tbuckley/cabot-search huggingface dataset:
A randomized controlled study for the long term follow-up of breast cancer survivors: A primary care physician (PCP) coordinated care delivery model.
Authors: Yong Alison Wang, Shih-Ping Chen, Chen-Fang Horng, Ling-Ling Hsieh, Kai-Hsin Hsu, Chen-Shin Chu, Shu-Yi Tsai, Yu-Hui Chan, Shih-Ming Shih, Chun-Chiu Cheng
Journal: Journal of Clinical Oncology (2016)

36 Background: Generalist involvement in cancer survivorship care is becoming a global trend, however, significant barriers exist. As a major cancer center in Taiwan, KF-SYSCC is implementing an academic institution-based comprehensive survivorship program, a PCP-coordinated care delivery model. Our goal is to promote health, manage chronic diseases, attend to psychosocial needs, and optimize health care resources without compromising cancer-related clinical outcome or patient satisfaction. Methods: We designed a randomized study with staggered transition of stage 0-3 breast cancer patients from oncologist care to the PCP-coordinated program at one or two years after cancer surgery. The outcomes for comparing the two care models include late effects of breast cancer treatment, anxiety and depression, health-related quality of life, recurrence-related clinical outcome, preventive care, chronic disease management, patient satisfaction, and health services utilization. Questionnaires were given every 6 months from 6 to 30 months after surgery. Results: Within six months, 270 eligible individuals were approached with an enrollment rate of 58% (target sample 1,200). The barriers for non-enrollment include: having established relationship with oncologist, transfer time too soon, lack of trust for non-oncologist, unwilling to change care provider, treatment not yet completed. The 113 non-participants did not differ from the 157 participants in age or cancer characteristics. Between the 1-year and 2-year transfer groups, there were no significant differences in demographics, tumor characteristics and treatment modalities. The initial BCPT and SF-36 questionnaires showed poorer performance in the areas of hot flashes, pain, cognition, weight, role physical, energy, and health perception, as compared with areas of bladder, vaginal, arm problems, physical and social functioning, mental health, and role emotional. Conclusions: We have started a randomized study to evaluate a generalist care model to survivorship care. Baseline patient characteristics were defined. Several barriers to the transition of the new care delivery model were identified.
Sources of variation in follow-up expenditure after radical cystectomy.
Authors: Goutham Vemana, Joel Vetter, Ling Chen, Gurdarshan Singh Sandhu, Seth A. Strope
Journal: Journal of Clinical Oncology (2014)

335 Background: Follow-up care after radical cystectomy is poorly defined with extensive variation in practice patterns. We sought to determine sources of these variations in care as well as examine the economic impact of standardization of care to guideline recommended care. Methods: Using linked SEER-Medicare data from 1992 to 2007, we determined follow-up care expenditures (time and geography standardized) for 24 months after surgery. Accounted costs included office visits, imaging studies, urine tests and blood work. A multilevel model was implemented to determine the impact of region, surgeon, and patient factors on care delivery. We then compared the actual expenditures on care in the Medicare system (interquartile range) to the expenditures if patients received care recommended by current clinical guidelines. Results: Expenditures over 24 months of follow-up were calculated per month and per patient. The mean and median monthly expenditures were $33 and $21 respectively (minimum $0, maximum $429, 25 th to 75 th percentile $9 to $43). The total variance of expenditure situated at the surgeon-level and SEER region-level was 9.9% and 4.0% respectively. After accounting for the region, the total variance of expenditure situated at the patient-level and surgeon-level was 14.95% and 7.81% respectively. The assessed cost of guideline follow-up recommendations varied from 0.78-9.05 times the calculated Medicare costs. The guideline recommended cost of follow-up was higher than actual Medicare expenditures in all but one category. Conclusions: While some regional and surgeon-level variations in care were found, most variation in expenditure on follow-up care was at the patient-level, largely based on comorbidity, node positivity, chemotherapy status, readmission rates, and final cancer stage. Standardization of care to current established guidelines would create larger expenditures for the Medicare system than current practice patterns.
Angiopoietin-like protein 2 as a novel biomarker for diagnosis and prognosis in esophageal cancer.
Authors: Shozo Ide, Yuji Toiyama, Tadanobu Shimura, Koichiro Mori, Tomofumi Noguchi, Hiroki Imaoka, Masato Okigami, Hiromi Yasuda, Takahito Kitajima, Susumu Saigusa, Masaki Ohi, Koji Tanaka, Toshimitsu Araki, Yasuhiro Inoue, Yasuhiko Mohri, Masato Kusunoki
Journal: Journal of Clinical Oncology (2015)

