tbuckley/cabot-search huggingface dataset:
Patient preference for prostate-specific antigen testing: A population-based analysis.
Authors: S. L. Chang, J. C. Presti, J. P. Richie
Journal: Journal of Clinical Oncology (2011)

188 Background: The AUA and American Cancer Society both recommend a shared decision-making process between clinicians and patients for prostate cancer screening with PSA testing. Data are limited data regarding patient preferences for PSA evaluation in the United States. We assessed the sociodemographic and clinical characteristics of men who proceeded with or opted out of PSA testing in a nationally representative population-based cohort. Methods: We analyzed male participants from the 2001 to 2008 cycles of the National Health and Nutrition Examination Survey (NHANES) who were 40 years old or older without a history of prostate cancer, recent prostate manipulation, or hormone therapy use (n = 6,032). All men underwent or refused PSA testing after a standardized explanation about prostate cancer screening by a physician. A multivariate logistic regression was conducted after adjusting for survey weights to identify independent sociodemographic and clinical predictors for opting out of PSA testing. Results: Overall, 5% of the study cohort refused PSA testing. The analysis revealed predictors for refusing PSA testing (Table). PSA testing preference was not influenced by a family history of prostate cancer, previous prostate cancer screening, education level, socioeconomic status, insurance status, or tobacco history. There were no significant time trends for PSA testing. Conclusions: Despite equal access to PSA testing in our study, there was unequal utilization. We found that Black men were more likely to refuse PSA testing. Our analysis also suggests that a perception of suboptimal health or uncertain future outlook may discourage men from undergoing PSA evaluation. These patient preferences for PSA evaluation should be factored into the shared decision-making process for prostate cancer screening. [Table: see text] No significant financial relationships to disclose.
Drug-Induced Cutaneous Vasculitis in Patients with Non-Hodgkin’s Lymphoma Receiving Bortezomib: A Possible Surrogate Marker of Response.
Authors: John Gerecitano, Andre Goy, Barbara MacGregor-Cortelli, Ellen Neylon, John Wright, Dixie Esseltine, David Schenkein, Mithat Gonen, Owen A. O’Connor
Journal: Blood (2005)
Human INF-α therapy in desmoid tumors: A retrospective study.
Authors: J. P. Poulsen, J. Engellau, A. Skeie, M. Sloth, B. Bjerkehagen, O. Zaikova, K. S. Hall
Journal: Journal of Clinical Oncology (2011)

e20505 Background: Aggressive fibromatosis (desmoid tumors) are locally invasive, nonmetastatic and have a high local recurrence rate after primary resection. For patients (pts) where surgery is not an option, effective medical treatments are needed. Positive responses with INF-α therapy are reported and supported by in vitro results, was our reason to treat pts with human leukocyte interferon-alpha (Multiferon [M]). Methods: M is an INF-α product obtained from the leukocyte fraction of human blood. The product is highly purified with multiple subtypes including α1, α2, α8, α10, α14 and α21. Pts from 2 sites were included in this retrospective study. Pts had progressive symptoms, were inoperable without considerable morbidity and for whom RT, chemotherapy or hormone therapy also were unwanted. Results: 11 patients were included and 5 are still on treatment. Average age was 38 years and average follow-up time is currently 344 days. Pts N1 to N8 were INF-α naïve, whereas S1 to S3 were changed from peginterferon treatment to M treatment due to suspected anti-interferon antibodies with progression of disease (S1 and S3) or livertoxicity (S2). Of the 8 naïve pts, 2 had PR, 5 had SD, 1 no follow-up MRI scan yet. Six of 8 pts experienced clinical improvement such as regression of pain, increased mobility or other relevant parameters. For N2 and N5 the MRI sequences revealed lower intensity signal, reflecting a greater amount of less active fibrotic tissue. N5 experienced 13% shrinkage in second largest tumor diameter. N1 reached max response of 60% decrease in largest diameter, after 1½ years treatment. Treatment was stopped after 31 mth and tumor still stable 5 mth later. For pts S1 to S3 all had SD, 2 had clinical improvement, 1 had clinical worsening. Conclusions: Treatment response emerges slowly. M may be a new promising treatment option for desmoid tumors. The presentation will present latest follow-up data. Pt Sex Age Tumor location Response Clinical improvement yes/no % change from baseline Follow-up time days N1 M 44 Abd PR Y -60 929 N2 F 28 Ex SD Y +6 661 N3 F 24 Ex SD N +11 191 N4 M 68 Head and Neck PR Y -38 620 N5 F 29 Gluteal SD Y 0 238 N6 M 29 Abd SD Y -7 137 N7 F 35 Tru SD N -6 57 N8 M 63 Ex - Y - - S1 F 29 Ex SD N +4 84 S2 F 17 Ex SD Y -3 558 S3 F 49 Tru SD Y -2 176 Abbreviations: Abd, abdominal; Tru, superficial trunk; Ex, extremity.
Locoregional recurrence after breast cancer surgery: A meta-analysis by molecular subtype.
Authors: A. J. Lowery, M. R. Kell, R. W. Glynn, M. J. Kerin, K. J. Sweeney
Journal: Journal of Clinical Oncology (2011)

