tbuckley/cabot-search huggingface dataset:
Should 3-weekly docetaxel (3WD) remain the standard for second-line therapy of advanced non-small-cell lung cancer (A-NSCLC)? Meta-analysis of 7 randomized clinical trials (RCTs) with 3WD comparator arms
Authors: F. De Marinis, H. Raftopoulos, E. Bria, C. Gridelli, A. Rossi, F. Grossi, R. J. Gralla
Journal: Journal of Clinical Oncology (2008)

8087 Background: 3WD was the reference standard for second-line treatment of A-NSCLC after demonstrating improved outcome over supportive care. RCTs with 3WD as a comparator were conducted, including single agent chemotherapy (SAC) (vinorelbine/ifosfamide, pemetrexed, vinflunine, oral topotecan) and gefitinib (G). The evaluation of 3WD as current standard is needed. Methods: Survival Hazard Ratios (HRs) were extracted from papers; Peto-Odds Ratio (OR) with 95% confidence interval (CI) were derived. Heterogeneity testing was applied. Absolute differences (AD) and the Number of patients Needed to Treat (NNT) were calculated. End-points were overall survival (OS) and overall response rate (ORR). A sensitivity analysis into 2 sub-groups according to comparator (SAC or G) and 3WD dose was performed. Different toxicity patterns did not allowed to analize overall tolerability, except for neutropenia. Quality of life was compared descriptively since different scales were used across studies (LCSS in 3 RCTs, FACT-L in 4 RCTs, and TOI scale in 2 RCTs). Results: 6 RCTs (4 SAC/3 G) with 4,291 patients were analyzed (table). When grouping by 3WD dose (75mg/m2 vs 60mg/m2), G-ORR was no longer significant (OR 1.15, 95% CI 0.80, 1.65; p=0.447). Grade 3–4 neutropenia was higher in 3WD arms when compared with SAC, with an AD of 12.9% which corresponds to a NNT of 7, although heterogeneous (p<0.0001). In terms of QoL, 4 trials favored comparators over 3WD in global scores (3 were G studies); in only 1 of these were differences ≥ 10%. Conclusions: This meta-analysis validates the ongoing role of 3WD as a reference standard for second-line therapy in A-NSCLC. In unselected patients, comparator agents have failed to demonstrate superiority in efficacy outcomes over 3WD. No major QoL differences were noted. However, a significant worst neutropenia is determined by 3WD, suggesting a restricted use in clinical practice. Pts (#RCTs) HR/OR (95% CI) p Het. (p) AD (%) NNT OS Overall 4,043 (6) 1.04 (0.97, 1.12) 0.20 0.64 - - SAC 1,947 (3) 1.05 (0.95, 1.16) 0.27 0.26 - - G 2,096 (3) 1.03 (0.93, 1.15) 0.48 0.74 - - ORR Overall 4,291 (7) 1.14 (0.91, 1.43) 0.24 0.04 - - SAC 2,195 (4) 0.84 (0.58, 1.22) 0.38 0.16 - - G 2,096 (3) 1.38 (1.03, 1.86) 0.029 0.15 2.8 35 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly, Roche, sanofi-aventis
Ipsilateral Breast Tumor Recurrence After Lumpectomy: Is It Time to Take the Bull by the Horns?
Authors: Eleftherios P. Mamounas
Journal: Journal of Clinical Oncology (2001)

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.2001.19.18.3798 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11559716 Ipsilateral Breast Tumor Recurrence After Lumpectomy: Is It Time to Take the Bull by the Horns? Eleftherios P. MamounasxEleftherios P. MamounasSearch for articles by this author Show More Northeastern Ohio Universities College of Medicine, Rootstown, OH, Aultman Cancer Center, Canton, OH https://doi.org/10.1200/JCO.2001.19.18.3798 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology
Aneuploidy fraction but not DNA index is important for the prognosis of patients with stage I and II breast cancer — 10-year results
Authors: M.F.X. Gnant, G.H. Blijham, A. Reiner, M. Schemper, M. Reynders, B. Schutte, C. van Asche, G. Steger, R. Jakesz
Journal: Annals of Oncology (1993)
Hospitalizations due to allergic reactions in Finnish and Swedish children during 1999-2011
Authors: J. E. Kivistö, J. L. P. Protudjer, J. Karjalainen, M. Wickman, A. Bergström, V. M. Mattila
Journal: Allergy (2016)

