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Eduvirgem, Renan Valério, and Maria Eugênia Moreira Costa Ferreira. "Achatina fulica na zona urbana de Maringá-PR: na perspectiva da análise ambiental." Revista Brasileira de Geografia Física 11, no. 7 (2018): 2391–411. http://dx.doi.org/10.26848/rbgf.v11.07.p2391-2411.
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Muhartono, Muhartono, Soraya Ramanisa, Hanna Mutiara, and Ria Janita Riduan. "HUBUNGAN ANTARA STATUS RESEPTOR ESTROGEN, RESEPTOR PROGESTERON DAN HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 DENGAN DERAJAT KEGANASAN KARSINOMA PAYUDARA INVASIF." Majalah Kedokteran Andalas 39, no. 2 (August 31, 2016): 65. http://dx.doi.org/10.22338/mka.v39.i2.p65-72.2016.
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Karsinoma payudara invasif (KPI) merupakan keganasan yang berasal dari epitel saluran kelenjar susu dan menginvasi jaringan sekitarnya. Pemeriksaan patologi anatomi biasanya menyertakan derajat keganasan (DKg) dan dilanjutkan dengan pemeriksaan imunohistokimia estrogen receptor (ER), progesterone receptor (PR) dan human epidermal growth factor receptor 2 (HER2) untuk menentukan terapi dan memperkirakan prognosis. Penelitian ini bertujuan untuk mengetahui hubungan status ER, PR, HER–2 dengan DKg pada KPI. Subjek penelitian yang digunakan adalah pasien KPI yang telah diperiksa DKg, status ER, PR dan HER–2 pada tahun 2014–2015 di RSUD Abdoel Moeloek Bandar Lampung. Hasil penelitian menunjukkan DKg low grade sebanyak 13 pasien (24,1%), high grade sebanyak 41 pasien (75,9%), status ER‒ sebanyak 32 pasien (50,3%), ER+ sebanyak 22 pasien (40,7%), PR‒ sebanyak 32 pasien (59,3%), PR+ sebanyak 22 (40,7%) dan HER2‒ sebanyak 33 pasien (61,1%), HER2+ sebanyak 21 pasien (38,9%). Hasil uji Chi‒Square antara ER dengan DKg nilai p=0,001, antara PR dengan DKg nilai p=0,002, antara HER2 dengan DKg nilai p=0,53. Simpulan, terdapat hubungan antara estrogen receptor dan progesterone receptor dengan derajat keganasan pada karsinoma duktal invasif.
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Luo, Yi-Bo, Jun-Yu Ma, Qing-Hua Zhang, Fei Lin, Zhong-Wei Wang, Lin Huang, Heide Schatten, and Qing-Yuan Sun. "MBTD1 is associated with Pr-Set7 to stabilize H4K20me1 in mouse oocyte meiotic maturation." Cell Cycle 12, no. 7 (April 2013): 1142–50. http://dx.doi.org/10.4161/cc.24216.
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Thomas Blum, Christopher, Marília Borgo, and André Cesar Furlaneto Sampaio. "ESPÉCIES EXÓTICAS INVASORAS NA ARBORIZAÇÃO DE VIAS PÚBLICAS DE MARINGÁ-PR." Revista da Sociedade Brasileira de Arborização Urbana 3, no. 2 (April 30, 2019): 78. http://dx.doi.org/10.5380/revsbau.v3i2.66347.
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Apesar da temática das espécies exóticas invasoras ser recente no meio científico, e praticamente desconhecida pela sociedade, a invasão biológica desencadeada por elas é a segunda maior causa de perda da biodiversidade no planeta. Quando introduzidas em novos ambientes, elas adaptam-se e ocupam agressivamente o espaço de espécies nativas, produzindo desequilíbrios muitas vezes irreversíveis. Este estudo procurou avaliar o contexto das espécies exóticas na arborização de vias públicas de Maringá. A análise baseou-se nos dados do Projeto Árvore – Censo Verde de Maringá, que cadastrou cerca de 90% das árvores encontradas na arborização. Constatou-se que, das 87 espécies registrados, apenas 24,1% são nativas da Floresta Estacional Semidecidual, bioma onde se insere Maringá. As demais são oriundas de outras formações vegetacionais do Brasil (20,6%) ou de outros países (55,2%). Dezesseis (18,4%) espécies exóticas registradas têm potencial de invasão, destacando-se Hovenia dulcis, Leucaena leucocephala, Melia azedarach e Tecoma stans como as que possuem maior capacidade de invasão biológica, dispersando-se vigorosamente a partir das vias públicas, através de florestas ciliares e áreas degradadas. Em futuros planejamentos de manejo da arborização deverá ser prevista a substituição gradativa destas espécies por outras, preferencialmente nativas da região.
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Luo, Taiming, and Alexei Yu Chirkov. "PHASE ENVELOPE CONSTRUCTION FOR MIXTURES USING HIGHLY ACCURATE HELMHOLTZ ENERGY EQUATION OF STATE." Tyumen State University Herald. Physical and Mathematical Modeling. Oil, Gas, Energy 6, no. 4 (2020): 8–27. http://dx.doi.org/10.21684/2411-7978-2020-6-4-8-27.
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Phase envelope construction for mixtures is very important in the oil and gas industry. The most widely used model for phase envelope construction is Peng — Robinson equation of state (PR-EOS) due to its simplicity. In order to construct phase envelopes of natural gas, a highly accurate Helmholtz energy equation of state GERG-2008 was proposed. In this work, the accuracy of phase envelopes calculated by a highly accurate equation of state GERG-2008, simplified GERG-2008 and traditional cubic PR-EOS was analyzed. The pressure-based algorithm is used to calculate phase envelopes. Phase envelopes of the methane—ethane mixtures were constructed and compared with reference data. The results show that phase envelopes can be constructed with GERG-2008 in high accuracy. PR-EOS has good accuracy in phase envelope construction under low pressure. The simplified GERG-2008 also works well under low pressure; however, as pressure increases, it performs worse than the simpler PR-EOS, especially in the vicinity of critical point. Besides, a modified density solver for the complicated GERG-EOS was proposed. Calculations show that the proposed density solver can provide reliable results.
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Ramadas, Poornima, Jennifer Leibovitch, Karan Ramakrishna, Prathik Krishnan, Dongliang Wang, and Sam Benjamin. "Receptor status conversion between primary and recurrent/metastatic breast cancer: A single institutional study." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e14735-e14735. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e14735.
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e14735 Background: Hormone receptor and HER2 status have both predictive and prognostic implications in breast cancer (BC). Studies report differences of 3% to 54% for Estrogen receptor (ER), 5% to 78% for Progesterone receptor (PR), and 0% to 34% for HER2 between primary (P) and recurrent/metastatic breast cancer (RMBC). To evaluate this difference, we conducted an observational single institution study in adult patients (pts) ≥ 18 years with RMBC. Methods: After IRB approval, we conducted a retrospective chart review of pts diagnosed with RMBC between January 1st, 2010 and October 31st, 2018, with history of PBC. We recorded age at PBC diagnosis, stage, tumor type, receptor status, initial treatment, age at RMBC diagnosis, if biopsy performed, receptor status and survival. We studied the differences in ER, PR and HER2 receptors between P and RMBC. Descriptive statistics was used for analysis. Results: We found a total of 179 pts in the time interval. Median age was 54 ± 13.2 years at PBC diagnosis, 98.9% females, 1.1% males. 187 events were recorded. At PBC diagnosis, 27.4% had Stage I, 37.4% had Stage II and 31.8% had Stage III disease. Tumor type was ductal in 83.8% and lobular in 12.2%. 78.8% was ER+, 68.7% was PR+ and 14% was HER2+. 70.9% received chemotherapy, 12.8% received HER2 therapy and 67% received hormonal therapy. Age at RMBC was median of 61 ± 13.1 years. Biopsy was done in 93.3%. Time between PBC and RMBC ranged from 7 and 324 months. 31.3% had local recurrence and 68.7% had distant disease. In RMBC, 59.2% was ER+, 41.9% was PR + and 13.4% was HER2 +. 58.7% are alive and 38% deceased. With RMBC, 19.2% who were ER+ became ER-, 4.9% who were ER- became ER+, 37.5% who were PR+ became PR-, 8.6% who were PR- became PR+, 23.1% who were HER2+ became HER2-, 4.5% who were HER2 - became HER2+. In pts who became ER-/PR-, 88.5% received hormonal therapy and 61.5% received chemotherapy at the time of PBC. In pts who became HER2-, 83.3% received HER2 therapy at the time of PBC. Conclusions: In our study, we found a difference of 24.1% in ER, 46.1% in PR and 27.6% in HER2 between PBC and RMBC. It is recommended that patients with RMBC should have a biopsy to evaluate the receptor status as it would impact treatment and survival.
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Dede, Isa, Gungor Utkan, Hakan Akbulut, Yuksel Urun, Dilsa Mizrak, and Fikri Icli. "Serum CEA and CA 15-3 levels according to breast cancer subtypes." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e11511-e11511. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e11511.
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e11511 Background: Carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 15-3 are frequently elevated in patients with metastatic breast cancer (MBC). In this study we aimed to correlate levels according to breast cancersubtypes with MBC. Methods: From January 2008 to December 2012, ninety-eight patients with MBC who were treated at Ankara University School Of Medicine, Department of Medical Onkology were included in this study.Serum levels of CEA and CA 15-3were measured and compared according to tumor estrogen receptor (ER), progesteron receptor (PR), and human epidermal growth factor receptor 2 (HER2) status. Results: In this cohort, overall ER,PR and HER2 positivity rates were 65 %,68%,and 58%, retrospectively. Positivite ER status was associated with elevated levels of CA 15-3 and cea. Of these, CA 15-3 levels elevated in 40.5% of ER positivite and 24.1 % of ER negativite patients (p=0.027). Similarly, 46.8 % of ER positivite and 18.2% of ER negativite patients had elevated levels of CEA (P=0.022). no association between PR and HER2 status and tumor markers was observed. Conclusions: The breast cancer subtypes are correlated with serum levels of tumor markers in patients with MBC. Tumor markers elevation may be associated with biological background of breast cancer subtypes. Further validation is needed to determine the role of these markers in diffrent tumor types for monitoring patients with MBC.
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Zhu, Huayuan, Hui Shen, Yilian Yang, Chong-Yang Ding, Yeqin Sha, Hongling Mi, Jingyan Qiu, et al. "Ibrutinib Plus Fludarabine, Cyclophosphamide, and Rituximab As the Treatment for Chronic Lymphocytic Leukemia/ Small Lymphocytic Leukemia: A Single-Center Real World Study." Blood 136, Supplement 1 (November 5, 2020): 29–30. http://dx.doi.org/10.1182/blood-2020-141747.
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Purpose: To evaluate the safety and efficacy of ibrutinib plus fludarabine, cyclophosphamide, and rituximab (iFCR) as the treatment for chronic lymphocytic leukemia (CLL)/ small lymphocytic leukemia (SLL) patients, we conducted time-limited, minimal residual disease (MRD)-driven real world study in The First Affiliated Hospital of Nanjing Medical University Methods: We enrolled patients aged 18 to 65 years old with CLL/SLL who required treatment. Oral Ibrutinib was given continuously (420 mg/day) from day 0, and patients were administered intravenously rituximab (375mg/m2 in day 0 of cycle 1; 500mg/m2 in day 0 of cycle 2-3), fludarabine (25mg/m2, days 1-3) and cyclophosphamide (250mg/m2, days 1-3), every 28-day cycles. All the patients received 3 cycles of iFCR in the first stage. Interim analysis was done according to the 2018 iwCLL criteria and MRD was detected by flow cytometry. Patients who achieved complete response (CR) or partial response (PR) with low MRD level (L-MRD, 10-4-10-2) or undetectable MRD (uMRD) level (<10-4) in peripheral blood (PB) were given 3 times of rituximab or the 4th cycle of iFCR, and then turned to ibrutinib maintenance. Patients who achieved PR with high MRD level (>10-2) in PB or bone marrow (BM), or with diameter of residual lymph node larger than 3cm were administered another 3 cycles of iFCR (6 in all) and followed by ibrutinib maintenance. The primary endpoint was the proportion of patients who achieved uMRD in the PB after 3 cycles of iFCR. The secondary endpoint was overall response rate (ORR), complete response rate (CR) and the number of adverse events (AE). Results: Between May 2019 and June 2020, 29 CLL/SLL patients were enrolled in this cohort with 27 CLL and 2 SLL. 26 of patients were the previously untreated and 3 of patients were relapse or treated before. The median age of patients was 53 years old. Unmutated IGHV was detected in 14 (50.0%) of 29 patients, 4 patients had del(17p) and/or TP53 mutation (13.8%), 7 patients had del(11q) (24.1%), 7 had NOTCH1 mutation (24.1%) and 7 had MYD88 mutation (24.1%). 8 patients (30.8%) were classified as low-risk group according to CLL-IPI, with 9 in intermediate-risk group (34.6%), 5 in high-risk group (19.2%) and 4 in very-high risk group (15.4%). At data cutoff (1st July, 2020), the median follow-up and treatment time was seven months (1-13 months) with 23 patients had completed at least two cycles of iFCR. At interim analysis, the ORR was 100% with 8 patients achieved CR (34.8%), 3 achieved CRi (13.0%) and 12 achieved PR (52.2%). 57.1% (12/21) achieved uMRD in both PB and BM, among which 6 of them (28.6%) achieved CR/CRi and 6 achieved PR (28.6%). All four patients with TP53 abnormalities achieved PR and two of them (50.0%) achieved uMRD in both PB and BM. One of 6 patients with del(11q) achieved CR (16.7%) and five achieved PR (83.3%), with 2 achieved uMRD in both PB and BM (33.3%). Among 13 assessable patients with unmutated IGHV, four of them achieved CR (30.8%) and nine achieved PR (69.2%), with 5 achieved uMRD in both PB and BM (38.5%). 18 patients had turned to ibrutinib maintenance with 12 of them finished 4th cycle of iFCR or 3 additional cycles of rituximab and could be assessed further. 10 of the patients achieved CR/CRi (83.3%) and 2 achieved PR (16.7%), with 8 achieved uMRD in both PB and BM (66.7%). The most common hematological toxicity events were neutropenia and thrombocytopenia and the non-hematological toxicity events were nausea and vomiting. The occurrence rate of grade 3 to 4 neutropenia and agranulocytic fever were 51.9% (15/29) and 17.2% (5/29) respectively. The most common ibrutinib-related AE were purpura, rash and diarrhea. The occurrence rate of AE induced discontinued ibrutinib more than 7 days, discontinued ibrutinib fewer than 7 days and ibrutinib decrement were 20.7%(6/29), 17.2%(5/29) and 20.7%(6/29) respectively. Conclusion: MRD-driven Ibrutinib plus FCR could achieve high response rate with uMRD in yonger fit patients with CLL/SLL, with manageable toxicity. Ibrutinib plus FCR could be one of the most promising choice as a time-limited regimen in the new drug era. Disclosures No relevant conflicts of interest to declare.
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Inglett, G. E., S. Maneepun, and N. Vatanasuchart. "Evaluation of hydrolyzed oat flour as a replacement for butter and coconut cream in bakery products Evaluación del uso de harina de avena en sustitución de la mantequilla y crema de coco en productos de pastelería." Food Science and Technology International 6, no. 6 (December 2000): 457–62. http://dx.doi.org/10.1177/108201320000600604.
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Hydrolyzed oat flour, called Oatrim, was found able to cr eate suitable food desserts when partially substituted for butter or coconut cr eam. In bakery pr oducts, a 25% Oatrim gel was substituted for butter in rice cookie, br ownie, and banana cake r ecipes. The cholester ol contents of the rice cookie, banana cake, and br ownie wer e reduced by 24.7%, 13.5%, and 24.1%, r espectively. Coconut cream was replaced with a 15% Oatrim suspension in the Thai desserts coconut custar d, coconut cream spread, and mungbean conserve. In these pr oducts, a substantial r eduction in saturated fat content was found: coconut custar d (60.6% reduction), mungbean conserve (76.4% r eduction), coconut cream spread (83.7% reduction). Although adequate textur e measurements wer e observed for most par- tially substituted products, the breaking strengths of the rice cookie and mungbean conserve wer e significantly increased over control foods. These data suggested that the use of the gel should be limited to less than 50% of the substitution. W ithin the experimental parameters examined, the baked goods and Thai desserts exhibited satisfactory sensory qualities in the 50% to 60% substitution range.
