tbuckley/cabot-search huggingface dataset:
High dose rate brachytherapy and external beam radiotherapy for local and locally advanced prostate cancer: Uni-institutional long term results.
Authors: Antonio Cassio Assis Pellizzon, Ricardo César Fogaroli, Maria Leticia GOBO Silva, Douglas Guedes, Michael .Chen, Guilhreme Gondim, Henderson Ramos
Journal: Journal of Clinical Oncology (2016)

319 Background: Dose-escalation is a determining factor that influences biochemical control (BC) of prostate cancer. High-dose rate brachytherapy (HDR) is one method for providing BC. Methods: Patients with histological diagnosis Gleason scored (GS), clinical stage T1 to T3a, no evidence of metastatic disease, prostate volume &gt; 20cc &lt; 60cc and initial PSA (PSAi) &lt; 60 mg/ml treated from 1997 to 2005 with an Institutional Policy of treatment were evaluated. Results: There were 273 patients treated with this treatment combination at AC Camargo Cancer Center, Sao Paulo, Brazil. The median age and FU time were 64.7 and 10.3 years, respectively. Two hundred thirteen (78.0%) patients had FU longer than 5 years. Actuarial 10-year OS, CSS and BC were 89.8%, 63.6% and 71.8%, respectively. On univariate analyses GS &lt; 7, clinical stage &lt; T2b, low risk group (LR), absence adjuvant androgen deprivation (ADT), age &gt; 65, PSAi &lt; 10, localized EBRT and three dimensional HDR planning were associated with improved CSS and BC. PSAi and age were not favorable associated to BC. Multivariate Cox regression analyses confirmed LR, GS &lt; 7, PSAi &lt; 10, absence of ADT, age &lt; 65 years as predictors of improved CSS and BC. For OS only LR was confirmed as predictive factor. Conclusions: The present data represents a unique single institution study at long FU for the given technique and the comparison with the current literature data confirms the excellent results achieved with this treatment combination.
Expression of the nuclear receptor, FXR, as CRC progresses from primary to lymph node to liver metastases.
Authors: Lily L. Lai, Armond Ohanian, David D. Smith, Xiyong Liu
Journal: Journal of Clinical Oncology (2012)

497 Background: Farnesoid X Receptor (FXR) is a nuclear receptor critical for cholesterol, triglyceride and glucose metabolism. In mouse models, loss of FXR results in tumorigenesis. FXR expression decreases from normal epithelium to cancer. Clinical studies identify FXR as a novel prognostic and predictive biomarker in CRC. We sought to further characterize FXR expression with clinical CRC progression. Methods: Under institutional approval, we reviewed the FFPE tissues from 20 St. IV CRC patients who underwent synchronous resection of previously untreated primary cancers, lymph nodes (LN), and liver metastases (Met) from 2000-2005. FXR expression, determined using immunohistochemical techniques, was scored on a 3-point scale (0 = no expression, 1 = moderate expression, 2 = high expression). Pair-wise differences were tested using two-tailed t-tests. Results: All 20 sets included tissues from 3 sites. We found that FXR protein levels decreased along the continuum of disease from primary to LN and from LN to Met in 15 of 20 sets of tissues. In 4 sets, there was no change in FXR expression. In 1 patient, FXR increased in the LN and Met. Overall, FXR expression decreased from primary to LN (**p&lt;0.001), from LN to Met (**p&lt;0.001) and from primary to Met (***p&lt;0.0001). Conclusions: FXR expression decreases as disease advances from primary to LN to Met. Our findings suggest that FXR regulation of metabolism in the cancer cell may be lost in CRC progression. Further studies are needed to determine if upregulation of FXR activity in localized CRC can inhibit progression to metastases.
Medical Schools in the United States, 2013-2014
Authors: Barbara Barzansky, Sylvia I. Etzel
Journal: JAMA (2014)

Thefollowingtablescontaindata thatarederivedmainly from the 2013-2014 Liaison Committee on Medical Education (LCME) Annual Medical School Questionnaire Part II. The questionnaire was sent in February 2014 to the deans of the 140 LCME-accredited medical schools with enrolled students.Therewasa 100%response rate.Eachquestionnaire was reviewed and attempts weremade to verify information and obtain missing data. Data for years other than 2013-2014 were obtained from previous LCME Annual Medical School Questionnaires. Author Affiliations:Division of UndergraduateMedical Education, American Medical Association, Chicago, Illinois. Corresponding Author: Barbara Barzansky, PhD, Division of Undergraduate Medical Education, AmericanMedical Association, 330 NWabash Ave, Ste 39300, Chicago, IL 60611 (barbara.barzansky@ama-assn.org). Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. Funding/Support: This research was funded solely by the AmericanMedical Association, which employs Dr Barzansky andMs Etzel.
Enhancing clinical trials accrual in an urban hospital setting.
Authors: N. B. Shuman, J. Wu, A. Malankar, Y. Novik
Journal: Journal of Clinical Oncology (2011)