Background Several authors have reported on allergic reactions that resulted in presentation to the emergency department. However, studies of the secular trend of hospitalizations for paediatric allergic reactions, including anaphylaxis, are scarce. The aim of this study was to describe the secular trends of hospitalizations for allergic reactions, including anaphylaxis, among children aged 0–19 years in Finland and Sweden, and to establish the trend of prescribed epinephrine auto-injectors (EAI) among paediatric populations. Methods Using national databases, we identified hospitalizations between 1999 and 2011 with the primary diagnosis of allergic reaction per International Classification of Diseases, 10th Revision. Results Hospitalizations for allergic reactions totalled 1987 in Finland and 5433 in Sweden. Incidence rates increased in both countries. In Finland, the incidence of admission was 7.8 per 100 000 person-years at the start of the study period and 15.8 at the end of the study period. The corresponding numbers among Swedish children were 13.7 and 31.8 per 100 000 person-years. In Finland, 60% of children hospitalized were aged under 10 years. In Sweden, this proportion was somewhat lower, at 48%. Most hospitalizations occurred between May and September. The prevalence of EAI prescriptions in Finland increased by fourfold during the study period. In Sweden, such an increase was not identified. Conclusions The incidence of allergic reactions leading to hospitalizations between 1999 and 2011 increased in Finland and Sweden among children aged 0 to 19 years. In Finland, the incidence was lower throughout the study period compared to Sweden. Younger children constituted the majority of hospitalized children.
Long-term outcome after hyper-CVAD and imatinib (IM) for de novo or minimally treated Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL).
Authors: D. A. Thomas, S. M. O'Brien, S. Faderl, F. Ravandi Kashani, W. G. Wierda, M. Andreeff, R. S. Garris, R. E. Champlin, J. E. Cortes, H. Kantarjian
Journal: Journal of Clinical Oncology (2010)

6506 Background: The selective ABL tyrosine kinase inhibitor (TKI) IM was added to hyper-CVAD (fractionated cyclophosphamide, vincristine [VCR], doxorubicin, dexamethasone alternating with methotrexate and cytarabine) [Thomas, Blood 103:4396, 2004]. The final program dosed IM 600 mg days 1-14 of induction, 600 mg continuously courses 2-8, 800 mg during 24 mos of maintenance therapy with monthly VCR-prednisone interrupted by 2 intensifications (hyper-CVAD + IM), then IM indefinitely. Allogeneic stem cell transplant (aSCT) was performed in first CR as feasible. Methods: Fifty-four pts with IM naive de novo or minimally treated Ph-ALL were accrued from 2001-2006. Forty-five pts were untreated (n = 39) or refractory to 1 course (n = 6); 9 were in CR. Median age was 51 yrs (17–84); 13% had CNS disease. Results: CR rate was 93% (1 CRp, 1 PR, 1 ED). Molecular CR rate (MCR) prior to aSCT was 52%. 16 pts (33%) had aSCT in first CR within 5 mos (1-13). In the de novo group, 14 pts (med age 37 yrs) underwent aSCT in first CR whereas 33 pts (med age 53 yrs) did not. In de novo pts ≤ 60 yrs of age, 3-yr survival (OS) rates with or without aSCT were 77% vs. 57% (p = 0.1), respectively. In de novo pts ≤ 40 yrs of age, 3-yr OS rates were 90% with aSCT (n = 10) vs. 33% without aSCT (n = 6), p = 0.05. 3-yr CR duration (CRD) rate was 76% for 13 pts who achieved MCR prior to aSCT (2 had aSCT) compared with 63% for 31 pts who did not (14 had aSCT), p = 0.2. Neither CD20 expression nor additional chromosomal aberrancies influenced outcome. With median follow-up 77 mos (27-101+), 6 pts overtly relapsed on therapy after median 15 mos (8-42); 5 pts relapsed after change in TKI therapy for persistent Ph or increasing bcr-abl transcripts. Two relapsed after aSCT without IM maintenance. In the de novo group, 5 of 10 evaluable relapses had ABL kinase domain mutations [E459K, Y253H, Y253F, F359V, V338G]. Outcome with hyper-CVAD + IM remains favorable compared with hyper-CVAD; 3-yr CRD and OS rates were 68% vs. 24% and 54% vs. 15%, respectively, p < 0.001. Conclusions: Emerging data favors aSCT in 1st CR in the TKI era, particularly in younger pts. Substitution of IM with second- or later-generation TKIs may further improve outcome. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis
Dose-response study of a cryopreserved, autologous, hapten-modified melanoma vaccine (Mvax)
Authors: D. Berd, E. Bloome, H. Schea, B. Pinteur, F. Fossiez, E. Garcia, L. Chalus
Journal: Journal of Clinical Oncology (2008)

