tbuckley/cabot-search huggingface dataset:
Use of KI67 and geminin expression to better define the proliferation status of invasive breast cancer.
Authors: K. J. Bloom, T. A. Bloom, A. Kyshtoobayeva
Journal: Journal of Clinical Oncology (2010)

e21037 Background: Gene expression signatures have highlighted the importance of proliferation markers in classifying breast cancer and predicting response to conventional chemotherapy. KI-67 is commonly used as a marker of proliferation, identifying tumor cells in the non-G0 state. Loddo et al (British Journal of Cancer 2009; 100: 959–970.) recently showed that KI-67 is a suboptimal marker of proliferation, since many tumor cells that express KI-67 undergo G1 arrest, exit the cell cycle or undergo apoptosis rather than complete the cell cycle. Geminin is a cell cycle protein that is complementary to KI-67 in that it is expressed in S-phase, G2 and early mitosis but not G1. This study looked at eighty invasive breast cancers and categorized them as showing low KI-67/low geminin, high KI-67/low geminin indicating G1 arrest or high KI-67/high geminin indicating actively proliferating cells. Methods: Four TMAs consisting of 20, 2 mm formalin fixed paraffin embedded cores of invasive breast cancer were stained with antibodies against KI-67 (MIB-1) and geminin. A cut-off of 15% was used to classify each tumor based on KI-67 expression and a cut-off of 7% was used to classify each tumor based on geminin expression. Results: Forty-seven (58.8%) tumor cores were classified as demonstrating low KI-67 expression and low geminin expression. Thirty-three (41.2%) tumor cores were classified as demonstrating high KI-67 expression, sixteen (48.5%) of which also showed high expression of geminin while seventeen (51.5%) showed low expression of geminin. Conclusions: Of the 41.2% of tumor cores showing a high proliferative index on immunostaining with KI-67, slightly more than half (51.5%) were not actively proliferating, as demonstrated by the low expression of geminin. This limited study confirms prior studies demonstrating that tumor lacking significant expression of KI-67 also lack expression of other proliferation markers; however, about half of tumors showing significant expression of KI-67 undergo G1 arrest, exit the cell cycle or die without dividing. No significant financial relationships to disclose.
A single-arm, open-label, phase 2 study of MGAH22 (margetuximab) [fc-optimized chimeric anti-HER2 monoclonal antibody (mAb)] in patients with relapsed or refractory advanced breast cancer whose tumors express HER2 at the 2+ level by immunohistochemistry and lack evidence of HER2 gene amplification by FISH.
Authors: Mark D. Pegram, Elizabeth Tan-Chiu, Kathy Miller, Hope S. Rugo, Denise A. Yardley, Seila Liv, Stanford J. Stewart, John Kalil Erban
Journal: Journal of Clinical Oncology (2014)

TPS671^ Background: Response to trastuzumab (T)-based chemoimmunotherapy in metastatic breast cancer segregates according to expression of the Fcg receptor, CD16A, allotypes with patients homozygous for the 158V variant having superior outcomes to patients expressing the 158F variant (Mussolino, J Clin Oncol 2008, 26:1789-1796). Margetuximab is a chimeric anti-HER2 mAb with antigen specificity and affinity similar to T’s and an Fc domain engineered for increased binding to both allotypes of CD16A. Margetuximab exhibited enhanced ADCC against HER2-positive tumor cells, including T-resistant and HER2-low expressing cells. Margetuximab demonstrated increased activity against HER2-low expressing human tumor xenografts. In toxicology, margetuximab was well tolerated (15-150 mg/kg) (Nordstrom, Breast Cancer Research 2011, 13:R123). In Phase 1 testing involving 34 heavily pre-treated patients with HER2-positive neoplasms, margetuximab was well tolerated - MTD not exceeded at 6 mg/kg qw. The major safety findings were infusion reactions, which responded promptly and were largely ameliorated by pre-medications. Margetuximab produced clinical benefit at doses as low as 0.1 mg/kg qw and best responses of PR were noted in 5 patients [Burris, J Clin Oncol 2013, 31 (suppl; abstr 3004)]. Methods: The current study employs a Simon 2-stage design to determine if margetuximab has sufficient activity (>/= 5 responses in 41 evaluable) to justify further development in advanced breast cancer patients whose tumors exhibit 2+ HER2 expression and lack evidence of gene amplification by central testing. Time-delimited endpoints will be captured. Exploratory objectives include: PK/PD, FcgR allotype-response, and cytokine-AE relationships, ability of patient PBMCs to mediate ADCC, lymphocyte subsets and activation markers; circulating tumor cells and circulating nucleic acids. Three evaluable patients have participated thus far in the study. Clinical trial information: NCT01828021.
Stopping antidepressants following depression
Authors: Tamara Pringsheim, Martina Kelly, Corrado Barbui
Journal: BMJ (2016)

#### What you need to know

Jocelyn started taking citalopram one year ago for her first recorded episode of depression. Her symptoms improved six weeks later. Now that she feels well, she asks if she can stop taking the pills.

