tbuckley/cabot-search huggingface dataset:
“The burden upon me”: The complexity of healthcare utilization among Medicare patients undergoing curative lung cancer treatment.
Authors: Carolyn Jean Presley, Pamela R. Soulos, James B. Yu, Cary Philip Gross
Journal: Journal of Clinical Oncology (2015)

7533 Background: Due to new lung cancer CT-screening guidelines and the aging American population, the use of curative treatment for early-stage non-small cell lung cancer (NSCLC) will increase among older adults. Yet little is known about the treatment burden to the patient and Medicare system in terms of healthcare system encounters and number of providers seen. Methods: We used the SEER-Medicare database to study Medicare fee-for-service patients aged 67-94 years who were diagnosed with stage I NSCLC from 2007 through 2009 and received curative treatment with either sublobar resection, lobectomy, or stereotactic body radiotherapy (SBRT). We examined healthcare utilization in the 30 days before through 12 months after treatment initiation, determining the total number of days in contact with the healthcare system as well as the number of unique physicians seen. We described care received in the acute, outpatient, post-acute, home care, and hospice settings. Results: Of the 4,214 patients, 90.9% received surgery and 9.1% SBRT. During the first 100 days post-treatment, an average of 1 in 4 days was spent in contact with the healthcare system (mean: 25 encounter-days excluding home health visits). Among patients who survived the entire 13-month follow-up period, there was an average of 50 days with at least one encounter. Approximately 3% of patients had ≥ 10 acute care encounter-days, while 97.7% had ≥ 10 outpatient encounter-days and 23.5% had ≥ 10 homecare encounter-days. The median number of physicians seen was 22 (interquartile range 16-31). Conclusions: The burden of receiving healthcare for older patients with NSCLC is substantial in terms of frequency of encounters and number of providers seen. Interventions are needed to improve patient-centered, streamlined cancer care.
Head and neck squamous cell carcinoma (HNSCC) in non-at risk patients: A case control study
Authors: F. Peyrade, E. Chamorey, H. Raybaud, O. Dassonville, R. J. Bensadoun, P. Y. Bondiau, G. Milano, M. Schneider, F. Demard
Journal: Journal of Clinical Oncology (2004)

5583 Background: Most clinical, molecular and histological investigations of HNSCC concern patients who were at risk due to overexposure to tobacco and alcohol. The clinical pattern and the biological pathway involved in-patients lacking these risk factors may be quite different. The aim of this study was to provide clinical, molecular and histological information's about HNSCC in patients without an history of tobacco and alcohol use. Methods: A retrospective review of 950 HNSCC treated in our institute between January 1996 and June 2003 was undertaken. Characteristics of patients with history of tobacco and alcohol use were compared with those who were not at risk. Among all patients, 58 (6.1%) of them had no history of tobacco and alcohol use. These patients have been apparied with 59 case control patients who had an history of tobacco and alcohol use. Results: We found no statistical difference between the two groups for age, cancer histology and treatment. Female were predominant in the non at-risk group (p<0.0001, OR: 12.9). Epidermal Growth Factor Receptor tumoral level (EGFR) was less expressed in the non at-risk group (mean+-sd, 88.2+-2.53 and 198.0+-3.15 fmol/mg protein for non at-risk and at risk patients, respectively). Disease free survival was significantly longer in the non at-risk group (logrank test, p=0.037). No difference was observed between the two groups in terms of overall survival. Conclusions: A female predominance in non at-risk HNSCC patients is confirmed. Tobacco and alcohol use may interfere with cellular signaling pathway involving the EGFR. The difference in DFS could be related to the important comorbidity classically encountered in the tobacco and alcohol user group. No significant financial relationships to disclose.
Abstract 020: Cell-sheet-based Bioengineered Human Cardiac Tissue Using Pluripotent Stem Cells For Heart Repair And Disease Models
Authors: Katsuhisa Matsuura, Tatsuya Shimizu, Nobuhisa Hagiwara, Teruo Okano
Journal: Circulation Research (2013)

