tbuckley/cabot-search huggingface dataset:
High-Resolution Genome Wide Copy Number Alteration (CNA) and Loss of Heterozigosity (LOH) Analysis in Chronic Myeloid Leukemia (CML) Shows That High and Intermediate Sokal Risk Pts (Pts) Have Multiple Losses Targeting Genes Involved in DNA Repair.
Authors: Simona Soverini, Sabrina Colarossi, Alessandra Gnani, Annalisa Astolfi, Serena Formica, Fausto Castagnetti, Francesca Palandri, Gabriele Gugliotta, Angela Poerio, Ilaria Iacobucci, Marilina Amabile, Giulia Marzocchi, Simona Luatti, Carolina Terragna, Sandra Durante, Nicoletta Testoni, Gianantonio Rosti, Michele Baccarani, Giovanni Martinelli
Journal: Blood (2009)
TMPRSS2-ERG status and biochemical recurrence following radiotherapy for intermediate-risk prostate cancer.
Authors: Alan Dal Pra, Fiona Warde, Adrian Shea Ishkanian, Alice Meng, Chad Malloff, Wan Lam, Jenna Sykes, Melania Pintile, Jeremy Squire, Theo van der Kwast, Andrew Evans, Michael Milosevic, Robert Glen Bristow
Journal: Journal of Clinical Oncology (2012)

11 Background: Approximately 50% of prostate cancers (PC) contain TMPRSS2-ERG gene fusions leading to ERG overexpression. Pre-clinical data suggest that these fusions are due to altered DNA double-strand break repair status which could have therapeutic ramification for the use of radiotherapy (RT) and PARP inhibitors. The aim of this study was to correlate TMPRSS2-ERG status to biochemical failure following clinical induction of DNA breaks in the form of image-guided radiotherapy (IGRT) in intermediate-risk PC. Methods: Pre-treatment biopsies from two separate cohorts of intermediate-risk PC patients (T1/T2, GS &lt; 8, PSA &lt; 20ng/ml) were analyzed: 1) 126 patients assessed by array Comparative Genomic Hybridization (aCGH) for TMPRSS2:ERG fusion; and 2) 121 patients assessed by tissue microarray (TMA) for ERG expression by immunohistochemistry (IHC). All patients received IGRT with a median dose of 79.8 Gy (60-79.8 Gy). TMPRSS2:ERG status was correlated to Gleason score, T stage, initial PSA and biochemical-free relapse rate (bFRR; Phoenix definition: nadir + 2ng/ml). Results: At a median follow-up time of 6.36 years, the biochemical relapse event rate was 37% and 18% in the aCGH and IHC cohorts, respectively. ERG expression by IHC was found in 49.6% of the 121 PC. TMPRSS2-ERG status was not correlated to increased Gleason score, pre-treatment PSA or T stage. On multivariate analyses in models containing clinical factors, TMPRSS2:ERG status (either using aCGH or IHC) was not prognostic for biochemical outcome (ERG expression: HR=0.78, 95% CI: 0.33-1.85; p= 0.568; TMPRSS2-ERG fusion: HR=0.71, 95% CI: 0.35-1.41; p=0.326). Conclusions: In two separate cohorts, TMPRSS2-ERG status was not prognostic for bRFR after IGRT. Although a trend was observed, these clinical data do not support the hypothesis that these cancers have DNA repair defects that render them significantly more radiosensitive when compared to other PC. Further clinical trials are required to understand the utility of TMPRSS2:ERG status and response to DNA damaging agents, including that of PARP inhibitors. The trans-Canadian PROFIT trial is completing accrual of close to 1200 patients allowing for TMPRSS2:ERG studies in a larger RT cohort.
Predictors of outcome and subgroup results from the integrated analysis of sipuleucel-T trials in metastatic castration-resistant prostate cancer.
Authors: C. S. Higano, E. J. Small, P. F. Schellhammer, P. Kantoff, C. H. Redfern, J. J. Nemunaitis, C. Nabhan, Y. Xu, J. B. Whitmore, M. W. Frohlich
Journal: Journal of Clinical Oncology (2010)