1053 Background: Molecular subtyping has confirmed that breast cancer comprises at least four genetically distinct entities, the phenotype of which influences both systemic and locoregional recurrence. The quantitative influence of subtype on ipsilateral locoregional recurrence (LRR) is unknown. The aim of this study was to systematically appraise the influence of breast cancer subtype on LRR following breast conserving therapy (BCT) and mastectomy. Methods: A comprehensive search for published studies that examined outcomes after BCT and/or mastectomy for patients according to breast cancer sub-type, was performed using Medline and cross referencing available data. Reviews of each study were conducted and data were extracted to perform meta-analysis. Primary outcome was LRR related to breast cancer subtype. Results: A total of 9,007 breast cancer patients who underwent either BCT (n=4790) or mastectomy (n=4217) were identified from studies examining LRR in relation to breast cancer subtype. Patients with luminal subtype tumor had lower risk of LRR than both triple-negative (OR=0.48; 95% CI 0.30−0.77) and Her2neu-overexpressing (OR= 0.27; 95% CI 0.18−0.39) tumours following BCT. Luminal tumours were also less likely to develop LRR than Her2neu-overexpressing (OR =0.7, 95% CI 0.52−0.95) or triple-negative tumours (OR=0.65, 95% CI=0.50−0.83) after mastectomy. Her2neu-overexpressing tumours have increased risk of LRR compared to triple-negative tumours (OR=1.7; CI 1.11−2.65) following BCT but there was no difference in LRR between Her2neu-overexpressing and triple-negative tumours following mastectomy (OR=0.9, 95% CI 0.64−1.28). Conclusions: Luminal tumors are associated with the lowest rates of LRR. Patients with triple negative and Her2/neu-overexpressing breast cancer subtypes are at increased risk of developing LRR following BCT or mastectomy. Breast cancer biologic subtype should be taken into account when considering local control of breast cancer and may be used to identify those at increased risk of local and regional recurrence who may benefit from more aggressive local treatment.
Aspirin Suppresses Growth in PI3K-Mutant Breast Cancer by Activating AMPK and Inhibiting mTORC1 Signaling
Authors: Whitney S. Henry, Tyler Laszewski, Tiffany Tsang, Francisco Beca, Andrew H. Beck, Sandra S. McAllister, Alex Toker
Journal: Cancer Research (2016)

