bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathological prognostic and predictive factors of malignant peripheral nerve sheath tumors (MPNST) survival and treatment efficacy.
Authors: Sobczuk Pawel , Teterycz Pawel , Zdzienicki Marcin , Napierala Marcin , Morysinski Tadeusz , Switaj Tomasz , Rutkowski Piotr , Czarnecka Anna Malgorzata 
Published: March 2020

e22537 Background: MPNST accounts for about 5% of soft tissue sarcomas. It is known to have high metastatic potential and poor prognosis, but reported long-term outcomes vary widely across published series. Our study aimed to determine factors affecting clinical outcome in a large cohort of patients (pts) with MPNSTs treated at reference sarcoma center. Methods: 289 consecutive pts (144 woman and 145 man) referred, diagnosed and treated between 03/1998 and 04/2018 were analyzed. Kaplan-Meier estimator and the log-rank test were used in survival analysis and multivariate Cox proportional hazards model was used to confirm the correlation. Results: Mean age at diagnosis was 50y (15-86). 39 (13.5%) pts were NF1 positive, 12 were primary diagnosed with metastatic disease. After median follow-up of 66.5 months (m) (95% confidence interval, CI 58.1 – 85.2) 151 pts continue treatment or follow-up. Median OS was 55.7m (39.3 - 148.9) in the whole group while 5y survival rate was 48.8% (CI: 42.8-55.7%). 37/167 pts with radical resection in reference center developed local recurrence, and 75/92 pts operated first in regional hospitals. Median DFS was 29.7m (CI: 16.1-58.3) in case of treatment in reference center and 4.1m (CI: 2.4-9.2) in case of regional hospital (p < 0.001).72 pts developed metastatic disease and were treated with chemotherapy. Median PFS on 1st line was 5.6m (CI: 3.3 - 8.1), There were no statistically significant differences in survival rates nor in response rates between doxorubicin- and ifosfamid-based regiments. Tumor size at diagnosis (HR:2.33, CI: 1.50-3.62), high grade (HR:3.31, CI:2.14-5.12) and R0 resection (HR:0.47, CI:0.30-0.72) were the strongest independent predictors of DFS and OS. (neo)adjuvant radiotherapy did not influenced LRFS in case of R0 resection but improved LRFS when complete resection was not feasible (HR: 0.22 CI: 0.08-0.58 p = 0.002). Conclusions: MPSNT is a highly aggressive tumor with poor prognosis. High quality surgery remains the mainstay of management for these patients, but multimodal treatment should be considered in majority of cases in MDT units. There is unmet need for new therapies in advanced/metastatic cases.
Profiling of targetable aberrations in advanced sarcoma.
Authors: Hamid Muhammad Saad , Al Masalmeh Nada , Poorman Kelsey Anne , Weise Amy M. 
Published: March 2020

e22559 Background: Soft tissue and bone sarcoma (STS/BS) are heterogeneous and difficult to treat malignancies. Recent advances in molecular testing improved our understanding of the disease biology. Methods: Retrospective data on non-GIST sarcoma cases were analyzed using next genomic sequencing (NGS) (MiSeq on 47 genes, NextSeq on 592 genes), immunohistochemistry (IHC), fusion transcript detection and copy number alterations (CNA) by Caris Life Sciences between July 2010 and November 2018 at Karmanos Cancer Institute. Targetable aberrations (TA) were identified by searching available literature on therapeutics tested in clinical trials. Results: Demographic data on 64 patients were analyzed; median age 56 (21-87y) and a 1:1 gender ratio. Most frequent histologies include Leimyosarcoma (LMS) 15.3% (n = 10) and Undifferentiated Pleomorphic Sarcoma (UPS) 12.5% (n = 8). Genetic aberrations occurred in 78% of cases, with a cumulative 302 aberrations and a mean 4.7 TA (1-11)/case. Frequent aberrations by methodologies include a) IHC: TOP2A 64.3% (n = 36), MGMT 53.9% (n = 28), TUBB3 49% (n = 24); b) NGS: TP53 37.8% (n = 17); c) CNA: CDK4 and MDM2 at 9.3% (n = 4) respectively; d) fusion transcript: NOTCH2 fusion (n = 1), p < 0.05. All cases were MSI stable. TA constituted 37.1% (n = 112) of the identified aberrations in the cohort and existed in 89.1% (n = 57) cases with a mean of 3.08 TA/case, p < 0.05. Frequent TA other than TOP2A, TP53, MGMT by histologies included a) LMS: RRM1 28.6% (n = 4), PI3KCA and ER/PR at 14.3% (n = 1) each respectively; b) UPS: TUBB3 50% (n = 4), PD-1 25% (n = 2); c) Sarcoma NOS: CDK4 28.6% (n = 2), TS 28.6% (n = 2), C-MET and EGFR at 14.3% (n = 1) each respectively; d) Well Differentiated/Dedifferentiated Liposarcoma: CDK4, MDM2 and PD-1 at 20% (n = 1) each respectively. Conclusions: Incorporating genomic profiling has helped personalize treatment to include clinical trial enrollment. Further drug development and prospective studies are required in this population.
Fast time estimation to predict levels of anxiety in cancer patients.
Authors: Tonev Ivan , Conev Nikolay Vladimirov , Valev Spartak Stoyanov , Panayotova Teodorika , Karanikolova Teodora , Donev Ivan 
Published: March 2020

