tbuckley/cabot-search huggingface dataset:
Wilms tumor outcome and biology in adolescent and young adult patients at Ann and Robert H. Lurie Children's Hospital of Chicago.
Authors: Christine Higham, Yasmin C. Gosiengfiao, David Otto Walterhouse, Elaine Morgan, Jennifer Reichek, Elizabeth Jones Perlman, Jill Woodman
Journal: Journal of Clinical Oncology (2014)

e21016 Background: While Wilms tumor is the most common primary renal malignancy in children, it is rare in adults. Historically, adults with Wilms tumor have had inferior outcomes compared with pediatric patients. Recent studies suggest that adult Wilms tumor patients when treated on a pediatric protocol fare better than patients who were not treated on a pediatric protocol (5 year event-free survival (EFS): 77% and 24%, respectively). The purpose of this study was to determine outcome of adolescent and young adult (AYA) Wilms tumor patients treated at Lurie Children’s and to identify factors, which may affect outcome. Methods: We performed a retrospective chart review of patients ≥10 years old who were diagnosed with and completed therapy for Wilms tumor at Lurie Children’s from 1994-2011. Results: Nine patients aged 10-26 years were identified. Stage distribution was: 1 stage I, 3 stage II, 1 stage III and 4 stage IV. Only 1 patient had unfavorable histology. EFS was 11%, and overall survival was 44% (median follow-up of 40 months). Median time to relapse was 16 months. Second complete response rate was 43%. The median time from presentation to treatment was 13 days with 3 of the 5 deceased patients having 26 or more days from presentation to treatment. All patients who relapsed > 16 months from diagnosis are alive (n=3) while those patients who relapsed prior to 16 months are deceased (n=4). Only one patient had significant delay in treatment due to toxicity. Available tumors were tested for loss of heterozygozity (1p loss (n=0) , 16 loss (n=1), and 1q gain (n=2)).The patient with 16 loss and 1q gain is alive without relapse (67 month follow up). The patient with 1q gain died from disease progression. Conclusions: The outcome for our cohort of AYA patients with Wilms tumor is worse than expected for patients treated with pediatric protocols. Tumor biology does not appear to explain the poorer outcome. Delay in initial referral and start of treatment may contribute to the inferior outcome.
Characterization of Autoantibodies to PF4/Heparin in a Rat Model of Cardiopulmonary Bypass.
Authors: Gowthami M. Arepally, H. Mayumi Homi, Fellery De Lange, Emily K.E. McCracken, Tina M. Goss, Shayela Suvarna, Hilary P. Grocott
Journal: Blood (2004)
VA and Medicare dual health care system use: Impacts on 3-year event-free survival for colon cancer.
Authors: E. Tarlov, T. Lee, T. Weichle, Q. Zhang, R. Durazo, R. A. Perrin, D. J. Bentrem, D. M. Hynes
Journal: Journal of Clinical Oncology (2011)

e16615 Background: We compared 3-year event-free survival of veterans with colon cancer who used Department of Veterans Affairs (VA) and Medicare healthcare to those who used VA only. Methods: We identified veterans diagnosed with stage I, II, or III colon cancer between 1999 and 2001 in VA central tumor registry and 8 regional NCI SEER registry records. Inclusion criteria included age 66 or older and Medicare fee-for-service enrollment. We searched VA utilization and Medicare claims data for healthcare events signaling cancer relapse or progression, defined separately for each stage. Using extended Cox models, we evaluated relationships between VA-Medicare dual use and relapse/progression events. Results: We identified 1,007, 1,169, and 898 patients diagnosed with stage I, II, and III colon cancer, respectively. Of those, 20%, 15%, and 11% received colon cancer care in both VA and non-VA settings. At 36 months, event-free survival rates were 84% (stage I), 53% (stage II), and 36% (stage III). Among stage I patients, dual users were twice as likely as non-dual users to experience a relapse/progression event (adjusted HR 2.01, CI95%: 1.40-2.88). African American race and distance to a VA outpatient facility greater than 4.6 miles were also associated with higher odds of a relapse/progression event. Among stage II and III patients, dual use was not associated with relapse/progression (adjusted HR 1.22, CI95%: 0.96-1.56 and HR 1.22 CI95%: 0.94-1.58, respectively). For stage II patients, older age, being unmarried, having a greater comorbidity burden, and higher tumor grade were associated with higher odds of a relapse/progression event. For stage III, patients who were older, had a greater comorbidity burden, higher tumor grade, or no adjuvant chemotherapy had higher odds of an event. Conclusions: Among VA- and Medicare-eligible veterans with stage I colon cancer, dual system healthcare use was associated with increased likelihood of a clinical event suggesting cancer relapse or progression within 3 years. Understanding the specific processes by which dual use leads to cancer relapse deserve further study.