e16564 Background: Facilitating clinical trials (CT) access to underserved populations in an urban hospital is an integral part of the NYUCI fellowship program. In 2009, to overcome barriers in CT enrollment at affiliate site, processes were targeted to promote awareness of available trials, simplify enrollment and enhance fellows’ participation in the CT process. This is a review of therapeutic CT accruals (TCTA) at affiliate site after reengineering the infrastructure. Methods: Under the direction of the site designated CT Medical Director and a CT nurse the CT program was comprehensively integrated into the outpatient clinic. With direct access to the faculty, fellows, patient navigators, and translation services the CT program was placed at the nucleus of clinic operations. The new infrastructure enabled education and support for investigational agent administration by the clinical staff and navigation of research patients through the complex medical system. It further increased visibility of the program and information on available trials. Lists of available trials were disseminated monthly to fellows, attending physicians, and major referring centers. Information about newly activated studies was disturbed to treating providers electronically. CT education sessions were offered to patients through support groups. New clinic patients were tracked and reviewed twice monthly for possible CTA. The affiliate CT leadership liaised with key personnel in the NYU CI and affiliate hospital to prioritize and promote appropriate CT and their activations. Results: TCTA from years ’07 through ‘10 were evaluated and analyzed. TCTA was stable from ‘07-‘09, and raised significantly in ‘10, 61%, as a result of these interventions. In ‘09, 30% (13/38) TCTA were enrolled by fellows, under the guidance of an investigator. In ‘10, patients enrolled on CT by fellows rose to 50% (30/61). Conclusions: With the centralized CT program, supported by fulltime research staff, visibility was increased and the enrollment process was simplified. Subsequently motivation of the fellows was increased, improving hands-on education in the CT process. As a result, there was more active screening and enrollment—which led to an approximately 61% increase TCTA in one year.
Extramedullary involvement correlates with late relapse after allogenic hematopoietic cell transplantation for acute leukemia
Authors: T. Kawakita, T. Matsui, Y. Inoue, T. Sakai, S. Takemoto, S. Nagakura, M. Hidaka, T. Kiyokawa, F. Kawano
Journal: Journal of Clinical Oncology (2008)

18005 Background: Allogenic hematopoietic cell transplantation (HCT) represents a potentially curative approach for patients with high risk acute leukemia due to graft versus leukemia (GVL) effect. Although there are some reports suggesting that GVL may not be prominent in extramedullary (EM) sites as in bone marrow (BM), relation between EM relapse and remission duration is unknown. Methods: In this retrospective analysis, 84 consecutive patients with acute leukemia who underwent HCT in a single institution between 1997 and 2006 were reviewed. Patients in there 1st or 2nd complete remission were divided in standard risk (SR) group, whereas relapsed or refractory patients were in high risk (HR) group. Results: Of 84 patients, 34 (40%) had ALL, 48 (57%) had AML, and 2 (2%) had AUL. 52 (62%) patients were in SR group, 32 (38%) were in HR group. Relapse occurred in 34 (40%) patients, including 10 (12%) EM involvement. All EM relapsed patients had subsequent BM relapse. Although relapse rate was higher in HR group (59%) than in SR (29%), EM involvement ratio was significantly higher in SR (47% vs 16%; p=0.049) than in HR. Interval from SCT to relapse was longer in patient with EM relapse (233 days vs 140 days; p= 0.035) than in patients without EM relapse. However, EM relapse rate did not show significant difference by acute GVHD grade. Conclusions: EM involvement correlates with late relapse and may be the trigger on BM relapse, especially in SR group. We hypothesize that because GVL can control leukemia in BM but can not in EM site where GVL effect is not prominent, leukemia cells will survive in EM site and relapse after longer RFS. No significant financial relationships to disclose.
Pemetrexed in second-line treatment in advanced NSCLC: An experience on 131 patients
Authors: A. Bearz, I. Garassino, R. Cavina, R. Talamini, A. Favaretto, M. Boccalon, C. Simonelli, S. Spazzapan, L. Fratino, U. Tirelli
Journal: Journal of Clinical Oncology (2008)