e23162 Background: Our study explored the potential relationship between the time estimation and the level of anxiety in cancer patients prior to starting chemotherapy. Methods: Time estimation was assessed in 90 chemonaïve patients with solid tumors by evaluating each subject’s prospective estimation of how fast one minute passed compared to the actual time. The median value (37 sec) of time estimation was used to stratify the patients into two categories of fast and slow time estimation. We used generalized anxiety disorder (GAD-7) as a screening tool for detecting levels of anxiety. Scores ≥10 we considered as clinically significant. Results: Patients with clinically significant levels of anxiety were 23 (25.5%). The pattern of the time estimation distributions significantly changed according to the reported levels of GAD-7 scales. Scores ≥10 correlated with fast time estimation and gender. Patients who scores ≥10 estimated time significantly faster than the rest (27.3±9.2 vs 43.4±17.3; p < 0.001). ROC analysis revealed that at the optimal cutoff value of time estimation, clinically significant levels of anxiety can be discriminated with an AUC = 0.78 (95% CI: 0.68-0.87, p < 0.001) and with a sensitivity of 78.3% and a specificity of 65.2%. Moreover, in a multivariate logistic regression model, fast time estimation was an independent predictor of clinically significant levels of anxiety (OR 7.07; 95% CI 2.2-22.8; p = 0.001). Conclusions: Time estimation is a novel potent indicator for moderate and severe levels of anxiety in cancer patients. This test is an easily performed, time-saving and nonintrusive ultrashort screening tool for clinically significant levels of anxiety.
Risk factors of psychological distress and quality of life in lung cancer patients.
Authors: Zhang Fan , Wang Junyan , Hong Lei , Xu Yu , Jiang Da , Wei Suju 
Published: March 2020

e23187 Background: Most patients with lung cancer have psychological problems, which has a significant impact on patients' rehabilitation, treatment and quality of life. Through the distress and quality of life assessment, to understand the risk factors of distress, in order to improve the quality of life of lung cancer patients. Methods: The investigation was consisted of 209 lung cancer patients who were treated in Fourth Hospital of Hebei Medical University from February 2014 to December 2015.Patients were assessed through the use of distress thermometer, problem list, quality of life questionnaire. Lung cancer patients were divided into a significant distress group and a non-significant distress group. Chi-square test was used to analyze the relationship between demographic characteristics, disease information and significant distress. Logistic regression analysis was used to analyze risk factors for distress. The Spearman rank correlation was used to analyze the correlation between the significant distress group and each area of the quality of life questionnaire. The test level was significantly different at P< 0.05. Results: The distress of majority lung cancer patients was 0-4 points, 68 cases were significant distress, significant distress rate was 32.5%. Logistic regression showed PS scores, family residence, informed condition were risk factors of significant distress( P< 0.001 < P= 0.035, P= 0.031). Economic problems were the most common cause of psychological distress in lung cancer patients. Other risk factors included the lack of time and energy to take care for the elderly/children, fear, sadness, dizziness and pain. The significant distress of lung cancer patients was negatively correlated with health status, physical function, emotional function, cognitive function, social function, and was positively correlated with symptoms as fatigue, nausea and vomiting, pain, shortness of breath, insomnia, loss of appetite and constipation. Conclusions: The incidence of significant distress in patients with lung cancer is 32.5%. PS score, fully informed, and family residence are the risks of significant distress in patients. The distress of lung cancer patients is significantly related to the quality of life.
Communication challenges among medical oncologists in Mexico.
Authors: Platas Alejandra , Jasqui Ariel , Pineda Claudia , Fonseca Alan , Platas Ana , García-García Marisol , Mesa-Chavez Fernanda , Villarreal-Garza Cynthia 
Published: March 2020

