tbuckley/cabot-search huggingface dataset:
Are Doses and Schedules of Small-Molecule Targeted Anticancer Drugs Recommended by Phase I Studies Realistic?
Authors: Desamparados Roda, Begoña Jimenez, Udai Banerji
Journal: Clinical Cancer Research (2015)

Abstract Tolerability of molecularly targeted agents (MTA) used in cancer therapeutics is determined in phase I trials. We reviewed the reported incidence of toxicity in phase III trials at doses and schedules recommended by phase I trials to evaluate whether these recommendations are realistic when drugs are used in larger populations of patients. We systematically reviewed a safety profile of small molecule (SM-MTA) and mAb MTA (MA-MTA) approved by the FDA in the last 12 years. There was a significantly increased percentage of grade 3 or 4 adverse events reported with SM-MTA compared with MA-MTA [40% vs. 27%; RR 1.5; 95% confidence interval (CI), 1.10–2.25, P = 0.038] in phase III studies. Importantly, a substantial proportion of patients (45%) treated with SM-MTA required dose modifications due to drug-related toxicity in phase III trials. However, this toxicity was associated to a definitive study drug discontinuation in only 9%. Overall, 25% of SM-MTA declared recommended phase II doses below MTD based on pharmacokinetic–pharmacodynamic data and these trials were associated with a significantly reduced number of dose modifications in registration trials (32% vs. 50%; RR 0.64; 95% CI, 0.43–0.88, P = 0.01). Tolerability is going to come into further focus due to the need for combinations of SM-MTA and other anticancer agents. There was a higher incidence of grade 3–4 toxicity in phase III trials in combinations versus single-agent SM-MTAs (64% vs. 37%; RR 1.73; 95% CI, 1.3–2.3, P = 0.001). These results indicate that phase I studies underestimate toxicity while recommending doses of SM-MTA. Clin Cancer Res; 22(9); 2127–32. ©2015 AACR.
P-228 Novel 3D Image of Colon Neoplasm Mucosal Tissues using Multiphoton Microscopy
Authors: J.M. Lee, E.S. Kim, I.K. Yoo, S.H. Kim, S.J. Nam, H.S. Choi, B. Keum, Y.T. Jeen, H.J. Chun, H.S. Lee, C.D. Kim
Journal: Annals of Oncology (2015)
Validation of CA-125 concentration nadir within the normal range following primary treatment as a predictor of survival for epithelial ovarian cancer (EOC)
Authors: A. Prat, J. Del Campo, S. Peralta, S. Cedres, A. Perez, A. Gil, J. Martinez-Palones, A. Garcia, J. Baselga
Journal: Journal of Clinical Oncology (2007)

