommended for its rigor across the required domains. Following template approval by the Comprehensive Cancer Committee (CCC), a workflow consisting of identifying patients’ last treatment and manual data entry by a Physician Assistant (PA) as well as automated data population in the Kaiser Permanente electronic medical record system was developed. Completed SCPs were then provided to patients during a clinic visit. The workflow process was refined as appropriate based on feedback from staff &amp; physicians. Results: Depending on the scope of treatment, mean preparation time is 10 minutes per plan using specific diagnosis codes via an electronic medical record system. Further, it takes 30 minutes for a PA or other Ancillary personnel to discuss the plan with a patient. Patient response was generally positive upon receipt of the plan. Conclusions: Successful SCP implementation is contingent upon engagement from multiple stakeholders. Per standard CoC 3.3, the implementation rate will increase annually from 10% in 2015 to 100% by 2019. Careful consideration to workflow processes and resources planning be must factored into achieving 100% compliance across all disease sites by 2019.
Safety and effectiveness of vinflunine in patients with metastatic transitional cell carcinoma of the urothelial tract (TCCU) after failure to one cisplatin-based systemic therapy in clinical practice.
Authors: Belen Gonzalez-Grajera, Javier Puente, Iciar Garcia Carbonero, Nicolas Mohedano, M. Pilar Lopez Criado, Jose Angel Arranz Arija, Aranzazu Gonzalez del Alba, Ovidio Fernandez Calvo, Maria L. Villalobos, Isabel Chirivella, Enrique Grande, Daniel E. Castellano
Journal: Journal of Clinical Oncology (2014)

332 Background: Vinflunine (VFL) is the first agent to show a survival improvement for platinum-refractory patients (pts) with metastatic TCCU in a phase III clinical trial. After EMA approval in September 2009, ESMO (Bellmunt, 2011) and SOGUG (Castellano, 2012) guidelines recommend VFL as second-line therapy. Methods: This is a multicenter and retrospective study to describe the experience with VFL in Spain. Pts with histologically confirmed metastatic TCCU were treated with VFL (280-320mg/m2 every 3 weeks) until progression or unacceptable toxicity. Pts were evaluated according to institutional local follow-up program. Results: From April 2010 to June 2013, we registered 102 pts in fifteen Spanish centers. All patients are evaluable for safety and 98 for efficacy. Median age: 67years (range 45-83), ECOG 0/1/2 previous to VFL (pts%): 31/61/8. Bladder carcinoma was the primary disease site in 84 pts and 46 % of them received cisplatinum-based chemotherapy. Metastatic involvement was: lymph nodes 67.7%, lung 36.4%, bone 28.1%, and liver 21.6%. The median number of cycles of VFL was 4 (1-18). The objective response rate was 25.5% (CR in 2 pts and PR in 23 pts), stable disease in 42.9% and progressive disease in 31.6%. The median follow-up was 6.6 months (0.4 to 43): median progression-free survival 3.9 months (95% CI, 2.3 to 5.5), median time to progression 4.3 months (95% CI, 2.6 to 5.9) and median overall survival 10 months (95% CI, 7.3 to 12.8). At the time of the analysis, 79.4%pts had progressive disease after VFL and 64.7% died. Grade 3/4 adverse events included: nausea/vomiting 13.8% of pts, neutropenia 12.8%, constipation 5.9%, and abdominal pain 4.9%. No toxic death were reported. Conclusions: This retrospective analysis confirms the benefit of VFL in patients with TCCU after failure in a platinum-containing chemotherapy regimen. Results of the randomized trial are reproducible in Spanish Oncology Centers on a daily clinical practice and its toxicity profile results are acceptable and manageable.
Phase I dose-escalation study of E7080, a multikinase inhibitor, in patients with advanced solid tumors
Authors: J. J. Nemunaitis, N. N. Senzer, R. Kurzrock, C. S. Ng, A. Das, R. S. Atienza, E. A. Zang, M. Jansen, S. Ashworth, D. S. Hong
Journal: Journal of Clinical Oncology (2008)

14583 Background: E7080, a multikinase inhibitor, has potent inhibitory activity against the split-kinase family of transmembrane growth factor receptors, including VEGFR1–3, PDGFRβ and FGFR1. In several subcutaneous xenograft models, E7080 inhibited tumor growth and reduced vascular density. Methods: This trial was conducted to determine the maximum tolerated dose (MTD) and dose-limiting toxicity of E7080 in patients (pts) with advanced solid tumors not amenable to conventional treatment. E7080 was given orally twice daily according to Schedule 1 (intermittent dosing with one week on and one week off, in cycles of 4 weeks) or Schedule 2 (continuous dosing in cycles of 4 weeks). Dose escalation proceeded according to an accelerated design of 100% increases in subsequent cohorts until first patient experienced ≥ CTC Grade 2 toxicity. Efficacy was evaluated using Response Evaluation Criteria in Solid Tumors. Pharmacodynamic (PD) assays of serum angiogenic factors were examined. Results: Based on preliminary data (September 24, 2007), 27 pts, 18 male, have been treated according to Schedule 1 (18) or 2 (9). Median age was 61.5 years(range 43- 84). Treated tumor types included: colorectal (5), ovarian (4), breast (3), endometrial (3), non-small cell lung (2), and others (10). Median number of cycles was 3 (range 2–14). No Grade 3 or 4 adverse events (AEs) were observed during Cycle 1. Fourteen pts (52%) experienced AEs > CTC Grade 1, included: Grade 2 increased creatinine (4), fatigue (3), proteinuria (3), and hypertension (2). Preliminary population pharmacokinetic (PK) analysis suggested that Cmax and AUC increased linearly with dose. Exploratory PD analysis showed no obvious association with best overall response, hypertension and exposure measures Cmin, Cmax, or AUC0–24 at steady-state. Responses included 2 partial responses (1 with medullary thyroid by 67% and 1 with endometrial by 40% for 6+ cycles), 11 stable disease (40% stable ≥ 4 cycles), and 9 progressive disease. Five pts had no post-baseline tumor assessment. MTD has yet to be reached. Conclusions: E7080 is tolerated with manageable toxicities in pts with advanced solid tumors. Preliminary results suggest anti-tumor activity and dose escalation continues. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eisai Medical Research Eisai Medical Research
Five-year experience of early enteral feeding in patients undergoing allogeneic stem cell transplantation following myeloablative conditioning for malignancy
Authors: I. Yakoub-Agha, M. Ben Rejeb, E. Tresch, C. Dendoncker, H. Baudelle, J. Jouet, D. Seguy
Journal: Journal of Clinical Oncology (2008)

