tbuckley/cabot-search huggingface dataset:
Sport medicine at its peak
Authors: E Laura Cruz
Journal: British Journal of Sports Medicine (2017)

Welcome to the CASEM issue of BJSM ! The Canadian Academy of Sport and Exercise Medicine is the only organisation in Canada dedicated to sport and exercise medicine physicians. Established almost 50 years ago, CASEM has been the leader in SEM education and training of new sport and exercise physicians throughout its existence.

In a typically Canadian manner, CASEM has quietly elevated itself, with all 850 or so members, to a well respected position on the international academic stage. Our members …
Impact of Hypoxia As Novel Microenvironmental Factor On Drug Susceptibility of Primary CLL Cells
Authors: Malte Huelsemann, Lukas P. Frenzel, Dunja Baatout, Julia Claasen, Sebastian Theurich, Laurent Kintzelé, Hans Jiro Becker, Michaela Patz, Christian P. Pallasch, Michael S. von Bergwelt-Baildon, Michael Hallek, Clemens-Martin Wendtner
Journal: Blood (2012)
Association of IGF1R overexpression (OE) with outcome in invasive urothelial carcinoma (UC) of urinary bladder.
Authors: Nilda Gonzalez-Ribbon, Jenny J. Kim, Alcides Chaux, Enrico Munari, Shiela F. Faraj, Carla Ellis, Rajni Sharma, Trinity Bivalacqua, Mark Schoenberg, Michael Anthony Carducci, George J. Netto
Journal: Journal of Clinical Oncology (2013)

4523 Background: Insulin-like growth factor-1 receptor (IGF1R) is a transmembrane tyrosine kinase receptor involved in cell proliferation and differentiation. IGF1R is overexpressed in several tumors including UC and is currently under investigation as a target of Rx. We here explore IGF1R expression in UC, its association with clinicopathologic parameters and prognostic role. Methods: Fivetissue microarrays (TMA) were constructed from 100 cystectomy specimens performed for invasive UC at our institution (1994 to 2007). Formalin-fixed paraffin-embedded paired tumor and benign samples were spotted 3-4 times each. Membranous IGF1R staining was evaluated using immunohistochemistry (G11, Ventana Medical Systems). A scoring method analogous to that of Her2 expression in breast cancer was used and the highest score was assigned to each tumor. IGF1R was considered overexpressed in cases with score 1. Endpoints of the study included overall survival (OS) and disease-specific survival (DSS). Patients were followed-up for a median of 33.5 months (range 1, 141 months). Results: IGF1R OE was found in 62% of UC. No differences were noted between normal urothelium and UC regarding IGF1R OE (74% vs. 60%; P=0.14). IGFR1 OE was more frequent in tumors from African-American patients compared to Caucasians (100% vs. 59%, P=0.04). Tumors at stage pT4 overexpressed IGF1R more frequently than tumors at stages pT1-pT3 (71% vs. 29%, P=0.005). No association with other analyzed clinicopathologic parameters such as patient's age or gender, muscularis propria invasion, or lymph node metastasis) was found. OS and disease-specific survival (DSS) rates were 58% and 69%, respectively. Patients with tumors overexpressing IGF1R had a lower OS and DSS compared to those without IGF1R OE (Mantel-Cox P=0.0007 and P=0.006, respectively). Using Cox proportional hazards regression, IGF1R OE remained a significant predictor of OS (HR=3.49, P=0.001) and DSS (HR=3.54, P=0.007) after adjusting for pathologic stage. Conclusions: OE of IGF1R was found in 62% of UC. High stage tumors overexpressed IGF1R more frequently than low stage tumors. Further, IGF1R OE was a significant independent predictor of OS and DSS in invasive UC.
Au Nanoclusters and Photosensitizer Dual Loaded Spatiotemporal Controllable Liposomal Nanocomposites Enhance Tumor Photodynamic Therapy Effect by Inhibiting Thioredoxin Reductase
Authors: Fuping Gao, Weiping Zheng, Liang Gao, Pengju Cai, Ru Liu, Yaling Wang, Qing Yuan, Yuliang Zhao, Xueyun Gao
Journal: Advanced Healthcare Materials (2017)

