tbuckley/cabot-search huggingface dataset:
Preoperative staging of oral cavity carcinoma with FDG-PET/CT
Authors: S. Maddipatla, R. A. Madero-Visbal, T. Graves, R. Franklin, J. Savell, R. Lovas, R. Manon, J. F. Tseng, D. Schwartz, T. D. Shellenberger
Journal: Journal of Clinical Oncology (2008)

6044 Background: Since the status of the regional lymph node basin at risk for spread is the most important prognostic factor for oral cavity carcinoma (OCC), accurate staging is critical to the optimal selection of treatment. The majority of patients with OCC undergo pathologic staging due to the inability of computed tomography (CT), magnetic resonance imaging (MRI), and ultrasonography to detect subclinical disease. However, more than half of patients without clinical evidence of disease who undergo neck dissection are found without evidence of microscopic disease and may incur unnecessary morbidity. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a functional imaging technique that may be superior to conventional imaging. We sought to correlate preoperative CT combined with FDG-PET with pathologic findings at neck dissection. Methods: In this prospective study, 20 patients with previously untreated squamous cell carcinoma of the oral cavity underwent contrast- enhanced CT of the head and neck combined with FDG- PET. Lymph nodes in each neck level were assessed for tracer uptake and quantified by standard uptake values (SUV). All patients underwent surgery including resection of the primary tumor and neck dissection of the regional nodes at risk. Neck dissection specimens were patholgically evaluated by serial step sections at 200 micron intervals of nodes from each level. Results: Among 20 patients, 552 lymph nodes were evaluated from 60 neck levels. 521 lymph nodes from 49 neck levels were found PET negative (SUV < 3.0). On pathologic evaluation, 505 PET/CT-negative lymph nodes were found without microscopic disease. The negative predictive value for PET/CT was 97% and the likelihood ratio for a negative PET/CT was 0.94 (95% CI 0.72 to 1.05). Conclusion: Preoperative PET/CT provided high specificity in the preoperative staging of the neck prior to treatment of OCC. A negative PET/CT scan may obviate the need for pathologic staging by neck dissection in selected patients with oral cavity carcinoma. No significant financial relationships to disclose.
The University of Chicago experience with a reduced intensity allogeneic peripheral blood stem cell transplant preparative regimen using fludarabine, cyclophosphamide, and antithymocyte globulin (ATG) in pts with a hematologic malignancy
Authors: D. A. Levitan, H. Harlin, S. M. Smith, K. Van Besien, R. A. Larson, T. F. Gajewski, T. M. Zimmerman
Journal: Journal of Clinical Oncology (2004)

6626 Background: Non-myeloablative preparative regimens have been used extensively in alloSCT. We hypothesized that a novel preparative regimen, fludarabine, cyclophosphamide, ATG, could result in hematopoetic engraftment, disease control, and low toxicity. Methods: Patients (pts) received fludarabine 30 mg/m2/d on d –9, -8, -7, -6, -5, cyclophosphamide 2gm/m2/d on day –5, and ATG 10 mg/m2/d on day –5, -4, -3, -2. Stem cells were from full HLA matched sibling donors. GVHD prophylaxis included tacrolimus 0.03 mg/kg/d starting day -4, to reach a level of 5–15ng/ml, and tapered to discontinue by day +90. Mycophenylate mofetil 1mg PO bid was started on day +1 and continued until day +60. T cell subsets were analyzed by flow cytometry, Results: 17 pts were treated on this study from June 1999 to October 2001. (3 AML, 1 MDS, 5NHL, 3 HD, 2MM, 2CLL/SLL, 1CMML) Median age was 60 yrs, (24–67). Pts had a median of 3 prior chemo regimens (0–5), including 5 with a prior autoSCT. Median ECOG PS was 1 (0–1). Median hospitalization was 21d (15–77). Median days to ANC>500 was 14 (0–21) and median days to plt>100 was 13 (0- not reached). Two deaths occurred prior to d100, both due to sepsis (d23, d61). No pt had acute GVHD. 3/17 pts had extensive chronic GVHD (2 liver, 1colon) Median donor chimerism at d30 was 67.5%, at d100 was 75%. Best response: CR 8pts, PR 2pts, SD 3 pts, PD 3pts. One pt died at d21 with RD. Median PFS of pts with SD, PR, or CR was 5.13 mos (2.6 –50+). Three pts had DLI after PD. (1 HD pt had no GVHD, but had PD; 1 NHL pt had grIV gut GVHD, died of sepsis d39 w/RD; 1MM pt had grIII liver GVHD, achieved a CR lasting 2 yrs) Data from T-cell subset analysis is available on 7 / 17 pts. At d33, pts with a CR or PR had more IL2-producingCD8+ (12.02 vs 3.20, p=0.0034), CD4+ (126.64 vs. 38.92, p=0.0294), and CD3+ (138.66 vs 42.11, p=0.02) T cells/μL.Conclusions: This regimen was well tolerated by this older group of heavily pretreated pts, but median donor chimerism was only 75% at d100. The numbers of T cells producing Th1 cytokines at d33 was higher in pts with a good clinical response. No significant financial relationships to disclose.
Abstract 15771: Impact of Contact Force Visualization During Left Atrial Mapping
Authors: Hisaki Makimoto, Tina Lin, Andreas Rillig, Andreas Metzner, Erik Wissner, Shibu Mathew, Sebastian Deiss, Peter Rausch, Masashi Kamioka, Alexander Bardyszewski, Christine Lemes, Karl-Heinz Kuck, Feifan Ouyang, Roland R Tilz
Journal: Circulation (2013)
Correlation of RASGRP1:APTX expression assay with response to tipifarnib plus etoposide in elderly patients with newly diagnosed AML.
Authors: T. I. Vener, C. Derecho, S. Galkin, J. Greer, M. J. Levis, C. D. Gocke, S. Malek, J. F. Palma, M. Raponi, Y. Wang, J. J. Wright, J. E. Karp
Journal: Journal of Clinical Oncology (2011)

