tbuckley/cabot-search huggingface dataset:
Circulating tumor cells (CTC) and pathological complete response (pCR) as independent prognostic factors in inflammatory breast cancer (IBC) in a pooled analysis of two multicentre phase II trials (BEVERLY 1 &amp; 2) of neoadjuvant chemotherapy combined with bevacizumab.
Authors: Jean-Yves Pierga, Francois-Clement Bidard, Aurelie Autret, Thierry Petit, Fabrice Andre, Florence Dalenc, Christelle Levy, Jean-Marc Ferrero, Gilles Romieu, Jacques Bonneterre, Florence Lerebours, Thomas Denis Bachelot, Pierre Kerbrat, Emmanuelle Charafe-Jaufret, Jérôme Lemonnier, Patrice Viens
Journal: Journal of Clinical Oncology (2015)

108 Background: We have reported that CTC detection is an independent prognostic factor in 52 primary HER2+ IBC (Pierga, CCR 2014). We present a pooled analysis of two prospective trials including 152 patients (pts). Predictive and prognostic value of Circulating Endothelial Cells (CEC) for response to bevacizumab was also analyzed. Methods: CTC and CEC were detected in 7.5 ml and 4 ml of blood respectively in the neoadjuvant setting in IBC (T4d) pts enrolled in two phase II multicentre trials, evaluating bevacizumab (15mg/kg q3w) in combination with sequential neoadjuvant chemotherapy (CT) of 4 cycles of FEC followed by 4 cycles of docetaxel in HER2 - tumor (BEVERLY 1) or docetaxel, trastuzumab in HER2 + (BEVERLY 2). The CellSearch System, combining EpCAM immunomagnetic selection followed by anti-cytokeratin (A45B/B3) and anti-HER2 staining for CTC and CD146 IMS and CD105 staining for CEC. Results: From 10/08 to 09/10, 152 pts were included and 137 were evaluable for CTC and CEC. Median follow-up was 43 months. At baseline, 55 pts had ≥ 1 detectable CTC (39%). After 4 cycles of CT, a dramatic drop in CTC to a rate of 9% was observed. pCR rate was 40% and was associated with absence of hormonal receptor and HER2 + status. No correlation was found between CTC and CEC levels or pCR rate. CTC detection at baseline independently predicted 3-year disease-free survival (DFS): (70% vs. 39% for pts with < 1 vs. ≥ 1 CTC/7.5 mL [p < 0.001, HR 2.80 (1.65-4.76)]) and 3-year overall survival (OS) (92% vs 56% HR 4.28 p < 0.001). At multivariate analysis, independent prognostic parameters for DFS were absence of hormonal receptors, no pCR, and CTC detection at base-line. CEC level at baseline or variations during treatment had no prognostic value. Conclusions: This is the largest prospectives trial in non-metastatic IBC evaluating CTC detection. We observed a high CTC detection rate of 39%, with a strong and independent prognostic value for DFS and OS. Combination of pCR after neoadjuvant treatment, with CTC at baseline, isolates a subgroup of IBCwith excellent survival. CTC count should be part of IBC stratification in prospective trials. Clinical trial information: NCT00820547.
Prelinical evaluation of selective inhibitors of nuclear export (SINE) CRM1 (XPO1) inhibitors in prostate cancer (PrCa).