16007 Background: Recent studies suggest that the CA-125 nadir within the normal range after surgery and chemotherapy treatment is a predictor of survival (Crawford, ASCO 2004; Crawford, Ann Oncol 2005) and relapse (Markman, J Clin Oncol 2006). In order to validate these previous findings, we have conducted a retrospective analysis of patients (pts) treated in our institution for EOC. Methods: Between March 1, 1997, and October 30, 2005, all pts treated for EOC at Vall d'Hebron University Hospital were identified from the tumor registry database and screened retrospectively for their standard prognostic factors (age at diagnosis (=65 vs. &gt;65), stage (III-IV vs. IC-II), and suboptimal vs. optimal cytorreduction). Inclusion criteria: an elevated CA-125 at time of diagnosis (&gt;35 U/mL); primary treatment (PT) that consisted in surgery and intravenous carboplatin/paclitaxel for a maximum of 6–9 cycles; complete clinical and radiological response to initial treatment with normalization of CA-125 (=35 U/mL); and disease status at the time of last follow-up. Standard Kaplan-Meier methods were used to plot the progression-free survival (PFS) of members of each of the nadir groups. The relative contribution of the different potential correlates of prognosis was assessed by the Cox proportional hazards method. Results: 123 pts were identified: 64 Group A (=10 U/mL), 42 Group B (11–20 U/mL), 17 Group C (21–35 U/mL). Median age: 56. Stage IC 25%, II 13%, III 52%, IV 10%. Median follow-up 39.2 months (m). Median PFS was 69.7 m, 27.7 m, and 15.8 m for A, B and C, respectively (p&lt; .0001, log-rank test). The Cox model showed a highly-significant impact on PFS in relation to CA-125 nadir levels, residual tumor after surgery and stage. Hazard ratios (HR) for PFS (95% CI) of B vs. A, C vs. B, and C vs. A were 1.98 (p= .034), 2.35 (p= .02), and 4.67 (p&lt; .001), respectively. HR for PFS (95% CI) of suboptimal vs. optimal cytorreduction and stage III-IV vs. IC-II were 1.84 (p= .058) and 3.2 (p= .002), respectively. Conclusions: The CA-125 nadir in the normal range following PT for EOC is a reproducible predictor of PFS in stage IC-IV. Prospective studies of maintenance-consolidation therapies or different approaches in selected pts based on CA-125 nadir seem warranted. No significant financial relationships to disclose.
MAP plus maintenance pegylated interferon α-2b (MAP-IFN) versus MAP alone in patients (pts) with resectable high-grade osteosarcoma and good histologic response to preoperative MAP: First results of the EURAMOS-1 good response randomization.
Authors: Stefan S. Bielack, Sigbjorn Smeland, Jeremy Whelan, Neyssa Marina, Jane Hook, Gordana Jovic, Mark D. Krailo, Trude Butterfass-Bahloul, Thomas Kühne, Mikael Eriksson, Lisa A. Teot, Hans Gelderblom, Leo Kager, Kirsten Sundby Hall, Richard Greg Gorlick, R. Lor Randall, Pancras C. W. Hogendoorn, Gabriele Calaminus, Matthew Robert Sydes, Mark L. Bernstein
Journal: Journal of Clinical Oncology (2013)

LBA10504 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June, 3, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Recurrent Ovarian Cancer: Evidence-Based Treatment
Authors: Robert F. Ozols
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.5.1161 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11870155 Recurrent Ovarian Cancer: Evidence-Based Treatment Robert F. OzolsxRobert F. OzolsSearch for articles by this author Show More Fox Chase Cancer Center, Philadelphia, PA https://doi.org/10.1200/JCO.2002.20.5.1161 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Role of neoadjuvant treatment regimens for locally advanced pancreatic cancer.
Authors: Mohammad Alfayez, Janet Shirley Graham, Sally Hall, David McIntosh, Vivienne MacLaren, Alexander McDonald, Clinton Ali, Aisling Hennessy, Hedvig Karteszi, Nigel Jamieson, Ross Carter, Colin McKay, Euan Dickson, Derek B Grose
Journal: Journal of Clinical Oncology (2015)