6534 Background: A two-gene ratio (RASGRP1:APTX) has previously been shown to be associated with response to the single agent farnesyltransferase inhibitor (FTI), tipifarnib, in patients with both newly diagnosed or relapsed and refractory acute myeloid leukemia (AML) (Raponi et al. Blood 2008, 111:2589). Here we demonstrated the utility of the 2-gene ratio to correlate with response to the combination therapy with tipifarnib and etoposide in an independent patient cohort of elderly patients with newly diagnosed AML from a Phase 2 study (Karp et al. Blood 2009, 113:4841). Methods: Taqman-based quantitative RT-PCR assays were designed and optimized in RUO and GMP formats for two tipifarnib-specific markers RASGRP1 and APTX, and an internal control marker HMBS, and successfully performed on pretreatment bone marrow aspirates of 32 patients evaluable for response. Results: A receiver operator characteristic analysis indicated a high correlation between both RT-PCR formats (Pearson R2 range for 3 markers, 0.97 to 1) with AUC = 0.83 (p=0.0009) when using complete remission (CR) as best response criteria. Based on the ROC curve analysis algorithm the 2-gene ratio cutoff of 5.1 was determined for the RUO RT-PCR protocol and 5.2 - for the GMP format with JY RNA as an external normalization control. Further improvements of the GMP assay resulted in a single-tube multiplexed RT-PCR format which was tested in the extended patient group (n=40). When using a cutoff of 5.2 the overall response rate increased from 28% to 78% with a negative predictive value of 87%. Kaplan Meier survival curve analysis of patients stratified using a ratio cutoff of 5.2 indicated a positive correlation in favor of utility of the 2-gene ratio assay (CR vs. NR with p = 0.023 and HR= 0.34). In addition, there was no association between the 2-gene ratio and clinical response or overall survival in a set of 41 newly diagnosed AML patients treated with two traditional chemotherapeutic regimens (AcDVP16 and FLAM). Conclusions: These data demonstrate that the RASGRP1:APTX qPCR assay correlates with response to tipifarnib in elderly newly diagnosed AML, and that the assay is specific for predicting response to tipifarnib.
ASET study: Long-term follow-up data of patients with metastatic renal cell carcinoma treated with MGN1601.
Authors: Viktor Gruenwald, Steffen Weikert, Ingo G. H. Schmidt-Wolf, Stefan Hauser, Ahmed Magheli, Matthias Schroff, Manuel Schmidt, Burghardt Wittig
Journal: Journal of Clinical Oncology (2014)