Authors: Sharon Shacham, Giovanni Luca Gravina, Enrico Ricevuto, Andrea Mancini, Lynda Chin, Sharon Shechter, Vincent Sandanayaka, Dilara McCauley, Michael Kauffman, Giulio Francesco Draetta, Claudio Festiccia
Journal: Journal of Clinical Oncology (2012)

e15200 Background: CRM1 (XPO1) is the sole exportin mediating transport of multiple tumor suppressor proteins (TSP) including p53, pRB, FOXO, APC and NPM1 out of the nucleus, abrograting their function. Many tumor types show overexpression of CRM1, thus extinguishing TSP function. CRM1 inhibition forces nuclear accumulation of TSPs inducing apoptosis in cancer cells. Methods: MSKCC PrCa gene database was used for mRNA analyses. Inhibition of CRM1 mediated NE was determined by IHC. MTT assays were used to determine cytotoxicity across divergent PrCa lines: LAPC-4 (p53wt, AR+, low Akt/mTOR); LnCaP (p53wt, AR+, high Akt/mTOR); LnCaP-C81 and LnCaP-C4-2B (p53wt, AR+, androgen independent, high Akt/mTOR); 22rv1 (p53wt, AR+, androgen independent, low Akt/mTOR); PC3 (p53-del, AR–, high Akt/mTOR), DU145 (p53mut, AR–, low Akt/mTOR). BPH1 and prostatic epithelial line EPN were used as non-neoplastic controls. 22rv1 xenografts were initiated in the flanks of SCID mice and treatment begun when tumors reached ~150mm 3 . Results: Analyses of nuclear pore complex (NPC)-related mRNA levels shows coordinate regulation of transcripts and allow PrCa to be segregated into high and low NPC expression. Low NPC expressing tumors tended to have reduced AR expression; APC, NPM1, and RB1 mRNA levels were also low (p&lt;10e-12) and p16INK4A levels were elevated. As NE is dysregulated in PrCa, we assessed the effects of SINE, irreversible CRM1 inhibitors, across PrCa cell lines. SINE block CRM1 mediated nuclear export of TSPs with IC50 values &lt;100 nM in all tested cell lines. SINE are selectively cytotoxic for neoplastic (EC50 10-1000nM) versus non-neoplastic lines (EC 50 &gt;5-20µM). SINE cytotoxic effects are independent all tested genetic alterations. In the aggressive, androgen independent 22rv1 xenograft, oral SINE KPT-251 showed dose-dependent inhibition of tumor growth and synergy with cisplatin. Conclusions: These data show that PrCa shows coordinate NPC regulation, and that selective blockade of CRM1 dependent NE represents a completely novel, neoplasia-selective and well-tolerated target for use as single agent or in combination with chemotherapy for PrCa.
Implications of following the guidelines for genetic testing and MRI use for breast cancer.
Authors: Fernanda C. G. Polubriaginof, Brian Drohan, Phil Bosinoff, Alan Semine, Claire Cronin, Frederick Millham, Taryn Rourke, Caroline Cole Block, Kevin S. Hughes
Journal: Journal of Clinical Oncology (2014)

1549 Background: Evidence-based medicine is based upon the use of established guidelines and algorithms to increase the quality and decrease the cost of medical care. Genetic testing for breast cancer gene mutations is offered to women who have a risk ≥ 10% of carrying a mutation or that meet the NCCN Guidelines. Screening with breast magnetic resonance imaging (MRI) is recommended for women who have a lifetime risk ≥ 20% of developing breast cancer. Our purpose is to evaluate the impact of using guideline based care for these medical issues. Methods: With institutional review board approval, we performed a retrospective analysis of data obtained from consecutive women who presented for breast imaging to the Newton Wellesley Hospital Breast Imaging Center from September 3, 2013 to December 31, 2013. Demographic characteristics and breast cancer risk factors were entered into software to evaluate risk (HughesRiskApps) for BRCA mutation, for genetic testing eligibility, for lifetime risk of breast cancer and for MRI eligibility. Risk of mutation was evaluated by Tyrer Cuzick Versions 6 and 7, BRCAPRO and the Myriad Model. Genetic testing eligibility was determined by risk of mutation ≥ 10% or by meeting the NCCN Guidelines. Lifetime risk of breast cancer was evaluated by Tyrer Cuzick Versions 6 and 7, BRCAPRO and Claus. Eligibility for MRI was determined by a lifetime risk ≥ 20% (Per ACS and NCCN Guidelines). Results: A total of 10,604, were evaluated, of whom 9,976 (94.08%) had no personal history of breast cancer and 628 (5.92%) had a personal history of breast cancer. See Table. Conclusions: Following the guidelines for BRCA testing and for MRI screening will result in a large number of women undergoing these services. It would be useful to evaluate whether following these guidelines does increase quality and decrease the cost of care. Genetic testing eligibility No. of patients (%) Without breast cancer (n=9,976) Risk of mutation ≥ 10% 346 (3.50%) Meets NCCN guidelines 1,683 (17.00%) With breast cancer (n=628) Risk of mutation ≥ 10% 105 (17.00%) Meets NCCN guidelines 403 (64.00%) Eligibility for MRI Without breast cancer (n=9,976) Lifetime risk ≥ 20% Tyrer Cuzick 6, BRCAPRO, Claus 558 (5.59%) Tyrer Cuzick 6 and 7, BRCAPRO, Claus 1,495 (14.98%)
Impact of adjuvant treatments on local and metastatic relapse of soft-tissue sarcoma patients in the setting of competing risks.