19114 Background: Pemetrexed has been registered as second line option for advanced Non Small Cell Lung Cancer (NSCLC). We collected data about 160 patients treated in second or further line therapy for advanced NSCLC in a post-registrative phase after progression to a previous treatment. We have already reported the data in Bearz A. et al, Lung Cancer in press, confirming the good profile of tolerability and efficacy shown in the registrative study (Hanna N et al, JCO 2004) with overall survival and progression free survival of 12 and 3 months respectively. Herein we analyzed the data about patients in second-line therapy only, 128, which we added data from 3 more patients. Patients and Methods: between May 2005 and March 2007 overall 131 patients with advanced NSCLC in progression to a first- line, platinum-based therapy, were treated with Pemetrexed 500 mg/sqm, q 21, in several Italian Institutions; M/F=95 (72.5%)/36 (27.5%), median age was 65.4 yrs (41–82), adeno-, squamous and other carcinoma in 67 (51%), 26 (19.8%), 38 (29%) respectively; PS 0–1 in 120 (91.6%), 2 in 11 patients (8.4%). Median overall survival and progression free survival were assessed by Kaplan and Meier method. Results: Analysis was performed up to October 31st 2007. Median overall survival was 12 months, the same as reported in the previous analysis; median progression free survival time was 3.1 months. Conclusion: we confirm the data observed with a miscellaneous of patients in second and further line of therapy and the promising overall survival reported for Pemetrexed in the post-registrative phase; progression free survival is even mildly improved when analysing patients in second-line therapy only. No significant financial relationships to disclose.
Prospective evaluation of a 12-gene assay on treatment recommendations in patients with stage II colon cancer.
Authors: Geetika Srivastava, Lindsay Anne Renfro, Robert J. Behrens, Margarita Lopatin, Calvin Chao, Gamini S. Soori, Shaker R. Dakhil, Rex Bradford Mowat, J. Phillip Kuebler, George P. Kim, Miroslaw Mazurczak, Mark Lee, Steven R. Alberts
Journal: Journal of Clinical Oncology (2013)

453 Background: A 12-gene assay (Oncotype DX Colon Cancer) has been clinically validated as a predictor of recurrence risk in stage 2 colon cancer patients following surgery. We conducted the first prospective study to characterize the impact of Recurrence Score results on medical oncologists’ recommendations regarding adjuvant chemotherapy in T3, Mismatch Repair-proficient (MMR-P) stage 2 colon cancer patients. Methods: Consecutive patients with resected stage 2A colon cancer who were candidates for adjuvant chemotherapy were consented and enrolled by 105 medical oncologists from 17 sites in the Mayo Clinic Cancer Research Consortium. Each patient’s tumor specimen was assessed by the Recurrence Score test (quantitative RT-PCR) and MMR (IHC). Prior to and after receiving these results, physicians completed surveys indicating their planned treatments given hypothetical or known MMR results, recorded as Observation (Obs), 5FU-based chemotherapy (5FU), or 5FU + Oxaliplatin (Oxal). Change in treatment recommendation intensity from baseline to follow-up was defined as: increased if change from Obs to 5FU +/- Oxal or from 5FU to 5FU+Oxal, decreased if change from 5FU + Oxal to 5FU or Obs, or from 5FU to Obs, or no change. Results: 187 of 221 patients enrolled were evaluable including 141 who were MMR-P (avg age 63, 65% ECOG PS 0, med tumor size 5 cm, 11% high grade, 91% with 12+ nodes examined). In the primary analysis treatment recommendations changed for 63 (45%) of 141 MMR-P patients, with intensity decreasing for 47 (33%) and increasing for 16 (11%). Recommendations for chemotherapy (5-FU +/- Oxal) decreased from 73 (52%) patients pre-assay to 42 (30%) post-assay. Increased treatment intensity was more likely at higher Recurrence Score values and decreased intensity at lower Recurrence Score values (p=0.011), and any change was more likely when MMR status was unknown at baseline (p = 0.041). Conclusions: In this prospective study, quantitative recurrence risk information provided by the Recurrence Score test was associated with treatment recommendation changes for 45% of T3 MMR-P stage II colon cancer patients. Use of the 12-gene assay may lead to overall reductions in chemotherapy.
Differential gene expression in prostate tissue according to vasectomy.
Authors: Kathryn M Wilson, Travis Gerke, Ericka Ebot, Jennifer A Sinnott, Jennifer R. Rider, Lorelei A. Mucci
Journal: Journal of Clinical Oncology (2016)