444 Background: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related mortality worldwide. Lymph node involvement and resection margin status play important roles in predicting relapse. Resectable disease occurs in only 15–20% of total patients who present with PDAC. Unfortunately, margin involvement (R1) occurs in 70–80% of these patients. Emerging evidence has shown that the use of neoadjuvant chemotherapy and localised radiotherapy to downsize the tumours and increase the margin clearance (R0) rate may improve the overall survival of PDAC patients.We report a neoadjuvant therapy approach in the non-clinical trial setting of our large, tertiary cancer centre. Methods: We prospectively collected the outcome data and toxicity of 53 patients diagnosed with borderline resectable or initially non-resectable PDAC between 2012 and 2014. These patients received either FOLFIRINOX (FFX) or Gemcitabine/Capecitabine (GemCap) combination chemotherapies. Following restaging by computed tomography (CT), the patients proceeded to preo-operative 5-FU-based chemo-radiotherapy, immediate resection or subsequent palliativetherapies. Results: The median age was 65 (range 30 – 79) at PDAC diagnosis. Sixty-one percent (n=32) were male with the commonest anatomical location being the head of the pancreas (58%, n=31). The median follow up for survivors is 13.7 months (range: 5.3–24.4). The median overall survival was 18.3 months (95%, CI: 12.0–24.5). There was no statistical difference between overall survival in patients receiving FFX and GemCap chemotherapies. The margin clearance rate (R0) was 36% (4/11) in patients who proceeded to resection after neoadjuvant chemotherapy alone. The rate was 100% (4/4) in patients who received additional chemoradiation prior to surgery. Conclusions: This case series reveals that neoadjuvant therapy improved survival of patients with PDAC. In addition, we showed an increase in the R0 resection rate in patients who underwent chemoradiation prior to surgery. Further work is ongoing but based on historical data we believe that this neoadjuvant approach may lead to a long term survival benefit.
Prolonged warm ischemia time is associated with graft failure and mortality after kidney transplantation
Authors: Karthik K. Tennankore, S. Joseph Kim, Ian P.J. Alwayn, Bryce A. Kiberd
Journal: Kidney International (2015)

Warm ischemia time is a potentially modifiable insult to transplanted kidneys, but little is known about its effect on long-term outcomes. Here we conducted a study of United States kidney transplant recipients (years 2000-2013) to determine the association between warm ischemia time (the time from organ removal from cold storage to reperfusion with warm blood) and death/graft failure. Times under 10 minutes were potentially attributed to coding error. Therefore, the 10-to-under-20-minute interval was chosen as the reference group. The primary outcome was mortality and graft failure (return to chronic dialysis or preemptive retransplantation) adjusted for recipient, donor, immunologic, and surgical factors. The study included 131,677 patients with 35,901 events. Relative to the reference patients, times of 10 to under 20, 20 to under 30, 30 to under 40, 40 to under 50, 50 to under 60, and 60 and more minutes were associated with hazard ratios of 1.07 (95% confidence interval, 0.99-1.15), 1.13 (1.06-1.22), 1.17 (1.09-1.26), 1.20 (1.12-1.30), and 1.23 (1.15-1.33) for the composite event, respectively. Association between prolonged warm ischemia time and death/graft failure persisted after stratification by donor type (living vs. deceased donor) and delayed graft function status. Thus, warm ischemia time is associated with adverse long-term patient and graft survival after kidney transplantation. Identifying strategies to reduce warm ischemia time is an important consideration for future study.
Allogeneic Stem Cell Transplantation for Philadelphia Chromosome–Positive Acute Myeloid Leukemia
Authors: Vijaya Raj Bhatt, Mojtaba Akhtari, R Gregory Bociek, Jennifer N Sanmann, Ji Yuan, Bhavana J Dave, Warren G Sanger, Anne Kessinger, James O Armitage
Journal: Journal of the National Comprehensive Cancer Network (2014)

Philadelphia chromosome-positive acute myeloid leukemia (Ph+-AML) has a poor response to anthracycline- and cytarabine-containing regimens, high relapse rate, and dismal prognosis. Although therapy with imatinib and allogeneic stem cell transplantation (allo-SCT) is promising, relatively short follow-up limits understanding of long-term results of these therapies. This report describes the outcomes of 3 cases of Ph+-AML diagnosed and transplanted at the University of Nebraska Medical Center between 2004 and 2011. These patients, young and without major comorbidities, received induction therapy with 7 days of cytarabine and 3 days of idarubicin along with imatinib and consolidation therapy with high-dose cytarabine (with or without imatinib). All patients underwent 10/10 HLA-matched peripheral blood allo-SCT (sibling donor for first and third patients and unrelated donor for the second patient; all had acute graft-versus-host disease (GVHD), and the first and third patients had chronic GVHD. All patients are currently alive and experiencing complete remission at 116, 113, and 28 months after diagnosis, respectively. This report shows that the use of allo-SCT with resultant graft-versus-leukemia effect and the addition of imatinib can result in long-term remission and possible cure in some patients with Ph+-AML.
Circulating microRNA-203 predicts prognosis and metastasis in human colorectal cancer
Authors: Keun Hur, Yuji Toiyama, Yoshinaga Okugawa, Shozo Ide, Hiroki Imaoka, C Richard Boland, Ajay Goel
Journal: Gut (2015)