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Agerberth, Birgitta, Hans Gunne, Jacob Odeberg, Per Kogner, Hans G. Boman, and Gudmundur H. Gudmundsson. "PR-39, a proline-rich peptide antibiotic from pig, and FALL-39, a tentative human counterpart." Veterinary Immunology and Immunopathology 54, no. 1-4 (November 1996): 127–31. http://dx.doi.org/10.1016/s0165-2427(96)05676-0.
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Pal, Rajinder, Gulshan Mahajan, Virender Sardana, Bavita Asthir, and Bhagirath Singh Chauhan. "Performance of Dry-Seeded Rice Genotypes under Varied Soil Moisture Regimes and Foliar-Applied Hormones." Plants 9, no. 4 (April 21, 2020): 539. http://dx.doi.org/10.3390/plants9040539.
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Plant hormones influence various physiological processes during the growth and development of plants, but their critical roles in influencing yield and antioxidant activities in dry-seeded rice (DSR) have not been adequately explored. This study aims to analyze the performance and antioxidant activity of contrasting genotypes of DSR in response to soil moisture regimes and foliar-applied hormones. The study comprised sixteen treatments that were evaluated under field conditions as per split-plot design in three replications. Treatments comprised combinations of two soil moisture tension regimes (10 kPa and 20 kPa) and two genotypes (PR-111, non-stay-green type and PR-123, stay-green type) applied to the main plots and foliar application of three hormones (gibberellic acid (GA3) 40 mg kg−1, abscisic acid (ABA) 20 mg kg−1, and cytokinin (CK) 40 mg kg−1)) and a control (unsprayed) to subplots. The non-stay-green genotype (PR-111) resulted in 34.6% more grain yield (6.48 t ha−1) than the stay-green genotype (PR-123) at the lower soil moisture tension regime (SMTR) (10 kPa) due to the increased number of filled grains per panicle and improvement in harvest index (HI). At the higher SMTR (20 kPa), the stay-green genotype (PR-123) produced 26.4% more grain yield (5.21 t ha−1) than non-stay green genotype (4.12 t ha−1) and showed enhanced superoxide dismutase (SOD) and peroxide dismutase (POD) activity that may have contributed in maintaining sink size through improved chlorophyll content. Grain yield (6.35 t ha−1) with foliar-applied GA3 (40 mg kg−1) at SMTR of 10 kPa was higher by 12.2% and 24.0% than with foliar-applied ABA (20 mg kg−1) and unsprayed treatments, respectively. Irrigation application at SMTR of 20 kPa and foliar application of ABA gave 24.1% higher grain yield (5.15 t ha−1) than the unsprayed treatment, but it was similar to foliar-applied GA3 and CK. This study implied that the stay-green genotype (PR-123) was more suitable under moisture stress conditions (20 kPa) in DSR, as it maintained sink size even under moisture stress conditions by improving dry matter translocation and enhancing SOD and POD activity. The study suggests the need to find out the endogenous level of these plant hormones in rice genotypes under a range of water regimes to develop high yielding and water use efficient genotypes of DSR.
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Mack, A. Kyle, Stephanie Pelligra, Richard J. Labotka, Robert Molokie, Young O. Kim, Alexis Thompson, and Diana J. Wilkie. "A Comparison of Two Pain Assessment Tools, the Adolescent Pediatric Pain Tool and PAINReportIt and Use of the Composite Pain Index in Sickle Cell Disease." Blood 116, no. 21 (November 19, 2010): 2648. http://dx.doi.org/10.1182/blood.v116.21.2648.2648.
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Abstract Abstract 2648 Introduction: Pain is a common acute and chronic complication of sickle cell disease (SCD) in pediatric patients. However there are very few pain assessment tools that can assess patients for the multidimensional components of pain. The Adolescent Pediatric Pain Tool (APPT) is a validated, self-administered paper and pencil pain assessment tool validated in children and adolescents. The McGill Pain questionnaire (MPQ) is a pain assessment tool validated in adolescents and adults. PAINReportIt (PR) is a self-administered, computerized version of the MPQ. The APPT and PR can each be administered in a single outpatient clinic visit. The Composite Pain Index (CPI), a multidimensional representation of pain, can be calculated with both the APPT and PR. It is calculated by summing the individual standardized-scores for each of the four pain dimensions: (1) number of sites, (2) intensity, (3) total pain rating index, and (4) the pain pattern score. The use of these tools can present pain as the all-important 5th vital sign and may assist providers in the treatment of the multiple components of pain in pediatric SCD. The aim of this study was to compare the use of two pain assessment tools, the APPT and PR in pediatric SCD patients with respect to the composite pain index and the multiple dimensions of pain. Patients/Methods: Patients with the following genotypes were eligible for this study: Hb SS, Hb SC, Hb Sb0-thalassemia, and Hb Sb+-thalassemia. Patients who were 14 years and older were eligible to complete both tools on a single, outpatient visit to a comprehensive SCD clinic. The number of pain sites, intensity and the CPI were analyzed with descriptive, correlation, and independent t-test statistics. Results: 57 patients completed both pain tools. The mean age was 17.5 +/− 2.6 years (mean +/− SD). There were 29 females (51%) and 28 males (49%). 84% of the patients had Hb SS; 14% had Hb SC and 2% had Hb Sb0-thalassemia. Pain was described in every body segment, with the most frequent sites including the: back, legs, chest, and abdomen. Pain intensity was moderate for the average subject (mean pain intensity score out of 10 was 3.7 +/− 2.6 for PR and 4.3 +/− 3.2 with the APPT, r=.46, p<.01). The mean CPI was 201.1 +/− 26.9 with PR and 200 +/− 30.5 with the APPT (mean +/− SD). There was a strong correlation with the CPI between PR and the APPT (r=.73, p<.01). Mean PR CPI scores were not significantly different for females (206.5 +/− 29.7) and males (195.6 +/− 22.9). Mean APPT CPI scores were significantly different (p=.01) for females (206.3 +/− 35) than males (193.5 +/− 24.1). There were no differences in mean APPT CPI scores by genotype or age groups. Conclusion: Pain in SCD patients is a common complication with significant morbidity. In this study we found on a single, outpatient comprehensive sickle cell clinic visit that patients had pain in every body segment and had pain in multiple body sites. Patients in this study had moderate pain during a routine outpatient clinic visit. The Composite Pain Index is a multidimensional representation of pain that can be determined with both the APPT and PR. This study demonstrates that both the APPT and PR produced similar CPI scores in pediatric and adult SCD patients. The gender differences in CPI scores produced by the APPT in comparison to PR is likely due to the APPT having only one pain intensity score (pain now) to contribute to the CPI whereas PR has 3 pain intensity scores (pain now, least and worst pain in previous 24 hours). The significance of this study is that the CPI may be an important outcome variable to allow researchers and clinicians to compare the complexities of the chronic pain that pediatric and adult patients with SCD experience. Disclosures: Labotka: HemaQuest Pharmaceuticals, Inc: Research Funding.
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Spagnuolo, Regina Stella, Renata Cristina Silva Baldo, and Ivan Amaral Guerrini. "Análise epidemiológica dos acidentes com material biológico registrados no Centro de Referência em Saúde do Trabalhador - Londrina-PR." Revista Brasileira de Epidemiologia 11, no. 2 (June 2008): 315–23. http://dx.doi.org/10.1590/s1415-790x2008000200013.
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OBJETIVO: Analisar a distribuição dos acidentes de trabalho com exposição a material biológico das fichas de notificação registradas no Centro de Referência de Saúde do Trabalhador de Londrina, traçando um perfil dos profissionais acidentados. MÉTODOS: Trata-se de um estudo retrospectivo descritivo, com abordagem quantitativa, realizado através de um levantamento nas 253 fichas de notificação de acidentes com material biológico que foram encaminhadas das instituições de saúde da área de abrangência ao Centro de Referência em Saúde do Trabalhador do município de Londrina-PR, no período de janeiro a dezembro de 2006. Os dados foram processados e tabulados eletronicamente, utilizando-se o programa Epi Info, de domínio público. RESULTADOS: Das 253 fichas de notificação de acidentes com material biológico analisadas, verificou-se que 92,5% foram causados por objetos perfuro-cortantes e 39,5% ocorreram em auxiliares de enfermagem. Constatou-se também que 73,5% eram do sexo feminino, 24,1% ocorreram em Unidades Básicas de Saúde, 74,3% encontravam-se com situação vacinal para Hepatite B atualizada e 49,8% ocorreram na rede pública de saúde. CONCLUSÃO: Com o levantamento do perfil dos profissionais acidentados com exposição a material biológico, o CEREST Londrina identificou que a profissão mais atingida foram os auxiliares de enfermagem, as mulheres, e que grande parte dos acidentes ocorreram nas UBSs com material perfuro-cortante. Mostrou-se que coletores de lixo passaram a fazer parte das profissões envolvidas nos acidentes.
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Silverman, Lewis R., David R. McKenzie, Bercedis L. Peterson, Carlos M. De Castro, John Ellerton, Kathryn N. Knapp, C. L. Beach, and Richard A. Larson. "Response Rates Using International Working Group (IWG) Criteria in Patients with Myelodysplastic Syndromes (MDS) Treated with Azacitidine." Blood 106, no. 11 (November 16, 2005): 2526. http://dx.doi.org/10.1182/blood.v106.11.2526.2526.
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Abstract The CALGB conducted a series of clinical trials with azacitidine (Vidaza®) administered subcutaneously or intravenously in patients with MDS using the FAB classification (JCO2002;20:2429). Since the publication of these CALGB studies (8421, 8921, 9221), new response criteria for evaluating new treatments for MDS have been published by the IWG (Blood2000;96:3671). Two general differences between the CALGB and IWG response criteria are the required duration of improvement (CALGB: ≥4 weeks; IWG: ≥8 weeks) and peripheral blood values (CALGB: different criteria for hemoglobin targets for males and females; IWG: same criteria for males and females). The results reported here are based on re-collected data from patients described in the published report. After applying the IWG response criteria, the overall response rate (CR+PR+HI) in the azacitidine groups were similar across studies 8421, 8921, and 9221: 44% (21/48), 40% (28/70), and 48% (47/99), respectively. Best Response using IWG Response Criteria for MDS in Studies 8421, 8921, and 9221 Median duration of any response (CR, PR or HI) in the 114 azacitidine-treated responders was 366 days (range: 56 to 4641+ days). The median duration of CR in the 32 azacitidine-treated responders was 379 days (range: 92 to 4412+ days). The median number of cycles from first treatment with azacitidine to any response (CR, PR or HI) was 3 cycles (range: 1 to 17 cycles). Although 75% of the responders achieved a response by cycle 4, the other 25% achieved a response as late as cycle 17. The majority (90%) of responders achieved a response by cycle 6. Best response was observed, on average, 2 cycles after the initial response. In summary, reanalysis of the response rates using IWG criteria demonstrate consistent results across three sequential studies and further validate the superiority of azacitidine over supportive care alone.
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Wu, Lingyun, Xiao Li, Chunkang Chang, Jiying Shu, Li Xu, and Zheng Zhang. "Combined Low-Dose Homoharringtonine, Cytarabine and Granulocyte Colony-Stimulating Factor for Patients with Advanced Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia Transformed From MDS." Blood 116, no. 21 (November 19, 2010): 4004. http://dx.doi.org/10.1182/blood.v116.21.4004.4004.
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Abstract Abstract 4004 A pilot study of the efficacy and toxicity of the low-dose cytarabine and homoharringtonine in combination with granulocyte colony-stimulating factor (G-CSF) (CHG protocol) in patients with advanced myelodysplastic syndromes (MDS) or MDS-transformed acute myeloid leukaemia (t-AML) was conducted. A total of 50 patients (31, advanced MDS; 19, t-AML) were enrolled in this study. All patients were administered the CHG regimen comprising low-dose cytarabine (25 mg/d, intravenous continuous infusion, days 1 C14), homoharringtonine (1 mg/d, intravenous continuous infusion, days 1 C14) and G-CSF (300 μg/d, subcutaneous injection, days 0 C14, intermitted when the peripheral WBC count reached >20 °Á 109/L). This regimen was followed by conventional chemotherapy as post-remission therapy when complete remission (CR) was achieved. The overall response rate was 68.0% after one course of the CHG regimen was applied. Of the total 50 patients, 24 (48.0%) achieved CR and 9 (18.0%) achieved partial remission (PR). The median overall survival (OS) was 14.1 months. Among the patients aged ≥ 70 years, the response rate was 81.0% (71.4% CR and 9.6% PR), while in patients aged < 70 years, the response rate was 55.2% (31.0% CR and 24.1% PR) (P < 0.01). There were no statistically significant differences for CR, PR and OS when the patients were grouped by blast percentage in bone marrow and karyotypes, respectively. 8 of the 24 CR patients who just received post-remission regimens of HA (homoharringtonine and cytarabine) and DA (daunorubicin and cytarabine) relapsed rapidly and just kept a mean CR of 4.3 months. Otherwise, the other 14 CR patients alternatively received succeeded chemotherapy, which combined mitoxantrone, idarubicin, pirarubicin or aclarubicin with cytarabine or decitabine. The mean CR duration of these 14 patients reached 15.5 months with 4 still maintaining continuous CR. No treatment-related deaths were observed. Myelosuppression was mild to moderate, and no severe non-haematological toxicity was observed. Thus, CHG priming regimen as an induction therapy is well tolerated and effective in advanced MDS or t-AML patients. Disclosures: No relevant conflicts of interest to declare.
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de la Cruz Vicente, Fátima, Maria Angeles Domiunguez Muñoz, Estrella Carrillo Cruz, José Francisco Márquez Malaver, Rocio Parody Porras, Jose Francisco Falantes González, Cristina Calderón Cabrera, et al. "Role of PET/CT Assesment before Autologous Stem Cell Transplantation in Relapsed or Refractory Lymphoma Patients." Blood 124, no. 21 (December 6, 2014): 3977. http://dx.doi.org/10.1182/blood.v124.21.3977.3977.
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Abstract BACKGROUND : Approximately 20 to 55% of patients diagnosed with lymphoma will relapse or show refractoriness after first line treatment. Salvage chemotherapy and autologous stem cell transplantation (ASCT) is the most commonly used approach in patients with chemosensitive disease. Nevertheless, active disease at the time of ASCT evaluated by PET/CT is correlated with a poor overall survival (OS). Despite this, it is not definitively established whether or not; tumor burden assessed by PET/CT at time of ASCT affects the outcome of these patients. OBJECTIVES: To analyze the predictive value of PET/CT performed before ASCT in terms of progression free survival (PFS) and overall survival (OS) among patients diagnosed with relapsed/refractory lymphoma with active disease at time of transplant. PATIENTS AND METHODS: Retrospective study of all consecutive patients diagnosed with relapsed or refractory lymphoma after at least one line of chemotherapy and who had active disease assessed by PET/CT at the time of ASCT between July/2001 and August/2012 in our institution. Partial response (PR) ≥ 90%, was defined as a decrease in tumor load higher that 90% as assessed by PET/CT without fulfilling criteria of complete response. Partial response was defined as a decrease in tumor load higher than 50% and lower than 90%. Progressive disease was defined as appearing new focus of disease or worsening previous involved areas. OS was analyzed by Kaplan-Meier test and “log rank test” was used to compare different groups (PR ≥ 90% vs PR or less). PFS was analyzed with “Cox Regression” test. RESULTS: Demographics and clinical data are summarized in table 1. Seven years PFS of patients with partial response ≥ 90% at ASCT was 71.4% versus 28.6% for patients in PR or less at transplant (p=0.09). Among patients who develop it median time to relapse or progression after ASCT was 4 months (1-40). ASCT related mortality was 3.4%. Rescue therapy after transplant consisted on chemotherapy in 71.4% of cases, radiotherapy in 19% and supportive care in 9.5%. Eight patients underwent allogeneic stem cell transplantation after ASCT (27.6%). After 18 months median follow-up (3-69), OS for the whole series was 48.3% at seven years. Patients who achieved PR ≥ 90% had a seven year OS of 72.7% versus 33.3% among patients with PR or less[HR 3.1 (CI 95% 0.9-11.4), p=0.05]. CONCLUSIONS 1) Patients with pre-ASCT PET/TC evaluation defined as ≥ 90% PR have a long term disease free and overall survival. 2) Conversely, patients receiving ASCT in a partial response lower than 90% have a poor long term disease free and overall survival, suggesting that this set of patients should be candidates to alternative therapeutic options such as first-line Allo-SCT or investigational drugs. TABLE 1. Patients characteristics N=29 Age, median (range) 34 (27-51) Sex M/F :58.6% / 41.4% DiagnosticHLNHLDLBC-LMantle cell lymphomaPeripheral T cell lymphomaLymphoblastic lymphomaTransformed follicular lymphoma 48.3% 51.7% 60% 13.3% 13.3% 6.7% 6.7% Ann Arbor stageIIIIIIIV 3.4% 37.9% 24.1% 34.5% Prognosis index (IPI,EORTC/IH)Low riskIntermediate riskHigh risk 10.7% 42.9% 46.4% Bulky mass 35.7% Extranodal disease 42.9% B symptoms 50 % Bone marrow involvement 7.1% Number of previous line therapy 3 (2-5) Previous response to treatmentPR≥90%PR or less 37.9% (n=11) 62.1% (n=19) Status disease at ASCTPrimary refractory diseaseRelapse after previous response 55.2% 44.8% Conditioning regimenBEAMBCNU + TTBCNU + TT + CY 93.1% 3.4% 3.4% HL: Hodgkin lymphoma; NHL: non-hodgkin lyphoma; DLBC Lymphoma: diffuse large B cell lymphoma; IPI: International Prognostic Index; IH: Hansenclever index; BEAM: Busulfan, etoposide, cytarabine, melphalan; TT: Thiotepa; CY: cyclophosphamide. Disclosures No relevant conflicts of interest to declare.