e23190 Background: Communication in oncology practice presents numerous challenges. Patients may react to the diagnosis and treatment information with unpredictable and difficult to manage emotions, which may distress clinicians and affect patient-physician relationships. An effective communication has shown a beneficial effect on satisfaction from both patients and providers, as well as on quality of health care provision and patients’ adherence, decision-making processes and outcomes. Aim: To identify the most important and hardest topics to discuss during consultation that pose a challenge for Mexican medical oncologists during their clinical practice. Methods: Physicians were reached out by a messaging platform to complete a survey that addressed the most relevant and difficult issues for discussion and the frequent challenges they face during information exchange. Results: A total of 115 oncologists completed the survey. Most of them identified treatment objectives, prognosis and treatment selection as important issues to discuss with patients. They coincided that the hardest matters to disclose were palliative care referral, treatment objectives, prognosis and recurrence. Also, oncologists reported that the most important challenges they face when communicating with patients are being honest without being hopeless (43%) and responding to patients’ emotions (21%). 92% expressed that they would like to receive formal training in communication skills. Conclusions: The issues regarded as highly important to discuss with patients were also the most difficult ones to address, possibly due to barriers related to patients’ emotional reactions when receiving bad news. The incorporation of a psychologist could promote calmness and trust, aid in information assimilation, and provide support to partners and relatives, as needed. Also, results showed the interest of oncologists in receiving formal training in communication skills, which reinforces the need to include this training as part of the medical oncology curriculum to ease transmission and comprehension of information. [Table: see text]
Identifying psychosocial distress in cancer patients in a community center.
Authors: Pandey Deepali , Syed Masood Pasha , Patil Shekhar , Hassan Mohamed , Frederick Matthew , LaCerte-Blais Donna , Blanchard Gary P. , Shepro David Scott , Siddiqui Ahmad Daniyal 
Published: March 2020

e23193 Background: Psychosocial distress is common in cancer patients. It can cause decreased treatment adherence, lesser treatment satisfaction, low quality of life, and lower survival rate. Distress management is critical to improving cancer survivorship. National Comprehensive Cancer Network (NCCN) Distress Thermometer (DT) is widely used to assess psychosocial problems in cancer patients in five categories - practical, family, emotional, spiritual and physical problems. The aim of our study is to identify the distress pattern in cancer patients undergoing chemotherapy in our center using DT adapted from the NCCN. Methods: This is a retrospective study. Total 192 cancer patients undergoing chemotherapy were included, who were screened with DT at initial visit. Patients were asked to rate their level of distress from 0-10 on DT and select categories. We collected data on distress score, selected categories, age, gender, and primary cancer site. Distress score < 4 were defined as low and = > 4 as high. Our objective was to evaluate distress categories and if distress level (high vs low) is dependent on age ( < 65 vs = > 65), gender, and primary cancer site (top 7 cancer types in our clinic by volume). Statistical test used - Chi-square. Results: Median age - 66.5 years (range: 29-96); Gender: Male/Female - 44.3%/55.7%. Median distress score - 3. Low distress was reported by 55.2% and high distress by 44.8%. Cancer types: Breast (29.7%); Lung (17.7%); Prostate (10.9%); Hematological malignancies (7.3%); Lymphoma (6.7%); Urothelial (6.7%); Head and Neck (6.2%); Others (13.4%). Overall, physical problems were the most common (63.5%) followed by emotional (56.3%), practical and family (32.3%), and spiritual (2.1%). Among patients with high distress, 84.9% reported emotional problems, while 83.7% reported physical problems. Distress level was not dependent on age, gender and primary cancer site. Conclusions: Emotional and physical problems are the most common problems among our study population with high distress level which requires further interventions/referrals. Identifying psychosocial needs of cancer patients with DT can help optimize their care.
A phase III trial to evaluate the efficacy of uproleselan (GMI-1271) with chemotherapy in patients with relapsed/refractory acute myeloid leukemia.
Authors: DeAngelo Daniel J. , Erba Harry Paul , Jonas Brian Andrew , O'Dwyer Michael , Marlton Paula , Huls Gerwin A , Liesveld Jane , Cooper Brenda W. , Bhatnagar Bhavana , Armstrong Michael , Fogler William , Chen Mary , Magnani John , Thackray Helen M. , Advani Anjali S. , Becker Pamela Sue 
Published: March 2020