LBA399 Background: The cell-based therapeutic cancer vaccine MGN1601 is a fixed combination of allogeneic tumor cells modified via MIDGE vectors to express IL-7, GM-CSF, CD80, and CD154 plus the immunomodulator dSLIM. In the ASET trial heavily pretreated patients with metastatic renal cell carcinoma (mRCC) were enrolled to assess safety, immunological effects, and clinical efficacy of MGN1601. Methods: The ASET study was a multicenter, single-arm phase 1/2 study. The treatment phase consisted of 8 intradermal vaccinations over 12 weeks. Following evaluation, patients with at least disease stabilization entered an extension phase (EP, 5 vaccinations over 120 weeks). Overall, 19 patients were included and received at least one MGN1601 injection (ITT); the majority (N=17) had ≥3 lines of previous therapy. Results: Of 19 patients, 10 (55%) completed the treatment phase per-protocol (PP); 9 patients discontinued the study due to disease progression (PD) or rapid deterioration. Overall, 110 adverse events were documented (grade 1-2: 80.9%) of which only 10 (9.1%) were drug-related. No drug-related serious adverse event was reported. PBMCs from patients increased cytokine secretion after re-stimulation with standard antigens, confirming an improved cellular immune function. Two patients achieved disease control (PR, SD) after 12 treatment weeks and continued in the extension phase: One patient had PD after 60 weeks, the other remains in sustained partial remission after completion of the EP. Median overall survival (OS) was 24.8 weeks in the ITT population and 115.3 weeks in the PP population. Univariate analysis of pre-treatment characteristics revealed absolute lymphocyte counts, neutrophil to lymphocyte ratios, platelets, MSKCC score, and liver metastasis as putative predictive factors of longer overall survival. Conclusions: MGN1601 administration was safe and showed promising OS in a population of heavily pretreated RCC patients who could receive therapy over 12 weeks (PP population). These results warrant further evaluation in a larger, controlled clinical trial. Baseline biomarkers and factors may allow identifying patients more likely to benefit from this innovative vaccination approach. Clinical trial information: NCT01265368.
Similar outcome of different treatment strategies in patients 16 to 60 years of age with acute myeloid leukemia (AML)
Authors: T. Buchner, H. Dohner, G. Ehninger, A. Ganser, J. Hasford, R. Hehlmann, D. Hoelzer, D. Niederwieser, M. Pfirrmann
Journal: Journal of Clinical Oncology (2008)

7080 Background: In order to compare current treatment strategies, four multicenter trial groups in Germany joined for a prospective, individual patient data based study. Methods: To guarantee comparability all patients before treatment started were randomized by phone call to the shared statistical center, to receive either the trial own treatment (90% patients) or a common standard treatment (10%). The common standard arm uniformly contained two courses of CALGB derived araC 100 mg/m²/dx7 and daunorubicin 60 mg/m2/d×3 and in patients attaining complete remission (CR) 3 courses of high-dose araC (HIDAC) 3 g/m2q12h×6. By their trial own treatment the participating trials addressed own strategies. Thus, HIDAC in induction (trial 1) and early allogeneic stem cell transplantation (SCT) (trial 2) were administered in patients with high-risk features and/or slow response. Randomized comparisons of one versus two induction courses by HIDAC/mitoxantrone, and prolonged maintenance versus autologous SCT were done in trial 3, and HIDAC 1g/m2 q12h × 8 versus 2g/m2/d × 4 in trial 4. These trial own randomizations did not result in significant differences of outcome. Results: The four trial populations and the standard arm will be compared according to intention-to-treat with the event-free survival as primary clinical endpoint. Differences will be tested using a log rank test as well as the probability of EFS at 3 years with 95% CI. The upcoming analyses will be after the end of patient's accrual. The current duration of follow-up is 15 (1–53) months. No significant financial relationships to disclose.
HDR brachytherapy with EBRT in node negative early stage oral cavity cancer
Authors: S. K. Jain, A. Kumar, J. K. Singh
Journal: Journal of Clinical Oncology (2004)