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Sharakhina, L. V., and A. V. Ranchin. "Advertising and Public Relations Professional Education in the Regions of Russia: Educational Organizations Branding Issues." Discourse 6, no. 2 (May 19, 2020): 44–60. http://dx.doi.org/10.32603/2412-8562-2020-6-2-44-60.
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Introduction. The Russian higher education market in the sphere of Public Relations and Advertising is represented in the paper. The basic approach to the market is shaped by the vision on higher education in the frame of service paradigm. The need to analyze and implement professional communication activities while promoting university education organizations is stressed by the authors. A special attention is put to the necessity of professional communication technologies, such as branding, their application to universities, because it influence such institutions managerial efficiency, helps to systemize a share of their voice, and it is already the necessity for the present day society.Methodology and sources. Theoretical and methodological basis of the paper was composed by scientific works of Russian researchers in the field of university branding, brand-management, including papers on Russian Federation regional universities branding. Empirical study base was designed by materials of regional leading universities, which give higher education in PR and Advertising. Underlying rationale for defining the leadership were the following: number of state-funded student places; 1st year students’ unified national exam results; the dynamics of prospective students in PR and Advertising on tuition payment basis enrollment. Russian regions, the most of enrollees are coming from to Saint Petersburg Electrotechnical University, were also unveiled. The elements of value-based branding platforms of departments responsible for Public Relations and Advertising education in regional leading higher education institutions are also brought in focus.Results and discussion. Empirical study revealed that PR and Advertising education departments of the universities studied did not fulfill their scientific and methodological potential in practice to the full extent. The education institutions examined in the research mostly communicate their objective quantitative indicators positioning Public Relations and Advertising education rather than core value messages. Thus it does not seem possible to typify these communication components as examples of branding process and brand element of university. It would help to structure the market share and influence positively on university promotion.Conclusion. Following the results of the study the authors conclude the necessity to apply communication technologies of brand development and brand management for structuring the market share and influencing positively on university promotion. It directly impacts on education institutions managerial efficiency and proves its relevance to modern society.
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Manso, Luis, Andres Garcia-Palomo, Ramon Perez-Carrion, Jose Ignacio Chacon, Xabier Mielgo Rubio, Isabel Gallegos Sancho, Javier Cassinello, et al. "Prognostic factors influencing the selection of bevacizumab combined with chemotherapy in patients with HER2-negative metastatic breast cancer in routine clinical practice: Oncosur-Avalox—Observational cross-sectional study." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e12020-e12020. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e12020.
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e12020 Background: Combining bevacizumab (BEV) with chemotherapy (CT) improves survival in HER2-negative metastatic breast cancer (MBC). We investigated the influence of age, ECOG, hormonal status, number of sites, location of metastases and patient decision on the selection of BEV combined with CT in MBC. Methods: Observational cross-sectional multicenter study in patients with HER2- negative MBC who have received first-line CT with BEV. Results: 219 patients were included: median age 51(44-63) yr; ECOG: 0=53%; 60.4% pre-menopausic; 23.9% triple-negative (TN);76.2 % hormone receptor positive (HR+).Metastatic disease: ≥3 sites=39.2% (TN: 22%; HR+: 43.9%); location: 45.2% bone, 37.4% liver, 30.1% lung. Most frequent BEV combinations were paclitaxel/BEV(60.7%) and docetaxel/BEV(12.8%); median no. of CT cycles: 6 (5- 8). A disease-free survival (DFS) ≥12 months was achieved by 82.8%; TN: 78.9%; HR+: 83.3%. Overall response rate (ORR) was 62.7%: 53.6% partial response (PR), 9.1% complete response (CR); 25.4% stable disease (SD) and 7.2% disease progression (4.8% non evaluated). TN:ORR 54.2% (47.9% PR), clinical benefit 80% (27.1% SD); HR+:ORR 65.8% (55.7% PR), clinical benefit 89.9% (24.1% SD). 66.2% presented at least one toxicity, mainly grade 1-2; 32% BEV-related: only 3 grade 3 toxicities; no grade 4. Receiving adjuvant hormonal therapy was associated to DFS ≥12 months (p<0.05). ER+ tumors (OR:0.326;95%CI:0.16-0.65;p=0.002) and patient decision after consider doctor opinion (OR:0.026;95%CI:0.01-0.74; p=0.085) were independent factors associated with the selection of paclitaxel-BEV in the overall population (TN or HR+). Liver metastases were significantly related to paclitaxel-BEV administration (p<0.01). Conclusions: First-line CT with BEV is an effective and safe scheme for patients with TN and HR+ MBC. ER+ tumors and patient decision after consider doctor opinion were identified as independent factors for the selection of paclitaxel-BEV therapy. The presence of liver metastases was significantly associated to the administration of a paclitaxel-BEV regimen.
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Lord, S. R., N. Vasudev, S. Knight, V. Speirs, and G. Hall. "Prognostic significance of immunohistochemical markers in endometrial cancer treated with chemotherapy." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e16551-e16551. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e16551.
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e16551 Background: The proportion of patients receiving chemotherapy for endometrial cancer is increasing both in the adjuvant and advanced setting. The literature describes many prognostic immunohistochemical factors in early stage endometrial cancer, the majority of whom will not receive chemotherapy. The aim of this study was to describe the biomarker expression for endometrial tumours treated with chemotherapy and to assess what constitutes a favourable and unfavourable profile for this patient group. Methods: For a subset of patients with either endometrioid, serous or a mixed mullerian morphology treated with chemotherapy at our centre between 1996 and 2008 an immunohistochemical profile of 14 biomarkers was studied (ERα, Erβ1, Erβ2, PR, PRB, P53, Rb, E-cad, MDM2, MIB-1, E2F1, p16, p13, and p21). A univariate analysis using cox regression of potential prognostic factors was then carried out. Results: In total 199 patients received chemotherapy for endometrial cancer over the 12 year period studied. Two year survival from commencement of chemotherapy for patients receiving adjuvant treatment was 45.2% and palliative treatment 28.1%. The commonest histological subtypes were endometrioid adenocarcinoma (40%), serous carcinoma (24.1%) and mixed mullerian tumours (14.6%). For the subset of 35 patients 38.2% of patients had positive immunohistochemical staining for ERα, 53% for PR, 73.5% for p16, and 94% for E2F1. Good prognosis was predicted by the strength of staining for E2F1 (HR 0.757, CI 0.216/0.902, p = 0.025) and poor prognosis by p16 (HR 1.470, CI 1.040/2.077, p = 0.029). Conclusions: Positive staining for ERα and PR was of similar frequency to previous studies of early stage endometrial cancer and did not significantly influence prognosis. Good prognosis correlated with E2F1 expression and poor prognosis with p16. A greater proportion of patients had serous morphology compared to published series of early stage endometrial cancer. Further study of prognostic factors in larger numbers of patients and built into prospective randomised trials may allow the creation of a prognostic model and guide the development of future clinical trials of targeted therapy. No significant financial relationships to disclose.
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Inwards, David James, David W. Hillman, Paul A. Fishkin, William L. White, Roscoe F. Morton, Shaker R. Dakhil, Daniel A. Nikcevich, Donald B. Wender, Tom R. Fitch, and Paul J. Kurtin. "Phase II Study of Rituximab and Cladribine (2-CDA) in Newly Diagnosed Mantle Cell Lymphoma (MCL) (N0189)." Blood 108, no. 11 (November 16, 2006): 2746. http://dx.doi.org/10.1182/blood.v108.11.2746.2746.
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Abstract Background: A previous trial of 2-CDA as a single agent for therapy of mantle cell lymphoma demonstrated this agent to be efficacious with an overall response rate of 81% (31% complete responses) (Blood 1999 Nov 15; 94:660a). A phase II study of the addition of rituximab to 2-CDA was conducted by the North Central Cancer Treatment Group based on improved outcomes achieved by the addition of rituximab to other regimens active in MCL. Methods: This one-stage phase II study was designed to determine the complete response (CR) or complete response/unconfirmed (CRu) rate. Central pathology confirmation of cyclin D1 positive mantle cell lymphoma was required. No previous therapy for lymphoma was allowed, with the exception of splenectomy. The schedule was rituximab 375 mg/m2 IV day 1; 2-CDA 5 mg/m2/d IV days 1–5 of a 4-week cycle. After 2 of the first 6 patients developed grade 4 neutropenia, subsequent patients received either pegfilgrastim or filgrastim support. Patients received 2–6 cycles of therapy, depending on response. Patients were required to achieve at least a PR after 2 cycles of therapy to continue on protocol therapy. Results: Patient characteristics of all 29 eligible pts: median age: 70 (range: 41–86); 21 male, 8 female; PS 0 (55.2%), PS 1 (41.4%), PS 2 (3.5%); stage II (6.9%), stage III (3.5%), stage IV (89.7%); prior splenectomy (20.7%). The only grade 4 adverse events occurring more than once were neutropenia (24.1%) and leucopenia (6.9%). One patient died of cerebral ischemia in the setting of pneumonia without neutropenia. Fifteen (51.7%; 95% CI: 32.5–70.6%) pts achieved a CR; only one has relapsed to date (665 days after starting therapy). Four additional pts achieved a PR. Ten pts have progressed with 4 pts progressing early at 17, 45, 46, and 71 days (two of whom have died). Ten pts (34.0%) went on to receive further therapy off study, 5 in less than a PR after 2 cycles, 2 in PR after study therapy, and 1 who went off study for a rash. Fourteen pts (48.3%) have progressed or gone on to receive additional therapy off study. At last contact, 26 (89.7%) were alive (median follow-up 14.3 months; range: 6–34). One year survival rate is 89.3% (95% CI: 78.5–100). Conclusions: Rituximab and cladribine were well tolerated for the treatment of MCL in a group of elderly patients. The response rate may have been underestimated due to the study design, which required at least a PR after 2 cycles to continue therapy. Despite this, 52% achieved a complete remission. Complete remissions attained with this regimen appear to be durable, with a single relapse to date among 15 patients achieving CR.
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Chen, Li-Tzong, Taroh Satoh, Min-Hee Ryu, Yee Chao, Ken Kato, Hyun Cheol Chung, Jen-Shi Chen, et al. "A phase 3 study of nivolumab in previously treated advanced gastric or gastroesophageal junction cancer (ATTRACTION-2): 2-year update data." Gastric Cancer 23, no. 3 (December 20, 2019): 510–19. http://dx.doi.org/10.1007/s10120-019-01034-7.
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Abstract Background Nivolumab showed improvement in overall survival (OS) in ATTRACTION-2, the first phase 3 study in patients with gastric/gastroesophageal junction (G/GEJ) cancer treated with ≥ 2 chemotherapy regimens. The 2-year follow-up results of ATTRACTION-2 are presented herein. Methods ATTRACTION-2 was a randomized, double-blind, placebo-controlled, phase 3 trial (49 sites; Japan, South Korea, and Taiwan). The median (min–max) follow-up period was 27.3 (24.1–36.3) months. The primary endpoint was OS. A subanalysis of OS was performed based on best overall response and tumor-programmed death ligand-1 (PD-L1) expression status. Results Overall, 493 of 601 screened patients were randomized (2:1) to receive nivolumab (330) or placebo (163). OS (median [95% confidence interval; CI]) was significantly longer in the nivolumab group (5.26 [4.60–6.37] vs 4.14 [3.42–4.86] months in placebo group) at the 2-year follow-up (hazard ratio [95% CI], 0.62 [0.51–0.76]; P < 0.0001). A higher OS rate was observed in the nivolumab vs placebo group at 1 (27.3% vs 11.6%) and 2 years (10.6% vs 3.2%). The OS benefit was observed regardless of tumor PD-L1 expression. Among patients with a complete or partial response (CR or PR) in the nivolumab group, the median OS (95% CI) was 26.6 (21.65—not applicable) months; the OS rates at 1 and 2 years were 87.1% and 61.3%, respectively. No new safety signals were identified. Conclusions Nivolumab treatment resulted in clinically meaningful long-term improvements in OS in patients with previously treated G/GEJ cancer. The long-term survival benefit of nivolumab was most evident in patients with a CR or PR.
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Noel, Marcus Smith, Andrea Wang-Gillam, Allyson J. Ocean, Sant P. Chawla, Vincent Chung, Giuseppe Del Priore, and Vincent J. Picozzi. "SM-88 therapy in high risk poor prognosis pancreatic cancer (PDAC)." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e15714-e15714. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e15714.
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e15714 Background: Refractory PDAC has no established therapy (JCO 37, 2019 supp 4; 226). SM-88 (D,L-alpha-metyrosine) is a novel oral therapy used with low doses of sirolimus, phenytoin and methoxsalen. Previous studies show safety and efficacy in compromised patients (JCO 37, 2019 supp 4; 200. JCO 37, 2019 supp 4; 310). We now report the dose optimization phase (NCT03512756). Methods: Randomized Phase 2 with dose optimization and expansion cohort of PDAC after 1 prior line, ECOG PS ≤2 and radiographic PD. Subjects randomized to 460 or 920 mg/d SM-88; all received phenytoin 50 mg, methoxsalen 10 mg and sirolimus 0.5 mg. Results: As of Jan 2019, 85 subjects consented, 41 ineligible, 38 randomized and 28 evaluable (1 cycle dosed). Average age 66.9 yrs, BMI 24.1, CA-19.9 median 2,562 (1.2 – 700,000), 2 prior lines 50%, 3 prior 14.3%, > 4 prior 21.4%; 85.7% had prior 5FU, 89.3% Gem, 71.4% taxanes, and 71.4% platinums. In both SM-88 doses, toxicity did not increase on treatment. AEs were not increased among high risk groups (age, sex, low BMI, low albumin, high CA-19.9 and prior radiotherapy). AEs increased with more prior lines of therapy, but were not dose dependent. There were 21 SAEs prior to dosing including 5 deaths among 14 patients. Two SAEs (rash and hypotension) were considered possibly related to SM-88 Therapy. No deaths were drug-related. 9 subjects had either a CEA or CA-19.9 decrease with 2 having both; 96.5% of subjects had CTCs detectable at baseline with 70% experiencing > 30% decline for at least 1 cycle with a median CTC best response decrease of 73%. Prior Lines of Therapy Subjects (n) Current Median OS 2-month Target Lesion Response CTCs Median Best OR % Alive 1 4 +5.7m 1 PR, 2 SD, 1 n/a* -74% 75% 2 14 +4.7m 6 SD, 3 PD, 5 n/a* -84% 79% 3+ 10 +3.5m 1 PR, 4 PD, 5 n/a* -55% 50% Total 28 +4.3m 2 PR, 8 SD, 7 PD, 11 n/a* -73% 68% *Not available RECIST clinical benefit (SD + PR) was 47.1% (8/17). 68% of subjects were alive at a median follow up of +4.3 months. EORTC global health and QOL measures did not deteriorate on treatment. Conclusions: Both doses of SM-88 were well tolerated without clinically significant toxicity. Anti-tumor activity was observed in this heavily pretreated population warranting expansion of the study for further efficacy evaluation. Clinical trial information: NCT03512756.
