tbuckley/cabot-search huggingface dataset:
External quality assurance of breast cancer pathologic reporting in Kenya
Authors: M. E. Trinkaus, S. Sayed, S. Gakinya, W. Hanna, Z. Moloo, Y. Rahim
Journal: Journal of Clinical Oncology (2009)

e11586 Background: Eighty percent of women diagnosed with breast cancer (BC) in East Africa present with advanced disease; current literature suggests a preponderance of triple negative/basal like breast cancer in this subset of African women. These studies are limited by their retrospective nature, small numbers, and unclear quality of pathologic specimen reporting. The objective of this study is to provide external quality assurance (EQA), quality control, and validation of hormone receptor and Her2 status of breast cancer specimens from Kenya. Methods: 108 retrospectively identified BC tumour blocks from the Aga Khan University Hospital (Nairobi, Kenya) during 2006–2008 will undergo repeat pathologic assessment for estrogen receptor (ER), progesterone receptor (PR), and Her2 status at Sunnybrook Health Sciences Center (Toronto, Canada).Currently at the Aga Khan University Pathology Lab, ER,PR and Her2 testing is performed manually once every two weeks using Heat Induced Antigen Retrieval and Dako reagents including the ENVISION detection system. Parallel controls of known tissue reactivity are also run; however there is currently no formal EQA. Results: Results will be used to identify areas of improvement in specimen handling and pathology reporting. Conclusions: Standardized and accurate pathologic assessment of BC specimens in East Africa is essential for establishing centres of excellence in Kenya and the wider East African region for hormone receptor and Her2 neu analysis. Results would contribute to understanding the prevalence of triple negative disease in East Africa, lead to improved treatment recommendations and patient outcomes, and serve as a foundation for prospective studies in East Africa. No significant financial relationships to disclose.
A Cure for Paroxysmal Nocturnal Hemoglobinuria Using Molecular Targeted Therapy Specific to a Driver Mutation
Authors: Takamasa Katagiri, Ryo Tominaga, Keisuke Kataoka, Akio Maeda, Hiroshi Gomyo, Ishikazu Mizuno, Tohru Murayama, Seishi Ogawa, Shinji Nakao
Journal: Blood (2015)
Interim safety results of a global early access protocol (EAP) of abiraterone acetate (AA) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) progressing after taxane-based chemotherapy.
Authors: Daniel J. George, Tracy McGowan, Gedske Daugaard, Thomas W. Flaig, Lajos Geczi, Sebastien J. Hotte, Paul N. Mainwaring, Fred Saad, Matthew R. Smith, Ciro Souza, Cora N. Sternberg, Miah Hiang Tay, Jose Manuel Tello Garrido, Anil Londhe, Vahid Naini, Mary Beth Todd, Arturo Molina
Journal: Journal of Clinical Oncology (2013)