Alemtuzumab Treatment for Aplastic Anemia (AA) and Low-Risk Myelodysplastic Syndrome (MDS): Preliminary Results.
Authors: Je-Hwan Lee, Seong-Jun Choi, Jung-Hee Lee, Miee Seol, Young-Shin Lee, Soo-Kyung Sim, Seong-Gil Ryu, Young-Ah Kang, Kyoo-Hyung Lee
Journal: Blood (2007)
A randomized prospective phase-III study comparing the acute oral mucositis of morning vs. afternoon radiotherapy (RT) in patients (pts) with squamous cell carcinoma of the head and neck (SCCHN): NCIC-CTG HN.3
Authors: G. A. Bjarnason, R. Mackenzie, I. Hodson, A. Nabid, L. J. Grimard, R. C. Jordan, S. M. El-Sayed, J. H. Hay, D. Tu, W. R. Parulekar
Journal: Journal of Clinical Oncology (2005)

LBA5500 Background: Acute oral mucositis is a dose limiting toxicity in SCCHN pts receiving RT. This study was based on the demonstration of a circadian rhythm in human oral mucosa proliferation with the majority of cells in G1-phase in the morning, S-phase in early afternoon, G2-phase in late afternoon and M-phase at night (Am J Pathol 154:613) with an associated rhythm in clock-gene expression (Am J Pathol 158:1793). Clock-genes control the circadian rhythm in cell proliferation (Cell 111:41, Science 302:255). Since cells in G1 are more radioresistant than cells in G2/M, it was hypothesized that morning RT might lead to less acute mucositis. Methods: A randomized prospective multi-centre phase-III study comparing morning (8–10 AM) vs. afternoon (4–6 PM) RT was completed. Pts with SCCHN receiving radical or postoperative RT encompassing a visible area of oral and/or oropharyngeal mucosa were eligible. Pts were stratified by RT dose (50 Gy/25 fractions (fr) vs. 60 Gy/30 fr vs. 60 Gy/25 fr vs. 66 Gy/33 fr vs. 70 Gy 35 fr), smoking status during RT and centre. Oral mucositis was scored using RTOG criteria and a validated scoring system (Cancer 85:2103). Standardized supportive care for mucositis was allowed. The primary endpoint was the incidence of RTOG grade 3/4 oral mucositis. In order to detect a 50% relative reduction in grade 3/4 mucositis from 35% with afternoon RT to 17.5% with morning RT with a two sided 0.05 significance level and 80% power, a total of 216 pts would be required (assuming a 5% drop out rate). Results: 216 pts were randomized between November-17–1999 and October-18–2004. The current median follow-up is 24 months. Data are being cleaned and the final analysis will be done in March 2005. Data from the primary endpoint and secondary endpoints (time to and duration of grade 2–4 mucositis, treatment delays, quality of life, weight changes, late toxicity, loco-regional control and survival) will be presented. The incidence of mucositis between the two arms will be compared using a Cochran Mantel Haenszel test, a Fishers exact test and a logistic regression model. Conclusions: To be reached after data become available. No significant financial relationships to disclose.
Genes regulating estradiol and estrone-conjugate levels in postmenopausal women with resected early-stage breast cancer detected by a genome-wide association study (GWAS).