3059 Background: A vaccine consisting of autologous tumor cells modified with the hapten, dinitrophenyl (DNP) induces T cell- mediated immunity to the tumor cells, as measured by delayed-type hypersensitivity (DTH). The manufacturing process has been modified so that vaccines are cryopreserved immediately after preparation and stored at -70° until administered. We herein report a phase I-II trial of the modified product to confirm that it is safe and induces DTH responses to autologous melanoma cells. Methods: Immunocompetent patients with stage IIIB, IIIC, or IV melanoma were assigned in a double-blinded manner to one of four vaccine dosage arms: 5.0×106, 2.5×106, 0.5×106, or 0 tumor cells (diluent only). A previously optimized treatment schedule was followed, which included an "induction" dose of vaccine without adjuvant, followed by cyclophosphamide 300 mg/m2, followed by 6 weekly injections of vaccine mixed with BCG and a boost at 6 months. DTH responses to autologous tumor cells, both DNP-modified (DNP-TC) and unmodified (UN-TC), were tested before and after the course of vaccine administration. The efficacy of each dosage level was analyzed by a two-step design. Results: From 8 clinical sites, 63 patients had negative baseline DTH responses and completed post-vaccine DTH testing. Their post-vaccine DTH responses to DNP-TC by dosage arm are shown in the Table below. In the 5.0×106 dosage arm, 9/24 (38%) patients tested developed DTH responses to UN-TC as well. Linear regression analysis of all 63 evaluable patients indicated a significant direct relationship between the doses of vaccine administered and the post-treatment DTH responses (squared multiple R=0.446, p<.001). Conclusions: The autologous, hapten- modified melanoma vaccine, in its frozen form, was immunologically active in metastatic melanoma. The highest dose tested induced T cell immunity to autologous melanoma cells without serious toxicity; these results define the appropriate dosage range for a recently initiated phase III randomized trial. Dosage Arm Total No. (+) (≥5 mm induration) Effective 0 8 2 0 0.5 × 106 16 8 + 2.5 × 106 10 4 0 5.0 × 106 29 22 ++ Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AVAX Technologies AVAX Technologies
Phase I dose escalation trial of tremelimumab (CP-675,206) administered in combination with PF-3512676 in patients with melanoma or other advanced cancers
Authors: C. Underhill, M. Millward, S. Lobb, J. McBurnie, S. Meech, J. Gomez-Navarro, D. Readett, C. A. Bulanhagui
Journal: Journal of Clinical Oncology (2009)

3046 Background: Tremelimumab, a fully human monoclonal antibody specific for cytotoxic T-lymphocyte antigen 4 (CTLA4), and PF-3512676, an oligodeoxynucleotide toll-like receptor 9 agonist, are both novel, targeted immune modulators that can elicit durable antitumor responses in patients with advanced cancer. The tolerability of the combination of these two agents was investigated. Methods: Eligibility criteria included advanced melanoma or other advanced cancer, ECOG performance status of 0 or 1, and no history of autoimmune disease. Patients received intravenous tremelimumab (6.0, 10.0, or 15.0 mg/kg) every 12 weeks plus 0.05 mg/kg subcutaneous PF-3512676 weekly. Further escalation of PF-3512676 (to 0.1 mg/kg and 0.2 mg/kg) was planned once the MTD of tremelimumab had been determined. Primary endpoint was safety of the treatment combination; secondary endpoints included clinical activity, pharmacokinetics (PK), and immunologic measurements. Results: To date, 15 patients (melanoma, n = 12; mesothelioma, n = 2; prostate, n = 1) have been treated in this study: 3 at dose level 1 (6 mg/kg tremelimumab + 0.05 mg/kg PF-3512676); 6 at dose level 2 (10 mg/kg tremelimumab + 0.05 mg/kg PF-351276); and 6 at dose level 3 (15 mg/kg tremelimumab + 0.05 mg/kg PF-3512676). There were two DLTs at dose level 3: G3 diarrhea (n=1) and G3 nausea and vomiting associated with biopsy-proven duodenitis (n=1). One DLT, G3 hypophysitis, occurred at dose level 2. Patients with DLTs responded to corticosteroid therapy. Common adverse events included mild to moderate PF-3512676 injection site reactions (n=14), mild to moderate flu-like symptoms (n=9), G1/2 diarrhea (n=9), and G1/2 nausea (n=8). Presently, there are 2 PRs (13%) and 5 SDs among the 15 patients. Updated safety, efficacy, and PK data will be reported. Conclusions: At dose levels tested to date, the combination of tremelimumab and PF-3512676 has been tolerable and showed evidence of antitumor activity in patients with advanced melanoma. The MTD for this combination has yet to be determined, and a fourth intermediate dose level (10 mg/kg tremelimumab + 0.1 mg/kg PF-3512676) is currently being explored. [Table: see text]
Cetuximab plus docetaxel-cisplatin (DC) as first-line treatment for locally advanced or metastatic gastric cancer: Preliminary results of a phase II study
Authors: J. Fahlke, K. Ridwelski, A. Florschuetz, E. Kettner, M. Leithaeuser, H. Kroehning, P. Stuebs, K. Zierau, H. Lippert
Journal: Journal of Clinical Oncology (2009)