Despite the high incidence of oncogenic mutations in PIK3CA, the gene encoding the catalytic subunit of PI3K, PI3K inhibitors have yielded little clinical benefit for breast cancer patients. Recent epidemiologic studies have suggested a therapeutic benefit from aspirin intake in cancers harboring oncogenic PIK3CA Here, we show that mutant PIK3CA-expressing breast cancer cells have greater sensitivity to aspirin-mediated growth suppression than their wild-type counterparts. Aspirin decreased viability and anchorage-independent growth of mutant PIK3CA breast cancer cells independently of its effects on COX-2 and NF-κB. We ascribed the effects of aspirin to AMP-activated protein kinase (AMPK) activation, mTORC1 inhibition, and autophagy induction. In vivo, oncogenic PIK3CA-driven mouse mammary tumors treated daily with aspirin resulted in decreased tumor growth kinetics, whereas combination therapy of aspirin and a PI3K inhibitor further attenuated tumor growth. Our study supports the evaluation of aspirin and PI3K pathway inhibitors as a combination therapy for targeting breast cancer. Cancer Res; 77(3); 790-801. ©2016 AACR.
SOFIA: Phase II study of neoadjuvant epirubicin, cyclophosphamide (EC) plus sorafenib (S) followed by paclitaxel (Pw) plus sorafenib (S) in women with primary breast cancer (BC; GBG 45).
Authors: B. Conrad, N. Harbeck, G. Von Minckwitz, M. Wuellner, M. Warm, K. Schwedler, B. Gerber, I. Schrader, H. Eidtmann, K. Mehta, S. Loibl
Journal: Journal of Clinical Oncology (2011)

1059 Background: Sorafenib is an oral RAF/RAS kinase inhibitor with antiangiogenetic potential. In metastatic BC it shows modest single agent activity but prolongs PFS in combination with capecitabine. EC-Pw or Pw-EC are standard neoadjuvant chemotherapy regimen suitable to be combined with new drugs. Methods: SOFIA is an open-label, multicentre, single-arm, phase II study. Inclusion criteria were: uni- or bilateral, HER2-, cT3, cT4 or cT2 cN+, M0 primary BC. Pts received 4x E 90 mg/m2 and C 600 mg/m2 i.v. q3w followed by 12 weeks Pw 80 mg/m2). S 800mg was given concomitantly the chemotherapy with a 3 day drug holiday around EC q1w (cohort1). PK samples were taken during the first 2 cycles. After an amendment S dose started with 200mg and escalated up to 800mg depending on pts individual toxicity in every EC cycle (cohort 2: EC-P) and P cycle (cohort 3: P-EC), respectively. Maximum achieved dose was maintained during cycles 5−8. Primary objective was the rate of pCR at time of surgery; main secondary objectives were the assessment of safety and clinical response. Results: 36 pts (12 in each cohort) were recruited median age was 45 years (range 28−68). 89% had a T2 tumour, 50% were N+; 53% had a G3, 83% a ductal invasive, and 64% a hormone receptor pos tumor, 36% TNBC. In cohort 1 the median daily dose was 400 mg and the cumulative dose 611400 mg. The following grade 1−4 toxicities were reported in pt: hand-foot syndrome (HFS) 4, other skin reactions 2, diarrhea 2, mucositis 1, hypertension 1, 7/12 pts discontinued early, due to AEs 5, progressive disease 2. In cohort 2 median daily S dose was 700mg and the cumulative dose 892,400 mg. Toxicities grade 1−4: HFS 6, other skin reactions 7, diarrhea 2, mucositis 1. 1 pt discontinued early due to allergic reaction. No patients stopped due to skin toxicities. The maximum tolerable dose was 400mg (n=2) 600mg (n=4) 800mg (n=6). Results on cohort 3 will be presented at the meeting. Conclusions: SOFIA is the first study evaluating S in a neoadjuvant setting in pts with primary BC. The individual dose escalation of S offers an excellent tool to reduce treatment discontinuation and HFS and with increasing the cumulative dose by at least 46%.
Leukemia Related Co-Stimulation / Co-Inhibition Predict T-Cell Attack of Acute Lymphoblastic Leukemia Mediated By Blinatumomab
Authors: Tobias Feuchtinger, Judith Feucht, Simone Kayser, David Gorodezki, Michaela Döring, Franziska Blaeschke, Hans Bösmüller, Leticia Quintanilla-Fend, Patrick Schlegel, Martin Ebinger, Peter J. Lang, Rupert Handgretinger
Journal: Blood (2015)
The impact of neoadjuvant weekly ixabepilone for high-risk prostate cancer: A phase I/II clinical trial.
Authors: Jodi Lyn Layton, Angela Marie Plette, Joseph F. Renzulli, E. Bradley Miller, Howard Safran, Anthony E. Mega
Journal: Journal of Clinical Oncology (2012)