Authors: Antoine Italiano, Axel Le Cesne, Jean Mendiboure, Jean-Yves Blay, Sophie Piperno-Neumann, Christine Chevreau, Corinne Delcambre, Nicolas Penel, Philippe Terrier, Dominique Ranchere-Vince, Marick Lae, Sophie Le Guellec, Jean-Jacques Michels, Yves Marie Robin, Sylvie Bonvalot
Journal: Journal of Clinical Oncology (2013)

10575 Background: Competing risk is the risk of an event that interferes with the probability of experiencing the disease-specific outcome of interest. Indeed, the occurrence of a competing risk (for instance death by local relapse or another cause) may preclude the onset of the event of interest (for instance metastatic relapse) or at least modify its probability. Competing risk is ignored by Kaplan Meier method and standard Cox survival model. Methods: 3369 adult patients with localized STS were included prospectively in the French Sarcoma Group (GSF) database from January 1990 to December 2009. The outcomes of interest were the cumulative probabilities of local (LR) and of metastatic (MR) relapse with death as a competing event. Estimations and 95% confidence intervals (CIs) were computed with the cumulative incidence function. Results: Median follow-up was 4.5 years. 1-year and 5-year cumulative incidence of LR were 6.4% (95% CI 5.6-7.3) and 25.9% (95% CI 24.2-27.6), respectively. Age, histological subtype, anatomic site and grade were independently associated with the cumulative probability of LR. After adjustment to these prognostic factors, adjuvant radiotherapy was associated with a significant impact on LR (HR=0.5 95% CI 0.4; 0.6, p &lt;0.001). The magnitude of this effect was similar whatever the grade or the anatomic site. Because of the competing effect of death, adjuvant chemotherapy had no significant impact on the cumulative probability of LR. 1-year and 5-year cumulative incidence of MR were 7.4% (95% CI 6.5-8.3) and 26.9% (95% CI 25.2-28.7), respectively. Tumor depth, histological subtype, tumor size and grade were independently associated with the cumulative incidence of MR. After adjustment to these prognostic factors, adjuvant chemotherapy was associated with a significant impact on MR (HR=0.5 95% CI 0.4-0.7, p &lt; 0.001) in grade 3 but not in grade 2 patients (HR=1.3 95% CI 0.9-1.9, p= 0.1). Conclusions: Adjuvant radiotherapy was associated with improved LR outcome even in patients with high risk of competing death from metastatic disease or other causes. Adjuvant chemotherapy was associated with improved MR outcome in patients with grade 3 but not grade 2 disease.