5059 Background: The COU-AA-301 phase 3 trial showed significantly longer overall survival for AA + prednisone (P) than P alone in mCRPC pts refractory to docetaxel. This global EAP was conducted in the same setting to collect additional safety data. Methods: Open-label EAP in pts with mCRPC who progressed after 1 - 2 chemotherapy regimens (≥ 1 taxane), resided in areas where AA was unavailable and were ineligible for ongoing clinical trials of AA. Pts received AA (1000 mg PO/d) plus P (5 mg bid) in 28 d cycles until disease progression. Only serious or clinically important adverse events (AEs) were to be reported by investigators. First interim results (clinical cut-off date: December 31, 2011), reported as part of regulatory submissions, are presented. Results: 1079 pts from 15 countries were included: N. America (47%), Europe (29%), Australia (13%), Latin America (7%), and Asia (3%). Median age: 70 years (range: 47 – 93); 89% of pts were White. Median treatment exposure, incl. pts still on treatment (285 pts), was ≈ 3 months. 620 pts (58%) received ≥ 4 treatment cycles, 58 pts (5%) received ≥ 8 cycles. 441 pts (41%) reported serious or clinically important AEs, which were treatment-related in 154 pts (14%). Most common grade 3-4 AEs: ↑ALP (6%), anemia (3%), hypertension (3%), back pain (2%), and fatigue (2%). Grade 3-4 AEs of special interest were infrequent: LFT abnormalities (8%), hypertension (3%), cardiac disorders (2%), hypokalemia (&lt; 1%), fluid retention/edema (&lt; 1%), osteoporotic fractures (&lt; 1%). Main reason for discontinuation (795 pts): disease progression, in 335 pts (31%). 253 pts (23%) discontinued after marketing authorization. Discontinuations due to treatment-emergent AEs, death, or withdrawal of consent were &lt; 6% each. Conclusions: The safety profile observed in these EAP interim results was consistent with that in the COU-AA-301 randomized, placebo controlled trial conducted in the same clinical setting. No new safety signals with AA plus P were detected in this expanded patient population, which included pts from Latin America and Asia, i.e. regions that did not participate in COU-AA-301. Clinical trial information: NCT01217697.
Comparison of Treatment Strategies in Patients over 60 Years with AML: Final Analysis of a Prospective Randomized German AML Intergroup Study
Authors: Dietger Niederwieser, Verena Sophia Hoffmann, Markus Pfirrmann, Haifa Kathrin Al-Ali, Sebastian Schwind, Vladan Vucinic, Rainer Krahl, Christoph Kahl, Hans-Heinrich Wolf, Ute Kreibich, Detlef Hähling, Ute Hegenbart, Carsten Hirt, Norma Peter, Axel Florschuetz, Kolja Reifenrath, Antje Schulze, Niklas Zojer, Sebastian Scholl, Christian Junghanss, Wolfram Pönisch, Simone Heyn, Herbert G. Sayer, Andreas Hochhaus, Thomas Heinicke, Thomas Fischer, Alwin Krämer, Peter Dreger, Georg Maschmeyer, Utz Krug, Maria Christina Sauerland, Achim Heinecke, Rüdiger Hehlmann, Eva Lengfelder, Wolfgang Hiddemann, Hubert Serve, Carsten Müller-Tidow, Wolfgang E Berdel, Thomas Büchner
Journal: Blood (2016)
The first two lines of chemotherapy for anthracycline-naïve metastatic breast cancer: A comparative study of efficacy between anthracyclines and nonanthracyclines.
Authors: Wei-Wu Chen, Twan Ying Chang, Shu-Min Huang, Ching-Hung Lin, Chiun Hsu, Ann-Lii Cheng, Yen-Shen Lu
Journal: Journal of Clinical Oncology (2012)

1061 Background: For anthracycline-naïve metastatic breast cancer (AN-MBC) patients, past evidence indicated that anthracyclines are beneficial in the first-two lines of palliative chemotherapy but with considerable toxicities. However, with the provision of newer chemotherapies, comparative studies addressing the efficacy between anthracyclines and non-anthracyclines in the first-two lines of palliative chemotherapy for AN-MBC were lacking. Methods: We collectedclinicopathological characteristics of AN-MBC patients who had received palliative chemotherapy in National Taiwan University Hospital between 2001 and 2006. Patients were classified as anthracycline or non-anthracycline group according to the first-two lines of chemotherapy. Kaplan-Meier method and log-rank test were used for the estimation and comparison of both overall survival (OS) and time to treatment failure of the first-two lines (TTF2).Cox proportional hazard model was used for OS and TTF2. Best composite response rate (BCRR) were compared with logistic regression test. Results: A total of 109 (43.1%) patients in the anthracycline group and 144 (56.9%) patients in non-anthracycline group were analyzed. Between these two groups, the distributions of clinicopathological variables were generally similar and their median OS (33.3 vs 34.2 months, p = 0.179), TTF2 (13.3 vs 12.7 months, p = 0.104), and BCRR (59.5 vs 61.1%, p = 0.81) were not significantly different. Subgroup analysis showed that patients in the anthracycline group had a trend toward better OS in the estrogen receptor (ER) negative/ human epidermal growth factor receptor type II (HER2) positive subtype (median OS 58.0 vs 31.2 months, p = 0.081). In multivariate analysis, patients in the anthracycline group had a trend toward better OS (HR 0.72, 95% CI 0.52 - 1.00, p = 0.052). However, the exclusion of ER-/Her2+ subtype attenuated the impact of early anthracycline treatment on OS (HR 0.82, 95% CI 0.56 - 1.18, p = 0.28). Conclusions: Our study demonstrated that anthracyclines may not be mandatory in the first-two lines of palliative chemotherapy for AN-MBC but may be more beneficial to ER-/Her2+ subtype patients.
Current metastatic melanoma treatment patterns in academic oncology.
Authors: Nrupen Anjan Bhavsar, Steven Wolf, Lynn Jackson Howie, Bradford Richard Hirsch, Lesley Ann Miller, Alan Oglesby, Bhakti Arondekar, April K. Salama, Amy Pickar Abernethy
Journal: Journal of Clinical Oncology (2015)