73 Background: Angiopoietin-like protein 2 (ANGPTL2) is a secreted glycoprotein with homology to the angiopoietins and overexpression of ANGPTL2 is known to act as a causative mediator of chronic inflammatory carcinogenesis. Recently, expression in tumor cells which are associated with tumor progression has been recognized in lung, breast, colon and gastric cancer. However, to our knowledge, functional and clinical significance of ANGPTL2 expression has not been investigated in esophageal cancer (EC). Aim: We investigated the functional roles of ANGPTL2 in vitro assay and evaluated the clinical significance of ANGPTL2 expression in both primary tumor and matched serum in patients with EC. Materials and Methods: First, in vitro assays were performed for functional analysis of ANGPTL2 using small interfering RNA (siRNA). Next, ANGPTL2 expression in EC tissues was evaluated by immunohistochemically (IHC) in 71 EC patients. Finally, we investigated serum ANGPLT2 levels from EC patients (n=71) and healthy controls (n=35) by ELISA. Results: Knockdown of ANGPTL2 expression decreased proliferative, invasive and migrated capacity in EC cell lines. ANGPTL2 expression in EC tissues was significantly elevated in EC patients with high T stage, squamous cell carcinoma, and high TNM stage. Kaplan–Meier analysis showed that patients with high expression of ANGPTL2 had significantly poorer overall (p&lt;0.01) and disease-free survival (p&lt;0.01) than those with low expression, respectively. Furthermore, multivariate analysis revealed that high ANGPTL2 expression in EC tissues was an independent predictive marker for poor prognosis (HR: 2.30, p=0.04). On the other hands, serum ANGPTL2 levels in EC patients was significantly elevated compared to healthy controls (p&lt;0.001), and it can discriminate EC patients from healthy controls with high accuracy (AUC=0.913). However, no significant association between serum ANGPTL2 levels and clinicopathological findings were recognized in EC patients. Conclusions: We have demonstrated several novel evidences for biological and clinical significance of ANGPTL2 in EC. This study indicates ANGPTL2 had the potential to be useful as a biomarker in EC.
Sequential monitoring and characterization of circulating tumor cells (CTCs) using the epic sciences platform in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) treated with recently approved therapeutics.
Authors: Roberta Ferraldeschi, Rachel Krupa, Jessica Louw, Eric Tucker, Natalee Bales, Dena Marrinucci, Penelope Flohr, Ines Figueiredo, David Lorente, Ryan Dittamore, Johann Sebastian De Bono, Gerhardt Attard
Journal: Journal of Clinical Oncology (2014)

78 Background: The enumeration and molecular characterization of circulating tumor cells (CTCs) may allow sequential evaluation of drug-induced changes and mechanisms of drug resistance that cannot be practically performed by tissue biopsies. Methods: We utilized the Epic Sciences platform to identify and characterize traditional CTCs (CK-CD45+) and other CTC subpopulations (CK-CD45- CTCs and small CTCs) in sequential samples obtained from metastatic castration-resistant prostate cancer (mCRPC) patients (pts) receiving abiraterone acetate (AA), enzalutamide (E), or cabazitaxel (C). Peripheral blood was collected pre-treatment, during treatment (at 1 to 4 weeks, to evaluate pharmacodynamics effects) and at progression. Nucleated cells were plated onto glass slides and subjected to immunofluorescence staining for CK, CD45, and AR, and CTC identification by fluorescent scanners. CTCs from a subset of patients were tested for PTEN loss and ERG rearrangements by FISH. CTCs from a second blood sample collected at the same time were captured and enumerated using CellSearch (Veridex). Fresh CRPC biopsies were available for 9 pts. Results: Initial results are available from 24 mCRPC pts (16 pts treated with AA; four with E; four with C; 17 out of 24 previously treated with docetaxel). Pre-treatment, the median CK+CD45- CTC count was 3.5 (range 0 to 98) cells/mL blood. Eleven pts had more than or equal to 5 CK+CD45- CTCs/mL pre-treatment and 5 out of 11 pts had an Epic CTC conversion to less than 5 CK+CD45- CTCs/mL with treatment. 8 out of 11 pts had a decline in CK+CD45- CTC count greater than 30%. Changes in AR expression and AR subcellular localization were observed during treatment as well as changes in count of CTC subpopulations. CellSearch count was available for 22 out of 24 pts. Twelve out of 22 had more than or equal to five CTCs/7.5mls captured using CellSearch, including 7 out of 12 with more than or equal to five CTCs/ml using Epic platform. Conclusions: Enumeration and molecular characterization of CTCs on the Epic Sciences platform during treatment is feasible and demonstrates drug-induced changes associated with changes in CTC count, AR expression and AR subcellular localization. These assays warrant further studies to validate their role as clinically useful biomarkers in mCRPC.
Recurrence of T1N0 oral tongue squamous cell carcinoma in Stockholm, Sweden 2000-2009.
Authors: M. Ryott
Journal: Journal of Clinical Oncology (2011)

