tbuckley/cabot-search huggingface dataset:
Chemotherapy for resected colorectal cancer pulmonary metastases: Utilization and outcomes in routine clinical practice.
Authors: Safiya Karim, Sulaiman Nanji, Kelly Brennan, C S. Pramesh, Christopher M. Booth
Journal: Journal of Clinical Oncology (2017)

236 Background: The role of chemotherapy in the setting of resected colorectal cancer pulmonary metastases (CRCPM) is not well defined. Here we describe utilization of peri-operative chemotherapy and outcomes among patients with resected CRCPM in the general population. Methods: All cases of CRCPM who underwent resection from 2002-2009 were identified using the Ontario Cancer Registry (OCR). Electronic treatment records identified peri-operative chemotherapy delivered within 16 weeks before or after pulmonary metastectomy (PM). Modified Poisson regression was used to evaluate factors associated with chemotherapy delivery. Cox proportional models were used to explore the association between post-operative chemotherapy and cancer-specific (CSS) and overall survival (OS). Results: The study population included 420 patients. Thirty-six percent of patients (151/420) received peri-operative chemotherapy. Among these patients, 75% (113/151) received post-operative chemotherapy. Factors that were independently associated with use of post-operative chemotherapy included higher socioeconomic status (SES) and no prior adjuvant chemotherapy (p &lt; 0.01). In adjusted analyses post-operative chemotherapy was not associated with improved CSS (HR 0.99, 95% CI 0.67-1.47) or OS (HR 0.93 95%CI 0.66-1.31). In exploratory analyses, among those patients who did not receive previous adjuvant therapy for the primary colorectal cancer, post-operative chemotherapy following lung metastatectomy was associated with HR 0.50 (95%CI 0.27-0.95) for OS and HR 0.59 (95%CI 0.27-1.27) for CSS. Conclusions: One third of patients with resected CRCPM in routine practice receive peri-operative chemotherapy. A randomized controlled trial is warranted to evaluate whether chemotherapy following resection of CRCPM is associated with improved survival.
Predictive factors to develop a second neoplasia in a Hodgkin disease cohort patients
Authors: A. Rubio-Martínez, V. Recasens, C. Martos, A. Montañés, G. García-Carpintero, L. Gómez-López, D. Rubio-Félix, P. Giraldo
Journal: Journal of Clinical Oncology (2004)

6707 Background: Hodgkin's lymphoma (HL) is a rare malignancy, incidence rate (IR): 2.4/105 inh/y, 85% can be cured. The importance of late effects of therapy have become more apparent. Purpose: to determine the IR of second malignancies (SM)in HL and to compare with cancer IR in general population during 1978–1998. Methods: a cohort of 295 patients diagnosed as having in the Hematology Department of Miguel Servet University Hospital was followed-up (population at risk: 533,946 inh). Data source: clinical reports and poblational based Cancer Registry. Variables: demographic data, date of HL diagnosis, histological subtype, stage, treatment schedule (chemotherapy, radiotherapy, combined), date SM diagnosis, subtype and location of cancer. Cohort was stratified according to age, gender and schedule of therapy. Other risk factors related to cancer were considered (smoke, toxic contacts, previous neoplasia). A bivariant study and we perform a lineal regression model and its coefficient have been done. Results: IR of HL in our population is 2.4 cases/105 inh/y (F:1.87; M:3.03); estimated cancer IR in our area: 255.2 SD 32.3 cases/105 inh/y (1978–1998). Mean age: 38.3 SD 26 y. M/F 67%/33%. Subtype: NE 71%, MC22%, LP 24; stage: IA 12.7%, IB 1.6%, IIA 27.9%, IIB 5%, IIIA 16.9%, IIIB 14.4% IVA 9.3% IVB 11.8%. Radiotherapy 16.1% (mantle 50%, inverted-Y 11.8 %, both: 1.6%;cobalt 59.3%, linear accelerator 4.2%; total dose 20–36 Gy), chemotherapy 39.8% (ABVD 14.4%, MOPP 15.5%, CMOPP 23.7%, CMOPP/ABVD 18.6%, ABVD/MOPP 15.2%), combined 44%. HL relapsed: 10.1%, mean time: 49 m. Developed a SM 15(12.7%), mean 102.3 m; range 9–285: 11 a non-hematological neoplasia: adenocarcinoma (colon, breast, lung, oropharynx, skin, cavum, parotida. thyroid) and 4 a hematological neoplasia (AML and NHL). The global risk of cancer in HL was 10.0 and 6.5 when only non hematological tumor were considered. No variable with predictive value was found in the model. Conclusions: The incidence of SM among long-time survivors of HL is higher than in normal population. In other essays the major risk has been observed in patients treated with radiotherapy either alone or combined with chemotherapy. No significant financial relationships to disclose.