Explain to Jocelyn that, before making a decision about her medication, you should review her symptoms, response to treatment, and history of depression. Explain that there is guidance for doctors and patients on medication for depression, and a discussion to tailor that guidance to her case would be useful. 

Review to what extent symptoms of depression persist (see box 1). For example, ask Jocelyn if she is enjoying life and if she is feeling confident? Use of structured tools such as the Patient Health Questionnaire-9 (PHQ9) can provide …
A randomized, phase II study of ATN-224 in patients with biochemically relapsed, hormone-naive prostate cancer: A DOD/PCF Prostate Cancer Clinical Trials Consortium trial
Authors: J. Lin, T. M. Beer, C. J. Ryan, P. Mathew, G. Wilding, M. Morris, J. A. Callahan, G. Gordon, S. Reich, M. A. Carducci
Journal: Journal of Clinical Oncology (2009)

5135 Background: ATN-224 (choline tetrathiomolybdate) is an orally active, small molecule that has antiangiogenic and antitumor effects in prostate cancer (PCa) models. ATN-224 targets Cu 2+ /Zn 2+ superoxide dismutase 1 (SOD1) and suppress the generation of H 2 O 2 leading to activation of a number of phosphatases, a group of negative growth regulatory enzymes. We hypothesized that ATN-224 may induce antitumor effect as an antiangiogenic (at 30 mg dose level) and possesses direct antitumor activity at higher dose (300 mg/day). Methods: PCa pts with PSA doubling time (PSADT) of &lt; 12 months, no radiographic evidence of metastasis, no hormonal therapy within 6 months were enrolled. All pts had testosterone &gt; 150 ng/dL at baseline. ATN-224 was administered at 2 dose levels. PSA progression was defined as at least a 50% increase in PSA and &gt;5 ng/mL increase from baseline or post-treatment nadir and confirmed. Endpoints included the proportion of pts who did not have PSA progression for 24 weeks, change in PSA slope/PSADT, and assessment of safety and tolerability. The study was not powered to detect difference between the two groups. Results: 52 pts were enrolled at 6 centers. Fourteen of 27 (52%) in the low dose and 6/25 (24%) in the high dose cohort were PSA progression free for 24 weeks. One patient in high dose cohort showed PSA &gt;50% decrease of 40 days duration. Pre- and on-treatment PSA kinetics are shown below. Median duration on study was 134 days in both groups. ATN-224 was well tolerated with a few reversible Grade 3/4 neutropenia and Grade 3 skin rash (both 4%). Conclusions: ATN-224 may have biologic activity in men with androgen-dependent PCa at low doses, as demonstrated by &gt; 50% of pts being PSA progression free at 6 month and a significant decrease in mean PSA slope. The implication of this study is not clear without a comparative design and ceruloplasmin correlation which is still pending. [Table: see text] [Table: see text]
Prognostic value of “Dworak” tumor regression grade (TRG) after pre-operative chemo-ratiotherapy in rectal cancer (RC)
Authors: F. Bertolini, L. Losi, F. Iachetta, P. Giacobazzi, E. Romagnani, C. Dealis, F. Bertoni, G. Luppi, C. Bengala, P. F. Conte
Journal: Journal of Clinical Oncology (2005)

