tbuckley/cabot-search huggingface dataset:
Promising preliminary results of erlotinib in previously chemotherapy treated Taiwanese NSCLC patients in a large expanded access program study
Authors: R. Perng
Journal: Journal of Clinical Oncology (2007)

7641 Background: Erlotinib is the first EGFR tyrosine kinase inhibitor which demonstrated the survival benefit to NSCLC patients in randomized trial. An expanded access program (EAP) was conducted to evaluate the efficacy and safety profiles of erlotinib in Taiwanese patients with NSCLC. Methods: Patients with proven stage IIIB/IV NSCLC and received at least first line standard chemotherapy or radiation therapy were enrolled in this study. No more than 2 prior chemotherapy regimens are permitted. All patients were given oral erlotinib, 150 mg/day till disease progression. Patients were monitored monthly and tumor assessments were evaluated every 2 months according to RECIST criteria. Results: From Apr. 2005 to Mar. 2006, 300 patients were entered from 15 medical centers in Taiwan. This interim study evaluated the first 297 patients (data cut-off date of November 8, 2006). Of them, 53% pts were male, 80% pts were with ECOG PS 0 or 1, 68% pts had adenocarcinoma, 62% pts receiving erlotinib as 2nd-line treatment, and 55% patients were non- smoker. The best response rate was 27.8% PR and 47.1% SD in 263 evaluable patients according to RECIST (disease control rate= 74.9%). Non-smoker (p=0.048 and 0.002), adenocarcinoma (p=0.001 and &lt;0.001), female (p=0.0005 and &lt;0.0001), and skin rash (Gr 3–4, p=0.0095 and 0.0019) were significantly correlate with best response and disease control to the treatment. Skin rash was a common adverse event (any grade: 83%, Gr 3–4: 15%). Erlotinib-related SAEs were seen in 4% patients and 3% patients discontinued treatment due to treatment-related SAEs. 24% of patients needed dose reductions, mainly due to skin rash. The median time to progression and median overall survival will be matured at the time of ASCO annual meeting. Conclusions: This is the largest multicenter prospective clinical study of NSCLC in Taiwan. This interim results demonstrating the superb response rates, time-to-progression and overall survival of erlotinib in a large population of Taiwanese or Chinese in previous chemotherapy or radiotherapy treated NSCLC patients. No significant financial relationships to disclose.
Phase II study of capecitabine (X) + docetaxel (T) as neoadjuvant treatment in patients (pts) with locally advanced breast cancer (LABC) including biological correlates
Authors: M. Bellet, M. Muñoz, B. Bellosillo, J. Corominas, T. Pena, M. Suárez, M. Maristany, J. Perich, I. Tusquets, X. Fabregat
Journal: Journal of Clinical Oncology (2006)