After PCI with stents for AF, adding rivaroxaban vs warfarin to antiplatelet drugs reduced bleeding
Authors: Shamir R. Mehta
Journal: Annals of Internal Medicine (2017)

ACP Journal Club21 March 2017After PCI with stents for AF, adding rivaroxaban vs warfarin to antiplatelet drugs reduced bleedingShamir R. Mehta, MD, MSc, FRCPC, FACCShamir R. Mehta, MD, MSc, FRCPC, FACCMcMaster University, Hamilton, Ontario, Canada (S.R.M.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2017-166-6-029 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationGibson CM, Mehran R, Bode C, et al. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med. 2016;375:2423-34. https://pubmed.ncbi.nlm.nih.gov/27959713Clinical Impact RatingsCardiology: Hematology: Reference1 Gibson CM, Pinto DS, Chi G, et al. Recurrent hospitalization among patients with atrial fibrillation undergoing intracoronary stenting treated with 2 treatment strategies of rivaroxaban or a dose-adjusted oral vitamin K antagonist treatment strategy. Circulation. 2017:135:323-33. [PMID: 27881555] Google Scholar Author, Article, and Disclosure InformationAffiliations: McMaster University, Hamilton, Ontario, Canada (S.R.M.)This article was published at Annals.org on 7 March 2017. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 21 March 2017Volume 166, Issue 6Page: JC29KeywordsAntiplatelet therapyAspirinAtrial fibrillationHemorrhageHospitalizationsIschemic strokeMyocardial infarctionPercutaneous coronary interventionStent implantationThrombosis ePublished: 21 March 2017 Issue Published: 21 March 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Gastrectomy after chemotherapy: A new paradigm for the treatment of stage IV gastric cancer.
Authors: Ho Seok Seo, Cho Hyun Park, Kyo Young Song, Yoon Ju Jung
Journal: Journal of Clinical Oncology (2017)

127 Background: Although there are several traditional treatment modalities for stage IV gastric cancer including chemotherapy, radiation therapy, palliative surgery, or best supportive care, survival result is unsatisfactory. Recently, gastrectomy after chemotherapy which is called conversion surgery or adjuvant surgery was introduced. Methods: In total, 419 patients who were diagnosed stage IV gastric cancer from 2010 to 2015 in eight Catholic Medical Center affiliated hospitals were divided into four groups; 212 for chemotherapy only group (G1), 124 for chemotherapy after primary gastrectomy group (G2), 23 for gastrectomy after chemotherapy group (G3), and 60 for best supportive care group (G4). To compensate chemotherapy effects, cases of complete remission, partial response, and stable disease were selectively analyzed. To identify the factors that affected survival rate, the result of surgery and the intent of surgery of the G3 were analyzed. Results: Three-year survival rate of the G3 was significantly higher than that of the G1 (42.8% vs 12.0%, p = 0.001). In case of the patients with a response to chemotherapy, three-year survival rate showed similar result (G3 vs G1, 46.1% vs 18.4%, p = 0.011). In the G3, R0 resection and curative intent of resection showed better three-year survival rate (R0 vs R1 or R2, 61.1% vs 16.2%, p = 0.003, curative vs palliative, 62.3% vs 23.8%, p = 0.031). Conclusions: The present study showed that gastrectomy after chemotherapy might improve the survival rate for the patients with stage IV gastric cancer, especially who could undergo R0 resection.
A randomized, open label, multicenter, phase 3, 2-arm study of androgen deprivation with leuprolide (L), ± docetaxel (D) for clinically asymptomatic prostate cancer (PC) subjects with a rising PSA following definitive local therapy: Safety results.