Authors: J. N. Ingle, B. L. Fridley, A. Buzdar, M. E. Robson, M. Kubo, M. Liu, I. Ibrahim-Zada, A. Batzler, G. D. Jenkins, M. P. Goetz, D. W. Northfelt, E. A. Perez, C. V. Williard, L. Wang, D. J. Schaid, Y. Nakamura, R. M. Weinshilboum
Journal: Journal of Clinical Oncology (2011)

1001 Background: There is large inter-individual variation in baseline estrone (E1), estradiol (E2), E1-conjugate (E1-C), androstenedione (A), and testosterone (T) levels in postmenopausal women with resected early stage breast cancer (Ingle et al., Ca Res 70:3278−86, 2010). We hypothesized that genetic variation can explain some of this variation in baseline (before anastrozole) hormone levels and performed a GWAS. Methods: Baseline plasma was obtained for E1, E2, E1-C, A, and T assays by GC-MS-MS. Genotypes were determined with the Illumina Human610-Quad BeadChip. Eigenstrat analyses were performed to control for population stratification (PS). Analysis of each baseline hormone level was assessed with each genotype using a quasi-likelihood model because of the skewness in baseline hormone levels, with adjustment for PS as well as body mass index, age and any additional clinical variables associated with baseline hormone levels (p<0.01). SNPs were imputed within 200 Kb on either side of regions containing SNPs with p < 3E-05 using HapMap. Results: 563,945 SNPs were used in the analyses. SNP genotypes were modeled in terms of the number of minor alleles (0, 1 or 2), with SNPs achieving genome-wide significance after Bonferroni correction (p<5E-08) identified for both E2 and E1-C. For E2 (n=757 patients), the genotyped SNP (rs1864729) with the lowest p-value (p=1.13E-08) was on chromosome (chr) 8 and had a multiplicative effect (ME: estimated fold change per minor allele) of 1.62 (95% CI: 1.38, 1.91), with the closest gene being TSPYL5 (Testis-specific Y-encoded-like protein 5), which we showed to be regulated by E2. There were 8 imputed SNPs near rs1864729 with lower p-values (1.03E-08-3.85E-09). For E1-C (n=752 patients), one nonsynonymous SNP (rs4149056) on chr 12 in the SLCO1B1 gene (which encodes an E1-C transporter) was significant (p=5E-08) with ME 1.41 (95% CI: 1.25, 1.60). Conclusions: This GWAS revealed novel loci associated with the baseline levels of E2 and E1-C in postmenopausal women that may be of importance for understanding the estrogen physiology of postmenopausal women and their response to aromatase inhibitor therapy.
Phase Ib trial of ALT-803, an IL-15 superagonist, plus Bacillus Calmette Guerin (BCG) for the treatment of patients with BCG-naïve non-muscle-invasive bladder cancer (NMIBC).
Authors: Charles Joel Rosser, Jeffrey Nix, Liza Hernandez, Peter R. Rhode, Hing C. Wong
Journal: Journal of Clinical Oncology (2016)

470 Background: Novel agents are necessary to treat NMIBC to avoid recurrence and progression. This phase Ib clinical trial evaluated the safety and toleraibility of ALT-803, an IL-15 superagonist, plus BCG in patients with BCG-naïve NMIBC. Methods: This is a Phase Ib trial using the 3+3 design to evaluate intravesical ALT-803 plus BCG 50 mg in BCG-naïve NMIBC patients, who would normally be eligible for intravesical BCG alone. The initial dose of ALT-803 was 100 μg/instillation with 2 dose-escalations allowed (200 μg/instillation and 400 μg/instillation) if dose limiting toxicities (DLTs) were not evident. Patients received intravesical ALT-803 in conjunction with BCG weekly for 6 consecutive weeks (Induction Phase). Patients then had routine follow-up with cystoscopy and voided urinary cytology (VUC) every 3 months for 2 years equating to confirmatory response assessment. Negative cystoscopy, VUC and/or biopsy yielded a complete response (CR). When appropriate for high-risk patients, physicians and patients were encouraged to receive maintenance BCG alone as per common practice patterns. Results: No patient in 100 μg/instillation of ALT-803/BCG and 200 μg/instillation of ALT-803/BCG reported an AE. One patient in 400 μg/instillation/BCG cohort developed a urinary tract infection requiring delay of intravesical treatment by 1 week. No grade 3/4 toxicities were noted. All patients have completed therapy without DLTs. To date, 4 patients have 12 month follow-up and are CR. The remaining 5 patients have no evidence of disease. However, follow-ups are currently approximately 3 months. Corollary immune studies are still pending. Conclusions: Intravesical ALT-803 plus BCG was safe and tolerable in patients with BCG-naive NMIBC. Further evaluation in expansion cohorts in a phase II trial is currently underway. Clinical trial information: NCT02138734.