3636 Background: Preoperative chemo-radiotherapy has been shown to improve local control in locally advanced rectal cancer. However the benefit in overall survival is still controversial. Moreover the prognostic value of down-staging after preoperative chemo-radiotherapy remains to be validated. Dworak and al. (Int Colorectal Dis, 1997) proposed a grading system to assess tumor regression. The end-point of this study was to validate the “Dworak” TRG in a large number on patients (pts). Methods: We analyzed retrospectively 112 pts with locally advanced uT3/uT4 N0/+ RC treated at our institution from May 1998 to June 2004. The pts received pre-operative pelvic irradiation (50 Gy in 25 fractions) and concomitant chemotherapy with: 5-FU c.i. in 77 pts (68%) or 5-FU c.i. + oxaliplatin in 22 pts (20%) or capecitabine in 13 pts (12%). Results: All pts underwent surgery within 7 weeks after the end of therapy and were valuable for pathological response and Dworak TRG. Post-operative stage was 0 in 16 pts (14.3%), I in 26 pts (23.3%); II in 33 pts (29.5%), III in 33 pts (28.6 %) and IV in 4 pts (4.5%). Dworak TRG was: 4 in 16 pts (14.3%), 3 in 25 pts (22.2%), 2 in 32 pts (28,4%), 1 in 36 pts (31,9%) and 0 in 3 pts (2,7%). Median follow-up was 27.3 months. Two years DFS according to stage 0, I, II and III was 100%, 91%, 80% and 61% respectively (p: 0.005). Two years DFS for Dworak TRG 4, 3, 2, 1 and 0 was 100%, 90%, 77, 70% and 33% respectively (p: 0.009). Dworak TRG analysis was performed in post-operative stage I, II and III: 2-years DFS was 68% and 83% in Dworak TRG 0–1 and 2–3 respectively (p: 0.07). Conclusions: Our study confirms the prognostic value of pathological stage and Dworak TRG after pre-operative treatment. Moreover in post-operative stage I II-III our analysis has demonstrated a trend in DFS improvement for pts with a high Dworak TRG. No significant financial relationships to disclose.
Combination chemotherapy for metastatic melanoma: the importance of tamoxifen.
Authors: P B Chapman
Journal: Journal of Clinical Oncology (1994)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1994.12.6.1336 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8201397 Combination chemotherapy for metastatic melanoma: the importance of tamoxifen. P B ChapmanxP B ChapmanSearch for articles by this author https://doi.org/10.1200/JCO.1994.12.6.1336 PDF "Combination chemotherapy for metastatic melanoma: the importance of tamoxifen.." Journal of Clinical Oncology, 12(6), pp. 1336–1337© 1994 by American Society of Clinical Oncology
A review of the patterns of docetaxel use for hormone refractory prostate cancer (HRPC) at the Princess Margaret Hospital
Authors: S. N. Chin, L. Wang, A. Lau, M. Moore, S. S. Sridhar
Journal: Journal of Clinical Oncology (2009)

e16161 Background: Docetaxel is standard of care for the treatment of HRPC, based on two large randomized clinical trials. The aim of this study was to determine if docetaxel use and effectiveness in routine clinical practice was similar to that seen in the TAX 327 randomized phase III clinical trial. Methods: A retrospective chart review was undertaken to assess patterns of docetaxel use for HRPC at our institution for the 2-year period since its approval for the first-line treatment of HRPC in 2005. Results: Eighty-eight patients, median age 71 and baseline PSA 107, received docetaxel in the first line setting. Main reasons for initiating docetaxel were rising PSA (90%) and progressive symptoms (71%). Eighteen percent of patients received docetaxel for rising PSA alone. A median of 7 cycles was administered. PSA response rates were 61%, time to response 1.5 months, and response duration 6.8 months. Disease progression was the most common reason for treatment discontinuation (36%). Main toxicities were fatigue (32%) and neuropathy (22%). Kaplan Meier survival analysis showed median duration of survival was 15.9 months (95% CI 12.4–20.5) from first drug use. 1-year survival was 0.63 (95% CI 0.52–0.72). Post-docetaxel, 36 patients received second-line treatment, mostly with mitoxantrone (89%). Second-line response rates were 22%, and median duration of response was 4 months. Conclusions: In routine clinical practice, docetaxel is a well-tolerated regimen for the treatment of HRPC. Response rates and toxicity profiles were comparable to the randomized trials. However, compared with the TAX 327 clinical trial, survival was slightly shorter than expected (15.9 vs. 18.9 months), possibly due to inclusion of patients with poorer performance status and comorbidities, who may be excluded from clinical trials. Second-line response rates were also comparable with previous reports. No significant financial relationships to disclose.
Somatization symptoms among patients using primary health care facilities in a rural community in Nigeria
Authors: J U Ohaeri, O A Odejide
Journal: American Journal of Psychiatry (1994)