5553 Background: Since inception goal of radiotherapy is to deliver high dose to tumor with maximum sparing of normal tissue with brachytherpy there is rapid fall of dose beyond implanted area, thus delivering high dose to target with sparing of surrounding normal tissue. In early stage node negative oral cavity cancer surgery and radiotherapy produces equal result but radiotherapy is considered superior as it causes less functional and cosmetic deficit. Method: We present 25 patient of oral cavity cancer treated with HDR brachytherapy alone or in combination with external beam radiotherapy (EBRT). Interstitial implant was done using flexible plastic tubing or rigid stainless steel needles under local or general anesthesia. A dose of 45 to 51 Gy in 15 to 17 fractions, 3 Gy per fraction, two fractions per day with a gap of 6hr in-between, was delivered with HDR brachytherpy alone. When combine with EBRT 24 to 30 Gy was delivered with HDR bracytherapy, and 36 to 40 Gy by EBRT. Result: Complete clinical response was noted, in all the patients at six weeks of completion of RT. Two out of twenty five patients have local recurrence and were salvaged by surgery. Nodal failure was observed in two patients and was managed by radical neck dissection. With mean follow-up of fourteen months, all patients are alive disease free. Localize grade III mucositice was observed in all the patients, no grade III and grade IV late complications is seen in any of the patients. Conclusions: HDR brachytherapy is highly effective in early stage oral cavity cancer; it gives excellent functional and cosmetic results in comparison with surgery. However long term follow-up is needed to comment further on these results. No significant financial relationships to disclose.
The quality of oncology education in undergraduate and postgraduate training programs
Authors: P. N. Fishman, W. Y. Cheung, J. Chung, S. Vijayaratnam, S. Verma
Journal: Journal of Clinical Oncology (2008)

6617 Background: The proportion of the population living with cancer is expected to continue to increase over the next decade. As a result, there is a need to ensure that current and future healthcare professionals are adequately prepared to manage the anticipated growth in cancer burden. We evaluated the quality of oncology education in Canadian undergraduate and postgraduate training programs. Methods: A self-administered survey was distributed to undergraduate schools (UGS) in medicine, nursing, and pharmacy as well as postgraduate residencies (PGR) in family medicine (FM) and internal medicine (IM) across Canada. Survey questions were designed to assess the programs' oncology content, degree of access to and opportunity for oncology-related rotations, and attitudes towards oncology education. Results: Of the 58 UGS and 26 PGR nationwide, response rates were 58.6% (34/58) for UGS and 69.2% (18/26) for PGR. Among undergraduate respondents, only 38.2% offered formal oncology courses. Cancer-related content constituted <10% of the curriculum and <10% of the final examination in 70.6% and 58.8% of UGS, respectively. For PGR, the majority of programs devoted more time to teaching other medical specialties than oncology: cardiology (89%), respirology (67%), nephrology (67%) and gastroenterology (61%). Mandatory oncology rotations were present in only 4 PGR and less than 10% of IM and FM residents spent clinical time in oncology electives. While most UGS and PGR agree that the oncology content of their programs needs to be increased, few anticipated such changes to occur within the next year. Conclusions: Oncology is under-represented in academic curriculums of current UGS and PGR programs. In order to meet future healthcare needs, strategies are required to help address this educational deficiency. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Oncology
Utility of image-guided peritoneal core biopsy and radiological findings in women with prior breast cancer and a new diagnosis of peritoneal carcinomatosis
Authors: E. Takeuchi, K. E. Anderson, G. D. Hall, T. J. Perren, J. A. Spencer
Journal: Journal of Clinical Oncology (2008)

1113 Background: Peritoneal carcinomatosis (PC) may be associated with various malignancies, including breast cancer. However, optimal treatment varies widely upon its etiology. In women with a past history of breast cancer a tissue diagnosis is important to guide management since many of these women are also at risk from the development of other malignancies which may mimic breast cancer metastatic to the peritoneum. Methods: From a cancer center database, we retrospectively identified women with prior breast cancer who subsequently had a new diagnosis of PC and who went on to have image-guided peritoneal core biopsy (IGPCB). Computed tomography (CT) performed at the time of presentation was reviewed, noting the nature and distribution of disease to identify features predictive of etiology. Results of biopsies were reviewed and compared to the initial breast cancer pathology where possible. Results: 35 women (median age 66 yrs; range 29–87 yrs) presenting with new PC (mean of 11.2 yrs after the original breast cancer diagnosis) were identified. Definitive histologic diagnosis was obtained by IGPCB in 34 (97%) cases. There were no significant complications after the biopsy. 27 (77%) had a new ovarian or primary peritoneal carcinoma, 2 (6%) a new Mullerian carcinosarcoma and only 6 (17%) had recurrent breast cancer of which 4 had lobular histology. A new diagnosis of gynecological cancers tended to be associated with more solid omental cakes and cystic solid ovarian masses, whereas in those with metastatic breast cancer the peritoneal infiltrate was more wispy. However, there was overlap and CT features alone could not be relied on to predict the final histologic diagnosis. Conclusions: A majority of women with prior breast cancer who presented with new PC had a new diagnosis of ovarian or primary peritoneal cancer. CT findings were insufficient to allow accurate prediction of the etiology of PC. Tissue diagnosis is therefore necessary to define management options and IGPCB provides a safe, accurate and rapid minimally invasive method for obtaining this. No significant financial relationships to disclose.
Real-time polymerase chain reaction technique determines absolute copy number of plasma methylated MGMT gene promoter copies in newly diagnosed malignant glioma patients
Authors: K. D. Weaver, L. Pierce, J. G. Herman, S. A. Grossman
Journal: Journal of Clinical Oncology (2008)