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Necchi, Andrea, Salvatore Lo Vullo, Daniele Raggi, Patrizia Giannatempo, Nicola Nicolai, Luigi Piva, Davide Biasoni, et al. "Dacomitinib (Daco) induction therapy for locally advanced (LA) or metastatic penile squamous cell carcinoma (PSCC): An open label, single-arm, phase II study." Journal of Clinical Oncology 35, no. 6_suppl (February 20, 2017): 399. http://dx.doi.org/10.1200/jco.2017.35.6_suppl.399.
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399 Background: The prognosis of patients (pts) with PSCC is primarily depending on the involvement of regional lymph nodes (LN). Owing to the limited efficacy of chemotherapy (ChT), new drugs are warranted. Daco is a potent, irreversible TKI of human EGFR/HER1, HER2 and HER4. Methods: In a phase 2 study (NCT01728233), pts received Daco 45 mg/d orally continuously. Inclusion criteria were SCC histology, and clinical stage N2-3 or M1; no prior ChT was allowed. Computed tomography (CT) and PET/CT scans were repeated q8 wks. Responding pts with LA-PSCC were offered radical surgery. The primary endpoint was the objective response-rate (ORR = CR+PR according to RECIST v1.1). The study was conducted according to a Bayesian design, based on predictive probability; the target was to demonstrate that the ORR exceeded 20%. Translational analyses on pre-Daco tumor samples included: EGFR and HER2 amplification (ampl), in-situ hybridization for HPV, and next generation sequencing. Results: From 06/13 to 09/16, 26 pts were treated. 7 (26.9%) had visceral metastases. 50% had pelvic and 57.7% clinically-involved bilateral LN. 1 CR + 7 PR were obtained (ORR = 30.4%, 95% credibility interval 14.9-48.6%). Median follow up = 16.6 months; 12-m PFS = 24.1% (95%CI: 11.1-52.3); 12-m OS = 50.7% (95%CI: 31.7-80.9). The current Bayesian posterior probability of exceeding the 20% ORR target is 89%. Tissue samples from 23 pts were analyzed. Only 2 pts were HPV+ (1SD, 1PD). EGFR ampl was found in 4 pts (1 CR, 1 PR, 2 SD) and it was confirmed in all post-Daco samples. TERT mutations (60%) were found in responders (R) only. Mutations in genes potentially associated with resistance to EGFR inhibitors ( HRAS, BRAF, PIK3CA, PTEN, STK11) were found in 47% non responders (NR) vs 25% R. HRAS and BRAF mutations segregated with NR (20%). Additional unfrequent mutations of druggable targets were found: RAC1, TSC1 and mTOR in R, FGFR2, RAD50, PDGFRB and FLT4 in NR, IGF2R in both. Conclusions: Dacomitinib was active in HPV-negative, advanced PSCC. Among multiple altered pathways, we were able to delineate the possible molecular profile of responders. An expansion cohort to confirm the translational findings is planned. Clinical trial information: NCT01728233.
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Gaponova, Tatyana, Andrey Misurin, Larisa Mendeleeva, Elena Varlamova, Elena Parovichnikova, and Valeryi Savchenko. "Expression of XIAP in Multiple Myeloma Patients." Blood 112, no. 11 (November 16, 2008): 5118. http://dx.doi.org/10.1182/blood.v112.11.5118.5118.
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Abstract Introduction of novel drugs, in particular, proteasome inhibitors, for the treatment of Multiple Myeloma (MM) patients has significantly improved treatment response and overall survival. One of the effects of proteasome inhibition is down-regulation of the transcription factor NF kB that stimulates the expression of apoptosis inhibitors (IAPs). The expression of IAPs protects cells from the death due to temporary apoptotic stimuli. The overexpression of IAPs is one of the characteristics of malignant cells. A crucial gene of the IAPs family is XIAP which encodes a protein which contains not only the caspase 3 and 7 blocking domain BIR2, but also a unique caspase 9 inhibiting domain BIR3. Therefore, XIAP is able to block both apoptosis pathways: one that depends on external signals and the other that depends on mitochondrial activity. In addition, the RING domain of XIAP has an E3 ubiquitin ligase activity. The aim of our study was to investigate the XIAP expression in MM patients at diagnosis and during chemotherapy, especially with proteosome inhibitors. Our study included 25 primary MM patients; all of them have given informed consent. The median age was 48 years (range 31–62). IgG MM was diagnosed in 22 cases, IgA MM in 1 and Light Chain MM in 2. Initial treatment consisted of 3 cycles of VAD. If CR or PR were not achieved, the treatment was changed to bortezomib 1.3 mg/m2 on days 1,4,8 and 11 and dexamethasone (dex) 40 mg daily on days 1–4 days (4–6 cycles). If CR or PR was attained, Stem Cell mobilization was performed with Cyclophosphamide 6 mg/m2 +G-CSF. Melphalan at 200 mg/m2 was given before auto-SCT. The XIAP expression level was analyzed before therapy (n=25), after VAD (n=12), after bortezomib (n=6) and after auto-SCT (n=4). XIAP expression was evaluated quantitatively by means of RQ-PCR using ABL gene expression for normalization. In primary MM patients the XIAP expression was found in 100%. The meaning of XIAP/ABL*100% varied in the range of 5 to 5382% (median 22%). 24% of MM patients demonstrated XIAP hyperexpression (XIAP/ABL*100%>40%). In the control group of healthy donors the XIAP expression level was not more 13%. We subdivided MM patient into two groups according to XIAP/ABL*100% meaning: I<40%, II>40%. The comparison of M-protein, beta-microglobulin and albumin levels did not reveal any difference between these two groups. However, in group II (with primary XIAP hyperexpression) we observed the decrease of XIAP expression paralled tumor reduction (from more then 40% to 5–20%). On the contrast, in group I the XIAP gene expression increased right after chemotherapy initiation to extremely high levels of 2425%. But, after high dose melphalan and auto-SCT, the XIAP level significantly decreased (22–157%) along with the attainment of CR or very good PR. The level of the XIAP gene expression was also evaluated after the bortezomib treatment. After 4–6 courses of bortesomib + dex in all 6 MM patients CR + PR were achieved, that correlated with XIAP reduction to 8–25%. Conclusion: In MM patients at diagnosis, the level of the XIAP expression is high. The decrease of the XIAP expression correlates with the chemotherapy and proteasome inhibitor treatment efficicacy. XIAP expression comes to the normal values at the time of CR and PR achievement.
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Descourt, Renaud, Laurent Greillier, Maurice Perol, Charles Ricordel, Jean-Bernard Auliac, Lionel Falchero, Pierre Demontrond, et al. "First-line pembrolizumab monotherapy for PD-L1-positive (TPS ≥ 50%) advanced non-small cell lung cancer (aNSCLC) in the real world: A national French bispective multicentric cohort—ESCKEYP trial (GFPC 05-2018)." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 9091. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.9091.
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9091 Background: To determine real-world outcomes with first line pembrolizumab monotherapy, for aNSCLC with PD-L1 TPS ≥50%. Methods: Bispective, national and multicentric study including consecutively aNSCLC patients who initiated first-line pembrolizumab monotherapy from May 5, 2017 (marketing authorization of pembrolizumab monotherapy in France) to Nov 22, 2019 (marketing authorization of pembrolizumab-chemotherapy for non-squamous aNSCLC). Data were collected on medical charts. Responses were locally assessed according to RECIST v1.1; overall survival (OS) and real-world progression-free survival (rwPFS) were assessed by Kaplan-Meier method. Results: 845 patients (pts) were included by 33 centres: 67.8% were men, PS 0/1/≥2: 25.5%/46.9%/27.6%, active/former/nonsmokers: 39.1%/51.7%/6.4%, adenocarcinoma: 70.8%; stage IV at diagnosis: 91.6%; median number of metastatic sites at baseline: 2±1 (brain (20.8%), liver (13.9%) and bone (35%)); KRAS mutated: 27.7%, PDL1 TPS > 75%: 53.7% At the cut off date (31 December 2020), on the 783/845 (92.7%) evaluable pts, CR, PR, disease stabilization and progression were reported on 4.7%, 42.6%, 24.1% and 28.6% of cases, respectively; 588 (69.6%) pts had discontinued pembrolizumab, 390 (66.4%) had a first disease progression; 320/390 (82.1%) received a second line treatment, mainly platinum-based chemotherapy (90.6%). With a median follow up of 25,8 [95%CI: 24,8-26,7] months, median rwPFS and median OS were 8,2 [95%CI: 6,9-9,5] and 22,6 [95%CI: 18,5-27,4] months, respectively; 6, 12, 18-months survival rates were 76,8%, 64,8% and 54,3%. 835 adverse events were reported in 48% of the patients, grade ≥3 in 13.8% of cases, mainly asthenia, colitis, pneumonitis. For evaluable patients receiving a platinum-based doublet in second line (266/290, 89%), CR, PR, disease stabilization and progression were reported on 1.9%, 41%, 35.3% and 21.8% of cases, respectively. Uni and multivariate analysis of factors related to OS will be presented at the congress. Conclusions: Despite a less stringent selection of patients, pembrolizumab as a single agent achieves similar tumor shrinkage, rwPFS and OS than those of pivotal clinical trials.
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Brás, Gil, Carlos Vaz, Luís Leite, Rosa Branca, Fernando Campilho, Susana Roncón, and Antonio M. Campos. "Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma in Relapse after Autologous Transplantation: A Single Institution Experience with Matched Related Donors." Blood 128, no. 22 (December 2, 2016): 5873. http://dx.doi.org/10.1182/blood.v128.22.5873.5873.
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Abstract INTRODUCTION: Relapse in Multiple Myeloma (MM) comprises a dismal prognosis. The proteasome inhibitors and immunomodulators increased the median overall survival (OS) in relapse from 12 to 24 months. For relapsing patients, high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) and also allogeneic HSCT have been considered valid options in recent consensus statement. The major concern about allogeneic HSCT is the high transplant-related mortality (TRM) even with Reduced Intensity Conditioning (RIC). AIMS: Single institution retrospective evaluation of RIC allogeneic HSCT from matched related donors, in a cohort of MM patients relapsing after autologous HSCT. RESULTS: Between 1998 and 2016, 43 MM patients received allogeneic HSCT. From this group, a cohort of 29 MM patients relapsing after autologous HSCT was selected, based on supracited inclusion criteria. The median age at allogeneic HSCT was 51 (33-62) years. Before allogeneic HSCT, 55,7% (N=16) were treated wih salvage chemotherapy alone, whereas 20,7% (N=6) received chemotherapy plus autologous HSCT. For allogeneic HSCT, the conditioning was fludarabine plus bussulphan. Acute graft-versus-host disease (GVHD) prophylaxis was cyclosporine plus mycophenolate mophetil in 25 (86,2%) and in vivo antithymocyte globulin plus cyclosporine in 4 (13,8%). All patients recieved matched related peripheral blood grafts. Responses to salvage treatment previous to allogeneic HSCT were: progressive/stable disease (PD/SD) 24,1%, partial response (PR) 41,4%, very good partial response/complete remission (VGPR/CR) 13,7%, unknown 20,7%. Best responses after allogeneic HSCT were: PD/SD 15,7%, PR 24,1%, VGPR/CR 58,6%, unknown 10,3%. Engraftment was achived in 86,2% (N=25) and full donor chimerism was observed, at least once, in 72,4% (N=21). The overall reported incidence of grade II-IV acute GVHD was 48,3% (N=14) and moderate/severe chronic GVHD was 34,5% (N=10). Cytomegalovirus (CMV) reactivation ocurred in 44,8% (N=13) and hemorrhagic cystitis in 10,3% (N=3). The median progression free survival (PFS) and overall survival (OS) was 24 (0-61) and 176 (0-376) months, respectively. The incidence of relapse/progression was 48% (N=14). In this setting, 42,9% (N=6) were treated with chemotherapy alone and 35,7% (N=5) with donor lymphocyte infusion (DLI). After DLI, 80% (N=4) achieved CR. The overall mortality and TRM were 48,3% (N=14) and 17,2% (N=5), respectively. Best response after allogeneic HSCT was the only factor that improved PFS and OS (p<0,05). CONCLUSION: In our cohort, the allogeneic HSCT as salvage treatment for MM relapsing after autologous HSCT showed ability to deepen responses after salvage chemotherapy/autologous HSCT and also to prolong OS. The diferences between PFS and OS probably reflect the increasing therapeutical options to rescue patients after progression/relapse (chemotherapy, immunossupression tapper and DLI). The scarce data concerning the cytogenetic risk and the short dimension of this cohort are major limitations to define the MM relapsing patients who benefit most of allogeneic HSCT. Disclosures No relevant conflicts of interest to declare.
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Case, Mary, Robert Fox, Donna Baek, and Chien Wai. "Extraction of Rare Earth Elements from Chloride Media with Tetrabutyl Diglycolamide in 1-Octanol Modified Carbon Dioxide." Metals 9, no. 4 (April 10, 2019): 429. http://dx.doi.org/10.3390/met9040429.
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Rare earth elements (REEs) are critical to our modern world. Recycling REEs from used products could help with potential supply issues. Extracting REEs from chloride media with tetrabutyl diglycolamide (TBDGA) in carbon dioxide could help recycle REEs with less waste than traditional solvents. Carbon dioxide as a solvent is inexpensive, inert, and reusable. Conditions for extraction of Eu from aqueous chloride media were optimized by varying moles percent of 1-octanol modifier, temperature, pressure, Eu concentration, TBDGA concentration, Cl− concentration, and HCl concentration. These optimized conditions were tested on a Y, Ce, Eu, Tb simulant material, REEs containing NdFeB magnets, and lighting phosphor material. The optimized conditions were found to be 23 °C, 24.1 MPa, 0.5 mol% 1-octanol, with an excess of TBDGA. At these conditions 95 ± 2% Eu was extracted from 8 M (mol/m3) HCl. Extraction from the mixed REE simulate material resulted in separation of Y, Eu, and Tb from the Ce which remained in the aqueous solution. The extraction on NdFeB magnet dissolved into 8 M HCl resulted in extraction of Pr, Nd, Dy, and Fe >97%. This results in a separation from B, Al, and Ni. Extraction from a trichromatic lighting phosphor leachate resulted in extraction of Y and Eu >93% and no extraction of Ba, Mg, and Al.
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Tsuchiya, Kaoru, Masayuki Kurosaki, Shun Kaneko, Toru Kimura, Hiroyuki Marusawa, Hirotaka Arai, Takehiko Abe, et al. "A nationwide multicenter study in patients with unresectable hepatocellular carcinoma treated with lenvatinib in real world practice in Japan." Journal of Clinical Oncology 37, no. 4_suppl (February 1, 2019): 364. http://dx.doi.org/10.1200/jco.2019.37.4_suppl.364.