SIRT4 Is a Lysine Deacylase that Controls Leucine Metabolism and Insulin Secretion
Authors: Kristin A. Anderson, Frank K. Huynh, Kelsey Fisher-Wellman, J. Darren Stuart, Brett S. Peterson, Jonathan D. Douros, Gregory R. Wagner, J. Will Thompson, Andreas S. Madsen, Michelle F. Green, R. Michael Sivley, Olga R. Ilkayeva, Robert D. Stevens, Donald S. Backos, John A. Capra, Christian A. Olsen, Jonathan E. Campbell, Deborah M. Muoio, Paul A. Grimsrud, Matthew D. Hirschey
Journal: Cell Metabolism (2017)
Association of CD133 polymorphisms and clinical outcome in metastatic colorectal cancer (mCRC) patients (pts) treated with either first-line 5-FU + bevacizumab (BV) or second-line irinotecan (IR)/cetuximab (CB) or IR alone
Authors: A. Pohl, W. Zhang, D. Yang, G. Lurje, Y. Ning, S. Khambata-Ford, C. Langer, M. Kahn, J. L. Teo, H. J. Lenz
Journal: Journal of Clinical Oncology (2009)

4062 Background: CD133 has been routinely used to identify colon cancer stem cells. A recent study indicated that elevated levels of CD133 plasma mRNA correlated with colon cancer recurrence. Furthermore plasma levels of CD133+ progenitor cells have been found to be decreased after treatment with BV. We tested whether potentially functional frequently occurring germline variations in the 3’UTR-region of the CD133 gene (rs2240688, rs3130 and rs2286455), might be associated with clinical outcome in first- and second-line treated mCRC pts. Methods: Genomic DNA was extracted either from peripheral blood (79 pts, who were enrolled in a phase-II clinical trial with FOLFOX/BV or XELOX/BV) or formalin-fixed paraffin-embedded tumor samples (186 pts, who were enrolled in the EPIC phase III clinical trial, US-sites only) of mCRC pts. Pts received either first-line treatment with FOLFOX/ BV (33 pts) or XELOX/BV (46 pts) or second-line treatment with CB/IR (84 pts, arm A) or IR (102 pts, arm B) alone. Genotyping was performed using PCR-RFLP assays. Results: 79 pts (47 men, 32 women) received FOLFOX/BV or XELOX/BV. Radiologic response: 43 pts (54%) CR/PR, 35 pts (45%) SD/PD. Median PFS was 10.8 months (95%CI: 8.1–14.9). The second cohort consisted of 186 pts (103 men, 83 women). Radiologic response: Arm A 11 pts (13%) CR/PR, 73 pts (87%) SD/PD. Arm B 6 pts (6%) CR/PR, 96 pts (94%) SD/PD. Median PFS (arm A) was 3.0 months (95%CI: 2.4–4.1) vs. 2.7 months (arm B,95%CI: 2.2–2.9). Combined analysis of rs2286455 and rs3130 showed a significant association with PFS (p= 0.010, log-rank test) in pts receiving FOLFOX/BV or XELOX/BV. In pts receiving IR alone rs2240688 was significantly associated with OS (p=0.0128, log-rank test). Multivariate analysis showed a significant association with PFS in first-line setting for rs2286455 and rs3130 (adjusted p=0.012) and a trend in second-line setting for rs2240688 (adjusted p=0.086). Conclusions: These are the first data to show that polymorphisms in CD133 predict outcome in mCRC pts in first- and second- line setting, suggesting that CD133 may be a potential predictive marker. These results need to be confirmed in larger prospective studies. [Table: see text]
Emerging Roles for MicroRNAs in Diabetic Microvascular Disease: Novel Targets for Therapy
Authors: Yu Zhang, Xinghui Sun, Basak Icli, Mark W. Feinberg
Journal: Endocrine Reviews (2017)