22073 Background: New methods for disease surveillance, quantification, and prognosis in malignant glioma are needed. Recent work has demonstrated that malignant gliomas release their DNA into the blood which bears the genetic and epigenetic aberrations in the intracranial lesion. We determined the actual plasma copy number of the methylated chemoresistance gene methylguanine methyltransferase (MGMT) in patients enrolled in clinical trials for malignant glioma as a prelude to biomarker development. Methods: This prospective NABTT CNS Consortium study was designed to determine if tumor specific plasma DNA could serve as an accurate biomarker. Plasma was collected from newly diagnosed high grade glioma patients prior to therapy and with each follow-up MRI. DNA was isolated from plasma of the first 19 patients enrolled and bisulfite treated. Quantitative PCR was performed with methylation-sensitive primers selective for the methylated MGMT promoter. A S. cerevisiae actin gene spike-in quantitative PCR technique was used to control for variations in DNA loss during the process. Resuts: Baseline plasma from 19 patients demonstrated an overall mean of 2.74 × 105 copies/mL (SEM: 7.67 × 104) of the MGMT promoter. The range of tumor specific DNA in these samples was 1.14 × 104 to 1.22 × 106 copies/mL. One of 19 patients demonstrated no detectable MGMT methylation. Conclusions: Tumor DNA in the blood of high grade glioma patients offers a unique platform to develop a biomarker to satisfy the needs of evolving treatments. This provides the possibility to assess tumor burden in a manner distinct from MRI scans which rely heavily on blood-brain barrier status. This study will eventually yield important information on initial tumor specific DNA concentrations in plasma and changes over the course of the patients' illness. No significant financial relationships to disclose.
Human selenium binding protein-1 (hSP56) inhibits anchorage-independent growth of PC-3 human prostate cancer cells and is down-regulated in primary human prostate tumor cells
Authors: A. J. Sytkowski, C. Gao, L. Feldman, C. Chen
Journal: Journal of Clinical Oncology (2005)

9564 Background: Reduced dietary selenium is associated with increased cancer risk, and selenium exhibits a chemopreventive effect for malignancies of several organs, including the prostate. Previously, we reported that the human selenium binding protein-1 gene, hSP56, the human homologue of a rodent protein implicated in chemoresistance, was highly expressed by slowly growing, androgen-sensitive LNCaP human prostate cancer cells but not by the more rapidly growing, androgen-insensitive PC-3 human prostate cancer cells (Cancer Research, 58:3150). Recently, Venkateswaran et al. reported that treatment of LNCaP cells with selenomethionine caused growth inhibition by G1 arrest and a marked reduction in S phase. In contrast, they saw no such effect on PC-3 cells, leading them to propose that hSP56 may mediate selenium’s growth inhibiting properties (Cancer Research, 62:540). We have now examined the effect of hSP56 expression on the anchorage-independent growth of PC-3 cells and have quantified the level of hSP56 expression in primary human prostate tumors. Methods: The ability of cells to grow in an anchorage-independent manner is a hallmark of cellular transformation, and it is an excellent in vitro assay for predicting tumorigenicity in vivo. We stably transfected PC-3 cells with an hSP56 expression vector (PC-3/hSP56 cells) or with vector alone (PC-3/vector cells) and grew them in soft agar. Primary human prostate tumors were studied by immunohistochemistry using an affinity purified highly specific rabbit antibody to hSP56. Results: When grown in soft agar, PC-3/vector cells gave rise to a large number of robust colonies, many of which were quite large. In contrast, PC-3/hSP56 cells gave rise to >10-fold fewer colonies, which were very small in size. Anchorage-dependent growth in flasks was similar for both cell lines. Using immunohistochemistry of primary prostate tumors, we found that hSP56 was expressed at high levels in normal epithelial cells but at far lower or undetectable levels in malignant cells. Conclusions: Our results suggest that reduced expression of hSP56 may play a role in the malignant phenotype of prostate cancer. No significant financial relationships to disclose.