664 Background: X and T have demonstrated synergy in preclinical studies and survival benefits in metastatic BC. We aimed to determine whether the high efficacy of XT could translate into the neoadjuvant setting. Methods: Expression levels (mRNA) of 3 enzymes involved in X intratumoral activation and metabolism (thymidylate synthase [TS], thymidine phosphorylase [TP] and dihydropyrimidine dehydrogenase [DPD]), were determined in tumor biopsies before treatment and their relationship with clinical and pathological response analyzed using Fisher’s Exact Test. Pts with stage IIIA/IIIB LABC, adequate organ function and KPS ≥80 received 4 cycles of X 1250mg/m 2 (1000mg/m 2 for age &gt;60) bid d1–14 and T 75mg/m 2 d1 q3w followed by surgery, adjuvant AC q3w × 4 ± tamoxifen according to ER and PR status. The primary endpoint was pCR. Results: We enrolled 34 pts with LABC IIIA (44%)/IIIB (56%): median age 52y (30–72); KPS ≥90 (76%); median tumor size 6.8cm (2–20); N0 (20%), N1 (41%), N2/3 (35%); ER+PR-/p53+/HER2+ (23/24/28%). 128 cycles of X and T were administered (median 4, range 1–5). Main G3/G4 toxicities were: HFS 32%, diarrhea 15%, asthenia 9%, stomatitis 6% and neutropenia 71%. There were no treatment-related deaths. 2 pts were withdrawn prematurely due to adverse events. The overall response in 32 evaluable pts was 78%, including 5 CRs and 20 PRs. 6/29 pts evaluable for pathological response had pCR (20%), and 10 (33%) had ≤10mm residual tumor (3 microscopic RD) in breast. Nodal involvement after chemotherapy was N0 (33%), N1 (33%), N2 (27%), N3 (7%), and the rate of breast-conserving surgery was 17%. High TP/DPD ratio was associated with CR (p=0.037) and both high TP/DPD and low TS/DPD ratio appeared to correlate with residual tumor ≤10 mm (p=0.028). Conclusions: Neoadjuvant XT appears to be highly active. Safety was similar to that reported in anthracycline-pretreated pts but with less stomatitis. In this small sample, a high TP/DPD ratio appears to correlate with clinical response and a favorable enzymatic profile (high TP/DPD and low TS/DPD ratio) may predict for high pCR. A further prospective study is required to validate this hypothesis. No significant financial relationships to disclose.
Patterns of care and outcomes of locally advanced breast cancer at the Cancer Centre of Southeastern Ontario
Authors: M. Mates, W. Hopman, Y. Madarnas
Journal: Journal of Clinical Oncology (2009)

e11614 Background: Preoperative chemotherapy (PCT) is the standard of care for locally advanced breast cancer (LABC). As part of a multicentre provincial initiative we undertook a review of practice patterns and outcomes for women with LABC at our institution. Methods: We reviewed electronic and paper records for M 0 pts receiving PCT for LABC between 1995–2007 at our institution, collecting demographic, disease and treatment-related, and outcome variables. Results: Sixty pts with LABC who received PCT were included in this review. Median age was 54y (31–80), 38% premenopausal. Median BMI was 28kg/m 2 , 78% were overweight or obese. Stage distribution: 10% IIB, 11% IIIA, 77% IIIB and 2% IIIC, of which 45% had inflammatory breast cancer (IBC). At biopsy 90% were invasive ductal carcinoma, 36% were ER and PR(-) and 25% were her2(+). Median time from surgical consultation to PCT was 22d (6–126). PCT was anthracycline-based alone in 85% of pts, 8% received a taxane, 3% also received preop endocrine therapy (ET), no pts received trastuzumab (T) preop. Pts received a median of 6 (3–8) cycles of PCT. Local therapy: mastectomy (M) in 82% of pts and partial M in 11%. Axillary surgery was done in only 92% of pts (axillary node dissection 90%, sentinel node biopsy 1pt) and 7% had no definitive breast or axillary surgery due to local progression (3) or refusal (1). All pts received radiotherapy. Postop systemic therapy: CT in 5% of pts, ET in 65% and T in 10% of pts. Clinical complete response (CR) rate was 28%. At definitive surgery 10% of pts had no residual disease in breast or axilla and 3 pts had only DCIS present, for a pathologic (p)CR rate of 15% using MDACC criteria. Median follow-up was 24mo (1–238). Median 5y DFS was not reached for the entire population and those with a pCR vs. 26mo for pts with IBC; corresponding 5y DFS rates were 58%, 78%, and 41% respectively. Median 5y OS was for the entire population was 52mo vs. 48mo for pts with a pCR and 47mo in the IBC group; corresponding 5y OS rates were 62%, 78% and 44% respectively. Conclusions: Management of LABC in our cohort is fairly uniform and consistent with current guidelines. Local outcomes of LABC managed with PCT are in keeping with the published literature and arguably better since almost half of our cohort is represented by IBC which carries a worse prognosis. No significant financial relationships to disclose.
Personalizing treatment with pemetrexed (PEM) in patients with malignant mesothelioma (MPM) and non-small cell lung cancer (NSCLC): The role of thimidylate synthase.
Authors: V. Saloura, L. Wang, D. Schwed, A. Vachani, C. J. Langer, S. Albelda
Journal: Journal of Clinical Oncology (2010)

