tbuckley/cabot-search huggingface dataset:
Taking control of cancer: Why women are choosing mastectomy.
Authors: Andrea Marie Covelli, Nancy N. Baxter, Margaret Fitch, Frances Catriona Wright
Journal: Journal of Clinical Oncology (2013)

9571 Background: Rates of both unilateral (UM) and bilateral mastectomy (BM) for early stage breast cancer (ESBC) have been increasing since 2003. Studies suggest that this is due to women playing a more active role in their decision making, however they do not describe why women are choosing this option. Methods: We conducted a qualitative study using grounded theory to identify factors influential in women’s choice for mastectomy. Purposive sampling was used to identify women across the Greater Toronto Area (Ontario, Canada), who were suitable candidates for breast conserving surgery (BCS) but underwent UM or BM. Data were collected through semi-structured interviews. Constant comparative analysis identified key ideas and themes. Results: Data saturation was achieved after 29 in-person interviews. 12 interviewees were treated at academic cancer centres, 6 at an academic non-cancer centre and 11 at community centres. 15 women underwent UM; 14 underwent BM. Median age was 55. ‘Taking control of cancer’ was the dominant theme that emerged. There were 7 subthemes: 1.the Diagnosis of cancer was received with shock and fear; 2.during Surgical Discussion both BCS and UM were discussed; BM was discouraged by the surgeon 3.women Misperceived Risk, misunderstanding recurrence and survival rates 4.Women’s choice for UM was due to fear of recurrence and/ or radiation 5.Women’s choice for BM was due to fear of recurrence, ‘never wanting to do this again’ and/or need for cosmetic balance 6.Sources of Information varied in importance, previous cancer experience had the greatest impact 7.women were actively Controlling Outcomes, more surgery was seen as greater control. Conclusions: Women seeking UM and BM for treatment of their early stage breast cancer manage their fear of recurrence and ‘never wanting to go through this again’ by undergoing more extensive surgery. The patient’s effort to control the cancer outcome is the driving factor behind women choosing mastectomy.
A phase II clinical trial of drug withdrawal in women with progressive breast cancer while on aromatase inhibitor therapy.
Authors: T. Cigler, M. J. Higgins, J. Szymonifka, A. H. Partridge, J. A. Ligibel, D. Finkelstein, S. E. Come, P. D. Ryan, P. E. Goss
Journal: Journal of Clinical Oncology (2011)

559 Background: The development of resistance to aromatase inhibitor (AI) therapy is common among women with metastatic hormone-receptor-positive breast cancer (MBC). Such patients are usually switched to second-line endocrine therapy (ET) or chemotherapy upon progression. A withdrawal response (WR) to ET has been reported, usually in association with tamoxifen cessation. Subsequent response to further ET has been documented suggesting that a WR may actually re-sensitize tumor cells to ET. We report the first prospective trial of AI withdrawal in women with progressive breast cancer while on AI therapy. The primary objective was to estimate the clinical benefit rate (CBR) after withdrawal of AI therapy. CBR was defined as proportion of subjects with a complete response (CR), or partial response (PR), or stable disease (SD) for greater than or equal to 6 months. Methods: Women who developed recurrent or progressive MBC while being treated with an AI were enrolled prospectively to a trial and observed off all therapy. Restaging studies were performed at 8, 16, and 24 weeks after AI discontinuation and every 12 weeks thereafter. Women were actively followed until progression of disease after which they were removed from study. The trial was planed to enroll 40 patients in two stages in order to have a 90% power to detect a true clinical benefit rate of 20%. Results: 24 patients were enrolled between Oct 2006 and Dec 2009 at which time the study closed due to slow accrual. No CR or PR was observed. The Kaplan-Meier estimate for CBR at 6 months was 52% [95% CI, 30% to 70%]. The median progression free survival from time of AI withdrawal for all patients is 14 months. One patient has remained progression free over 30 months from time of AI withdrawal. Conclusions: Despite suboptimal patient accrual, we have shown that a significant proportion of patients with MBC progressing on AI therapy can experience prolonged disease stabilization after withdrawal of therapy. This is an inexpensive and non-toxic management option that has the potential to re-sensitize to further ET and prolong time to initiation of chemotherapy. A prospective trial of intermittent AI therapy is also underway.
A 24-Year-Old Man With a Left Frontal Brain Mass
Authors: Adrienne L. Carey, Muhammed U. Khan, N. Cary Engleberg
Journal: JAMA (2017)