<h3>Background and aims</h3> Distant metastasis is a major cause of deaths in patients with colorectal cancer (CRC), which is partly due to lack of robust metastasis-predictive biomarkers. In spite of the important function of microRNA (miR)-203 in cancer metastasis, its clinical significance in CRC metastasis remains unknown. Here, we evaluated the potential role of serum miR-203 as a non-invasive biomarker for CRC metastasis. <h3>Methods</h3> MiR-203 expression was quantified by quantitative reverse-transcription PCR in 58 pairs of primary CRC (pCRC) and corresponding matched liver metastasis (LM), as well as 186 serum and 154 matched tissue specimens from patients with CRC in cohort 1. Next, we performed validation of miR-203 levels in serum from 144 patients with CRC in an independent cohort (cohort 2). Mouse models of CRC-associated metastases were established to identify the source of circulating miR-203. Expression patterns of miR-203 in tissues were determined by in situ hybridisation. <h3>Results</h3> MiR-203 expression was significantly upregulated in LM compared with matched pCRC tissues. Serum miR-203 levels were significantly upregulated in a stage-dependent manner, and high miR-203 expression was associated with poor survival in patients with CRC in both patient cohorts. Increased miR-203 levels in serum indicated high risk for poor prognosis (HR=2.1), as well as metastasis to lymph nodes (OR=2.5), liver (OR=6.2), peritoneum (OR=7.2) and distant organs (OR=4.4). Serum miR-203 levels were significantly higher in animals with liver or systemic metastasis compared with controls. <h3>Conclusions</h3> High levels of serum miR-203 associate with poor survival and metastasis, suggesting it to be a promising non-invasive prognostic and metastasis-predictive biomarker in patients with CRC.
Final efficacy results from OAM4558g, a randomized phase II study evaluating MetMAb or placebo in combination with erlotinib in advanced NSCLC.
Authors: D. R. Spigel, T. J. Ervin, R. Ramlau, D. B. Daniel, J. H. Goldschmidt, G. R. Blumenschein, M. J. Krzakowski, G. Robinet, C. Clement-Duchene, F. Barlesi, R. Govindan, T. Patel, S. V. Orlov, M. S. Wertheim, J. Zha, A. Pandita, W. Yu, R. L. Yauch, P. H. Patel, A. C. Peterson
Journal: Journal of Clinical Oncology (2011)