e21001 Background: PEM was first approved for the treatment of MPM in combination with cisplatin, more recently as first line and maintenance therapy for advanced nonsquamous NSCLC. TS levels may predict response to PEM; high levels of expression are speculated to predict resistance to PEM. To evaluate whether TS protein levels, rather than histologic type, could be used to select patients with NSCLC and MPM for treatment with PEM, we assessed the variability of expression of TS in NSCLC and MPM tissue samples. Methods: We pursued semi-quantification of TS protein levels by immunohistochemistry (IHC) on tissue microarrays from 83 adenocarcinoma, 92 squamous, large cell, not-other-specified (NOS) NSCLC and 40 MPM samples. An IHC scoring system (IRS) was implemented based on stains: IRS scores of 0-2, 3-7 and 8-12 signified low, moderate and high TS protein expression respectively. Results: Of 49 squamous-cell samples, 22% had low expression of TS, indicating that PEM could potentially be effective in a subset of patients with squamous lung cancer. 24% expressed high levels of TS, 55% had an IRS greater than 6, in contrast to 23% of the adenocarcinoma samples. Of 83 adenocarcinoma samples, 56.5% and 9.6% had moderate and high expression of TS respectively. Similarly, 47% and 35% of the MPM samples showed moderate and high levels of TS expression respectively (Table). Correlation of clinical response to PEM with levels of TS expression is ongoing. Conclusions: Based on these preliminary data, TS levels are highly variable across both NSCLC and MPM tissue samples, and a substantial minority of patients with squamous histology may have a molecular profile that correlates with sensitivity to PEM. The role of TS as a biomarker for personalized therapy with PEM in patients with NSCLC and MPM requires prospective validation. TS expression Tumor type Negative (IRS = 0-2) Low (IRS = 3-7) High (IRS = 8-12) Mesothelioma (n = 40) 17.5% 47.5% 35% Adeno (n = 83) 33.6% 56.5% 9.6% Squamous, large cell, and NOS (n=92) 23.8% 50.8% 25% Squamous (n = 49) 22.2% 50.8% 24.4% Large cell (n = 11) 18% 54% 27.2% NOS/BAC (n = 12) 16.6% 41.5% 41.6% No significant financial relationships to disclose.
Tamara Henryka Madej
Authors: Amanda Vipond
Journal: BMJ (2016)

Tamara Madej (Pomeroy) trained as an anaesthetist in Leeds. She had been as a clinical student at the Radcliffe Infirmary in Oxford from 1976 to 1979, one of only a few women on the course. It was here that Tamara discovered her love of anaesthetics. She was a keen and hardworking student but also enjoyed life with dancing, music, cooking, and expeditions. She spent an interesting elective in Bangkok and Chiang Mai. During her specialty training she spent a year in Calgary, Canada, and was a lecturer at the Leeds academic unit. She took up her …
Do we need a new word for patients?
Authors: R. Thode, W. Bain, R. Stevens, D. Kernick, M. Acar
Journal: BMJ (1999)

