tbuckley/cabot-search huggingface dataset:
Chemotherapy for Muscle-Invasive Bladder Cancer: Better Late Than Never?
Authors: Guru Sonpavde, Jennifer B. Gordetsky, Mark E. Lockhart, Jeffrey W. Nix
Journal: Journal of Clinical Oncology (2016)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.A 64-year-old man with a history of cigarette smoking but no significant comorbidities presented with hematuria and dysuria. Computed tomography scans demonstrated a mass and thickening of the bladder wall and no evidence of metastasis. His laboratory evaluation showed normal blood cell counts and comprehensive metabolic panel with a calculated creatinine clearance of more than 60 mL per minute. A transurethral resection of the bladder tumor and biopsy identified transitional cell carcinoma or urothelial carcinoma invading the muscularis propria of the bladder. On the basis of the bladder-confined mass on computed tomography scan, the tumor was assigned a clinical stage of cT2N0. The patient was advised to undergo neoadjuvant chemotherapy followed by radical cystectomy (RC). The patient had multiple concerns regarding neoadjuvant chemotherapy, particularly toxicities, especially the possibility of chronic neurologic and renal toxicities, and the potential harm from delay of RC, especially if the bladder cancer was resistant to chemotherapy. After a discussion of approximately 1 hour, he elected to proceed with upfront RC and extended lymph node dissection in conjunction with construction of a neobladder. Pathology revealed pathologic extravesical urothelial carcinoma, with disease in one of 25 lymph nodes removed (ypT3N1). Four weeks after RC, he returned to discuss further management with the medical oncologist. He exhibited an Eastern Cooperative Oncology Group performance status of 0, normal blood cell counts, and a calculated creatinine clearance of more than 60 mL per minute.
Phase II study of sequential chemotherapy with cisplatin (P) in combination with infusional 5FU/LV (PFL) followed by irinotecan (Ir) + 5FU/LV (IrFL) followed by docetaxel (T) + 5FU/LV (TFL) in patients (pts) with metastatic gastric carcinoma (MGC) by the Gruppo Oncologio Nord-Ovest (GONO)
Authors: F. Loupakis, G. Masi, S. Bursi, V. Picone, L. Mentuccia, C. Granetto, E. Fea, R. Murr, A. Antonuzzo, A. Falcone
Journal: Journal of Clinical Oncology (2007)

15059 Background: 5FU in combination with P can be considered a standard treatment for MGC. Ir and T are active agents with not complete cross-resistance with P and 5FU. The combination of Ir or T with P and 5FU is feasible but with substantial toxicities. A different way to include Ir and T in the first-line treatment of MGC is to use them sequentially to a P and 5FU containing regimen. Methods: we conducted a phase II study of first-line sequential chemotherapy in MGC pts with measurable disease (RECIST criteria). Treatment consisted of: 3 cycles of PFL (biweekly P 50 mg/sqm d1, LV 200 mg/sqm d1 and 5FU 3200 mg/sqm 48-h c.i. starting on d1) followed by 3 cycles of IrFL (biweekly Ir 180 mg/sqm d1 and 5FU/LV) followed by 3 cycles of TFL (biweekly T 50 mg/sqm d1 and 5FU/LV). Evaluation of disease was performed every 3 cycles. Results: 46 pts have been enrolled. Pts characteristics are: median age = 60 years (37–75), M/F = 36/10, sites of disease (single/multiple) 9/37, ECOG PS 0/1 = 27/19. Treatment was well tolerated. Grade 3–4 non-haematological toxicities were: diarrhea in 2,5% pts with PFL; diarrhea and asthenia in 2,5% and stomatitis in 5% pts with IrFL; stomatitis in 5,7% pts with TFL. Grade 3/4 neutropenia was observed in 14% pts with PFL, 15% with IrFL and 22,9% pts with TFL. Nor febrile neutropenia neither toxic deaths have occurred. Two pts had not evaluable disease and 6 are still receiving treatment. We observed 1 CR and 8 PR with PFL (RR 24%) among the 38 evaluable pts. IrFL improved responses in 10 pts while 4 pts progressed and TFL further improved responses in 6 pts while 5 pts progressed. Response rate at the end of the planned 9 cycles was 40% (4 CR, 11 PR; 95% CI 25–58%). At a median follow-up of 15.5 mos median TTP is 6.8 mos and median OS is 13.5 mos. Conclusions: this sequential treatment is feasible with a very favourable safety profile and produces encouraging results in terms of activity and efficacy in a population of unselected MGC patients. Final data will be presented at the meeting. Partially supported by A.R.C.O. Foundation. No significant financial relationships to disclose.
Temozolomide and intravenous irinotecan for refractory Ewing’s sarcoma: A retrospective review
Authors: L. M. Wagner, N. McAllister, A. Rausen, B. McCarville, R. Goldsby, K. Albritton
Journal: Journal of Clinical Oncology (2005)