158 Background: Potential benefits of neoadjuvant chemotherapy are tumor downstaging and treatment of micrometastatic disease. A prior study using docetaxel yielded no pathologic complete responses and concerns for increased operative morbidity. In Phase II studies, ixabepilone has promising activity in metastatic prostate cancer. Our study is a Phase I/II clinical trial evaluating neoadjuvant, weekly ixabepilone in men with high-risk prostate cancer opting for radical prostatectomy. Methods: Men with high risk prostate cancer defined as either Gleason 8-10, cT3 disease, high volume Gleason 4+3 and a palpable nodule or a PSA&gt;20 ng/ml were eligible. Men received weekly ixabepilone 16-20/m 2 for 12-16 weeks prior to surgery. Fifteen men underwent robotic prostatectomy; one patient who had an open prostatectomy. Initial PSA response, post-operative PSA values, pathology, and evaluation of adverse events were recorded. Results: We enrolled 16 men with a mean follow-up of 15.25 months at time of review. All had pretreatment Gleason scores of 4+3 or higher. With neoadjuvant treatment, PSA values decreased in 14/16 men (mean 46.8%); increased in 2/16 men. None reached an undetectable pre-operative PSA. Nine men experienced an adverse event requiring dose modification or cessation of chemotherapy (neuropathy or allergic reaction). Only 5/16 men completed planned treatment. Mean operative time, EBL, and hospital stay were 189 minutes, 184mL, and1.5 days, respectively; all consistent with institutional and national norms. Post surgery 15/16 (94%) had pT3 disease, 8/16 (50%) had a positive surgical margin and 2/16 (12.5%) had positive regional lymph nodes. There were no pathologic complete responses. Only 1/16 (6.25%) had a biochemical relapse. Conclusions: While a PSA response is achieved, there is substantial toxicity with neoadjuvant weekly ixabepilone. Men were able to undergo prostatectomy without increased morbidity after neoadjuvant therapy. Extracapsular extension and positive surgical margins remained common in this population with high-risk disease. Assessment of biochemical recurrence rates and time to treatment failure will require longer, planned follow-up.
BNIP3 Is Downregulated in Myelodysplastic Syndromes and Acute Myeloid Leukemia and Is a Potential Molecular Target for Decitabine
Authors: Mariana Lazarini, Joao Machado-Neto, Adriana S. S. Duarte, Fernando V Pericole, Patricia Favaro, Karin Spat Albino Barcellos, Fabiola Traina, Sara T. Olalla Saad
Journal: Blood (2012)
Single Cell Network Profiling (SCNP)-Based Classifier to Predict Response to Induction Therapy in Pediatric Patients with De Novo Acute Myeloid Leukemia (AML): Validation Study Results,
Authors: Norman J. Lacayo, Todd A. Alonzo, Urte Gayko, Matt Westfall, Norman Purvis, Santosh Putta, James Hackett, Aileen Cleary Cohen, Robert B. Gerbing, Gary V Dahl, Alan S. Gamis, Soheil Meshinchi
Journal: Blood (2011)
Single-fraction radiosurgery for the treatment of renal tumors in singular renal units.
Authors: M. D. Staehler, P. Nuhn, A. Karl, M. Bader, C. Stief, B. Wowra, A. Muacevic
Journal: Journal of Clinical Oncology (2011)

