tbuckley/cabot-search huggingface dataset:
Final results from ASPECCT: Randomized phase 3 non-inferiority study of panitumumab (pmab) vs cetuximab (cmab) in chemorefractory wild-type (WT) <i>KRAS</i> exon 2 metastatic colorectal cancer (mCRC).
Authors: Timothy Jay Price, Marc Peeters, Tae Won Kim, Jin Li, Stefano Cascinu, Paul Ruff, Attili Venkatasatya Suresh, Anne L. Thomas, Sergei Tjulandin, Kathy Zhang, Roger Sidhu, Swaminathan Murugappan
Journal: Journal of Clinical Oncology (2015)

3586 Background: The primary analysis of ASPECCT demonstrated that pmab was non-inferior to cmab for overall survival (OS) in chemorefractory WT KRASmCRC. Here, we report the final analysis of ASPECCT. Methods: In ASPECCT, patients (pts) had WT KRASmCRC, ECOG performance status (PS) ≤2, prior irinotecan, oxaliplatin, and fluorouracil treatment, and no prior anti-EGFR therapy. Pts were stratified by geographic region (North America/Western Europe/Australia vs rest of world) and ECOG PS (0-1 vs 2) and randomized 1:1 to receive pmab 6 mg/kg q2w or cmab 400 mg/m2 followed by 250 mg/m2 qw. The primary endpoint was OS assessed for non-inferiority (retention of ≥50% of the cmab effect vs best supportive care [BSC]; HR=0.55 [95% CI: 0.41 - 0.74] based on NCIC CTG C0.17). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. All pts were followed for survival for up to 2 years after the last pt was randomized and a final analysis of efficacy and safety was conducted. No formal hypothesis testing was performed. Results: 999 pts were randomized and treated: 499 pmab and 500 cmab. 90% of pts had died at the time of this analysis (78% in the previously reported primary analysis). Baseline demographics and disease characteristics were similar between arms. Non-inferiority results for OS are shown (Table). Overall, any grade and grade 3-4 adverse events (AEs) were similar between arms. AEs of interest were (pmab vs cmab): grade 3-4 skin toxicity 13% vs 10%, grade 3-4 infusion reactions 0.5% vs 2%, and grade 3-4 hypomagnesemia 7% vs 3%. Conclusions: Consistent with the primary analysis, the final analysis of ASPECCT showed that pmab was non-inferior to cmab for OS in chemorefractory WT KRASmCRC. Safety profiles were as expected for pmab and cmab. Clinical trial information: NCT01001377. Pmab N = 499 Cmab N = 500 Median OS, mos (95% CI) 10.2 (9.4-11.4) 9.9 (9.0-10.8) HR (95% CI) 0.94 (0.82-1.07) P value 0.0002 OS retention rate* 1.11 (0.88-1.33) Median PFS, mos (95% CI) 4.2 (3.2-4.8) 4.4 (3.2-4.8) HR (95% CI) 0.98 (0.87-1.12) ORR,% (95% CI) 21.6 (18.1-25.5) 19.2 (15.8-22.9) *Rate of cmab OS benefit (cmab:BSC) retained by pmab.
IL3-Receptor Signaling Is Dispensable For The Generation and Maintenance Of Jak2V617F-Induced Myeloproliferative Neoplasm (MPN
Authors: Therese Vu, Claudia Bruedigam, Rebecca Austin, Catherine Paine-Kuhn, Hayley S. Ramshaw, Angel F. Lopez, Geoff Hill, Ann Mullally, Steven W Lane
Journal: Blood (2013)
Kaposi sarcoma–associated herpesvirus: immunobiology, oncogenesis, and therapy
Authors: Dirk P. Dittmer, Blossom Damania
Journal: Journal of Clinical Investigation (2016)