Authors: Michael J. Morris, Martin Edwin Gleave, Andrew J. Armstrong, Michael Anthony Carducci, Fred Saad, Kristine Peregrino Lacuna, Howard I. Scher
Journal: Journal of Clinical Oncology (2014)

5022 Background: The optimal approach to PC patients (pts) who biochemically relapse following a radical prostatectomy (RP) is not known. Pts with a rapidly rising PSA are at high risk of early metastasis and death. We conducted a phase III study in such pts to determine the clinical benefit of adding chemotherapy to early hormonal therapy (ADT). All pts have been treated. Here we report the safety results. Methods: Pts with PC who underwent a RP ± salvage RT and developed a rising PSA with a doubling time ≤ 9 months (mo) and no evidence of metastasis were eligible. PSA ≥ 1 ng/mL and testosterone (T) ≥ 100 ng/dl were required. Prior ADT ≤ 6 mo was allowed. Pts were randomized (1:1) to receive L 22.5 mg q3 mo x 18 mo, bicalutamide 50 mg x 30 days, with (Arm A) or without (Arm B) D 75 mg/m2 q3 weeks x 10 cycles. The primary endpoint was PFS at 18 mo post treatment (tx), with T recovery > 50 ng/dl. A sample size of 412 was calculated to detect a HR of 1.6 with 90% power. Results: 400 pts received tx (Arm A = 196, Arm B = 204) and 352 pts completed tx (Arm A = 170, Arm B = 182). 87% of pts treated in Arm A and 89% of pts treated in Arm B completed tx. Pts in Arm A received a mean of 9 cycles of D (range: 1-10), with 79.1% receiving all cycles. Pt compliance for L and bicalutamide was 100%. A greater % of Arm A pts experienced tx-related adverse events (AEs) (93.9 vs. 66.7%), AEs ≥ Gr 3 (48 vs. 10.8%), and serious AEs (25 vs. 9.8%). Most common AEs in Arm A were alopecia (Gr 1-2), fatigue, hot flush, edema, and diarrhea (Gr 1-4), and in Arm B were hot flush (Gr 1-4) and fatigue (Gr 1-2). Most common Gr ≥ 3 AEs in Arm A were neutropenia (15.8%), febrile neutropenia (6.6%), fatigue (4.6%), hyperglycemia (2.6%), and peripheral neuropathy (2.0%). In Arm B, no AE of Gr ≥ 3 occurred in more than 1 pt. Conclusions: ADT for 18 mo ± D for 10 cycles is feasible when given to pre-metastatic castration-sensitive PC pts. As expected, tx in Arm A was concordant with the known D safety profile. Collection of data for analysis of the primary endpoint is ongoing. Clinical trial information: NCT01813370.
Nimotuzumab plus paclitaxel and cisplatin as first-line treatment for esophageal squamous cell cancer: A single center prospective clinical trial.
Authors: Xiaodong Zhang, Ming Lu, Xicheng Wang, Jie Li, Yan Li, Jian Li, Xiaotian Zhang, Jing Gao, Jun Zhou, Zhihao Lu, Jifang Gong, Jun Jia, Yan Cui, Jing Yu, Lin Shen
Journal: Journal of Clinical Oncology (2013)

4097 Background: The aim of this present phase II study is to explore the safety and efficacy of paclitaxel (T), cisplatin (C), and nimotuzumab (N), a humanized anti-EGFR monoclonal antibody combination (TCN) as first-line treatment in advanced esophageal squamous cell cancer (ESCC). Methods: Patients with histologically confirmed advanced ESCC, measureable tumor, and no prior chemotherapy and radiotherapy except adjuvant treatment were enrolled. Patients were given cisplatin 60mg/m 2 , paclitaxel 175mg/m 2 per 21 days for at least 2 cycles. The nimotuzumab was given 200mg weekly. Radiotherapy was admitted for patients with unresectable local advanced disease after 4 cycle of TCN treatment. The primary endpoints were safety and objective response rate (ORR). The secondary endpoints were progression-free survival (PFS) and over-all survival (OS). The expression of EGFR and ERCC1 were also analyzed by histoimmunochemical staining. Results: Between Mar. 2011 and Dec. 2012, 55 patients with advanced ESCC were enrolled and 53 (96.4%) were eligible for evaluation. The ORR was 54.7% (29/53) and the DCR was 94.3% (50/53). The expression of EGFR and ERCC1 were detected in 46 and 31 patients respectively. The ORR had no relation to both the expression of EGFR (55.3% vs 62.5%, p=0.71) and ERCC1 (41.7% vs 58.3%, p=0.47). As a median follow-up of 15months, the median PFS was 10.5 months (95% CI 8.7 to 12.3 months).The TCN combination treatment was well tolerated and the most common adverse events were alopecia (86.8%), leukopenia (84.9%), anorexia (84.9%), vomiting (73.6%), fatigue (73.6%), pain (66.0%), and anaemia (39.6%). And 18 (34%) patients had Grade 3 to 4 leukopenia. The median OS have not yet been reached. Conclusions: In this study, the ORR, DCR and PFS are superior to previous published studies. The addition of anti-EGFR treatment of nimotuzumab to standard chemotherapy was well tolerated with no serious AEs. But the expression of EGFR by IHC could not predict the outcome of nimotuzumab treatment. A phase III study of TCN followed by radiotherapy in unresectable local advanced ESCC had been designed to explore the survival benefits. Clinical trial information: NCT01336049.