We have developed an original scaffold-free tissue engineering approach, “cell sheet engineering”, and this technology has been already applied to regenerative medicine of various organs including heart. As the bioengineered three-dimensional cardiac tissue is expected to not only function for repairing the broad injured heart but also to be the practicable heart tissue models, we have developed the cell sheet-based perfusable bioengineered three-dimensional cardiac tissue. Recently we have also developed the unique suspension cultivation system for the high-efficient cardiac differentiation of human iPS cells. Fourteen-day culture with the serial treatments of suitable growth factors and a small compound in this stirring system with the suitable dissolved oxygen concentration produced robust embryoid bodies that showed the spontaneous beating and were mainly composed of cardiomyocytes (~80%). When these differentiated cells were cultured on temperature-responsive culture dishes after the enzymatic dissociation, the spontaneous and synchronous beating was observed accompanied with the intracellular calcium influx all over the area even after cell were detached from culture dishes as cell sheets by lowering the culture temperature. The cardiac cell sheets were mainly composed of cardiomyocytes (~80%) and partially mural cells (~20%). Furthermore, extracellular action potential propagation was observed between cell sheets when two cardiac cell sheets were partially overlaid, and this propagation was inhibited by the treatment with some anti-arrhythmic drugs. When the triple layered cardiac tissue was transplanted onto the subcutaneous tissue of nude rats, the spontaneous pulsation was observed over 2 months and engrafted cardiomyocytes were vascularized with the host tissue-derived endothelial cells. These findings suggest that cardiac cell sheets formed by hiPSC-derived cardiomyocytes might have sufficient properties for the creation of thickened cardiac tissue. Now we are developing the vascularized thickened human cardiac tissue by the repeated layering of cardiac cell sheets on the artificial vascular bed in vitro.
Polymer-delivered, subcutaneously administered leuprolide acetate provides consistent and prolonged drug delivery in castrate men with advanced prostate cancer.
Authors: Lane Childs, Stuart Atkinson, John A. McLane, Steve A. Garrett
Journal: Journal of Clinical Oncology (2017)

e586 Background: Leuprolide acetate (LA), a LHRH agonist, is standard of care in ADT in prostate cancer and used to suppress serum testosterone (T) to castrate level. Previously, in a head-to-head comparison of long-acting, polymer-delivered, subcutaneously administered LA (SC-LA) and microsphere intramuscularly administered LA depot (IM-LA) in healthy subjects, SC-LA demonstrated extended drug delivery compared to IM-LA, as well as prolonged T suppression. The objective of this study was to evaluate the safety and pharmacokinetics (PK) of SC-LA in orchiectomized, advanced prostate cancer patients to confirm and compare PK results with the head-to-head study. Methods: In this open label, single dose study, male, orchiectomized prostate cancer patients (ages 45-85) received a single dose of 7.5 mg SC-LA (labeled for 1 month dose interval). Blood samples were taken at baseline and at all scheduled visits up to day 56. LA concentration in serum was analyzed with HPLC. PK parameters AUC, Cmax, Tmax (time to Cmax), t 1/2 and concentration-time data were evaluated and adverse events (AEs) were assessed. Results: The study was conducted in 8 males with adenocarcinoma of the prostate (mean age = 72.5 y). Following administration, there was an initial rapid absorption phase with maximal concentrations observed at 2-6 hours. Serum LA fell slowly over 4-6 days and remained above 0.1ng/mL, the level associated with T suppression, for a mean of 37 days (range 28-49). Mean Cmax was 26.3 ±12.6 ng/mL with a mean Tmax of 3.79 ±1.39 h. AUC was 999 ±247 ng*h/mL. There were no serious treatment-related AEs and no subjects discontinued the study due to an AE. Conclusions: LA administered as a single, monthly SC dose via polymer delivery in orchiectomized prostate cancer patients showed extended drug delivery and T suppression 3 weeks past the dosing interval, mirroring extended PK in healthy subjects. Taken together, the PK profile of SC-LA demonstrates effective drug release throughout and beyond the labelled dosing interval.
GDF15 as a potential predictive biomarker for TPF induction chemotherapy in oral squamous cell carcinoma.
Authors: Lai-ping Zhong, Cheng-zhe Yang, Ying Liu, Dong-wang Zhu, Chen-ping Zhang
Journal: Journal of Clinical Oncology (2014)