Abstract Chronic, low-grade systemic inflammation and impaired microvascular function are critical hallmarks in the development of insulin resistance. Accordingly, insulin resistance is a major risk factor for type 2 diabetes and cardiovascular disease. Accumulating studies demonstrate that restoration of impaired function of the diabetic macro- and microvasculature may ameliorate a range of cardiovascular disease states and diabetes-associated complications. In this review, we focus on the emerging role of microRNAs (miRNAs), noncoding RNAs that fine-tune target gene expression and signaling pathways, in insulin-responsive tissues and cell types important for maintaining optimal vascular homeostasis and preventing the sequelae of diabetes-induced end organ injury. We highlight current pathophysiological paradigms of miRNAs and their targets involved in regulating the diabetic microvasculature in a range of diabetes-associated complications such as retinopathy, nephropathy, wound healing, and myocardial injury. We provide an update of the potential use of circulating miRNAs diagnostically in type I or type II diabetes. Finally, we discuss emerging delivery platforms for manipulating miRNA expression or function as the next frontier in therapeutic intervention to improve diabetes-associated microvascular dysfunction and its attendant clinical consequences.
Development and implementation of clinical pathways across a network of blood cancer programs.
Authors: Laura Ione Brougher, Rocky Lee Billups, Tonya Cox, Therese Dodd, Charles F. LeMaistre
Journal: Journal of Clinical Oncology (2017)

161 Background: The Sarah Cannon Blood Cancer Network (SCBCN) is comprised of 7 blood cancer and Hematopoietic Cell Therapy (HCT) programs providing care for complex blood cancer patients. Network commitment to achieving standardization of care for quality and clinical platforms led to process design for development of evidence-based pathways. Methods: Standard operating procedures and a document control process were developed by the network quality management (QM). With oversight by physician leaders, initial efforts focused on standardizing patient selection criteria for HCT followed by formation of disease-specific work groups (leukemia, lymphoma, multiple myeloma, HCT). Physician-led and composed of key network team members (PharmDs, QM professionals, SCBCN leaders, research staff), the groups are responsible for developing evidence-based diagnostic and treatment pathways/algorithms for hematologic malignancies. Members participate in monthly teleconferences to develop the pathways. Annual review and deviation tracking are conducted, providing a mechanism for subsequent pathway revisions reflecting changing treatment paradigms and updated clinical evidence. QM oversees implementation and tracking across the network. Deviation tracking is managed locally using pathway-associated algorithms, with attending physician attestation to either compliance or pathway deviation/reason (e.g. co-morbidity, age, disease status, enrolled on clinical trial, other). Results are reported quarterly with review by QM. Results: See table. To date, 13 HCT pathways (18 algorithms) have been developed and released to SCBCN programs. Final approval is pending for 5 disease-based pathways (19 algorithms). Conclusions: The first compliance report will be submitted to QM in December, 2016. While deviation tracking has been paper-based, work efforts are underway to implement an electronic solution, enabling automated real-time monitoring. Implementation is expected in early 2017. [Table: see text]
Isolation of circulating tumor cells in colon cancer patients by size and chromosomal abnormalities.