4550 Background: Sipuleucel-T is an investigational autologous active cellular immunotherapy for treatment of metastatic castration resistant prostate cancer. Reported here is an analysis of the homogeneity of the sipuleucel-T treatment effect across studies and within subgroups, and of predictors of overall survival (OS) in this population. Methods: OS for 3 randomized, double blind, placebo controlled trials was analyzed using a Cox regression model with treatment, adjusted for baseline PSA (ln) and LDH (ln), stratified by study. >20 subgroups were assessed using the same model with the addition of subgroup main effect and subgroup by treatment interaction terms. Continuous subgroup variables were dichotomized based on median value. Predictors of OS were identified using a multivariate Cox regression model. Results: The integrated analysis included 737 randomized patients (488 sipuleucel-T: 249 placebo) with median follow-up of 36 months. There was a significant sipuleucel-T treatment effect (HR=0.735, 95% CI:0.613, 0.882, P <0.001), which was found to be homogeneous across the 3 trials (study by treatment interaction P=0.66). A positive treatment effect (HR<1) was observed in all subgroups representing ≥10% of patients, including those defined by age, race, ECOG performance status, number of bone metastases, and previous chemotherapy use. Independent baseline predictors of OS in this patient population included ECOG status, number of bone metastases, nodal disease, age, weight, PSA, LDH, hemoglobin, and time from diagnosis to randomization. Alkaline phosphatase, Gleason sum, and prostatectomy were significantly associated with OS, but were not identified as independent predictors. Conclusions: The integrated analysis of 3 sipuleucel-T trials revealed consistent results across trials and within subgroups. The identification of ECOG status, PSA, LDH, and hemoglobin as significant predictors of OS in this population is consistent with those identified previously (Halabi 2003, Armstrong 2007) ; however, the identification of number of bone metastases, age, weight, nodal disease, and time from diagnosis to randomization represent new findings. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Dendreon Dendreon Dendreon Dendreon Dendreon FDA
Correlates and mediators of worry about breast cancer recurrence.
Authors: N. K. Janz, S. T. Hawley, M. S. Mujahid, J. Graff, A. S. Hamilton, S. J. Katz
Journal: Journal of Clinical Oncology (2010)

9098 Background: Worry about recurrence (worry) is a persistent concern of women with breast cancer; however, little is known about racial/ethnic differences or mechanisms in the health care experience that may explain differences. Methods: 3,133 women with nonmetastatic breast cancer diagnosed from 6/05-2/07 and reported to Detroit or Los Angeles SEER registries were surveyed (mean 9 months post-diagnosis). Latina and African American (AA) women were oversampled (final n= 2,268, response rate 72.4%). A worry scale was constructed as the mean response to 3 items (5-point Likert) measuring worry about cancer returning to same breast, other breast, or spreading to other parts of the body (higher scores = more worry). Race/ethnicity categories were white, AA, and Latina (categorized into low vs. high acculturation by the Short Acculturation Scale for Hispanics). The worry scale was regressed on race/ethnicity controlling for sociodemographics (e.g., age, education), and then clinical (e.g., stage, comorbidites, frequency of pain, fatigue), risk (e.g., smoker, family history) and treatment (surgery, radiation, chemotherapy) factors. Health system factors that may mediate associations were next considered (e.g., symptom management, care coordination; specified as low, moderate, high). Results: Low acculturated Latinas reported more worry than other groups (adjusted for sociodemographics), worry scores 3.62 vs. 3.06, 2.47, 2.78 for higher acculturated Latinas, AAs, and whites, p<0.001). Factors independently associated with worry were younger age, smoker, comorbidities, more pain and fatigue, and radiation (ps <0.05). Less worry was associated with more coordinated care (3.39, 3.06, 2.92, for low, moderate, and high, p=0.038) and better management of symptoms (3.29, 3.00, 2.96 for low, moderate, and high, p=0.010) controlling for sociodemographics, and clinical/risk/treatment factors. Race/ethnicity remained significant and essentially unchanged adjusted for all factors (p <.0.001). Conclusions: Less acculturated Latina breast cancer patients were vulnerable to the highest levels of worry about recurrence. Interventions aimed at improving symptom management and coordinating care hold promise in reducing worry. No significant financial relationships to disclose.
Expression and prognostic significance of human epidermal growth factor receptors 1, 2, and 3 by histological type in periampullary adenocarcinoma.
Authors: Jacob Elebro, Carl Fredrik Warfvinge, Margareta Heby, Bjorn Nodin, Jakob Eberhard, Karin Jirstrom
Journal: Journal of Clinical Oncology (2016)