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364 Background: Lenvatinib(LEN) has been approved as a single agent for patients with unresectable hepatocellular carcinoma (u-HCC) since Mar 2018 in Japan. A few results from a large sample size cohort of LEN therapy in real world practice has been reported. Therefore, we performed a retrospective nationwide multicenter study. Methods: A total of 116 u-HCC patients received LEN from March 2018 at 14 sites in Japan were registered. Tumour assessments in accordance with RECICT ver1.1 and modified RECIST were done using dynamic CT or MRI within 4-8 weeks and every 6-8 weeks thereafter. Adverse events (AEs) were graded according to the CTCAE ver4.0. Results: Median age was 72 (46-91)years, 88 (75.9%) patients were male, and median body weight was 60 (30-94) kg. The baseline liver function was Child-Pugh class A in 106 (91.4%) patients. Seventy-three (62.9%) patients were BCLC stage C. As the 2nd-line therapy (after sorafenib), 28 (24.1%) patients received LEN and 17 (14.7%) patients did as the 3rd-line (after regorafenib). Median observation time was 2.5 months and one patient died from HCC progression. The imaging findings of 49 (42.2%) patients were evaluated at 4-8weeks. Based on mRECIST, CR was shown in 3 (6.1%), PR in 14 (28.6%), SD in 23 (46.9%), and PD in 6 (12.2%). In the 3 patients, target lesions of liver showed PR, however bone metastases had progressed. [overall response rate (ORR) 34.7%, disease control rate (DCR) 81.6%]. ORR and DCR of tyrosine kinase inhibitor (TKI) naïve patients (n = 26) were 34.6% and 80.8%, while those of TKI experienced (n = 23) were 34.8% and 82.6%. The most common any-grade AEs were hypertension (52.0%), diarrhoea (32.1%), decreased appetite (63.5%) and fatigue (49.4%). Hand-food skin reaction (HFSR) was observed in 28% of patients. Conclusions: The efficacy of LEN therapy in real world practice in Japan was similar to the phase 3 clinical trial, even though elderly patients with lower body weight were included in this study. The incidence of HFSR during LEN in real world practice was lower than that of the sorafenib group in the phase 3 trial of LEN. Decrease appetite and fatigue must be carefully monitored and managed during LEN therapy.
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Shi, Yuan-Kai, Mei Dong, Xiao-Nan Hong, Wei-Jing Zhang, Ji-Feng Feng, Jun Zhu, Li Yu, et al. "Phase II study of chidamide (CS055), a new subtype-selective oral histone deacetylase inhibitor, in patients with relapsed or refractory peripheral T-cell lymphoma." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 8525. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.8525.
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8525 Background: Chidamide (CS055) is a new benzamide type of histone deacetylase (HDAC) inhibitor with subtype selective activity against HDAC1, 2, 3 and 10. Chidamide has shown well-tolerated and favorable PK profiles in patients (pts) with advanced solid tumors and lymphomas. This phase II study was to evaluate the efficacy and safety of chidamide in relapsed or refractory peripheral T-cell lymphoma (PTCL). Methods: 102 PTCL pts were enrolled. In the exploratory trial, pts were randomized to receive chidamide 30mg or 50mg twice per week for 2 weeks, followed by 1 week of rest. In the pivotal trial, chidamide was administered 30mg twice per week w/o drug-free holiday. The primary endpoint was overall response rate (ORR). Responses were assessed using IWC criteria. Results: In the exploratory trial, 19 pts were enrolled with 9 and 10 to the 30mg and 50mg arms, respectively. ORR was 11.1% (1 CR) in the 30mg arm and 40.0% (1 CR, 1 CRu, 2 PR) in the 50mg arm. One pt in the 50mg arm experienced drug-related grade 4 thrombocytopenia. In the pivotal trial, 83 pts were enrolled. Most pts were stage III (35.2%) or IV (45.9%). 23 pts (29.1%) had confirmed responses out of 79 evaluable pts in the pivotal trial (8 CR, 3 CRu, and 12 PR). Responses of 19 pts (24.1%) maintained for ≥12 weeks. ORR with 27.8% was obtained by the Independent Review Committee. 68 pts (81.9%) experienced at least 1 AE in the pivotal trial, with 52.9% of AEs ≤ grade 2. The most common AEs were thrombocytopenia (50.6%), leucocytopenia (39.8%), neutropenia(21.7%), and fatigue (9.6%). 1 pt had a grade 3 QTc prolongation. 7 pts (8.4%) experienced at least one SAE, in which a grade 4 thrombocytopenia was considered to be drug-related. 2 pts with responses (CR) have received chidamide for > 43 months w/o evidence of cumulative toxicity. Conclusions: Chidamide as an oral single agent had significant and durable activity in pts with relapsed or refractory PTCL. Toxicities with the therapy were generally tolerable and manageable. The overall differences in pathological subtypes of pts enrolled and clinical profiles between chidamide and the two existing drugs, pralatrexate and romidepsin, will be discussed. Clinical trial information: ChiCTR-TNC-10000811.
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Shinozaki, Eiji, Megumi Ishiguro, Eiji Nakatani, Tatsuro Yamaguchi, Masato Nakamura, Yuji Miyamoto, Hitoshi Ojima, et al. "A phase II study of panitumumab with FOLFOX or FOLFIRI as first-line chemotherapy for KRAS-wild type metastatic colorectal cancer: The PaFF-J study." Journal of Clinical Oncology 35, no. 4_suppl (February 1, 2017): 722. http://dx.doi.org/10.1200/jco.2017.35.4_suppl.722.
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722 Background: For the patients with unresectable metastatic colorectal cancer (mCRC), response to the1st line chemotherapy has strong impact on their prognosis. Shrinkage of tumors may result in conversion to surgical resection and, concurrently, improved their survival. We conducted a multicenter phase II trial to investigate the efficacy and safety of panitumumab (Pmab) with chemotherapy as the 1st line treatment in Japanese patients with mCRC. Methods: Patients with no prior chemotherapy for unresectable, KRAS wild type mCRC, 20-80 years, and PS 0-1 were arbitrarily received either FOLFOX + Pmab or FOLFIRI + Pmab. Patients were evaluated every 8 weeks until progression. The primary endpoint was overall response rate (ORR), the secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), R0 resection rate, and safety. Results: A total of 162 patients (140 with FOLFOX + Pmab and 22 with FOLFIRI + Pmab) were analyzed. Median follow-up was 28.2 months, median age at enrollment was 64.5 years, and 17.9% of the patients was recurrent disease. Number of target organ was 1 in 35.2%, 2 in 40.7%, and ≥ 3 in 24.1% of the subjects. Median administered cycle was 7, and median treatment duration was 16 weeks. ORR was 51.2% (95%CI: 43.3-59.2), and DCR was 82.1% (95%CI: 75.3-87.7). ≥ 30% tumor shrinkage (PR-in) was observed in 115 patients (71.0%). Median time to PR-in and maximum shrinkage was 10 and 16 weeks, respectively. Surgical resection was done in 66 patients (40.7%), of which R0 was in 43 patients; R0 resection rate was 26.5% (95%CI: 19.9-34.0). Median PFS and OS was 9.2 (95%CI: 7.2-11.4) and 33.8 months (95%CI: 29.4-43.1), respectively. ≥ Grade 3 adverse events with > 5% incidence were neutropenia (31.8%), stomatitis (10.5%), rash acneiform (9.9%), paronychia (9.3%), anorexia (8.6%), and diarrhea (6.2%). Conclusions: In our study, OS was favorable with high R0 resection rate, whereas ORR, DCR, PFS and toxicities were similar to those in previously reported studies. Because the maximum tumor shrinkage was observed around 16 weeks, optimal timing for considering conversion surgery might be 16 weeks from the start of treatment. Clinical trial information: UMIN000004991.
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Nguyen, Van Chu, Tien Quang Nguyen, Thi Ngoc Ha Vu, Thi Huyen Phung, Thi Phuong Hoa Nguyen, Ngoc Duong Nguyen, and Dinh Roanh Le. "Application of St Gallen Categories in Predicting Survival for Patients With Breast Cancer in Vietnam." Cancer Control 26, no. 1 (January 1, 2019): 107327481986279. http://dx.doi.org/10.1177/1073274819862794.
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Breast cancer is a heterogeneous disease with different tumor subtypes. Identifying risk categories will help make better treatment decisions. Hence, this study aimed to predict the survival outcomes of invasive breast cancer in Vietnam, using St Gallen 2007 classification. This study was conducted on 501 patients with breast cancer who had surgical operations, but had not received neoadjuvant chemotherapy, from 2011 to 2013. The clinicopathological characteristics were recorded. Immunohistochemistry staining was performed on ER, PR, HER2/neu, and Ki67 markers. For HER2/neu(2+), fluorescence in situ hybridization was used as the test. All patients with breast cancer were stratified according to 2007 St Gallen categories. Kaplan-Meier and log-rank models were used to analyze survival rates. There were 3.8% cases classified as low risk (LR), 72.1% as intermediate risk (IR1: 60.1% and IR2: 12.0%), and 24.1% as high risk (HR1: 11.8% and HR2: 12.3%). Patients who were LR had the best prognosis, with a 5-year overall survival (OS) rate of 100%. Intermediate-risk patients were at 92.3%. High-risk patients had the worst prognosis, with a 5-year OS proportion of 69.3% ( P < .05). For disease-free survival (DFS), risk categories were categorized as LR: 100%, IR: 90.3%, and HR: 69.3% ( P < .05). Three main risk categories of breast cancer had a distinct OS and DFS. These findings suggest that the 2007 St Gallen risk category could be used to stratify patients with breast cancer into different risk groups in Vietnam.
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Duarte, Erich Dos Reis. "Plantabilidade e suas Variáveis no Estabelecimento da Cultura de Soja." Revista Brasileira de Agrotecnologia 11, no. 3 (September 19, 2021): 07–13. http://dx.doi.org/10.18378/rebagro.v11i3.9126.
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As variáveis capazes de aumentar a produtividade de uma lavoura, está na qualidade da operação de semeadura. A velocidade de deslocamento dos maquinários, associado à profundidade de deposição das sementes influenciam de forma direta no desenvolvimento e de um estande das plantas de soja. O experimento foi conduzido no Sitio Santa Maria no Município de Bandeirantes-PR localizado entre as coordenadas 23°05'58.6"S 50°25'56.9"W, no ano de 2020 e 2021 e teve por objetivo avaliar a influência das velocidades de deslocamento com facão sendo 5; 6,5; 8; e com disco duplo com 5; 6,5; 8; e 9,5 km h-1 e as profundidades de semeadura de 2,3,4 e 5 cm com sistema de disco duplo na lavoura de Soja. Na abertura do sulco, visando a colocação das sementes e fertilizante, utilizaram-se dois mecanismos: rompedores do tipo facão e disco duplo. A roda compactadora utilizada foi do tipo roda metálica lisa em forma de V. Foram determinados os níveis de pressões aplicadas sobre o solo (12,2, 18,5 e 24,1 e 28,5 kPa) por meio de uma célula de carga, com os sensores de linha ligados e desligados. A profundidade de semeadura influenciou as variáveis estudadas, assim como da velocidade de deslocamento adotada. A maior profundidade ocasionou redução da média de produtividade, assim como também a pressão em kPa aumentada foi benéfica a produtividade da cultura da soja de forma significativa.
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Perales, Miguel-Angel, Christina Cho, Anne Eaton, Alison J. Moskowitz, Victoria Nguyen, Anne Marie R. Gonzales-Dadiz, Sean Devlin, et al. "A Prospective Study of Allogeneic Hematopoietic Stem Cell Transplantation in Relapsed/ Refractory Hodgkin Lymphoma." Blood 126, no. 23 (December 3, 2015): 4383. http://dx.doi.org/10.1182/blood.v126.23.4383.4383.
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Abstract INTRODUCTION: Patients with Hodgkin Lymphoma (HL) relapsing post autologous transplant (ASCT) are not cured with standard chemotherapy. In addition, a subset of patients with relapsed or primary-refractory HL fare poorly with ASCT. Such patients may benefit from allogeneic transplantation (allo-HCT) with its graft-versus-lymphoma (GVL) effect. METHODS: We performed a phase II study of salvage therapy (ST) followed by allo-HCT in adult patients with relapsed/refractory (rel/ref) HL (NCT00574496, Fig. 1a). Conditioning was dictated by PET status after ST, with NMA flu/cy/TBI 200 cGy for patients in CR and RIC mel/flu for those with PR/SD. Patients in the intent-to-treat (ITT) cohort were enrolled prior to ST and proceeded to allo-HCT if in CR, PR, or SD after 1 line of ST. The primary endpoint was successful allo-HCT and PFS at 1 year after allo-HCT (estimated as a proportion as all patients had at least 1 year of followup). Landmark analysis (from end of ST) with Kaplan-Meier curves and log-rank test were used to compare OS and PFS in the ITT cohort. A second cohort of patients referred with CR, PR, or SD after ST received HCT on protocol, but was not included in the ITT analysis. No differences in OS or PFS after HCT were seen between ITT and non-ITT cohorts, and patients were combined for further analysis. OS and PFS from time of HCT were estimated using all HCT patients, and PFS was compared based on baseline covariates. Cumulative incidence of GVHD, relapse/POD and nonrelapse mortality (NRM) were estimated using competing risks methodology. P-values less than 0.05 were considered significant. RESULTS: From 6/2008 to 6/2014, 25 patients were consented, 15 on the ITT analysis and 10 on the post-ST arm (Table 1). All had relapse after ASCT, primary refractory or high-risk HL relapsed within 1 year of 1st-line therapy. Allografts (n = 18) were PBSC from matched or single-allele mismatched related (n = 8) or unrelated (n = 3) donor, or double unit cord blood grafts (n = 7). Eleven were in PET CR before HCT and 7 in PR. ITT analysis (n=15): 5 patients had POD on ST and were ineligible for allo-HCT. Of the remaining 9, 1 withdrew during conditioning. 1-year and 3-year OS were 50% (95% CI 22.5, 100) and 16.7% (95% CI 2.8, 99.7), respectively, in patients with POD after ST, and 100% at both time points if no POD after ST (Fig 1b). At median 5.6 years of follow-up, 5 patients survive. The percent of patients successfully meeting the primary endpoint was 33% (95% CI 13, 61). Allo-HCT analysis (n=18): Cumulative incidence (CI) of grade 2-4 and 3-4 aGVHD at d+100 were 23.3% (95% CI 13.1, 55.3) and 11.1% (95% CI 1.70, 30.4), respectively. CI of cGVHD at 1 year and 3 years was 11.1% (95% CI 1.7, 30.7) and 35.6% (95% CI 13.2-59.0), respectively, and of mild severity in all but 1 patient. 3-year CI of relapse/POD was 34.3% (95% CI 13.2-56.7), and NRM 23.6% (95% CI 6.8, 46.1). Estimated 3-year PFS was 42.1% (95% CI 24.1, 73.6) and OS 70.3% (95% CI 51.5, 96.1) (Fig 1c). There was no significant association between PFS and disease stage or status (CR vs. PR). There was a trend toward poorer PFS in the 5 patients without prior ASCT (3 year PFS 20.0% vs. 50.8%, p = 0.088), 3 of whom had primary refractory HL. CONCLUSION: We demonstrate that allo-HCT provides long-term survival for a substantial portion of patients with rel/ref HL. Though limited by small sample size, the ITT analysis showed more than 1/3 of patients never attained sufficient disease control for allo-HCT, and have a dismal prognosis. Of note, none had received brentuximab or a checkpoint inhibitor, and the long-term impact of these agents in those patients remains to be seen. In patients undergoing allo-HCT with chemosensitive disease, proceeding to allo-HCT in PET PR vs. CR had no significant negative impact on PFS in this limited sample. The trend toward poor outcomes in patients who had not previously undergone ASCT likely reflects poor prognosis in patients with primary refractory disease. Factors informing prognosis after allo-HCT, and interventions to attenuate risk, remain an important area for further investigation. Table. Patient characteristics Median (range) age in yrs Median (range) prior lines of therapy N (%) prior ASCT Stage at relapse Disease status pre-ST Disease status pre-HCT ITT (n = 15) 32 (22-51) 3 (1-4) 8 (53.3) III: 4 IV: 11 1st relapse: 6 ≥ 2nd relapse: 5 Refractory: 4 7 CR 2 PR 5 POD 1 withdrew All HCT (n = 18) 36 (24-53) 4 (2-6) 13 (72.2) II: 1 III: 4 IV: 13 1st relapse: 3 ≥ 2nd relapse: 11 Refractory: 4 11 CR 7 PR Disclosures Perales: BeTheMatch/ National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Astellas: Honoraria; Merck: Honoraria; Amgen: Honoraria. Giralt:TAKEDA: Consultancy, Honoraria, Research Funding; JAZZ: Consultancy, Honoraria, Research Funding, Speakers Bureau; AMGEN: Consultancy, Research Funding; SANOFI: Consultancy, Honoraria, Research Funding; CELGENE: Consultancy, Honoraria, Research Funding. Straus:Millenium Pharmaceuticals: Research Funding. Moskowitz:GSK: Research Funding; Merck: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding.