Photodynamic therapy (PDT) is a minimally invasive therapeutic procedure of tumors with high selectivity and low side effect. However, it is usually not efficient in long‐lasting tumor control. One of the main reasons is tumor cells develop some protective mechanisms that help them to deal with oxidative stress in the environment. The thioredoxin system in cancer is an important antioxidant defense system. Au nanoclusters could effectively inhibit thioredoxin reductase (TrxR) in tumor cell cytoplasm. Herein, Au nanoclusters and photosensitizer Chlorine 6 (Ce6) are co‐loaded in spatiotemporal controllable liposomal nanocomposites. pH responsive molecule inserted in lipid bilayer greatly contributes to the instability of the lipid membrane in lysosomal at low pH environment. Then the payloads can rapidly release into cytoplasm. Au nanoclusters effectively inhibit TrxR in cytoplasm and enhance the photodynamic‐induced intracellular reactive oxygen‐free radical concentration, improving the effect of PDT. Breast cancer is chosen as a tumor model and the Au nanoclusters and photosensitizer co‐loaded liposomal nanocomposites are studied to improve the effect of PDT both in vitro and in vivo, and its corresponding mechanism is investigated. This study develops a new application of gold nanoclusters and provides a new train of thoughts for enhancing the effect of PDT.
Patterns of care in elderly patients with squamous cell carcinoma of the head and neck: A SEER-Medicare analysis.
Authors: Noam Avraham VanderWalde, Anne-Marie Meyer, Seth D Tyree, Leah L. Zullig, William Ruffin Carpenter, Mark C Weissler, Carol G. Shores, David N. Hayes, Bhishamjit S. Chera
Journal: Journal of Clinical Oncology (2012)

5539 Background: Head and neck squamous cell carcinoma (HNSCC) is predominantly a disease of the elderly, however age and co-morbidity may affect therapy decisions. The purpose of this study was to assess the patterns of care of elderly HNSCC patients and identify factors associated with non-receipt of surgery and chemoradiation (CRT). Methods: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database (1992-2007) we identified a retrospective cohort of non-metastatic HNSCC patients and categorized them into treatment cohorts. Comparisons were made between surgery vs. non-surgery, and CRT vs. non-CRT cohorts. Multivariate logistic regression models examined factors associated with non-receipt of treatment. Variables included tumor location, stage, year of diagnosis, age, gender, marital status, race, comorbidity, race-comorbidity interaction, SEER region, socioeconomic variables, and hospital affiliations. Results: The final cohort of 11,336 were 63% male and 83% white. 52% had no co-morbidities, 44% had oral cavity HNSCC, 52% were diagnosed between 2002 and 2007, 58% had surgery, and 21% received CRT. For the CRT vs. non-CRT model, increasing age (OR = 0.93; 95% CI 0.92 -0.94) and non-whites with co-morbidity (OR = 0.71; 95% CI 0.55 – 0.92) were associated with decreased likelihood of receiving CRT. More advanced staged disease, oropharyngeal tumor location, and diagnosis after 2002 were associated with increased likelihood of receiving CRT. For the surgery versus non-surgery model, age was not associated with receipt of surgery (OR 0.99; 95% CI 0.99-1.00), nor was existence of comorbidity in white patients (OR 0.97; 95% CI 0.88-1.05). However, recent year of diagnosis, non-oral cavity tumor location, and advanced stage were all associated with reduced likelihood of receiving surgery. During the 15 year surveillance period, patients were less likely to receive surgery, and CRT was used more often. Conclusions: Age may influence the non-receipt of CRT in this elderly cohort but does not appear to be significantly associated with the non-receipt of surgery. There has been an increasing trend in the receipt of CRT with a decrease in surgery over the past 15 years.
What is optimal timing of post prostatectomy radiotherapy? Is adjuvant radiotherapy equivalent to early salvage radiotherapy? The “RAVES” phase III randomized clinical trial.
Authors: Maria Pearse, Andrew Kneebone, Gillian M. Duchesne, Richard Fisher, Carol Fraser-Browne, Mark Frydenberg, Annette Haworth, Chakiath Jose, David John Joseph, Tee Lim, John Matthews, Jeremy Millar, Mark Sidhom, Nigel Spry, Colin Tang, Sandra Turner, Scott G. Williams, Kirsty Wiltshire, Henry Woo, Ian D. Davis
Journal: Journal of Clinical Oncology (2012)