Authors: Ignacio Matos, Rebeca Lozano, Emilio Fonseca, Jesus MariÂa Hernandez, Arantxa Amores, Lina Lopez, Carolina Lopez, Maria Angeles Hernandez, Juan Luis Hernandez, Juan J. Cruz
Journal: Journal of Clinical Oncology (2013)

e22058 Background: Determining the number of circulating tumor cells (CTCs) in patients with metastatic colorectal cancer (CRC) has shown to be a prognostic factor, recent studies have proven the existence of EpCAM and cytokeratin negative CTCs. These cells present morphological and genetic alterations. Our study is based on an algorithm determined by the selection of the size of the cells and the genetic alterations detected by FISH which enables the isolation of CTCs in CRC patients by an automated system of fluorescence. Methods: Patients with metastatic CRC with normal blood differential and healthy controls between June 2011 and June 2012 were chosen. The objective was to show the differences between the quantification of morphogenetically altered cells in peripheral blood obtained from control and patients. The selected cells were over 7 micra in size and presented two or more genetic alterations. A combination of four probe sets was used: centromeric probe for CEP3, CEP7 and CEP17 and LSI p16INK4A 9p21.3. Fluorescent signals in specimens were quantified using an automated fluorescent system (Metafer) that is capable of scanning and classifying hundreds of cells under fluorescent illumination and allows for detection of cells according to nuclear size &gt; 7 um and FISH pattern based on the algorithm that we have developed. Results: We selected 28 healthy individuals and 45 patients with CRC. In all the cases, 1,000 cells were analyzed in each individual. Only 30 cells &gt;7 micra being found in the controls out of the 28,000 cells analyzed (0.1%). In the case of the patients, 640 cells were found (1.42%), the difference becoming statistically relevant after the T-test (p=0.003). None of the controls presented cells with two or more genetic alterations and over 7 micra in size, whereas 38% of the patients presented these characteristics despite having received treatment. The most frequent chromosomal changes were trisomy 3 and 17 (26% and 18%, respectively). Conclusions: This method allows us to select genetically abnormal circulating cells in a simple and automatic way. This opens the door for future studies to analyze the prognostic factor and the response rate to treatment under this method.
A phase II study of cisplatin (P), S-1 (S), and concurrent thoracic radiotherapy (TRT) for locally advanced non-small cell lung cancer (LA-NSCLC): Okayama Lung Cancer Study Group trial 0501.
Authors: Daizo Kishino, Naoyuki Nogami, Yoshihiko Segawa, Keisuke Aoe, Hiroshi Ueoka, Nagio Takigawa, Shingo Harita, Masahiro Tabata, Mitsune Tanimoto, Katsuyuki Kiura
Journal: Journal of Clinical Oncology (2012)

7042 Background: We previously reported an efficacy and safety of fractionated schedule ofP and docetaxel (D) (days 1, 8, 29, and 36, each) and concurrent TRT (DP-TRT) for LA-NSCLC (JCO 2010). Although the median survival time (MST: 26.3 months) was excellent, grade 3 or greater pneumonitis (10%) and esophagitis (14%) were observed and treatment-related death was 3%.Thus, further improvement in the safety as well as efficacy is strongly warranted. S, an oral fluoropyrimidine, is a new active agent possessing a radio-sensitizing effect. Additionally, combining S and P offered an active and safe regimen for metastatic NSCLC. The objective of this study was to assess the efficacy and safety of S + P with concurrent TRT for LA-NSCLC. Methods: Patients with stage IIIA/IIIB, aged ≤75 years and PS 0-1, and without any prior chemotherapy were eligible for this study. Patients were treated with P (40 mg/m² on day 1, 8, 29 and 36) and S (40 mg/m²/dose b.i.d. on days 1-14 and 29-42) and TRT (60 Gy/30 fr over 6 weeks starting on day 1). Primary endpoint was response rate (RR), and required sample size was 48 patients. Results: Between 2006 and 2009, 48 patients were enrolled (37 men; median age, 66 years; PS 0/1, 36/14; IIIA/IIIB, 23/25; sq/non-sq, 22/26). Partial response was observed in 37 patients (77%; 95% confidence interval: 63-88%). The response rate was higher in older patients (≥65 yrs) than younger (&lt;65 yrs) (89% vs. 64%, p=0.041). At a median follow-up of 40 months, median progression-free survival and MST were 9.3 months and 31.3 months, respectively. No difference in efficacy (response and survivals) was observed stratified by histology (sq vs. non-sq). Toxicities were generally mild, including G3/4 neutropenia (44%), G3/4 thrombocytopenia (13%), G3 febrile neutropenia (8%) and G3 pneumonitis (4%). No one developed Gr3/4 esophagitis. No toxic deaths occurred. Conclusions: This chemoradiotherapy regimen yielded a favorable overall survival data. Also, it was well-tolerated in patients with LA-NSCLC as compared with concurrent DP-TRT therapy especially in term of TRT-related toxicities. A phase III trial of this regimen vs. DP-TRT is now planned.