8526 Background: Preclinical models show sequence-dependent synergy with temozolomide (T) + irinotecan (I), and a pediatric Phase I trial has been reported (Clin Cancer Res; 10: 840–8). Because responses were seen in patients with Ewing’s sarcoma (ES), additional patients were treated with these commercially available drugs following study completion. Methods: We reviewed data from all patients with refractory ES treated with combined T + I at 3 institutions, including 7 patients treated on the above Phase I trial. Results: Fourteen patients (median 18 yrs, range 7–33) have received a total of 74 courses to date (median =5). All received standard 5-drug therapy initially, and 8 had stem cell transplants (6 tandem) for metastatic disease. Four relapsed on initial therapy; others relapsed a median of 7 mos (range 5–13) after completion. All but four received from 1–5 prior treatment regimens, and 8 patients received prior pelvic irradiation. Relapse sites were primary bone (5), lung (8), bone metastases (6), and marrow (2). Patients received oral T 100 mg/m2/day on days 1–5 + intravenous I at 10 mg/m2/day (10), 15 mg/m2/day (3), or 20 mg/m2/day (1) on days 1–5 and 8–12. Subsequent courses were planned every 21 days (7) or 28 days (7). Grade 3–4 diarrhea or vomiting was seen in 14% of courses. Excluding the 2 patients with marrow disease, grade 3–4 neutropenia or thrombocytopenia occurred in 9 (14%) of 66 courses; 2 patients received G-CSF. One complete, 2 partial, and 3 minor responses (31%, 44%, and 46% reduction in tumor volume) were seen in 12 evaluable patients. Additionally, 2 patients without measurable disease were progression-free for 6 and 13 months before electively stopping therapy. Two more patients continue on therapy past course 6 with stable or responding disease. Nine patients (64%) had substantial symptomatic relief with the first course of treatment, irrespective of ultimate response. Over 80% of I doses were administered at home. Conclusion: T + I is tolerable in heavily pretreated patients, and shows activity in highly refractory ES. Home administration was safe and is reasonable for palliative care. A formal Phase II study using uniform doses and schedules will better define activity. No significant financial relationships to disclose.
Outbreak of hand, foot and mouth disease caused by Coxsackie A16 virus in a childcare centre in Croatia, February to March 2011
Authors: S Ljubin-Sternak, V Slavic-Vrzic, T Vilibić-Čavlek, B Aleraj, I Gjenero-Margan
Journal: Eurosurveillance (2011)