7505 Background: Met is associated with a poor outcome in many cancers, including NSCLC. Met activation is a mechanism of resistance to EGFR inhibition, supporting dual inhibition of Met/EGFR. MetMAb is a monovalent monoclonal antibody that specifically binds the Met receptor. Methods: OAM4558g is a global randomized, double-blind phase II study comparing MetMAb plus erlotinib (ME) to placebo plus erlotinib (PE) in 2nd/3rd line NSCLC. Tissue collection was mandatory to assess c-Met IHC expression levels (Met Dx). Co-primary endpoints were PFS in the Met Dx+ and ITT populations. Safety and OS were additional endpoints. Following the initial unblinding, Met Dx- patients (pts) were removed from ME. Results: 128 NSCLC pts were equally randomized to receive ME or PE. 95% of tissue was evaluable for c-Met IHC, 88% for EGFR and KRAS mutations (mut), and 75% for MET FISH. Baseline characteristics were well balanced. 54% of pts had Met Dx+ NSCLC, which was associated with a worse outcome (OS HR 2.52, PE cohort). A total of 99 PFS and 70 OS events have occurred, median follow up is 9.9mos. In the Met Dx+ group, ME resulted in a statistically and clinically significant improvement in both PFS and OS. An OS benefit from ME was observed in MET FISH+ NSCLC as well as in FISH-/IHC+; removing pts with EGFR mut did not alter results. Selective benefit of ME was not observed in other subgroups. E-related toxicities were comparable between treatment arms. Conclusions: Met Dx+ NSCLC represented more than half the population and was associated with a worse outcome. The addition of M to E in these pts significantly improved PFS and OS, resulting in a near 3-fold reduction in the risk of death. This benefit was not exclusive to EGFR mut or MET FISH+ and was observed in FISH-/IHC+ pts suggesting IHC is a more sensitive predictor of benefit from MetMAb. Median (mo) Population N PFS HR OS HR PE ME 95% CI P c-Met IHC+ 65 0.47 1.5 3.0 0.26–0.85 0.01 0.37 4.6 12.6 0.20–0.71 0.002 MET FISH+ (≥5 copies) 19 0.47 2.4 12.6 0.15–1.49 0.19 FISH-/IHC+ 37 0.44 3.6 7.1 0.17–1.15 0.09 FISH-/IHC+/EGFR wt 32 0.59 3.6 7.1 0.22–1.59 0.29 c-Met IHC-* 56 3.02 9.2 5.5 1.13–8.11 0.021 ITT* 128 1.09 8.2 7.1 0.62–1.91 0.76 * Initial data cut.
O009 : A prospective study of hepatitis B reactivation in patients with prior HBV exposure undergoing hematopoietic stem cell transplantation: Reactivation association with graft-versus-host disease
Authors: W.-K. Seto, T.S.Y. Chan, Y.-Y. Hwang, D.K.-H. Wong, K.S.-H. Liu, H. Gill, Y.-F. Lam, J. Fung, A.K.W. Lie, C.-L. Lai, Y.-L. Kwong, M.-F. Yuen
Journal: Journal of Hepatology (2015)
The tumor-targeting core–shell structured DTX-loaded PLGA@Au nanoparticles for chemo-photothermal therapy and X-ray imaging
Authors: Yongwei Hao, Bingxiang Zhang, Cuixia Zheng, Rui Ji, Xiangyi Ren, Fangfang Guo, Shili Sun, Jinjin Shi, Hongling Zhang, Zhenzhong Zhang, Lei Wang, Yun Zhang
Journal: Journal of Controlled Release (2015)
Management of chronic refractory cough
Authors: Peter G Gibson, Anne E Vertigan
Journal: BMJ (2015)

Chronic refractory cough (CRC) is defined as a cough that persists despite guideline based treatment. It is seen in 20-46% of patients presenting to specialist cough clinics and it has a substantial impact on quality of life and healthcare utilization. Several terms have been used to describe this condition, including the recently introduced term cough hypersensitivity syndrome. Key symptoms include a dry irritated cough localized around the laryngeal region. Symptoms are not restricted to cough and can include globus, dyspnea, and dysphonia. Chronic refractory cough has factors in common with laryngeal hypersensitivity syndromes and chronic pain syndromes, and these similarities help to shed light on the pathophysiology of the condition. Its pathophysiology is complex and includes cough reflex sensitivity, central sensitization, peripheral sensitization, and paradoxical vocal fold movement. Chronic refractory cough often occurs after a viral infection. The diagnosis is made once the main diseases that cause chronic cough have been excluded (or treated) and cough remains refractory to medical treatment. Several treatments have been developed over the past decade. These include speech pathology interventions using techniques adapted from the treatment of hyperfunctional voice disorders, as well as the use of centrally acting neuromodulators such as gabapentin and pregabalin. Potential new treatments in development also show promise.
Injuries in women's international ice hockey: an 8-year study of the World Championship tournaments and Olympic Winter Games
Authors: Markku Tuominen, Michael J Stuart, Mark Aubry, Pekka Kannus, Kari Tokola, Jari Parkkari
Journal: British Journal of Sports Medicine (2015)