Utility of annual screening serum testosterone level in men on surveillance for clinical stage I testicular cancer.
Authors: Eric Winquist, Alexandra Rowe, Stan VanUum, D. Scott Ernst, Kylea R. Potvin, Maureen Quinn, Grace Bradish
Journal: Journal of Clinical Oncology (2017)

144 Background: Testicular cancer occurs in young men and is usually cured leaving survivors with many life years at risk from long term treatment effects. Risks increase with treatment intensity and include cardiovascular disease associated with the metabolic syndrome (Haugnes 2012, de Haas 2013). Testosterone deficiency (TD) is associated with metabolic syndrome &amp; reduced QoL (Huddart 2005). Serum testosterone levels (STLs) are also influenced by underlying testicular dysgenesis &amp; the effects of ageing (Skakkebaek 2001, Oldenburg 2016). We added annual screening STL to our surveillance protocols in 2013 &amp; reviewed the value of this practice. Methods: Men followed in our Testicular Surveillance Clinic from 01 Jan 2006 to 31 Dec 2015 were identified electronically &amp; data extracted retrospectively. Men eligible for this analysis had clinical stage I (CS I) testicular cancer treated with unilateral orchiectomy alone. Outcomes of interest were STLs, Endocrinology referral (Endo) &amp; treatment with androgen replacement therapy (ART). TD was defined by 3 cutoffs of most recent screening STL: &lt; 8.6 nmol/L [age 20-49] (or &lt; 6.7 nmol/L [age &gt; 50]) (local laboratory), &lt; 10.1 nmol/L (Huddart 2005), or &lt; 12.1 nmol/L (EAA &amp; EAU). Results: 77 eligible men were identified: median age 34 years (range, 15-65), seminoma/nonseminoma/mixed/other (45/27/4/1). By the 3 STL cutoffs, TD was present in 13 (16.9% [95%CI, 9.3-27.1%), 22 (28.6% [18.8-40.0%] &amp; 37 (48.1% [36.5-59.7%]); respectively. Nine men (11.4%) were referred to Endo, 1 had morning STL pending &amp; 1 was using OTC ART. Of 8 men assessed by Endo, 5 (6.5%) were prescribed ART. Six men had no screening STL done (3 nonadherent, 1 prostate cancer &amp; 2 unknown). Two men were discharged from clinic with unequivocal low STL. Conclusions: Annual screening STL appears to be useful and may be necessary. 15 CS I men (19.5%) in our clinic had unequivocal TD &amp;/or were referred to an Endo. An additional 20 men (26%) had STLs in a range associated with reduced QoL. Almost half had STLs considered suitable for ART in the presence of symptoms. Two men (2.6%) were discharged with low STLs unaddressed. Guidelines for the optimal assessment and management of men with positive screening for TD are needed.
Newly Acquired Molecular Mutations and SNP-A Lesions Alters the Natural History of Trisomy 8 Myeloid Neoplasms
Authors: Yang Liu, Paul Elson, Ali Tabarroki, Valeria Visconte, Edy Hasrouni, Manoj Bupathi, Betty K. Hamilton, Fabiola Traina, Hien K. Duong, Heesun J. Rogers, Yogen Saunthararajah, Rami S. Komrokji, Mikkael A. Sekeres, Ramon V Tiu
Journal: Blood (2012)