5550 Background: T1N0 oral tongue squamous cell carcinoma (OTSCC) has an aggressive behavior with a high locoregional recurrence rate rendering in poor prognosis. Elective neck dissection is becoming standard but still remains a controversial topic. This study presents locoregional recurrence data between the years 2000-2009 in Stockholm, Sweden. Between the years 2000-2006 patients were treated with observation of the neck and since then elective neck dissection. Methods: Seventy-four patients with T1N0 OTSCC were evaluated; 44 patients (group 1) were observed while 30 patients (group 2) were treated with elective neck dissection (END). Results: Follow up time was limited to 60 months with a mean follow up time of 40 months. Local recurrence occurred in 11% (5/44) and 3% (1/30) and regional recurrence occurred in 25% (11/44) and 7% (2/30) in group 1 and 2 respectively. Regional recurrences were predominately found in level IIA and III. Contralateral recurrence was seen in level IIA. No recurrences were seen in level I. Occult metastases were found in 17% (5/30). Conclusions: Fewer recurrences were seen in patients when elective neck dissection was added to treatment in T1N0 oral tongue squamous cell carcinoma.
Influence of KRAS mutation on recurrence patterns in patients undergoing hepatic resection of colorectal metastases.
Authors: Nancy E. Kemeny, Joanne F. Chou, Marinela Capanu, Alexandra N. Gewirtz, Andrea Cercek, T. Peter Kingham, William R. Jarnagin, Yuman Fong, Ronald P. DeMatteo, Peter J. Allen, Jinru Shia, Celina Ang, Efsevia Vakiani, Michael Ian D'Angelica
Journal: Journal of Clinical Oncology (2013)

398 Background: There have been conflicting results about whether KRAS mutation influences outcome in patients (pts) with colorectal cancer. In pts who underwent liver resection, Karagkounis reported a worse recurrence and survival in KRAS mutated (MUT) patients (ASCO 2012, abs 3616). Methods: In 105 pts who underwent liver resection and received adjuvant (adj) hepatic arterial infusion and systemic chemotherapy and in whom KRAS data was available, we evaluated recurrence patterns and survival. Correlation between KRAS and clinical factors such as prior chemotherapy, post operative CEA, clinical risk score, and stage at diagnosis was evaluated using Fisher’s exact test and the Wilcoxon rank sum test. Kaplan-Meier methods were used to estimate median overall recurrence free survival (RFS) and overall survival (OS) at 4 years. Log-rank test was used to determine whether survival functions differed by KRAS mutation status. Cumulative incidence function was used to estimate the probability of time from adj therapy to bone, brain, lung and liver metastases separately. Results: Of 105 patients, 76 were KRAS wildtype (WT), and 29 were KRAS MUT (26-G12 and 3-G13). The median RFS was 26 months for KRAS WT pts and 15 months for KRAS MUT pts (p=0.08). OS at 4 years was 88% [95% CI: 78%-94%] for KRAS WT and 78% [95% CI: 57%-90%] for KRAS MUT pts (p= 0.15). Cumulative incidence of developing bone, brain, lung, and liver metastases by 2 years is presented in the Table. The cumulative incidence of bone and brain metastases at 2 years was 0% and 0% in KRAS WT pts versus 16.4% [95% CI: 1.1%-31.7%] and 4.7% [95% CI: 0%-14.1%] in KRAS MUT pts (Table). There was no association between clinical factors and KRAS status. Conclusions: KRAS MUT pts appeared to have worse OS and RFS, although we were unable to show a significant difference between KRAS WT and MUT for OS and RFS. In addition, cumulative incidence of bone and brain metastases at 2 years appeared to be higher for KRAS MUT pts as compared to WT pts. Results are based on small sample size and further investigation is needed. [Table: see text]
Comparative efficacy of sorafenib dose in patients with advanced hepatocellular carcinoma (HCC) with varying liver dysfunction.
Authors: Sukeshi R. Patel, Raed Moh'd Taiseer Al-Rajabi, Norma Ketchum, Ting-Wei Lu, Brad H. Pollock, Joel Michalek, Devalingam Mahalingam
Journal: Journal of Clinical Oncology (2015)