A 24-year-old man with 1 week of headache, gait imbalance, coordination difficulties, and personality changes tested positive for HIV, with a CT scan of the brain showing an aggressive solitary lesion extending through the corpus callosum. What would you do next?
Phase I Trial of Belinostat and Bortezomib in Patients with Relapsed or Refractory Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia in Blast Crisis - One Year Update
Authors: Beata Holkova, Prithviraj Bose, Mary Beth Tombes, Ellen Shrader, Wen Wan, Caryn Weir-Wiggins, Elizabeth Stoddert, Heidi Sankala, Maciej Kmieciak, John D. Roberts, Guillermo Garcia-Manero, Steven Grant
Journal: Blood (2012)
312P Elevated serum CA125 predicts recurrence in patients with completely resected ovarian clear cell carcinoma
Authors: T. Ebata, M. Yunokawa, S. Bun, E. Noguchi, A. Shimomura, T. Shimoi, K. Yonemori, C. Shimizu, Y. Fujiwara, T. Kato, K. Tamura
Journal: Annals of Oncology (2016)
Prognostic Significance of Early Treatment Response in Pediatric Relapsed Acute Myeloid Leukemia: Results from the International Study Relapsed AML 2001/01.
Authors: Gertjan J. Kaspers, M. Zimmermann, D. Reinhardt, R. Tamminga, B. Gibson, H. Armendariz, M. Dworzak, S. Ha, L. Hovi, A. Maschan, N. Philippe, B. Razzouk, C. Rizzari, P. Smisek, O. Smith, B. Stark, A. Will, U. Creutzig
Journal: Blood (2007)
Performance assessment of blood based RAS mutation testing: Concordance of results obtained from prospectively collected samples
Authors: M.P. Saunders, C. Cooney, D. Edelstein, S. Mullamitha, M. Braun, S. Moghadam, P. Ronga, F.S. Jones, A. Telaranta-Keerie, R.A. Adams
Journal: Annals of Oncology (2016)
The effect of a reduction in alcohol consumption on blood pressure: a systematic review and meta-analysis
Authors: Michael Roerecke, Janusz Kaczorowski, Sheldon W Tobe, Gerrit Gmel, Omer S M Hasan, Jürgen Rehm
Journal: The Lancet Public Health (2017)

Although it is well established that heavy alcohol consumption increases the risk of hypertension, little is known about the effect of a reduction of alcohol intake on blood pressure. We aimed to assess the effect of a reduction in alcohol consumption on change in blood pressure stratified by initial amount of alcohol consumption and sex in adults.
Long-term benefit (LTB) of sunitinib (SU) treatment for metastatic renal cell carcinoma (mRCC): Retrospective analysis for clinical biomarkers identification.
Authors: Oren Smaletz, Matias Chacon, Ludmila de Oliveira Koch, Daniela Regina de Carvalho Rocha, Fernanda Camila Cardoso
Journal: Journal of Clinical Oncology (2012)

465 Background: Prospective studies with sunitinib in mRCC have shown median progression-free survival (mPFS) of 11 months (first line) and 8.3 months (second line). In order to identify patients with LTB with SU, we describe the clinical characteristics of patients with mRCC treated with SU with an mPFS of 15 months or more. Methods: This is a retrospective chart review of patients with mRCC treated with SU in two hospitals, Alexander Fleming Institute Buenos Aires in Argentina and Hospital Israelita Albert Einstein in Sao Paulo, Brazil. Inclusion criteria included patients treated with SU who had a PFS of at least 15 months. Results: Between September 1995 and August 2009, 29 cases were identified. Patient demographics were: median age of 56 years, 65% male, 96% with previous nephrectomy, Eastern Cooperative Oncology Group performance status (PS) of either 0 (52%) or 1 (48%), 93% had clear cell histology, 69% received prior systemic therapy, and 78% had ≤ 2 metastatic sites (mostly in the lungs, liver and bone). Patients were started on SU 50 mg 4 weeks on treatment/2 weeks off treatment (4/2) (n=26) or 37.5 mg 6 weeks continuous dosing (n=3). For those patients starting on 4/2, dose reduction was necessary in 59% of the patients to maintain SU therapy. Median duration of therapy was 23.7 months. During treatment, 24 patients (83%) developed hypertension. Response rates were as follows: complete response 7% (n=2), partial response 38% (n=11), stable disease 52% (n=15); data missing for one patient. Conclusions: LTB is seen in patients who are young, have good performance status, and either 1 or 2 metastatic sites. Dose reductions are common in order to maintain treatment while benefiting from SU. Treatment with SU as either first- or second-line therapy did not appear to influence outcome. Hypertension is a common finding and serves as a predictive marker during treatment, but study limitations preclude the identification of pre-treatment predictive factors.
EXTH-10. A NOVEL SMALL MOLECULE THERAPY SENSITIZES HIGH-GRADE GLIOMA TO TEMOZOLOMIDE CHEMOTHERAPY
Authors: Amin Kassam, Richard Rovin
Journal: Neuro-Oncology (2016)