TPS4690 Background: Three randomised trials have demonstrated a significant benefit of adjuvant post prostatectomy radiotherapy in patients with positive margins, extra capsular extension or seminal vesicle involvement, and it should be regarded as current standard of care. However, adopting this approach will expose nearly half of such patients to unnecessary radiotherapy and potential treatment morbidity. Salvage radiotherapy, if given early, is recognised to be effective. The RAVES trial is designed to compare these two approaches, and was developed in collaboration with the Trans Tasman Radiation Oncology Group (TROG), Australian and New Zealand Urogenital and Prostate Trials Group (ANZUP) and the Urological Society of Australia and New Zealand (USANZ). It aims to test the hypothesis that active surveillance with early salvage radiotherapy is non-inferior to adjuvant radiotherapy with respect to risk of biochemical failure (defined as PSA level ≥ 0.40 ng/mL and rising). Methods: Patients must have at least one of the following risk factors: positive margins, extracapsular extension or seminal vesicle involvement. They must start radiotherapy within 4 months of radical prostatectomy (RP) and have an undetectable PSA (≤ 0.10 ng/ml) prior to randomisation. Patients receiving androgen deprivation or who have an artificial hip are excluded. Eligible patients are randomised to either: Arm 1: Adjuvant RT (64Gy in 32#) commenced within 4 months of RP, or Arm 2: Active surveillance with 3 monthly PSA tests and commencement of early salvage RT (64Gy in 32#) if PSA rises ≥ 0.20 ng/ml. Stratification is by seminal vesicle invasion, Gleason Score, pre-operative PSA, margin positivity (no/yes) and radiotherapy institution. A sample size of 470 patients is required to detect a 10% non-inferiority margin in the 5-year biochemical failure-free rate between the adjuvant and active surveillance arms. As of 31 Jan 2012, 186 patients have been recruited across 26 centres in Australia and New Zealand. A meta analysis with the MRC RADICALS and GETUG-17 trials will be prospectively designed to detect a survival difference between the two approaches.
Annals Graphic Medicine - Anatomy of a Donut Hole
Authors: Grace E. Farris
Journal: Annals of Internal Medicine (2017)

Web Exclusives2 May 2017Annals Graphic Medicine - Anatomy of a Donut HoleFREEGrace E. Farris, MDGrace E. Farris, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G16-0024 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Disclosures: The author has disclosed no conflicts of interest. Form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G16-0024.Author/Illustrator Information: Grace E. Farris, MD, is an assistant professor of medicine at Icahn School of Medicine at Mount Sinai and chief of hospital medicine at Mount Sinai West hospital in New York, New York.Corresponding Author: Grace E. Farris, MD, Mount Sinai West, Department of Medicine, 1000 Tenth Avenue, New York, NY 10019; e-mail, Grace.[email protected]org.Author Contributions: Conception and design: G.E. Farris.Drafting of the article: G.E. Farris.Final approval of the article: G.E. Farris.This article was published at Annals.org on 28 March 2017. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byA Letter to New InternsDarren B. Taichman, MD, PhD, Darilyn V. Moyer, MD, and Christine Laine, MD, MPH 2 May 2017Volume 166, Issue 9Page: W53-W57KeywordsConflicts of interestDisclosureHealth careHospital medicine ePublished: 28 March 2017 Issue Published: 2 May 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Definitive thoracic radiotherapy in oligometastatic stage IV non-small cell lung cancer (NSCLC).
Authors: Annemarie Therese Fernandes, Eric Xanthopoulos, Elizabeth Handorf, Surbhi Grover, Sonam Sharma, Beth Eaby-Sandy, Tracey L. Evans, James Stevenson, Corey J. Langer, Nandita Mitra, Smith Apisarnthanarax, Lilie Lin, Ramesh Rengan
Journal: Journal of Clinical Oncology (2012)

e18032 Background: Intrathoracic tumor control in patients (pts) with metastatic NSCLC is controversial as most die of distant disease. But a subset of good performance status pts with minimal burden of extrathoracic disease may benefit aggressive treatment. We report outcomes in a subset of pts with oligometastatic NSCLC treated with definitive radiotherapy (RT) to the primary tumor. Methods: We identified29 stage IV pts from 01/04 - 08/10 who had ECOG ≤2 and ≤4 metastases who received ≥50 Gy thoracic RT with chemotherapy. Pts were assessed for local control, overall survival and toxicity. An exploratory analysis was performed matching these pts to pts receiving chemotherapy (CT) alone. Results: In the 29 chemoradiotherapy (CRT) pts, median age was 57 yrs, 72% had ECOG 1 and 91% were staged with PET. Median survival was 22 months. Eight patients had grade 2+ pneumonitis. Nineteen patients had grade 2+ esophagitis. Next, 2 CT pts were matched with each CRT pt on 4 factors: age, ECOG, and presence of multi-organ or contralateral lung disease. We excluded 4 CRT pts who did not match 2 CT controls. Median survival was 22 vs 9 months (p &lt;0.01) for patients given CRT vs CT. Median time to local failure was 18 vs 6 months (p = 0.01). Median survival in locally controlled pts was 39 vs 19 months in pts with local failure (p = 0.02). On multivariable analysis, radiation (p &lt;0.01, OR = 0.33), multiple metastatic organs at diagnosis (p &lt;0.01, OR = 2.14), and gender (p &lt;0.01, OR = 0.41) were associated with overall survival. Conclusions: Treatment ofNSCLC patients with oligometastatic disease with definitive dose radiation therapy may provide a local control and overall survival benefit in a subset of patients with minimal extrathoracic burden of disease.
Implementation of an electronic surveillance database for patients with colorectal cancer.
Authors: Yan Li, Michael Rizzo, Pamela Kim Washington, Olakunle Ajayi, Matthew Dixon
Journal: Journal of Clinical Oncology (2017)