369 Background: Sorafenib (SOR) is the only FDA-approved systemic therapy for advanced hepatocellular carcinoma (HCC). In clinical practice, there are limited efficacy data related to dose modifications, which are often required. Given the high prevalence of HCC in South Texas, we assessed the efficacy and safety of SOR therapy in relation to dose and Child Pugh score (CP). Methods: Retrospective analysis of HCC patients (pts) receiving SOR from 2008-2013. Median progression-free survival (mPFS) and median overall survival (mOS) were estimated from Kaplan-Meier curves and groups were statistically compared with the log rank test. The magnitude of association between dichotomous factors and survival was estimated with the hazard ratio (HR). A proportional hazards regression model was used to assess the significance of SOR (low, high) by CP (A, B) interaction. Results: 107 pts were included. Median age 57 (41-93). Males 83%. Hispanic 72%, White 24%. ECOG PS 0–1 93%. Causes of cirrhosis: Hepatitis C 67%, Hepatitis B 5%, EtOH 60%. Portal vein thrombosis 33%, extrahepatic disease 39%. CP (available for 106 pts): A 57%, B 43%. mOS was 10.2 months (mo) (95% CI: 7.8-13.5); mPFS was 5.2 mo (95% Cl: 3.8-7.2). In subgroup analysis, mOS for 800 mg/day was 12.8 mo vs 6.6 mo for 400 mg/day (HR 0.59, p=0.04). mPFS for 800 mg/day was 5.9 mo vs 3.5 mo for 400 mg/day (HR 0.66, p=0.07). In CP A pts, higher SOR dose did not improve survival; however, in CP B pts, there were statistically significant improvements in mPFS and mOS (Table). The effect of dosage varied significantly with CP category (A, B) for both OS (p=0.002) and PFS (p=0.03). Conclusions: Historically, CP B advanced HCC pts have worse survival and tolerability to higher doses of SOR when compared to CP A. Our study suggests CP B pts should be considered for SOR 800 mg/day to improve survival with optimal management of toxicity but warrants further prospective studies. [Table: see text]
Real-World Treatment Patterns, Healthcare Resource Utilization, and Costs in Patients with Newly Diagnosed Acute Myeloid Leukemia (AML)
Authors: Eytan M. Stein, Dominick Latremouille-Viau, Annie Guerin, Sherry Shi, Patrick Gagnon-Sanschagrin, Gaetano Bonifacio, George J Joseph
Journal: Blood (2016)
A Comparative Analysis of Outcomes in Primary Myelodysplastic Syndrome (MDS) and Therapy-Related MDS Reveals Two Subgroups with Differing Risk Profiles: Implications for the Application of a Prognostic Classification.
Authors: Caroline Alvares, Sue Ashley, Radovan Saso, Gita Patel, Amrana Qureshi, Michael Potter, Mark Ethell, Jennifer Treleaven, Claire Dearden, Gareth Morgan
Journal: Blood (2005)
Targeting colon cancer metabolism through a long noncoding RNA.
Authors: Maria Hatziapostolou, Marina Koutsioumpa, Filippos Kottakis, Dimitrios Iliopoulos, Christos Polytarchou
Journal: Journal of Clinical Oncology (2015)