# “Users” isn't an appropriate alternative {#article-title-2} EDITOR—Part of Tallis's response to Neuberger's idea of doing away with the word “patients” is to suggest that, if the debate is worth pursuing, the next step would be to research what people actually think about the word “patient.”1 Although I'm certain that a small study in Australia will not be the last word on this particular word, might I draw attention to Nair's report last year in the Medical Journal of Australia? 2 Nair studied 308 outpatients at John Hunter Hospital, Newcastle, New South Wales, and concluded that over four fifths of all patients approached, and over nine tenths of those aged over 60, preferred the term patient to “client” or “customer.” The term “user” more commonly refers to users of injected drugs than to users of the health service and thus could lead to some interesting confusions over time should it be adopted. 1. 1.↵1. Neuberger J, 2. Tallis R . Do we need a new word for patients? BMJ 1999; 318: 1756–1758. [OpenUrl][1][FREE Full Text][2] 2. 2.↵1. Nair BR . Patient, client or customer. Med J Aust 1998; 169: 593. [OpenUrl][3][PubMed][4][Web of Science][5] # Continue to call them patients but treat them like customers {#article-title-5} EDITOR—Neuberger's article reminds me that in 1993 I was chief executive of Royal Brompton Hospital in London.1 We had a healthy internal debate then about what name we should use for those people who came to the hospital when we became an … [1]: {openurl}?query=rft.jtitle%253DBMJ%26rft.stitle%253DBMJ%26rft.issn%253D0007-1447%26rft.aulast%253DNeuberger%26rft.auinit1%253DJ.%26rft.volume%253D318%26rft.issue%253D7200%26rft.spage%253D1756%26rft.epage%253D1758%26rft.atitle%253DDo%2Bwe%2Bneed%2Ba%2Bnew%2Bword%2Bfor%2Bpatients%253F%2B%2595%2BLet%2527s%2Bdo%2Baway%2Bwith%2B%2522patients%2522%2B%2595%2BCommentary%253A%2BLeave%2Bwell%2Balone%26rft_id%253Dinfo%253Apmid%252F10381717%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=FULL&journalCode=bmj&resid=318/7200/1756&atom=%2Fbmj%2F319%2F7222%2F1436.2.atom [3]: {openurl}?query=rft.jtitle%253DMedical%2BJournal%2Bof%2BAustralia%26rft.stitle%253DMedical%2BJournal%2Bof%2BAustralia%26rft.aulast%253DNair%26rft.auinit1%253DB.%2BR.%26rft.volume%253D169%26rft.issue%253D11-12%26rft.spage%253D593%26rft.epage%253D593%26rft.atitle%253DPatient%252C%2Bclient%2Bor%2Bcustomer%253F%26rft_id%253Dinfo%253Apmid%252F9887902%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [4]: /lookup/external-ref?access_num=9887902&link_type=MED&atom=%2Fbmj%2F319%2F7222%2F1436.2.atom [5]: /lookup/external-ref?access_num=000077556700011&link_type=ISI
The Best Things in Life Are Not Always Free
Authors: M L Taymor
Journal: New England Journal of Medicine (1970)

This letter from a Massachusetts physician urges other physicians to take the responsibility of doing abortions on women who need them by using emotional illness as the justification factor.  Massachusetts law inacted in 1845 says unlawful abortion is punishable but a lawful abortion is defined by a case in 1944 as one indicated in the general opinion of competent practitioners in the community in which he practices.   Furthermore this abortion was performed to preserve maternal health which was determined by the courts to include mental health.  Until Massachusetts changes its laws it is suggested that physicians work within the existing one.
Neoplastic Transformation and Chromosomal Aberrations Induced by &lt;italic&gt;N&lt;/italic&gt;-Methyl-&lt;italic&gt;N&lt;/italic&gt;′ -Nitro-&lt;italic&gt;N&lt;/italic&gt;-Nitrosoguanidine in Hamster Lung Cells in Tissue Culture
Authors: N. Inui, S. Takayama, T. Sugimura
Journal: JNCI Journal of the National Cancer Institute (1972)