TPS7066 Background: Binding of E-selectin (E-sel) to sialyl Lex, the E-sel ligand (E-sel-L), on the leukemic cell surface activates cell survival pathways and promotes chemotherapy resistance in AML. Expression of E-sel-L is associated with increased relapse and poor survival. Uproleselan (GMI-1271), a novel E-sel antagonist, disrupts cell survival pathway activation, enhances chemotherapy response and protects from toxicity such as mucositis with improved survival in vivo. Preclinical data support combination with multiple agents to achieve improved chemosensitivity and toxicities. A phase I/II study of uproleselan added to chemotherapy in R/R AML showed promising remission rates (CR/CRi) and survival outcomes, and reduced rates of mucositis. High E-sel-L expression on leukemic blasts in the bone marrow, rather than connoting treatment resistance and poor survival, instead correlated with longer survival than expected with addition of uproleselan. Breakthrough Therapy Designation was granted by FDA for treatment of patients with R/R AML. A pivotal phase 3 study (NCT03616470) is underway to assess the efficacy and safety of uproleselan with standard salvage chemotherapy in R/R AML. Methods: This study is a global, randomized, double-blind, phase 3 trial in adults aged 18-75 years with R/R AML and fit for chemotherapy. Patients may have primary refractory AML (received 1 prior induction containing an anthracycline and cytarabine), or be in untreated first or second relapse; prior HSCT is allowed. Treatment is MEC (mitoxantrone, etoposide, cytarabine) or FAI (fludarabine, cytarabine, idarubicin) induction regimen with blinded study drug (Uproleselan:placebo at 1:1 ratio) administered 1 day prior (sentinel dose) and then BID through 2 days post chemotherapy. Consolidation (HIDAC/IDAC) with uproleselan/placebo (same assignment) up to 3 cycles is allowed. The primary endpoint is overall survival; key secondary endpoints include the incidence of severe oral mucositis during induction and CR/CRh rate. Measurable residual disease, E-sel-L expression on leukemic cells, event free survival, safety, and pharmacokinetics will also be evaluated. Clinical trial information: NCT03616470.
Phase 2 study of zanubrutinib (BGB-3111) in patients with relapsed/refractory marginal zone lymphoma (R/R MZL).
Authors: Opat Stephen , Marcus Robert , Portell Craig Anthony , Reed William , Co Melannie , Huang Jane , Trotman Judith 
Published: March 2020

TPS7568 Background: Bruton tyrosine kinase (BTK) plays a critical role in B-cell receptor signaling, mediating B-cell proliferation, migration, adhesion and survival. BTK inhibition has emerged as a strategy for targeting B-cell malignancies, including MZL. In preclinical studies, zanubrutinib was shown to be a potent, irreversible, highly specific BTK inhibitor with excellent oral bio-availability and favorable pharmacokinetic/pharmacodynamic properties. Clinical data to date have shown that complete and sustained 24-hour BTK occupancy is associated with durable responses and suggested that zanubrutinib is generally well tolerated with low rates of serious adverse events. Preliminary results from the MZL cohort enrolled in the open-label, multicenter, phase 1 study demonstrated responses in 7 of 9 patients for an overall response rate (ORR) of 78%. Cumulative safety data also showed that zanubrutinib monotherapy was associated with infrequent incidence of atrial fibrillation and major hemorrhage and infrequent drug discontinuation due to treatment-related adverse events. This study is designed to evaluate the safety and efficacy of zanubrutinib in patients with R/R MZL. Methods: This ongoing global phase 2, single-arm, open-label study is examining zanubrutinib monotherapy in patients with R/R MZL who have received one or more prior lines of systemic therapy. Patients are treated with oral zanubrutinib at 160 mg twice-daily until progressive disease, unacceptable toxicity, or withdrawal of consent. Eligible patients must have histologically confirmed MZL, have received prior anti-CD20 antibody therapy, and have measurable disease. Disease response is assessed per the 2014 Lugano Classification for non-Hodgkin lymphoma. The primary endpoint is ORR determined by independent review committee (IRC). Key secondary endpoints include ORR by investigator assessment, time to and duration of response, time to treatment discontinuation, progression-free survival (all determined by IRC and investigator assessments), and overall survival and safety. Recruitment is ongoing.
ZUMA-12: A phase 2 multicenter study of axicabtagene ciloleucel (axi-cel) as a first-line therapy in patients (pts) with high-risk large B-cell lymphoma (LBCL).
Authors: Neelapu Sattva Swarup , Chavez Julio C. , Lin Yi , Munoz Javier , Ujjani Chaitra Shankar , Riedell Peter , De Vos Sven , Oluwole Olalekan O. , Kekre Natasha , Yang Yin , Goyal Lovely , Backhouse Kate , Milletti Francesca , Kawashima Jun , Herrera Alex Francisco 
Published: March 2020