258 Background: Periampullary adenocarcinoma, including pancreatic cancer, is a heterogeneous group of tumors with dismal prognosis. The human epithelial growth factor receptor family consists of four closely related members EGFR (HER1) - HER4. HER-targeting drugs have a beneficial effect on survival in several types of cancer, but the benefits have been modest in pancreatic cancer and the prognostic value of HER-expression remains unclear. The aim of this study was therefore to examine the expression and prognostic value of EGFR, HER2 and HER3 in periampullary cancer, with particular reference to histological subtype. Methods: Immunohistochemical expression of EGFR, HER2 and HER3 was analyzed in tissue microarrays with 175 periampullary adenocarcinomas consecutively operated at the University hospitals of Lund and Malmö, Sweden, 2001 – 2011, with follow up data on RFS and OS for up to 5 years. Results: The expression of EGFR and HER2 was similar in pancreatobiliary (PB) and intestinal (I) type tumors but HER3 was more often highly expressed in I-type tumors (52% vs 21%, p &lt; 0.001). In PB-type tumors there were no associations between expression of HERs and clinicopathological parameters or survival. In I-type tumors, high EGFR expression was associated with larger tumors and high expression of HER3 was inversely associated with growth in peripancreatic fat (p = 0.003) and T-stage (p = 0.006). HER2 expression was not associated with any clinicopathological parameter. In I-type tumors, high expression of EGFR was associated with shorter OS and RFS in univariable Cox regression analysis (HR = 2.74, CI 1.32-5.69 for OS and HR = 2.58, CI 1.23-5.38 for RFS) but not in multivariable analysis. HER2 expression was not prognostic. High HER3 expression was associated with a prolonged RFS in univariable (HR = 0.45, CI 0.21-0.95) but not in multivariable analysis. Conclusions: High EGFR expression is an unfavorable prognostic factor and high HER3 expression a favorable prognostic factor in I-type periampullary cancer. Expression of HERs in PB-type tumors had no evident prognostic value. The prognostic value of HERs in periampullary cancer thus differ by histological subtype.
IDH Mutations and Trisomy 8 In Myelodysplastic Syndromes and Acute Myeloid Leukemia
Authors: Domenica Caramazza, Terra Lasho, Christy Finke, Naseema Gangat, David Dingli, Ryan Knudson, Sergio Siragusa, Curtis A. Hanson, Animesh Pardanani, Rhett Ketterling, Ayalew Tefferi
Journal: Blood (2010)
Immunomodulatory Influence by Interferon alpha and Imatinib Mesylate in Chronic Myeloid Leukemia.
Authors: Kazuaki Yokoyama, Tokiko Nagamura-Inoue, Shin Nakayama, Ikuo Ishige, Nobuhiro Ohno, Satoshi Takahashi, Kaoru Uchimaru, Toru Iseki, Arinobu Tojo
Journal: Blood (2007)
Development of a PSA tracking system for patients wtih prostate cancer following definitive radiotherapy to enhance rural health.
Authors: Michael G. Chang, Kristine DeSotto, Paul Taibi, Sandra Troeschel
Journal: Journal of Clinical Oncology (2016)