Hamster-lung fibroblast cells were transformed into neoplastic cells in vitro by exposure to N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) for 24 hours. Cultured cells were morphologically changed about 27–48 days after treatment with 6.8 × 10−5 M of the carcinogen. The transformed fusiform cells were randomly oriented—piling-up and criss-crossing —and grew continuously in vitro for over 200 days. Chromosomal alteration was observed in MNNG-treated cells almost as soon as the morphologic transformation. This numerical change of chromosomes in the treated cells did not recur, even when the transformed cells produced tumor in later stages. The variation in chromosome number was clearly smaller for neoplastic cells than that of merely transformed cells. These cells could produce neoplasms when transferred to the cheek pouch of a hamster after 160 days in culture. Histologically, the tumors were fibrosarcomas. Untreated cells in the control and those treated with 6.8 × 10−5 M of MNNG failed to produce either transformed cells or tumors.
Insights into Relationships Between Serum Ferritin and Liver Iron Concentration Trends during 12 Months of Iron Chelation Therapy with Deferasirox – a Post-Hoc Analysis from the Epic Study
Authors: John B Porter, Mohsen Elalfy, Ali T Taher, Lee Lee Chan, Szu-Hee Lee, Pranee Sutcharitchan, Yesim Aydinok, Subhashish Chakravarty, Ali El-Ali, Amal El-Beshlawy
Journal: Blood (2014)
Cytotoxicity of Antisera to a Myelogenous Leukemia Cell Line With the Philadelphia Chromosome23
Authors: Mary E. Whitson, Carmen B. Lozzio, Bismarck B. Lozzio, Carl J. Wust, Takuo Sonoda, Bruce Avery
Journal: JNCI Journal of the National Cancer Institute (1976)

Rabbit antisera to myelogenous leukemia (ML) cells were raised; ML cells from line K-562 that has the Philadelphia (Ph1) chromosome were used as antigen. Antibody-dependent, complement-mediated cytotoxicity was demonstrated by the trypan blue test and51Cr release assay for cultured ML cells, whereas no cytotoxicity was demonstrated for cells from B (SB) and T (MOLT 4) lymphoblastoid cell lines. The antisera showed no cross-reactivity for normal human peripheral leukocytes or purified granulocytes. A low level (<8%) of cytotoxicity was directed against cell membrane-associated fetal bovine serum proteins. Absorption of the immune serum with normal human bone marrow cells of first-trimester human whole embryo cells reduced the cytotoxic titer to a similar extent; this suggested the possibility of cross-reactivity between ML cells and fetal antigen(s). However, the ML antigen(s) was unrelated to carcinoembryonic antigen (CEA), since absorption with CEA had no effect on the serum cytotoxic titer. The anti-ML sera were cytotoxic for cells taken from 10 patients with chronic myelogenous leukemia and from 3 with acute myelegenous leukemia. In contrast, the leukocytes of 1 of 4 patients with acute lymphocytic leukemia, and 3 of 7 with chronic lymphocytic leukemia shared similar antigenic determinants as demonstrated by cytotoxicity tests. The significance of the cross-reactivity of some lymphatic and ML cells may be the result of the use of rabbit sera that did not distinguish antigens common to both granulocytic and lymphocytic cells, or it may reflect an “immature” or “blastic” antigen present on many leukemia cells.
Control of acute toxicity with amifostine and pelvic chemoradiotherapy
Authors: M. Tate, L. Wilson, C. Silverman, W. Helm, L. Parker, D. Metzinger, K. Paris, L. Carrascosa, C. Yashar
Journal: Journal of Clinical Oncology (2006)

15058 Background: Amifostine is an FDA approved normal tissue radioprotector for head and neck carcinoma. Several studies have also demonstrated a radioprotective role in pelvic malignancies. However, literature also shows that amifostine has substantial toxicity. We examined patient compliance with combined chemoradiotherapy and daily amifostine subcutaneous injections, the incidence of acute toxicity, and the efficacy of interventions. Methods: Patients undergoing pelvic radiotherapy and concurrent chemotherapy were eligible. Patients received daily subcutaneous injections of 500 mg amifostine 30 to 60 minutes before radiotherapy. Injection pain, erythema, and rash were recorded daily, as was patient blood pressure before and after receiving amifostine and radiotherapy. Treating physicians evaluated patients at least weekly. Symptoms were recorded and graded using the NCI Common Toxicity Criteria. The protocol was amended early in accrual to include nausea prophylaxis guidelines. Results: Nineteen patients have been entered into this study. Fourteen had cervix cancer, four had rectal cancer, and one had anal cancer. Four patients (21%) received &lt;1 week of amifostine. Seven (37%) received &lt;50% of their planned injections. Fifty three percent received &gt;80% of their injections, while 32% received the full course of amifostine. Of those that prematurely discontinued amifostine, 1 withdrew before receiving any injections, 1 transferred to another facility, 6 withdrew because of nausea, 2 secondary to rash, 2 secondary to injection pain. One developed paresthesias. Of those that withdrew because of nausea, all but one received &gt;50% of the planned injections. Twenty six percent experienced grade 3 nausea. When comparing patients that did not receive nausea prophylaxis with those that did, grade two or three nausea dropped from 100% to 29%. No patients developed grade 3 rash. Two patients experienced hypotension. Nine patients (47%) complained of injection site pain. Conclusions: Subcutaneous amifostine is reasonably well tolerated when used with pelvic radiotherapy. Nausea was a significant side effect seen in this study. Assuring adequate hydration and use of prophylactic antiemetic medication significantly decreased nausea. [Table: see text]
Ebola transmission ends in Guinea
Authors: Zosia Kmietowicz
Journal: BMJ (2015)