Differences in Clinical and Molecular Characteristics and Outcome in Prefibrotic and Overt Primary Myelofibrosis According to 2016 WHO Criteria. a Study on 639 Patients of the Agimm Group
Authors: Paola Guglielmelli, Giada Rotunno, Annalisa Pacilli, Elisa Rumi, Vittorio Rosti, Federica Delaini, Margherita Maffioli, Tiziana Fanelli, Alessandro Pancrazzi, Lisa Pieri, Daniela Pietra, Silvia Salmoiraghi, Carmela Mannarelli, Francesco Passamonti, Alessandro Rambaldi, Giovanni Barosi, Tiziano Barbui, Mario Cazzola, Alessandro M. Vannucchi
Journal: Blood (2016)
Murine Model of Fetal and Neonatal Alloimmune Thrombocytopenia Mediated by Anti-GPIb α Versus Anti-β3 Integrin Antibodies.
Authors: Siavash Piran, Pingguo Chen, Guangheng Zhu, Hong Yang, Michelle Webster, Jerry Ware, Zaverio M. Ruggeri, John Freedman, Heyu Ni
Journal: Blood (2006)
Safety, pharmacology, and preliminary clinical activity of MM-151: An oligocolnal anti-EGFR theraputic in patients with cetuximab-resistant CRC and other refractory solid tumors.
Authors: Christopher Hanyoung Lieu, Muralidhar Beeram, Wael A. Harb, Jeffrey D. Kearns, Callum Mortimer Sloss, Rachel Nering, Alex A. Adjei, Beni B. Wolf
Journal: Journal of Clinical Oncology (2015)

647 Background: MM-151 is an oligoclonal anti-EGFR antibody combination designed to provide enhanced targeting of the EGFR network. This work describes the first in human experience of MM-151 alone and in combination with irinotecan. Methods: A standard 3+3 design was used to assess safety and tolerability of MM-151 monotherapy (QW, Q2W, Q3W) and MM-151 (QW) in combination with irinotecan 180mg/m2 (Q2W). A monotherapy expansion cohort has begun in cetuximab-resistant CRC. Results: Results presented are based on preliminary data as of September 2, 2014, for MM-151 monotherapy (n=65; QW/Q2W) and MM-151 in combination with irinotecan (n=10). The most common tumor types were CRC (29 [39%]), NSCLC (9 [12%]), HNSCC (8 [11%]). The monotherapy RP2D has been defined as 10.5 mg/kg QW and dosing continues at 18 mg/kg Q2W. Most adverse events were CTCAE grades 1 and 2. The most common AEs were toxicities related to the EGFR-pathway, including rash (70%), hypomagnesemia (24%), fatigue, dry skin, and diarrhea (21%). IRR was initially observed at high frequencies; however, standardized pre-medication and a modified infusion schedule significantly decreased this frequency. At doses &gt;9 mg/kg QW, trough total antibody levels at steady state were in the expected therapeutic range. Of the CRC patients enrolled, 3 experienced Partial Responses (PRs) per RECIST criteria and a total of 8 (31%) pts had SD for &gt;4 months. Initial biomarker data suggests particular clinical activity in triple-wildtype, EGFR-ligand positive CRC patients. Combination therapy with irinotecan continues with MM-151 at 9 mg/kg QW and 3 PRs have been observed (CRC, HNSCC, melanoma). Initial safety data is consistent with known toxicities of MM-151 and irinotecan. Preliminary results from the monotherapy expansion cohort (10.5 mg/kg QW) in CTX-refractory CRC will also be presented. Conclusions: These results demonstrate that MM-151 monotherapy has an acceptable tolerability profile and objective clinical activity alone and in combination with irinotecan. Results also support further clinical evaluation in triple-wildtype, EGFR-ligand positive CRC and other EGFR dependent cancers. Clinical trial information: NCT01520389.