Kaposi sarcoma–associated herpesvirus (KSHV), also known as human herpesvirus 8, is the etiologic agent underlying Kaposi sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. This human gammaherpesvirus was discovered in 1994 by Drs. Yuan Chang and Patrick Moore. Today, there are over five thousand publications on KSHV and its associated malignancies. In this article, we review recent and ongoing developments in the KSHV field, including molecular mechanisms of KSHV pathogenesis, clinical aspects of KSHV-associated diseases, and current treatments for cancers associated with this virus.
Randomized Phase II Trial of Gefitinib With and Without Pemetrexed as First-Line Therapy in Patients With Advanced Nonsquamous Non–Small-Cell Lung Cancer With Activating Epidermal Growth Factor Receptor Mutations
Authors: Ying Cheng, Haruyasu Murakami, Pan-Chyr Yang, Jianxing He, Kazuhiko Nakagawa, Jin Hyoung Kang, Joo-Hang Kim, Xin Wang, Sotaro Enatsu, Tarun Puri, Mauro Orlando, James Chih-Hsin Yang
Journal: Journal of Clinical Oncology (2016)

To determine whether the addition of pemetrexed to gefitinib (P+G) provides clinical benefit, compared with gefitinib monotherapy, in patients with advanced nonsquamous (NS) non-small-cell lung cancer (NSCLC) and activating epidermal growth factor receptor (EGFR) mutations.Chemotherapy-naïve for advanced NSCLC patients from China, Japan, Korea, and Taiwan (35 sites) with advanced, EGFR-mutant, NS NSCLC were randomly assigned (2:1; computer-generated, interactive voice response) to open-label pemetrexed (500 mg/m(2) on day 1 of every 21-day cycle) plus gefitinib (250 mg/d [n = 129]) or gefitinib alone (n = 66). The primary end point was progression-free-survival (PFS); secondary end points were time to progressive disease, overall survival, tumor response rates, duration of response, and safety. All end points were assessed in the intent-to-treat and safety population (P+G, n = 126; gefitinib alone, n = 65).PFS was significantly longer with P+G (median, 15.8 months; 95% CI, 12.6 to 18.3 months) than with gefitinib (median, 10.9 months; 95% CI, 9.7 to 13.8 months; adjusted hazard ratio [HR], 0.68; 95% CI, 0.48 to 0.96; one-sided P = .014; two-sided P = .029). Results of EGFR exon 19 deletion and EGFR exon 21 L858R point mutation subgroup analyses were consistent with the intent-to-treat result. P+G, compared with gefitinib alone, resulted in significantly longer time to progressive disease (median, 16.2 v 10.9 months, respectively; HR, 0.66; 95% CI, 0.47 to 0.93) and numerically longer duration of response (median, 15.4 v 11.3 months, respectively; HR, 0.74; 95% CI, 0.50 to 1.08). Tumor response rates did not differ. Overall survival data are immature. Drug-related grade 3 or 4 adverse events were more common with P+G, but toxicities were manageable.P+G improved PFS compared with gefitinib alone in East Asian patients with advanced NS NSCLC and activating EGFR mutations. This combination may offer EGFR mutation-positive patients new treatment options and improved clinical outcomes compared with the current standard of care.
Identification of factors influencing chemotherapy-induced nausea and vomiting (CINV) treatment compliance – results from quantitative market research.
Authors: Pierfrancesco Ruffo, Roger Panteri, Stefano Costa, Vittoria Piovesana
Journal: Journal of Clinical Oncology (2016)

e18158 Background: Antiemetic guidelines recommend the combination of a neurokinin-1 receptor antagonist (NK1 RA), a 5-hydroxytryptamine-3 receptor antagonist (5HT3 RA), and dexamethasone for prophylaxis in patients (pts) at high risk of CINV. While these recommendations can decrease CINV incidence, guidelines adherence is often suboptimal, possibly due to the complexity of prophylactic regimens. Even when guidelines are adhered to by physicians, incorrect home administration of follow-up antiemetic(s) by pts may still occur. Simplification of antiemetic regimens using an agent such as NEPA, an oral fixed combination of the NK1 RA netupitant and the 5HT3 RA palonosetron, only requiring a single-dose administration before chemotherapy, may improve adherence/compliance. Methods: Quantitative market research was performed to identify potential factors for noncompliance to antiemetic regimens and if there is a need for therapy simplification. An online questionnaire was completed by 300 oncologists from Italy, France, Germany, Spain, and the UK who prescribe antiemetics and see ≥ 50 pts/month. Pooled data are presented. Results: Oncologists reported an incidence of emesis in antiemetic-treated pts of 15% and 21% (acute), and 18% and 26% (delayed) for pts receiving moderately or highly emetogenic chemotherapy, respectively. Use of weaker antiemetic regimens (ie, monotherapy instead of combination) and mistakes in administration were identified among the causes of lack of response by 31% and 17% (acute), and 33% and 21% (delayed) of oncologists. Overall, respondents reported that 35% of their pts made mistakes (ie, missed/delayed doses) during antiemetic therapy administration at home. Pts’ compliance to antiemetic prophylaxis was perceived as an issue by 42% of oncologists. Conclusions: Pts’ noncompliance to antiemetic treatment is of concern to oncologists. Mistakes/issues in administration were identified as potential reasons for treatment failure, which occur more commonly during treatment at home. A simple, effective single-dose combination therapy (ie, NEPA) may be a valuable option and increase antiemetic guideline compliance.
Fellowship characteristics associated with fellows' interest in pursuing clinical research: A National Comprehensive Cancer Network (NCCN) survey.
Authors: J. M. Hinkel, J. L. Vandergrift, E. M. Lepisto, K. A. Minogue, F. M. Stewart
Journal: Journal of Clinical Oncology (2010)