The somatic presentation of psychic distress among Africans is different from that in the West, and the prevalence of somatization symptoms suggests that they could be usefully incorporated in screening instruments. This report examines the prevalence of somatization symptoms among users of health care facilities in a rural community in southwestern Nigeria. It also examines the correlation between the presence of these symptoms and scores on instruments that assess psychiatric morbidity.Over a 5-month period in 1991, 865 adults using five primary health care facilities or seeking help from voluntary village health assistants were assessed with the 28-item General Health Questionnaire and two World Health Organization instruments, the Self-Reporting Questionnaire and the Brief Disability Questionnaire. The somatization symptoms investigated included feelings of heat, peppery and crawling sensations, and numbness.About 20% of the subjects admitted experiencing at least one somatization symptom, while 8.2% fulfilled operational criteria for probable psychiatric "caseness" on the basis of somatization alone. The rate of caseness according to the General Health Questionnaire was 6.4%. The presence of any of the somatization symptoms was significantly correlated with scores on the other test instruments. There were no sex differences in the pattern of somatization.These symptoms are reliable indexes of psychic distress. In this culture, the sensitivity of standard screening instruments fashioned in the West can be improved by using these symptoms to replace the somatization symptoms contained in those instruments.
The Ecology and Evolutionary Dynamics of Meiotic Drive
Authors: Anna K. Lindholm, Kelly A. Dyer, Renée C. Firman, Lila Fishman, Wolfgang Forstmeier, Luke Holman, Hanna Johannesson, Ulrich Knief, Hanna Kokko, Amanda M. Larracuente, Andri Manser, Catherine Montchamp-Moreau, Varos G. Petrosyan, Andrew Pomiankowski, Daven C. Presgraves, Larisa D. Safronova, Andreas Sutter, Robert L. Unckless, Rudi L. Verspoor, Nina Wedell, Gerald S. Wilkinson, Tom A.R. Price
Journal: Trends in Ecology & Evolution (2016)
Abstract 11289: Transient Ischemic Dilatation During Stress Echocardiography: A Marker of Significant Myocardial Ischemia
Authors: Akihisa Kataoka, Marielle Scherrer-Crosbie, Khaled A Dajani, Patrick Garceau, Jeffrey L Hastings, Jeffrey A Kohn, Elizabeta Srbinovska-Kostovska, Daniele Poggio, Muhamed Saric, Roxy Senior, Kozhaya Sokhon, Leslee Shaw, Harmony Reynolds, Michael H Picard
Journal: Circulation (2013)

Purpose: Left ventricular (LV) transient ischemic dilatation (TID) during myocardial perfusion imaging (MPI) is considered a marker of extensive coronary artery disease and a predictor of future ca...
Chordoma: A rare bone tumor: A single institutional experience on a case series of 23 patients
Authors: V. Ferraresi, C. Nuzzo, C. Zoccali, V. Graziano, V. Graziano, N. Salducca, M. Zeuli, D. Giannarelli, D. Pellegrini, F. Cognetti
Journal: Journal of Clinical Oncology (2009)

e21519 Background: Chordoma is a rare primary bone tumor arising from primitive notochord remnants of axial skeleton. Adequate surgery still remains the mainstay of its therapeutic treatment. Methods: Our review has been focused on the clinical characteristics, type of treatment, and prognosis of 23 consecutive cases of chordomas observed from 2004 until today and followed by the same team of specialists (orthopedic surgeons and medical oncologists). Results: From June 2004 to December 2008, 23 pts with various stage of disease went to our observation. Male/female: 18/5. Median age at diagnosis: 60 yrs (range: 40 -74). Sites of origin: sacrum (10 pts), spine (12 pts), and skull base (1 pt). Ten pts (44%) had primary disease, 9 pts (39%) had recurrent disease, and 4 pts (17%) had developed metastatic lesions. Surgery was part of the treatment in 21 out of 23 pts. Surgical margins were rated as wide/marginal in 17 pts and intralesional in 4 pts. Adjuvant proton radiotherapy has been delivered to 2 pts. Conventional radiotherapy was performed in 4 pts. The rate of local relapse after primary surgical excision was 76%. The median time to recurrence was 14 months (range: 2–113).Sixteen pts with inoperable/unresectable or metastatic PDGFR β expressing disease were treated with imatinib mesylate (IM) in the context of a clinical trial and a subsequent expanded access program (Stacchiotti S., proc ASCO 2007. abstr. 10003). One pts received weekly cisplatin in combination with IM after progression during IM therapy. The 5-year survival rate of the entire series was 76 %. Two out of 17 pts (12%) surgically treated with adequate margins are still alive and without evidence of disease; two other pts died without evidence of disease. Conclusions: Despite the progress of current surgical techniques and some encouraging results with the use of targeted therapy, chordoma results, generally, in a long-lasting disabling and life-affecting disease. Nevertheless, specific experience of the multidisciplinar team is an important prerequisite to improve patients’ quality of life and, hopefully, outcome. No significant financial relationships to disclose.
A prospective study of the effects of once weekly bortezomib on markers of bone metabolism in patients with multiple myeloma (MM)
Authors: S. Peles, N. M. Fisher, F. Gao, M. H. Tomasson, J. F. Dipersio, R. Vij
Journal: Journal of Clinical Oncology (2006)