6037 Background: Randomized trials have not shown major survival benefits when induction chemotherapy plus standard therapy is compared with standard therapy alone in patients with oral squamous cell carcinoma (OSCC). Induction chemotherapy is likely to be effective for biologically distinct subgroups and biomarker development may lead to identification of patients whose tumors are likely to respond to a particular treatment. Methods: We evaluated immunohistochemical staining for GDF15 in pretreatment biopsy specimens of 230 out of 256 OSCC patients who were treated in a prospective, randomized, phase three trial on induction chemotherapy including docetaxel, cisplatin and 5-fluorouracil (TPF). Relationship between GDF15 intervention and cell proliferation, migration, invasion, colony formation, and tumorigenicity was analyzed using in vitro and in vivo OSCC models. Results: LowGDF15 expression predicts a better survival in OSCC patients, especially overall survival (P=0.049, HR=0.597) and distant metastasis free survival (P=0.031, HR=0.562). Low GDF15 expression also predicted a better clinical response to TPF induction chemotherapy in comparison to high GDF15 expression (P=0.004). Decreased GDF15 expression in OSCC lines significantly inhibited cell proliferation, migration, invasion, colony formation, and tumorigenesis through increased phosphorylation of AKT and ERK1/2 (P<0.05). Likewise, overexpression of GDF15 significantly promoted cell proliferation, migration, invasion, and colony formation through decreased phosphorylation of AKT and ERK1/2 (P<0.05). Conclusions: GDF15 expression can be used as a prognostic biomarker for OSCC. A low GDF15 expression level predicts a high clinical response rate to TPF induction chemotherapy in OSCC patients. GDF15 promotes tumorigenesis and progression through phosphorylation of AKT and ERK1/2 in OSCC.
Positron emission tomography/computed tomography (PET/CT) for the diagnosis of recurrent cancer (PETREC): A multicenter, prospective cohort study.
Authors: John J. You, Richard I. Inculet, Sukhbinder K. Dhesy-Thind, Adrien M. Chan, Marc Freeman, Kathryn J. Cline, Kathleen I. Pritchard, Ian S. Dayes, Chu-Shu Gu, Jim A Julian, Karen Y. Gulenchyn, William K. Evans, Mark Norman Levine
Journal: Journal of Clinical Oncology (2012)

6049 Background: The clinical utility of PET/CT in patients with suspected cancer recurrence remains unclear. The aim of this multi-center, prospective, comparative effectiveness study is to assess the impact of PET/CT on clinical management of patients with suspected cancer recurrence. Methods: Patients were eligible if cancer recurrence (non-small cell lung, breast, head and neck, ovarian, esophageal, Hodgkin’s or non-Hodgkin’s lymphoma) was clinically suspected, and if conventional imaging (e.g. X-ray, ultrasound, CT, or MRI) was non-diagnostic. As a pre-requisite to PET/CT booking, clinicians were asked at enrolment to indicate their planned management if PET/CT were not available. Patients then underwent 18 FDG-PET/CT. Clinicians were then asked to indicate their management plan based on PET/CT findings. Patients were followed up once at 3 months. The primary outcome was change in planned management after PET/CT and was assessed independently and in duplicate by external outcome adjudicators using all available source documents. Results: 101 patients (mean age 64 y, 45% male, median 1.3 y since last treatment) were enrolled from 4 centers in Ontario, Canada between April 2009 and June 2011. Distribution of tumor types was: non-small cell lung (55%), breast (19%), ovarian (10%), esophageal (6%), lymphoma (6%), head and neck (4%). 8 patients did not complete the study (non-adherence to protocol, 2; death, 5; disease progression prior to PET/CT, 1), of whom 2 did not receive PET/CT. PET/CT changed planned management in 52 (53%) patients (Table). At 3 months, planned management was carried out in 46/52 (88%) patients. Conclusions: In patients with suspected cancer recurrence, PET/CT changes planned management from non-treatment to treatment for approximately 1 in every 3 patients (“number needed to scan” = 3) and contributes importantly to clinical management. [Table: see text]
MDSC clinical assay for disease surveillance in prostate cancer.
Authors: Grace Chang, Irene Kang, Ahva Shahabi, Malini Nadadur, Kanthi Athreya, Evren Suer, David Canter, Mo-Li Chen, Sue Ellen Martin, Monish Aron, Susan G. Groshen, Alan L. Epstein, Jacek K. Pinski
Journal: Journal of Clinical Oncology (2015)