Gleason &lt;6 (G6) prostate cancer (PC) at radical prostatectomy (RP): Does a high-risk setting truly exist? A recursive partitioning analysis (RPA).
Authors: Mark C Smith, James Kyle Russo, Chad Tracy, Darrion Mitchell, Sarah Mott, John Michael Buatti, John Morgan Watkins
Journal: Journal of Clinical Oncology (2016)

132 Background: G6PC is associated with low rates of PSA failure (bF) after primary treatment. The present study seeks to determine whether a "high-risk" subpopulation of G6PC with lower PSA relapse-free survival (bRFS) may be identified within a large population of men with mature follow-up who underwent RP for curative-intent. Methods: Patients were retrospectively identified for inclusion by cT1-2 PC with PSA &lt;30 at diagnosis, managed by RP alone, with final pathology demonstrating G6PC. Exclusion criteria were: pT3b or pN1, pre- or post-RP (adjuvant) radiotherapy (RT) or hormone therapy, or PSA follow-up (&lt;12 months). The Kaplan-Meier method was employed for survival probability estimation. RPA by conditional inference analysis was applied to identify variables associated with bF. Results: From 2003-2009, 284 patients were eligible for this analysis. The median age was 60 yrs (range, 44-76), 233 (82%) were T1c, and median PSA was 5.3 (92% &lt;10 ng/dL). The median biopsy to RP interval was 50 days (11-410, with 97% &lt;180 days). Eighty patients (28%) had a positive margin (M+). At a median follow-up of 92.6 months (16.9-160.9, with 45% followed &gt;8 years), 32 patients (11%) had bF, with estimated 5/8yr bRFS rates of 91%/89%. Univariate analysis identified M+, EPE, detectable initial post-RP PSA (at &lt;26wks post-RP), longer biopsy to RP interval, and smaller RP specimen volume as significantly associated with bF, with M+ and longer biopsy to RP interval significant at multivariate analysis. RPA identified only M+ as a stratification factor, with 5/8yr bRFS estimates of 79/74% for M+ vs. 96/95% for M-. No other factors permitted further substratification of risk. Of note, 7 of 12 patients who underwent salvage RT alone remained disease-free at last follow-up, including 7 of 8 whose highest pre-salvage RT PSA was &lt;0.6. Conclusions: G6PC managed by RP alone is generally associated with high rates of bRFS; however, in the M+ setting, irrespective of other clinical factors, early bF rates &gt;20% are observed. Adjuvant RT should be considered in G6PC M+ cases; however, close surveillance with early salvage RT may be a reasonable alternative.
Effect of protons on bone marrow and small-bowel exposure for patients receiving neoadjuvant radiotherapy for resectable rectal cancer.