Pancreatic Cancer: “A Riddle Wrapped in a Mystery inside an Enigma”
Authors: Erkut Borazanci, Chi V. Dang, Robert W. Robey, Susan E. Bates, John A. Chabot, Daniel D. Von Hoff
Journal: Clinical Cancer Research (2017)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most difficult-to-treat cancers. With an increasing incidence and inability to make major progress, it represents the very definition of unmet medical need. Progress has been made in understanding the basic biology—systematic genomic sequencing has led to the recognition that PDAC is not typically a heavily mutated tumor, although there are exceptions. The most consistently mutated genes are KRAS, CDKN2A, TP53, and SMAD4/DPC4. Study of familial PDAC has led to the recognition that a variety of defects in DNA repair genes can be associated with the emergence of pancreatic cancer. Recent studies suggest that epigenetics may play a larger role than previously recognized. A major new understanding is the recognition that PDAC should be considered a composite of tumor cells, as well as pancreatic stellate cells, immune cells, and extracellular matrix. The individual components contribute to metabolic aberration, immune dysfunction, and chemotherapy resistance, and therapeutic innovations may be needed to address them individually. It has also been recognized that metastatic seeding from PDAC occurs very early in the disease course—in an estimated 73% of cases, once the tumor reaches 2 cm. The implication of this is that therapies directed toward micrometastatic disease and increasing fractional cell kill are most needed. Neoadjuvant approaches have been taken to increase resectability and improve outcome. So much work remains, and most critical is the need to understand how this tumor originates and develops. Clin Cancer Res; 23(7); 1629–37. ©2017 AACR. See all articles in this CCR Focus section, “Pancreatic Cancer: Challenge and Inspiration.”