368 Background: High-dose local radiation treatment (stereotactic radiosurgery [SRS]) was added for selected patients to improve local control and overall survival in metastases. We report on toxicity and local tumor control in patients with renal tumors who were treated with aggressive local irradiation using a single fraction SRS with the Cyberknife in singular renal units to avoid hemodialysis. Methods: n=18 patients with renal tumors and an eastern cooperative oncology group (ECOG) status of 0 or 1 were treated with SRS. Patients with surgically removable renal lesions were not included. Prior to SRS gold markers were planted into the renal parenchyma under ultrasonographic guidance. Results: Nine patients had transitional carcinoma of the renal pelvis, six patients had renal cell carcinoma and three had other tumor entities. No skin toxicity occurred after SRS, and SRS did not induce other side effects. Local tumor control 9 months after SRS was 98% (95% CI: 89-99%). There were no treatment related deaths, and late complications after SRS were not noted so far. Renal function so far remained stable without a change in serum creatinine. Conclusions: SRS for selected patients with renal tumors is safe and effective. Single-fraction delivery as an outpatient procedure allows for convenient integration of SRS into various oncological treatment concepts. Further studies are needed to determine the limits of SRS in this setting. No significant financial relationships to disclose.
Autophagy Induction of Acute Myeloid Leukemia (AML) Cells after Treatment with Low Dose-Cytarabine (Ara-C) and Enhanced Cytocidal Effect on AML Cells by Combined Treatment with Ara-C Plus Lenograstim.
Authors: Keisuke Miyazawa, Juri Toyotake, Munekazu Naito, Masahiro Itoh, Kazuma Ohyashiki
Journal: Blood (2007)
Treatment patterns and costs following metastatic breast cancer diagnosis in U.S. women: A SEER-Medicare analysis.
Authors: D. C. A. Taylor, M. Sanon, K. Clements, S. Balu, C. Faria, A. Teitelbaum
Journal: Journal of Clinical Oncology (2011)

150 Background: To use SEER-Medicare data to evaluate treatment (tx) patterns and health care costs in U.S. women with metastatic breast cancer (MBC). Methods: Key inclusion criteria included women diagnosed (dx) with breast cancer in 2001-2005 with 1) enrollment in Medicare 12 mo prior to dx through follow-up (2008) or death; 2) initial dx of “distant” disease or 2 indications of secondary malignancy &gt;2 mo after initial dx; and 3) indication of tx with injectable hormonal, chemotherapy (chemo) or targeted/biologic therapies. Lines of tx were designated as: 1 st -line if 1st agent (or agents, if on same day) after dx of MBC; new agents administered &gt; 42 d after the previous agent are a new line, as well as an agent administered &gt; 60 d after last dose of the same agent. Oral medication data were not available. Kaplan-Meier techniques estimated lifetime total health costs by partitioning data into 30-d intervals starting with MBC dx date and then summing the product of mean cost in each interval by the probability of survival to the start of the interval. Bootstrapping methods were used to generate 95% confidence intervals (CI). Results: The table lists the top 5 injectable tx for first, second, and third line, with associated mean lifetime costs. Conclusions: In this population, the injectable fulvestrant was the most commonly used first-line tx, with vinorelbine most frequently used in second- and third-line settings for MBC. Mean lifetime cost of MBC was $110,000. [Table: see text]
The Effect of Adherence-Encouraging Interventions on Adherence to Tyrosine Kinase Inhibitor Treatment in Chronic Myeloid Leukemia (TAKE-IT): A Pre-Post Intervention Pilot Study
Authors: Avi Leader, Noam Benyamini, Sabina De Geest, Juliet Dreyer, Bronya Calvarysky, Sara Gechler, Alina Amitai, Osnat Jarchowsky-Dolberg, Giora Sharf, Eric Tousset, Opher Caspi, Martin Ellis, Itai Levi, Anat Gafter-Gvili, Pia Raanani
Journal: Blood (2015)
New quantitation method for monitoring cytarabine incorporated into DNA of leukemic cells from patients receiving cytarabine therapy
Authors: Takahiro Yamauchi, Takanori Ueda
Journal: Cancer Research (2004)