We describe an outbreak of hand, foot and mouth disease (HFMD) in a childcare centre in a district of Zagreb county, north-west Croatia. A total of eleven cases of HFMD occurred in the childcare centre and another nine were reported from nearby areas in the district. Coxsackie A16 virus was diagnosed in 13 clinical specimens obtained from 11 symptomatic and asymptomatic children. All cases resolved without complications.
Post-traumatic stress disorder and interleukin 6 – Authors' reply
Authors: Ives Cavalcante Passos, Mirela Paiva Vasconcelos-Moreno, Leonardo Gazzi Costa, Maurício Kunz, Elisa Brietzke, Joao Quevedo, Giovanni Salum, Pedro V S Magalhães, Flávio Kapczinski, Márcia Kauer-Sant'Anna
Journal: The Lancet Psychiatry (2016)
Defining The Optimal Dose Of Alemtuzumab In Unrelated Donor Reduced Intensity Allografts: A UK Retrospective Study
Authors: Kile Green, Rob Sellar, Laura Jardine, Janice Ward, Paul Ferguson, Pip Nicolson, Kim Pearce, Venetia Bigley, Graham Jackson, Sandeep Nagra, Anne M Dickinson, Kirsty Thomson, Stephen Mackinnon, Charles Craddock, Matthew P. Collin, Karl S Peggs
Journal: Blood (2013)
Differences between old (70-80 years) and very old (80+ years) cancer patients: Results from the IN-GHO registry.
Authors: F. Honecker, U. Wedding, K. Rettig, S. Huschens, C. Bokemeyer
Journal: Journal of Clinical Oncology (2010)

9085 Background: Elderly cancer patients (pts) are a heterogeneous population. Data from clinical trials in very old cancer pts is scarce, and little is known about treatment decisions and outcomes. The internet based IN-GHO registry prospectively collects data of elderly cancer pts from >100 centers in Germany and Austria. Methods: Data from 1580 cancer pts were analysed, comparing results between two subgroups: pts 70-80 years (1199) and pts 80+ years (381) by Chi-square or Mann-Whitney U test. Analyses included results from a comprehensive geriatric assessment (CGA), physicians' rating (fit vs compromised vs frail) and pts' self rating of fitness for treatment (Likert scale 1= very fit to 6 = very unfit), type (combination vs. monotherapy vs. no) and dosage (full vs. adapted) of treatment, as well as mortality within 5-7 months. Results: Mean age was 76.7 years (range 70-97), 43.9 % were male, 71.5% had a solid tumor, and 28.5% a hematological malignancy. 80+ pts showed a significantly higher proportion of both female pts and hematological malignancies (p=0.015 and p<0.001). Physicians rated fitness for treatment as fit 56.8%, compromised 37.8%, or frail 5.4%. Pts rated their fitness for treatment as 1= 19.5%, 2 = 31.3%, 3 = 27.5%, 4 = 15.9%, 5 = 4.7%, 6 = 1.1%. More pts 80+ years were judged compromised or frail, both by physicians' or pts' assessment (p<0.01 and p=0.018), whereas the incidence of one or more geriatric syndromes (dementia, incontinence, falls, depression) was not different. Significant differences were observed in several parameters of CGA between the two groups. Significantly more pts 80+ years received either no therapy, or monotherapy and/or dose- adapted treatment (all p<0.001). However, death rates within 5-7 months were not different between the two groups. Conclusions: The internet based registry is a valuable tool to gain data on prognostic factors, treatment, and outcome in old and very old cancer pts. In several items of CGA, significant differences exist between age groups 70-80 and 80+ years, documenting higher incidences of limitations in very old cancer pts. Results of CGA should be validated in treatment algorithms for this population. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Janssen-Ortho Janssen-Ortho Johnson & Johnson Janssen-Ortho
Treatment of acquired immunodeficiency syndrome--related Kaposi's sarcoma with lymphoblastoid interferon.
Authors: A Rios, P W Mansell, G R Newell, J M Reuben, E M Hersh, J U Gutterman
Journal: Journal of Clinical Oncology (1985)