Despite best medical therapy, high-grade glioma (HGG) has a poor prognosis, creating an urgent need for better therapies. The DNA-alkylating agent temozolomide (TMZ) is the standard HGG chemotherapy. However, TMZ benefits only a subset of patients, mainly because O-6-methylguanine-DNA methyltransferase (MGMT) repairs the TMZ-induced DNA damages, establishing TMZ resistance in many HGGs. Recent reports suggest peroxiredoxin (PRDX4) is an intriguing therapeutic target. PRDX4 decreases reactive oxygen species (ROS), decreases endoplasmic reticulum (ER) stress, and activates MGMT through STAT3. We have previously shown that these multiple oncostimulatory effects are mitigated by the safe, naturally occurring compound piperlongumine (PL), a specific inhibitor of PRDX4. We thus hypothesized that inactivation of PRDX4 by piperlongumine can sensitize HGGs to TMZ chemotherapy. We treated several MGMT expressing and non-expressing HGG cell lines with various doses of PL and TMZ. We then assessed cell proliferation and related molecular changes. We also tested in vivo efficacy of PL plus TMZ in an orthotopic mouse model of HGG. Piperlongumine pretreatment sensitized TMZ-resistant HGG cells to TMZ in vitro, resulting in significantly increased HGG cell death. The underlying mechanism of the synergistic effect may include STAT3 inactivation. Finally, piperlongumine plus TMZ treatment prolonged the survival of orthotopic mouse model of HGGs. Piperlongumine is a safe, natural compound with minimal toxicity to normal cells. Moreover, piperlongumine crosses the blood brain barrier. Therefore, utilizing piperlongumine to sensitize TMZ-resistant HGGs should be considered as a putative HGG therapy. At the conclusion of this session, participants will be able to: Describe the mechanisms of action of PRDX4, describe the mechanism of action of piperlongumine, and review the effect of PL and TMZ on HGG cells in culture and in xenograft models.
Comprehensive stem cell transplant (SCT) outcome data submission.
Authors: Roy B. Jones, Charles Martinez, J. Douglas Rizzo, Dianne Reeves
Journal: Journal of Clinical Oncology (2012)