e20119 Background: Treatment options for metastatic melanoma have changed rapidly over the past few years. Little evidence on patient experiences and outcomes in routine academic practice is available. Methods: A retrospective database was created of melanoma patients treated at Duke University between 6/30/09-6/30/13. Patients were eligible they if were >=18 years, had unresectable/metastatic disease (stage IIIC/IV), and had > 6 months of follow-up data. Demographic, clinical, treatment, and adverse event data were abstracted from the clinical chart. Descriptive statistics were used to report on the study population and treatments. Results: 274 patients met the inclusion criteria. They were predominantly male (66%) and Caucasian (93%) with a median age of 62 years and good functional status (89% of ECOG 0 or 1). A majority weretreated with at least one line of therapy (65%); the most common 1st line therapies included ipilimumab (25%), IL-2 (15%), temozolomide (6%), and vemurafenib (6%). Prior to FDA approval of vemurafenib (Vem) in August 2011 (n=60), 28% of patients received no systemic therapy (ST), 28% were treated with IL-2, 15% with ipilimumab (Ipi), and 7% with temozolomide (Tem). Among BRAF negative patients after Vem approval (n=72), 18% received no ST, 58% were treated with Ipi, 8% with Tem, and 7% with IL-2. Among BRAF positive patients after Vem approval (n=56), 25% received no ST, 25% were treated with Vem, 23% with Ipi, 7% with a combination of Vem and Ipi, and 7% with Il-2. Common toxicities during first line therapy included rash/acne, fatigue, nausea, constipation, and decreased appetite/anorexia/weight loss. Conclusions: The introduction of BRAF testing and novel immunotherapies are changing practice patterns in the academic oncology setting, as well as toxicities experienced by patients. As new drugs are marketed, patterns will continue to evolve. Common first-line therapies. BEFORE Vem approval AFTER Vem approval (Among patients tested for BRAF) n=60 n % BRAF- BRAF+ n=72 n % n=56 n % NST 17 28 Ipi 42 58 NST 14 25 IL-2 17 28 NST 13 18 Vem 14 25 Ipi 9 15 Tem 6 8 Ipi 13 23 Tem 4 7 IL-2 5 7 Tem 1 2 Vem 1 2 Vem 0 0 IL-2 4 7 Vem/Ipi 0 0 Vem/Ipi 0 0 Vem/Ipi 4 7 Other 12 20 Other 6 8 Other 6 11 NST = No ST, Vem = Vemurafenib, Tem = Temozolomide, Ipi = Ipilimumab.
Final results of phase I/II trial of vorinostat in combination with cyclophosphamide, etoposide, prednisone, and rituximab (R-CVEP) for elderly patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).
Authors: David J. Straus, Paul A. Hamlin, Matthew J. Matasar, Maria Lia Palomba, Pamela Drullinsky, Andrew David Zelenetz, John F. Gerecitano, Ariela Noy, Audrey M. Hamilton, Brett Wegner, Zhigang Zhang, Rebecca L. Elstrom, David Cella
Journal: Journal of Clinical Oncology (2012)

8054 Background: Standard treatment of relapsed/refractory DLBCL in elderly patients who are not candidates for autologous stem cell transplantation (auSCT) has not been established. Cyclophosphamide (C), etoposide (E), prednisone (P) and procarbazine (CEPP) has been used by many clinicians based on limited data (Blood 76: 1293-98, 1990). Vorinostat (V) is a histone deacetylase inhibitor that is approved for relapsed cutaneous T-cell lymphoma and has activity in B-cell lymphomas. This trial defined the maximum tolerated dose (MTD) of V added to standard therapy and determined the response rate of this combination. Methods: Patients ≥age 60 with relapsed/refractory DLBCL not candidates for auSCT were enrolled on R-CVEP (R 375mg/m 2 IV, d1; C 600mg/m 2 d1 and 8, E 70mg/m 2 IV d1, 140mg/m 2 d2 and 3; V PO and Pred 60mg/m 2 PO d1-10) every 28 days for 6 cycles. In the phase I component V was administered at doses of 300mg/d or 400mg/d for 10 days. The phase I was a 3 + 3 design and the phase II a two stage design requiring 8/20 complete responses (CR) for expansion. Assessment of response utilized end-of-treatment positron emission tomography (PET) (JCO 25: 579-86, 2007). Quality of life (QOL) was measured with the FACT-Lym v.4. Results: 27 pts. were enrolled. 1 died before treatment. For 26 pts: median age 76 yrs. (69-88), 14 females and 12 males, baseline PS (ECOG) 1 (0-2). Median follow-up for survivors: 9.2 mo. Phase I: 6 pts. at 300mg/d (no dose-limiting toxicity-DLT), 6 pts. at 400mg/d (2 grade 3 neutropenia = DLT). MTD 300mg/d x 10d. For 20 pts. at V 300mg/m 2 (6 phase I + 14 phase II): 2 off study for toxicity, 1 withdrew consent, 6 CR (30%), 5 partial response (PR) (25%), 6 progressed (30%). Phenotypic overall responses (OR): germinal center (GC) 4/8 (2 CR), non-GC 6/10 (3 CR), transformed CLL 1/2 (1 CR). Median progression-free survival: 10 mo. QOL results will be presented. Conclusions: OR rate for V added to conventional chemotherapy and R was 55% (CR 30%, PR 25%) in relapsed/refractory DLBCL in elderly pts. not candidates for auSCT. This could provide a baseline for comparison with future clinical trials in this understudied population.
Phase II trial of tesetaxel, an oral taxane, as second-line therapy for patients with advanced gastroesophageal cancer.
Authors: Mary Frances Mulcahy, Jackie S. Baker, Weijing Sun, Sun Young Rha, Hassan Danesi, Loretta Itri, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2012)