TPS7574 Background: Pts with LBCL who have persistent disease assessed by dynamic PET after rituximab-based induction therapy have an increased risk of death (Casasnovas, et al. Blood. 2017). Axi-cel is an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy approved for the treatment of pts with relapsed/refractory LBCL with ≥ 2 prior systemic therapies. In ZUMA-1, the registrational study of axi-cel in pts with refractory LBCL, the objective response rate (ORR) was 91% (70% complete response [CR] rate) in pts with double-expressor or high-grade LBCL with ongoing responses in 48% after a median follow-up of 27.1 mos (Locke FL, et al. Lancet Oncol 2019). Furthermore, pts with fewer prior lines of therapy and lower tumor burden had higher rates of ongoing responses and manageable safety (Locke et al. ASCO 2018. 3039). ZUMA-12 will investigate the efficacy and safety of axi-cel as a first-line therapy in newly diagnosed pts with high-risk LBCL who have PET-positive disease after 2 cycles of induction therapy. Methods: This Phase 2 study has a planned enrollment of ≈40 pts aged ≥ 18 y with high-risk LBCL, defined by the presence of MYC and BCL2 and/or BCL6 translocations by FISH or an IPI score ≥ 3 any time before enrollment, and an ECOG performance status of 0 – 1. Before enrollment, pts must have a Deauville score of 4 – 5 (Barrington SF et al. J Clin Oncol. 2014) after 2 cycles of chemoimmunotherapy that includes an anti-CD20 monoclonal antibody and anthracycline. After leukapheresis, pts with bulky or rapidly progressing disease may receive optional non-chemotherapy bridging therapy. Following conditioning therapy with cyclophosphamide (500 mg/m2) and fludarabine (30 mg/m2) for 3 days, pts will receive a single infusion of axi-cel at a target dose of 2 × 106 CAR T cells/kg. The primary endpoint is investigator-assessed CR rate per the Lugano classification (Cheson et al. J Clin Oncol. 2014). Key secondary endpoints include ORR, duration of response, event-free survival, progression-free survival, overall response, safety, relapse with CNS disease and levels of blood CAR T cells and serum cytokines over time. Accrual is ongoing. Clinical trial information: NCT03761056.
A multicenter, open label, uncontrolled, phase II clinical trial evaluating the safety and efficacy of venetoclax in combination with atezolizumab and obinutuzumab in richter transformation of CLL.
Authors: Montillo Marco , Rossi Davide , Zucca Emanuele , Frustaci Anna Maria , Pileri Stefano , Cavalli Franco , Tedeschi Alessandra 
Published: March 2020

TPS7575 Background: Diffuse large B-cell (DLBCL) transformation from chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), Richter Syndrome (RS), has poor prognosis. Venetoclax, Bcl-2 inhibitor, has shown activity either in DLBCL and DLBCL-type RS. Atezolizumab is a humanized immunoglobulin monoclonal antibody (MoAb) targeting PD-L1 on tumor-infiltrating immune cells or tumor cells and prevents interaction with the PD-1 receptor and B7.1. Obinutuzumab, anti CD-20 MoAb compared to rituximab, presents a greater antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis and direct cell death. Preliminary data of atezolizumab alone or in combination with obinutuzumab showed to be safe and promising in heavily pretreated DLBCL. We present a phase II trial evaluating safety and efficacy of venetoclax, atezolizumab, obinutuzumab combination in RS. Methods: Eligible pts are: ≥18 years, ECOG PS ≤2, diagnosis of DLBCL RS from CLL/SLL. Exclusion criteria: pretreated RS, prior therapy with venetoclax or atezolizumab, CNS involvement, history of autoimmune disease. The study consists of 2 phases. In the run-in phase 9 pts will be enrolled in three cohorts of 3 subjects each. If no more than 1 pt in each of the 3 groups experiences during the first 3 cycles: treatment-related death or grade 4 non-infective/non-hematologic adverse event; the expansion phase will follow enrolling up to 31 pts. Treatment consists of 35 cycles with: obinutuzumab (1000 mg C1-8), atezolizumab (1200 mg C1-18), venetoclax (400 mg/d C1-35). Primary endpoint of the study is safety and tolerability for the run-in phase; efficacy (overall response, complete remissions, response duration, progression free and overall survival) for the expansion phase. Safety and efficacy are also secondary endpoints of each phase. Exploratory consists of MRD monitored by flow cytometry and ultra-deep NGS of disease markers; correlation between outcome and disease biomarkers. EUDRACT 2018-005028-40. Clinical trial information: 2018-005028-40.