293 Background: All U.S. transplant centers must report comprehensive SCT outcome data to a federal registry. The current electronic data capture method requires manual data entry of 700+ unique data elements into an internet application, FormsNet (Center for International Blood and Marrow Transplant Research). Data is routinely copied from program databases or the EMR by manual transcription, an inefficient, inaccurate and expensive process. A method was needed to allow electronic transmission of outcome data directly from these databases to the mandated SCT Outcomes Database (SCTOD). Methods: We designed an interface engine (IE) to transmit structured data through a caGRID subnet (AGNIS) directly to the SCTOD from a proprietary MDACC SCT database using a secure, auditable method. To make this method applicable to other centers, we collaborated with the NCI and others to expand the Biomedical Research Informatics Domain Group (BRIDG) standard data model to support a full set of granular data elements (&gt;1,900) required to describe SCT outcomes. The IE was modified to transmit SCT data from the expanded BRIDG database to the SCTOD. The IE and expanded BRIDG database model will be made available to all centers without charge. In this way centers interfacing data to this new structure can transmit data to the SCTOD without transcription. Results: The BRIDG oversight committee has approved the extended model and made its structure and content publically available. The IE has been used to transmit &gt;4,000 data forms from MDACC to the SCTOD. The full set of SCT common data elements (CDE) has been published in the Cancer Data Standards Repository of the NCI. The American Society of Blood and Marrow Transplantation is publishing an RFA to identify 1-3 vendors qualified to interface data from center-specific systems to the BRIDG database. Conclusions: Comprehensive and direct electronic data transmission to the SCTOD is feasible and can be done without modifying individual center’s legacy applications. The plan will make appropriate tools available to all transplant centers. This paradigm should be applicable to other areas of oncology.
In Vivo Eradication of Human Clonigenic Acute Lymphoblastic Leukemic Cells Expressing the Wilms Tumor Protein, WT-1, by HLA Restricted WT-1 Specific T-Cells in NOD/SCID Mice Monitored by Bioluminescent Imaging.
Authors: Ekaterina Doubrovina, Mikhail Doubrovin, Elena Kanaeva, Richard J. O’Reilly
Journal: Blood (2007)
Common SNPs within or near Three Immune Response Genes Implicated in the Risk of FVIII Immunogenicity in Hemophilia A Do Not Influence Steady-State Levels of Their Encoded mRNAs
Authors: Tom E. Howard, Eugene Drigalenko, Matthew P. Johnson, Shelley S. Cole, Benjamin Kim, Kevin R. Viel, Zuben E. Sauna, Joanne E. Curran, John Blangero, Laura A. Almasy, Harald H. Göring
Journal: Blood (2012)
High Expression of MUM1/IRF4 mRNA Is Associated with a Shorter Overall Survival in Patients with Multiple Myeloma.
Authors: Daniel Heintel, Niklas Zojer, Kathrin Strasser-Weippl, Michael Vesely, Heinz Gisslinger, Johannes Drach, Alexander Gaiger, Ulrich Jäger, Heinz Ludwig
Journal: Blood (2005)
CSIG-30. A NOVEL INTERACTING PARTNER FOR PID1, A GROWTH INHIBITOR IN PEDIATRIC AND ADULT BRAIN TUMORS
Authors: Anat Erdreich-Epstein, Xiuhai Ren, Sean Robinson, Mark Frey
Journal: Neuro-Oncology (2016)

PID1 is an inhibitor of insulin receptor signaling which we had reported to be a novel inhibitor of medulloblastoma and glioma cell growth, and whose mRNA level is highly correlated with survival across multiple independent datasets of these tumors. PID1 harbors a phosphotyrosine binding domain and is therefore predicted to interact with proteins harboring NPXY motifs. We therefore hypothesized that PID1 will interact with phosphotyrosine-binding (PTB) domain containing protein(s) that may be important in brain tumors, and will modulate its/their signaling. Here we report PID1 interactions with one of these proteins and determine its biological consequences. Experiments consisted of immunoprecipitations, transient transfections, and western blotting. Functionally, assays included cell culture, flow cytometry for proliferation using BrdU/7AAD and apoptosis using AnnexinV/7AAD. Plasmids were pCMV-AN-HA-PID1(2) or control or the protein of interest in pcDNA3.1. Cells used were glioblastoma, medulloblastoma, atypical teratoid rhabdoid (ATRT), HEK293, and cells deficient or intact in PID1. We demonstrate co-immunoprecipitation of PID1 with the interacting protein partner in HEK293T cells overexpressing both proteins and in native brain tumor cells with/without overexpression. While tyrosine phosphorylation of the NPXY motifs was not required for the interaction, mutating the kinase domain or overall inhibition of tyrosine phosphorylation inhibited this protein’s interaction with PID1. Different domains in PID1 differentially co-IPd with this protein. Interestingly, cells without PID1 showed increased growth factor-dependent tyrosine phosphorylation of this protein and increased growth factor-induced proliferation. These data point to PID1 as a novel interacting partner and regulator of this protein’s biological effects and signaling.
A phase I study of INNO-406 in patients with advanced Philadelphia chromosome-positive (Ph+) leukemias who are resistant or intolerant to imatinib and may have also failed second-generation tyrosine kinase inhibitors
Authors: J. Pinilla-Ibarz, H. M. Kantarjian, J. E. Cortes, P. le Coutre, A. Nagler, A. Hochhaus, D. Jones, S. Kimura, J. Giampalmi, L. Gleich, O. G. Ottmann
Journal: Journal of Clinical Oncology (2008)