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Komrokji, Rami S., Amy E. DeZern, Katrina Zell, Najla H. Al Ali, Christopher Estling, Cassie Zimmerman, Wesley Hand, et al. "Validation of International Working Group (IWG) Response Criteria in Higher-Risk Myelodysplastic Syndromes (MDS): A Report on Behalf of the MDS Clinical Research Consortium (MDS CRC)." Blood 126, no. 23 (December 3, 2015): 909. http://dx.doi.org/10.1182/blood.v126.23.909.909.
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Introduction The primary goal for treatment of higher-risk MDS patients (pts) is to improve overall survival (OS) and delay acute myeloid leukemia (AML) evolution. The IWG 2006 response criteria are used in clinical trials and in clinical practice for assessing efficacy of MDS therapies. These criteria were originally proposed by an international group of experts based on available data and consensus. In an ad hoc landmark analysis of the AZA-001 study using the 2006 IWG criteria, pts who achieved hematological improvement (HI), complete response (CR), marrow CR (mCR), or partial response (PR) demonstrated improved OS. The aim of this study is to validate the IWG 2006 response criteria among a large cohort of higher-risk MDS pts. Methods Pts with higher-risk MDS (intermediate-2 (Int-2) or High Risk by International Prognostic Scoring System (IPSS)) who had received treatment and for whom details of response and outcome were available were included from the MDS CRC database. Pts were also classified per IPSS-R. The best response to treatment was categorized per the published IWG 2006 response criteria as CR, PR, mCR, HI, stable disease (SD) or progressive disease (PD). The primary endpoint was OS. Results We identified 646 treated higher-risk MDS pts. Table-1 summarizes baseline characteristics. The first line treatment was hypomethylating agent-based therapy (HMA) in 470 pts (74%). The median duration of follow up was 23.2 months (mo) (95% CI: (19.9, 26.5). Median OS from diagnosis was significantly longer for pts with int-2 IPSS risk disease IPSS (26.2 mo (21.5, 29.7)) compared to those who were High Risk (18.8 mo (15.9, 23.6); (p = 0.026). Median OS from diagnosis also differed by IPSS-R category (p < 0.001): for pts with Low risk (n = 6) it was not reached; Intermediate risk it was 41.7 mo (31.8, NR); High Risk it was 28.4 mo (24.1, 33.2); and for pts with Very High it was 16.5 mo (15.3, 19.1). The best IWG 2006 response rate for first line therapy among evaluable pts (n=597) was CR in 93 pts (16%), mCR in 10 (2%), PR in 57(10%), HI in 60 (10%), SD in 233 (39%), and PD in 144 (24%). The median OS based on IWG 2006 best response for first line therapy was 41 mo for CR, 12 mo for mCR, 26 mo for PR, 13 mo for HI, 14 mo for SD and 7 mo for PD. (p <0.001). CR was associated with better outcome compared to all other response groups. Pts with PR, HI, and SD had better outcome compared to PD, and similar outcome among the 3 groups. There was no difference in rate of AML transformation among response groups except in PD pts compared to others. For pts who were treated with HMA as first line therapy, the best response rates by IWG 2006 criteria were CR in 15%, mCR in 2%, PR in 10%, HI in 12%, SD in 40% and PD in 21%. Median OS in mo from time of HMA therapy based on response was: CR 19 (16.3, NR), mCR: 9 (7.1, NR), PR: 13 (8.8, NR), HI: 11 (7.7, 19.0), SD: 11.0 (8.5, 12.6), and PD: 3 (2.3, 3.9). (p <0.001) The best response by IWG 2006 criteria remained predictive of OS after adjusting for IPSS-R risk group. HR 0.30 (95% CI 0.2-0.4) for CR, and 0.57 (95% CI 0.45-0.7) for mCR/PR/HI compared to PD, (p <0.001) Conclusions: The best response by IWG 2006 criteria to first line therapy in higher-risk MDS correlates with OS. Pts who achieved CR had the best OS, while pts who achieved SD or better response had improved outcome compared to PD, with mCR having an OS equivalent to SD. The CR by IWG 2006 response criteria can be used as a surrogate endpoint for OS in higher-risk MDS pts in randomized Phase II studies determining comparison arms of Phase III trials, and for regulatory purposes. Table 1. Baseline characteristics Variable Total n=646 Age Median 68 Gender Male 399/645(62%) Race White 566/633 (89%) t-MDS Yes 161/545/514 (30%) WHO RA RARS RCMD RAEB-I RAEB-II MDS-U MDS/MPN CMML 5/527 (1%) 7/527 (1%) 69/527 (13%) 1153/527 (29%) 284/527 (54%) 3/527 (1%) 5/527 (1%) 1/527 (1%) IPSS Intermediate-II High 468/646 (72%) 178/646 (28%) R-IPSS Very low Low Intermediate High Very High 0 6/621 (1%) 74/621 (12%) 211/621 (34%) 330/621 (53%) IPSS karyotype Good Intermediate Poor 135/642 (21%) 118/642 (18%) 389 /642 (61%) IPSS-R karyotype Very good Good Intermediate Poor Very poor 7/642 (1%) 137/642 (21%) 134/642 (21%) 118/642 (18%) 246/642 (38%) Allogeneic transplant Yes 158/554 (29%) First line therapy HMA Chemotherapy IMiDClinical trial other 470/634 (74%) 57/634 (9%) 43/634 (7%) 25/634 (4%) 38/634 (6%) Lab (mean) Hgb (n=514) Platelets (n=514) ANC (n=514) Bone marrow blasts (n=639) 9.2 94 1.6 10% Disclosures Komrokji: Novartis: Research Funding, Speakers Bureau; Incyte: Consultancy; Pharmacylics: Speakers Bureau; Celgene: Consultancy, Research Funding. Steensma:Incyte: Consultancy; Amgen: Consultancy; Celgene: Consultancy; Onconova: Consultancy. Sekeres:TetraLogic: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees.
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Zubkov, Pavel T., and Eduard I. Narygin. "The effect of viscous dissipation on natural convection in a square cavity." Tyumen State University Herald. Physical and Mathematical Modeling. Oil, Gas, Energy 5, no. 3 (October 14, 2019): 118–30. http://dx.doi.org/10.21684/2411-7978-2019-5-3-118-130.
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This article studies the natural convection of a viscous, incompressible fluid in a square cavity in a gravitational field. The temperature of vertical walls is constant. The temperature of the left wall is higher than temperature of the right wall; the horizontal walls are considered thermally insulated. The initial condition for the temperature of a fluid in a square caviry is the constant and equals the temperature of the right wall. The initial condition for the velocity is zero. We consider only those cases where the obtained flow in the cavity is laminar. All thermophysical characteristics are assumed constant, except for one when the motion equation accounts for the gravity. Mathematical model is the Boussinesq approximation but the equation of conservation of energy contains Rayleigh dissipation function.<br> In this article, the authors have researched the effect of viscous dissipation on natural convection heat transfer in square field. The results show that viscous dissipation significantly affects the heat transfer through the cavity. This problem was solved with the finite volume method by algorithm SIMPLER for Pr=1, Gr=10<sup>4</sup>, and 10<sup>−5</sup>≤Ec≤10<sup>−3</sup>.
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Jeong, Dae-Chul, Hui Sung Hwang, Bin Cho, Nak Gyun Chung, Pil Sang Chang, Dae Hyung Lee, Young Joo Kwon, et al. "Anabolic Androgen (Oxymetholone) Improved Failure Free Survival in Childhood Severe Aplastic Anemia Responding to Immunosuppressive Therapy." Blood 108, no. 11 (November 16, 2006): 982. http://dx.doi.org/10.1182/blood.v108.11.982.982.
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Abstract Immunosuppressive therapy (IST) has been extensively used as first line treatment in children with severe aplastic anemia (SAA), who do not have a suitable donor for hematopoietic stem cell transplantation (HSCT). Several studies have reported that androgens may enhance the response to IST. We retrospectively investigated the effects of androgen on survival. The patient population consisted of 112 children with diagnosis with SAA at St. Mary’s Hospital between 1991 and 2004. All patients received horse type anti-lymphocyte (ALG) or rabbit type anti-thymocyte globulin (ATG), and methylprednisolone, cyclosporin A without G-CSF. Forty-seven children began oral administration of oxymetholone (OMT, 2mg/kg/day) at post-IST 4 weeks for 3 months. We assessed response at post-IST 4 weeks, 6 months on the basis of Camitta’s criteria. Treatment failure was defined as transfusion dependency, death, clonal evolution, and progression to HSCT. We analyzed failure free survival (FFS) and overall survival (OS) in childhood SAA treated with IST. There were no differences in patient characteristics but children treated with ALG received more OMT than those treated with ATG (P < 0.01). The response rate at post-IST 6 months was 57.1%, 24.1% showing a complete response (CR) and 33.0% a partial response (PR). A high CR rate was identified in those treated with OMT administration (P = 0.04). Factors associated with response to therapy were type of anti-globulin utilized, response at post-IST 4 weeks, and the administration of OMT (P < 0.01). The relapse rate was 40.6%, and was noted to be higher in those given ALG. The OS and FFS in this study was 77.6 ± 4.3% and 54.5 ± 5.1% respectively at 8 year. Factors associated with FFS were response at post-IST 6 months (P < 0.01, RR: 2.155, 1.246 ~ 3.728) and the administration of OMT (P = 0.04, RR: 1.830, 1.026 ~ 3.265) in multivariate analysis, although type of anti-globulin was also included in univariate analysis. The FFS was higher in those treated with OMT (74.3 ± 6.4%) than those who were not given OMT (33.5 ± 7.3%) at 8 year. With regards to the type of response, the FFS was higher in those administered OMT (80.0 ± 10.3%) than those not given OMT (26.4 ± 14.9%) (P = 0.02, RR: 2.273, 1.1624 ~ 12.064) amongst patients who showed PR, although there was no significant difference in FFS amongst patients who showed CR with OMT (94.7 ± 9.0%) or without OMT (83.3 ± 15.2%) at 8 year (P = 0.76). The factor associated with OS was response at post-IST 6 months (P = 0.013, RR: 3.30, 1.28 ~ 8.52) in multivariate analysis, although severity at diagnosis was also included in univariate analysis.Our data revealed that OMT improved FFS in childhood SAA responding to IST, especially in those with PR. In this retrospective study, we concluded that the addition of short term OMT to IST as first line therapy significantly improved CR rate and FFS in childhood SAA patients without a suitable HLA-matched donor.
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Pinto, Navin R., Arlene Naranjo, Emily Hibbitts, Xiangming Ding, Rachelle Tibbetts, Rebekah Kennedy, Ruthann Pfau, et al. "Segmental chromosome aberrations and clinical response impact outcome of inss stage III patients ≥18 months with unfavorable histology and without MYCN amplification: A Children’s Oncology Group (COG) report." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 10502. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.10502.
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10502 Background: Patients with INSS stage III neuroblastoma represent a heterogeneous population with respect to disease presentation and prognosis and controversy exists regarding the most effective treatment algorithms. Patients ≥18 months of age with INSS Stage 3 tumors that are unfavorable histology (UH) and MYCN-non-amplified ( MYCN-NA) represent a small cohort of patients with an outcome intermediate of those with favorable histology tumors and MYCN amplified tumors. The presence of Segmental Chromosome Aberrations (SCA) may predict outcome; however, their impact specifically in this cohort of patients has not been reported. Methods: Eligible patients enrolled on therapeutic protocols A3973 (n=34), ANBL0532 (n=27), and biology protocol ANBL00B1 (n=101 with 29 treated on A3973/ANBL0532) with stage III disease, MYCN–NA, UH and age ≥18 months at diagnosis were analyzed. Copy number alterations and loss of heterozygosity (LOH) for relevant loci were scored for gains/losses by two independent reviewers. Results: The 5-year EFS/OS for children ≥18 months with stage III, MYCN–NA, UH disease treated on A3973 and ANBL0532 was 73.0±8.1%/87.9±5.9% and 61.4±10.2%/ 73.0±9.2%, respectively, with no statistical differences in EFS or OS between the two cohorts (p=0.1286 and p=0.2180, respectively). In the combined cohort of patients enrolled on A3973 and ANBL0532, statistically significant differences were found (p(s) <0.0001) in patients with CR/VGPR (n=39) and PR (n=13) having better outcomes than <PR (n=5) (5-year EFS: 74.0±7.6% vs. 75.0±12.5% vs. 0%; 5-year OS: 84.4±6.2% vs. 100% vs. 20.0±17.9%). Subjects with chromosome 11q loss/LOH had an inferior outcome in comparison to those without 11q loss/LOH (10-year EFS: 44.4+/-24.1% vs. 78.1+/-9.4%, p=0.01; 10-year OS: 62.4+/-15.9% vs. 85.9+/-7.8%, p=0.02)). Patients with 1p loss/LOH and 2p gain also showed trend towards worse event-free survival (p=0.086 and p=0.088, not statistically significant) but not in overall survival. Conclusions: High-risk therapy that included single myeloablative therapy led to an 81.6±5.3%5-year OS in patients ≥18 months with UH and MYCN–NA stage III neuroblastoma. Response to therapy is a powerful predictor of survival and the presence of chromosome 11q loss/LOH is also associated with inferior outcomes. These patients should continue to be treated on high-risk clinical trials.
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Silverman, Lewis R., David R. McKenzie, Bercedis L. Peterson, Richard M. Stone, Bayard L. Powell, Christy Mayo, Jay T. Backstrom, and Richard A. Larson. "Response Rates in Patients with Acute Myeloid Leukemia (AML), Treated with Azacitidine, Using WHO and International Working Group (IWG) Criteria for Myelodysplastic Syndrome (MDS)." Blood 106, no. 11 (November 16, 2005): 1848. http://dx.doi.org/10.1182/blood.v106.11.1848.1848.
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Abstract The CALGB conducted a series of clinical trials with azacitidine (Vidaza®) administered subcutaneously or intravenously in patients with MDS using the FAB classification (JCO2002;20:2429). Since completion of these CALGB studies (8421, 8921, 9221), a new classification system was developed by the WHO that distinguishes MDS from AML (blasts > 20%). Although studies with azacitidine in patients with AML had previously shown activity, the 75 mg/m2/day dose in the CALGB studies was lower than previously studied. Using the WHO system, the diagnosis for CALGB study patients was redefined and patients with AML were analyzed separately. Most of the 105 patients were previously considered refractory anemia with excess blasts in transformation (RAEB-T). Also, new treatment response criteria for MDS were published by the IWG (Blood2000; 96:3671). Using IWG response criteria, azacitidine patients with WHO AML in studies 8421, 8921, or 9221 had an overall response rate (CR+PR+HI) of 48% (12/25), 32% (9/28), and 37% (10/27), respectively. Best Response using IWG Response Criteria for WHO AML Patients in Studies 8421, 8921, and 9221 Median duration of any response (CR, PR or HI) in the 33 azacitidine-treated responders was 279 days (range: 61 to 724 days). The median duration of CR in the 8 azacitidine-treated responders was not achieved; however, the 25th percentile was 115 days (range: 92 to 274+ days). In Study 9221, the median duration of transfusion independence (defined as ≥56 days) in patients independent at baseline was significantly longer in the azacitidine group compared with supportive care for red blood cells (azacitidine [n=8]: 411 days vs. supportive care [n=9]: 133 days, p=0.02) and platelets (azacitidine [n=13]: 363 days vs. supportive care [n=18]: 125 days, p=0.004). In the azacitidine group, 22% (6/27) of patients had a hemoglobin improvement to >11 g/dL that was maintained for ≥56 days compared with 8% (2/25) in the supportive care group (p=0.2). The proportions of patients with ANC >1500/m3 and platelets >100,000/mm3 lasting for ≥56 days were similar between the treatment arms. Azacitidine patients with WHO AML had a longer median survival (19.3 months) compared with the supportive care group (12.9 months) (p=0.2). Further studies investigating azacitidine in patients with AML with dysplasia are warranted.