4746  Cytarabine (1-beta-D-arabinofuranosylcytosine, ara-C) is one of the most effective anticancer agents for the treatment of acute myeloid leukemia (AML). After being transported into leukemic cells, the drug is phosphorylated to ara-C triphosphate, the intracellular active metabolite, and thereafter incorporated into DNA to terminate DNA synthesis. Clinical pharmacokinetics demonstrated the intracellular ara-C triphosphate as a crucial determinant for the therapeutic efficacy. In the in vitro studies, however, ara-C-induced cytotoxicity was primarily determined by the extent of the incorporation of ara-C into DNA of leukemic blasts. Nevertheless, the level of ara-C in DNA has hardly been evaluated in clinic because of the lack of appropriate quantitation methods. Here, we established a new method of monitoring ara-C incorporated into DNA in vivo. The procedure was as followed. The acid insoluble fraction containing DNA was extracted from leukemic cells. DNA was separated from this fraction using a classical Schmit-Thanheuser-Schneider method. The isolated DNA was then enzymatically digested into nucleosides. ara-C was subsequently fractionated from the nucleosides using high-performance liquid chromatography. After lyophilization of the ara-C fraction, the amount of ara-C therein was eventually measured using radioimmunoassay with anti-ara-C sera. First, the method was validated. The recovery of each step was over 90%, and the inter-assay variation was minimal (% coefficient of variation around 30%) despite the multi-step procedure. The quantitation limit was 1 pmol/ 10,000,000 cells. Second, ara-C incorporation into DNA was measured in cultured leukemic cells. When human leukemia HL 60 cells were incubated with ara-C, the ara-C level in DNA increased in both concentration- and time-dependent manners. The values determined using this new method were in accordance with those measured by scintilation counting using tritiated ara-C in the parallel experiment. Finally, this method was applied to measuring ara-C incorporated into DNA of clinical samples in vivo. When 1 g/m  \( \frac{1}{2}\) 2; ara-C was infused for 1 h in an AML patient (72 year-old, female), the level of ara-C incorporation into DNA were 15 pmol/10,000,000 cells at 5 h after the end of the infusion. When 2 g/m  \(\frac{1}{2}\) 2; ara-C was infused for 2 h (51 years old, female, AML), ara-C in DNA was 110 pmol/10,000,000 cells at 3 h thereafter. In conclusion, The method we established here was applicable to quantitating ara-C incorporation into DNA of leukemic cells in clinic. Therapeutic drug monitoring at the DNA level (genomic TDM) during ara-C treatment may individualize the therapy of leukemia.
68 years—a record breaking thoracoplasty?
Authors: Eddie Spiegelhalter
Journal: BMJ (2016)

I first coughed up blood in 1945 when I was working as a 22 year old sanitary inspector in the RAF in southern Italy, and I feared tuberculosis as I had just seen a colour film featuring Chopin coughing blood on his keyboard. I was examined, x rayed, and told was all clear. But they missed the high cavity in my lung, and in April 1946, when just about to take up a dream post as hygiene inspector for the whole of RAF Middle East Command, I collapsed in Heliopolis transit camp producing cupfuls of blood. “Hello,” I thought, “something is wrong,” and, thanks to tuberculosis, that was the end of my RAF career.



Eddie Spiegelhalter in 1945



I was taken by hospital train to the British Military Hospital in Jerusalem, where they tried an artificial pneumothorax, which didn’t …