39 Background: Patients with prostate cancer (PC) may benefit from early intervention when they experience relapse/recur. About 50% of our PC patients are rural and experience barriers to care due to distance, cost, and convenience. We sought to create a PSA tracking system with the Veterans Administration’s (VA) Electronic Medical Record (EMR) that would provide a remote way to monitor disease progression after definitive radiotherapy (XRT) by annual PSA testing alone. Methods: Using VA’s EMR, we developed a query tool to identify all patients ever treated at our center with XRT for prostate cancer who were alive, had not been seen in our clinic in more than a year, did not have metastatic disease, and had a rising PSA of at least 0.5 ng/ml above nadir, or who had no PSA drawn within 15 months. Results: Among roughly 50,000 unique patients in the McGuire VAMC EMR, we found 1,858 patients treated with XRT for PC more than 5 years ago between 1997 and 2015. Of these 1,190 were still alive and 455 had not been seen by our clinic in 400 days or more. Of these 455 patients, 159 patients had not had a PSA drawn within 15 months and/or their most recent PSA was more than 0.5 ng/ml above nadir, triggering a chart review followed by either a phone call, repeat testing, in person follow up visit, or removal from follow up monitoring if clinically indicated. 296 patients were receiving appropriate care outside of our clinic and had no sign of significant rise in PSA. An analysis by the VA showed annual savings of $60,360 per year in fuel costs by avoiding unnecessary visits. Conclusions: The VA’s robust EMR and a new query tool can identify patients with prostate cancer who are lost to follow up or who needed intervention from among thousands of patients in the EMR, improving quality while reducing cost and unnecessary time and travel for rural and all patients. More importantly, our tool could be modified to improve survival for all VA patients with prostate cancer by creating a VA-wide PSA failure detection system. The system would alert providers to any patient who may benefit from early salvage radiotherapy or hormonal therapy before their disease progresses beyond the therapeutic window of benefit.
Response to Comment on Hofer et al. International Comparison of Smoking and Metabolic Control in Patients With Type 1 Diabetes. Diabetes Care 2016;39:e177–e178
Authors: Sabine E. Hofer, Kellee Miller, Julia M. Hermann, Daniel J. DeSalvo, Michaela Riedl, Irl B. Hirsch, Wolfram Karges, Roy W. Beck, Reinhard W. Holl, David M. Maahs
Journal: Diabetes Care (2017)

We thank the editors for the opportunity to respond to the comment made by Balkau et al. (1) on our recent article (2).

Balkau et al. (1) were interested in detailed information about HbA1c in the overall group stratified by registry. As stated in the text, HbA1c was similar between the two registries. In the T1D Exchange Registry (TIDX), HbA1c was 8.6% (SE 0.06) in current smokers, 8.0% (0.05) in former smokers, …
Influence of genetic variants of genes potentially associated with colorectal brain metastases on overall survival.
Authors: Stefan Stremitzer, Anna Sophie Berghoff, Nico Benjamin Volz, Wu Zhang, Dongyun Yang, Sebastian Stintzing, Yan Ning, Yu Sunakawa, Shinichi Yamauchi, Ana Sebio, Rita Elie El-Khoueiry, Peter Birner, Matthias Preusser, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2014)

487 Background: Brain metastases (BM) in colorectal cancer (CRC) are rare, developing in only 0.3-9% of the patients, and considered a late-stage manifestation of the disease. The aim of this study was to investigate whether genetic variants of genes involved in BM-related pathways, such as integrin, invasion- and adhesion-mediating, angiogenic and tumor suppressing pathways, are associated with outcome. Methods: Genomic DNA was extracted from formalin-fixed paraffin embedded resected BM from 70 patients with histologically proven CRC. Single nucleotide polymorphisms (SNP) in seven genes (CXCR4, MMP9, ST6GALNAC5, ITGAV, ITGB1, ITGB3, KLF4) were analyzed by direct Sanger DNA sequencing and evaluated for association with overall survival (OS) from resection of BM. Only SNPs with an allele frequency of ≥ 10% were analyzed. Results: In univariate analysis, rs17577 (MMP9) and rs4642 (ITGB3) showed a significant difference in OS [(G/G 7.4 months, G/A 5.1 months; HR (95% CI) 1.83 (0.95-3.53), p = 0.0440) and (A/A 9.4 months, A/G 4.8 months, G/G 4.3 months; HR (95% CI) 0.81 (0.44-1.49) and 2.14 (0.98-4.67), p = 0.0354), respectively]. In multivariate analysis adjusted for baseline characteristics [primary tumor site (right colon, left colon, rectal), chemotherapy before BM (yes/no), BM location (supratentorial, infratentorial, both), Karnofsky performance status (&lt;80, 80-100)], rs2236599 (KLF4), and rs10171481 (ITGAV) are significant in OS [(G/G 7.4 months, G/A or A/A 4.8 months; HR (95% CI) 3.19 (1.55-6.53), p = 0.0016) and (A/A 5.7 months, A/G 4.4 months, G/G 15.5 months; HR (95% CI) 0.61 (0.29-1.29) and 0.25 (0.10-0.60), p = 0.0082), respectively]. Conclusions: This study suggests for the first time a prognostic effect of the SNPs involved in the BM pathway. Further analyses are needed to confirm these findings.
Activation of the macrophage-stimulating protein (MSP)-RON axis in malignant pleural mesothelioma.
Authors: D. Easty, S. G. Gray, A. Baird, A. Soltermann, D. Nonaka, D. A. Fennell, I. Opitz, H. I. Pass, L. Mutti, D. M. o'Donnell, K. J. O'Byrne
Journal: Journal of Clinical Oncology (2011)