604 Background: Long non-coding RNAs (lncRNAs) have gained massive attention in recent years as a potentially new and crucial layer of gene regulation. We studied the function of the lncRNA HOTAIR in colorectal cancer, one of the most common causes of cancer mortality worldwide. Methods: Molecular profiling was performed in colonic normal (40) and cancer (160) tissues. Gene expression was evaluated by qRT-PCR and gene expression arrays. LncRNA-protein interactions were investigated by RNA-immunoprecipitation, mass spectrometry and mutational analyses. Chromatin immunoprecipitation followed by DNA sequencing (ChIP-Seq) was employed for the histone acetylome analysis. Subcutaneous xenograft mouse models were used to evaluate tumor growth in vivo. Results: HOTAIR is significantly upregulated (&gt;30 fold) in colon cancer and inversely correlates with patient survival. Molecular profiling revealed a gene signature downstream of HOTAIR that links metabolic pathways to colon cancer cell growth and invasiveness. RNA immunoprecipitation/mass spectrometry analysis revealed the interaction of HOTAIR with the histone acetyltransferase PCAF. Mutational analyses identified the domains of both the lincRNA and acetyltransferase responsible for their interaction and function. Histone acetylome analysis demonstrated that HOTAIR is required for the recruitment and activity of PCAF towards a set of genes involved in the mTOR/insulin receptor/PI3K-Akt pathways. In specific, 44 genes involved in these pathways are regulated by Lysine 27 histone H3 acetylation, catalyzed by PCAF only when recruited by HOTAIR. Genome-wide profiling of colon cancer and normal colonic tissues revealed that the expression of this gene set correlates positively with HOTAIR levels and inversely with patient survival. Knockdown of either HOTAIR or PCAF sensitized colon cancer cells to dietary restriction and inhibited tumor growth in subcutaneous xenograft mouse models. Conclusions: Our results provide the mechanistic link between an lncRNA, a transcription activating chromatin mark and metabolic signaling in colorectal cancer. In conclusion, we identified a novel RNA-protein complex that affects growth factor/metabolic pathways essential for colon oncogenesis.
Propensity score–based comparison of outcomes with 3D conformal radiotherapy (3D-CRT) versus intensity-modulated radiation therapy (IMRT) in treatment of esophageal cancer.
Authors: Steven H. Lin, Bevan H Myles, Lu Wang, Peter F. Thall, Ara A. Vaporciyan, Reza J. Mehran, Stephen Swisher, Jeffrey H Lee, Manoop S. Bhutani, Dipen Maru, Jaffer A. Ajani, James D. Cox, Ritsuko Komaki, Zhongxing X. Liao
Journal: Journal of Clinical Oncology (2012)

66 Background: Although 3D-CRT is the current standard for treatment of esophageal cancers, IMRT improves dose conformality and reduces radiation exposure to normal tissue. There is no assessment of long term clinical outcomes comparing these two modalities. Methods: Between 1998-2008, 676 patients (3D-CRT=413, IMRT=263) with stage Ib-IVa (AJCC 2002 edition) esophageal cancers were treated with chemoradiation with or without surgery. To correct for potential bias inherent in observational studies, we employed inverse probability of treatment weighted (IPW) methods based on propensity scores. IPW survival plots and IPW log rank tests were used to adjust for potential bias in treatment selection. Treatment probabilities (propensity scores) were estimated using logistic regression. Results: IMRT patients were less likely to receive induction chemotherapy (35.7% vs 46.7%, p&lt;0.01) and had poorer performance status (KPS≤80: 66.5% vs 50.0%, p&lt;0.01). A fitted multivariate IPW-adjusted Cox model showed that overall survival was significantly associated with age (HR 1.10 for 10 years older, p=0.02), KPS (≤70 vs 90-100, HR 1.5, p=0.0002), having surgery (HR 0.56, p&lt;0.0001), lower vs upper esophagus (HR 1.4, p=0.009), stage (3-4a vs 1-2, HR 2.6, p&lt;0.01), and radiation modality (IMRT vs 3D-CRT, HR 0.68, p&lt;0.0001). 3D-CRT patients had a greater risk of dying at 5 years compared to IMRT (72.6% vs 52.9%, p&lt;0.0001) without a difference in cancer-specific mortality (Gray’s test p=0.86), time to local recurrence (p=0.27) or distant metastasis (p=0.13). Cumulative incidence of documented cardiac deaths trended higher in the 3D-CRT group (p=0.16), but most deaths were due to unknown causes (5 year estimate: 13.4% in 3D-CRT vs 4.2% in IMRT, Gray’s test p&lt;0.0001). Analyses using propensity score as a covariate gave very similar results. Conclusions: There was a substantially higher risk of non-cancer related deaths in 3D-CRT versus IMRT. While the true cause of death cannot be determined for many 3D-CRT patients, our results suggest that improvements in radiation technology may improve treatment-related mortality in management of esophageal cancer.