6157 Background: A survey of oncology fellows was conducted in February 2009 to gauge fellows' interest in pursuing clinical research post-fellowship and to identify factors associated with an interest in post-fellowship research. Methods: A survey was developed by NCCN analytical staff and expert clinicians. The survey was distributed to 166 oncology fellows who attended the 2009 NCCN Annual Conference. Overall, 125 (75%) fellows completed the survey. Results: Respondents' specialties were hematology/oncology (66%), radiation oncology (18%), medical oncology/solid tumor (15%), and surgical oncology (1%). A majority were active in clinical (63%), lab (5%), or both clinical and lab (18%) research. Most were very (54%) or somewhat (33%) interested in conducting clinical research post-fellowship. More than half (58%) had received formal instruction in clinical research skills. Interest in research post-fellowship was greater for fellows currently active in clinical research (Mann-Whitney U = 2.06, p = 0.04), and among those who received formal instruction in clinical research skills (Mann-Whitney U = 3.48, p < 0.001). Fellows who felt better prepared to enter academics/research/practice also reported greater interest in clinical research (rs = 0.333, p < 0.001). Interest in research post-fellowship was not significantly related to level of satisfaction with program characteristics including: ability to conduct research, mentorship, clinical responsibilities, and protected time (rs = 0.163, p = 0.09). A strong relationship was observed between fellows' interest in clinical research post- fellowship and their interest in practicing in an academic setting (rs = 0.499, p < 0.001). Conclusions: A majority of fellows surveyed in this study expressed interest in conducting research post-fellowship. Current research activity and receipt of formal clinical research training were associated with a greater interest in post-fellowship research. Only 58% of fellows reported having received formal clinical research training. Interest in conducting clinical research was strongly associated with an interest in practicing in an academic setting. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration HCPLive - MDNG HCPLive - MDNG
Influence of patient beliefs and patient knowledge on adherence to hormone treatment for breast cancer.
Authors: K. P. Joseph, R. Franco, K. Fei, N. Bickell
Journal: Journal of Clinical Oncology (2010)

6072 Background: This multicenter study examined the perception among all newly diagnosed early stage breast cancer patients as to differences in adherence to hormonal therapy was related to factors such as patient knowledge and beliefs regarding hormonal treatment. Methods: Patients were enrolled from multiple hospital centers in New York City in this IRB approved study. Of 100 women determined to need hormonal treatment, 82 were prescribed treatment and 75 were still taking hormonal treatment at the time of the study. Of these women, 20 were African American, 73 were white, 33 were Hispanic, 6 were Asian/Pacific Islander and 2 other. Patients with early-stage breast cancer who had recently undergone surgical treatment were recruited 6 months post surgery. All patients were telephone surveyed to assess predisposing knowledge, attitudes and beliefs about breast cancer, their needs and barriers to treatment and their use of patient assistance programs for this cancer episode. Results: Adherent patients tend to be younger than nonadherent patients (54 vs. 62, p = 0.02). There is no significant difference among ethnic groups between adherent vs. nonadherent groups. 86% of adherent patients have a greater knowledge of hormonal therapy compared to 64% of nonadherent patients (p = 0.04). 71% of nonadherent patients believe hormonal therapy is harmful compared with 47% of adherent patients (p = NS). Adherence is not affected by cost of medication, side effects, or type of insurance. Whites (47%) and Hispanics(25%) believe that the use of hormonal treatment is harmful although this was not significant. Patients with more knowledge have less mistrust in the medical system. Conclusions: Differences in adherence do not appear to be related to racial differences, side effects of hormonal treatments, cost of treatment or insurance type. Although patients are aware that hormonal treatment can be harmful they are nevertheless willing to take the treatment. Adherence to treatment is more dependent on patient beliefs than knowledge and understanding this can help physicians treat nonadherent patients appropriately. No significant financial relationships to disclose.
The better bisphosphonate in patients with bone metastasis: Zoledronic acid or ibandronic acid? A study from Eastern India
Authors: R. Pandey, S. Dey, A. Mukhopadhyay
Journal: Journal of Clinical Oncology (2009)