Gefitinib monotherapy in previously treated advanced non-small cell lung cancer (NSCLC): An immunohistochemical (IHC) analysis of EGFR and its downstream molecules
Authors: S. W. Han, P. G. Hwang, D. H. Chung, J. H. Kim, D. W. Kim, T. Y. Kim, D. S. Heo, Y. J. Bang, N. K. Kim
Journal: Journal of Clinical Oncology (2004)

7096
Molecular markers expression in mediastinal nodes from resected stage I non-small cell lung cancer (NSCLC): Prognostic impact and potential role as markers of occult micrometastasis
Authors: B. Massuti, J. Galbis, C. Alenda, F. M. Peiró, J. Martí, B. Baswitch, J. M. Rodriguez-Paniagua, R. Rosell, M. Taron, S. Benlloch
Journal: Journal of Clinical Oncology (2007)

21016 Background: 5-y surv in surgically resected St I NSCLC is 60–70% whereas in cases with affected lymph nodes (LN) it is &lt; 50%. The main risk factor for recurrence is nodal disease. Current histopathologic analysis can miss occult micrometastases in nodal tissues at initial diagnosis. Detection of micromets with a more sensitive technique would be useful to define a high-risk population selecting patients (p) for postop treatment. We assessed the role of several genes mRNA expression in pathological negative LN from resected St I NSCLC p as markers of occult micromets and correlated the results with relapse, and survival. Methods: Paired tumor and histological negative LN (n=344) obtained by systematic mediastinal lymphadenectomy from 38 surgically resected St I NSCLC p were analyzed for the presence of 12 genes mRNA expression using RT-Q-PCR in an ABIPRISM 7500. RNA was extracted using ABIPRISM 6100. Specifically designed primers and probes were purchased from Applied Biosystems as Assay-on-demand; GADPH was used as an endogenous control. Samples were also analyzed by ICH for LN staging. Results: 38 NSCLC p; 12 adenoca, 16 squamous cell, 10 undifferentiated . From the 12 tested genes CEA and PLUNC were found with high expression in lung tissue and low or null expression in normal LN. We consider molecular + LN those in which expression of CEA or PLUNC was detected. In the 344 pathological negative LN, 13% (44/344) were positive for CEA, 16% (54/344) for PLUNC. The expression patterns were similar for both markers. At a median follow-up of 24 mo (9–46) 11 p had died from NSCLC and 1 had died without recurrence. None of the living p had tumor recurrence. For the prognostic assessment, molecular + LN were classified as N1 and N2. Median DFS was 15 ± 11.74 mo in p with N2 molecular + nodes was and has not yet reached in cases of molecular (-) LN (p=0.028). Median survival of p with N2 molecular positive nodes was 17.3 ± 5.7 mo and has not yet reached (p= 0.0083) for molecular (-) LN. Conclusions: CEA and PLUNC mRNA expression could be used as molecular markers of occult micrometastases in mediastinal LN showing a prognostic effect . CEA and PLUNC expression provides a tool for selecting high-risk p considered for adjuvant therapies No significant financial relationships to disclose.
Influence of provider and health system factors on uptake and disparities in breast cancer gene expression profile testing.
Authors: Katherine Elizabeth Reeder-Hayes, Stephanie B. Wheeler, Megan Roberts, Ke Meng, Xi Zhou, Christopher Baggett, Anne-Marie Meyer
Journal: Journal of Clinical Oncology (2017)

250 Background: Gene expression profiles (GEPs) have been rapidly and widely adopted to guide chemotherapy decisions in early hormone receptor-positive (HR+) breast cancer, but not all eligible patients receive testing. Patient-level predictors of testing have been reported. However, the role of provider and insurance factors in GEP use has not been well described. Racial disparities in access to testing are also under-studied. Methods: We used state cancer registry data linked to claims from multiple insurance payers to identify 11,958 patients eligible for GEP testing between 2005 and 2012. For each patient, we characterized specialty and breast cancer volume for the provider deemed most likely to make the testing decision. We identified claims for the most commonly used GEP (OncotypeDX) and used adjusted incidence rate models to examine predictors of testing, stratified by nodal status (N0 versus N1). Results: Overall, 26% of eligible patients were tested with rates increasing over time. In multivariable analyses among N0 patients, black women were 12% less likely than clinically similar whites to be tested. Patients treated by a general surgeon were less likely to be tested than those treated by oncologic specialists, while those seen by middle-volume providers were significantly more likely to be tested than patients of the highest-volume providers. Black women with N1 disease were 27% less likely to be tested. Among N1 patients, testing was most common among patients of highest-volume providers and declined consistently with provider volume. Private insurance increasing the likelihood of testing for N0, but not N1 disease. Conclusions: Insurance status and provider characteristics appear to influence the likelihood of GEP testing for early breast cancer, but do not fully explain racial disparities in access to testing. Black women are less likely than whites to receive testing in either the node-negative or node-positive setting after adjustment for clinical factors. These date suggest a need to develop quality programs that enable uptake of appropriate breast cancer genomic tests, with a focus on elimination of disparities.