e17508 Background: Evidence supports a role for macrophage activity in mesothelioma genesis. Malignant pleural mesothelioma (MPM) is resistant to chemotherapy, and receptor tyrosine kinases (RTK) represent novel therapeutic targets. We previously identified macrophage stimulating 1 receptor (MST1R/RON) as frequently activated in MPM. Immunohistochemistry (IHC) studies found high positivity for RON staining was an independent predictor of favourable prognosis (J Clin Oncol 28:15s, 2010 (suppl; abstr 10583). The RON ligand, macrophage stimulating protein (MSP), promotes phagocytosis and terminal differentiation of macrophages. We hypothesized that MSP may play a role in MPM genesis. Methods: We investigated the expression and function of MSP in MPM. IHC was performed for MSP on a TMA array of FFPE samples resected from 352 patients. MSP was immunoprecipated from MPM cell conditioned medium and detected by Western Blot analysis. ELISA was used to study MSP in serum derived from n=20 patients with MPM vs n=20 normal. Expression of RON was analysed on a second set of FFPE samples of MPM. We repeated IHC using antisera specific for full length RON. Results: Immunoprecipitation and western blot analysis detected MSP in conditioned medium from MPM cell lines. The presence of MSP message was confirmed by RT-PCR in MPM cells. On ELISA, sera from patients with MPM contained immunoreactive MSP, although amounts were not significantly different from control patients. IHC was performed on a TMA array of FFPE samples. Ninety three % showed MSP expression as follows: weak (32%), moderate (38%), intense (21%). Full length RON was detected in mesothelioma using specific antisera. Most mesotheliomas (86%) were double positives (RON/MSP), small subpopulations expressed MSP (5%) or RON (6%) alone, and 2% were double negatives. Correlation of the IHC scores with clinico-pathological and outcomes variables is ongoing. Conclusions: RON staining is an independent predictor of favourable prognosis. MSP is frequently expressed in MPM. Co-expression of MSP and RON in MPM cells may indicate an autocrine signalling pathway and paracrine activation of macrophages. The MSP-RON axis may be a novel therapeutic target in mesothelioma.
Parental disclosure of genetic test results to young adults, adolescents and children
Authors: A. R. Bradbury, C. K. Daugherty, S. Auh, F. J. Hlubocky, S. Cummings, M. White, O. I. Olopade
Journal: Journal of Clinical Oncology (2005)