e20524 Background: Ibandronic acid is a third generation bisphosphonate which acts by inhibition of osteoclasts. Zoledronic acid also has a similar mechanism of action. This study was designed to study superiority or inferiority of either agent over other in terms of efficacy in reducing bone pain and complications in patients with bone metastases. Methods: From Jan 2005 to Dec 2008, 240 patients of various malignancies with bone metatstasis were enrolled and were randomized on a 1:1 basis to receive monthly IV infusions of ibandronate or zoledronate and were analysed for pain relief, skeletal related events and adverse events. Results: Patients in both the arms were well matched for their diagnosis, stage of disease, burden of skeletal disease and performance status. Different diagnoses were, carcinoma breast (n=99), carcinoma prostate (n=54), myeloma (n=48), carcinoma lung (n=23), others (n=20). Median follow up was 18 months. At 18 months, mean increases in British Pain Inventory pain scores were lower with zoledronate compared to ibandronate (0.43 vs 0.88 [p=0.02]). Analgesic use as defined by 4 point analgesic scale was less with zoledronate as compared to ibandronate. Incidence of skeletal related events was not significantly different between two arms (33% for zoledronate vs 39% for ibandronate [p=0.2]). Median time to first skeletal related event was not reached in either arm. At 18 months of median follow up, percentage of patients with skeletal related events were 39% in zoledronate arm vs 43% in ibandronate arm (p=0.06). Zoledronate caused fever in 30 (12.5%) patients and hypocalcemia in 10 patients. Ibandronte caused hypocalcemia in 3 patients. No cases of osteonecrosis of jaw were observed. Conclusions: Zoledronate is the preferred bisphosphonate in developing countries for its shorter infusion time and availability of cheaper generic brands. This study also indicates that it may be slightly better than ibandronate in reducing bone pain and preventing skeletal related events. No significant financial relationships to disclose.
Deaths from heart disease in UK fall, but prevalence is unchanged
Authors: Susan Mayor
Journal: BMJ (2016)

Cardiovascular disease (CVD) mortality in the United Kingdom has decreased significantly over the past 30 years, but its prevalence has shown little change, and major differences exist in the burden of CVD among the four constituent countries and between men and women, a review has found.1

The review, published in Heart , analysed trends in CVD mortality, morbidity, and treatment in the UK as a whole and separately in England, Wales, Scotland, and Northern Ireland using national annual statistics and figures on hospital admissions, prevalence, and treatment from 1979 …
Randomised controlled trial of long-term maintenance corticosteroid therapy in patients with autoimmune pancreatitis
Authors: Atsushi Masamune, Isao Nishimori, Kazuhiro Kikuta, Ichiro Tsuji, Nobumasa Mizuno, Tatsuo Iiyama, Atsushi Kanno, Yuichi Tachibana, Tetsuhide Ito, Terumi Kamisawa, Kazushige Uchida, Hideaki Hamano, Hiroaki Yasuda, Junichi Sakagami, Akira Mitoro, Masashi Taguchi, Yasuyuki Kihara, Hiroyuki Sugimoto, Yoshiki Hirooka, Satoshi Yamamoto, Kazuo Inui, Osamu Inatomi, Akira Andoh, Kazuyuki Nakahara, Hiroyuki Miyakawa, Shin Hamada, Shigeyuki Kawa, Kazuichi Okazaki, Tooru Shimosegawa
Journal: Gut (2016)