Twelve homosexual patients with Kaposi's sarcoma associated with the acquired immune deficiency syndrome (AIDS) were treated with a preparation of purified human lymphoblastoid interferon (Wellferon [Burroughs Wellcome, Research Triangle Park, NC]). They were given a dose of 20 X 10(6) U/m2 intramuscularly daily for approximately two months. Responders continued their treatment on a maintenance schedule of 20 X 10(6) U/m2 three times a week. Four patients experienced complete remissions, and four experienced partial remissions that resulted in a total response rate of 67%. The median duration of treatment was 14 weeks (7 to 28+ weeks), and the median response duration was 28+ weeks (19 to 29+ weeks). Of the four patients in complete remission, one relapsed at 25 weeks and one at 26 weeks; the other two remained in complete remission at 28 and 29+ weeks. The clinical toxicity consisted of chills, fever, fatigue, and asthenia. Hematologic toxicity was similar to that previously described for other preparations of alpha-interferon and consisted of moderate leukopenia and thrombocytopenia. Asthenia, a condition present in all 12 patients, was severe in 50%. A minimal tumor burden, the absence of circulating interferon before treatment, and a performance status of greater than or equal to 90% on the Karnofsky scale were related to an improved response rate. Measurement of immunologic parameters showed significant declines in the already impaired T cell levels, lymphocyte blastogenic response to concanavalin A, monocyte-mediated antibody-dependent cellular cytotoxicity, and monocyte-adherence. Activation of natural killer cells was not noted, and no life-threatening infections occurred during treatment. These data suggest that human lymphoblastoid interferon is an active agent in the treatment of Kaposi's sarcoma, and its use warrants further study in a larger number of patients.
Impact of Early Breast Cancer Screening on Mortality Among Young Survivors of Childhood Hodgkin’s Lymphoma
Authors: David C. Hodgson, Cecilia Cotton, Pavel Crystal, Paul C. Nathan
Journal: JNCI Journal of the National Cancer Institute (2016)

Female survivors treated with thoracic radiation therapy (RT) for childhood cancer experience increased risks of breast cancer (BC). There are currently no data quantifying the potential mortality gains of early BC screening among such survivors. A mathematical model of BC development was used to evaluate the marginal benefit of early-initiated screening of female survivors of adolescent Hodgkin's lymphoma (HL) starting at age 25 years on BC mortality compared with screening initiated at age 40 years. Sensitivity analyses were performed to evaluate the robustness of the estimates over a plausible range of conditions. For survivors treated at age 15 years, the absolute risk of BC mortality by age 75 years was predicted to decrease from 16.65% with no early screening to 16.28% (annual mammography), 15.40% (annual MRI), 15.38% (same-day annual mammography and MRI), and 15.37% (alternating mammography and MRI every six months). Approximately 80 patients would need to be invited to MRI-based screening to prevent one BC death. In sensitivity analyses, the number needed to invite to MRI-based screening to prevent one BC death ranged from 71 to 333. Combinations of MRI plus mammography were predicted to produce 99.52 false positives per 1000 screenings done between age 25 to 39 years. These findings are the first to indicate that early MRI-based screening should reduce BC mortality among women treated with RT for adolescent HL. The magnitude of this benefit is superior to that described for other accepted screening indications although MRI can produce a substantial rate of false-positive results.
Programming Mechanical and Physicochemical Properties of 3D Hydrogel Cellular Microcultures via Direct Ink Writing
Authors: Joselle M. McCracken, Adina Badea, Mikhail E. Kandel, A. Sydney Gladman, David J. Wetzel, Gabriel Popescu, Jennifer A. Lewis, Ralph G. Nuzzo
Journal: Advanced Healthcare Materials (2016)