Ebola virus disease is no longer being transmitted in Guinea, the World Health Organization said on 29 December, 42 days after the last person confirmed to have the disease tested negative for the second time.

Guinea is the last of the three countries most affected by the disease to be declared free of transmission. Sierra Leone was declared to have interrupted the chain of transmission on 7 November 2015 and Liberia on 3 …
FDG-PET/CT (PET) in the early prediction of benefit from first-line chemotherapy plus bevacizumab (bev) in metastatic colorectal cancer (mCRC).
Authors: Lisa Salvatore, Fotios Loupakis, Chiara Cremolini, Marta Schirripa, Carlotta Antoniotti, Federica Marmorino, Federica Zoratto, Francesca Bergamo, Isa Maura Brunetti, Elisabetta Pfanner, Gianluca Masi, Dario Genovesi, Elena Filidei, Assuero Giorgetti, Alfredo Falcone
Journal: Journal of Clinical Oncology (2013)

e14531 Background: The conventional assessment of response according to RECIST seems not optimal to estimate the actual benefit from antiangiogenic agents. A recent experience suggests the potential role of PET in the early prediction of benefit from first-line chemotherapy in mCRC. The objective of the present study was to evaluate the metabolic PET response to one single cycle of chemotherapy plus bev in mCRC patients (pts). Methods: PET was carried out at baseline and on day 13 in 51 unresectable mCRC pts, treated with biweekly bev-containing regimens; computed tomography (CT) scan was performed at baseline and every 2 months. PET response was defined by &gt;15% decrease in FDG uptake in the dominant proportion of lesions, in the absence of metabolically progressive lesions. CT response was defined according to RECIST 1.0. Results: PET response rate was 73%. PET responders achieved longer PFS compared to PET non-responders (median PFS: 11.0 vs 8.3 months; HR=0.45 [95%CI 0.14-0.93] p=0.035). RECIST CT response rate was 62% and 57%, in PET responders and non-responders, respectively (p=0.76). At an exploratory analysis, among pts (N=15) reporting a RECIST-defined stable disease (SD), those with a percentage decrease in FDG uptake higher than the median value (&gt;33%) had significantly longer PFS in comparison to those with a lower PET response (median PFS: 9.4 vs 7.4 months; HR=0.2 [95%CI 0.005-0.24] p=0.0006). Conclusions: Early PET response, assessed after one single cycle of chemotherapy plus bev, predicts PFS, while it does not correlate with traditional RECIST response. In the subgroup of pts reporting a RECIST SD, the early reduction in FDG uptake correlates with PFS. On the basis of our results, early PET response on day 13th could representan early predictor of benefit from bev plus chemotherapy in mCRC.
Abstract 16461: Hyperhomocysteinemia Promotes Inflammatory Pyroptosis and Apoptosis via Caspase-1-Inflammasome Signaling in Endothelial Cells
Authors: Hang Xi, Xiaohua Jiang, Ying Yin, Xiaofeng Yang, Hong Wang
Journal: Circulation (2012)

Rationale: Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease. HHcy accelerates atherosclerosis and induces endothelial damage. Objective: To examine whether caspa...