1016 Background: Genetic testing of minors for adult-onset diseases has generally been discouraged. One study reported 53% of parents with a BRCA1/2 mutation discussed test results with their minor children. Thus, despite a restriction on genetic testing in minors, limited evidence suggests many teenagers and children are informed of their genetic risk. Methods: We sought to evaluate the rate of parental disclosure to adult and minor children, under the age of 25, within our Cancer Risk Clinic. BRCA1/2 mutation carriers were interviewed by telephone and asked to recall their experience with, motivations for, and opinions regarding, communication of genetic test results to their children under the age of 25 years old. Open-ended survey responses were coded for descriptive analysis. Results: To date, 42 BRCA1/2 carriers have been interviewed, with 88% of participants women; 93% Caucasian. Median age of probands: 45 years old. Subjects had a total of 91 children; 60% female. The median age of the children at time of testing was 12 years old (30% were between 18 and 25 years old; 31% were 10–17 years old; 39% < 10 years old). 52% (22/42) of parents discussed the hereditary risk of cancer with at least one child, and 48% (20/42) specifically disclosed genetic test Results: In those with children less than 18, 30% (10/33) had discussed test results with their children. Of those who did not disclose, 41% (12/29) reported plans to disclose before, or at the age of 18. Overall, 70% of parents either have disclosed, or plan to disclose prior to, or at, the age of 18. When asked if they felt genetic testing of minors should be permitted, 67% (28/42) responded no, 29% (12/42) were in favor and 5% (2/42) were undecided. Conclusions: A significant number of BRCA mutation carriers have communicated, or plan to communicate, their genetic test results to their children prior to the recommended age of genetic testing. Despite this, most mutation carriers do not agree with direct testing of children. Further research is needed to describe the communication process among BRCA mutation carriers and their children, and the impact of these communications on children and family dynamics. No significant financial relationships to disclose.
Comparison of adding cetuximab (Cmab) or panitumumab (Pmab) to irinotecan (IRI)-based chemotherapy in salvage line against <i>KRAS</i> wild-type patients with metastatic colorectal cancer (mCRC): Analysis of HGCSG0901 and 1002.
Authors: Koshi Fujikawa, Satoshi Yuki, Takahide Sasaki, Yasuo Takahashi, Ichiro Iwanaga, Minoru Uebayashi, Soh Saitoh, Masahiko Koike, Michio Nakamura, Yasushi Sato, Mineo Kudo, Miki Tateyama, Yasuyuki Kawamoto, Hiroyuki Hisai, Mayuko Saito, Manabu Onodera, Tomofumi Takagi, Yuh Sakata, Yoshito Komatsu
Journal: Journal of Clinical Oncology (2014)

598 Background: Cmab and Pmab have antitumor activity and acceptable safety profiles in patients (pts) with mCRC. Although IRI-based chemotherapy combined with Cmab or Pmab has demonstrated the effectiveness in salvage-line, there has been no reported trials comparing these antibodies directly. Methods: Data of 96 pts with mCRC treated by Cmab plus IRI-based chemotherapy (Cmab/IRI) from HGCSG 0901 and 27 pts treated by Pmab plus IRI-based chemotherapy (Pmab/IRI) from HGCSG1002 were retrospectively analyzed. All patients with KRAS wild type were refractory to or intolerant for 5-FU/ irinotecan/ oxaliplatin and also were never administered anti-EGFR-antibodies. Survival analyses were performed with Kaplan-Meier method, log-rank test and Cox proportional hazards model. Results: Patient characteristics were as below (Cmab/IRI vs. Pmab/IRI); male/female 58/38 vs. 16/11, median age (range) 63(38-80) vs. 64(49-81), PS 0/1/2 52/35/9 vs. 21/6/0, number of metastatic organs 1/2/3- 29/37/30 vs. 6/12/7, prior bevacizumab administration 62.5% vs. 92.6% (p = 0.002). MST was 9.9 months in the Cmab/IRI and 14.9 months in the Pmab/IRI (p = 0.196). PFS was 4.8 months in the Cmab/IRI, as compared with 5.4 months in the Pmab (p = 0.083); the corresponding RR was 25.0 % and 18.5% (p = 0.611). After adjusting other prognostic factors with Cox proportional hazard model, the administration of Cmab/Pmab made significant difference neither for OS (HR 0.908, 95% CI 0.513-1.610, p = 0.742), nor PFS (HR 0.732, 95% CI 0.447-1.199, p = 0.732). Conclusions: In this integration analysis of two studies, there were no significant difference in efficacy between Cmab and Pmab with IRI-based chemotherapy in the salvage-line treatment of pts with mCRC.