4077 Background: Tesetaxel is a novel, orally administered taxane. It is not a substrate for P-glycoprotein, and preclinical data suggest tesetaxel has potent antitumor activity that exceeds standard taxanes in human tumor xenografts while causing substantially less neuropathy. Tesetaxel is not associated with hypersensitivity, thus eliminating the need for premedication and extended observation. A prior study showed an overall major response rate (ORR) of 20% with tesetaxel used as 2nd-line therapy in patients (pts) with advanced gastric cancer. We previously showed that “flat” (i.e., non weight-based) dosing with tesetaxel was associated with excessive variability; therefore, we amended the final trial design to evaluate whether we could extend the prior observations in a confirmatory Phase 2 trial using the MTD. Methods: Eligibility included: adenocarcinoma of stomach/GE junction; 1 prior fluoropyrimidine-platinum regimen; ECOG PS 0-1; and adequate organ function. Tesetaxel was administered orally once every 3 weeks starting at 27 mg/m 2 escalated to 35 mg mg/m 2 pending tolerance. ORR was the primary endpoint; estimated overall survival (OS) was secondary. Results: To date, 24 pts -- from a final target of 27 – have been enrolled (10 men, 14 women; median age, 58 yrs [range, 26-81]). Preliminary ORR in 15 evaluable cases to date are shown in the table below. At this time, only 4 pts have died and median survival is too early to estimate. Grade 3-4 adverse events have included neutropenia (27%), anemia, fatigue (13% each), and anorexia (7%). One pt (7%) experienced Grade 3 peripheral neuropathy. There have been no episodes of febrile neutropenia. Conclusions: Oral tesetaxel administered once every 3 weeks is active against gastric cancer in the 2nd-line setting. The observed 20% ORR confirms earlier data and appears at least equivalent to docetaxel (ORR= 5%-19%), as reported in 4 prior studies in this population. Tesetaxel was well tolerated and was not been associated with hypersensitivity. We expect to present final ORR and estimated OS from this trial. [Table: see text]
External validation and optimization of international consensus clinical target volumes for adjuvant radiation in bladder cancer.
Authors: Abhinav V. Reddy, John Paul Christodouleas, Tianming Wu, Norm D. Smith, Gary D. Steinberg, Stanley L. Liauw
Journal: Journal of Clinical Oncology (2017)

336 Background: International Consensus (IC) clinical target volumes (CTVs) have been proposed to standardize radiation field design in the treatment of patients at high risk for local regional failure (LRF) after radical cystectomy. The purpose of this study was to externally validate the IC CTVs in a cohort of post-surgical patients followed for LRF, and identify revisions that might improve its performance. Methods: Of 334 patients with pT3-4 bladder cancer treated with radical cystectomy, 58 (17%) developed LRF, of which 52 had CTs available for review. Images with LRF were exported into a treatment planning system, and IC CTVs were contoured and evaluated for adequacy of coverage of each LRF, with respect to both the patient and each of six pelvic subsites: common iliac (CI), obturator region (OR), external and internal iliac (EI/II), presacral (PS), cystectomy bed (CB), or other pelvic site. Revisions to the IC contours were proposed based on the findings. Results: Of the 52 patients with documented LRF, 13 (25%) patients had LRFs that were outside of the IC CTV involving 17 pelvic subsites: 5 near the CI CTV, 5 near the OR CTV, 1 near the EI/II, and 6 near the CB. The 5 CI failures were located superior to the CTV and the 5 OR failures were located medial to the CTV. Increasing the superior boundary of the CI to a vessel-based definition of the aortic bifurcation, and increasing the medial extension of the OR by an additional 9 mm, decreased the rate of patients with LRF outside of the IC CTV to 7 (13%) patients. Conclusions: “Modified IC CTVs” inclusive of a slight adjustment superiorly for the common iliac region, and medially for the obturator region, may reduce the risk for pelvic failure in patients treated with adjuvant radiation therapy.
An open-label, randomized, controlled clinical trial to explore the curative effects between the treatment of capecitabine and andrographolide and the single capecitabine in the patients with pathological and/or histologic diagnosed unresectable, advanced, recurrent, and metastatic colorectal cancer.
Authors: Yongqian Shu, Jing Sun, Peifen Cai, Weicheng Wang, Xiao Han, Yanhong Gu
Journal: Journal of Clinical Oncology (2017)