e15592 Background: Based on promising published data, this multicenter, phase II study was initiated to investigate a combined treatment using DC and cetuximab in the first-line setting for patients with gastric cancer. Methods: Patients aged 18–75 years with stage III (T4, nonresectable) or stage IV gastric cancer, ECOG performance status (PS) ≤2, and life expectancy ≥3 months were recruited to receive cetuximab (400 mg/m 2 on day 1 then 250 mg/m 2 q1w) and DC (D 75 mg/m 2 and C 75 mg/m 2 ; both as 1-h infusions on day 1 and then q3w). Treatment was stopped in the event of disease progression, intolerable toxicity, or consent withdrawal. Tumor staging was performed after cycle 3 and then every 12 weeks. The primary endpoint was overall response rate and secondary endpoints included time to progression, overall survival and toxicity. Planned accrual was 79 patients. A per-protocol interim response analysis was planned for the initial 20 evaluable patients. Results: Preliminary data are available for 30 patients; median age 64 [range: 40–73] years; median ECOG PS 1 [range: 0–2]; adenocarcinoma 87%. Median cycles administered were 3 [range: 1–14] and the median follow-up was 1.63 months. The overall response rate was 27.3% (complete response, n=1; partial response, n=5). Stable disease was observed in 10 patients, and disease progression in 6 patients. The most relevant NCI-CTC grade 3–4 hematologic events per patient were leukopenia and neutropenia (73%), anemia (13%), and febrile neutropenia (10%). Major grade 3–4 nonhematologic toxicities were nausea (30%), vomiting (20%), diarrhea (13%), acne (13%), and fatigue (13%). Conclusions: DC and cetuximab were well tolerated and resulted in promising response rates and a predictable toxicity profile. The study is ongoing. No significant financial relationships to disclose.
James Thomas Scott
Authors: H J Scott
Journal: BMJ (2015)

James Thomas Scott (“Tom “) enjoyed a fine reputation as a consultant physician at Charing Cross Hospital. He was a gifted teacher, clinical scientific researcher, and mentor. He left a legacy of clinical excellence and diagnostic acumen to the future leaders of academic and clinical rheumatology.

Tom was born and brought up in Mill Hill in north west London. He was an only child and his father, a civil servant in the postal services, died when he was 11. Tom was awarded a scholarship from the junior to the senior branch at University College School in Hampstead. During the war years he had to cycle to and from the school, where he excelled in all his academic activities. He was particularly gifted at Classics, studying Greek and Latin, but he was guided into a career of medicine because at the time he was advised that it had better career prospects. He trained at St Mary’s Hospital Medical School in Paddington. He was active in undergraduate activities: he rowed for the medical school and also took part in theatrical, dramatic, and operatic activities. He completed a house post in medicine at St Mary’s Hospital and a surgical house post in Lincoln. He moved on to Harefield Hospital as a junior registrar in medicine and deferred his national service until he acquired his membership of the Royal …
Small Cell Lung Cancer in Elderly Patients: A Review
Authors: Taofeek K. Owonikoko, Suresh Ramalingam
Journal: Journal of the National Comprehensive Cancer Network (2008)