Background We report the incidence, type, mechanism and severity of ice hockey injuries in women's international ice hockey championships. Methods All injuries in the International Ice Hockey Federation World Women's Championship, World Women's under-18 Championship and Olympic Winter Games tournaments were analysed over an 8-year period using a strict injury definition, standardised reporting and team physician diagnosis. Results 168 injuries were recorded in 637 games over an 8-year period resulting in an injury rate (IR) of 6.4 per 1000 player-games and 22.0/1000 player-game hours. The IRs were 2.7/1000 player-games for the lower body, 1.4 for the upper body, 1.3 for the head and face and 0.9 for the spine and trunk. Contusion was the most common injury followed by a sprain. The most commonly injured site was the knee (48.6% of lower body injuries; IR 1.3/1000 player-games). The Medial collateral ligament sprain occurred in 37.1% and ACL rupture in 11.4% of knee injuries. A concussion (74.3%; IR 1.0/1000 player-games) was the most common head injury. Conclusions and recommendations The risk of injury to female ice hockey players at World Championship and Olympic tournaments was about half of that observed in the men's Championships. Full facial protection decreases the risk of lacerations and should be continued in all future female tournaments. More effective prevention strategies for knee, ankle and shoulder injuries are needed in women's ice hockey. Improved concussion education is necessary to promote more consistent diagnosis and return to play protocols.
Macrophage incorporation into a 3D perfusion tri-culture model of human breast cancer
Authors: Teresa M DesRochers, Lillia Holmes, Lauren O'Donnell, Christina Mattingly, Stephen Shuford, Mark A O'Rourke, Mary B Rippon, William J Edenfield, Matthew R Gevaert, David E Orr, Howland E Crosswell
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Immunotherapy has recently shown promising clinical activity in multiple tumor types but standard in vitro immuno-oncology models for preclinical and clinical predictivity are lacking. Macrophages have been shown to have both tumor promoting and tumor preventing properties
Clinical Features and Outcome in Newly Diagnosed Hodgkin Lymphoma Patients Presenting with PET/CT-Ascertained Focal Skeletal Lesions.
Authors: Tarec Christoffer El-Galaly, Martin Hutchings, Karen Juul Mylam, Peter de Nully Brown, Anne Bukh, Peter Kamper, Hans Erik Johnsen, Francesco d'Amore
Journal: Blood (2012)
Observations on Incidence of Gallstone Disease
Authors: R MARGOLESE, B MITMAKER, A D TEITLEBAUM, H C BALLON
Journal: JAMA (1963)

In an attempt to ascertain whether a real increase in the incidence of gallstone disease existed at the Jewish General Hospital, Montreal, it was determined that, from 1935-1960 inclusive, 1846 gallbladder operations were performed. The operative mortality was 0.9%. The yearly trend in the number of gallbladder operations performed was generally found to be upward. Significant statistical increases were noted in 1959 and 1960. During the same years significant increases were noted in the proportion of males treated, particularly in the eighth decade of life. As a percentage of total surgical discharges, during 1960, the incidence of gallbladder operations exceeded that of appendectomies, which are being performed less frequently than previously. The peak incidence for gallbladder operations, for both sexes, occurred during the fifth decade of life. These observations suggest that in this hospital population a real increase in the incidence of gallbladder operations has probably occurred. It was not possible to form an opinion regarding possible changes in the clinical aspects of gallbladder disease.
In high-risk pregnant women, an individualized lifestyle intervention reduced gestational diabetes mellitus
Authors: Lorraine Lipscombe
Journal: Annals of Internal Medicine (2015)

Source Citation Koivusalo SB, Rönö K, Klemetti MM, et al. Gestational diabetes mellitus can be prevented by lifestyle intervention: the Finnish Gestational Diabetes Prevention study (RADIEL): a randomized controlled trial. Diabetes Care. 2015;Jul 29. [Epub ahead of print]. 26223239