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Kim, Richard D., Dae Won Kim, Olatunji B. Alese, Daneng Li, Neal Shah, Michael J. Schell, Jun Min Zhou, and Vincent Chung. "A phase II study of nivolumab in patients with advanced refractory biliary tract cancers (BTC)." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 4097. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.4097.
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4097 Background: Biliary tract cancers (BTC) are often typically diagnosed at an advanced stage. There is no established second line option for patients with advanced BTC who have failed one prior systemic therapy. The phase II study evaluated safety and efficacy of nivolumab, anti PD-1 antibody in refractory BTC patients. Methods: Pts with histologically proven BTC who progressed on at least one line but no more than three lines of systemic therapy received nivolumab 240mg IV q2weeks for 16 weeks and then 480 mg IV every 4 weeks until disease progression or unacceptable toxicity. The primary endpoint of the study was objective response rate (ORR) by RECIST 1.1 every 8 weeks. The Simon two staged design was used to assess ORR.18 patients were accrued and if one response was seen, the plan was to accrue additional 34 patients. Secondary endpoints were PFS, OS and safety profile. Results: At data cutoff (Jan 14, 2018), 54 patients with BTC (female: 50%, Median age: 65 years) were enrolled. The primary sites of tumor were intrahepatic cholangiocarcinoma (63%) extrahepatic (11%), and gallbladder (26%). 30 pts (56%) failed 1 line of therapy and 24 (44%) failed more than one line of therapy. 45 pts (1 pt withdrew consent, 1pt just enrolled prior to data cutoff and 7 pts came off the study due to clinical progression) were evaluable for response rate. Out of 45 pts, 10 pts (22%) achieved PR (1 unconfirmed PR) and 17 pts (37.8%) achieved SD. DCR was 60%. All patients who responded were microsatellite stable. For evaluable 45 pts with median follow up of 13.34 months, median PFS was 3.98 months (95% CI: 2.33-5.98) and the median OS was 14.22 months (95% CI: 6.64-NA). 6 and 12month OS was 71.4 and 52.3% and 6 and 12 month PFS was 35.2% and 24.1% respectively. Most common treatment related AEs (TRAE) was alkaline phosphatase increased (24.5%). Grade III/IV TRAEs were seen in 11 pts (20.4%); most common were hyponatremia (3 pts) and elevated alkaline phosphatase (2 pts). No treatment related AEs led to discontinuation of the study drug. Tissue samples were collected in all pts with planned correlative studies underway including the PDL 1 status. Conclusions: Nivolumab was well tolerated and has shown promising efficacy in refractory BTC including durable responses lasting 2 years. Further randomized trial is warranted in refractory BTC. Clinical trial information: NCT02829918.
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Venugopal, Parameswaran, Stephanie A. Gretory, John Showel, Jamile Shammo, Sari Enschede, Melissa Larson, Teresa Obrien, Tatiana D. Sokolovsky, and Aaron Means. "Rituximab (Rituxan) Combined with ESHAP Chemotherapy Is Highly Active in Relapsed/ Refractory Aggressive Non-Hodgkin’s Lymphoma." Blood 104, no. 11 (November 16, 2004): 4636. http://dx.doi.org/10.1182/blood.v104.11.4636.4636.
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Abstract Patients with relapsed/refractory aggressive lymphoma have limited options for achieving long-term remission other than stem cell transplantation. ESHAP is active in aggressive NHL and has the added advantage of being a non-anthracycline regimen. However, the response rate and remission duration with ESHAP chemotherapy alone are low in this group of patients. Encouraged by the increased efficacy of chemo-immunotherapy combinations like CHOP + Rituximab (Rituxan) in untreated aggressive lymphoma, and the in vitro synergy of Rituximab with cisplatin, cyclophosphamide and steroids, we studied the safety and efficacy of ESHAP + Rituximab combination in this group of patients. Standard ESHAP regimen (Etoposide 40 mg/m2/d IV/2h day1–4; Methylprednisolone 500 mg/m2 IV days 1–4; Cytarabine 2 g/m2 IV/3h day 5 and Cisplatin 25 mg/m2/d CIV days 1–4) was administered. Rituximab 375 mg/m2 IV was administered in the following manner: 2 doses separated by one week prior to the first cycle of ESHAP and 2 doses administered similarly after completion of the sixth cycle of ESHAP; one dose of Rituximab each was also given 48 hours prior to the third and fifth cycle of ESHAP. Treatment cycles were repeated every 28 days x 6. GMCSF (Leukine) and Erythropoietin (Procrit) were used at the discretion of the investigator. 14 patients were enrolled in the study. Median age was 55.5 years (range 37–70); there were 12 males and 2 females. 11/14 (71%) of patients had advanced disease (stage III/IV). Extranodal disease sites included kidney, lungs and adrenals. Histology was Diffuse Large Cell: 13 (93%) and Mantle Cell Lymphoma: 1 (7%). All patients had prior therapy: 1st relapse 11, 2nd relapse 1 and 3rd relapse 2. Prior therapies included CHOP, modified CHOP, Fludarabine-based regimen, Rituxan and Bexxar. 7 patients (50%) achieved CR, 2 PR, 1 stable disease and 4 PD. Among the 6 patients who received all 6 cycles of therapy, 4/6 (67%) achieved CR and 2/6 (33%) PR, (ORR 100%). Duration of response in patients who received all 6 cycles: All Responders: 26.3 months (1–53.3) and Patients who achieved CR: 35 months (24.1–53.3). Significant toxicity included grade III/IV hematologic in 43% and grade III/IV infection/febrile neutropenia in 21%. Conclusion: ESHAP combined with Rituximab appears to be more active than ESHAP alone with no additional toxicity other than infusion-related adverse events in patients with relapsed/refractory aggressive lymphoma. Patients who achieved CR with this regimen appear to have longer remissions. Prospective, controlled trials are warranted.
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Stone, MJ, EA Sausville, JW Fay, D. Headlee, RH Collins, WD Figg, M. Stetler- Stevenson, et al. "A phase I study of bolus versus continuous infusion of the anti-CD19 immunotoxin, IgG-HD37-dgA, in patients with B-cell lymphoma." Blood 88, no. 4 (August 15, 1996): 1188–97. http://dx.doi.org/10.1182/blood.v88.4.1188.bloodjournal8841188.
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IgG-HD37-SMPT-dgA is a deglycosylated ricin A chain (dgA)-containing immunotoxin (IT) prepared by conjugating the monoclonal murine (MoAb) anti-CD19 antibody, HD37, to dgA using the heterobifunctional hindered disulfide linker, N-succinimidyl-oxycarbonyl-alpha-methyl-alpha-(2- pyridyldithio) toluene (SMPT). In this report, we have used two regimens for the administration of IgG-HD37-SMPT-dgA to patients with non-Hodgkin's lymphoma (NHL) in two concomitant phase I trials. One trial examined four intermittent bolus infusions administered at 48- hour intervals. The other studied a continuous infusion (CI) administered over the same 8-day period. In the intermittent bolus regimen, the maximum tolerated dose (MTD) was 16 mg/m2/8 d and the dose- limiting toxicity (DLT) consisted of vascular leak syndrome (VLS), aphasia, and evidence of rhabdomyolysis encountered at 24 mg/m2/8 d. Using the CI regimen, the MTD was defined by VLS at 19.2 mg/m2/8 d. At the MTD of both regimens, a novel toxicity, consisting of acrocyanosis with reversible superficial distal digital skin necrosis in the absence of overt evidence of systemic vasculitis, occurred in 3 patients. Of 23 evaluable patients on the bolus schedule, there was 1 persisting complete response (CR; > 40 months) and 1 partial response (PR). Of 9 evaluable patients on the continuous infusion regimen, there was 1 PR. Pharmacokinetic parameters for the bolus regimen at the MTD showed a mean maximum serum concentration (Cmax) of 1,209 +/- 430 ng/mL, with a median T1/2 beta for all courses of 18.2 hours (range, 10.0 to 80.0 hours), a volume of distribution (Vd) of 10.9 L (range, 3.1 to 34.5 L), and a clearance (CL) of 0.45 L/h (range, 0.13 to 2.3 L/h). For the CI regimen at MTD, the mean Cmax was 963 +/- 473 ng/mL, with a median T1/2 beta for all courses of 22.8 hours (range, 24.1 to 30.6 hours), a Vd of 9.4 L (range, 4.4 to 19.5 L), and a CL of 0.32 L/h (range, 0.12 to 0.55 L/h). Twenty-five percent of the patients on the bolus infusion regimen and 30% on the CI regimen made antibody against mouse Ig (HAMA) and/or ricin A chain antibody (HARA). We conclude that this IT can be administered safely and that both regimens achieve comparable peak serum concentrations at the MTD; these concentrations are similar to those achieved previously using other regimens with IgG-dgA ITs at their respective MTDs. Thus, toxicity is related to the serum level of the IT and does not differ with different targeting MoAbs.
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Rubio-Martinez, Araceli, Luis Palomera, Valle Recasens, Maria J. Najera, Matilde Perella, Fernando Puente, Luis Perdiguer, Daniel Rubio-Felix, Pilar Mayayao, and Pilar Giraldo. "Evaluation of Response to Anti-CD20 (Rituximab) Trial in Relapsed Follicular Lymphoma after Six Years in Follow-Up." Blood 106, no. 11 (November 16, 2005): 4784. http://dx.doi.org/10.1182/blood.v106.11.4784.4784.
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Abstract Background: Follicular Lymphoma (FL) is characterized by t(14:18)(q32;q21) in 80% patients. Persistence of expression bcl2/JH gene translocation is related to frequent relapses in FL. Purpose: To determine the efficacy of Fludarabine-Mitoxantrone (FLD/MTX) + monoclonal anti CD20 antibody (Rituximab) to induce clinical and molecular response in relapsed FL in base to the presence of bcl-2. Methods: Prospective trial in 31 patients with relapsed FL. An outpatient regimen i.v./28d: FLD 30 mg/m2 1–3 + MTX 10 mg/m2 1 followed by Rituximab (375 mg/m2/weekly x4). Eligibility criteria: adults patients with both (relapsed FL by biopsy + bcl-2 immunohistochemistry expression in nodal biopsy), ECOG<3, normal renal function and liver tests. Exclusion criteria: previous anti-CD20 therapy, chemotherapy within 4 weeks previously, other malignancies, AIDS or other infectious disease. Patients were eligible for registration previous inform consent. Evaluation at baseline included: complete blood counts, serum and urine biochemistry, b2 microglobuline and LDH, body scan, bone marrow (BM) biopsy and PCR-ELISA for t(14;18) in BM. Patients were classified according ECOG, clinical stage and FLIPI. Follow-up monitoring: after FLD/MTX and 2 months after Rituximab, including clinical examination, laboratory, scan, BM examination and t(14;18). Response criteria: Complete remision (CR):resolution tumour mass and BM involvement; partial remission (PR):>75% reduction in tumour mass and BM infiltration <10%. Progression: increase in measurable mass lesion >25% during therapy. Molecular remision (MR): negative PCR-ELISA assay in BM. Statistical analysis: descriptive and frequency distribution, overall survival (OS), relapsed free survival (RFS). Survival curves were estimated using Kaplan-Meier survival analysis. Results: Mar-99 to July03, 31 patients with relapsed FL were enrolled. Mean age: 56.00± 12.44 (range 32–77); M/F: 13/18. ECOG: 0(22), 1(5), 2(2), 3(2). Clinical stage II(4), III(8), IV(19). Previous therapies 1(19), 2(4), and 3 or more(8), FLIPI 0 (3), 1(6), 2(15), 3(7). PCR t(14:18) was positive in BM in 12 cases (40 %). Response: after FLD-MTX, clinical response was obtained in 27 patients, CR 13 (43.3%) and PR 14(46.67%), 2 failed. One not valuable. Rituximab started in 27/28 patients with clinical response (1 refused). After Rituximab: CR 23 (81.4%), PR 4(13.3%) and 2 failures (6.4%) After Rituximab (26 responsive patients): 22 (84.6%) achieved MR, 4 (15.3%) persist PCR-ELISA positive in BM. PBSCT was underwent in 14 CR patients (63.6%). OS: 117 months (range 36–200), median RFS 44,22 months (range 0–73). Relapse was observed in 13(43,3%) and 8 died, only one patient had persistence of t(14;18), mean time to relapse 24.1 m (0–57), 3 patients relapsed after PBSCT. Four patients in CR have died by other causes. Nowadays17 patients remain alive and 12 are in CR. Conclusions: The response to FLD-MTX is obtained in 90 % of patients with relapsed FL, with CR rates 43.3%. The addition of Rituximab does not influence on overall response but improves CR rates (81.4%). The median RFS of group is 117 months only 13 patients developed relapse apparently it is not related to persistence of t(14;18).
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Sun, Ying, Wan Liang, Qingyun Liu, Tingting Zhao, Hechao Zhu, Lin Hua, Zhong Peng, et al. "Epidemiological and genetic characteristics of swine pseudorabies virus in mainland China between 2012 and 2017." PeerJ 6 (October 23, 2018): e5785. http://dx.doi.org/10.7717/peerj.5785.
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The outbreak of pseudorabies (PR) in many Bartha-K61 vaccinated farms in China in late 2011 has seriously damaged the pig industry of one of the largest producers of pork products in the world. To understand the epidemiological characteristics of the pseudorabies virus (PRV) strains currently prevalent in China, a total of 16,256 samples collected from pig farms suspected of PRV infection in 27 Provinces of China between 2012 and 2017 were evaluated for detection of PRV. Since the extensive use of gE-deleted PRV vaccine in China, the PRV-gE was applied for determining wild-type virus infection by PCR. Of the 16,256 samples detected, approximately 1,345 samples were positive for the detection of PRV-gE, yielding an average positive rate of 8.27%. The positive rates of PRV detection from 2012 to 2017 were 11.92% (153/1284), 12.19% (225/1846), 6.70% (169/2523), 11.10% (269/2424), 5.57% (147/2640), and 6.90% (382/5539), respectively. To understand the genetic characteristics of the PRV strains currently circulating, 25 PRV strains isolated from those PRV-gE positive samples were selected for further investigation. Phylogenetic analysis based on gB, gC, and gE showed that PRV strains prevalent in China had a remarkably distinct evolutionary relationship with PRVs from other countries, which might explain the observation that Bartha-K61 vaccine was unable to provide full protection against emergent strains. Sequence alignments identified many amino acid changes within the gB, gC, and gE proteins of the PRVs circulating in China after the outbreak compared to those from other countries or those prevalent in China before the outbreak; those changes also might affect the protective efficacy of previously used vaccines in China, as well as being associated in part with the increased virulence of the current PRV epidemic strains in China.
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Alexander, Vinita M., Alan N. Gordon, David H. Howard, and Namita Khanna. "Outcomes and Cost Analysis of Surveillance Strategies After Initial Treatment for Women With Recurrent Ovarian Cancer." International Journal of Gynecologic Cancer 27, no. 7 (September 2017): 1333–42. http://dx.doi.org/10.1097/igc.0000000000001040.
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ObjectiveThe aim of this study was to determine whether there is a survival or cost benefit dependent on detection strategy of recurrent ovarian cancer (ie, imaging, physical examination findings, report of symptoms, or rising cancer antigen 125 [CA-125] levels).Methods/MaterialsA retrospective chart review of 112 ovarian cancer patients was conducted, and method of detection of recurrent disease was determined from medical records. The following primary outcomes were determined using Cox proportional hazards regression model: progression-free survival (PFS) after diagnosis of recurrence and time to death after diagnosis of recurrence (overall survival [OS]). Several approaches to disease surveillance were proposed, and a cost model was applied.ResultsMedian time to recurrence was 13.5 months. Overall, 6.3% presented with only physical examination findings; 24.1%, with elevating CA-125 levels; 34.8%, with imaging; and 32.1%, with symptoms. Most patients presenting with recurrent disease diagnosed by rising CA-125 were white (62.9%); those with imaging and symptomatic recurrences were blacks (56.4% and 57.1%, respectively). There was a small but not statistically significant OS benefit for recurrence detected via CA-125 (P = 0.85; OS per detection method: PE, 20.7 months; CA-125, 26.8 months; imaging, 17.8 months; and symptoms, 6.6 months). We modeled costs of surveillance in our patient cohort; up to 40.8% of cases of ovarian cancer recurrences would have been missed if no imaging were obtained during surveillance.ConclusionsResults indicate minimal differences in PFS and statistically insignificant differences in OS, depending on detection method. Notably, black patients with Medicaid presented most often with symptomatic recurrences, which surprisingly did not affect patient OS and PFS; and interestingly, pr\ivate or self-pay insurance was associated with decreased OS among black patients. From our cost analysis, we estimate that the most cost-effective surveillance strategy for the first year costs $9.2 million annually and includes office visit biannually, biannual CA-125 levels, and annual asymptomatic imaging.