e16091 Background: Myeloid-derived suppressor cells (MDSC) are a population of endogenous cells induced by tumor antigens to mediate immune tolerance within cancer patients. Our study objective is to compare MDSC levels in varying stages of prostate cancer patients and with prostate specific antigen (PSA) levels. We hypothesize that the MDSC assay will provide information reflective of prostate cancer status based on tumor immunogenicity and burden that is complementary to the androgen receptor-driven PSA. Methods: In this prospective correlative study, we proposed a flow cytometry-based immunoassay to detect and quantify serum MDSC using specific monoclonal antibodies targeted against human MDSC. We measured MDSC in patients with varying stages of prostate cancer and compared MDSC to PSA levels. Analysis of variance using the log transformed baseline MDSC levels was used to determine differences in geometric mean MDSC among the groups; p-values were adjusted for multiple comparisons using the Student-Newman-Keuls test. Results: A total of 55 patients were recruited to three groups: cancer-free controls, localized, and radiographically-proven metastatic prostate cancer patients. There was an overall statistically significant difference in the mean MDSC levels among the three groups (p = 0.003). The highest mean MDSC was among metastatic prostate cancer patients (3.1%, 95% CI: 2.3-4.1), which was notably different from patients with localized disease (1.4%, 95% CI: 0.9-2.0; p = 0.004) and controls (1.7%, 95% CI: 0.96-3.9; p = 0.040). PSA level measured at the time of study enrollment was not found to be correlated with MDSC level (p = 0.29). Conclusions: The MDSC assay represents an entirely different approach for monitoring disease burden in prostate cancer by measuring the tumor antigen's ability to induce immune tolerance in the host independent of the androgen receptor signaling pathway. Further studies are needed to assess the utility of this novel marker in guiding the therapeutic management of patients with prostate cancer.
Circulating tumor cells (CTCs) and plasma cell free DNA (cfDNA) androgen receptor amplification (<i>AR</i>amp)-based prognosis in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Manish Kohli, Jian Li, Meijun Du, David W. Hillman, Winston Tan, Rachel Carlson, Liguo Wang, Liewei Wang, Minetta C. Liu, Huijuan Zhang, Peng Zhang, Liang Wang
Journal: Journal of Clinical Oncology (2017)

152 Background: Plasma cfDNA ARcopy number variations (CNV) have been suggested to have prognostic significance in mCRPC stage. We compared plasma AR amplification ( ARamp) with CTC counts (the only FDA approved prognostic marker in mCRPC stage) in a prospective trial of patients (pts) progressing on androgen deprivation therapy. Methods: Plasma and CTC counts were obtained concurrently as part of a prospective clinical trial in mCRPC stage pts initiating abiraterone acetate (NCT# 01953640). Plasma cfDNA was purified using DNA Blood Mini Kit (Qiagen, Valencia, CA) and AR CNVs were detected using QuantStudio3D digital PCR system (Life Technologies, Carlsbad, CA, USA). CTC enumeration was performed using the FDA cleared CellSearch platform. The distributions of overall survival (OS) time based on ARamp status and CTC counts ( &lt; 5 vs ≥ 5 cells) were estimated using the Kaplan-Meier method. Log-rank tests were used to test association of ARamp status and CTC counts with overall survival (OS). Univariate and multivariate logistic regression models and ROC evaluated association of OS at 24 months by ARamp status and CTCs ≥ 5. Results: Between 05/2013 and 09/2015, 92 pts were enrolled of which complete CTC, plasma and outcome data was available for 70 pts. Median age of the cohort (range) was 72 yrs (39-91); Median PSA–16.2 ng/ml (range: 0.9-2026.0); Median CTC count was 2.0 (range: 0-372); 58/70 pts had bone metastases; 38/70 had high volume and 32/70 had low volume metastatic disease at the time of sample collection. The median (range) follow up time at the time of this analysis was: 26.5 (7.9-37.0) months at which time 28/70 patients had died. ARamp was present in 19/70 pts while 51/70 did not have amplification. 24/70 had CTCs ≥ 5. A significant association of increased ARamp status with OS (p &lt; 0.0001, log-rank test; AUC: 0.66) as well as with CTC counts ≥ 5 (p = 0.001, log-rank test; AUC: 0.67) was observed. Combining CTC status and plasma ARamp status the AUC was 0.75. Conclusions: Plasma cfDNA ARamp status and CTC counts have comparable and clinically meaningful prognostic marker value in mCRPC stage patients.
Quantification of Erythroblast- and Myelocyte-Derived mRNAs in Plasma Exosomes As an Indicator of Bone Marrow Status in Patients with Various Types of Anemias and Myeloproliferative Disorders
Authors: Masato Mitsuhashi, Taku Murakami, Teodora Kuzmanovic, Cassandra M. Hirsch, Hideki Makishima, Jaroslaw P Maciejewski
Journal: Blood (2016)
A randomized phase II study of thalidomide with or without erythropoietin (EPO) in metastatic renal cell carcinoma (RCC)
Authors: C. Famoyin, C. Byrnes, S. Roberts, J. Gollob, M. Atkins, J. Mier, Y.-J. Ko, S. Gautam, D. McDemott
Journal: Journal of Clinical Oncology (2004)

4747
Is there any significant difference between tumor regression grade systems of rectal cancer?
Authors: Atthaphorn Trakarnsanga, Mithat Gonen, Jinru Shia, Garrett Michael Nash, Larissa K. F. Temple, Jose G. Guillem, Philip Paty, Karyn A. Goodman, Marc Gollub, Leonard Saltz, Martin R. Weiser
Journal: Journal of Clinical Oncology (2012)