Small cell lung cancer (SCLC) accounts for approximately 13% of all lung cancer cases. Approximately 40% of those cases are diagnosed in patients older than 70 years, and this proportion continues to rise in contrast to the continued decline in incidence of SCLC among the general population. The optimal strategy to manage limited-stage SCLC involves a combined modality approach with platinum-based chemotherapy and external-beam thoracic radiation therapy. For extensive-stage disease, platinum-based combination chemotherapy is a mainstay of therapy. Elderly patients present unique challenges in terms of drug metabolism and organ reserve, which impact the outcome of therapeutic interventions. However, limited data are available to guide management decisions for SCLC in elderly patients, and therefore this article discusses recommendations for treatment.
Impact of prior endocrine therapy on radiographic progression-free survival (rPFS) in patients (pts) with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC): Results from COU-AA-302.
Authors: Stephane Oudard, Thian San Kheoh, Margaret K. Yu, Matthew R. Smith, Eric Jay Small, Peter F.A. Mulders, Karim Fizazi, Dana E. Rathkopf, Fred Saad, Howard I. Scher, Joaquim Bellmunt, Mary-Ellen Taplin, Ian D. Davis, Dirk L. Schrijvers, Andrew Protheroe, Arturo Molina, Thomas W. Griffin, Johann Sebastian De Bono, Charles J. Ryan
Journal: Journal of Clinical Oncology (2014)

14 Background: Abiraterone acetate (AA), a prodrug of abiraterone, which is a selective androgen biosynthesis inhibitor, prolongs overall survival (OS) in mCRPC pts and is approved for use in this population. An exploratory analysis was conducted to determine the impact of prior endocrine therapy on clinical benefit of AA in COU-AA-302, a randomized phase 3 study of pts with chemotherapy-naive mCRPC. Methods: 1,088 pts (testosterone &lt; 50 ng/dL; receiving continuous gonadotropin-releasing hormone [GnRH] agonist if not orchiectomized) were randomized 1:1 to AA (1 g) + prednisone (P) (5 mg BID) or placebo + P alone. rPFS and OS were co-primary end points. rPFS was defined as time to first occurrence of bone scan progression by PCWG2 criteria, progression by CT/MRI by modified RECIST 1.0 criteria, or death, whichever came first. Comparison of the treatment effect on rPFS (investigator review at 55% of OS events) was made for the subgroups above or below the median duration of prior endocrine therapy in 2 categories: either prior GnRH agonist or prior antiandrogens. Cox model was used to obtain the HR and associated 95% CI with statistical inference by log rank statistic. Results: Most pts received prior GnRH agonists and antiandrogens (Table). rPFS was significantly more favorable with AA than P irrespective of the median duration of prior GnRH agonist or antiandrogen therapy. Increased median rPFS was observed in pts with longer prior exposure to GnRH agonists or antiandrogens comparing within both AA and P treatment groups. Conclusions: As shown in this COU-AA-302 exploratory analysis, duration of prior endocrine therapy, as analyzed after the onset of mCRPC, does not appear to impact clinical benefit of AA in pts with chemotherapy-naive mCRPC. Clinical trial information: NCT00887198. [Table: see text]
Abstract 15341: Mild Hypothermia Preserves Myocardial Conduction During Ischemia by Both Maintaining Gap Junction Localization and Preserving Sodium Channel Function
Authors: Michelle M Jennings, Lance D Wilson, Joseph S Piktel
Journal: Circulation (2014)

Introduction: Acute cardiac ischemia induces arrhythmogenic conduction velocity (CV) slowing and conduction block. Previously, we found in a canine model of global ischemia that mild hypothermia (MH, 32°C) attenuates ischemia-induced CV slowing, reducing arrhythmia susceptibility. We sought to determine the mechanism by which MH preserved myocardial CV. CV is dependent upon both cellular excitability (via sodium channels) and electrical coupling (via gap junctions, GJ, at the intercalated disk, ICD). Ischemic remodeling of connexin 43 (Cx43), the primary ventricular GJ protein, causes CV slowing. Hypothesis: MH prevents ischemia-induced CV slowing by preserving both GJ coupling and sodium channel (NaCh) excitability. Methods: Canine left ventricle wedge preparations at control (C, 36°C) or MH were subjected to 15 minutes of no-flow ischemia. Cx43 localization was assessed by confocal IF and Cx43 remodeling by western blot. In additional preparations, analysis of the action potential upstroke rise time (RT...