TPS819 Background: Colorectal cancer (CRC) is one of the most commonly diagnosed solid tumors worldwide. Current therapies for the treatment of CRC mainly comprise fluoropyromidine-based chemotherapies that are used individually or in combination with oxaliplatin or/with target therapy. Andrographolide, a natural diterpenoid from Andrographispaniculata, has been reported to exert antibacterial, antiviral, anti-inflammation and neuroprotectiveactivities. Our previous studies have proved that Andrographolide can inhibit tumor growth in mice at a relatively high dose(about 200 mg/kg).The aim of the study is to make a comparison of PFS, RR, and OS of the elderly CRC between the treatment of xeloda and andrographolide and the signal xeloda.We look forward to these findings highlight the potential possibility of using this natural, safe and relatively inexpensivecompound as potential adjunctive treatments in improving the overall treatment response of patients with CRC in future. Methods: This is an open-label, randomized, controlled clinical trial. Patients older than or equal to 65, by pathological and/or histologic diagnosed unresectable, advanced, recurrent andmetastatic CRC, will be enrolled. These patients’ tumors must be clearly measured by radiographic technology. All cases of chemotherapy patients randomly divided into two groups, experimental group (xeloda with andrographolide): xeloda: 1250mg/m2 , po bid, d1–14, q3w; andrographolide: 500mg, ivd qd, d1–14, q3w; control group (xeloda): 1250mg/m2, po bid, d1–14, q3w, 21d/cycle. After each 2 cycles, patients will be examined by imageological tests (CT and/or MRI) or tumour biomarkers (CEA and CA199) to estimate the curative effects. Until the tumor progression or after 6 cycles, patients will be removed from this study. PFS is set as the primary endpoint while secondary endpoints include overall survival (OS), overall response rate (ORR), and health-related quality of life (HRQoL). Recruitment has begun in Jan 2014 and about 52 patients has joined this study. Clinical trial information: NCT01993472.
Physician-Assisted Suicide
Authors: Patrick Pullicino
Journal: Annals of Internal Medicine (1997)

Letters15 July 1997Physician-Assisted SuicidePatrick Pullicino, MD, PhDPatrick Pullicino, MD, PhDBuffalo General Hospital; Buffalo, NY 14203Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-2-199707150-00050 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:As pointed out by Drickamer and colleagues [1], physician-assisted suicide is changing the physician–patient relationship. It is clear that physicians as a group are divided in their willingness to assist suicide: Of 938 physicians in Washington, 40% were willing to help a patient to commit suicide but 39% held that assisted suicide is never ethically justified [2]. With the reports from the Netherlands that involuntary euthanasia has followed the legalization of voluntary euthanasia [3], concern will increase among patients about what would happen to them if they became too ill to participate in end-of-life decisions. Physicians are ...References1. Drickamer MA, Lee MA, Ganzini L. Practical issues in physician-assisted suicide. Ann Intern Med. 1997; 126:146-51. Google Scholar2. Cohen JS, Fihn SD, Boyko EJ, Jonsen AR, Wood RW. Attitudes toward assisted suicide and euthanasia among physicians in Washington State. N Engl J Med. 1994; 331:89-94. Google Scholar3. Van der Maas PJ, van der Wal G, Haverkate I, de Graaf CL, Kester JG, Onwuteaka-Philipsen BD, et al. Euthanasia, physician-assisted suicide, and other medical practices involving the end of life in the Netherlands, 1990-1995, N Engl J Med. 1996; 335:1699-705. Google Scholar Author, Article, and Disclosure InformationAffiliations: Buffalo General Hospital; Buffalo, NY 14203 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 July 1997Volume 127, Issue 2Page: 174KeywordsEuthanasiaInternetSuicide Issue Published: 15 July 1997 CopyrightCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...