Corticosteroid has been established as the standard therapy for autoimmune pancreatitis (AIP), but the requirement for maintenance corticosteroid therapy is controversial. We conducted a randomised controlled trial to clarify the efficacy of maintenance corticosteroid therapy in patients with AIP.We conducted a multicentre, tertiary setting, randomised controlled trial. After the induction of remission with the initial oral prednisolone (PSL) treatment, maintenance therapy with PSL at 5-7.5 mg/day was continued for 3 years or withdrawn at 26 weeks. The primary endpoint was relapse-free survival over 3 years and the secondary endpoint was serious corticosteroid-related complications. All analyses were performed on an intention-to-treat basis.Between April 2009 and March 2012, 49 patients with AIP were randomly assigned to the maintenance therapy group (n=30) or the cessation group (n=19). Baseline characteristics were not different between the two groups. Relapses occurred within 3 years in 11 out of 19 (57.9%) patients assigned to the cessation group, and in 7 of 30 (23.3%) patients in the maintenance therapy group. The relapse rate over 3 years was significantly lower in the maintenance therapy group than that in the cessation group (p=0.011). The relapse-free survival was significantly longer in the maintenance therapy group than that in the cessation group (p=0.007). No serious corticosteroid-related complications requiring discontinuation of PSL were observed.Maintenance corticosteroid therapy for 3 years may decrease relapses in patients with AIP compared with those who discontinued the therapy at 26 weeks.UMIN000001818; Results.
Detection of p57KIP2 Gene Methylation Is Useful Marker for Minimal Residual Disease in Diffuse Large B Cell Lymphoma.
Authors: Kazumi Hagiwara, Hirokazu Nagai, Toshiya Yokozawa, CHiaki Kato, Motohiro Hamaguchi, Tomomitsu Hotta, Keizo Horibe
Journal: Blood (2007)
Synergistic Effects of a Novel Water-Soluble Small Molecule, ON 013105, and Rituximab on Mantle Cell Lymphoma In Vitro and In Vivo
Authors: Anil Prasad, Ashutosh Shrivastava, Ramana Reddy, Amanda M. Gillum, E. Premkumar Reddy, Jerome E. Groopman
Journal: Blood (2010)
Genetic Screening of Anderson-Fabry Disease in Probands Referred From Multispecialty Clinics
Authors: Valentina Favalli, Eliana Disabella, Mariadelfina Molinaro, Marilena Tagliani, Anna Scarabotto, Alessandra Serio, Maurizia Grasso, Nupoor Narula, Carmela Giorgianni, Clelia Caspani, Monica Concardi, Manuela Agozzino, Calogero Giordano, Alexandra Smirnova, Takahide Kodama, Lorenzo Giuliani, Elena Antoniazzi, Riccardo G. Borroni, Camilla Vassallo, Filippo Mangione, Laura Scelsi, Stefano Ghio, Carlo Pellegrini, Marialuisa Zedde, Laura Fancellu, GianPietro Sechi, Antonello Ganau, Stefania Piga, Annarita Colucci, Daniela Concolino, Maria Teresa Di Mascio, Danilo Toni, Marina Diomedi, Claudio Rapezzi, Elena Biagini, Massimiliano Marini, Maurizia Rasura, Maurizio Melis, Antonia Nucera, Donata Guidetti, Michelangelo Mancuso, Umberto Scoditti, Pamela Cassini, Jagat Narula, Luigi Tavazzi, Eloisa Arbustini
Journal: Journal of the American College of Cardiology (2016)
Identification of distinct protein Signatures Associated with genetic Abnormalities In Acute Lymphoblastic Leukemia
Authors: Roland P. Kuiper, Blanca Scheijen, Agata Pastorczak, Simon V. van Reijmersdal, Deborah A. Thomas, Niangxiang Zhang, Kevin R. Coombes, Hagop M. Kantarjian, Elias J. Jabbour, Eveline S.J.M De Bont, Frank N. van Leeuwen, Steven M. Kornblau
Journal: Blood (2013)
Self-responsibility for Our Good Health
Authors: Maria Luisa Gasparri, Michael D. Mueller, Andrea Papadia
Journal: JAMA Oncology (2016)

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