298 Background: We previously found that vasectomy was associated with an increased risk of prostate cancer, and particularly, risk of lethal prostate cancer in the Health Professionals Follow-up Study (HPFS). However, the possible biological basis for this finding is unclear. In this study, we explored possible biological mechanisms by assessing differences in gene expression in the prostate tissue of men with and without a history of vasectomy prostate cancer diagnosis. Methods: Within the HPFS, vasectomy data and gene expression data (20,254 genes) was available from archival tumor tissue from 263 cases, 124 of whom also had data for adjacent normal tissue. To relate expression of individual genes to vasectomy we used linear regression adjusting for age and year at diagnosis. We ran gene set enrichment analysis to identify pathways of genes associated with vasectomy. Results: Among 263 cases, 67 (25%) reported a vasectomy prior to cancer diagnosis. Mean age at diagnosis was 66 years among men without and 65 years among men with vasectomy. Median time between vasectomy and prostate cancer diagnosis was 25 years. Gene expression in tumor tissue was not associated with vasectomy status. In adjacent normal tissue, three individual genes were associated with vasectomy with Bonferroni-corrected p-values of &lt; 0.10: RAPGEF6, OR4C3, and SLC35F4. Gene set enrichment analysis found five pathways upregulated and seven pathways downregulated in men with vasectomy compared to those without in normal prostate tissue with a FDR &lt; 0.05. Upregulated pathways included several immune-related gene sets and G-protein-coupled receptor gene sets. Conclusions: We identified significant differences in gene expression profiles in normal prostate tissue according to vasectomy status among men treated for prostate cancer. The fact that such differences existed several decades after vasectomy provides support for the idea that vasectomy may play a role in the etiology of prostate cancer.
Randomized phase II study of 6 versus 12 months of adjuvant imatinib for patients with intermediate- or high-risk GIST.
Authors: Kazuya Muguruma, Yukinori Kurokawa, Toshimasa Tsujinaka, Junya Fujita, Takuya Nakai, Arimichi Takabayashi, Masako Hiramatsu, Masanori Terashima, Yoshiki Iwasaki, Junichi Hasegawa, Toshihiko Kira, Toshio Shimokawa, Seiichi Hirota, Toshirou Nishida
Journal: Journal of Clinical Oncology (2013)

9 Background: The Z9001 study revealed adjuvant imatinib for 1 year significantly improved RFS in GIST patients (pts). The SSGXVIII study compared 3 years with 1 year of adjuvant imatinib for high risk GIST pts, but there was no study to evaluate shorter period of imatinib administration than 1 year. We conducted a randomized phase II study to compare 6 months (6-mo) with 12 months (12-mo) adjuvant imatinib for intermediate or high risk GIST pts. Methods: Inclusion criteria included ECOG-PS of 0 or 1, age between 20 and 79 years, and primary KIT-positive GIST with intermediate or high risk according to the Fletcher criteria. Pts were randomized assigned to the 6-mo or 12-mo treatment of imatinib 400 mg/day after complete resection. The primary endpoint was recurrence-free survival (RFS). The study was designed as a randomized screening trial to evaluate non-inferiority with margin of hazard ratio 1.67, 1-sided alpha 0.2 and power 0.8. Results: Ninety-two pts were randomly allocated the 6-mo group (n=45) or the 12-mo group (n=47) between Dec 2007 and Aug 2011, which was well balanced for baseline characteristics. One patient was ineligible due to non-GIST (desmoid) tumor at a central review. The proportions of pts completed their assigned adjuvant treatment were 80% in the 6-mo and 70% in the 12-mo group. The first interim analysis was conducted at Sep 2012 with the median follow-up time of 33 months. The 1- and 2-year RFS were 82% and 65% in the 6-mo group and 96% and 86% in the 12-mo group, respectively. Hazard ratio of recurrence was 1.81 (95%CI: 0.84-3.91), and the 2-sided log-rank p value was 0.12. Adjuvant imatinib was well tolerated, with one patient of Gr. 4 rash and no treatment-related death. Because of the lower efficacy of the 6-mo group than expected, the Data and Safety Monitoring Committee recommended the early release of first interim analysis results. Conclusions: Adjuvant Imatinib for 6-mo was inferior in efficacy to that for 12-mo in terms of RFS. Shortening of the adjuvant imatinib duration is not recommended for intermediate or high risk GIST pts. Clinical trial information: UMIN000000950.
Breast imaging boot camp: A mammography quality improvement initiative.
Authors: Danielle Dupuy, Louise Miller, Christine B. Weldon, Jennifer M. Orsi, Terry Macarol, Anne Marie Murphy, Julia R. Trosman
Journal: Journal of Clinical Oncology (2012)