7018 Background: INNO-406 is an oral dual Abl/Lyn kinase inhibitor, which is up to 55-times more potent than imatinib (I). Numerous Bcr- Abl mutant proteins are sensitive to INNO-406 in vitro, including the F317L mutant. Methods: This is a Phase I study in Ph+ leukemia patients (pts) with resistance or intolerance to I (who may have also failed second generation TKIs) treated with INNO- 406 orally at doses ranging from 30 mg once daily (qd) to 480 mg twice daily (bid). Part 1, the dose finding portion of the study, is completed. Enrollment continues in the expansion phase (Part 2) of the study at the MTD of 240 mg bid. Results: INNO-406 was administered to 46 pts in Part 1 of the study. Pts had CML in chronic phase (CP, n=21), accelerated phase (AP, n=9), or blast phase (BP, n=7), or Ph+ ALL (n=9). Previous treatment included I only (n=14), I + nilotinib (N) or dasatinib (D) (n=23), I + N + D (n=9). In Part 2, 10 pts with CML-CP have been enrolled. Previous treatment included I only (n=5), I + D (n=2), I + N (n=3). Common mutations on study entry included Y253H (n=4), G250E (n=4), F317L (n=3), and T315I (n=2). Currently, 19 pts remain on study. Discontinuations were due to: disease progression (n=29), pursue other treatment options (n=5), and toxicity (n=3). Complete cytogenetic responses (CCyR) were seen in 3 pts in Part 1 of the study, including a CCyR in a CML-CP pt intolerant to both I and D. Response data for Part 2 of the study will be updated. Drug-related grade 3/4 adverse events included: reversible elevations of liver transaminases and bilirubin, thrombocytopenia, and acute renal failure. No grade 3/4 pleural effusions, peripheral edema, or pericardial effusions were seen and a minimal mean QTc effect was observed. No drug-related severe neutropenias were seen. Conclusions: INNO-406 has been well tolerated with responses seen in these heavily pretreated pts. The recommended phase II dose is 240 mg bid. Pivotal phase II studies are planned for 2008. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Medpace Inc Innovive Pharmaceuticals Innovive Pharmaceuticals Innovive Pharmaceuticals Innovive Pharmaceuticals
Correlation of immune responses and survival in a phase II study of belagenpumatucel-L in non-small cell lung cancer
Authors: H. Fakhrai, A. Tong, J. Nemunaitis, D. L. Shawler
Journal: Journal of Clinical Oncology (2009)

3013 Background: Belagenpumatucel-L (Lucanix), a therapeutic vaccine comprised of 4 TGF-β2 antisense gene-modified allogeneic non-small cell lung cancer (NSCLC) cell lines, was tested in a phase II trial in which subjects with stage IIIB/IV NSCLC received intradermal injections of the vaccine every 4–8 weeks. Methods: We performed 2 cellular immunity assays and 2 humoral immunity assays on subjects in the trial. To measure the overall immune status, pretreatment peripheral blood mononuclear cells (PBMC) were stimulated by PMA/ionomycin and assessed by formation of IFN-γ ELISPOT. We also measured in vitro IFN-γ ELISPOT formation by subjects’ PBMC following vaccination. The two humoral assays looked at the induction of anti-belagenpumatucel-L antibodies and anti-HLA antibodies. Results: Subjects were classified as immune response positive (IR + ) if they were positive for 3 or 4 of the assays described above. The remaining subjects were classified as immune response negative (IR - ). There were 11 subjects who were IR + and 24 who were IR-negative. The IR + subjects had a median survival of 32.5 months (95% CI, 25.2 to 39.8) compared to 11.6 months (95% CI, 5.6 to 17.6) for IR - subjects (p=0.011, log-rank test). Subjects were also classified as clinical responders or nonresponders based on their tumor assessment after 4 months on trial. 10/19 subjects classified as clinical responders were IR + compared to only 1/16 nonresponders (p=0.004, Fisher's exact test). Conclusions: These data demonstrate a strong correlation between the achievement of a combination of cellular and humoral immune responses and a significant increase in overall survival in the subjects treated with belagenpumatucel-L and suggest that both components of the immune system are important for the induction of clinically significant antitumor immunity by the vaccine. [Table: see text]