3583 Background: Tumor regression grade (TRG) is a measure of histopathologic response of rectal cancer to preoperative chemoradiation (CRT) and correlates with outcomes. Several TRG systems have been reported including Mandard (5, 3 tier), Dowrak/Rodel (5, 3 tier), Memorial Sloan Kettering Cancer Center (MSKCC), and American Joint Committee of Cancer (AJCC). The purpose of this study is to compare the different TRG systems and determine which one(s) best predict recurrence and survival. Methods: Review of prospective maintained database from 1998 to 2007 identified 563 patients with locally advanced rectal cancer (T3/4 and/or N1) and treated with long-course CRT followed by total mesorectal excision. TRG was determined by measuring proportion of tumor mass replaced by fibrosis. Patients were then classified into the various TRG schemes which were compared by analyzing association with recurrence and survival using concordance index (CI) and reclassification index. CI is a measure that summarizes the predictive strength of a marker. Computing and contrasting CI across several markers is a way of selecting the best prognostic marker. Results: 75% of patients were noted to have clinical stage III disease by endorectal ultrasound or rectal MRI. Following resection with median follow-up of 39.3 months, 2% developed local recurrence and 17% developed distant metastasis. The median interval time between completion of CRT and surgery is 48 days. 20% demonstarted complete pathological response. CI of the 3 tier Mandard, 3 tier Dowrak/Rodel, MSKCC and AJCC are 0.665, 0.653, 0.683, and 0.694, respectively (higher number indicates better prediction). The AJCC was significantly more accurate in predicting recurrence than the 3- tier Mandard (p=0.002), and Dowrak/Rodel (p=0.006). AJCC had a higher CI than MSKCC although it did not reach significance (p=0.068). Comparing the 3 tier systems, MSKCC was most accurate and correctly reclassified 17 % and 23 % of the patients Mandard and Dowrak/Rodel systems, respectively. Conclusions: TRG predicts recurrence and survival following combined modality therapy for rectal cancer. The TRG system that recently was proposed in the 7 th AJCC staging is currently the most accurate predictor.
A DNA methylation signature for stemness in acute myeloid leukemia.
Authors: Timothy J. Triche, Stephen Capone, Akil Abid Merchant, Preet M Chaudhary, Giridharan Ramsingh
Journal: Journal of Clinical Oncology (2014)

7104 Background: In an effort to assign immunophenotypes to AML samples where no immunohistochemistry had been recorded, we trained a DNA methylation classifier using Illumina HumanMethylation450 beadarray data from normal and malignant cells with known immunophenotype. Remarks from clinical malignant hematologists led us to investigate whether a resulting CD34-associated signature was also prognostic. Methods: Data from flow-sorted cells and from blasts with immunohistochemistry results were used to identify differentially methylated regions, which we then ranked and fit via logistic regression as predictors of CD34, CD33, CD14, and myeloperoxidase status. A strong DNA methylation signature was associated with CD34 immunophenotype in normal hematopoeitic stem/progenitor cells (HSPCs), cultured peripheral blood HSPCs from other groups, and CD34-positive TCGA AML samples. In cross-validation, a panel of 20 differentially methylated regions correctly predicted immunophenotype for 96% of AML, normal CD34+ cells, normal CD14+ cells, and normal neutrophil granulocytes when true labels were masked. When we plotted percent methylation across each region in unsorted TCGA AML blast samples and our own, a gradient appeared, with normal CD34+ cells at one extreme, normal CD14+ cells near the other, and AML blasts in between. We thus fit reduced signatures, as well as the normalized rank for each AML, as predictors of overall and relapse-free survival in the TCGA AML cohort (N=191 samples with usable data) using the 'glmnet' package in R. Results: The DNA methylation “stemness” score was a significant (p < 0.02) predictor of poorer overall and event-free survival in TCGA AML cases. The individual differentially methylated regions comprising the signature overlapped numerous intronic and intergenic enhancer elements, microRNAs, Piwi RNAs, and noncoding transcripts known to play roles in specification of hematopoeitic cell fates. Many of the associated transcripts are expressed at low but detectable levels in normal CD34+ HSPCs but not in progeny, or vice versa. Conclusions: Epigenetic plasticity, as reflected by HSPC-like DNA methylation, is a negative prognostic factor for overall and event-free survival in AML.
Peritransplant Complications and Long-Term Outcomes of Patients with Newly Diagnosed POEMS Syndrome after Upfront Autologous Stem Cell Transplantation
Authors: Jian Li, Ming-hui Duan, Wei Zhang, Chen Wang, Xu-fei Huang, Tie-nan Zhu, Hua-cong Cai, Xin-xin Cao, Dao-bin Zhou
Journal: Blood (2016)