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Friedlander, Michael L., Kenneth Russell, Sherri Millis, Zoran Gatalica, Ryan Bender, and Andreas Voss. "Molecular Profiling of Clear Cell Ovarian Cancers: Identifying Potential Treatment Targets for Clinical Trials." International Journal of Gynecologic Cancer 26, no. 4 (May 2016): 648–54. http://dx.doi.org/10.1097/igc.0000000000000677.
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BackgroundAdvanced stage/recurrent clear cell ovarian cancers (CCOCs) are characterized by a low response to chemotherapy and a poor prognosis. There is growing interest in investigating novel/molecular targeted therapies in patients with CCOC in histotype-specific trials. However, CCOCs are not a uniform entity and comprise a number of molecular subtypes and it is unlikely that a single approach to treatment will be appropriate for all patients. The aim of this study was to analyze the results of a multiplatform profiling panel in CCOCs to identify potential therapeutic targets.Patients and MethodsTumor profiling was performed on 521 CCOCs. They were grouped into pure (n = 422) and mixed (n = 99) CCOC for analysis. Testing included a combination of DNA sequencing (including next-generation sequencing) using a 46-gene panel, immunohistochemistry, fluorescent or chromogenic in situ hybridization, and RNA fragment analysis.ResultsThe most common findings were in the PIK3CA/Akt/mTOR pathway, with 61% of all CCOCs showing a molecular alteration in one of these pathway components. Next-generation sequencing revealed PIK3CA mutations in 50% of pure CCOCs. Significant differences were observed between pure and mixed CCOCs with respect to hormone receptor expression (9% vs 34.7% for ER, 13.45 vs 26.4% for PR), cMET (24.1% vs 11.6%), PD-1 tumor infiltrating lymphocytes (48.1% vs 100%), expression of PD-L1 (7.4% vs 25%), and TOPO1 (41% vs 27.1%) on immunohistochemistry, whereas next-generation sequencing revealed significant differences in mutation frequency in PIK3CA (50% vs 18.5%), TP53 (18.1% vs 57.7%), KRAS (12.4% vs 3.7%), and cMET (1.9% vs 11.1%).ConclusionsThis large study confirms that the PIK3CA/Akt/mTOR pathway is commonly altered in CCOCs, and highlights the significant differences between pure and mixed CCOCs. Clear cell ovarian cancers are molecularly heterogeneous and there are a number of potential therapeutic targets which could be tested in clinical trials.
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Dhruva, Anand, Lloyd E. Damon, Charles Linker, Thomas G. Martin, and Willis H. Navarro. "A Retrospective Review of Outcomes of Patients with Chronic Myelomoncytic Leukemia Treated with 5-Azacitidine." Blood 106, no. 11 (November 16, 2005): 4931. http://dx.doi.org/10.1182/blood.v106.11.4931.4931.
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Abstract The chemotherapeutic agent 5-azacytidine (5-AZA) is an active agent in the treatment of myelodysplastic syndrome (MDS). Phase III data with 5-AZA for MDS of all types suggest a response rate (CR+PR) of 23% and hematologic improvement rate of 37% (Silverman, et al, 2002, JCO, 20:2429). We reviewed the outcomes of patients with the MDS subtype chronic myelomonocytic leukemia (CMML) in order to better characterize outcomes for patients with this specific subtype. Methods: Retrospective analysis of outcomes in 13 patients (median age 67; range 50–82) with CMML, who were drawn from a group of 165 consecutive patients treated with 5-AZA between 1991 and 2004 at UCSF on an NCI Special Exception Program, was performed. All patients signed informed consent to participate in the Expanded Access Protocol and IRB approval at UCSF was obtained to retrospectively review this data. IPSS of patients were 2 LOW, 7 INT-1, 3 INT-2, and 1 HIGH. 11 patients had CMML-1 and 2 patients had CMML-2. Responses were determined using the MDS International Working Group (Cheson et al., 2000 Blood96:3671) criteria. Results: Three patients (23%) had CR and 6 patients (46%) had HI at 4 months. 9/13 patients had a response at 4 months for an overall response rate of 69% (95% CI 38.6% to 90.0%). Cytogenetic responses were seen in 1 out of 4 evaluable patients. The median AML free survival was 11 months. The median overall survival was 14 months. Figure Figure Conclusions: For patients with CMML, 5-AZA provides an effective treatment option with significant improvements in peripheral blood counts, marrow blasts, and transfusion requirements. The overall response rate of 69% correlates well with larger studies in MDS.
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Reece, Donna E., Young Trieu, Alida Pokoradi, Wei Xu, Sharon Fung, Christine Chen, Vishal Kukreti, Joseph Mikhael, Suzanne Trudel, and A. Keith Stewart. "Effect of the Percent Decrease in Monoclonal Protein with Induction Therapy on the Outcome after Autologous Stem Cell Transplantation in Patients with IgG and IgA Multiple Myeloma." Blood 110, no. 11 (November 16, 2007): 950. http://dx.doi.org/10.1182/blood.v110.11.950.950.
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Abstract One potential approach to improve the results of autologous stem cell transplantation (ASCT) in multiple myeloma (MM) involves the use of more potent induction regimens; the achievement of deeper remission pre-ASCT should translate into longer progression-free (PFS) and overall survival (OS). To evaluate this hypothesis, we assessed the influence of the percent reduction in serum monoclonal protein (M protein) pre-ASCT in patients (pts) treated with dexamethasone-based regimens (most often VAD) on the best response, PFS and OS achieved after ASCT. Between 2000–2006, 376 pts with IgG (267) or IgA (109) non-progressive MM underwent ASCT. Median age was 59 (21–73) yrs; 60% were male. The median hemoglobin at diagnosis was 103 g/L, creatinine 98 μmol/L, β2-microglobulin 241 nmol/L and albumin 35 g/L. Maintenance therapy was given to 84 (22%) after ASCT and consisted of corticosteroids in 29, thalidomide in 10, both in 41 and other regimens in 4 pts. Patients were divided into 4 groups based on the per cent reduction in M protein after induction therapy: group A, ≥ 99%; group B, 90–98%; group C, 50–89%; group D, < 50%. Post-ASCT responses included complete remission (CR), very good partial remission (VGPR) (≥ 90% reduction in M protein), PR (≥ 50% reduction) and stable disease (SD). Median follow-up from diagnosis is 37.4 mos and from ASCT 24.1 mos. For all pts, the median OS from diagnosis is 90.8 mos (95% CI 73.9–129.1 mos) and from ASCT 63.9 mos (95% CI 50.8–69.4 mos), while the median PFS from ASCT is 21.3 mos (95% CI 19.1–23.3 mos). Maintenance therapy had no significant effect on PFS (p=0.49) or OS (p=0.59). The post-ASCT results in evaluable patients according to the percent reduction in M protein after induction therapy are summarized below. We conclude: High-grade remissions after dexamethasone-based induction therapy are uncommon, with only 2% achieving ≥ 99% and 13% achieving 90–98% reduction in serum M protein; post-ASCT CR and VGPR rates were higher in these 2 groups; there was no significant difference in PFS or OS-based on protein response prior to transplant; whether newer induction regimens, which incorporate novel agents and which produce more CRs and VGPRs before ASCT, will confer better PFS and OS post-ASCT will be of great interest. Table 1 Group N CR (%)1 VGPR (%)1 PR (%)1 SD (%)1 Median PFS (mo)2 Median OS (mo)3 1p<0.001;2p=0.77;3p=0.79 A 7 50 50 Not reached Not reached B 47 19 64 17 23.3 Not reached C 232 14 17 68 1 20.7 59.1 D 87 11 7 54 28 21.1 69.4 Figure Figure Figure Figure
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Miletskiy, V. P., and O. A. Nikifоrova. "Evolution of Political Simulacra in Digital Society (on the Examples of “fake news” and “post-truth”)." Discourse 6, no. 3 (July 20, 2020): 64–77. http://dx.doi.org/10.32603/2412-8562-2020-6-3-64-77.
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Introduction. The paper deals with the evolution of “fake-news” and “post-truth” in the digital society, which can be qualified as simulations of virtual space. The authors formulate a hypothesis that disclosure of the features of social evolution of “fake news” and “post truth” as political simulaсra is possible on the basis of a multi-paradigm approach that combines the explanatory potential of sociology of communication, political sociology, systemic, interactive approach, concepts of cultivation and agenda.Methodology and sources. The methodological basis is a multi-paradigm approach to the study of “fake news” and “post truth” as “simulacras” of virtual space, distributed mainly "on the World Wide Web" in the form of deliberately false or distorting messages, memes, posts, repost, tweets, retweets, trolling, etc., allowing to unite heuristic possibilities of system-sociological and interactive approaches, theory of communicative action, concepts of cultivation and agenda.Results and discussion. The authors argue that “fake news” as an information unit of mainly political and communicative space is a natural product of digitalization development, which arises from the “post truth”. Today the artificial construction of political news has a practical impact on the behavior of businessmen, public figures, political leaders, etc., as well as to influence the real socio-economic processes and political and legal sphere on a global scale. The problem of belief in "fake news" is considered, the study of which, based on multi-paradigm methodology, allows to reveal it properly and find possible solutions.Conclusion. Consideration of the evolution of “fake news” and “post truth” in digital society shows that they act as certain political simulacras of virtual space with using the manipulative technologies. “Fake-news” and “posttruth” pose a threat to society as a whole, create “obstacles” for their study and complicate communicative interaction, replacing real socio-political communications and tangible political actions with their imitation in virtual space or, for example, as a politically convenient truth, form a certain synthetic simulacrum in political-communicative practice, which combines PR-shows and media manipulations.
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Petrucci, Maria Teresa, Igor W. Blau, Paolo Corradini, Meletios A. Dimopoulos, Johannes Drach, Pilar Giraldo, Adriana Teixeira, and Joan Blade. "Efficacy and Safety of Re-Treatment with Bortezomib (Velcade©) in Patients with Multiple Myeloma: Results from a Prospective International Phase II Trial." Blood 112, no. 11 (November 16, 2008): 3690. http://dx.doi.org/10.1182/blood.v112.11.3690.3690.
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Abstract Background: Bortezomib has been shown to be effective in the treatment of multiple myeloma (MM). However, the data on response to re-treatment with bortezomib is very limited, mostly coming from small retrospective studies. Response to re-treatment is particularly relevant in patients with relapsing incurable conditions such as MM. The primary objective of this first international prospective phase II trial was to determine the best response to bortezomib re-treatment in patients with MM. Secondary objectives included safety profile, duration of response, time to progression, best M protein response and the evaluation of the best investigator-assessed response compared to the best response reported to the previous bortezomib treatment. Methods: Patients with secretory MM were eligible if they had responded (CR or PR) to a bortezomib-based most recent treatment and had a treatment-free interval of at least 6 months since the last bortezomib dose. They needed to meet the PD criteria as defined by European Group for Blood and Marrow Transplantation (EBMT). Patients received bortezomib starting at the last tolerated dose in the previous bortezomib regimen (1.3 or 1.0 mg/m2). Bortezomib was administered alone or in combination with dexamethasone at investigator discretion. Bortezomib was administered as an intravenous injection on days 1, 4, 8 and 11 of a 21-day cycle up to a maximum of 8 cycles. Response was evaluated every 6 weeks according to EBMT criteria. Adverse events (AEs) were assessed from informed consent until at least 30 days after treatment and were graded by the NCI-CTCAE. This clinical trial closed to recruitment on 30th June 2008 after reaching the planned sample size of 128 patients, with 57 patients still receiving treatment. The results presented include the efficacy and safety data available for 100 patients who had completed at least 2 treatment cycles at the time of data cut-off (16 July 2008) or who had withdrawn from therapy for any reason. Results: The 100 patients (M: 59, F: 41; median age 66 years) who received at least 1 dose of bortezomib are included in the current safety analysis. The median time from diagnosis of MM was 4.5 years (range 0–14 years) and 59% had received 3 or more lines of prior therapy (including the previous bortezomib therapy). Karnofsky performance status was £ 70% in 16% of patients. Twenty-six percent of patients had achieved a complete response (CR) with the last bortezomib regimen. The median treatment free interval since the previous bortezomib treatment was 14.3 months. Eighty-seven percent of the patients received at least 3 cycles and the median number of completed cycles was 5 cycles. Dexamethasone was added to the bortezomib treatment in 69% of patients. In the 97 patients eligible for the current efficacy analysis, the overall response rate (ORR) by EBMT criteria [CR+PR] was 26.8% (CI=18.3– 36.8), with 3.1% complete responses, whilst ORR + minimal response (MR) was 46.4%. The ORR did not differ in patients treated with bortezomib plus dexamethasone (27.9%, CI=17.7– 40.1) versus those treated with bortezomib alone (24.1%, CI=10.3–43.5). The median time to at least PR was 43 days, with a median time to best response of 64 days. The most commonly reported related grade 3/4 adverse events were thrombocytopenia (24%), neutropenia (5%) and diarrhea (5%). Peripheral neuropathy (PN) was observed in 20% of patients, with grade 3 PN reported in 6% of patients only. Serious TEAE’s were reported in 23% of patients and 10% of patients discontinued bortezomib due to related TEAE’s including 6 cases of PN. TEAE’s leading to death were reported in three patients. Conclusions: Response after re-treatment with bortezomib alone or in combination with dexamethasone in heavily pre-treated multiple myeloma patients was still high, and the adverse event profile was consistent with the already known safety profile. Updated results will be presented at time of the meeting.
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Tomirotti, M., and B. Galassi. "Oral vinorelbine in first line treatment of NSCLC in elderly: Updated results of a low dose schedule in a single institution experience." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 18192. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.18192.
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18192 Background: Oral Vinorelbine has been reported as an effective treatment option for advanced NSCLC in patients not suitable for CDDP containing schedules. Methods: With the aim to improve the toxicity profile of oral Vinorelbine therapy in the elderly setting, from 01/2004 to 05/2006, 31 patients with stage IIIB-IV NSCLC were treated with single agent oral Vinorelbine at the dose of 60 mg/m2 day 1,8,15 every 3 weeks. Median age of patients was 75 (range 65 to 82) and M/F ratio 1,6. All patients were untreated and received oral Vinorelbine as first line chemotherapy. 24/31 pts were first diagnosed and not suitable for surgery (14/24 locally advanced, 4/24 not operable for comorbidity, 6/24 stage IV at diagnosis), 7/31 recurring after surgery. Pathology reports 15/31 adenocarcinoma, 9/31 squamous, 7/31 non-small cells (citology). Sites of distant metastases were as follow: liver in 13%, bone in 16%, mediastinal lymph nodes in 71%. Median Karnofsky performance status was 80 (range 60–90). Results: Adverse event were experienced by 35% of patients, but were generally mild (grade 1–2). In particular fatigue was reported by 13%, parhestesias by 16%, gastrointestinal disconfort (mild nausea/diarrea) by 26%, costipation/abdominal pain by 10%, trombocytopenia by 6%; no patient experienced anorexia, emesis nor febrile neutropenia. Dose reduction was never required.Complete reversal of adverse effects was always documented. No patient experienced CR; 6/31 (19%) PR and 8/31 (26%) SD were reported with clinical benefit in 14/31 patients (45%). Median time to progression and overall survival were 4,2 and 9 months, not different from data reported in recent literature for higher intensity schedule (Gridelli C, et al.: Eur J Cancer 40:2424–43, 2004) Conclusions: Treatment with oral Vinorelbine at the 60 mg/m2 day 1,8,15 every 3 weeks schedule has a low toxicity profile and seems to be better tolerated than the conventional dose of 80 mg/m2, representing a valide alternative for elderly patients with advanced NSCLC. No significant financial relationships to disclose.