231 Background: An electronic surveillance database was created to monitor patients for five years following curative treatment for colorectal cancer. The database serves as an alert system and data repository for imaging, serology, and colonoscopy surveillance tests preloaded for each patient in accordance with NCCN guidelines based upon TNM cancer staging. Methods: The chiefs of Surgery and Oncology defined end-user specifications for the Filemaker Pro database. Key features include preloaded tests based upon NCCN guidelines, expected date of completion, and exam results. The database also tracks tests overdue or ordered but not yet obtained. A new workflow consisting of a monthly report of new colorectal cases from Pathology and a meeting of surgical and oncology physicians and physician assistants to review the report, update the database with new patients, and identify patients due for follow-up was established. Results: 250 cases are currently being monitored. By 2019, the database is poised to be the largest in Kaiser Permanente (KP) dedicated to active surveillance following colorectal cancer treatment. Conclusions: In addition to ensuring that individual patients obtain surveillance tests at the intervals based upon national guidelines for each TNM classification, the database can also be used to assess surveillance results and recurrence rates. The database format has also proven invaluable for other services. The Thoracic service recently created a database modeled after colorectal surveillance to begin tracking lung cancer patients. Beginning in 2016, the colorectal database became a Regional KP initiative and will be incorporated into HealthConnect (electronic medical record).
UNIRAD: Multicenter, double-blind, phase III study of everolimus plus ongoing adjuvant therapy in ER<sup>+</sup>, HER2<sup>-</sup> breast cancer.
Authors: Thomas Denis Bachelot, Sylvie Chabaud, Anne-Laure Martin, J Lemonnier, Mario Campone, Fabrice Andre
Journal: Journal of Clinical Oncology (2013)

TPS653 Background: Advances in adjuvant treatment and highly effective endocrine therapies have resulted in better prognosis and survival among patients (pts) with hormone-receptor-positive (HR + ; ER + and/or PgR + ) breast cancer (BC). Despite this, high risk pts (&gt;3N + and/or T3/4) are likely to relapse during/after adjuvant therapy. In a pivotal phase 3 trial (BOLERO-2), everolimus (EVE, an oral mammalian target of rapamycin [mTOR] inhibitor), plus exemestane demonstrated clinical efficacy in postmenopausal pts with HR + , human epidermal growth factor receptor-2–negative (HER2 – ) advanced BC progressing on non-steroidal aromatase inhibitors. Administering EVE earlier, concurrent with adjuvant endocrine therapy (ET) may lower relapse rates, especially in pts with high and/or persistent nodal involvement after neoadjuvant therapy. This study (UNIRAD) will evaluate the safety and effectiveness of adding EVE to adjuvant ET in pts with ER + , HER2 – non-metastatic BC, who are disease-free following 3y of adjuvant ET. Methods: This multi-center, double-blind, phase 3 study will randomize adult (≥18y) women with non-metastatic ER + , HER2 - BC, any T, pN + (≥4 if initial therapy and ≥1 after neoadjuvant therapy), who are disease-free following 3y of adjuvant ET to EVE (10mg/d) plus ongoing ET versus placebo (PBO) plus ongoing ET for a total adjuvant therapy duration of 5y. Stratification is by country, ET (tamoxifen or aromatase inhibitors), previous adjuvant versus neoadjuvant therapy, and age (≤70 versus &gt;70y). Follow-up will continue for 5y after treatment. The primary endpoint is disease-free survival (DFS) with EVE versus PBO. Secondary endpoints include overall survival (OS), event-free survival, distant metastasis-free survival, DFS and OS in selected subgroups, safety, incidence of secondary cancers, quality of life, and predictive value of mTOR activation markers on DFS. Results: Accrual to the UNIRAD study will begin in March 2013 (planned N = 1984). Updated information will be presented. Clinical trial information: 2012-003187-44.
A phase II study of biweekly irinotecan and mitomycin C combination therapy in patients with fluoropyrimidine-resistant advanced gastric cancer: the Japan Clinical Oncology Group trial (JCOG0109)
Authors: T. Hamaguchi, A. Ohtsu, I. Hyodo, Y. Arai, H. Takiuchi, H. Fujii, K. Yamaguchi, M. Yoshida, K. Shirao
Journal: Journal of Clinical Oncology (2004)