7043 Background: The aim of this work was to investigate the evolution of our practices regarding nutritional support and its impact on early outcomes over the last 5 years. Methods: From Jan 01 to Dec 05, 121 pts who underwent myeloablative allo-SCT were offered EN. Among them, 94 (78%) agreed to receive EN (EN group) and 27 (22%) refused the naso-gastric tube (NGT)(without EN group: WEN group) and received either parenteral nutrition (PN) (n=22) or oral feeding only (n=5). The NGT was inserted shortly after transplantation. Overnight NGT feeding, was gradually increased within 5 days. In case of intolerance toward EN, additional or total PN was given. Results: The two groups were comparable in terms of transplantation modalities. Median duration of EN was 14 days (1–59) and 61 pts received no additional PN while the median duration of the PN was 12 days (2–70). There was no significant difference between the two groups regarding duration of hospitalization, nutritional status and mucositis. However: engraftment, 100% vs 93%, p=.05, duration of neutropenia, 20d (10–64) vs 25d (18–100), p<.001 and thrombopenia 27d (6–100) vs 56d (50–100), p=.014; serum albumine level at discharge < 35g/L, 45% vs 76%, p=.005 for EN-group vs WEN-group, respectively. Pts with EN developed less often acute grade III/IV GVHD (9% vs 37%; p=0.001) and non-bacterial infections (9% vs 41%; p=.0002). In addition, pts with EN had better 100-day survival (92% vs. 67%, P=0.001) with less infection- related deaths. In multivariate analysis the absence of EN was the only factor adversely influencing 100-day survival (CI 95%: 1.55–14.9 0.646; P=.007). In order to evaluate the practices over time regarding nutritional support in our unit, we compared the initial period (2001–02) when pts (n=41) had the choice between EN and PN with the second period (2003–05) when EN was offered systematically (n=80). In the second period, pts received less often PN (73% vs. 31%, p<.001) and more often EN (49% vs. 93%, p<.001). In addition, EN started earlier after transplantation (p=.004). Conclusions: EN has been well tolerated and dramatically reduced the proportion of pts requiring PN. When possible EN should be preferred to PN in pts undergoing myeloablative allo-CST. No significant financial relationships to disclose.
Measuring adherence to a Choosing Wisely recommendation in a regional oncology clinic.
Authors: Kathryn S. Egan, Gary H. Lyman, Karma L. Kreizenbeck, Catherine R. Fedorenko, April Alfiler, Heather Noble, Tracy Kusnir-Wong, Ada Mohedano, F. Marc Stewart, Benjamin E. Greer, Scott David Ramsey
Journal: Journal of Clinical Oncology (2016)

196 Background: Natural language processing (NLP) has the potential to significantly ease the burden of manual abstraction of unstructured electronic text when measuring adherence to national guidelines. We incorporated NLP into standard data processing techniques such as manual abstraction and database queries in order to more efficiently evaluate a regional oncology clinic’s adherence to ASCO’s Choosing Wisely colony stimulating factor (CSF) recommendation using clinical, billing, and cancer registry data. Methods: Database queries on the clinic’s cancer registry yielded the study population of patients with stage II-IV breast, non-small cell lung (NSCL), and colorectal cancer. We manually abstracted chemotherapy regimens from paper prescription records. CSF orders were collected through queries on the clinic’s facility billing data, when available; otherwise through a custom NLP program and manual abstraction of the electronic medical record. The NLP program was designed to identify clinical note text containing CSF information, which was then manually abstracted. Results: Out of 31,725 clinical notes for the eligible population, the NLP program identified 1,487 clinical notes with CSF-related language, effectively reducing the number of notes requiring abstraction by up to 95%. Between 1/1/2012-12/31/2014, adherence to the ASCO CW CSF recommendation at the regional oncology clinic was 89% for a population of 322 patients. Conclusions: NLP significantly reduced the burden of manual abstraction by singling out relevant clinical text for abstractors. Abstraction is often necessary due to the complexity of data collection tasks or the use of paper records. However, NLP is a valuable addition to the suite of data processing techniques traditionally used to measure adherence to national guidelines.