3D hydrogel scaffolds are widely used in cellular microcultures and tissue engineering. Using direct ink writing, microperiodic poly(2‐hydroxyethyl‐methacrylate) (pHEMA) scaffolds are created that are then printed, cured, and modified by absorbing 30 kDa protein poly‐ l ‐lysine (PLL) to render them biocompliant in model NIH/3T3 fibroblast and MC3T3‐E1 preosteoblast cell cultures. Spatial light interference microscopy (SLIM) live cell imaging studies are carried out to quantify cellular motilities for each cell type, substrate, and surface treatment of interest. 3D scaffold mechanics is investigated using atomic force microscopy (AFM), while their absorption kinetics are determined by confocal fluorescence microscopy (CFM) for a series of hydrated hydrogel films prepared from prepolymers with different homopolymer‐to‐monomer ( M r ) ratios. The observations reveal that the inks with higher M r values yield relatively more open‐mesh gels due to a lower degree of entanglement. The biocompatibility of printed hydrogel scaffolds can be controlled by both PLL content and hydrogel mesh properties.
The Relationship Between the Grade of Peripheral Neuropathy and the Skin Blood Perfusion in Chemotherapy-Induced Peripheral Neuropathy Patients, and the Effects of Compression Therapy
Authors: T. Ohno, T. Mine, H. Yoshioka, M. Kosaka, S. Matsuda, M. De Kerckhove, C. De Kerckhove, K. Inoue, M. Haraguchi, M. Kitajima, S. Ito, H. Tokai, T. Tanaka, J. Irie
Journal: Annals of Oncology (2014)
A role model for iconoclasts
Authors: Kamran Abbasi
Journal: Journal of the Royal Society of Medicine (2015)

David Sackett’s death earlier this year earned widely published obituaries. Known as the father of evidence-based medicine, Sackett transformed the way clinicians, researchers and medical editors think about evidence. Sackett challenged orthodoxy and the lazy assumptions of experts. In this month’s article from the James Lind Library, in possibly his last contribution to a medical journal, Sackett explains why he became a clinician-trialist.1

As Sackett developed as a clinician and his diagnostic skills improved, he became increasingly frustrated with the ‘profession’s collective ignorance’ about how he should treat patients or whether he should treat them at all. These frustrations shaped Sackett’s career, influenced the profession whose collective ignorance he disliked and helped patients receive better treatments.

Researchers and students of methodology in doubt over the reasons for four of the fundamental pillars of randomised controlled trials will find a clear explanation in Sackett’s account. His observations and experiences influenced the establishment of random allocation of treatments, concealment of treatment allocation from patients and clinicians, intention to treat analyses and blinded outcomes assessment.

The importance of evidence is underlined by one of this month’s research papers. Chana et al.2 examine the sacred cow of using cardiothoracic ratio on chest X-ray to detect cardiac dysfunction. In a retrospective analysis of 400 patients at two UK hospitals, the researchers find that, in the context of an acute admission, cardiothoracic ratio measured on postero-anterior or antero-posterior chest X-rays has limited value in detecting ventricular dysfunction.

You sense that Sackett would have approved of the questioning nature of this study. Challenging the profession’s collective ignorance may be hazardous for clinicians but generally reduces the hazard that patients are exposed to. Iconoclasts, alive or dead, will never be short of admirers.
Multicenter randomized phase II trial of methotrexate (MTX) and temozolomide (TMZ) versus MTX, procarbazine (PCB), vincristine (VINC), and cytarabine (Ara-C) for primary CNS lymphoma (PCNSL) in elderly patients.
Authors: A. M. Omuro, L. Taillandier, O. L. Chinot, H. Ghesquieres, C. Soussain, V. Delwail, S. Choquet, M. Tanguy, T. Lamy, K. Hoang-Xuan
Journal: Journal of Clinical Oncology (2010)