4071 Background: Fluoropyrimidine (F) derivatives have remained the mainstay of treatment for advanced gastric cancer (AGC). Irinotecan (CPT-11) is active as a single agent against AGC. Preclinical evidence indicates that mitomycin C ( MMC) acts synergistically with CPT-11. The objective of the present study was to evaluate the efficacy and toxicity of a combined CPT-11 and MMC regimen in patients (pts) with AGC that in resistant to F-based regimens. Methods: Eligibility criteria included histologically proven AGC, disease progression during F-based regimens or disease recurrence within 6 months of the completion of F-based adjuvant treatment, an age of 75 years or younger, PS 0 to 2, measurable disease, adequate organ functions, and written informed consent. Each course of chemotherapy consisted of 5 mg/m2 of MMC by bolus injection and 150 mg/m2 of CPT-11 by 90-minute infusion. Courses were repeated every 2 weeks. The total dose of MMC was limited to 50mg/m2. Results: Between April 2002 and July 2003, 45 pts were enrolled. The patients' characteristics were as follows: median age, 64 years (range, 36–75 years); male/female, 33/12 and PS 0/1/2, 24/21/0. Forty (89%) pts had previously received chemotherapy for metastatic disease, while 5 had received only adjuvant chemotherapy. The total and median number of administrations was 281 and 6 (range, 1–10). Grade 4 neutropenia and thrombocytopenia occurred in 29% and 2% of the pts, respectively. Febrile neutropenia occurred in 9% of the pts. Grade 3 anorexia, nausea, and diarrhea occurred in 20%, 13%, and 2%, respectively. Twelve PRs were obtained among the 45 eligible pts, and the overall response rate was 27% (95% confidence interval: 14–40%). The median time to progression was 4.1 months, while median survival time is too early to evaluate. Conclusions: A combination of CPT-11 and MMC appears to be an active and feasible treatnent strategy in patients with F-resistant AGC. This regimen warrants further clinical investigation, although follow-up data on survival should be taken into consideration. No significant financial relationships to disclose.
Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as prognostic factors for locally advanced pancreatic cancer patients.
Authors: Byung Min Lee, Seung Yeun Chung, Jee Suk Chang, Kyong Joo Lee, Si Young Song, Jinsil Seong
Journal: Journal of Clinical Oncology (2017)

326 Background: It is well known that locally advanced pancreatic cancer patients have a poor prognosis. Recently, hematologic markers showing systemic inflammatory status such as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have aroused much attention due to its potential to predict patient survival. In this study, we investigated whether pre-treatment NLR and PLR independently and in combination would be significant prognostic factors for survival in locally advanced pancreatic cancer patients. Methods: A total of 497 locally advanced (borderline resectable and unresectable) pancreatic cancer patients who received neoadjuvant or definitive chemoradiotherapy (CCRT) between January 2005 and December 2015 were included in this study. NLR and PLR prior to the start of treatment within 2 weeks were defined as pre-treatment NLR and PLR. We divided the patients with the median values of pre-treatment NLR and PLR; NLR &lt; 2.44 group (n = 248), NLR ≥ 2.44 group (n = 249), PLR &lt; 149 group (n = 248) and PLR ≥ 149 (n = 249) group. Overall survival (OS) and progression-free survival (PFS) were compared between each group for NLR and PLR. Results: Median overall survival was 15.7 months (range, 2.3-128.5 months). For NLR, the OS, PFS rates were significantly lower in the NLR ≥ 2.44 group, with 1-year OS rates of 67.9% and 61.5% (p = 0.003) and 1-year PFS rates of 38.1% and 32.4% (p = 0.003), for NLR &lt; 2.44 and ≥ 2.44 group, respectively. The PLR ≥ 149 group also showed significantly poorer OS and PFS than PLR &lt; 149 group. The 1-year OS rates were 68.1% and 61.3% (p = 0.029) and 1-year PFS rates were 37.9% and 32.5% (p = 0.027), for PLR &lt; 149 and ≥ 149 group, respectively. When multivariate analysis was performed, NLR ≥ 2.44 remained as a significant adverse factor for OS (p = 0.011) and PFS (p = 0.026). PLR &gt; 149 also proved to be a significant factor for poorer OS (p = 0.003) and PFS (p = 0.021). Conclusions: Elevated pre-treatment NLR and PLR independently and in combination significantly predicted poor OS and PFS. Pre-treatment NLR and PLR are useful prognostic factors for OS and PFS in locally advanced pancreatic cancer patients.