138 Background: In mammography, compression, and positioning are key quality factors. ACR standards suggest that compression should ensure that a breast is taut (drawn tight with no slack). In environmental scans, semi-structured interviews with cross discipline providers from Chicago mammography facilities, we found wide variation in radiology technologist’s understanding of standard compression and views. Optimal compression was reported from 12-45 lbs and some sites reported that four views are taken regardless of breast size. This discovery led to a mammography technologist training program as a quality improvement intervention. Methods: The Chicago Breast Cancer Quality Consortium contracted with Louise Miller, AART, CRT, and RTRM to lead a Breast Imaging Boot Camp and partnered with 4 hospitals to carry out the training. There were three components of the boot camp: a 1-day seminar for all mammography technologists, 1 day of hands on training for a limited number of techs and a train the trainer component where selected techs went through a 3-day intensive program with the goal of preparing them to provide ongoing education to the Chicago mam-tech community. A preliminary tool was developed and used randomly by radiologists during the training to examine the amount of tissue in the image from one year to the next, the presence or absence of an Inter-mammary fold and cleavage. Results: More than 120 radiology technologists attended a day-long seminar, 10 received hands on training, 4 of the 10 were trained to be future trainers. Participants rated their overall impression of the day-long seminar between 4 and 5 on a 5-point scale. During the hands-on training, radiologists assessing the images commented on significant improvements in image quality from the previous year’s mammogram. A quantitative evaluation process has been developed to examine the efficacy of the training and measure impact on mammography quality. This evaluation involves a 3 month and 1-year assessment that will take place in September of 2012 and again in May of 2013. Results of first evaluation will be available for presentation. Conclusions: Results from the evaluation will help review effectiveness of technologists post-training techniques and identify areas to improve.
Immune impact induced by PSA-tricom, a therapeutic vaccine for prostate cancer.
Authors: Ravi Amrit Madan, Kwong Yok Tsang, Caroline Jochems, Jennifer L. Marte, Jo A Tucker, James W. Hodge, Harpreet Singh, Ira Surolia, Geraldine Helen O'Sullivan Coyne, David J. Liewehr, Seth M. Steinberg, Christopher Ryan Heery, Jeffrey Schlom, James L. Gulley
Journal: Journal of Clinical Oncology (2014)

245 Background: PSA-TRICOM is a vector-based therapeutic cancer vaccine designed to generate a targeted anti-tumor immune response against prostate-specific antigen (PSA)–expressing tumor cells. Early clinical trials have evaluated the immunologic impact of this vaccine and demonstrated promising clinical activity. PSA-TRICOM is being evaluated in a phase III trial in metastatic castration resistant prostate cancer (mCRPC). Methods: We recently conducted a broad overview of both published and new data which analyzed the immune responses to PSA-TRICOM. Immune responses included ELISPOT for antigen-specific immune response and flow-cytometry analysis of peripheral immune cells. Results: 104 patients (pts) with prostate cancer were tested for T-cell responses and 59 out of 104 (57%) demonstrated a greater than or equal to 2-fold increase in PSA-specific T cells 4 weeks after vaccine. The responders had a median 5-fold increase relative to pre-vaccine levels. For most pts PSA-specific immune responses (likely memory cells) seen 28 days following the most recent vaccine are quantitatively similar to levels of circulating influenza-specific T cells in the same pts. In addition, 19 out of 28 pts (68%) evaluated demonstrated immune responses to tumor-associated antigens not present in the vaccine (antigen spreading). Since PSA-TRICOM is designed to generate a cellular (TH1 immune response), it is not surprising that 2 out of 349 pts (&lt;1.0%) demonstrated evidence of PSA antibody induction following vaccine. This suggests that post-vaccine PSA kinetics were not affected by PSA antibodies. Conclusions: PSA-TRICOM has demonstrated the ability to generate immune responses. Despite these findings, it is important to note that systemic immune response to PSA may underestimate the true therapeutic immune response since it does not measure cells that trafficked to tumor or antigen spreading. Furthermore, while the entire PSA gene is the vaccine, only one epitope of PSA is specifically evaluated in the T-cell responses. Further immune analysis continues in an ongoing phase III of PSA-TRICOM in mCRPC (NCT01322490), accruing worldwide, and two trials combining PSA-TRICOM with enzalutamide (biochemical recurrence/ NCT01875250 and mCRPC/ NCT01867333) currently accruing at NCI. Clinical trial information: multiple trials.