Authors: Romaine Charles Nichols, Soon N. Huh, Nataliya Getman, Meng Wei Ho, Zuofeng Li, Ziad Awad, Robert Anthony Zaiden, Nancy Price Mendenhall, William M. Mendenhall, Bradford S. Hoppe
Journal: Journal of Clinical Oncology (2012)

669 Background: Determine the potential role for protons in the preoperative treatment of resectable rectal cancer. Methods: Eight consecutive patients with resectable (T2-T3) rectal cancers underwent 3D conformal photon (3DCRT); intensity-modulated photon (IMRT); and 3D conformal proton (PT) treatment planning. Initial target volumes (PTV1) were contoured using the RTOG anorectal atlas guidelines. Boost target volumes (PTV2) consisted of the gross rectal tumor plus a uniform 2cm expansion. Plans delivered 45Gray (Gy) or Cobalt Gray Equivalent (CGE) to the PTV1 and a 5.4 Gy (CGE) boost to the PTV2. Ninety-five percent of PTVs received 100% of the target dose and 100% of the PTVs received 95% of the target dose. Standard normal tissue constraints were utilized. Wilcoxon paired t-tests were performed to compare various dosimetric points between the 3 plans for each patient. Results: All plans met all normal-tissue constraints and were isoeffective in terms of PTV coverage. Proton plans offered significantly reduced median normal-tissue exposure over the 3DCRT and IMRT plans with respect to: pelvic bone marrow (PBM) at the V5Gy, V10Gy, V15Gy and V20Gy levels and small bowel (SB) at the V10Gy and V20Gy levels. Proton plans also offered significantly reduced median normal-tissue exposure over the 3DCRT plans with respect to the SB at the V30Gy and V40Gy levels. Conclusions: 1.) By reducing bone marrow exposure, protons may reduce the acute hematologic toxicity of neoadjuvant chemoradiation and increase the likelihood of uninterrupted chemotherapy delivery. Bone marrow sparing may also facilitate the delivery of salvage chemotherapy for patients who go on to develop hematogenous metastasis. 2.) By reducing small bowel exposure, protons may reduce toxicity and possibly facilitate the use of more aggressive concomitant chemotherapy with radiotherapy. [Table: see text]
Glutaredoxin 2 and oxidative stress identification of two testis/cancer specific isoforms of human Grx2 in neuro-and medulloblastomas.
Authors: Christoph Hudemann, Maria Lonn, Baldur Sveinbjornsson, John Johnsen, Per Kogner, Arne Holmgren, Christopher Lillig
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

LB-266 

Oxidative stress constitutes a constant threat to the integrity of proteins, lipids, and DNA. Once repair- and turnover processes fail to remove oxidative damage, crucial cellular processes like apoptosis or growth are being disturbed and can lead to cancer etc. Protein thiols in form of cysteine residues are key players in redox sensing and regulation. The thioredoxin family of proteins consists, among others, of Trxs (thioredoxins) and Grxs (glutaredoxins). Those small (9-16 kDa) glutathione dependent thiol-disulphide oxidoreductases share a dicysteine active site motif (Cys-X-X-Cys) in a common structure called the Trx-fold enabling them to specifically reduce oxidized proteins. So far 3 different human Grxs have been identified in human, the well characterized cytosolic hGrx1, the mainly mitochondrial hGrx2 and the monothiol hGrx5. We have shown that transient knock down of hGrx2 sensitizes HeLa cells towards cell death induced by doxorubicin and phenyl arsene oxide, two commonly used anti-cancer compounds. Immunohistochemistry on patient samples revealed an highly elevated expression of hGrx2 in neuro- and medullablastomas. We identified 3 transcript variants of hGrx2. The mitochondrial hGrx2a is ubiquitously expressed, emphasizing the general importance for mitochondrial redox homeostasis. The new cytosolic variant hGrx2c and the cytosolic / nuclear hGrx2b are expressed exclusively in testis and various cancer cell lines. Our data presents the first indications for hGrx2 outside the mitochondria. Furthermore, in vitro data revealed that hGrx2a and hGrx2c form an inactive holo-dimer coordinated by a GSH-mixed 2-Iron-2-Sulfur cluster. During oxidative stress conditions, the GSSG/GSH ratio increases, the dimer gets disassembled and hGrx2a/c get activated. This 2Fe/2S cluster therefore represents a GSH-dependent redox sensor at the crossroad between cell death and survival. hGrx2b is unable to form a holo-complex, in contrary to previous results we found that this testis/cancer specific isoform is present in both the cytosol and the nucleus. Our results provide evidence for the presence of three hGrx2 protein isoforms in vivo and suggest additional roles of this oxidative stress-induced and apoptosis inhibiting protein in cellular differentiation and tumor progression.