TPS144 Background: This study is an effort to establish treatment alternatives for elderly (>60y) PCNSL pts, who in the context of an aging population already comprise >55% of pts. High dose MTX and radiotherapy (RT) are the mainstay of PCNSL treatment, but pts over 60 are not candidates because of RT-related neurotoxicity risks (90-100% among surviving pts). Therefore, developing age-specific treatments and optimized MTX regimens is crucial. TMZ is an emerging option in PCNSL due to blood brain barrier crossing properties, favorable toxicity and single agent activity. We treated 23 elderly pts in a pilot study of MTX 3 g/m2 and TMZ 100 mg/m2. Objective response rate (ORR) was 55%; median event-free survival (EFS)= 8 m; median overall survival (OS)= 35 m. Toxicity profile was excellent, prompting a phase II study in a joint effort of the ANOCEF and GOELAMS groups (10 institutions), sponsored by the French government. To optimize the regimen, we adopted a dose-dense TMZ schedule, aiming to overcome chemoresistance mediated by MGMT; prophylactic G-CSF was used to decrease toxicity and avoid dose reductions that may compromise drug brain penetration. Because of lack of historic controls, a randomized phase II design was used, with a standard regimen (MPV-A, Abrey 2000) as a control arm. Methods: Newly diagnosed PCNSL pts over 60 and KPS≥40 are eligible. 1 cycle=28 days. Experimental arm: 3 cycles of MTX (3.5 g/m2 D1 and D15) and TMZ (100-150 mg/m2 D1-5 and 15-19). Control arm: 3 cycles of MTX (3.5 g/m2 D1 and D15), PCB 100 mg/m2 (D1-7), VINC (1.4 mg/m2 D1 and 15), followed by Ara-C consolidation (3g/m2/d X2). The primary endpoint is 1-y progression-free survival. A one-stage Fleming design was used for each arm (minimal: 25%, interesting: 45%, α= 5%, β=10%), N=46/arm, total 92 pts. Secondary endpoints: EFS, ORR, OS and toxicity. Correlative studies: neuropsychological evaluation, quality of life (EORTC QLQ-30/ BM 20), analysis of genetic variants in methionine metabolism predicting MTX toxicity, tumor MGMT and gene expression profiling. Enrollment has been on time (N=81), demonstrating that a randomized study in elderly PCNSL is feasible. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche AstraZeneca, Roche, Schering-Plough Genentech, Roche, Schering-Plough
Fluoranthenes: Quantitative Determination in Cigarette Smoke, Formation by Pyrolysis, and Tumor-Initiating Activity&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN4"&gt;4&lt;/xref&gt;
Authors: Dietrich Hoffmann, Gunter Rathkamp, Stephen Nesnow, Ernest L. Wynder
Journal: JNCI Journal of the National Cancer Institute (1972)

A method for the determination of fluoranthene in cigarette smoke was developed. The nonvolatile particulate matter of cigarette smoke was distributed between 2 solvent pairs, chromatographed on alumina, and the fluoranthene concentrate analyzed by gas chromatography, highspeed liquid chromatography, and paper chromatography. 9-14C-phenanthrene and 9-14C-benz[α]anthracene served as internal standards. The mainstream smoke of an 85-mm U.S. blended nonfilter cigarette contained 263 ng of fluoranthene, 116 ng of 1-, 3-, and 7-methylfluoranthene, 68 ng of 2- and 8-methylfluoranthene, and more than 100 ng of dimethylfluoranthenes. Pyrolysis experiments suggested that in cigarette smoke the fluoranthenes were partially formed via the Diels-Alder addition of acenaphthylenes with volatile dienes. Of the 5 possible monomethylfluoranthenes, 2- and 3-methylfluoranthenes were active as tumor initiators as were 2,3-and 7,8-dimethylfluoranthenes. 2-Methylfluoranthene was also active as a complete carcinogen. These results and the relatively high concentrations of active methylfluoranthenes in the “tar” suggest that these alkylfluoranthenes contribute to the tumor-initiating activity of tobacco smoke.—J Natl Cancer Inst 49: 1165–1175, 1972.
Altering the course of schizophrenia: progress and perspectives
Authors: Mark J. Millan, Annie Andrieux, George Bartzokis, Kristin Cadenhead, Paola Dazzan, Paolo Fusar-Poli, Jürgen Gallinat, Jay Giedd, Dennis R. Grayson, Markus Heinrichs, René Kahn, Marie-Odile Krebs, Marion Leboyer, David Lewis, Oscar Marin, Philippe Marin, Andreas Meyer-Lindenberg, Patrick McGorry, Philip McGuire, Michael J. Owen, Paul Patterson, Akira Sawa, Michael Spedding, Peter Uhlhaas, Flora Vaccarino, Claes Wahlestedt, Daniel Weinberger
Journal: Nature Reviews Drug Discovery (2016)