7548 Background: Increased osteoclast activity in MM leads to bone resorption, osteoporosis and osteolytic bone lesions. Urinary excretion of N-telopeptide (NTX), a marker of bone resorption, decreases by 20–70% following treatment with bisphosphonates. Preclinical studies have shown bortezomib to decrease osteoclast function through inhibition of NF-kB. However, no clinical data exists on the effect of bortezomib on markers of bone resorption. Methods: Six cycles of consolidation bortezomib 1.3mg/m 2 were given once weekly for 4 of every 5 weeks, 90–120 days post transplant. Urinary NTX excretion and serum osteocalcin were measured on day 1 of cycles 1, 2 and 3 of therapy. Bisphosphonates were prohibited from 42 days prior to stem cell collection and until cycle 3 of consolidation therapy. Results: 33 of 40 enrolled patients received bortezomib consolidation. Patient population and disease characteristics (no. of patients): male (22), female (11), median age 56 years (range 39–70), Stage II (9), Stage III (24), IgG (22), IgA (9), free light chain (2). The median duration between discontinuation of bisphosphonates and initiation of consolidation bortezomib was 158 days (Range 110–196). Only one patient had a &gt;50% reduction in myeloma paraprotein. Nevertheless, excretion of NTX declined by a mean of 32% over baseline values after 2 cycles of consolidation therapy. The only patient with an increase in NTX of &gt;30% was also the only patient with evidence of disease progression during this period of therapy. Contrary to reports of proteasome inhibition resulting in increased osteoblastic bone formation, a decline was seen in osteocalcin. Conclusions: Bortezomib has an inhibitory effect on osteoclastic bone resorption in MM similar to that with bisphosphonates even in the absence of effects on malignant plasma cells. Bisphosphonates may result in nephrotoxicity and osteonecrosis of the jaw and bortezomib represents an alternative agent that may control both the myeloma and bone disease. [Table: see text] No significant financial relationships to disclose.
Phase II trial of neoadjuvant docetaxel and carboplatin with filgrastim (G-CSF) support in patients with locally advanced breast cancer
Authors: S. Karmarkar, D. Jones, S. Hatch, F. Klementich, K. Ansari, B. Grube, C. Chao, C. Townsend
Journal: Journal of Clinical Oncology (2004)

789 Background: Many women with Locally Advanced Breast Cancer (LABC) have a poor outcome with surgical resection alone. Neoadjuvant therapy is safe and may convert marginally resectable lesions to those more amenable to surgery. Taxanes are synergistic with platinum agents, both are active in LABC when used in front-line therapy. We are investigating a neoadjuvant regimen of Docetaxel (D) with Carboplatin (C) in women with LABC. Methods: Eligibility criteria include previously untreated measurable Stage IIB/IIIA/IIIB breast cancer; SWOG PS 0–2; adequate bone marrow, hepatic, and renal function; provision of written informed consent. Pts receive Docetaxel 90 mg/m2 and Carboplatin AUC = 6, on day 1 with filgrastim 480mcg SC on days 2–10 of a 21-day cycle. After 4 cycles, pts undergo appropriate surgical resection; those with residual disease receive adjuvant chemotherapy and radiotherapy administered as indicated. Pts with ER+ or PR+ tumors receive 5 years of endocrine therapy. Results: 22 pts have been enrolled; 16 are evaluable for toxicity and response. 11 pts underwent surgery. The median age is 54 (range 41–75 years) 11/16 caucasian, 2/16 black and 3/16 hispanic. 12/16 had Stage IIIA or IIIB lesions. T2 -1/16, T3 -10/16 and T4 -4/16 disease. 11 are ER+ and 7 are HER2+. All evaluable patients have responded clinically with 5 cCR and 11 cPR. Four patients have pCR in the primary lesion. The therapy was well tolerated. Alopecia is universal. Grade 3–4 toxicities include myalgias (2 pts), diarrhea (1 pt) & fatigue/asthenia (5 pts). Four pts experienced grade 3 nausea. There has been 1 episode of grade 3 myelosuppression with infection. One pt stopped therapy due to hypersensitivity. One pt has had local relapse. Conclusions: This is a well-tolerated and active regimen. The addition of Filgrastin allows a dose intense neoadjuvant regimen to be administered. Preliminary pCR findings are promising. Patient accrual is continuing. No significant financial relationships to disclose.